CEBPA facilitates LOXL2 and LOXL3 transcription to promote BCL-2 stability and thus enhances the growth and metastasis of lung carcinoma cells in vitro.

Lung carcinoma (LC) is a complicated and highly heterogeneous disease with high morbidity and mortality. Both lysyl oxidase-like (LOXL) 2 and 3 act in cancer progression. This work endeavors to illustrate the influence of LOXL2/LOXL3 on LC progression and the underlying mechanisms. LOXL family genes and CCAAT enhancer binding protein A (CEBPA) were analyzed in the TCGA database for their expression patterns in LC patients and their correlations with the patient's prognosis. CEBPA, LOXL2, and LOXL3 expression levels were determined in LC cells. Gain- and loss-of-function assays were conducted, followed by assays for cell proliferation, epithelial-mesenchymal transition (EMT), apoptosis, invasion, and migration. The binding of CEBPA or B cell lymphoma protein (BCL)-2 to LOXL2/LOXL3 was verified. The ubiquitination level of BCL-2 and histone acetylation level of LOXL2/LOXL3 in LC cells were analyzed. Database analyses revealed that LC patients had high CEBPA, LOXL2, and LOXL3 expression, which were related to poor prognosis. LC cells also exhibited high CEBPA, LOXL2, and LOXL3 levels. LOXL2/LOXL3 knockdown subdued EMT, proliferation, migration, and invasion while enhancing the apoptosis of LC cells. LOXL2/LOXL3 could bind to CEBPA and BCL-2. LOXL2/LOXL3 knockdown upregulated BCL-2 ubiquitination level and diminished BCL-2 expression in LC cells. CEBPA recruited Tip60 to enhance histone acetylation and transcription of LOXL2/LOXL3 in LC cells. BCL-2 overexpression abolished the impacts of LOXL2/LOXL3 knockdown on LC cells. In conclusion, CEBPA boosts LOXL2 and LOXL3 transcription to facilitate BCL-2 stability by recruiting Tip60 and thus contributes to LC cell growth and metastasis.

Pharmacodynamic advantages and characteristics of traditional Chinese medicine in prevention and treatment of ischemic stroke.

Ischemic stroke (IS) is a severe cerebrovascular disease with a high incidence, mortality, and disability rate. The first-line treatment for IS is the use of recombinant tissue plasminogen activator (r-tPA). Regrettably, numerous patients encounter delays in treatment due to the narrow therapeutic window and the associated risk of hemorrhage. Traditional Chinese medicine (TCM) has exhibited distinct advantages in preventing and treating IS. TCM enhances cerebral microcirculation, alleviates neurological disorders, regulates energy metabolism, mitigates inflammation, reduces oxidative stress injuries, and inhibits apoptosis, thereby mitigating brain damage and preventing IS recurrence. This article summarizes the etiology, pathogenesis, therapeutic strategies, and relationship with modern biology of IS from the perspective of TCM, describes the advantages of TCM in the treatment of IS, and further reviews the pharmacodynamic characteristics and advantages of TCM in the acute and recovery phases of IS as well as in post-stroke complications. Additionally, it offers valuable insights and references for the clinical application of TCM in IS prevention and treatment, as well as for the development of novel drugs.

Atomic Diffusion Rate Dominated Fabrication of High Entropy Phosphide with Heterogeneous Aggregation for Oxygen Evolution Reaction.

The synthesis of high-entropy phosphide (HEP) remains a great challenge owing to the different migration rates of different metallic atoms. Herein, a new metal organic gel (MOG) precursor strategy is proposed for HEP synthesis by controlling the migration rate of different atoms in an organic gel. The MOG precursor with five kinds of metal and phosphor species homogeneously dispersing is formed through a facile solvothermal method, which is calcined at 900 °C to obtain carbon-supported HEP FeCoNiMnCdP (MPC-5). The difference in the atom radius and the influence of MOG on the migration rate result in heterogeneous aggregation of different atoms in the product, which increases the defects in the product to a certain extent. In addition, the presence of carbon and nitrogen in the gel simultaneously realizes carbon coating and nitrogen doping. Combining the above advantages, the MPC-5 shows excellent oxygen evolution reaction (OER) catalytic performance with an overpotential of 250 mV at 10 mA·cm-2, superior to many recently reported OER electrocatalysts. This work provides a new strategy to solve the differences in the migration rates of different metals to obtain pure phase high-entropy phosphides, which is conducive to the further development of high-entropy materials and their applications in the energy and catalysis fields.

Peripheral origin exosomal microRNAs aggravate glymphatic system dysfunction in diabetic cognitive impairment.

Cognitive dysfunction is one of the common central nervous systems (CNS) complications of diabetes mellitus, which seriously affects the quality of life of patients and results in a huge economic burden. The glymphatic system dysfunction mediated by aquaporin-4 (AQP4) loss or redistribution in perivascular astrocyte endfeet plays a crucial role in diabetes-induced cognitive impairment (DCI). However, the mechanism of AQP4 loss or redistribution in the diabetic states remains unclear. Accumulating evidence suggests that peripheral insulin resistance target tissues and CNS communication affect brain homeostasis and that exosomal miRNAs are key mediators. Glucose and lipid metabolism disorder is an important pathological feature of diabetes mellitus, and skeletal muscle, liver and adipose tissue are the key target insulin resistance organs. In this review, the changes in exosomal miRNAs induced by peripheral metabolism disorders in diabetes mellitus were systematically reviewed. We focused on exosomal miRNAs that could induce low AQP4 expression and redistribution in perivascular astrocyte endfeet, which could provide an interorgan communication pathway to illustrate the pathogenesis of DCI. Furthermore, the mechanisms of exosome secretion from peripheral insulin resistance target tissue and absorption to the CNS were summarized, which will be beneficial for proposing novel and feasible strategies to optimize DCI prevention and/or treatment in diabetic patients.

One-Step Phase Separation for Core-Shell Carbon@Indium Oxide@Bismuth Microspheres with Enhanced Activity for CO2 Electroreduction to Formate.

It is a substantial challenge to construct electrocatalysts with high activity, good selectivity, and long-term stability for electrocatalytic reduction of carbon dioxide to formic acid. Herein, bismuth and indium species are innovatively integrated into a uniform heterogeneous spherical structure by a neoteric quasi-microemulsion method, and a novel C@In2 O3 @Bi50 core-shell structure is constructed through a subsequent one-step phase separation strategy due to melting point difference and Kirkendall effect with the nano-limiting effect of the carbon structure. This core-shell C@In2 O3 @Bi50 catalyst can selectively reduce CO2 to formate with high selectivity (≈90% faradaic efficiency), large partial current density (24.53 mA cm-2 at -1.36 V), and long-term stability (up to 14.5 h), superior to most of the Bi-based catalysts. The hybrid Bi/In2 O3 interfaces of core-shell C@In2 O3 @Bi will stabilize the key intermediate HCOO* and suppress CO poisoning, benefiting the CO2 RR selectivity and stability, while the internal cavity of core-shell structure will improve the reaction kinetics because of the large specific surface area and the enhancement of ion shuttle and electron transfer. Furthermore, the nano-limited domain effect of outmost carbon prevent active components from oxidation and agglomeration, helpful for stabilizing the catalyst. This work offers valuable insights into core-shell structure engineering to promote practical CO2 conversion technology.

Crystal Face Dominated Fabrication of Prussian Blue Analogue with Oriented Growth and Naturally Nonpreferred Unsaturated Coordination Center.

Defects, such as unsaturated coordination centers and vacancies, can fundamentally change materials' inherent properties and growth habits. The development of defect engineering has promoted the application of many technologies, but it is still a great challenge to selectively manufacture defect sites in existing material systems. It is shown here that in situ site-directed tailoring of metal sites in Prussian blue analogs (PBA) can be achieved according to the reducibility differences of different metal atoms, forming naturally nonpreferred unsaturated coordination centers. Meanwhile, the in situ capture of small reducing molecule can realize site-directed tailoring of crystal facets during crystal growth and results in oriented 1D growth. As an oxygen evolution reaction catalyst, the resulted PBA with the nonpreferred unsaturated coordination centers shows a low overpotential of 239 mV at 10 mA cm-2 in alkali, superior to the original PBAs and the previously reported defective PBA derivatives, which can be ascribed to the unsaturated coordination active center and the unique 1D structure. This work opens up opportunities for producing naturally nonpreferred unsaturated coordination center in nanomaterials for broad applications.

Two-Dimensional Imide-Based Covalent Organic Frameworks with Tailored Pore Functionality as Separators for High-Performance Li-S Batteries.

Modifying the separator of lithium-sulfur batteries (LSBs) is considered to be one of the most effective strategies for relieving the notorious polysulfide shuttle effect. Constructing a stable, lightweight, and effective LSB separator is still a big challenge but highly desirable. Herein, a stable and lightweight imide-based covalent organic framework (COF-TpPa) is facilely fabricated on reduced graphene oxide (rGO) through an oxygen-free solvothermal technique. With the directing effect of rGO and changing the side functional group of the monomer, the morphology and the pore tailoring of COF-TpPa can be simultaneously achieved and two-dimensional (2D) COF nanosheets with different functionalities (such as -SO3H and -Cl) are successfully constructed on rGO films. The specific functional groups inside the COF's pore channels and the narrowed pore size result in efficient absorption and restriction of Li2Sn for weakening the "shuttle effect". Meanwhile, the 2D COF nanosheets on the rGO is a favorable morphology for better exploiting pores inside the COF materials. As a result, the COF-SO3H-modified separator, consisting of rGO and COF-TpPa-SO3H, exhibits a high specific capacity (1163.4 mA h/g at 0.2 C) and a desirable cyclic performance (60.2% retention rate after 1000 cycles at 2.0 C) for LSBs. Our study provides a feasible strategy to rationally design functional COFs and boosts their applications in various energy storage systems.

Deep learning and machine intelligence: New computational modeling techniques for discovery of the combination rules and pharmacodynamic characteristics of Traditional Chinese Medicine.

It has been increasingly accepted that Multi-Ingredient-Based interventions provide advantages over single-target therapy for complex diseases. With the growing development of Traditional Chinese Medicine (TCM) and continually being refined of a holistic view, "multi-target" and "multi-pathway" integration characteristics of which are being accepted. However, its effector substances, efficacy targets, especially the combination rules and mechanisms remain unclear, and more powerful strategies to interpret the synergy are urgently needed. Artificial intelligence (AI) and computer vision lead to a rapidly expanding in many fields, including diagnosis and treatment of TCM. AI technology significantly improves the reliability and accuracy of diagnostics, target screening, and new drug research. While all AI techniques are capable of matching models to biological big data, the specific methods are complex and varied. Retrieves literature by the keywords such as "artificial intelligence", "machine learning", "deep learning", "traditional Chinese medicine" and "Chinese medicine". Search the application of computer algorithms of TCM between 2000 and 2021 in PubMed, Web of Science, China National Knowledge Infrastructure (CNKI), Elsevier and Springer. This review concentrates on the application of computational in herb quality evaluation, drug target discovery, optimized compatibility and medical diagnoses of TCM. We describe the characteristics of biological data for which different AI techniques are applicable, and discuss some of the best data mining methods and the problems faced by deep learning and machine learning methods applied to Chinese medicine.

Zi Shen Wan Fang Attenuates Neuroinflammation and Cognitive Function Via Remodeling the Gut Microbiota in Diabetes-Induced Cognitive Impairment Mice.

Background : Cognitive dysfunction is a critical complication of diabetes mellitus, and there are still no clinically approved drugs. Zi Shen Wan Fang (ZSWF) is an optimized prescription composed of Anemarrhenae Rhizoma, Phellodendri Chinensis Cortex, and Cistanches Herba. The purpose of this study is to investigate the effect of ZSWF on DCI and explore its mechanism from the perspective of maintaining intestinal microbial homeostasis in order to find an effective prescription for treating DCI. Methods: The diabetes model was established by a high-fat diet combined with intraperitoneal injections of streptozotocin (STZ, 120 mg/kg) and the DCI model was screened by Morris water maze (MWM) after 8 weeks of continuous hyperglycemic stimulation. The DCI mice were randomly divided into the model group (DCI), the low- and high-ZSWF-dose groups (9.63 g/kg, 18.72 g/kg), the mixed antibiotic group (ABs), and the ZSWF combined with mixed antibiotic group (ZSWF + ABs). ZSWF was administered orally once a day for 8 weeks. Then, cognitive function was assessed using MWM, neuroinflammation and systemic inflammation were analyzed by enzyme-linked immunosorbent assay kits, intestinal barrier integrity was assessed by hematoxylin-eosin (HE) staining and Western blot and high performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). Furthermore, the alteration to intestinal flora was monitored by 16S rDNA sequencing. Results: ZSWF restored cognitive function in DCI mice and reduced levels of proinflammatory cytokines such as IL-1ß, IL-6, and TNF-α. Moreover, ZSWF protected the integrity of the intestinal barrier by increasing intestinal ZO-1 and occludin protein expression and decreasing urinary lactulose to mannitol ratio. In addition, ZSWF reshaped the imbalanced gut microbiota in DCI mice by reversing the abundance changes of a wide range of intestinal bacteria at the phyla and genus levels. In contrast, removing gut microbiota with antibiotics partially eliminated the effects of ZSWF on improving cognitive function and reducing inflammation, confirming the essential role of gut microbiota in the improvement of DCI by ZSWF. Conclusion: ZSWF can reverse cognitive impairment in DCI mice by remolding the structure of destructed gut microbiota community, which is a potential Chinese medicine prescription for DCI treatment.

MiR-143-3p Increases the Radiosensitivity of Breast Cancer Cells Through FGF1.

Breast cancer is a common malignant tumor in women. At present, the main treatment for breast cancer is radiotherapy. Due to the difference in radiosensitivity between individuals or tumor cells, the effect of radiotherapy is not good. Therefore, in radiotherapy, how to use various auxiliary means to reduce the radiation resistance of tumor, Therefore, it has become an important research topic to improve the radiosensitivity of the tumor. Fibroblast growth factor-1 (FGF1) plays an important role in tumor migration. Therefore, the study of miR-143-3p increasing the radiosensitivity of breast cancer cells through FGF1 is proposed in this paper. In this study, a control group experiment was set up to study. During the experiment, the relative expression of miR-143-3p was detected by fluorescent quantitative PCR of miRNA, and the cell irradiation experiment was created to analyze the radiosensitivity of breast cancer cells by comparing their survival fraction. The results of this study showed that when the radiation dose was 0, the survival scores of the three groups were all 1. The survival fraction of the experimental group decreased from 0.26 ± 0.045 to 0.068 ± 0.008 when the dose was added to 4Gy. The survival fraction of the experimental group was always greater than that of the two control groups. The results of this study show that miR-143-3p can increase the radiosensitivity of breast cancer cells through FGF1.

Robust hollow Bowl-like α-Fe2O3 nanostructures with enhanced electrochemical lithium storage performance.

The design and synthesis of hollow-nanostructured transition metal oxide-based anodes is of great importance for long-term operation of lithium ion batteries (LIBs). Herein, a special hollow bowl-like α-Fe2O3 nanostructure is controllably synthesized through a facile hydrothermal technique and exhibits great electrochemical lithium storage performance when used as LIBs anode. Under a facile hydrothermal condition, α-Fe2O3 nanostructures evolve from solid pie-like structure to hollow bowl-like structure and finally α-Fe2O3 nanorings through the regulation of HPO4- derived from ionized Na3PO4·12H2O and Ostwald ripening process. The designed hollow bowl-like α-Fe2O3 nanostructure not only has the merits of hollow structure, which can accelerate the diffusion of lithium ions and electrons, but also shows great mechanical strength to disperse stress when compared to solid pie-like and ring-like α-Fe2O3 nanostructures, which would avoid collapse during charge/discharge process. As a result, the as-synthesized hollow bowl-like α-Fe2O3 nanostructure displays an initial reversible capacity of 1616 mAh g-1 at a current density of 1 A g-1, an excellent cycling performance with a reversible capacity of 1018 mAh g-1 after 500 cycles and an outstanding rate capability (68.1% capacity retention at current densities from 100 to 2000 mA g-1). This work provides not only a novel hollow bowl-like α-Fe2O3 nanostructure with high specific surface area and stable structure as potential electrode materials for energy storage, but also a facile self-templated strategy free of any surfactants and templates for hollow nanostructures.

Research Progress in the Study of Startle Reflex to Disease States.

The startle reflex is considered a primitive physiological reflex, a defense response that occurs in the organism when the body feels sudden danger and uneasiness, characterized by habituation and sensitization effects, and studies on the startle reflex often deal with pre-pulse inhibition (PPI) and sensorimotor gating. Under physiological conditions, the startle reflex is stable at a certain level, and when the organism is in a pathological state, such as stroke, spinal cord injury, schizophrenia, and other diseases, the reflex undergoes a series of changes, making it closely related to the progress of disease. This paper summarizes the startle reflex in physiological and pathological states by reviewing the databases of PubMed, Web of Science, Cochrane Library, EMBASE, China Biology Medicine, China National Knowledge Infrastructure, VIP Database for Chinese Technical Periodical, Wanfang Data, and identifies and analyzes the startle reflex and excessive startle reaction disorder.

A Universal Strategy for Carbon-Supported Transition Metal Phosphides as High-Performance Bifunctional Electrocatalysts towards Efficient Overall Water Splitting.

Exploring cost-effective and general approaches for highly active and stable bifunctional transition metal phosphide (TMP) electrocatalysts towards overall water splitting is greatly desirable and challenging. Herein, a general strategy combining sol-gel and a carbonization-assisted route was proposed to facilely fabricate a series of TMP nanoparticles, including CoP, MoP, FeP, Cu2P, Ni2P, PtP2, FeNiP, CoNiP, and FeCoNiP, coupled in an amorphous carbon matrix with one-step carbon composite formation. The resultant NiFeP@C exhibits excellent activities as a bifunctional electrocatalyst toward oxygen evolution reaction (OER) and hydrogen evolution reaction (HER) with low overpotentials of 260 and 160 mV, respectively, at 10 mA/cm2 in 1 M KOH solution. With the NiFeP@C electrocatalyst as both electrode materials, an integrated electrolyzer can deliver 47.0 mA/cm2 of current density at 1.60 V, better than the assembled Pt/C20∥IrO2 counterpart. The encapsulation of NiFeP nanoparticles in the carbon matrix effectively prevents their corrosion and leads to almost unfading catalytic activities for more than 20 h for either the HER, OER, or overall water splitting, outperforming recently reported bifunctional electrocatalysts. The coexistence of Ni, Fe, P, and C would have synergetic effects to accelerate charge transfer and promote electrocatalytic activity. This universal strategy for TMP-based composites opens up a new avenue to explore TMPs as multifunctional materials for various applications.

A lotus-inspired janus hybrid film enabled by interfacial self-assembly and in situ asymmetric modification.

A lotus leaf inspired Janus hybrid film was exquisitely fabricated through a self-assembly process at the air/water interface with subsequent in situ asymmetric modification at the oil/water interface. The interfacial asymmetric decoration strategy thus provides a novel pathway for achieving a 2D Janus hybrid film with asymmetric wettability and functionality.

Morphological and Pathological Characteristics of Brain in Diabetic Encephalopathy.

Diabetes mellitus is a metabolic disease often accompanied by a series of complications, such as diabetic nephropathy, retinopathy, and diabetic foot. The survival time of diabetics has been significantly prolonged due to advancements in medicine. However, the prolonged survival time for diabetics can increase the prevalence of diabetic central nervous system disease. Diabetic encephalopathy (DE) has become one of the main complications of the disease, and the main clinical manifestation of DE is cognitive dysfunction. However, the typical morphological and pathological characteristics of the brain in DE are rarely systematically reported. Thus, this phenomenon severely restricts the diagnosis and treatment of DE. This article presents a description of the pathology characteristics of DE, including atrophy of the brain (gray matter, white matter, and hippocampus), changes in cerebrovascular morphology and function, impairment of synaptic plasticity, and dysfunction of neuroglia. In addition, abnormalities in the glymphatic clearance system of the brain are closely related to the progression of DE. A review of typical brain morphological and pathological characteristics would aid in the diagnosis and treatment of DE.

Combined acupuncture and HuangDiSan treatment affects behavior and synaptophysin levels in the hippocampus of senescence-accelerated mouse prone 8 after neural stem cell transplantation.

Sanjiao acupuncture and HuangDiSan can promote the proliferation, migration and differentiation of exogenous neural stem cells in senescence-accelerated mouse prone 8 (SAMP8) mice and can improve learning and memory impairment and behavioral function in dementia-model mice. Thus, we sought to determine whether Sanjiao acupuncture and HuangDiSan can elevate the effect of neural stem cell transplantation in Alzheimer's disease model mice. Sanjiao acupuncture was used to stimulate Danzhong (CV17), Zhongwan (CV12), Qihai (CV6), bilateral Xuehai (SP10) and bilateral Zusanli (ST36) 15 days before and after implantation of neural stem cells (5 × 105) into the hippocampal dentate gyrus of SAMP8 mice. Simultaneously, 0.2 mL HuangDiSan, containing Rehmannia Root and Chinese Angelica, was intragastrically administered. Our results demonstrated that compared with mice undergoing neural stem cell transplantation alone, learning ability was significantly improved and synaptophysin mRNA and protein levels were greatly increased in the hippocampus of mice undergoing both Sanjiao acupuncture and intragastric administration of HuangDiSan. We conclude that the combination of Sanjiao acupuncture and HuangDiSan can effectively improve dementia symptoms in mice, and the mechanism of this action might be related to the regulation of synaptophysin expression.

Acupuncture for patients with mild to moderate Alzheimer's disease: a randomized controlled trial.

BACKGROUND: Alzheimer's disease (AD) is the most common cause of dementia. However, none of medical treatment can stop or reverse the underlying neurodegenerative of AD at present. Acupuncture has attracted more and more attention in recent years due to its efficacy and very few side effects. Lately, a systematic review has thought that the evidence on the effectiveness of acupuncture in improving the cognitive function of AD patients was not powerful enough. Therefore, the aim of this study is to explore the efficacy and safety of acupuncture in patients with mild to moderate AD. METHODS: This was a randomized, controlled, parallel-group, exploratory study with 4-week baseline (T0), 12-week treatment phase (T1) and 12-week follow-up period (T2). Patients with mild to moderate AD meeting the included criteria were randomly allocated into either acupuncture or donepezil hydrochloride groups. The acupuncture group(AG) was given acupuncture treatment three times per week and the donepezil hydrochloride group(DG) group was administered donepezil hydrochloride once daily (5 mg/day for the first 4 weeks and 10 mg/day thereafter). Primary efficacy was measured using Alzheimer's disease Assessment Scale-Cognitive (ADAS-cog) and Clinician's Interview-Based Impression of Change-Plus (CIBIC-Plus). The second outcomes were measured with 23-Item Alzheimer's disease Cooperative Study Activities of Daily Living Scales (ADAS-ADL23) and Neuropsychiatric Index (NPI). RESULTS: Of 87 participants enrolled in the study, 79 patients finished their treatment and follow-up processes. The ADAS-cog scores for AG group showed obvious decreases at T2 and ∆(T2-T0)when compared with DG group, and significant between-group differences were detected (all p < 0.05). The mean CIBIC-Plus values for the AG group at T1 and T2 were much lower than that for the DG group, and there were significant differences between the two groups (푃<0.05). There were no significant between-group differences in the scores of ADAS-ADL23 and NPI during the study period. Treatment discontinuations due to adverse events were 0 (0%) and 4 (9.09%) for the AG and DG groups, respectively. CONCLUSIONS: Acupuncture is safe, well tolerated and effective in improving the cognitive function, global clinical status of AD. TRIAL REGISTRATION: ChiCTR-IOR-17010465 (Retroactively registered on 18 JAN 2017).