Three new species of Oocyclus Sharp, 1882, with additional records from China (Coleoptera, Hydrophilidae, Laccobiini).

Three new species of the water scavenger beetle genus Oocyclus Sharp, 1882 from China (Oocyclusextensus sp. nov., from Xizang, O.latiorificialis sp. nov. and O.ximaensis sp. nov. from Yunnan) are described and illustrated in detail. Additional faunistic data, illustrations of habitus and male genitalia, and a key to Chinese species are provided.

Role of mitochondria-associated membranes in the hippocampus in the pathogenesis of depression.

BACKGROUND: Pathological changes, such as microglia activation in the hippocampus frequently occur in individuals with animal models of depression; however, they may share a common cellular mechanism, such as endoplasmic reticulum (ER) stress and mitochondrial dysfunction. Mitochondria associated membranes (MAMs) are communication platforms between ER and mitochondria. This study aimed to investigate the role of intracellular stress responses, especially structural and functional changes of MAMs in depression. METHODS: We used chronic social defeat stress (CSDS) to mimic depression in C57 mice to investigate the pathophysiological changes in the hippocampus associated with depression and assess the antidepressant effect of electroacupuncture (EA). Molecular, histological, and electron microscopic techniques were utilized to study intracellular stress responses, including the ER stress pathway reaction, mitochondrial damage, and structural and functional changes in MAMs in the hippocampus after CSDS. Proteomics technology was employed to explore protein-level changes in MAMs caused by CSDS. RESULTS: CSDS caused mitochondrial dysfunction, ER stress, closer contact between ER and mitochondria, and enrichment of functional protein clusters at MAMs in hippocampus along with depressive-like behaviors. Also, EA showed beneficial effects on intracellular stress responses and depressive-like behaviors in CSDS mice. LIMITATION: The cellular specificity of MAMs related protein changes in CSDS mice was not explored. CONCLUSIONS: In the hippocampus, ER stress and mitochondrial damage occur, along with enriched mitochondria-ER interactions and MAM-related protein enrichment, which may contribute to depression's pathophysiology. EA may improve depression by regulating intracellular stress responses.

Augmented microglial endoplasmic reticulum-mitochondria contacts mediate depression-like behavior in mice induced by chronic social defeat stress.

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 Cx3cr1CreER/+Hspa9f/+ 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.

Natural products targeting autophagy and apoptosis in NSCLC: a novel therapeutic strategy.

Lung cancer is the leading cause of cancer-related mortality worldwide, with non-small cell lung cancer (NSCLC) being the predominant type. The roles of autophagy and apoptosis in NSCLC present a dual and intricate nature. Additionally, autophagy and apoptosis interconnect through diverse crosstalk molecules. Owing to their multitargeting nature, safety, and efficacy, natural products have emerged as principal sources for NSCLC therapeutic candidates. This review begins with an exploration of the mechanisms of autophagy and apoptosis, proceeds to examine the crosstalk molecules between these processes, and outlines their implications and interactions in NSCLC. Finally, the paper reviews natural products that have been intensively studied against NSCLC targeting autophagy and apoptosis, and summarizes in detail the four most retrieved representative drugs. This paper clarifies good therapeutic effects of natural products in NSCLC by targeting autophagy and apoptosis and aims to promote greater consideration by researchers of natural products as candidates for anti-NSCLC drug discovery.

Bullatine A has an antidepressant effect in chronic social defeat stress mice; Implication of microglial inflammasome.

Inflammatory microglia and P2X7R are involved in the development of stress-induced depression. Endoplasmic reticulum (ER) stress and mitochondrial damage play an important role in depression and microglial activation. Bullatine A (BLA) has anti-inflammatory and anti-rheumatic effects, and can be used as a P2X7R antagonist. We found that Bullatine A can effectively inhibit the calcium overload of mitochondria and the increase of ER and mitochondrial colocalization caused by eATP (extracellular ATP) in BV2-cells. Bullatine A can also inhibit the activation of PERK-elF-2α unfolded protein response (UPR), lysosome production and the increase of NLRP3 inflammasome protein expression in BV2-cells Both intragastric administration and intra-hippocampal microinjection of Bullatine A can significantly improve the despair behavior but not anhedonia of Chronic chronic social defeat stress (CSDS) mice. Bullatine A may have a beneficial therapeutic effect in treating diseases related to stress stimulation, such as depression.

[Protective effect of ophiopogonin D against isoproterenol-induced cardiomyocyte injury and targets].

This study aims to unveil the effect of ophiopogonin D(OPD) on isoproterenol(ISO)-induced apoptosis of rat cardiomyocytes and the possible targets, which is expected to provide clues for further research on the myocardial protection of ophiopogonins. Cell count kit-8(CCK-8) assay was used to detect viability of cells treated with OPD and ISO, Western blot to examine the effect of OPD and ISO on the expression of endoplasmic reticulum stress-related Bip, Bax, Perk, ATF4, caspase-12, and CHOP, flow cytometry to determine cell apoptosis rate, and Hoechst 33258 and Tunel staining to observe cell apoptosis and morphological changes. In addition, the probe for calcium ion-specific detection was employed to investigate calcium ion release from the endoplasmic reticulum, and OPD-bond epoxy-activated agarose solid-phase microspheres were prepared and used as affinity matrix to capture OPD-binding target proteins in H9 c2 cell lysate. For the target proteins of OPD identified by high-resolution mass spectrometry, the related signal pathways were enriched and the potential targets of OPD against cardiomyocyte injury were discussed. The experimental result showed that 10 µmol·L~(-1) ISO can significantly induce the expression of endoplasmic reticulum stress-related proteins and promote cell apoptosis. Different concentration of OPD can prevent the damage of myocardial cells caused by ISO. According to mass spectrometry results, 19 proteins, including Fam129 a and Pdia6, were involved in multiple signaling pathways such as the unfolded protein reaction bound by the ERN1 sensor, tricarboxylic acid cycle, and Nrf2 signal transduction pathway. The above results indicate that OPD protects cardiomyocytes by regulating multiple signaling pathways of target proteins and affecting cell cycle progression.

Ultrasensitive detection of UO2 2+ based on dopamine-functionalized MoOx quantum dots.

Uranium is an important nuclear fuel and the risk of human exposure to uranium increases as increasing amounts of uranium-containing waste enter the environment due to the rapid growth of nuclear power. Therefore, rapid, sensitive, and portable uranium detection is a promising approach to effectively control and monitor uranium contamination. To achieve this goal, abundant oxygen- and nitrogen-containing groups were introduced to molybdenum oxide quantum dot (MoOx QDs) surfaces with dopamine (DA) modification. Due to the excellent coordination ability of oxygen- and nitrogen-containing groups with uranium, the obtained DA-functionalized MoOx QDs (DA-MoOx QDs) showed a strong binding affinity for uranium and sensitivity was increased nearly 1000-fold compared with MoOx QDs alone. The limit of detection was 3.85 nM, which is higher than most of the reported nanomaterials. Moreover, the DA-MoOx QD-based method showed high selectivity and uranium could be clearly detected under masking with ethylenediaminetetraacetic acid even when the concentration of other metal ions was 100-fold higher than that of uranium, showing a very promising method for uranium contamination control and monitoring.

Chromatin accessibility analysis identifies the transcription factor ETV5 as a suppressor of adipose tissue macrophage activation in obesity.

Activation of adipose tissue macrophages (ATMs) contributes to chronic inflammation and insulin resistance in obesity. However, the transcriptional regulatory machinery involved in ATM activation during the development of obesity is not fully understood. Here, we profiled the chromatin accessibility of blood monocytes and ATMs from obese and lean mice using assay for transposase-accessible chromatin sequencing (ATAC-seq). We found that monocytes and ATMs from obese and lean mice exhibited distinct chromatin accessibility status. There are distinct regulatory elements that are specifically associated with monocyte or ATM activation in obesity. We also discovered several transcription factors that may regulate monocyte and ATM activation in obese mice, specifically a predicted transcription factor named ETS translocation variant 5 (ETV5). The expression of ETV5 was significantly decreased in ATMs from obese mice and its downregulation was mediated by palmitate stimulation. The decrease in ETV5 expression resulted in macrophage activation. Our results also indicate that ETV5 suppresses endoplasmic reticulum (ER) stress and Il6 expression in macrophages. Our work delineates the changes in chromatin accessibility in monocytes and ATMs during obesity, and identifies ETV5 as a critical transcription factor suppressing ATM activation, suggesting its potential use as a therapeutic target in obesity-related chronic inflammation.

Nanoparticle-delivered siRNA targeting Bruton's tyrosine kinase for rheumatoid arthritis therapy.

Rheumatoid arthritis (RA) is a systemic autoimmune disease that can cause irreversible joint deformity. There is still no cure for RA, and current therapeutics, including methotrexate and adalimumab, cause serious off-target effects and systemic immunosuppression, which in turn increases the risk of infection. Bruton's tyrosine kinase (BTK) in macrophages and B cells has been demonstrated to be a promising therapeutic target for RA. However, high doses of BTK inhibitors are required for efficient BTK suppression, which limits their clinical use. Small interfering RNA (siRNA) is promising for the silencing of specific genes and has been used for the treatment of multiple diseases. To deliver siRNA into macrophages and B cells for BTK gene silencing, we employed cationic lipid-assisted PEG-b-PLGA nanoparticles (CLANs) to encapsulate siRNA. We demonstrated that macrophages and B cells were able to efficiently ingest the CLANs both in vitro and in vivo. Thereafter, we encapsulated siRNA targeting BTK (siBTK) into the CLANs, denoted as CLANsiBTK, and demonstrated that CLANsiBTK significantly inhibited BTK expression in macrophages and B cells. In a collagen-induced mouse arthritis model, CLANsiBTK treatment dramatically reduced joint inflammation and other RA symptoms but showed no toxicity, proving that using CLANsiBTK is a promising approach for RA therapy.

Overcoming tumor resistance to cisplatin by cationic lipid-assisted prodrug nanoparticles.

Chemotherapy resistance has become a major challenge in the clinical treatment of lung cancer which is the leading cancer type for the estimated deaths. Recent studies have shown that nanoparticles as drug carriers can raise intracellular drug concentration by achieving effectively cellular uptake and rapid drug release, and therefore reverse the acquired chemoresistance of tumors. In this context, nanoparticles-based chemotherapy represents a promising strategy for treating malignancies with chemoresistance. In the present study, we developed cationic lipid assisted nanoparticles (CLAN) to deliver polylactide-cisplatin prodrugs to drug resistant lung cancer cells. The nanoparticles were formulated through self-assembly of a biodegradable poly(ethylene glycol)-block-poly(lactide) (PEG-PLA), a hydrophobic polylactide-cisplatin prodrug, and a cationic lipid. The cationic nanoparticles were proven to significantly improve cell uptake of cisplatin, leading to an increased DNA-Pt adduct and significantly promoted DNA damage in vitro. Moreover, our study reveals that cationic nanoparticles, although are slightly inferior in blood circulation and tumor accumulation, are more effective in blood vessel extravasation. The CLANs ultimately enhances the cellular drug availability and leads to the reversal of cisplatin resistance.

Promoting tumor penetration of nanoparticles for cancer stem cell therapy by TGF-ß signaling pathway inhibition.

Cancer stem cells (CSCs), which hold a high capacity for self-renewal, play a central role in the development, metastasis, and recurrence of various malignancies. CSCs must be eradicated to cure instances of cancer; however, because they can reside far from tumor vessels, they are not easily targeted by drug agents carried by nanoparticle-based drug delivery systems. We herein demonstrate that promoting tumor penetration of nanoparticles by transforming growth factor ß (TGF-ß) signaling pathway inhibition facilitates CSC therapy. In our study, we observed that although nanoparticles carrying siRNA targeting the oncogene polo-like kinase 1 (Plk1) efficiently killed breast CSCs derived from MDA-MB-231 cells in vitro, this intervention enriched CSCs in the residual tumor tissue following systemic treatment. However, inhibition of the TGF-ß signaling pathway with LY364947, an inhibitor of TGF-ß type I receptor, promoted the penetration of nanoparticles in tumor tissue, significantly ameliorating the intratumoral distribution of nanoparticles in MDA-MB-231 xenografts and further leading to enhanced internalization of nanoparticles by CSCs. As a result, synergistic treatment with a nanoparticle drug delivery system and LY364947 inhibited tumor growth and reduced the proportion of CSCs in vivo. This study suggests that enhanced tumor penetration of drug-carrying nanoparticles can enhance CSCs clearance in vivo and consequently provide superior anti-tumor effects.