Activation of aryl hydrocarbon receptor (AhR) alleviates depressive-like behaviors in LPS-induced mice.

The role of the aryl hydrocarbon receptor (AhR) in regulating oxidative stress and immune responses has been increasingly recognized. However, its involvement in depression and the underlying mechanisms remain poorly understood. This study aimed to investigate the effect of 6-formylindolo[3,2-b]carbazole (FICZ), an endogenous AhR ligand, on a lipopolysaccharide (LPS)-induced depression model and the underlying mechanism. After being treated with FICZ (50 mg/kg), male C57BL/6J mice received intraperitoneal injection of LPS and underwent behavioral tests 24 h later. The levels of inflammatory cytokines, including IL-1ß, IL-6, and TNF-α, were measured in the hippocampus and serum using enzyme-linked immunosorbent assay (ELISA). The expression levels of CYP1A1, AhR and NLRP3 were analyzed using qPCR and Western blot. The results showed that, compared with control group, LPS alone significantly down-regulated the expression levels of CYP1A1 mRNA and AhR protein in the hippocampus of mice, reduced glucose preference, prolonged immobility time in forced swimming test, increased IL-6 and IL-1ß levels in the hippocampus, increased serum IL-1ß level, and up-regulated NLRP3 mRNA and protein expression levels in mouse hippocampus, while FICZ significantly reversed the aforementioned effects of LPS. These findings suggest that AhR activation attenuates the inflammatory response associated with depression and modulates the expression of NLRP3. The present study provides novel insights into the role of AhR in the development of depression, and presents AhR as a potential therapeutic target for the treatment of depression.

Repression of LSD1/KDM1A activity improves the response of liver cancer cells to the lenvatinib.

BACKGROUND/AIM: Lenvatinib, a multikinase inhibitor, has become a second-line treatment option for unresectable liver cancer, while its monotherapy response rate is limited. Hence, we aim to investigate whether one of the epigenetic inhibitors will be synthetic lethal with Lenvatinib in liver cancer cells. MATERIALS AND METHODS: We performed high-throughput drug screening in combination with Lenvatinib. And we employed CCK-8-based Bliss Synergy Score analysis, colony formation and western blotting to confirm our screening results in both HepG2 and HCCC9810 cells. RESULTS: We identified that LSD1 inhibitor Pulrodemstat in combination with Lenvatinib dramatically suppressed the PI3K-AKT signaling and induced a more significant activation of Caspase3 compared to Lenvatinib monotherapy. CONCLUSION: Pulrodemstat synergized with Lenvatinib based on suppression of PI3K-AKT signaling and activation of apoptotic signaling.

Evaluation of the Efficacy of Stem Cells Therapy in the Periodontal Regeneration: A Meta-Analysis and Mendelian Randomization Study.

Stem cell therapy for periodontal defects has shown good promise in preclinical studies. The purpose of this study was to evaluate the impact of stem cell support on the regeneration of both soft and hard tissues in periodontal treatment. PubMed, Cochrane Library, Embase, and Web of Science were searched and patients with periodontal defects who received stem cell therapy were included in this study. The quality of the included articles was assessed using Cochrane's tool for evaluating bias, and heterogeneity was analyzed using the I2 method. An Mendelian randomization investigation was conducted using abstract data from the IEU public databases obtained through GWAS. Nine articles were included for the meta-analysis. Stem cell therapy effectively rebuilds periodontal tissues in patients with periodontal defects, as evidenced by a reduction in probing depth, clinical attachment level  and bone defect depth . And delta-like homolog 1 is a protective factor against periodontal defects alternative indicator of tooth loosening. The findings of this research endorse the utilization of stem cell treatment for repairing periodontal defects in individuals suffering from periodontitis. It is recommended that additional extensive clinical investigations be carried out to validate the efficacy of stem cell therapy and encourage its widespread adoption.

Research on prevention and control technology of classified rockburst in TBM construction of deeply buried tunnels.

Rock blasting and other geological disasters occur frequently in the TBM construction of deeply buried tunnels and seriously threaten construction safety and progress. Therefore, it is extremely important to conduct scientific research for effective prevention and control of rockbursts in construction. Based on a large number of field rockburst data, this study analyses the influence of rockburst on construction safety and efficiency by using statistical theory and summarizes the temporal and spatial characteristics of rockburst time, location and influence range. Using these results, combined with the characteristics of the TBM structure and construction method, classification prevention and control objectives, theoretical criteria and prevention and control technology of rock bursts are proposed. A theoretical system of classified prevention and control of rockburst is constructed, which is cooperatively controlled by microseismic monitoring, TBM equipment, TBM excavation and support measures. The system is verified to provide practical protection, demonstrating that this report provides an important reference for the prevention and control of rock bursts in ultradeep tunnels.

Type 1 diabetes, glycemic traits, and risk of dental caries: a Mendelian randomization study.

Background: Regarding past epidemiological studies, there has been disagreement over whether type 1 diabetes (T1DM) is one of the risk factors for dental caries. The purpose of this study was to determine the causative links between genetic susceptibility to T1DM, glycemic traits, and the risk of dental caries using Mendelian randomization (MR) approaches. Methods: Summary-level data were collected on genome-wide association studies (GWAS) of T1DM, fasting glucose (FG), glycated hemoglobin (HbA1c), fasting insulin (FI), and dental caries. MR was performed using the inverse-variance weighting (IVW) method, and sensitivity analyses were conducted using the MR-Egger method, weighted median, weighted mode, replication cohort, and multivariable MR conditioning on potential mediators. Results: The risk of dental caries increased as a result of genetic susceptibility to T1DM [odds ratio (OR) = 1.044; 95% confidence interval (CI) = 1.015-1.074; p = 0.003], with consistent findings in the replication cohort. The relationship between T1DM and dental caries was stable when adjusted for BMI, smoking, alcohol intake, and type 2 diabetes (T2DM) in multivariable MR. However, no significant correlations between the risk of dental caries and FG, HbA1c, or FI were found. Conclusion: These results indicate that T1DM has causal involvement in the genesis of dental caries. Therefore, periodic reinforcement of oral hygiene instructions must be added to the management and early multidisciplinary intervention of T1DM patients, especially among adolescents and teenagers, who are more susceptible to T1DM.

Tooth ultrastructure changes induced by a nonsense mutation in the FAM83H gene: insights into the diversity of amelogenesis imperfecta.

OBJECTIVES: The current research on single-nucleotide polymorphism (SNP) mutation sites at different positions of the FAM83H gene and their phenotypic changes leading to amelogenesis imperfecta (AI) is inconsistent. We identified a previously reported heterozygous nonsense mutation c.1192C>T (p.Q398*) in the FAM83H gene and conducted a comprehensive analysis of the dental ultrastructure and chemical composition changes induced by this mutation. Additionally, we predicted the protein feature affected by this mutation site. The aim was to further deepen our understanding of the diversity of AI caused by different mutation sites in the FAM83H gene. METHODS: Whole-exome sequencing (WES) and Sanger sequencing were used to confirm the mutation sites. Physical features of the patient's teeth were investigated using various methods including cone beam computer tomography (CBCT), scanning electron microscopy (SEM), contact profilometry (roughness measurement), and a nanomechanical tester (nanoindentation measurement). The protein features of wild-type and mutant FAM83H were predicted using bioinformatics methods. RESULTS: One previously discovered FAM83H heterozygous nonsense mutation c.1192C>T (p.Q398*) was detected in the patient. SEM revealed inconsistent dentinal tubules, and EDS showed that calcium and phosphorus were lower in the patient's dentin but higher in the enamel compared to the control tooth. Roughness measurements showed that AI patients' teeth had rougher occlusal surfaces than those of the control tooth. Nanoindentation measurements showed that the enamel and dentin hardness values of the AI patients' teeth were both significantly reduced compared to those of the control tooth. Compared to the wild-type FAM83H protein, the mutant FAM83H protein shows alterations in stability, hydrophobicity, secondary structure, and tertiary structure. These changes could underlie functional differences and AI phenotype variations caused by this mutation site. CONCLUSIONS: This study expands the understanding of the effects of FAM83H mutations on tooth structure. CLINICAL RELEVANCE: Our study enhances our understanding of the genetic basis of AI and may contribute to improved diagnostics and personalized treatment strategies for patients with FAM83H-related AI.

The involvement of NLRP3 inflammasome in CUMS-induced AD-like pathological changes and related cognitive decline in mice.

BACKGROUND: Numerous studies have found that inhibiting the expression of NLRP3 inflammasome can significantly improve depressive-like behaviors in mice, but the research on its effect on cognitive decline in depression and its mechanism is still lacking. This study aimed to elucidate the role of NLRP3 inflammasome in cognitive decline in depression and explore the common neuro-immunological mechanisms of depression and Alzheimer's disease (AD). METHODS: Male C57BL/6 mice were subjected to chronic unpredictable mild stress (CUMS) for 5 weeks, treatment group was administered with the NLRP3 inhibitor MCC950 (10 mg/kg, i.p.), fluoxetine served as positive control. Then, the mice were assessed for cognitive behaviors and depression-like behaviors, and changes of microglia and neurons in hippocampus and levels of Aß metabolic pathway and tau protein were measured. To explore the mechanism of NLRP3 activation on neurons, we performed in vitro studies using BV2 microglia and mouse primary neurons. Furthermore, we focused on the role of NLRP3 inflammasome in the function of neurons and the expression of AD pathological indicators. RESULTS: CUMS induced depressive-like behaviors and cognitive decline in mice, which could be reversed by inhibiting NLRP3 inflammasome. MCC950, a specific NLRP3 inhibitor, alleviated CUMS-induced neuron injury and AD-like pathological changes, including the abnormal expression of Aß metabolic pathway and the hyper-phosphorylation of tau protein. LPS (1 µg/mL) + ATP (1 mM) treatment activated the expression of NLRP3 inflammasome and IL-1ß in vitro. In vitro experiment also proved that inhibiting the expression of NLRP3 inflammasome in microglia can restore the Aß metabolic pathway to normal, decrease neuronal tau protein phosphorylation and protect neurons. CONCLUSIONS: Inhibition of NLRP3 inflammasome effectively alleviated CUMS-induced depressive-like behaviors and cognitive decline in mice, and inhibited the activation of AD physiological indicators.

Novel Fluoride- and Chloride-containing Bioactive Glasses for Use in Air Abrasion.

OBJECTIVES: To investigate the degradation, fluorapatite formation, biological safety and cutting efficiency on dentine of the mixed fluoride- and chloride-containing bioactive glasses (BGs). METHODS: Two series of mixed fluoride- and chloride-containing glasses (GPFCl and GPF2.3Cl series) were synthesized using a melt-quench method. Glass transition temperature (Tg) and the bioactivity in term of glass degradation and fluorapatite formation were evaluated in Tris buffer solution. The cutting efficiency of the powdered BGs (GPF2.3Cl series) on dentine via air abrasion was investigated using white light profilometry and scanning electron microscope. The cytotoxicity of GPF2.3Cl series on human periodontal ligament stem cells (hPLSCs) and oral fibroblasts (OFB) were examined by MTT. RESULTS: These BGs are highly degradable and able to form fluorapatite within 3h of immersion. The formation of CaF2 was also found in the high fluoride-containing BGs. The faster glass degradation was evidenced in the BGs with higher chloride. A significant reduction of Tg from 790°C to 463°C was seen with increasing in calcium halide content. Air abrasion on dentine using the low and intermediate chloride-containing glasses demonstrates clear depressions, while no depression was found using the high chloride-containing glass. Moreover, the studied BGs showed no cytotoxicity to hPLSCs and OFB. CONCLUSIONS: The glasses with mixed fluoride and chloride integrate the benefits from the presence of both, showing rapid glass degradation, fast fluorapatite formation, excellent biocompatibility and controllable hardness to provide a selective cutting efficiency on dentine. CLINICAL SIGNIFICANCE: The developed BGs air abrasive with tunable hardness by varying chloride content can selectively cut different dental tissues. In clinic, a relatively hard BG is of great interest for caries preparation, while a soft glass is attractive for tooth cleaning.

Effects of Pelvic Floor Muscle Training Combined with Estriol on Pelvic Floor Dysfunction after Total Hysterectomy Applied in Perimenopause.

Objective: Total hysterectomy (TH) is becoming more and more common in clinical practice, and many patients suffer from postoperative complications such as pelvic floor dysfunction (PFD). How to prevent and treat PFD is an important part of the current clinical work, and it is important to improve patients' postoperative quality of life. This study was to investigate the effect of pelvic floor muscle training (PFMT) combined with estriol on PFD after TH in perimenopause. Methods: Totally, 95 patients who developed PFD receiving TH in our hospital between January 2020 and June 2021 were selected. They were randomly divided into a PFMT+ET (estriol therapy) group (n = 49) and CT group (conventional treatment, n = 46). After treatment, the two groups were compared in terms of pelvic floor muscle tension (systolic pressure and resting pressure of the vagina), female sexual function index (pain, satisfaction, orgasm, sexual arousal, sexual desire, and lubrication), and the degree of PFD (persistent time of vaginal muscle contraction, 1-hour pad test, residual urine volume, and frequency of urinary incontinence). Results: After 4 months of treatment, vaginal systolic pressure and resting pressure were significantly increased in both groups, with higher levels in the PFMT+ET group. Also, the improvement in female sexual function index score and persistent time of vaginal muscle contraction was observed to be greater in the PFMT+ET group than in the CT group. Additionally, PFMT combined with estriol resulted in lower levels of urinary leakage in the 1-hour pad test, residual urine volume, and frequency of urinary incontinence. Conclusions: The postoperative intervention of PFMT combined with estriol in perimenopausal patients with TH can significantly improve vaginal muscle contraction, improve the quality of sexual life, and reduce the degree of PFD, which has a good application prospect.

Improving the Sensitivity of Nanofibrous Membrane-Based ELISA for On-Site Antibiotics Detection.

An ultrasensitive and portable colorimetric enzyme-linked immunosorbent assay (ELISA) sensor for antibiotics was fabricated by immobilizing antibodies inside the largely porous and highly hydrophilic nanofibrous membranes. Different from regular electrospun nanofibrous membranes where antibodies may frequently be blocked by the heterogeneous porous structure and sterically crowded loaded on the surface, the controlled microporous structure and increased hydrophilicity of nanofibrous membranes could improve the diffusion properties of antibodies, reduce the sterically crowding effect, and dramatically improve the sensitivity of the membrane-based ELISA. The limitation of detection (LOD) for chloramphenicol (CAP) reached 0.005 ng/mL, around 200 times lower than the conventional paper-based ELISA, making quantitative analysis and portable on-site detection achievable via the use of smartphones. The successful design and fabrication of the nanofibrous membrane-based ELISA with novel features overcome the structural drawbacks of regular electrospun nanofibrous membranes and provide new paths to develop highly sensitive on-site detection of hazardous chemical agents.

Production of Organizational Chiral Structures by Design.

Organizational chirality on surfaces has been of interest in chemistry and materials science due to its scientific importance as well as its potential applications. Current methods for producing organizational chiral structures on surfaces are primarily based upon the self-assembly of molecules. While powerful, the chiral structures are restricted to those dictated by surface reaction thermodynamics. This work introduces a method to create organizational chirality by design with nanometer precision. Using atomic force microscopy-based nanolithography, in conjunction with chosen surface chemistry, various chiral structures are produced with nanometer precision, from simple spirals and arrays of nanofeatures to complex and hierarchical chiral structures. The size, geometry, and organizational chirality is achieved in deterministic fashion, with high fidelity to the designs. The concept and methodology reported here provide researchers a new and generic means to carry out organizational chiral chemistry, with the intrinsic advantages of chiral structures by design. The results open new and promising applications including enantioselective catalysis, separation, and crystallization, as well as optical devices requiring specific polarized radiation and fabrication and recognition of chiral nanomaterials.

Single-Crystalline Germanium Nanocrystals via a Two-Step Microwave-Assisted Colloidal Synthesis from GeI4.

Colloidal germanium (Ge) nanocrystals (NCs) are of great interest with possible applications for photovoltaics and near-IR detectors. In many examples of colloidal reactions, Ge(II) precursors are employed, and NCs of diameter ∼3-10 nm have been prepared. Herein, we employed a two-step microwave-assisted reduction of GeI4 in oleylamine (OAm) to prepare monodispersed Ge NCs with a size of 18.9 ± 1.84 nm. More importantly, the as-synthesized Ge NCs showed high crystallinity with single-crystal nature as indicated by powder X-ray diffraction, selected area electron diffraction, and high-resolution transmission electron microscopy. The Tauc plot derived from photothermal deflection spectroscopy measurement on Ge NCs thin films shows a decreased bandgap of the Ge NCs obtained from GeI4 compared with that of the Ge NCs from GeI2 with a similar particle size, indicating a higher crystallinity of the samples prepared with the two-step reaction from GeI4. The calculated Urbach energy indicates less disorder in the larger NCs. This disorder might correlate with the fraction of surface states associated with decreased particle size or with the increased molar ratio of ligands to germanium. Solutions involved in this two-step reaction were investigated with 1H NMR spectroscopy and high-resolution mass spectrometry (MS). One possible reaction pathway is proposed to unveil the details of the reaction involving GeI4 and OAm. Overall, this two-step synthesis produces high-quality Ge NCs and provides new insight on nanoparticle synthesis of covalently bonding semiconductors.

Nanoscale Raman Characterization of a 2D Semiconductor Lateral Heterostructure Interface.

The nature of the interface in lateral heterostructures of 2D monolayer semiconductors including its composition, size, and heterogeneity critically impacts the functionalities it engenders on the 2D system for next-generation optoelectronics. Here, we use tip-enhanced Raman scattering (TERS) to characterize the interface in a single-layer MoS2/WS2 lateral heterostructure with a spatial resolution of 50 nm. Resonant and nonresonant TERS spectroscopies reveal that the interface is alloyed with a size that varies over an order of magnitude─from 50 to 600 nm─within a single crystallite. Nanoscale imaging of the continuous interfacial evolution of the resonant and nonresonant Raman spectra enables the deconvolution of defect activation, resonant enhancement, and material composition for several vibrational modes in single-layer MoS2, MoxW1-xS2, and WS2. The results demonstrate the capabilities of nanoscale TERS spectroscopy to elucidate macroscopic structure-property relationships in 2D materials and to characterize lateral interfaces of 2D systems on length scales that are imperative for devices.

High phosphate content in bioactive glasses promotes osteogenesis in vitro and in vivo.

OBJECTIVES: High phosphate content was found to significantly increase apatite formation of bioactive glasses (BGs) in vitro. However, there is very limited understanding of the effect of phosphate contents on osteogenesis which is important for clinical applications. The aims of this study were to investigate how phosphate content influences apatite formation ability of bioactive glasses in α-MEM culture medium and whether high phosphate content in bioactive glasses promotes osteogenesis in vitro and in vivo. METHODS: Four phosphate containing bioactive glasses were synthesized via a melt-quench method and characterized using X-ray powder Diffraction (XRD), TGA-DSC and Fourier transform infra-red spectroscopy (FTIR). The apatite formation ability in α-MEM culture medium and the in vitro and in vivo osteogenic potential of these bioactive glass were explored. RESULTS: FTIR spectra confirmed faster apatite formation with an increase in phosphate content. The culture media containing ions released from the BGs showed enhanced cell viability and alkaline phosphatase activity of osteoblasts. Osteoblasts cultured with extracted BGs culture media generally showed increased proliferation, mineralized nodule formation, osteogenic and angiogenic genes expression with an increase in phosphate content in the glass compositions. An in vivo study demonstrated a larger amount of new bone formation in the calvarial defects implanted with high phosphate containing BG granules compared with that of BG without the presence of phosphate at 8 weeks post-surgery. SIGNIFICANT: The presence of higher phosphate content accelerates apatite formation and promotes osteogenesis, indicating that both apatite formation and osteogenesis of bioactive glasses can be tailored by varying phosphate content for specific clinical needs and personalized treatments.

Evaluation of Hand Tendon Movement by Using High-Frequency Ultrasound Vector Doppler Imaging.

OBJECTIVE: Injuries to the hands, wrists, and fingers often involve damage to the tendons. The ability to measure tendon movements during the rehabilitation process can provide clinicians with important information in the quantification of tendon injuries. Conventionally, the tendon is considered a single spring-like structure during force transmission, and its twisted structure is neglected. Recently, clinicians believed that the twisted fiber structure (which enables tendon rotation during movement) of the tendon can provide it with a degree of elasticity and improve the efficiency of force transmission. However, observation of the hand tendon rotation in vivo by using the current imaging modalities is difficult. METHODS: In this study, a 40-MHz high-frequency vector Doppler imaging (HFVDI) was used to visualize the movement of the hand tendon during muscle contraction. The performance of HFVDI was verified using a rotation phantom experiment. Two human experiments were designed in the present study: 1) participants were allowed to bend their distal and proximal interphalangeal (DIP and PIP) joints of fingers freely and 2) the PIP joint of the finger was fixed such that only the DIP could be moved. The HFVDIs of the flexor digitorum superficialis (FDS) and flexor digitorum profundus (FDP) tendons were obtained in the transverse and longitudinal views to observe the movements of the hand tendon during finger movements. RESULTS: The average longitudinal displacements of the FDS and FDP were approximately 3-4 mm for free bending of the finger; however, it was reduced when only the DIP was moved. The rotational phenomenon of the FDS and FDP tendons was observed in the transverse view, which demonstrated the different rotational behaviors of the FDS and FDP fibers during muscle contraction. CONCLUSION: All the results validated the potential of HFVDI as a novel tool for visualizing tendon rotation and would be useful in providing quantitative information regarding tendon function to determine the rehabilitation process following injuries.