SpatialRef: a reference of spatial omics with known spot annotation.

Spatial omics technologies have enabled the creation of intricate spatial maps that capture molecular features and tissue morphology, providing valuable insights into the spatial associations and functional organization of tissues. Accurate annotation of spot or domain types is essential for downstream spatial omics analyses, but this remains challenging. Therefore, this study aimed to develop a manually curated spatial omics database (SpatialRef, https://bio.liclab.net/spatialref/), to provide comprehensive and high-quality spatial omics data with known spot labels across multiple species. The current version of SpatialRef aggregates >9 million manually annotated spots across 17 Human, Mouse and Drosophila tissue types through extensive review and strict quality control, covering multiple spatial sequencing technologies and >400 spot/domain types from original studies. Furthermore, SpatialRef supports various spatial omics analyses about known spot types, including differentially expressed genes, spatially variable genes, Gene Ontology (GO)/KEGG annotation, spatial communication and spatial trajectories. With a user-friendly interface, SpatialRef facilitates querying, browsing and visualizing, thereby aiding in elucidating the functional relevance of spatial domains within the tissue and uncovering potential biological effects.

Serum thrombospondin-1 serves as a novel biomarker and agonist of gemcitabine-based chemotherapy in intrahepatic cholangiocarcinoma.

BACKGROUND: At present, the first-line treatment for advanced intrahepatic cholangiocarcinoma (ICC) is gemcitabine combined with cisplatin, but a considerable portion of ICC patients exhibit resistance to gemcitabine. Therefore, finding sensitisers for gemcitabine chemotherapy in ICC patients and predicting molecular markers for chemotherapy efficacy have become urgent needs. METHODS: In this study, PDX models were established to conduct gemcitabine susceptibility tests. The selected PDX tissues of the chemotherapy-sensitive group and drug-resistant group were subjected to transcriptome sequencing and protein chip technology to identify the key genes. Sixty-one ICC patients treated with gemcitabine chemotherapy were recruited for clinical follow-up validation. RESULTS: We found that thrombospondin-1 (TSP1) can predict gemcitabine chemosensitivity in ICC patients. The expression level of TSP1 could reflect the sensitivity of ICC patients to gemcitabine chemotherapy. Functional experiments further confirmed that TSP1 can increase the efficacy of gemcitabine chemotherapy for ICC. A mechanism study showed that TSP1 may affect the intake of oleic acid by binding to the CD36 receptor. CONCLUSIONS: In summary, we found a key molecule-TSP1-that can predict and improve the sensitivity of ICC patients to gemcitabine chemotherapy, which is of great significance for the treatment of advanced cholangiocarcinoma.

HBV/Pregenomic RNA Increases the Stemness and Promotes the Development of HBV-Related HCC Through Reciprocal Regulation With Insulin-Like Growth Factor 2 mRNA-Binding Protein 3.

BACKGROUND AND AIMS: HBV-pgRNA (pregenomic RNA) has been proposed for predicting the response of nucleos(t)ide analogue (NA) treatment, guiding discontinuation of NA therapy and monitoring the emergence of viral mutations. However, the contributions of HBV-pgRNA to HCC remain open for study. APPROACH AND RESULTS: Double-center cohorts of serum samples with undetectable serum HBV-DNA (below the lower limit of detection) were obtained from long-term NA-treated (≥48 weeks) HBV-related HCC patients. The correlation between serum pgRNA concentration and the prognosis of HCC were analyzed. The role pgRNA played in HCC development was assessed both in vitro and in vivo. Our findings revealed that for patients who underwent long-term NA therapy with undetectable serum HBV-DNA, patients with high serum pgRNA expression had a poorer overall survival rate and higher cumulative recurrence rate after hepatectomy. Experiments demonstrated that pgRNA promotes proliferation, stemness, and tumorigenicity of HCC cells. Mechanistically, we found that pgRNA could up-regulate the expression of insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3), a well-proven oncoprotein, at the posttranscriptional level. Furthermore, interferon (IFN)-α-2a could degrade the stability of pgRNA through increasing its N6-methyladenosine (m6A) RNA modification. Collectively, our findings uncover that serum pgRNA could serve as a potential biomarker for predicting the prognosis and recurrence of HCC in patients who received long-term NA therapy with undetectable serum HBV-DNA; and the pgRNA-IGF2BP3 axis plays an important role in the development of HBV-related HCC. Moreover, IFN-α-2a could reduce the stability of pgRNA by increasing its m6A RNA modification level, thereby suppressing the development of HBV-related HCC. CONCLUSIONS: In conclusion, our studies reveal a significance and mechanism of HBV-pgRNA in increasing stemness features and offer a potential prognostic marker and a therapeutic target for HBV-related HCC.

Molecular Detection and Genotyping of Toxoplasma gondii from Pigs for Human Consumption in Zhejiang and Jiangsu Provinces, Eastern China.

Toxoplasma gondii infections are common in humans and animals worldwide. Ingestion of raw or undercooked meat containing tissue cysts of T. gondii is one major source of transmission of this parasite. It is important to guarantee the meat quality of China since our pork industry produces about half of the world's pork. In this study, a total of 746 pig samples were collected from Zhejiang and Jiangsu provinces in eastern China, and examined for T. gondii infection by PCR amplification targeting B1 gene. In this study, we found that 57 of 746 (7.6%) pigs were positive for B1 gene, with 8.5% (48/562) in Zhejiang province and 4.9% (9/184) in Jiangsu province, respectively. The positive DNA samples were further genotyped at 11 genetic markers, including SAG1, 5'-and 3'-SAG2, alternative SAG2, SAG3, BTUB, GRA6, L358, PK1, c22-8, c29-2, and an apicoplast locus Apico through PCR-restriction fragment length polymorphism (PCR-RFLP) technology. Two genotypes (ToxoDB 9 and ToxoDB 10) of T. gondii were identified by PCR-RFLP in Zhejiang province. However, both genotypes were not determined from Jiangsu province, which is speculated on the low DNA concentration and the small number of samples. These results indicate that T. gondii infection is endemic in pigs in eastern China and may raise public food safety concerns, suggesting more interventions for T. gondii-related risks are needed in the future.

[Study on mechanism of Rehmanniae Radix Praeparata for treatment of osteoarthritis based on network pharmacology and molecular docking].

The mechanism of Rehmanniae Radix Praeparata against osteoarthritis was investigated based on network pharmacology, molecular docking, and in vitro experiments in the present study. Osteoclast models were established via receptor activator of nuclear factor-κB ligand(RANKL) and macrophage colony-stimulating factor(M-CSF) inducing RAW264.7 cells. Further, the influence of Rehmanniae Radix Praeparata on the activity of tartrate-resistant acid phosphatase(TRAP) was evaluated and the efficacy of Rehmanniae Radix Praeparata in the treatment of osteoarthritis was verified. The active components of Rehmanniae Radix Praeparata were obtained from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) and literature, and the potential targets of the components were collected from SwissTargetPrediction. Osteoarthritis disease targets were searched in Online Mendelian Inheritance in Man(OMIM), Therapeutic Target Database(TTD), GeneCards, and DisGeNET. The intersection targets of Rehmanniae Radix Praeparata and osteoarthritis were obtained by Venny platform. The protein-protein interaction(PPI) network was constructed by Cytoscape 3.8.2, and key targets were obtained based on topology algorithm. The Database for Annotation, Visualization and Integrated Discovery(DAVID) was used to perform Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis. Finally, the mRNA expression of the key targets was determined by RT-qPCR and the binding activity between the components and key targets was validated by molecular docking. The results showed that Rehmanniae Radix Prae-parata inhibited the TRAP activity, thus inhibiting bone resorption by osteoclasts and treating osteoarthritis. By network pharmacology, 14 active components of Rehmanniae Radix Praeparata and 126 intersection targets were obtained. The network pharmacology enrichment results revealed 432 biological processes and 139 signaling pathways. Key targets such as proto-oncogene tyrosine-protein kinase Src(SRC), signal transducer and activator of transcription 3(STAT3) and transcription factor p65(RELA) were obtained according to the degree in topological analysis. SRC was highly expressed in osteoclasts, which accelerated the development of osteoarthritis. Therefore, SRC was selected for subsequent verification, and Rehmanniae Radix Praeparata decreased the gene expression level of SRC. The molecular docking showed that acteoside, isoacteoside, raffinose had good bonding activity with SRC, suggesting that they might be the critical components in treating osteoarthritis. In conclusion, Rehmanniae Radix Praeparata can inhibit bone resorption by osteoclasts and balance the metabolism of articular cartilage and subchondral bone via acting on SRC, thus playing a therapeutic role in osteoarthritis. In addition, Rehmanniae Radix Praeparata may exert overall efficacy on osteoarthritis through other targets such as STAT3 and RELA, and other related pathways such as PI3 K-AKT and IL-17 signaling pathways.

[Analysis on targets of regulating Qi and activating blood based on activity spectrum of targets].

The traditional Chinese medicines(TCM) for activating blood circulation and the TCM for regulating Qi are often used in combination in clinical practice. However, their mechanisms are still unclear. The activity spectrum of targets can fuse the active components, targets and intensity of action, which provides support for the discussion of efficacy targets. The chemical components of common TCM sets for activating blood circulation and regulating Qi, as well as the negative sets not for activating blood circulation and re-gulating Qi were obtained from the database of TCM. By the similarity analysis of chemical components in TCM for activating blood circulation and DrugBank database, the predicted targets of chemical components in TCM for activating blood circulation were obtained, and the similarity value of the two was taken as the activity value of the active components and predicted targets. Then, the component-target activity value was weighted. The activity values of herb acting on the same target were fused to construct activity spectra of targets of the herbs for activating blood circulation, herbs for regulating Qi and negative herbs. The targets whose activity values of activating blood circulation and regulating Qi were higher than those of negative herbs were selected as potential targets of efficacy. Protein-protein interaction networks were constructed for topological, GO and KEGG enrichment analysis to determine the key targets of efficacy of activating blood circulation and regulating Qi. The component-target activity information collected from DrugBank database contained 4 499 compounds, 627 targets and 11 295 action relationships. The activating blood function protein-protein interaction network contained 206 nodes and 1 728 edges, while the regulating Qi function protein-protein interaction network contained 230 nodes and 986 edges. The enrichment analysis of topology, GO and KEGG showed that TCM for activating blood circulation mainly exerted its anti-inflammatory, neuroprotective and angiogenic effects on signaling cascade pathway mediated by VEGF/VEGFR2, ERK signaling pathway, calcium signaling pathway and PI3 K-AKT signaling pathway, and the key targets included mitogen activated protein kinases 3(MAPK3), proto-oncogene tyrosine-protein kinase Src(SRC), mitogen activated protein kinases 1(MAPK1), epidermal growth factor receptor(EGFR), phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform(PIK3 CA), peroxisome proliferators-activated receptor gamma(PPARG), nitric oxide synthase 3(NOS3), prostaglandin G/H synthetase 2(PTGS2), matrix metalloproteinase-9(MMP9), and vascular endothelial growth factor A(VEGFA). TCM for regulating Qi mainly exerted anti-inflammatory and neuroprotective effects by acting on MAPK signaling pathway and PI3 K-AKT signaling pathway, and the key targets included mitogen activated protein kinases 8(MAPK8), SRC, mitogen activated protein kinases 14(MAPK14), and RAC-alpha serine/threonine-protein kinase(AKT1), mitogen activated protein kinases 3(MAPK3). Based on the activity spectrum of targets, the targets of the TCM for activating blood and the targets of the TCM for regulating Qi were analyzed to provide reference for the study of efficacy targets of TCM, and also provide some scientific basis for clinical application.

Frequency, Risk Factors, and Outcome of Active Tuberculosis following Allogeneic Hematopoietic Stem Cell Transplantation.

We aimed to investigate the frequency, risk factors, and outcome of active tuberculosis (TB) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). This retrospective, nested, case-control study reviewed data from 6236 patients who received allo-HSCT from January 2008 to December 2018 at a single center; thirty-three patients (0.5%) with active TB and 99 controls without active TB after allo-HSCT were identified. We performed propensity score matching by randomly selecting 3 controls for each identified active TB patient according to the time of transplantation and follow-up period. History of pretransplant active TB previously treated and inactive at time of transplantation (P< .001) was an independent risk factor. No significant differences in overall survival (P= .342), nonrelapse mortality (P= .497), or incidence of relapse (P= .807) were found. Thirty (90.9%) patients were treated with 4-drug (isoniazid, rifampicin/three rifapentine, pyrazinamide, and ethambutol) or 3-drug combination first-line therapy, with a response rate of 76.7%. Twenty-six (78.8%) patients were treated with first-line and second-line combined therapy, and the response rate was 76.9%. Five (15.2%) patients developed hepatotoxicity. In conclusion, history of pretransplant active TB previously treated and inactive at time of transplantation was an independent risk factor of active TB after allo-HSCT. No significant differences in prognosis between the TB and control groups were found. More studies are needed to help develop standardized therapeutic strategies for patients with post-transplant TB.

Identification of MiR-211-5p as a tumor suppressor by targeting ACSL4 in Hepatocellular Carcinoma.

BACKGROUND: Liver cancer is among the most common malignancy worldwide. Hepatocellular carcinoma (HCC), the principal histological subtype of liver cancer, is globally the third most common cause of cancer-related mortality. The high rates of recurrence and metastasis contribute to the poor prognosis of HCC patients. In recent years, increasing evidence has shown that microRNAs (miRNAs) are involved in the tumorigenesis, progression, and prognosis of HCC. METHODS: To screen for key candidate miRNAs in HCC, three microarray datasets were downloaded from Gene Expression Omnibus (GEO). The sole common differentially expressed miRNA (DEmiR) observed in the above three datasets using a Venn diagram was microRNA-211-5p (miR-211-5p). The expression of miR-211-5p from HCC tissues was measured in several HCC cell lines. Additionally, using Kaplan-Meier plots, the potential prognostic value of miR-211-5p in HCC was analyzed. Cell counting kit-8 (CCK-8) and transwell assays examined the ability of miR-211-5p to induce cell proliferation, migration, and invasion in HCC cultures. The interaction of miR-211-5p and Acyl-CoA Synthetase Long Chain Family Member 4 (ACSL4) was assessed both theoretically and using a luciferase reporter assay. Finally, the ability of miR-211-5p to modulate tumorigenesis in HCC in vivo was assessed after establishing a xenograft model. RESULTS: qRT-PCR demonstrated that the relative expression of miR-211-5p was considerably down-regulated in HCC tissues and cell lines compared with normal tissue. Kaplan-Meier plots indicated that HCC patients with decreased expression of miR-211-5p had poor overall survival. Upregulation of miR-211-5p in vitro consistently suppressed cell proliferation, migration, and invasion. In contrast, enhanced expression of ACSL4 promoted a malignant phenotype in HCC cells. Importantly, we discovered that ACSL4 was a direct downstream target of miR-211-5p in HCC, and that miR-211-5p suppressed the malignant phenotype by inhibition of ACSL4 expression. Furthermore, miR-211-5p overexpression impaired tumorigenesis and growth of HCC in vivo. CONCLUSIONS: Targeting miR-211-5p and the downstream gene ACSL4 will possibly provide novel insight and represents a promising approach to future therapy of HCC patients.

The Modulation of Trehalose Metabolism by 20-Hydroxyecdysone in Antheraea pernyi (Lepidoptera: Saturniidae) During its Diapause Termination and Post-Termination Period.

Trehalose plays a crucial role in the diapause process of many insects, serving as an energy source and a stress protectant. Trehalose accumulation has been reported in diapause pupae of Antheraea pernyi; however, trehalose metabolic regulatory mechanisms associated with diapause termination remain unclear. Here, we showed that the enhanced trehalose catabolism was associated with an increase in endogenous 20-hydroxyecdysone (20E) in hemolymph of A. pernyi pupae during their diapause termination and posttermination period. Injection of 20E increased the mRNA level of trehalase 1A (ApTre-1A) and trehalase 2 (ApTre-2) of A. pernyi diapause pupae in a dose-dependent manner but did not affect the mRNA level of trehalase 1B (ApTre-1B). Meanwhile, exogenous 20E increased the enzyme activities of soluble and membrane-bound trehalase, leading to a decline in hemolymph trehalose. Conversely, the expression of ApTre-1A and ApTre-2 were down-regulated after the ecdysone receptor gene (ApEcRB1) was silenced by RNA interference or by injection of an ecdysone receptor antagonist cucurbitacin B (CucB), which inhibits the 20E pathway. Moreover, CucB treatment delayed adult emergence, which suggests that ApEcRB1 might be involved in regulating pupal-adult development of A. pernyi by mediating ApTre-1A and ApTre-2 expressions. This study provides an overview of the changes in the expression and activity of different trehalase enzymes in A. pernyi in response to 20E, confirming the important role of 20E in controlling trehalose catabolism during A. pernyi diapause termination and posttermination period.

MicroRNA-138 Aggravates Inflammatory Responses of Macrophages by Targeting SIRT1 and Regulating the NF-κB and AKT Pathways.

BACKGROUND/AIMS: With increased understanding of sepsis, mortality is decreasing. However, there is still a lack of effective therapeutic strategy. The inflammatory response of macrophages is critical during sepsis. METHODS: Macrophages were stimulated with LPS. Western blotting and qRT-PCR were used to detect inflammatory responses. Then, the inhibitor of microRNA-138 was transfected and Western blotting, qRT-PCR, H&E staining and ELISA were used to verify the role of microRNA-138 in inflammation. Then target gene prediction databases were used to predict the potential target of microRNA-138. Both animal and cell models under LPS challenges were established to verify the regulation of SIRT1 and microRNA-138 during inflammation. RESULTS: The present study showed that microRNA-138 was increased in macrophages stimulated with LPS. Additionally, the NF-κB and AKT pathways were both activated. The pre-treatment of microRNA-138 inhibitor decreased inflammatory factors, downregulated the NF-κB pathway, activated the AKT pathway and protected against organ damage in mice challenged with LPS. SIRT1 was demonstrated as a potential target of microRNA-138In macrophages stimulated with LPS, the inhibition effect of microRNA-138 inhibitor on inflammation was lost by SIRT1 siRNA pre-treatment. In the animal model, the protective effect of microRNA-138 antagomir disappeared in SIRT1 knockout mice. CONCLUSION: We demonstrated that miR-138 participated in the inflammatory process by inhibiting SIRT1 and activating the NF-κB pathway.

An Electrostatically Self-Assembled Thin Film Made of Zn-Substituted Tungstoborate and Rhodamine B with Photoelectrochemical Properties.

An electrostatically self-assembled multilayer thin film consisting of alternating layers of Keggin polyoxometalate of Zn-substituted tungstoborate (BW11Zn) and Rhodamine B (RhB) has successfully been prepared on a quartz and indium-tin oxide (ITO) glass substrate. The ultraviolet-visible (UV-vis) absorption spectra demonstrated that the electrostatically self-assembled film of (BW11Zn/RhB)n was uniformly deposited layer by layer, and the RhB molecules in the film formed the J-aggregation. The photoelectrochemical investigations showed that the films generated stable cathodic photocurrents that originated from RhB, and the maximal cathodic photocurrent density generated by an eight-layer film was 4.9 µA/cm2 while the film was irradiated with 100 mW/cm2 polychromatic light of 730 nm > λ > 325 nm at an applied potential of 0 V versus a saturated calomel electrode.

Up-regulation of TDAG51 is a dependent factor of LPS-induced RAW264.7 macrophages proliferation and cell cycle progression.

CONTEXT: As a component of the outer membrane in Gram-negative bacteria, lipopolysaccharide (LPS)-induced proliferation and cell cycle progression of monocytes/macrophages. It has been suggested that the proapoptotic T-cell death-associated gene 51 (TDAG51) might be associated with cell proliferation and cell cycle progression; however, its role in the interaction between LPS and macrophages remains unclear. OBJECTIVE: We attempted to elucidate the role(s) of TDAG51 played in the interaction between LPS and macrophages. MATERIALS AND METHODS: We investigated TDAG51 expression in RAW264.7 cells stimulated with LPS and examined the effects of RNA interference-mediated TDAG51 down-regulation. We used CCK-8 assay and flow cytometry analysis to evaluate the interaction between TDAG51 and LPS-induced proliferation and cell cycle progression in RAW264.7 cells. RESULTS: Our findings indicate that TDAG51 is up-regulated in LPS-stimulated RAW264.7 cells, the TDAG51 siRNA effectively reduced TDAG51 protein up-regulation following LPS stimulation in RAW264.7 cells, the significant changes of the proliferation and cell cycle progression of RAW264.7 cells in TDAG51 Knockdown RAW264.7 cells treated with LPS were observed. CONCLUSION: These findings suggested that TDAG51 up-regulation is a dependent event during LPS-mediated proliferation and cell cycle progression, and which increase our understanding of the interaction mechanism between LPS and macrophages.

Glucagon-Like Peptide 1 Protects against Hyperglycemic-Induced Endothelial-to-Mesenchymal Transition and Improves Myocardial Dysfunction by Suppressing Poly(ADP-Ribose) Polymerase 1 Activity.

Under high glucose conditions, endothelial cells respond by acquiring fibroblast characteristics, that is, endothelial-to-mesenchymal transition (EndMT), contributing to diabetic cardiac fibrosis. Glucagon-like peptide-1 (GLP-1) has cardioprotective properties independent of its glucose-lowering effect. However, the potential mechanism has not been fully clarified. Here we investigated whether GLP-1 inhibits myocardial EndMT in diabetic mice and whether this is mediated by suppressing poly(ADP-ribose) polymerase 1 (PARP-1). Streptozotocin diabetic C57BL/6 mice were treated with or without GLP-1 analog (24 nmol/kg daily) for 24 wks. Transthoracic echocardiography was performed to assess cardiac function. Human aortic endothelial cells (HAECs) were cultured in normal glucose (NG) (5.5 mmol/L) or high glucose (HG) (30 mmol/L) medium with or without GLP-1analog. Immunofluorescent staining and Western blot were performed to evaluate EndMT and PARP-1 activity. Diabetes mellitus attenuated cardiac function and increased cardiac fibrosis. Treatment with the GLP-1 analog improved diabetes mellitus-related cardiac dysfunction and cardiac fibrosis. Immunofluorescence staining revealed that hyperglycemia markedly increased the percentage of von Willebrand factor (vWF)(+)/alpha smooth muscle actin (α-SMA)(+) cells in total α-SMA(+) cells in diabetic hearts compared with controls, which was attenuated by GLP-1 analog treatment. In cultured HAECs, immunofluorescent staining and Western blot also showed that both GLP-1 analog and PARP-1 gene silencing could inhibit the HG-induced EndMT. In addition, GLP-1 analog could attenuate PARP-1 activation by decreasing the level of reactive oxygen species (ROS). Therefore, GLP-1 treatment could protect against the hyperglycemia-induced EndMT and myocardial dysfunction. This effect is mediated, at least partially, by suppressing PARP-1 activation.

HMGB1 mediates hyperglycaemia-induced cardiomyocyte apoptosis via ERK/Ets-1 signalling pathway.

Apoptosis is a key event involved in diabetic cardiomyopathy. The expression of high mobility group box 1 protein (HMGB1) is up-regulated in diabetic mice. However, the molecular mechanism of high glucose (HG)-induced cardiomyocyte apoptosis remains obscure. We aimed to determine the role of HMGB1 in HG-induced apoptosis of cardiomyocytes. Treating neonatal primary cardiomyocytes with HG increased cell apoptosis, which was accompanied by elevated levels of HMGB1. Inhibition of HMGB1 by short-hairpin RNA significantly decreased HG-induced cell apoptosis by reducing caspase-3 activation and ratio of Bcl2-associated X protein to B-cell lymphoma/leukemia-2 (bax/bcl-2). Furthermore, HG activated E26 transformation-specific sequence-1 (Ets-1), and HMGB1 inhibition attenuated HG-induced activation of Ets-1 via extracellular signal-regulated kinase 1/2 (ERK1/2) signalling. In addition, inhibition of Ets-1 significantly decreased HG-induced cardiomyocyte apoptosis. Similar results were observed in streptozotocin-treated diabetic mice. Inhibition of HMGB1 by short-hairpin RNA markedly decreased myocardial cell apoptosis and activation of ERK and Ets-1 in diabetic mice. In conclusion, inhibition of HMGB1 may protect against hyperglycaemia-induced cardiomyocyte apoptosis by down-regulating ERK-dependent activation of Ets-1.

Spatio-temporal pattern and coordinated development of eco-compensation performance of 101 cities in the Yangtze River Economic Belt.

Eco-compensation is an important component of ecological civilization construction. Therefore, it is of great significance to elucidate the spatial and temporal pattern of eco-compensation performance and its internal coupling and coordinated features to promote ecological civilization construction. We proposed that eco-compensation performance consists of benefit and efficiency, and used the projection pursuit and super-efficiency SBM-DEA models to measure the eco-compensation benefit and efficiency of 101 cities in the Yangtze River Economic Belt from 2010 to 2021 and to analyze their spatial and temporal patterns. Finally, we used the coupling coordination degree model to reveal the coupling and coordinated features of eco-compensation performance. The results showed that the temporal trends of eco-compensation benefit and efficiency were "W" and "U" shaped. The eco-compensation benefit in eastern or mega-cities was the highest, whereas the eco-compensation efficiency in western or small/medium-sized cities was the highest. Coupling coordination degree of eco-compensation performance was in the coordinated development stage from 2010 to 2012, with a concentration of agglomeration effects in the central region. It was in the transition/adjustment stage from 2013 to 2020, with low-value areas concentrated and scattered high-value areas, and smaller regional differences. It was in the coordinated development stage in 2021, with a clear agglomeration effect in the eastern region. Cities in the Yangtze River Economic Belt should incorporate the eco-compensation performance coupling coordination mechanism into their optimized eco-compensation policy plans based on the stage of coordinated development, to achieve their environmental improvement goals.

Effect of the Caregivers-to-Caregivers Training Programme on informed caregivers of persons with mental disorders: A pilot study.

OBJECTIVE: Many people with mental disorders are cared for by informed caregivers, but they usually have limited care-related training and lack caregiving capacity and support networks. In order to provide professional training and social support for informed caregivers, we designed the Caregivers-to-Caregivers Training Programme (C2C) and performed a pilot study to assess its effect. METHODS: Caregivers of persons with mental disorders who participated in the C2C were asked to participate in a quasi-experimental study to assess their knowledge and skills development, self-care ability, trainer engagement, and training content. A total of 800 participants completed self-designed evaluation questionnaires and two open-ended questions to gather suggestions and feedback. Assessments were carried out at pretest (baseline), post-test, and at 2-month follow-up. Results were analyzed using one-way repeated measures analysis of variance (ANOVA) and pairwise comparison method. RESULTS: At post-test, 667 assessments were considered valid and 515 were deemed valid at 2-month follow-up. One-way repeated-measures ANOVA showed that the main effect of the scores on knowledge and skills development and self-care ability from baseline to 2-month follow-up was significant (p < .001). Results of pairwise comparison method showed that the scores on each item of knowledge and skills development and self-care ability at post-test and at 2-month follow up were higher than those at baseline (p < .001). The scores on items of trainer engagement and training content were all above average (4/5). The open-ended questions resulted in 678 comments indicating that participants gained significant support from other caregivers and healthcare professionals in the alliance and wanted more and continuously updated material. CONCLUSION: This study demonstrated that C2C effectively improved the development of caregivers' knowledge, skills, and their self-care ability. Available social support for caregivers was better than average, including professional support and peer support.

Multi-omics pan-cancer analysis reveals the prognostic values and immunological functions of PPA2, with a spotlight on breast cancer.

Background: Recently, the role of inorganic pyrophosphatase 2 (PPA2) has been remaining merely superficial in many tumors. Hence, the aim was to analyze the potential functions of PPA2 in pan-cancer, focusing on its role in breast cancer. Methods: A systematic pan-cancer analysis conducted primarily utilizing various open databases such as TCGA and GTEx. We explored the clinical value of PPA2 as well as various biological functions, including expression levels and subcellular localization, multi-dimensional immune-correlation analysis, co-expression networks, and gene heterogeneity. In addition, we not only verified the function of PPA2 through cell experiments but also analyzed PPA2 at the single-cell level and its drug sensitivity. Results: PPA2 is abnormally expressed in various tumors, and it is mainly distributed in mitochondria. Furthermore, the indicators (OS, DSS, DFI, and PFI) of analysis hint that PPA2 exhibits significant prognostic value. At the same time, the genomic heterogeneity (including TMB, MSI, MATH, and NEO) of PPA2 in pan-cancer was analyzed. Across multiple tumors, the results showed a close correlation between PPA2 expression levels and different immune signatures (such as immune cell infiltration). All of these indicate that PPA2 could potentially be applied in the guidance of immunotherapy. We also have demonstrated that PPA2 promoted the process of breast cancer. Finally, some potential therapeutic agents (such as Fulvestrant) targeting the abnormal expression of PPA2 are revealed. Conclusion: In conclusion, the results demonstrated the great value of PPA2 in pan-cancer research, as well as its potential as a therapeutic target for breast tumors.

Acquired methemoglobinemia in a third trimester puerpera and her premature infant with sodium nitrite poisoning: A case report.

BACKGROUND: The common cause of sodium nitrite poisoning has shifted from previous accidental intoxication by exposure or ingestion of contaminated water and food to recent alarming intentional intoxication as an employed method of suicide/exit. The subsequent formation of methemoglobin (MetHb) restricts oxygen transport and utilization in the body, resulting in functional hypoxia at the tissue level. In clinical practice, a mismatch of cyanotic appearance and oxygen partial pressure usually contributes to the identification of methemoglobinemia. Prompt recognition of characteristic mismatch and accurate diagnosis of sodium nitrite poisoning are prerequisites for the implementation of standardized systemic interventions. CASE SUMMARY: A pregnant woman was admitted to the Department of Critical Care Medicine at the First Affiliated Hospital of Harbin Medical University due to consciousness disorders and drowsiness 2 h before admission. Subsequently, she developed vomiting and cyanotic skin. The woman underwent orotracheal intubation, invasive mechanical ventilation (IMV), and correction of internal environment disturbance in the ICU. Her premature infant was born with a higher-than-normal MetHb level of 3.3%, and received detoxification with methylene blue and vitamin C, supplemental vitamin K1, an infusion of fresh frozen plasma, as well as respiratory support via orotracheal intubation and IMV. On day 3 after admission, the puerpera regained consciousness, evacuated the IMV, and resumed enteral nutrition. She was then transferred to the maternity ward 24 h later. On day 7 after admission, the woman recovered and was discharged without any sequelae. CONCLUSION: MetHb can cross through the placental barrier. Level of MetHb both reflects severity of the sodium nitrite poisoning and serves as feedback on therapeutic effectiveness.

Dynamic lymphocyte-CRP ratio as a predictor: a single-centre retrospective study on disease severity and progression in adult COVID-19 patients.

OBJECTIVE: To assess the efficacy of dynamic changes in lymphocyte-C-reactive protein ratio (LCR) on differentiating disease severity and predicting disease progression in adult patients with Coronavirus disease 2019 (COVID-19). METHODS: This single-centre retrospective study enrolled adult COVID-19 patients categorized into moderate, severe and critical groups according to the Diagnosis and Treatment of New Coronavirus Pneumonia (ninth edition). Demographic and clinical data were collected. LCR and sequential organ failure assessment (SOFA) score were calculated. Lymphocyte count and C-reactive protein (CRP) levels were monitored on up to four occasions. Disease severity was determined concurrently with each LCR measurement. RESULTS: This study included 145 patients assigned to moderate (n = 105), severe (n = 33) and critical groups (n = 7). On admission, significant differences were observed among different disease severity groups including age, comorbidities, neutrophil proportion, lymphocyte count and proportion, D-Dimer, albumin, total bilirubin, direct bilirubin, indirect bilirubin, CRP and SOFA score. Dynamic changes in LCR showed significant differences across different disease severity groups at different times, which were significantly inversely correlated with disease severity of COVID-19, with correlation coefficients of -0.564, -0.548, -0.550 and -0.429 at four different times. CONCLUSION: Dynamic changes in LCR can effectively differentiate disease severity and predict disease progression in adult COVID-19 patients.

Preparation, structural characterization, biological activity, and nutritional applications of oligosaccharides.

Oligosaccharides are low-molecular-weight carbohydrates between monosaccharides and polysaccharides. They can be extracted directly from natural products by physicochemical methods or obtained by chemical synthesis or enzymatic reaction. Oligosaccharides have important physicochemical and physiological properties. Their research and production involve many disciplines such as medicine, chemical industry, and biology. Functional oligosaccharides, as an excellent functional food base, can be used as dietary fibrer and prebiotics to enrich the diet; improve the microecology of the gut; exert antitumour, anti-inflammatory, antioxidant, and lipid-lowering properties. Therefore, the industrial applications of oligosaccharides have increased rapidly in the past few years. It has great prospects in the field of food and medicinal chemistry. This review summarized the preparation, structural features and biological activities of oligosaccharides, with particular emphasis on the application of functional oligosaccharides in the food industry and human nutritional health. It aims to inform further research and development of oligosaccharides and food chemistry.