Discovery of Drugs Targeting Mutant p53 and Progress in Nano-Enabled Therapeutic Strategy for p53-Mutated Cancers.

Mutations in the p53 gene are frequently observed in various cancers, prompting the initiation of efforts to restore p53 function as a therapeutic approach several decades ago. Nevertheless, only a limited number of drug development initiatives have progressed to late-stage clinical trials, and to date, no p53-targeted therapies have received approval in the USA or Europe. This situation can be attributed primarily to the characteristics of p53 as a nuclear transcription factor, which lacks the conventional features associated with drug targets and has historically been considered "undruggable".

Multifunctional Interfacial Molecular Bridging Strategy Enables Efficient and Stable Inverted Perovskite Solar Cells.

Interface engineering in inverted perovskite solar cells (PSCs) faces critical challenges arising from nonideal interfacial contact, defect accumulation, impeded carrier transport, and energy-level misalignment between the perovskite and electron transport layer, for example, phenyl-C61-butyric acid methyl ester (PCBM). These interfacial deficiencies collectively induce nonradiative recombination and degrade device stability. Herein, a multifunctional interfacial molecular bridging strategy using (benzhydrylthio)acetic acid (DSA) addresses the upper interfacial issues of inverted PSCs, achieving three synergistic roles.

Association of genetic variants in MIR17HG and in the promoter of MIR17HG with susceptibility to cancer in Chinese Han population: a systematic review and meta-analysis.

Background: The association between microRNA 17-92 cluster host gene (MIR17HG) polymorphisms and the risk of cancer has been evaluated in studies, here, we attempted to elucidate the relationship between 6 single nucleotide polymorphisms (SNPs) of MIR17HG (rs17735387 G > A, rs7336610 C > T, rs1428 C > A, rs7318578 A > C, rs72640334 C > A, and rs75267932 A > G), 3 SNPs in the promoter of MIR17HG (rs9588884 C > G, rs982873 T > C, and rs1813389 A > G) and susceptibility to cancer in Chinese Han population.

Methods: Systematic literature research from databases were performed with strict eligibility criteria to include the relevant studies for this meta-analysis. Association between the SNPs of MIR17HG and cancer risk was estimated by pooling the odds ratios (ORs) with 95% confidence interval (95% CI) in five genetic models (allelic model, dominant model, recessive model, homozygous model, and heterozygous model).

HOGA1 Suppresses Renal Cell Carcinoma Growth via Inhibiting the Wnt/β-Catenin Signalling Pathway.

Changes in hydroxyproline metabolism are reported to promote tumorigenesis. HOGA1 is a useful marker for diagnosing primary hyperoxaluria 3, catalysing the final step of mitochondrial hydroxyproline metabolism from 4-hydroxy-2-oxoglutarate (HOG) to glyoxylate and pyruvate; however, its specific mechanism in RCC remains unclear. This study investigated the role of HOGA1 in the pathogenesis of ccRCC.

c-di-GMP inhibits rRNA methylation and impairs ribosome assembly in the presence of kanamycin.

Cyclic diguanosine monophosphate (c-di-GMP) is a ubiquitous bacterial secondary messenger with diverse functions. A previous Escherichia coli proteome microarray identified that c-di-GMP binds to the 23S rRNA methyltransferases RlmI and RlmE. Here we show that c-di-GMP inhibits RlmI activity in rRNA methylation assays, and that it modulates ribosome assembly in the presence of kanamycin.

Hypoxia-triggered ERRα acetylation enhanced its oncogenic role and promoted progression of renal cell carcinoma by coordinating autophagosome-lysosome fusion.

Estrogen-related receptor α (ERRα) is dysregulated in many types of cancer and exhibits oncogenic activity by promoting tumorigenesis and metastasis of cancer cells. However, its defined role in renal cell carcinoma (RCC) has not been fully elucidated. To reveal the biological function of ERRα and determine the underlying regulatory mechanism in RCC, the quantitative proteomics analysis and mechanism investigation were conducted.

Biomimetic Nano-Regulator that Induces Cuproptosis and Lactate-Depletion Mediated ROS Storm for Metalloimmunotherapy of Clear Cell Renal Cell Carcinoma.

Herein, a ccRCC targeting nanodrug is designed to enhance chemodynamic therapy (CDT) as well as activate cuproptosis and tumor immunotherapy via ccRCC cell membrane modifying CuO@GdO yolk-like particles (CGYL) loaded with lactate oxidase (LOx) (mCGYL-LOx). Benefiting from the homologous targeting effect of Renca cell membranes, the mCGYS-LOx can be effectively internalized by Renca cells, open the "gate", and then release LOx and copper (Cu) ions. LOx can catalyze excessive lactate in Renca cells into HO, following that the produced HO is further converted by Cu ions to the highly toxic ·OH, contributing to tumor CDT.

CHES1 modulated tumorigenesis and senescence of pancreas cancer cells through repressing AKR1B10.

Pancreatic ductal adenocarcinoma (PDAC), is characteristic by a heterogeneous tumor microenvironment and gene mutations, conveys a dismal prognosis and low response to chemotherapy and immunotherapy. Here, we found that checkpoint suppressor 1 (CHES1) served as a tumor repressor in PDAC and was associated with patient prognosis. Functional experiments indicated that CHES1 suppressed the proliferation and invasion of PDAC by modulating cellular senescence.

TEAD1, MYO7A and NDUFC2 are novel functional genes associated with glucose metabolism in BXD recombinant inbred population.

Aim: The liver is an important metabolic organ that governs glucolipid metabolism, and its dysfunction may cause non-alcoholic fatty liver disease, type 2 diabetes mellitus, dyslipidaemia, etc. We aimed to systematic investigate the key factors related to hepatic glucose metabolism, which may be beneficial for understanding the underlying pathogenic mechanisms for obesity and diabetes mellitus.

Materials And Methods: Oral glucose tolerance test (OGTT) phenotypes and liver transcriptomes of BXD mice under chow and high-fat diet conditions were collected from GeneNetwork.

Experimental study on the microwave radiation disinfection of E. coli on SiC composite filter.

Filter is an important component in the air-conditioning system. The airborne microorganisms can be intercepted and further multiply on the filter, which might cause a secondary pollution. The present work proposed a SiC composite filter (SCF), namely combining the filter with the absorbing material SiC.

Specific pupylation as IDEntity reporter (SPIDER) for the identification of protein-biomolecule interactions.

Protein-biomolecule interactions play pivotal roles in almost all biological processes. For a biomolecule of interest, the identification of the interacting protein(s) is essential. For this need, although many assays are available, highly robust and reliable methods are always desired.

Cell-liposome delivery system based on neuroinflammation to target the amygdala for ameliorating depressive-like behaviors.

Depression is a serious psychiatric disorder with unsatisfactory outcomes due to difficulties in delivering therapeutic molecules from the periphery to the brain. Neuroinflammation plays a key role in neurobiology and the treatment of depression. Neutrophils can cross the blood-brain barrier (BBB) and infiltrate key brain regions related to the pathophysiology of depression during neuroinflammation.

Acetylation of Checkpoint suppressor 1 enhances its stability and promotes the progression of triple-negative breast cancer.

Checkpoint suppressor 1 (CHES1), a transcriptional regulator, had been dysregulated in many types of malignancies including breast cancer, and its expression level is strongly associated with progression and prognosis of patients. However, the underlying regulatory mechanisms of CHES1 expression in the breast cancer and the effects of post-translational modifications (PTMs) on its functional performance remain to be fully investigated. Herein, we found that CHES1 had a high abundance in triple-negative breast cancer (TNBC) and its expression was tightly associated with malignant phenotype and poor outcomes of patients.

NIR-II Fluorescence Imaging-Guided Oxygen Self-Sufficient Nano-Platform for Precise Enhanced Photodynamic Therapy.

Tumor hypoxia and systemic toxicity seriously affect the efficacy of photodynamic therapy (PDT) and are considered as the "Achilles' heel" of PDT. Herein, to combat such limitations, an intelligent orthogonal emissions LDNP@SiO -CaO and folic acid-polyethylene glycol-Ce6 nanodrug is rationally designed and fabricated not only for relieving the hypoxic tumor microenvironment (TME) to enhance PDT efficacy, but also for determining the optimal triggering time through second near-infrared (NIR-II) fluorescence imaging. The designed nanodrug continuously releases a large amount of O , H O , and Ca ions when exposed to the acidic TME.

Age- and Severity-Associated Humoral Immunity Response in COVID-19 Patients: A Cohort Study from Wuhan, China.

Age has been found to be the single most significant factor in COVID-19 severity and outcome. However, the age-related severity factors of COVID-19 have not been definitively established. In this study, we detected SARS-CoV-2-specific antibody responses and infectious disease-related blood indicators in 2360 sera from 783 COVID-19 patients, with an age range of 1−92 years.

Amorphous ferric oxide-coating selenium core-shell nanoparticles: a self-preservation Pt(IV) platform for multi-modal cancer therapies through hydrogen peroxide depletion-mediated anti-angiogenesis, apoptosis and ferroptosis.

A self-preservation Pt(IV) nanoplatform, amorphous ferric oxide-coating selenium core-shell nanoparticles (iAIO@NSe-Pt), was developed for HO depletion-mediated tumor anti-angiogenesis, apoptosis, and ferroptosis. Upon entry into the blood, the ferric oxide shell effectively blocked the contact Pt(IV) prodrug with reduced molecules, then avoided the inactivation of the Pt(IV) prodrug and increased its accumulation in the tumor. After entering cancer cells, iAIO@NSe-Pt caused a series of cascade reactions: (1) AIO on the surface of iAIO@NSe-Pt quickly dissolved, released an abundance of Fe(II) because of the weakly acidic tumor microenvironment, and then catalyzed cellular HO into highly toxic ˙OH, resulting in cellular HO deficiency and cell ferroptosis.

Estrogen-Related Receptor α: A Significant Regulator and Promising Target in Bone Homeostasis and Bone Metastasis.

Bone homeostasis is maintained with the balance between bone formation and bone resorption, which is involved in the functional performance of osteoblast and osteoclast. Disruption of this equilibrium usually causes bone disorders including osteoporosis, osteoarthritis, and osteosclerosis. In addition, aberrant activity of bone also contributes to the bone metastasis that frequently occurs in the late stage of aggressive cancers.

PDGFB targeting biodegradable FePt alloy assembly for MRI guided starvation-enhancing chemodynamic therapy of cancer.

The application of chemodynamic therapy (CDT) for cancer is a serious challenge owing to the low efficiency of the Fenton catalyst and insufficient HO expression in cells. Herein, we fabricated a PDGFB targeting, biodegradable FePt alloy assembly for magnetic resonance imaging (MRI)-guided chemotherapy and starving-enhanced chemodynamic therapy for cancer using PDGFB targeting, pH-sensitive liposome-coated FePt alloys, and GOx (pLFePt-GOx). We found that the Fenton-catalytic activity of FePt alloys was far stronger than that of traditional ultrasmall iron oxide nanoparticle (UION).

15-Month Health Outcomes and the Related Risk Factors of Hospitalized COVID-19 Patients From Onset: A Cohort Study.

Objective: The long-term impact of COVID-19 on patient health has been a recent focus. This study aims to determine the persistent symptoms and psychological conditions of patients hospitalized with COVID-19 15 months after onset, that patients first developed symptoms. The potential risk factors were also explored.

Anti-SARS-CoV-2 IgG responses are powerful predicting signatures for the outcome of COVID-19 patients.

Introduction: The COVID-19 global pandemic is far from ending. There is an urgent need to identify applicable biomarkers for early predicting the outcome of COVID-19. Growing evidences have revealed that SARS-CoV-2 specific antibodies evolved with disease progression and severity in COIVD-19 patients.

CuO dot-decorated Cu@GdO core-shell hierarchical structure for Cu(i) self-supplying chemodynamic therapy in combination with MRI-guided photothermal synergistic therapy.

Theoretically, the Fenton catalytic efficiency of the Cu-based nanoplatform is approximately 160 times that of traditional Fe-based agents. However, the coordination interaction between Cu(ii) and intracellular GSH significantly inhibits the high catalytic activity of Cu(i) generation, dramatically decreasing the Fenton-like catalytic efficiency. Herein, we designed a completely new and highly efficient hierarchical structural nanoplatform to enhance the mimic-peroxidase activity through utilizing comproportionation between CuO and elemental Cu core to self-supply Cu(i).

COVID-ONE-hi: The One-stop Database for COVID-19-specific Humoral Immunity and Clinical Parameters.

Coronavirus disease 2019 (COVID-19), which is caused by SARS-CoV-2, varies with regard to symptoms and mortality rates among populations. Humoral immunity plays critical roles in SARS-CoV-2 infection and recovery from COVID-19. However, differences in immune responses and clinical features among COVID-19 patients remain largely unknown.