Association of gut microbiome and metabolites with onset and treatment response of patients with pemphigus vulgaris.

Background: Gut dysbiosis and gut microbiome-derived metabolites have been implicated in both disease onset and treatment response, but this has been rarely demonstrated in pemphigus vulgaris (PV). Here, we aim to systematically characterize the gut microbiome to assess the specific microbial species and metabolites associated with PV. Methods: We enrolled 60 PV patients and 19 matched healthy family members, and collected 100 fecal samples (60 treatment-naïve, 21 matched post-treatment, and 19 controls). Metagenomic shotgun sequencing and subsequent quality control/alignment/annotation were performed to assess the composition and microbial species, in order to establish the association between gut microbiome with PV onset and treatment response. In addition, we evaluated short-chain fatty acids (SCFAs) in PV patients through targeted metabolomics analysis. Results: The diversity of the gut microbiome in PV patients deviates from the healthy family members but not between responder and non-responder, or before and after glucocorticoid treatment. However, the relative abundance of several microbial species, including the pathogenic bacteria (e.g., Escherichia coli) and some SCFA-producing probiotics (e.g., Eubacterium ventriosum), consistently differed between the two groups in each comparison. Escherichia coli was enriched in PV patients and significantly decreased after treatment in responders. In contrast, Eubacterium ventriosum was enriched in healthy family members and significantly increased particularly in responders after treatment. Consistently, several gut microbiome-derived SCFAs were enriched in healthy family members and significantly increased after treatment (e.g., butyric acid and valeric acid). Conclusions: This study supports the association between the gut microbiome and PV onset, possibly through disrupting the balance of gut pathogenic bacteria and probiotics and influencing the level of gut microbiome-derived SCFAs. Furthermore, we revealed the potential relationship between specific microbial species and glucocorticoid treatment.

Iridoid from Eucommia ulmoides Oliv. Exerts Antiarthritis Effects by Inhibiting the JAK2/STAT3 Signaling Pathway In Vivo and In Vitro.

The purpose of this study was to investigate the anti-inflammatory effects of EU-Idd both in vivo and in vitro. In vivo, we used the collagen-induced arthritis (CIA) rat model to investigate the efficacy of EU-Idd on rheumatoid arthritis. Hematoxylin-eosin staining and Safranin O-fast green staining were used to evaluate the pathological status of the ankle joints in CIA rats. Micro-CT scanning was used to investigate bone erosion of the ankle joints. In vitro, the effect of EU-Idd on Th17 cell differentiation was identified by flow cytometry. TRAP staining was used to detect osteoclast cells. HFLS-RA model cells, induced by tumor necrosis factor-α(TNF-α), were used to evaluate the anti-inflammatory effects of EU-Idd while the levels of related inflammatory cytokines and JAK2/STAT3 proteins were detected by RT-qPCR and western blotting. EU-Idd alleviated joint inflammation in CIA rats and exerted protective effects on the ankle joints. EU-Idd also prevented the differentiation of CD4+ T cells into Th17 cells, reduced the number of osteoclasts, and improved the expression levels of bone metabolism-related proteins including OPG and RANKL. Moreover, EU-Idd inhibited the invasion and migration of HFLS-RA cells and downregulated the expression of related inflammatory cytokine genes and the protein expression levels of p-JAK2 and p-STAT3, both in vivo and in vitro. EU-Idd exerts anti-inflammatory and osteoprotective effects by regulating the JAK2/STAT3 pathway in rheumatoid arthritis. These results are beneficial to excavate new pharmaceutical ingredients for rheumatoid arthritis from iridoid.

Single-cell sequencing of immune cells after marathon and symptom-limited cardiopulmonary exercise.

Vigorous-intensity leisure-time physical activity, such as marathon, has become increasingly popular, but its effect on immune functions and health is poorly understood. Here, we performed scRNA-seq analysis of peripheral blood mononuclear cells (PBMCs) after a bout of symptom-limited cardiopulmonary exercise (CPX) test or marathon. Time-series single-cell analysis revealed the detailed series of landscapes of immune cells in response to short and long vigorous-intensity activities. Reduction of effective T cells was observed with the cell migration and motility pathways enriched in circulation following marathon. Baseline values of PBMCs abundance were reached around 1 h after CPX and 24 h following marathon, but longer time was required for expression recovery of cytotoxicity genes. The ratio of effector/naive T cells was found to change uniformly among the participants and could serve as a better indicator for exercise intensity than the CD4+/CD8+ T cell ratio. Moreover, we identified time-dependent monocyte state transitions after marathon.

Association between methionine sulfoxide and risk of moyamoya disease.

Objective: Methionine sulfoxide (MetO) has been identified as a risk factor for vascular diseases and was considered as an important indicator of oxidative stress. However, the effects of MetO and its association with moyamoya disease (MMD) remained unclear. Therefore, we performed this study to evaluate the association between serum MetO levels and the risk of MMD and its subtypes. Methods: We eventually included consecutive 353 MMD patients and 88 healthy controls (HCs) with complete data from September 2020 to December 2021 in our analyzes. Serum levels of MetO were quantified using liquid chromatography-mass spectrometry (LC-MS) analysis. We evaluated the role of MetO in MMD using logistic regression models and confirmed by receiver-operating characteristic (ROC) curves and area under curve (AUC) values. Results: We found that the levels of MetO were significantly higher in MMD and its subtypes than in HCs (p < 0.001 for all). After adjusting for traditional risk factors, serum MetO levels were significantly associated with the risk of MMD and its subtypes (p < 0.001 for all). We further divided the MetO levels into low and high groups, and the high MetO level was significantly associated with the risk of MMD and its subtypes (p < 0.05 for all). When MetO levels were assessed as quartiles, we found that the third (Q3) and fourth (Q4) MetO quartiles had a significantly increased risk of MMD compared with the lowest quartile (Q3, OR: 2.323, 95%CI: 1.088-4.959, p = 0.029; Q4, OR: 5.559, 95%CI: 2.088-14.805, p = 0.001). Conclusion: In this study, we found that a high level of serum MetO was associated with an increased risk of MMD and its subtypes. Our study raised a novel perspective on the pathogenesis of MMD and suggested potential therapeutic targets.

Therapeutics of Charcot neuroarthropathy and pharmacological mechanisms: A bone metabolism perspective.

Charcot neuroarthropathy (CN) is a chronic, destructive, and painless damage of the skeletal system that affects the life quality of patients. CN, with an unclear mechanism, is characterized with invasive destruction of bones and a serious abnormality of bone metabolism. Unfortunately, development of an effective prevention and treatment strategy for CN is still a great challenge. Of note, recent studies providing an insight into the molecular mechanisms of bone metabolism and homeostasis have propelled development of novel CN therapeutic strategies. Therefore, this review aims to shed light on the pathogenesis, diagnosis, and treatment of CN. In particular, we highlight the eminent role of the osteoprotegerin (OPG)-receptor activator of nuclear factor-κB (RANK)-RANK ligand (RANKL) system in the development of CN. Furthermore, we summarize and discuss the diagnostic biomarkers of CN as well as the potential pharmacological mechanisms of current treatment regimens from the perspective of bone metabolism. We believe that this review will enhance the current state of knowledge on the diagnosis, prevention, and therapeutic efficacy of CN.

Effects of Deep Hyperthermia Combined with Intraperitoneal Chemotherapy on Liver-Kidney Function, Immune Function, and Long-Term Survival in Patients with Abdominal Metastases.

Objectives: To analyze the effects of deep hyperthermia combined with intraperitoneal chemotherapy on liver-kidney function, immune function, and long-term survival in patients with abdominal metastases. Methods: A total of 88 patients with abdominal metastases confirmed in the hospital were enrolled as the research objects between August 2018 and August 2021. They were randomly divided into control group (n = 44) and observation group (n = 44). The control group was treated with intraperitoneal chemotherapy, while observation group was additionally treated with deep hyperthermia. The general clinical data of patients were recorded. The short-term and long-term curative effects were evaluated. The occurrence of side effects in both groups was recorded. Before and after treatment, levels of alanine transaminase (ALT) and aspartate transaminase (AST) were detected by full-automatic biochemical analyzer. The level of blood urea nitrogen (BUN) was detected by the urease electrode method. The level of serum creatinine (Scr) was detected by the picric acid method. The levels of CD3 +, CD4 +, CD8 +, and NK cells were detected by BD FACSCalibur flow cytometer. Results: There was no significant difference in clinical data between the two groups (P > 0.05). In the observation group, ORR was significantly higher than that in the control group (54.55% vs 29.55%) (P < 0.05), OS was significantly longer than that in the control group (P < 0.05), and median survival time and mPFS were longer than those in the control group. After treatment, the levels of ALT, AST, BUN, and Scr were significantly increased in the control group (P < 0.05), but there was no significant difference in peripheral blood CD3 +, CD4 +, and CD4 +/CD8 + ratio or count of NK cells before and after treatment (P > 0.05). Before and after treatment, there was no significant difference in the levels of ALT, AST, BUN, and Scr in the observation group (P > 0.05). After treatment, peripheral blood CD3 +, CD4 +, and CD4 +/CD8 + ratio and count of NK cells were all increased in the observation group, significantly higher than those in the control group (P < 0.05). The incidence of chemotherapy side effects in the observation group was significantly lower than that in the control group (P < 0.05). Conclusion: The short-term and long-term curative effects of deep hyperthermia combined with intraperitoneal chemotherapy are good on patients with intraperitoneal metastases, with less damage to liver-kidney function. It is beneficial to enhance immune function of patients, with mild side effects.

Increasing Nonfossil Fuel Contributions to Atmospheric Nitrate in Urban China from Observation to Prediction.

China's nitrogen oxide (NOx) emissions have undergone significant changes over the past few decades. However, nonfossil fuel NOx emissions are not yet well constrained in urban environments, resulting in a substantial underestimation of their importance relative to the known fossil fuel NOx emissions. We developed an approach using machine learning that is accurate enough to generate a long time series of the nitrogen isotopic composition (δ15N) of atmospheric nitrate using high-level accuracies of air pollutants and meteorology data. Air temperature was found to be the critical driver of the variation of nitrate δ15N at daily resolution based on this approach, while significant reductions of aerosol and its precursor emissions played a key role in the change of nitrate δ15N on the yearly scale. Predictions from this model found a significant decrease in nitrate δ15N in Chinese megacities (Beijing and Guangzhou as representative cities in the north and south, respectively) since 2013, implying an enhanced contribution of nonfossil fuel NOx emissions to nitrate aerosols (up to 22%-26% in 2021 from 18%-22% in 2013 quantified by an isotope mixing model), as confirmed by the Weather Research and Forecasting model coupled with online chemistry (WRF-Chem) simulation. Meanwhile, the declining contribution in coal combustion (34%-39% in 2013 to 31%-34% in 2021) and increasing contribution of natural gas combustion (11%-14% in 2013 to 14%-17% in 2021) demonstrated the transformation of China's energy structure from coal to natural gas. This approach provides missing records for exploring long-term variability in the nitrogen isotope system and may contribute to the study of the global reactive nitrogen biogeochemical cycle.

Prevalence of Reversed Genome Organizations for Viruses in the Family Iflaviridae, Order Picornavirales.

Viruses in the order Picornavirales possess a positive-strand RNA genome that encodes structural proteins (SPs) and nonstructural proteins (NSPs). According to the recent report of the International Committee on Taxonomy of Viruses (ICTV), there are 8 families in Picornavirales, and monopartite picornaviruses in each family exhibit distinct types of genome organizations with rearranged genes coding for SPs and NSPs, namely, TypeI (5'-SPs-NSPs-3') and TypeII (5'-NSPs-SPs-3'). In the present study, 2 iflaviruses with the 2 genome types were unexpectedly identified in a damselfly host species, suggesting that these 2 genome types coexisted in the same host species, and the families of order Picornavirales might be more complex than previously thought. The consequent systematic homologous screening with all the publicly available picornaviruses successfully revealed a considerable number of candidates rearranged genome types of picornaviruses in various families of Picornavirales. Subsequently, phylogenetic trees were reconstructed based on RNA dependent RNA polymerase and coat protein, which evidently confirmed the prevalence of the 10 typeII iflaviruses in the Iflaviridae family. This suggests that genome types may not be relevant to viral taxonomy in this family. However, candidate picornaviruses with reversed genome types in the Secoviridae and Dicistroviridae families require further investigation. All in all, as the number of newly discovered viruses increases, more viruses with non-canonical genome arrangements will be uncovered, which can expand our current knowledge on the genome complexity and evolution of picornaviruses. IMPORTANCE Monopartite viruses in the order Picornavirales exhibit distinct genome arrangement of nonstructural proteins and structural proteins for each of the 8 families. Recent studies indicated that at least 4 ifla-like viruses possessed reversed genome organization in the family Iflaviridae, raising the possibility that this phenomenon may commonly present in different families of picornaviruses. Since we discovered 2 iflaviruses with exchanged structural and nonstructural proteins simultaneously in the damselfly, a systematic screening was subsequently performed for all of the current available picornaviruses (1,543 candidates). The results revealed 10 picornaviruses with reversed genome organization in the family Iflaviridae, implying that this phenomenon might prevalence in the order Picornavirales. These results will contribute to a better understanding for the future study on the genome complexity and taxonomy of picornaviruses.

Setmelanotide optimization through fragment-growing, molecular docking in-silico method targeting MC4 receptor.

Obesity has emerged as a global issue, but with the complex structures of multiple related important targets and their agonists or antagonists determined, the mechanism of ligand-protein interaction may offer new chances for developing new generation agonists anti-obesity. Based on the molecule surface of the cryo-EM protein structure 7AUE, we tried to replace D-Ala3 with D-Met in setmelanotide as the linker site for fragment-growing with De novo evolution. The simulation results indicate that the derivatives could improve the binding abilities with the melanocortin 4 receptor and the selectivity over the melanocortin 1 receptor. The improved selectivity of the newly designed derivatives is mainly due to the shape difference of the molecular surface at the orthosteric peptide-binding pocket between melanocortin 4 receptor and melanocortin 1 receptor. The new extended fragments could not only enhance the binding affinities but also function as a gripper to seize the pore, making it easier to balance and stabilize the other component of the new derivatives. Although it is challenging to synthesize the compounds designed in silico, this study may perhaps serve as a trigger for additional anti-obesity research.Communicated by Ramaswamy H. Sarma.

Database Construction of Two-Dimensional Charged Building Blocks for Functional-Oriented Material Design.

Databases for charge-neutral two-dimensional (2D) building blocks (BBs), i.e., 2D materials, have been built for years due to their applications in nanoelectronics. Though lots of solids are constructed from charged 2DBBs, a database for them is still missing. Here, we identify 1028 charged 2DBBs from Materials Project database using a topological-scaling algorithm. These BBs host versatile functionalities including superconductivity, magnetism, and topological properties. We construct layered materials by assembling these BBs considering valence state and lattice mismatch and predict 353 stable layered materials by high-throughput density functional theory calculations. These materials can not only inherit their functionalities but also show enhanced/emergent properties compared with their parent materials: CaAlSiF displays superconducting transition temperature higher than NaAlSi; Na2CuIO6 shows bipolar ferromagnetic semiconductivity and anomalous valley Hall effect that are absent in KCuIO6; LaRhGeO possesses nontrivial band topology. This database expands the design space of functional materials for fundamental research and potential applications.

Effects of different external factors on urban roadside plants for the reduction of airborne fine particulate matters.

With the progress of urbanization and industrialization in China, the consumption of fossil fuels blows up. The burning of fossil fuels releases large amounts of particulate matter, leads to smog, and the air quality is gradually getting worsen. Previous studies have shown that vegetation can effectively reduce airborne particles with different size fractions. And large amounts of previous studies pointed to the adsorption ability of urban forest for particles larger than 2.5 µm. The capacity of roadside plants for the capture of fine particles, especially for those smaller than 2.5 µm has been rarely reported. In this study, five external factors including leaf orientation, leaf height, planting location, planting form, and pollution concentration were tested to evaluate their impact on the dust retention capacity of different roadside plants. The results indicate that significant interspecies was found between tested plant species, and with the change of different external factors, the capturing capacity for the same roadside plants varied. The change of leaf orientation has limited effects on the amount of captured fine particles for the tested plants. While, the amount of captured particulate matter by leaves was inversely proportional to its growth height. Plants locating in the central of the road showed significantly higher capturing capacity than they, when they was set alongside the road. The total amount of captured fine particle by Ligustrum japonicum locating in the central green belt of road was about 5 times higher than it when it was planted in the green belt alongside the road. In addition, the correlation between the capturing capacity of roadside plants and its distance to the street curb was found to be negative.

Plants have been widely accepted as an environmentally friendly air particulate filter that can effectively remove fine particulate matter which can be harmful to humans. By analyzing the dust retention of plant leaves, this paper discussed the influence of different factors such as traffic pressure, planting position, and leaf orientation on the capture ability of roadside plants, in addition, we investigated particulate matter with a smaller size (PM_0.22). The mainly objective of this study is to investigate the factors affecting the dust retention efficiency of roadside plants and roadside plants as phytoremediation to improve city air quality which consists with the purpose of the journal.

Expression of Tryptophan Metabolism Enzymes in Patients with Diffuse Large B-cell Lymphoma and NK/T-cell Lymphoma.

BACKGROUND: Metabolites of tryptophan (Trp) metabolism in the tumor microenvironment play crucial immunosuppressive roles in various cancers. However, the role of Trp metabolism in diffuse large B-cell lymphoma (DLBCL) or natural killer/T-cell lymphoma (NK/TCL) remains unelucidated. METHODS: We investigated the potential role of Trp metabolism in a cohort of 43 patients with DLBCL and 23 with NK/TCL. We constructed tissue microarrays and performed in situ staining of Trp-catabolizing enzymes and PD-L1 using immunohistochemistry (IHC). RESULTS: We observed 14.0% positive staining of IDO1 in DCBCL and 60.9% in NK/TCL; 55.8% of IDO2 in DCBCL and 95.7% in NK/TCL; 79.1% of TDO2 in DCBCL and 43.5% in NK/TCL; 29.7% of IL4I1 in DCBCL and 39.1% in NK/TCL. However, IDO1, IDO2, TDO2, and IL4I1 positivity did not significantly differ between PD-L1+ and PD-L1- biopsy tissue samples of NK/TCL; nonetheless, a positive correlation of IDO1 (r = 0.87, p < 0.001), IDO2 (r = 0.70, p < 0.001), TDO2 (r = 0.63, p < 0.001), and IL4I1 (r = 0.53, p < 0.05) with PD-L1 expression was observed in the TCGA-DLBCL dataset. Finally, immunohistochemical (IHC) analysis revealed the lack of superior prognostic effect with higher expression of Trp enzymes in DLBCL and NK/TCL. Furthermore, IDO1, IDO2, TDO2, and IL4I1 expression, as well as survival rates, did not significantly differ across all groups in the TCGA-DLBCL cohort. CONCLUSION: Collectively, our findings provide novel insights into the enzymes involved in Trp metabolism in DLBCL and NK/TCL and their association with PD-L1 expression, which offers potential strategies to combine Trp-metabolism enzyme inhibitors with anti-PD-L1 or other immunotherapeutic strategies in clinical DLBCL or NK/TCL treatment.

Epstein-Barr virus immediate-early protein Zta mediates the proliferation and migration of HER2-overexpressing cancer cells.

Epstein-Barr virus immediate-early protein Zta plays an active role in altering cellular gene expression, which may be fundamentally linked to the viral life cycle, cell cycle, cell growth, and differentiation. HER2 is associated with a wide variety of human cancers, and its knockdown significantly reverses the malignant features of HER2-positive cancers. The aim of this study was to investigate the potential role of Zta in regulating HER2 expression and phenotype changes of MDA-MB-453 cells. Our results indicate that ectopic expression of Zta resulted in downregulation of the HER2 protein in cancer cells (MDA-MB-453, SKBR-3, BT474, and SKOV-3). The Zta protein significantly decreased HER2 mRNA and protein expression in MDA-MB-453 cells in a dose-dependent manner. Mechanistically, Zta recognized and targeted the promoter of HER2 gene, reducing the transcriptional activity of the HER2 gene. Zta induced G0/G1 arrest of MDA-MB-453 cells, inhibiting their proliferation and migration activity. These data suggest that Zta may act as a transforming suppressor of the HER2 gene.

Quantitative structural analysis of hemifacial microsomia mandibles in different age groups.

Introduction: This study aims to quantitively analyze mandibular ramus and body deformities, assessing the asymmetry and progression in different components. Methods: This is a retrospective study on hemifacial microsomia children. They were divided into mild/severe groups by Pruzansky-Kaban classification and into three age groups (<1 year,1-5 years, 6-12 years old). Linear and volumetric measurements of the ramus and the body were collected via their preoperative imaging data to compare between the different sides and severities, using independent and paired tests, respectively. The progression of asymmetry was assessed by changes in affected/contralateral ratios with age using multi-group comparisons. Results: Two hundred and ten unilateral cases were studied. Generally, the affected ramus and body were significantly smaller than those on the contralateral side. Linear measurements on the affected side were shorter in the severe group. Regarding affected/contralateral ratios, the body was less affected than the ramus. Progressively decreased affected/contralateral ratios of body length, dentate segment volume, and hemimandible volume were found. Discussion: There were asymmetries in mandibular ramus and body regions, which involved the ramus more. A significant contribution to progressive asymmetry from the body suggests treatment focus in this region.

Prevalence and Procedural Risk of Intracranial Atherosclerotic Stenosis Coexisting With Unruptured Intracranial Aneurysm.

BACKGROUND: Coexistence of intracranial atherosclerotic stenosis (ICAS) and unruptured intracranial aneurysms (UIAs) is increasingly encountered in clinical practice. This study aims to determine the prevalence of ICAS in patients with UIAs and procedural ischemic risk associated with ICAS when treating UIAs. METHODS: Based on the CAIASA study (Coexistence of Atherosclerotic Intracranial Arterial Stenosis With Intracranial Aneurysms), we prospectively included patients undergoing treatment procedures for UIAs from October 2015 to December 2020 at Beijing Tiantan Hospital, China. We used computed tomography angiography or digital subtraction angiography to diagnose ICAS (stenosis≥50%). Multivariable logistic regression and propensity-score matching were performed to evaluate the risk of procedure-related ischemic stroke and unfavorable outcome associated with ICAS. The ICAS score was used to explore the association between different burden of ICAS and procedure-related ischemic risk. RESULTS: Among 3949 patients who underwent endovascular or open surgical procedures for UIAs, 245 (6.2%) had ICAS. After exclusion, 15.7% (32/204) of patients with ICAS experienced procedure-related ischemic stroke compared with 5.0% (141/2825) of patients without ICAS. From the unmatched and matched cohort, ICAS was significantly associated with increased risk of procedure-related ischemic stroke (unmatched: adjusted odds ratio=3.11 [1.89-5.11]; and matched: adjusted odds ratio=2.99 [1.38-6.48]). This association became more evident among patients not receiving antiplatelet therapy (Pinteraction=0.022). For patients undergoing different treatment modalities, similar increased risks were observed (clipping: adjusted odds ratio=3.43 [1.73-6.79]; and coiling: adjusted odds ratio=3.59 [1.94-6.65]). Higher ICAS score was correlated with higher procedural ischemic risk (Ptrend<0.001). CONCLUSIONS: The occurrence of ICAS is not infrequent in patients with UIAs. ICAS confers an ~2-fold increased procedural ischemic risk, irrespective of clipping or coiling. Previous antiplatelet therapy may decrease the risk. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02795078.

High-Dispersive Pd Nanoparticles on Hierarchical N-Doped Carbon Nanocages to Boost Electrochemical Co2 Reduction to Formate at Low Potential.

Electrochemical CO2 reduction reaction (CO2 RR) to value-added chemicals/fuels is an effective strategy to achieve the carbon neutral. Palladium is the only metal to selectively produce formate via CO2 RR at near-zero potentials. To reduce cost and improve activity, the high-dispersive Pd nanoparticles on hierarchical N-doped carbon nanocages (Pd/hNCNCs) are constructed by regulating pH in microwave-assisted ethylene glycol reduction. The optimal catalyst exhibits high formate Faradaic efficiency of >95% within -0.05-0.30 V and delivers an ultrahigh formate partial current density of 10.3 mA cm-2 at the low potential of -0.25 V. The high performance of Pd/hNCNCs is attributed to the small size of uniform Pd nanoparticles, the optimized intermediates adsorption/desorption on modified Pd by N-doped support, and the promoted mass/charge transfer kinetics arising from the hierarchical structure of hNCNCs. This study sheds light on the rational design of high-efficient electrocatalysts for advanced energy conversion.

Synthesis of a versatile 1H-indene-3-carboxylate scaffold enabled by visible-light promoted Wolff rearrangement of 1-diazonaphthalen-2(1H)-ones.

Herein, we have developed a sequential visible-light-promoted Wolff rearrangement of 1-diazonaphthalen-2(1H)-ones, followed by capturing the in situ generated ketene intermediates with various alcohols, producing diverse 1H-indene-3-carboxylates in moderate to good yields under mild reaction conditions. The broad substrate scope, high functional group tolerance, and robust conditions make the resulting derivative a versatile platform for the synthesis of plenty of bioactive molecules.

The value of CT-based energy imaging to discriminate dominant side lesions in primary aldosteronism.

Purpose: The current clinical discrimination of the dominant side of primary aldosteronism (PA) mainly relies on invasive adrenal venous sampling (AVS) examination. This study investigated the feasibility of dual-energy CT energy imaging parameters as a novel biomarker in identifying bilateral adrenal dominant lesions. Methods: Fifty PA patients with bilateral lesions who underwent CT and AVS of the adrenal glands at Shaanxi Provincial People's Hospital from October 2019 to June 2021 were retrospectively analyzed. Forty-eight patients had successful bilateral blood collection and two failed right-sided blood collection due to venous variation. Forty patients who were classified based on AVS underwent unilateral adrenalectomy and pathological findings confirmed adenoma in all cases. Quantitative dual-energy CT parameters were measured for all adrenal lesions, and the differences in dual-energy CT energy spectrum imaging parameters between the dominant and nondominant adrenal lesions were compared. Results: Among forty-eight PA patients with bilateral lesions, forty patients with preoperative AVS-determined lesions on the dominant side underwent unilateral adrenalectomy, and eight patients without the dominant side were treated with medication. The iodine concentration difference (ICD) in the arteriovenous phase was more significant in the 40 cases of primary aldosteronism with dominant adrenal lesions than in the nondominant adrenal lesions (1.18 ± 0.45 vs 0.41 ± 0.42). The NICAP was higher in the dominant adrenal lesions than in the non-dominant lesions (0.39 ± 0.39 vs 0.14 ± 0.05). The sensitivity and specificity of the diagnosis of the dominant adrenal lesion were 88.2% and 82.4% using the ICD of 0.68 as the threshold value. Conclusion: Conventional CT has lower diagnostic value for dominant adrenal lesions, and CT-based energy imaging can be a new assessment method as a complement to AVS in identifying bilateral dominant adrenal lesions.

Preparation and Evaluation of Liposomes Containing Ethanol and Propylene Glycol as Carriers for Nicotine.

BACKGROUND: Nicotine is a fat-soluble substance that is easily absorbed through the skin and mucosal tissues of the human body. However, its properties, such as light exposure, heat decomposition, and volatilization, restrict its development and application in external preparations. OBJECTIVE: This study focused on the preparation of stable nicotine-encapsulated ethosomes. METHODS: During their preparation, two water-phase miscible osmotic promoters, ethanol and propylene glycol (PG), were added to obtain a stable transdermal delivery system. Skin nicotine delivery was enhanced through the synergistic action of osmotic promoters and phosphatidylcholine in binary ethosomes. Various characteristics of the binary ethosomes were measured, including the vesicle size, particle size distribution, and zeta potential. In order to optimize the ratio of ethanol and PG, the skin permeability test was performed on mice in vitro in a Franz diffusion cell to compare cumulative skin permeabilities. The penetration depth and fluorescence intensity of rhodamine-B-entrapped vesicles in isolated mouse skin samples were observed using laser confocal scanning microscopy. RESULTS: When ethanol:PG was used in a ratio of 5:5 (w/w), binary ethosomes were found to be the most stable, had the highest encapsulation rate (86.13±1.40), smallest particle size (106.0±11.0) nm, maximum transdermal depth (180 µm), and maximum fluorescence intensity (160 AU). Nicotine-encapsulated ethosomes (ethanol: PG=5:5, w/w) were an efficient and stable transdermal delivery system. CONCLUSION: The nicotine-encapsulated ethosomes containing ethanol and PG are considered to be safe and reliable as a transdermal administration agent, which does not irritate the skin.