Colorectal cancer (CRC) is a major cause of cancer-related mortality worldwide. Copines-1 (CPNE1) has been shown to be overexpressed in various cancers; however, the role of CPNE1 in CRC remains unknown. Therefore, it is of great importance to elucidate the role of CPNE1 in CRC and its underlying mechanism of action.

Long-term immunoreactivity to mycobacterial antigens in Bovis Calmette-Guérin (BCG)-vaccinated population is not well investigated. Herein, 361 volunteer healthy donors (HDs) with neonatal BCG vaccination from Shanghai region (China) were enrolled. They were subdivided into ESAT-6/CFP10- (E6C10-) and ESAT-6/CFP10+ (E6C10+) groups based on gamma-interferon release assays (IGRAs). Three mycobacterial antigens, including Rv0934, Rv3006, and Rv3841, were subjected to the determination of immunoreactivity by ELISPOT assay. The immunoreactivities to three mycobacterial antigens were firstly compared among TB patients (N=39), E6C10+ HDs (N=78, 21.61% of HDs) and E6C10- HDs (N=283, 78.39% of HDs). It was revealed that Rv3006 was dominant upon M.tb infection, while Rv3841 was likely to be more responsive upon latent TB infection. In E6C10- population, the immunoreactivity to Rv3841 maintained along with aging, whereas those to Rv3006 and Rv0934 attenuated in E6C10- HDs older than 45 years old. Our study implies the shift of dominant antigens at different infection statuses, providing the clues for the selection of mycobacterial antigens in vaccine development and precision revaccination in the future.

African swine fever, caused by African swine fever virus (ASFV), is a highly contagious hemorrhagic disease of domestic pigs. The current continent-wide pandemic has persisted for over 10 years, and its economy-devastating effect was highlighted after spreading to China, which possesses half of the world pig industry. So far, development of an effective and safe vaccine has not been finished largely due to the knowledge gaps in pathogenesis and immunology, particularly the role of cytokines in the host's immune response. Therefore, we performed experiments in domestic pigs to analyze the kinetics of representative circulating interferons (IFNs), interleukins (ILs), growth factors, tumor necrosis factors (TNFs), and chemokines induced by infection of type II virulent ASFV SY18. Pigs infected with this Chinese prototypical isolate developed severe clinical manifestations mostly from 3 days post inoculation (dpi) and died from 7 to 8 dpi. Serum analysis revealed a trend of robust and sustained elevation of pro-inflammatory cytokines including TNF-α, IFN-α, IL-1β, IL-6, IL-8, IL-12, IL-18, RANTES (regulated upon activation, normal T cell expressed and secreted), and IFN-γ-induced protein 10 (IP-10) from 3 dpi, but not the anti-inflammatory cytokines IL-10 and transforming growth factor-β (TGF-β). Moreover, secondary drastic increase of the levels of TNF-α, IL-1β, IL-6, and IL-8, as well as elevated IL-10, was observed at the terminal phase of infection. This pattern of cytokine secretion clearly drew an image of a typical cytokine storm characterized by delayed and dysregulated initiation of the secretion of pro-inflammatory cytokine and imbalanced pro- and anti-inflammatory response, which paved a way for further understanding of the molecular basis of ASFV pathogenesis.

Perceiving biological motion (BM) is crucial for human survival and social interaction. Many studies have reported impaired BM perception in autism spectrum disorder, which is characterised by deficits in social interaction. Children with attention deficit hyperactivity disorder (ADHD) often exhibit similar difficulties in social interaction. However, few studies have investigated BM perception in children with ADHD. Here, we compared differences in the ability to process local kinematic and global configurational cues, two fundamental abilities of BM perception, between typically developing and ADHD children. We further investigated the relationship between BM perception and social interaction skills measured using the Social Responsiveness Scale and examined the contributions of latent factors (e.g. sex, age, attention, and intelligence) to BM perception. The results revealed that children with ADHD exhibited atypical BM perception. Local and global BM processing showed distinct features. Local BM processing ability was related to social interaction skills, whereas global BM processing ability significantly improved with age. Critically, general BM perception (i.e. both local and global BM processing) may be affected by sustained attentional ability in children with ADHD. This relationship was primarily mediated by reasoning intelligence. These findings elucidate atypical BM perception in ADHD and the latent factors related to BM perception. Moreover, this study provides new evidence that BM perception is a hallmark of social cognition and advances our understanding of the potential roles of local and global processing in BM perception and social cognitive disorders.

IgA nephropathy (IgAN) is still one of the leading causes of end-stage kidney disease (ESRD), and complement system activation is a key to the pathogenesis of IgAN. The role of complement C3a/C3aR and C5a/C5aR in late stage of IgAN remains unknown. Renal specimens of 75 IgAN patients at the stage 4 CKD were stained using immunofluorescence and immunohistochemistry. The primary outcome was a composite of end-stage renal disease (ESRD) and death. Associations of complement components with baseline clinicopathological characteristics and outcomes were assessed using multivariable Cox regression and Spearman analyses. During a median follow-up of 15.0 months, 27 patients progressed to ESRD and none died. Lower eGFR [hazards ratio (HR), 0.827, 95% confidence interval (CI), 0.732-0.935; P = 0.002] and glomerular C3 deposition (HR, 3.179, 95% CI, 1.079-9.363; P = 0.036) were predictive of time to ESRD in stage 4 CKD IgAN. Higher expression of C3a (P = 0.010), C3aR (P = 0.005), C5a (P = 0.015), and C5aR (P < 0.001) was identified in ESRD group than in non-ESRD group. Glomerular C3a/C3aR and C5a/C5aR deposits were both correlated with a lower baseline eGFR, higher baseline 24 h-urinary protein (24 h-UP) and faster decline of eGFR. Besides, C3a and C5a deposits were found in patients with high S (S1) and T (T1/2) scores, respectively. Complement C3a/C3aR and C5a/C5aR in IgAN patients with stage 4 CKD may portend a faster deterioration of kidney function.

Accumulating evidence has revealed the gut bacteria dysbiosis and brain hippocampal functional and structural alterations in major depressive disorder (MDD). However, the potential relationship between the gut microbiota and hippocampal function alterations in patients with MDD is still very limited. Data of resting-state functional magnetic resonance imaging were acquired from 44 unmedicated MDD patients and 42 demographically matched healthy controls (HCs). Severn pairs of hippocampus subregions (the bilateral cornu ammonis [CA1-CA3], dentate gyrus (DG), entorhinal cortex, hippocampal-amygdaloid transition area, and subiculum) were selected as the seeds in the functional connectivity (FC) analysis. Additionally, fecal samples of participants were collected and 16S rDNA amplicon sequencing was used to identify the altered relative abundance of gut microbiota. Then, association analysis was conducted to investigate the potential relationships between the abnormal hippocampal subregions FC and microbiome features. Also, the altered hippocampal subregion FC values and gut microbiota levels were used as features separately or together in the support vector machine models distinguishing the MDD patients and HCs. Compared with HCs, patients with MDD exhibited increased FC between the left hippocampus (CA2, CA3 and DG) and right hippocampus (CA2 and CA3), and decreased FC between the right hippocampal CA3 and bilateral posterior cingulate cortex. In addition, we found that the level of proinflammatory bacteria (i.e., Enterobacteriaceae) was significantly increased, whereas the level of short-chain fatty acids producing-bacteria (i.e., Prevotellaceae, Agathobacter and Clostridium) were significantly decreased in MDD patients. Furthermore, FC values of the left hippocampal CA3- right hippocampus (CA2 and CA3) was positively correlated with the relative abundance of Enterobacteriaceae in patients with MDD. Moreover, altered hippocampal FC patterns and gut microbiota level were considered in combination, the best discrimination was obtained (AUC = 0.92). These findings may provide insights into the potential role of gut microbiota in the underlying neuropathology of MDD patients.

In vertebrates, bony fishes possess not only innate immune cells but also T and B cells that are equivalent to those in mammals. However, the precise sub-cluster of immune cells in teleost fish remains largely unknown. Herein, we developed a dynamic bacterial infection model in turbot (Scophthalmus maximus) and created a fish immune cell landscape (FICL) for a primary lymphoid organ (head kidney), a secondary lymphoid organ (spleen), and barrier tissues (gills and posterior intestine). Moreover, through comprehensive characterization of the expression profiles of 16 clusters, including dendritic cells-like (DCs-like), macrophages (MΦs), neutrophils, NK cells, as well as 12 sub-clusters of T and B cells, we found that CD8+ CTLs, CD4-CD8- T, Th17 and ILC3-2 like cells possess a bifunctional role associated with cytotoxicity and immunoregulation during bacterial infection. To our knowledge, these results could provide a useful resource for a better understanding of immune cells in teleost fish and could act as a comprehensive knowledge base for assessing the evolutionary mechanism of adaptive immunity in vertebrates.

Adenosine deaminases acting on RNA 1 (ADAR1), an RNA editing enzyme, holds a role in cancer, inflammation, and immunity. However, its specific function in the nephropathy and high-glucose-induced human renal tubular epithelial cells (HK-2) injury in diabetic db/db mice is not clear.

Alternative splicing generates cancer-specific transcripts and is now recognized as a hallmark of cancer. However, the critical oncogenic spliceosome-related proteins involved in triple-negative breast cancer (TNBC) remain elusive. Here, we explored the expression pattern of spliceosome-related proteins in TNBC, non-TNBC, and normal breast tissues from The Cancer Genome Atlas breast cancer (TCGA-BRCA) cohort, revealing higher expression of nearly half of spliceosome-related proteins in TNBC than their counterparts. Among these TNBC-specific spliceosome-related proteins, the expression of SNRPB2 was associated with poor prognosis in patients with TNBC. In TNBC cells, the knockdown of SNRPB2 strongly suppressed cell proliferation and invasion and induced cell cycle arrest. Mechanistically, transcriptome data showed that SNRPB2 knockdown inactivated E2F1 signaling, which regulated the cell cycle. We further validated the downregulation of several cell cycle genes in SNRPB2 knockdown cells. Moreover, the analysis showed that SNRPB2 knockdown triggered the alteration of many alternative splicing events, most of which were skipping of exon. In TNBC cells, it was found that SNRPB2 knockdown led to the skipping of exon 6 in MDM4 pre-mRNA, generating MDM4-S transcript and downregulating MDM4 protein expression. More importantly, downregulation of MDM4 decreased retinoblastoma 1 (Rb1) protein expression, which is a target of MDM4 and a regulator of E2F1 signaling. In summary, the current study revealed an SNRPB2/MDM4/Rb axis in promoting the progression of TNBC, providing novel insights and novel targets for combating TNBC.

Climate-sensitive northern cryosphere inland waters emit greenhouse gases (GHGs) into the atmosphere, yet their total emissions remain poorly constrained. We present a data-driven synthesis of GHG emissions from northern cryosphere inland waters considering water body types, cryosphere zones, and seasonality. We find that annual GHG emissions are dominated by carbon dioxide ([Formula: see text] teragrams of CO2; [Formula: see text]) and methane ([Formula: see text] teragrams of CH4), while the nitrous oxide emission ([Formula: see text] gigagrams of N2O) is minor. The annual CO2-equivalent (CO2e) GHG emissions from northern cryosphere inland waters total [Formula: see text] or [Formula: see text] petagrams of CO2e using the 100- or 20-year global warming potentials, respectively. Rivers emit 64% more CO2e GHGs than lakes, despite having only one-fifth of their surface area. The continuous permafrost zone contributed half of the inland water GHG emissions. Annual CO2e emissions from northern cryosphere inland waters exceed the region's terrestrial net ecosystem exchange, highlighting the important role of inland waters in the cryospheric land-aquatic continuum under a warming climate.

Hemin, a heme-like compound with significant biological activity, shows promise as an iron supplement for humans. Nonetheless, its poor solubility in water greatly impedes its absorption and utilization. To surmount this obstacle, researchers have chosen various cyclodextrins with distinct cavity sizes and derivative groups to act as hosts, forming inclusion complexes with hemin chloride. Among these, γ-cyclodextrin has been identified as the optimal carrier, based on a thorough evaluation of its encapsulation efficiency, solubility, and molecular docking. Multiple characterization techniques further confirmed the formation of these inclusion complexes. Results from IEC-6 cell experiments indicated that the cytotoxicity of the inclusion complexes was lower than that of FeSO4. Static and dynamic gastrointestinal simulation digestion systems were established, and the results showed that the bioavailability of the inclusion complex was significantly higher than that of raw hemin. Additionally, only about 0.29% of hemin chloride is digested by gastric enzymes, whereas 9.52% is digested by pancreatic enzymes in the static gastrointestinal simulation digestion system, with similar outcomes observed in the dynamic system. These findings suggest that targeted digestion in the intestine significantly enhances the bioavailability of hemin chloride by forming inclusion complexes in vitro.

Individuals with diabetes frequently face serious challenges, including delayed wound healing and increased risk of infection. Notably, the regeneration of hair follicles plays a crucial role in accelerating diabetic skin damage repair, reducing the risk of infection, and enhancing overall skin health. Research has predominantly emphasized the re-epithelialization of diabetic wounds, with a paucity of in-depth studies on hair follicle regeneration. In the current study, we explored the effects of a bioactive amphibian-derived peptide, Cy RL-QN15, on promoting hair regeneration in a diabetic skin model. In vivo experiments demonstrated that local treatment with Cy RL-QN15 not only accelerated wound healing of scalded skin on the backs of diabetic Kunming (KM) mice but also improved growth of damaged hair follicles. Additionally, back-shaved diabetic C57BL/6 mice showed a significant increase in the growth of newly formed hair after 28 days of continuous Cy RL-QN15 treatment. Further analysis indicated that the hair-regenerating effects of Cy RL-QN15 were closely associated with the proliferation and migration of hair follicle stem cells (HFSCs). Cy RL-QN15 enhanced intracellular β-catenin expression by binding to the Frizzled-7 receptor on the surface of HFSCs. The up-regulation in β-catenin modulated the levels of downstream proteins, such as c-MYC, Cyclin D1, and Lef1, ultimately inducing hair regeneration. This study not only reveals the robust effects of the bioactive peptide Cy RL-QN15 in hair follicle regeneration but also provides novel avenues for the development of more targeted and effective therapeutics for diabetic wound healing in the future.

There is limited research on predicting the recovery of consciousness in patients with acute disorders of consciousness (aDOC). The purpose of this study is to investigate the altered characteristics of the local neuronal activity indicated by the amplitude of low-frequency fluctuations (ALFF) and functional connectivity (FC) of the hippocampus network in patients with aDOC caused by neurological injury and to explore whether these characteristics can predict the recovery of consciousness.

Electroacupuncture (EA) has been shown to promote functional recovery after cerebral ischemia-reperfusion (I/R) injury. However, the contribution of mitochondrial dynamics to recovery remains unclear. The aim of this study was to investigate whether mitochondrial dynamics are involved in the effects of EA on cerebral I/R injury.

Osteoarthritis (OA) is a prevalent chronic degenerative disease that affects the bones and joints, particularly in middle-aged and elderly individuals. It is characterized by progressive joint pain, swelling, stiffness, and deformity. Notably, treatment with a heat shock protein 90 (HSP90) inhibitor has significantly curtailed cartilage destruction in a rat model of OA. Although the monoclonal antibody 9B8 against HSP90 is recognized for its anti-tumor properties, its potential therapeutic impact on OA remains uncertain. This study investigated the effects of 9B8 on OA and its associated signaling pathways in interleukin-1β (IL-1β)-stimulated human chondrocytes and a rat anterior cruciate ligament transection (ACLT) model. A specific concentration of 9B8 preserved cell viability against IL-1β-induced reduction. In vitro, 9B8 significantly reduced the expression of extracellular matrix-degrading enzyme such as disintegrin and metallopeptidase-4 (ADAMTS4) of thrombospondin motifs, matrix metalloproteinase-13 (MMP-13), as well as cellular inflammatory factors such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), which were upregulated by IL-1β. In vivo, 9B8 effectively protected the articular cartilage and subchondral bone of the rat tibial plateau from ACLT-induced damage. Additionally, gene microarray analysis revealed that IL-1β substantially increased the expression of SLC2A1, PFKP, and ENO2 within the HIF-1 signaling pathway, whereas 9B8 suppressed the expression of these genes. Thus, 9B8 effectively mitigates ACLT-induced osteoarthritis in rats by modulating the HIF-1 signaling pathway, thereby inhibiting overexpression involved in glycolysis. These results collectively indicate that 9B8 is a promising novel drug for the prevention and treatment of OA.

To investigate the effect of MALAT1 on the modulating the radiosensitivity of lung adenocarcinoma, through regulation of the expression of the miR-140/PD-L1 axis.

In pneumonia, the deficient or delayed pathogen clearance can lead to pathogen proliferation and subsequent overactive immune responses, inducing acute lung injury (ALI). While screening human genome coding genes using our peripheral blood cell chemotactic platform, we unexpectedly find SLP adaptor and CSK interacting membrane protein (SCIMP), a protein with neutrophil chemotactic activity secreted during ALI. However, the specific role of SCIMP in ALI remains unclear. In this study, we investigate the secretion of SCIMP in exosomes (SCIMPexo) by macrophages after bacterial stimulation, both in vitro and in vivo. We observe a significant increase in the levels of SCIMPexo in bronchoalveolar lavage fluid and serum of pneumonia patients. We also find that bronchial perfusion with SCIMPexo or SCIMP N-terminal peptides increases the survival rate of the ALI model. This occurs due to the chemoattraction and activation of peripheral neutrophils dependent on formyl peptide receptor 1/2 (FPR1/2). Conversely, exosome suppressors and FPR1/2 antagonists decrease the survival rate in the lethal ALI model. Scimp-deficient and Fpr1/2-deficient mice also have lower survival rates and shorter survival times than wild-type mice. However, bronchial perfusion of SCIMP rescues Scimp-deficient mice but not Fpr1/2-deficient mice. Collectively, our findings suggest that the macrophage-SCIMP-FPRs-neutrophil axis plays a vital role in the innate immune process underlying ALI.

Visual saliency refers to the human's ability to quickly focus on important parts of their visual field, which is a crucial aspect of image processing, particularly in fields like medical imaging and robotics. Understanding and simulating this mechanism is crucial for solving complex visual problems. In this paper, we propose a salient object detection method based on boundary enhancement, which is applicable to both 2D and 3D sensors data. To address the problem of large-scale variation of salient objects, our method introduces a multi-level feature aggregation module that enhances the expressive ability of fixed-resolution features by utilizing adjacent features to complement each other. Additionally, we propose a multi-scale information extraction module to capture local contextual information at different scales for back-propagated level-by-level features, which allows for better measurement of the composition of the feature map after back-fusion. To tackle the low confidence issue of boundary pixels, we also introduce a boundary extraction module to extract the boundary information of salient regions. This information is then fused with salient target information to further refine the saliency prediction results. During the training process, our method uses a mixed loss function to constrain the model training from two levels: pixels and images. The experimental results demonstrate that our salient target detection method based on boundary enhancement shows good detection effects on targets of different scales, multi-targets, linear targets, and targets in complex scenes. We compare our method with the best method in four conventional datasets and achieve an average improvement of 6.2% on the mean absolute error (MAE) indicators. Overall, our approach shows promise for improving the accuracy and efficiency of salient object detection in a variety of settings, including those involving 2D/3D semantic analysis and reconstruction/inpainting of image/video/point cloud data.

High-fat diet (HFD)-induced obesity is a crucial risk factor for metabolic syndrome, mainly due to adipose tissue dysfunctions associated with it. However, the underlying mechanism remains unclear. This study has used genetic screening to identify an obesity-associated human lncRNA LINK-A as a critical molecule bridging the metabolic microenvironment and energy expenditure in vivo by establishing the HFD-induced obesity knock-in (KI) mouse model. Mechanistically, HFD LINK-A KI mice induce the infiltration of inflammatory factors, including IL-1β and CXCL16, through the LINK-A/HB-EGF/HIF1α feedback loop axis in a self-amplified manner, thereby promoting the adipose tissue microenvironment remodeling and adaptive thermogenesis disorder, ultimately leading to obesity and insulin resistance. Notably, LINK-A expression is positively correlated with inflammatory factor expression in individuals who are overweight. Of note, targeting LINK-A via nucleic acid drug antisense oligonucleotides (ASO) attenuate HFD-induced obesity and metabolic syndrome, pointing out LINK-A as a valuable and effective therapeutic target for treating HFD-induced obesity. Briefly, the results reveale the roles of lncRNAs (such as LINK-A) in remodeling tissue inflammatory microenvironments to promote HFD-induced obesity.

Isolated nocturnal hypertension (INH) is a special type of out-of-office hypertension. Its determinants and pathophysiology remain unclear. In a nested case-control study, we intend to investigate the host, environmental, and genetic factors in relation to INH. Among 2030 outpatients screened from December 2008 till June 2015, 128 patients with INH were identified, and then 128 normotensives were matched according to sex and age. INH was an elevated nocturnal blood pressure (BP ≥120/70 mmHg) in the presence of a normal daytime BP (< 135/85 mmHg). Host factors included age, sex, body mass index, smoking and drinking, sleep time and duration, heart rate, serum lipids, and serum creatinine. Environmental cues encompassed season, ambient temperature, atmospheric pressure, humidity, and wind speed, and genetic cues 29 single-nucleotide polymorphisms (SNPs) in 12 clock genes. Daytime and nighttime BPs averaged 124.9/80.7  and 114.5/73.7 mmHg, respectively, in the INH patients and 121.0/76.5 and 101.8/63.3 mmHg in the normotensive controls. Stepwise logistic regression analyses revealed that INH was associated with nighttime heart rate (P = .0018), sleep duration (P = .0499), and relative humidity (P = .0747). The odds ratios (95% CI) for each 10 beats/min faster nighttime heart rate and 10% lower relative humidity were 1.82 (1.25-2.65) and 0.82 (0.67-1.00), respectively. Irrespective of the genetic models, no significant association was observed between INH and the SNPs (P ≥ .054). In conclusion, INH was associated with host and environmental factors rather than genetic markers.