Icariin improves oxidative stress injury during ischemic stroke via inhibiting mPTP opening.

BACKGROUND: Ischemic stroke presents a significant threat to human health due to its high disability rate and mortality. Currently, the clinical treatment drug, rt-PA, has a narrow therapeutic window and carries a high risk of bleeding. There is an urgent need to find new effective therapeutic drugs for ischemic stroke. Icariin (ICA), a key ingredient in the traditional Chinese medicine Epimedium, undergoes metabolism in vivo to produce Icaritin (ICT). While ICA has been reported to inhibit neuronal apoptosis after cerebral ischemia-reperfusion (I/R), yet its underlying mechanism remains unclear. METHODS: PC-12 cells were treated with 200 µM H2O2 for 8 h to establish a vitro model of oxidative damage. After administration of ICT, cell viability was detected by Thiazolyl blue tetrazolium Bromide (MTT) assay, reactive oxygen species (ROS) and apoptosis level, mPTP status and mitochondrial membrane potential (MMP) were detected by flow cytometry and immunofluorescence. Apoptosis and mitochondrial permeability transition pore (mPTP) related proteins were assessed by Western blotting. Middle cerebral artery occlusion (MCAO) model was used to establish I/R injury in vivo. After the treatment of ICA, the neurological function was scored by ZeaLonga socres; the infarct volume was observed by 2,3,5-Triphenyltetrazolium chloride (TTC) staining; HE and Nissl staining were used to detect the pathological state of the ischemic cortex; the expression changes of mPTP and apoptosis related proteins were detected by Western blotting. RESULTS: In vitro: ICT effectively improved H2O2-induced oxidative injury through decreasing the ROS level, inhibiting mPTP opening and apoptosis. In addition, the protective effects of ICT were not enhanced when it was co-treated with mPTP inhibitor Cyclosporin A (CsA), but reversed when combined with mPTP activator Lonidamine (LND). In vivo: Rats after MCAO shown cortical infarct volume of 32-40%, severe neurological impairment, while mPTP opening and apoptosis were obviously increased. Those damage caused was improved by the administration of ICA and CsA. CONCLUSIONS: ICA improves cerebral ischemia-reperfusion injury by inhibiting mPTP opening, making it a potential candidate drug for the treatment of ischemic stroke.

Icariin Ameliorates D-galactose-induced Cell Injury in Neuron-like PC12 Cells by Inhibiting MPTP Opening.

OBJECTIVE: Icariin (ICA) has a good neuroprotective effect and can upregulate neuronal basal autophagy in naturally aging rats. Mitochondrial dysfunction is associated with brain aging-related neurodegenerative diseases. Abnormal opening of the mitochondrial permeability transition pore (mPTP) is a crucial factor in mitochondrial dysfunction and is associated with excessive autophagy. This study aimed to explore that ICA protects against neuronal injury by blocking the mPTP opening and down-regulating autophagy levels in a D-galactose (D-gal)-induced cell injury model. METHODS: A cell model of neuronal injury was established in rat pheochromocytoma cells (PC12 cells) treated with 200 mmol/L D-gal for 48 h. In this cell model, PC12 cells were pre-treated with different concentrations of ICA for 24 h. MTT was used to detect cell viability. Senescence associated ß-galactosidase (SA-ß-Gal) staining was used to observe cell senescence. Western blot analysis was performed to detect the expression levels of a senescence-related protein (p21), autophagy markers (LC3B, p62, Atg7, Atg5 and Beclin 1), mitochondrial fission and fusion-related proteins (Drp1, Mfn2 and Opa1), and mitophagy markers (Pink1 and Parkin). The changes of autophagic flow were detected by using mRFP-GFP-LC3 adenovirus. The intracellular ultrastructure was observed by transmission electron microscopy. Immunofluorescence was used to detect mPTP, mitochondrial membrane potential (MMP), mitochondrial reactive oxygen species (mtROS) and ROS levels. ROS and apoptosis levels were detected by flow cytometry. RESULTS: D-gal treatment significantly decreased the viability of PC12 cells, and markedly increased the SA-ß-Gal positive cells as compared to the control group. With the D-gal stimulation, the expression of p21 was significantly up-regulated. Furthermore, D-gal stimulation resulted in an elevated LC3B II/I ratio and decreased p62 expression. Meanwhile, autophagosomes and autolysosomes were significantly increased, indicating abnormal activation of autophagy levels. In addition, in this D-gal-induced model of cell injury, the mPTP was abnormally open, the ROS generation was continuously increased, the MMP was gradually decreased, and the apoptosis was increased. ICA effectively improved mitochondrial dysfunction to protect against D-gal-induced cell injury and apoptosis. It strongly inhibited excessive autophagy by blocking the opening of the mPTP. Cotreatment with ICA and an mPTP inhibitor (cyclosporin A) did not ameliorate mitochondrial dysfunction. However, the protective effects were attenuated by cotreatment with ICA and an mPTP activator (lonidamine). CONCLUSION: ICA inhibits the activation of excessive autophagy and thus improves mitochondrial dysfunction by blocking the mPTP opening.

Regulating tumor innervation by nanodrugs potentiates cancer immunochemotherapy and relieve chemotherapy-induced neuropathic pain.

Sympathetic nerves play a pivotal role in promoting tumor growth through crosstalk with tumor and stromal cells. Chemotherapy exacerbates the infiltration of sympathetic nerves into tumors, thereby providing a rationale for inhibiting sympathetic innervation to enhance chemotherapy. Here, we discovered that doxorubicin increases the density and activity of sympathetic nerves in breast cancer mainly by upregulating the expression of nerve growth factors (NGFs) in cancer cells. To address this, we developed a combination therapy by co-encapsulating small interfering RNA (siRNA) and doxorubicin within breast cancer-targeted poly (lactic-co-glycolic acid) (PLGA) nanoparticles, aiming to suppress NGF expression post-chemotherapy. Incorporating NGF blockade into the nanoplatform for chemotherapy effectively mitigated the chemotherapy-induced proliferation of sympathetic nerves. This not only bolstered the tumoricidal activity of chemotherapy, but also amplified its stimulatory impact on the antitumor immune response by increasing the infiltration of immunostimulatory cells into tumors while concurrently reducing the frequency of immunosuppressive cells. Consequently, the combined nanodrug approach, when coupled with anti-PD-L1 treatment, exhibited a remarkable suppression of primary and deeply metastatic tumors with minimal systematic toxicity. Importantly, the nanoplatform relieved chemotherapy-induced peripheral neuropathic pain (CIPNP) by diminishing the expression of pain mediator NGFs. In summary, this research underscores the significant potential of NGF knockdown in enhancing immunochemotherapy outcomes and presents a nanoplatform for the highly efficient and low-toxicity treatment of breast cancer.

Advances in conductive hydrogels for neural recording and stimulation.

The brain-computer interface (BCI) allows the human or animal brain to directly interact with the external environment through the neural interfaces, thus playing the role of monitoring, protecting, improving/restoring, enhancing, and replacing. Recording electrophysiological information such as brain neural signals is of great importance in health monitoring and disease diagnosis. According to the electrode position, it can be divided into non-implantable, semi-implantable, and implantable. Among them, implantable neural electrodes can obtain the highest-quality electrophysiological information, so they have the most promising application. However, due to the chemo-mechanical mismatch between devices and tissues, the adverse foreign body response and performance loss over time seriously restrict the development and application of implantable neural electrodes. Given the challenges, conductive hydrogel-based neural electrodes have recently attracted much attention, owing to many advantages such as good mechanical match with the native tissues, negligible foreign body response, and minimal signal attenuation. This review mainly focuses on the current development of conductive hydrogels as a biocompatible framework for neural tissue and conductivity-supporting substrates for the transmission of electrical signals of neural tissue to speed up electrical regeneration and their applications in neural sensing and recording as well as stimulation.

Implantable Neural Microelectrodes: How to Reduce Immune Response.

Implantable neural microelectrodes exhibit the great ability to accurately capture the electrophysiological signals from individual neurons with exceptional submillisecond precision, holding tremendous potential for advancing brain science research, as well as offering promising avenues for neurological disease therapy. Although significant advancements have been made in the channel and density of implantable neural microelectrodes, challenges persist in extending the stable recording duration of these microelectrodes. The enduring stability of implanted electrode signals is primarily influenced by the chronic immune response triggered by the slight movement of the electrode within the neural tissue. The intensity of this immune response increases with a higher bending stiffness of the electrode. This Review thoroughly analyzes the sequential reactions evoked by implanted electrodes in the brain and highlights strategies aimed at mitigating chronic immune responses. Minimizing immune response mainly includes designing the microelectrode structure, selecting flexible materials, surface modification, and controlling drug release. The purpose of this paper is to provide valuable references and ideas for reducing the immune response of implantable neural microelectrodes and stimulate their further exploration in the field of brain science.

A metal-organic framework complex for enhancing tumor treatments through synergistic effect of chemotherapy and photodynamic therapy.

Porphyrin-based metal-organic frameworks (PMOFs) are a kind of crystal hybrid material with broad application prospects in energy, catalysis, biomedicine, and other fields. In this study, the La-TCPP PMOF nanocrystal was constructed using a porphyrin ligand and La ion. This material can produce a high loading rate on doxorubicin (DOX) owing to its special porous structure. The high loading rate of drug molecules and the reactive oxygen species (ROS) of the porphyrin ligand enable La-TCPP@DOX nanocrystal to produce a powerful killing effect on cancer cells under the synergistic attack of chemotherapy (CT) and photodynamic therapy (PDT). Finally, by modifying the targeted aptamer, the actual therapeutic effect of this special La-TCPP@DOX@Apt material on tumors was confirmed by applying the established mouse tumor model. The composite nanomaterial not only avoids the side effects caused by high concentrations of chemotherapeutic drugs, but also overcomes the limitation of PDT owing to insufficient light penetration and can inhibit and kill solid tumors under the condition of synergistic attack. This study is a complement to PMOF crystal materials, and its tumor-killing ability was achieved by loading drugs and introducing targeting molecules, which proves that the synergistic attack can more effectively inhibit and treat solid tumors. These studies have a reference and guiding significance for the treatment of cancer patients.

SLC35D3 promotes white adipose tissue browning to ameliorate obesity by NOTCH signaling.

White adipose tissue browning can promote lipid burning to increase energy expenditure and improve adiposity. Here, we show that Slc35d3 expression is significantly lower in adipose tissues of obese mice. While adipocyte-specific Slc35d3 knockin is protected against diet-induced obesity, adipocyte-specific Slc35d3 knockout inhibits white adipose tissue browning and causes decreased energy expenditure and impaired insulin sensitivity in mice. Mechanistically, we confirm that SLC35D3 interacts with the NOTCH1 extracellular domain, which leads to the accumulation of NOTCH1 in the endoplasmic reticulum and thus inhibits the NOTCH1 signaling pathway. In addition, knockdown of Notch1 in mouse inguinal white adipose tissue mediated by orthotopic injection of AAV8-adiponectin-shNotch1 shows considerable improvement in obesity and glucolipid metabolism, which is more pronounced in adipocyte-specific Slc35d3 knockout mice than in knockin mice. Overall, in this study, we reveal that SLC35D3 is involved in obesity via NOTCH1 signaling, and low adipose SLC35D3 expression in obesity might be a therapeutic target for obesity and associated metabolic disorders.

Antioxidant N-acetylcysteine removing ROS: an antifouling strategy inspired by mussels.

Marine biofouling is a thorny issue that causes serious economic losses and adverse ecological impacts on marine ecosystems. Effective and promising antifouling strategies such as surface hydration, flow shear force, and lubricant injection have been developed to address this challenge. However, for the complex marine environment, they still appear inadequate. Mussels are a common fouling organism with strong surface adhesion ability. However, when hypoxia and the oxidative cross-linking reaction of 3,4-dihydroxy phenyl-L-alanine (DOPA) in the structure of adhesion proteins are disrupted, their adhesion ability will be greatly reduced. Inspired by this, we developed an effective antifouling strategy based on reactive oxygen species (ROS) scavenging using N-acetylcysteine (NAC) and evaluated its performance. As a ROS scavenger interfered with the oxidative cross-linking reaction of DOPA in an aqueous solution, the adhesion of DOPA was also affected on the surface of NAC functionalized polyvinyl chloride (PVC) (PVC-NAC). In addition, the colonization level of mussels and the adhesion rate of marine bacteria and benthic diatoms on PVC-NAC were low. The antifouling strategy proposed in this paper was eco-friendly and broad-spectrum, and may provide a new idea for solving marine biofouling and reducing the environmental and economic impacts of fouling organisms.

Saponins of Panax japonicus ameliorates cardiac aging phenotype in aging rats by enhancing basal autophagy through AMPK/mTOR/ULK1 pathway.

Heart disease is a significant health concern for elderly individuals, with heart aging being the primary cause. Recent studies have shown that autophagy can play a protective role in preventing cardiac aging. Our previous research confirmed that Chikusetsu saponin IVa, a fundamental component of Saponins of Panax japonics (SPJ), can enhance basic autophagy levels in cardiomyocyte of isoproterenol induced cardiac fibrosis mice. However, it remains unclear whether SPJ possesses a protective effect on cardiac dysfunction during the natural aging process. Rats were randomly divided into four groups: adult control group (6 months old), aging group (24 months old), aging group treated with 10 mg/kg SPJ, and aging group treated with 30 mg/kg SPJ. The heart function, blood pressure, and heart mass index (HMI) were measured. Hematoxylin and eosin staining (H&E) and Wheat Germ Agglutinin (WGA) staining were used to observe the changes in morphology, while Masson staining was used to examine collagen deposition in the rat hearts and CD45 immunohistochemistry was conducted to examine the macrophage infiltration in heart tissues. TUNEL kit was used to detect apoptosis level of cardiomyocyte, and western blot was used to evaluate autophagy-related proteins as well as AMPK/mTOR/ULK1 pathway-related markers. SPJ treatment improved the cardiac function, reduced HMI, attenuated myocardial fiber disorder, inhibited inflammatory cell infiltration, and decreased collagen deposition and cardiomyocyte apoptosis in aging rats. Additionally, SPJ treatment decreased the expression of aging-related proteins and restored the expression of autophagy-related markers. SPJ activated autophagy through the activation of AMPK, which in turn increased the phosphorylation of ULK1(Ser555), while inhibited the phosphorylation of mTOR and ULK1(Ser757). Our study demonstrates that SPJ improves the cardiac function of aging rats by enhancing basal autophagy through the AMPK/mTOR/ULK1 pathway. These results offer a theoretical foundation and empirical evidence to support the clinical advancement of SPJ in enhancing age-related cardiac dysfunction.

Differentially expressed transcripts study during pregnancy and postpartum anestrus of yak (Bos grunniens).

Background: Yak is the main livestock species in the plateau area, and its reproductive performance is low, usually two years or three years. A very few of yaks recover within a certain period of time after delivery and smoothly enter the next estrous cycle, while most of them enter the postpartum anestrus and show no estrus performance. However, the key biological factors and influencing mechanisms that cause postpartum anestrus in yaks are not clear. Objective: To study the expression of differential transcripts in ovaries of yak during pregnancy and postpartum anestrus. Methods: Each three yaks in pregnancy and anestrus under natural grazing conditions in Haiyan County, Qinghai Province were selected and slaughtered, and their ovaries were collected and sent to Biomarker Technologies. Oxford Nanopore Technologies single-molecule real-time electrical signal sequencing technology was used to perform full-length transcriptome sequencing. Astalavista software was used to identify the types of alternative splicing events in yak estrus and pregnancy, and TAPIS pipeline was used to identify alternative polyadenylation. Results: The results showed that there were 1751 differentially expressed transcripts (DETs) between pregnancy and anestrus in yak, of which 808 were upregulated and 943 were downregulated. GO analysis showed that the biological processes of DETs were mainly reproductive, reproductive and rhythmic processes. KEGG analysis showed that the DET cell junction-related adhesion junction protein (ß-catenin) and amino terminal kinase (JNK) were involved in FAs (local adhesion). Phosphatidylinositol-3-kinase (PI3K) is involved in the PI3K/AKT/mTOR signaling pathway. Circadian rhythm output cycle failure (Clock) and brain and muscle tissue aromatic hydrocarbon receptor nuclear transporter-like protein 1 (Bmal1) are involved in circadian rhythm signaling pathway. Conclusion: This study found that ß-catenin, JNK, PI3K, Clock and Bmal1 were closely related to postpartum anestrus in yak.

Discovery of novel isopropanolamine inhibitors against MoTPS1 as potential fungicides with unique mechanisms.

The resistance and ecotoxicity of fungicides seriously restrict our ability to effectively control Magnaporthe oryzae. Discovering fungicidal agents based on novel targets, including MoTPS1, could efficiently address this situation. Here, we identified a hit VS-10 containing an isopropanolamine fragment as a novel MoTPS1 inhibitor through virtual screening, and forty-four analogs were synthesized by optimizing the structure of VS-10. Utilizing our newly established ion-pair chromatography (IPC) and leaf inoculation methods, we found that compared to VS-10, its analog j11 exhibited substantially greater inhibitory activity against both MoTPS1 and the pathogenicity of M. oryzae. Molecular simulations clarified that the electrostatic interactions between the bridging moiety of isopropanolamine and residue Glu396 of contributed significantly to the binding of j11 and MoTPS1. We preliminarily revealed the unique fungicidal mechanism of j11, which mainly impeded the infection of M. oryzae by decreasing sporulation, killing a small portion of conidia and interfering with the accumulation of turgor pressure in appressoria. Thus, in this study, a novel fungicide candidate with a unique mechanism targeting MoTPS1 was screened and discovered.

Cardiac organoid: multiple construction approaches and potential applications.

The human cardiac organoid (hCO) is three-dimensional tissue model that is similar to an in vivo organ and has great potential on heart development biology, disease modeling, drug screening and regenerative medicine. However, the construction of hCO presents a unique challenge compared with other organoids such as the lung, small intestine, pancreas, liver. Since heart disease is the dominant cause of death and the treatment of such disease is one of the most unmet medical needs worldwide, developing technologies for the construction and application of hCO is a critical task for the scientific community. In this review, we discuss the current classification and construction methods of hCO. In addition, we describe its applications in drug screening, disease modeling, and regenerative medicine. Finally, we propose the limitations of the cardiac organoid and future research directions. A detailed understanding of hCO will provide ways to improve its construction and expand its applications.

Research development of porphyrin-based metal-organic frameworks: targeting modalities and cancer therapeutic applications.

Porphyrins are naturally occurring organic molecules that have attracted widespread attention for their potential in the field of biomedical research. Porphyrin-based metal-organic frameworks (MOFs) that utilize porphyrin molecules as organic ligands have gained attention from researchers due to their excellent results as photosensitizers in tumor photodynamic therapy (PDT). Additionally, MOFs hold significant promise and potential for other tumor therapeutic approaches due to their tunable size and pore size, excellent porosity, and ultra-high specific surface area. Active delivery of nanomaterials via targeted molecules for tumor therapy has demonstrated greater accumulation, lower drug doses, higher therapeutic efficacy, and reduced side effects relative to passive targeting through the enhanced permeation and retention effect (EPR). This paper presents a comprehensive review of the targeting methods employed by porphyrin-based MOFs in tumor targeting therapy over the past few years. It further discusses the applications of porphyrin-based MOFs for targeted cancer therapy through various therapeutic methods. The objective of this paper is to provide a valuable reference and source of ideas for targeted therapy using porphyrin-based MOF materials and to inspire further exploration of their potential in the field of cancer therapy.

Dengue determinants: Necessities and challenges for universal dengue vaccine development.

Dengue illness can range from mild illness to life-threatening haemorrhage. It is an Aedes-borne infectious disease caused by the dengue virus, which has four serotypes. Each serotype acts as an independent infectious agent. The antibodies against one serotype confer homotypic immunity but temporary protection against heterotypic infection. Dengue has become a growing health concern for up to one third of the world's population. Currently, there is no potent anti-dengue medicine, and treatment for severe dengue relies on intravenous fluid management and pain medications. The burden of dengue dramatically increases despite advances in vector control measures. These factors underscore the need for a vaccine. Various dengue vaccine strategies have been demonstrated, that is, live attenuated vaccine, inactivated vaccine, DNA vaccine, subunit vaccine, and viral-vector vaccines, some of which are at the stage of clinical testing. Unfortunately, the forefront candidate vaccine is less than satisfactory, and its performance depends on serostatus and age factors. The lessons from clinical studies depicted ambiguity concerning the efficacy of dengue vaccine. Our study highlighted that viral structural heterogeneity, epitope accessibility, autoimmune complications, genetic variants, genetic diversities, antigen competition, virulence variation, host-pathogen specific interaction, antibody-dependent enhancement, cross-reactive immunity among Flaviviruses, and host-susceptibility determinants not only influence infection outcomes but also hampered successful vaccine development. This review integrates dengue determinants allocated necessities and challenges, which would provide insight for universal dengue vaccine development.

Effects of melatonin on development and hormone secretion of sheep theca cells in vitro.

Theca cells (TCs) play a unique role in the structure and function of the ovary. They are not only the structural basis of the follicle but also the androgen-secreting cells in female mammals, which can affect the normal development and atresia of the follicle. The results showed that melatonin receptor (MTR) MT1 and MT2 were expressed on sheep TCs. In the present study, the effects of different concentrations of MT at 0, 10-10, 10-8, 10-6 and 10-4 M/L on sheep TCs with regards to the antioxidant levels, proliferation, apoptosis and steroid hormone secretion were investigated. The results showed that in sheep TCs, all concentrations of MT significantly decreased reactive oxygen species (ROS) concentration and BAX expression; increased Cat, Sod1, and BCL-2 expression. The proliferation viability of TCs was significantly inhibited in all groups except for 10-10 M/L MT, and the expression of cyclin D1 and CDK4 was significantly reduced. MT significantly increased StAR expression and progesterone secretion in TCs, but there was no significant effect on androgen secretion and CYP11A1, CYP17A1 and 3ß-HSD expression in all groups. MT-induced progesterone secretion was completely inhibited by Luzindole (a nonspecific MT1 and MT2 inhibitor) and partially inhibited by 4p-PDOT (specific MT2 inhibitor). MT-induced progesterone secretion can be inhibited by LY294002 (PI3K/AKT pathway inhibitor). This study indicated that MT inhibits apoptosis and proliferation of in vitro cultured sheep TCs, which has implications for slowing ovarian atresia and aging. MT activates the PI3K/Akt pathway to mediate the synthesis and secretion of progesterone by TCs. This study provides a basis for further exploration of the role of TCs on follicle development and ovarian steroid hormone secretion.

Nutritional risk factors for all-cause mortality of critically ill patients: a retrospective cohort study.

OBJECTIVES: This study aimed to explore the predictive value of single and multiple risk factors for the clinical outcomes of critically ill patients receiving enteral nutrition and to establish an effective evaluation model. DESIGN: Retrospective cohort study. SETTING: Data from the 2020-2021 period were collected from the electronic records of the First Affiliated Hospital, Nanjing Medical University. PARTICIPANTS: 459 critically ill patients with enteral nutrition in the geriatric intensive care unit were included in the study. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was 28-day mortality. The secondary outcomes were 28-day invasive mechanical ventilation time, intensive care unit stay, Nutrition Risk Screening 2002 (NRS2002) score and Acute Physiology and Chronic Health Evaluation II (APACHE II) score. RESULTS: Independent prognostic factors, including prealbumin/procalcitonin (PCT) ratio and APACHE II score, were identified using a logistic regression model and used in the nomogram. The area under the receiver operating characteristic curve and concordance index indicated that the predictive capacity of the model was 0.753. Moreover, both the prealbumin/PCT ratio and the combination model of PCT, prealbumin and NRS2002 had a higher predictive value for clinical outcomes. Subgroup analysis also identified that a higher inflammatory state (PCT >0.5 ng/mL) and major nutritional risk (NRS2002 >3) led to worse clinical outcomes. In addition, patients on whole protein formulae bore less nutritional risk than those on short peptide formulae. CONCLUSIONS: This nomogram had a good predictive value for 28-day mortality in critically ill patients receiving enteral nutrition. Both the prealbumin/PCT ratio and the combination model (PCT, prealbumin and NRS2002), as composite models of inflammation and nutrition, could better predict the prognosis of critically ill patients.

Lanthanide-based MOFs: synthesis approaches and applications in cancer diagnosis and therapy.

Metal-organic frameworks (MOFs) have attracted considerable attention as emerging nanomaterials. Based on their tunable size, high porosity, and large specific surface area, MOFs have a wide range of applications in the fields of chemistry, energy, and biomedicine. However, the MOF materials obtained from lanthanides with a unique electronic configuration as inorganic building units have unique properties such as optics, magnetism, and radioactivity. In this study, various synthetic methods for preparing MOF materials using lanthanides as inorganic building units are described. Combined with the characteristics of lanthanides, their application prospects of lanthanide-based MOFs in tumor diagnosis and treatment are emphasized. The authors hope to provide methodological reference for the construction of MOF materials of rare-earth elements, and to provide ideas and inspiration for their practical applications in the field of biomedicine.

Heavy Metal Ions Detection Using Nanomaterials-Based Aptasensors.

Heavy metals ions as metallic pollutants are a growing global issue due to their adverse effects on the aquatic ecosystem, and human health. Unfortunately, conventional detection methods such as atomic absorption spectrometry exhibit a relatively low limit of detection and hold numerous disadvantages, and therefore, the development of an efficient method for in-situ and real-time detection of heavy metal residues is of great importance. The aptamer-based sensors offer distinct advantages over antibodies and emerged as a robust sensing platform against various heavy metals due to their high sensitivity, ease of production, simple operations, excellent specificity, better stability, low immunogenicity, and cost-effectiveness. The nucleic acid aptamers in conjugation with nanomaterials can bind to the metal ions with good specificity/selectivity and can be used for on-site monitoring of metal ion residues. This review aimed to provide background information about nanomaterials-based aptasensor, recent advancements in aptamer conjunction on nanomaterials surface, the role of nanomaterials in improving signal transduction, recent progress of nanomaterials-based aptasening procedures (from 2010 to 2022), and future perspectives toward the practical applications of nanomaterials-based aptasensors against hazardous metal ions for food safety and environmental monitoring.

Blood pressure undulation of peripheral thrombolysis period in acute ischemic stroke is associated with prognosis.

BACKGROUND: Evidence suggests that patients with higher blood pressure variability (BPV) have a higher risk for stroke but the relationship between BPV and stroke outcomes is unknown in those who underwent intravenous thrombolysis (IVT) for acute ischemic stroke (AIS). The objective of this study is to investigate the association among BPV, BP values and stroke outcomes. METHODS: A retrospective analysis of about 510 consecutive thrombolysis cases for AIS from January 2015 to March 2019 in a single-center database were done. Then, these patients were followed-up for 3 months. We used univariate and multivariable models to evaluate the relationship between mean BP values, BPV and the risk of stroke outcomes from prior IVT to 72 h after IVT. Meanwhile, we also used COX regression to assess the hazard ratios of stroke outcomes with BPV within 3 months. Furthermore, we tested the effect of BP level at various time-points (prior to IVT and at 0, 2, 4, 8, 12, 24, 48 and 72 h after IVT) on development of postthrombolytic stroke outcomes. RESULTS: Higher BPV from prior IVT to 72 h after IVT was associated with higher risk of stroke outcomes within 3 months [SBPV of recurrent stroke: odds ratios (OR) = 5.298, 95% confidence interval (CI) 1.339-10.968, P = 0.018; DBPV of recurrent stroke: OR = 6.397, 95% CI 1.576-25.958, P = 0.009, respectively]. In addition, patients with recurrent stroke had significantly higher mean SBP (OR=1.037, 95% CI 1.006-1.069, P = 0.019). Furthermore, higher BP at different time points were associated with greater risk of recurrent stroke from prior IVT to 72 h after IVT. CONCLUSION: Higher BPV and SBP from prior IVT to 72 h after IVT was associated with higher risk of stroke outcomes within 3 months.

Transcriptome and proteome analysis of pregnancy and postpartum anoestrus ovaries in yak.

BACKGROUND: Domestic yaks are the most important livestock species on the Qinghai-Tibetan Plateau. Adult female yaks normally breed in the warm season (July to September) and enter anestrous in the cold season (November to April). Nevertheless, it is unclear how ovarian activity is regulated at the molecular level. OBJECTIVES: The peculiarities of yak reproduction were assessed to explore the molecular mechanism of postpartum anestrus ovaries in yaks after pregnancy and parturition. METHODS: Sixty female yaks with calves were observed under natural grazing in Haiyan County, Qinghai Province. Three yak ovaries in pregnancy and postpartum anestrus were collected. RNA sequencing and quantitative proteomics were employed to analyze the pregnancy and postpartum ovaries after hypothermia to identify the genes and proteins related to the postpartum ovarian cycle. RESULTS: The results revealed 841 differentially expressed genes during the postpartum hypoestrus cycle; 347 were up-regulated and 494 genes were down-regulated. Fifty-seven differential proteins were screened: 38 were up-regulated and 19 were down-regulated. The differential genes and proteins were related to the yak reproduction process, rhythm process, progesterone-mediated oocyte maturation, PI3K/AKT signaling pathway, and MAPK signaling pathway categories. CONCLUSIONS: Transcriptome and proteomic sequencing approaches were used to investigate postpartum anestrus and pregnancy ovaries in yaks. The results confirmed that BHLHE40, SF1IX1, FBPX1, HSPCA, LHCGR, BMP15, and ET-1R could affect postpartum hypoestrus and control the state of estrus.