Curcumin preconditioning enhances the neuroprotective effects of olfactory mucosa-derived mesenchymal stem cells on experimental intracerebral hemorrhage.

Oxidative stress is essential in brain injury after intracerebral hemorrhage (ICH). Ferroptosis, iron-dependent oxidative cell death, overwhelms the antioxidant system. Recently, Olfactory mucosa-derived mesenchymal stem cells (OM-MSCs) hold great potential for treating ferroptosis-mediated oxidative brain damage after ICH. However, massive grafted cell death, possibly caused by a hostile host brain microenvironment, lessens the effectiveness of OM-MSCs. Therefore, it is necessary to develop strategies to upregulate the therapeutic efficacy of OM-MSCs in ICH. Curcumin, a well-established traditional herbal substance, has potent antioxidant property. In the present study, curcumin preconditioning might enhance the anti-oxidative activity of OM-MSCs, thereby augmenting the therapeutic efficacy of OM-MSCs in ICH. In vitro model of ICH, we demonstrated that curcumin-preconditioned OM-MSCs co-culture is more effective in attenuating the cell injury, oxidative stress, and ferroptosis of neuronal cells compared to the native OM-MSCs treatment. In vivo model of ICH, transplantation of curcumin-preconditioned OM-MSCs also showed better neuroprotective effects. Moreover, curcumin pretreatment promoted the survival of OM-MSCs under a conditioned medium from hemin-insulted neurons by improving the anti-oxidative capacities of OM-MSCs. Collectively, our investigation suggested that curcumin preconditioning effectively enhanced the survival and neuroprotective effects of OM-MSCs in the ICH model by upregulating the anti-oxidative capacities of OM-MSCs. Curcumin-preconditioned OM-MSCs might be taken as a novel therapeutic strategy for treating ICH.

A Novel Combined Nomogram Model for Predicting the Pathological Complete Response to Neoadjuvant Chemotherapy in Invasive Breast Carcinoma of No Specific Type: Real-World Study.

Objective: To explore the value of a predictive model combining the multiparametric magnetic resonance imaging (mpMRI) radiomics score (RAD-score), clinicopathologic features, and morphologic features for the pathological complete response (pCR) to neoadjuvant chemotherapy (NAC) in invasive breast carcinoma of no specific type (IBC-NST). Methods: We enrolled, retrospectively and consecutively, 206 women with IBC-NST who underwent surgery after NAC and obtained pathological results from August 2018 to October 2021. Four RAD-scores were constructed for predicting the pCR based on fat-suppression T2-weighted imaging (FS-T2WI), diffusion-weighted imaging (DWI), contrast-enhanced T1-weighted imaging (T1WI+C) and their combination, which was called mpMRI. The best RAD-score was combined with clinicopathologic and morphologic features to establish a nomogram model through binary logistic regression. The predictive performance of the nomogram was evaluated using the area under receiver operator characteristic (ROC) curve (AUC) and calibration curve. The clinical net benefit of the model was evaluated using decision curve analysis (DCA). Results: The mpMRI RAD-score had the highest diagnostic performance, with AUC of 0.848 among the four RAD-scores. T stage, human epidermal growth factor receptor-2 (HER2) status, RAD-score, and roundness were independent factors for predicting the pCR (P < 0.05 for all). The combined nomogram model based on these factors achieved AUCs of 0.930 and 0.895 in the training cohort and validation cohort, respectively, higher than other models (P < 0.05 for all). The calibration curve showed that the predicted probabilities of the nomogram were in good agreement with the actual probabilities, and DCA indicated that it provided more net benefit than the treat-none or treat-all scheme by decision curve analysis in both training and validation datasets. Conclusion: The combined nomogram model based on the mpMRI RAD-score combined with clinicopathologic and morphologic features may improve the predictive performance for the pCR of NAC in patients with IBC-NST.

UBIAD1 alleviates ferroptotic neuronal death by enhancing antioxidative capacity by cooperatively restoring impaired mitochondria and Golgi apparatus upon cerebral ischemic/reperfusion insult.

BACKGROUND: Neuronal death due to over-oxidative stress responses defines the pathology of cerebral ischemic/reperfusion (I/R) insult. Ferroptosis is a form of oxidative cell death that is induced by disruption of the balance between antioxidants and pro-oxidants in cells. However, the potential mechanisms responsible for cerebral I/R-induced ferroptotic neuronal death have not been conclusively determined. UBIAD1, is a newly identified antioxidant enzyme that catalyzes coenzyme Q10 (CoQ10) and vitamin K2 biosynthesis in the Golgi apparatus membrane and mitochondria, respectively. Even though UBIAD1 is a significant mediator of apoptosis in cerebral I/R challenge, its roles in ferroptotic neuronal death remain undefined. Therefore, we investigated whether ferroptotic neuronal death is involved in cerebral I/R injury. Further, we evaluated the functions and possible mechanisms of UBIAD1 in cerebral I/R-induced ferroptotic neuronal death, with a major focus on mitochondrial and Golgi apparatus dysfunctions. RESULTS: Ferroptosis occurred in cerebral I/R. Ferroptotic neuronal death promoted cerebral I/R-induced brain tissue injury and neuronal impairment. UBIAD1 was expressed in cerebral tissues and was localized in neurons, astrocytes, and microglia. Under cerebral I/R conditions overexpressed UBIAD1 significantly suppressed lipid peroxidation and ferroptosis. Moreover, upregulated UBIAD1 protected against brain tissue damage and neuronal death by alleviating I/R-mediated lipid peroxidation and ferroptosis. However, UBIAD1 knockdown reversed these changes. Enhanced UBIAD1-mediated ferroptosis elevated the antioxidative capacity by rescuing mitochondrial and Golgi apparatus dysfunction in cerebral I/R-mediated neuronal injury. They improved the morphology and biofunctions of the mitochondria and Golgi apparatus, thereby elevating the levels of SOD, T-AOC and production of CoQ10, endothelial nitric oxide synthase (eNOS)-regulated nitric oxide (NO) generation as well as suppressed MDA generation. CONCLUSIONS: The neuroprotective agent, UBIAD1, modulates I/R-mediated ferroptosis by restoring mitochondrial and Golgi apparatus dysfunction in damaged brain tissues and neurons, thereby enhancing antioxidative capacities. Moreover, the rescue of impaired mitochondrial and Golgi apparatus as a possible mechanism of regulating ferroptotic neuronal death is a potential treatment strategy for ischemic stroke.

Are fetal gender and gestational age related to the size of cisterna magna?

OBJECTIVES: The purpose of this article was to explore whether the gestational age(GA)and gender could affect the size of the cisterna magna (CM). METHODS: This study that included pregnant women who were between 20 ∼ 39+6. The recorded included BPD, HC, anteroposterior diameter of CM and gender. The fetuses were divided into normal and isolated enlargement of the CM (IECM)group for statistical analysis. RESULTS: Seven hundred ninety six fetuses with normal CM, 412 cases were boys and 384 cases were girls. 73 fetuses with IECM, 59 cases were boys and 14 cases were girls. The anteroposterior diameter of the CM increased with GA during 20-26+6 weeks. After 27 weeks, the anteroposterior diameter of CM became stable. In the IECM group, the mean anteroposterior of male and female fetuses were 1.31 ± 0.18 cm and 1.24 ± 0.15 cm, respectively. The IECM fetus accounted for 8.4% of the total number of fetuses, male IECM accounted for 14.3% of normal male fetus, and female fetus was 3.6%, which showed that male fetus had a higher rate of IECM than female (χ2 = 21.6, p<.001). CONCLUSIONS: There is a gender difference between normal fetuses and IECM fetuses. Based on our finding, it is reasonable to establish the normal value of CM according to the gender difference.

Complete mitochondrial genome of Procapra picticaudata, with phylogenetic implication.

The Tibetan gazelle Procapra picticaudata is endemic to the Tibetan plateau. The species is listed as a Near Threatened (NT) species by the IUCN Red List of Threatened Animals and the Red List of China's Vertebrates. In this study, we sequenced the complete mitochondrial genome of P. picticaudata and examined its phylogenetic position with other nine species in Artiodactyla. The complete mitochondrial genome is 16,620 bp in length and contained 22 transfer RNA genes, 2 ribosomal RNA genes, 13 protein-coding genes, and 1 control region. Our data would provide reference information for further study of this species and be useful for evolutionary and phylogenetics studies for this NT species.

Localized Self-Growth of Reconfigurable Architectures Induced by a Femtosecond Laser on a Shape-Memory Polymer.

Architectures of natural organisms especially plants largely determine their response to varying external conditions. Nature-inspired shape transformation of artificial materials has motivated academic research for decades due to wide applications in smart textiles, actuators, soft robotics, and drug delivery. A "self-growth" method of controlling femtosecond laser scanning on the surface of a prestretched shape-memory polymer to realize microscale localized reconfigurable architectures transformation is introduced. It is discovered that microstructures can grow out of the original surface by intentional control of localized laser heating and ablation, and resultant structures can be further tuned by adopting an asymmetric laser scanning strategy. A distinguished paradigm of reconfigurable architectures is demonstrated by combining the flexible and programmable laser technique with a smart shape-memory polymer. Proof-of-concept experiments are performed respectively in information encryption/decryption, and microtarget capturing/release. The findings reveal new capacities of architectures with smart surfaces in various interdisciplinary fields including anti-counterfeiting, microstructure printing, and ultrasensitive detection.

UGT74AN1, a Permissive Glycosyltransferase from Asclepias curassavica for the Regiospecific Steroid 3-O-Glycosylation.

A permissive steroid glycosyltransferase (UGT74AN1) from Asclepias curassavica exhibited robust capabilities for the regiospecific C3 glycosylation of cardiotonic steroids and C21 steroid precursors, and unprecedented promiscuity toward 53 structurally diverse natural and unnatural compounds to form O-, N-, and S-glycosides, along with the catalytic reversibility for a one-pot transglycosylation reaction. These findings highlight UGT74AN1 as the first regiospecific catalyst for cardiotonic steroid C3 glycosylation and exhibit significant potential for glycosylation of diverse bioactive molecules in drug discovery.

An Efficient Strategy Based on Liquid-Liquid Extraction with Three-Phase Solvent System and High Speed Counter-Current Chromatography for Rapid Enrichment and Separation of Epimers of Minor Bufadienolide from Toad Meat.

This study presents an efficient strategy based on liquid-liquid extraction with three-phase solvent system and high speed counter-current chromatography for rapid enrichment and separation of epimers of minor bufadienolide from toad meat. The reflux extraction conditions were optimized by response surface methodology first, and a novel three-phase solvent system composed of n-hexane/methyl acetate/acetonitrile/water (3:6:5:5, v/v) was developed for liquid-liquid extraction of the crude extract. This integrative extraction process could enrich minor bufadienolide from complex matrix efficiently and minimize the loss of minor targets induced by repeated extraction with different kinds of organic solvents occurring in the classical liquid two-phase extraction. As a result, four epimers of minor bufadienolide were greatly enriched in the middle phase and total content of these epimers of minor bufadienolide was increased from 3.25% to 46.23%. Then, the enriched four epimers were separated by HSCCC with a two-phase solvent system composed of chloroform/methanol/water (4:2:2, v/v) successfully. Furthermore, we tested Na+,K+-ATPase (NKA) inhibitory effect of the four epimers. 3ß-Isomers of bufadienolide showed stronger (>8-fold) inhibitory activity than 3α-isomers. The characterization of minor bufadienolide in toad meat and their significant difference of inhibitory effect on NKA would promote the further quantitative analysis and safety evaluation of toad meat as a food source.

Probing the stereoselectivity of OleD-catalyzed glycosylation of cardiotonic steroids.

The glycosyltransferase OleD variant as a catalyst for the glycosylation of four pairs of epimers of cardiotonic steroids (CTS) are assessed. The results of this study demonstrated that the OleD-catalyze glycosylation of CTS is significantly influenced by the configuration at C-3 and the A/B fusion mode. 3ß-OH and A/B ring cis fusion are favoured by OleD (ASP). An epoxide ring at C-14 and C-15 further increases the bioconversion rate; while an acetyl group at C-16 and lactone ring type at C-17 did not influence the biotransformation. A high conversion rate corresponded to a low K m value. A molecular docking simulation showed that filling of hydrophobic pocket II and interaction with residue Tyr115 may play an important role in the glycosylation reactions catalyzed by OleD glycosyltransferases. Furthermore, the glycosylation products showed a stronger inhibitory activity for Na+, K+-ATPase than the corresponding aglycones. This study provides the first stereoselective properties for OleD (ASP) catalyzed glycosylation.