Association between vitamin D levels and risk of periodontitis in patients with metabolic syndrome.

Background/purpose: The relationship between Vitamin D (VD) and periodontitis in patients with metabolic syndrome (MetS) was unclear. This study was to investigate the relationship between VD and periodontitis in MetS patients. Materials and methods: This cross-sectional study collected the data of 2165 MetS patients from the National Health and Nutrition Examination Survey (NHANES). The weighted univariate and multivariable Logistic regression models were applied to identify covariates and evaluate the association between 25-hydroxy vitamin D (25(OH)D) [25(OH)D]2 + 25(OH)D3 and periodontitis in patients. Odds ratio (OR) [95% confidence interval (CI)] was effect size. Subgroup analysis was performed in people with or without diabetes, dyslipidemia, hypertension, cardiovascular disease (CVD) and central obesity groups. Results: In the unadjusted model, compared with patients with 25(OH)D2 + 25(OH)D3 < 50 nmol/L, those with 25(OH)D2 + 25(OH)D3 ≥ 50 nmol/L might be associated with decreased risk of periodontitis in MetS patients (OR = 0.70, 95% CI: 0.57-0.85). After adjusting for confounders including age, gender, race, education, poverty income ratio (PIR), smoking, diabetes, VD intake and supplement and number of missing teeth, 25(OH)D2 + 25(OH)D3 ≥ 50 nmol/L was correlated with reduced risk of periodontitis in MetS patients (OR = 0.76, 95% CI: 0.60-0.97). Subgroup analysis revealed that in patients with CVD (OR = 0.60, 95% CI: 0.37-0.98), dyslipidemia (OR = 0.75, 95% CI: 0.57-0.97), and patients with central obesity (OR = 0.73, 95% CI: 0.57-0.95), decreased risk of periodontitis was identified in 25(OH)D2 + 25(OH)D3 ≥ 50 nmol/L. Conclusion: VD was associated with the risk of periodontitis in patients with MetS, which suggest the importance of VD supplement in patients with MetS and provide a reference for the management of periodontitis in patients with MetS.

Enhanced Electrochemical Catalysis: Hydrogen Evolution Using Bimetallic Sulfides on Nickel Foam.

Hydrogen is considered clean energy with broad application prospects for the 21st century, and water electrolysis plays a crucial role in hydrogen production. However, economic limitations and large overpotential values hinder its development. In this study, we deposited nickel (Ni), iron (Fe), and sulfur (S) onto nickel foam (NF) using the constant potential method to form the Ni-S-Fe/NF catalyst, which exhibited an exceptionally low overpotential (31 mV) at a current density of -10 mA cm-2, and a Tafel slope of 75.1 mV dec-1 in 1 M sodium hydroxide. It showed a minor charge resistance (1.256 Ω). The amorphous phase structure and optimized catalyst composition promoted outstanding hydrogen evolution activity. This work offers valuable perspectives on the industrial application of hydrogen production.

Gate Voltage- and Bias Voltage-Tunable Staggered-Gap to Broken-Gap Transition Based on WSe2/Ta2NiSe5 Heterostructure for Multimode Optoelectronic Logic Gate.

Two-dimensional (2D) materials with superior properties exhibit tremendous potential in developing next-generation electronic and optoelectronic devices. Integrating various functions into one device is highly expected as that endows 2D materials great promise for more Moore and more-than-Moore device applications. Here, we construct a WSe2/Ta2NiSe5 heterostructure by stacking the p-type WSe2 and the n-type narrow gap Ta2NiSe5 with the aim to achieve a multifunction optoelectronic device. Owing to the large interface potential barrier, the heterostructure device reveals a prominent diode feature with a large rectify ratio (7.6 × 104) and a low dark current (10-12 A). Especially, gate voltage- and bias voltage-tunable staggered-gap to broken-gap transition is achieved on the heterostructure device, which enables gate voltage-tunable forward and reverse rectifying features. As results, the heterostructure device exhibits superior self-powered photodetection properties, including a high detectivity of 1.08 × 1010 Jones and a fast response time of 91 µs. Additionally, the intrinsic structural anisotropy of Ta2NiSe5 endows the heterostructure device with strong polarization-sensitive photodetection and high-resolution polarization imaging. Based on these characteristics, a multimode optoelectronic logic gate is realized on the heterostructure via synergistically modulating the light on/off, polarization angle, gate voltage, and bias voltage. This work shed light on the future development of constructing high-performance multifunctional optoelectronic devices.

Structure-guided engineered urethanase from Candida parapsilosis with pH and ethanol tolerance to efficiently degrade ethyl carbamate in Chinese rice wine.

Urethane hydrolase can degrade the carcinogen ethyl carbamate (EC) in fermented food, but its stability and activity limit its application. In this study, a mutant G246A and a double mutant N194V/G246A with improved cpUH activity and stability of Candida parapsilosis were obtained by site-directed mutagenesis. The catalytic efficiency (Kcat/Km) of mutant G246A and double mutant N194V/G246A are 1.95 times and 1.88 times higher than that of WT, respectively. In addition, compared with WT, the thermal stability and pH stability of mutant G246A and double mutant N194V/G246A were enhanced. The ability of mutant G246A and double mutant N194V/G246A to degrade EC in rice wine was also stronger than that of WT. The mutation increased the stability of the enzyme, as evidenced by decreased root mean square deviation (RMSD) and increased hydrogen bonds between the enzyme and substrate by molecular dynamics simulation and molecular docking analysis. The molecule modification of new cpUH promotes the industrial process of EC degradation.

Macrophage membrane-camouflaged pH-sensitive nanoparticles for targeted therapy of oral squamous cell carcinoma.

BACKGROUND: Oral cancer is the most common malignant tumor of the head and neck, and 90% of cases are oral squamous cell carcinoma (OSCC). Chemotherapy is an important component of comprehensive treatment for OSCC. However, the clinical treatment effect of chemotherapy drugs, such as doxorubicin (DOX), is limited due to the lack of tumor targeting and rapid clearance by the immune system. Thus, based on the tumor-targeting and immune evasion abilities of macrophages, macrophage membrane-encapsulated poly(methyl vinyl ether alt maleic anhydride)-phenylboronic acid-doxorubicin nanoparticles (MM@PMVEMA-PBA-DOX NPs), briefly as MM@DOX NPs, were designed to target OSCC. The boronate ester bonds between PBA and DOX responded to the low pH value in the tumor microenvironment, selectively releasing the loaded DOX. RESULTS: The results showed that MM@DOX NPs exhibited uniform particle size and typical core-shell structure. As the pH decreased from 7.4 to 5.5, drug release increased from 14 to 21%. The in vitro targeting ability, immune evasion ability, and cytotoxicity of MM@DOX NPs were verified in HN6 and SCC15 cell lines. Compared to free DOX, flow cytometry and fluorescence images demonstrated higher uptake of MM@DOX NPs by tumor cells and lower uptake by macrophages. Cell toxicity and live/dead staining experiments showed that MM@DOX NPs exhibited stronger in vitro antitumor effects than free DOX. The targeting and therapeutic effects were further confirmed in vivo. Based on in vivo biodistribution of the nanoparticles, the accumulation of MM@DOX NPs at the tumor site was increased. The pharmacokinetic results demonstrated a longer half-life of 9.26 h for MM@DOX NPs compared to 1.94 h for free DOX. Moreover, MM@DOX NPs exhibited stronger tumor suppression effects in HN6 tumor-bearing mice and good biocompatibility. CONCLUSIONS: Therefore, MM@DOX NPs is a safe and efficient therapeutic platform for OSCC.

Dual rare genetic diseases in five pediatric patients: insights from next-generation diagnostic methods.

BACKGROUND: Clinicians traditionally aim to identify a singular explanation for the clinical presentation of a patient; however, in some cases, the diagnosis may remain elusive or fail to comprehensively explain the clinical findings. In recent years, advancements in next-generation sequencing, including whole-exome sequencing, have led to the incidental identification of dual diagnoses in patients. Herein we present the cases of five pediatric patients diagnosed with dual rare genetic diseases. Their natural history and diagnostic process were explored, and lessons learned from utilizing next-generation diagnostic technologies have been reported. RESULTS: Five pediatric cases (3 boys, 2 girls) with dual diagnoses were reported. The age at diagnosis was from 3 months to 10 years. The main clinical presentations were psychomotor retardation and increased muscular tension, some accompanied with liver dysfunction, abnormal appearance, precocious puberty, dorsiflexion restriction and varus of both feet, etc. After whole-exome sequencing, nine diseases were confirmed in these patients: Angelman syndrome and Krabbe disease in case 1, Citrin deficiency and Kabuki syndrome in case 2, Homocysteinemia type 2 and Copy number variant in case 3, Isolated methylmalonic acidemia and Niemann-Pick disease type B in case 4, Isolated methylmalonic acidemia and 21-hydroxylase deficiency in case 5. Fifteen gene mutations and 2 CNVs were identified. Four novel mutations were observed, including c.15292de1A in KMT2D, c.159_164inv and c.1427G > A in SLC25A13, and c.591 C > G in MTHFR. CONCLUSIONS: Our findings underscore the importance of clinicians being vigilant about the significance of historical and physical examination. Comprehensive clinical experience is crucial for identifying atypical clinical features, particularly in cases involving dual rare genetic diseases.

Photodynamic therapy for recalcitrant plantar warts: Case reports and a literature review.

Plantar wart is one of the most recalcitrant types of cutaneous warts with a high recurrence rate. Recalcitrant plantar warts are resistant to traditional treatments such as cryotherapy. Photodynamic therapy (PDT) is a modern, non-invasive method utilized to treat benign and malignant skin disorders. Several previous studies have reported the effective application of PDT treatment for plantar warts. We reported three cases of recalcitrant plantar warts successfully treated with PDT.

[Effects of maltodextrin on water adsorption and thermodynamic properties of Codonopsis Radix spray-dried powder].

This study aims to reveal the effects of maltodextrin(MD) on the water adsorption and thermodynamic properties of Codonopsis Radix(DS) spray-dried powder by determining the moisture and energy changes of the powder in the process of moisture absorption. The static weighing method was used to obtain the isothermal water adsorption data of the spray-dried powder in 6 saturated salt solutions(KAc, MgCl_2·6H_2O, K_2CO_3, NaBr, NaCl, and KCl) at 3 temperatures(25, 35, and 45 ℃). Six models were used for fitting of the water adsorption process, and the most suitable model was selected based on the model performance. Furthermore, the corresponding net equivalent adsorption heat and differential entropy were calculated, and the adsorption entropy change was integrated. The linear relationship between net equivalent adsorption heat and differential entropy was drawn based on the entropy-enthalpy complementarity theory. The results showed that the water adsorption properties of DS and DS-MD spray-dried powder followed the type Ⅲ isotherm and was well fitted by the GAB model. The monolayer water content M_0 decreased with the increase in temperature. At the same temperature, the M_0 of DS spray-dried powder decreased after the addition of MD. The net equivalent adsorption heat and differential entropy of DS and DS-MD spray-dried powder decreased with the increase in water content, which presented a linear relationship. The addition of MD decreased the water activity corresponding to the lowest integral adsorption entropy of the powder, and the system became more stable. The results indicated that the spray-dried powder became more stable after the addition of MD.

Facile construction of sandwich ELISA based on double-nanobody for specific detection of α-hemolysin in food samples.

α-hemolysin (Hla), a toxin secreted by Staphylococcus aureus (S. aureus), has been proved to be involved in the occurrence and aggravation of food poisoning. Hence, it is quite essential to establish its rapid detection methods to guarantee food safety. Sandwich ELISA based on nanobody is well known to be viable for toxins, but there is absence of nanobody against Hla, let alone a pair for it. Therefore, in this paper, we screened specific nanobodies by bio-panning and obtained the optimal nanobody pair for sandwich ELISA firstly. Then, RANbody, a novel nanobody owning both recognition and catalytic capability, is generated in a single step and at low cost through molecular recombination technology. Subsequently, sandwich ELISA was developed to detect Hla based on the nanobody and RANbody, that not only eliminated the use of secondary antibodies and animal-derived antibody, but also reduced detection time and cost, compared with traditional sandwich ELISA. Lastly, the performance has been evaluated, especially for specificity which showed no response to other hemolysins and a low limit of detection of 10 ng/mL. Besides, the proposed sandwich ELISA exhibits favorable feasibility and was successfully employed for the detection of Hla in milk and pork samples.

The causal relationship between gut microbiota and biliary tract cancer: comprehensive bidirectional Mendelian randomization analysis.

Background: Growing evidence has shown that gut microbiome composition is associated with Biliary tract cancer (BTC), but the causality remains unknown. This study aimed to explore the causal relationship between gut microbiota and BTC, conduct an appraisal of the gut microbiome's utility in facilitating the early diagnosis of BTC. Methods: We acquired the summary data for Genome-wide Association Studies (GWAS) pertaining to BTC (418 cases and 159,201 controls) from the Biobank Japan (BBJ) database. Additionally, the GWAS summary data relevant to gut microbiota (N = 18,340) were sourced from the MiBioGen consortium. The primary methodology employed for the analysis consisted of Inverse Variance Weighting (IVW). Evaluations for sensitivity were carried out through the utilization of multiple statistical techniques, encompassing Cochrane's Q test, the MR-Egger intercept evaluation, the global test of MR-PRESSO, and a leave-one-out methodological analysis. Ultimately, a reverse Mendelian Randomization analysis was conducted to assess the potential for reciprocal causality. Results: The outcomes derived from IVW substantiated that the presence of Family Streptococcaceae (OR = 0.44, P = 0.034), Family Veillonellaceae (OR = 0.46, P = 0.018), and Genus Dorea (OR = 0.29, P = 0.041) exerted a protective influence against BTC. Conversely, Class Lentisphaeria (OR = 2.21, P = 0.017), Genus Lachnospiraceae FCS020 Group (OR = 2.30, P = 0.013), and Order Victivallales (OR = 2.21, P = 0.017) were associated with an adverse impact. To assess any reverse causal effect, we used BTC as the exposure and the gut microbiota as the outcome, and this analysis revealed associations between BTC and five different types of gut microbiota. The sensitivity analysis disclosed an absence of empirical indicators for either heterogeneity or pleiotropy. Conclusion: This investigation represents the inaugural identification of indicative data supporting either beneficial or detrimental causal relationships between gut microbiota and the risk of BTC, as determined through the utilization of MR methodologies. These outcomes could hold significance for the formulation of individualized therapeutic strategies aimed at BTC prevention and survival enhancement.

Targeted inhibition of autophagy in hepatic stellate cells by hydroxychloroquine: An effective therapeutic approach for the treatment of liver fibrosis.

BACKGROUND AND PURPOSE: Liver fibrosis is a wound-healing reaction which is the main cause of chronic liver diseases worldwide. The activated hepatic stellate cell (aHSC) is the main driving factor in the development of liver fibrosis. Inhibiting autophagy of aHSC can prevent the progression of liver fibrosis, but inhibiting autophagy of other liver cells has opposite effects. Hence, targeted inhibition of autophagy in aHSC is quite necessary for the treatment of liver fibrosis, which prompts us to explore the targeted delivery system of small molecule autophagy inhibitor hydroxychloroquine (HCQ) that can target aHSC and alleviate the liver fibrosis. METHODS: The delivery system of HCQ@retinol-liposome nanoparticles (HCQ@ROL-LNPs) targeting aHSC was constructed by the film dispersion and pH-gradient method. TGF-ß-induced HSC activation and thioacetamide (TAA)-induced liver fibrosis mice model were established, and the targeting ability and therapeutic effect of HCQ@ROL-LNPs in liver fibrosis were studied subsequently in vitro and in vivo. RESULTS: HCQ@ROL-LNPs have good homogeneity and stability. They inhibited the autophagy of aHSC selectively by HCQ and reduced the deposition of extracellular matrix (ECM) and the damage to other liver cells. Compared with the free HCQ and HCQ@LNPs, HCQ@ROL-LNPs had good targeting ability, showing enhanced therapeutic effect and low toxicity to other organs. CONCLUSION: Construction of HCQ@ROL-LNPs delivery system lays a theoretical and experimental foundation for the treatment of liver fibrosis and promotes the development of clinical therapeutic drugs for liver diseases.

Surgical management of lower limb radiculopathy following acute singe-level osteoporotic vertebral fracture of lower lumbar spine in geriatric patient: a retrospective study.

BACKGROUND: Radiculopathy of the lower limb after acute osteoporotic vertebral fractures (OVFs) in the lower lumbar spine is uncommon in geriatric patients. Moreover, surgical intervention is generally recommended in patients who are irresponsive to conservative treatment. Determining an optimum surgical strategy is challenging considering the poor general condition of this population. Thus, herein, we established an algorithm for surgically managing this clinical scenario, hoping to provide a reference for making a surgical decision. METHODS: We retrospectively studied patients who suffered from new-onset radiculopathy of the lower limb after acute single-level OVFs in the lower lumbar spine and eventually underwent surgical intervention at our department. Information on the demographics, bone quality, AO spine classification of the vertebral fracture, pre-existing degenerative changes, including foraminal stenosis and lumbar disc herniation, and surgical intervention type was collected. Additionally, clinical outcomes, including preoperative and postoperative visual analog scale (VAS) scores for back and leg pain, Oswestry disability index (ODI), and MacNab criterion for response to surgery, were evaluated. RESULTS: From September 2019 to December 2021, a total of 22 patients with a mean age of 68.59 ± 9.74 years were analyzed. The most involved vertebra was L5 (54.5%), followed by L4 (27.3%) and L3 (18.2%). Among the 22 patients, 15 (68.2%) were diagnosed with the A1 type fracture of AO classification, and among them, 11 (73.3%) were characterized by the collapse of the inferior end plate (IEP). Three patients (13.6%) suffered from A2-type fractures, whereas four patients (18.2%) suffered from A3-type fractures. Pre-existing degenerative changes were observed in 12 patients (54.5%) of the patients. A total of 16 patients (72.7%) were treated by percutaneous kyphoplasty (PKP). Additionally, three patients underwent posterior instrumentation and fusion, two patients underwent a secondary endoscopic foraminoplasty, and one patient underwent a secondary radiofrequency ablation. The mean follow-up period was 17.42 ± 9.62 months. The mean VAS scores for leg and back pain and ODI decreased significantly after the surgery (P < 0.05). The total satisfaction rate at the last follow-up was 90.9% per the Macnab criterion. CONCLUSION: Patients with OVFs in the IEP are predisposed to suffer from radiculopathy of the lower limb. PKP alone or in combination with other minimally invasive surgical strategies is safe and effective in treating stable fractures. Additionally, aggressive surgical intervention should be considered in patients with unstable fractures or severe foraminal encroachment.

MiRNA-21-5p induces chicken hepatic lipogenesis by targeting NFIB and KLF3 to suppress the PI3K/AKT signaling pathway.

The liver plays a critical role in metabolic activity and is the body's first immune barrier, and maintaining liver health is particularly important for poultry production. MicroRNAs (miRNAs) are involved in a wide range of biological activities due to their capacity as posttranscriptional regulatory elements. A growing body of research indicates that miR-21-5p plays a vital role as a modulator of liver metabolism in various species. However, the effect of miR-21-5p on the chicken liver is unclear. In the current study, we discovered that the fatty liver had high levels of miR-21-5p. Then the qPCR, Western blot, flow cytometry, enzyme-linked immunosorbent assay, dual-luciferase, and immunofluorescence assays were, respectively, used to determine the impact of miR-21-5p in the chicken liver, and it turned out that miR-21-5p enhanced lipogenesis, oxidative stress, and inflammatory responses, which ultimately induced hepatocyte apoptosis. Mechanically, we verified that miR-21-5p can directly target nuclear factor I B (NFIB) and kruppel-like factor 3 (KLF3). Furthermore, our experiments revealed that the suppression of NFIB promoted apoptosis and inflammation, and the KLF3 inhibitor accelerated lipogenesis and enhanced oxidative stress. Furthermore, the cotransfection results suggest that the PI3K/AKT pathway is also involved in the process of miRNA-21-5p-mediate liver metabolism regulation. In summary, our study demonstrated that miRNA-21-5p plays a role in hepatocyte lipogenesis, oxidative stress, inflammation, and apoptosis, via targeting NFIB and KLF3 to suppress the PI3K/AKT signal pathway in chicken.

miR-21-5p is a typical noncoding RNA that could inhibit messenger RNA expression by targeting the 3ʹ-untranslated region to participate in fatty liver-related disease formation and progression. We demonstrated that miRNA-21-5p plays a role in hepatocyte lipogenesis, oxidative stress, inflammation, and apoptosis, via targeting nuclear factor I B and kruppel-like factor 3 to suppress the PI3K/AKT signal pathway in chicken. This research established the regulatory network mechanisms of miR-21-5p in chicken hepatic lipogenesis and fatty liver syndrome.

Topological disruption of low- and high-order functional networks in presbycusis.

Prior efforts have manifested that functional connectivity (FC) network disruptions are concerned with cognitive disorder in presbycusis. The present research was designed to investigate the topological reorganization and classification performance of low-order functional connectivity (LOFC) and high-order functional connectivity (HOFC) networks in patients with presbycusis. Resting-state functional magnetic resonance imaging (Rs-fMRI) data were obtained in 60 patients with presbycusis and 50 matched healthy control subjects (HCs). LOFC and HOFC networks were then constructed, and the topological metrics obtained from the constructed networks were compared to evaluate topological differences in global, nodal network metrics, modularity and rich-club organization between patients with presbycusis and HCs. The use of HOFC profiles boosted presbycusis classification accuracy, sensitivity and specificity compared to that using LOFC profiles. The brain networks in both patients with presbycusis and HCs exhibited small-world properties within the given threshold range, and striking differences between groups in topological metrics were discovered in the constructed networks (LOFC and HOFC). NBS analysis identified a subnetwork involving 26 nodes and 23 signally altered internodal connections in patients with presbycusis in comparison to HCs in HOFC networks. This study highlighted the topological differences between LOFC and HOFC networks in patients with presbycusis, suggesting that HOFC profiles may help to further identify brain network abnormalities in presbycusis.

Exploring the mechanism of Tingli Pill in the treatment of HFpEF based on network pharmacology and molecular docking.

To explore the mechanism of action of Tingli Pill (TLP) in the treatment of heart failure with preserved ejection fraction (HFpEF) by using network pharmacology and molecular docking technology. The active components and targets of TLP were screened using the TCMSP and UniProt databases. HFpEF-related targets were identified using the OMIM and GeneCards databases. Drug-disease intersection targets were obtained via Venny 2.1.0, as well as establishing the "component-target" network and screening out the core active components. Construct a protein-protein interaction network of intersecting targets using the STRING database as well as Cytoscape software and filter the core targets. Gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis of core targets were performed using the Metascape database. The core active components of TLP for HFpEF were quercetin, kaempferol, ß-sitosterol, isorhamnetin and hederagenin. The core targets of TLP for HFpEF were JUN, MAPK1, TP53, AKT1, RELA, TNF, MAPK14, and IL16. Gene ontology enrichment analysis obtained 1528 biological processes, 85 cell components, and 140 molecular functions. The Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis yielded 1940 signaling pathways, mainly involved in lipid and atherosclerosis, regulation of apoptotic signaling pathway, PI3K-Akt signaling pathway, HIF-1 signaling pathway, oxidative stress, TNF signaling pathway, and IL-17 signaling pathway. TLP has the characteristics of multi-component, multi-target, and multi-pathway in the treatment of HFpEF. This study lays the foundation for revealing the pharmacodynamic substances and mechanism of TLP in the treatment of HFpEF.

Mitochondrial Targeted Thermosensitive Nanocarrier for Near-Infrared-Triggered Precise Synergetic Photothermal Nitric Oxide Chemotherapy.

Nitric oxide (NO) intervenes, that is, a potential treatment strategy, and has attracted wide attention in the field of tumor therapy. However, the therapeutic effect of NO is still poor, due to its short half-life and instability. Therapeutic concentration ranges of NO should be delivered to the target tissue sites, cell, and even subcellular organelles and to control NO generation. Mitochondria have been considered a major target in cancer therapy for their essential roles in cancer cell metabolism and apoptosis. In this study, mesoporous silicon-coated gold nanorods encapsulated with a mitochondria targeted and the thermosensitive lipid layer (AuNR@MSN-lipid-DOX) served as the carrier to load NO prodrug (BNN6) to build the near-infrared-triggered synergetic photothermal NO-chemotherapy platform (AuNR@MSN(BNN6)-lipid-DOX). The core of AuNR@MSN exhibited excellent photothermal conversion capability and high loading efficiency in terms of BNN6, reaching a high value of 220 mg/g (w/w), which achieved near-infrared-triggered precise release of NO. The outer biocompatible lipid layer, comprising thermosensitive phospholipid DPPC and mitochondrial-targeted DSPE-PEG2000-DOX, guided the whole nanoparticle to the mitochondria of 4T1 cells observed through confocal microscopy. In the mitochondria, the nanoparticles increased the local temperature over 42 °C under NIR irradiation, and a high NO concentration from BNN6 detected by the NO probe and DSPE-PEG2000-DOX significantly inhibited 4T1 cancer cells in vitro and in vivo under the synergetic photothermal therapy (PTT)-NO therapy-chemotherapy modes. The built NIR-triggered combination therapy nanoplatform can serve as a strategy for multimodal collaboration.

The application of phenylboronic acid pinacol ester functionalized ROS-responsive multifunctional nanoparticles in the treatment of Periodontitis.

Periodontitis is an inflammatory disease induced by the complex interactions between the host immune system and the microbiota of dental plaque. Oxidative stress and the inflammatory microenvironment resulting from periodontitis are among the primary factors contributing to the progression of the disease. Additionally, the presence of dental plaque microbiota plays a significant role in affecting the condition. Consequently, treatment strategies for periodontitis should be multi-faceted. In this study, a reactive oxygen species (ROS)-responsive drug delivery system was developed by structurally modifying hyaluronic acid (HA) with phenylboronic acid pinacol ester (PBAP). Curcumin (CUR) was encapsulated in this drug delivery system to form curcumin-loaded nanoparticles (HA@CUR NPs). The release results indicate that CUR can be rapidly released in a ROS environment to reach the concentration required for treatment. In terms of uptake, HA can effectively enhance cellular uptake of NPs because it specifically recognizes CD44 expressed by normal cells. Moreover, HA@CUR NPs not only retained the antimicrobial efficacy of CUR, but also exhibited more pronounced anti-inflammatory and anti-oxidative stress functions both in vivo and in vitro. This provides a good potential drug delivery system for the treatment of periodontitis, and could offer valuable insights for dental therapeutics targeting periodontal diseases.

Transforaminal endoscopic lumbar discectomy with two-segment foraminoplasty for the treatment of very highly migrated lumbar disc herniation: a retrospective analysis.

BACKGROUND: The surgical resection of very highly migrated lumbar disc herniation (VHM-LDH) is technically challenging owing to the absence of technical guidelines. Hence, in the present study, we introduced the transforaminal endoscopic lumbar discectomy (TELD) with two-segment foraminoplasty to manage VHM-LDH and evaluated its radiographic and midterm clinical outcomes. MATERIALS AND METHODS: The present study is a retrospective analysis of 33 consecutive patients with VHM-LDH who underwent TELD with two-segment foraminoplasty. The foraminoplasty was performed on two adjacent vertebrae on the basis of the migration direction of disc fragments to fully expose the disc fragments and completely decompress the impinged nerve root. The operation duration, blood loss, intra- and postoperative complications, and recurrences were recorded. Additionally, imageological observations were evaluated immediately after the procedure via magnetic resonance image and computerized tomography. Clinical outcomes were evaluated by calculating the visual analog scale (VAS) score and Oswestry Disability Index (ODI). The MacNab criterion was reviewed to assess the patients' opinions on treatment satisfaction. The resection rate of bony structures were quantitatively evaluated on postoperative image. The segmental stability was radiologically evaluated at least a year after the surgery. Additionally, surgery-related and postoperative complications were evaluated. RESULTS: The average age of the patients was 56.87 ± 7.77 years, with a mean follow-up of 20.95 ± 2.09 months. The pain was relieved in all patients immediately after the surgery. The VAS score and ODI decreased significantly at each postoperative follow-up compared with those observed before the surgery (P < 0.05). The mean operation duration, blood loss, and hospital stay were 56.17 ± 16.21 min, 10.57 ± 6.92 mL, and 3.12 ± 1.23 days, respectively. No residual disc fragments, iatrogenic pedicle fractures, and segmental instability were observed in the postoperative images. For both up- and down- migrated herniation in the upper lumbar region, the upper limit value of resection percentage for the cranial SAP, caudal SAP, and pedicle was 33%, 30%, and 34%, respectively; while those in the lower lumbar region was 42%, 36%, and 46%, respectively. At the last follow-up, the satisfaction rate of the patients regarding the surgery was 97%. Surgery-related complications including dural tear, nerve root injury, epidural hematoma, iatrogenic pedicle fractures, and segmental instability were not observed. One patient (3%) suffered from the recurrence of LDH 10 months after the initial surgery and underwent revision surgery. CONCLUSIONS: The TELD with two-segment foraminoplasty is safe and effective for VHM-LDH management. Proper patient selection and efficient endoscopic skills are required for applying this technique to obtain satisfactory outcomes.

Genetically determined type 1 diabetes mellitus and risk of osteoporosis.

BACKGROUND: Observational evidence suggests that type 1 diabetes mellitus (T1DM) is associated with the risk of osteoporosis (OP). Nevertheless, it is not apparent whether these correlations indicate a causal relationship. To elucidate the causal relationship, a two-sample Mendelian randomization (MR) analysis was performed. METHODS: T1DM data was obtained from the large genome-wide association study (GWAS), in which 6683 cases and 12,173 controls from 12 European cohorts were involved. Bone mineral density (BMD) samples at four sites were extracted from the GEnetic Factors for OSteoporosis (GEFOS) consortium, including forearm (FA) (n = 8143), femoral neck (FN) (n = 32,735), lumbar spine (LS) (n = 28,498), and heel (eBMD) (n = 426,824). The former three samples were from mixed populations and the last one was from European. Inverse variance weighting, MR-Egger, and weighted median tests were used to test the causal relationship between T1DM and OP. A series of sensitivity analyses were then conducted to verify the robustness of the results. RESULTS: Twenty-three independent SNPs were associated with FN-BMD and LS-BMD, twenty-seven were associated with FA-BMD, and thirty-one were associated with eBMD. Inverse variance-weighted estimates indicated a causal effect of T1DM on FN-BMD (odds ratio (OR) =1.033, 95 % confidence interval (CI): 1.012-1.054, p = 0.002) and LS-BMD (OR = 1.032, 95 % CI: 1.005-1.060, p = 0.022) on OP risk. Other MR methods, including weighted median and MR-Egger, calculated consistent trends. While no significant causation was found between T1DM and the other sites (FA-BMD: OR = 1.008, 95 % CI: 0.975-1.043, p = 0.632; eBMD: OR = 0.993, 95 % CI: 0.985-1.001, p = 0.106). No significant heterogeneity (except for eBMD) or horizontal pleiotropy was found for instrumental variables, suggesting these results were reliable and robust. CONCLUSIONS: This study shows a causal relationship between T1DM and the risk of some sites of OP (FN-BMD, LS-BMD), allowing for continued research to discover the clinical and experimental mechanisms of T1DM and OP. It also contributes to the recommendation if patients with T1DM need targeted care to promote bone health and timely prevention of osteoporosis.