Natural variations of maize ZmLecRK1 determine its interaction with ZmBAK1 and resistance patterns to multiple pathogens.

Maize (Zea mays L.) is one of the most important crops in the world, but its yield and quality are seriously affected by diverse diseases. Identifying broad-spectrum resistance genes is crucial for developing effective strategies to control the disease in maize. In a genome-wide study in maize, we identified a G-type lectin receptor kinase ZmLecRK1 as a new resistance protein against Pythium aphanidermatum, one of the causal pathogens of stalk rot in maize. Genetic analysis showed that the specific ZmLecRK1 allele can confer resistance to multiple pathogens in maize. The resistant variant of ZmLecRK1-mediated cell death and disease resistance require the co-receptor leucine-rich repeat kinase ZmBAK1. A naturally occurring A404S variant in the extracellular domain of ZmLecRK1 determines the ZmLecRK1-ZmBAK1 interaction and the formation of ZmLecRK1-related protein complexes. The amino acid S404, as found in the ZmLecRK1 susceptibility variant, constitutes the ancestral version and is conserved among the majority of grass species, while the resistance variant with A404 is only present in a few maize inbred lines. Substitution of S by A at position 404 in ZmLecRK1-like proteins of sorghum and rice greatly enhances their ability to induce cell death. We propose that selection for the ZmLecRK1 resistance variant enhances its binding affinity to the co-receptor ZmBAK1, thereby enhancing the formation of active complexes for defense. Finally, transcriptomic analysis suggests that ZmLecRK1 likely regulates gene expression related to pathways in cell wall organization or biogenesis in response to pathogen infection. Our work highlights the biotechnological potential for generating disease-resistant crops by precisely modulating the activity of ZmLecRK1 and its homologs through targeted base editing.

Heterologous expression of sulfur: quinone oxidoreductase (Sqr) to improve Thioalkalivibrio versutus D301 desulfurization performance.

AIMS: Heterologous expression of sulfur: quinone oxidoreductase (Sqr) from Halomonas mongoliensis JS01, which is responsible for oxidizing sulfide to elemental sulfur, in Thioalkalivibrio versutus (T. versutus) D301 improves desulfurization. METHODS AND RESULTS: We expressed sqr in T. versutus D301 by conjugative transfer and then assayed its desulfurization capacity in an airlift reactor and analyzed its transcriptome at -380 mV ORP. Our findings demonstrate that the D301-sqr+ strain, utilizing sodium sulfide as a sulfur source under optimal ORP conditions (-380 mV), achieved an elemental sulfur yield of 95%. This represents an 8% increase over the T. versutus D301. Moreover, the sodium sulfide utilization rate for D301-sqr+ showed a marked improvement [0.741 vs. 0.651 mmol∙(l·h)-1], with a concurrent increase in the rate of elemental sulfur production when compared to the T. versutus D301 (0.716 vs. 0.518 mmol ∙(l·h)-1). Transcriptome analysis revealed that the flavocytochrome c (fcc) and the sox system were differentially transcriptionally down-regulated in D301-sqr+ compared with the T. versutus D301. CONCLUSIONS: Heterologous expression of the gene sqr altered the transcription of related genes in T. versutus D301 sulfur oxidation pathway, increasing the yield of elemental sulfur and the rate of sulfur oxidation, and making D301-sqr+ more potential for industrial applications.

Armed on the back: Hidden biomineralized scales in the ventral girdle of chiton Acanthopleura loochooana.

Flexible protective armors are found in large animals such as fish skins, snake skins, and pangolin scales. For small-sized invertebrates, such armors are paid less attention and overlooked. Chitons, a type of marine mollusk, possess mineralized armors covering the whole dorsal body. The dorsal scales in the girdle tissue are well known, in this study, we reported hidden mineralized scales in the ventral side of chiton Acanthopleura loochooana girdles for the first time. The ventral surface is covered with scales with ca. 40 µm in length, forming continuous but overlapped scales. Additionally, scales are formed from aragonitic spicule-like and square-like scales, embedded in the cuticle layer. Nanoindentation testing results showed that the hardness and elastic modulus of ventral scales were ∼20 % higher compared to those in the dorsal scales, exhibiting good hardness and wear resistance. The combination of the ventral scales and cuticle, along with the regular arrangement of ventral scales, may allow chitons to simultaneously address complex and variable attachment interfaces while also providing wear-resistant protection. This study provides insights for designing protective structures that balance flexibility and durability. STATEMENT OF SIGNIFICANCE: Biomineralization is universal in nature and provides protection and support for animals. However, mineralization of dermal skin is not commonly seen. Herein, for the first time, we reported hidden minerals covering the whole ventral side of skin in a small marine animal, chitons. Calcium carbonate minerals are arranged regularly and manifest different morphology in different regions. Additionally, these minerals are embedded in a continuous cuticle layer covering the whole animal. The material also indicates a higher wear-resistant property. This study extends our understanding of the diverse functionality of biominerals and provides a prototype for designing wear-resistant materials.

Palladium-Catalyzed Regioselective Monofluoroallylation of Indoles with gem-Difluorocyclopropanes.

We present a palladium-catalyzed ring-opening reaction that induces indoles to cross-couple with gem-difluorocyclopropanes. The reaction proceeds through a domino process of C-C bond activation and C-F bond elimination, followed by C-C(sp2) coupling to produce various 2-fluoroallylindoles. This method is characterized by its high functional group tolerance, good yields and high regioselectivity, under base-free conditions. The synthetic utility of the products is illustrated by the functionalization of the NH and C2 positions of the indole scaffold.

A hyper-distance-based method for hypernetwork comparison.

Hypernetwork is a useful way to depict multiple connections between nodes, making it an ideal tool for representing complex relationships in network science. In recent years, there has been a marked increase in studies on hypernetworks; however, the comparison of the difference between two hypernetworks has received less attention. This paper proposes a hyper-distance (HD)-based method for comparing hypernetworks. The method is based on higher-order information, i.e, the higher-order distance between nodes and Jensen-Shannon divergence. Experiments carried out on synthetic hypernetworks have shown that HD is capable of distinguishing between hypernetworks generated with different parameters, and it is successful in the classification of hypernetworks. Furthermore, HD outperforms current state-of-the-art baselines to distinguish empirical hypernetworks when hyperedges are randomly perturbed.

Effects and neural mechanisms of different physical activity on major depressive disorder based on cerebral multimodality monitoring: a narrative review.

Major depressive disorder (MDD) is currently the most common psychiatric disorder in the world. It characterized by a high incidence of disease with the symptoms like depressed mood, slowed thinking, and reduced cognitive function. Without timely intervention, there is a 20-30% risk of conversion to treatment-resistant depression (TRD) and a high burden for the patient, family and society. Numerous studies have shown that physical activity (PA) is a non-pharmacological treatment that can significantly improve the mental status of patients with MDD and has positive effects on cognitive function, sleep status, and brain plasticity. However, the physiological and psychological effects of different types of PA on individuals vary, and the dosage profile of PA in improving symptoms in patients with MDD has not been elucidated. In most current studies of MDD, PA can be categorized as continuous endurance training (ECT), explosive interval training (EIT), resistance strength training (RST), and mind-body training (MBT), and the effects on patients' depressive symptoms, cognitive function, and sleep varied. Therefore, the present study was based on a narrative review and included a large number of existing studies to investigate the characteristics and differences in the effects of different PA interventions on MDD. The study also investigated the characteristics and differences of different PA interventions in MDD, and explained the neural mechanisms through the results of multimodal brain function monitoring, including the intracranial environment and brain structure. It aims to provide exercise prescription and theoretical reference for future research in neuroscience and clinical intervention in MDD.

Synthesis and biological evaluation of sulfonamide derivatives containing imidazole moiety as ALK5 inhibitors.

Four series of sulfonamide derivatives (13a-b, 14a-d, 15a-b, and 16a-d) were synthesized and evaluated for their activin receptor-like kinase 5 (ALK5) inhibitory activities. Of these, compounds 13b (IC50 = 0.130 µM) and 15a (IC50 = 0.130 µM) showed the highest inhibitory activities against ALK5 kinase, with activities similar to the positive control LY-2157299. Notably, we discovered that introduction of sulfonamide group at the 2-position of the central imidazole ring significantly increased ALK5 inhibitory activity. Compounds 13b and 15a did not show toxicity in A549 cells up to the maximum concentration of 50 µM, and effectively inhibited TGF-ß1-induced Smad-signaling and cell motility in A549 cells. The results indicate that compounds 13b and 15a are worth of further development as anticancer agents.

Standby extracorporeal membrane oxygenation: a better strategy for high-risk percutaneous coronary intervention.

Background: The incidence of cardiac arrest (CA) during percutaneous coronary intervention (PCI) is relatively rare. However, when it does occur, the mortality rate is extremely high. Extracorporeal cardiopulmonary resuscitation (ECPR) has shown promising survival rates for in-hospital cardiac arrests (IHCA), with low-flow time being an independent prognostic factor for CA. However, there is no definitive answer on how to reduce low-flow time. Methods: This retrospective study, conducted at a single center, included 39 patients who underwent ECPR during PCI between January 2016 and December 2022. The patients were divided into two cohorts based on whether standby extracorporeal membrane oxygenation (ECMO) was utilized during PCI: standby ECPR (SBE) (n = 13) and extemporaneous ECPR (EE) (n = 26). We compared the 30-day mortality rates between these two cohorts and investigated factors associated with survival. Results: Compared to the EE cohort, the SBE cohort showed significantly lower low-flow time (P < 0.01), ECMO operation time (P < 0.01), and a lower incidence of acute kidney injury (AKI) (P = 0.017), as well as peak lactate (P < 0.01). Stand-by ECMO was associated with improved 30-day survival (p = 0.036), while prolonged low-flow time (p = 0.004) and a higher SYNTAX II score (p = 0.062) predicted death at 30 days. Conclusions: Standby ECMO can provide significant benefits for patients who undergo ECPR for CA during PCI. It is a viable option for high-risk PCI cases and may enhance the overall prognosis. The low-flow time remains a critical determinant of survival.

A high-precision oasis dataset for China from remote sensing images.

High-resolution oasis maps are imperative for understanding ecological and socio-economic development of arid regions. However, due to the late establishment and relatively niche nature of the oasis discipline, there are no high-precision datasets related to oases in the world to date. To fill this gap, detailed visual interpretation of remote sensing images on Google Earth Professional or Sentinel-2 was conducted in summer 2020, and for the first time, a high-precision dataset of China's oases (abbreviation HDCO) with a resolution of 1 meter was constructed. HDCO comprises 1,466 oases with a total area of 277,375.56 km2. The kappa coefficient for this dataset validated by the field survey was 0.8686 and the AUC value for the ROC curve was 0.935. In addition, information on the geographic coordinates, climatic conditions, major landforms, and hydrological features of each oasis was added to the attribute table of the dataset. This dataset enables researchers to quantitatively monitor location and area of oases, fosters exploration of the relationship between oases and human under climate change and urbanization.

Research on the Mechanism and Propagation Characteristics of Combustion and Explosion of Natural Gas/Ammonia/Hydrogen Mixed Gas Fuel.

The addition of ammonia and hydrogen into natural gas fuel is an effective method to reduce carbon emissions. This study aims to investigate the effect of adding ammonia and hydrogen on the mechanism of natural gas combustion and emission characteristics. Based on a self-developed mixed gas deflagrate experimental platform, the deflagrate characteristics, emission characteristics, and chemical reaction kinetics mechanism of mixed gas fuels under different composition ratios (natural gas 0-100%, hydrogen 10-85%, and ammonia 0-100%) were studied. The results indicate that the propagation of the deflagration shock wave can be categorized into an initial stage (L < 3 m) and a development stage (L > 3 m) based on the observed trend of shock wave intensity variation with distance. The intensity of the deflagration shock wave for the mixed gases increases monotonically as the hydrogen content ratio rises. In contrast, the impact of the ammonia content ratio on the shock wave intensity exhibits a distinct pattern that varies with changes in the equivalence ratio and hydrogen content ratio. In terms of carbon emissions per unit of heat value produced by the fuel, adding hydrogen to natural gas proves to be more effective at reducing carbon emissions than adding ammonia. When the ammonia content ratio is 50% and the hydrogen content ratio is 40%, the combustion performance of the mixed gas fuel is similar to that of natural gas, but its carbon emissions are lower than 30% of natural gas, making it a new type of mixed fuel with potential application value; the interaction between reflected pressure waves and flames is the main reason for the fluctuation of deflagrate shock wave pressure; ammonia lowers the temperature of the reaction system by reducing the concentration of OH radicals.

Myoepithelioma-Like Tumor of the Vulvar Region: A Clinicopathologic Study of Four Cases.

Myoepithelioma-like tumors of the vulvar region (MELTVR) are solid tumors found in the vulva of adult women. They have a similar histopathology to myoepithelioma but differ in immunohistochemical phenotype and genetic changes. In this study, we report four examples of MELTVR, occurred in the external genitalia and mons pubis of adult women aged 32 to 39 years. The tumors presented as subcutaneous masses without obvious tenderness. The tumors were composed of a mixture of myxoid and nonmyxoid components, and myxoid areas accounted for 5% to 80% of the tumor volume. The tumor cells were spindle-shaped or epithelioid, with abundant cytoplasm, vesicular nuclei, and small nucleoli. The nuclear atypia was mild to moderate, with 0 to 10 mitotic figures per 10 high-power fields. Immunohistochemically, all four tumors showed consistent positivity for EMA, calponin and ER; three tumors exhibited PR expression. All tumors were negative for S100 protein and SMA. AE1/AE3 expression was absent in all except one tumor, which showed rare positivity. SMARCB1/INI1 expression was deficient in all tumors. EWSR1 and FUS rearrangements were absent. All tumors were treated through surgery. All patients were alive without recurrence on most recent follow-up. Together, this overview of four additional tumors of MELTVR offers further insight into this rare and poorly understood disease.

Hypersensitive MR Angiography for Diagnosis of Ischemic Stroke and Reperfusion Subarachnoid Hemorrhage.

Stroke is an acute injury of the central nervous system caused by the disorders of cerebral blood circulation, which has become one of the major causes of disability and death. Hemorrhage, particularly subarachnoid hemorrhage (SAH), is one of the poorest prognostic factors in stroke, which is related to the thrombolytic therapy, and has been considered very dangerous. In this context, the MR angiography with high sensitivity and resolution has been developed based on biocompatible paramagnetic ultrasmall NaGdF4 nanoprobes. Owing to the appropriate hydrodynamic diameter, the nanoprobe can be confined inside the blood vessels and it only extravasates at the vascular injury site when the bleeding occurs. Relying on this property, the three-dimensional (3D) anatomic structures of artery occlusion of stroke rat can be precisely visualized; reperfusion-related SAH has been successfully visualized and identified. Benefiting from the long blood half-life of the nanoprobe, the observation window of MR angiography can last for the whole period of reperfusion, thereby monitoring the probable SAH in real time during thrombolytic therapy. More importantly, through reconstruction of multiparametric MRI, the arterial occlusion, cerebral ischemic region, and SAH can be simultaneously visualized in vivo in a 3D manner for the first time. Therefore, the current study provides a novel approach for both noninvasive 3D vascular visualization and hemorrhage alert, which possesses great prospects for clinical translation.

9-O-monoethyl succinate berberine effectively blocks the PI3K/AKT signaling pathway by targeting Wnt5a protein in inhibiting osteosarcoma growth.

BACKGROUND: Osteosarcoma (OS) is the most common primary bone malignancy, mainly affecting children, adolescents, and young adults, followed by the elderly, with a high propensity for local invasion and metastasis. Although surgery combined with chemotherapy has greatly improved the prognosis of patients with OS, the prognosis for metastatic or recurrent OS is still unsatisfactory. The research community has struggled to develop an effective chemotherapy treatment regimen for this tumor. For the creation of an OS drug, our research team has effectively developed and manufactured a new drug named 9-O-monoethyl succinate berberine (B2). PURPOSE: In this study, we aimed to investigate the roles and functions of B2 in the treatment of OS. METHODS: Human OS cell lines and mouse OS cell lines were used in vitro cell experiments, while BALB/c mice and BALB/c nude mice were used in vivo animal experiments. To investigate the molecular mechanism of B2 treatment, antibody microarray analysis, proteomic analysis, quantitative real-time PCR, immunohistochemical labeling, and western blotting analysis were mostly carried out. We assessed the impact of B2 on OS therapy and the underlying molecular pathways based on in vivo and in vitro studies. RESULTS: Our findings demonstrated that B2 has the ability to inhibit the proliferation, migration, and invasion of OS cell lines, while also induce apoptosis in vitro. Additionally, our results suggested that B2 could effectively impede the growth of OS and has less heart and lung damage than cisplatin in vivo. In terms of mechanism, we discovered that the Wnt5a protein is significantly expressed in OS cell lines. Knockdown of Wnt5a can restrict OS cell lines proliferation, and overexpression of Wnt5a had the opposite results. B2 also had a strong affinity with Wnt5a and can inhibit the PI3K/AKT signaling pathway by targeting Wnt5a. Tumor cells proliferation can be inhibited by blocking the PI3K/AKT signaling pathway, and Wnt5a-mediated inactivation of the PI3K/AKT signaling pathway after B2 treatment. In vitro and in vivo experiments with Wnt5a overexpression, B2 significantly inhibited tumor growth, migration, and invasion. Moreover, B2 and Wnt5a also have a strong structural binding ability (binding energy of -7.567 ± 0.084 kcal/mol, binding values of 2.860 ± 0.434 µM), and three hydrogen bonds are generated at the docking positions of amino acids GLN286, ASN288, and ASN292. CONCLUSION: In summary, our study confirmed for the first time that the growth of OS is related to abnormal overexpression of Wnt5a protein, and designed a novel small molecule inhibitor named B2 targeting Wnt5a protein, which inhibits OS growth by mediating PI3K/AKT signaling pathway by targeting Wnt5a protein. Our research laid the groundwork for the promotion of B2 as a new anticancer drug and revealed an innovative chemotherapeutic strategy for OS therapy.

Effects of Hydrogen Blending Ratio and Equivalence Ratio on the Dynamic Characteristics of Deflagration Shock Waves of CH4/H2 Mixtures.

To evaluate the explosion hazard of CH4/H2 mixtures, experiments were conducted in a long and closed pipeline with a length-to-diameter ratio of 51 and built-in obstacles, and the characteristic parameters of deflagration shock waves were analyzed under different hydrogen blending ratios (0 ≤ λ ≤ 100%) and equivalence ratios (0.5 ≤ Φ ≤ 3). The results indicate that within the range of Φ = 0.8-1.2, the explosion overpressure (P P) exhibits a "two-zone" structure distribution. When 0 ≤ λ ≤ 80%, P P shows an initial increase and then a decrease in both regions, while deflagration to detonation transition (DDT) occurs in the second evolution region when λ = 100%, which is caused by the different strengths of the positive feedback mechanism coupled with flames and shock waves. The P max, (dP/dt)max, and V a show a trend of first increasing and then decreasing and monotonically increasing with the increase of the equivalence ratio and hydrogen blending ratio, respectively, and reach their maximum values at Φ = 1.0 and λ = 100%. For CH4/H2 mixtures with low hydrogen blending ratios (λ = 0 and 20%), the P max and (dP/dt)max in the fuel-lean conditions (Φ = 0.9 and 0.8) are higher than those in the fuel-rich conditions (Φ = 1.1 and 1.2), while the CH4/H2 mixtures under high hydrogen blending ratios (λ = 80 and 100%) are the opposite. Overall, the increase in H2 at a high hydrogen blending ratio and the increase in the equivalence ratio at a fuel-lean condition significantly enhance the average V a. In addition, chemical kinetics analysis found that R38 and R52 elementary reactions are the dominant elementary reactions that promote and inhibit temperature increase, respectively. Their temperature sensitivity coefficients are negatively correlated with the hydrogen blending ratio and positively correlated with the equivalence ratio. The research results provide vital information for evaluating the explosion hazards of CH4/H2 mixtures and developing safety protection measures.

Isolation and screening of fungi for enhanced agarwood formation in Aquilaria sinensis trees.

Agarwood is a resinous heartwood of Aquilaria sinensis that is formed in response to mechanical wounding. In the present study pre-treatment of Aquilaria sinensis was carried out, and then the dominant fungi were isolated and purified from the surface and electroshock holes of trees. The isolated Trichoderma sp. and Neurospora sp. were then screened for resistance against benzyl acetone and then inoculated into healthy Aquilaria sinensis trees. After six months, the agarwood was collected for analysis. The chemical composition of incense was analyzed using gas chromatography-mass spectroscopy, and 82 chemical constituents were identified. Agarwood products formed by using Trichoderma sp. and Neurospora sp. consisted of 50.22% and 48.71% ether extracts, respectively, which surpassed the 10% threshold specified by the Chinese Pharmacopoeia. Similarly, relative aromatic contents in the two agarwood products were 30.1% and 32.86%, while proportions of sesquiterpene constituents were 10.21% and 11.19%, respectively. These two agarwood-specific chemical constituents accounted for a large proportion of the total chemical composition, which showed that the generated agarwood was of good quality. The results of the study revealed that both Trichoderma sp. and Neurospora sp. were able to effectively induce agarwood production in Aquilaria sinensis trees in 6 months. This study expands the library of fungi that promote the production of agarwood from Aquilaria sinensis trees.

Clinical outcomes of aortic root repair using pericardial autograft for acute type a aortic dissection.

BACKGROUND: For acute type A aortic dissection involving the aortic root with root diameter no more than 45 mm, there are various aortic root repair techniques. In this study, a novel surgical technique using a pericardial autograft for aortic root repair was introduced. We described its surgical steps in detail and compare its clinical outcomes with direct suture technique. METHODS: Between July 2017 and August 2022, 95 patients with acute type A aortic dissection who underwent aortic root repair were enrolled, including aortic root repair using pericardial autograft (group A, n = 49) or direct suture (group B, n = 46). The patient's clinical data were retrospectively analyzed, and a 5-year follow-up was conducted. RESULTS: The 30-day mortality, re-exploration for bleeding, postoperative new-onset renal failure requiring continuous renal replacement therapy, stroke, and paraplegia occurred in 3%, 4%, 11%, 5%, and 2% of the overall patients, respectively. There was no significant difference in the 30-day mortality and complication rate between the two groups. The 30-day mortality and re-exploration for bleeding marked the primary endpoint events. Logistic regression analysis indicated that there was a significant correlation between the primary endpoint events and surgical technique (odds ratio, 0.002; 95% confidence interval, 0-0.159; P = 0.026). The aortic valve insufficiency of the two groups were significantly improved after operation (group A, P < 0.001; group B, P < 0.001). During follow-up, there was no significant difference in short-term survival between the two groups after surgery (log-rank P = 0.75), and all patients were free from reoperation for aortic disease. CONCLUSIONS: Patients who underwent aortic root repair using pericardial autograft tended to have reduced 30-day mortality and a lower risk of re-exploration for bleeding. Using pericardial autograft for aortic root repair is a safe and useful approach for patients with acute type A aortic dissection involving the aortic root.

The developmental pattern related to fatty acid uptake and oxidation in the yolk sac membrane and jejunum during embryogenesis in Muscovy duck.

This study aimed to investigate the developmental change of body growth and gene expression related to fatty acid uptake and oxidation in the yolk sac membrane (YSM) and jejunum during embryogenesis in Muscovy ducks. The weights of embryos and yolk sac (YS) (5 embryos per replicate, n = 6) were recorded on embryonic days (E)16, E19, E22, E25, E28, E31, and the day of hatch (DOH). The fat and fatty acid contents in YSM, jejunal histology, and gene expression related to fatty acid metabolism in YSM and jejunum were determined in each sampling time. Among the nonlinear models, the maximum growth is estimated at 2.83 (E22.5), 2.67 (E22.1), and 2.60 (E21.3) g/d using logistic, Gompertz, and Von Bertalanffy models, respectively. The weight of YS, and ether extract-free YS as well as the amounts of fat and fatty acids in YS decreased (P < 0.05) linearly, whereas the villus height, crypt depth, villus height/crypt depth, and musculature thickness in jejunum increased (P < 0.05) linearly during embryogenesis. The mRNA expression of CD36, SLC27A4, and FABP1 related to fatty acid uptake as well as the mRNA and protein expressions of PPARα and CPT1 related to fatty acid oxidation increased in a quadratic manner (P < 0.05) in both YS and jejunum, and the maximum values were achieved during E25 to E28. In conclusion, the maximum growth rate of Muscovy duck embryos was estimated at 2.60 to 2.83 g/d on E21.3 to E23.5, while the accumulations of lipid and fatty acid in YS were decreased in association with the increased absorptive area of morphological structures in jejunum. The gene and protein expression involved in fatty acid metabolism displayed a similar enhancement pattern between YSM and jejunum during E25 to E28, suggesting that fatty acid utilization could be strengthened to meet the energy demand for embryonic development.

H2Se-evolving bio-heterojunctions promote cutaneous regeneration in infected wounds by inhibiting excessive cellular senescence.

Pathogenic infection leads to excessive senescent cell accumulation and stagnation of wound healing. To address these issues, we devise and develop a hydrogen selenide (H2Se)-evolving bio-heterojunction (bio-HJ) composed of graphene oxide (GO) and FeSe2 to deracinate bacterial infection, suppress cellular senescence and remedy recalcitrant infected wounds. Excited by near-infrared (NIR) laser, the bio-HJ exerts desired photothermal and photodynamic effects, resulting in rapid disinfection. The crafted bio-HJ could also evolve gaseous H2Se to inhibit cellular senescence and dampen inflammation. Mechanism studies reveal the anti-senescence effects of H2Se-evolving bio-HJ are mediated by selenium pathway and glutathione peroxidase 1 (GPX1). More critically, in vivo experiments authenticate that the H2Se-evolving bio-HJ could inhibit cellular senescence and potentiate wound regeneration in rats. As envisioned, our work not only furnishes the novel gasotransmitter-delivering bio-HJ for chronic infected wounds, but also gets insight into the development of anti-senescence biomaterials.

Clinical and magnetic resonance imaging outcomes in pediatric-onset MS patients on fingolimod and ocrelizumab.

BACKGROUND: Observational studies looking at clinical a++nd MRI outcomes of treatments in pediatric MS, could assess current treatment algorithms, and provide insights for designing future clinical trials. OBJECTIVE: To describe baseline characteristics and clinical and MRI outcomes in MS patients initiating ocrelizumab and fingolimod under 18 years of age. METHODS: MS patients seen at 12 centers of US Network of Pediatric MS were included in this study if they had clinical and MRI follow-up and started treatment with either ocrelizumab or fingolimod prior to the age of 18. RESULTS: Eighty-seven patients initiating fingolimod and 52 initiating ocrelizumab met the inclusion criteria. Before starting fingolimod, mean annualized relapse rate was 0.43 (95 % CI: 0.29 - 0.65) and 78 % developed new T2 lesions while during treatment it was 0.12 (95 % CI: 0.08 - 1.9) and 47 % developed new T2 lesions. In the ocrelizumab group, the mean annualized relapse rate prior to initiation of treatment was 0.64 (95 % CI: 0.38-1.09) and a total of 83 % of patients developed new T2 lesions while during treatment it was 0.09 (95 % CI: 0.04-0.21) and none developed new T2 lesions. CONCLUSION: This study highlights the importance of evaluating current treatment methods and provides insights about the agents in the ongoing phase III trial comparing fingolimod and ocrelizumab.