Investigation of hub genes and immune status in heart transplant rejection using endomyocardial biopsies.

T cell-mediated rejection (TCMR) and antibody-mediated rejection (ABMR) are severe post-transplantation complications for heart transplantation (HTx), whose molecular and immunological pathogenesis remains unclear. In the present study, the mRNA microarray data set GSE124897 containing 645 stable, 52 TCMR and 144 ABMR endomyocardial biopsies was obtained to screen for differentially expressed genes (DEGs) between rejected and stable HTx samples and to investigate immune cell infiltration. Functional enrichment analyses indicated roles of the DEGs primarily in immune-related mechanisms. Protein-protein interaction networks were then constructed, and ICAM1, CD44, HLA-A and HLA-B were identified as hub genes using the maximal clique centrality method. Immune cell infiltration analysis revealed differences in adaptive and innate immune cell populations between TCMR, ABMR and stable HTx samples. Additionally, hub gene expression levels significantly correlated with the degree and composition of immune cell infiltration in HTx rejection samples. Furthermore, drug-gene interactions were constructed, and 12 FDA-approved drugs were predicted to target hub genes. Finally, an external GSE2596 data set was used to validate the expression of the hub genes, and ROC curves indicated all four hub genes had promising diagnostic value for HTx rejection. This study provides a comprehensive perspective of molecular and immunological regulatory mechanisms underlying HTx rejection.

Identifying Hub Genes, Key Pathways and Immune Cell Infiltration Characteristics in Pediatric and Adult Ulcerative Colitis by Integrated Bioinformatic Analysis.

BACKGROUND AND AIMS: In the present study, we investigated the differentially expressed genes (DEGs), pathways and immune cell infiltration characteristics of pediatric and adult ulcerative colitis (UC). METHODS: We conducted DEG analysis using the microarray dataset GSE87473 containing 19 pediatric and 87 adult UC samples downloaded from the Gene Expression Omnibus. Gene ontology and pathway enrichment analyses were conducted using Metascape. We constructed the protein-protein interaction (PPI) network and the drug-target interaction network of DEGs and identified hub modules and genes using Cytoscape and analyzed immune cell infiltration in pediatric and adult UC using CIBERSORT. RESULTS: In total, 1700 DEGs were screened from the dataset. These genes were enriched mainly in inter-cellular items relating to cell junctions, cell adhesion, actin cytoskeleton and transmembrane receptor signaling pathways and intra-cellular items relating to the splicing, metabolism and localization of RNA. CDC42, POLR2A, RAC1, PIK3R1, MAPK1 and SRC were identified as hub DEGs. Immune cell infiltration analysis revealed higher proportions of naive B cells, resting memory T helper cells, regulatory T cells, monocytes, M0 macrophages and activated mast cells in pediatric UC, along with lower proportions of memory B cells, follicular helper T cells, γδ T cells, M2 macrophages, and activated dendritic cells. CONCLUSIONS: Our study suggested that hub genes CDC42, POLR2A, RAC1, PIK3R1, MAPK1 and SRC and immune cells including B cells, T cells, monocytes, macrophages and mast cells play vital roles in the pathological differences between pediatric and adult UC and may serve as potential biomarkers in the diagnosis and treatment of UC.

Risk of Mortality of Catheter-Related Bloodstream Infections Caused by Acinetobacter Species: Is Early Removal of the Catheters Associated With a Better Survival Outcome?

PURPOSE: Bloodstream infections (BSIs) caused by Acinetobacter species have been extensively reported, however, which majorly focused on respiratory tract infections. The risk of mortality and the effect of early catheter removal on survival in catheter-related BSIs (CRBSIs) caused by Acinetobacter spp. remain unclear. This study aims to investigate that. METHODS: This is a retrospective multicentric study conducted in Taiwan from 2012 to 2014. Patients with at least 1 positive blood culture and catheter culture for the same Acinetobacter spp., showing symptoms and signs of CRBSIs, were included (n = 119). Risk factors for 30-day mortality were analyzed using a logistic regression model. The characteristics of patients with early catheter removal (within 48 hours after CRBSIs) were compared to those without removal matching for age, sex, and disease severity. RESULTS: There were no differences in 30-day mortality with regard to causative Acinetobacter spp., catheter type, site, and appropriateness of antimicrobial therapy. Patients with higher Acute Physiologic and Chronic Health Evaluation (APACHE) II scores (odds ratio [OR]: 1.12; 95% confidence interval [CI]: 1.02-1.23; P = .014), shock (OR: 6.43; 95% CI: 1.28-32.33; P = .024), and longer hospitalization before CRBSIs (OR: 1.04; 95% CI: 1.00-1.08; P = .027) had a significantly higher 30-day mortality rate. Early removal of catheters after CRBSIs was not associated with better survival benefits. CONCLUSION: Higher disease severity (APACHE II score), shock, and longer hospitalization before bacteremia were independently associated with a higher 30-day mortality in CRBSIs caused by Acinetobacter spp. In previous published guidelines, infected catheters were suggested to be removed in CRBSIs caused by gram-negative bacilli. Even though early removal of catheters did not associate with a better survival outcome in current results, it should be judiciously evaluated according to the clinical conditions and risks individually. For better elucidation of these issues, further well-controlled prospective study may be warranted.

Investigation of the Therapeutic Effect of Salbutamol on Endometriosis in a Mouse Model.

Endometriosis is an immune chronic inflammatory disease, and there are currently no more effective drugs for treating endometriosis due to its unknown etiology. Salbutamol is a ß2-adrenergic receptor (ß2AR) agonist commonly used to treat asthma by selectively activating ß2 receptors on airway smooth muscle and leukocytes, exerting bronchial dilation and synergistic anti-inflammatory effects. In recent years, ß2AR agonists have been used in endometriosis studies, and we speculate that salbutamol may have a therapeutic effect on endometriosis. The purpose of this research was to explore the therapeutic effect of salbutamol on endometriosis mice. The mouse endometriosis model was established and treated with different doses of salbutamol. Endometrial lesions were harvested for pathological diagnosis, immunohistochemistry (IHC), Masson staining, and toluidine blue analysis. We found that the number and size of endometriotic lesions were all significantly decreased after 3 weeks of treatment with different doses of salbutamol on endometriosis model mice (P < 0.05). After Salbutamol treatment, the amount of mast cells (toluidine blue) and macrophages (F4/80) in the lesions as well as the expressions of interleukin (IL)-1ß, tumor necrosis factor (TNF)-ɑ, platelet-derived growth factor subunit B (PDGFB), CD31, transforming growth factor (TGF)-ß, Masson staining, BCL2, TUBB3, substance P (SP), and nerve growth factor (NGF) were significantly reduced (P < 0.05). These results suggested that salbutamol could effectively treat endometriosis in mice by reducing immune inflammatory cells and factors, angiogenesis, and fibrosis, increasing apoptosis of endometriotic lesions, and decreasing neurogenesis.

Boosting thermoelectric performance of single-walled carbon nanotubes-based films through rational triple treatments.

Single-walled carbon nanotubes (SWCNTs)-based thermoelectric materials, valued for their flexibility, lightweight, and cost-effectiveness, show promise for wearable thermoelectric devices. However, their thermoelectric performance requires significant enhancement for practical applications. To achieve this goal, in this work, we introduce rational "triple treatments" to improve the overall performance of flexible SWCNT-based films, achieving a high power factor of 20.29 µW cm-1 K-2 at room temperature. Ultrasonic dispersion enhances the conductivity, NaBH4 treatment reduces defects and enhances the Seebeck coefficient, and cold pressing significantly densifies the SWCNT films while preserving the high Seebeck coefficient. Also, bending tests confirm structural stability and exceptional flexibility, and a six-legged flexible device demonstrates a maximum power density of 2996 µW cm-2 at a 40 K temperature difference, showing great application potential. This advancement positions SWCNT films as promising flexible thermoelectric materials, providing insights into high-performance carbon-based thermoelectrics.

Karst tiankeng shapes the differential composition and structure of bacterial and fungal communities in karst land.

Karst tiankeng are important biodiversity conservation reservoirs. However, the unique habitats of karst tiankeng affect microbial community structure remained poorly understood. In this study, we collected soil samples from karst tiankeng (TK) and karst land (KL) and subjected to high-throughput sequencing. Based on the classification of the total, abundance, and rare taxa for bacteria and fungi, a multivariate statistical analysis was carried out. The results revealed that bacterial community Shannon diversity and Pielou's evenness were highest in TK. The rare taxa were ubiquitous in all soil samples, while the higher Shannon diversity of the abundant taxa of TK may be related to the habitat preferences of species and niche differentiation. The community composition of bacterial and fungal sub-communities exhibited significant dissimilarity between TK and KL. The redundancy analysis further demonstrated that abundant taxa were environmentally more constrained than rare taxa. The bacterial and fungal networks of KL were more complex than TK. The keystones of the network transforms may suggest their significant role in the ecological function of the karst tiankeng ecosystem. This study represents the first reports of the characteristics of bacterial and fungal communities in karst tiankeng.

Integrating Spatial Transcriptomics and Single-nucleus RNA Sequencing Reveals the Potential Therapeutic Strategies for Uterine Leiomyoma.

Uterine leiomyoma is the most common gynecological tumor in reproductive women. Tumor-host interface is a complex ecosystem with intimate cell-cell communications and a critical scenario for tumor pathogenesis and progression. The pseudocapsule is the main tumor-host interface of uterine leiomyoma, but its cellular spatial disposition and gene expression are poorly explored. This study mapped the cellular architecture and corresponding gene profiles of the leiomyoma and its surrounding pseudocapsule by integrating spatial transcriptomics and single-nucleus RNA-sequencing at the first time. Here, we reported that estrogen receptor alpha and progesterone receptor mediated the occurrence and development of uterine leiomyoma and that estrogen receptor beta involved in the angiogenesis, which explained the effectiveness of hormonotherapy. Therapeutic targets including ERK1/ERK2 pathway and IGF1-IGF1R were found and might be applied for non-hormonal therapy of uterine leiomyoma. Furthermore, the injection of prostaglandin E2 was initially presented for bleeding control during myomectomy, injection site should be located at the junction between pseudocapsule and leiomyoma, and surrounding pseudocapsule should not be eliminated. Collectively, a single-cell and spatially resolved atlas of human uterine leiomyoma and its surrounding pseudocapsule was established. The results revealed potentially feasible strategies for hormonotherapy, non-hormonal targeted therapy and bleeding control during myomectomy.

An Update on the Multifaceted Role of NF-kappaB in Endometriosis.

Endometriosis remains a common but challenging gynecological disease among reproductive-aged women with an unclear pathogenesis and limited therapeutic options. Numerous pieces of evidence suggest that NF-κB signaling, a major regulator of inflammatory responses, is overactive in endometriotic lesions and contributes to the onset, progression, and recurrence of endometriosis. Several factors, such as estrogen, progesterone, oxidative stress, and noncoding RNAs, can regulate NF-κB signaling in endometriosis. In the present review, we discuss the mechanisms by which these factors regulate NF-κB during endometriosis progression and provide an update on the role of NF-κB in affecting endometriotic cells, peritoneal macrophages (PMs) as well as endometriosis-related symptoms, such as pain and infertility. Furthermore, the preclinical drugs for blocking NF-κB signaling in endometriosis are summarized, including plant-derived medicines, NF-κB inhibitors, other known drugs, and the potential anti-NF-κB drugs predicted through the Drug-Gene Interaction Database. The present review discusses most of the studies concerning the multifaceted role of NF-κB signaling in endometriosis and provides a summary of NF-κB-targeted treatment in detail.

The characterization of microbial communities and associations in karst tiankeng.

The karst tiankeng is a special and grand negative terrain on the surface, that maintains a unique ecosystem. However, knowledge about bacterial and fungal communities in karst tiankengs is still limited. Therefore, soil samples from five karst tiankengs were collected and subjected to high-throughput sequencing of 16S rRNA and ITS genes, and multivariate statistical analysis. The results showed abundant and diversified bacterial and fungal communities in karst tiankeng. The bacterial communities were dominated by Proteobacteria and Acidobacteria, and the fungal communities were dominated by Ascomycota and Basidiomycota. Statistical analysis revealed significant differences in bacterial and fungal communities among the five karst tiankengs, which may indicate that the distribution of bacterial and fungal communities was driven by separate karst tiankengs. The co-occurrence network structure was characterized by highly modularized assembly patterns and more positive interactions. The keystone taxa were mainly involved in nutrient cycling and energy metabolism. The null model analysis results showed that the stochastic process, especially dispersal limitation, tended to be more important in controlling the development of bacterial and fungal communities in karst tiankeng. The bacterial community structure was significantly associated with soil properties (SWC, TN, AN, and BD), while the fungal community structure was significantly associated with soil properties (SWC and TP) and plant diversity. These results can expand our knowledge of the karst tiankeng microbiome.

Does Tibetan Household Livelihood Capital Enhance Tourism Participation Sustainability? Evidence from China's Jiaju Tibetan Village.

Identifying effective transformations to reduce poverty and approach rural sustainability is at the core of the first sustainable development goal of the United Nations. This article offers scientific support for continued efforts in sustaining rural development and livelihood resilience. Many studies have examined drivers of livelihood transition from farming to non-farm activities, especially participation in tourism against the backdrop of rural tourism development. However, few studies have identified ways to measure the level of tourism participation or have discussed how household-level capital influences decisions regarding tourism participation made by Tibetan ethnic households. This article assesses the role of livelihood capital in the adoption of tourism activities at the household level in Jiaju Tibetan Village, an ethnic region that is experiencing struggling agricultural business and developing tourism sector. Using household survey data, this study presents an ordinal logistic regression model to identify the determinants of the household tourism participation level. The results showed that households' tourism participation was influenced by physical capital (e.g., proximity to major roads, odds ratio = 2.83 at p = 0.024; fixed capitals, odds ratio = 101.19 at p = 0.039), human capital (e.g., availability of family labor, odds ratio = 0.25 at p = 0.004; availability of skilled member, odds ratio = 2.91 at p = 0.002), and social capital (e.g., relatives in governmental sectors, odds ratio = 5.22 at p = 0.044; government payments, odds ratio = 8.78 at p = 0.04), while the influence of financial capital was not significant. The proximity to major roads, availability of skilled members, fixed assets, and direct and indirect support from the government to households were significantly and positively associated with tourism participation level. The effects of household labor availability and annual family income remain unclear. Overall, household livelihood capital plays a critical role in the enhancement of tourism participation in Jiaju Tibetan Village. Our findings have implications for understanding the shift of on-farm occupation to off-farm activities in tourism and for the pursuit of policies contributing to poverty reduction and rural revitalization in China as well as to the Sustainable Development Goals.

Heat Adaptive Capacity: What Causes the Differences Between Residents of Xiamen Island and Other Areas?

Extreme heat events caused by climate change have serious adverse effects on residents' health in many coastal metropolises in southeast China. Adaptive capacity (AC) is crucial to reduce heat vulnerability in the human-environment system. However, it is unclear whether changes in individual characteristics and socioeconomic conditions likely amplify or attenuate the impacts of residents' heat adaptive capacity (HAC) changes. Moreover, which public policies can be implemented by the authorities to improve the HAC of vulnerable groups remains unknown. We conducted a questionnaire survey of 630 residents of Xiamen, a typical coastal metropolis, in 2018. The effects of individual and household characteristics, and government actions on the residents' HAC were examined by using ordinal logistic regression analysis. Results show that the majority (48.10%) of Xiamen residents had a "medium" HAC level, followed by a "high" level (37.14%). On Xiamen Island, residents who settled locally for one-three years and spent less than one hour outdoors might report weaker HAC, and their HAC would not improve with increased air conditioning units in household. In other areas of Xiamen, residents with more rooms in their households, no educational experience, and building areas <50 m2 might report better HAC. Further, vulnerable groups, such as local residents and outdoor workers on Xiamen Island, people lacking educational experience and renters in other areas of Xiamen, showed better AC to hot weather than those in previous studies. Low-income groups should be given more attention by local governments and community groups as monthly household income played a positive role in improving Xiamen residents' HAC. Rational green spaces planning and cooling services, such as street sprinkling operations, provided by municipal departments can effectively bring benefits to Xiamen residents. Identification of basic conditions of AC has significant implications for practical promoting targeted measures or policies to reduce health damages and livelihood losses of urban residents during extreme heat events.

Functional traits of Fagaceae plants in shady and sunny slopes in karst degraded tiankeng.

In the negative terrain habitat of the karst degraded tiankeng, the shady and sunny slopes are dramatically different, which results in substantial variations in plant communities. With the degraded tiankeng Shenxiantang in Zhanyi, Yunnan as an example, we explored the functional traits of Fagaceae plants in the shady and sunny slopes, which would help reveal the value of tiankeng as species diversity conservation pool. The results showed that soil nutrients in the shady slope were more than those in the sunny slope. Leaf area, specific leaf area and leaf dry weight of Faga-ceae plants in the shady slope were significantly larger than those in the sunny slope. Leaf thickness was significantly lower than that in the sunny slope. Dry matter content of leaves was less than that of the sunny slope. The main environmental factors affecting functional traits of Fagaceae plants in the shady slope were soil total potassium concentration and soil moisture, while soil total phosphorus concentration was the key factor in the sunny slope. The extent of variation of leaf functional traits in shady slope was less than that in the sunny slope. Fagaceae plants mainly adapted to the shady slope habitat by changing the leaf dry weight to increase photosynthetic rate and carbon accumulation abi-lity. Sunny slope obtained more resource by keeping smaller specific leaf area and increasing the extent of variation of the leaf area. The succession rate of plant community in the shady slope of the degraded tiankeng Shenxiantang was significantly faster than that in the sunny slope. The dominance of Fagaceae plants gradually decreased in the shady slope, but remained to be the constructive species in the sunny slope.

The Role of DLLs in Cancer: A Novel Therapeutic Target.

Delta-like ligands (DLLs) control Notch signaling. DLL1, DLL3 and DLL4 are frequently deregulated in cancer and influence tumor growth, the tumor vasculature and tumor immunity, which play different roles in cancer progression. DLLs have attracted intense research interest as anti-cancer therapeutics. In this review, we discuss the role of DLLs in cancer and summarize the emerging DLL-relevant targeting methods to aid future studies.

Relationship of Platelet Glycoprotein IIb/IIIa and CD62P With Hypercoagulable State After Oncologic Surgery.

The biomarkers for predicting venous thromboembolic events (VTEs) after oncologic surgery are still lacking. The current study aimed to analyze the relationships of CD62P and GP IIb/IIIa with hypercoagulation after oncologic surgery. A total of 76 patients with primary abdominopelvic tumors in our hospital were enrolled. The patients were divided into groups A (malignancy with no VTE group), B (malignancy with VTE group), and C (benign with no VTE group). Twenty healthy volunteers were selected as control. The plasma CD62P (4.69 ± 2.55 vs. 1.76 ± 0.48) and the GP IIb/IIIa (9.28 ± 3.79 vs. 1.76 ± 0.48) levels in group A were significantly higher than those in the control group preoperatively. The CD62P (31.46 ± 17.13 vs. 13.51 ± 7.43, P < 0.05), GP IIb/IIIa (42.33 ± 21.82 vs. 13.51 ± 7.43, P < 0.05), and D-dimer (7.33 ± 2.34 vs. 2.03 ± 0.55, P < 0.05) levels in group B were markedly higher 7 days after operation compared with those in group A. The CD62P and the GP IIb/IIIa exhibited a positive correlation with the hypercoagulable state after oncologic surgery.

The oncogenic role of Jagged1/Notch signaling in cancer.

Aberrant activation of Notch signaling plays an oncogenic role in cancer development. Jagged1 (JAG1) is an important Notch ligand that triggers Notch signaling through cell-cell interactions. JAG1 overexpression has been reported in many different types of cancer and correlates with a poor clinical prognosis. JAG1/Notch signaling controls oncogenic processes in different cell types and cellular contexts. Furthermore, JAG1/Notch signaling cascades activate a number of oncogenic factors that regulate cellular functions such as proliferation, metastasis, drug-resistance, and angiogenesis. To suppress the severe toxicity of pan-Notch inhibitors, JAG1 is attracting increasing attention as a source of therapeutic targets for cancers. In this review, the oncogenic role of JAG1/Notch signaling in cancer is discussed, as well as implications of strategies to inhibit JAG1/Notch signaling activity.

The role of oncogenic Notch2 signaling in cancer: a novel therapeutic target.

Deregulated Notch signaling is a key factor thought to facilitate the stem-like proliferation of cancer cells, thereby facilitating disease progression. Four subtypes of Notch receptor have been described to date, with each playing a distinct role in cancer development and progression, therefore warranting a careful and comprehensive examination of the targeting of each receptor subtype in the context of oncogenesis. Clinical efforts to translate the DAPT, which blocks Notch signaling, have been unsuccessful due to a combination of serious gastrointestinal side effects and a lack of complete blocking efficacy. There is therefore a clear need to identify better therapeutic strategies for targeting and manipulating Notch signaling. Notch2 is a Notch receptor that is commonly overexpressed in a range of cancers, and which is linked to a unique oncogenic mechanism. Successful efforts to block Notch2 signaling will depend upon doing so both efficiently and specifically in patients. As such, in the present review we will explore the role of Notch2 signaling in the development and progression of cancer, and we will assess agents and strategies with the potential to effectively disrupt Notch2 signaling and thereby yield novel cancer treatment regimens.

Recent advances in synthetic methods and applications of silver nanostructures.

As the advanced functional materials, silver nanoparticles are potentially useful in various fields such as photoelectric, bio-sensing, catalysis, antibacterial and other fields, which are mainly based on their various properties. However, the properties of silver nanoparticles are usually determined by their size, shape, and surrounding medium, which can be modulated by various synthesis methods. In this review, the fabrication methods for synthesizing silver nanoparticles of different shapes and specific size are illustrated in detail. Besides, the corresponding properties and applications of silver nanoparticles are also discussed in this paper.

Haemophilus aphrophilus associated spleen abscess: an unusual presentation of subacute endocarditis.

The HACEK group of bacteria (Haemophilus spp., Actinobacillus actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens, Kingella spp.), is uncommon pathogens of infective endocarditis, but can cause life-threatening events such as heart failure or formation of lethal emboli. Here we report a 58-year-old Asian man with a past history of congenital valvular heart disease who presented with sudden onset of left flank pain followed by fever with chills for 2 weeks. Abdominal computed tomography (CT) indicated a 1.6 cm abscess in the spleen. Culturing indicated the presence of Haemophilus aphrophilus. We diagnosed the patient with subacute endocarditis complicated with spleen abscess. The patient recovered fully after two weeks antibiotic (Ceftriaxone) treatment. Clinicians should give further attention to infective endocarditis caused by bacteria in the HACEK group in patients with metastatic infection such as spleen abscess with suspected valvular heart disease.