TPG-functionalized PLGA/PCL nanofiber membrane facilitates periodontal tissue regeneration by modulating macrophages polarization via suppressing PI3K/AKT and NF-κB signaling pathways.

Traditional fibrous membranes employed in guided tissue regeneration (GTR) in the treatment of periodontitis have limitations of bioactive and immunomodulatory properties. We fabricated a novel nTPG/PLGA/PCL fibrous membrane by electrospinning which exhibit excellent hydrophilicity, mechanical properties and biocompatibility. In addition, we investigated its regulatory effect on polarization of macrophages and facilitating the regeneration of periodontal tissue both in vivo and in vitro. These findings showed the 0.5%TPG/PLGA/PCL may inhibit the polarization of RAW 264.7 into M1 phenotype by suppressing the PI3K/AKT and NF-κB signaling pathways. Furthermore, it directly up-regulated the expression of cementoblastic differentiation markers (CEMP-1 and CAP) in periodontal ligament stem cells (hPDLSCs), and indirectly up-regulated the expression of cementoblastic (CEMP-1 and CAP) and osteoblastic (ALP, RUNX2, COL-1, and OCN) differentiation markers by inhibiting the polarization of M1 macrophage. Upon implantation into a periodontal bone defect rats model, histological assessment revealed that the 0.5%TPG/PLGA/PCL membrane could regenerate oriented collagen fibers and structurally intact epithelium. Micro-CT (BV/TV) and the expression of immunohistochemical markers (OCN, RUNX-2, COL-1, and BMP-2) ultimately exhibited satisfactory regeneration of alveolar bone, periodontal ligament. Overall, 0.5%TPG/PLGA/PCL did not only directly promote osteogenic effects on hPDLSCs, but also indirectly facilitated cementoblastic and osteogenic differentiation through its immunomodulatory effects on macrophages. These findings provide a novel perspective for the development of materials for periodontal tissue regeneration.

Exploring Novel Applications for Hydrogels Derived from Modified Celluloses.

The valorization of lignocellulosic biomass by-products holds significant economic and ecological potential, considering their global overproduction. This paper introduces the fabrication of a novel wheat-straw-based hydrogel and a new microcellulose-based hydrogel through 2,2,6,6-tetramethylpiperidinyl-1-oxy (TEMPO) oxidation. In this study, Fourier transform infrared (FTIR) analysis was employed for the detection of carboxyl groups, neutralization titration was conducted using a conductivity meter, viscosity analysis was performed using a rheometer, and transmittance analysis was carried out using a spectrophotometer. Two novel hydrogels based on TEMPO oxidation have been developed. Among them, the bio-based hydrogel derived from oxidized wheat straw exhibited exceptional printability and injectability. We found that the oxidation degree of microcellulose reached 56-69%, and the oxidation degree of wheat straw reached 56-63%. The cross-linking of 4% oxidized wheat straw and calcium chloride was completed in 400 seconds, and the viscosity exceeded 100,000 Pa·s. In summary, we have successfully created low-cost hydrogels through the modification of wheat straw and microcellulose, transforming lignocellulosic biomass by-products into a sustainable source of polymers. This paper verifies the future applicability of biomass materials in 3D printing.

Effective disinfecting of negative pressure pipelines of DCUs reduces the risk of cross infection in dental care.

Objectives: Microbial contamination of various accessory parts of the dental chair units (DCUs) is an essential source of cross infection, while the accessories of the crucial suction function are usually overlooked. In this study, we aim to find an effective disinfectant and a cost-effective method to remove bacterioplankton and bacterial biofilm deposited in the negative pressure suction pipelines to control cross infection during dental treatment. Methods: Double-chain quaternary ammonium salt disinfectant (Orotol Plus®), 3% hydrogen peroxide solution plus multi-enzyme cleaning agent and chlorine disinfectant are used to clean and disinfect the negative pressure pipelines of DCUs. Microbiological examinations, air condition detection, corrosion tests and gene sequencing are performed. Results: Little bacteria grow in the pipelines disinfected with double-chain quaternary ammonium salt disinfectants, destruction of biofilms in these pipelines appears, and multi-resistant bacteria cannot be detected. Minimal damage to metal sheets and fittings is caused by double-chain quaternary ammonium salt disinfectants. Conclusion: Double-chain quaternary ammonium salt disinfectant has excellent bactericidal ability and anti-biofilm effect, and it is less corrosive to the fittings of the pipelines. Thus, the double-chain quaternary ammonium salt disinfectant is a potential novel disinfectant for negative pressure suction pipelines of DCUs to control cross infection during dental treatment. Clinical significance: It is essential to add all these data to our dental practice to control cross infection with a broader landscape.

Spatiotemporal transcriptome atlas reveals the regional specification of the developing human brain.

Different functional regions of brain are fundamental for basic neurophysiological activities. However, the regional specification remains largely unexplored during human brain development. Here, by combining spatial transcriptomics (scStereo-seq) and scRNA-seq, we built a spatiotemporal developmental atlas of multiple human brain regions from 6-23 gestational weeks (GWs). We discovered that, around GW8, radial glia (RG) cells have displayed regional heterogeneity and specific spatial distribution. Interestingly, we found that the regional heterogeneity of RG subtypes contributed to the subsequent neuronal specification. Specifically, two diencephalon-specific subtypes gave rise to glutamatergic and GABAergic neurons, whereas subtypes in ventral midbrain were associated with the dopaminergic neurons. Similar GABAergic neuronal subtypes were shared between neocortex and diencephalon. Additionally, we revealed that cell-cell interactions between oligodendrocyte precursor cells and GABAergic neurons influenced and promoted neuronal development coupled with regional specification. Altogether, this study provides comprehensive insights into the regional specification in the developing human brain.

Prognostic and clinicopathological significance of MMP12 in various cancers: a meta-analysis and bioinformatics analysis.

Background: Cancer is one of the top causes of mortality worldwide. The matrix metalloproteinase MMP12 is highly expressed in some cancers, but there is a lack of meta-analyses proving the correlation between MMP12 and cancer. Materials & methods: A literature search was performed using Web of Science, PubMed and other databases. Quantitative meta-analysis of the data was carried out. The Cancer Genome Atlas was further used to validate our results. Results: High MMP12 expression was associated with poorer overall survival and poorer 5-year overall survival. Elevated expression of MMP12 predicted shorter overall survival in six cancers and worse disease-free survival in four malignancies based on validation using the Gene Expression Profiling Interactive Analysis online analysis tool. Conclusion: Elevated MMP12 expression is likely a marker of poor prognosis in various cancers.

What is this summary about? This study looked at how a gene called MMP12 affects the survival time and health of cancer patients. The MMP12 gene makes a protein that helps cancer cells grow. We studied information from 38 research studies involving 9582 patients. We wanted to learn how the gene MMP12 is connected to the prognosis and survival of people who have cancer. What was the result? The study found that patients with less MMP12 tended to live longer. Based on this, we can say that having less of the protein MMP12 may be better for patients. By contrast, high levels of MMP12 were linked to more advanced cancer stages, so this protein may aid cancer growth. What do these results mean? These findings can help doctors diagnose cancer and predict what might happen to patients. If we can control this gene, we might find new treatments to stop cancer from growing and help people live longer. However, we need to do more research to be sure about these findings and to understand this gene better.

An investigation into the response of the soil ecological environment to tourist disturbance in Baligou.

The purpose of this study is to understand the response patterns of the soil ecological environment of the Macau Wetland Park to different levels of tourist interference and to provide a scientific basis for the rational development of the Bali Gou ecological tourism plan and the protection and management of the scenic area's ecological environment. Combine the methods of field collection and laboratory physical and chemical data analysis to analyze the impact of the strength of tourism disturbance on the soil ecological environment of Baligou. During the tourist activities in Baligou, the human factors in the process have an impact on the physical aspects of the scenic area's soil, such as soil bulk density, color tone, porosity, compactness, capacity, and leaf litter. In addition, pH value, soil enzyme activity, organic matter, and heavy metals in the soil have caused some interference. The overall data show that the dynamic of soil indicators is background area < buffer area < disturbed area,where the sample area is affected by human trampling and infrastructure construction and other disturbances leading to regular changes in the content of Pb and Cr in the sample soil, while the content of other heavy metals is lower than the national standard.The range of the most extreme values of the SRI integrated soil ecological response evaluation index was A1 disturbance area = 4.679 and C1 background area = 1.263, respectively. The larger the value of the SRI response index, the greater the impact and negative effect of the disturbance influence of tourism activities on the soil ecological environment of the scenic area, and the higher the level of response of the soil ecological environment of the scenic area to the disturbance of tourism activities. Moderate and reasonable tourism development activities play a role in promoting soil quality in scenic areas. Therefore, it is suggested to carry out reasonable ecological environment planning and take certain macro-measures to prevent the deterioration of the soil ecological environment, so as to achieve a win-win situation of ecological environmental protection while developing the tourism economy in scenic areas.

A generalized AI method for pathology cancer diagnosis and prognosis prediction based on transfer learning and hierarchical split.

Objective.This study aims to propose a generalized AI method for pathology cancer diagnosis and prognosis prediction based on transfer learning and hierarchical split.Approach.We present a neural network framework for cancer diagnosis and prognosis prediction in pathological images. To enhance the network's depth and width, we employ a hierarchical split block (HS-Block) to create an AI-aided diagnosis system suitable for semi-supervised clinical settings with limited labeled samples and cross-domain tasks. By incorporating a lightweight convolution unit based on the HS-Block, we improve the feature information extraction capabilities of a regular network (RegNet). Additionally, we integrate a Convolutional Block Attention Module into the first and last convolutions to optimize the extraction of global features and local details. To address limited sample labels, we employ a dual-transfer learning (DTL) mechanism named DTL-HS-Regnet, enabling semi-supervised learning in clinical settings.Main results.Our proposed DTL-HS-Regnet model outperforms other advanced deep-learning models in three different types of cancer diagnosis tasks. It demonstrates superior feature extraction ability, achieving an average sensitivity, specificity, accuracy, and F1 score of 0.9987, 1.0000, 1.0000 and 0.9992, respectively. Furthermore, we evaluate the model's capability to directly extract prognosis prediction information from pathological images by constructing patient cohorts. The results show that the correlation between DTL-HS-Regnet predictions and the presence of cancer-associated fibroblasts is comparable to that of pathologists.Significance.Our proposed AI method offers a generalized approach for cancer diagnosis and prognosis prediction in pathology. The outstanding performance of the DTL-HS-Regnet model demonstrates its potential for improving current practices in image digital pathology, expanding the boundaries of cancer treatment in two critical areas.

Quantitative Analysis of Quality of Life and Exploration of Influencing Factors in Patients Undergoing Radical Prostatectomy.

OBJECTIVE: To quantify and evaluate the quality of life of patients undergoing radical prostatectomy using the FACT-P scoring system, and to explore the predictive factors for postoperative quality of life. METHODS: Clinical data of 249 patients who underwent radical prostatectomy in our hospital from January 2021 to October 2022 were analyzed. According to the surgical method and whether the subjective quality of life of the patient decreased significantly, the patients were divided into groups, and the predictive factors for changes in subjective quality of life after surgery were analyzed. RESULTS: A total of 192 cases were finally obtained (45 cases of fascia internal approach, 147 cases of traditional radical prostatectomy), and patients who underwent fascia internal approach (FACT-P: 110.15 ± 10.55) had better postoperative quality of life than those who underwent extra-fascial radical prostatectomy (FACT-P: 102.30 ± 6.75) (P < .01). One hundred fourteen patients reported a decrease in subjective quality of life, while 78 did not. The preoperative FACT-P score was an independent predictive factor (OR=0.719, P < .01), and when the preoperative score was <116 points, the possibility of no decrease in quality of life after surgery was higher. CONCLUSION: Fascia internal approach should be performed as much as possible for suitable surgical patients, and for patients with a preoperative FACT-P score ≥116 points, the possibility of a decrease in quality of life after surgery should be fully communicated.

Molecular and functional characterization of two granulocyte colony stimulating factors in goldfish (Carassius auratus L.).

Granulocyte colony-stimulating factor (GCSF) is a member of the hematopoietic growth factor family that acts primarily on neutrophils and neutrophilic precursors to promote cell proliferation and differentiation. Although multiple GCSF genes have been found in teleosts, knowledge of their functions during fish hematopoietic development is still limited. Here, we report for the first time the molecular and functional characterization of two goldfish GCSFs (gfGCSF-a and gfGCSF-b). The open reading frame (ORF) of the gfGCSF-a and gfGCSF-b cDNA transcript consisted respectively of 624 bp and 678 bp with its ORF encoding 207 and 225 amino acids (aa), with a 17 aa signal peptide for each gene and a conserved domain of the IL-6 superfamily. Treatment of goldfish head kidney leukocytes (HKLs) with LPS increased gfGCSF-a and gfGCSF-b mRNA expression levels, also exposure of HKLs to either heat-killed or live A. hydrophila, induced transcriptional upregulation of gfGCSF-a and gfGCSF-b levels. Recombinant gfGCSF-a and gfGCSF-b protein (rgGCSF-a and rgGCSF-b) induced a dose-dependent production of TNFα and IL-1ß from goldfish neutrophils. In vitro experiments showed rgGCSF-a and rgGCSF-b differentially promoted the proliferation and differentiation of leukocytes in goldfish. Furthermore, treatment of HKLs with rgGCSF-a showed significant upregulation of mRNA levels of the hematopoietic transcription factor GATA2, Runx1, MafB, and cMyb, while gfGCSF-b induces not only all four transcriptional factors mentioned above but also CEBPα. Our results indicate that goldfish GCSF-a and GCSF-b are important regulators of neutrophil proliferation and differentiation, which could stimulate different stages and lineages of hematopoiesis.

Prognostic and clinicopathological significance of TRIM21 in various cancers: A meta and bioinformatic analysis.

BACKGROUND: Tripartite motif-containing protein 21 (TRIM21), a member of the ubiquitin ligase family, makes a significant contribution to the ubiquitination of multiple tumor marker proteins associated with tumor cell proliferation, metastasis and selective apoptosis. As the research further develops, an increasing number of studies have manifested that the TRIM21 expression level can be considered an indicator of cancer prognosis. However, the interrelationship between TRIM21 and multiple forms of carcinogens has not been demonstrated in a meta-analysis. METHODS: We performed a systematic literature retrieval in various electronic databases including PubMed, Embase, Web of Science, Wanfang and China National Knowledge Infrastructure. Besides, the hazard ratio (HR) and the pooled relative risk (RR) were integrated in the assessment of cancer incidence and cancer mortality by Stata SE15.1. Additionally, we used an online database based on The Cancer Genome Atlas (TCGA) to further validate our results. RESULTS: A total of 17 studies were included, totaling 7239 participants. High expression of TRIM21 was significantly correlated with better OS (HR = 0.74; 95% CI: 0.57-0.91; P < .001) and progression-free survival (PFS) (HR = 0.66; 95% CI: 0.42-0.91; P < .001). We found that high TRIM21 expression predicted significant impact on clinical characteristics like decreased lymph node metastasis (RR = 1.12; 95% CI: 0.97-1.30; P < .001), tumor stage (RR = 1.06; 95% CI: 0.82-1.37; P < .001) and tumor grade (RR = 1.07; 95% CI: 0.56-2.05; P < .001). However, TRIM21 expression had no significant impact on other clinical characteristics such as age (RR = 1.06; 95% CI: 0.91-1.25; P = .068), sex (RR = 1.04; 95% CI: 0.95-1.12; P = .953), or tumor size (RR = 1.14; 95% CI: 0.97-1.33; P = .05). Based on the Gene Expression Profiling Interactive Analysis (GEPIA) online analysis tool, TRIM21 was significantly downregulated in 5 cancers while significantly upregulated in 2 cancers, and the descending expression of TRIM21 predicted shorter OS in 5 cancers, worse PFS in 2 malignancies, while the elevated expression of TRIM21 predicted shorter OS and worse PFS in 2 carcinomas. CONCLUSIONS: TRIM21 could serve as a new biomarker for patients with solid malignancies and could be a potential therapeutic target for patients.

Planting and mowing cover crops as livestock feed to synergistically optimize soil properties, economic profit, and environmental burden on pear orchards in the Yangtze River Basin.

BACKGROUND: Pears, as an important cash crop, are currently facing great issues due to unsustainable management practices. Cover cropping is a sustainable management strategy that can improve soil fertility and increase fruit yield, while it may also stimulate greenhouse gas emissions. Therefore, synergizing multiple indicators to achieve sustainable development is critical. This study introduces a new management system, namely the planting and mowing of ryegrass as a livestock feed system (PRSS), and analyzes its impact on soil quality, economic benefits, and environmental burdens. RESULTS: Our results indicated that PRSS could increase soil pH from 5.08 to 5.48 and decrease the content of soil alkali-hydrolyzable nitrogen, total phosphate, and available phosphate (26.96-59.89%) while also enhancing yield (+38.51%) compared with the traditional natural grass management system (TMS). The average soil methane fluxes in PRSS were 72.67 µg m-2 day-1 , higher than those of TMS (61.28 µg m-2 day-1 ). However, the gross primary production was lower than TMS (-37.24%), and no significant difference was observed in soil nitrous oxide fluxes. In different scenarios, the total profit of PRSS mode 1 (mowing ryegrass and selling to a livestock company) and PRSS mode 2 (mowing ryegrass and feeding own sheep) were 10 706.21 $ ha-1 and 26 592.87 $ ha-1 respectively. These values are respectively2.36 times and 5.85 times higher than that of TMS. The total global warming potential of TMS (18.19 t CO2 -eq ha-1 ) was 1.29 t CO2 -eq ha-1 higher and 2.89 t CO2 -eq ha-1 lower than that of PRSS mode 1 and mode 2 respectively. CONCLUSION: Compared with traditional natural grass, planting and mowing ryegrass in pear orchards can optimize soil properties, increase fruit yield, and reduce global warming potential. Different modes can greatly increase revenue but have varying impacts on environmental burdens. These findings can help rebuild the links between farmland and specialized livestock production, contributing to sustainable development in the pear industries. © 2023 Society of Chemical Industry.

A comprehensive analysis of the expression and the prognosis for LOX-1 in multiple cancer types.

Lectin-likeoxidized low-density lipoprotein receptor (LOX-1) has been identified to beinvolved in the development of atherosclerosis. There is an increasing experimental evidence which indicated that LOX-1 was implicated in cancer tumorigenesis. However, the expression and the prognostic value of LOX-1 in multiple cancers still require the further analysis. Pubmed, Embase and the Cochrane Library were used for the literature review collection with the confined date up to 31 December 2021. Ten studies including 1982 patients were performed in meta-analysis according to the inclusion and exclusion criteria. Oncomine, Gene Expression Profiling Interactive Analysis(GEPIA), Kaplan-Meier plotter and Tumor Immune Estimation Resource (TIMER) were utilized to analyze the differential expression and the prognostic value of LOX-1 in different cancers. Records from Gene Expression Omnibus (GEO) database were applied for the verification test. The meta-pooled result demonstrated that elevated LOX-1 predicted a poor survival in some cancers (HR = 1.95, 95%CI 1.46-2.44, P < 0.001). In this sense, further analysis using databases found the expression of LOX-1 was higher in breast cancer, colorectal cancer, gastric cancer and pancreatic cancer while the lower expression in lung squamous cell carcinoma was observed. Moreover, the expression of LOX-1 was related to the tumor stages of colorectal cancer, gastric cancer and pancreatic cancer. The survival analysis revealed that LOX-1 was a potential prognostic factor for the patients with colorectal cancer, gastric cancer, pancreatic cancer and lung squamous cell carcinoma. Consequently, this study may provide a novel insight for the expression and the prognostic value of LOX-1 in specific cancers.

A meta-analysis and bioinformatics analysis of P4HB expression levels in the prognosis of cancer patients.

BACKGROUND: P4HB (prolyl 4-hydroxylase, beta polypeptide) is a human chromosomal gene that encodes an endoplasmic reticulum (ER) molecular chaperone protein with oxidoreductase, chaperone and isomerase activities. Recent studies indicated that P4HB may have clinical significance, with elevated P4HB expression reported in cancer patients, but its impact on tumor prognosis is not yet clear. To our knowledge, this is the first meta-analysis to show an association between P4HB expression and the prognosis of various cancers. METHODS: We conducted a systematic literature search in the PubMed, PubMed Central, Web of Science, Embase, CNKI, Wanfang and Weipu databases, followed by a quantitative meta-analysis using Stata SE14.0 and R statistics software 4.2.1. The hazard ratio (HR) and relative risk (RR) were analyzed to evaluate the relationships of P4HB expression levels with overall survival (OS), disease-free survival (DFS), and clinicopathological parameters of cancer patients. Subsequently, P4HB expression in various cancer types was validated using the Gene Expression Profiling Interactive Analysis (GEPIA) online database. RESULTS: Ten articles containing the data of 4121 cancer patients were included in the analysis, and a significant correlation of high P4HB expression with apparently shorter OS was found (HR, 1.90; 95% CI, 1.50-2.40; P < 0.01), while there was no significant correlation with gender (RR, 1.06; 95% CI, 0.91-1.22; P = 0.084), or age. Additionally, GEPIA online analysis revealed significant upregulation of P4HB in 13 types of cancer. Among them, P4HB overexpression was associated with shorter OS in 9 and worse DFS in 11 cancer types. CONCLUSIONS: Upregulation of P4HB is correlated with worse prognosis in various cancers, which could provide new ideas for the development of P4HB-related diagnostic biomarkers and new therapeutic targets.

Multifunctional Dinuclear Dy-Based Coordination Complex Showing Visible Photoluminescence, Single-Molecule Magnet Behavior, and Proton Conduction.

A new Dy-based complex, [Dy2(phen)4(PAA)4](ClO4)2 (1), was obtained by using 4-hydroxyphenyl acetate (HPAA) as a ligand and 1,10-phenanthroline as an auxiliary ligand. Complex 1 shows a dinuclear structure and a 2D supramolecular layer constructed by π-π stacking interactions. The complex displays a characteristic Dy(III) emission. Moreover, magnetic susceptibility measurements revealed that 1 exhibits a single-molecule magnet (SMM) behavior. In addition, it also shows a proton conductivity of 1.08 × 10-5 S cm-1 under 353 K and 100% relative humidity conditions, which is mainly assigned to H-bonded networks formed by the undeprotonated and uncoordinated phenolic groups of HPAA ligands and guest water molecules. Remarkably, 1 is the first example of a dinuclear complex showing photoluminescence, SMM behavior, and proton conduction.

[Clinical and genetic analysis of a pedigree affected with hereditary dentinogenesis imperfecta type II].

OBJECTIVE: To explore the clinical and genetic characteristics of a Chinese pedigree affected with hereditary dentinogenesis imperfecta (DGI) type II. METHODS: Clinical data of the pedigree members were collected. Genomic DNA was extracted from peripheral blood samples and subjected to whole exome sequencing. RESULTS: Clinical characteristics of the affected family members have included amber teeth along with significant attrition, constricted roots and dentine hypertrophy leading to pulpal obliteration, which were suggestive of DGI type II. All of the affected members were found to have harbored a novel heterozygous c.2837delA (p.Asp946Valfs*368) variant of the DSPP gene which was predicted to be likely pathogenic. CONCLUSION: The c.2837delA variant of the DSPP gene probably underlay the disease in this pedigree. Above finding has expanded the variant spectrum of DSPP gene and provided a basis for molecular diagnosis and genetic counseling for this pedigree.

The inhibition mechanism of polyphenols from Phyllanthus emblica Linn. fruit on acetylcholinesterase: A interaction, kinetic, spectroscopic, and molecular simulation study.

The present study aimed to investigate the inhibition mechanism of polyphenols from Phyllanthus emblica Linn. fruit (PEF, family Euphorbiaceous) on acetylcholinesterase (AChE). Interaction assay, enzyme kinetics, spectroscopic methods, and molecular simulations were performed. Results showed that myricetin, quercetin, fisetin, and gallic acid were the most active components in PEF, because of their low docking scores and strong inhibition ability on AChE with IC50 values of 0.1974 ± 0.0047, 0.2589 ± 0.0131, 1.0905 ± 0.0598 and 1.503 ± 0.0728 mM, respectively. Among them, the results of kinetic study showed that myricetin, quercetin, and fisetin reversibly inhibited AChE in a competitive manner, while gallic acid inhibited it through a noncompetition type. The interaction assay implied that a combination of the four polyphenols at the selected concentrations manifested a synergistic inhibition effect on AChE in a mixed inhibition type. Fluorescence and UV-vis spectrophotometry revealed that the active PEF polyphenols could strongly quench the intrinsic fluorescence of AChE via a static quenching mechanism. Circular dichroism spectroscopy analysis indicated that the active PEF polyphenols gave rise to the secondary structure changes of AChE by increasing the content of α-helix and reducing ß-sheet and random coil conformation. The molecular dynamics simulation results validated that all the four docked polyphenol-AChE complexes were relatively stable according to their root-mean-square distance, root-mean-square fluctuations, solvent accessible surface area, radius of gyration values and hydrogen bonds evaluations during the whole simulation process. Overall, our study provides a creative insight into the further utilization of PEF polyphenols as functional components in exploring natural AChE inhibitors.

The mystery of the life tree: the placentas†.

The placenta is the interface between the fetal and maternal environments during mammalian gestation, critically safeguarding the health of the developing fetus and the mother. Placental trophoblasts origin from embryonic trophectoderm that differentiates into various trophoblastic subtypes through villous and extravillous pathways. The trophoblasts actively interact with multiple decidual cells and immune cells at the maternal-fetal interface and thus construct fundamental functional units, which are responsible for blood perfusion, maternal-fetal material exchange, placental endocrine, immune tolerance, and adequate defense barrier against pathogen infection. Various pregnant complications are tightly associated with the defects in placental development and function maintenance. In this review, we summarize the current views and our recent progress on the mechanisms underlying the formation of placental functional units, the interactions among trophoblasts and various uterine cells, as well as the placental barrier against pathogen infections during pregnancy. The involvement of placental dysregulation in adverse pregnancy outcomes is discussed.

Decoding the temporal and regional specification of microglia in the developing human brain.

Region-related heterogeneity and state transitions of microglia are important for brain development and neurological pathogenesis. However, regional specialization and state transition in microglia during early human CNS development remain unclear. Here, we profile single-cell transcriptomes of microglia from distinct regions of the developing human brain, and combined with experimental verification, we define and characterize early microglial fate determinations related to regional specification and state transition. We identified several subclasses of neuronal gene-enriched microglia with regional specification that dynamically and transiently appeared as early brain regions formed. In contrast, immune-related microglia were regionally specialized at later stages of CNS development. Surprisingly, we discovered that region-specialized immune-related microglia exit from a relative resting state and transition into distinct active states. In addition, we experimentally verified the microglial state transition. Finally, we showed that the state transition is conserved but that there are molecular differences in developing microglia in humans and mice.

Cellular and molecular atlas of the placenta from a COVID-19 pregnant woman infected at midgestation highlights the defective impacts on foetal health.

OBJECTIVES: The impacts of the current COVID-19 pandemic on maternal and foetal health are enormous and of serious concern. However, the influence of SARS-CoV-2 infection at early-to-mid gestation on maternal and foetal health remains unclear. MATERIALS AND METHODS: Here, we report the follow-up study of a pregnant woman of her whole infective course of SARS-CoV-2, from asymptomatic infection at gestational week 20 to mild and then severe illness state, and finally cured at Week 24. Following caesarean section due to incomplete uterine rupture at Week 28, histological examinations on the placenta and foetal tissues as well as single-cell RNA sequencing (scRNA-seq) for the placenta were performed. RESULTS: Compared with the gestational age-matched control placentas, the placenta from this COVID-19 case exhibited more syncytial knots and lowered expression of syncytiotrophoblast-related genes. The scRNA-seq analysis demonstrated impaired trophoblast differentiation, activation of antiviral and inflammatory CD8 T cells, as well as the tight association of increased inflammatory responses in the placenta with complement over-activation in macrophages. In addition, levels of several inflammatory factors increased in the placenta and foetal blood. CONCLUSION: These findings illustrate a systematic cellular and molecular signature of placental insufficiency and immune activation at the maternal-foetal interface that may be attributed to SARS-CoV-2 infection at the midgestation stage, which highly suggests the extensive care for maternal and foetal outcomes in pregnant women suffering from COVID-19.

Dyslipidemia in Chinese Pancreatic Cancer Patients: A Two-Center Retrospective Study.

Background: Pancreatic cancer (PC) is one of the most aggressive and lethal malignancies in the world. High cholesterol intake may have a certain association with an elevated risk of PC, though dyslipidemia in PC patients has rarely been reported. In this study, we compared serum lipids levels between PC and non-PC tumor patients and assessed their prognostic value in PC. Methods: 271 patients treated at Wuhan Union Hospital from January 2012 to December 2016 and 204 individuals at Shanghai General Hospital from January 2018 to December 2019 were recruited. Their demographic parameters, laboratory data, pathological information, and clinical outcomes were extracted and analyzed. The mRNA expressions of related lipoprotein, low density lipoprotein receptor (LDLR) and high density lipoprotein binding protein (HDLBP), in PC tissues and paired noncancerous tissues and follow-up information were assessed based on the GEO database (GSE15471 and GSE62165) and TCGA database. Results: A total of 172 non-PC tumor patients and 260 PC patients were finally eligible for our analysis. PC patients exhibited higher levels of serum triglyceride, cholesterol, and low-density lipoprotein (LDL) and a lower serum high-density lipoprotein (HDL) level on admission versus the non-PC tumor group. In PC patients, LDLR mRNA expression was upregulated, and HDLBP mRNA expression was downregulated in cancerous tissues compared to these levels in paired noncancerous tissues. The survival analysis revealed that dyslipidemia had a non-significant association with a poor prognosis, but PC patients with a high LDLR level were at risk of poor survival. Conclusion: Dyslipidemia is detected in PC patients but has a non-significant relation to PC prognosis. However, LDLR may be a potential predictive marker for PC prognosis.