Improving Hybrid Tin Halide Films by Tin Trifluoromethanesulfonate for Lead-Free Perovskite Solar Cells.

Tin-based perovskite solar cells (Sn-PSCs) without toxic lead ions outperform other types of lead-free PSCs in terms of photovoltaic performance. To avoid the oxidation of Sn2+ cations and the formation of vacancy defects, most reports involve the addition of SnF2 to the perovskite precursor solution, but hybrid tin halide (Sn-PVK) films still suffer from poor crystallinity and stability. In this work, we used an alternative additive of tin trifluoromethanesulfonate (Sn(OTF)2). Compared to SnF2, the solubility of Sn(OTF)2 in the precursor solution is greatly improved, and the crystal nucleation process is delayed, resulting in the enhancement of crystal growth. The coordination ability of the OTF- anions suppresses the oxidation of Sn2+ cations, which promotes the stability of Sn-PVK films. By replacing the conventional additive of SnF2 with Sn(OTF)2, the device achieves an increase in power conversion efficiency from 7.96% to 10.3%, while the stability of the devices is improved simultaneously.

Evaluation of Rhododendri Mollis Flos and its representative component as a potential analgesic.

Rhododendri Mollis Flos (R. mole Flos), the dried flowers of Rhododendron mole G. Don, have the ability to relieve pain, dispel wind and dampness, and dissolve blood stasis, but they are highly poisonous. The significance of this study is to explore the analgesic application potential of R. mole Flos and its representative component. According to the selected processing methods recorded in ancient literature, the analgesic activities of wine- and vinegar-processed R. mole Flos, as well as the raw product, were evaluated in a writhing test with acetic acid and a formalin-induced pain test. Subsequently, the HPLC-TOP-MS technique was utilized to investigate the changes in active components before and after processing once the variations in activities were confirmed. Based on the results, rhodojaponin VI (RJ-Vl) was chosen for further study. After processing, especially in vinegar, R. mole Flos did not only maintain the anti-nociception but also showed reduced toxicity, and the chemical composition corresponding to these effects also changed significantly. Further investigation of its representative components revealed that RJ-VI has considerable anti-nociceptive activity, particularly in inflammatory pain (0.3 mg/kg) and peripheral neuropathic pain (0.6 mg/kg). Its toxicity was about three times lower than that of rhodojaponin III, which is another representative component of R. mole Flos. Additionally, RJ-VI mildly inhibits several subtypes of voltage-gated sodium channels (IC50 > 200 µM) that are associated with pain or cardiotoxicity. In conclusion, the chemical substances and biological effects of R. mole Flos changed significantly before and after processing, and the representative component RJ-VI has the potential to be developed into an effective analgesic.

Appropriate control measure design by rapidly identifying risk areas of volatile organic compounds during the remediation excavation at an organic contaminated site.

Many organic contaminated sites require on-site remediation; excavation remediation processes can release many volatile organic compounds (VOCs) which are key atmospheric pollutants. It is therefore important to rapidly identify VOCs during excavation and map their risk areas for human health protection. In this study, we developed a rapid analysis and assessment method, aiming to and reveal the real-time distribution of VOCs, evaluate their human health risks by quantitative models, and design appropriate control measures. Through on-site diagonal distribution sampling and analysis, VOCs concentration showed a decreasing trend within 5 m from the excavation point and then increased after 5 m with the increase in distance from the excavation point (p < 0.05). The concentrations of VOCs near the dominant wind direction were higher than the concentrations of surrounding pollutants. In contrast with conventional solid-phase adsorption (SPA) and thermal desorption gas chromatography-mass spectrometry (TD-GC/MS) methods for determining the composition and concentration of VOCs, the rapid measurement of VOCs by photo-ionization detector (PID) fitted well with the chemical analysis and modeling assessment of cancer/non-cancer risk. The targeting area was assessed as mild-risk (PID < 10 ppm), moderate-risk (PID from 10 to 40 ppm), and heavy-risk (PID > 40 ppm) areas. Similarly, the human health risks also decreased gradually with the distance from the excavation point, with the main risk area located in the dominant wind direction. The results of rapid PID assessment were comparable to conventional risk evaluation, demonstrating its feasibility in rapidly identifying VOCs releases and assessing the human health risks. This study also suggested appropriate control measures that are important guidance for personal protection during the remediation excavation process.

Discovery and druggability evaluation of pyrrolamide-type GyrB/ParE inhibitor against drug-resistant bacterial infection.

The bacterial ATP-competitive GyrB/ParE subunits of type II topoisomerase are important anti-bacterial targets to treat super drug-resistant bacterial infections. Herein we discovered novel pyrrolamide-type GyrB/ParE inhibitors based on the structural modifications of the candidate AZD5099 that was withdrawn from the clinical trials due to safety liabilities such as mitochondrial toxicity. The hydroxyisopropyl pyridazine compound 28 had a significant inhibitory effect on Gyrase (GyrB, IC50 = 49 nmol/L) and a modest inhibitory effect on Topo IV (ParE, IC50 = 1.513 µmol/L) of Staphylococcus aureus. It also had significant antibacterial activities on susceptible and resistant Gram-positive bacteria with a minimum inhibitory concentration (MIC) of less than 0.03 µg/mL, which showed a time-dependent bactericidal effect and low frequencies of spontaneous resistance against S. aureus. Compound 28 had better protective effects than the positive control drugs such as DS-2969 (5) and AZD5099 (6) in mouse models of sepsis induced by methicillin-resistant Staphylococcus aureus (MRSA) infection. It also showed better bactericidal activities than clinically used vancomycin in the mouse thigh MRSA infection models. Moreover, compound 28 has much lower mitochondrial toxicity than AZD5099 (6) as well as excellent therapeutic indexes and pharmacokinetic properties. At present, compound 28 has been evaluated as a pre-clinical drug candidate for the treatment of drug-resistant Gram-positive bacterial infection. On the other hand, compound 28 also has good inhibitory activities against stubborn Gram-negative bacteria such as Escherichia coli (MIC = 1 µg/mL), which is comparable with the most potent pyrrolamide-type GyrB/ParE inhibitors reported recently. In addition, the structure-activity relationships of the compounds were also studied.

Assessment of the Purity of IMM-H014 and Its Related Substances for the Treatment of Metabolic-Associated Fatty Liver Disease Using Quantitative Nuclear Magnetic Resonance Spectroscopy.

An accurate, rapid, and selective quantitative nuclear magnetic resonance method was developed and validated to assess the purity of IMM-H014, a novel drug for the treatment of metabolic-associated fatty liver disease (MAFLD), and four related substances (impurities I, II, III, and IV). In this study, we obtained spectra of IMM--H014 and related substances in deuterated chloroform using dimethyl terephthalate (DMT) as the internal standard reference. Quantification was performed using the 1H resonance signals at δ 8.13 ppm for DMT and δ 6.5-7.5 ppm for IMM-H014 and its related substances. Several key experimental parameters were investigated and optimized, such as pulse angle and relaxation delay. Methodology validation was conducted based on the International Council for Harmonization guidelines and verified with satisfactory specificity, precision, linearity, accuracy, robustness, and stability. In addition, the calibration results of the samples were consistent with those obtained from the mass balance method. Thus, this research provides a reliable and practical protocol for purity analysis of IMM-H014 and its critical impurities and contributes to subsequent clinical quality control research.

Exploration and Biological Evaluation of 1,3-Diamino-7H-pyrrol[3,2-f]quinazoline Derivatives as Dihydrofolate Reductase Inhibitors.

Dihydrofolate reductase (DHFR), a core enzyme of folate metabolism, plays a crucial role in the biosynthesis of purines and thymidylate for cell proliferation and growth in both prokaryotic and eukaryotic cells. However, the development of new DHFR inhibitors is challenging due to the limited number of scaffolds available for drug development. Hence, we designed and synthesized a new class of DHFR inhibitors with a 1,3-diamino-7H-pyrrol[3,2-f]quinazoline derivative (PQD) structure bearing condensed rings. Compound 6r exhibited therapeutic effects on mouse models of systemic infection and thigh infection caused by methicillin-resistant Staphylococcus aureus (MRSA) ATCC 43300. Moreover, methyl-modified PQD compound 8a showed a strong efficacy in a murine model of breast cancer, which was better than the effects of taxol. The findings showcased in this study highlight the promising capabilities of novel DHFR inhibitors in addressing bacterial infections as well as breast cancer.

Identification and Determination of Impurities in a New Therapeutic Agent for Fatty Liver Disease.

Methyl 7,7'-dimethoxy-5'-(morpholinomethyl)-[4,4'-bibenzo[d][1,3] dioxole]-5-carboxylate methanesulfonate (IMM) is an innovative drug for the treatment of nonalcoholic fatty liver disease (NAFLD) owing to its high efficacy and low toxicity. In this study, five minor impurities (I, II, III, IV, and V) were identified and analyzed using spectroscopic evidence, chemical synthetic methods, and liquid chromatography-tandem mass spectrometry (LC-MS/MS). The impurities included hydrolysates and oxidation by-products extracted from both the drug in its final formulation and during synthesis. Toxicity prediction revealed potential carcinogenicity of impurity V containing an N-oxygen fragment. A reliable and selective HPLC method for the quantitative analysis of impurities I-IV and a sensitive HPLC-MS/MS method for potential genotoxic impurity V were developed and optimized. The methods were validated based on the International Council for Harmonization guidelines. Satisfactory linearity was obtained for the analytes over the range of 0.1-2.0 µg/mL for impurities I-IV and 0.3-30.0 ng/mL for impurity V, and in all cases, the fitting correlation coefficients exceeded 0.999. The obtained limits of detection values were 0.05 ng/mL and 0.005 µg/mL for impurity V and impurities I-IV, respectively. The precision and repeatability of the methods were less than 1.08% and 8.72% for each impurity. The recovery percentages of all impurities were in the range of 91.18%-111.27%, with the relative standard deviation of less than 3.69%. The greenness assessment of the HPLC method and the HPLC-MS/MS method were evaluated by using AGREE software with a score value of 0.72 and 0.68, respectively. The recommended procedures that were accurate, specific, and ecofriendly were applied to the existing active pharmaceutical ingredients of IMM, and they generated satisfactory results.

Development and In Vitro-In Vivo Correlation Evaluation of IMM-H014 Extended-Release Tablets for the Treatment of Fatty Liver Disease.

This study aimed to develop extended-release tablets containing 25 mg IMM-H014, an original drug formulated by a direct powder pressing method based on pharmaceutical-grade hydrophilic matrix polymers such as hydroxypropyl methylcellulose, to establish an in vitro-in vivo correlation (IVIVC) to predict bioavailability. The tablets' mechanical properties and in vitro and in vivo performance were studied. The formulation was optimized using a single-factor experiment and the reproducibility was confirmed. The in vitro dissolution profiles of the tablet were determined in five dissolution media, in which the drug released from the hydrophilic tablets followed the Ritger-Peppas model kinetics in 0.01 N HCl medium for the first 2 h, and in phosphate-buffered saline medium (pH 7.5) for a further 24 h. Accelerated stability studies (40 °C, 75% relative humidity) proved that the optimal formulation was stable for 6 months. The in vivo pharmacokinetics study in beagle dogs showed that compared to the IMM-H014 immediate release preparation, the maximum plasma concentration of the extended-release (ER) preparation was significantly decreased, while the maximum time to peak and mean residence time were significantly prolonged. The relative bioavailability was 97.9% based on the area under curve, indicating that the optimal formulation has an obvious ER profile, and a good IVIVC was established, which could be used to predict in vivo pharmacokinetics based on the formulation composition.

Physical Characterization and Safety Evaluation of Folic Acid-conjugated Mesoporous Silica Nanoparticles Loaded with Rhodojaponin III.

BACKGROUND: Rhodojaponin III (RJ-III), a characteristic diterpene of Rhododendron molle G. Don, has a wide range of pharmacological activities including anti-inflammatory, antihypertensive, and analgesic effects. However, further research and development have been limited because of its intense acute toxicity and poor pharmacokinetic profile. OBJECTIVE: In this study, we propose the construction of folic acid-conjugated mesoporous silica nanoparticles (FA-MSNs) as carriers to deliver RJ-III in an attempt to reduce acute toxicity and improve biomedical applications by prolonging drug release and targeting delivery. METHODS: FA-MSNs were synthesized and characterized. RJ-III was then loaded into FA-MSNs (RJIII@ FA-MSNs), and the in vitro drug release profile was assessed. Subsequently, the RJ-III@FAMSNs' cytotoxicity and targeting efficiency were explored in lipopolysaccharide-activated RAW 264.7 cells, and their acute toxicity was investigated in mice. RESULTS: Spherical FA-MSNs were approximately 122 nm in size. Importantly, the RJ-III@FA-MSNs showed prolonged RJ-III release in vitro. Moreover, in lipopolysaccharide-activated RAW 264.7 cells, RJ-III@FA-MSNs not only reduced the cytotoxicity of RJ-III (P < 0.01), but also showed a good targeting effect from the results of cellular uptake. Additionally, the acute toxicity results demonstrated that RJ-III@FA-MSNs improved the LD50 value of RJ-III in mice by intraperitoneal injection 10-fold. CONCLUSION: This is the first study to use FA-MSNs as carriers of RJ-III to reduce the acute toxicity of RJ-III. The results confirm the potential for targeted delivery of RJ-III in inflammatory cells to enhance efficacy, as well as providing data for future investigations on anti-inflammatory activity.

SAPHO Syndrome with Palmoplantar Pustulosis as the First Manifestation Successfully Treated with Adalimumab.

Introduction: Synovitis-acne-pustulosis-hyperostosis-osteitis (SAPHO) syndrome is an acronym for synovitis, pustulosis, acne, hyperostosis, and osteitis, and clinically manifests as dermatological and musculoskeletal damage. Two major manifestations that co-occur in a single patient are rare. Methods/Results: This literature describes a 44-year-old male affected by SAPHO syndrome, whose first manifestation was palmoplantar pustulosis (PPP). Symptomatic treatments such as anti-inflammatory and analgesics did not work well for him. Adalimumab provided noteworthy improvement in the neck and thoracic back pain improvement after two weeks. The palmoplantar pustules were alleviated after four weeks. Conclusion: The literature on SAPHO syndrome therapy is increasing. Thus, adalimumab is a novel therapeutic agent. This report demonstrates the efficiency of adalimumab in SAPHO syndrome.

Ultrasonic Nebulization-Accelerated Gas-Phase Enrichment Following In Situ Microplasma Desorption for Analysis of Trace Heavy Metals by Optical Emission Spectrometry.

Despite the great potential of microplasma optical emission spectrometry (OES) for on-site analysis, it remains a challenge to achieve the fast, sensitive, batch, and multielement analysis of trace heavy metals in a complex matrix. Herein, a novel ultrasonic nebulization-accelerated gas-phase enrichment (GPE) following in situ microplasma desorption sampling approach is employed for the determination of trace heavy metals by a miniature dielectric barrier discharge (DBD)-OES device. The volatile heavy metal species obtained by hydride generation (HG) can be quickly separated from the complex matrix under the action of ultrasonic nebulization, adsorbed on the surface of the activated carbon electrode tip for GPE, and then in situ desorbed and excited by DBD microplasma to achieve multielement OES analysis. With an array nebulizer plate, a batch of 10 samples can be handled for GPE in 40 s, and DBD-OES analysis is maintained at a rate of 6 s per sample. Under the optimized conditions, the detection limits for simultaneous determinations of Hg, Cd, Cu, and Sn are 0.005, 0.01, 0.03, and 0.04 µg L-1, respectively, and the detection sensitivities are about 164, 157, 132, and 91-fold improved with respect to those of the conventional HG-DBD-OES mode, respectively. The accuracy and practicability are verified by measuring several certified reference materials. This fast GPE plus in situ DBD-OES analysis strategy possesses the features of simple operation, time-savings, and low cost, contributing to volatile species transport, matrix interference elimination, and device miniaturization for field applications.

Evaluating the Performance of Transformer-based Language Models for Neuroatypical Language.

Difficulties with social aspects of language are among the hallmarks of autism spectrum disorder (ASD). These communication differences are thought to contribute to the challenges that adults with ASD experience when seeking employment, underscoring the need for interventions that focus on improving areas of weakness in pragmatic and social language. In this paper, we describe a transformer-based framework for identifying linguistic features associated with social aspects of communication using a corpus of conversations between adults with and without ASD and neurotypical conversational partners produced while engaging in collaborative tasks. While our framework yields strong accuracy overall, performance is significantly worse for the language of participants with ASD, suggesting that they use a more diverse set of strategies for some social linguistic functions. These results, while showing promise for the development of automated language analysis tools to support targeted language interventions for ASD, also reveal weaknesses in the ability of large contextualized language models to model neuroatypical language.

Infrared Single-Frame Small Target Detection Based on Block-Matching.

The robust detection of small targets is one of the crucial techniques in an infrared system. It is still a challenge to detect small targets under complex backgrounds. Aiming at the problem where infrared small target detection is easily disturbed by complex backgrounds, an infrared single frame detection method based on a block-matching approach is proposed in this paper. Firstly, the input infrared image is processed by extracting blocks from it. A new infrared model is constructed by finding blocks that are similar to each such block. Then, the small target detection based on the block-matching model is formulated as an optimization problem of recovering low-rank and sparse matrices, which are effectively solved using robust principal component analysis. Finally, the results of processing are reconstructed to obtain the target and background images. A simple segmentation method is used to segment the target image. The experimental results from the actual infrared sequences show that the proposed method has better background suppression ability under complex backgrounds and better detection performance than conventional baseline methods.

A General Method to Edit Histone H3 Modifications on Chromatin Via Sortase-Mediated Metathesis.

The post-translational modifications (PTMs) on the tail of histone H3 control chromatin structure and influence epigenetics and gene expression. The current chemical methods including unnatural amino acid incorporation and protein splicing enable preparations of the histone with diverse PTMs in cellular contexts, but they are not applicable to edit native chromatin. The manipulation of histone-modifying enzymes alter the endogenous histone PTMs but the lack of specificity of most histone-modifying enzymes prevents precise control of specific H3 tail PTM patterns. Here we report a new method to edit the N-tail of histone H3 via sortase mediated metathesis (SMM). The sortase can install desired PTM patterns into histone H3 on nucleosomes in vitro and in cellulo. This study expands the application scope of sortase from ligation to metathesis in live cells using cell-penetrating peptides (CPPs). In addition, it offers a strategy to edit PTMs of cellular histone H3 with potential for the development of precise epigenome editing.

Rhodojaponin III-Loaded Chitosan Derivatives-Modified Solid Lipid Nanoparticles for Multimodal Antinociceptive Effects in vivo.

Background: Rhodojaponin III (RJ-III) is a bioactive diterpenoid, which is mainly found in Rhododendron molle G. Don (Ericaceae), a potent analgesia in traditional Chinese medicine with several years of clinical applications in the country. However, its clinical use is limited by its acute toxicity and poor pharmacokinetic profiles. To reduce such limitations, the current study incorporated RJ-III into the colloidal drug delivery system of hydroxypropyl trimethyl ammonium chloride chitosan (HACC)-modified solid lipid nanoparticles (SLNs) to improve its sustained release and antinociceptive effects in vivo for oral delivery. Results: The optimized RJ-III@HACC-SLNs were close to spherical, approximately 134 nm in size, and with a positive zeta potential. In vitro experiments showed that RJ-III@HACC-SLNs were stable in the simulated gastric fluid and had a prolonged release in PBS (pH = 6.8). Pharmacokinetic results showed that after intragastric administration in mice, the relative bioavailability of RJ-III@HACC-SLNs was 87.9%. Further, it was evident that the peak time, half-time, and mean retention time of RJ-III@HACC-SLNs were improved than RJ-III after the administration. In addition, pharmacodynamic studies revealed that RJ-III@HACC-SLNs markedly reduced the acetic acid, hot, and formalin-induced nociceptive responses in mice (P < 0.001), and notably increased the analgesic time (P < 0.01). Moreover, RJ-III@HACC-SLNs not only showed good biocompatibility with Caco-2 cells in vitro but its LD50 value was also increased by 1.8-fold as compared with that of RJ-III in vivo. Conclusion: These results demonstrated that RJ-III@HACC-SLNs improved the pharmacokinetic characteristics of the RJ-III, thereby exhibiting toxicity-attenuating potential and antinociceptive enhancing properties. Consequently, HACC-SLNs loaded with RJ-III could become a promising oral formulation for pain management that deserves further investigation in the future.

A rare case of condyloma acuminatum caused by HPV73 and HPV33 infection.

Condyloma acuminatum (CA) is a sexually transmitted disease caused by human papillomavirus (HPV) infection, mainly by HPV DNA types 6 and 11. Except for HPV16 and HPV18, CA caused by other intermediate or high-risk subtypes is rare in clinical settings. Here, we report a case that was positive for HPV73 and 33 and negative for other common subtypes. This case highlights that caution should be taken in cases that are negative for common HPV subtypes but have typical clinical manifestations. That the detection of other subtypes and tissue biopsy should not be ignored.

Cryotherapy combined with photodynamic therapy for successful treatment of condyloma acuminatum in special sites such as the nipple and the nasal vestibule: A series of two case reports.

Condyloma acuminatum is a benign tumor principally resulting from a human papillomavirus type 6 or 11 infection. The lesions mostly damage the genital and perianal squamous epithelium and skin but occasionally emerge outside the perianal and genital regions. We studied the cases of a 29-year-old man with left nasal vestibule vegetation and a 22-year-old woman with left nipple vegetation. Each was diagnosed with condyloma acuminatum by histopathological examination and a human papillomavirus DNA test. The two patients received cryotherapy combined with 5-aminolevulinic acid photodynamic therapy and experienced no relapses during follow-up. These results suggest that physicians cannot ignore condyloma acuminatum outside the perianal and genital regions during diagnosis and treatment. Additionally, cryotherapy combined with 5-aminolevulinic acid photodynamic therapy is not only safe and effective for the treatment of condyloma acuminatum in special sites, but it is also less destructive to the affected regions. Thus, cryotherapy combined with 5-aminolevulinic acid photodynamic therapy may have more advantages than traditional therapy in the treatment of condyloma acuminatum in special sites.

A new option for the treatment of condyloma acuminatum in the male urethra: Multimodal ultrasound image-guided scraping and photodynamic therapy (USP).

OBJECTIVES: Condyloma acuminatum (CA) is a sexually transmitted disease with a high recurrence rate due to the rapid replication of human papillomavirus (HPV) and its subtle immune escape mechanism, which makes the diagnosis and treatment of CA in the male urethra particularly difficult. This study aims to evaluate the efficacy of comprehensive treatments for male urethral CA after accurate localization of warts under ultrasound guidance. METHODS: The study included 15 men with intraurethral CA. Before treatment, the urethra was examined by ultrasonography and HPV-PCR. After examination of the invisible urethral warts, wart curettage (penetrating operation with a special stainless steel medical curettage tool) combined with ALA-PDT was used for treatment. The ultrasound and HPV load were reviewed 1 week after treatment, and again at 1, 3, and 6 months after treatment. RESULTS: All patients achieved satisfactory results 1 week after the last treatment. The viral load of human papilloma was significantly reduced or turned negative, ultrasound imaging exploration showed no neoplasm in the urethra, and no obvious intraoperative or postoperative complications were observed. The side effects in patients included a mild burning or tingling sensation confined to the treated area. After a 6 month follow-up period, only 2 patient relapsed. CONCLUSION: The combined diagnosis and treatment of CA in the male urethra under the guidance of multi-mode ultrasound imaging is an effective, economical, safe, and well-tolerated treatment method.

Evaluation of Rhodojaponin III from Rhododendron molle G. Don on oral antinociceptive activity, mechanism of action, and subacute toxicity in rodents.

ETHNOPHARMACOLOGICAL RELEVANCE: In Chinese traditional medicine, Rhododendron molle G. Don is a recognized herb to ease pain. Rhodojaponin III (RJ-III) has been identified as the main pharmacological activity and toxic component of the herb; however, oral antinociception and mechanism of RJ-III have not yet been investigated. AIM OF THE STUDY: The significance of this study is to evaluate the effects of RJ-III on nociceptive and neuropathic pain, and to preliminarily explore the underlying mechanisms and subacute toxicity. MATERIALS AND METHODS: The antinociception of RJ-III was evaluated by hot plate, tail-immersion, acetic acid writhing, formalin test and chronic constriction injury (CCI) model in rodents. An experimental validation was conducted using whole-cell patch clamp technique based on the most likely mechanisms of action after screening and prediction by molecular docking study. In addition, the oral subacute toxicity of RJ-III was assessed. RESULTS: Behavioral experiments showed that RJ-III (0.20 mg/kg) reduced the latency of the nociceptive response in the hot plate and tail-immersion tests. Acetic acid and formalin-induced pain were significantly inhibited by RJ-III (0.10 and 0.05 mg/kg, respectively). Furthermore, 0.30 mg/kg of RJ-III improved hyperalgesia in the CCI-induced rats. Based on molecular docking results, electrophysiological experiments were used to demonstrate mild inhibition of voltage-gated sodium channel-related subtypes. Additionally, oral subacute toxicity that may cause leukopenia and abnormal liver function requires further attention in subsequent studies. CONCLUSION: RJ-III mildly blocks voltage-gated sodium channel to inhibit nociceptive pain and peripheral neuralgia, but 0.375 mg/kg and above may cause side effect after long-term oral administration.

A concise and efficient total synthetic route of active stilbene dimer (±)-ε-viniferin.

A concise and efficient procedure for the total synthesis of natural stilbene dimer (±)-ε-viniferin was accomplished with high overall yield. Demethylation of the key intermediate methyl 3-arylbenzofuran-4-carboxylate was achieved successfully through bromination followed by BBr3-or BCl3/TBAI-mediated ether cleavage reaction. Pd/C and bromobenzene-catalyzed MOM ether cleavage was successfully carried out to aquire (±)-ε-viniferin.