NMDA-induced lesions of the nucleus accumbens core increase the innately rewarding saccharin solution intake and methamphetamine-induced conditioned place preference but not conditioned taste aversion in rats.

The role of the nucleus accumbens (NAc) core in determining the valence of innately rewarding saccharin solution intake, methamphetamine (MAMPH)-induced conditioned taste aversion (CTA), and conditioned place preference (CPP) reward remains unclear. The present study utilized the "pre- and post-association" experimental paradigm (2010) to test whether the rewarding and aversive properties of MAMPH can be modulated by an N-methyl-D-aspartic acid (NMDA) lesion in the NAc core. Moreover, it tested how an NAc core NMDA lesion affected the innate reward of saccharin solution intake.

Engineered extracellular vesicles with DR5 agonistic scFvs simultaneously target tumor and immunosuppressive stromal cells.

Small extracellular vesicles (sEVs) are nanosized vesicles. Death receptor 5 (DR5) mediates extrinsic apoptosis. We engineer DR5 agonistic single-chain variable fragment (scFv) expression on the surface of sEVs derived from natural killer cells.

Comparison of Clinical Characteristics and Mortality Outcome in Critical COVID-19 Patients Infected with Alpha and Omicron Variants.

Objective: Early reports have indicated that the Omicron variant of coronavirus disease 2019 (COVID-19) may be associated with low mortality. However, the mortality rate of critical patients in Taiwan with COVID-19 caused by different variants has not been well described.

Methods: This retrospective cohort study was conducted at the Linkou Branch of Chang Gung Memorial Hospital, Taiwan, from April 2020 to September 2022.

Alterations in Striatal Architecture and Biochemical Markers' Levels During Postnatal Development in the Rat Model of an Attention Deficit/Hyperactivity Disorder (ADHD).

Attention deficit/hyperactivity disorder (ADHD) is defined as a neurodevelopmental condition. The precise underlying mechanisms remain incompletely elucidated. A body of research suggests disruptions in both the cellular architecture and neuronal function within the brain regions of individuals with ADHD, coupled with disturbances in the biochemical parameters.

Tumor-Infiltrating Lymphocytes in Necrotic Tumors after Melanoma Neoadjuvant Anti-PD-1 Therapy Correlate with Pathologic Response and Recurrence-Free Survival.

Purpose: Neoadjuvant anti-PD-1 therapy in melanoma may increase tumor-infiltrating lymphocytes (TIL), and more TIL are associated with better treatment response. A major pathologic response (MPR) in melanoma after neoadjuvant anti-PD-1 therapy usually comprises tumor necrosis and fibrosis. The role of TIL in necrotic tumor necrosis (nTIL) has not been explored.

Age-related changes in the architecture and biochemical markers levels in motor-related cortical areas of SHR rats-an ADHD animal model.

Introduction: Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder whose exact pathophysiology has not been fully understood yet. Numerous studies have suggested disruptions in the cellular architecture and neuronal activity within brain structures of individuals with ADHD, accompanied by imbalances in the immune system, oxidative stress, and metabolism.

Methods: This study aims to assess two functionally and histologically distinct brain areas involved in motor control and coordination: the motor cortex (MC) and prefrontal cortex (PFC).

Combination anti-PD-1 and anti-CTLA-4 therapy generates waves of clonal responses that include progenitor-exhausted CD8 T cells.

Combination checkpoint blockade with anti-PD-1 and anti-CTLA-4 antibodies has shown promising efficacy in melanoma. However, the underlying mechanism in humans remains unclear. Here, we perform paired single-cell RNA and T cell receptor (TCR) sequencing across time in 36 patients with stage IV melanoma treated with anti-PD-1, anti-CTLA-4, or combination therapy.

Estimation equation of limb lean soft tissue mass in Asian athletes using bioelectrical impedance analysis.

Background: The lean soft tissue mass (LSTM) of the limbs is approximately 63% of total skeletal muscle mass. For athletes, measurement of limb LSTM is the basis for rapid estimation of skeletal muscle mass. This study aimed to establish the estimation equation of LSTM in Asian athletes using bioelectrical impedance analysis (BIA).

NAD deficiency primes defense metabolism via O-escalated jasmonate biosynthesis in plants.

Nicotinamide adenine dinucleotide (NAD) is a redox cofactor and signal central to cell metabolisms. Disrupting NAD homeostasis in plant alters growth and stress resistance, yet the underlying mechanisms remain largely unknown. Here, by combining genetics with multi-omics, we discover that NAD deficiency in qs-2 caused by mutation in NAD biosynthesis gene-Quinolinate Synthase retards growth but induces biosynthesis of defense compounds, notably aliphatic glucosinolates that confer insect resistance.

Clinical Validation of a Deep Learning-Based Software for Lumbar Bone Mineral Density and T-Score Prediction from Chest X-ray Images.

Screening for osteoporosis is crucial for early detection and prevention, yet it faces challenges due to the low accuracy of calcaneal quantitative ultrasound (QUS) and limited access to dual-energy X-ray absorptiometry (DXA) scans. Recent advances in AI offer a promising solution through opportunistic screening using existing medical images. This study aims to utilize deep learning techniques to develop a model that analyzes chest X-ray (CXR) images for osteoporosis screening.

The P2X7 Hypothesis of Central Post-Stroke Pain.

The present study examined how P2X7 receptor knockout (KO) modulates central post-stroke pain (CPSP) induced by lesions of the ventrobasal complex (VBC) of the thalamus in behaviors, molecular levels, and electrical recording tests. Following the experimental procedure, the wild-type and P2X7 receptor KO mice were injected with 10 mU/0.2 μL type IV collagenase in the VBC of the thalamus to induce an animal model of stroke-like thalamic hemorrhage.

Combined JAK inhibition and PD-1 immunotherapy for non-small cell lung cancer patients.

Persistent inflammation driven by cytokines such as type-one interferon (IFN-I) can cause immunosuppression. We show that administration of the Janus kinase 1 (JAK1) inhibitor itacitinib after anti-PD-1 (programmed cell death protein 1) immunotherapy improves immune function and antitumor responses in mice and results in high response rates (67%) in a phase 2 clinical trial for metastatic non-small cell lung cancer. Patients who failed to respond to initial anti-PD-1 immunotherapy but responded after addition of itacitinib had multiple features of poor immune function to anti-PD-1 alone that improved after JAK inhibition.

[Effects and Mechanisms of Polystyrene Microplastics on Extracellular Antibiotic Resistance Genes in Wastewater].

Microplastics (MPs) and antibiotic resistance genes (ARGs) are typical co-existing emerging pollutants in wastewater treatment plants. MPs have been shown to alter the distribution pattern of ARGs in sludge, but their effects on free extracellular ARGs (feARGs) in wastewater remain unclear. In this study, we used fluorescence quantitative PCR to investigate the dynamics of feARGs (including , , , and ) in wastewater and their transition mechanisms after 60 d of exposure to typical MPs (polystyrene, PS).

Multi-microdialysis analytical system to monitor acetaminophen and its pharmacokinetic interaction with A. bidentata in rat blood, forelimb extensor muscle, brain striatum, and the knee joint cavity.

Acetaminophen (APAP), or paracetamol, is one of the most widespread and commonly used non-prescription pain medication in the world, and is effective at managing wide range of pain, including headache, muscle ache, and minor arthritic pain. While the pharmacokinetics of APAP is generally understood, there is a lack of data for its transfer ratio especially into the knee. A novel multi-microdialysis model was developed to simultaneously sample from blood, forelimb extensor muscle, brain striatum, and the knee joint cavity in the same experimental subject to investigate the potential interaction between APAP and Achyranthes bidentata Blume (A.

SpliceAPP: an interactive web server to predict splicing errors arising from human mutations.

Background: Splicing variants are a major class of pathogenic mutations, with their severity equivalent to nonsense mutations. However, redundant and degenerate splicing signals hinder functional assessments of sequence variations within introns, particularly at branch sites. We have established a massively parallel splicing assay to assess the impact on splicing of 11,191 disease-relevant variants.

A Clinical Analysis of Anti-Programmed Death-Ligand 1 (PD-L1) Immune Checkpoint Inhibitor Treatments Combined with Chemotherapy in Untreated Extensive-Stage Small-Cell Lung Cancer.

Real-world clinical experience of using anti-programmed death-ligand 1 (PD-L1) immune checkpoint inhibitors (ICIs) combined with chemotherapy in the first-line treatment of extensive-stage small-cell lung cancer (SCLC) patients has rarely been reported. In this study, we aimed to perform a retrospective multicenter clinical analysis of extensive-stage SCLC patients receiving first-line therapy with anti-PD-L1 ICIs combined with chemotherapy. Between November 2018 and March 2022, 72 extensive-stage SCLC patients receiving first-line atezolizumab or durvalumab in combination with chemotherapy, according to the cancer center databases of Linkou, Chiayi, and Kaohsiung Chang Gung Memorial Hospitals, were retrospectively included in the analysis.

NF-κB Decoy Oligodeoxynucleotide-Loaded Poly Lactic-co-glycolic Acid Nanospheres Facilitate Socket Healing in Orthodontic Tooth Movement.

Orthodontic space closure following tooth extraction is often hindered by alveolar bone deficiency. This study investigates the therapeutic use of nuclear factor-kappa B (NF-κB) decoy oligodeoxynucleotides loaded with polylactic-co-glycolic acid nanospheres (PLGA-NfDs) to mitigate alveolar bone loss during orthodontic tooth movement (OTM) following the bilateral extraction of maxillary first molars in a controlled experiment involving forty rats of OTM model with ethics approved. The decreased tendency of the OTM distance and inclination angle with increased bone volume and improved trabecular bone structure indicated minimized alveolar bone destruction.

Parvalbumin interneuron deficiency in the prefrontal and motor cortices of spontaneously hypertensive rats: an attention-deficit hyperactivity disorder animal model insight.

Background: Attention deficit hyperactivity disorder (ADHD) is characterized by impairments in developmental-behavioral inhibition, resulting in impulsivity and hyperactivity. Recent research has underscored cortical inhibition deficiencies in ADHD via the gamma-aminobutyric acid (GABA)ergic system, which is crucial for maintaining excitatory-inhibitory balance in the brain. This study explored postnatal changes in parvalbumin (PV) immunoreactivity, indicating GABAergic interneuron types, in the prefrontal (PFC) and motor (MC) cortices of spontaneously hypertensive rats (SHRs), an ADHD animal model.

SDF-1 involvement in orthodontic tooth movement after tooth extraction.

The stromal cell-derived factor 1 (SDF-1)/chemokine receptor type 4 (CXCR4) axis plays a key role in alveolar bone metabolism during orthodontic tooth movement (OTM). Herein, the effects of the SDF-1/CXCR4 axis on the regional acceleratory phenomenon (RAP) in OTM velocity and on changes in the surrounding periodontium after adjacent tooth extraction in rats were investigated. Six-week-old male Wistar/ST rats underwent left maxillary first molar (M1) extraction and mesial OTM of the left maxillary second molar (M2) with a 10-g force closed-coil spring.

Factors associated with prolonged progression-free survival of patients treated with first-line afatinib for advanced epidermal growth factor receptor-mutated non-small cell lung cancer.

Background: This study aimed to investigate the factors associated with prolonged progression-free survival (PFS) (>36 months) of advanced non-small cell lung cancer (NSCLC) patients harboring epidermal growth factor receptor (EGFR) mutations treated with first-line afatinib.

Methods: We performed a retrospective analysis of data of patients with advanced EGFR-mutated NSCLC receiving first-line afatinib at two tertiary care referral centers, Linkou and Kaohsiung Chang Gung Memorial Hospital, in Taiwan between June 2014 and April 2022.

Results: The data of 546 treatment-naïve EGFR-mutated advanced NSCLC patients were analyzed.