Preparation and Evaluation of a Novel 99mTc-Labeled Niraparib Isonitrile Complex as a Potential PARP-1 Imaging Agent.

Poly ADP-ribose polymerase (PARP) plays an important role in the DNA repair process and has become an attractive target for cancer therapy in recent years. Given that niraparib has good clinical efficacy as a PARP inhibitor, this study aimed to develop radiolabeled niraparib derivatives for tumor imaging to detect PARP expression and improve the accuracy of stratified patient therapy. The niraparib isonitrile derivative (CNPN) was designed, synthesized, and radiolabeled to obtain the [99mTc]Tc-CNPN complex with high radiochemical purity (>95%). It was lipophilic and stable in vitro. In HeLa cell experiments, the uptake of [99mTc]Tc-CNPN was effectively inhibited by the ligand CNPN, indicating the binding affinity for PARP. According to the biodistribution studies of HeLa tumor-bearing mice, [99mTc]Tc-CNPN has moderate tumor uptake and can be effectively inhibited, demonstrating its specificity for targeting PARP. The SPECT imaging results showed that [99mTc]Tc-CNPN had tumor uptake at 2 h postinjection. All of the results of this study indicated that [99mTc]Tc-CNPN is a promising tumor imaging agent that targets PARP.

Synthesis and Evaluation of 99mTc-Labeled DPro-Gly-Containing Tracers Targeting PSMA.

The specific expression of prostate-specific membrane antigen (PSMA) makes it an ideal target for the diagnosis and treatment of prostate cancer. Currently, many 99mTc-labeled PSMA-targeted tracers have been developed. However, the high renal uptake of these 99mTc-labeled tracers is a common problem that limits their clinical application. In this work, the ligand (EUKPG) using DPro-Gly as the linker was synthesized and three 99mTc-labeled complexes ([99mTc]Tc-EUKPG-EDDA, [99mTc]Tc-EUKPG-TPPTS, [99mTc]Tc-EUKPG-TPPMS) with different coligands were prepared and evaluated. Among them, [99mTc]Tc-EUKPG-EDDA showed the most favorable pharmacokinetic properties, with significantly reduced uptake in the kidney (14.04 ± 0.23% ID/g), rapid clearance and low uptake in nontarget organs, thus making it to exhibit high tumor-to-background ratios (tumor/blood: 7.47, tumor/muscle: 12.65). Affinity studies have shown that it has high specificity for PSMA both in vivo and in vitro. Therefore, [99mTc]Tc-EUKPG-EDDA has great potential as a promising molecular tracer to target PSMA for tumor imaging.

Synthesis of (Furyl)Methyl Disulfides via Tandem Reaction of Conjugated Ene-Yne-Ketones with Acetyl-Masked Disulfide Nucleophiles.

In this study, we outline a general method for the construction of various (furyl)methyl disulfides from acetyl-masked disulfide nucleophiles and ene-yne-ketones. This protocol is feathered by metal-free, simple experimental conditions, high efficiency, and scalable potential, which make it attractive and practical.

Transition-Metal-Free Disulfuration of Amides with Trisulfide Dioxides via Formation of Unaccessible S-S-N Bonds.

Under transition-metal-free conditions, trisulfide dioxides were used as disulfurating reagents to react with a wide range of amides, affording various substituted N-disulfanyl amides in good yields. Furthermore, the gram-scale experiment has confirmed the practicability of this approach.

Role of arterial blood glucose and interstitial fluid glucose difference in evaluating microcirculation and clinical prognosis of patients with septic shock: a prospective observational study.

BACKGROUND: Microcirculation abnormality in septic shock is closely associated with organ dysfunction and mortality rate. It was hypothesized that the arterial blood glucose and interstitial fluid (ISF) glucose difference (GA-I) as a marker for assessing the microcirculation status can effectively evaluate the severity of microcirculation disturbance in patients with septic shock. METHODS: The present observational study enrolled patients with septic shock admitted to and treated in the intensive care unit (ICU) of a tertiary teaching hospital. The parameters reflecting organ and tissue perfusion, including lactic acid (Lac), skin mottling score, capillary refill time (CRT), venous-to-arterial carbon dioxide difference (Pv-aCO2), urine volume, central venous oxygen saturation (ScvO2) and GA-I of each enrolled patient were recorded at the time of enrollment (H0), H2, H4, H6, and H8. With ICU mortality as the primary outcome measure, the ICU mortality rate at any GA-I interval was analyzed. RESULTS: A total of 43 septic shock patients were included, with median sequential organ failure assessment (SOFA) scores of 10.5 (6-16), and median Acute Physiology and Chronic Health Evaluation (APACHAE) II scores of 25.7 (9-40), of whom 18 died during ICU stay. The GA-I levels were negative correlation with CRT (r = 0.369, P < 0.001), Lac (r = -0.269, P < 0.001), skin mottling score (r=-0.223, P < 0.001), and were positively associated with urine volume (r = 0.135, P < 0.05). The ICU mortality rate of patients with septic shock presenting GA-I ≤ 0.30 mmol/L and ≥ 2.14 mmol/L was significantly higher than that of patients with GA-I at 0.30-2.14 mmol/L [65.2% vs. 15.0%, odds ratio (OR) = 10.625, 95% confidence interval (CI): 2.355-47.503]. CONCLUSION: GA-I was correlated with microcirculation parameters, and with differences in survival. Future studies are needed to further explore the potential impact of GA-I on microcirculation and clinical prognosis of septic shock, and the bedside monitoring of GA-I may be beneficial for clinicians to identify high-risk patients.

Radiosynthesis and Bioevaluation of 99mTc-Labeled Isocyanide Ubiquicidin 29-41 Derivatives as Potential Agents for Bacterial Infection Imaging.

To develop a novel 99mTc-labeled ubiquicidin 29-41 derivative for bacterial infection single-photon emission computed tomography (SPECT) imaging with improved target-to-nontarget ratio and lower nontarget organ uptake, a series of isocyanide ubiquicidin 29-41 derivatives (CNnUBI 29-41, n = 5-9) with different carbon linkers were designed, synthesized and radiolabeled with the [99mTc]Tc(I)+ core, [99mTc][Tc(I)(CO)3(H2O)3]+ core and [99mTc][Tc(V)N]2+ core. All the complexes are hydrophilic, maintain good stability and specifically bind Staphylococcus aureus in vitro. The biodistribution in mice with bacterial infection and sterile inflammation demonstrated that [99mTc]Tc-CN5UBI 29-41 was able to distinguish bacterial infection from sterile inflammation, which had an improved abscess uptake and a greater target-to-nontarget ratio. SPECT imaging study of [99mTc]Tc-CN5UBI 29-41 in bacterial infection mice showed that there was a clear accumulation in the infection site, suggesting that this radiotracer could be a potential radiotracer for bacterial infection imaging.

Synthesis and Bioevaluation of Novel Technetium-99m-Labeled Complexes with Norfloxacin HYNIC Derivatives for Bacterial Infection Imaging.

To seek a novel 99mTc-labeled quinolone derivative for bacterial infection SPECT imaging that aims to lower nontarget organ uptake, a novel norfloxacin 6-hydrazinoicotinamide (HYNIC) derivative (HYNICNF) was designed and synthesized. It was radiolabeled with different coligands, such as tricine, trisodium triphenylphosphine-3,3',3″-trisulfonate (TPPTS), sodium triphenylphosphine-3-monosulfonate (TPPMS), and ethylenediamine-N,N'-diacetic acid (EDDA), to obtain three 99mTc-labeled norfloxacin HYNIC complexes, namely, [99mTc]Tc-tricine-TPPTS-HYNICNF, [99mTc]Tc-tricine-TPPMS-HYNICNF, and [99mTc]Tc-EDDA-HYNICNF. These complexes were purified (RCP > 95%) and evaluated in vitro and in vivo for targeting bacteria. All three complexes are hydrophilic, maintain good stability, and specifically bind Staphylococcus aureus in vitro. The biodistribution in mice with bacterial infection demonstrated that [99mTc]Tc-EDDA-HYNICNF showed a higher abscess uptake and lower nontarget organ uptake and was able to distinguish bacterial infection and sterile inflammation. Single photon emission computed tomography (SPECT) image study in bacterial infection mice showed there was a visible accumulation in the infection site, suggesting that [99mTc]Tc-EDDA-HYNICNF is a potential radiotracer for bacterial infection imaging.

Preparation and Evaluation of [18F]AlF-NOTA-PBB for PET Imaging of Cyclin-dependent Kinase 4/6 in Tumors.

Cyclin-dependent kinases (CDKs), especially cyclin-dependent kinase 4/6 (CDK4/6), have been targets for the development of specific tumor imaging agents. Palbociclib is a highly selective CDK4/6 inhibitor. In this study, to develop a novel 18F-labeled palbociclib derivative for specific tumor imaging, we designed and synthesized a ligand (NOTA-PBB) consisting of palbociclib as the targeted pharmacophore and NOTA as the macrocyclic bifunctional chelator. The corresponding [18F]AlF-NOTA-PBB complex was prepared with high radiochemical purity (98.4 ± 0.15%) and yield (58.7 ± 4.5%) within 35 min without requiring HPLC purification through a simple one-step 18F-labeling strategy of NOTA-AlF chelation chemistry. The radiotracer was lipophilic (log P = 0.095 ± 0.003) and had good stability in vitro and in vivo. The cellular uptake studies performed on the MCF-7 breast cancer cell line (ER-positive and HER2-negative) showed that radioactive uptake was blocked by preincubating with a molar dose of palbociclib and it had a nanomolar binding affinity to CDK4/6 (IC50 = 16.23 ± 1.84 nM), demonstrating a CDK4/6-mediated uptake mechanism. Its ex vivo biodistribution in nude mice-bearing MCF-7 tumors showed obvious tumor uptake and a high tumor/muscle ratio of [18F]AlF-NOTA-PBB, and tumor uptake was inhibited with 100 µg of palbociclib, demonstrating specific binding to CDK4/6. Radioactivity accumulation in MCF-7 tumors was observed in PET imaging with [18F]AlF-NOTA-PBB. Based on the results of this work, [18F]AlF-NOTA-PBB has the promising capability as a CDK4/6-targeted tumor imaging agent.

Reduction-Responsive Docetaxel Prodrug Encapsulated within Human Serum Albumin Nanoparticles for Cancer Therapy.

Docetaxel (DTX), a semisynthetic analogue of paclitaxel, is often used to treat cancers. Owing to its poor aqueous solubility, the current formulation of DTX for clinical applications involves using high surfactant and ethanol concentrations, causing hypersensitivity reactions. To overcome this issue, we developed a reduction-responsive DTX prodrug encapsulated within human serum albumin (HSA) nanoparticles (DTX-SS-COOH/HSA NPs). First, the DTX prodrug was conjugated to undecanoic acid through a disulfide bond (DTX-SS-COOH) via a four-step reaction. Subsequently, DTX-SS-COOH/HSA NPs were prepared via the desolvation method. The NPs exhibited a spherical structure with a diameter range of 140-220 nm, as revealed by dynamic light scattering and transmission electron microscopy. Fluorescence quenching analysis confirmed the formation of DTX-SS-COOH/HSA, which was ascribed to electrostatic interactions and hydrophobic forces. Notably, NPs with a feed mole ratio corresponding to DTX-SS-COOH/HSA = 9:1 demonstrated high drug-loading and encapsulation efficiency of 12.84 and 93.11%, respectively, alongside good stability. Moreover, the reduced responsiveness experiment revealed an accelerated DTX release in the presence of glutathione. An in vivo pharmacokinetic study indicated that DTX-SS-COOH/HSA NPs demonstrated considerably a prolonged circulation time (6.2-fold) compared to that of free DTX. Ultimately, the antitumor test of MDA-MB-231 tumor-bearing mice revealed that DTX-SS-COOH/HSA NPs were superior to DTX/HSA NPs for tumor growth inhibition. Thus, DTX-SS-COOH/HSA NPs represent a promising DTX nanoformulation for clinical application.

Trivalent mRNA Vaccine against SARS-CoV-2 and Variants with Effective Immunization.

mRNA vaccines encoding a single spike protein effectively prevent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, the emergence of SARS-CoV-2 variants leads to a wide range of immune evasion. Herein, a unique trivalent mRNA vaccine based on ancestral SARS-CoV-2, Delta, and Omicron variant spike receptor-binding domain (RBD) mRNAs was developed to tackle the immune evasion of the variants. First, three RBD mRNAs of SARS-CoV-2, Delta, and Omicron were coencapsulated into lipid nanoparticles (LNPs) by using microfluidic technology. After that, the physicochemical properties and time-dependent storage stability of the trivalent mRNA vaccine nanoformulation were tested by using dynamic light scattering (DLS). In vitro, the trivalent mRNA vaccine exhibited better lysosomal escape ability, transfection efficiency, and biocompatibility than did the commercial transfection reagent Lipo3000. In addition, Western blot analyses confirmed that the three RBD proteins can be detected in cells transfected with the trivalent mRNA vaccine. Furthermore, ex vivo imaging analysis indicated that the livers of BALB/c mice had the strongest protein expression levels after intramuscular (IM) injection. Using a prime-boost strategy, this trivalent vaccine elicited robust humoral and T-cell immune responses in both the high-dose and low-dose groups and showed no toxicity in BALB/c mice. Three specific IgG antibodies in the high-dose group against SARS-CoV-2, Delta, and Omicron variants approached ∼1/1,833,333, ∼1/1,866,667, and ∼1/925,000, respectively. Taken together, two doses of inoculation with the trivalent mRNA vaccine may provide broad and effective immunization responses against SARS-CoV-2 and variants.

A Simple Kit Formulation for Preparation and Exploratory Human Studies of a Novel 99mTc-Labeled Fibroblast Activation Protein Inhibitor Tracer for Imaging of the Fibroblast Activation Protein in Cancers.

Fibroblast activation protein (FAP) is a potential target for tumor diagnosis and treatment because it is selectively expressed on the cell membrane of cancer-associated fibroblasts in most solid tumor stroma. The aim of this study was to develop a 99mTc-labeled fibroblast activation protein inhibitor (FAPI) tracer, evaluate its imaging efficacy in nude mice, and further explore its biodistribution in healthy volunteers and uptake in tumor patients. An FAPI-derived ligand (DP-FAPI) containing d-proline was designed and synthesized as a linker, and a stable hydrophilic 99mTc-labeled complex ([99mTc]Tc-DP-FAPI) was obtained by kit formulation. In vitro cellular uptake and saturation binding assays were performed in FAP-transfected HT-1080 cells (FAP-HT-1080). The biodistribution was characterized, and micro-single-photon emission computed tomography (SPECT) imaging was performed in BALB/c nude mice bearing U87 MG tumors. Furthermore, a first-in-man application was performed in four healthy volunteers and three patients with gastrointestinal tumors. In vitro, the nanomolar Kd values of [99mTc]Tc-DP-FAPI indicated that it had significantly high target affinity for FAP. Biodistribution and micro-SPECT imaging studies showed that [99mTc]Tc-DP-FAPI exhibited high uptake and high tumor-to-nontargeted ratios. The calculated effective dose for [99mTc]Tc-DP-FAPI was approximately <5 mSv in four healthy volunteers. In three patients with gastrointestinal tumors, [99mTc]Tc-DP-FAPI quantitative SPECT/CT revealed high and reliable uptake. [99mTc]Tc-DP-FAPI exhibited high selectivity and affinity for FAP in vitro. The safety and effectiveness of [99mTc]Tc-DP-FAPI in primary tumor imaging have been confirmed by animal and clinical studies, revealing the potential clinical application value of this tracer.

Multi-laser sensor for simultaneous multi-gas measurements using off-axis cavity-enhanced absorption spectroscopy with an opposite two-way configuration.

An opposite two-way off-axis cavity-enhanced absorption spectroscopy-based multi-gas sensor is reported. More than two lasers can be employed in the sensor for simultaneous detection of different gas species. An approximately two times improvement in magnitude of the 2f signal and the signal-to-noise ratio is achieved because the concave spherical mirrors outside each end of the cavity and the narrow bandpass filters before the detectors can act as re-injection mirrors to re-inject the light into the cavity in the scheme. The performance of the sensor is demonstrated by simultaneous measurement of CO2 and CH4 in the atmosphere. This Letter highlights a new, to the best of our knowledge, strategy for simultaneous multi-gas measurement in a single integrated cavity by employing as many as four lasers.

Preparation and Bioevaluation of 99mTc-Labeled FAP Inhibitors as Tumor Radiotracers to Target the Fibroblast Activation Protein.

Fibroblast activation protein (FAP) is overexpressed in cancer-associated fibroblasts (CAFs) in a majority of human epithelial cancers. With low expression in normal organs, FAP has become a promising molecular target for tumor theranostics. To develop a lower cost and more widely available alternative to positron emission tomography (PET), two isocyanide-containing FAP inhibitors (CN-C5-FAPI and CN-PEG4-FAPI) were synthesized and radiolabeled with 99mTc to obtain [99mTc][Tc-(CN-C5-FAPI)6]+ and [99mTc][Tc-(CN-PEG4-FAPI)6]+ in high yields (>95%). They showed good stability in saline and mouse serum. The partition coefficient (log P) values of [99mTc][Tc-(CN-C5-FAPI)6]+ and [99mTc][Tc-(CN-PEG4-FAPI)6]+ were -0.86 ± 0.03 and -2.38 ± 0.07, respectively, indicating that they were good hydrophilic complexes. The low nanomolar IC50 values of CN-C5-FAPI and CN-PEG4-FAPI indicated that they had specificity to FAP. In vitro cellular uptake and blocking experiments implied a FAP-targeted uptake mechanism. The nanomolar Kd values from the saturation binding assay indicated that they had significantly high target affinity to FAP. The biodistribution and blocking study in BALB/c nude mice bearing U87MG tumors showed that both exhibited specific tumor uptake. [99mTc][Tc-(CN-PEG4-FAPI)6]+ showed a higher tumor uptake and a higher tumor/nontarget ratio than [99mTc][Tc-(CN-C5-FAPI)6]+. The results of micro-single-photon emission computed tomography (SPECT) imaging studies of [99mTc][Tc-(CN-C5-FAPI)6]+ and [99mTc][Tc-(CN-PEG4-FAPI)6]+ were in accordance with the biodistribution results, suggesting that [99mTc][Tc-(CN-PEG4-FAPI)6]+ is a promising tumor imaging agent for targeting FAP.

Novel 99mTc labeled complexes with bisphosphonate isocyanide: Radiosynthesis and evaluation as potential bone-seeking agents.

In order to develop 99mTc-labeled complexes with bisphosphonate isocyanide as novel bone imaging agents, two bisphosphonate isocyanide derivatives (CNALN and CNPAM) were synthesized and radiolabeling was performed for preparing the corresponding [99mTc]Tc(I) complexes. [99mTc]Tc-CNALN and [99mTc]Tc-CNPAM were obtained with high radiochemical purity and showed good in vitro stability. Both of them were hydrophilic and had high affinity to hydroxyapatite. The biodistribution studies in mice revealed [99mTc]Tc-CNALN showed higher bone/background ratios at 60 min post-injection. In single photon emission computed tomography (SPECT) imaging study, [99mTc]Tc-CNALN had an obvious accumulation in bone, suggesting it would be a promising bone-seeking agent.

Comparison of biochemical composition of commercial sea cucumbers, Apostichopus japonicus and Parastichopus californicus, under the same culture conditions.

BACKGROUND: Apostichopus japonicus and Parastichopus californicus are two of the most important and profitable commercial sea cucumbers along the North Pacific coast. This study compared the body wall production rate (BWPR), proximate composition, amino acid, fatty acid, trace element and vitamin composition, and nonspecific immune enzyme activities of A. japonicus and P. californicus cultured in an artificial pond. RESULTS: The BWPR, crude fat and ash content in the body walls of A. japonicus and P. californicus showed remarkable differences (P < 0.05). For the 18 amino acids tested, differences in the contents of 15 were significant (P < 0.05) between the two species, except for threonine, methionine and histidine, and their first limiting amino acids were both methionine+cysteine. There were seven saturated and ten unsaturated fatty acids in their body walls, and except for 18:1 and 20:1, the content differences of the other 15 fatty acids were all significant (P < 0.05). Furthermore, between the two sea cucumbers, differences in the content of seven trace elements (Cu, Fe, Mn, Zn, Cr, Ni, Se) and six vitamins (B1, B3, B5, B9, C, E) were significant (P < 0.05). The activities of superoxide dismutase (SOD), catalase (CAT), acid phosphatase (ACP) and alkaline phosphatase (AKP) also showed distinct differences (P < 0.05). CONCLUSION: There are greater differences in the biochemical compositions and contents between A. japonicus and P. californicus, each with its own unique quality advantages. A. japonicus and P. californicus have high nutritional value, which are both the superior sea cucumbers. © 2022 Society of Chemical Industry.

Radiolabeling and evaluation of a novel [99mTcN]2+ complex with deferoxamine dithiocarbamate as a potential agent for bacterial infection imaging.

In order to find a 99mTc-labeled deferoxamine radiotracer for bacterial infection imaging, deferoxamine dithiocarbamate (DFODTC) was successfully synthesized and it was radiolabeled with [99mTcN]2+ core to prepare the 99mTcN(DFODTC)2 complex. 99mTcN(DFODTC)2 was obtained with high radiochemical purity without further purification. The complex was lipophilic and exhibited good in vitro stability. According to the result of bacterial binding study, the binding of 99mTcN(DFODTC)2 to bacteria was specific. Biodistribution in mice study indicated that 99mTcN(DFODTC)2 had a higher uptake in bacterial infection tissues than in turpentine-induced abscesses at 120 min after injection, which showed that the radiotracer could differentiate between bacterial infection and sterile inflammation. SPECT/CT images showed that there was a clear accumulation in infection sites, suggesting that 99mTcN(DFODTC)2 could be a potential bacterial infection imaging radiotracer.

Preparation and Evaluation of Novel Folate Isonitrile 99mTc Complexes as Potential Tumor Imaging Agents to Target Folate Receptors.

In order to seek novel technetium-99m folate receptor-targeting agents, two folate derivatives (CN5FA and CNPFA) were synthesized and radiolabeled to obtain [99mTc]Tc-CN5FA and [99mTc]Tc-CNPFA complexes, which exhibited high radiochemical purity (>95%) without purification, hydrophilicity, and good stability in vitro. The KB cell competitive binding experiments indicated that [99mTc]Tc-CN5FA and [99mTc]Tc-CNPFA had specificity to folate receptor. Biodistribution studies in KB tumor-bearing mice illustrated that [99mTc]Tc-CN5FA and [99mTc]Tc-CNPFA had specific tumor uptake. Compared with [99mTc]Tc-CN5FA, the tumor/muscle ratios of [99mTc]Tc-CNPFA were higher, resulting in a better SPECT/CT imaging background. According to the results, the two 99mTc complexes have potential as tumor imaging agents to target folate receptors.

Design, Preparation, and Evaluation of a Novel 99mTcN Complex of Ciprofloxacin Xanthate as a Potential Bacterial Infection Imaging Agent.

In order to seek novel technetium-99m bacterial infection imaging agents, a ciprofloxacin xanthate (CPF2XT) was synthesized and radiolabeled with [99mTcN]2+ core to obtain the 99mTcN-CPF2XT complex, which exhibited high radiochemical purity, hydrophilicity, and good stability in vitro. The bacteria binding assay indicated that 99mTcN-CPF2XT had specificity to bacteria. A study of biodistribution in mice showed that 99mTcN-CPF2XT had a higher uptake in bacterial infection tissues than in turpentine-induced abscesses, indicating that it could distinguish bacterial infection from sterile inflammation. Compared to 99mTcN-CPFXDTC, the abscess/blood and abscess/muscle ratios of 99mTcN-CPF2XT were higher and the uptakes of 99mTcN-CPF2XT in the liver and lung were obviously decreased. The results suggested that 99mTcN-CPF2XT would be a potential bacterial infection imaging agent.

Accuracy of Complete-Arch Scans Obtained by Intraoral Scanner and Smartphone Three-Dimensional Scanning Applications With Different Smartphone Position Setups: An In Vitro Study.

INTRODUCTION: The high cost of intraoral scanners (IOS) for complete-arch scans makes them less accessible for many dental practitioners. As a viable alternative, smartphone scanner applications (SMP) provide comparable scanning capabilities at a significantly low cost. However, there is limited data on the accuracy of SMP, especially when used in various smartphone positions. This study aimed to compare the three-dimensional (3D) and linear accuracy of complete-arch scans acquired by an IOS and SMP (KIRI Engine, KIRI Innovations, Guangdong, China) at three shooting angles (0°, 45°, and 90° for SMP_3A) and two shooting angles (30° and 60° for SMP_2A). METHODS: A stone dental cast was scanned with a laboratory scanner as a reference, with 11 scans performed by an IOS, SMP_2A, and SMP_3A. In 3D analysis, trueness and precision were evaluated through superimposition with the reference scan and within each group, respectively, using the best-fit algorithm of Geomagic Wrap software (3D Systems, Inc., Rock Hill, SC). Trueness in linear discrepancy was assessed by comparing the occlusal-cervical and mesiodistal dimensions of reference teeth (canine, premolar, and molar), intercanine width, and intermolar width on the digital casts to measurements of the stone cast, while precision was measured using the coefficient of variance. Differences between groups were analyzed using the Friedman test, followed by the Dunn-Bonferroni post hoc test with a significance level set at 0.05. RESULTS: IOS exhibited significantly lower trueness than SMP_2A (p = 0.003) with significantly greater width discrepancies on canines (p = 0.001) and molars (p < 0.001). Discrepancy patterns differed among the three scanning methods. The IOS showed greater discrepancies on the occlusal surfaces of posterior teeth. While SMP_3A demonstrated higher variation on the palatal surfaces and interproximal areas of posterior teeth. For precision, SMP_3A (p = 0.028) and SMP_2A (p = 0.003) showed a significantly lower precision in 3D analysis, but a comparable reproducibility in linear measurement to IOS. CONCLUSION: TRIOS IOS (3Shape, Copenhagen, Denmark) exhibited lower trueness in 3D and linear accuracy analyses for complete-arch scans. The positions of the smartphone significantly enhanced trueness at the undercut region. SMP_2A and SMP_3A can be a potential alternative for precise linear measurement in complete-arch scans with selective use.

Brain Targeting Nanomedicines: Pitfalls and Promise.

Brain diseases are the most devastating problem among the world's increasingly aging population, and the number of patients with neurological diseases is expected to increase in the future. Although methods for delivering drugs to the brain have advanced significantly, none of these approaches provide satisfactory results for the treatment of brain diseases. This remains a challenge due to the unique anatomy and physiology of the brain, including tight regulation and limited access of substances across the blood-brain barrier. Nanoparticles are considered an ideal drug delivery system to hard-to-reach organs such as the brain. The development of new drugs and new nanomaterial-based brain treatments has opened various opportunities for scientists to develop brain-specific delivery systems that could improve treatment outcomes for patients with brain disorders such as Alzheimer's disease, Parkinson's disease, stroke and brain tumors. In this review, we discuss noteworthy literature that examines recent developments in brain-targeted nanomedicines used in the treatment of neurological diseases.