P-Incorporation Induced Enhancement of Lattice Oxygen Participation in Double Perovskite Oxides to Boost Water Oxidation.

Activating the lattice oxygen in the catalysts to participate in the oxygen evolution reaction (OER), which can break the scaling relation-induced overpotential limitation (> 0.37 V) of the adsorbate evolution mechanism, has emerged as a new and highly effective guide to accelerate the OER. However, how to increase the lattice oxygen participation of catalysts during OER remains a major challenge. Herein, P-incorporation induced enhancement of lattice oxygen participation in double perovskite LaNi0.58Fe0.38P0.07O3-σ (PLNFO) is studied. P-incorporation is found to be crucial for enhancing the OER activity. The current density reaches 1.35 mA cmECSA -2 at 1.63 V (vs RHE), achieving a sixfold increase in intrinsic activity. Experimental evidences confirm the dominant lattice oxygen participation mechanism (LOM) for OER pathway on PLNFO. Further electronic structures reveal that P-incorporation shifts the O p-band center by 0.7 eV toward the Fermi level, making the states near the Fermi level more O p character, thus facilitating LOM and fast OER kinetics. This work offers a possible method to develop high-performance double perovskite OER catalysts for electrochemical water splitting.

Neuromuscular electrical stimulation effect on mRNA expression of skeletal muscle in elderly.

Considering the increasing number of elderly in the world, this research aimed to investigate the effect of neuromuscular electrical stimulation (NMES) on changes in muscle mRNA abundance of a number of gene targets for improving the balance of the elderly. Twenty-six elderly undertook 30 minutes of quadriceps NMES (50 Hz, current at the limit of tolerance). Vastus lateralis muscle biopsies were obtained at rest immediately before and 24 hours after the intervention. The expression of 384 targeted mRNA transcripts was assessed by Real-time TaqMan PCR. A significant change in expression from baseline was determined using the ΔΔCT method with a false discovery rate (FDR) of <5%. The results showed that the biological functions of upregulated genes included muscle protein turnover, hypertrophy, inflammation, and muscle growth, while downregulated genes included mitochondrial and cell signaling functions. In general conclusion, it can be said that NMES can improve balance in the elderly. Therefore, considering the importance of balance in old people, it is suggested to use this method to improve the balance of the elderly.

Effect of Electrical Stimulation Followed by Exercises in Postnatal Diastasis Recti Abdominis via MMP2 Gene Expression.

Since abdominal muscle training is one of the most important ways to treat rectal diastasis, it is necessary to design and provide appropriate exercises to treat this problem. One of the complementary methods to achieve higher intensity training is the use of electrical muscle stimulation along with voluntary activity, which causes maximum recall in muscle units. Therefore, in the current study, the effect of electrical stimulation followed by exercises was evaluated in postnatal diastasis recti abdominis via MMP2 gene expression. For this purpose, we studied on thirty-two women who had rectal diastasis for six months and were referred to a physiotherapy clinic by a gynecologist. They were divided into the control group (n=16) and the intervention group (n=16). The distance between the two blocks of the rectus abdominis muscle and the thickness of the abdominal muscles at rest was determined by ultrasound. In the intervention group, electrical stimulation and strengthening exercises of oblique muscles were performed for six weeks. The control group did not perform any specific exercises. After six weeks, another ultrasound was performed. The expression of the MMP2 gene was measured by the real-time PCR method. Comparison of the distance between the two blocks of rectus abdominis muscle (above the umbilicus and below the umbilicus) before and after six weeks showed that in the experimental group after intervention in both areas had a significant decrease (above the umbilicus = 0.001 and below the umbilicus P = 0.03), while this distance in the control group did not decrease significantly (p >0.05). Also, in the upper part of the umbilicus, the distance between the two rectus abdominis muscle blocks in two groups after the intervention showed a significant difference (p = 0.04). Evaluation of MMP2 gene expression showed that there was no significant difference between the two groups before the intervention (p >0.05). However, after the intervention, the expression of this gene decreased significantly in the intervention group (p = 0.007). In general, the present study results showed that electrical stimulation of abdominal muscles with strengthening exercises of internal and external oblique muscles could reduce rectal diastasis and increase the thickness of these muscles in people with rectal diastasis.

Versatile Octapod-Shaped Hollow Porous Manganese(II) Oxide Nanoplatform for Real-Time Visualization of Cargo Delivery.

Multifunctional nanoplatforms featuring promising properties including excellent loading efficiency, real-time monitoring, and improved cargo bioavailability and bioselectivity are in great demand by the biomedical research community. During the development of such nanoplatforms, stimuli-responsive nanoparticles (NPs) as a smart nanoplatform have recently received extensive attention. Herein, we report small-sized octapod-shaped hollow porous manganese(II) oxide (HPMO) NPs as a stimuli-responsive T1-activatable nanoplatform for tumor-specific cargo delivery and real-time monitoring. The HPMO NPs functionalized by zwitterionic dopamine sulfonate (ZDS) can act as a versatile platform to load organic dyes or chemotherapeutic drugs with high loading efficiency. The obtained Cargo@HPMO would decompose into paramagnetic Mn2+ ions and subsequently release cargoes in mild acidic conditions, especially in tumor microenvironment and lysosome. The released Mn2+ can enhance T1 magnetic resonance signal for real-time monitoring of the cargo delivery in vivo. This octapod-shaped Cargo@HPMO can act as a smart and versatile nanoplatform with pH-responsive multimodal imaging and site-specific drug delivery for the development of accurate diagnosis and effective therapy for cancer.

Targeted arsenite-loaded magnetic multifunctional nanoparticles for treatment of hepatocellular carcinoma.

Arsenic trioxide (ATO), an FDA-approved drug for acute promyelocytic leukemia, also has great potential for treatment of solid tumors. Drug delivery powered by recent advances in nanotechnology has boosted the efficacy of many drugs, which is enlightening for applications of ATO in treating solid tumors. Herein, we reported arsenite-loaded multifunctional nanoparticles that are capable of pH-responsive ATO release for treating hepatocellular carcinoma (HCC) and real-time monitoring via magnetic resonance imaging. We fabricated these nanoparticles (designated as magnetic large-pore mesoporous silica nanoparticle (M-LPMSN)-NiAsO x ) by loading nanoparticulate ATO prodrugs (NiAsO x ) into the pores of large-pore mesoporous silica nanoparticles (LPMSNs) that contain magnetic iron oxide nanoparticles in the center. The surface of these nanodrugs was modified with a targeting ligand folic acid (FA) to further enhance the drug efficacy. Releasing profiles manifest the responsive discharging of arsenite in acidic environment. In vitro experiments with SMMC-7721 cells reveal that M-LPMSN-NiAsO x -FA nanodrugs have significantly higher cytotoxicity than traditional free ATO and induce more cell apoptosis. In vivo experiments with mice bearing H22 tumors further confirm the superior antitumor efficacy of M-LPMSN-NiAsO x -FA over traditional free ATO and demonstrate the outstanding imaging ability of M-LPMSN-NiAsO x -FA for real-time tumor monitoring. These targeted arsenite-loaded magnetic mesoporous silica nanoparticles integrating imaging and therapy hold great promise for treatment of HCC, indicating the auspicious potential of LPMSN-based nanoplatforms.

Application Analysis of Low-Pressure Perfusion Combined with Occluder in Holmium Laser Lithotripsy for Patients with Middle and Upper Ureteral Calculi.

BACKGROUND: Ureteroscopic holmium laser lithotripsy has become one of the main methods of treating ureteral calculi. However, in the treatment of middle and upper ureteral calculi, ureteroscopy is difficult to operate owing to the high location of calculi. Thus, how to improve the treatment effect and reduce the stone migration has become the focus in clinical settings. On this basis, we evaluated the application effect of low-pressure perfusion combined with occluder in holmium laser lithotripsy for patients with middle and upper ureteral calculi. METHODS: This retrospective study selected 107 patients with middle and upper ureteral calculi who underwent low-pressure perfusion combined with ureteroscopic holmium laser lithotripsy from January 2021 to December 2022. We excluded 7 patients who did not meet the criteria, and ultimately included 100 patients. According to whether the occluder was used during the surgery, 100 patients were divided into groups A (n = 52, occluder) and B (n = 48, without occluder). The stone-migration rate during surgery, stone-clearance rate at 3 months after surgery, perioperative indicators, postoperative complication rate, and postoperative quality of life between the two groups were compared. RESULTS: The stone-migration rate in group A was significantly lower than that in group B, with statistically significant difference (p < 0.05). Both groups had no significant difference in stone-clearance rate at 3 months after surgery (p > 0.05). Group A had a significantly lower index of EuroQol (EQ) Five Dimensions Questionnaire and significantly higher score of EQ-Visual Analogue Scale than group B (all p < 0.001). CONCLUSIONS: Compared with the simple application of low-pressure perfusion, the combined application of low-pressure perfusion and occluder in ureteroscopic holmium laser lithotripsy can effectively reduce the stone migration and improve the postoperative quality of life.

Tuning the high-entropy perovskite as efficient and reliable electrocatalysts for oxygen evolution reaction.

Due to their unique electronic structure, atomic arrangement and synergistic effect, high-entropy materials are being actively pursued as electrocatalysts for oxygen evolution reaction (OER) in water splitting. However, a relevant strategy to improve high-entropy materials is still lacking. Herein, substitutional doping on the La-site in high-entropy perovskite La1-x Sr x (CrMnFeCoNi)0.2O3 is reported as an efficient OER catalyst. Sr doping is found to be crucial to enhancing the OER activity. The overpotential for the best catalyst La0.3Sr0.7(CrMnFeCoNi)0.2O3 is only 330 mV at 10 mA cm-2, achieving a reduction of 120 mV in overpotential compared to La(CrMnFeCoNi)0.2O3, which is attributed to the enhancement in intrinsic catalytic activity. Experimental evidences including in situ electrochemical impedance spectroscopy (EIS) and X-ray photoelectron spectroscopy (XPS) indicate Sr doping induces the formation of high-valence Cr6+, Mn4+, Fe4+, Co4+ and Ni3+ species, which can accelerate the faster charge transfer at the interface, thereby increasing the intrinsic catalytic activity. The assembled two-electrode overall water splitting system operates stably at 10 mA cm-2 for 200 h without attenuation. This work offers an important method for developing a high-performance, high-entropy perovskite OER catalyst for hydrogen production by electrochemical water splitting.

Engineering iron-based nanomaterials for breast cancer therapy associated with ferroptosis.

Ferroptosis has received increasing attention as a novel nonapoptotic programmed death. Recently, iron-based nanomaterials have been extensively exploited for efficient tumor ferroptosis therapy, as they directly release high concentrations of iron and increase intracellular reactive oxygen species levels. Breast cancer is one of the commonest malignant tumors in women; inhibiting breast cancer cell proliferation through activating the ferroptosis pathway could be a potential new target for patient treatment. Here, we briefly introduce the background of ferroptosis and systematically review the current cancer therapeutic strategies based on iron-based ferroptosis inducers. Finally, we summarize the advantages of these various ferroptosis inducers and shed light on future perspectives. This review aims to provide better guidance for the development of iron-based nanomaterial ferroptosis inducers.

Au-Fe3O4 Janus nanoparticles for imaging-guided near infrared-enhanced ferroptosis therapy in triple negative breast cancer.

Triple-negative breast cancer (TNBC) is insensitive to conventional therapy due to its highly invasive nature resulting in poor therapeutic outcomes. Recent studies have shown multiple genes associated with ferroptosis in TNBC, suggesting an opportunity for ferroptosis-based treatment of TNBC. However, the efficiency of present ferroptosis agents for cancer is greatly restricted due to lack of specificity and low intracellular levels of H2O2 in cancer cells. Herein, we report a nano-theranostic platform consisting of gold (Au)-iron oxide (Fe3O4) Janus nanoparticles (GION@RGD) that effectively enhances the tumor-specific Fenton reaction through utilization of near-infrared (NIR) lasers, resulting in the generation of substantial quantities of toxic hydroxyl radicals (•OH). Specifically, Au nanoparticles (NPs) converted NIR light energy into thermal energy, inducing generation of abundant intracellular H2O2, thereby enhancing the iron-induced Fenton reaction. The generated •OH not only lead to apoptosis of malignant tumor cells but also induce the accumulation of lipid peroxides, causing ferroptosis of tumor cells. After functionalizing with the activity-targeting ligand RGD (Arg-Gly-Asp), precise synergistic treatment of TNBC was achieved in vivo under the guidance of Fe3O4 enhanced T2-weighted magnetic resonance imaging (MRI). This synergistic treatment strategy of NIR-enhanced ferroptosis holds promise for the treatment of TNBC.

Application of nanomaterials in the treatment of intracerebral hemorrhage.

Intracerebral hemorrhage (ICH) is a non-traumatic hemorrhage caused by the rupture of blood vessels in the brain parenchyma, with an acute mortality rate of 30%‒40%. Currently, available treatment options that include surgery are not promising, and new approaches are urgently needed. Nanotechnology offers new prospects in ICH because of its unique benefits. In this review, we summarize the applications of various nanomaterials in ICH. Nanomaterials not only enhance the therapeutic effects of drugs as delivery carriers but also contribute to several facets after ICH such as repressing detrimental neuroinflammation, resisting oxidative stress, reducing cell death, and improving functional deficits.

A valuable subarachnoid space named the occipito-atlantal cistern.

The cisterna magna has been defined as the space between the inferior margin of the cerebellar vermis to the level of the foramen magnum, while an enlarged dorsal subarachnoid space at the occipito-cervical junction extending from the foramen magnum to the upper border of the axis (C2) is still ignored. Recently, the myodural bridge complex is proved to drive the cerebral spinal fluid flowing via this region, we therefore introduce the "occipito-atlantal cistern (OAC)" to better describe the subarachnoid space and provide a detailed rationale. The present study utilized several methods, including MRI, gross anatomical dissection, P45 sheet plastination, and three-dimensional visualization. OAC was observed to be an enlarge subarachnoid space, extending from the foramen magnum to the level of the C2. In the median sagittal plane, OAC was a funnel shape and its anteroposterior dimensions were 15.92 ± 4.20 mm at the level of the C0, 4.49 ± 1.25 mm at the level of the posterior arch of the C1, and 2.88 ± 0.77 mm at the level of the arch of the C2, respectively. In the median sagittal plane, the spino-dural angle of the OAC was calculated to be 35.10 ± 6.91°, and the area of OAC was calculated to be 232.28 ± 71.02 mm2. The present study provides OAC is a subarachnoid space independent from the cisterna magna. Because of its distinctive anatomy, as well as theoretical and clinical significance, OAC deserves its own name.

The Important Role of Zinc in Neurological Diseases.

Zinc is one of the most abundant metal ions in the central nervous system (CNS), where it plays a crucial role in both physiological and pathological brain functions. Zinc promotes antioxidant effects, neurogenesis, and immune system responses. From neonatal brain development to the preservation and control of adult brain function, zinc is a vital homeostatic component of the CNS. Molecularly, zinc regulates gene expression with transcription factors and activates dozens of enzymes involved in neuronal metabolism. During development and in adulthood, zinc acts as a regulator of synaptic activity and neuronal plasticity at the cellular level. There are several neurological diseases that may be affected by changes in zinc status, and these include stroke, neurodegenerative diseases, traumatic brain injuries, and depression. Accordingly, zinc deficiency may result in declines in cognition and learning and an increase in oxidative stress, while zinc accumulation may lead to neurotoxicity and neuronal cell death. In this review, we explore the mechanisms of brain zinc balance, the role of zinc in neurological diseases, and strategies affecting zinc for the prevention and treatment of these diseases.

Acid-triggered in vivo aggregation of Janus nanoparticles for enhanced imaging-guided photothermal therapy.

Poor tumor delivery efficiency remains a significant challenge for the integrated nanoplatform for diagnosis and treatment. Nanotherapeutics capable of aggregation in response to the tumor microenvironment has received considerable attention because of its ability to enhance tumor delivery efficiency and accumulation. We prepared smart Au-Fe3O4 Janus nanoparticles (GIJ NPs) modified with mixed-charged ligands (3,4-dihydroxyhydrocinnamic acid [DHCA] and trimethylammonium dopamine [TMAD]). The obtained GIJ@DHCA-TMAD could be stable at the pH of the blood and normal tissues, but aggregated into larger particles in response to the tumor acidic microenvironment, leading to greatly enhanced accumulation in cancer cells. The hydrodynamic diameters of GIJ@DHCA-TMAD increased from 28.2 to 105.7 nm when the pH decreased from 7.4 to 5.5. Meanwhile, the T 2 magnetic resonance imaging (MRI) contrast capability, photoacoustic imaging (PAI) performance, and photothermal conversion efficiency of GIJ@DHCA-TMAD were also enhanced with increasing diameter. Tumor-specific enhanced MRI and PAI can precisely locate tumor boundaries and can be used to perform preliminary photothermal tumor ablation therapy: the pH-sensitive GIJ@DHCA-TMAD can be used in dual-mode, tumor-specific imaging-guided photothermal therapy to better meet the multiple requirements for in vivo applications.

Zwitterion-Coated Ultrasmall MnO Nanoparticles Enable Highly Sensitive T1-Weighted Contrast-Enhanced Brain Imaging.

Manganese oxide nanoparticles (NPs) have attracted increasing attention recently as contrast agents (CAs) for magnetic resonance imaging (MRI). However, the clinical translation and popularization of conventional MnO NPs are hampered by their relatively poor imaging performance. Herein, we report the construction of ultrasmall MnO NPs (USMnO) via a one-pot synthetic approach that show a much better capability of T1-weighted contrast enhancement for MRI (r1 = 15.6 ± 0.4 mM-1 s-1 at 0.5 T) than MnCl2 and conventional large-sized MnO NPs (MnO-22). These USMnO are further coated with zwitterionic dopamine sulfonate (ZDS) molecules, which improves their biocompatibility and prevents nonspecific binding of serum albumins. Interestingly, USMnO@ZDS are capable of passing through the blood-brain barrier (BBB), which enables the acquisition of clear images showing brain anatomic structures with T1-weighted contrast-enhanced MRI. Therefore, our USMnO@ZDS could be used as a promising MRI CA for the flexible and accurate diagnosis of brain diseases, which is also instructive for the construction of manganese-based CA with a high MRI performance.

Multiple organelle-targeted near-infrared fluorescent probes toward pH and viscosity.

Organelles, including mitochondria (mito), lysosomes (lyso), endoplasmic reticulum (ER), Golgi apparatus (Golgi), and ribosome et al., play a vital role in maintaining the regular work of the cell. Viscosity is an essential parameter in the cellular microenvironment. Herein, four viscosity-sensitive near-infrared fluorescent probes DMPC, DEPC, DHDM and DHDV that can simultaneously target multiple organelles were synthesized. As the viscosity increased, the fluorescence intensity of the probes gradually increased due to the hindrance of the rotation of the carbon-carbon single bond. The fluorescence intensity of DHDV increased by about 453 times, and the fluorescence quantum yield also increased from 0.051 to 0.681. Cell experiments indicated the probes could simultaneously target four kinds of organelles, and the four probes could also track mitochondria with no dependence on membrane potential. Further experiments showed that the probes could detect viscosity changes in lyso and mito. In addition, the probes also demonstrated the advantages of low cytotoxicity, good anti-interference and stability, providing a simple and effective tool for studying the activity of organelles with changing viscosity signals.

Therapeutic strategies for intracerebral hemorrhage.

Stroke is the second highest cause of death globally, with an increasing incidence in developing countries. Intracerebral hemorrhage (ICH) accounts for 10-15% of all strokes. ICH is associated with poor neurological outcomes and high mortality due to the combination of primary and secondary injury. Fortunately, experimental therapies are available that may improve functional outcomes in patients with ICH. These therapies targeting secondary brain injury have attracted substantial attention in their translational potential. Here, we summarize recent advances in therapeutic strategies and directions for ICH and discuss the barriers and issues that need to be overcome to improve ICH prognosis.

Recent advances in engineering iron oxide nanoparticles for effective magnetic resonance imaging.

Iron oxide nanoparticle (IONP) with unique magnetic property and high biocompatibility have been widely used as magnetic resonance imaging (MRI) contrast agent (CA) for long time. However, a review which comprehensively summarizes the recent development of IONP as traditional T 2 CA and its new application for different modality of MRI, such as T 1 imaging, simultaneous T 2/T 1 or MRI/other imaging modality, and as environment responsive CA is rare. This review starts with an investigation of direction on the development of high-performance MRI CA in both T 2 and T 1 modal based on quantum mechanical outer sphere and Solomon-Bloembergen-Morgan (SBM) theory. Recent rational attempts to increase the MRI contrast of IONP by adjusting the key parameters, including magnetization, size, effective radius, inhomogeneity of surrounding generated magnetic field, crystal phase, coordination number of water, electronic relaxation time, and surface modification are summarized. Besides the strategies to improve r 2 or r 1 values, strategies to increase the in vivo contrast efficiency of IONP have been reviewed from three different aspects, those are introducing second imaging modality to increase the imaging accuracy, endowing IONP with environment response capacity to elevate the signal difference between lesion and normal tissue, and optimizing the interface structure to improve the accumulation amount of IONP in lesion. This detailed review provides a deep understanding of recent researches on the development of high-performance IONP based MRI CAs. It is hoped to trigger deep thinking for design of next generation MRI CAs for early and accurate diagnosis.

Iron Neurotoxicity and Protection by Deferoxamine in Intracerebral Hemorrhage.

Intracerebral hemorrhage (ICH) is a subtype of stroke that is characterized by high morbidity and mortality, for which clinical outcome remains poor. An extensive literature indicates that the release of ferrous iron from ruptured erythrocytes in the hematoma is a key pathogenic factor in ICH-induced brain injury. Deferoxamine is an FDA-approved iron chelator that has the capacity to penetrate the blood-brain barrier after systemic administration and binds to iron. Previous animal studies have shown that deferoxamine attenuates ICH-induced brain edema, neuronal death, and neurological deficits. This review summarizes recent progress of the mechanisms by which deferoxamine may alleviate ICH and discusses further studies on its clinical utility.

Neuroprotection by Ozanimod Following Intracerebral Hemorrhage in Mice.

The destruction of the blood-brain barrier (BBB) after intracerebral hemorrhage (ICH) is associated with poor prognosis. Modulation of sphingosine 1-phosphate receptor (S1PR) may improve outcomes from ICH. Ozanimod (RPC-1063) is a newly developed S1PR regulator which can selectively modulate type 1/5 sphingosine receptors. Here, we studied the impact of Ozanimod on neuroprotection in an experimental mouse model of ICH, induced by injecting collagenase type VII into the basal ganglia. Ozanimod was administered by gavage 2 h after surgery and once a day thereafter until sacrifice. The results demonstrate that Ozanimod treatment improved neurobehavioral deficits in mice and decreased weight loss after ICH. Ozanimod significantly reduced the density of activated microglia and infiltrated neutrophils in the perihematoma region. Furthermore, Ozanimod reduced hematoma volume and water content of the ICH brain. The results of TUNEL staining indicate that Ozanimod mitigated brain cell death. The quantitative data of Evans blue (EB) staining showed that Ozanimod reduced EB dye leakage. Overall, Ozanimod reduces the destruction of the BBB and exert neuroprotective roles following ICH in mice.

RNA-seq reveals transcriptional differences in anthocyanin and vitamin biosynthetic pathways between black and white rice.

Anthocyanins and vitamins in black rice are the micronutrients vital to human health, both of which predominantly accumulate in the bran fraction. Some studies have demonstrated that black rice contains more vitamins compared with common white rice, indicating potential association between anthocyanin and vitamin accumulation. In this study, transcriptomes of pericarps collected from 27 black rice accessions and 49 white rice accessions at 10 days after flowering (DAF) were sequenced and analyzed. We identified 830 differentially expressed genes (DEGs) including 58 transcription factors (TFs) between black and white rice. Among 58 differentially expressed transcription factors, OsTTG1 was confirmed to be the one and only WD40 repeat protein regulating anthocyanin biosynthesis in the pericarp. Moreover, we identified 53 differentially expressed synthetic-related genes among 42 main synthesis enzymes in the biosynthesis pathway of seven vitamins including ß-carotene, vitamin B1, vitamin B2, vitamin B5, vitamin B7, vitamin B9 and vitamin E. Collectively, our results provide valuable insights into the molecular mechanism of biosynthesis of anthocyanins and vitamins and the potential effect of anthocyanin biosynthesis on vitamin biosynthesis in black rice.