Targeting mutant p53: Evaluation of novel anti-p53 monoclonal antibodies as diagnostic tools.

About 50% of all cancers carry a mutation in p53 that impairs its tumor suppressor function. The p53 missense mutation p53 (p53 in mice) is a hotspot mutation in various cancer types. Therefore, monoclonal antibodies selectively targeting clinically relevant mutations like p53 could prove immensely value.

Core-genome guided novel therapeutic targets identification and chimeric vaccine designing against Rickettsia rickettsii.

Rocky Mountain Spotted Fever, caused by the gram-negative intracellular bacteria Rickettsia rickettsii, is a serious tick-borne infection with a fatality rate of 20-30%, if not treated. Since it is the most serious rickettsial disease in North America, modified prevention and treatment strategies are of critical importance. In order to find new therapeutic targets and create multiepitope vaccines, this study integrated subtractive proteomics with reverse vaccinology.

Single-Cell RNA sequencing reveals mitochondrial dysfunction in microtia chondrocytes.

Microtia is a congenital malformation characterized by underdevelopment of the external ear. While chondrocyte dysfunction has been implicated in microtia, the specific cellular abnormalities remain poorly understood. This study aimed to investigate mitochondrial dysfunction in microtia chondrocytes using single-cell RNA sequencing.

NPC1 controls TGFBR1 stability in a cholesterol transport-independent manner and promotes hepatocellular carcinoma progression.

Niemann-Pick disease type C protein 1 (NPC1), classically associated with cholesterol transport and viral entry, has an emerging role in cancer biology. Here, we demonstrate that knockout of Npc1 in hepatocytes attenuates hepatocellular carcinoma (HCC) progression in both DEN (diethylnitrosamine)-CCl induced and MYC-driven HCC mouse models. Mechanistically, NPC1 significantly promotes HCC progression by modulating the TGF-β pathway, independent of its traditional role in cholesterol transport.

Rapid climate action is needed: comparing heat vs. COVID-19-related mortality.

The impacts of climate change on human health are often underestimated or perceived to be in a distant future. Here, we present the projected impacts of climate change in the context of COVID-19, a recent human health catastrophe. We compared projected heat mortality with COVID-19 deaths in 38 cities worldwide and found that in half of these cities, heat-related deaths could exceed annual COVID-19 deaths in less than ten years (at + 3.

Application of urinary peptide-biomarkers in trauma patients as a predictive tool for prognostic assessment, treatment and intervention timing.

Treatment of severely injured patients represents a major challenge, in part due to the unpredictable risk of major adverse events, including death. Preemptive personalized treatment aimed at preventing these events is a crucial objective of patient management; however, the currently available scoring systems provide only moderate guidance. Biomarkers from proteomics/peptidomics studies hold promise for improving the current situation, ultimately enabling precision medicine based on individual molecular profiles.

Cooperative condensation of RNA-DIRECTED DNA METHYLATION 16 splicing isoforms enhances heat tolerance in Arabidopsis.

Dissecting the mechanisms underlying heat tolerance is important for understanding how plants acclimate to heat stress. Here, we identify a heat-responsive gene in Arabidopsis thaliana, RNA-DIRECTED DNA METHYLATION 16 (RDM16), which encodes a pre-mRNA splicing factor. Knockout mutants of RDM16 are hypersensitive to heat stress, which is associated with impaired splicing of the mRNAs of 18 out of 20 HEAT SHOCK TRANSCRIPTION FACTOR (HSF) genes.

GmERF13 mediates salt inhibition of nodulation through interacting with GmLBD16a in soybean.

While the genetic regulation of nodule formation has been well explored, the molecular mechanisms by which abiotic stresses, such as salt stress, impede nodule formation remain largely elusive. Here, we identify four APETALA2/Ethylene Responsive Factor (AP2/ERF) transcription factors, GmERF13s, that are induced by salt stress and play key roles in salt-repressed nodulation. Loss of GmERF13 function increases nodule density, while its overexpression suppresses nodulation.

Depth heterogeneity of lignin-degrading microbiome and organic carbon processing in mangrove sediments.

Mangrove ecosystems are globally recognized for their blue carbon (C) sequestration capacity. Lignocellulosic detritus constitutes the primary C input to mangrove sediments, but the microbial processes involved in its bioprocessing remain unclear. Using lignocellulosic analysis and metagenomic sequencing across five 100-cm sediment cores, we found a high proportion of lignin (95.

Integrated proteogenomic characterization of ampullary adenocarcinoma.

Ampullary adenocarcinoma (AMPAC) is a rare and heterogeneous malignancy. Here we performed a comprehensive proteogenomic analysis of 198 samples from Chinese AMPAC patients and duodenum patients. Genomic data illustrate that 4q loss causes fatty acid accumulation and cell proliferation.

Anti-PD-1 exacerbates bleomycin-induced lung injury in mice via Caspase-3/GSDME-mediated pyroptosis.

Immune checkpoint inhibitors (ICIs) have significant therapeutic effects but can also cause fatal lung injury. However, the lack of mouse animal models of ICI-related lung injury (ICI-LI) has limited the in-depth exploration of its pathogenesis. In clinical practice, underlying lung diseases increase the risk of lung injury.

Integration of Immune Responses and Transcriptomic Signatures Reveals the Efficacy of Maternal Genetic Vaccination in a Pregnant Model and Its Neonates.

Maternal vaccination is essential for safeguarding both mother and foetus from infectious diseases. This study investigated the immunogenicity and efficacy of a maternal ORF-B2L genetic vaccine in a pregnant rat model, focusing on maternal-neonatal immune modulation, placental and neonatal spleen transcriptomics and the underlying mechanisms contributing to neonatal immune development. Female rats received intramuscular injections of either a gene vaccine (GV) containing 200 μg of recombinant ORF-B2L DNA and 50 μg of a subunit protein or an empty plasmid as a control.

[Pathological diagnosis of solid pancreatic lesions with endoscopic ultrasound-guided fine needle aspiration: a series study of 311 cases].

To investigate the combined application of cytology, cell block histology and immunohistochemistry to improve the diagnostic accuracy of solid pancreatic lesions in endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) samples. The pathological data of EUS-FNA in 311 cases of solid pancreatic lesions submitted to the Second Hospital of Hebei Medical University, Shijiazhuang, China from May 2019 to September 2023 were retrospectively analyzed. The cases included pancreatic ductal adenocarcinoma (PDAC, 172 cases), solid pseudopapillary neoplasm (SPN, 12 cases), neuroendocrine tumors (PNET, 14 cases) and chronic pancreatitis (113 cases).

[Detection and interpretation of PD-L1 in urologic neoplasms].

Immune checkpoint inhibitors targeting PD-1/PD-L1 are gradually being applied in the treatment of advanced urinary system tumors. Immunohistochemical analysis of PD-L1 expression is the most popular method for screening suitable patients for immunotherapy and predicting therapeutic efficacy. The current application status of PD-L1 detection for urinary system tumors (mainly urothelial carcinoma), methods of the different antibody tests and the precautions, challenges and solutions in the interpretation of immunostaining were summarized in this review.

Implementing and evaluating the comprehensive integration of physical activity into a major health system: study design and protocol.

Introduction: The healthcare sector has great potential for promoting physical activity (PA) for chronic disease prevention, treatment and management; however, multiple adoption and implementation barriers exist, ranging from practice integration to information flow. In 2016, Exercise is Medicine Greenville (EIMG), a comprehensive clinic-to-community approach that involves PA assessment, recommendation and/or prescription and provider-based referral of patients to community-based PA programmes, was launched by Prisma Health in Greenville, South Carolina, USA. Since inception, variability has emerged in adoption and implementation, impacting patient reach, referral rates and engagement in the community-based PA programmes, highlighting the need for closer evaluation and refinement of strategies to maximise programme impact.

Home high-flow therapy during recovery from severe chronic obstructive pulmonary disease (COPD) exacerbation: a mixed-methods feasibility randomised control trial.

Introduction: Patients recovering from severe acute exacerbations of chronic obstructive pulmonary disease (AECOPD) have a 30-day readmission rate of 20%. This study evaluated the feasibility of conducting a randomised controlled trial to evaluate clinical, patient-reported and physiological effects of home high-flow therapy (HFT) in addition to usual medical therapy, in eucapnic patients recovering from AECOPD to support the design of a phase 3 trial.

Methods: A mixed-methods feasibility randomised controlled trial (quantitative primacy, concurrently embedded qualitative evaluation) (ISRCTN15949009) recruiting consecutive non-obese patients hospitalised with AECOPD not requiring acute non-invasive ventilation.

Thermal ablation included in multimodality treatment predicts enhanced survival in advanced non-small cell lung cancer: a propensity score-matched outcome study.

Background: Advanced non-small cell lung cancer (NSCLC) presents significant treatment challenges, with limited effective therapies for late-stage patients. This study aimed to evaluate the impact of adding thermal ablation (TA) in treatment regimens for advanced NSCLC to improve survival outcomes.

Methods: A retrospective cohort study was conducted at a medical center in Taiwan, analyzing data from 1,083 patients diagnosed with stage IIIB or IV NSCLC between 2008 and 2020.

Lebrikizumab is associated with improvements in patient-reported symptoms and quality-of-life measures across Eczema Area and Severity Index response categories: pooled results from phase-3 randomized ADvocate1 and ADvocate2 studies in patients with moderate-to-severe atopic dermatitis.

Background: Lebrikizumab monotherapy significantly improved signs and symptoms in patients with moderate-to-severe atopic dermatitis (AD) in phase 3 Advocate1 and ADvocate2 studies.

Objective: To evaluate improvements in patient-reported symptoms and quality-of-life (QoL) measures by Eczema Area and Severity Index (EASI) response categories using pooled Advocate1 and ADvocate2 data (post hoc analysis).

Methods: In the 52-week (W) (16-W induction + 36-W maintenance) double-blind, placebo-controlled ADvocate1 and ADvocate2 studies, patients were randomized (2:1) to receive subcutaneous lebrikizumab 250 mg or placebo every 2 weeks.

Androgens induce renal synthesis of urinary lipocalin-family protein, a potential inter-sexual transmitter in viviparous rockfish.

In viviparous black rockfish (Sebastes schlegelii), the kidney of reproductive-phase males actively produces lipocalin-type prostaglandin D synthase homolog (LPGDSh) protein, which is presumably involved in intersexual communication when emitted in the urine. The present study was undertaken to discover whether androgens and their nuclear receptors (Ars) are engaged in regulation of renal LPGDSh protein synthesis in black rockfish. Quantitative real-time polymerase chain reaction, in conjunction with immunohistochemistry and highly sensitive enzyme-linked immunosorbent assay, revealed that intra-abdominal administration of a synthetic androgen, 17α-methyltestosterone (MT), to juvenile black rockfish induced their renal expression of LPGDSh transcript and protein.

Peripheral inflammation enhances opioid-induced gastrointestinal motility inhibition via up-regulating spinal mu opioid receptor.

Opioids are potent analgesics in clinical pain management but exert variable analgesia in different pain types. Opioid-induced constipation is a common side effect of opioid therapy, and whether opioids induce different gastrointestinal motility inhibitions in different pain types is unknown. In this study, we evaluated the antinociceptive effects and inhibition of upper gastrointestinal transit and colonic bead expulsion of morphine, DAMGO, and Deltorphin in mouse CFA chronic inflammatory pain, SNI chronic neuropathic pain, and carrageenan chronic inflammatory pain models.

The P-type ATPase gene AHA5 is involved in proanthocyanidins accumulation in Medicago truncatula.

Proanthocyanidins (PAs) are the second most abundant plant phenolic natural products. The proton membrane H-ATPase (AHA) is required for PA transportation in vacuoles, but it remains unclear which AHA gene(s) encode tonoplast proton pump in M. truncatula.

MtrAB two-component system is crucial for the intrinsic resistance and virulence of Mycobacterium abscessus.

Mycobacterium abscessus (Mab) poses serious therapeutic challenges, largely due to its intrinsic resistance to many antibiotics. The development of targeted therapeutic strategies necessitates the identification of bacterial factors that contribute to its reduced susceptibility to antibiotics and/or to the killing by its host cells. In this study, we discovered that Mab strains with disrupted mtrA, mtrB or both, or a gene-edited mtrA encoding MtrA with Tyr102Cys mutation, exhibited highly increased sensitivity to various drugs compared to the wild-type Mab.

Advances in research on metabolic dysfunction-associated steatotic liver disease.

The global increase in obesity-related metabolic disorders has led to metabolic dysfunction-associated steatotic liver disease (MASLD) emerging as one of the most prevalent chronic liver disease worldwide. Despite growing concerns, the exact pathogenesis of MASLD remains unclear and no definitive treatments have been made available. Consequently, the need for comprehensive research on MASLD is more critical than ever.

Current status, opportunities and challenges of exosomes in diagnosis and treatment of osteoarthritis.

Osteoarthritis (OA) is a progressive joint disease that is a frequent reason for pain and physical dysfunction in adults, with enormous social and economic burden. Although ongoing scientific efforts in recent years have made considerable progress towards understanding of the disease's molecular mechanism, the pathogenesis of OA is still not fully known, and its clinical challenge remains. Thus, elucidating molecular events underlying the initiation and progression of OA is crucial for developing novel diagnostic and therapeutic approaches that could facilitate effective clinical management of the illness.

Pathogenicity of tick-derived lymphocytic choriomeningitis virus in BALB/c mice.

Background: Lymphocytic choriomeningitis virus (LCMV) is a zoonotic pathogen primarily transmitted by rodents. Recently, LCMV has been detected in ticks from northeastern China; however, the pathogenicity of this virus in murine models remains to be elucidated.

Results: Here, we examined the tick-derived LCMV strain JX14 by inoculating BALB/c mice with 3.