Plant receptor-like protein activation by a microbial glycoside hydrolase.

Plants rely on cell-surface-localized pattern recognition receptors to detect pathogen- or host-derived danger signals and trigger an immune response1-6. Receptor-like proteins (RLPs) with a leucine-rich repeat (LRR) ectodomain constitute a subgroup of pattern recognition receptors and play a critical role in plant immunity1-3. Mechanisms underlying ligand recognition and activation of LRR-RLPs remain elusive. Here we report a crystal structure of the LRR-RLP RXEG1 from Nicotiana benthamiana that recognizes XEG1 xyloglucanase from the pathogen Phytophthora sojae. The structure reveals that specific XEG1 recognition is predominantly mediated by an amino-terminal and a carboxy-terminal loop-out region (RXEG1(ID)) of RXEG1. The two loops bind to the active-site groove of XEG1, inhibiting its enzymatic activity and suppressing Phytophthora infection of N. benthamiana. Binding of XEG1 promotes association of RXEG1(LRR) with the LRR-type co-receptor BAK1 through RXEG1(ID) and the last four conserved LRRs to trigger RXEG1-mediated immune responses. Comparison of the structures of apo-RXEG1(LRR), XEG1-RXEG1(LRR) and XEG1-BAK1-RXEG1(LRR) shows that binding of XEG1 induces conformational changes in the N-terminal region of RXEG1(ID) and enhances structural flexibility of the BAK1-associating regions of RXEG1(LRR). These changes allow fold switching of RXEG1(ID) for recruitment of BAK1(LRR). Our data reveal a conserved mechanism of ligand-induced heterodimerization of an LRR-RLP with BAK1 and suggest a dual function for the LRR-RLP in plant immunity.

Convergent evolution of immune receptors underpins distinct elicitin recognition in closely related Solanaceous plants.

Elicitins are a large family of secreted proteins in Phytophthora. Clade 1 elicitins were identified decades ago as potent elicitors of immune responses in Nicotiana species, but the mechanisms underlying elicitin recognition are largely unknown. Here we identified an elicitin receptor in Nicotiana benthamiana that we named REL for Responsive to ELicitins. REL is a receptor-like protein (RLP) with an extracellular leucine-rich repeat (LRR) domain that mediates Phytophthora resistance by binding elicitins. Silencing or knocking out REL in N. benthamiana abolished elicitin-triggered cell death and immune responses. Domain deletion and site-directed mutagenesis revealed that the island domain (ID) located within the LRR domain of REL is crucial for elicitin recognition. In addition, sequence polymorphism in the ID underpins the genetic diversity of REL homologs in various Nicotiana species in elicitin recognition and binding. Remarkably, REL is phylogenetically distant from the elicitin response (ELR) protein, an LRR-RLP that was previously identified in the wild potato species Solanum microdontum and REL and ELR differ in the way they bind and recognize elicitins. Our findings provide insights into the molecular basis of plant innate immunity and highlight a convergent evolution of immune receptors towards perceiving the same elicitor.

BAK1 protects the receptor-like kinase BIR2 from SNIPER2a/b-mediated degradation to promote pattern-triggered immunity in Nicotiana benthamiana.

The detection of microbial infections by plants induces the rapid formation of immune receptor complexes at the plasma membrane. However, how this process is controlled to ensure proper immune signaling remains largely unknown. Here, we found that the Nicotiana benthamiana membrane-localized leucine-rich repeat receptor-like kinase BAK1-INTERACTING RLK 2 (NbBIR2) constitutively associates with BRI1-ASSOCIATED RECEPTOR KINASE 1 (NbBAK1) in vivo and in vitro and promotes complex formation with pattern recognition receptors. In addition, NbBIR2 is targeted by 2 RING-type ubiquitin E3 ligases, SNC1-INFLUENCING PLANT E3 LIGASE REVERSE 2a (NbSNIPER2a) and NbSNIPER2b, for ubiquitination and subsequent degradation in planta. NbSNIPER2a and NbSNIPER2b interact with NbBIR2 in vivo and in vitro and are released from NbBIR2 upon treatment with different microbial patterns. Furthermore, accumulation of NbBIR2 in response to microbial patterns is tightly associated with NbBAK1 abundance in N. benthamiana. NbBAK1 acts as a modular protein that stabilizes NbBIR2 by competing with NbSNIPER2a or NbSNIPER2b for association with NbBIR2. Similar to NbBAK1, NbBIR2 positively regulates pattern-triggered immunity and resistance to bacterial and oomycete pathogens in N. benthamiana, whereas NbSNIPER2a and NbSNIPER2b have the opposite effect. Together, these results reveal a feedback regulatory mechanism employed by plants to tailor pattern-triggered immune signaling.

TH1L involvement in colorectal cancer pathogenesis by regulation of CCL20 through the NF-κB signalling pathway.

TH1L (also known as NELF-C/D) is a member of the Negative Elongation Factor (NELF) complex, which is a metazoan-specific factor that regulates RNA Polymerase II (RNAPII) pausing and transcription elongation. However, the function and molecular mechanisms of TH1L in cancer progression are still largely unknown. In this study, we found that TH1L was highly expressed in colorectal cancer (CRC) tissues and the faeces of CRC patients. Overexpression of TH1L significantly enhanced the proliferation and migration of CRC cells, while its knockdown markedly suppressed these processes. In mechanism, RNA sequencing revealed that CCL20 was upregulated in TH1L-overexpressed CRC cells, leading to activation of the NF-κB signalling pathway. Rescue assays showed that knockdown of CCL20 could impair the tumour-promoting effects of THIL in CRC cells. Taken together, these results suggest that TH1L may play a vital role via the CCL20/NF-κB signalling pathway in CRC proliferation and migration and may serve as a potential target for diagnosis and therapy of CRC.

The ETI-dependent receptor-like kinase 1 positively regulates effector-triggered immunity by stabilizing NLR-required for cell death 4 in Nicotiana benthamiana.

Leucine-rich repeat receptor-like kinases (LRR-RLKs) comprise the largest class of membrane-localized receptor-like kinases in plants. Leucine-rich repeat receptor-like kinases are key immune sectors contributing to pattern-triggered immunity (PTI), but whether LRR-RLK mediates effector-triggered immunity (ETI) in plants remains unclear. In this study, we evaluated the function of LRR-RLKs in regulating ETI by using a virus-induced gene silencing (VIGS)-based reverse genetic screening assay, and identified a LRR-RLK named ETI-dependent receptor-like kinase 1 (EDK1) required for ETI triggered by the avirulence effector AVRblb2 secreted by Phytophthora infestans and its cognate receptor Rpi-blb2. Silencing or knockout of EDK1 compromised immunity mediated by Rpi-blb2 and the cell death triggered by recognition of AVRblb2. NLR-required for cell death 4 (NRC4), a signaling component acts downstream of Rpi-blb2, was identified that interacts with EDK1 using the LC-MS analysis and the interaction was further evaluated by co-immunoprecipitation. EDK1 promotes protein accumulation of NRC4 in a kinase-dependent manner and positively regulates resistance to P. infestans in Nicotiana benthamiana. Our study revealed that EDK1 positively regulates plant ETI through modulating accumulation of the NLR signaling component NRC4, representing a new regulatory role of the membrane-localized LRR-RLKs in plant immunity.

Construction of a Three-Phase MnS2/Co4S3/Ni3S2 Heterostructure for Boosting Oxygen Evolution.

The rational construction of highly efficient electrocatalysts for the oxygen evolution reaction (OER) plays a critical role in energy conversion systems. Designing heterostructures is a common and effective strategy to improve the performance of electrocatalysts. In this paper, an MnS2/Co4S3/Ni3S2 heterostructure was synthesized on Ni foam using a one-step vulcanization method. It provides a modified electronic structure and plentiful three-phase heterogeneous interfaces that can effectively enrich the active sites and accelerate electron transfer, thereby improving the OER activity. Thanks to the heterostructure, the MnS2/Co4S3/Ni3S2 exhibits a low overpotential of 265 and 304 mV for the OER to reach current densities of 50 and 100 mA/cm2, respectively. Furthermore, the surface reconstruction of MnS2/Co4S3/Ni3S2 has been investigated, which revealed the formation of metal hydr(oxy)oxides evolved during the OER process. This work provides a facile strategy for constructing three-phase heterostructures, shedding light on the development of high-performance, nonprecious metal-based OER electrocatalysts.

Factors related to suicidal ideation of schizophrenia patients in China: a study based on decision tree and logistic regression model.

This study aimed to investigate the factors associated with suicidal ideation in schizophrenia patients in China using decision tree and logistic regression models. From October 2020 to March 2022, patients with schizophrenia were chosen from Chifeng Anding Hospital and Daqing Third Hospital in Heilongjiang Province. A total of 300 patients with schizophrenia who met the inclusion criteria were investigated by questionnaire. The questionnaire covered general data, suicidal ideation, childhood trauma, social support, depressive symptoms and psychological resilience. Logistic regression analysis revealed that childhood trauma and depressive symptoms were risk factors for suicidal ideation in schizophrenia (OR = 2.330, 95%CI: 1.177 ~ 4.614; OR = 10.619, 95%CI: 5.199 ~ 21.688), while psychological resilience was a protective factor for suicidal ideation in schizophrenia (OR = 0.173, 95%CI: 0.073 ~ 0.409). The results of the decision tree model analysis demonstrated that depressive symptoms, psychological resilience and childhood trauma were influential factors for suicidal ideation in patients with schizophrenia (p < 0.05). The area under the ROC for the logistic regression model and the decision tree model were 0.868 (95% CI: 0.821 ~ 0.916) and 0.863 (95% CI: 0.814 ~ 0.912) respectively, indicating excellent accuracy of the models. Meanwhile, the logistic regression model had a sensitivity of 0.834 and a specificity of 0.743 when the Youden index was at its maximum. The decision tree model had a sensitivity of 0.768 and a specificity of 0.8. Decision trees in combination with logistic regression models are of high value in the study of factors influencing suicidal ideation in schizophrenia patients.

Relationship between medication burden and medication experience in stable patients with schizophrenia: the mediating effect of medication belief.

BACKGROUND: Individuals with schizophrenia require prolonged antipsychotic medication treatment. But more than 50% of individuals with schizophrenia experience adverse medication experiences during their antipsychotic treatments. Such individuals often adjust or discontinue medication, leading to disease relapse and impaired social functioning. Psychiatric nurses should pay close attention to the medication experiences of individuals with schizophrenia. This research explore the relationship between medication burden and medication experience, as well as the mediating effect of medication belief in stable patients with schizophrenia. METHODS: A convenience sample of hospitalized stable patients with schizophrenia were selected from Daqing Third Hospital and Baiyupao Hospital from September 2023 to December 2023. A survey was conducted with them using a questionnaire consisting of general information questionnaire, The Subjective Well-being Under Neuroleptic Treatment Scale(SWN), The Living with Medicines Questionnaire(LMQ), Beliefs about Medicines Questionnaire-Specific (BMQ-Specific). Pearson correlation analysis was used to explore the correlation between LMQ, BMQ-Specific and SWN scores, and multiple linear regression analysis was used to explore the influencing factors of medication experience in patients with schizophrenia. AMOS 24.0 was used to construct the structural equation modeling(SEM), and the mediation effect of the SEM was tested using Bootstrap method. RESULTS: According to the sample size calculation requirements of structural equation model, a total of 300 samples were required in this study, and 400 effective questionnaires were actually collected in this study, which met the sample size requirements for constructing structural equation models. Bootstrap test showed that the mediation effect was significant. The total effect of medication burden on medication experience was significant (Z=-12.146, 95%CI (-0.577, -0.417), P < 0.001). The indirect effect of medication burden on medication experience, that is, the mediating effect of medication belief was significant (Z=-4.839, 95%CI (-0.217, -0.096), P < 0.001). The direct effect of medication burden on medication experience was significant (Z=-7.565, 95%CI (-0.437, -0.257), P < 0.001). This model belongs to partial mediation model. CONCLUSIONS: Psychiatric nurses can enhance the patients' medication experience by reducing medication burden and strengthening medication beliefs. Therefore, the results also provide theoretical references and decision-making foundations for psychiatric nursing professionals to develop appropriate management strategies for individuals with schizophrenia.

MiR-652-3p promotes malignancy and metastasis of cancer cells via inhibiting TNRC6A in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) was one of the most prevalent life-threatening cancers. Metastasis is the leading cause of cancer-related death in HCC. MiRNAs play essential roles in cancer metastasis. METHODS: Expression of miR-652-3p in HCC was assessed. Function experiments of miR-652-3p and trinucleotide repeat-containing gene 6A protein (TNRC6A) were performed both in vitro and in vivo. mRNA sequencing, PCR, and western blot were performed to verify the target genes and pathway of miR-652-3p. The lung metastasis and xenograft cancer model in nude mice was established to investigate the effects of the miR-652-3p and TRNC6A on tumor metastasis in vivo. The relationship between the expression of the miR-652-3p, TNRC6A and the prognosis of HCC patients was analyzed. RESULTS: Upregulated miR-652-3p was found in the tumor tissues of HCC, especially in metastatic HCC patients. Overexpression of miR-652-3p promoted and knockdown of miR-652-3p suppressed HCC metastasis both in vitro and in vivo. MiR-652-3p promoted HCC metastasis via regulating the EMT pathway. TNRC6A was identified as a direct target of miR-652-3p, and the knockdown of TNRC6A restored repressed EMT and HCC metastasis caused by the inhibition of miR-652-3p. Clinical results revealed that high expression of miR-652-3p and low expression of TNRC6A were positively correlated to shortened overall survival and disease-free survival in HCC patients. CONCLUSIONS: MiR-652-3p promotes EMT and HCC metastasis by inhibiting TNRC6A expression in HCC. MiR-652-3p and TNRC6A may serve as potential biomarkers to predict prognosis in HCC patients with metastasis.

Construction and verification of aggressive behavior risk prediction model in stable patients with schizophrenia.

BACKGROUND: Among all types of mental disorders, individuals with schizophrenia exhibit the highest frequency of aggressive behavior. This disrupts the healthcare environment and poses threats to family life and social harmony. Present approaches fail to identify individuals with schizophrenia who are predisposed to aggressive behavior. In this study, we aimed to construct a risk prediction model for aggressive behavior in stable patients with schizophrenia, which may facilitate early identification of patients who are predisposed to aggression by assessing relevant factors, enabling the management of high-risk groups to mitigate and prevent aggressive behavior. METHODS: A convenience sample of stable inpatients with schizophrenia were selected from Daqing Municipal Third Hospital and Chifeng Municipal Anding Hospital from March 2021 to July 2023. A total of 429 patients with stable schizophrenia who met the inclusion criteria were included. A survey was conducted with them using a questionnaire consisting of general information questionnaire, Positive and Negative Symptom Scale, Childhood Trauma Questionnaire-Short Form, Connor-Davidson Resilience Scale and Self-esteem Scale. Patients enrolled in this study were divided into aggressive and non-aggressive groups based on whether there was at least one obvious and recorded personal attack episode (including obvious wounding and self-injurious behavior) following diagnosis. Binary Logistic regression was used to determine the influencing factors, and R software was used to establish a nomogram model for predicting the risk of aggressive behavior. Bootstrap method was used for internal validation of the model, and the validation group was used for external validation. C statistic and calibration curve were used to evaluate the prediction performance of the model. RESULTS: The model variables included Age, Duration of disease, Positive symptom, Childhood Trauma, Self-esteem and Resilience. The AUROC of the model was 0.790 (95% CI:0.729-0.851), the best cutoff value was 0.308; the sensitivity was 70.0%; the specificity was 81.4%; The C statistics of internal and external validation were 0.759 (95%CI:0.725-0.814) and 0.819 (95%CI:0.733-0.904), respectively; calibration curve and Brier score showed good fit. CONCLUSIONS: The prediction model has a good degree of discrimination and calibration, which can intuitively and easily screen the high risk of aggressive behavior in stable patients with schizophrenia, and provide references for early screening and intervention.

Perception of risk of relapse among patients with first episode and recurrent schizophrenia: a descriptive phenomenological study.

BACKGROUND: Patients suffering from schizophrenia are at a higher risk of relapse. The perception of the risk of relapse in patients is critical for relapse prevention. In the field of psychiatry, the study of risk perception of relapse has been neglected. METHODS: We carried out a qualitative study using a descriptive phenomenological approach. Data were collected at two psychiatric hospitals in China. In total, 22 patients with schizophrenia were recruited through purposive sampling. Face to face semi-structured in-depth interviews were conducted. Interview recordings were transcribed by the research team, and transcripts were analysed by two independent coders with Colaizzi's descriptive analysis framework. The consolidated criteria for reporting qualitative research checklist were used for reporting. RESULTS: The data of first-episode patients yielded three themes: (i) lack of knowledge about disease recognition and medical treatment; (ii) overoptimistic estimation of the risk of relapse; (iii) perceived importance of treatment. For first-relapse patients : (i) initial awareness of relapse warning signs; (ii) lack of systematic and accurate assessment of disease information; (iii) the perception that drug withdrawal is related to relapse. Patients with multiple relapses: (i) susceptibility to relapse: confusion and powerlessness; (ii) the severity of relapse: suicidal thoughts and behavior; (iii) effects of perceived benefits and barriers of medication behaviour. CONCLUSIONS: In schizophrenic patients with first-episode, first-relapse, and multiple relapses, there were dynamic changes in the perception of disease relapse risk and medication behaviour. Medical workers must improve risk awareness education. They should provide patients with scientific, accurate, and timely communication channels, and dynamically assess and manage the risk of relapse in various patients.

The relationship between depression and subjective cognitive decline in older adults of China: the mediating role of general self-efficacy.

Subjective cognitive decline (SCD) is common in older adults and may also be an early marker for future cognitive impairment. Depression is an important influencing factor for subjective cognitive decline in old age. However, the mediating effects of general self-efficacy in depression and subjective cognition are yet to be explored. This study included 308 participants who were ≥60 years. Participants were asked to complete the self-report measures of the Geriatric Depression Scale-15 (GDS-15), Subjective Cognitive Decline-Questionnaire (SCD-Q), and General Self-Efficacy Scale (GSES). We used correlations, regressions, and structural equation models for the analyses. The bootstrapping method was performed to confirm the mediation effect. The subjective cognitive decline was found to be significantly and positively correlated to depression. Bootstrapping mediation analyses indicated that depression could affect SCD not only directly but also indirectly through general self-efficacy. General self-efficacy partly played a mediating role between depression and SCD. Hence, community workers and clinicians should actively help the elderly experiencing low levels of general self-efficacy to reduce their SCD.

The relationship between self-esteem and mental disability in patients with schizophrenia: the mediating role of resilience and the moderating role of gender.

This study aims to verify the mediating role of resilience between self-esteem and mental disability and to analyze the moderating role of gender in the relationship between resilience and mental disability in patients with schizophrenia. Patients with schizophrenia have been selected from Harbin Psychiatric (Baiyupao) Hospital and Daqing Third Hospital in Heilongjiang Province from January to December 2021. The study recruited a total of 220 patients with schizophrenia, including 120 males and 100 females to measure their self-esteem, resilience and mental disability. The results were as follows: Self-esteem and resilience are important protective factors that have a buffering effect on mental disability. The mediating effect of resilience on self-esteem and mental disability is stronger in males than in females. The results provide new ideas for delaying mental disability and for formulating intervention programs and applying them to clinical practice. The study indicates that psychiatric medical staff should not only treat the patients with schizophrenia psychotic symptoms but also improve their self-esteem and resilience through effective intervention to reduce the occurrence of mental disability.

Optimization of a peptide ligand for the adhesion GPCR ADGRG2 provides a potent tool to explore receptor biology.

The adhesion GPCR ADGRG2, also known as GPR64, is a critical regulator of male fertility that maintains ion/pH homeostasis and CFTR coupling. The molecular basis of ADGRG2 function is poorly understood, in part because no endogenous ligands for ADGRG2 have been reported, thus limiting the tools available to interrogate ADGRG2 activity. It has been shown that ADGRG2 can be activated by a peptide, termed p15, derived from its own N-terminal region known as the Stachel sequence. However, the low affinity of p15 limits its utility for ADGRG2 characterization. In the current study, we used alanine scanning mutagenesis to examine the critical residues responsible for p15-induced ADGRG2 activity. We next designed systematic strategies to optimize the peptide agonist of ADGRG2, using natural and unnatural amino acid substitutions. We obtained an optimized ADGRG2 Stachel peptide T1V/F3Phe(4-Me) (VPM-p15) that activated ADGRG2 with significantly improved (>2 orders of magnitude) affinity. We then characterized the residues in ADGRG2 that were important for ADGRG2 activation in response to VPM-p15 engagement, finding that the toggle switch W6.53 and residues of the ECL2 region of ADGRG2 are key determinants for VPM-p15 interactions and VPM-p15-induced Gs or arrestin signaling. Our study not only provides a useful tool to investigate the function of ADGRG2 but also offers new insights to guide further optimization of Stachel peptides to activate adhesion GPCR members.

Plasmonic Hydrogen Sensors.

Hydrogen is regarded as the ultimate fuel and energy carrier with a high theoretical energy density and universality of sourcing. However, hydrogen is easy to leak and has a wide flammability range in air. For safely handling hydrogen, robust sensors are in high demand. Plasmonic hydrogen sensors (PHS) are attracting growing interest due to the advantages of high sensitivity, fast response speed, miniaturization, and high-degree of integration, etc. In this review, the mechanism and recent development (mainly after the year 2015) of hydrogen sensors based on plasmonic nanostructures are presented. The working principle of PHS is introduced. The sensing properties and the effects of resonance mode, configuration, material, and structure of the plasmonic nanostructures on the sensing performances are discussed. The merit and demerit of different types of plasmonic nanostructures are summarized and potential development directions are proposed. The aim of this review is not only to clarify the current strategies for PHS, but also to give a comprehensive understanding of the working principle of PHS, which may inspire more ingenious designs and execution of plasmonics for advanced hydrogen sensors.

Phytophthora sojae apoplastic effector AEP1 mediates sugar uptake by mutarotation of extracellular aldose and is recognized as a MAMP.

Diseases caused by Phytophthora pathogens devastate many crops worldwide. During infection, Phytophthora pathogens secrete effectors, which are central molecules for understanding the complex plant-Phytophthora interactions. In this study, we profiled the effector repertoire secreted by Phytophthora sojae into the soybean (Glycine max) apoplast during infection using liquid chromatography-mass spectrometry. A secreted aldose 1-epimerase (AEP1) was shown to induce cell death in Nicotiana benthamiana, as did the other two AEP1s from different Phytophthora species. AEP1 could also trigger immune responses in N. benthamiana, other Solanaceae plants, and Arabidopsis (Arabidopsis thaliana). A glucose dehydrogenase assay revealed AEP1 encodes an active AEP1. The enzyme activity of AEP1 is dispensable for AEP1-triggered cell death and immune responses, while AEP-triggered immune signaling in N. benthamiana requires the central immune regulator BRASSINOSTEROID INSENSITIVE 1-associated receptor kinase 1. In addition, AEP1 acts as a virulence factor that mediates P. sojae extracellular sugar uptake by mutarotation of extracellular aldose from the α-anomer to the ß-anomer. Taken together, these results revealed the function of a microbial apoplastic effector, highlighting the importance of extracellular sugar uptake for Phytophthora infection. To counteract, the key effector for sugar conversion can be recognized by the plant membrane receptor complex to activate plant immunity.

Transcriptome expression profiles associated with diabetic nephropathy development.

The objective of this study was to identify different transcriptome expression profiles involved in the pathogenesis of diabetic nephropathy (DN) and to illustrate the diagnostic and therapeutic potential of mRNAs, long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs) in DN progression. The participants were divided into four groups: normoalbuminuria (group DM), microalbuminuria (group A2), macroalbuminuria (group A3) and healthy controls (group N). There were three individuals in each group for sequencing. Transcriptome sequencing analysis was performed on the peripheral blood of all the participants to identify the differential expression of mRNAs, lncRNAs, and circRNAs between intervention groups and controls. The functional enrichment analysis, the short time-series expression miner (STEM) program, and the miRNA-circRNA-mRNA network were further conducted. To verify the reproducibility of transcriptome sequencing, 10 and 30 blood samples were collected from the control and diseased groups, respectively. Four candidate biomarkers were selected from differentially expressed circRNAs (circ_0005379, circ_0002024, and circ_0000567, and circ_0001017) and their concentrations in the blood were measured using quantitative PCR (qPCR). In the comparison of A2 with N, 549 mRNAs, 1259 lncRNAs, and 12 circRNAs were screened. In the comparison of A3 with N, 1217 mRNAs, 1613 lncRNAs, and 24 circRNAs were screened. Moreover, in the comparison of diabetes mellitus (DM) with N, 948 mRNAs, 1495 lncRNAs, and 25 circRNAs were screened. Functional enrichment analysis showed that differentially expressed mRNAs were related to insulin secretion, insulin resistance, and inflammation, while differentially expressed lncRNAs were mainly associated with crossover junction endodeoxyribonuclease activity. In STEM analysis, a total of 481 mRNAs and 152 differential expression circRNAs showed a significant tendency. The key relationships in the miRNA-circRNA-mRNA network were identified, such as hsa-miR-103a-3p-circ_0005379-PTEN, hsa-miR-497-5p-circ_0002024-IGF1R and hsa-miR-1269a-circ_0000567-SOX6. In addition, qPCR showed consistent results with RNA sequencing. We found that differentially expressed mRNAs, lncRNAs, and circRNAs participated in DN development. Circ_0005379, circ_0002024, and circ_0000567 could be adopted as potential biomarkers for DN.

Gene signature for the prediction of the trajectories of sepsis-induced acute kidney injury.

BACKGROUND: Acute kidney injury (AKI) is a common complication in sepsis. However, the trajectories of sepsis-induced AKI and their transcriptional profiles are not well characterized. METHODS: Sepsis patients admitted to centres participating in Chinese Multi-omics Advances In Sepsis (CMAISE) from November 2020 to December 2021 were enrolled, and gene expression in peripheral blood mononuclear cells was measured on Day 1. The renal function trajectory was measured by the renal component of the SOFA score (SOFArenal) on Days 1 and 3. Transcriptional profiles on Day 1 were compared between these renal function trajectories, and a support vector machine (SVM) was developed to distinguish transient from persistent AKI. RESULTS: A total of 172 sepsis patients were enrolled during the study period. The renal function trajectory was classified into four types: non-AKI (SOFArenal = 0 on Days 1 and 3, n = 50), persistent AKI (SOFArenal > 0 on Days 1 and 3, n = 62), transient AKI (SOFArenal > 0 on Day 1 and SOFArenal = 0 on Day 3, n = 50) and worsening AKI (SOFArenal = 0 on Days 1 and SOFArenal > 0 on Day 3, n = 10). The persistent AKI group showed severe organ dysfunction and prolonged requirements for organ support. The worsening AKI group showed the least organ dysfunction on day 1 but had higher serum lactate and prolonged use of vasopressors than the non-AKI and transient AKI groups. There were 2091 upregulated and 1,902 downregulated genes (adjusted p < 0.05) between the persistent and transient AKI groups, with enrichment in the plasma membrane complex, receptor complex, and T-cell receptor complex. A 43-gene SVM model was developed using the genetic algorithm, which showed significantly greater performance predicting persistent AKI than the model based on clinical variables in a holdout subset (AUC: 0.948 [0.912, 0.984] vs. 0.739 [0.648, 0.830]; p < 0.01 for Delong's test). CONCLUSIONS: Our study identified four subtypes of sepsis-induced AKI based on kidney injury trajectories. The landscape of host response aberrations across these subtypes was characterized. An SVM model based on a gene signature was developed to predict renal function trajectories, and showed better performance than the clinical variable-based model. Future studies are warranted to validate the gene model in distinguishing persistent from transient AKI.

Comparative study on the gastrointestinal- and immune- regulation functions of Hedysari Radix Paeparata Cum Melle and Astragali Radix Praeparata cum Melle in rats with spleen-qi deficiency, based on fuzzy matter-element analysis.

CONTEXT: Hedysari Radix Praeparata Cum Melle (HRPCM) and Astragali Radix Praeparata Cum Melle (ARPCM) are used interchangeably in clinics to treat spleen-qi deficiency (SQD) symptom mainly including gastrointestinal dysfunction and decreased immunity, which has unknown differences in efficacy. OBJECTIVE: To investigate the differences between HRPCM and ARPCM on intervening gastrointestinal- and immune-function with SQD syndrome. MATERIALS AND METHODS: After the SQD model was established, the Sprague-Dawley (SD) rats were randomly divided into nine groups (n = 10): normal; model; Bu-Zhong-Yi-Qi Pills; 18.9, 12.6 and 6.3 g/kg dose groups of HRPCM and ARPCM. Gastrointestinal function including d-xylose, gastrin, amylase vasoactive intestinal peptide, motilin, pepsin, H+/K+-ATPase, Na+/K+-ATPase, sodium-glucose cotransporter 1 (SGLT1), glucose transporter 2 (GLUT2) and immune function including spleen and thymus index, blood routine, interleukin (IL)-2, IL-6, interferon-γ (IFN-γ), tumour necrosis factor-α (TNF-α), immunoglobulin (Ig) M, IgA, IgG and delayed-type hypersensitivity (DTH) were detected. Finally, the efficacy differences were analysed comprehensively by the fuzzy matter-element method. RESULTS: In regulating immune, the doses differences in efficacy between HRPCM and ARPCM showed in the high-dose (18.9 g/kg), but there were no differences in the middle- and low- dose (12.6 and 6.37 g/kg); the efficacy differences were primarily reflected in levels of IL-6, IFN-γ, TNF-α and IgM in serum, and the mRNA expression of IL-6 and IFN-γ in the spleen. In regulating gastrointestinal, the efficacy differences were primarily reflected in the levels of D-xylose, MTL, and GAS in serum, and the mRNA and protein expression of SGLT1 and GLUT2 in jejunum and ileum. DISCUSSION AND CONCLUSIONS: HRPCM is more effective than ARPCM on regulating gastrointestinal function and immune function with SQD syndrome. Therefore, we propose that HRPCM should be mainly used to treat SQD syndrome in the future.

Double Lock Label Based on Thermosensitive Polymer Hydrogels for Information Camouflage and Multilevel Encryption.

Developing extra safety encryption technologies to prevent information leakage and combat fakes is in high demand but is challenging. Herein, we propose a "double lock" strategy based on both lower critical solution temperature (LCST) and upper critical solution temperature (UCST) polymer hydrogels for information camouflage and multilevel encryption. Two types of hydrogels were synthesized by the method of random copolymerization. The number of -CO-NH2 groups in the network structure of the hydrogels changed the enthalpic or entropic thermo-responsive hydrogels, and ultimately precisely controlled their phase transition temperature. The crosslink density of the polymer hydrogels governs the diffusion kinetics, resulting in a difference in the time for their color change. The combination of multiple LCST and UCST hydrogels in one label realized information encryption and dynamic information identification in the dimensions of both time and temperature. This work is highly interesting for the fields of information encryption, anti-counterfeiting, and smart responsive materials.