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The paraventricular thalamus is a relay station connecting brainstem and hypothalamic signals that represent internal states with the limbic forebrain that performs associative functions in emotional contexts. Zhu et al. found that paraventricular thalamic neurons represent multiple salient features of sensory stimuli, including reward, aversiveness, novelty, and surprise. The nucleus thus provides context-dependent salience encoding. The thalamus gates sensory information and contributes to the sleep-wake cycle through its interactions with the cerebral cortex. Ren et al. recorded from neurons in the paraventricular thalamus and observed that both population and single-neuron activity were tightly coupled with wakefulness. Science , this issue p. 423 , p. 429 Neurons in the paraventricular thalamic nucleus are both necessary and sufficient for maintaining arousal. Clinical observations indicate that the paramedian region of the thalamus is a critical node for controlling wakefulness. However, the specific nucleus and neural circuitry for this function remain unknown. Using in vivo fiber photometry or multichannel electrophysiological recordings in mice, we found that glutamatergic neurons of the paraventricular thalamus (PVT) exhibited high activities during wakefulness. Suppression of PVT neuronal activity caused a reduction in wakefulness, whereas activation of PVT neurons induced a transition from sleep to wakefulness and an acceleration of emergence from general anesthesia. Moreover, our findings indicate that the PVT–nucleus accumbens projections and hypocretin neurons in the lateral hypothalamus to PVT glutamatergic neurons’ projections are the effector pathways for wakefulness control. These results demonstrate that the PVT is a key wakefulness-controlling nucleus in the thalamus.

Oil and gas pipeline security is critical to national infrastructure, yet existing monitoring systems often lack the sensitivity and real-time responsiveness required to detect subtle intrusion events. This study presents a novel multimodal sensing and interaction frame-work that integrates phase-sensitive optical time-domain reflectometry (φ-OTDR)–based distributed acoustic sensing (DAS) with an optimized one-dimensional convolutional neural network (1-D CNN) architecture. The approach leverages both raw fiber optic vi-bration signals and carefully selected handcrafted features, enabling robust automatic in-trusion classification across multiple event types including manual tapping, mechanical excavation, and human footsteps. By incorporating transfer learning from publicly avail-able human activity datasets, the model achieves enhanced feature generalization, result-ing in a classification accuracy exceeding 95%. This work demonstrates the potential of combining advanced multimodal sensing technologies with deep learning-based interac-tive analytics for real-time pipeline security monitoring, paving the way for intelligent in-frastructure protection systems. Future efforts will focus on expanding dataset diversity, integrating multi-sensor fusion, and enhancing adaptive interaction capabilities for field deployment.

Background Depression is a heterogeneous disorder, with the exact neuronal mechanisms causing the disease yet to be discovered. Recent work suggests it is accompanied by neuro-inflammation, characterized, in particular, by microglial activation. However, microglial activation and its involvement in neuro-inflammation and stress-related depressive disorders are far from understood. Methods We utilized multiple detection methods to detect the neuro-inflammation in the hippocampus of rats after exposure to chronic mild stress (CMS). Male Sprague Dawley (SD) rats were subjected to chronic mild stressors for 12 weeks. Microglial activation and hippocampal neuro-inflammation were detected by using a combinatory approach of in vivo [18F] DPA-714 positron emission computed tomography (PET) imaging, ionized calcium-binding adapter molecule 1 and translocator protein (TSPO) immunohistochemistry, and detection of NOD-like receptor protein 3 (NLRP3) inflammasome and some inflammatory mediators. Then, the rats were treated with minocycline during the last 4 weeks to observe its effect on hippocampal neuro-inflammation and depressive-like behavior induced by chronic mild stress. Results The results show that 12 weeks of chronic mild stress induced remarkable depressive- and anxiety-like behavior, simultaneously causing hippocampal microglial activation detected by PET, immunofluorescence staining, and western blotting. Likewise, activation of NLRP3 inflammasome and upregulation of inflammatory mediators, such as interleukin-1β (IL-1β), IL-6, and IL-18, were also observed in the hippocampus after exposure to chronic stress. Interestingly, the anti-inflammatory mediators, such as IL-4 and IL-10, were also increased in the hippocampus following chronic mild stress, which may hint that chronic stress activates different types of microglia, which produce pro-inflammatory cytokines or anti-inflammatory cytokines. Furthermore, chronic minocycline treatment alleviated the depressive-like behavior induced by chronic stress and significantly inhibited microglial activation. Similarly, the activation of NLRP3 inflammasome and the increase of inflammatory mediators were not exhibited or significantly less marked in the minocycline treatment group. Conclusion These results together indicate that microglial activation mediates the chronic mild stress-induced depressive- and anxiety-like behavior and hippocampal neuro-inflammation.

In recent years, immune checkpoint inhibitors (ICIs) represented by PD‐1/PD‐L1 monoclonal antibodies have shown some good efficacy in various solid tumors such as gastric cancer. However, only about less than 30% of patients benefit from ICIs, and some patients experience rapid tumor growth posttreatment, known as hyperprogressive disease (HPD). Collectively, the overall survival of HPD patients is significantly shorter compared to patients with traditional disease progression, and there is no unified criterion for diagnosing HPD. Some biological mechanisms of HPD in gastric cancer caused by ICIs are still unclear, and factors associated with the occurrence of HPD are uncertain. Notably, it is believed that intrinsic factors, such as abnormal expression of oncogenic genes, and extrinsic factors, including remodeling of the tumor microenvironment, “drift” of immune cell subtypes, may be related to the occurrence of HPD in gastric cancer. Due to its immune stimulatory effects, ICIs may activate certain oncogenic pathways within the tumor, resulting in the appearance of tumor HPD phenomena through increased expression and mutations of some genes, as well as disruption of the balance between immune cells and tumor cells in the tumor microenvironment. Therefore, this review summarizes the mechanisms, predictive biomarkers, prevention, and treatment methods of HPD after immune checkpoint blockade therapy, providing a theoretical basis for making a judgment on the efficacy of ICI treatment for gastric cancer. This review summarizes the mechanisms, predictive biomarkers, prevention, and treatment methods of HPD after immune checkpoint blockade therapy, providing a theoretical basis for making a judgment on the efficacy of ICI treatment for gastric cancer.

Neutrophil extracellular traps (NETs) have been found to play a role in the development of autoimmune diseases. In the past two years, studies have demonstrated a significantly increase of NETs in skin tissues during the early stages of IgAV, indicating their involvement in disease activity among children with IgAV. However, the presence of NETs in IgAV animal models has not yet been reported. The objective of this study is to investigate whether NETs are involved in the pathogenesis of IgA vasculitis (IgAV) rats. Twenty-four SD rats were randomly divided into three groups: the ovalbumin group, the gliadin group, and the control group. The IgAV rat models were established administering Indian ink with ovalbumin (ovalbumin group) or gliadin (gliadin group) with Freund's complete adjuvant. The cell-free DNA (cf-DNA) was quantified by using dsDNA quantification kit, while the levels of Immunoglobulins, complement C3 and myeloperoxidase-DNA (MPO-DNA) in serum were tested using enzyme linked immunosorbent assay (ELISA). The IgA, complement C3 and NETs in tissues were detected through multiple immunofluorescences. Both the ovalbumin group and gliadin group showed IgA and C3 deposition in various tissues, including the glomerular mesangial region, skin, and digestive tract, while the control group showed no such deposition. The levels of circulatory cf-DNA and MPO-DNA, which are components of NETs, were significantly elevated in both ovalbumin and gliadin groups compared with the control group. Furthermore, the presence of NETs were found in gastrointestinal and renal tissues of the ovalbumin and gliadin groups, but not in the control group. IgAV model rat can be established through the combination of ovalbumin and gliadin with Indian ink and Freund's complete adjuvant. This study provides the first confirmation that NETs are involved in the pathogenesis of IgAV rat.

The communication between tumor-derived elements and stroma in the metastatic niche has a critical role in facilitating cancer metastasis. Yet, the mechanisms tumor cells use to control metastatic niche formation are not fully understood. Here we report that in the lung metastatic niche, high-metastatic hepatocellular carcinoma (HCC) cells exhibit a greater capacity to convert normal fibroblasts to cancer-associated fibroblasts (CAFs) than low-metastatic HCC cells. We show high-metastatic HCC cells secrete exosomal miR-1247-3p that directly targets B4GALT3, leading to activation of β1-integrin–NF-κB signaling in fibroblasts. Activated CAFs further promote cancer progression by secreting pro-inflammatory cytokines, including IL-6 and IL-8. Clinical data show high serum exosomal miR-1247-3p levels correlate with lung metastasis in HCC patients. These results demonstrate intercellular crosstalk between tumor cells and fibroblasts is mediated by tumor-derived exosomes that control lung metastasis of HCC, providing potential targets for prevention and treatment of cancer metastasis. How tumor cells control metastatic niche formation is not fully understood. Here, the authors show in a lung metastatic niche, high-metastatic hepatocellular carcinoma cells secrete exosomal miR-1247-3p that leads to activation of β1-integrin-NF-κBsignalling, converting fibroblasts to cancer-associated fibroblasts.

As an important measure of enterprise governance, internal control can enhance the organizational rationality of the enterprise, ensure that the enterprise consciously assumes social responsibility for the protection of the natural environment and resources, and promote the sustainable development of the national economy. Using data from China’s A-share heavy pollution industry listed companies from 2009 to 2018, this study explored the relationships among internal control quality, enterprise environmental protection investment, and financial performance. The results show that the quality of internal control has a significant positive impact on enterprise environmental protection investment and financial performance. Enterprise environmental protection investment has a significant positive impact on financial performance and plays a partial intermediary role in the positive impact of internal control quality on financial performance. While expanding the theory of resource-based concepts, this study clarified the positive impact of corporate environmental management and practical behavior on corporate value and provides a theoretical basis for companies to actively implement environmental protection responsibilities, strengthen internal environmental management capabilities, and enhance corporate value. At the same time, it also provides a basis for the government to issue relevant environmental protection policies, strengthen enterprise internal control construction guidelines, and encourage third-party organizations to evaluate the effectiveness of enterprise internal control.

Cold stress poses a serious threat to the survival and bloom of . The enhancement of the cold tolerance of is the central concern of our research. The WRKY transcription factor (TF) family was paid great attention to in the field of abiotic stress. The gene was obtained from . The predicted protein contained two typical WRKY domains and two C2H2 zinc-finger motifs. Under cold stress, in leaves was more greatly induced than that in stems and roots. The overexpression (OE) in increased cold tolerance compared with wild-type (WT). Under cold stress, the OE lines possessed showed greater recovery after cold-treatment restoration ratios, proline content, soluble sugar content, and activities of antioxidant enzymes than WT; the relative electrolyte conductivity (EL), the accumulation of malondialdehyde (MDA), hydrogen peroxide (H O ), and superoxide anion (O ) are lower in OE lines than that in WT. In addition, a series of cold-response genes of OE lines were compared with WT. The results revealed that worked as a positive regulator by up-regulating transcription levels of cold-responsive genes. The genes above can contribute to the elevation of antioxidant activities, maintain the membrane stability, and raise osmotic regulation ability, leading to the enhancement of the survival capacity under cold stress. According to this work, could serve as an essential gene to confer enhanced cold tolerance in plants.

Background Pharmacologic stress ulcer prophylaxis (SUP) is recommended in critically ill patients with high risk of stress-related gastrointestinal (GI) bleeding. However, as to patients receiving enteral feeding, the preventive effect of SUP is not well-known. Therefore, we performed a meta-analysis of randomized controlled trials (RCTs) to evaluate the effect of pharmacologic SUP in enterally fed patients on stress-related GI bleeding and other clinical outcomes. Methods We searched PubMed, Embase, and the Cochrane database from inception through 30 Sep 2017. Eligible trials were RCTs comparing pharmacologic SUP to either placebo or no prophylaxis in enterally fed patients in the ICU. Results were expressed as risk ratio (RR) and mean difference (MD) with accompanying 95% confidence interval (CI). Heterogeneity, subgroup analysis, sensitivity analysis and publication bias were explored. Results Seven studies (n = 889 patients) were included. There was no statistically significant difference in GI bleeding (RR 0.80; 95% CI, 0.49 to 1.31, p  = 0.37) between groups. This finding was confirmed by further subgroup analyses and sensitivity analysis. In addition, SUP had no effect on overall mortality (RR 1.21; 95% CI, 0.94 to 1.56, p  = 0.14), Clostridium difficile infection (RR 0.89; 95% CI, 0.25 to 3.19, p  = 0.86), length of stay in the ICU (MD 0.04 days; 95% CI, −0.79 to 0.87, p  = 0.92), duration of mechanical ventilation (MD −0.38 days; 95% CI, −1.48 to 0.72, p  = 0.50), but was associated with an increased risk of hospital-acquired pneumonia (RR 1.53; 95% CI, 1.04 to 2.27; p  = 0.03). Conclusions Our results suggested that in patients receiving enteral feeding, pharmacologic SUP is not beneficial and combined interventions may even increase the risk of nosocomial pneumonia.

Extracellular ATP (eATP) signaling through the P2X7 receptor pathway is widely believed to trigger NLRP3 inflammasome assembly in microglia, potentially contributing to depression. However, the cellular stress responses of microglia to both eATP and stress itself remain largely unexplored. Mitochondria-associated membranes (MAMs) is a platform facilitating calcium transport between the endoplasmic reticulum (ER) and mitochondria, regulating ER stress responses and mitochondrial homeostasis. This study aims to investigate how MAMs influence microglial reaction and their involvement in the development of depression-like symptoms in response to chronic social defeat stress (CSDS). CSDS induced ER stress, MAMs’ modifications, mitochondrial damage, and the formation of the IP3R3-GRP75-VDAC1 complex at the ER-mitochondria interface in hippocampal microglia, all concomitant with depression-like behaviors. Additionally, exposing microglia to eATP to mimic CSDS conditions resulted in analogous outcomes. Furthermore, knocking down GRP75 in BV2 cells impeded ER-mitochondria contact, calcium transfer, ER stress, mitochondrial damage, mitochondrial superoxide production, and NLRP3 inflammasome aggregation induced by eATP. In addition, reduced GRP75 expression in microglia of Cx3cr1 CreER/+ Hspa9 f/+ mice lead to reduce depressive behaviors, decreased NLRP3 inflammasome aggregation, and fewer ER-mitochondria contacts in hippocampal microglia during CSDS. Here, we show the role of MAMs, particularly the formation of a tripartite complex involving IP3R3, GRP75, and VDAC1 within MAMs, in facilitating communication between the ER and mitochondria in microglia, thereby contributing to the development of depression-like phenotypes in male mice. Malfunctioning of cellular organelles, such as the endoplasmic reticulum (ER) and mitochondria, can have a role in stress-induced pathophysiological changes. Here, the authors show that increased mitochondria‐associated endoplasmic reticulum membranes contacts related to ATP-P2X7 receptor signaling contribute to stress responses in microglia and the development of depression-like behavior in male mice.