Nonlinear analysis and recognition of epileptic EEG signals in different stages.

It is a hot problem in epilepsy research to detect and predict seizures by EEG signals. Clinically, it is generally observed that there are only sudden abnormal signals during the ictal stage, but there is no significant difference in the EEG signal between the interictal and preictal stages. To solve the problem that preictal signals are difficult to recognize clinically, and then effectively improve the recognition efficiency of epileptic seizures, so, in this paper, some nonlinear methods are comprehensively used to extract the hidden information in the EEG signals in different stages, namely, phase space reconstruction (PSR), Poincaré section (PS), synchroextracting transform (SET) and machine learning for EEG signal analysis. Firstly, PSR based on C-C method is used, and the results show that there are different diffuse attractor trajectories of the signals in different stages. Secondly, the confidence ellipse (CE) is constructed by using the scatter diagram of the corresponding trajectory on PS, and the aspect ratio and area of the ellipse are calculated. The results show that there is an interesting transitional phenomenon in preictal stage. To recognize ictal and preictal signals, time-frequency (TF) spectrums which are processed by SET are fed into the convolutional neural networks (CNN) classifier. The accuracy of recognize ictal and preictal signals reaches 99.7% and 93.7% respectively. To summarize, our results based on nonlinear method provide new research ideas for seizures detection and prediction.

[Identification of novel genetic loci associated with major depressive disorder and the hippocampus in a European population using the condFDR method].

OBJECTIVE: To identify additional loci associated with depression and the hippocampus (HIP) through genome-wide association study. METHODS: The depression-related genome-wide association study (GWAS) meta summary data was downloaded from the official website of the Psychiatric Genomics Consortium, which had involved 170 756 cases and 329 443 controls. The left and right hippocampal volume GWAS data sets were downloaded from the UK Biobank, which involved 33 224 participants. The conditional false discovery rate (condFDR) was used to identify novel genetic loci for depression and left and right hippocampal volumes, and a conjunctional false discovery rate (conjFDR) was used to evaluate the enrichment of pleiotropic loci between depression and left and right hippocampal volumes. RESULTS: Respectively, 7, 13, and 12 new loci have been associated with depression, left hippocampal volume and right hippocampal volume, with a significant threshold of condFDR < 0.01. A site of rs1267073 locus was found to be shared by the depression and right hippocampal volume with a threshold of conjFDR < 0.01. CONCLUSION: Above findings have provided more insights into the genetic mechanisms underlying the volume of hippocampus and the risk for depression. The results may also provide evidence for future clinical trials for treating depression.

Spatiotemporally Controllable Covalent Bonding of RNA for Multi-Protein Interference.

Many diseases are associated with genetic mutation and expression of mutated proteins, such as cancers. Therapeutic approaches that selectively target the synthesis process of multiple proteins show greater potential compared to single-protein approaches in oncological diseases. However, conventional agents to regulate the synthesis of multiple protein still suffer from poor spatiotemporal selectivity and stability. Here, a new method using a dye-peptide conjugate, PRFK, for multi-protein interference with spatiotemporal selectivity and reliable stability, is reported. By using the peptide sequence that targets tumor cells, PRFK can be efficiently taken up, followed by specific binding to the KDELR (KDEL receptor) protein located in the endoplasmic reticulum (ER). The dye generates 1O2 under light irradiation, enabling photodynamic therapy. This process converts the furan group into a cytidine-reactive intermediate, which covalently binds to mRNA, thereby blocking protein synthesis. Upon treating 4T1 cells, the proteomics data show alterations in apoptosis, ferroptosis, proliferation, migration, invasion, and immune infiltration, suggesting that multi-protein interference leads to the disruption of cellular physiological activities, ultimately achieving tumor treatment. This study presents a multi-protein interference probe with the potential for protein interference within various subcellular organelles in the future.

Spinal histamine H4 receptor mediates chronic pruritus via p-ERK in acetone-ether-water (AEW)-induced dry skin mice.

Dry skin is common to many pruritic diseases and is difficult to improve with oral traditional antihistamines. Recently, increasing evidence indicated that histamine H4 receptor (H4R) plays an important role in the occurrence and development of pruritus. Extracellular signal-regulated kinase (ERK) phosphorylation activation in the spinal cord mediates histamine-induced acute and choric itch. However, whether the histamine H4 receptor regulates ERK activation in the dry skin itch remains unclear. In the study, we explore the role of the histamine H4 receptor and p-ERK in the spinal cord in a dry skin mouse model induced by acetone-ether-water (AEW). q-PCR, Western blot, pharmacology and immunofluorescence  were applied in the study. We established a dry skin itch model by repeated application of AEW on the nape of neck in mice. The AEW mice showed typically dry skin histological change and persistent spontaneous scratching behaviour. Histamine H4 receptor, instead of histamine H1 receptor, mediated spontaneous scratching behaviour in AEW mice. Moreover, c-Fos and p-ERK expression in the spinal cord neurons were increased and co-labelled with GRPR-positive neurons in AEW mice. Furthermore, H4R agonist 4-methyhistamine dihydrochloride (4-MH)induced itch. Both 4-MH-induced itch and the spontaneous itch in AEW mice were blocked by p-ERK inhibitor U0126. Finally, intrathecal H4R receptor antagonist JNJ7777120 inhibited spinal p-ERK expression in AEW mice. Our results indicated that spinal H4R mediates itch via ERK activation in the AEW-induced dry skin mice.

Hyperreactio luteinalis and follicle-stimulating hormone receptor gene activation mutations: A case report.

INTRODUCTION AND IMPORTANCE: Spontaneous ovarian luteal hyperfunction after pregnancy is associated with activating mutations in the follicle-stimulating hormone receptor gene, and clarification of the etiology can help with subsequent treatment. PRESENTATION OF CASE: A 32-year-old woman presented with enlarged ovaries and bilateral ovarian polycystic echoes at 12 weeks of both pregnancies. The first pregnancy underwent transabdominal bilateral ovarian aspiration at 17 weeks and was spontaneously aborted 4 days after the procedure. After the discovery of bilateral ovarian polycystic echoes in the second pregnancy, genetic testing suggested the presence of activating mutations in the follicle-stimulating hormone receptor (FSHR) gene, resulting in ovarian luteinization, and the patient's condition was stabilized after conservative treatment. CLINICAL DISCUSSION: Ovarian luteal hyperfunction may be associated with hyperandrogenemia, thyroid-stimulating hormone abnormalities, abnormal testosterone levels, and genetic mutations. When ovarian luteal hyperfunction occurs, it is recommended to search for the etiology and treat the symptoms. CONCLUSION: Patients presenting with spontaneous ovarian hyperlutealization should be operated on cautiously, treated conservatively, closely observed, and managed for complications, and genetic testing should be performed to clarify the etiology if necessary.

Charge adaptive phytochemical-based nanoparticles for eradication of methicillin-resistant staphylococcus aureus biofilms.

The intrinsic resistance of MRSA coupled with biofilm antibiotic tolerance challenges the antibiotic treatment of MRSA biofilm infections. Phytochemical-based nanoplatform is a promising emerging approach for treatment of biofilm infection. However, their therapeutic efficacy was restricted by the low drug loading capacity and lack of selectivity. Herein, we constructed a surface charge adaptive phytochemical-based nanoparticle with high isoliquiritigenin (ISL) loading content for effective treatment of MRSA biofilm. A dimeric ISL prodrug (ISL-G2) bearing a lipase responsive ester bond was synthesized, and then encapsulated into the amphiphilic quaternized oligochitosan. The obtained ISL-G2 loaded NPs possessed positively charged surface, which allowed cis-aconityl-d-tyrosine (CA-Tyr) binding via electrostatic interaction to obtain ISL-G2@TMDCOS-Tyr NPs. The NPs maintained their negatively charged surface, thus prolonging the blood circulation time. In response to low pH in the biofilms, the fast removal of CA-Tyr led to a shift in their surface charge from negative to positive, which enhanced the accumulation and penetration of NPs in the biofilms. Sequentially, the pH-triggered release of d-tyrosine dispersed the biofilm and lipase-triggered released of ISL effectively kill biofilm MRSA. An in vivo study was performed on a MRSA biofilm infected wound model. This phytochemical-based system led to ∼2 log CFU (>99 %) reduction of biofilm MRSA as compared to untreated wound (P < 0.001) with negligible biotoxicity in mice. This phytochemical dimer nanoplatform shows great potential for long-term treatment of resistant bacterial infections.

Endoscopic ultrasound-guided biliary drainage vs percutaneous transhepatic bile duct drainage in the management of malignant obstructive jaundice.

BACKGROUND: Malignant obstructive jaundice (MOJ) is a condition characterized by varying degrees of bile duct stenosis and obstruction, accompanied by the progressive development of malignant tumors, leading to high morbidity and mortality rates. Currently, the two most commonly employed methods for its management are percutaneous transhepatic bile duct drainage (PTBD) and endoscopic ultrasound-guided biliary drainage (EUS-BD). While both methods have demonstrated favorable outcomes, additional research needs to be performed to determine their relative efficacy. AIM: To compare the therapeutic effectiveness of EUS-BD and PTBD in treating MOJ. METHODS: This retrospective analysis, conducted between September 2015 and April 2023 at The Third Affiliated Hospital of Soochow University (The First People's Hospital of Changzhou), involved 68 patients with MOJ. The patients were divided into two groups on the basis of surgical procedure received: EUS-BD subgroup (n = 33) and PTBD subgroup (n = 35). Variables such as general data, preoperative and postoperative indices, blood routine, liver function indices, myocardial function indices, operative success rate, clinical effectiveness, and complication rate were analyzed and compared between the subgroups. RESULTS: In the EUS-BD subgroup, hospital stay duration, bile drainage volume, effective catheter time, and clinical effectiveness rate were superior to those in the PTBD subgroup, although the differences were not statistically significant (P > 0.05). The puncture time for the EUS-BD subgroup was shorter than that for the PTBD subgroup (P < 0.05). Postoperative blood routine, liver function index, and myocardial function index in the EUS-BD subgroup were significantly lower than those in the PTBD subgroup (P < 0.05). Additionally, the complication rate in the EUS-BD subgroup was lower than in the PTBD subgroup (P < 0.05). CONCLUSION: EUS-BD may reduce the number of punctures, improve liver and myocardial functions, alleviate traumatic stress, and decrease complication rates in MOJ treatment.

LEUTX regulates porcine embryonic genome activation in somatic cell nuclear transfer embryos.

Emerging evidence highlights the regulatory role of paired-like (PRD-like) homeobox transcription factors (TFs) in embryonic genome activation (EGA). However, the majority of PRD-like genes are lost in rodents, thus prompting an investigation into PRD-like TFs in other mammals. Here, we showed that PRD-like TFs were transiently expressed during EGA in human, monkey, and porcine fertilized embryos, yet they exhibited inadequate expression in their cloned embryos. This study, using pig as the research model, identified LEUTX as a key PRD-like activator of porcine EGA through genomic profiling and found that LEUTX overexpression restored EGA failure and improved preimplantation development and cloning efficiency in porcine cloned embryos. Mechanistically, LEUTX opened EGA-related genomic regions and established histone acetylation via recruiting acetyltransferases p300 and KAT2A. These findings reveal the regulatory mechanism of LEUTX to govern EGA in pigs, which may provide valuable insights into the study of early embryo development for other non-rodent mammals.

A novel halloysite nanotubes-based hybrid monolith for in-tube solid-phase microextraction of polar cationic pesticides.

The accurate determination of polar cationic pesticides in food poses a challenge due to their high polarity and trace levels in complex matrices. This study hypothesized that the use of halloysite nanotubes (HNTs) can significantly enhance the extraction efficiency and sensitivity of these analytes because of their rich hydroxyl groups and cation exchange sites. Therefore, we chemically incorporated HNTs with organic polymer monoliths for in-tube solid-phase microextraction (SPME). This novel hybrid monolith extended service life, improved adsorption capacity, and exhibited excellent extraction performance for polar cationic pesticides. Based on these advancements, a robust and sensitive in-tube SPME-HILIC-MS/MS method was constructed to determine trace levels of polar cationic pesticides in complex food matrices. The method achieved limits of detection of 1.9, 2.1, and 0.1 µg/kg for maleic hydrazide, amitrole, and cyromazine, respectively. The spiked recoveries in five food samples ranged from 80.2 to 100.8%, with relative standard deviations below 10.7%.

Antibacterial properties of natural products from marine fungi reported between 2012 and 2023: a review.

The oceans are rich in diverse microorganisms, animals, and plants. This vast biological complexity is a major source of unique secondary metabolites. In particular, marine fungi are a promising source of compounds with unique structures and potent antibacterial properties. Over the last decade, substantial progress has been made to identify these valuable antibacterial agents. This review summarizes the chemical structures and antibacterial activities of 223 compounds identified between 2012 and 2023. These compounds, effective against various bacteria including drug-resistant strains such as methicillin-resistant Staphylococcus aureus, exhibit strong potential as antibacterial therapeutics. The review also highlights the relevant challenges in transitioning from drug discovery to product commercialization. Emerging technologies such as metagenomics and synthetic biology are proposed as viable solutions. This paper sets the stage for further research on antibacterial compounds derived from marine fungi and advocates a multidisciplinary approach to combat drug-resistant bacteria.

Urinary eicosanoid levels in early life and risk of atopic disease in childhood.

BACKGROUND: Eicosanoids are lipid mediators including thromboxanes (TXs), prostaglandins (PGs), and leukotrienes with a pathophysiological role in established atopic disease. However, their role in the inception of disease is unclear. This study aimed to investigate the association between urinary eicosanoids in early life and development of atopic disease. METHODS: This study quantified the levels of 21 eicosanoids in urine from children from the COPSAC2010 (Copenhagen Prospective Studies on Asthma in Childhood 2010) (age 1 year, n = 450) and VDAART (Vitamin D Antenatal Asthma Reduction Trial) (age 3 years, n = 575) mother-child cohorts and analyzed the associations with development of wheeze/asthma, atopic dermatitis, and biomarkers of type-2 inflammation, applying false discovery rate of 5% (FDR5%) multiple testing correction. RESULTS: In both cohorts, analyses adjusted for environmental determinants showed that higher TXA2 eicosanoids in early life were associated with increased risk of developing atopic dermatitis (P < FDR5%) and type-2 inflammation (P < .05). In VDAART, lower PGE2 and PGI2 eicosanoids and higher isoprostanes were also associated with increased risk of atopic dermatitis (P < FDR5%). For wheeze/asthma, analyses in COPSAC2010 showed that lower isoprostanes and PGF2 eicosanoids and higher PGD2 eicosanoids at age 1 year associated with an increased risk at age 1-10 years (P < .05), whereas analyses in VDAART showed that lower PGE2 and higher TXA2 eicosanoids at age 3 years associated with an increased risk at 6 years (P < FDR5%). CONCLUSIONS: This study suggests that early life perturbations in the eicosanoid metabolism are present before the onset of atopic disease in childhood, which provides pathophysiological insight in the inception of atopic diseases.

Novel mechanistic insights into Cr(VI) and Cr(III) induced discrepancies of cellular toxicity and oxidative injury events in Eisenia fetida.

Chromium (Cr) poses a high ecological risk, however the toxic mechanisms of Cr in different valence states to soil organisms at cellular and molecular levels are not exactly. In this study, the Eisenia fetida coelomocytes and Cu/Zn-superoxide dismutase (Cu/Zn-SOD) were chosen as the target subjects to investigate the effects and mechanisms of cellular toxicity induced by Cr(VI) and Cr(III). Results indicated that Cr(VI) and Cr(III) significantly reduced the coelomocytes viability. The level of reactive oxygen species (ROS) was markedly increased after Cr(VI) exposure, which finally reduced antioxidant defense abilities, and induced lipid peroxidation and cellular membrane damage in earthworm coelomocytes. However, Cr(III) induced lower levels of oxidative stress and cellular damage with respect to Cr(VI). From a molecular perspective, the binding of both Cr(VI) and Cr(III) with Cu/Zn-SOD resulted in protein backbone loosening and reduced ß-Sheet content. The Cu/Zn-SOD showed fluorescence enhancement with Cr(III), whereas Cr(VI) had no obvious effect. The activity of Cu/Zn-SOD continued to decrease with the exposure of Cr. Molecular docking indicated that Cr(III) interacted more readily with the active center of Cu/Zn-SOD. Our results illustrate that oxidative stress induced by Cr(VI) and Cr(III) plays an important role in the cytotoxic differences of Eisenia fetida coelomocytes and the binding of Cr with Cu/Zn-SOD can also affect the normal structures and functions of antioxidant defense-associated protein.

Elucidating the photodegradation mechanism of octylisothiazolinone and dichlorooctylisothiazolinone in surface water: An in-depth comprehensive analysis.

Octylisothiazolinone (OIT) and Dichlorooctylisothiazolinone (DCOIT), widely used antibacterial agents in coatings, have seen a sharp increase in use in response to the Coronavirus disease 2019 (Covid-19) pandemic, ultimately leading to their increase in the aquatic environment. However, their photodegradation process in surface water is still unclear. The purpose of this study is to investigate the photodegradation kinetics and mechanisms of OIT and DCOIT in natural water environments. Under simulated solar irradiation, they undergo direct photolysis in both natural freshwater and seawater mainly via their excited singlet states, while no self-sensitization photolysis was observed. The direct photolysis rate constants of OIT and DCOIT were 1.19 ± 0.07 and 0.57 ± 0.03 h-1, respectively. In addition, dissolved organic matter (DOM), NO3- and Cl- in natural waters did not contribute significantly to the photodegradation, and the light screening effect of DOM was identified as the main inhibiting factor. The photodegradation half-life of OIT was estimated to be 0.66 to 1.69 days, while the half-life of DCOIT was as high as 20.9 days during winter in surface water at 30°N latitude. Ring opening of the N-S bond and covalent bond breaking between CN are the main pathways for the photodegradation of OIT and DCOIT, which is verified by density-functional theory calculations. Ecological Structure Activity Relationships (ECOSAR) results indicate that OIT and DCOIT have "Very Toxic" biological toxicity, and the acute toxicity of their products is significantly reduced. It is noteworthy that the toxicity of the products of DCOIT is generally higher than that of OIT, and the chronic toxicity of most of the products is still above the "Toxic" level. Therefore, an in-depth understanding of the photodegradation mechanisms of OIT and DCOIT in aqueous environments is crucial for accurately assessing their ecological risks in natural water environments.

From metabolic to epigenetic: Insight into trained macrophages in atherosclerosis (Review).

Atherosclerosis (AS) is a chronic inflammatory disease caused by the deposition of lipoproteins and sequent immune responses. Within the atherosclerotic plaque, macrophages are the most abundant immune cells and play a great part as protagonists and promoters of AS. In the past decade, the concept of 'trained immunity' has emerged, which highlights the memory characteristics of innate immunity, thus opening up a new avenue of research. Evidence suggests that trained immunity may regulate the onset and progression of AS with trained macrophages playing an important and dynamic role in atherogenesis. The present review provided a summary of concepts related to trained immunity and its relationship with AS. Furthermore, different phenotypes of macrophages responding to various stimuli within the atherosclerotic plaque were presented, along with the complex mechanisms of metabolic and epigenetic reprogramming in the cells. Finally, several promising therapeutic approaches for AS cardiovascular disease were discussed, which may shed light on new clinical strategies.

Development and validation of a plasmalogen score as an independent modifiable marker of metabolic health: population based observational studies and a placebo-controlled cross-over study.

BACKGROUND: Decreased levels of circulating ethanolamine plasmalogens [PE(P)], and a concurrent increase in phosphatidylethanolamine (PE) are consistently reported in various cardiometabolic conditions. Here we devised, a plasmalogen score (Pls Score) that mirrors a metabolic signal that encompasses the levels of PE(P) and PE and captures the natural variation in circulating plasmalogens and perturbations in their metabolism associated with disease, diet, and lifestyle. METHODS: We utilised, plasma lipidomes from the Australian Obesity, Diabetes and Lifestyle study (AusDiab; n = 10,339, 55% women) a nationwide cohort, to devise the Pls Score and validated this in the Busselton Health Study (BHS; n = 4,492, 56% women, serum lipidome) and in a placebo-controlled crossover trial involving Shark Liver Oil (SLO) supplementation (n = 10, 100% men). We examined the association of the Pls Score with cardiometabolic risk factors, type 2 diabetes mellitus (T2DM), cardiovascular disease and all-cause mortality (over 17 years). FINDINGS: In a model, adjusted for age, sex and BMI, individuals in the top quintile of the Pls Score (Q5) relative to Q1 had an OR of 0.31 (95% CI 0.21-0.43), 0.39 (95% CI 0.25-0.61) and 0.42 (95% CI 0.30-0.57) for prevalent T2DM, incident T2DM and prevalent cardiovascular disease respectively, and a 34% lower mortality risk (HR = 0.66; 95% CI 0.56-0.78). Significant associations between diet and lifestyle habits and Pls Score exist and these were validated through dietary supplementation of SLO that resulted in a marked change in the Pls Score. INTERPRETATION: The Pls Score as a measure that captures the natural variation in circulating plasmalogens, was not only inversely related to cardiometabolic risk and all-cause mortality but also associate with diet and lifestyle. Our results support the potential utility of the Pls Score as a biomarker for metabolic health and its responsiveness to dietary interventions. Further research is warranted to explore the underlying mechanisms and optimise the practical implementation of the Pls Score in clinical and population settings. FUNDING: National Health and Medical Research Council (NHMRC grant 233200), National Health and Medical Research Council of Australia (Project grant APP1101320), Health Promotion Foundation of Western Australia, and National Health and Medical Research Council of Australia Senior Research Fellowship (#1042095).

Exogenous Eugenol Alleviates Salt Stress in Tobacco Seedlings by Regulating the Antioxidant System and Hormone Signaling.

Salt stress seriously affects crop growth, leading to a decline in crop quality and yield. Application of exogenous substances to improve the salt tolerance of crops and promote their growth under salt stress has become a widespread and effective means. Eugenol is a small molecule of plant origin with medicinal properties such as antibacterial, antiviral, and antioxidant properties. In this study, tobacco seedlings were placed in Hoagland's solution containing NaCl in the presence or absence of eugenol, and physiological indices related to stress tolerance were measured along with transcriptome sequencing. The results showed that eugenol improved the growth of tobacco seedlings under salt stress. It promoted carbon and nitrogen metabolism, increased the activities of nitrate reductase (NR), sucrose synthase (SS), and glutamine synthetase (GS) by 31.03, 5.80, and 51.06%. It also activated the enzymatic and non-enzymatic antioxidant systems, reduced the accumulation of reactive oxygen species in the tobacco seedlings, and increased the activities of superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), and ascorbate peroxidase (APX) by 24.38%, 18.22%, 21.60%, and 28.8%, respectively. The content of glutathione (GSH) was increased by 29.49%, and the content of superoxide anion (O2-) and malondialdehyde (MDA) were reduced by 29.83 and 33.86%, respectively. Promoted osmoregulation, the content of Na+ decreased by 34.34, K+ increased by 41.25%, and starch and soluble sugar increased by 7.72% and 25.42%, respectively. It coordinated hormone signaling in seedlings; the content of abscisic acid (ABA) and gibberellic acid 3 (GA3) increased by 51.93% and 266.28%, respectively. The transcriptome data indicated that the differentially expressed genes were mainly enriched in phenylpropanoid biosynthesis, the MAPK signaling pathway, and phytohormone signal transduction pathways. The results of this study revealed the novel role of eugenol in regulating plant resistance and provided a reference for the use of exogenous substances to alleviate salt stress.

Influence of different abutment materials on the color of implant-supported restoration: A laboratory study.

PURPOSE: To investigate the effect of different abutments and crowns on the color of implant-supported restorations. METHODS: Zirconia and lithium disilicate (e.max) disks with A2 shade were fabricated to represent two crowns. The implant abutments were untreated titanium, opaqued titanium, anodized titanium, A2 shade zirconia and white zirconia. 4.0 mm-thickness zirconia and e.max specimens were used as references respectively. The crowns were placed on tested abutments with a drop of clear glycerin between them and the color was measured using a digital spectrophotometer. CIELab values were recorded to evaluate color differences (ΔE) between tested specimens and the references. RESULTS: Titanium abutments presented higher color differences than zirconia. The ΔE values with untreated titanium were higher than those with opaqued titanium. No differences were found between untreated titanium and anodized titanium for zirconia crowns. The ΔE values of zirconia crowns showed no significant differences between shade A2 zirconia and white zirconia abutments; e.max crowns showed a significant difference. The zirconia crown ΔE values were lower than those of e.max for all titanium and A2 zirconia abutments. Lithium disilicate crowns and zirconia abutments may be more suitable for implant-supported restorations. Opaqued titanium abutment may improve color in esthetic regions when a ceramic abutment cannot be used. CLINICAL SIGNIFICANCE: Lithium disilicate crowns and zirconia abutments may be an effective method to achieve excellent color matching in esthetic regions with implant-supported restorations.

PE/PPE mutations in the transmission of Mycobacterium tuberculosis in China revealed by whole genome sequencing.

OBJECTIVE: This study aims to examine the impact of PE/PPE gene mutations on the transmission of Mycobacterium tuberculosis (M. tuberculosis) in China. METHODS: We collected the whole genome sequencing (WGS) data of 3202 M. tuberculosis isolates in China from 2007 to 2018 and investigated the clustering of strains from different lineages. To evaluate the potential role of PE/PPE gene mutations in the dissemination of the pathogen, we employed homoplastic analysis to detect homoplastic single nucleotide polymorphisms (SNPs) within these gene regions. Subsequently, logistic regression analysis was conducted to analyze the statistical association. RESULTS: Based on nationwide M. tuberculosis WGS data, it has been observed that the majority of the M. tuberculosis burden in China is caused by lineage 2 strains, followed by lineage 4. Lineage 2 exhibited a higher number of transmission clusters, totaling 446 clusters, of which 77 were cross-regional clusters. Conversely, there were only 52 transmission clusters in lineage 4, of which 9 were cross-regional clusters. In the analysis of lineage 2 isolates, regression results showed that 4 specific gene mutations, PE4 (position 190,394; c.46G > A), PE_PGRS10 (839,194; c.744 A > G), PE16 (1,607,005; c.620T > G) and PE_PGRS44 (2,921,883; c.333 C > A), were significantly associated with the transmission of M. tuberculosis. Mutations of PE_PGRS10 (839,334; c.884 A > G), PE_PGRS11 (847,613; c.1455G > C), PE_PGRS47 (3,054,724; c.811 A > G) and PPE66 (4,189,930; c.303G > C) exhibited significant associations with the cross-regional clusters. A total of 13 mutation positions showed a positive correlation with clustering size, indicating a positive association. For lineage 4 strains, no mutations were found to enhance transmission, but 2 mutation sites were identified as risk factors for cross-regional clusters. These included PE_PGRS4 (338,100; c.974 A > G) and PPE13 (976,897; c.1307 A > C). CONCLUSION: Our results indicate that some PE/PPE gene mutations can increase the risk of M. tuberculosis transmission, which might provide a basis for controlling the spread of tuberculosis.

Hypermethylation and low expression of FOXM1 predisposes women to unexplained recurrent miscarriage by impairing trophoblast stem cell proliferation.

Recurrent miscarriage (RM) is a distressing pregnancy complication with an unknown etiology. Increasing evidence indicates the relevance of dysregulation of human trophoblast stem cells (hTSCs), which may play a role in the development of RM. However, the potential molecular regulatory mechanism underlying the initiation and maintenance of hTSCs is yet to be fully elucidated. In this study, we performed data analysis and identified Forkhead box M1 (FOXM1) as a potential factor associated with RM. FOXM1 is a typical transcription factor known for its involvement in various pathophysiological processes, while the precise function of FOXM1 functions in hTSCs and RM remains incompletely understood. Utilizing RNA-seq, CUT&Tag, ChIP-qPCR, and sodium bisulfite conversion methods for methylation analysis, we elucidate the underlying regulatory mechanisms of FOXM1 in hTSCs and its implications in RM. Our findings demonstrate the relative high expression of FOXM1 in proliferating cytotrophoblasts (CTBs) compared to differentiated extravillous cytotrophoblasts (EVTs) and syncytiotrophoblasts (STBs). Besides, we provide evidence supporting a significant correlation between FOXM1 downregulation and the incidence of RM. Furthermore, we demonstrate the significant role of FOXM1 in regulating hTSCs proliferation and cell cycle through the transcriptional regulation of CDKN3, CCNB2, CCNA2, MAD2L1 and CDC25C. Notably, we observed a correlation between the downregulation of FOXM1 in RM and hypermethylation in its promoter region. Collectively, these results provide insights into the impact of FOXM1 on trophoblast regulation and offer a novel perspective on RM.