Relationship between vaginal and oral microbiome in patients of human papillomavirus (HPV) infection and cervical cancer.

BACKGROUND: The aim of this study was to assess the microbial variations and biomarkers in the vaginal and oral environments of patients with human papillomavirus (HPV) and cervical cancer (CC) and to develop novel prediction models. MATERIALS AND METHODS: This study included 164 samples collected from both the vaginal tract and oral subgingival plaque of 82 women. The participants were divided into four distinct groups based on their vaginal and oral samples: the control group (Z/KZ, n = 22), abortion group (AB/KAB, n = 17), HPV-infected group (HP/KHP, n = 21), and cervical cancer group (CC/KCC, n = 22). Microbiota analysis was conducted using full-length 16S rDNA gene sequencing with the PacBio platform. RESULTS: The vaginal bacterial community in the Z and AB groups exhibited a relatively simple structure predominantly dominated by Lactobacillus. However, CC group shows high abundances of anaerobic bacteria and alpha diversity. Biomarkers such as Bacteroides, Mycoplasma, Bacillus, Dialister, Porphyromonas, Anaerococcus, and Prevotella were identified as indicators of CC. Correlations were established between elevated blood C-reactive protein (CRP) levels and local/systemic inflammation, pregnancy, childbirth, and abortion, which contribute to unevenness in the vaginal microenvironment. The altered microbial diversity in the CC group was confirmed by amino acid metabolism. Oral microbial diversity exhibited an inverse pattern to that of the vaginal microbiome, indicating a unique relationship. The microbial diversity of the KCC group was significantly lower than that of the KZ group, indicating a link between oral health and cancer development. Several microbes, including Fusobacterium, Campylobacter, Capnocytophaga, Veillonella, Streptococcus, Lachnoanaerobaculum, Propionibacterium, Prevotella, Lactobacillus, and Neisseria, were identified as CC biomarkers. Moreover, periodontal pathogens were associated with blood CRP levels and oral hygiene conditions. Elevated oral microbial amino acid metabolism in the CC group was closely linked to the presence of pathogens. Positive correlations indicated a synergistic relationship between vaginal and oral bacteria. CONCLUSION: HPV infection and CC impact both the vaginal and oral microenvironments, affecting systemic metabolism and the synergy between bacteria. This suggests that the use of oral flora markers is a potential screening tool for the diagnosis of CC.

Microbiome signatures in ischemic stroke: A systematic review.

Microbial structural changes and dysfunction play an important role in the development of cerebral ischemia. We searched PubMed, Embase, Web of Science, and Cochrane Library and conducted a systematic review to assess the relationship between the human microbiome and ischemic stroke. A total of 24 studies were included, and the intestinal bacterial communities detected in both stroke and healthy people were dominated by 4 main phyla, including Firmicutes, Bacteroidetes, Proteobacteria, and Actinobacteria. Significant diversity (alpha and beta) in patients with ischemic versus nonischemic stroke was observed in nine out of 18 studies, and 3 studies showed that the severity of ischemic stroke affected microbial diversity. The imbalance of bacteria that produce short-chain fatty acids (SCFAs) changes the bacterial metabolic pathway, and disorders in the level of bacterial metabolites (trimethylamine N-oxide TMAO) lead to significant changes in intestinal flora function, which may aggravate the severity of stroke and affect its prognosis. Further studies are needed to explore the relationship between the microbiome and ischemic stroke.

Co-Co Dinuclear Active Sites Dispersed on Zirconium-doped Heterostructured Co9 S8 /Co3 O4 for High-current-density and Durable Acidic Oxygen Evolution.

Developing cost-effective and sustainable acidic water oxidation catalysts requires significant advances in material design and in-depth mechanism understanding for proton exchange membrane water electrolysis. Herein, we developed a single atom regulatory strategy to construct Co-Co dinuclear active sites (DASs) catalysts that atomically dispersed zirconium doped Co9 S8 /Co3 O4 heterostructure. The X-ray absorption fine structure elucidated the incorporation of Zr greatly facilitated the generation of Co-Co DASs layer with stretching of cobalt oxygen bond and S-Co-O heterogeneous grain boundaries interfaces, engineering attractive activity of significantly reduced overpotential of 75 mV at 10 mA cm-2 , a breakthrough of 500 mA cm-2 high current density, and water splitting stability of 500 hours in acid, making it one of the best-performing acid-stable OER non-noble metal materials. The optimized catalyst with interatomic Co-Co distance (ca. 2.80 Å) followed oxo-oxo coupling mechanism that involved obvious oxygen bridges on dinuclear Co sites (1,090 cm-1 ), confirmed by in situ SR-FTIR, XAFS and theoretical simulations. Furthermore, a major breakthrough of 120,000 mA g-1 high mass current density using the first reported noble metal-free cobalt anode catalyst of Co-Co DASs/ZCC in PEM-WE at 2.14 V was recorded.

FZD7, Regulated by Non-CpG Methylation, Plays an Important Role in Immature Porcine Sertoli Cell Proliferation.

The regulatory role of non-CpG methylation in mammals has been important in whole-genome bisulfite sequencing. It has also been suggested that non-CpG methylation regulates gene expression to affect the development and health of mammals. However, the dynamic regulatory mechanisms of genome-wide, non-CpG methylation during testicular development still require intensive study. In this study, we analyzed the dataset from the whole-genome bisulfite sequencing (WGBS) and the RNA-seq of precocious porcine testicular tissues across two developmental stages (1 and 75 days old) in order to explore the regulatory roles of non-CpG methylation. Our results showed that genes regulated by non-CpG methylation affect the development of testes in multiple pathways. Furthermore, several hub genes that are regulated by non-CpG methylation during testicular development-such as VEGFA, PECAM1, and FZD7-were also identified. We also found that the relative expression of FZD7 was downregulated by the zebularine-induced demethylation of the first exon of FZD7. This regulatory relationship was consistent with the results of the WGBS and RNA-seq analysis. The immature porcine Sertoli cells were transfected with RNAi to mimic the expression patterns of FZD7 during testicular development. The results of the simulation test showed that cell proliferation was significantly impeded and that cell cycle arrest at the G2 phase was caused by the siRNA-induced FZD7 inhibition. We also found that the percentage of early apoptotic Sertoli cells was decreased by transfecting them with the RNAi for FZD7. This indicates that FZD7 is an important factor in linking the proliferation and apoptosis of Sertoli cells. We further demonstrated that Sertoli cells that were treated with the medium collected from apoptotic cells could stimulate proliferation. These findings will contribute to the exploration of the regulatory mechanisms of non-CpG methylation in testicular development and of the relationship between the proliferation and apoptosis of normal somatic cells.

FSH promotes immature porcine Sertoli cell proliferation by activating the CCR7/Ras-ERK signaling axis.

In brief: The appropriate growth and functions of Sertoli cells are crucial to testis development and spermatogenesis in mammals. This study reveals a novel mechanism of follicle-stimulating hormone in immature porcine Sertoli cell proliferation. Abstract: Follicle-stimulating hormone (FSH) is a major Sertoli cell mitogen that binds to the FSH receptor. Sertoli cells are indispensable for testis development and spermatogenesis. However, the regulatory mechanisms of FSH in immature Sertoli cell proliferation have not been determined, particularly in domestic animals. In the present study, we identified the regulatory mechanisms of FSH during immature porcine Sertoli cell proliferation. Transcriptome analysis revealed 114 differentially expressed genes that were induced by FSH treatment, which contains 68 upregulated and 46 downregulated genes. These differentially expressed genes were enriched in multiple pathways, including the Ras signaling pathway. Knockdown of the CC-chemokine receptor 7 (CCR7) gene, which was upregulated by FSH, inhibited cell cycle progression by arresting cells in the G1 phase and reduced the cell proliferation and ERK1/2 phosphorylation. In addition, Kobe0065 inhibited Ras signaling in a similar manner as CCR7 knockdown. Furthermore, FSH abolished the effects of Ras signaling pathway inhibition and CCR7 knockdown. Collectively, FSH promotes immature porcine Sertoli cell proliferation by activating the CCR7/Ras-ERK signaling axis. Our results provide novel insights into the regulatory mechanism of FSH in porcine testis development and spermatogenesis by deciding the fate of immature porcine Sertoli cells.

Effect of Core Stability Training on Unstable Support Surfaces in Postoperative Rehabilitation of Thoracolumbar Vertebral Compression Fractures in the Elderly.

Objective: Thoracolumbar vertebral compression fractures (TVCF) are caused by anterior flexion or vertical downward violence to the spine (Sezer et al. 2021). This study is aimed at investigating the effect of core stability training (CST) on unstable support surfaces in the postoperative rehabilitation of TVCF in the elderly. Methods. Ninety-eight patients with TVCF who underwent surgical treatment in our hospital from July 2021 to April 2022 were selected as study subjects. Then, they were divided into a research group receiving unstable support surface CST and a control group with conventional rehabilitation training according to the random number table method. Before and after the training, the X-ray machine was positioned and the anterior margin and middle height ratio and the posterior convex Cobb angle of the injured vertebrae were observed, and the balance detector was used to detect patients' eye opening and closing trajectory length, Romberg rate, and to perform gait test. Patients' pain, lumbar spine function, and quality of life were subsequently assessed using the Visual Analogue Scale (VAS), Oswestry Dysfunction Index (ODI), Generic Quality of Life Inventory-74 (GQOL-74), and patient satisfaction with rehabilitation was investigated. Results. After rehabilitation training, there was no statistically marked difference in eye-opening trajectory length between both groups (P > 0.05). The research group had higher scores than the control group in all dimensions of the anterior border of the injured vertebra, middle height ratio, and GQOL-74, while the posterior convex Cobb angle, closed-eye trajectory length, Romberg rate, VAS, and ODI were lower than the control group (P < 0.05). The research group also revealed better gait improvement and higher rehabilitation satisfaction than the control group after training (P < 0.05). Conclusion: Unstable support surface CST can effectively improve postoperative vertebral body rehabilitation, balance function, gait, pain conditions, and lumbar spine function in elderly TVCF patients, and enhance their quality of life and rehabilitation satisfaction. This trial is registered with ChiCTR2000014547.

Utilization of Interfacial Charge Storage toward Ultra-high Capacity: Li2SO4 Sealed Micron Sized Iron Oxides as Anode for Lithium Batteries.

The interfacial charge storage is derived from spin-polarized electrons stored on the surface of iron metal nanoparticles, and reasonable utilization can achieve a capacity far beyond the traditional conversion mechanism. Generally, iron oxide is easy to crack, pulverize, and fall off due to its poor conductivity and large volume change during cycling, and causes serious side reactions with the electrolyte. Herein, this pulverization phenomenon was intentionally utilized to in situ form nano-sized iron particles and create a large number of Fe/Li2O interfaces. Specifically, a Li+ conductor like Li2SO4 was utilized to seal micron sized iron oxides and also work as an aggregation barrier. Thus, the in situ formed nanoparticles were separated from the electrolyte and could provide huge capacity through interfacial charge storage. Therefore, the specific capacity of this unique composite continues to rise upon activation cycling and finally reaches 1708 mA h g-1, which is more than twice its theoretical capacity based on the conversion mechanism. The gradually increasing interfacial charge storage capacity was also directly confirmed by X-ray photoelectron spectroscopy tests. This novel strategy provides new opportunities for the design and commercialization of advanced energy storage systems.

circBTBD7 Promotes Immature Porcine Sertoli Cell Growth through Modulating miR-24-3p/MAPK7 Axis to Inactivate p38 MAPK Signaling Pathway.

Sertoli cells are the crucial coordinators to guarantee normal spermatogenesis and male fertility. Although circular RNAs (circRNAs) exhibit developmental-stage-specific expression in porcine testicular tissues and have been thought of as potential regulatory molecules in spermatogenesis, their functions and mechanisms of action remain largely unknown, especially in domestic animals. A novel circBTBD7 was identified from immature porcine Sertoli cells using reverse transcription PCR, Sanger sequencing, and fluorescence in situ hybridization assays. Functional assays illustrated that circBTBD7 overexpression promoted cell cycle progression and cell proliferation, as well as inhibited cell apoptosis in immature porcine Sertoli cells. Mechanistically, circBTBD7 acted as a sponge for the miR-24-3p and further facilitated its target mitogen-activated protein kinase 7 (MAPK7) gene. Overexpression of miR-24-3p impeded cell proliferation and induced cell apoptosis, which further attenuated the effects of circBTBD7 overexpression. siRNA-induced MAPK7 deficiency resulted in a similar effect to miR-24-3p overexpression, and further offset the effects of miR-24-3p inhibition. Both miR-24-3p overexpression and MAPK7 knockdown upregulated the p38 phosphorylation activity. The SB202190 induced the inhibition of p38 MAPK pathway and caused an opposite effect to that of miR-24-3p overexpression and MAPK7 knockdown. Collectively, circBTBD7 promotes immature porcine Sertoli cell growth through modulating the miR-24-3p/MAPK7 axis to inactivate the p38 MAPK signaling pathway. This study expanded our knowledge of noncoding RNAs in porcine normal spermatogenesis through deciding the fate of Sertoli cells.

MiR-191 promotes the porcine immature Sertoli cell proliferation by targeting the BDNF gene through activating the PI3K/AKT signaling pathway.

The number of Sertoli cells in the testis is a major regulator on the sperm production capacity. MicroRNAs (miRNAs) participate in regulating the proliferation and apoptosis of porcine immature Sertoli cells. However, the functions and mechanisms of action of most identified miRNAs in porcine Sertoli cells remain largely unknown. In the present study, based on our previous results from an EdU-based high-content screening assay, we further studied the mechanism of action of miR-191 on the proliferation and apoptosis of porcine immature Sertoli cells through flow cytometry, Western blotting, and dual-luciferase activity analyses. The results demonstrated that overexpression of miR-191 promoted cell cycle progression from G1 phase to the S and G2 phases, enhanced cell proliferation, and inhibited apoptosis in the porcine immature Sertoli cells, whereasmiR-191 inhibition resulted in the opposite effects. The results from a luciferase reporter assay showed that miR-191 directly targeted the 3'-UTR of theBDNF gene. BDNF knockdown also promoted cell cycle progression to the S phase, cell proliferation and inhibited cell apoptosis, which were consistent with the effects of the miR-191overexpression. A co-transfection experiment showed that BDNF knockdown abolished the effects of miR-191 inhibition. Furthermore, both miR-191 overexpression and BDNFinhibition elevated the phosphorylation of PI3K and AKT, the key components of the PI3K/AKT signaling pathway, whereas BDNFinhibition offset the effects of the miR-191 knockdown. Overall, these data indicated that miR-191 promotes cell proliferation and inhibits apoptosis in porcine immature Sertoli cells by targeting theBDNF gene through activating the PI3K/AKT signaling pathway. This study provides a novel scientific basis for further investigation on the biological functions of miR-191 on porcine spermatogenesis.

Construction of a high-density genetic map using specific length amplified fragment markers and identification of a quantitative trait locus for anthracnose resistance in walnut (Juglans regia L.).

BACKGROUND: Walnut (Juglans regia, 2n = 32, approximately 606 Mb per 1C genome) is an economically important tree crop. Resistance to anthracnose, caused by Colletotrichum gloeosporioides, is a major objective of walnut genetic improvement in China. The recently developed specific length amplified fragment sequencing (SLAF-seq) is an efficient strategy that can obtain large numbers of markers with sufficient sequence information to construct high-density genetic maps and permits detection of quantitative trait loci (QTLs) for molecular breeding. RESULTS: SLAF-seq generated 161.64 M paired-end reads. 153,820 SLAF markers were obtained, of which 49,174 were polymorphic. 13,635 polymorphic markers were sorted into five segregation types and 2,577 markers of them were used to construct genetic linkage maps: 2,395 of these fell into 16 linkage groups (LGs) for the female map, 448 markers for the male map, and 2,577 markers for the integrated map. Taking into account the size of all LGs, the marker coverage was 2,664.36 cM for the female map, 1,305.58 cM for the male map, and 2,457.82 cM for the integrated map. The average intervals between two adjacent mapped markers were 1.11 cM, 2.91 cM and 0.95 cM for three maps, respectively. 'SNP_only' markers accounted for 89.25% of the markers on the integrated map. Mapping markers contained 5,043 single nucleotide polymorphisms (SNPs) loci, which corresponded to two SNP loci per SLAF marker. According to the integrated map, we used interval mapping (Logarithm of odds, LOD > 3.0) to detect our quantitative trait. One QTL was detected for anthracnose resistance. The interval of this QTL ranged from 165.51 cM to 176.33 cM on LG14, and ten markers in this interval that were above the threshold value were considered to be linked markers to the anthracnose resistance trait. The phenotypic variance explained by each marker ranged from 16.2 to 19.9%, and their LOD scores varied from 3.22 to 4.04. CONCLUSIONS: High-density genetic maps for walnut containing 16 LGs were constructed using the SLAF-seq method with an F1 population. One QTL for walnut anthracnose resistance was identified based on the map. The results will aid molecular marker-assisted breeding and walnut resistance genes identification.

[Simulation Analysis of the Pulse Signal on the Electricity Network of Cardiovascular System].

Pulse waves contain abundant physiological and pathological information of human body. Research of the relationship between pulse wave and human cardiovascular physiological parameters can not only help clinical diagnosis and treatment of cardiovascular diseases, but also contribute to develop many new medical instruments. Based on the traditional double elastic cavity model, the human cardiovascular system was established by using the electric network model in this paper. The change of wall pressure and blood flow in artery was simulated. And the influence of the peripheral resistance and vessel compliance to the distribution of blood flow in artery was analyzed. The simulation results were compared with the clinical monitoring results to predict the physiological and pathological state of human body. The result showed that the simulation waveform of arterial wall pressure and blood flow was stabile after the second cardiac cycle. With the increasing of peripheral resistance, the systolic blood pressure of artery increased, the diastolic blood pressure had no significant change, and the pulse pressure of artery increased gradually. With the decreasing of vessel compliance, the vasoactivity became worse and the pulse pressure increased correspondingly. The simulation results were consistent with the clinical monitoring results. The increasing of peripheral resistance and decreasing of vascular compliance indicated that the incidence of hypertension and atherosclerosis was increased.