Spleen-targeted NeoPol-mL242 mRNA vaccine induces robust T-cell responses in a hepatocellular carcinoma model.

Personalized neoantigen peptide vaccines have shown remarkable anti-tumor activity across diverse cancer types. With the rapid advancement of messenger RNA (mRNA) delivery technologies during the coronavirus disease of 2019 (COVID-19) pandemic, mRNA-based cancer vaccines have emerged as a promising therapeutic approach because of their scalable production, safety, and capacity to elicit potent immune responses. However, the predominant distribution of mRNA delivery systems in the liver may lead to hepatic damage and restrict therapeutic accessibility.

In vivo genome editing of human haematopoietic stem cells for treatment of blood disorders using mRNA delivery.

Ex vivo autologous haematopoietic stem cell (HSC) gene therapy provides a promising treatment option for haematological disorders. However, current methods involve complex processes and chemotherapeutic conditioning, leading to limited accessibility for treatment and major side effects. Here we develop antibody-free targeted lipid nanoparticles (LNPs) for mRNA delivery to HSCs in vivo, enabling efficient base editing of the γ-globin gene (HBG1/2) promoter target in human HSCs to reactivate fetal haemoglobin in derived erythroid cells.

The Evolution, Immunopathogenesis and Biomarkers of Type 2 Inflammation in Common Allergic Disorders.

The prevalence of allergic diseases, including allergic rhinitis, chronic rhinosinusitis, asthma, eosinophilic esophagitis, food and drug allergies, and atopic dermatitis, has been increasing globally over the past few decades. Allergic diseases are closely linked to type 2 immunity, which is characterized by the coordinated interplay between innate and adaptive immune responses. Significant advancements have been achieved in elucidating the cellular and molecular mechanisms that govern type 2 immunity, chiefly mediated by type 2 cytokines, including IL-4, IL-5, IL-9, and IL-13, which are primarily secreted by T helper 2 cells and group 2 innate lymphoid cells.

Prefrontal cortex excitatory neurons show distinct response to heroin-associated cue and social stimulus after prolonged heroin abstinence in mice.

Substance use disorder (SUD) has been linked with social impairments. The social cognitive dysfunctions can further increase the risk of the development of SUD or relapse. Therefore, understanding the neural mechanism of substance exposure-associated social impairments is beneficial for the development of novel prevention or treatment strategies for SUD.

Sleeping Beauty mRNA-LNP enables stable rAAV transgene expression in mouse and NHP hepatocytes and improves vector potency.

Recombinant adeno-associated virus (rAAV) vector gene delivery systems have demonstrated great promise in clinical trials but continue to face durability and dose-related challenges. Unlike rAAV gene therapy, integrating gene addition approaches can provide curative expression in mitotically active cells and pediatric populations. We explored a novel in vivo delivery approach based on an engineered transposase, Sleeping Beauty (SB100X), delivered as an mRNA within a lipid nanoparticle (LNP), in combination with an rAAV-delivered transposable transgene.

Recombinant human brain natriuretic peptide attenuates ischemic brain injury in mice by inhibiting oxidative stress and cell apoptosis via activation of PI3K/AKT/Nrf2/HO-1 pathway.

Ischemic stroke followed by cerebral artery occlusion is a main cause of chronic disability worldwide. Recombinant human brain natriuretic peptide (rhBNP) has been reported to alleviate sepsis-induced cognitive dysfunction and brain I/R injury. However, the function and molecular mechanisms of rhBNP in ischemic brain injury have not been clarified.

[Effects of Biochar Amendment on NO Emission and Its Functional Genes in Pepper Growing Soil in Tropical Areas].

Biochar application may mitigate NO emissions and increase crop yield, yet little is known about microbial dynamics variation. To investigate the potential of increasing yield and reducing emissions of biochar in tropical areas and the dynamic mechanism of related microorganisms, a pot experiment was conducted to investigate the biochar application on pepper yield, NO emissions, and dynamic variation of related microorganisms. Three treatments were applied:2% biochar amendment (B), conventional fertilization (CON), and no nitrogen (CK).

Management of Crown-root Fracture with 180-degree Rotation Replantation: a Report of 2 Cases.

Intentional replantation involves a combination of periodontics, endodontics, prosthodontics and oral surgery. Crown-root fracture management is still complicated nowadays. A fracture line extending longitudinally to the subgingival area and intruding bioogical width could affect infection control, gingival health and crown restoration.

IGF-1 Microinjection in the Prefrontal Cortex Attenuates Fentanyl-Seeking Behavior in Mice.

Background: Opioid use disorder (OUD) is a chronic relapsing psychiatric disorder with an enormous socioeconomic burden. Opioid overdose deaths have reached an epidemic level, especially for fentanyl. One of the biggest challenges to treat OUD is the relapse to drug seeking after prolonged abstinence.

Opioid induces increased DNA damage in prefrontal cortex and nucleus accumbens.

Opioid use disorder (OUD) is a chronic disease characterized by compulsive opioid taking and seeking, affecting millions of people worldwide. The high relapse rate is one of the biggest challenges in treating opioid addiction. However, the cellular and molecular mechanisms underlying relapse to opioid seeking are still unclear.

Insulin-like growth factor 1 regulates excitatory synaptic transmission in pyramidal neurons from adult prefrontal cortex.

Insulin-like growth factor 1 (IGF1) influences synaptic function in addition to its role in brain development and aging. Although the expression levels of IGF1 and IGF1 receptor (IGF1R) peak during development and decline with age, the adult brain has abundant IGF1 or IGF1R expression. Studies reveal that IGF1 regulates the synaptic transmission in neurons from young animals.

Publishing clinical prActice GuidelinEs (PAGE): Recommendations from editors and reviewers.

Transparency Ecosystem for Research and Journals in Medicine (TERM) working group summarized the essential recommendations that should be considered to review and publish a high-quality guideline. These recommendations from editors and reviewers included 10 components of essential requirements: systematic review of existing relevant guidelines, guideline registration, guideline protocol, stakeholders, conflicts of interest, clinical questions, systematic reviews, recommendation consensus, guideline reporting and external review. TERM working group abbreviates them as PAGE (essential requirements for Publishing clinical prActice GuidelinEs), and recommends guideline authors, editors, and peer reviewers to use them for high-quality guidelines.

Fabrication and characterization of soy β-conglycinin-dextran-polyphenol nanocomplexes: Improvement on the antioxidant activity and sustained-release property of curcumin.

In this study, glycated soy β-conglycinin (β-CG) stabilized curcumin (Cur) composites were fabricated by a unique reversible self-assembly character of β-conglycinin-dextran conjugates (β-CG-DEX). Intrinsic fluorescence and far-UV CD spectra revealed that glycation did not affect the self-assembly property of β-CG in the pH-shifting treatment. The structure of β-CG-DEX could be unfolded at pH 12.

Molecular and cellular mechanisms for differential effects of chronic social isolation stress in males and females.

Chronic social isolation stress during adolescence induces susceptibility for neuropsychiatric disorders. Here we show that 5-week post-weaning isolation stress induces sex-specific behavioral abnormalities and neuronal activity changes in the prefrontal cortex (PFC), basal lateral amygdala (BLA), and ventral tegmental area (VTA). Chemogenetic manipulation, optogenetic recording, and in vivo calcium imaging identify that the PFC to BLA pathway is causally linked to heightened aggression in stressed males, and the PFC to VTA pathway is causally linked to social withdrawal in stressed females.

[Misdiagnosis of Acute Renal Artery Thrombosis as Acute Abdominal Disease:Report of One Case].

Renal artery thrombosis can cause acute occlusion of unilateral or bilateral renal arteries,and kidney failure would be induced if it is not diagnosed and treated in time.Therefore,rapid and correct treatment is especially important for renal artery thrombosis.Due to the lack of specificity of clinical manifestations,this disease in commonly misdiagnosed or missed and thus has a low early diagnosis rate.

Targeting histone demethylase LSD1 for treatment of deficits in autism mouse models.

Large-scale genetic studies have revealed that the most prominent genes disrupted in autism are chromatin regulators mediating histone methylation/demethylation, suggesting the central role of epigenetic dysfunction in this disorder. Here, we show that histone lysine 4 dimethylation (H3K4me2), a histone mark linked to gene activation, is significantly decreased in the prefrontal cortex (PFC) of autistic human patients and mutant mice with the deficiency of top-ranking autism risk factor Shank3 or Cul3. A brief treatment of the autism models with highly potent and selective inhibitors of the H3K4me2 demethylase LSD1 (KDM1A) leads to the robust rescue of core symptoms of autism, including social deficits and repetitive behaviors.

A novel variant of in a pedigree with pure hereditary spastic paraplegia in Yunnan Province.

Background: Hereditary spastic paraplegia (HSP) is a rare group of genetically heterogeneous, neurodegenerative disorders. The aim of this study was to identify pathological candidate genes and variants in a large pedigree cohort of 11 purely HSP patients in Yunnan Province.

Methods: Whole-exome sequencing (WES) was applied to 2 HSP patients and 1 control patient to screen out the candidate gene variants.

Differentiation Between Primary Central Nervous System Lymphoma and Atypical Glioblastoma Based on MRI Morphological Feature and Signal Intensity Ratio: A Retrospective Multicenter Study.

Objectives: To investigate the value of morphological feature and signal intensity ratio (SIR) derived from conventional magnetic resonance imaging (MRI) in distinguishing primary central nervous system lymphoma (PCNSL) from atypical glioblastoma (aGBM).

Methods: Pathology-confirmed PCNSLs (n = 93) or aGBMs (n = 48) from three institutions were retrospectively enrolled and divided into training cohort (n = 98) and test cohort (n = 43). Morphological features and SIRs were compared between PCNSL and aGBM.

Inhibition of Long non-coding RNA zinc finger antisense 1 improves functional recovery and angiogenesis after focal cerebral ischemia via microRNA-144-5p/fibroblast growth factor 7 axis.

Long non-coding RNA zinc finger antisense 1 (ZFAS1) has been probed in cerebral ischemia, while the regulatory mechanism of ZFAS1 in focal cerebral ischemia (FCI) via binding to microRNA (miR)-144-5p remains rarely explored. This study aims to decipher the function of ZFAS1 on FCI via sponging miR-144-5p to modulate fibroblast growth factor 7 (FGF7). The focal cerebral ischemia rat model was established by occlusion of the middle cerebral artery (MCAO) Lentivirus vectors altering ZFAS1, miR-144-5p or FGF7 expression were injected into rats before MCAO.

Early social isolation stress increases addiction vulnerability to heroin and alters c-Fos expression in the mesocorticolimbic system.

Rationale: Adverse psychosocial factors during early childhood or adolescence compromise neural structure and brain function, inducing susceptibility for many psychiatric disorders such as substance use disorder. Nevertheless, the mechanisms underlying early life stress-induced addiction vulnerability is still unclear, especially for opioids.

Objectives: To address this, we used a mouse heroin self-administration model to examine how chronic early social isolation (ESI) stress (5 weeks, beginning at weaning) affects the behavioral and neural responses to heroin during adulthood.

[Effects of Biochar Addition Under Different Water Management Conditions on NO Emission From Paddy Soils in Northern Hainan].

Alternating dry and wet conditions affect the main processes of NO production, such as nitrification and denitrification. Such conditions are very common in tropical rice-growing areas, such as Hainan. As a type of soil amendment, biochar is widely used to improve physical and chemical properties of soil and to reduce soil greenhouse gas emissions.

[Effects of Coconut Chaff Biochar Amendment on Methane and Nitrous Oxide Emissions from Paddy Fields in Hot Areas].

Based on the rice-vegetable crop rotation model, in-situ measurements of nitrous oxide (NO) and methane (CH) emissions were conducted in double-cropping rice fields in Hainan to determine the impact of coconut chaff biochar on greenhouse gas emissions. The experiment involved four treatments:conventional farming fertilization (CON), nitrogen fertilizer combined with 20 t ·hm biochar (B1), nitrogen fertilizer combined with 40 t ·hm biochar (B2), and no nitrogen fertilizer, as the control (CK). The NO and CH emissions were measured using static chamber-gas chromatography during the two paddy seasons, and the global warming potential (GWP) and greenhouse gas intensity (GHGI) were also estimated.