Analysis of lake changes and their influence factors in the three river regions from 2000 to 2020 in the Sanjiangyuan Region, China.

An important factor for investigating climate change in the Sanjiangyuan is the evolution of the spatio-temporal pattern of lakes in this region. The present study used the Google Earth Engine (GEE) platform to extract lakes from 2000 to 2020. The present approach created a lake distribution dataset yearly and analyzed spatial and temporal patterns over 20 years. The analysis of lakes focused on the reaction of the Sanjiangyuan Lakes area to changes in climate, glaciers, and permafrost. The findings indicated that the Sanjiangyuan region contains 143 lakes, the majority of which are predominantly small, measuring 1-10 km2. The small lakes account for 60.14 % of the total and are primarily located in the source regions of the Yangtze River and Yellow River. The findings demonstrated that the Sanjiangyuan lakes experienced a significant expansion over the past two decades, particularly from 2011 to 2020. These lakes are divided into expanded, atrophic, and stable categories. Expanded lakes showed significant inter-annual trends in expansion, while atrophic lakes showed smaller fluctuations. The area of stable lakes experienced a consistent decline after 2010, despite a consistent expansion tendency from 2001 to 2010. Moreover, the results indicated that alterations in the size of glaciers and ice reserves in the Sanjiangyuan region have had the greatest influence on the fluctuation in lake area. Among the factors that affect the climate, temperature had the most significant effect on the change in lake area, followed by precipitation.

Activation of Bi2MoO6/Zn0.5Cd0.5S charge transfer through interface chemical bonds and surface defects for photothermal catalytic CO2 reduction.

The photocatalytic reduction of CO2 to high-value fuels has been proposed as a solution to the energy crisis caused by the depletion of energy resources. Despite significant advancements in photocatalytic CO2 reduction catalyst development, there are still limitations such as poor CO2 adsorption/activation and low charge transfer efficiency. In this study, we employed a defect-induced heterojunction strategy to construct atomic-level interface Cd-O bonds and form Bi2MoO6/Zn0.5Cd0.5S heterojunctions. The sulfur vacancies (VS) formed in Bi2MoO6/Zn0.5Cd0.5S acted as activation sites for CO2 adsorption. While the interfacial stability provided by the Cd-O bonds served as an electron transfer channel that facilitated the movement of electrons from the interface to the catalytic site. The VS and Cd-O bonds simultaneously influence the distribution of charge, inducing the creation of an interface electric field that facilitates the upward displacement of the center of the d-band. This enhances the adsorption of reaction intermediates. The optimized Bi2MoO6/Zn0.5Cd0.5S heterostructure exhibited high selectivity and stability of photoelectrochemical properties for CO, generating 42.97 µmol⋅g-1⋅h-1 of CO, which was 16.65-fold higher than Zn0.5Cd0.5S under visible light drive. This research provides valuable insights for designing photocatalyst interfaces with improved CO2 adsorption conversion efficiency.

A lysosome-located and rhodamine-based fluorescence probe for recognizing hydrogen polysulfide.

Hydrogen polysulfide (H2Sn, n≥2), as a kind of active sulfur species (RSS), has become a hot topic in RSS. It can regulate the biological activity of many proteins through S-sulfhydrylation of cysteine residues (protein Cys-SSH), and has a protective effect on cells. Although there have been some studies on hydrogen polysulfide, its production, degradation pathway and regulation mechanism still need further be researched. In presented study, an original lysosome-localized fluorescent probe for determining H2Sn was developed utilizing rhodamine as the fluorogen. The probe used morpholine as the locating unit of lysosomes and chose 2-fluoro-5-nitrobenzoate as the recognizing group. Before adding H2Sn, the proposed probe displayed a spironolactone structure and emitted very weak fluorescence. After adding H2Sn, a conjugated xanthene was formed and the probe demonstrated green fluorescence. When the H2Sn concentration was varied from 6.0×10-7 mol·L-1 to 10.0×10-5 mol·L-1, the fluorescence intensity of the probe was linearly dependent on the H2Sn concentration. And the detection limit was 1.5×10-7 mol·L-1. The presented probe owned a fast response speed, good selectivity, excellent sensitivity and broad pH work scope. In addition, the probe had been well utilized to sense endogenic and exogenic H2Sn in lysosomes.

Carbon dots-based stimuli-responsive hydrogel for in-situ detection of thiram on fruits and vegetables.

Stimuli-responsive hydrogel possesses a strong loading capacity to embed luminescent indicators for constructing food safety sensors, which are suitable for field application. In this work, a fluorescent hydrogel sensor was fabricated by incorporating Ag+-modified carbon dots (CDs-Ag+) into a sodium alginate (SA) hydrogel for in-situ detection of thiram. The fluorescence of CDs was quenched due to the combined effects of electrostatic adsorption and electron transfer between Ag+ and CDs. The formation of an AgS bond between thiram and Ag+ facilitates the release of CDs, causing subsequently fluorescence recovery. Combined with smartphone and analysis software, the fluorescence color change of the hydrogel sensor was converted into data information for quantitative detection of thiram. Such a sample-to-result step is completed within 10 min. Notably, the in-situ detection experiment of thiram in fruit and vegetable samples confirmed the practical application of the hydrogel sensor. Therefore, the hydrogel sensor provides a new research direction for the in-situ detection of pesticide residues in the monitoring of food safety.

miR-9-5p and miR-221-3p Promote Human Mesenchymal Stem Cells to Alleviate Carbon Tetrachloride-Induced Liver Injury by Enhancing Human Mesenchymal Stem Cell Engraftment and Inhibiting Hepatic Stellate Cell Activation.

Mesenchymal stem cells (MSCs) have shown great potential for the treatment of liver injuries, and the therapeutic efficacy greatly depends on their homing to the site of injury. In the present study, we detected significant upregulation of hepatocyte growth factor (HGF) in the serum and liver in mice with acute or chronic liver injury. In vitro study revealed that upregulation of miR-9-5p or miR-221-3p promoted the migration of human MSCs (hMSCs) toward HGF. Moreover, overexpression of miR-9-5p or miR-221-3p promoted hMSC homing to the injured liver and resulted in significantly higher engraftment upon peripheral infusion. hMSCs reduced hepatic necrosis and inflammatory infiltration but showed little effect on extracellular matrix (ECM) deposition. By contrast, hMSCs overexpressing miR-9-5p or miR-221-3p resulted in not only less centrilobular necrosis and venous congestion but also a significant reduction of ECM deposition, leading to obvious improvement of hepatocyte morphology and alleviation of fibrosis around central vein and portal triads. Further studies showed that hMSCs inhibited the activation of hepatic stellate cells (HSCs) but could not decrease the expression of TIMP-1 upon acute injury and the expression of MCP-1 and TIMP-1 upon chronic injury, while hMSCs overexpressing miR-9-5p or miR-221-3p led to further inactivation of HSCs and downregulation of all three fibrogenic and proinflammatory factors TGF-ß, MCP-1, and TIMP-1 upon both acute and chronic injuries. Overexpression of miR-9-5p or miR-221-3p significantly downregulated the expression of α-SMA and Col-1α1 in activated human hepatic stellate cell line LX-2, suggesting that miR-9-5p and miR-221-3p may partially contribute to the alleviation of liver injury by preventing HSC activation and collagen expression, shedding light on improving the therapeutic efficacy of hMSCs via microRNA modification.

Identification of apoptosis-immune-related gene signature and construction of diagnostic model for sepsis based on single-cell sequencing and bulk transcriptome analysis.

Introduction: Sepsis leads to multi-organ dysfunction due to disorders of the host response to infections, which makes diagnosis and prognosis challenging. Apoptosis, a classic programmed cell death, contributes to the pathogenesis of various diseases. However, there is much uncertainty about its mechanism in sepsis. Methods: Three sepsis gene expression profiles (GSE65682, GSE13904, and GSE26378) were downloaded from the Gene Expression Omnibus database. Apoptosis-related genes were obtained from the Kyoto Encyclopedia of Genes and Genomes Pathway database. We utilized LASSO regression and SVM-RFE algorithms to identify characteristic genes associated with sepsis. CIBERSORT and single cell sequencing analysis were employed to explore the potential relationship between hub genes and immune cell infiltration. The diagnostic capability of hub genes was validated across multiple external datasets. Subsequently, the animal sepsis model was established to assess the expression levels of hub genes in distinct target organs through RT-qPCR and Immunohistochemistry analysis. Results: We identified 11 apoptosis-related genes as characteristic diagnostic markers for sepsis: CASP8, VDAC2, CHMP1A, CHMP5, FASLG, IFNAR1, JAK1, JAK3, STAT4, IRF9, and BCL2. Subsequently, a prognostic model was constructed using LASSO regression with BCL2, FASLG, IRF9 and JAK3 identified as hub genes. Apoptosis-related genes were closely associated with the immune response during the sepsis process. Furthermore, in the validation datasets, aside from IRF9, other hub genes demonstrated similar expression patterns and diagnostic abilities as observed in GSE65682 dataset. In the mouse model, the expression differences of hub genes between sepsis and control group revealed the potential impacts on sepsis-induced organ injury. Conclusion: The current findings indicated the participant of apoptosis in sepsis, and apoptosis-related differentially expressed genes could be used for diagnosis biomarkers. BCL2, FASLG, IRF9 and JAK3 might be key regulatory genes affecting apoptosis in sepsis. Our findings provided a novel aspect for further exploration of the pathological mechanisms in sepsis.

Caregivers' experiences in helping individuals with severe and enduring mental health challenges integrate into the community: A qualitative descriptive study in Singapore.

WHAT IS KNOWN ABOUT THE SUBJECT: Individuals with severe and enduring mental health challenges continued to consume mental health services for an average of 13 years as they needed multiple acute psychiatric admissions due to the challenges they experienced in their everyday activities. As caregivers of individuals with severe and enduring mental health challenges, they often bear the brunt of caregiving through their assistance with activities of daily living (ADL), providing emotional support and ensuring medication compliance for their loved ones. When caring for their loved ones, caregivers often reported psychological stress, social isolation and emotional exhaustion due to stressors such as uncertainty of the future, the lack of support from professional services and the isolation from their own social network and support mechanism. WHAT THE PAPER ADDS TO EXISTING KNOWLEDGE: Insights from this study revealed that caregivers for individuals with severe and enduring mental health challenges went through a lonely and exhausting journey fraught with psychological, physical, social and financial challenges, echoing the caregiving needs and the prevalence of the caregiver burden. WHAT ARE THE IMPLICATIONS FOR PRACTICE: Insights shared by the caregivers demonstrated the need for a centralised point of contact to navigate Singapore's fragmented mental healthcare sector. Peer-support groups should be further promoted because they offer the benefits of information exchange, mutual support and a sense of empowerment and hopefulness, which may help ease the caregiver burden. Life skills training, such as teaching how to communicate empathetically with family members, resolve conflicts using open communication, maintain a structured daily routine and solve pragmatic problems in daily life, is more critical for individuals with severe and enduring mental health challenges. This will help them learn how to manage their well-being, live independently, and stabilise their conditions. Lastly, public awareness campaigns should honour caregivers by highlighting their strength, resilience, and dedication. The state can provide financial assistance in the form of tax relief for their income per annum or caregiver allowance to alleviate the financial stress that caregivers are facing. ABSTRACT: Introduction The progressive deinstitutionalisation of mental healthcare has increasingly shifted care responsibilities from healthcare professionals to family caregivers for individuals with severe mental illness. Caregivers must balance many obligations, which often compromise their overall health and well-being, while helping their loved ones integrate into the community. Aim To identify and understand caregivers' needs and challenges as they help individuals with severe and enduring mental health challenges integrate into the community. Methods This study used a descriptive qualitative approach to explore the experiences and challenges of caregivers for individuals with severe and enduring mental health challenges when integrating back into the community. A semi-structured guide was used during the video-conferencing interviews conducted between December 2021 and November 2022. This study was reported according to the 32-item Consolidated Criteria for Reporting Qualitative Research (COREQ) checklist. Findings Fourteen caregivers were individually interviewed by the primary author. Most caregivers were female, with an average of 15 years of experience caring for their loved ones. Using Braun and Clark's six-phase thematic framework, we inductively generate the themes and subthemes from the data. The two themes were (i) challenges (whose subthemes included personal challenges in caregiving, the lack of awareness, and stigma and employment) and (ii) support (whose subthemes included the importance of socialisation for individuals with mental health conditions, existing avenues of support and potential areas for support). Discussion Our findings informed the contemporary needs of caregivers caring for individuals with severe and enduring mental health challenges integrating into the community. Like the global challenges for people with mental health issues, psychosocial support and other supplementary support are still common themes in mental health settings. The findings further specifically highlighted the importance of accessible points of contact as resources and employment-enabling and sustaining initiatives to help manage caregivers' emotional and system challenges, which addresses the gaps identified in the findings. Caregivers' peer-support groups, life skills training and public mental health awareness are also necessitated by the caregivers' voices. Implications for Practice Priority areas include having a centralised point of contact within the community for caregivers. Government or not-for-profit organisations can take the lead by initiating employment-enabling initiatives for individuals with severe and enduring mental health challenges and their caregivers.

Exosomal let-7a-5p derived from human umbilical cord mesenchymal stem cells alleviates coxsackievirus B3-induced cardiomyocyte ferroptosis via the SMAD2/ZFP36 signal axis. / 人脐带间å 质干细胞来源的外泌体let-7a-5p通过SMAD2/ZFP36ä¿¡å·è½´å‡è½»æŸ¯è¨å¥‡ç— æ¯’B3诱导的心肌细胞铁死亡.

Viral myocarditis (VMC) is one of the most common acquired heart diseases in children and teenagers. However, its pathogenesis is still unclear, and effective treatments are lacking. This study aimed to investigate the regulatory pathway by which exosomes alleviate ferroptosis in cardiomyocytes (CMCs) induced by coxsackievirus B3 (CVB3). CVB3 was utilized for inducing the VMC mouse model and cellular model. Cardiac echocardiography, left ventricular ejection fraction (LVEF), and left ventricular fractional shortening (LVFS) were implemented to assess the cardiac function. In CVB3-induced VMC mice, cardiac insufficiency was observed, as well as the altered levels of ferroptosis-related indicators (glutathione peroxidase 4 (GPX4), glutathione (GSH), and malondialdehyde (MDA)). However, exosomes derived from human umbilical cord mesenchymal stem cells (hucMSCs-exo) could restore the changes caused by CVB3 stimulation. Let-7a-5p was enriched in hucMSCs-exo, and the inhibitory effect of hucMSCs-exolet-7a-5p mimic on CVB3-induced ferroptosis was higher than that of hucMSCs-exomimic NC (NC: negative control). Mothers against decapentaplegic homolog 2 (SMAD2) increased in the VMC group, while the expression of zinc-finger protein 36 (ZFP36) decreased. Let-7a-5p was confirmed to interact with SMAD2 messenger RNA (mRNA), and the SMAD2 protein interacted directly with the ZFP36 protein. Silencing SMAD2 and overexpressing ZFP36 inhibited the expression of ferroptosis-related indicators. Meanwhile, the levels of GPX4, solute carrier family 7, member 11 (SLC7A11), and GSH were lower in the SMAD2 overexpression plasmid (oe-SMAD2)+let-7a-5p mimic group than in the oe-NC+let-7a-5p mimic group, while those of MDA, reactive oxygen species (ROS), and Fe2+ increased. In conclusion, these data showed that ferroptosis could be regulated by mediating SMAD2 expression. Exo-let-7a-5p derived from hucMSCs could mediate SMAD2 to promote the expression of ZFP36, which further inhibited the ferroptosis of CMCs to alleviate CVB3-induced VMC.

The impact of 5-aminosalicylates on the efficacy of mesenchymal stem cell therapy in a murine model of ulcerative colitis.

Inflammatory bowel disease (IBD) is distinguished by persistent immune-mediated inflammation of the gastrointestinal tract. Previous experimental investigations have shown encouraging outcomes for the use of mesenchymal stem cell (MSC)-based therapy in the treatment of IBD. However, as a primary medication for IBD patients, there is limited information regarding the potential interaction between 5-aminosalicylates (5-ASA) and MSCs. In this present study, we employed the dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) mouse model to examine the influence of a combination of MSCs and 5-ASA on the development of UC. The mice were subjected to weight measurement, DAI scoring, assessment of calprotectin expression, and collection of colons for histological examination. The findings revealed that both 5-ASA and MSCs have demonstrated efficacy in the treatment of UC. However, it is noteworthy that 5-ASA exhibits a quicker onset of action, while MSCs demonstrate more advantageous and enduring therapeutic effects. Additionally, the combination of 5-ASA and MSC treatment shows a less favorable efficacy compared to the MSCs alone group. Moreover, our study conducted in vitro revealed that 5-ASA could promote MSC migration, but it could also inhibit MSC proliferation, induce apoptosis, overexpress inflammatory factors (IL-2, IL-12P70, and TNF-α), and reduce the expression of PD-L1 and PD-L2. Furthermore, a significant decrease in the viability of MSCs within the colon was observed as a result of 5-ASA induction. These findings collectively indicate that the use of 5-ASA has the potential to interfere with the therapeutic efficacy of MSC transplantation for the treatment of IBD.

Operationalizing the Consolidated Framework for Implementation Research to build and support the lived experience workforce in direct health service provision.

BACKGROUND: The involvement of people with lived experience (LEX) workers in the development, design, and delivery of integrated health services seeks to improve service user engagement and health outcomes and reduce healthcare gaps. Yet, LEX workers report feeling undervalued and having limited influence on service delivery. There is a need for systematic improvements in how LEX workforces are engaged and supported to ensure the LEX workforce can fully contribute to integrated systems of care. OBJECTIVE: This study aimed to operationalize the Consolidated Framework for Implementation Research (CFIR) using a rigorous scoping review methodology and co-creation process, so it could be used by health services seeking to build and strengthen their LEX workforce. SEARCH STRATEGY: A systematic literature search of four databases was undertaken to identify peer-reviewed studies published between 2016 and 2022 providing evidence of the inclusion of LEX workers in direct health service provision. DATA EXTRACTION AND SYNTHESIS: A descriptive-analytical method was used to map current evidence of LEX workers onto the CFIR. Then, co-creation sessions with LEX workers (n = 4) and their counterparts-nonpeer workers (n = 2)-further clarified the structural policies and strategies that allow people with LEX to actively participate in the provision and enhancement of integrated health service delivery. MAIN RESULTS: Essential components underpinning the successful integration of LEX roles included: the capacity to engage in a co-creation process with individuals with LEX before the implementation of the role or intervention; and enhanced representation of LEX across organizational structures. DISCUSSION AND CONCLUSION: The adapted CFIR for LEX workers (CFIR-LEX) that was developed as a result of this work clarifies contextual components that support the successful integration of LEX roles into the development, design, and delivery of integrated health services. Further work must be done to operationalize the framework in a local context and to better understand the ongoing application of the framework in a health setting. PATIENT OR PUBLIC CONTRIBUTION: People with LEX were involved in the operationalization of the CFIR, including contributing their expertise to the domain adaptations that were relevant to the LEX workforce.

A cost analysis of upscaling access to continuity of midwifery carer: Population-based microsimulation in Queensland, Australia.

OBJECTIVE: To quantify the economic impact of upscaling access to continuity of midwifery carer, compared with current standard maternity care, from the perspective of the public health care system. METHODS: We created a static microsimulation model based on a whole-of-population linked administrative data set containing all public hospital births in one Australian state (Queensland) between July 2017 to June 2018 (n = 37,701). This model was weighted to represent projected State-level births between July 2023 and June 2031. Woman and infant health service costs (inpatient, outpatient and emergency department) during pregnancy and birth were summed. The base model represented current standard maternity care and a counterfactual model represented two hypothetical scenarios where 50 % or 65 % of women giving birth would access continuity of midwifery carer. Costs were reported in 2021/22 AUD. RESULTS: The estimated cost savings to Queensland public hospital funders per pregnancy were $336 in 2023/24 and $546 with 50 % access. With 65 % access, the cost savings were estimated to be $534 per pregnancy in 2023/24 and $839 in 2030/31. A total State-level annual cost saving of $12 million in 2023/24 and $19 million in 2030/31 was estimated with 50 % access. With 65 % access, total State-level annual cost savings were estimated to be $19 million in 2023/24 and $30 million in 2030/31. CONCLUSION: Enabling most childbearing women in Australia to access continuity of midwifery carer would realise significant cost savings for the public health care system by reducing the rate of operative birth.

Alleviatory Role of Panax Notoginseng Saponins in Modulating Inflammation and Pulmonary Vascular Remodeling in Chronic Obstructive Pulmonary Disease: mechanisms and Implications.

COPD is an inflammatory lung disease that limits airflow and remodels the pulmonary vascular system. This study delves into the therapeutic potential and mechanistic underpinnings of Panax notoginseng Saponins (PNS) in alleviating inflammation and pulmonary vascular remodeling in a COPD rat model. Symmap and ETCM databases provided Panax notoginseng-related target genes, and the CTD and DisGeNET databases provided COPD-related genes. Intersection genes were subjected to protein-protein interaction analysis and pathway enrichment to identify downstream pathways. A COPD rat model was established, with groups receiving varying doses of PNS and a Roxithromycin control. The pathological changes in lung tissue and vasculature were examined using histological staining, while molecular alterations were explored through ELISA, RT-PCR, and Western blot. Network pharmacology research suggested PNS may affect the TLR4/NF-κB pathway linked to COPD development. The study revealed that, in contrast to the control group, the COPD model exhibited a significant increase in inflammatory markers and pathway components such as TLR4, NF-κB, HIF-1α, VEGF, ICAM-1, SELE mRNA, and serum TNF-α, IL-8, and IL-1ß. Treatment with PNS notably decreased these markers and mitigated inflammation around the bronchi and vessels. Taken together, the study underscores the potential of PNS in reducing lung inflammation and vascular remodeling in COPD rats, primarily via modulation of the TLR4/NF-κB/HIF-1α/VEGF pathway. This research offers valuable insights for developing new therapeutic strategies for managing and preventing COPD.

Analysis of huanglongbing-associated RNA-seq data reveals disturbances in biological processes within Citrus spp. triggered by Candidatus Liberibacter asiaticus infection.

Introduction: Huanglongbing (HLB), a disease that's ubiquitous worldwide, wreaks havoc on the citrus industry. The primary culprit of HLB is the gram-negative bacterium Candidatus Liberibacter asiaticus (CLas) that infects the phloem, but its damaging mechanism is yet to be fully understood. Methods and results: In this study, a multitude of tools including weighted correlation network analysis (WGCNA), protein-protein interaction (PPI) network analysis and gene expression profiling are employed to unravel the intricacies of its pathogenesis. The investigation pinpoints various central genes, such as the ethylene-responsive transcription factor 9 (ERF9) and thioredoxin reductase 1 (TrxR1), that are associated with CLas invasion and resultant disturbances in numerous biological operations. Additionally, the study uncovers a range of responses through the detection of differential expressed genes (DEGs) across different experiments. The discovery of core DEGs leads to the identification of pivotal genes such as the sieve element occlusion (SEO) and the wall-associated receptor kinase-like 15 (WAKL15). PPI network analysis highlights potential vital proteins, while GO and KEGG pathway enrichment analysis illustrate a significant impact on multiple defensive and metabolic pathways. Gene set enrichment analysis (GSEA) indicates significant alterations in biological processes such as leaf senescence and response to biotic stimuli. Discussion: This all-encompassing approach extends valuable understanding into the pathogenesis of CLas, potentially aiding future research and therapeutic strategies for HLB.

Genome-wide characterization of heavy metal-associated isoprenylated plant protein gene family from Citrus sinensis in response to huanglongbing.

Introduction: Heavy metal-associated isoprenylated plant proteins (HIPPs) play vital roles in maintaining heavy metal balance and responding to both biotic and abiotic stresses in vascular plants. However, the role of HIPPs in the response to Huanglongbing (HLB), a harmful disease of citrus caused by the phloem-colonizing bacterium Candidatus Liberibacter asiaticus (CLas), has not been examined. Methods and results: In this study, a total of 26 HIPP genes were identified in Citrus sinensis, and they were grouped into 5 clades. The CsHIPP genes are distributed on 8 chromosomes and exhibited considerable synteny with HIPPs found in Arabidopsis thaliana. Additionally, we analyzed the gene structure, conserved motifs and domains of the CsHIPPs. Various cis-acting elements related to plant hormones and stress responses were identified in the promoters of CsHIPPs. Public transcriptome data and RT-qPCR analysis showed that the expression level of CsHIPP03 was significantly reduced in samples infected by CLas and Xanthomonas citri ssp. citri (Xcc). Furthermore, silencing the homologous gene of CsHIPP03 in Nicotiana benthamiana increased the disease resistance of plants to bacteria. Discussion: Our results provide a basis for functional studies of HIPP gene family in C. sinensis, highlighting their functions in bacterial resistance, and improve our understanding to the susceptibility mechanism of HLB.

DKK1 Activates the PI3K/AKT Pathway via CKAP4 to Balance the Inhibitory Effect on Wnt/ß-Catenin Signaling and Regulates Wnt3a-Induced MSC Migration.

Wnt/ß-catenin signaling plays a crucial role in the migration of mesenchymal stem cells (MSCs). However, our study has revealed an intriguing phenomenon where Dickkopf-1 (DKK1), an inhibitor of Wnt/ß-catenin signaling, promotes MSC migration at certain concentrations ranging from 25 to 100 ng/mL while inhibiting Wnt3a-induced MSC migration at a higher concentration (400 ng/mL). Interestingly, DKK1 consistently inhibited Wnt3a-induced phosphorylation of LRP6 at all concentrations. We further identified cytoskeleton-associated protein 4 (CKAP4), another DKK1 receptor, to be localized on the cell membrane of MSCs. Overexpressing the CRD2 deletion mutant of DKK1 (ΔCRD2), which selectively binds to CKAP4, promoted the accumulation of active ß-catenin (ABC), the phosphorylation of AKT (Ser473) and the migration of MSCs, suggesting that DKK1 may activate Wnt/ß-catenin signaling via the CKAP4/PI3K/AKT cascade. We also investigated the effect of the CKAP4 intracellular domain mutant (CKAP4-P/A) that failed to activate the PI3K/AKT pathway and found that CKAP4-P/A suppressed DKK1 (100 ng/mL)-induced AKT activation, ABC accumulation, and MSC migration. Moreover, CKAP4-P/A significantly weakened the inhibitory effects of DKK1 (400 ng/mL) on Wnt3a-induced MSC migration and Wnt/ß-catenin signaling. Based on these findings, we propose that DKK1 may activate the PI3K/AKT pathway via CKAP4 to balance the inhibitory effect on Wnt/ß-catenin signaling and thus regulate Wnt3a-induced migration of MSCs. Our study reveals a previously unrecognized role of DKK1 in regulating MSC migration, highlighting the importance of CKAP4 and PI3K/AKT pathways in this process.

Economic evaluations performed alongside randomized implementation trials in clinical settings: a systematic review.

BACKGROUND: Economic evaluations alongside implementation trials compare the outcomes and costs of competing implementation strategies to identify the most efficient strategies. The aims of this systematic review were to investigate how economic evaluations are performed in randomized implementation trials in clinical settings and to assess the quality of these evaluations. METHODS: A systematic literature review was conducted on 23 March 2023 to identify studies that reported on economic evaluations embedded in randomized implementation trials in clinical settings. A systematic search was applied across seven databases, and references of relevant reviews were screened for additional studies. The Drummond Checklist was used to assess the quality and risk of bias of included economic evaluations. Study characteristics and quality assessments were tabulated and described. RESULTS: Of the 6,550 studies screened for eligibility, 10 met the inclusion criteria. Included studies were published between 1990 and 2022 and from North America, the United Kingdom, Europe, and Africa. Most studies were conducted in the primary and out-patient care setting. Implementation costs included materials, staffing, and training, and the most common approach to collecting implementation costs was obtaining expense and budget reports. Included studies scored medium to high in terms of economic methodological quality. CONCLUSIONS: Economic evidence is particularly useful for healthcare funders and service providers to inform the prioritization of implementation efforts in the context of limited resources and competing demands. The relatively small number of studies identified may be due to lack of guidance on how to conduct economic evaluations alongside implementation trials and the lack of standardized terminology used to describe implementation strategies in clinical research. We discuss these methodological gaps and present recommendations for embedding economic evaluations in implementation trials. First, reporting implementation strategies used in clinical trials and aligning these strategies with implementation outcomes and costs are an important advancement in clinical research. Second, economic evaluations of implementation trials should follow guidelines for standard clinical trial economic evaluations and adopt an appropriate costing and data collection approach. Third, hybrid trial designs are recommended to generate evidence for effective and cost-effective implementation strategies alongside clinical effectiveness and cost-effectiveness. TRIAL REGISTRATION: The review was prospectively registered with PROSPERO (CRD42023410186).

Long-Term Effect of Having a Child at Risk of Developmental Delays on Parental Labor Force Participation.

OBJECTIVE: This study aimed to examine the long-term influence of having a child at risk of different developmental delays (communication, mobility, self-care, relating, learning, coping, or behaving) on parental labor force participation as the child grows. METHOD: A retrospective cohort was conducted using data from the Longitudinal Study of Australian Children survey, Waves 1-8 covering birth to 15 years of age of children. Multivariable logistic regressions were used to explore the odds ratio of mothers being out of the labor force at different children's ages. Cox proportional hazards models were utilized to identify the 'risk' of mothers returning to the workforce after leaving. All models were adjusted for the mother's age, education attainment, and employment status at time of birth, as well as marital status at the current wave. RESULTS: There were 5,107 records of children, and 266 of them were at risk of any developmental delays at age 4-5 years. This sample represents 243, 026 children born in Australia in 2003/04. After adjusting for potential confounders, mothers of children at risk of each type of developmental delay (except mobility and self-care) had greater odds of being out of, and not returning to the labor force from children aged 2-3 to 14-15 years, when compared to mothers of children who are not at risk of developmental delays. Similar differences were found for fathers but were distinctly small and with narrower fluctuations, compared to mothers. CONCLUSION: Policies and programs funded by the government are greatly needed to support the mothers of children at risk of developmental delays.

Bioinformatics reveals diagnostic potential of cuproptosis-related genes in the pathogenesis of sepsis.

Background: Multiple modes of cell death occur during the development of sepsis. Among these patterns, cuproptosis has recently been identified as a regulated form of cell death. However, its impact on the onset and progression of sepsis remains unclear. Method: We screened a dataset of gene expression profiles from patients with sepsis using the GEO database. Survival analysis was performed to analyze the relationship between cuproptosis-related genes (CRGs) and prognosis. Hub genes were identified through univariate Cox regression analysis. The diagnostic value of hub genes in sepsis was tested in both training sets (GSE65682) and validation sets (GSE134347). To examine the association between hub genes and immune cells, single-sample gene set enrichment analysis (ssGSEA) and Pearson correlation analysis were employed. Additionally, the CRGs were validated in a septic mouse model using real-time quantitative PCR (qRT-PCR) and immunohistochemistry (IHC). Results: In sepsis, most CRGs were upregulated, with only DLD and MTF1 downregulated. High expression of three genes (GLE, LIAS, and PDHB) was associated with better prognosis, but only two hub genes (LIAS, PDHB) reached statistical significance. The receiver operating characteristic (ROC) analysis for diagnosing sepsis showed LIAS had a range of 0.793-0.906, while PDHB achieved values of 0.882 and 0.975 in the training and validation sets, respectively. ssGSEA analysis revealed a lower number of immune cells in the sepsis group, and there was a correlation between immune cell population and CRGs (LIAS, PDHB). Analysis in the septic mouse model demonstrated no significant difference in mRNA expression levels and IHC staining between LIAS and PDHB in heart and liver tissues, but up-regulation was observed in lung tissues. Furthermore, the mRNA expression levels and IHC staining of LIAS and PDHB were down-regulated in renal tissues. Conclusions: Cuproptosis is emerging as a significant factor in the development of sepsis. LIAS and PDHB, identified as potential diagnostic biomarkers for cuproptosis-associated sepsis, are believed to play crucial roles in the initiation and progression of cuproptosis-induced sepsis.

A fluorene-bridged double carbonyl/amine multiresonant thermally activated delayed fluorescence emitter for efficient green OLEDs.

Herein, we report a fluorene-bridged double carbonyl/amine-based MR TADF emitter DDiKTa-F, formed by locking the conformation of the previously reported compound DDiKTa. Using this strategy, DDiKTa-F exhibited narrower, brighter, and red-shifted emission. The OLEDs with DDiKTa-F emitted at 493 nm and showed an EQEmax of 15.3% with an efficiency roll-off of 35% at 100 cd m-2.

Complement components regulates ferroptosis in CVB3 viral myocarditis by interatction with TFRC.

BACKGROUND: Dysregulated cell death machinery and an excessive inflammatory response in Coxsackievirus B3(CVB3)-infected myocarditis are hallmarks of an abnormal host response. Complement C4 and C3 are considered the central components of the classical activation pathway and often participate in the response process in the early stages of virus infection. METHODS: In our study, we constructed a mouse model of CVB3-related viral myocarditis via intraperitoneal injection of Fer-1 and detected myocarditis and ferroptosis markers in the mouse myocardium. Then, we performed co-IP and protein mass spectrometry analyses to explore which components interact with the ferroptosis gene transferrin receptor (TFRC). Finally, functional experiments were conducted to verify the role of complement components in regulating ferroptosis in CVB3 infection. RESULTS: It showed that the ferroptosis inhibitor Fer-1 could alleviate the inflammation in viral myocarditis as well as ferroptosis. Mechanistically, during CVB3 infection, the key factor TFRC was activated and inhibited by Fer-1. Fer-1 effectively prevented the consumption of complement C3 and overload of the complement product C4b. Interestingly, we found that TFRC directly interacts with complement C4, leading to an increase in the product of C4b and a decrease in the downstream complement C3. Functional experiments have also confirmed that regulating the complement C4/C3 pathway can effectively rescue cell ferroptosis caused by CVB3 infection. CONCLUSIONS: In this study, we found that ferroptosis occurs through crosstalk with complement C4 in viral myocarditis through interaction with TFRC and that regulating the complement C4/C3 pathway may rescue ferroptosis in CVB3-infected cardiomyocytes.