Impact Response Features and Penetration Mechanism of UHMWPE Subjected to Handgun Bullet.

Ensuring military and police personnel protection is vital for urban security. However, the impact response mechanism of the UHMWPE laminate used in ballistic helmets and vests remains unclear, making it hard to effectively protect the head, chest, and abdomen. This study utilized 3D-DIC technology to analyze UHMWPE laminate's response to 9 mm lead-core pistol bullets traveling at 334.93 m/s. Damage mode and response characteristics were revealed, and an effective numerical calculation method was established that could reveal the energy conversion process. The bullet penetrated by 1.03 mm, causing noticeable fiber traction, resulting in cross-shaped failure due to fiber compression and aggregation. Bulge transitioned from circular to square, initially increasing rapidly, then slowing. Maximum in-plane shear strain occurred at ±45°, with values of 0.0904 and -0.0928. Model accuracy was confirmed by comparing strain distributions. The investigation focused on bullet-laminate interaction and energy conversion. Bullet's kinetic energy is converted into laminate's kinetic and internal energy, with the majority of erosion energy occurring in the first four equivalent sublaminates and the primary energy change in the system occurring at 75 µs in the fourth equivalent sublayer. The results show the damage mode and energy conversion of the laminate, providing theoretical support for understanding the impact response mechanism and improving the efficiency of protective energy absorption.

Preparation of magnetic polyacrylamide hydrogel with chitosan for immobilization of glutamate decarboxylase to produce γ-aminobutyric acid.

Gamma-aminobutyric acid (GABA) is an vital neurotransmitter, and the reaction to obtain GABA through biocatalysis requires coenzymes, which are therefore limited in the production of GABA. In this study, polyacrylamide hydrogels doped with chitosan and waste toner were synthesized for glutamate decarboxylase (GAD) and coenzyme co-immobilization to realize the production of GABA and the recovery of coenzymes. Enzymatic properties of immobilized GAD were discussed. The immobilized enzymes have significantly improved pH and temperature tolerance compared to free enzymes. In terms of reusability, after 10 repeated reuses of the immobilized GAD, the residual enzyme activity of immobilized GAD still retains 100% of the initial enzyme activity, and the immobilized coenzyme can also be kept at about 32%, with better stability and reusability. And under the control of no exogenous pH, immobilized GAD showed good performance in producing GABA. Therefore, in many ways, the new composite hydrogel provides another way for the utilization of waste toner and promises the possibility of industrial production of GABA.

Osteogenic effect and mechanism of IL-10 in diabetic rat jaw defect mode.

OBJECTIVE: The aim of this study was to investigate the effect of IL-10 on the phenotype polarization of macrophages and osteogenesis in diabetes mellitus type 2 (T2DM) rat jaw defects. METHODS: Lipopolysaccharide (LPS) and interleukin-10 (IL-10) were chosen to induce the polarization of macrophages. In vitro assessment included wound-healing assay, western blotting, and alizarin red staining after co-culture of the bone marrow-derived mesenchymal stem cells (BMSCs) and induced macrophages. For in vivo study, IL-10 was loaded on GelMA-Heparin and applied to bone defects of the alveolar ridge in diabetic rats, while Bio-Oss Collagen, simple GelMA-Heparin, and blank control groups were set for contrast experiment. The mandibles of rats were processed for micro-computed tomography, histology, and immunohistochemistry 1 week and 4 weeks after the operation. RESULTS: IL-10 induced expression of arginase 1, TGF-ß1, EGR2, and Mannose Receptor (CD206), whereas LPS induced expression of iNOS, TNF-α, IL-6, CD80. The BMSCs co-cultured with macrophages induced by IL-10 showed increased migration, osteogenic differentiation, and mineralization in vitro. Notably, the IL-10-laden GelMA-Heparin group showed quicker new bone formation and a higher M2/M1 ratio of macrophages in the jawbone defect area compared with the control groups. CONCLUSIONS: IL-10 can stably induce macrophages to M2 type, thereby influencing BMSCs and improving the osteogenesis of jaw bone defects.

[Progress of mechanism research on the neurotransmitters in treatment of insomnia with acupuncture by regulating sleep architecture].

Low-quality sleep in patients with insomnia is closely related to sleep architecture imbalance and neurotransmitter impairment. Acupuncture may reduce the duration of light sleep and its proportion, increase the time of deep sleep and rapid- eye-movement sleep as well as their proportions so as to modulate the sleep architecture for insomnia. The paper summarized the related studies of acupuncture for improving sleep architecture through regulating serotonin, norephinephrine, dopamine, γ-aminobutyric acid, acetylcholine and orexin; and explored the effects of acupuncture on the neurotransmitters and their specific performance in regulating sleep architecture. It is anticipated that the review may provide the literature evidences of acupuncture for improving sleep quality in patients with insomnia, and the approaches to the mechanism research of acupuncture for regulating sleep architecture.

Networks of placental DNA methylation correlate with maternal serum PCB concentrations and child neurodevelopment.

BACKGROUND: Gestational exposure to polychlorinated biphenyls (PCBs) has been associated with elevated risk for neurodevelopmental disorders. Placental epigenetics may serve as a potential mechanism of risk or marker of altered placental function. Prior studies have associated differential placental DNA methylation with maternal PCB exposure or with increased risk of autism spectrum disorder (ASD). However, sequencing-based placental methylomes have not previously been tested for simultaneous associations with maternal PCB levels and child neurodevelopmental outcomes. OBJECTIVES: We aimed to identify placental DNA methylation patterns associated with maternal PCB levels and child neurodevelopmental outcomes in the high-risk ASD MARBLES cohort. METHODS: We measured 209 PCB congeners in 104 maternal serum samples collected at delivery. We identified networks of DNA methylation from 147 placenta samples using the Comethyl R package, which performs weighted gene correlation network analysis for whole genome bisulfite sequencing data. We tested placental DNA methylation modules for association with maternal serum PCB levels, child neurodevelopment, and other participant traits. RESULTS: PCBs 153 + 168, 170, 180 + 193, and 187 were detected in over 50% of maternal serum samples and were highly correlated with one another. Consistent with previous findings, maternal age was the strongest predictor of serum PCB levels, alongside year of sample collection, pre-pregnancy BMI, and polyunsaturated fatty acid levels. Twenty seven modules of placental DNA methylation were identified, including five which significantly correlated with one or more PCBs, and four which correlated with child neurodevelopment. Two modules associated with maternal PCB levels as well as child neurodevelopment, and mapped to CSMD1 and AUTS2, genes previously implicated in ASD and identified as differentially methylated regions in mouse brain and placenta following gestational PCB exposure. CONCLUSIONS: Placental DNA co-methylation modules were associated with maternal PCBs and child neurodevelopment. Methylation of CSMD1 and AUTS2 could be markers of altered placental function and/or ASD risk following maternal PCB exposure.

A meta-analysis of pre-pregnancy maternal body mass index and placental DNA methylation identifies 27 CpG sites with implications for mother-child health.

Higher maternal pre-pregnancy body mass index (ppBMI) is associated with increased neonatal morbidity, as well as with pregnancy complications and metabolic outcomes in offspring later in life. The placenta is a key organ in fetal development and has been proposed to act as a mediator between the mother and different health outcomes in children. The overall aim of the present work is to investigate the association of ppBMI with epigenome-wide placental DNA methylation (DNAm) in 10 studies from the PACE consortium, amounting to 2631 mother-child pairs. We identify 27 CpG sites at which we observe placental DNAm variations of up to 2.0% per 10 ppBMI-unit. The CpGs that are differentially methylated in placenta do not overlap with CpGs identified in previous studies in cord blood DNAm related to ppBMI. Many of the identified CpGs are located in open sea regions, are often close to obesity-related genes such as GPX1 and LGR4 and altogether, are enriched in cancer and oxidative stress pathways. Our findings suggest that placental DNAm could be one of the mechanisms by which maternal obesity is associated with metabolic health outcomes in newborns and children, although further studies will be needed in order to corroborate these findings.

Metabolites of medicine food homology-derived endophytic fungi and their activities.

Medicine food homology (MFH) substances not only provide essential nutrients as food but also have corresponding factors that can prevent and help treat nutritional imbalances, chronic disease, and other related issues. Endophytic fungi associated with plants have potential for use in drug discovery and food therapy. However, the endophytic fungal metabolites from MFH plants and their effects have been overlooked. Therefore, this review focuses on the various biological activities of 108 new metabolites isolated from 53 MFH-derived endophytic fungi. The paper explores the potential nutritional and medicinal value of metabolites of MFH-derived endophytic fungi for food and medical applications. This research is important for the future development of effective, safe, and nontoxic therapeutic nutraceuticals for the prevention and treatment of human diseases.

Exploring Sex Differences in Key Frequency Bands and Channel Connections for EEG-based Emotion Recognition.

Previous studies have demonstrated the existence of sex differences in emotion recognition by comparing the performance of same-sex and cross-sex training strategies. However, the EEG properties behind the sex differences have not been fully explored. To fill this research gap, we aim to investigate the sex differences in key frequency bands and channel connections of EEG signals. The single-modality attentive simple graph convolutional network (ASGC) is applied to three datasets SEED, SEED-IV and SEED-V under subject-dependence conditions. The classification rates are 90.86 ±4.84%, 83.14 ± 8.84% and 78.33±7.83%, respectively. The adjacency matrices learned by ASGC indicate that females and males have similar channel-connection patterns, but the degree of importance of channel connections varies by sex. Additionally, by comparing the classification results of 5 frequency bands, we find that males and females represent similar frequency band characteristics, i.e., high-frequency bands achieve better performance, indicating that these frequency bands are more related to emotion processing. Finally, we conduct the cross-subject experiment using ASGC and find that the same-sex strategy outperforms the cross-sex strategy, which is consistent with previous studies. The results also imply that males may be more suitable for sex generalization. However, this finding needs the support of more samples and advanced algorithms.

Prenatal vitamin intake in first month of pregnancy and DNA methylation in cord blood and placenta in two prospective cohorts.

BACKGROUND: Prenatal vitamin use is recommended before and during pregnancies for normal fetal development. Prenatal vitamins do not have a standard formulation, but many contain calcium, folic acid, iodine, iron, omega-3 fatty acids, zinc, and vitamins A, B6, B12, and D, and usually they contain higher concentrations of folic acid and iron than regular multivitamins in the US Nutrient levels can impact epigenetic factors such as DNA methylation, but relationships between maternal prenatal vitamin use and DNA methylation have been relatively understudied. We examined use of prenatal vitamins in the first month of pregnancy in relation to cord blood and placenta DNA methylation in two prospective pregnancy cohorts: the Early Autism Risk Longitudinal Investigation (EARLI) and Markers of Autism Risk Learning Early Signs (MARBLES) studies. RESULTS: In placenta, prenatal vitamin intake was marginally associated with -0.52% (95% CI -1.04, 0.01) lower mean array-wide DNA methylation in EARLI, and associated with -0.60% (-1.08, -0.13) lower mean array-wide DNA methylation in MARBLES. There was little consistency in the associations between prenatal vitamin intake and single DNA methylation site effect estimates across cohorts and tissues, with only a few overlapping sites with correlated effect estimates. However, the single DNA methylation sites with p-value < 0.01 (EARLI cord nCpGs = 4068, EARLI placenta nCpGs = 3647, MARBLES cord nCpGs = 4068, MARBLES placenta nCpGs = 9563) were consistently enriched in neuronal developmental pathways. CONCLUSIONS: Together, our findings suggest that prenatal vitamin intake in the first month of pregnancy may be related to lower placental global DNA methylation and related to DNA methylation in brain-related pathways in both placenta and cord blood.

[Acupoint compatibility effect and mechanism of Shenmen (HT7) and Sanyinjiao (SP6) in improving daytime fatigue and sleepiness of insomnia].

OBJECTIVE: To observe the acupoint compatibility effect of Shenmen (HT7) and Sanyinjiao (SP6) in improving daytime fatigue and sleepiness of insomnia, and its mechanism in regulating hypothalamic-pituitary-adrenal (HPA) axis and suprachiasmatic nucleus-pineal gland-melatonin (SCN-PG-MT) system. METHODS: Ninety patients with insomnia were randomly divided into HT7, SP6 and HT7-SP6 (HT7 plus SP6) groups, with 30 cases in each group. Electroacupuncture (EA,5 Hz/25 Hz) was applied to HT7, SP6 or HT7-SP6 in each group for 30 min. The EA treatment was conducted once daily, 5 days a week for 2 weeks. Before and after treatment, the Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS) were observed, separately. The contents of serum adrenocorticotrophic hormone (ACTH), cortisol (CS) and melatonin (MT) were detected by ELISA. RESULTS: Compared with before treatment, the sleep quality, sleep time, sleep efficiency, sleep disturbance, daytime dysfunction scores and total score of PSQI in the three groups after treatment were decreased (P<0.05), the time to fall asleep score of PSQI and total score of ESS were decreased in the SP6 and HT7-SP6 groups (P<0.05). After treatment, the sleep quality, time to fall asleep, sleep efficiency, daytime dysfunction scores, total score of PSQI and total score of ESS in the HT7-SP6 group were lower than those in the HT7 group (P<0.05), the sleep quality, sleep efficiency and total score of PSQI in the SP6 group were lower than those in the HT7 group (P<0.05). Compared with before treatment, the serum ACTH and CS levels in the three groups were decreased (P<0.05), and the serum MT levels in the SP6 and HT7-SP6 groups were increased (P<0.05). After treatment, the ACTH and CS levels in the HT7-SP6 group were lower than those in the HT7 group (P<0.05), and the serum MT levels in the SP6 and HT7-SP6 groups were higher than that in the HT7 group (P<0.05). CONCLUSION: The compatibility of HT7 and SP6 has a synergism effect on the improvement of night sleep quality and daytime fatigue and sleepiness of insomnia patients, the mechanism may be related with its function in down-regulating the serum ACTH and CS levels and increasing the serum MT content. SP6 has a better effect than HT7, and plays a major role in acupoint compatibility.

Exosomal MMP-1 transfers metastasis potential in triple-negative breast cancer through PAR1-mediated EMT.

PURPOSE: Triple-negative breast cancer (TNBC) is a subtype of breast cancer with high risk of distant metastasis, in which the intercellular communication between tumor cells also plays a role. Exosomes can be released by tumor cells and promote distant metastasis through intercellular communication or changes in tumor microenvironment, it is an optimized transportation facility for biologically active payloads. This was a hypothesis-generating research on role of exosomal payload in TNBC distant metastasis. METHODS: Exosomes isolated from supernatant of MDA-MB-231 and MDA-MB-231-HM (a highly pulmonary metastatic variant of parental MDA-MB-231 cells) were characterized. MMP-1 level was detected using mass spectrometry and western blot. Transwell assay, wound healing and CCK-8 assay were employed to explore the effect of exosomal MMP-1 on the metastatic capability of TNBC cells in vitro. Human breast cancer lung metastasis model in nude mice was established to observe the effect of exosomal MMP-1 in vivo. Tissue microarray and blood samples of TNBC patients were applied to analyze the relevance between MMP-1 with metastasis. RESULTS: MDA-MB-231-HM cells secrete exosomes enriched MMP-1, which can be taken up and enhance invasion and migration activities of TNBC cells, including MDA-MB-231, MDA-MB-468 and BT549. After ingesting exosomes enriched with MMP-1, cells secret more MMP-1, which may interact with membrane G protein receptor protease activated receptor 1 (PAR1), thereby initiating epithelial-mesenchymal transition (EMT) to enhance capability of migration and invasion. The lung colonization model shows that the expressions of MMP-1 and PAR1 in the metastases of the 231-HM-exo treated mice were both upregulated. Clinically, the enrichment of MMP-1 can be detected in exosomes extracted from serum of patients with metastasis at higher concentration than that in pre-operative patients. Moreover, in patients with multiple distant metastases, the level of MMP-1 in exosomes is also higher than that in patients with single lesion. CONCLUSION: MMP-1 from TNBC cells of high metastasis potential can promote the distant metastasis of transform those with low metastasis potential through PAR1-mediated EMT and is likely to be a potential molecular marker.

Characteristics of Harmful Algal Species in the Coastal Waters of China from 1990 to 2017.

Harmful algal blooms (HABs) have occurred frequently in coastal waters of China, imposing negative effects on the marine ecological environment. A dataset of HABs and terrestrial runoff was collected and analyzed in this study, and factors responsible for HABs were further explored. Frequency and expansion of HABs peaked between 2001 and 2007, and although they have declined slightly since then, they have remained quite high. Frequency and accumulative area of HABs peaked in 2004-2005, and most occurred from April to August during these years. HABs occurred frequently in the Changjiang (Yangtze River) estuary, and Prorocentrum donghaiense, Noctiluca scientillans, Karenia mikimotoi, and Skeletonema costatum were the main algal species. The increases of eutrophication, the abnormal sea surface temperature caused by climate and ocean currents, and the species invasion caused by the discharge of ballast water may be important factors for the long-term outbreak of HABs in the Chinese coastal waters. These findings provide a better understanding of HABs in China, which will be helpful to further prevention and control.

Placental methylome reveals a 22q13.33 brain regulatory gene locus associated with autism.

BACKGROUND: Autism spectrum disorder (ASD) involves complex genetics interacting with the perinatal environment, complicating the discovery of common genetic risk. The epigenetic layer of DNA methylation shows dynamic developmental changes and molecular memory of in utero experiences, particularly in placenta, a fetal tissue discarded at birth. However, current array-based methods to identify novel ASD risk genes lack coverage of the most structurally and epigenetically variable regions of the human genome. RESULTS: We use whole genome bisulfite sequencing in placenta samples from prospective ASD studies to discover a previously uncharacterized ASD risk gene, LOC105373085, renamed NHIP. Out of 134 differentially methylated regions associated with ASD in placental samples, a cluster at 22q13.33 corresponds to a 118-kb hypomethylated block that replicates in two additional cohorts. Within this locus, NHIP is functionally characterized as a nuclear peptide-encoding transcript with high expression in brain, and increased expression following neuronal differentiation or hypoxia, but decreased expression in ASD placenta and brain. NHIP overexpression increases cellular proliferation and alters expression of genes regulating synapses and neurogenesis, overlapping significantly with known ASD risk genes and NHIP-associated genes in ASD brain. A common structural variant disrupting the proximity of NHIP to a fetal brain enhancer is associated with NHIP expression and methylation levels and ASD risk, demonstrating a common genetic influence. CONCLUSIONS: Together, these results identify and initially characterize a novel environmentally responsive ASD risk gene relevant to brain development in a hitherto under-characterized region of the human genome.

An effective immobilization of ß-glucosidases by partly cross-linking enzyme aggregates.

Enzyme immobilization provides ideal operating conditions for enzymes stabilization and sustainable recycling. In this work, as a kind of clay material, montmorillonite (MTL) was chosen for immobilizing the ß-glucosidase extracted from Agrocybe aegirit. The immobilized ß-glucosidase via partly cross-linking enzyme aggregates (pCLEAs) formed by self-catalysis provided biocatalysts with satisfactory thermal and pH stability. Compared to the glutaraldehyde cross-linked, the immobilized ß-glucosidase (ß-G-pCLEAs@MTL) exhibited significantly higher immobilization efficiency (IE) and immobilization yield (IY), which were 80.6% and 76.9%, respectively. The ß-G-pCLEAs@MTL also showed better stability and preferable reusability. And the activity of the ß-G-pCLEAs@MTL remained 85.0% after 5 cycles and 74.7% after 10 cycles. Therefore, the method based on the pre- crosslinking to form pCLEAs and after-immobilization can effectively improve IY and IE. In addition, MTL seems to be a good alternative carrier to immobilize other enzymes for industrial application.

[Combined use of Shenmen (HT 7) and Sanyinjiao (SP 6) to improve the anxiety and depression in patients with insomnia: a randomized controlled trial].

OBJECTIVE: To observe the effect of electroacupuncture (EA) at Shenmen (HT 7) and Sanyinjiao (SP 6) on anxiety and depression in patients with insomnia, and to explore the mechanism of its compatibility effect. METHODS: Ninety patients of insomnia were randomly divided into a combination group, a Shenmen group and a Sanyinjiao group, 30 cases in each group. In addition, 37 cases with anxiety (12 cases in the combination group, 13 cases in the Shenmen group and 12 cases in the Sanyinjiao group) and 42 cases with depression (14 cases in the combination group, 14 cases in the Shenmen group and 14 cases in the Sanyinjiao group) were identified. The patients in the combination group, Shenmen group and Sanyinjiao group were treated with EA (dilatational wave, frequency of 5 Hz/25 Hz) at Shenmen (HT 7)-Sanyinjiao (SP 6), Shenmen (HT 7) and Sanyinjiao (SP 6), respectively, 30 min each treatment, once a day. The consecutive 5 days of treatments were taken as a course of treatment, and 2 courses of treatment were given. The insomnia severity index (ISI), self-rating anxiety scale (SAS) and self-rating depression scale (SDS) scores were evaluated before and after treatment, and the serum contents of dopamine (DA) and norepinephrine (NE) were measured. RESULTS: Compared before treatment, the ISI, SAS and SDS scores in the three groups were all decreased after treatment (P<0.05), and the ISI score in the combination group was lower than that in the Shenmen group (P<0.05). Among the patients with anxiety, compared before treatment, the ISI, SAS scores and serum contents of DA were all decreased after treatment in the three groups (P<0.05), and the serum contents of NE in the combination group and Shenmen group were decreased after treatment (P<0.05); the SAS score and serum contents of NE in the combination group and Shenmen group as well as the ISI score in the combination group were lower than those in the Sanyinjiao group (P<0.05). Among the patients with depression, compared before treatment, the ISI, SDS scores and serum contents of DA were all decreased after treatment in the three groups (P<0.05), and the serum contents of NE in the combination group and Shenmen group were decreased after treatment (P<0.05); the ISI, SDS scores and serum contents of NE in the combination group as well as SDS score in the Shenmen group were lower than those in the Sanyinjiao group (P<0.05). CONCLUSION: EA at Shenmen (HT 7) and Sanyinjiao (SP 6) has advantages over EA at Sanyinjiao (SP 6) on improving insomnia, anxiety and depression. Shenmen (HT 7) plays a major role in improving anxiety and depression. Shenmen (HT 7) and Sanyinjiao (SP 6) may play a compatibility effect of regulating consciousness and sleeping by reducing the level of serum NE.

Cornuside Alleviates Diabetes Mellitus-Induced Testicular Damage by Modulating the Gut Microbiota.

BACKGROUND: Male reproductive damage, as a common complication of diabetes mellitus (DM), is getting more attention lately. We aimed to explore the protective effects and mechanism of cornuside (Cor) modulating gut microbiota to alleviate diabetes mellitus- (DM-) induced testicular damage. METHODS: KK-Ay mice with reproductive damage were randomly divided into the model and Cor treatment groups, and the C57BL/6J mice were used as the normal group. These mice were orally administered Cor for 8 weeks. RESULTS: Cor administration ameliorated the diabetes-related symptoms of polydipsia and polyphagia and lowered the fasting blood glucose (FBG) level. The results of pathological injury showed that Cor improved testicular lesions (the rupture of seminiferous tubules, degeneration of germ cells, and structural shrinkage and separation from each other) in DM model mice. Cor significantly increased the testis/body weight ratio, testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) levels in KK-Ay mice. Cor also protected from reproductive damage by inhibiting apoptosis in the testes of KK-Ay mice. Moreover, Cor significantly increased the sperm count and sperm motility. Additionally, 16S rDNA sequencing analysis showed that Cor could notably reverse the changes in the distribution of gut microbiota and decrease the abundance of Weissella confusa (Weissella), Clostridium sp. ND2 (Clostridium sensu stricto 1), uncultured bacterium (Roseburia), Anaerotruncus colihominis DSM 17241 (Anaerotruncus), [Clostridium] leptum (Anaerotruncus), unidentified (Ruminococcus 1), and uncultured bacterium (Bilophila), which may be a potential biomarker for diagnosing the testicular injury caused by DM. Meanwhile, the heat map of phylum level suggested that the testicular injury caused by DM is closely related to gut microbiota. CONCLUSIONS: Cor could alleviate DM-induced testicular damage, probably by modulating the gut microbiota.

Research hotspots and trends of microRNA in periodontology and dental implantology: a bibliometric analysis.

BACKGROUND: Periodontal disease is a leading cause of tooth loss, and microRNA (miRNA) has been shown to regulate various biological processes. This study aimed to quantitatively analyze the literature related to miRNA in periodontology and dental implantology and summarize the research hotspots and trends in this field. METHODS: Literature records from 1985 to 2020 were obtained from the Web of Science Core Collection database. After manual selection, the data was used for cooperative network analysis, keyword co-occurrence analysis, and reference co-citation analysis and visualized by CiteSpace. RESULTS: A total of 287 papers were analyzed between 2007 and 2020, and more than 95% of them were published in the past decade. The largest number of publications were from China, followed by the USA and Japan. The direct cooperation among the productive institutions was not close. At present, most of the research belongs to the discipline of dentistry, oral surgery, cell biology, and molecular biology. Literature clusters generated by reference co-citation analysis and keyword co-occurrence network showed that previous studies mainly focused on four hotspots: periodontal ligament stem cells (PDLSCs), the pathological process of periodontitis, osteogenic differentiation/bone regeneration, and the competing endogenous RNA (ceRNA) network. CONCLUSIONS: The therapeutic potential of miRNA in promoting bone formation and how the ceRNA network contributes to miRNA regulation at a deeper level have become the two main research trends of this field.

Catalpol ameliorates endothelial dysfunction and inflammation in diabetic nephropathy via suppression of RAGE/RhoA/ROCK signaling pathway.

Catalpol is an iridoid glycoside compound isolated from the root of Rehmannia glutinosa, which has been reported to be a promising candidate for the treatment of diabetic diseases. The present study aimed at investigating the effects and potential mechanism of catalpol on endothelial dysfunction and inflammation in diabetic nephropathy (DN). We constructed DN mice and advanced glycation end products (AGEs)-induced mouse glomerular endothelial cells (mGECs) injury model. The results demonstrated that catalpol effectively improved renal pathology and decreased levels of urine protein, serum creatinine, and blood urea nitrogen in DN mice. Catalpol significantly reduced endothelial dysfunction and inflammatory infiltration of macrophages in DN mice and AGEs-induced mGECs. To further study the protective mechanism of catalpol, we transfected DN mice with recombinant adeno-associated virus expressing receptor of AGEs (RAGE) and intervened AGEs-induced mGECs with inhibitors. Catalpol reversed endothelial dysfunction and inflammation aggravated by RAGE overexpression in DN mice. Meanwhile, catalpol significantly inhibited the RAGE/Ras homolog gene family member A (RhoA)/Rho-associated kinase (ROCK) pathway in DN mice with RAGE overexpression. Moreover, the combination of catalpol with inhibitors of RAGE, RhoA and ROCK exerted stronger anti-endothelial dysfunction and anti-macrophage infiltration effects on AGEs-induced mGECs compared with catalpol alone. In short, this study indicated that catalpol could ameliorate endothelial dysfunction and inflammation via suppression of RAGE/RhoA/ROCK pathway, hereby delaying the progression of DN.

Combination of the Herbs Radix Rehmanniae and Cornus Officinalis Mitigated Testicular Damage From Diabetes Mellitus by Enhancing Glycolysis via the AGEs/RAGE/HIF-1α Axis.

Radix Rehmanniae and Cornus Officinalis (RR-CO) have been widely used as "nourishing Yin and tonifying kidney" herb pairs for the treatment of diabetes mellitus (DM) and its complications in traditional Chinese medicine (TCM). Based on the theory of "kidney governing reproduction" in TCM, the aim of this study was to investigate the therapeutic effects of RR-CO on DM-induced reproduction damage through regulating testicular glycolysis. Moreover, the regulation of AGEs/RAGE/HIF-1α axis on the testicular glycolysis process has also been studied. Spontaneous DM model KK-Ay mice were used to investigate the protective effect of RR, CO, RR-CO on DM-induced reproductive disturbances. RR, CO, RR-CO improved DM-induced renal and testicular morphology damages. Moreover, the impaired spermatogenesis, germ cell apoptosis and motility in testis induced upon DM were also attenuated by RR, CO or RR-CO, accompanied by an increased level of glycolysis metabolomics such as l-lactate, d-Fructose 1,6-bisphosphate, etc. Meanwhile, glucose membrane transporters (GLUT1, GLUT3), monocarboxylate transporter 4 (MCT4) expression, lactate dehydrogenase (LDH) activity, HIF-1α were upregulated by RR, CO and RR-CO treatment compared with the model group, whereas AGE level and RAGE expression were decreased with the drug administration. The RR-CO group was associated with superior protective effects in comparison to RR, CO use only. Aminoguanidine (Ami) and FPS-ZM1, the AGEs and RAGE inhibitors, were used as a tool drug to study the mechanism, showing different degrees of protection against DM-induced reproductive damage. This work preliminarily sheds light on the herb pair RR-CO exhibited favorable effects against DM-induced reproductive disturbances through enhancing testicular glycolysis, which might be mediated by AGEs/RAGE/HIF-1α axis.

Exosomal annexin A6 induces gemcitabine resistance by inhibiting ubiquitination and degradation of EGFR in triple-negative breast cancer.

Exosomes are carriers of intercellular information that regulate the tumor microenvironment, and they have an essential role in drug resistance through various mechanisms such as transporting RNA molecules and proteins. Nevertheless, their effects on gemcitabine resistance in triple-negative breast cancer (TNBC) are unclear. In the present study, we examined the effects of exosomes on TNBC cell viability, colony formation, apoptosis, and annexin A6 (ANXA6)/EGFR expression. We addressed their roles in gemcitabine resistance and the underlying mechanism. Our results revealed that exosomes derived from resistant cancer cells improved cell viability and colony formation and inhibited apoptosis in sensitive cancer cells. The underlying mechanism included the transfer of exosomal ANXA6 from resistant cancer cells to sensitive cancer cells. Isobaric peptide labeling-liquid chromatography-tandem mass spectrometry and western blotting revealed that ANXA6 was upregulated in resistant cancer cells and their derived exosomes. Sensitive cancer cells exhibited resistance with increased viability and colony formation and decreased apoptosis when ANXA6 was stably overexpressed. On the contrary, knockdown ANXA6 restored the sensitivity of cells to gemcitabine. Co-immunoprecipitation expression and GST pulldown assay demonstrated that exosomal ANXA6 and EGFR could interact with each other and exosomal ANXA6 was associated with the suppression of EGFR ubiquitination and downregulation. While adding lapatinib reversed gemcitabine resistance induced by exosomal ANXA6. Moreover, ANXA6 and EGFR protein expression was correlated in TNBC tissues, and exosomal ANXA6 levels at baseline were lower in patients with highly sensitive TNBC than those with resistant TNBC when treated with first-line gemcitabine-based chemotherapy. In conclusion, resistant cancer cell-derived exosomes induced gemcitabine resistance via exosomal ANXA6, which was associated with the inhibition of EGFR ubiquitination and degradation. Exosomal ANXA6 levels in the serum of patients with TNBC might be predictive of the response to gemcitabine-based chemotherapy.