Magnetic-free polarization rotation in an atomic vapor cell.

Magnetic-free nonreciprocal optical devices have attracted great attention in recent years. Here, we investigated the magnetic-free polarization rotation of light in an atom vapor cell. Two mechanisms of magnetic-free nonreciprocity have been realized in ensembles of hot atoms, including electromagnetically induced transparency and optically-induced magnetization. For a linearly polarized input probe light, a rotation angle up to 86.4° has been realized with external control and pump laser powers of 10 mW and is mainly attributed to the optically-induced magnetization effect. Our demonstration offers a new approach to realize nonreciprocal devices, which can be applied to solid-state atom ensembles and may be useful in photonic integrated circuits.

Endoscopic combined intrarenal surgery composed of micro-perc and retrograde intrarenal surgery in the treatment of complex kidney stones in children.

OBJECTIVE: This research aims to explore the efficiency and safety of endoscopic combined intrarenal surgery (Micro-ECIRS) composed of micro-percutaneous nephrolithotomy (Micro-perc) and retrograde intrarenal surgery (RIRS) in the Galdakao-modified supine Valdivia (GMSV) position for a single session for the treatment of complex nephrolithiasis in children. MATERIALS AND METHODS: This study retrospectively reviewed patients aged < 18 years who underwent Micro-ECIRS in the GMSV position for renal stones larger than 2 cm under ultrasound guidance between August 2020 to May 2022 at our institution. RESULTS: A total of 13 patients (8 males and 5 females) received Micro-ECIRS for renal stones under ultrasound guidancewhile adopting the GMSV position. The average stone size was 2.7 cm (range: 2.1-3.7 cm). Among them, 6 patients had left kidney stones, 5 patients had right kidney stones, and 2 patients had bilateral kidney stones. The mean operative time was 70.5 min (range: 54-93 min). The mean hospital stay was 6.4 days (range: 4-9 days). The mean hemoglobin decrease was 8.2 g/L (range: 5.1-12.4 g/L). The total number of kidneys that had complete stone clearance was 8 kidneys at 48 h postoperatively, 11 kidneys at 2 weeks postoperatively, and 14 kidneys at 1 month postoperatively. CONCLUSION: Our results demonstrate that Micro-ECIRS while patients are in the GMSV position is a safe and effective method for the treatment of complex children nephrolithiasis. However, all children made three hospital visits and received anesthesia three times. Further research is needed to confirm these findings.

Formation of Supernarrow Borophene Nanoribbons.

Borophenes have sparked considerable interest owing to their fascinating physical characteristics and diverse polymorphism. However, borophene nanoribbons (BNRs) with widths less than 2 nm have not been achieved. Herein, we report the experimental realization of supernarrow BNRs. Combining scanning tunneling microscopy imaging with density functional theory modeling and ab initio molecular dynamics simulations, we demonstrate that, under the applied growth conditions, boron atoms can penetrate the outermost layer of Au(111) and form BNRs composed of a pair of zigzag (2,2) boron rows. The BNRs have a width self-contained to ∼1 nm and dipoles at the edges to keep them separated. They are embedded in the outermost Au layer and shielded on top by the evacuated Au atoms, free of the need for post-passivation. Scanning tunneling spectroscopy reveals distinct edge states, primarily attributed to the localized spin at the BNRs' zigzag edges. This work adds a new member to the boron material family and introduces a new physical feature to borophenes.

Anisotropic Growth of One-Dimensional Carbides in Single-Walled Carbon Nanotubes with Strong Interaction for Catalysis.

Tungsten and molybdenum carbides have shown great potential in catalysis and superconductivity. However, the synthesis of ultrathin W/Mo carbides with a controlled dimension and unique structure is still difficult. Here, inspired by the host-guest assembly strategy with single-walled carbon nanotubes (SWCNTs) as a transparent template, we reported the synthesis of ultrathin (0.8-2.0 nm) W2C and Mo2C nanowires confined in SWCNTs deriving from the encapsulated W/Mo polyoxometalate clusters. The atom-resolved electron microscope combined with spectroscopy and theoretical calculations revealed that the strong interaction between the highly carbophilic W/Mo and SWCNT resulted in the anisotropic growth of carbide nanowires along a specific crystal direction, accompanied by lattice strain and electron donation to the SWCNTs. The SWCNT template endowed carbides with resistance to H2O corrosion. Different from normal modification on the outer surface of SWCNTs, such M2C@SWCNTs (M = W, Mo) provided a delocalized and electron-enriched SWCNT surface to uniformly construct the negatively charged Pd catalyst, which was demonstrated to inhibit the formation of active PdHx hydride and thus achieve highly selective semihydrogenation of a series of alkynes. This work could provide a nondestructive way to design the electron-delocalized SWCNT surface and expand the methodology in synthesizing unusual 1D ultrathin carbophilic-metal nanowires (e.g., TaC, NbC, ß-W) with precise control of the anisotropy in SWCNT arrays.

Single-center experience of micro-perc in the treatment of children with 1.0-2.0 cm sized kidney stones in the Galdakao-modified supine Valdivia position.

OBJECTIVE: We aimed to explore the applicability and safety of micro-percutaneous nephrolithotomy (micro-perc) in the treatment of children with kidney stones in the Galdakao-modified supine Valdivia (GMSV) position under the guidance of whole-course ultrasound. MATERIALS AND METHODS: Patients were aged < 18 years in the GMSV position who underwent micro-perc for kidney stones under ultrasound guidance between August 2020 and May 2022 at our institution were reviewed retrospectively. RESULTS: A total of 23 patients, 15 males and 8 females, received micro-perc. The average stone size was 1.6 cm (range 1.1-2.0 cm). Among them, 12 patients had left kidney stones, 10 patients had right kidney stones, and 1 patient had bilateral kidney stones. The mean operative time was 55.3 min (range 35-86 min). The mean hospital stay was 2.9 days (range 2-4 days). The mean hemoglobin decrease was 1.7 g/L (range 0.9-3.2 g/L). A total of 17 patients had complete stone clearance at 48 h postoperatively. A total of 22 patients had complete stone clearance at 2 weeks postoperatively. CONCLUSION: Our results demonstrate that micro-perc under ultrasound guidance is a safe and effective method for the treatment of children with kidney stones in the GMSV position. Further research is warranted to confirm these results.

Aldh inhibitor restores auditory function in a mouse model of human deafness.

Genetic hearing loss is a common health problem with no effective therapy currently available. DFNA15, caused by mutations of the transcription factor POU4F3, is one of the most common forms of autosomal dominant non-syndromic deafness. In this study, we established a novel mouse model of the human DFNA15 deafness, with a Pou4f3 gene mutation (Pou4f3Δ) identical to that found in a familial case of DFNA15. The Pou4f3(Δ/+) mice suffered progressive deafness in a similar manner to the DFNA15 patients. Hair cells in the Pou4f3(Δ/+) cochlea displayed significant stereociliary and mitochondrial pathologies, with apparent loss of outer hair cells. Progression of hearing and outer hair cell loss of the Pou4f3(Δ/+) mice was significantly modified by other genetic and environmental factors. Using Pou4f3(-/+) heterozygous knockout mice, we also showed that DFNA15 is likely caused by haploinsufficiency of the Pou4f3 gene. Importantly, inhibition of retinoic acid signaling by the aldehyde dehydrogenase (Aldh) and retinoic acid receptor inhibitors promoted Pou4f3 expression in the cochlear tissue and suppressed the progression of hearing loss in the mutant mice. These data demonstrate Pou4f3 haploinsufficiency as the main underlying cause of human DFNA15 deafness and highlight the therapeutic potential of Aldh inhibitors for treatment of progressive hearing loss.

Joint effects of temperature and copper exposure on developmental and gene-expression responses of the marine copepod Tigriopus japonicus.

There is growing contamination of copper (Cu) in the marine environment, particularly after the ban of organotin compounds and the increase of the use of Cu-based antifouling paints. Although there are increasing research interests in temperature-dependent chemical toxicity to aquatic organisms, most existing studies focused on acute impacts of chemicals at high concentrations. This study aimed to investigate the interacting effect of temperature and copper exposure at environmentally relevant concentrations on survival and development in the marine copepod Tigriopus japonicus with a partial life-cycle toxicity test. Expressions of five stress response genes in the copepod, namely two glutathione S-transferases (GST-S and GST-O), two heat shock proteins (HSP70 and HSP90), and glutathione reductase (GR) were also investigated. The copepod's survival was significantly impaired at 15 °C after development to adult stage, while its developmental time reduced significantly with increasing temperature. Copper at the two environmentally relevant test concentrations had no significant impacts on these apical endpoints whereas the interaction between Cu and temperature was more significant in modulating gene expressions. GST-S, GST-O and HSP90 genes in copepods exposed to 100 µg Cu L-1 were significantly upregulated at 20 °C. At 32 °C, most genes were either insignificantly expressed or down-regulated, compared to the control, likely suggesting that thermal stress inhibited the copepod's antioxidative defense system. Overall, the results revealed that the joint Cu and thermal stresses have significantly elicited antioxidative system in the copepods. It clearly demonstrated the need for more fundamental studies about potential impacts of different environmental factors such as temperature on chemical toxicity under realistic scenario of marine pollution.

Phytochemical Constituents from the Seeds of Capsella bursa-pastoris and Their Antioxidant Activities.

Phytochemical investigation of 70% EtOH extract of the seeds of Capsella bursa-pastoris led to the isolation of a new cyclobutane organic acid (1), and fourteen known compounds, including two organosulfur compounds (2, 3), two quinonoids (4, 5), five flavonoids (6-10), three sterols (11-13) and two other types (14, 15). The structures of the compounds were elucidated by extensive spectroscopic analyses as well as comparison of their spectroscopic data with those reported in the literature. The antioxidant capacities of all compounds and extractive fractions were evaluated by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical-scavenging test and ferric reducing antioxidant power (FRAP) assay. Then the antioxidative substances were evaluated for their neuroprotective effects against H2O2-induced HT22 cell injury. The results indicated the strong scavenging ability to free radical of the extractive fractions and compounds 1-3, 8-10 and 13, and the ferric reducing antioxidant power of the extractive fractions and compounds 1-3, 8 and 10, which were close to or higher than that of the positive control trolox. The EtOAc fraction, n-BuOH fraction, and compounds 1, 3 and 8 can protect HT-22 cells from oxidative damage.

The significance of recent diversification in the Northern Hemisphere in shaping the modern global flora revealed from the herbaceous tribe of Rubieae (Rubiaceae).

The global herbaceous flora is probably shaped by both ancient and/or recent diversification, companied with the impacts from geographic differences between the Northern and Southern Hemispheres. Therefore, its biogeographic pattern with respect to temporal and spatial divergence is far from full understanding. Tribe Rubieae, the largest herbaceous tribe in the woody-dominant Rubiaceae, provides an excellent opportunity for studying the macroevolution of worldwide colonization. Here, we aim to reconstruct the evolutionary history of Rubieae with regard to climate fluctuation and geological history in the Cenozoic. A total of 204 samples of Rubieae representing all the distribution areas of the tribe were used to infer its phylogenetic and biogeographic histories based on two nrDNA and six cpDNA regions. The ancestral area of Rubieae was reconstructed using a time-calibrated phylogeny in RASP and diversification rates were inferred using Bayesian analysis of macroevolutionary mixtures (BAMM). Our results show Rubieae probably originated in European region during the middle Oligocene, with the two subtribes separating at 26.8 million years ago (Ma). All the genera in Rubieae formed separate clades between 24.79 and 6.23 Ma. The ancestral area of the subtribe Rubiinae was the Madrean-Tethyan plant belt and the North Atlantic land bridge (NALB) provided passage between North America and Europe for Rubiinae. The subtribe Galiinae clade originated in Europe/central Asia during the late Oligocene. Two diversification shifts were detected within Rubieae in the late Neogene. Most extant Rubieae species diverged recently during the Neogene within clades that generally were established during the late Paleogene. The tribe shows complex migration/dispersal patterns within the North Hemisphere combined with multiple recent dispersals into Southern Hemisphere. Our results highlighted the important role of recent biogeographic diversification in the Northern Hemisphere in shaping the modern global herbaceous flora during the latest and rapid worldwide expansion in the Neogene.

High-quality compressed sensing imaging with limited detector bits using sparse measurements and multiple dithers.

High-flux measurement characteristics of compressed sensing (CS) imaging causes the imaging system prone to be disturbed by quantization. To realize high-quality CS imaging with limited detector bits, an improved imaging method combining sparse measurements and multiple dithers is proposed to reduce the dynamic range of the measured signals and increase that of effective detection. Simulations and experiments show that compared with traditional CS imaging, the proposed system decreases reconstruction errors caused by quantization distortions and may reduce the required number of detector bits to 1. The effects of detector noise and system parameters are discussed to validate the feasibility and performance of this method.

Chronic oral administration of adipoRon reverses cognitive impairments and ameliorates neuropathology in an Alzheimer's disease mouse model.

Circulating adiponectin (APN) levels decrease with age and obesity. On the other hand, a reduction in APN levels is associated with neurodegeneration and neuroinflammation. We previously showed that aged adiponectin knockout (APN-/-) mice developed Alzheimer's like pathologies, cerebral insulin resistance, and cognitive impairments. More recently, we also demonstrated that APN deficiency increased Aß-induced microglia activation and neuroinflammatory responses in 5xFAD mice. There is compelling evidence that deregulated insulin activities or cerebral insulin resistance contributes to neuroinflammation and Alzheimer's disease (AD) pathogenesis. Here, we demonstrated that APN levels were reduced in the brain of AD patients and 5xFAD mice. We crossbred 5xFAD mice with APN-/- mice to generate APN-deficient 5xFAD (5xFAD;APN-/-). APN deficiency in 5xFAD mice accelerated amyloid loading, increased cerebral amyloid angiopathy, and reduced insulin-signaling activities. Pharmacokinetics study demonstrated adipoRon (APN receptor agonist) was a blood-brain barrier penetrant. AdipoRon improved neuronal insulin-signaling activities and insulin sensitivity in vitro and in vivo. Chronic adipoRon treatment improved spatial memory functions and significantly rescued neuronal and synaptic loss in 5xFAD and 5xFAD;APN-/- mice. AdipoRon lowered plaque and Aß levels in AD mice. AdipoRon also exerted anti-inflammatory effects by reducing microglial and astrocytes activation as well as suppressing cerebral cytokines levels. The microglial phagocytic activity toward Aß was restored after adipoRon treatment. Our results indicated that adipoRon exerts multiple beneficial effects providing important therapeutic implications. We propose chronic adipoRon administration as a potential treatment for AD.

NLRP3 inflammasome links vascular senescence to diabetic vascular lesions.

Vascular senescence is inextricably linked to the onset and progression of cardiovascular diseases (CVDs), which are the main cause of mortality in people with Type 2 diabetes (T2DM). Previous studies have emphasized the importance of chronic aseptic inflammation in diabetic vasculopathy. Here, we found the abnormal activation of NLRP3 inflammasome in the aorta of both old and T2DM mice by immunofluorescence and Western Blot analysis. Histopathological and isometry tension analysis showed that the presence of T2DM triggered or aggravated the increase of vascular aging markers, as well as age-associated vascular impairment and vasomotor dysfunction, which were improved by NLRP3 deletion or inhibition. Differential expression of aortic genes links to senescence activation and vascular remodeling supports the favorable benefits of NLRP3-/- during T2DM. In vitro results based on primary mice aortic endothelial cells (MAECs) and vascular smooth muscle cells (VSMCs) demonstrate that NLRP3 deficiency attenuated premature senescence and restored proliferation and migration capability under-stimulation, and partially ameliorated replicative senescence. These results provide an insight into the critical role of NLRP3 signaling in T2DM-induced vascular aging and loss of vascular homeostasis, and provide the possibility that targeting NLRP3 inflammasome might be a promising strategy to prevent diabetic vascular senescence and associated vascular lesions.

Correction: Pentacyclic spermidine alkaloids with radioprotective and anti-inflammatory activities from Orychophragmus violaceus.

Correction for 'Pentacyclic spermidine alkaloids with radioprotective and anti-inflammatory activities from Orychophragmus violaceus' by Zan-Xin Xu et al., Org. Biomol. Chem., 2021, 19, 9844-9848, DOI: 10.1039/D1OB01973B.

The accuracy and influencing factors of Doppler echocardiography in estimating pulmonary artery systolic pressure: comparison with right heart catheterization: a retrospective cross-sectional study.

BACKGROUND: Noninvasive assessment of pulmonary artery systolic pressure by Doppler echocardiography (sPAPECHO) has been widely adopted to screen for pulmonary hypertension (PH), but there is still a high proportion of overestimation or underestimation of sPAPECHO. We therefore aimed to explore the accuracy and influencing factors of sPAPECHO with right heart catheterization (RHC) as a reference. METHODS: A total of 218 highly suspected PH patients who underwent RHC and echocardiography within 7 days were included. The correlation and consistency between tricuspid regurgitation (TR)-related methods and RHC results were tested by Pearson and Bland-Altman methods. TR-related methods included peak velocity of TR (TR Vmax), TR pressure gradient (TR-PG), TR mean pressure gradient (TR-mPG), estimated mean pulmonary artery pressure (mPAPECHO), and sPAPECHO. With mPAP ≥ 25 mm Hg measured by RHC as the standard diagnostic criterion of PH, the ROC curve was used to compare the diagnostic efficacy of sPAPECHO with other TR-derived parameters. The ratio (sPAPECHO-sPAPRHC)/sPAPRHC was calculated and divided into three groups as follows: patients with an estimation error between - 10% and + 10% were defined as the accurate group; patients with an estimated difference greater than + 10% were classified as the overestimated group; and patients with an estimation error greater than - 10% were classified as the underestimated group. The influencing factors of sPAPECHO were analyzed by ordinal regression analysis. RESULTS: sPAPECHO had the highest correlation coefficient (r = 0.781, P < 0.001), best diagnostic efficiency (AUC = 0.98), and lowest bias (mean bias = 0.07 mm Hg; 95% limits of agreement, - 32.08 to + 32.22 mm Hg) compared with other TR-related methods. Ordinal regression analysis showed that TR signal quality, sPAPRHC level, and pulmonary artery wedge pressure (PAWP) affected the accuracy of sPAPECHO (P < 0.05). Relative to the good signal quality, the OR values of medium and poor signal quality were 0.26 (95% CI: 0.14, 0.48) and 0.23 (95% CI: 0.07, 0.73), respectively. Compared with high sPAPRHC level, the OR values of low and medium sPAPRHC levels were 21.56 (95% CI: 9.57, 48.55) and 5.13 (95% CI: 2.55, 10.32), respectively. The OR value of PAWP was 0.94 (95% CI: 0.89, 0.99). TR severity and right ventricular systolic function had no significant effect on the accuracy of sPAPECHO. CONCLUSIONS: In this study, we found that all TR-related methods, including sPAPECHO, had comparable and good efficiency in PH screening. To make the assessment of sPAPECHO more accurate, attention should be paid to TR signal quality, sPAPRHC level, and PAWP.

Cystathionine ß-synthase expression correlates with tumor development and poor prognosis in lung squamous cell carcinoma patients.

The purpose of this study was to investigate the correlation between the expression of cystathionine ß-synthase (CBS) in lung squamous cell carcinoma (LUSC) and the microvascular density (MVD) and clinicopathological features. Firstly, the expression status of CBS in diffuse carcinoma and LUSC was searched through the public bioinformatics database. Subsequently, immunohistochemical staining and scoring were performed on tumor tissues and matched normal tissues from 108 LUSC patients to assess CBS expression; the MVD of tumor tissues was also detected. The results showed that CBS was overexpressed in some tumor tissues, including LUSC. Immunohistochemical results showed that the positive expression rate of CBS in tumor tissues (63.0%) was higher than that in normal tissues (17.6%). The expression of CBS was correlated with T (p=0.01), N (p=0.004), TNM (p=0.011) stages, and tumor differentiation degrees (p<0.001), with the increase of T, N, and TNM stages or the decrease of differentiation, the expression level of CBS also increased. In addition, the expression level of CBS was positively correlated with MVD (r=0.6997, p<0.0001). Survival analysis showed that the survival rate of the CBS negative expression group was better than that of the positive expression group (p=0.004). Cox multivariate analysis showed that CBS expression status (p<0.001), T stages (p=0.020), and TNM stages (p=0.021) were independent factors affecting the prognosis of LUSC. In conclusion, the high expression of CBS affects tumor development and is associated with the poor prognosis of LUCS, which may be used as a biomarker to evaluate prognosis and find a new direction for the treatment of LUSC.

Methylation- and homologous recombination deficiency-related mutant genes predict the prognosis of lung adenocarcinoma.

BACKGROUND: Lung adenocarcinoma (LUAD) is a lung cancer subtype with poor prognosis. We investigated the prognostic value of methylation- and homologous recombination deficiency (HRD)-associated gene signatures in LUAD. METHODS: Data on RNA sequencing, somatic mutations, and methylation were obtained from TCGA database. HRD scores were used to stratify patients with LUAD into high and low HRD groups and identify differentially mutated and expressed genes (DMEGs). Pearson correlation analysis between DMEGs and methylation yielded methylation-associated DMEGs. Cox regression analysis was used to construct a prognostic model, and the distribution of clinical features in the high- and low-risk groups was compared. RESULTS: Patients with different HRD scores showed different DNA mutation patterns. There were 272 differentially mutated genes and 6294 differentially expressed genes. Fifty-seven DMEGs were obtained; the top 10 upregulated genes were COL11A1, EXO1, ASPM, COL12A1, COL2A1, COL3A1, COL5A2, DIAPH3, CAD, and SLC25A13, while the top 10 downregulated genes were C7, ERN2, DLC1, SCN7A, SMARCA2, CARD11, LAMA2, ITIH5, FRY, and EPHB6. Forty-two DMEGs were negatively correlated with 259 methylation sites. Gene ontology and pathway enrichment analysis of the DMEGs revealed enrichment of loci involved in extracellular matrix-related remodeling and signaling. Six out of the 42 methylation-associated DMEGs were significantly associated with LUAD prognosis and included in the prognostic model. The model effectively stratified high- and low-risk patients, with the high-risk group having more patients with advanced stage disease. CONCLUSION: We developed a novel prognostic model for LUAD based on methylation and HRD. Methylation-associated DMEGs may function as biomarkers and therapeutic targets for LUAD. Further studies are needed to elucidate their roles in LUAD carcinogenesis.

Concentration-response of six marine species to all-trans-retinoic acid and its ecological risk to the marine environment.

Being a class of vitamin A's main derivatives, retinoic acids (RAs) are important to animals' growth and development. Previous studies demonstrated that exposure of excessive amounts of RAs would lead to malformation and abnormal development in aquatic animals such as amphibians and fishes. Currently, there are only limited toxicity data of RAs available for freshwater species, while those for marine species are seriously lacking. This study aimed to fill such data gap by conducting toxicity tests on six marine species (i.e., one microalga, four invertebrates and one fish) towards the exposure to all-trans-RA (at-RA), which is the most widely distributed RA in the environment. Results showed that the embryo of medaka fish Oryzias melastigma was the most sensitive towards the exposure of at-RA while the gastropod Monodonta labio was the least sensitive. A species sensitivity distribution (SSD) was constructed based on the experimental results generated from the present study. An interim marine-specific predicted no-effect concentration (PNEC) of at-RA was derived at 2300 ng/L. By computing the hazard quotients using the interim marine-specific PNEC and available measured and predicted concentrations of RAs, we found the current levels of RAs posed no immediate risks to the marine environment of Hong Kong. The interim marine-specific PNEC was more than 500-fold of freshwater-specific PNEC (i.e., 3.93 ng/L), indicating that marine species were generally less sensitive than their freshwater counterparts towards RAs. This was the first study to document the concentration-response of various marine species towards at-RA exposure and construct the marine-specific SSD for assessing the ecological risk of at-RA towards the marine environment. Since various forms of RAs and their metabolites often coexist in aquatic environments, further studies should investigate their combined toxicity to an array of marine species of different trophic levels with consideration of chronic exposure scenarios.

Cardiac efficacy and toxicity of aconitine: A new frontier for the ancient poison.

Aconitine (AC) is well-known as the main toxic ingredient and active compound of Aconitum species, of which several aconites are essential herbal medicines of Traditional Chinese Medicine (TCM) and widely applied to treat diverse diseases for their excellent anti-inflammatory, analgesic, and cardiotonic effects. However, the cardiotoxicity and neurotoxicity of AC attracted a lot of attention and made it a favorite botanic poison in history. Nowadays, the narrow therapeutic window of AC limits the clinical application of AC-containing herbal medicines; overdosing on AC always induces ventricular tachyarrhythmia and heart arrest, both of which are potentially lethal. But the underlying cardiotoxic mechanisms remained chaos. Recently, beyond its cardiotoxic effects, emerging evidence shows that low doses of AC or its metabolites could generate cardioprotective effects and are necessary to aconite's clinical efficacy. Consistent with TCM's theory that even toxic substances are powerful medicines, AC thus could not be simply identified as a toxicant or a drug. To prevent cardiotoxicity while digging the unique value of AC in cardiac pharmacology, there exists a huge urge to better know the characteristic of AC being a cardiotoxic agent or a potential heart drug. Here, this article reviews the advances of AC metabolism and focuses on the latest mechanistic findings of cardiac efficacy and toxicity of this aconite alkaloid or its metabolites. We also discuss how to prevent AC-related cardiotoxicity, as well as the issues before the development of AC-based medicines that should be solved, to provide new insight into the paradoxical nature of this ancient poison.

Identification of circular RNAs as novel biomarkers and potentially functional competing endogenous RNA network for myelodysplastic syndrome patients.

Circular RNAs (circRNAs) have been identified to exert vital biological functions and can be used as new biomarkers in a number of tumors. However, little is known about the functions of circRNAs in myelodysplastic syndrome (MDS). Here, we aimed to investigate circRNA expression profiles and to investigate the functional and clinical value of circRNAs in MDS. Differential expression of circRNAs between MDS and control subjects was analyzed using circRNA arrays, in which we identified 145 upregulated circRNAs and 224 downregulated circRNAs. Validated by real-time quantitative PCR between 100 MDS patients and 20 controls, three upregulated (hsa_circRNA_100352, hsa_circRNA_104056, and hsa_circRNA_104634) and three downregulated (hsa_circRNA_103846, hsa_circRNA_102817, and hsa_circRNA_102526) circRNAs matched the arrays. The receiver operating characteristic curve analysis of these circRNAs showed that the area under the curve was 0.7266, 0.8676, 0.7349, 0.7091, 0.8806, and 0.7472, respectively. Kaplan-Meier survival analysis showed that only hsa_circRNA_100352, hsa_circRNA_104056, and hsa_circRNA_102817 were significantly associated with overall survival. Furthermore, we generated a competing endogenous RNA network focused on hsa_circRNA_100352, hsa_circRNA_104056, and hsa_circRNA_102817. Analyses using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes showed that the three circRNAs were linked with some important cancer-related functions and pathways.

Pentacyclic spermidine alkaloids with radioprotective and anti-inflammatory activities from Orychophragmus violaceus.

Two pairs of novel pentacyclic spermidine alkaloid enantiomers, (±)-orychoviolines A and B ((±)-1 and (±)-2), were isolated from the seeds of Orychophragmus violaceus and represented the first example of a 2-piperidinone-fused hydrodibenzofuran skeleton, constructed from a 6/5/6/6 tetracyclic system and an 18 atomic ring. The most unexpected novelty was the formation of one more piperidinone ring by a connection between C-6 and N-7. Their structures and absolute configurations were determined by spectroscopic analyses, X-ray crystallography, and ECD analysis. Compared to Ex-RAD (sodium salt of 4-carboxystyryl-4-chlorobenzylsulfone), (-)-1 exhibited a significant radioprotective effect on cell survival and DNA damage. (-)-1 also exhibited remarkable anti-inflammatory activity by inhibiting the production of NO in RAW 264.7 cells activated by lipopolysaccharide with an IC50 value of 20.3 ± 1.58 µM, which was equivalent to that of dexamethasone.