αO-Conotoxin GeXIVA[1,2] Suppresses In Vivo Tumor Growth of Triple-Negative Breast Cancer by Inhibiting AKT-mTOR, STAT3 and NF-κB Signaling Mediated Proliferation and Inducing Apoptosis.

Breast cancer is one of the leading causes of cancer mortality worldwide, and triple-negative breast cancer (TNBC) is the most problematic subtype. There is an urgent need to develop novel drug candidates for TNBC. Marine toxins are a valuable source for drug discovery. We previously identified αO-conotoxin GeXIVA[1,2] from Conus generalis, which is a selective antagonist of α9 nicotinic acetylcholine receptors (nAChRs). Recent studies indicated that α9 nAChR expression is positively correlated with breast cancer development; thus, α9 nAChR could serve as a therapeutic target for breast cancer. In this study, we aimed to investigate the in vivo antitumor effects of GeXIVA[1,2] on TNBC and to elucidate its underlying anticancer mechanism. Our data showed that GeXIVA[1,2] effectively suppressed 4T1 tumor growth in vivo at a very low dose of 0.1 nmol per mouse. Our results uncovered that the antitumor mechanism of GeXIVA[1,2] simultaneously induced apoptosis and blocked proliferation. Further investigations revealed that GeXIVA[1,2]-induced Caspase-3-dependent apoptosis was achieved through regulating Bax/Bcl-2 balance, and GeXIVA[1,2]-inhibited proliferation was mediated by the downregulation of the AKT-mTOR, STAT3 and NF-κB signaling pathways. Our study provides valuable arguments to demonstrate the potential of GeXIVA[1,2] as a novel marine-derived anticancer drug candidate for the treatment of TNBC.

Rare MED12L Variants Are Associated with Susceptibility to Guttate Psoriasis in the Han Chinese Population.

INTRODUCTION: According to the common disease/rare variant hypothesis, it is important to study the role of rare variants in complex diseases. The association of rare variants with psoriasis has been demonstrated, but the association between rare variants and specific clinical subtypes of psoriasis has not been investigated. METHODS: Gene-based and gene-level meta-analyses were performed on data extracted from our previous study data sets (2,483 patients with guttate psoriasis and 8,292 patients with non-guttate psoriasis) for genotyping. Then, haplotype analysis was performed for rare loss-of-function variants located in MED12L, and protein function prediction was performed for MED12L. Gene-based analysis at each stage had a moderate significance threshold (p < 0.05). A χ2 test was then conducted on the three potential genes, and the merged gene-based analysis was used to confirm the results. We also conducted association analysis and meta-analysis for functional variants located on the identified gene. RESULTS: Through these gene-level analyses, we determined that MED12L is a guttate psoriasis susceptibility gene (p = 9.99 × 10-5), and the single-nucleotide polymorphism with the strongest association was rs199780529 (p_combine = 1 × 10-3, p_meta = 2 × 10-3). CONCLUSIONS: In our study, a guttate psoriasis-specific subtype-associated susceptibility gene was confirmed in a Chinese Han population. These findings contribute to a better genetic understanding of different subtypes of psoriasis.

Study on a Noncontact Microdroplet Separation Method under the Action of Corona Discharge.

Precision manipulation of various liquids is essential in many fields such as various thermal, optical, and medical applications. This paper proposes an effective noncontact microdroplet separation method that is based on the action of corona discharge. A blade-plate electrode is constructed to generate an ionic wind, thereby enabling the droplet to be separated according to the shape of the blade electrode. Line, curve, S-shape, and parallel separation of the droplet can be realized in the experiment setup. Furthermore, experiment parameters, including the driving voltage, cutting speed, the distance of the upper and lower electrodes, cutting depth, etc., are discussed. Experimental results show that the proposed method is feasible and effective and can be used in application scenarios that require precise manipulation of droplets.

Prenatal PM2.5 exposure increases the risk of adverse pregnancy outcomes: evidence from meta-analysis of cohort studies.

Adverse pregnancy outcomes (APOs) are a significant cause of fetal death. A wide range of maternal psychological, social, and environmental factors may contribute to these outcomes. Mounting epidemiological studies have indicated that PM2.5 may result in these unfavorable consequences. Previously published meta-analyses have been updated and extended. Cohort studies were searched from three databases (up to July 24, 2023), and their quality was assessed by Newcastle-Ottawa Scale (NOS). Publication bias was examined by Egger's test and funnel plot. Despite a large number of studies showing similar results, the inconsistencies between these findings require careful generalization before concluding. This meta-analysis included 67 cohort studies from 20 countries, and the findings revealed that maternal PM2.5 exposure and five APOs were correlated significantly throughout pregnancy: preterm birth (PTB) (RR = 1.05; 95% CI: 1.03, 1.07); low birth weight (LBW) (RR = 1.02; 95% CI: 1.01, 1.04); small for gestational age (SGA) (RR = 1.03; 95% CI: 1.01, 1.04); stillbirth (RR = 1.24; 95% CI: 1.06, 1.45); and change in birthweight (weight change = -6.82 g; 95% CI: -11.39, -2.25). A positive association was found between APOs and PM2.5 exposure in this meta-analysis, and the degree of increased risk of APOs varied due to different gestation periods. Therefore, it is necessary to protect pregnant women at specific times.

Two birds with one stone: Ratiometric sensing platform overcoming cross-interference for multiple-scenario detection and accurate discrimination of tetracycline analogs.

Environmental pollution caused by tetracycline antibiotics (TCs) is a major concern for public health worldwide. Trace detection and reliable discrimination of tetracycline and its analogs are consequently essential to determine the distribution characteristics of various tetracycline family members. Here, a dual-response sensor was constructed by integrating the fluorescence emission of fluorescein isothiocyanate (FITC) doped SiO2 and Eu3+. A portable Lab-on-Paper device is further fabricated through probe immobilization, which allows convenient visual detection of tetracycline using a smartphone. In addition, for the coexistence of multiple tetracycline analogs, dimensionality reduction via principal component analysis is applied to the spectra, realizing accurate differentiation of the four most widely used tetracycline analogs (tetracycline (TC), chlortetracycline (CTC), oxytetracycline (OTC), and doxycycline (DOX)). The dual-response nanoplatform enabled a wide-gamut color variation crossing from green to red, with limit of detection (LOD) of 2.9 nM and 89.8 nM for spectrometer- and paper-based sensors, respectively. Analytical performance was examined in multiple real samples, including food, environmental, and biological settings, confirming robust environmental adaptability and resistance. Compared to previous TC sensors, this method has several notable improvements, including improved ecological safety, accessibility, reproducibility, practicality, and anti-cross-interference capacity. These results highlight the potential of the proposed "two birds with one stone" strategy, providing an integrated methodology for synchronous quantitative detection and derivative identification toward environmental contaminants.

Pyroptosis in neurodegenerative diseases: from bench to bedside.

The central nervous system regulates all aspects of physiology to some extent. Neurodegenerative diseases (NDDs) lead to the progressive loss and dysfunction of neurons, which are particularly evident in Alzheimer's disease, Parkinson's disease, and many other conditions. NDDs are multifactorial diseases with complex pathogeneses, and there has been a rapid increase in the prevalence of NDDs. However, none of these diseases can be cured, making the development of novel treatment strategies an urgent necessity. Numerous studies have indicated how pyroptosis induces inflammation and affects many aspects of NDD. Therefore, components related to pyroptosis are potential therapeutic candidates and are attracting increasing attention. Here, we review the role of pyroptosis in the pathogenesis of NDDs and potential treatment options. Additionally, several of the current drugs and relevant inhibitors are discussed. Through this article, we provide theoretical support for exploring new therapeutic targets and updating clinical treatment strategies for NDDs. Notably, pyroptosis, a recently widely studied mode of cell death, is still under-researched compared to other traditional forms of cell death. Moreover, the focus of research has been on the onset and progression of NDDs, and the lack of organ-specific target discovery and drug development is a common problem for many basic studies. This urgent problem requires scientists and companies worldwide to collaborate in order to develop more effective drugs against NDDs.

Role of brahma-related gene 1/brahma-associated factor subunits in neural stem/progenitor cells and related neural developmental disorders.

Different fates of neural stem/progenitor cells (NSPCs) and their progeny are determined by the gene regulatory network, where a chromatin-remodeling complex affects synergy with other regulators. Here, we review recent research progress indicating that the BRG1/BRM-associated factor (BAF) complex plays an important role in NSPCs during neural development and neural developmental disorders. Several studies based on animal models have shown that mutations in the BAF complex may cause abnormal neural differentiation, which can also lead to various diseases in humans. We discussed BAF complex subunits and their main characteristics in NSPCs. With advances in studies of human pluripotent stem cells and the feasibility of driving their differentiation into NSPCs, we can now investigate the role of the BAF complex in regulating the balance between self-renewal and differentiation of NSPCs. Considering recent progress in these research areas, we suggest that three approaches should be used in investigations in the near future. Sequencing of whole human exome and genome-wide association studies suggest that mutations in the subunits of the BAF complex are related to neurodevelopmental disorders. More insight into the mechanism of BAF complex regulation in NSPCs during neural cell fate decisions and neurodevelopment may help in exploiting new methods for clinical applications.

Optimization of Lactoferrin-Derived Amyloid Coating for Enhancing Soft Tissue Seal and Antibacterial Activity of Titanium Implants.

A poor seal of the titanium implant-soft tissue interface provokes bacterial invasion, aggravates inflammation, and ultimately results in implant failure. To ensure the long-term success of titanium implants, lactoferrin-derived amyloid is coated on the titanium surface to increase the expression of cell integrins and hemidesmosomes, with the goal of promoting soft tissue seal and imparting antibacterial activity to the implants. The lactoferrin-derived amyloid coated titanium structures contain a large number of amino and carboxyl groups on their surfaces, and promote proliferation and adhesion of epithelial cells and fibroblasts via the PI3K/AKT pathway. The amyloid coating also has a strong positive charge and possesses potent antibacterial activities against Staphylococcus aureus and Porphyromonas gingivalis. In a rat immediate implantation model, the amyloid-coated titanium implants form gingival junctional epithelium at the transmucosal region that resembles the junctional epithelium in natural teeth. This provides a strong soft tissue seal to wall off infection. Taken together, lactoferrin-derived amyloid is a dual-function transparent coating that promotes soft tissue seal and possesses antibacterial activity. These unique properties enable the synthesized amyloid to be used as potential biological implant coatings.

Manifestation and Mechanisms of Abnormal Mineralization in Teeth.

Tooth biomineralization is a dynamic and complicated process influenced by local and systemic factors. Abnormal mineralization in teeth occurs when factors related to physiologic mineralization are altered during tooth formation and after tooth maturation, resulting in microscopic and macroscopic manifestations. The present Review provides timely information on the mechanisms and structural alterations of different forms of pathological tooth mineralization. A comprehensive study of these alterations benefits diagnosis and biomimetic treatment of abnormal mineralization in patients.

A biomaterial-based therapy using a sodium hyaluronate/bioglass composite hydrogel for the treatment of oral submucous fibrosis.

Oral submucous fibrosis (OSF) is a chronic, inflammatory and potentially malignant oral disorder. Its pathophysiology is extremely complex, including excessive collagen deposition, massive inflammatory infiltration, and capillary atrophy. However, the existing clinical treatment methods do not fully take into account all the pathophysiological processes of OSF, so they are generally low effective and have many side effects. In the present study, we developed an injectable sodium hyaluronate/45S5 bioglass composite hydrogel (BG/HA), which significantly relieved mucosal pallor and restricted mouth opening in OSF rats without any obvious side effects. The core mechanism of BG/HA in the treatment of OSF is the release of biologically active silicate ions, which inhibit collagen deposition and inflammation, and promote angiogenesis and epithelial regeneration. Most interestingly, silicate ions can overall regulate the physiological environment of OSF by down-regulating α-smooth muscle actin (α-SMA) and CD68 and up-regulating CD31 expression, as well as regulating the expression of pro-fibrotic factors [transforming growth factor-ß1 (TGF-ß1), interleukin-10 (IL-10), tumor necrosis factor-α (TNF-α) and tissue inhibitors of metalloproteinase-1 (TIMP-1)] and anti-fibrotic factors [interleukin-1ß (IL-1ß)] in macrophage. In conclusion, our study shows that BG/HA has great potential in the clinical treatment of OSF, which provides an important theoretical basis for the subsequent development of new anti-fibrotic clinical preparations. STATEMENT OF SIGNIFICANCE: : Oral submucous fibrosis (OSF) is a chronic, inflammatory and potentially malignant mucosal disease with significant impact on the quality of patients' life. However, the existing clinical treatments have limited efficacy and many side effects. There is an urgent need for development of specific drugs for OSF treatment. In the present study, bioglass (BG) composited with sodium hyaluronate solution (HA) was used to treat OSF in an arecoline-induced rat model. BG/HA can significantly inhibit collagen deposition, regulate inflammatory response, promote angiogenesis and repair damaged mucosal epithelial cells, and thereby mitigate the development of fibrosis in vivo.

A smartphone-based platform for ratiometric visualization of SARS-CoV-2 via an oligonucleotide probe.

COVID-19 necessitates the development of reliable and convenient diagnostic tools. In this work, a facile 3D-printed smartphone platform was constructed that achieved reliable visual detection of SARS-CoV-2 by eliminating the effect of ambient light and fixing the camera position relative to the sample. The oligonucleotide probe is modified with orange-red-emitting TAMRA working as an internal standard and green-emitting FAM serving as a sensitive sensing agent. Under 365-nm UV excitation, the emission wavelengths of TAMRA and FAM are 580 nm and 518 nm, respectively. When the probes interact with the targets, the green fluorescence gradually restores while the orange-red fluorescence remains stable. Thus, a striking color transition from orange-red to green could be observed by the naked eye. The detection limit of SARS-CoV-2 nucleic acid is 0.23 nM, and the entire process of color change could be completed in 25 min. Furthermore, the RGB value analysis of the sample solution was conducted using a smartphone for reliable and reproducible discrimination of SARS-CoV-2. The proposed smartphone platform might establish a general method for visual detection of SARS-CoV-2 nucleic acid as well as other virus-related diseases.

In-vitro differentiation of human embryonic stem cells into spinal cord neural stem cells.

In-vitro differentiation of human embryonic stem cells into spinal cord neural stem cells (NSCs) can help researchers better understand the cellular processes associated with spinal cord development and regeneration, and provide therapeutic strategies for spinal cord disorders. However, effective and consistent methods for the generation of human spinal cord NSCs are rare. Objective of the study is to establish methods for the in-vitro induction and long-term maintenance of human spinal cord NSCs. H9 cells were treated with neural induction medium for 10 days under single-cell seeding condition, followed by treatment with neural maintenance medium and replacement with NSC medium after five passages. The identity of the generated cells was determined by immunofluorescence, immunoblotting, and cleavage under targets and tagmentation (CUT&Tag) assays. After the neural induction, OCT4, an embryonic stem cell marker, was significantly reduced, whereas NESTIN and PAX6, two NSC markers, were clearly increased. After the neural maintenance, most of the H9-derived cells consistently expressed NESTIN and PAX6 together with SOX1 and HOXC9, two spinal cord markers. The Homer known motif enrichment results of the CUT&Tag assay confirmed the expression of HOXC9 in the H9-derived spinal cord NSCs, which can be maintained for more than 40 days under an in vitro culture system. This study sheds new light on effective induction and maintenance of human spinal cord NSCs.

An artificially designed elastin-like recombinant polypeptide improves aging skin.

BACKGROUND: As a substrate for cell growth, elastin can promote the regeneration and remodeling of the epidermis, which plays an important role in delaying skin aging. However, elastin proteins are more than 700 amino acids long and cannot be absorbed through the skin, which prevents the direct utilization of elastin in the prevention and treatment of aging skin. METHODS: We designed an elastin-like recombinant polypeptide (ELR) which could be absorbed through the skin based on the property of hexapeptide VGVAPG. Thirty healthy Chinese Han female participants which met the criteria were enrolled in this study and all of them completed the tests including elasticity, tightness, and wrinkle detection. The participants used this polypeptide for 4 weeks and were tested in three visits: one day before trial started (D0), and 14 and 28 days after the trial (D14 and D28, respectively). Paired t-tests or Wilcoxon signed-rank tests for non-parametric measures were used to determine the difference between D0 and D14, or D0 and D28. RESULTS: The skin elasticity level in the thirty participants was significantly increased after using ELR for 28 days (P=0.024), and the average value of skin firmness (Uf) declined from 3.313 (D0) to 3.292 (D14) and 3.265 (D28), although there was no statistically significant difference between treatment and pre-treatment. Furthermore, the wrinkle count (D14: P<0.001; D28: P<0.001), wrinkles volume (D14: P<0.001; D28: P=0.008), and wrinkles area (D14: P<0.001; D28: P<0.001) of Crow's feet were significantly improved by using ELR for 14 days or 28 days. CONCLUSION: Continuous use of ELR could significantly improve skin elasticity and reduce wrinkles.

White Blood Cell Counts to High-Density Lipoprotein Cholesterol Ratio, as a Novel Predictor of Long-Term Adverse Outcomes in Patients After Percutaneous Coronary Intervention: A Retrospective Cohort Study.

Background: White blood cell (WBC) counts and high-density lipoprotein cholesterol (HDL-C) are widely available in clinical practice. However, the predictive value for cardiovascular disease (CVD) is uncertain. In the present study, we firstly assessed the prognostic value of WBC to HDL-C ratio (WHR) in patients with coronary artery disease (CAD) who underwent percutaneous coronary intervention (PCI). Methods: Six thousand and fifty patients with CAD after PCI from a retrospective cohort study (identifier: ChiCTR-INR-16010153) were evaluated initially. Three hundred and seventy-one patients were excluded due to HDL cholesterol data not available, malignancy, dementia, psoriasis or eczema, systemic connective tissue disorders, multiple sclerosis, chronic liver disease, and chronic obstructive pulmonary disorder. Finally, 5,679 patients were included in the study. The primary outcome was long-term mortality. Secondary endpoints were mainly major adverse cardiovascular and cerebrovascular events (MACCEs), defined as a combination of stroke, cardiac death, stent thrombosis, recurrent myocardial infarction, and target vessel revascularization. The mean follow-up time of this study was 35.9 ± 22.5 months. We defined the best cutoff value of MHR according to the receiver operating curve (ROC), and then patients were divided into high and low WHR groups according to the cutoff value. We analyzed the data in both an acute coronary syndrome group (ACS) and a stable CAD subgroup, respectively. Results: Overall, there were 293 cases of long-term mortality during the follow-up period. According to the cutoff value (WHR = 8.25), 1,901 ACS patients were divided into high WHR group (n = 724) and low WHR group (n = 1,177). Compared to low WHR group, the incidence of all-cause mortality (ACM, 5.5 vs. 3.6%, p = 0.048) and cardiac death (4.7vs. 2.9%, p = 0.042) were significantly higher in the high WHR group. In stable CAD group, we also found the incidence of ACM and cardiac death were significantly higher in the high group compared to that in the low group. We did not find significant difference between the high and the low WHR group in the incidence of MACCEs. The multivariate Cox proportional hazards model showed that increased WHR level was independently correlated with the mortality. In the high WHR group, the risk of ACM increased two times in ACS [adjusted HR = 2.036 (1.258-3.296), p = 0.004] and 1.5 times in stable CAD [adjusted HR = 1.586 (1.178-2.136), p = 0.002]. Conclusion: The present study indicated that an increased WBC count to HDL-C ratio was independently associated with long-term mortality in CAD patients who underwent PCI.

MicroRNA-4429 suppresses proliferation of prostate cancer cells by targeting distal-less homeobox 1 and inactivating the Wnt/ß-catenin pathway.

BACKGROUND: Emerging evidence suggests that microRNAs (miRNAs) play multiple roles in human cancers through regulating mRNAs and distinct pathways. This paper focused on the functions of miR-4429 in prostate cancer (PCa) progression and the molecules involved. METHODS: Expression of miR-4429 in PCa tissues and cells was determined. Upregulation of miR-4429 was introduced in PCa cells to examine its role in the malignant behaviors of cells. The putative target mRNA of miR-4429 involved in PCa progression was predicted from a bioinformatic system and validated through luciferase assays. Overexpression of distal-less homeobox 1 (DLX1) was further induced in cells to validate its implication in miR-4429-mediated events. The activity of Wnt/ß-catenin pathway was determined. RESULTS: miR-4429 was poorly expressed in PCa tissues and cells. Artificial upregulation of miR-4429 significantly reduced proliferation, growth, invasion, migration and resistance to death of cancer cells and inactivated the Wnt/ß-catenin pathway. DLX1 mRNA was found as a target of miR-4429. Upregulation of DLX1 restored the malignant behaviors of PCa cells which were initially suppressed by miR-4429, and it activated the Wnt/ß-catenin pathway. CONCLUSION: Our study highlights that miR-4429 inhibits the growth of PCa cells by down-regulating DLX1 and inactivating the Wnt/ß-catenin pathway. This finding may offer novel insights into PCa treatment.

Gut Microbiome-Based Diagnostic Model to Predict Coronary Artery Disease.

In the present study, we aimed to characterize gut microbiome and develop a gut microbiome-based diagnostic model in patients with coronary artery disease (CAD). Prospectively, we collected 309 fecal samples from Central China and Northwest China and carried out the sequencing of the V3-V4 regions of the 16S rRNA gene. The gut microbiome was characterized, and microbial biomarkers were identified in 152 CAD patients and 105 healthy controls (Xinjiang cohort, n = 257). Using the biomarkers, we constructed a diagnostic model and validated it externally in 34 CAD patients and 18 healthy controls (Zhengzhou cohort, n = 52). Fecal microbial diversity was increased in CAD patients compared to that in healthy controls (P = 0.021). Phylum Bacteroidetes was increased in CAD patients versus healthy controls (P = 0.001). Correspondingly, 48 microbial markers were identified through a 10-fold cross-validation on a random forest model, and an area under the curve (AUC) of 87.7% (95% CI: 0.832 to 0.916, P < 0.001) was achieved in the Xinjiang cohort (development cohort, n = 257). Notably, an AUC of 90.4% (95% CI: 0.848 to 0.928, P < 0.001) was achieved using combined analysis of gut microbial markers and clinical variables. This model provided a robust tool for the prediction of CAD. It could be widely employed to complement the clinical assessment and prevention of CAD.

Conditional deletion of Adrb2 in mesenchymal stem cells attenuates osteoarthritis-like defects in temporomandibular joint.

ß2-adrenergic signal transduction in mesenchymal stem cells (MSCs) induces subchondral bone loss in osteoarthritis (OA) of temporomandibular joints (TMJs). However, whether conditional deletion of ß2-adrenergic receptor (Adrb2) in nestin+ MSCs can alleviate TMJ-OA development remains unknown. In this study, nestin-Cre mice were crossed with Adrb2 flox mice to generate mice lacking Adrb2 expression specifically in the nestin+ MSCs (Adrb2-/-), and TMJ-OA development in such mice was investigated. Adrb2 flox mice (Adrb2+/+) and Adrb2-/- mice were subjected to unilateral anterior crossbite (UAC), while mice in the control group were subjected to sham operation. Adrb2+/+ and Adrb2-/- mice in the control group showed no distinguishable phenotypic changes in body weight and length, mandibular condylar size, and other histomorphological parameters of the condylar subchondral bone. A significant increase in subchondral bone loss and cartilage degradation was observed in Adrb2+/+ UAC mice; the former was characterized by decreased bone mineral density, bone volume fraction, and trabecular plate thickness, and increased trabecular separation, osteoclast number and osteoclast surface, and pro-osteoclastic factor expression; the latter was characterized by decreased cartilage thickness, chondrocyte density, proteoglycan area, and collagen II and aggrecan expression, but increased matrix metalloproteinase and alkaline phosphatase expression and percentage area of calcified cartilage. Adrb2 deletion in nestin+ MSCs largely attenuated UAC-induced increase in condylar subchondral bone loss, cartilage degradation, and aberrant calcification at the osteochondral interface. Thus, Adrb2-expressing MSCs in the condylar subchondral bone play an important role in TMJ-OA progression and may serve as novel therapeutic targets for TMJ-OA.

Progress in the application of metal and metal oxide nanoparticles in the antibacterial modification of dental materials / 口腔疾病防治

@#The colonization of microorganisms planted on the surface of teeth and restoration materials is the main cause of oral disease and treatment failure. How to improve the antibacterial properties of dental materials is a hot topic in dentistry. Nano-sized antibacterial materials have attracted much attention. Among them, metal and metal oxide nanoparticles are prominent due to their strong and broad-spectrum antibacterial activity. Thus, in recent years, many studies have used metal and metal oxide nanoparticles to develop antimicrobial dental materials for resin restoration, root canal therapy, orthodontic treatment, and implant surface and removable denture repair and have found that the antibacterial properties of nano-sized materials are significantly enhanced. However, the mechanical properties and esthetic properties of the modified materials are affected, so it is still necessary to explore appropriate modification methods. In addition, most of the experiments are carried out in vitro, which cannot accurately simulate the oral environment. Therefore, the antibacterial effect, cytotoxicity and immune response of these materials in vivo still need further research and exploration. This paper reviewed the potential antibacterial mechanisms and the safety of those nanoparticles and their applications in dentistry.

[Methods of removing failed implants].

Implant restoration has become one of the most regular methods of restoring dentition defect or edentulous. Implant placement and osseointegration are partly unreserved (fracture, implant is not in the correct three-dimensional position and cannot be repaired, peri-implantitis-affected nonmobile implants) need to be removed. This article reviews the different methods of removing implants and discusses the limitations of each method, as well as the complications that may occur during the procedure.

[Mid-frequency transcutaneous electrical acupoint stimulation combined with tamoxifen for the treatment of oligoasthenozoospermia].

OBJECTIVE: To explore the feasibility, safety and clinical effect of mid-frequency transcutaneous electrical acupoint stimulation (TEAS) combined with oral tamoxifen (TAM) in the treatment of oligoasthenozoospermia. METHODS: We randomly and equally assigned 120 patients with idiopathic oligoasthenozoospermia to receive oral TAM, mid-frequency TEAS, or TAM+TEAS, all for 8 weeks. Before and after treatment, we recorded the semen volume, total sperm count, sperm concentration, sperm motility, percentage of progressively motile sperm (PMS), and the levels of follicle-stimulating hormone (FSH), luteotrophic hormone (LH) and testosterone (T) in the peripheral serum and compared these parameters among the three groups of patients. RESULTS: Compared with the baseline, none of the patients showed significant improvement in the semen volume (P >0.05) but all exhibited remarkably elevated levels of serum FSH, LH and T after treatment (P <0.05); TAM significantly improved the total sperm count (ï¼»25.16 ± 2.05ï¼½ vs ï¼»42.65 ± 5.78ï¼½ ×106, P <0.05) and sperm concentration (ï¼»12.15 ± 2.51ï¼½ vs ï¼»24.31 ± 2.59ï¼½ ×106/ml, P <0.05), but not total sperm motility (ï¼»21.78 ± 8.81ï¼½ vs ï¼»22.61 ± 5.75ï¼½ %, P >0.05) or PMS (ï¼»15.87 ± 7.81ï¼½ vs ï¼»16.76 ± 5.86ï¼½ %, P >0.05); TEAS markedly increased total sperm motility (ï¼»24.81 ± 8.27ï¼½ vs ï¼»32.43 ± 4.97ï¼½ %, P <0.05) and PMS (ï¼»19.71 ± 9.15ï¼½ vs ï¼»27.17 ± 5.09ï¼½%, P <0.05), but not the total sperm count (ï¼»23.23 ± 3.14ï¼½ vs ï¼»25.87 ± 4.96ï¼½ ×106, P >0.05) or sperm concentration (ï¼»11.27 ± 2.24ï¼½ vs ï¼»14.12 ± 2.47ï¼½ ×106/ml, P >0.05); TAM+TEAS, however, improved not only the total sperm count (ï¼»26.17 ± 5.05ï¼½ vs ï¼» 51.14 ± 3.69ï¼½×106, P <0.05) and sperm concentration (ï¼»12.78 ± 2.41ï¼½ vs ï¼»27.28 ± 1.98ï¼½ ×106/ml, P <0.05), but also total sperm motility (ï¼»23.89 ± 9.05ï¼½ vs ï¼»37.12 ± 5.33ï¼½%, P <0.05) and PMS (ï¼»17.14 ± 8.04ï¼½ vs ï¼»31.09 ± 7.12ï¼½%, P <0.05). The total effectiveness rate was significantly higher in the TAM+TEAS group than in the TAM and TEAS groups (97.5% vs 72.5% and 75.0%, P <0.05). CONCLUSIONS: Mid-frequency TEAS combined with tamoxifen can significantly improve semen quality and increase sex hormone levels in patients with idiopathic oligoasthenozoospermia.