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Abstract 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).

IntroductionSepsis 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.MethodsThree 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.ResultsWe 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.ConclusionThe 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.

Abstract Background Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease (ILD) with unknown etiology, characterized by sustained damage repair of epithelial cells and abnormal activation of fibroblasts, the underlying mechanism of the disease remains elusive. Methods To evaluate the role of Tuftelin1 (TUFT1) in IPF and elucidate its molecular mechanism. We investigated the level of TUFT1 in the IPF and bleomycin-induced mouse models and explored the influence of TUFT1 deficiency on pulmonary fibrosis. Additionally, we explored the effect of TUFT1 on the cytoskeleton and illustrated the relationship between stress fiber and pulmonary fibrosis. Results Our results demonstrated a significant upregulation of TUFT1 in IPF and the bleomycin (BLM)-induced fibrosis model. Disruption of TUFT1 exerted inhibitory effects on pulmonary fibrosis in both in vivo and in vitro. TUFT1 facilitated the assembly of microfilaments in A549 and MRC-5 cells, with a pronounced association between TUFT1 and Neuronal Wiskott-Aldrich syndrome protein (N-WASP) observed during microfilament formation. TUFT1 can promote the phosphorylation of tyrosine residue 256 (Y256) of the N-WASP (pY256N-WASP). Furthermore, TUFT1 promoted transforming growth factor-β1 (TGF-β1) induced fibroblast activation by increasing nuclear translocation of pY256N-WASP in fibroblasts, while wiskostatin (Wis), an N-WASP inhibitor, suppressed these processes. Conclusions Our findings suggested that TUFT1 plays a critical role in pulmonary fibrosis via its influence on stress fiber, and blockade of TUFT1 effectively reduces pro-fibrotic phenotypes. Pharmacological targeting of the TUFT1-N-WASP axis may represent a promising therapeutic approach for pulmonary fibrosis.

Because of the high blood flow and high pressure, the aortic arch, which sends out 3 branches including the innominate artery that separates the right common carotid artery and the right subclavian artery, the left common carotid artery, and the left subclavian artery, is an important blood vessel supplying the brain and spinal cord, so the risk of aneurysms in this area is very high. The main risk is that the rupture can cause massive bleeding; the secondary is that some aortic arch lesions can cause insufficient blood supply to the brain or spinal cord. If early diagnosis can be detected, it could be treated completely with minimally invasive or open surgery. Therefore, especially for this kind of patient, the significance of treatment is great, and better results can be obtained through treatment. Here is a 48-year-old female patient with dysplasia of the distal aortic arch, multiple aortic parietal aneurysms, and abnormal origin of the left subclavian artery, which originates from the tortuous and twisted aorta.

Abstract 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.

IntroductionHuanglongbing (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 resultsIn 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.DiscussionThis all-encompassing approach extends valuable understanding into the pathogenesis of CLas, potentially aiding future research and therapeutic strategies for HLB.

IntroductionHeavy 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 resultsIn 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.DiscussionOur 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.

Background: Organophosphates (OPs) can directly poison various types of mammalian cells, only with several awkward bottom-up antagonists. A top-down nanoscavenger was developed to radically and etiologically prevent cell damage, while insufficient subcellular or molecular blocking mechanisms were explored. Methods: The top-down nanoscavengers were first developed and carefully characterized. EL4 cells were then adopted as model cells to clarify the protective effects and mechanisms of nanoscavengers. After detecting the cell viability and apoptosis, oxidative stress and mitochondrial injury markers, DNA damage index as well as relevant apoptotic factors were sequentially examined to clarify what damage the top-down nanoscavengers inhibited. Results: The well-characterized nanoscavengers exerted a top-down and etiological protective effects on EL4 cell viability via radically eliminating OPs and blocking OP-cell interactions. As a result, the intracellular oxidative stress-related markers including ROS production and abnormal antioxidants, mitochondrial injuries as well as DNA damage were inhibited. Accordingly, above damage-induced apoptosis was also blocked. Conclusion: In conclusion, this study clarified the protective mechanisms of a novel enzyme-based nanoscavengers for OP-challenged cells and provided a potent antidote for OP poisoning.

Abstract In the research on strong alkali‐surfactant‐polymer flooding scaling prediction, the variation characteristics of ion concentration in the produced fluid are obviously consistent with those of scale component content. Consequently, studying the variation tendency of ion concentration in produced fluid is helpful for further revealing the scaling tendency. Given the periodicity and chaos characteristics of the ion concentration data of the produced fluid, an echo state network (ESN) is used to realize the relevant time series forecasting. Simultaneously, to cope with the failure of the ESN in selecting suitable reservoir parameters according to different characteristics of time series, a modified discrete particle swarm optimization algorithm based on objective space decomposition is used to optimize the reservoir parameters. The experimental results indicate that the improved ESN presents the lowest error and is the closest to the target value.

Abstract Prophylactic pharmacotherapy for health care in patients with high risk of cardiac arrest (CA) is an elusive and less explored strategy. Melatonin has possibilities used as a daily nutraceutical to trigger the cellular adaptation. We sought to find the effects of long-term daily prophylactic supplement with melatonin on the victim of CA. Rats were divided into sham, CA, and melatonin + CA (Mel + CA) groups. The rats in the Mel + CA group received daily IP injection of melatonin 100 mg/kg for 14 days. CA was induced by 8 min asphyxia and followed by manual cardiopulmonary resuscitation. The endpoint was 24 h after resuscitation. Survival, neurological outcome, and hippocampal mitochondrial integrity, dynamics and function were assessed. Survival was significantly higher in the Mel + CA group than the CA group (81 vs. 42%, P = 0.04). Compared to the CA group, neurological damage in the CA1 region and the level of cytochrome c, cleaved caspase-3 and caspase-9 in the Mel + CA group were decreased (P

In long-distance, high-elevation gravitational water supply systems, it is essential to incorporate energy dissipation to lower pipeline pressures. The energy dissipation box is a novel device for pressure reduction, extensively utilized in gravitational flow transition systems. Despite its appealing contribution, systematic selection methods still need to be used regarding its optimum location. Hence, this paper considers the sum-of-the-maximum hydrostatic pressure head (SMHPH) and derives an extreme location equation for the energy dissipation box (EDB) in the design stage, and then, it comprehensively accounts for the overcurrent capacity and proposes a theoretical comparison and selection method for the optimal location (OL) between the critical and extreme locations. A theoretical analysis with an engineering case study is conducted to compare the theoretical OL, and numerical simulations are carried out to compare the pressure protection effect of the same box cross-sectional area and initial water volume of the theoretical OL and other possible locations with different initial water depths. The results show that the location of the EDB in the design stage should comprehensively consider the overcurrent capacity and the SMHPH. On the basis of both conditions, the oscillation amplitudes of the pressure gradient beyond the box are significantly decreased as the OL approaches closer to the downstream pipe. If the initial water depth in the box is large, the EDB provides greater protection to the pressure head (PH) by decreasing the cross-sectional area and then maximizing the utilization of water depth in the box and decreasing the volume of the EDB.

Reactive oxygen species (ROS) are pivotal in signal transduction processes in plant–pathogen interactions. The ROS signaling pathways involved in Candidatus Liberibacter asiaticus (CLas) and Xanthomonas citri subspecies citri (Xcc) infections in Citrus sinensis (sweet orange) are unclear. In this study, we comprehensively identified ROS metabolism-associated genes, including 9 NADPH oxidase (RBOH), 14 superoxide dismutase (SOD), 1 catalase (CAT), 9 peroxiredoxin (PrxR), 5 ascorbate peroxidase (APX), 4 glutathione peroxidase (GPX), 3 monodehydroascorbate reductase (MDAR), 2 dehydroascorbate reductase (DHAR), 2 glutathione reductase (GR), 24 thioredoxin (Trx), and 18 glutaredoxin (GLR) genes in C. sinensis. An analysis revealed variable gene structures but conserved motifs and domains in ROS subfamilies. A comparative synteny analysis with Arabidopsis thaliana and Vitis vinifera indicated evolutionary conservation of most ROS metabolism-associated genes, with some originating from gene duplication events post-species divergence in C. sinensis. Expression profiling revealed five up-regulated genes and four down-regulated genes during both CLas and Xcc infections. Promoter analysis revealed numerous stress-responsive elements in the promoter of ROS metabolism-associated genes. Protein–protein interaction network analysis highlighted the involvement of ROS metabolism in various biological processes. A comparison of ROS metabolism-associated genes between C. sinensis and Poncirus trifoliata indicated multiple gene gain and loss events within ROS subfamilies of C. sinensis. This study enhances our understanding of ROS metabolism in C. sinensis and sheds light on citrus–pathogen interactions.

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.

IntroductionRestored cardiopulmonary function is efficiently achieved by utilizing extracorporeal membrane oxygenation (ECMO). Nevertheless, the incidence of Clostridioides difficile infection (CDI) associated with ECMO is relatively uncommon.Case presentationIn this report, we present the case of a 59-year-old male with severe chest pain due to acute myocardial infarction, subsequently necessitating ECMO support. During the first day of hospitalization, pulmonary infections were observed, and piperacillin-tazobactam was prescribed for 7 days at low dosages. However, the patient developed severe diarrhea 4 days later. After ruling out common pathogens, we suspected the occurrence of CDI and performed genetic testing for C. difficile toxin, confirming our diagnosis. The prescription of vancomycin resulted in slight improvement, while fecal microbiota transplantation (FMT) proved to be more effective.ConclusionIn this case, temporary application of ECMO was applied, and the anti-infective treatment relied on the use of antibiotics at short-term, low-dose, and low CDI risk. Hence, the occurrence of CDI was considered an uncommon event, which may serve as a reference for future cases.

Abstract Background Organophosphate (OP)-induced delayed neurological damage is attributed to permanent neuropathological lesions caused by irreversible OP-neurocyte interactions, without potent brain-targeted etiological antidotes to date. The development of alternative therapies to achieve intracerebral OP detoxification is urgently needed. Methods We designed a brain-targeted nanoreactor by integrating enzyme immobilization and biomimetic membrane camouflaging protocols with careful characterization, and then examined its blood–brain barrier (BBB) permeability both in vitro and in vivo. Subsequently, the oxidative stress parameters, neuroinflammatory factors, apoptotic proteins and histopathological changes were measured and neurobehavioral tests were performed. Results The well-characterized nanoreactors exerted favourable BBB penetration capability both in vitro and in vivo, significantly inhibiting OP-induced intracerebral damage. At the cellular and tissue levels, nanoreactors obviously blocked oxidative stress, cellular apoptosis, inflammatory reactions and brain histopathological damage. Furthermore, nanoreactors radically prevented the occurrence of OP-induced delayed cognitive deficits and psychiatric abnormality. Conclusion The nanoreactors significantly prevented the development of OP-induced delayed neurological damage, suggesting a potential brain-targeted etiological strategy to attenuate OP-related delayed neurological and neurobehavioral disorders. Graphical Abstract

Abstract Continuously variable transmission (CVT) of noncircular gear has the technical advantages of large bearing capacity and high transmission efficiency. The key technology of CVT with noncircular gear has been broken through some countries, and is in the stage of deep application research. Although the characteristics and design methods of noncircular gear pairs have been continuously studied in China, the noncircular gear CVT is still in the preliminary exploration and research stage. The linear functional noncircular gear pair, whose transmission ratio is a linear function in the working section, to realize continuously variable transmission was the research object in this paper. According to the required transmission ratio in the working section, the transmission ratio function in the non-working section was constructed by using a polynomial. And then the influence of pitch curve parameters in the working section on which in the non-working section was also analyzed to obtain the pitch curve suitable for transmission of this gear pair. In addition, for improving the stability and bearing capacity of gear transmission, the noncircular gear pair transmission with high contact ratio was designed. Furthermore, the accurate value of the contact tooth length was calculated based on the gear principle and the characteristics of the involute tooth profile, from this the contact tooth length error was calculated by comparing the accurate value with its actual value obtained by the rolling experiment. Finally, an indirect method to verify the contact ratio by detecting the contact length error of the tooth profile was proposed.

Endothelial dysfunction is a critical and initiating factor of the vascular complications of diabetes. Inflammation plays an important role in endothelial dysfunction regulated by epigenetic modifications. N6-methyladenosine (m6A) is one of the most prevalent epigenetic modifications in eukaryotic cells. In this research, we identified an m6A demethylase, fat mass and obesity-associated protein (FTO), as an essential epitranscriptomic regulator in diabetes-induced vascular endothelial dysfunction. We showed that enhanced FTO reduced the global level of m6A in hyperglycemia. FTO knockdown in endothelial cells (ECs) resulted in less inflammation and compromised ability of migration and tube formation. Compared with EC Ftofl/fl diabetic mice, EC-specific Fto-deficient (EC FtoΔ/Δ) diabetic mice displayed less retinal vascular leakage and acellular capillary formation. Furthermore, methylated RNA immunoprecipitation sequencing (MeRIP-Seq) combined with RNA-Seq indicated that Tnip1 served as a downstream target of FTO. Luciferase activity assays and RNA pull-down demonstrated that FTO repressed TNIP1 mRNA expression by erasing its m6A methylation. In addition, TNIP1 depletion activated NF-κB and other inflammatory factors, which aggravated retinal vascular leakage and acellular capillary formation, while sustained expression of Tnip1 by intravitreal injection of adeno-associated virus alleviated endothelial impairments. These findings suggest that the FTO-TNIP1-NF-κB network provides potential targets to treat diabetic vascular complications.

Abstract Background To investigate the prevalence and predictors of retinal breaks reopening after vitrectomy with air tamponade in rhegmatogenous retinal detachment (RRD). Methods A retrospective cohort study was conducted in Shanghai General Hospital. Chart review was performed among 1715 patients with primary RRD who received pars plana vitrectomy (PPV) with air tamponade as initial management. Patients were followed up for recurrence. The clinical features of the eyes with retinal breaks reopening were recorded. Logistic regression was constructed to investigate the predictors for breaks reopening. Results A total of 137 (7.99%) patients had recurrent retinal detachment after PPV with air tamponade. The causes of surgery failure included new or missed retinal breaks (48.9%), reopening of original tears (43.8%) and proliferative vitreoretinopathy (7.3%). The median time to recurrence for the patients with breaks reopening was 18.0 days. Multivariate logistic regression indicated that the presence of retinal break(s) ≥ 1.5 disc diameters (DD) (odds ratio [OR]: 2.68, 95% confidence interval [CI]: 11.04–6.92, P = 0.041), and shorter period for restricted activities (OR: 0.94, 95% CI: 0.89–0.99, P = 0.020) were the independent predictors for breaks reopening. Conclusions Breaks reopening is an important cause for retinal redetachment after PPV with air tamponade in primary RRD. The first 2–4 weeks after surgery is the “risk period” for breaks reopening. Special attention should be paid for patients with retinal break(s) ≥ 1.5 DD. A prolonged period for restricted activities is recommended.

Abstract Background Traditional Chinese Medicine (TCM) nurse‐led clinics (NLC) is an innovative working model in China, representing the specialization and extension of nurses’ role. However, as a pioneer in TCM nursing, this new model of working is facing both opportunities and challenges because it is known little about the operational status of NLCs. Aims To explore the experiences of nurses who work in NLC in TCM hospitals. Materials & Methods A focused ethnographic study was conducted in three TCM hospitals affiliated with Guangzhou University of Chinese Medicine. We interviewed eleven nurses in those hospitals and observed seven of them working with patients. We used snowball sampling for data collection including interview, non‐participant observation and documents from medical records. All the data were processed as following steps: (a) coding for descriptive labels; (b) sorting for patterns; (c) identifying outliers or negative cases; (d) generalizing with construction and theories and (e) noting reflective remarks. Results Nurse‐led clinics help nurses develop their skills and knowledge that are highly recognized by public since they meet the growing needs of patients and also relieve the workload of physicians in the hospitals. However, lack of specialization is still a major challenge in NLCs due to insufficiency of full‐time staff with specialized education, nurse‐led practice without standardized guidelines, restrictions on prescription right of nurses, and also inadequate support from hospitals. Discussions As a revolutionary innovation of working model for nurses in TCM hospitals, NLCs could improve quality of care and lead to a comprehensive promotion of nursing career. However, there are several challenges on providing high quality care for patients whilst improving educational development of nurses. This study suggests that nurses, hospital administration and the government should cooperate with each other to develop standard nursing programs for NLCs. Conclusions It is imperative to identify nursing roles, collect available resources, and develop supportive policies and training programs to enhance the quality of NLCs.

BackgroundUnwarranted extended length of stay (LOS) increases the risk of hospital-acquired complications, morbidity, and all-cause mortality and needs to be recognized and addressed proactively.ObjectiveThis systematic review aimed to identify validated prediction variables and methods used in tools that predict the risk of prolonged LOS in all hospital admissions and specifically General Medicine (GenMed) admissions.MethodLOS prediction tools published since 2010 were identified in five major research databases. The main outcomes were model performance metrics, prediction variables, and level of validation. Meta-analysis was completed for validated models. The risk of bias was assessed using the PROBAST checklist.ResultsOverall, 25 all admission studies and 14 GenMed studies were identified. Statistical and machine learning methods were used almost equally in both groups. Calibration metrics were reported infrequently, with only 2 of 39 studies performing external validation. Meta-analysis of all admissions validation studies revealed a 95% prediction interval for theta of 0.596 to 0.798 for the area under the curve. Important predictor categories were co-morbidity diagnoses and illness severity risk scores, demographics, and admission characteristics. Overall study quality was deemed low due to poor data processing and analysis reporting.ConclusionTo the best of our knowledge, this is the first systematic review assessing the quality of risk prediction models for hospital LOS in GenMed and all admissions groups. Notably, both machine learning and statistical modeling demonstrated good predictive performance, but models were infrequently externally validated and had poor overall study quality. Moving forward, a focus on quality methods by the adoption of existing guidelines and external validation is needed before clinical application.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42021272198.

AbstractCOPD 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-1β. 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.

The regulation of apple (Malus domestica) fruit texture during ripening is complex and a fundamental determinant of its commercial quality. In climacteric fruit, ripening-related processes are regulated by ethylene (ET), and jasmonate (JA) is also involved in the ethylene biosynthesis pathway, mainly through the transcription factor MYC2. However, the molecular genetic mechanism for fruit ripening processes between the JA and ET signaling pathways still needs to be elucidated. In order to explore how JA regulates apple fruit ripening through ERF4, we used ‘Gala’ and ‘Ralls Janet’ fruit at different developmental stages as experimental materials to determine the fruit firmness and related gene expression analysis. Meanwhile, we carried out different hormone treatments on ‘Gala’ fruit at ripening stage. Here, we show that ERF4 is a core JA signaling hub protein JASMONATE ZIM-DOMAIN (JAZ) interactor that affects ethylene signaling pathways. During fruit development, ERF4 represses the expression of ACS1 and ACO1 by interacting with JAZ, as well as with the JA-activated transcription factor MYC2. Ripening is promoted in JAZ-suppressed apples. Thus, ERF4 acts as a molecular link between ethylene and JA hormone signals, and the natural variation of the ERF4 Ethylene-responsive binding factor-associated amphiphilic repression (EAR) motif decreases repression of ethylene biosynthesis genes.

Fusion welding of 7000 series aluminum alloy is plagued by cracking from a fine equiaxed zone (FQZ). Here, the authors quantify key softening mechanisms, show the damage accumulation sequence, and propose a hybrid laser/arc welding strategy to mitigate the FQZ and increase weld strength and toughness.

Abstract CVB3 is a single positive-strand enterovirus, and a common pathogen in myocarditis etiology. Although a number of antiviral candidates are under development, specific targeted therapy is not available for CVB3. Ferroptosis is a new type of regulatory cell death discovered in recent years. In this study, our team provided the first evidence that ferroptosis existed in CVB3 infection in vivo and in vitro by iron overload, and massive accumulation of lipid peroxides. Mechanistically, we construct a classical model of HeLa cells following a time-course infection (6, 12, 24, 36, 48 h) with CVB3 (MOI = 10). We demonstrated that the TFRC gene plays an important role in promoting ferroptosis in CVB3 infection and downregulation of TFRC attenuated the ferroptosis. Interestingly, we observed that TFRC was nuclear translocation induced by the CVB3, which was predominantly localized in the cell membrane, but redistributed to the nucleus during CVB3 infection. Moreover, we found that the transcription factor Sp1 was an essential factor that could bind to the TFRC promoter and upregulate the TFRC transcription. Collectively, these results suggest that the Sp1/TFRC/Fe axis may provide a new target for the development of therapies against CVB3 infection.

Objective Systematic review of length of stay (LOS) prediction models to assess the study methods (including prediction variables), study quality, and performance of predictive models (using area under receiver operating curve (AUROC)) for general surgery populations and total knee arthroplasty (TKA). Method LOS prediction models published since 2010 were identified in five major research databases. The main outcomes were model performance metrics including AUROC, prediction variables, and level of validation. Risk of bias was assessed using the PROBAST checklist. Results Five general surgery studies (15 models) and 10 TKA studies (24 models) were identified. All general surgery and 20 TKA models used statistical approaches; 4 TKA models used machine learning approaches. Risk scores, diagnosis, and procedure types were predominant predictors used. Risk of bias was ranked as moderate in 3/15 and high in 12/15 studies. Discrimination measures were reported in 14/15 and calibration measures in 3/15 studies, with only 4/39 externally validated models (3 general surgery and 1 TKA). Meta-analysis of externally validated models (3 general surgery) suggested the AUROC 95% prediction interval is excellent and ranges between 0.803 and 0.970. Conclusion This is the first systematic review assessing quality of risk prediction models for prolonged LOS in general surgery and TKA groups. We showed that these risk prediction models were infrequently externally validated with poor study quality, typically related to poor reporting. Both machine learning and statistical modelling methods, plus the meta-analysis, showed acceptable to good predictive performance, which are encouraging. Moving forward, a focus on quality methods and external validation is needed before clinical application.

Bacterial biofilms often hinder the healing of infected chronic wounds. Hence, it is significant to explore ways to destroy bacterial biofilms. In this work, a photothermal therapy strategy of designing Au clusters modified ZIF-8 MOFs (Au@ZIF-8) as peroxidase-like catalytic nanozyme was proposed for bacterial infected wound healing. Under near-infrared laser (NIR), the prepared Au@ZIF-8 present enhanced peroxidase-like activity and excellent photothermal response properties. Au@ZIF-8 achieved bacterial membrane disruption rate of 66.3% and MRSA clearance rate up to 97%. Au@ZIF-8 also catalyzed endogenous H2O2 to ·OH and achieved almost 97.4% healing rate in animal experiments. The prepared Au@ZIF-8 with peroxidase-like catalytic nanozyme properties has great potential in the treatment of infected diabetic wounds through bacterial membranes disruption and protein leakage promotion.

This paper aims to propose a multicriteria decision analysis (MCDA) method to evaluate and select solvent in a dispersive liquid-liquid microextraction (DLLME) approach. The DLLME is applied to the determination of itraconazole and hydroxy itraconazole in plasma by high performance liquid chromatography with fluorescence detection (HPLC-FLD). To achieve this goal, extraction efficiency, chromatographic resolution, and greenness of solvent were identified as the three indicators in MCDA. Then, Technique for Order of Preference by Similarity to Ideal Solution (TOPSIS) was employed to evaluate and select the solvent. Weight assignment was set up by integrating the subjective scoring from experienced analysts and the objective approach using Shannon’s entropy weight method. Under chosen parameters (extraction solvent: 1-decanol 40 μL, dispersing solvent: methanol 400 μL), the method was validated satisfactorily and applied successfully to the analysis of itraconazole and hydroxy itraconazole in real human plasma samples. The results show that the comprehensive weighted TOPSIS analysis is a promising tool to choose experimental conditions toward an integrative goal. It can provide analysts with a decision making reference to maintain a balance between the analytical performance and eco-friendliness.

American ginseng (Panax quinquefolius L.) is known for its health benefits, which are attributed to various terpenoids. However, the specific composition and activities of these terpenoids in forest-grown wild American ginseng remain understudied. This study aimed to characterize the terpenoid composition, particularly triterpene saponins, in forest-grown wild American ginseng. The analysis revealed that triterpene saponins, notably American ginseng ginsenosides (AGGs), are the predominant active components, as identified through LC-MS/MS and HPLC. A subsequent in vitro evaluation of AGGs showcased their potent antioxidant capabilities, displaying the dose-dependent scavenging of free radicals and reducing agents. Moreover, AGGs demonstrated efficacy in reducing oxidative injury and intracellular ROS levels in RAW 264.7 macrophages treated with H2O2. In addition to their antioxidant properties, AGGs exhibited anti-inflammatory effects, significantly inhibiting NO and inflammatory substance production in lipopolysaccharide-treated RAW 264.7 macrophages. These findings highlight the potential of AGG-rich forest-grown wild American ginseng as a functional food with promising implications for improving human health.

Abstract Background At present, “Belt and Road” (“B&R”) member states (accounting for about 61.78% of the world’s population) face different types of cancer threats to varying degrees. We analyzed the incidence and mortality and risk factors of cancer in the member countries of the “B&R” to explore the basis of health and medical cooperation between countries and provide a foundation for formulating cancer prevention and control policies for building a healthy "B&R." Methods Data were derived from the Global Cancer Observatory and Cancer Country Profiles in 2020. Incidence and mortality were age-standardized rates (ASRs). Population attributable fractions (PAFs) was applied to measure risk factors of cancers in the “B&R” countries. The mortality­to­incidence ratio (MIR) was calculated by dividing the mortality rate by the incidence rate. Results A total of 26 cancers were included in the study. Lung, breast, colorectal, stomach, liver, prostate, cervical, esophageal, thyroid, and uterine cancers were the most common and highest in age-standardized mortality in the “B&R” countries. For men, Hungary had the highest cancer age-standardized incidence and mortality (ASR, 289.3 per 100,000 and ASR, 235.7 per 100,000, respectively), followed by Latvia (ASR, 288.6 per 100,000 and ASR, 196.5 per 100,000, respectively). In females, the highest incidence rates were estimated in Greece (ASR, 238.7 per 100,000), and the highest mortality rate was Brunei (ASR, 192.3 per 100,000). All countries were in the middle or high HDI range, with about half (46.88%) of countries achieving high HDI, mostly in Central and Eastern Europe (13 countries) and West Asia (10 countries). The United Arab Emirates had the highest MIR in male and female (1.59 vs 2.19). Tobacco products, infectious factors, and ultraviolet rays were the three main cancer risk factors in the “B&R” countries. Conclusion The overall burden of cancer in the countries along the “B&R” remains substantial, while the corresponding cancer prevention and control policies need to be improved. Strengthening health cooperation among member countries will contribute to a joint response to the risks and challenges posed by cancer.

Abstract Background Existing studies have illustrated how the onset of physical disability or dementia negatively impacts economic wellbeing and increases out of pocket costs. However, little is known about this relationship in older individuals. Consequently, this study aimed to identify how the onset of physical disability or dementia in older adults affects economic wellbeing and out of pocket costs, and to explore the impact of gender in the context of Australia. Methods The data was collected from a large, randomized clinical study, ASPirin in Reducing Events in the Elderly (ASPREE). Two generalized linear models (with and without interaction effects) of total out of pocket costs for those who did and did not develop physical disability or dementia were generated, with adjustment for sociodemographic characteristics at baseline. Results We included 8,568 older Australian individuals with a mean age of 74.8 years and 53.2% being females. After adjustment for the baseline sociodemographic characteristics, the onset of physical disability did statistically significantly raise out of pocket costs (cost ratio = 1.25) and costs among females were 13.1% higher than males. Conclusions This study highlights that classifying different types of health conditions to identify the drivers of out of pocket costs and to explore the gender differences in a long-term follow-up is of importance to examine the financial impact on the older population. These negative financial impacts and gender disparities of physical disability and dementia must be considered by policymakers.

BackgroundSARS-CoV-2 infection is a respiratory infectious disease similar to influenza virus infection. Numerous studies have reported similarities and differences in the clinical manifestations, laboratory tests, and mortality between these two infections. However, the genetic effects of coronavirus and influenza viruses on the host that lead to these characteristics have rarely been reported.MethodsCOVID-19 (GSE157103) and influenza (GSE111368, GSE101702) datasets were downloaded from the Gene Expression Ominbus (GEO) database. Differential gene, gene set enrichment, protein-protein interaction (PPI) network, gene regulatory network, and immune cell infiltration analyses were performed to identify the critical impact of COVID-19 and influenza viruses on the regulation of host gene expression.ResultsThe number of differentially expressed genes in the COVID-19 patients was significantly higher than in the influenza patients. 22 common differentially expressed genes (DEGs) were identified between the COVID-19 and influenza datasets. The effects of the viruses on the regulation of host gene expression were determined using gene set enrichment and PPI network analyses. Five HUB genes were finally identified: IFI27, OASL, RSAD2, IFI6, and IFI44L.ConclusionWe identified five HUB genes between COVID-19 and influenza virus infection, which might be helpful in the diagnosis and treatment of COVID-19 and influenza. This knowledge may also guide future mechanistic studies that aim to identify pathogen-specific interventions.

Background. Cancer affects millions of people each year and imposes a huge economic and social burden worldwide. Cuproptosis is a recently discovered novel mode of cell death. The exact function of the cuproptosis-related gene dihydrolipoamide dehydrogenase (DLD) and its role in pan-cancer is unknown. Methods. Data were retrieved from the GTEx, TCGA, and multiple online websites. These data were used to assess the expression, prognosis, and diagnostic value of DLD in various tumors. The relationship of DLD with immune microenvironment immunomodulators, immune checkpoints, tumor mutational load (TMB), microsatellite instability (MSI), and oncology drug sensitivity was explored by correlation analysis. Results. The mRNA and protein expression of DLD differs in most cancers. Survival analysis showed that DLD was associated with prognosis with KIRC, KIRP, KICH, and UCS. DLD had a strong diagnostic value in KIRC, GBM, PAAD, and LGG (AUC > 0.9). DLD promoter methylation affects the aberrant expression of LIHC, LUSC, PAAD, READ, and THCA. DLD was negatively correlated with stromal score, immune score, and ESTIMATE score in UCEC, TGCT, LUSC, and SARC. In UCS, resting memory CD4 T cells and activated NK cells were significantly correlated with DLD expression. Significant correlations were also observed between DLD expression and immunomodulators, immune checkpoints, TMB, and MSI in various cancers. Importantly, we also identified a number of potential drugs that may target DLD. Conclusion. DLD expression is associated with a variety of tumor prognoses and plays an integral role in tumorigenesis, tumor metabolism, and immunity.

Abstract Background The global COVID-19 pandemic has led to the need for educators to explore online platforms in delivering lessons to students. Home-based learning is one of the most commonly-used teaching methods that allow learning to take place despite a physical separation between the students and the educators. Methods A descriptive qualitative approach was used to explore the experiences of nursing undergraduates when using home-based learning as a pedagogy during the COVID-19 pandemic. Data were collected from twenty-three nursing students (n = 14 in year one; n = 9 in year two) of their full-time pre-registration nursing program in a public-funded university in Singapore. Semi-structured interviews using an interview guide was conducted through Zoom-based video-conferencing from November 2020 to January 2021. The interview lasted between 45 and 65 min (median = 45 min). Data collection took place concurrently with thematic analysis through Braun and Clarke’s six-step approach. This study was reported according to the Consolidated Criteria for Reporting Qualitative Research. Results Three main themes identified during the data analysis were: (1) challenges of home-based learning, where students detailed their experiences and difficulties encountered during the process; (2) the effectiveness of home-based learning, which explored the pedagogy’s impact on the students’ learning experience; and (3) students’ motivation to learn, where the effects on student morale and motivation in partaking in learning tasks were discussed. Conclusions Results from this study suggested that universities should incorporate more home-based learning opportunities as home-based learning to continue playing a crucial role in the foreseeable future. Universities should continue to incorporate more home-based learning opportunities into the existing nursing curriculaa in order to test their capacities and address technical challenges in online learning. Future studies should also consider incorporating other pedagogical strategies when conducting lessons online.

Abstract Background Healing of MRSA (methicillin-resistant Staphylococcus aureus) infected deep burn wounds (MIDBW) in diabetic patients remains an obstacle but is a cutting-edge research problem in clinical science. Surgical debridement and continuous antibiotic use remain the primary clinical treatment for MIDBW. However, suboptimal pharmacokinetics and high doses of antibiotics often cause serious side effects such as fatal complications of drug-resistant bacterial infections. MRSA, which causes wound infection, is currently a bacterium of concern in diabetic wound healing. In more severe cases, it can even lead to amputation of the patient's limb. The development of bioactive nanomaterials that can promote infected wound healing is significant. Results The present work proposed a strategy of using EGCG (Epigallocatechin gallate) modified black phosphorus quantum dots (BPQDs) as therapeutic nanoplatforms for MIDBW to achieve the synergistic functions of NIR (near-infrared)-response, ROS-generation, sterilization, and promoting wound healing. The electron spin resonance results revealed that EGCG-BPQDs@H had a more vital photocatalytic ability to produce singlet oxygen than BPQDs@H. The inhibition results indicated an effective bactericidal rate of 88.6% against MRSA. Molecular biology analysis demonstrated that EGCG-BPQDs significantly upregulated CD31 nearly fourfold and basic fibroblast growth factor (bFGF) nearly twofold, which were beneficial for promoting the proliferation of vascular endothelial cells and skin epidermal cells. Under NIR irradiation, EGCG-BPQDs hydrogel (EGCG-BPQDs@H) treated MIDBW area could rapidly raise temperature up to 55 °C for sterilization. The MIBDW closure rate of rats after 21 days of treatment was 92.4%, much better than that of 61.1% of the control group. The engineered EGCG-BPQDs@H were found to promote MIDBW healing by triggering the PI3K/AKT and ERK1/2 signaling pathways, which could enhance cell proliferation and differentiation. In addition, intravenous circulation experiment showed good biocompatibility of EGCG-BPQDs@H. No significant damage to major organs was observed in rats. Conclusions The obtained results demonstrated that EGCG-BPQDs@H achieved the synergistic functions of photocatalytic property, photothermal effects and promoted wound healing, and are promising multifunctional nanoplatforms for MIDBW healing in diabetics. Graphical Abstract

Coronary artery disease (CAD) is the most common cardiovascular disease worldwide. In this study, we investigated the pathogenesis of CAD. We downloaded the GSE98583 dataset, including 12 CAD samples and 6 normal samples, from the Gene Expression Omnibus (GEO) database and screened differentially expressed genes (DEGs) in CAD versus normal samples. Next, we performed functional enrichment analysis, protein-protein interaction (PPI) network, and functional module analyses to explore potential functions and regulatory functions of identified DEGs. Next, transcription factors (TFs) and microRNAs (miRNAs) targeting DEGs were predicted. In total, 456 DEGs were identified in CAD and normal samples, including 175 upregulated and 281 downregulated genes. These genes were enriched in the intestinal immune network for immunoglobulin A production and the mitogen-activated protein kinase signaling pathway (e.g., TGFBR2 and EGF). The PPI network contained 212 genes, and HIST1H2BJ, HIST1H2AC, EGF, and EP300 were hub genes with degrees higher than 10. Four significant modules were identified from the PPI network, with genes in the modules mainly enriched in the inflammatory response, protein ubiquitination involved in ubiquitin-dependent protein catabolic processes, protein transport, and mitochondrial translational elongation, respectively. Two TFs (E2F1 and FOXK1) and five miRNAs (miR-122A, miR-516-5P, miR-507, miR-342, and miR-520F) were predicted to target 112 DEGs. miR-122A reportedly targets both LRP10 and IQGAP1 in the TF-miRNA target regulatory network. The abnormal expression of TGFBR2, EGF, LRP10, and IQGAP1 may be implicated in CAD pathogenesis. Our study provides targets and potential regulators for investigating CAD pathogenesis.

Background: Given the high incidence and high mortality of cervical cancer (CC) among women in developing countries, identifying reliable biomarkers for the prediction of prognosis and therapeutic response is crucial. We constructed a prognostic signature of cuproptosis-related long non-coding RNAs (lncRNAs) as a reference for individualized clinical treatment.Methods: A total of seven cuproptosis-related lncRNAs closely related to the prognosis of patients with CC were identified and used to construct a prognostic signature via least absolute shrinkage and selection operator regression analysis in the training set. The predictive performance of the signature was evaluated by Kaplan–Meier (K-M) analysis, receiver operating characteristic (ROC) analysis, and univariate and multivariate Cox analyses. Functional enrichment analysis and single-sample gene set enrichment analysis were conducted to explore the potential mechanisms of the prognostic signature, and a lncRNA–microRNA–mRNA network was created to investigate the underlying regulatory relationships between lncRNAs and cuproptosis in CC. The associations between the prognostic signature and response to immunotherapy and targeted therapy were also assessed. Finally, the prognostic value of the signature was validated using the CC tissues with clinical information in my own center.Results: A prognostic signature was developed based on seven cuproptosis-related lncRNAs, including five protective factors (AL441992.1, LINC01305, AL354833.2, CNNM3-DT, and SCAT2) and two risk factors (AL354733.3 and AC009902.2). The ROC curves confirmed the superior predictive performance of the signature compared with conventional clinicopathological characteristics in CC. The ion transport-related molecular function and various immune-related biological processes differed significantly between the two risk groups according to functional enrichment analysis. Furthermore, we discovered that individuals in the high-risk group were more likely to respond to immunotherapy and targeted therapies including trametinib and cetuximab than those in the low-risk group. Finally, CC tissues with clinical data from my own center further verify the robustness of the seven-lncRNA risk signature.Conclusion: We generated a cuproptosis-related lncRNA risk signature that could be used to predict prognosis of CC patients. Moreover, the signature could be used to predict response to immunotherapy and chemotherapy and thus could assist clinicians in making personalized treatment plans for CC patients.

Based on reverse engineering, product innovation design and 3D-printing technology, a technical route for the rapid design and development of helmet products has been constructed, and optimize the product production process, reduce the product development cycle, improve production efficiency, and complete the personalized design of helmets to improve the comfort of personnel wearing. The point cloud data of the physical model were collected by the 3D scanner, and imported to the reverse processing software (Geomagic Studio) for data processing, surface reconstruction and surface fitting. In this way, the section curve of the repaired head surface was extracted. Then, the extracted information was sent to the forward design software (SolidWorks) through the parameter exchange command for the forward design of the helmet, and the 3D model was subsequently printed. Effectively solve the traditional design method for complex surface modelling design and manufacturing, forward software measurement deviation, modelling design process is complex and tedious, time-consuming and labor-intensive, cannot well meet the product design, processing and manufacturing process is relatively cumbersome, long production cycle and other design defects, speed up enterprise product development, shorten the cycle and reduce costs. Furthermore, the adoption of 3D printing technology to output the designed 3D digital model effectively shortens the product development cycle.

ABSTRACT: Introduction: Female Genital Sexual Arousal Disorder (FGSAD) seriously affects women's quality of life and Sexual life, but it still lacks ideal FGSAD animal models for further study. Aim: To establish a specific model of female genital sexual arousal disorder and explore the mechanisms resulting in FGSAD. Methods: After delivery, female rats were guided by expansions of the vagina and ovariectomy (VD+OVX, n = 10); in VD group female rats were just extended by the vagina (VD, n = 10), in OVX group female rats were treated with ovariectomy (OVX, n = 10);the remaining had 1 longitudinal incision as sham group(n = 10). Outcomes: Vaginal dilatation combined with ovariectomy in rats may reflect female genital sexual arousal disorder with high reproducibility and stability. Results: Vaginal tissue of female rats in OVX group and VD+OVX group showed an increase in blood flow, decrease in muscle content compared to the sham group. The proportion of collagen fiber I/III decreased and the elastic fiber showed significant rupture and fragmentation; Structural reticular integrity was also significantly separated and broken from the muscle fibers. However, there was no significant difference in vaginal blood flow, fibers and vascular between VD group and Sham group. The damage of vaginal tissue in VD+OVX group was more significant than that in OVX and VD groups. Clinical Translation: We have constructed a specific animal model that can provide clinical insights into the mechanism of FGSAD and serves as a good avenue for further research of its treatment. Strengths and Limitations: Vaginal dilatation combined with ovariectomy in rats is a specific animal model with high reproducibility and stability, but we do acknowledge the shortcomings and limitation present in our study. Since genital arousal disorder has many different etiologies that impact the vagina, the clitoris and surrounding tissues, there is no “gold standard” model that different models attempt to investigate different etiologies. Conclusion: The female genital sexual arousal disorder model established by vaginal dilatation combined with ovariectomy is a novel rat model with simple induction conditions, which pathogenic mechanism of female genital sexual arousal disorders maybe connected with the change of VEGF and MMP-9 in vaginal fibromuscular system and microvascular.Li G, Yu P, Hu Y, et al. Establishment of Rat Model of Female Genital Sexual Arousal Disorder. Sex Med 2022;XX:XXXXXX.

BackgroundKawasaki disease (KD) is an acute systemic vasculitis of unknown etiology. The rs8108402 C/T single nucleotide polymorphism (SNP) is located in the promoter region of miR-181-c/d gene and the intron of Nanos3 gene. The miR-181 family contributes to the pathogenesis of cardiovascular and inflammatory disorders, while Nanos3 is involved in DNA transcription regulation and cell proliferation. However, no studies have examined the association between miR-181c/d and Nanos3 polymorphisms and the susceptibility and progression of KD.ObjectiveThe purpose of our study is to examine the association of miR-181c/miR-181d/Nanos3 gene locus rs8108402 C/T polymorphism with KD susceptibility, intravenous immunoglobulin (IVIG) responsiveness, and the development of coronary artery lesions (CAL).MethodsPeripheral blood specimens from 100 children with KD and 100 healthy children were collected. The polymorphism of rs8108402 C/T was detected using polymerase chain reaction-sequencing-based typing technique.ResultsThere were statistically significant differences in C and T allele frequency distributions between the KD group and healthy controls for the polymorphic site rs8108402 C/T (P = 0.002). The distribution of the genotypes CC, CT, and TT also presented statistical significant difference between the KD and control groups (P = 0.003). Compared to the rs8108402 C allele, the T allele was associated with increased KD susceptibility (OR = 2.080, 95% CI = 1.317∼3.283). However, there were no significant associations discovered between the rs8108402 C/T polymorphism and CAL formation or IVIG unresponsiveness in the study.ConclusionSNP rs8108402 C/T located in the miR-181c/d promoter and Nanos3 intronic region is associated with susceptibility to Kawasaki disease but not with the development of coronary artery lesions or IVIG unresponsiveness in Chinese children.

Laryngeal cancer is the most common malignant tumor for which there is still a lack of effective treatment. Traditional radiotherapy, chemotherapy, and surgery all have significant side effects. Therefore, multifunctional collaborative therapeutic nanoplatforms are attractive to patients with laryngeal cancer. In this study, a near-infrared responsive IR780-modified MXene (Ti3C2) nanosheet was proposed as a strategy for targeted therapy to achieve the synergistic functions of photothermal (PTT) therapy, photodynamic (PDT) therapy and mitochondrial pathway apoptosis. Electron spin resonance results showed that Ti3C2@IR780 could produce singlet linear oxygen for PDT. Molecular biology studies showed that Ti3C2@IR780 had the outstanding ability to generate ROS to disrupt mitochondrial function, resulting in apoptosis of cancer cells up to 60.51%. In vivo experiments showed that Ti3C2@IR780 could effectively aggregate at tumor sites. The temperature of the tumor region could reach 63.7 °C in the presence of near-infrared light. Tumor growth was inhibited by 92% during the treatment, and there was no recurrence. Results of the sections showed an 88.1% reduction in microtumor vascularity with Ti3C2@IR780 treatment for 21 days compared to the control group. These findings suggest that this multifunctional nanoplatform with synergistic NIR-sensitive properties can effectively inhibit tumor growth, providing an ideal strategy for cancer treatment.

Dryland winter wheat (Triticum aestivum L.) production plays an extremely important role in the southeast of the Loess Plateau. Planting patterns have great influence on improving soil water storage and yield, and should be matched with different seeding rates. In order to assess the effect of different sowing methods on the drought resistance and stable yield of dryland wheat, a field experiment was conducted in Wenxi County Dryland Wheat Experimental Base in Shanxi Province, China. In the current study, the effects of three planting techniques (drilling sowing, furrow sowing, and film-mulched sowing) and four seeding rates (150, 225, 300, and 375 kg ha−1) were examined on water storage, dry matter formation, yield, and water use efficiency (WUE). The results showed that furrow sowing (FS) and film-mulched sowing (FM) treatments increased soil water storage in the 0–300 cm soil layer at overwintering and jointing stages. In addition, FS and FM increased soil water consumption in the 0–300 cm soil layer from overwintering to maturity of wheat. Furthermore, FS and FM significantly increased the dry matter accumulation from the overwintering to the mature stage, promoted its accumulation in vegetative organs and translocation to grains after anthesis, viz., increased yield by 6.2% and 7.9%, and WUE by 4.6% and 5.3%, respectively, as compared with those of the drilling sowing (DS) treatments. Pearson’s correlation analysis showed that grain yield had a significantly positive correlation with soil water storage at overwintering and jointing. Moreover, grain yield was significantly positively correlated with soil water consumption in the 0–300 cm soil layer from jointing to maturity. Additionally, the seeding rate of 150 kg ha−1 with FS could obtain higher WUE and grain yield. Therefore, it is strongly recommended that the seeding rate of 150 kg ha−1 is used with FS to improve the grain yield and WUE of dryland agricultural systems in China.

As a representative sulfur-containing volatile organic compounds (S-VOCs), CH3SH has attracted widespread attention due to its adverse environmental and health risks. The performance of Mn-based catalysts and the effect of their crystal structure on the CH3SH catalytic reaction have yet to be systematically investigated. In this paper, two different crystalline phases of tunneled MnO2 (α-MnO2 and β-MnO2) with the similar nanorod morphology were used to remove CH3SH, and their physicochemical properties were comprehensively studied using high-resolution transmission electron microscope (HRTEM) and electron paramagnetic resonance (EPR), H2-TPR, O2-TPD, Raman, and X-ray photoelectron spectroscopy (XPS) analysis. For the first time, we report that the specific reaction rate for α-MnO2 (0.029 mol g−1 h−1) was approximately 4.1 times higher than that of β-MnO2 (0.007 mol g−1 h−1). The as-synthesized α-MnO2 exhibited higher CH3SH catalytic activity towards CH3SH than that of β-MnO2, which can be ascribed to the additional oxygen vacancies, stronger surface oxygen migration ability, and better redox properties from α-MnO2. The oxygen vacancies on the catalyst surface provided the main active sites for the chemisorption of CH3SH, and the subsequent electron transfer led to the decomposition of CH3SH. The lattice oxygen on catalysts could be released during the reaction and thus participated in the further oxidation of sulfur-containing species. CH3SSCH3, S0, SO32−, and SO42− were identified as the main products of CH3SH conversion. This work offers a new understanding of the interface interaction mechanism between Mn-based catalysts and S-VOCs.

Neighborhood rough model is widely used in feature selection with high dimension, fuzzy, continuous and discrete attributes, incomplete data and so on, and the application of neighborhood rough model depends on neighborhood threshold. In the application of the model, the point-value neighborhood threshold is not adaptive, which leads to low classification accuracy and high time complexity of the algorithm. In order to solve the above problems, a feature selection approach based on IFDS (Incomplete Fuzzy Hybrid Decision System) and DPSO (Discrete Particle Swarm Optimization Algorithm) with variable thresholds is proposed. Firstly, a neighborhood rough model capable of simultaneously processing fuzzy, hybrid and incomplete data was established. The average reachable distance was introduced to construct the attribute neighborhood threshold set and reduce the interference of noise data on classification accuracy. Secondly, we constructed the DPSO particle fitness function using the feature subset length, the significance of the attribute and the negative domain of the neighborhood, and improved the inertia weight computing method, so as to enhance the feature selection speed and the feature subset quality. Finally, the simulation experiment was performed using the real industrial production data. The experiment effect shows that this method has obvious advantages in improving the classification accuracy, optimizing the search speed and the optimal feature subset quality.

The emergence of blockchain technology has significantly changed the underlying infrastructure of existing information technology and will fundamentally affect the production modes of enterprises. However, because the application of blockchain is still in its infancy, it is difficult for an enterprise to develop a comprehensive assessment of various types of blockchain service providers in the market. Hence, enterprises need scientific decision tools to estimate which blockchain service provider is appropriate. However, few studies have focused on this phenomenon. Therefore, to address this challenge, this investigation proposes a novel integrated multi-attribute group decision-making (MAGDM) method to help enterprises estimate which blockchain vendor is more appropriate by considering more comprehensive influence factors. The proposed method is defined in an intuitionistic fuzzy environment and integrates entropy and the best-worst method (BWM) for comprehensive weighting of decision makers (DMs), subjective criteria and objective criteria in the decision-making process to make the decision results more reliable and reasonable. A numerical example and comparison are provided to illustrate the practicability and usefulness of the method. This study enriches the theory and methodology of blockchain technology and MAGDM analysis.

The three-dimensional (3D) morphological information of wheat grains is an important parameter for discriminating seed health, wheat yield, and wheat quality. High-throughput acquisition of 3D indicators of wheat grains is of great importance for wheat cultivation management, genetic breeding, and economic value. Currently, the 3D morphology of wheat grains still relies on manual investigation, which is subjective, inefficient, and poorly reproducible. The existing 3D acquisition equipment is complicated to operate and expensive, which cannot meet the requirements of high-throughput phenotype acquisition. In this paper, an automatic, economical, and efficient method for the 3D morphometry of wheat grain is proposed. A line laser binocular camera was used to obtain high-quality point-cloud data. A wheat grain 3D model was constructed by point-cloud segmentation, finding, clustering, projection, and reconstruction. Based on this, 3D morphological indicators of wheat grains were calculated. The results show that the root mean square error (RMSE) and mean absolute percentage error (MAPE) of the length were 0.2256 mm and 2.60%, the width, 0.2154 mm and 5.83%, the thickness, 0.2119 mm and 5.81%, and the volume, 1.7740 mm3 and 4.31%. The scanning time was around 12 s and the data processing time was around 3.18 s under a scanning speed of 25 mm/s. This method can achieve the high-throughput acquisition of the 3D information of wheat grains, and it provides a reference for in-depth study of the 3D morphological indicators of wheat and other grains.

Introduction: It has been demonstrated HOE-642 ameliorates ischemic contracture, prevents post-resuscitation diastolic dysfunction, and favors the earlier return of contractile function. This study is the first report to explore the optimal dose of HOE-642 in protecting the neuronal mitochondrial function after cardiac arrest. Methods: Cardiac arrest was induced by 8 min asphyxia in rats. There were Sham (S), Normothermic (NORM), and Hypothermic (HYPO) groups. The NORM or HYPO groups consist of four subgroups: NORM/HYPO + HOE-642 0, 1, 3, and 5 mg/kg. Survival and NDS were evaluated after 24 h of resuscitation. ΔΨm, mitochondrial swelling, ROS production, and mitochondrial complex IIV activity of the hippocampus were detected. Results: Survival in the HYPO + 1 mg group was the best and significantly higher than in the NORM + 0 mg and NORM + 1 mg groups. NDS in the HYPO + 0 mg, HYPO + 1 mg, and HYPO + 3 mg groups was significantly lower than in the NORM + 0 mg group. ΔΨm in the NORM + 1 mg (n = 5) group was significantly higher than in the NORM + 0 mg (n = 8), NORM + 3 mg (n = 5), and NORM + 5 mg (n = 5) groups. The ROS production in the NORM + 1 mg and NORM + 3 mg groups were significantly lower than in the NORM + 0 mg and NORM + 5 mg groups. Complex I and III activities in the HYPO + 1 mg (n = 5) group were significantly higher than in the HYPO + 3 mg (n = 5), and HYPO + 5 mg (n = 5) groups. Complex II and IV activities in the NORM + 3 mg and HYPO + 3 mg groups were significantly higher than in the NORM + 0 mg, NORM + 1 mg, and HYPO + 0 mg (n = 4)groups. Conclusions: HOE-642 1 or 3 mg/kg showed benefits compared to HOE-642 5 mg/kg used when initiating resuscitation. When combined with hypothermia after cardiac arrest, HOE-642 1 or 3 mg/kg improved survival and neurological function compared with hypothermia or HOE-642 alone, however, HOE-642 5 mg/kg plus hypothermia did not.

Auxin’s role in the post-ripening of peaches is widely recognized as important. However, little is known about the processes by which auxin regulates fruit post-ripening. As one of the early auxin-responsive genes, it is critical to understand the role of small auxin-up RNA (SAUR) genes in fruit post-ripening and softening. Herein, we identified 72 PpSAUR auxin-responsive factors in the peach genome and divided them into eight subfamilies based on phylogenetic analysis. Subsequently, the members related to peach post-ripening in the PpSAUR gene family were screened, and we targeted PpSAUR43. The expression of PpSAUR43 was decreased with fruit post-ripening in melting flesh (MF) fruit and was high in non-melting flesh (NMF) fruit. The overexpression of PpSAUR43 showed a slower rate of firmness decline, reduced ethylene production, and a delayed fruit post-ripening process. The MADS-box gene family plays an important regulatory role in fruit ripening. In this study, we showed with yeast two-hybrid (Y2H) and bimolecular fluorescence complementation (BIFC) experiments that PpSAUR43 can interact with the MADS-box transcription factor PpCMB1(PpMADS2), which indicates that PpSAUR43 may inhibit fruit ripening by suppressing the function of the PpCMB1 protein. Together, these results indicate that PpSAUR43 acts as a negative regulator involved in the peach post-ripening process.

Modern railway axles frequently experience external damages, which results in deteriorated fatigue performance and a need for careful maintenance. Herein, the shot peening (SP)-induced strengthening of high-speed railway axle EA4T alloy or 25CrMo4 steel subjected to foreign object damage (FOD) and the effect of this strengthening on fatigue strength were elucidated using the electron backscattered diffraction, transmission electron microscopy, X-ray diffraction and nanoindentation techniques. An improved backward statistical inference method was employed to construct probabilistic fatigue S-N curves based on the results of high cycle fatigue test and thus derive reliable endurance limits for unFODed and FODed specimens subjected or not subjected to SP treatment.  Eventually, El-Haddad model and the Wöhler curve were combined with the modified Miner damage accumulation theory to develop a three-dimensional Kitagawa-Takahashi diagram in the nominal stress framework. The above diagram was shown to well correlate the fatigue damage accumulation and the critical FOD defect size of externally impacted railway axles with knee-point life and fatigue S-N curve slope.