Unlocking the NIR-II AIEgen for High Brightness through Intramolecular Electrostatic Locking.

Fluorescent imaging and biosensing in the near-infrared-II (NIR-II) window holds great promise for non-invasive, radiation-free, and rapid-response clinical diagnosis. However, it's still challenging to develop bright NIR-II fluorophores. In this study, we report a new strategy to enhance the brightness of NIR-II aggregation-induced emission (AIE) fluorophores through intramolecular electrostatic locking. By introducing sulfur atoms into the side chains of the thiophene bridge in TSEH molecule, the molecular motion of the conjugated backbone can be locked through intramolecular interactions between the sulfur and nitrogen atoms. This leads to enhanced NIR-II fluorescent emission of TSEH in both solution and aggregation states. Notably, the encapsulated nanoparticles (NPs) of TSEH show enhanced brightness, which is 2.6-fold higher than TEH NPs with alkyl side chains. The in vivo experiments reveal the feasibility of TSEH NPs in vascular and tumor imaging with a high signal-to-background ratio and precise resection for tiny tumors. In addition, polystyrene nanospheres encapsulated with TSEH are utilized for antigen detection in lateral flow assays, showing a signal-to-noise ratio 1.9-fold higher than the TEH counterpart in detecting low-concentration antigens. This work highlights the potential for developing bright NIR-II fluorophores through intramolecular electrostatic locking and their potential applications in clinical diagnosis and biomedical research.

Exploring the interplay between triple-negative breast cancer stem cells and tumor microenvironment for effective therapeutic strategies.

Triple-negative breast cancer (TNBC) is a highly aggressive and metastatic malignancy with poor treatment outcomes. The interaction between the tumor microenvironment (TME) and breast cancer stem cells (BCSCs) plays an important role in the development of TNBC. Owing to their ability of self-renewal and multidirectional differentiation, BCSCs maintain tumor growth, drive metastatic colonization, and facilitate the development of drug resistance. TME is the main factor regulating the phenotype and metastasis of BCSCs. Immune cells, cancer-related fibroblasts (CAFs), cytokines, mesenchymal cells, endothelial cells, and extracellular matrix within the TME form a complex communication network, exert highly selective pressure on the tumor, and provide a conducive environment for the formation of BCSC niches. Tumor growth and metastasis can be controlled by targeting the TME to eliminate BCSC niches or targeting BCSCs to modify the TME. These approaches may improve the treatment outcomes and possess great application potential in clinical settings. In this review, we summarized the relationship between BCSCs and the progression and drug resistance of TNBC, especially focusing on the interaction between BCSCs and TME. In addition, we discussed therapeutic strategies that target the TME to inhibit or eliminate BCSCs, providing valuable insights into the clinical treatment of TNBC.

Habitat selection drives diatom community assembly and network complexity in sediment-laden riverine environments.

Microbial communities assemble stochastically and deterministically, but how different assembly processes shape diatom community structure across riverine habitats is unclear, especially in sediment-laden environments. In this study, we deciphered the mechanisms of riverine diatom community assembly in the water column and riverbed substrate with varying sediment concentrations. Water and sediment samples were collected from 44 sampling sites along the Yellow River mainstream during two seasons. Diatom communities were characterized based on high-throughput sequencing of the 18S ribosomal RNA genes coupled with multivariate statistical analyses. A total of 198 diatom species were taxonomically assigned, including 182 free-living and particle-attached species and 184 surface-sediment species. Planktonic communities were structurally different from benthic communities, with Cyclotella being dominant mainly in the middle and lower reaches of the river with higher sediment concentrations. Both stochastic and deterministic processes affected diatom community assembly in different habitats. Species dispersal was more important in the water than in the substrate, and this process was strengthened by increased sediment concentration across habitats. Diatom communities exhibited lower network complexity and enhanced antagonistic or competitive interactions between species in response to higher sediment concentrations compared with lower sediment concentrations mainly in the source region of the river. Differences in the species composition and community diversity of planktonic diatoms were closely correlated with the proportion of bare land area, nitrogen nutrients, precipitation, and sediment concentration. In particular, particle-attached diatoms responded sensitively to environmental factors. These findings provide strong evidence for sediment-mediated assembly and interactions of riverine diatom communities.

Emodin improves renal fibrosis in chronic kidney disease by regulating mitochondrial homeostasis through the mediation of peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC-1α).

Chronic kidney disease (CKD) is a leading public health issue associated with high morbidity worldwide. However, there are only a few effective therapeutic strategies for CKD. Emodin, an anthraquinone compound from rhubarb, can inhibit fibrosis in tissues and cells. Our study aims to investigate the antifibrotic effect of emodin and the underlying molecular mechanism. A unilateral ureteral obstruction (UUO)-induced rat model was established to evaluate the effect of emodin on renal fibrosis development. Hematoxylin and eosin staining, Masson's trichrome staining, and immunohistochemistry staining were performed to analyze histopathological changes and fibrotic features after emodin treatment. Subsequently, a transforming growth factor-beta 1 (TGF-ß1)-induced cell model was used to assess the inhibition of emodin on cell fibrosis in vitro. Furthermore, Western blot analysis and real-time quantitative reverse transcription-polymerase chain reaction were performed to validate the regulatory mechanism of emodin on renal fibrosis progression. As a result, emodin significantly improved histopathological abnormalities in rats with UUO. The expression of fibrosis biomarkers and mitochondrial biogenesis-related proteins also decreased after emodin treatment. Moreover, emodin blocked TGF-ß1-induced fibrotic phenotype, lipid accumulation, and mitochondrial homeostasis in NRK-52E cells. Conversely, peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC-1α) silencing significantly reversed these features in emodin-treated cells. Collectively, emodin plays an important role in regulating PGC-1α-mediated mitochondria function and energy homeostasis. This indicates that emodin exhibits great inhibition against renal fibrosis and acts as a promising inhibitor of CKD.

Nkx1.2 deletion decreases fat production in zebrafish.

OBJECTIVE: This study aimed to investigate the role of Nkx1-2, a transcription factor with the NK homeobox domain, in the regulation of fat production. METHODS: Gene expression was analyzed using quantitative real-time polymerase chain reaction or transcriptome sequencing. CRISPR/Cas9 technology was employed to generate nkx1.2 knockout zebrafish and nkx1.2-deleted 3T3-L1 cells. Lipid droplet production in zebrafish larvae was visually quantified using Nile red staining, whereas lipid droplets in 3T3-L1 cells were stained with Oil red O. The binding of Nkx1-2 to the promoter was verified through an electrophoretic mobility shift assay experiment. RESULTS: Nkx1-2 plays crucial roles in the regulation of fat production in zebrafish. Knockout of nkx1.2 in zebrafish leads to weight loss, accompanied by significantly reduced lipid droplet production and decreased visceral and liver fat content. Furthermore, genes related to lipid biosynthesis are significantly downregulated. In 3T3-L1 preadipocytes, Nkx1-2 induces differentiation into mature adipocytes by binding to the cebpa promoter, thereby activating its transcription. Additionally, the expression of nkx1.2 is regulated by the p38 MAPK, JNK, or Smad2/3 signaling pathways in 3T3-L1 cells. CONCLUSIONS: Our findings suggest that Nkx1-2 functions as a positive regulator of fat production, playing a critical role in adipocyte differentiation and lipid biosynthesis.

The MdMYB44-MdTPR1 repressive complex inhibits MdCCD4 and MdCYP97A3 expression through histone deacetylation to regulate carotenoid biosynthesis in apple.

Carotenoids are photosynthetic pigments and antioxidants that contribute to different plant colors. However, the involvement of TOPLESS (TPL/TPR)-mediated histone deacetylation in the modulation of carotenoid biosynthesis through ethylene-responsive element-binding factor-associated amphiphilic repression (EAR)-containing transcription factors (TFs) in apple (Malus domestica Borkh.) is poorly understood. MdMYB44 is a transcriptional repressor that contains an EAR repression motif. In the present study, we used functional analyses and molecular assays to elucidate the molecular mechanisms through which MdMYB44-MdTPR1-mediated histone deacetylation influences carotenoid biosynthesis in apples. We identified two carotenoid biosynthetic genes, MdCCD4 and MdCYP97A3, that were confirmed to be involved in MdMYB44-mediated carotenoid biosynthesis. MdMYB44 enhanced ß-branch carotenoid biosynthesis by repressing MdCCD4 expression, whereas MdMYB44 suppressed lutein level by repressing MdCYP97A3 expression. Moreover, MdMYB44 partially influences carotenoid biosynthesis by interacting with the co-repressor TPR1 through the EAR motif to inhibit MdCCD4 and MdCYP97A3 expression via histone deacetylation. Our findings indicate that the MdTPR1-MdMYB44 repressive cascade regulates carotenoid biosynthesis, providing profound insights into the molecular basis of histone deacetylation-mediated carotenoid biosynthesis in plants. These results also provide evidence that the EAR-harboring TF/TPL repressive complex plays a universal role in histone deacetylation-mediated inhibition of gene expression in various plants.

[Effects of tetramethylpyrazine on pharmacokinetics in plasma and brain dialysate and neuropathic pain in rat model of spared sciatic nerve injury].

This study aims to explore the effects of tetramethylpyrazine(TMP) on pharmacokinetics in plasma and brain dialysate and neuropathic pain in the rat model of partial sciatic nerve injury(SNI), and to investigate the correlation between the analgesic effect of TMP and its concentrations in the plasma and brain dialysate. Male SD rats were randomized into Sham, SNI, and SNI+TMP groups. Mechanical stimulation with von frey filaments and cold spray method were employed to evaluate the mechanical sensitivity and cold sensitivity of rats. Another two groups, Sham+TMP and SNI+TMP, were used to intubate the common jugular vein and implant microdialysis probes into the anterior cingulate gyrus(ACC), respectively.After intraperitoneal injection of TMP at a dose of 80 mg·kg~(-1), automatic blood collection and intracerebral microdialysis(perfusion rate of 1 µL·min~(-1)) systems were used to collect the blood and brain dialysate for 24 h. HSS T3 C_(18) reversed-phase chromatographic column(2.1 mm×50 mm, 2.5 µm) was used for liquid chromatographic separation. Gradient elution was carried out with the mobile phase of methanol-water(containing 0.005% formic acid) at a flow rate of 0.25 mL·min~(-1). Electrospray ion source was used for mass spectrometry, and the scanning mode was multi-reaction monitoring under the positive ion mode. The ion pairs for quantitative analysis were TMP m/z 137/122 and aspirin m/z 179/137, respectively. DAS 2.11 was used to calculate the pharmacokinetic parameters. The optimal time of TMP to exert the analgesia effect and inhibit cold pain sensitivity was 60 min after treatment. The TMP in the plasma and brain dialysate of SNI rats showed the T_(max) of 15 min and 30 min, the C_(max) of(2 866.43±135.39) and(1 462.14±197.38) µg·L~(-1), the AUC_(0-t) of(241 463.30±28 070.31) and(213 115.62±32 570.07) µg·min·L~(-1), the MRT_(0-t) of(353.13±47.73) and(172.16±12.72) min, and the CL_Z of 0.73 and 0.36 L·min·kg~(-1), respectively. The analgesic effect of TMP had a significant correlation with the blood drug concentration in the ACC, which indicated that this method was suitable for the detection of TMP in rat plasma and brain dialysate. The method is accurate, reliable, and sensitive and can realize the important value of the application of correlation analysis theory of "automatic blood collection-microdialysis/PK-PD" in the research on neuropathic pain.

Integrating bulk and single-cell sequencing data to construct a Scissor+ dendritic cells prognostic model for predicting prognosis and immune responses in ESCC.

Esophageal squamous cell carcinoma (ESCC) is characterized by molecular heterogeneity with various immune cell infiltration patterns, which have been associated with therapeutic sensitivity and resistance. In particular, dendritic cells (DCs) are recently discovered to be associated with prognosis and survival in cancer. However, how DCs differ among ESCC patients has not been fully comprehended. Recently, the advance of single-cell RNA sequencing (scRNA-seq) enables us to profile the cell types, states, and lineages in the heterogeneous ESCC tissues. Here, we dissect the ESCC tumor microenvironment at high resolution by integrating 192,078 single cells from 60 patients, including 4379 DCs. We then used Scissor, a method that identifies cell subpopulations from single-cell data that are associated bulk samples with genomic and clinical information, to stratify DCs into Scissorhi and Scissorlow subtypes. We applied the Scissorhi gene signature to stratify ESCC scRNAseq patient, and we found that PD-L1, TIGIT, PVR and IL6 ligand-receptor-mediated cell interactions existed mainly in Scissorhi patients. Finally, based on the Scissor results, we successfully developed a validated prognostic risk model for ESCC and further validated the reliability of the risk prediction model by recruiting 40 ESCC clinical patients. This information highlights the importance of these genes in assessing patient prognosis and may help in the development of targeted or personalized therapies for ESCC.

Donor-Acceptor Modulating of Ionic AIE Photosensitizers for Enhanced ROS Generation and NIR-II Emission.

Photosensitizers (PSs) with aggregation-induced emission (AIE) characteristics are competitive candidates for bioimaging and therapeutic applications. However, their short emission wavelength and nonspecific organelle targeting hinder their therapeutic effectiveness. Herein, a donor-acceptor modulation approach is reported to construct a series of ionic AIE photosensitizers with enhanced photodynamic therapy (PDT) outcomes and fluorescent emission in the second near-infrared (NIR-II) window. By employing dithieno[3,2-b:2',3'-d]pyrrole (DTP) and indolium (In) as the strong donor and acceptor, respectively, the compound DTP-In exhibits a substantial redshift in absorption and fluorescent emission reach to NIR-II region. The reduced energy gap between singlet and triplet states in DTP-In also increases the reactive oxygen species (ROS) generation rate. Further, DTP-In can self-assemble in aqueous solutions, forming positively charged nanoaggregates, which are superior to conventional encapsulated nanoparticles in cellular uptake and mitochondrial targeting. Consequently, DTP-In aggregates show efficient photodynamic ablation of 4T1 cancer cells and outstanding tumor theranostic in vivo under 660 nm laser irradiation. This work highlights the potential of molecular engineering of donor-acceptor AIE PSs with multiple functionalities, thereby facilitating the development of more effective strategies for cancer therapy.

Inflammation and Acinar Cell Dual-Targeting Nanomedicines for Synergistic Treatment of Acute Pancreatitis via Ca2+ Homeostasis Regulation and Pancreas Autodigestion Inhibition.

Severe acute pancreatitis (AP) is a life-threatening pancreatic inflammatory disease with a high mortality rate (∼40%). Existing pharmaceutical therapies in development or in clinical trials showed insufficient treatment efficacy due to their single molecular therapeutic target, poor water solubility, short half-life, limited pancreas-targeting specificity, etc. Herein, acid-responsive hollow mesoporous Prussian blue nanoparticles wrapped with neutrophil membranes and surface modified with the N,N-dimethyl-1,3-propanediamine moiety were developed for codelivering membrane-permeable calcium chelator BAPTA-AM (BA) and trypsin activity inhibitor gabexate mesylate (Ga). In the AP mouse model, the formulation exhibited efficient recruitment at the inflammatory endothelium, trans-endothelial migration, and precise acinar cell targeting, resulting in rapid pancreatic localization and higher accumulation. A single low dose of the formulation (BA: 200 µg kg-1, Ga: 0.75 mg kg-1) significantly reduced pancreas function indicators to close to normal levels at 24 h, effectively restored the cell redox status, reduced apoptotic cell proportion, and blocked the systemic inflammatory amplified cascade, resulting in a dramatic increase in the survival rate from 58.3 to even 100%. Mechanistically, the formulation inhibited endoplasmic reticulum stress (IRE1/XBP1 and ATF4/CHOP axis) and restored impaired autophagy (Beclin-1/p62/LC3 axis), thereby preserving dying acinar cells and restoring the cellular "health status". This formulation provides an upstream therapeutic strategy with clinical translation prospects for AP management through synergistic ion homeostasis regulation and pancreatic autodigestion inhibition.

Microglial phagolysosome dysfunction and altered neural communication amplify phenotypic severity in Prader-Willi Syndrome with larger deletion.

Prader-Willi Syndrome (PWS) is a rare neurodevelopmental disorder of genetic etiology, characterized by paternal deletion of genes located at chromosome 15 in 70% of cases. Two distinct genetic subtypes of PWS deletions are characterized, where type I (PWS T1) carries four extra haploinsufficient genes compared to type II (PWS T2). PWS T1 individuals display more pronounced physiological and cognitive abnormalities than PWS T2, yet the exact neuropathological mechanisms behind these differences remain unclear. Our study employed postmortem hypothalamic tissues from PWS T1 and T2 individuals, conducting transcriptomic analyses and cell-specific protein profiling in white matter, neurons, and glial cells to unravel the cellular and molecular basis of phenotypic severity in PWS sub-genotypes. In PWS T1, key pathways for cell structure, integrity, and neuronal communication are notably diminished, while glymphatic system activity is heightened compared to PWS T2. The microglial defect in PWS T1 appears to stem from gene haploinsufficiency, as global and myeloid-specific Cyfip1 haploinsufficiency in murine models demonstrated. Our findings emphasize microglial phagolysosome dysfunction and altered neural communication as crucial contributors to the severity of PWS T1's phenotype.

IL-6 Enhances the Activation of PI3K-AKT/mTOR-GSK-3ß by Upregulating GRPR in Hippocampal Neurons of Autistic Mice.

Autism spectrum disorder (ASD) is a neurological disorder associated with brain inflammation. The underlying mechanisms could be attributed to the activation of PI3K signaling in the inflamed brain of ASD. Multiple studies highlight the role of GRPR in regulating ASD like abnormal behavior and enhancing the PI3K signaling. However, the molecular mechanism by which GRPR regulates PI3K signaling in neurons of individuals with ASD is still unclear. In this study, we utilized a maternal immune activation model to investigate the effects of GRPR on PI3K signaling in the inflamed brain of ASD mice. We used HT22 cells with and without GRPR to examine the impact of GRP-GRPR on the PI3K-AKT pathway with IL-6 treatment. We analyzed a dataset of hippocampus samples from ASD mice to identify hub genes. Our results demonstrated increased expression of IL-6, GRPR, and PI3K-AKT signaling in the hippocampus of ASD mice. Additionally, we observed increased GRPR expression and PI3K-AKT/mTOR activation in HT22 cells after IL-6 treatment, but decreased expression in HT22 cells with GRPR knockdown. NetworkAnalyst identified GSK-3ß as the most crucial gene in the PI3K-AKT/mTOR pathway in the hippocampus of ASD. Furthermore, we found that IL-6 upregulated the expression of GSK-3ß in HT22 cells by upregulating GRP-GRPR. Our findings suggest that IL-6 can enhance the activation of PI3K-AKT/mTOR-GSK-3ß in hippocampal neurons of ASD mice by upregulating GRPR.

Discovery of Trisubstituted N-Phenylpyrazole Containing Diamides with Improved Insecticidal Activity.

To increase the structural diversity of insecticides and meet the needs of effective integrated insect management, the structure of chlorantraniliprole was modified based on a previously established three-dimensional quantitative structure-activity relationship (3D-QSAR) model. The pyridinyl moiety in the structure of chlorantraniliprole was replaced with a 4-fluorophenyl group. Further modifications of this 4-fluorophenyl group by introducing a halogen atom at position 2 and an electron-withdrawing group (e.g., iodine, cyano, and trifluoromethyl) at position 5 led to 34 compounds with good insecticidal efficacy against Mythimna separata, Plutella xylostella, and Spodoptera frugiperda. Among them, compound IV f against M. separata showed potency comparable to that of chlorantraniliprole. IV p against P. xylostella displayed a 4.5 times higher potency than chlorantraniliprole. In addition, IV d and chlorantraniliprole exhibited comparable potencies against S. frugiperda. Transcriptome analysis showed that the molecular target of compound IV f is the ryanodine receptor. Molecular docking was further performed to verify the mode of action and insecticidal activity against resistant P. xylostella.

Abscisic acid activates transcription factor module MdABI5-MdMYBS1 during carotenoid-derived apple fruit coloration.

Carotenoids are major pigments contributing to fruit coloration. We previously reported that the apple (Malus domestica Borkh.) mutant fruits of 'Beni Shogun' and 'Yanfu 3' show a marked difference in fruit coloration. However, the regulatory mechanism underlying this phenomenon remains unclear. In this study, we determined that carotenoid is the main factor influencing fruit flesh color. We identified an R1-type MYB transcription factor, MdMYBS1, which was found to be highly associated with carotenoids and abscisic acid (ABA) contents of apple fruits. Overexpression of MdMYBS1 promoted, and silencing of MdMYBS1 repressed, ß-branch carotenoids synthesis and ABA accumulation. MdMYBS1 regulates carotenoid biosynthesis by directly activating the major carotenoid biosynthetic genes encoding phytoene synthase (MdPSY2-1) and lycopene ß-cyclase (MdLCYb). 9-cis-epoxycarotenoid dioxygenase 1 (MdNCED1) contributes to ABA biosynthesis, and MdMYBS1 enhances endogenous ABA accumulation by activating the MdNCED1 promoter. In addition, the basic leucine zipper domain transcription factor ABSCISIC ACID-INSENSITIVE5 (MdABI5) was identified as an upstream activator of MdMYBS1, which promotes carotenoid and ABA accumulation. Furthermore, ABA promotes carotenoid biosynthesis and enhances MdMYBS1 and MdABI5 promoter activities. Our findings demonstrate that the MdABI5-MdMYBS1 cascade activated by ABA regulates carotenoid-derived fruit coloration and ABA accumulation in apple, providing avenues in breeding and planting for improvement of fruit coloration and quality.

Deep sequencing of proteotoxicity modifier genes uncovers a Presenilin-2/beta-amyloid-actin genetic risk module shared among alpha-synucleinopathies.

Whether neurodegenerative diseases linked to misfolding of the same protein share genetic risk drivers or whether different protein-aggregation pathologies in neurodegeneration are mechanistically related remains uncertain. Conventional genetic analyses are underpowered to address these questions. Through careful selection of patients based on protein aggregation phenotype (rather than clinical diagnosis) we can increase statistical power to detect associated variants in a targeted set of genes that modify proteotoxicities. Genetic modifiers of alpha-synuclein (ɑS) and beta-amyloid (Aß) cytotoxicity in yeast are enriched in risk factors for Parkinson's disease (PD) and Alzheimer's disease (AD), respectively. Here, along with known AD/PD risk genes, we deeply sequenced exomes of 430 ɑS/Aß modifier genes in patients across alpha-synucleinopathies (PD, Lewy body dementia and multiple system atrophy). Beyond known PD genes GBA1 and LRRK2, rare variants AD genes (CD33, CR1 and PSEN2) and Aß toxicity modifiers involved in RhoA/actin cytoskeleton regulation (ARGHEF1, ARHGEF28, MICAL3, PASK, PKN2, PSEN2) were shared risk factors across synucleinopathies. Actin pathology occurred in iPSC synucleinopathy models and RhoA downregulation exacerbated ɑS pathology. Even in sporadic PD, the expression of these genes was altered across CNS cell types. Genome-wide CRISPR screens revealed the essentiality of PSEN2 in both human cortical and dopaminergic neurons, and PSEN2 mutation carriers exhibited diffuse brainstem and cortical synucleinopathy independent of AD pathology. PSEN2 contributes to a common-risk signal in PD GWAS and regulates ɑS expression in neurons. Our results identify convergent mechanisms across synucleinopathies, some shared with AD.

Curcumol Attenuates Portal Hypertension and Collateral Shunting Via Inhibition of Extrahepatic Angiogenesis in Cirrhotic Rats.

Liver cirrhosis can cause disturbances in blood circulation in the liver, resulting in impaired portal blood flow and ultimately increasing portal venous pressure. Portal hypertension induces portal-systemic collateral formation and fatal complications. Extrahepatic angiogenesis plays a crucial role in the development of portal hypertension. Curcumol is a sesquiterpenoid derived from the rhizome of Curcumae Rhizoma and has been confirmed to alleviate liver fibrosis by inhibiting angiogenesis. Therefore, our study was designed to explore the effects of curcumol on extrahepatic angiogenesis and portal hypertension. To induce cirrhosis, Sprague Dawley rats underwent bile duct ligation (BDL) surgery. Rats received oral administration with curcumol (30 mg/kg/d) or vehicle (distilled water) starting on day 15 following surgery, when BDL-induced liver fibrosis had developed. The effect of curcumol was assessed on day 28, which is the typical time of BDL-induced cirrhosis. The results showed that curcumol markedly reduced portal pressure in cirrhotic rats. Curcumol inhibited abnormal splanchnic inflow, mitigated liver injury, improved liver fibrosis, and attenuated portal-systemic collateral shunting in cirrhotic rats. These protective effects were partially attributed to the inhibition on mesenteric angiogenesis by curcumol. Mechanically, curcumol partially reversed the BDL-induced activation of the JAK2/STAT3 signaling pathway in cirrhotic rats. Collectively, curcumol attenuates portal hypertension in liver cirrhosis by suppressing extrahepatic angiogenesis through inhibiting the JAK2/STAT3 signaling pathway.

Association between obstructive sleep apnea and low bone mass in adults: a systematic review and meta-analysis.

Introduction: This study aimed to synthesize existing evidence on the potential association between obstructive sleep apnea (OSA) and low bone mass in adults. Methods: Electronic searches of four main databases were performed. The inclusion criteria consisted of observational studies investigating the relationship between OSA and bone mass, osteoporosis, fractures, or bone metabolism markers in adult population. Bone mineral density (BMD) and T score of lumbar and femur neck, incidence of osteoporosis and fractures, bone metabolism marker levels were extracted as primary outcomes. Results: Among the 693 relevant publications, 10 studies consisting of 158,427 participants met with the inclusion and exclusion criteria. Meta-analysis showed a significant lower BMD of lumbar (mean difference (MD) = - 0.03; 95% CI - 0.05, - 0.01; I2 = 46%), femur neck (MD = - 0.06; 95% CI - 0.12, 0.00; I2 = 71%), and a significant lower T score of lumbar (MD = - 0.42; 95% CI - 0.79, - 0.05; I2 = 63%) in the OSA group. The results suggested that both male (odds ratio (OR) = 2.03; 95% CI 1.23, 3.35; I2 = 38%) and female (OR = 2.56; 95% CI 1.96, 3.34; I2 = 0%) had higher risk of osteoporosis in the OSA group. Besides, meta-analysis also showed that bone-specific alkaline phosphatase was significantly lower in OSA patients (MD = - 1.90; 95% CI - 3.48, - 0.32; I2 = 48%). Conclusions: A potential association between OSA and lower bone mass in adults is preliminarily proved. It also seems plausible that both male and female with OSA have a higher risk of osteoporosis. Supplementary Information: The online version contains supplementary material available at 10.1007/s41105-023-00481-1.

Age-, sex- and proximal-distal-resolved multi-omics identifies regulators of intestinal aging in non-human primates.

The incidence of intestinal diseases increases with age, yet the mechanisms governing gut aging and its link to diseases, such as colorectal cancer (CRC), remain elusive. In this study, while considering age, sex and proximal-distal variations, we used a multi-omics approach in non-human primates (Macaca fascicularis) to shed light on the heterogeneity of intestinal aging and identify potential regulators of gut aging. We explored the roles of several regulators, including those from tryptophan metabolism, in intestinal function and lifespan in Caenorhabditis elegans. Suggesting conservation of region specificity, tryptophan metabolism via the kynurenine and serotonin (5-HT) pathways varied between the proximal and distal colon, and, using a mouse colitis model, we observed that distal colitis was more sensitive to 5-HT treatment. Additionally, using proteomics analysis of human CRC samples, we identified links between gut aging and CRC, with high HPX levels predicting poor prognosis in older patients with CRC. Together, this work provides potential targets for preventing gut aging and associated diseases.

Pulmonary salivary gland tumor-hyalinizing clear cell carcinoma: a literature review.

Primary pulmonary hyalinizing clear cell carcinoma (HCCC) is a very rare lung tumor that accounts for less than 0.09% of all primary lung tumors and has no specific epidemiology. The correct diagnosis requires imaging, laboratory, pathological, immunohistochemical, and molecular examination. The most typical feature of pulmonary HCCC is the clear cell component with clear stroma. In addition, the fusion gene EWSR1::ATF1 due to t(12;22)(q13;q12) is essential for the pathological diagnosis of pulmonary HCCC. The main treatment for pulmonary HCCC is surgery. This review focus on the pathological features, immunohistochemical examination, mutation analysis and treatment of pulmonary HCCC.

Differential effects of specific emotions on spatial decision-making: evidence from cross-frequency functionally independent brain networks.

Emotions significantly shape the way humans make decisions. However, the underlying neural mechanisms of this influence remain elusive. In this study, we designed an experiment to investigate how emotions (specifically happiness, fear, and sadness) impact spatial decision-making, utilizing EEG data. To address the inherent limitations of sensor-level investigations previously conducted, we employed standard low-resolution brain electromagnetic tomography and functional independent component analysis to analyze the EEG data at the cortical source level. Our findings showed that across various spectral-spatial networks, positive emotion activated the decision-making network in the left middle temporal gyrus and inferior temporal gyrus, in contrast to negative emotions. We also identified the common spectral-spatial networks and observed significant differences in network strength across emotions. These insights further revealed the important role of the gamma-band prefrontal network. Our research provides a basis for deciphering the roles of brain networks in the impact of emotions on decision-making.