Microglial adenosine A receptor in the paraventricular thalamic nucleus regulates pain sensation and analgesic effects independent of opioid and cannabinoid receptors.

Introduction: The paraventricular thalamic nucleus (PVT) is recognized for its critical role in pain regulation, yet the precise molecular mechanisms involved remain poorly understood. Here, we demonstrated an essential role of the microglial adenosine A receptor (AR) in the PVT in regulating pain sensation and non-opioid analgesia.

Method And Results: Specifically, AR was predominantly expressed in ionized calcium binding adapter molecule 1 (Iba1)-positive microglia cells within the PVT, with expression levels remaining unchanged in mice experiencing persistent inflammatory pain induced by complete Freund's adjuvant (CFA).

Noradrenergic inputs from the locus coeruleus to anterior piriform cortex and the olfactory bulb modulate olfactory outputs.

Norepinephrine (NE) released from locus coeruleus (LC) noradrenergic (NAergic) neurons plays a pivotal role in the regulation of olfactory behaviors. However, the precise circuits and receptor mechanisms underlying this function are not well understood. Here, in DBH-Cre mice model, we show that LC NAergic neurons project directly to both anterior piriform cortex (aPC) and the olfactory bulb (OB).

Dysfunctional S1P/S1PR1 signaling in the dentate gyrus drives vulnerability of chronic pain-related memory impairment.

Memory impairment in chronic pain patients is substantial and common, and few therapeutic strategies are available. Chronic pain-related memory impairment has susceptible and unsusceptible features. Therefore, exploring the underlying mechanisms of its vulnerability is essential for developing effective treatments.

Disorder-specific neurodynamic features in schizophrenia inferred by neurodynamic embedded contrastive variational autoencoder model.

Neurodynamic models that simulate how micro-level alterations propagate upward to impact macroscopic neural circuits and overall brain function may offer valuable insights into the pathological mechanisms of schizophrenia (SCZ). In this study, we integrated a neurodynamic model with the classical Contrastive Variational Autoencoder (CVAE) to extract and evaluate macro-scale SCZ-specific features, including subject-level, region-level parameters, and time-varying states. Firstly, we demonstrated the robust fitting of the model within our multi-site dataset.

The nonpathogenic role of hyponatremia in the onset of osteoporosis: A Mendelian randomization study.

The relationship between hyponatremia and osteoporosis is controversial, and it remains unclear if there is a causal link between the two. This study employed a 2-sample Mendelian randomization (MR) analysis to investigate the potential causal relationship between hyponatremia and osteoporosis. The instrumental variables were derived from genome-wide association studies conducted in European populations.

Hypoglycemic effects of a new heteropolysaccharide from common bean (Phaseolus vulgaris L.) seeds in type 2 diabetes mellitus mice via modulating gut microbiota.

Type 2 diabetes poses significant health issues worldwide; however, relatively few effective treatment strategies are currently available. This research seeks to explore the potential hypoglycemic impact of compounds derived from common bean (Phaseolus vulgaris L.) by structurally characterizing a new type of heteropolysaccharide (CIE2-F) and evaluating its hypoglycemic effects in a murine model.

Seasonality influences skin bacterial community structure and anti-Bd function in two anuran species.

Microorganisms on amphibian skin reduce disease susceptibility and play an important role in pathogen defense. We hypothesized that anuran skin bacterial communities would change in response to seasonal variation and host species. To test this hypothesis, we used 16S rRNA amplicon sequencing to identify cutaneous bacterial communities of two frogs from the Qinling Mountains of China, and .

Repurposed genipin targeting UCP2 exhibits antitumor activity through inducing ferroptosis in glioblastoma.

Uncoupling protein-2 (UCP2) controls the antioxidant response and redox homeostasis in cancer and is considered a potent molecular target for cancer treatment. However, the specific mechanism of UCP2 inhibition and its role in glioblastoma (GBM) have not yet been elucidated. Here, we attempt to identify a UCP2 inhibitor and study the underlying molecular mechanism in GBM.

Biomimetic Nano-delivery of Small-Molecule Piceatannol Modulates Tumor Stemness and Suppresses Colorectal Cancer Metastasis via Hippo/YAP1/SOX9 Signaling.

Suppressing tumor metastasis is a crucial strategy for improving survival rates in patients with colorectal cancer (CRC), with cancer stem cells (CSCs) being the primary drivers of metastasis. Current therapeutic approaches targeting CSCs are limited, and their molecular mechanisms remain unclear. To address this challenge, a biomimetic nanoparticle delivery system, CMD-BHQ3-PTL/DOX@RBCM is developed, to deliver the stem cell regulator, piceatannol (PTL).

Thalamic Volumes and Functional Networks Linked With Self-Regulation Dysfunction in Major Depressive Disorder.

Aims: Self-regulation (SR) dysfunction is a crucial risk factor for major depressive disorder (MDD). However, neural substrates of SR linking MDD remain unclear.

Methods: Sixty-eight healthy controls and 75 MDD patients were recruited to complete regulatory orientation assessments with the Regulatory Focus Questionnaire (RFQ) and Regulatory Mode Questionnaire (RMQ).

Comparative efficacy and safety of Chinese patent medicines as an adjunctive therapy for diabetic peripheral neuropathy: systematic review and network meta-analysis of randomized controlled trials.

Context: Diabetic peripheral neuropathy (DPN) is the most common complication of diabetes mellitus. Chinese patent medicines (CPMs) are widely used in clinical practice to treat DPN.

Objective: This study aims to summarize the latest evidence on the harms and benefits of CPMs as adjunctive therapy for DPN.

Wu Mei Wan suppresses colorectal cancer stemness by regulating Sox9 expression via JAK2/STAT3 pathway.

Ethnopharmacological Relevance: Wu Mei Wan (WMW) is a traditional Chinese herbal formula with a long-standing history in Chinese medicine, valued for its therapeutic properties. However, its potential anti-cancer effects, especially against colorectal cancer (CRC), have not been fully elucidated.

Aim Of The Study: This study aims to investigate the effects of WMW on colorectal cancer stemness and to elucidate the underlying molecular mechanisms, focusing on the modulation of Sox9 expression via the JAK2/STAT3 signaling pathway.

Excited-State Conjugation/De-Conjugation Driven Nonradiative Thermal Deactivation for Developing Fluorogenic Probes to Diagnose Cancers.

Fluorogenic probes have shown great potential in imaging biological species as well as in diagnosing diseases, especially cancers. However, the fluorogenic mechanisms are largely limited to a few photophysical processes to date, typically including photoinduced electron transfer (PeT), fluorescence resonant energy transfer (FRET), and intramolecular charge transfer (ICT). Herein, by calculations and experiments, we set forth that the inhibition of the excited-state π-conjugation in -ester Si-rhodamine or the de-π-conjugation in -ester cyanine 5 via the "" conversion can operate as a general fluorogenic mechanism to fabricate fluorogenic probes.

Diminished functional segregation and resilience are associated with symptomatic severity and cognitive impairments in schizophrenia: a large-scale study.

Background: The research findings on the topological properties of functional connectomes (TP-FCs) in patients with schizophrenia (SZPs) exhibit inconsistencies and contradictions, which can be attributed to limitations such as small sample sizes and heterogeneous data processing techniques.

Aims: To address these limitations, we conducted a large-scale study. Uniform data processing flows were employed to investigate the aberrant TP-FCs and the associations between TP-FCs and symptoms or cognitions (A-TP-SCs) in SZPs.

Development and evaluation of 3D composite scaffolds with piezoelectricity and biofactor synergy for enhanced articular cartilage regeneration.

The inability of articular cartilage to self-repair following injuries frequently precipitates osteoarthritis, profoundly affecting patients' quality of life. Given the limitations inherent in current clinical interventions, an urgent need exists for more effective cartilage regeneration methodologies. Previous studies have underscored the potential of electrical stimulation in cartilage repair, thus motivating the investigation of innovative strategies.

Expression and function identification of senescence-associated genes under continuous drought treatment in grapevine ( L.) leaves.

Unlabelled: Natural leaf senescence is critical for plant fitness. Drought-induced premature leaf senescence affects grape yield and quality. However, reports on the regulatory mechanisms underlying premature leaf senescence under drought stress are limited.

In situ biomineralization reinforcing anisotropic nanocellulose scaffolds for guiding the differentiation of bone marrow-derived mesenchymal stem cells.

Nanocellulose (NC) is a promising biopolymer for various biomedical applications owing to its biocompatibility and low toxicity. However, it faces challenges in tissue engineering (TE) applications due to the inconsistency of the microenvironment within the NC-based scaffolds with target tissues, including anisotropy microstructure and biomechanics. To address this challenge, a facile swelling-induced nanofiber alignment and a novel in situ biomineralization reinforcement strategies were developed for the preparation of NC-based scaffolds with tunable anisotropic structure and mechanical strength for guiding the differentiation of bone marrow-derived mesenchymal stem cells for potential TE application.

Supplementation with Combined Additive Improved the Production of Dairy Cows and Their Offspring with Maintenance of Antioxidative Stability.

Oxidative stress damage in periparturient cows decreases both production and their health; supplementation with complex additives during the periparturient period has been used as an important strategy to enhance the antioxidant status and production of dairy cows. The periparturient cows not only risk a negative energy balance due to reduced dry matter intake but also represent a sensitive period for oxidative stress. Therefore, we have developed an immunomodulatory and nutritional regulation combined additive (INC) that hopefully can improve the immune status and production of cows during the periparturient period and their offspring health and growth by improving their antioxidant stress status.

Mapping Brain Synergy Dysfunction in Schizophrenia: Understanding Individual Differences and Underlying Molecular Mechanisms.

To elucidate the brain-wide information interactions that vary and contribute to individual differences in schizophrenia (SCZ), an information-resolved method is employed to construct individual synergistic and redundant interaction matrices based on regional pairwise BOLD time-series from 538 SCZ and 540 normal controls (NC). This analysis reveals a stable pattern of regionally-specific synergy dysfunction in SCZ. Furthermore, a hierarchical Bayesian model is applied to deconstruct the patterns of whole-brain synergy dysfunction into three latent factors that explain symptom heterogeneity in SCZ.

Abscisic Acid Induces DNA Methylation Alteration in Genes Related to Berry Ripening and Stress Response in Grape ( L).

Abscisic acid (ABA) is a major regulator of nonclimacteric fruit ripening, with its processes involving epigenetic mechanisms. It remains unclear whether DNA methylation is associated with ABA-regulated ripening. In this study, we investigated the patterns of DNA methylation and gene expression following ABA treatment in grape berries by using whole-genome bisulfite sequencing and RNA-sequencing.

Midbrain glutamatergic circuit mechanism of resilience to socially transferred allodynia in male mice.

The potential brain mechanism underlying resilience to socially transferred allodynia remains unknown. Here, we utilize a well-established socially transferred allodynia paradigm to segregate male mice into pain-susceptible and pain-resilient subgroups. Brain screening results show that ventral tegmental area glutamatergic neurons are selectively activated in pain-resilient mice as compared to control and pain-susceptible mice.

Occipital connectivity networks mediate the neural effects of childhood maltreatment on depressive symptoms in major depressive disorder.

Background: Childhood maltreatment (CM) is a well-established risk factor for major depressive disorder (MDD). The neural mechanisms linking childhood maltreatment experiences to changes in brain functional networks and the onset of depression are not fully understood.

Methods: In this study, we enrolled 66 patients with MDD and 31 healthy controls who underwent resting-state fMRI scans and neuropsychological assessments.