Quantitative analysis of the illegal addition of Atenolol in Panax notoginseng based on NIR-MIR spectral data fusion and calibration transfer.

To address the issue of the common illegal addition of Atenolol in Panax notoginseng, we propose an approach that realizes multivariate calibration transfer between different particle sizes based on near-infrared (NIR) and mid-infrared (MIR) spectral data fusion. To achieve high prediction accuracy, we construct three data fusion schemes (full-spectrum fusion, feature-level fusion, and decision-level fusion) that combine NIR and MIR spectral data. Among three data fusion schemes, the feature-level fusion based on the UVE-SPA-PLS model for 120-mesh spectral data achieves optimal prediction accuracy. Here, a Piecewise Direct Standardization (PDS) algorithm has been applied to calibration transfer from 100-mesh and 80-mesh to 120-mesh to reduce the influence of particle size and improve the robustness of the model. The correlation coefficient (R2) of 100-mesh, and 80-mesh prediction sets can reach 0.9861 and 0.9823, respectively. The corresponding root mean square error (RMSE) are 0.1545 and 0.2045, respectively. This research provides a method for illegal additions in precious herbs and reduces the effect of particle size on spectral modeling, enabling high-precision quantitative detection. In addition, it has important application prospects in reducing experimental losses of precious medicinal materials and ensuring the safe use of Chinese and Western medicines, which provides an alternative method for non-destructive testing.

Endodontic management considerations for Type III dens invaginatus based on anatomical characteristics: A case series.

Dens invaginatus (DI) is a developmental anomaly of the teeth characterised by the in-folding of the enamel into the dentin. Oehlers' Type III DI is the most serious form, in which the inherently invaginated channels communicate with periodontal and dental pulp tissue, increasing the risk of bacterial contamination. However, varying and complex anatomical features make diagnosis and treatment challenging. Conventional endodontic therapies promote healing by avoiding unnecessary interventions (e.g., surgical or other invasive treatments). Radiographic examination can reveal the structural details of such malformations. We obtained multiple procedural details for treating Type III DI based on radiographic analyses from our clinical experience. In addition, we introduce a new classification strategy for the management of Type III DI that is more applicable to treatment needs. This study aimed to discuss the anatomical features and current treatment considerations of Type III DI.

Overcoming the Low-Stability Bottleneck in the Clinical Translation of Liposomal Pressurized Metered-Dose Inhalers: A Shell Stabilization Strategy Inspired by Biomineralization.

Currently, several types of inhalable liposomes have been developed. Among them, liposomal pressurized metered-dose inhalers (pMDIs) have gained much attention due to their cost-effectiveness, patient compliance, and accurate dosages. However, the clinical application of liposomal pMDIs has been hindered by the low stability, i.e., the tendency of the aggregation of the liposome lipid bilayer in hydrophobic propellant medium and brittleness under high mechanical forces. Biomineralization is an evolutionary mechanism that organisms use to resist harsh external environments in nature, providing mechanical support and protection effects. Inspired by such a concept, this paper proposes a shell stabilization strategy (SSS) to solve the problem of the low stability of liposomal pMDIs. Depending on the shell material used, the SSS can be classified into biomineralization (biomineralized using calcium, silicon, manganese, titanium, gadolinium, etc.) biomineralization-like (composite with protein), and layer-by-layer (LbL) assembly (multiple shells structured with diverse materials). This work evaluated the potential of this strategy by reviewing studies on the formation of shells deposited on liposomes or similar structures. It also covered useful synthesis strategies and active molecules/functional groups for modification. We aimed to put forward new insights to promote the stability of liposomal pMDIs and shed some light on the clinical translation of relevant products.

Expert consensus on difficulty assessment of endodontic therapy.

Endodontic diseases are a kind of chronic infectious oral disease. Common endodontic treatment concepts are based on the removal of inflamed or necrotic pulp tissue and the replacement by gutta-percha. However, it is very essential for endodontic treatment to debride the root canal system and prevent the root canal system from bacterial reinfection after root canal therapy (RCT). Recent research, encompassing bacterial etiology and advanced imaging techniques, contributes to our understanding of the root canal system's anatomy intricacies and the technique sensitivity of RCT. Success in RCT hinges on factors like patients, infection severity, root canal anatomy, and treatment techniques. Therefore, improving disease management is a key issue to combat endodontic diseases and cure periapical lesions. The clinical difficulty assessment system of RCT is established based on patient conditions, tooth conditions, root canal configuration, and root canal needing retreatment, and emphasizes pre-treatment risk assessment for optimal outcomes. The findings suggest that the presence of risk factors may correlate with the challenge of achieving the high standard required for RCT. These insights contribute not only to improve education but also aid practitioners in treatment planning and referral decision-making within the field of endodontics.

Genome-wide analysis of acid tolerance genes of Enterococcus faecalis with RNA-seq and Tn-seq.

Enterococcus faecalis, a formidable nosocomial and community-acquired opportunistic pathogen, can persist a wide range of extreme environments, including low pH and nutrient deficiency. Clarifying the survival mechanism of E. faecalis in low-pH conditions is the key to combating the infectious diseases caused by E. faecalis. In this study, we combined transcriptome profiling (RNA-seq) and transposon insertion sequencing (TIS) to comprehensively understand the genes that confer these features on E. faecalis. The metadata showed that genes whose products are involved in cation transportation and amino acid biosynthesis were predominantly differentially expressed under acid conditions. The products of genes such as opp1C and copY reduced the hydrion concentration in the cell, whereas those of gldA2, gnd2, ubiD, and ubiD2 mainly participated in amino metabolism, increasing matters to neutralize excess acid. These, together with the folE and hexB genes, which are involved in mismatch repair, form a network of E. faecalis genes necessary for its survival under acid conditions.

IMPORTANCE: As a serious nosocomial pathogen, Enterococcus faecalis was considered responsible for large numbers of infections. Its ability to survive under stress conditions, such as acid condition and nutrient deficiency was indispensable for its growth and infection. Therefore, understanding how E. faecalis survives acid stress is necessary for the prevention and treatment of related diseases. RNA-seq and TIS provide us a way to analyze the changes in gene expression under such conditions.

Fibroblast growth factor 7 protects osteoblasts against oxidative damage through targeting mitochondria.

The pathophysiology of osteoporosis is significantly influenced by the impaired functioning of osteoblasts, which is particularly caused by oxidative stress. Nevertheless, the underlying mechanisms responsible for this phenomenon are still not well understood. The objective of this study was to elucidate the impact of fibroblast growth factor 7 (FGF7) on the behavior of osteoblasts under conditions of oxidative stress. The osteoblast-like MC3T3 cells were pretreated with recombinant FGF7 in the presence of oxidative stress induced by hydrogen peroxide (H2 O2 ). We first provided the evidence that the endogenous FGF7 was significantly increased in osteoblasts in response to the increased H2 O2 levels. Recombined FGF7 demonstrated a remarkable capacity to resist the detrimental effects of H2 O2 -induced oxidative stress, including the increase in cell apoptosis, decrease in osteoblast viability, and impairment in osteogenic differentiation capacity, on osteoblasts. Furthermore, we extensively explored the mechanism underlying these protective effects and discovered a remarkable modulation of reactive oxygen species (ROS) homeostasis in H2 O2 -treated cells following the pronounced expression of FGF7, which significantly differed from the control group. Additionally, we observed that FGF7 exerted partial preservation on both the morphology and function of mitochondria when exposed to oxidative stress conditions. Furthermore, FGF7 exhibited the ability to enhance the activation of the p38/MAPK signaling pathway while concurrently suppressing the JNK/MAPK signaling pathway in response to oxidative stress. These results underscore the promising role and underlying mechanisms of FGF7 in preserving osteoblast homeostasis in the face of oxidative stress.

Nano-Formulations for Pulmonary Delivery: Past, Present, and Future Perspectives.

With the development of nanotechnology and confronting the problems of traditional pharmaceutical formulations in treating lung diseases, inhalable nano-formulations have attracted interest. Inhalable nano-formulations for treating lung diseases allow for precise pulmonary drug delivery, overcoming physiological barriers, improving aerosol lung deposition rates, and increasing drug bioavailability. They are expected to solve the difficulties faced in treating lung diseases. However, limited success has been recorded in the industrialization translation of inhalable nano-formulations. Only one relevant product has been approved by the FDA to date, suggesting that there are still many issues to be resolved in the clinical application of inhalable nano-formulations. These systems are characterized by a dependence on inhalation devices, while the adaptability of device formulation is still inconclusive, which is the most important issue impeding translational research. In this review, we categorized various inhalable nano-formulations, summarized the advantages of inhalable nano-formulations over conventional inhalation formulations, and listed the inhalable nano-formulations undergoing clinical studies. We focused on the influence of inhalation devices on nano-formulations and analyzed their adaptability. After extensive analysis of the drug delivery mechanisms, technical processes, and limitations of different inhalation devices, we concluded that vibrating mesh nebulizers might be most suitable for delivering inhalable nano-formulations, and related examples were introduced to validate our view. Finally, we presented the challenges and outlook for future development. We anticipate providing an informative reference for the field.

The Necessity to Investigate In Vivo Fate of Nanoparticle-Loaded Dissolving Microneedles.

Transdermal drug delivery systems are rapidly gaining prominence and have found widespread application in the treatment of numerous diseases. However, they encounter the challenge of a low transdermal absorption rate. Microneedles can overcome the stratum corneum barrier to enhance the transdermal absorption rate. Among various types of microneedles, nanoparticle-loaded dissolving microneedles (DMNs) present a unique combination of advantages, leveraging the strengths of DMNs (high payload, good mechanical properties, and easy fabrication) and nanocarriers (satisfactory solubilization capacity and a controlled release profile). Consequently, they hold considerable clinical application potential in the precision medicine era. Despite this promise, no nanoparticle-loaded DMN products have been approved thus far. The lack of understanding regarding their in vivo fate represents a critical bottleneck impeding the clinical translation of relevant products. This review aims to elucidate the current research status of the in vivo fate of nanoparticle-loaded DMNs and elaborate the necessity to investigate the in vivo fate of nanoparticle-loaded DMNs from diverse aspects. Furthermore, it offers insights into potential entry points for research into the in vivo fate of nanoparticle-loaded DMNs, aiming to foster further advancements in this field.

Nicolau Syndrome with Severe Facial Ischemic Necrosis after Endodontic Treatment: A Case Report.

Nicolau syndrome (NS) is a rare complication resulting from intramuscular injections. It is characterized by severe pain at the injection site and the development of purplish discoloration. Only a limited number of case reports have been published documenting the adverse effects associated with the injection of calcium hydroxide (CH) beyond the apex during endodontic treatment. Here, we present the case of a 16-year-old female with NS after the injection of CH during the root canal treatment. The radiography examination revealed distal occlusion of the right maxillary and facial arteries. This caused a substantial area of skin necrosis to develop on the patient's face, resulting in permanent scarring. NS is associated with the displacement of CH beyond the apex. To minimize the risk of NS, dentists should exercise caution by avoiding forced injection of CH during treatment, particularly when the root canal is actively bleeding.

Amino acid-based supramolecular chiral hydrogels promote osteogenesis of human dental pulp stem cells via the MAPK pathway.

Critical-size defects (CSDs) of the craniofacial bones cause aesthetic and functional complications that seriously impact the quality of life. The transplantation of human dental pulp stem cells (hDPSCs) is a promising strategy for bone tissue engineering. Chirality is commonly observed in natural biomolecules, yet its effect on stem cell differentiation is seldom studied, and little is known about the underlying mechanism. In this study, supramolecular chiral hydrogels were constructed using L/d-phenylalanine (L/D-Phe) derivatives. The results of alkaline phosphatase expression analysis, alizarin red S assay, as well as quantitative real-time polymerase chain reaction and western blot analyses suggest that right-handed D-Phe hydrogel fibers significantly promoted osteogenic differentiation of hDPSCs. A rat model of calvarial defects was created to investigate the regulation of chiral nanofibers on the osteogenic differentiation of hDPSCs in vivo. The results of the animal experiment demonstrated that the D-Phe group exhibited greater and faster bone formation on hDPSCs. The results of RNA sequencing, vinculin immunofluorescence staining, a calcium fluorescence probe assay, and western blot analysis indicated that L-Phe significantly promoted adhesion of hDPSCs, while D-Phe nanofibers enhanced osteogenic differentiation of hDPSCs by facilitating calcium entry into cells and activate the MAPK pathway. These results of chirality-dependent osteogenic differentiation offer a novel therapeutic strategy for the treatment of CSDs by optimising the differentiation of hDPSCs into chiral nanofibers.

Editorial on Special Issue "Design and Optimization of Pharmaceutical Gels".

The efficacy of many bioactive agents, including drugs, food supplements, and vaccines, is limited because of their poor chemical stability, low water solubility, and low oral bioavailability [...].

Nanomedicines for targeted pulmonary delivery: receptor-mediated strategy and alternatives.

Pulmonary drug delivery of nanomedicines is promising for the treatment of lung diseases; however, their lack of specificity required for targeted delivery limit their applications. Recently, a variety of pulmonary delivery targeting nanomedicines (PDTNs) has been developed for enhancing drug accumulation in lung lesions and reducing systemic side effects. Furthermore, with the increasing profound understanding of the specific microenvironment of different local lung diseases, multiple targeting strategies have been employed to promote drug delivery efficiency, which can be divided into the receptor-mediated strategy and alternatives. In this review, the current publication trend on PDTNs is analyzed and discussed, revealing that the research in this area has been attracting much attention. According to the different unique microenvironments of lung lesions, the reported PDTNs based on the receptor-mediated strategy for lung cancer, lung infection, lung inflammation and pulmonary fibrosis are listed and summarized. In addition, several other well-established strategies for the design of these PDTNs, such as charge regulation, mucus delivery enhancement, stimulus-responsive drug delivery and magnetic force-driven targeting, are introduced and discussed. Besides, bottlenecks in the development of PDTNs are discussed. Finally, we highlight the challenges and opportunities in the development of PDTNs. We hope that this review will provide an overview of the available PDTNs for guiding the treatment of lung diseases.

Rivastigmine nasal spray for the treatment of Alzheimer's Disease: Olfactory deposition and brain delivery.

Alzheimer's disease (AD) is characterized by a gradual decline in cognitive function and memory impairment, significantly impacting the daily lives of patients. Rivastigmine (RHT), a cholinesterase inhibitor, is used to treat mild to moderate AD via oral administration. However, oral administration is associated with slow absorption rate and severe systemic side effects. RHT nasal spray (RHT-ns), as a nose-to-brain delivery system, is more promising for AD management due to its efficient brain delivery and reduced peripheral exposure. This study constructed RHT-ns for enhancing AD treatment efficacy, and meanwhile the correlation between drug olfactory deposition and drug entering into the brain was explored. A 3D-printed nasal cast was employed to quantify the drug olfactory deposition. Brain delivery of RHT-ns was quantified using fluorescence tracking and Desorption Electrospray Ionization Mass Spectrometry (DESI-MS) analysis, which showed a good correlation to the olfactory deposition. F2 (containing 1% (w/v) viscosity modifier Avicel® RC-591) with high olfactory deposition and drug brain delivery was further investigated for pharmacodynamics study. F2 exhibited superiority in AD treatment over the commercially available oral formulation. In summary, the present study showed the successful development of RHT-ns with improved olfactory deposition and enhanced brain delivery. It might provide new insight into the design and development of nose-to-brain systems for the treatment of AD.

[Effect of bleaching combined with Er:YAG or Nd:YAG laser on shear bond strength and microleakage of resin restoration].

PURPOSE: To evaluate the effects of bleaching combined with Er:YAG laser or Nd:YAG laser on bond strength and microleakage of resin fillings on enamel surface. METHODS: Sixty-four pieces of enamel specimens prepared from isolated teeth were randomly divided into 4 groups(n=16): control group, simple bleaching group, bleaching combined with Er: YAG laser group and bleaching combined with Nd:YAG laser group. Then the shear bond strength and the depth of microleakage were tested, and the fracture mode of the specimen was observed under microscope. SPSS 26.0 software package was used for statistical analysis. RESULTS: After bleaching simply, the bond strength of the restoration was significantly decreased, and the marginal microleakage was significantly increased(P＜0.05). There was no significant difference in shear bond strength and microleakage depth between the group bleaching combined with Er: YAG laser and control group(P＞0.05). The shear bond strength after bleaching combined with Nd:YAG laser was significantly reduced (P＜0.05), but there was no significant difference in the depth of microleakage compared with unbleached microleakage(P＞0.05). Bonding interface fracture was the main fracture mode for all groups. CONCLUSIONS: Compared to traditional bleaching, bleaching combined with laser has certain clinical advantages due to its less influence on bond strength and microleakage of resin fillings.

Dual peptides-modified cationic liposomes for enhanced Lung cancer gene therapy by a gap junction regulating strategy.

BACKGROUND: Gene therapy for lung cancer has emerged as a novel tumor-combating strategy for its superior tumor specificity, low systematical toxicity and huge clinical translation potential. Especially, the applications of microRNA shed led on effective tumor ablation by directly interfering with the crucial gene expression, making it one of the most promising gene therapy agents. However, for lung cancer therapy, the microRNA treatment confronted three bottlenecks, the poor tumor tissue penetration effect, the insufficient lung drug accumulation and unsatisfied gene transfection efficiency. To address these issues, an inhalable RGD-TAT dual peptides-modified cationic liposomes loaded with microRNA miR-34a and gap junction (GJ) regulation agent all-trans retinoic acid (ATRA) was proposed, which was further engineered into dry powder inhalers (DPIs). RESULTS: Equipped with a rough particle surface and appropriate aerodynamic size, the proposed RGD-TAT-CLPs/ARTA@miR-34a DPIs were expected to deposit into the deep lung and reach lung tumor lesions guided by targeting peptide RGD. Assisted by cellular transmembrane peptides TAT, the RGD-TAT-CLPs/ARTA@miR-34a was proven to be effectively internalized by cancer cells, enhancing gene transfection efficiency. Then, the GJ between tumor cells was upregulated by ARTA, facilitating the intercellular transport of miR-34a and boosting the gene expression in the deep tumor. CONCLUSION: Overall, the proposed RGD-TAT-CLPs/ARTA@miR-34a DPIs could enhance tumor tissue penetration, elevate lung drug accumulation and boost gene transfection efficiency, breaking the three bottlenecks to enhancing tumor elimination in vitro and in vivo. We believe that the proposed RGD-TAT-CLPs/ARTA@miR-34a DPIs could serve as a promising pulmonary gene delivery platform for multiple lung local disease treatments.

Piezoresistive Theory and Numerical Calculation for Carbon Nanotube Polymer Composite.

A three-dimensional theory has been established for the piezoresistivity of carbon nanotube (CNT) polymer composites. Based on the Mori-Tanaka method in meso-mechanics theory and considering quantum tunneling effect between CNTs, an approach to calculate equivalent electrical conductivity of composites was proposed. On this basis, a piezoresistive theory, which incorporates the effect of composites' geometric nonlinearity, was developed for CNT polymer composites. The theory is dependent only on some basic physical parameters of the materials. A finite element formula of the theory for the numerical calculation of piezoresistivity was presented from the analysis of both elastic and electric fields. Numerical simulations demonstrated that the results predicted by the theory were in good agreement with those of the experimental tests. Parameter sensitivity analysis revealed that when both the potential barrier height of the matrix and the initial average separation distance between CNTs increased, the piezoresistivity obviously increased. However, with the increase in aspect ratio and CNT conductivity, the piezoresistivity decreased gradually. A practical engineering application of this theory is also provided.

Experts consensus on the procedure of dental operative microscope in endodontics and operative dentistry.

The dental operative microscope has been widely employed in the field of dentistry, particularly in endodontics and operative dentistry, resulting in significant advancements in the effectiveness of root canal therapy, endodontic surgery, and dental restoration. However, the improper use of this microscope continues to be common in clinical settings, primarily due to operators' insufficient understanding and proficiency in both the features and established operating procedures of this equipment. In October 2019, Professor Jingping Liang, Vice Chairman of the Society of Cariology and Endodontology, Chinese Stomatological Association, organized a consensus meeting with Chinese experts in endodontics and operative dentistry. The objective of this meeting was to establish a standard operation procedure for the dental operative microscope. Subsequently, a consensus was reached and officially issued. Over the span of about four years, the content of this consensus has been further developed and improved through practical experience.

Utilization of Lyotropic Liquid Crystalline Gels for Chronic Wound Management.

Management of chronic wounds is becoming a serious health problem worldwide. To treat chronic wounds, a suitable healing environment and sustained delivery of growth factors must be guaranteed. Different therapies have been applied for the treatment of chronic wounds such as debridement and photodynamic therapy. Among them, growth factors are widely used therapeutic drugs. However, at present, growth factor delivery systems cannot meet the demand of clinical practice; therefore new methods should be developed to meet the emerging need. For this reason, researchers have tried to modify hydrogels through some methods such as chemical synthesis and molecule modifications to enhance their properties. However, there are still a large number of limitations in practical use like byproduct problems, difficulty to industrialize, and instability of growth factor. Moreover, applications of new materials like lyotropic liquid crystalline (LLC) on chronic wounds have emerged as a new trend. The structure of LLC is endowed with many excellent properties including low cost, ordered structure, and excellent loading efficiency. LLC can provide a moist local environment for the wound, and its lattice structure can embed the growth factors in the water channel. Growth factor is released from the high-concentration carrier to the low-concentration release medium, which can be precisely regulated. Therefore, it can provide sustained and stable delivery of growth factors as well as a suitable healing environment for wounds, which is a promising candidate for chronic wound healing and has a broad prospective application. In conclusion, more reliable and applicable drug delivery systems should be designed and tested to improve the therapy and management of chronic wounds.

miR-325-3p Reduces Proliferation and Promotes Apoptosis of Gastric Cancer Cells by Inhibiting Human Antigen R.

Human antigen R (HuR), also known as ELAVL1, is a widely expressed RNA-binding protein (RBP) that has a significant impact on the development and advancement of tumors. Our previous study found that 5-fluorouracil (5-FU) may impede the proliferation and increase apoptosis in gastric cancer cells by reducing the nucleocytoplasmic shuttling of HuR. However, how posttranscriptional regulation influences HuR functions in gastric cancer remains to be elucidated. Here, we demonstrated that miR-325-3p has the potential to regulate the expression level of HuR by directly binding to its 3'UTR, which in turn led to a significant reduction in proliferation and an increase in apoptosis in gastric cancer cells. In addition, xenograft experiment showed that knockdown of HuR or overexpression of miR-325-3p group exhibited smaller tumor sizes after transplant of gastric cancer cells into zebrafish larvae. Thus, our findings offer new insights into the pathogenesis of gastric cancer and may potentially assist in identifying novel targets for drug therapy.

Guard against internal and external: An antibacterial, anti-inflammation and healing-promoting spray gel based on lyotropic liquid crystals for the treatment of diabetic wound.

The diabetic wound is a prevalent and serious complication of diabetes, which easily deteriorates due to susceptibility to infection and difficulty in healing, causing a high risk of amputation and economic burden to patients. Bacterial infection, persistent excessive inflammation, and cellular and angiogenesis disorders are the main reasons for the difficulty of diabetic wound healing. In this study, glycerol monooleate (GMO) was used to prepare lyotropic liquid crystal hydrogel (LLC) containing the natural antimicrobial peptide LL37 and carbenoxolone (CBX) to achieve antibacterial, anti-inflammation, and healing promotion for the treatment of diabetic wounds. The shear-thinning properties of the LLC precursor solution allowed it to be administered in the form of a spray, which perfectly fitted the shape of the wound and transformed into a gel after absorbing wound exudate to act as a wound protective barrier. The faster release of LL37 realized rapid sterilization of wounds, controlled the source of inflammation, and accelerated wound healing. The inflammatory signaling pathway was blocked by the subsequently released CBX, and the spread of the inflammatory response was inhibited and then further weakened. In addition, CBX down-regulated connexin (Cx43) to assist LL37 to promote cell migration and proliferation better. Combined with the pro-angiogenic effect of LL37, the healing of diabetic wounds was significantly accelerated. All these advantages made LL37-CBX-LLC a promising approach for the treatment of chronic diabetic wounds.