Epithelial–mesenchymal transition (EMT) is defined as a cellular process during which epithelial cells acquire mesenchymal phenotypes and behavior following the downregulation of epithelial features. EMT and its reversed process, the mesenchymal-epithelial transition (MET), and the special form of EMT, the endothelial-mesenchymal transition (EndMT), have been thought as a universal dogma controlling developmental and pathological processes. More than half a century of EMT study has made it a large research field and a mainstream concept. However, discrepancies and disputes over EMT and EMT research have also grown over time. Particularly, neither the epithelial and mesenchymal states/properties nor their regulatory networks nor specific markers have been defined, rendering the EMT, MET and EndMT concepts groundless. Moreover, EMT and MET effects should not be a cause, but rather a consequence of or an accompanying effect during developmental and pathological processes. EMT and MET represented by the change in cell shapes or adhesiveness or symbolized by EMT factors are biased interpretation of the overall change in cellular property and regulatory networks during development and cancer progression. The true meaning of EMT effects in some developmental and pathological processes, such as fibrosis, needs re-evaluation. But the core EMT factors are actually a few components of the regulatory networks of neural stemness, which determines tumorigenicity and pluripotency. The EMT effects in cancer progression and neural crest formation are wrong attribution of the role of neural stemness during cancer progression and the cell-intrinsic property of neural crest cells to the unknown mesenchymal state. It is time to reassess the significance of EMT and its related concepts in scientific research.

Canine mammary tumors represent one of the leading malignant pathology in female dogs, displaying the importance of efficient therapeutic findings, beside the golden standard surgery, able to limit the development of the disease. Studies in human cancers demonstrated that Doxorubicin presents a good effect in different biological processes like apoptosis, autophagy, cell cycle, cell invasion and epithelial to mesenchymal transition. Our study following the effects of Doxorubicin on two canine mammary cancer cell lines P114 and CMT-U27, showing an inhibitory effect in cell proliferation and an expression alteration of the EMT related genes.

Chronic rhinosinusitis is a common inflammatory disease of paranasal sinuses, which causes rhinorrhea, nasal congestion and hyposmia. The genetic predisposition or the exposure to irritants can sustain the inflammatory response and the development of nasal polyposis. Nasal polyps are benign and teardrop-shaped growths that project in the nasal cavities and originate from the ethmoid sinuses. This inflammatory process is associated with high expression of IL-5 cytokine and infiltration of eosinophils. Humanized monoclonal antibodies targeting IL-5 or its receptor, represent a therapeutic strategy in the treatment of nasal polyposis in combination with corticosteroids. The molecular pathogenesis of nasal polyps in CRS patients is associated to the epithelial-mesenchymal transition (EMT), a process in which epithelial cells lose their typical phenotype acquiring a mesenchymal phenotype. TGFβ/SMAD, ERK, and Wnt/β-catenin pathways are altered in EMT during the nasal tissue remodeling. miRNA and inhibitor molecules targeting these altered signaling pathways are able to interfere with EMT; which could lead to alternative therapies. Nasal polyps are an alternative source of mesenchymal stem cells which can be easily isolated from surgical biopsies. A molecular understanding of the biology of PO-MSCs will contribute to delineating inflammatory process underlying the development of nasal polyps.

Extracellular vesicles (EVs), such as exosomes or oncosomes are released with molecules unfavorable for survival from cells. In addition, accumulating evidence has shown that tumor cells often eject anti-cancer drugs such as chemotherapeutics and targeted drugs within EVs, a novel mechanism of drug resistance. The EV-releasing, drug resistance phenotype is often coupled with cellular dedifferentiation and transformation, cells undergoing epithelial-mesenchymal transition (EMT) and taking on a cancer stem cell phenotype. Recent studies have shown that the release of EVs is also involved in immunosuppression. The concept of the resistance-associated secretory phenotype (RASP) is reviewed herein.

Approximately 20% of patients with colorectal cancer (CRC) are diagnosed with a mucinous subtype of this tumor, have a worse prognosis, and often show resistance to available therapies. Molecules from the mucin family are involved in the regulation of epithelial-mesenchymal transition (EMT), which significantly determines the cancer aggressiveness. This study aimed to examine the diagnostic and prognostic significance of mucinous histology and EMT markers in patients with early-onset CRC and their association with disease severity and tumor characteristics. The study included tumor tissue samples from 106 patients diagnosed with CRC before the age of 45, 53 with mucinous and 53 with non-mucinous tumors. The EMT status was determined by immunohistochemical analysis of E-cadherin and Vimentin in tissue sections. Mucinous tumors had a significantly higher cytoplasmic E-cadherin score (P=0.043), they were significantly less differentiated (P=0.007), more advanced (P=0.005), and predominately affected right colon (P=0.030) in comparison to non-mucinous tumors. Epithelial tumors were significantly better differentiated (P=0.034) and with less prominent tumor budding (P < 0.001) than mesenchymal tumors. The process of EMT appears to be more prominent in tumors of younger patients regardless of mucinous histology. EMT status may represent a useful prognostic tool in early-onset CRC.

The secretory pathway Ca2+-ATPase SPCA2 is a tumor suppressor in triple receptor negative breast cancer (TNBC), a highly aggressive molecular subtype that lacks tailored treatment options. Low expression of SPCA2 in TNBC confers poor survival prognosis in patients. Previous work has established that re-introducing SPCA2 to TNBC cells restores basal Ca2+ signaling, represses mesenchymal gene expression, mitigates tumor migration in vitro and metastasis in vivo. In this study, we examined the effect of histone deacetylase inhibitors (HDACi) in TNBC cell lines. We show that the pan-HDACi vorinostat and the class I HDACi romidepsin induce dose-dependent upregulation of SPCA2 transcript with concurrent downregulation of mesenchymal markers and tumor cell migration characteristic of epithelial phenotype. Silencing SPCA2 abolished the ability of HDACi to reverse epithelial to mesenchymal transition (EMT). Independent of ATPase activity, SPCA2 elevated resting Ca2+ levels to activate downstream components of non-canonical Wnt/Ca2+ signaling. HDACi treatment led to SPCA2-dependent phosphorylation of CAMKII and -catenin, turning Wnt signaling off. We conclude that SPCA2 mediates the efficacy of HDACi in reversing EMT in TNBC by a novel mode of non-canonical Wnt/Ca2+ signaling. Our findings provide incentive for screening epigenetic modulators that exploit Ca2+ signaling pathways to reverse EMT in breast tumors.

Background: Ovarian cancer is the leading cause of death from gynecological malignancies with serous carcinoma being the most common histopathologic subtype. Epithelial-Mesenchymal Transition (EMT) correlates with an increased metastatic potential, whereas the transcription factor SOX11 is overexpressed in diverse malignancies. Methods: In the present study, we aim to evaluate the potential role of the immunohistochemical expression of SOX11 in 30 serous ovarian carcinomas in association with E-cadherin and Vimentin expression as well as with patients’ clinicopathological data. Results: Most of the examined cases showed concurrent expression of E-cadherin and Vimentin, whereas SOX11 was expressed in a minority of the cases (26,7%). Interestingly, the positive cases had more frequently a metastatic disease at the time of diagnosis compared to the negative cases (p=0.09), an association, however, of marginal significance. Moreover, there was a negative correlation between E-Cadherin and SOX11 expression (p=0,0077) and a positive correlation between Vimentin and SOX11 expression (p=0,0130). Conclusions: The present work, for the first time, provides preliminary evidence SOX11 overexpression alongside E-cadherin loss in the promotion of EMT in serous ovarian cancer, thereby endorsing tumor metastasis.

Epithelial-to-mesenchymal transition (EMT) plays a role in chronic obstructive pulmonary diseases (COPD). Cyclic adenosine monophosphate (cAMP) can inhibit transforming growth factor-β1 (TGF-β1) mediated EMT. Although compartmentalization via A-kinase anchoring proteins (AKAPs) is central to cAMP signaling, functional studies on their therapeutic value in the lung EMT process are lacking. Bronchial epithelial (BEAS-2B, primary HAE cells) were exposed to TGF-β1. Epithelial (E-cadherin, ZO-1) and mesenchymal markers collagen Ӏ (mRNA, protein) were analyzed. St-Ht31 disrupted AKAP-PKA interactions. TGF-β1 release was measured by ELISA. TGF-β1-sensitive AKAPs Ezrin, AKAP95 and Yotiao were silenced using siRNA. Cell migration was analyzed by wound healing assay, xCELLigence, Incucyte. Prior to TGF-β1, dibutyryl-cAMP (dbcAMP), fenoterol, rolipram, cilostamide, forskolin were used to elevate intracellular cAMP. TGF-β1 induced morphological changes, decreased E-cadherin but increased collagen Ӏ and cell migration, a process reversed by PF-670462. TGF-β1 altered (mRNA, protein) expression of Ezrin, AKAP95 and Yotiao. St-Ht31 decreased E-cadherin (mRNA, protein), but counteracted TGF-β1-induced collagen Ӏ upregulation. Cigarette smoke (CS) increased TGF-β1 release, activated TGF signaling, augmented cell migration and reduced E-cadherin expression, a process blocked by TGF-β1 neutralizing antibody. Silencing of Ezrin, AKAP95 and Yotiao diminished TGF-β1-induced collagen Ӏ expression, as well as TGF-β1-induced cell migration. Fenoterol, rolipram, and cilostamide, in AKAP silenced cells pointed to distinct cAMP compartments. We conclude that Ezrin, AKAP95 and Yotiao promote TGF-β1-mediated EMT, linked to a TGF-β1 release by CS. AKAP members define the ability of fenoterol, rolipram and cilostamide to modulate the EMT process, and are potential relevant targets in the treatment of COPD.

Rutin has been reported as a potential anti-cancer agent for several decades. This study evaluated the effects of rutin on the proliferation, metastasis, and angiogenesis of MDA-MB-231 and MCF-7 breast cancer cell lines. Increasing concentrations of rutin significantly stimulated the proliferation of MDA-MB-231 and MCF-7 cells compared to controls. Wound scratch assay demonstrated that rutin had an inducing effect on the migration of the cells. In MDA-MB-231 and MCF-7 cells, rutin upregulated MKI67, VIM, CDH2, FN1, and VEGFA and downregulated CDH1 and THBS1 genes. It also increased N-cadherin and VEGFA and decreased E-cadherin and thrombospondin 1 protein expression. Our data indicated that rutin could stimulate proliferation, migration, and pro-angiogenic activity in two different breast cancer cell lines. This phytoestrogen induced invasion and migration of both cell lines by a mechanism involving the EMT process. This suggests that rutin may act as a breast cancer-promoting phytoestrogen.

Pyrocumulonimbus (pyroCb) thunderclouds, produced from extreme bushfires, can initiate frequent cloud-to-ground (CG) lightning strikes containing extended continuing currents. This, in turn, can ignite new spotfires and inflict massive harm on the environment and infrastructures. This study presents a 3D numerical thundercloud model for estimating the lightning of different types and its striking zone for the conceptual tripole thundercloud structure which is theorized to elucidate the lightning phenomenon in pyroCb storms. More emphasis is given to the lower positive charge structure thundercloud to thoroughly examine various electrical parameters including the longitudinal electric field, electric potential, and surface charge density. The simulation outcomes on pyroCb thunderclouds with a tripole structure confirm the presence of negative longitudinal electric field initiation at the cloud’s lower region. This initiation is accompanied by enhancing the lower positive charge region, resulting in an overall positive electric potential increase. Consequently, negative surface charge density appears underneath the pyroCb thundercloud which has the potential to induce positive cloud-to-ground (+CG) lightning flashes. The suggested model would establish the basis for identifying the potential area impacted by lightning and could also be expanded to analyze the dangerous conditions that may arise in wind energy farms or power substations in times of severe pyroCb events.

The epithelial-mesenchymal transition (EMT) is a major event in idiopathic pulmonary fibrosis pathogenesis. Here, we investigated whether growth arrest-specific protein 6 (Gas6) plays a protective role in lung fibrosis via suppression of the EMT and fibroblast activation. rGas6 ad-ministration inhibited the EMT in isolated mouse ATII cells 14 days post-BLM treatment based on morphologic cellular alterations, changes in mRNA and protein expression profiles of EMT markers, and induction of EMT-activating transcription factors. BLM-induced increases in gene expression of fibroblast activation-related markers and the invasive capacity of primary lung fi-broblasts in primary lung fibroblasts were reversed by rGas6 administration. Furthermore, the hydroxyproline content and collagen accumulation in interstitial areas with damaged alveolar structures in lung tissue were reduced by rGas6 administration. Targeting Gas6/Axl signaling events with specific inhibitors of Axl (BGB324), COX-2 (NS-398), EP1/EP2 receptor (AH-6809), or PGD2 DP2 receptor (BAY-u3405) reversed the inhibitory effects of rGas6 on EMT and fibroblast activation. Finally, we confirmed the antifibrotic effects of Gas6 using Gas6−/− mice. Therefore, Gas6/Axl signaling events play a potential role in inhibition of EMT process and fibroblast acti-vation via COX-2-derived PGE2 and PGD2 production, ultimately preventing the development of pulmonary fibrosis.

The FOLFOX scheme, based on the association of 5-fluorouracil and oxaliplatin, is the most frequently indicated chemotherapy scheme for patients diagnosed with metastatic colorectal cancer. Nevertheless, development of chemoresistance is one of the major challenges associated with this disease. It has been reported that epithelial-mesenchymal transition (EMT) is implicated in microRNA-driven modulation of tumor cells response to 5-fluorouracil and oxaliplatin. Besides, from pharmacogenomic research it is known that overexpression of genes encoding dihydropyrimidine dehydrogenase (DPYD), thymidylate synthase (TYMS), methylenetetrahydrofolate reductase (MTHFR), the DNA repair enzymes ERCC1, ERCC2, and XRCC1, and the phase 2 enzyme GSTP1 impair the response to FOLFOX. It has been observed that EMT is associated with overexpression of DPYD, TYMS, ERCC1, and GSTP1. In this review we investigated the role of miRNAs as EMT promotors in tumor cells, and its potential effect on upregulation of DPYD, TYMS, MTHFR, ERCC1, ERCC2, XRCC1 and GSTP1 expression, which would lead to resistance of CRC tumor cells to 5-fluorouracil and oxaliplatin. This constitutes a potential mechanism of epigenetic regulation involved in late-onset of acquired resistance in mCRC patients under FOLFOX chemotherapy. Expression of these biomarkers microRNA could serve as tools for personalized medicine, and as potential therapeutic targets in the future.

The Epithelial-Mesenchymal-Transition (EMT) phenotype, identified as a significant clinical indicator in cancer, manifests as a biological process where cells transition from epithelial to mesenchymal characteristics. Physiologically, EMT plays a crucial role in tissue remodeling, promoting healing, repair, and responding to various tissue damages. This study investigates the impact of BNE-RRC on oral cancer cells (KB) and reveals its significant effects on cancer cell growth, migration, invasion, and EMT. BNE-RRC induces the epithelial-like morphology in KB cells, effectively reversing EMT to Mesenchymal-Epithelial Transition (MET). Extraordinarily, sustained culture of cancer cells with BNE-RRC for 14 days maintains an epithelial status even after treatment withdrawal, suggesting BNE-RRC as a potential therapeutic agent for cancer. These findings highligh the promise of BNE-RRC as a comprehensive therapeutic agent in cancer treatment by inhibiting cancer cell growth, migration, and invasion, while also orchestrating a reversal of the EMT process. The study proposes that BNE-RRC could be effective agent for cancer treatment.

Under different pathophysiological conditions endothelial cells lose endothelial phenotype and gain mesenchymal cell-like phenotype via a process known as endothelial-to-mesenchymal transition (EndMT). At the molecular level, endothelial cells lose the expression of endothelial cell-specific markers such as CD31/platelet-endothelial cell adhesion molecule, von Willebrand factor, and vascular-endothelial cadherin and gain the expression of mesenchymal cell markers such as α-smooth muscle actin, N-cadherin, vimentin, fibroblast specific protein-1 and collagens. EndMT is induced by numerous different pathways triggered and modulated by multiple different and often redundant mechanisms in a context-dependent manner depending on the pathophysiological status of the cell. EndMT plays an essential role in embryonic development, particularly in atrioventricular valve development, however, EndMT is also implicated in pathogenesis of several genetically determined and acquired diseases including malignant, cardiovascular, inflammatory, and fibrotic disorders. Among cardiovascular diseases aberrant EndMT is reported in atherosclerosis, pulmonary hypertension, valvular disease, fibroelastosis and cardiac fibrosis. Accordingly, understanding the mechanisms behind cause and/or effect of EndMT to eventually target EndMT appears to be a promising strategy to treat aberrant EndMT-associated diseases. However, this approach is limited by a lack of precise functional and molecular pathways, causes and/or effects, and lack of robust animal model and human data about EndMT in different diseases. Here, we review different mechanisms in EndMT and the role of EndMT in various cardiovascular diseases.

Objective: Aims to investigate the effects of empagliflozin (EMPA), a sodium-glucose co-transporter 2 (SGLT2) inhibitor, on renal fibrosis in male diabetic Sprague-Dawley (SD) rat model. Methods: Streptozotocin(STZ) were injected to establish diabetes model, EMPA (10 mg/kg·d) or normal saline (NS) were administered for four weeks. The changes in renal fibrosis-related biomarkers, include vimentin (VIM), collagen types I(Col-I), collagen types III(Col-III), fibroblast-specific protein 1(FSP-1), connective tissue growth factor (CTGF), fibronectin (FN) were evaluated. Renal pathology, serum glucose levels and urinary protein excretion were also assessed. Results: Biomarkers of renal fibrosis were significantly reduced in the EMPA group compared to those in the NS group after 4-week treatment, including VIM (519.84±83.37 vs. 663.27±91.84 ng/ml, P<0.05), Col-I (21.27±1.46 vs. 25.71±2.82 ng/ml , P<0.05) and Col-III (7.06±1.12 vs. 9.43±1.36 ng/ml, P<0.05), FSP-1 (4.38±0.81 vs. 5.70±0.78 ng/ml, P<0.05), and CTGF (1147±217 vs. 1556±235 pg/ml, P<0.05),respectively. Nevertheless, compared to normal control (NC) group, the levels of renal fibrosis-related biomarkers in the EMPA group showed no significant differences except for VIM, which was VIM (336.66±28.87 vs. 519.84±83.37 ng/mL, P<0.001). NS group rats showed notable renal tubular dilation and casts, EMPA group exhibited only mild tubular dilation. Conclusion: These findings suggest that empagliflozin reverse renal fibrosis potentially through inhibiting CTGF-mediated epithelial-mesenchymal transition.

Epithelial ovarian cancer (EOC) remains the most lethal gynecologic malignancy, largely due to metastasis and drug resistant recurrences. Fifteen percent of ovarian tumors carry mutations in BRCA1 or BRCA2, rendering them vulnerable to treatment with PARP inhibitors such as olaparib. Recent studies have shown that TGFβ can induce “BRCAness” in BRCA wild-type cancer cells. Given that TGFβ is a known driver of epithelial to mesenchymal transition (EMT), and the con-nection between EMT and metastatic spread in EOC and other cancers, we asked if TGFβ and EMT alter susceptibility of EOC to PARP inhibition. Epithelial EOC cells were transiently treated with soluble TGFβ and their clonogenic potential, expression and function of EMT and DNA repair genes, and response to PARP inhibitors compared with untreated controls. A second epithelial cell line was compared to its mesenchymal derivative for EMT and DNA repair gene expression and drug responses. We found that TGFβ and EMT resulted in downregulation of genes responsible for homologous recombination (HR) and sensitized cells to olaparib. HR efficiency was reduced in a dose-dependent manner. Furthermore, mesenchymal cells displayed sensitivity to olaparib, cis-platin, and the DNA-PK inhibitor Nu-7441. Therefore, treatment of disseminated, mesenchymal tumors may represent an opportunity to expand clinical utility of PARP inhibitors and similar agents.

Acute Myeloid Leukemia (AML) is a diverse malignancy originating from myeloid progenitor cells, with significant genetic and clinical variability. Modern classification systems like those from the World Health Organization (WHO) and European LeukemiaNet use immunophenotyping, molecular genetics, and clinical features to categorize AML subtypes. This classification highlights crucial genetic markers such as FLT3, NPM1 mutations, and the MLL-AF9 fusion, which are essential for prognosis and directing targeted therapies. The MLL-AF9 fusion protein is often linked with therapy-resistant AML due, highlighting the risk of relapse due standard chemotherapeutic regimes. In this sense, factors like the ZEB, SNAI, and TWIST gene families, known for their roles in epithelial-mesenchymal transition (EMT) and cancer metastasis, also regulate hematopoiesis and may serve as effective therapeutic targets in AML. These genes contribute to cell proliferation, differentiation, and extramedullary hematopoiesis, suggesting new possibilities for treatment. Advancing our understanding of the molecular mechanisms that promote AML, especially how the bone marrow microenvironment affects invasion and drug resistance, is crucial. This comprehensive insight into the molecular and environmental interactions in AML emphasizes the need for ongoing research and more effective treatments.

: Carcinoma-associated fibroblasts (CAFs) are highly accumulated in the tumor surrounding stroma of primary epithelial ovarian cancer (OC). CAFs exert important functions for the vascularization, growth and progression of ovarian tumor cells. However, no attention has been shown to their origin so far. It has been mainly assumed that CAFs in primary OC arise from the activation of resident fibroblasts. Here, we compare CAFs with ovarian location to CAFs found in peritoneal implants from patients with advanced OC. Our findings show that CAFs from primary tumors and peritoneal metastases share the expression of mesothelial-related markers. Therefore, as in peritoneal carcinomatosis, CAFs in primary ovarian carcinomas could be originated via a mesothelia-to-mesenchymal transition (MMT) process. The detection of mesothelial-derived CAFs in tumors confined to the ovary and associated biomarkers could be the key to early detection of peritoneal spread in affected patients.

The Epithelial- Mesenchymal Transition (EMT) is a biological phenomenon associated with explicit phenotypic and molecular changes in cellular traits. Unlike the earlier-held popular belief of it being a binary process, EMT is now thought of as a landscape including diverse hybrid E/M phenotypes manifested by varying degrees of the transition. These hybrid cells can co-express both epithelial and mesenchymal markers and/or functional traits, and can possess the property of collective cell migration, enhanced tumor-initiating ability, and immune/targeted therapy-evasive features, all of which are often associated with worse patient outcomes. These characteristics of the hybrid E/M cells have led to a surge in studies that map their biophysical and biochemical hallmarks that can be helpful in exploiting their therapeutic vulnerabilities. This review discusses recent advances made in investigating hybrid E/M phenotype(s) from diverse biophysical and biochemical aspects by integrating live cell-imaging, cellular morphology quantification and mathematical modeling, and highlights a set of questions that remain unanswered about the dynamics of hybrid E/M states.

Establishing macrometastases at distant organs is a highly challenging process for cancer cells, with extremely high attrition rates. A very small percentage of disseminated cells have the ability to dynamically adapt to their changing micro-environments through reversibly switching to another phenotype, aiding metastasis. Such plasticity can be exhibited along one or more axes – epithelial-mesenchymal plasticity (EMP) and cancer stem cells (CSCs) being the two most studied, and often tacitly assumed to be synonymous. Here, we review the emerging concepts related to EMP and CSCs across multiple cancers. Both processes are multi-dimensional in nature; for instance, EMP can be defined on morphological, molecular and functional changes, which may or may not be synchronized. Similarly, self-renewal, multi-lineage potential, and anoikis and/or therapy resistance may not all occur simultaneously in CSCs. Thus, arriving at rigorous functional definitions for both EMP and CSCs is crucial. These processes are dynamic, reversible, and semi-independent in nature; cells traverse the inter-connected high-dimensional EMP and CSC landscapes in diverse paths, each of which may exhibit a distinct EMP-CSC coupling. Our proposed model offers a potential unifying framework for elucidating the coupled decision-making along these dimensions and highlights a key set of open questions to be answered.

We have previously developed several successful decellularization strategies yielding porcine cardiac extracellular matrices (pcECMs), which exhibit tissue-specific bioactivity and bioinductive capacity when cultured with various pluri- and multipotent stem cells. Here, we studied the tissue-specific effects of the pcECM on seeded human mesenchymal stem cells (hMSCs) phenotype using reverse transcribed quantitative polymerase chain reaction (RT-qPCR) arrays for cardio-vascular related genes. We further corroborated interesting findings at the protein level (flow cytometry and immunological stains) as well as bioinformatically using several mRNA sequencing and protein databases of normal and pathologic adult tissue expression, as well as during human embryonic organogenesis. We discovered that upon seeding of human mesenchymal stem cells (hMSCs) on the pcECM they displayed partial MET toward endothelial phenotypes (CD31+) and morphologies, which were preceded by an early spike (~day 3 onward after seeding) in HAND2 expression at both the mRNA and protein levels compared to plate controls. CRISPR-Cas9 knockout (KO) of HAND2 and its associated antisense long non-coding RNA (HAND2-AS1) regulatory region resulted in proliferation arrest, hypertrophy, and senescent-like morphology. Bioinformatic analyses revealed that HAND2 and HAND2-AS1 are highly correlated in expression, are expressed in many different tissue types albeit at distinct yet tightly regulated expression levels. Deviation (down or up regulation) from these basal tissue expression levels are associated with a long list of pathologies. We thus suggest that HAND2 expression levels may finetune cell plasticity possibly affecting senescence and mesenchymal-to-epithelial transition states, through yet unknown mechanisms. Targeting this pathway may represent a promising new therapeutic approach for a wide range of diseases, including cancer, degenerative disorders, and aging. Nevertheless, further investigations are required to better understand the molecular players involved, potential inducers and inhibitors of this pathway, and eventually potential therapeutic applications.

One of the most used markers of cancer stem cells in several cancers, including colorectal cancer and breast cancer, is CD44. CD44 is a glycoprotein that traverses the cell membrane and binds to many ligands including hyaluronan resulting in activation of signaling cascades. Several reports have shown conflicting data on the expression of CD44 and that the expression depends on modes of investigations and subtypes of cancers. In addition, the correlation between CD44 expression and drug resistance, immune infiltration, EMT, metastasis and patients prognosis in several cancer types remains unclear. This study investigated CD44 expression in several cancers and explored its relationship with tumorigenesis using various publicly available databases, including The Cancer Genome Atlas, GEPIA, Oncomine, Genomics of Drug Sensitivity in Cancer and Tumor Immune Estimation Resource. Our analysis reveals that CD44 is differentially expressed in different cancers. CD44 expression is significantly associated with cancer patients’ survival in gastric, pancreatic and colorectal cancers. In addition, CD44 expression is closely linked with immune infiltration and immune suppressive features in pancreatic, colon adenocarcinoma and stomach cancer. High CD44 expression was significantly correlated with the expression of drug resistance-, EMT- and metastasis- linked genes. Tumors expressing high CD44 have higher mutation burden and afflict older patients than tumors expressing low CD44. Cell lines expressing high CD44 are more resistant to anti-cancer drugs compared to those expressing low CD44. Protein-protein interaction investigations and functional enrichment analysis showed that CD44 interacts with gene products related to cell-substrate adhesion, migration, platelet activation, and cellular response to stress. KEGG pathway analysis revealed that these genes play key roles in biological adhesion, cell component organization, locomotion, G-α-signaling and the response to stimulus. Overall, this investigation reveals that CD44 play significant roles in tumorigenesis, can be used as a prognostic biomarker in several cancers and can be therapeutically targeted in cancer therapy.

To clarify whether changes in biological features of breast tumor cells and intra-tumor immunity after neoadjuvant chemotherapy (NAC) may correlate with pathological responses and prognosis in breast cancer patients treated with NAC, we investigated various biomarkers using both pre- and post-NAC tumor samples. The study subjects were 24 primary breast cancer patients, who were treated with NAC at the Department of Breast and Thyroid Surgery, Kawasaki Medical School Hospital between 2010 and 2011. All of them had a non-pathological complete response (pCR) to NAC and their pre- and post-NAC tumor samples were available for biomarker assays. Ki67 labeling index, apoptosis, factors related to cancer stem cells and epithelial-mesenchymal transition, tumor infiltrating lymphocytes (TILs), and expression levels of CD-8, CD-4, FoxP3, PD-L1, and PD-1 were studied using the paired samples. Biological characteristics of residual tumors such as nuclear grade (NG) and vascular invasion (v) were also investigated. The median age was 53 years-old and 14 patients had stage III tumors, while 10 had stage II tumors. A higher expression level of CD8, CD4, or PD-1 in pre-NAC samples and of CD8, CD4 or PD-L1 in post-NAC samples was significantly correlated with a better pathological response to NAC. Positivity of ZEB1, vimentin, and v or NG 3 in post-NAC samples was significantly correlated with either worse disease-free survival (DFS) or worse overall survival (OS) by univariate analyses. Multivariate analyses for DFS and OS revealed that positivity for v and vimentin expression in residual tumors were independent prognostic factors in this study. These findings indicate that activated intra-tumor immune microenvironments may play significant roles in pathological responses to NAC, and that the up-regulation of vimentin and v-positivity in residual tumors may be pivotal prognostic factors in non-pCR cases to NAC.

The epithelial-mesenchymal (E/M) hybrid state has emerged as an important mediator of elements of cancer progression, facilitated by epithelial mesenchymal plasticity (EMP). We review here evidence for the presence, prognostic significance, and therapeutic potential of the E/M hybrid state in carcinoma. We further assess modelling predictions and validation studies to demonstrate stabilised E/M hybrid states along the spectrum of EMP, as well as computational approaches for characterising and quantifying EMP phenotypes, with particular attention to the emerging realm of single-cell approaches through RNA sequencing and protein-based techniques.

Epithelial-mesenchymal transition (EMT) has been well recognized for its essential role in cancer progression as well as normal tissue development. In cancer cells, activation of EMT permits the cells to acquire migratory and invasive abilities and stem-like properties. However, simple categorization of cancer cells into epithelial and mesenchymal phenotypes misleads the understanding of the complicated metastatic process, and contradictory results from different studies also indicate the limitation of application of EMT theory in cancer metastasis. Nowadays, growing evidence suggests the existence of an intermediate status between epithelial and mesenchymal phenotypes, i.e., the “hybrid epithelial-mesenchymal (hybrid E/M)”state, provides a possible explanation for those conflicting results. Appearance of hybrid E/M phenotype offers a more plastic status for cancer cells to adapt the stressful environment for proceeding metastasis. In this article, we review the biological importance of the dynamic changes between the epithelial and the mesenchymal states. The regulatory mechanisms encompassing the translational, post-translational, and epigenetic control for this complex and plastic status are also discussed .

Cancer cells can acquire a spectrum of stable hybrid epithelial/mesenchymal (E/M) states during epithelial-mesenchymal transition (EMT). Cells in these hybrid E/M phenotypes often combine epithelial and mesenchymal features and tend to migrate collectively commonly as small clusters. Such collectively migrating cancer cells play a pivotal role in seeding metastases and their presence in cancer patients indicates an adverse prognostic factor. Moreover, cancer cells in hybrid E/M phenotypes tend to be more associated with stemness which endows them with tumor-initiation ability and therapy resistance. Most recently, cells undergoing EMT have been shown to promote immune suppression for better survival. A systematic understanding of the emergence of hybrid E/M phenotypes and the connection of EMT with stemness and immune suppression would contribute to more effective therapeutic strategies. In this review, we first discuss recent efforts combining theoretical and experimental approaches to elucidate mechanisms underlying EMT multi-stability (i.e. the existence of multiple stable phenotypes during EMT) and the properties of hybrid E/M phenotypes. Following we discuss non-cell-autonomous regulation of EMT by cell cooperation and extracellular matrix. Afterwards, we discuss various metrics that can be used to quantify EMT spectrum. We further describe possible mechanisms underlying the formation of clusters of circulating tumor cells. Last but not least, we summarize recent systems biology analysis of the role of EMT in the acquisition of stemness and immune suppression.

Malignant Pleural Mesothelioma (MPM) is an aggressive cancer associated to asbestos exposure. MPM pathogenesis has been related both to oxidative stress, evoked by and in response to asbestos fibers exposure, and the Epithelial Mesenchymal Transition (EMT), an event induced by oxidative stress itself and related to cancer proliferation and metastasis. Asbestos related primary oxidative damage is counteracted in the lung by various redox-sensitive factors, often hyperactivated in some cancers. Among these redox-sensitive factors, Apurinic-apyrimidinic endonuclease 1 (APE-1)/Redox effector factor 1 (Ref-1) has been demonstrated to be overexpressed in MPM and lung cancer, but the molecular mechanism has not yet fully understood. Moreover, asbestos exposure has been associated to induced EMT event, via some EMT transcription factors, such as Twist, Zeb-1 and Snail-1, in a possible crosstalk with oxidative stress and inflammation events. To demonstrate this hypothesis, we inhibited/silenced Ref-1 in MPM cells: as a consequence, both EMT (Twist, Zeb-1 and Snail-1) markers and cellular migration/proliferation were significantly inhibited. Take as a whole, these results show, for the first time, a crosstalk between oxidative stress and EMT in MPM carcinogenesis and invasiveness, so improving the knowledge to better address a preventive and therapeutic approach against this aggressive cancer.

With the continuous progress in modern medicine, the early detection rate of gastric cancer has increased, and the mortality rate has decreased. However, gastric cancer remains the third leading cause of cancer-related death worldwide, with a high recurrence rate. Metastasis is the leading cause of death and recurrence of gastric cancer, which greatly hinders treatment success. Cancer development is a complex process involving multiple sequential steps. In the metastatic cascade, local invasion may be considered an initial, crucial step in the development of a malignant tumor, which leads to distant metastasis. Epithelial-mesenchymal transformation (EMT) is one of the most important developmental processes that occur during tumor invasion. EMT confers certain basic abilities to cancer cells, such as migration, invasion and anti-apoptotic ability, thus initiating and increasing metastasis. However, little is known about the molecular mechanisms that promote EMT and gastric cancer cell metastasis. A number of recent studies have found that circular RNAs（circRNAs）are associated with gastric cancer EMT, regulating the EMT process and promoting the occurrence and development of tumors. Because of their unique continuous circular structure, circRNAs have relatively high stability in plasma and cells, making them more suitable as diagnostic biomarkers in malignant tumors. Therefore, understanding the mechanism of circRNAs in EMT in gastric cancer is an important research direction to actively prevent tumor metastasis and improve the therapeutic effect on advanced malignant tumors.

Pulmonary arteriovenous malformations (PAVMs) are vascular anomalies resulting in abnormal connection between pulmonary arteries and veins. In 80% of cases, PAVMs are present from birth, but clinical manifestations are rarely seen in childhood. These congenital malformations are typically associated with Hereditary Hemorrhagic Telangiectasia (HHT), a rare disease that affects 1 in 5,000/8,000 individuals. HHT disease is frequently caused by mutations in genes involved in the TGF-β pathway. However, approximately 15% of patients do not have a genetic diagnosis and, among the genetically diagnosed, more than 33% do not meet the Curaçao Criteria. This makes clinical diagnosis even more challenging in the pediatric age group. Here, we introduce an 8 years old patient bearing a severe phenotype of multiple diffuse PAVMs caused by an unknown mutation which ended in lung transplantation. Phenotypically, the case of study follows a molecular pattern HHT-like. Therefore, molecular biology and cellular functional analysis has been performed in primary endothelial cells (ECs) isolated from the explanted lung. The findings revealed a loss of functionality in lung endothelial tissue and a stimulation of endothelial to mesenchymal transition. Understanding the molecular basis of this transition could potentially offer new therapeutic strategies to delay lung transplantation in severe cases.

Off-grid electrification planning increasingly recognizes the importance of productive use of electricity (PUE) to promote community value creation and (financial) project sustainability. To ensure a sustainable and efficient integration in the community and energy system, PUE assets must carefully be evaluated to match both the community needs and the residential electricity demand patterns. We propose a novel methodology interlinking qualitative interviews, statistical analysis, and energy system modelling to optimize decision-making for PUE integration in off-grid energy systems in rural Madagascar by aligning relevant PUE effectively with anticipated residential electricity demand patterns based on socio-economic determinants of the community. We find that a possible contribution of the PUE to reducing the electricity costs depends signifi-cantly on three factors: 1. the residential electricity consumption patterns that are influenced by the socio-economic composition of the community, 2. the degree of flexibility of i) PUE assets and ii) operational preferences of the PUE user, and 3. the capacity of community members to finance and operate PUE assets. Our study demonstrates that significant cost reductions for PUE-integrated off-grid energy systems can be achieved by applying our proposed methodology. When matching PUE and residential consumption patterns, the integration of PUE assets in residential community energy system can reduce the financial risk of operators, provided the PUE enterprise operates reliably and sustainably. We highlight that the consideration of local value chains and co-creation approaches are essential to ensure the energy system is addressing the community’s needs, creates value for the community, enhances the project´s financial sustainability, and is achieving the overall objectives of decentralized energy system planning.

HSF1 is a well-known Heat Shock Protein expression regulator in response to stress. It also regulates processes important for growth, development, or tumorigenesis. Here, we studied the HSF1 influence on the phenotype of non-tumorigenic human mammary epithelial (MCF10A and MCF12A) and several triple-negative breast cancer cell lines. MCF10A and MCF12A differ by HSF1 levels, morphology, growth in the matrigel, expression of epithelial (CDH1) and mesenchymal (VIM) markers (MCF10A are epithelial cells, MCF12A resemble mesenchymal cells). HSF1 down-regulation led to reduced proliferation rate and spheroid formation in matrigel by MCF10A cells, while it did not affect the MCF12A proliferation but led to CDH1 up-regulation and the formation of better-organized spheroids. HSF1 overexpression in MCF10A resulted in reduced CDH1 and increased VIM expression, and the acquisition of elongated fibroblast-like morphology. The above results suggest that elevated levels of HSF1 may direct mammary epithelial cells toward a mesenchymal phenotype while lowering HSF1 could reverse the mesenchymal phenotype to an epithelial one. Therefore, HSF1 may be involved in the remodeling of mammary gland architecture over the female lifetime. Moreover, HSF1 levels positively correlated with the invasive phenotype of triple-negative breast cancer cells, and their growth was inhibited by the HSF1 inhibitor, DTHIB.

Pancreatic ductal adenocarcinoma (PDAC) is mostly diagnosed at advanced or even metastasized stages limiting patient´s prognosis. Metastasis requires high tumor cell plasticity implying phenotypic switching in response to changing environments. Here, Epithelial-Mesenchymal-Transition (EMT), being associated with the gain of cancer stem cell (CSC) properties, and its reversion are important. Since it is poorly understood whether different CSC-phenotypes exist along the EMT-axis and how these impact malignancy-associated properties, we aimed to characterize CSC-populations of epithelial and mesenchymal PDAC cells. Single-cell cloning revealed CSC (Holoclone) and non-CSC (Paraclone) clones from the PDAC cell lines Panc1 and Panc89. Panc1 Holoclone cells showed a mesenchymal phenotype dominated by high expression of the stemness marker Nestin, while Panc89 Holoclone cells exhibited a SOX2-dominated epithelial phenotype. Panc89 Holoclone cells showed enhanced cell growth and self-renewal capacity but slow cluster-like invasion. Contrarily, Panc1 Holoclone cells showed slower cell growth and self-renewal ability but were highly invasive. Moreover, cell variants differentially responded to chemotherapy. In vivo, Panc1 and Panc89 cell variants significantly differed regarding number and size of metastases as well as organ manifestation leading to different survival outcomes. Overall, these data support the existence of different CSC-phenotypes along the EMT-axis in PDAC manifesting in different metastatic propensities.

Protein degradation is a biological phenomena essential for cellular homeostasis and survivor. Selective protein degradation is performed by the ubiquitination system which selectively target proteins that need to be eliminated and lead them to proteasome degradation. In this review, we focus on the ubiquitin-conjugating enzyme E2 O (UBE2O) and highlight the role of UBE2O in many biological and physiological process. We further discuss the UBE2O implications in various human diseases, particularly in leukemias and solid cancers and suggest how UBE2O targeting could be novel strategy in the treatment of different human neoplasia.

Atopic dermatitis (AD) is a chronic inflammatory condition which significantly affects quality of life in both patients and their caregivers. Calcineurin inhibitors (CNI) are a class of immunosuppressive drugs predominantly inhibiting T cell mediated immune processes. CNI form complex by binding with immunophilins and in turn inhibit calcineurin and suppress downstream inflammatory pathway. Tacrolimus and pimecrolimus are topical CNI approved for the treatment of mild to severe AD in both children and adults. Application site reactions are frequently seen. They have been issued with black box warning towards increased risk of malignancies but supportive evidence is lacking. Cyclosporine, though highly effective, is used off-label for AD management. It is used for controlling acute flares of AD due to its very rapid onset of action. Nephrotoxicity and hypertension are its serious complications. CNI have not been reported with teratogenicity and may be used conditionally during pregnancy and lactation.

This study addresses the implementation of the International Financial Reporting Standard 9 (IFRS 9) in the European Union as of January 1, 2018, replacing the International Accounting Standard 39 (IAS 39) to introduce a new model for recognizing Loan Loss Provisions (LLP) based on Expected Credit Loss (ECL). This model responds to criticisms of the former Incurred Credit Loss (ICL) system for its inability to reflect credit losses in a timely manner, potentially exacerbating the effects of financial crises (Bushman &amp; Williams, 2015; Gebhardt &amp; Novotny-Farkas, 2011). The study focuses on the effects of adopting the ECL model on the level of Loan Loss Allowances (LLA) in loans, own equity, and the Common Equity Tier 1 (CET1) ratio across 13 Portuguese commercial banks. A mean comparison test is used to evaluate scenarios before and after the application of the ECL model, highlighting the importance of regulator actions and the adequacy of loss recognition policies, including the effects of Regulation (EU) 2017/2395 of December 12. The results obtained demonstrate significant negative impacts on the net values of loans, own equity, and the CET1 ratio upon adopting the IFRS 9 ECL model, due to the widespread increase in LLAs.

Biopolymer gels have gained tremendous potential for therapeutic applications due to their biocompatibility, biodegradability, and ability to adsorb and bind biological fluids, making them attractive for drug delivery and therapy. The versatility of biopolymer gels in theranostic backgrounds, with a focus on integrating imaging features and facilitating real-time monitoring of drug delivery. Different methods of delivery are explored imaging agents into biopolymer gels, including encapsulation, surface functionalization, nanoparticle encapsulation and layer-by-layer assembly techniques. Integration of Agents and Real-Time Monitoring Drug Delivery We summarize the synthesis methods, general properties, and mechanisms of biopolymer gels functionality, demonstrating their broad applications as multimodal systems for imaging-based therapeutics. These techniques not only enable multiple imaging but also provide signal enhancement and imaging a targeted facilitates, increasing the diagnostic accuracy and therapeutic efficacy. In addition, current techniques for incorporating imaging agents into biopolymer gels are discussed, and their role in precise drug delivery and monitoring.

This paper investigates the efficacy of YOLOv8 variants for vehicle detection and license plate detection within smart parking applications, emphasizing performance under varying ambient lighting conditions. The proposed system is to seize full video frames, extracts regions of interest containing vehicles, and feeds them into separate, pre-trained YOLOv8 models – one dedicated to vehicle detection and another for license plate detection. Four YOLOv8 variants, nano, small, medium, and large, are evaluated. As a pre-processing step, the images are processed with the help of OpenCV and Pillow libraries to adjust the luminosity and increase the images’ DPI so that they would be easy to perceive by the Tesseract OCR engine. Sixteen potential combinations arise from pairing the four YOLOv8 models for vehicle and license plate detection tasks. To identify the most suitable combinations, we employ the Multi-Criteria Decision-Making method, specifically Technique for Order of Preference by Similarity to Ideal Solution (TOPSIS) analysis. This analysis considers 4 critical metrics: Precision, mean average precision at 95% Intersection of Union threshold, Recall and Total Inference Time. The objective is to achieve an optimal balance between high accuracy and real-time processing. Following the selection of optimal YOLOv8 combinations through TOPSIS analysis, we assess their performance under varying ambient light intensity (measured in lux). This evaluation aims to identify the most robust model combinations that ensure accurate vehicle and license plate recognition across the diverse lighting conditions encountered in real-world environment.

Background and Objectives: Acute lung injury (ALI) is an inflammatory response in the lung caused by bacteria, viruses, trauma and other factors that results in lack of alveolar surfactant and subsequently respiratory distress. Endothelial-to-mesenchymal transition (EndoMT) is closely related to ALI-induced pulmonary fibrosis development and progression. This study examined the effect of milk fat globulin factor 8 (MFGE8) knockdown and overexpression on lipopolysaccharide (LPS)-induced EndoMT. Methods: Total MFGE8 activity in patients with acute respiratory distress syndrome (ARDS) and healthy volunteers was assessed using a colorimetric kit. In vitro, cell morphology was observed by microscopy, and invasion and migration were tested by Transwell and scratch assays. Specific siRNAs were transfected into HLMECs to downregulate MFGE8, and CD31 and α-SMA protein expression was detected by fluorescence microscopy and FCM. MFGE8, BMP, Smad 1, Smad4, Smad5, Snail, CD31 and α-SMA protein and gene expression was assessed by western blotting (WB) and qRT‒PCR. In vivo, the changes in cell morphology and alveolar septum in the lung of mice (C57BL/6, aged 7-8 weeks, male) were observed by H&E staining. In addition, ECM deposition in lung tissue was detected by Masson staining. CD31 and α-SMA protein expression in lung tissue was measured by WB. Results: The serum level of MFGE8 was lower in the ARDS group than in the control group. MFGE8 was identified as a protective factor associated with hospital survival. In vitro, the treatment of human lung microvascular endothelial cells (HLMECs) with LPS for 96 h clearly changed the cells from the typical cobblestone shape of ECs to spindle-like fibroblasts. The scratch and Transwell assay results indicated that endothelial cell migration and invasion were enhanced in the LPS group compared with the control group. Fluorescence microscopy, FCM, WB and PCR showed that LPS greatly inhibited CD31 (endothelial marker) expression and increased α-SMA (mesenchymal marker) expression. These data showed that LPS could induce EndoMT in HLMECs. Notably, siRNA-treated HLMECs yielded the same results. The administration of rhMFGE8 to HLMECs in the LPS or LPS+siRNA group ameliorated the changes in cell morphology and decreased cell migration and invasion. rhMFGE8 attenuated the effect of LPS or LPS+siRNA on EndoMT induction by increasing CD31 and decreasing α-SMA protein and gene expression. Moreover, activation of BMP/Smad1/5-Smad4 signalling in response to LPS and Snail (related to EndoMT transcription factors) expression were increased by MFGE8 knockdown but inhibited by rhMFGE8. In vivo, H&E staining revealed a thickened alveolar septum in the LPS group, and the thickness increased over time; in contrast, rhMFGE8 reversed this effect. ECM deposition occurred early in ALI induced by LPS and increased over time, and the administration of rhMFGE8 reversed this effect. WB showed that LPS inhibited CD31 protein expression and increased α-SMA protein expression in lung tissue. Conclusions: rhMFGE8 exerts a protective effect early in LPS-induced EndoMT through BMP/Smad1/5/Smad4 signalling and could be a therapeutic target in ALI.

This article touched upon various issues regarding vulnerability, disparities amongst community settings, and the effect of air pollution on the populace (low-income communities). Furthermore, the paper emphasized environmental ethics approaches like anthropocentric, nature-centric, and deep-ecological approaches. More so, it addresses the importance of handling these disparities, particularly from the geopolitical dimension, and recommends cross-border cooperation and accountability in promoting environmental justice in India.

The theory of the origin of carcinomas suggests that neoplasias from epithelial tissues are the consequence of the reactivation of developmental programs. It proposes a model in which the epithelial cells undergo cellular transitions due to replicative senescence and inflammation towards a mesenchymal-undifferentiated phenotype with cancerous behavior. The conserved pattern of histological progression and the molecular biology of carcinomas is congruent with the view of cancer as a developmental disease. In support of the theory, the experimental literature regarding the molecular, cellular, and histopathological mechanisms associated with epithelial carcinogenesis were aligned according to the premises of the hypothesis. Thereby identified a generic process in the carcinogenesis of the breast, endometrium, prostate, colon, lung, pancreas, bladder, liver, and cervix. Then, is provided a methodology overview of modeling in systems biology derived from previous research testing the hypothesis. The results illustrate the value of the complex systems approach to recover behavior that cannot be inferred only by traditional methods. Specifically, the model suggests that the consistency in the cell types and the directionality of the observed cellular transitions during epithelial carcinogenesis arise from structural constraints in the molecular networks associated with the carcinomas. Overall, the results of the dynamical analysis agree with the premises of the hypothesis and provide an insightful perspective of the potential mechanisms underlying the cellular plasticity displayed during epithelial carcinogenesis. In an era of big data and yet few advances in the underlying causes of chronic diseases, the manuscript also aims to inspire molecular biologists to integrate existing empirical evidence with systems biology modeling in the pursuit of understanding.

Mesenchymal stem cells (MSCs) are one of the main residents in the bone marrow (BM), having an essential role in the regulation of hematopoietic stem cell (HSCs) differentiation and proliferation. Myelodysplastic syndromes (MDS) are a group of myeloid disorders impacting hematopoietic stem and progenitor cells (HSCPs) and characterised by BM failure, ineffective haematopoiesis, cytopenia, a high risk of transformation through the expansion of MDS clones together with additional genetic defects. It has been indicated that MSCs play anti-tumorigenic roles such as cell cycle arrest and pro-tumorigenic roles including induction of metastasis in MDS and leukaemia. Growing evidence has shown that MSCs have impaired functions in MDS, such as decreased proliferation capacity, differentiation ability, haematopoiesis support, immunomodulation function, and increased inflammatory alterations within the BM through some intracellular pathways such as Notch and Wnt and extracellular modulators secreted by MSCs abnormally, including increased expressions of inflammatory factors and decreased expressions of hematopoietic factors, contributing to the development and progression of MDS. Therefore, MSCs can be targeted for the treatment of MDS and leukaemia. However, it remains unclear what drives MSCs to behave abnormally. In this review, dysregulations in MSCs and their contributions to myeloid haematological malignancies will be discussed.

The extent of access to energy of displaced populations in settlements and camps in Africa is largely 14 unknown. A multitude of contextual factors, such as the location and the characteristics of housing, 15 the legal status, the socio-cultural background, and the availability of humanitarian and public ser- 16 vices impact the living conditions and the needed energy services. Limitations in accessing energy 17 services have direct, multilayered, and far-reaching implications, including impacts on health, nu- 18 trition, education, protection, and livelihood. The objective of this article is to contribute to a more 19 comprehensive overview of the current state of energy access in displacement contexts on the Afri- 20 can continent by identifying and utilizing existing data. After a screening of the vast and various 21 available information, setting up of a database, consolidating the gathered data as well as assessing 22 the quality through a quality assessment method, the currently available information is visualized 23 and discussed. Considerable differences in the access to electricity for displaced persons across the 24 countries are found. For both electricity and clean cooking, the availability for displaced persons 25 ranges from nearly no access at all up to an access rate of 100%. More strikingly, the results also 26 show that besides South Africa and countries in the Maghreb region, the access to both clean cook- 27 ing and electricity for displaced persons is very low. At the same time, the fragmented data availa- 28 bility, the poor data quality, and the questionable expediency of available data allows neither solid 29 theoretical conclusions nor planning of effective practical implementation measures. Novel inter- 30 disciplinary research, conceptual frameworks and indicators are needed for the purpose of compa- 31 rability and consistency. Future research has the potential to more comprehensively capture the 32 current state of access to energy in displacements contexts and in a next step to examine how energy 33 is interwoven in the lives of displaced people to derive a set of more detailed context-sensitive en- 34 ergy indicators. It is essential that the concerned persons, the displaced persons themselves are in- 35 cluded in the research in a meaningful way.

The realization of a perfect absorber A = 1 with transmittance and reflectance T=R=0 by a thin metasurface is one of the hot topics in recent nanophotonics prompted by energy harvesting and sensor applications (A + R + T =1 is the energy conservation). Here we tested optical properties of over 400 structures of metal-insulator-metal (MIM) metasurfaces for a range of variation in thickness of insulator, the diameter of a disc and intra-disc distance experimentally and numerically. Conditions of a near-perfect absorption A > 95% with simultaneously occurring anti-reflection property (R < 5%) were experimentally determined. Differences between the bulk vs. nano-thin film properties at mid-IR of the used materials can be of interest for plasmonic multi-metal alloys and high entropy metals.

The transition to sustainable energy systems in the Middle East and North Africa (MENA) region addresses critical challenges of environmental protection, energy security, and socio-economic resilience. Using neo-institutional theory, this paper examines the intricate relationship between formal and informal institutions and their significant impact on the region’s energy transition. Despite the MENA region’s abundant renewable energy resources, numerous institutional barriers, such as governance inefficiencies, regulatory inconsistencies, and entrenched socio-cultural norms, significantly hinder this transition. Through a review of existing literature, this study presents a comprehensive analytical framework designed to overcome these barriers, with a focus on the Just and Sustainable Energy Transition model. This strategic model emphasizes equity, sustainability, and inclusive governance as pillars for reform. The study offers detailed recommendations for institutional change and underscores the importance of collaborative efforts among governments, industry stakeholders, and international partners to unlock the MENA region’s renewable energy potential, advance global sustainability goals, and ensure a more secure and resilient energy future.

In recent years, bioengineered and biotechnological products have gained tremendous attention to identify unique biologic features associated with oncology. To overwhelm the complexity of tumor personalized medicines (PM) or vaccines could be a promising way-out to be considered. Cancer is a heterogeneous disease. This characteristic variability of cancer provides itself to the emergent era of PM i.e., precision oncology. The prime objective of PM is merely to deliver the right treatment to the right patient at the right time. For instance, imatinib was effectively targeted chronic myeloid leukemia. To date, attainment in using PM approaches to cancer treatment have been mixed. The next-generation sequencing (NGS), and the use of several biomarkers (e.g., HER2, BRAF, ALK, etc.), to drive precise cancer treatment through a timely and cost-effective manner. In current review, author summarizes the advancement in the field of PM such as CRISPR-Cas9, NGS, pharmacogenomics, and the benefits of machine learning techniques. The precise communication between healthcare professionals, regulatory bodies, and patients is essential to translate advances in PM into immense benefits for patients with cancer globally.

The search of DNA polymorphisms useful for the genetic improvement of dairy farm animals lasts more than 40 years with relevant findings in cattle for milk traits, where the best combination of alleles for dairy processing have been found in casein genes and in the DGAT1. Nowadays, similar results are not reached yet in river buffaloes despite advanced genomic technologies and accurate phenotype records are available. The aim of the present study was to investigate and validate in a larger buffalo population the effect on six milk traits of four single nucleotide polymorphisms (SNP) in the CSN1S1, CSN3, SCD and LPL genes, previously reported to be associated with or affect dairy traits in smaller populations often belonging to one farm. A total of 800 buffaloes were genotyped. Daily milk yield (dMY, kg), protein yield (dPY, kg) and fat yields (dFY, kg), fat and protein contents (dFP, % and dPP, %), somatic cell count (SCC, 103cell/ml) and urea (mg/dl) were individually recorded in each month for the whole lactation from 2010 to 2021. A total of 15,742 individual milk test day records (2,496 lactations) were available on 680 buffalo cows with 3.6±1.7 parity (from 1 to 13) and 6.1±1.2 test day records per lactation on average. Three out four SNP in CSN1S1, CSN3 and LPL were associated with at least one of analyzed traits. In particular, the CSN1S1 (AJ005430:c.578C&gt;T) gave favorable associations with all yield traits (dMY, p=0.022; dPY, p=0.014 ; dFY, p=0.029) and SCS (p=0.032), whereas the CSN3 (HQ677596: c.536C&gt;T) positively associated with SCS (p=0.005) and milk urea (p=0.04). Favorable effect on dMY (p=0.028), dFP (p=0.027) and dPP (p=0.050) were observed for the LPL. Conversely, SCD did not show any association with milk traits. This is the first example of confirmation study carried out in the Mediterranean river buffalo for genes of economic interest in dairy field and it represents a very important indication for the preselection of young bulls destined to breeding programs in the view of a more sustainable dairy production.

Accurate determination of the concentration of alcohols and their metabolites is important in forensics and in several life science areas. A new method has been developed to quantify alcohols and their oxidative products using a headspace gas chromatography- mass spectrometer and isotope-labelled internal standards. This work demonstrates the application of this method, specifically in quantifying the concentration of oxidative products of alcohol and other minor alcohols found in hand sanitizers, which have become an essential household item since the COVID-19 pandemic. Apart from the major component, the minor alcohols found in hand sanitizers include methanol, isopropanol, and n-propanol. In ethanol-based hand sanitizers, a significant amount of acetaldehyde was observed as an oxidation product, while in isopropanol-based hand sanitizers, acetone was observed. The concentration of acetaldehyde in ethanol-based hand sanitizers significantly increased with storage time and temperature, whereas no such increase of acetone concentration was observed in isopropanol-based hand sanitizers with storage time and temperature.

Senna rugosa is a species found in the Cerrado and used in folk medicine as a vermifuge and in the treatment of poisonous snakebites accidents. In this work, we identified the main secondary metabolites present in ethanolic extracts of the leaves (ELSR) and roots (ERSR) of S. rugosa and evaluated the potential cytoprotective effect against cellular macromolecular damage, as well as the cytotoxic properties of the extracts on the K562 and Jurkat leukemic cell lines. The identification of metabolites was done by liquid chromatography coupled with mass spectrometry. The antioxidant activities were investigated by direct ABTS•+ and DPPH• radical scavenging methods, protection against oxidative damage in proteins and DNA. The cytotoxic properties were investigated against healthy cells, isolated from human peripheral blood (PBMC) and leukemic cell lines. The leaf extract contains catechin, rutin, epigallocatechin derivatives, kaempferol glycosides, luteolin, and dimeric and trimeric procyanidins, while the root extract profile shows obtusichromoneside derivatives, 2-methoxystypandrone, stilbene derivatives, naphthopyranones, and flavanone derivatives. The extracts showed antioxidant activity, with IC50 of 4.86 ± 0.51 µg/mL and 8.33 ± 0.90 µg/mL in the ABTS assay for ELSR and ERSR, respectively. And in the DPPH• assay, the IC50 was 19.98 ± 1.96 µg/mL for ELSR and 13.37 ± 1.05 µg/mL for ERSR. The extracts protected macromolecules against oxidative damage at concentrations of 5 µg/mL. The cytotoxicity test against leukemic strains was observed after 24 and 48 hours of treatment. After 48 h, results against the K562 cell line demonstrate IC50 of 242.54 ± 2.38 µg/mL and 223.00 ± 2.34 µg/mL for ELSR and ERSR , respectively. While against the Jurkat cell line, these extracts showed IC50 of 171.45 ± 2.25 µg/mL and 189.30 ± 2.27 µg/mL, respectively Results on PBMC viability, demonstrate that the extracts showed selectivity for the leukemic cell lines. Together, our results reveal that the leaves and roots of S. rugosa have completely distinct and complex chemical compositions. This study expands the repertoire of identified chemical compounds and underscores their significant pharmacological potential in conditions related to oxidative stress and leukemia.

Antibacterial bone cements (ABCs), such as antibiotic-loaded bone cements (ALBCs), have been widely utilized in clinical treatments. Currently, bone cements loaded with vancomycin, gentamicin, tobramycin, or clindamycin are approved by the US Food and Drug Administration. However, traditional ALBCs exhibit drawbacks like burst release and bacterial resistance. Therefore, there is a demand for the development of antibacterial bone cements containing novel agents. In this review, we summarize the latest advancements in ABCs. More importantly, we provide an overview and outlook on novel antibacterial agent-loaded bone cements, including metallic antibacterial agents, pH-switchable antibacterial agents, cationic polymers, N-halamines, non-leaching acrylic monomers, antimicrobial peptides, etc. Offering novel perspectives for designing ABCs and treating bone infections.

The nuclear factor-ĸB (NF-ĸB) transcriptional system is a major effector pathway involved in inflammatory responses. Previous studies found that a Gardenia decoction (GD) inhibited the expression of NF-κB in a lipopolysaccharide (LPS)-stimulated mouse intestinal injury model. Herein, we hypothesized that geniposide (GE), a component of Gardenia jasminoides Ellis, also exerts anti-inflammatory effects and inhibits NF-ĸB activity in LPS-induced intestinal epithelial cells (IEC-6). IEC-6 cells were stimulated with LPS, following which the effects of GE on NF-ĸB signaling in the IEC-6 cells were examined by western blotting to detect IĸB phosphorylation/degradation. The expression of NF-κB was determined by immunofluorescence assay (IFA). Enzyme-linked immunosorbent assay (ELISA) was used to detect the inhibitory effect of GE on the release of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) activated by LPS in IEC-6 cells. In addition, the migration ability of IEC-6 cells was observed by the scratch method. These results showed that GE dose-dependently downregulated levels of the proinflammatory cytokines TNF-α, IL-6 and IL-1β that had been upregulated by LPS and suppressed the phosphorylation of IĸB and NF-ĸB induced by LPS. Our findings indicated that GE could reduce LPS-induced NF-ĸB signaling and proinflammatory expression in IEC-6 cells and significantly enhance the migration of IEC-6 cells. Moreover, GE inhibited the expression of NF-κB, nuclear transfer, and transcriptional activity in IEC-6 cells. GE could block the synthesis of inflammatory factors of IEC-6 cells by inhibiting activation of the IĸB/NF-κB signaling pathway induced by LPS.

In the process of sewage coagulation treatment, quartz sand is often used as a heavy medium to accelerate the settling rate of flocs, but it will adversely affect the removal efficiency of pollutants. The factors that affect the coagulation effect and can be controlled manually include the quartz sand dosage, coagulant dosage, sewage pH, stirring time, settling time, etc, their reasonable setting is critical to. This paper was to study the optimal conditions of quartz sand enhanced coagulation(QSEC), first, single-factor tests were conducted to preliminarily explore the optimal range of influencing factors, and then response surface methodology（RSM）tests were performed to accurately determine the optimums of significant factors. The results showed that the addition of quartz sand can’t improve the water quality of coagulation treatment, but it can significantly accelerate the coagulation settlement process, the quartz sand dosage, the coagulant dosage and sewage pH all impacted significantly on its coagulation effect, and existed inflection points. A model that could guide QSEC was obtained by RSM tests. The model optimization and experimental validation showed that the optimal QSEC conditions for treating domestic sewage were as follows: the polyaluminum chloride(PAC) dosage, cationic polyacrylamide(CPAM) dosage, the sewage pH, quartz sand dosage, stirring time and settling time were 0.97 g·L-1, 2.25 mg·L-1, 7.22, 2 g·L-1, 5 minutes and 30 minutes, respectively, and the turbidity of treated sewage was reduced to 1.15 NTU.

Corneal ulcers are a common and potentially vision-threatening condition in horses that can be challenging to treat with conventional therapies alone. This case report describes the successful treatment of a non-healing corneal ulcer in a 28-year-old Hispano-Bretón mare using the secretome derived from adipose tissue-derived mesenchymal stem cells (ASCs). Despite initial treatment with antibiotics, anti-inflammatory drugs, and surgical debridement, the corneal ulcer failed to heal properly, exhibiting persistent epithelial defects and stromal complications. As an alternative regenerative approach, the ASC secretome, a rich source of trophic factors, cytokines, and extracellular vesicles, was topically administered to the affected eye. Remarkably, within one week of secretome treatment, the clinical signs of blepharospasm and epiphora resolved, and the corneal ulcer exhibited complete re-epithelialization, regained transparency, and reduced neovascularization. No recurrence was observed during the 1.5-year follow-up period. This case highlights the potential therapeutic benefits of ASCs secretome in promoting corneal wound healing and suggests its promise as a novel cell-free therapy for treating refractory corneal ulcers in horses.

Several recent studies have indicated that miR-30a plays critical roles in various biological processes and diseases. However, the mechanism of miR-30a participation in the regulation of idiopathic pulmonary fibrosis (IPF) is ambiguous. Our previous study demonstrated that miR-30a may function as a novel therapeutic target for lung fibrosis by blocking mitochondrial fission, which is dependent on dynamin-related protein-1 (Drp-1). However, the regulatory mechanism between miR-30a and Drp-1 has yet to be investigated. In addition, whether miR-30a can act as a potential therapeutic has not been verified in vivo. In this study, the miR-30a expression in IPF patients was evaluated. Computational analysis and a dual luciferase reporter system assay were used to identify the target gene of miR-30a, and cell transfection was used to confirm this relationship. Ten-eleven translocation 1 (TET1) was validated as a direct target of miR-30a, and the transfection of miR-30a mimic/inhibitor significantly reduced/increased the expression of TET1 protein. Further experiment verified that the interference on TET1(siRNA) could inhibit the hydroxymethlation of the Drp-1 promoter. Finally, miR-30a agomir was designed and applied to identify and validate the therapeutic effect of miR-30a in vivo. Our study demonstrated that miR-30a could inhibit the TET1 expression by base pairing with complementary sites in the 3′ untranslated region to regulate the hydroxymethlation of the Drp-1 promoter. Furthermore, miR-30a could act as a potential therapeutic target for IPF.

Aiming to improve medical diagnosis and treatment, artificial intelligence (AI) has emerged as a transformational force in the healthcare industry. In this article, we examine how AI is increasingly being used to improve healthcare, with an emphasis on how it is changing medical diagnosis and treatment. We explore the opportunities, threats, and ethical concerns of incorporating AI into healthcare practice. In addition, we feature important AI applications in radiology, pathology, cardiology, and cancer. AI has great potential to improve patient outcomes, diagnostic accuracy, and the ability to provide individualized treatment plans in the future if it is used and refined with care.

To elucidate mesenchymal stromal cells (MSC)-tumor intricate and ambiguous interactions, the reliable cell labeling and tracking techniques are imperative. Traditional methods of cell labelling have limitations mostly relevant to need for genetic modification what demands the exploration for alternative strategies. Here, we propose using fluorescent photoconvertible microcapsules containing Rhodamine B (RhB) to study mMSC migration in brain tumors. These 3 μm sized microcapsules are readily internalised by cells and undergo photoconversion under 561 nm laser exposure with fluorescence blue shift on demand. Optimal photoconversion was achieved with a laser irradiation duration of 0.4 ms, which provide a maximal brightness of photoconverted label without an excessive laser exposure on cells. Capsules modified with polyallylamine hydrochloride demonstrated the best potential for intracellular uptake without significantly affecting cell viability, motility, or proliferation. The optimal ratio of 20 capsules per mMSC was determined for labeling. Moreover, migration of individual mMSCs within 2D and 3D glioblastoma cell (EPNT-5) colonies over 2 days and in vivo tumor settings over 7 days was tracked. Our study unveils a robust platform for investigating MSC-tumor dynamics, offering insights into therapeutic strategies. Photoconvertible microcapsules could also become an indispensable tool for studying complex fundamental processes of cell-cell interactions for a wide range of problems in biology and medicine.

Sustainable agriculture is essential to provide food security for a growing world population without further sacrificing the integrity of the environment. To make progress towards agricultural sustainability we must consider ecological and socioeconomic processes within the agricultural socio-ecosystem and involve stakeholders in the research process. We propose an innovative experimental approach for examining how natural regulation of ecosystems may provide an alternative to increasing external inputs in agriculture while improving the socio-economic welfare of farmers. These “social-ecological experiments” go further to participatory action research by not only involving stakeholders in the research process but also by manipulating simultaneously socioeconomic and ecological processes under real field conditions to give a faster route to sustainability. Social-ecological experiments are undertaken in real field conditions, explicitly involving stakeholders, and help untangle the drivers of social-ecological dynamics under various land management and farming practices. Social-ecological experiments are distinct from adaptive management and scenario-planning approaches as they highlight the interactions between ecological and social processes, manipulate the social and ecological processes shaping the system and show causal links between patterns and processes. As an example, we describe a social-ecological experiment for reducing herbicide use. Social-ecological experiments offer great opportunities for increasing stakeholders’ acceptance of environmental policies implemented through adaptive management. These experiments may help to identify management practices that optimize multiple objectives, deliver a portfolio of ecosystem services and satisfy key stakeholders.

Metabolites present in the hemolymph of honey bees play a crucial role in modulating the metamorphic process within the species. However, the precise alterations in metabolite composition, along with the associated variances and regulatory pathways implicated during the larvae-to-pupae metamorphosis of honey bees, remain incompletely elucidated. In this investigation, we gathered hemolymph samples from honey bee larvae at three distinct physiological stages-feeding, prepupal, and pupae and subjected them to metabolite analysis utilizing the liquid chromatography-mass spectrometry (LC-MS) technique. Employing principal component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA), we identified significant differential metabolites and conducted a metabolic pathway analysis on those differentially up-regulated during the prepupal and pupae stages. Notably, metabolites up-regulated in the hemolymph of prepupal stage larvae primarily governed glucose metabolism and fat digestion and absorption, while those in pupae stage larvae were involved in regulating chitin and lipopolysaccharide precursor formation, as well as the biosynthesis of phenylalanine, tyrosine, and tryptophan. These findings bear significant implications for advancing our comprehension of the metamorphic processes in honey bees.

The electronic properties of calcium intercalated graphite (CaC6) as a function of pressure are revisited using density functional theory (DFT). The electronic band structures of CaC6, like many other layered superconducting materials, display cosine-shaped bands at or near the Fermi level (FL). Such bands encompass bonding/antibonding information with a strong connection to superconducting properties. Using an hexagonal cell representation for CaC6, construction of a double supercell in the c-direction effects six-folding in reciprocal space of the full cosine function, explicitly revealing the bonding/antibonding relationship divide at the cosine midpoint. Similarly, folding of the Fermi surface (FS) reveals physical phenomena relevant to electronic topological transitions (ETT) with application of pressure. For CaC6, the peak value for the superconducting transition temperature, Tc, occurs at about 7.5 GPa, near to the observed pressure of the calculated ETT. At this pressure, the radius of the nearly spherical Ca 4s-orbital FS coincides with three times the distance from the G centre point to the Brillouin zone (BZ) boundary of the 2c supercell (which is equal to half the identically defined distance for the primitive rhombohedral BZ). In addition, the ETT coincides with alignment of the non-bonding (inflection) point of the cosine band (the point at which the sign of the cosine amplitude modulation is reversed) with the FL. At other calculated pressure conditions, the Ca 4s-orbital FS undergoes topological changes that correspond and can be correlated to experimentally determined changes in Tc. The ETT is a key mechanism that circumscribes the known significant drop in Tc for CaC6 as a function of increasing pressure.

Tertiary lymphoid structures (TLSs) have become the focus of antitumor immunity. However, the prognostic significance of TLSs in epithelial ovarian cancer (EOC) treated with primary debulking surgery (PDS) or interval debulking surgery (IDS) remains unelucidated. This retrospective study examined the prognostic value of TLSs in tumor tissues obtained during PDS and IDS. Pathological specimens were collected from patients with EOC who underwent PDS or IDS between 2017 and 2020 at the National Cancer Center Hospital East. The correlation of tumor-infiltrating lymphocyte frequency, TLS presence, and PD-L1 expression with progression-free survival (PFS) and overall survival (OS) and the correlation between TLS and PD-L1 expression were analyzed. Overall, 25 specimens (15 from PDS and 10 from IDS) were analyzed. The presence of TLS was associated with a significantly longer OS in patients who underwent PDS but not in patients who underwent IDS. No correlation was identified between TLS and PFS in patients with PDS or with IDS. However, TLS was positively correlated with PD-L1 positivity. The prognostic impact of TLS, specifically in pre-chemotherapy specimens, and a positive correlation between TLS and PD-L1 indicate the potential of TLS as a meaningful biomarker for understanding antitumor immunity and developing immunotherapy for EOC.

Rheumatoid arthritis (RA) is an autoimmune disease in which joints are gradually de-stroyed, and early diagnosis and treatment before joint deformation or destruction is im-portant. The detection of novel RA biomarkers in saliva may facilitate the early detection of RA before the onset of disease. In this study, we conducted a comprehensive proteomic analysis of salivary proteins from RA model mice. Proteins were identified by Western blotting and enzyme-linked immunosorbent assay in serum, saliva, and ankle joints from DBA/1JJmsSlc mice, a model of rheumatoid arthritis. Ankle joints and submandibular glands were hematoxylin and eosin stained and immunostained, and the results were compared with those of control mice. Citrullinated α1 antitrypsin (A1AT, 46 kDa) was commonly detected in saliva, serum, and ankle joints of severe RA model mice, and was confirmed by proteome analysis. Western blotting detected a band corresponding to 46 kDa in serum, saliva and ankle joints, and immunostaining of ankle joints with A1AT an-tibody showed a strong positive signal in the synovium. In DBA/1JJmsSlc mice, not only cyclic citrullinated peptide antibodies but also A1AT may be involved in protein citrulli-nation and contribute to the development and severity of RA.

The origin of cancer remains one of the most important enigmas in modern biology. This paper presents a hypothesis for the origin of carcinomas in which cellular aging and inflammation enable the recovery of cellular plasticity that may ultimately result in cancer. The process is described as the result of dedifferentiation undergone by epithelial cells in hyperplasia due to replicative senescence towards a mesenchymal cell state with potential cancerous behavior. In support of the hypothesis, the molecular, cellular, and histopathological evidence was critically reviewed and reinterpreted when necessary to postulate a plausible generic model for the origin and progression of carcinomas. In addition, the implications of this theoretical framework for the current strategies of cancer treatment are discussed against recent evidence of the molecular events underlying the epigenetic switches involved in the resistance of breast carcinomas. Subsequently, is proposed an epigenetic landscape for their progression and a potential mechanism to restrain the degree of dedifferentiation and malignant behavior. Finally, is suggested a novel understanding of the involution and carcinogenesis of tissues associated with aging as a perspective that might inspire integrative approaches in the study and management of chronic diseases.

Biochar is a carbonaceous material derived from the thermochemical conversion of biomass under oxygen-lean conditions. Its properties render it many applications in agriculture, environmental remediation, and catalysis. Commonly produced by pyrolysis under a nitrogen atmosphere, the biochar composition is influenced mainly by residence time, heating rate, and process temperature. The existing literature primarily assesses biochar properties, such as ultimate, proximate, calorific, porosity, and combustibility, generated under various thermo-conversion conditions. However, there is a notable lack of sufficient investigation and attention given to the practical application of biochar. This article seeks to bridge that gap by enhancing the comprehension of the necessary experimental assessment for specific biochar applications and proposing process optimization methods using Multi-Criteria Decision Analysis (MCDA). By delving into these aspects, the study offers a concise overview of biochar production and presents a comprehensive panorama based on articles and patents. Additionally, the research explores the physicochemical characterization techniques associated with biochar and its various applications in conjunction with MCDA. This comprehensive approach aims to uncover valuable insights that could further advance the practical and sustainable utilization of biochar in a wide range of fields.

We study the coupling of two topologcal subsystems in distinct topological states, and show that it leads to a precursor behavior of the topological phase transition in the overall system. This behavior is solely determined by the symmetry classes of the subsystem Hamiltonians and coupling terms, and is marked by the persistent existence of subgap states within the bulk energy gap. By investigating the critical current of Josephson junctions involving topological superconductors, we also illustrate that such subgap states play crucial roles in physical properties of nanoscale devices or materials.

Numerical simulations of standard situations in the transition region from gas kinetics to fluid dynamics at small Mach numbers indicate a clear dependence of the simulation results on the underlying kinetic model (here: nonlinear and linearized Boltzmann collision operator vs. BGK relaxation model). We develop an improved mathematical framework (trace theory) to explain these differences. In particular we reveal certain deficiencies for the classical BKG system as well as for the standard Navier Stokes approach.

The aim of this article is to review hydrogen combustion applications within the energy transition framework. Hydrogen blends are also included, from the well known hydrogen enriched natural gas (HENG) to the hydrogen and ammonia blends whose chemical kinetics is still not clearly defined. Hydrogen and hydrogen blends combustion characteristics will be firstly summarized, in terms of standard properties like the laminar flame speed and the adiabatic flame temperature, but also evidencing the critical role of hydrogen preferential diffusion in burning rate enhancement and the drastic reduction in radiative emission with respect to natural gas flames. Then, combustion applications in both thermo-electric power generation (based on internal combustion engines, i.e., gas turbines and piston engines) and hard-to-abate industry (requiring high temperature kilns and furnaces) sectors will be considered, highlighting the main issues due to hydrogen addition related to safety, pollutant emissions, and potentially negative effects on industrial products (e.g., glass, cement and ceramic).

Urbanization-induced land use transition results in a decline in ecosystem services, which has implications for regional ecological security. In order to explore the relationship between ecosystem services and land use transition, this paper utilizes the InVEST model, geographically weighted regression model to examine the impact of land use transition on ecosystem services in the Dongting Lake area (DLA). The results showed that (1) During the period 2000-2020, the intensity and motivation of land-use transition showed obvious spatial and temporal heterogeneity with the variation of urbanization development. (2) Habitat quality and Carbon sequestrations showed a downward trend. In contrast, food supply followed an upward trend; soil conservation and water yield services initially increased and dropped later. The overall spatial changes in habitat quality and Carbon sequestration appear to be insignificant. Food supply shows significant differences in the plains compared to other areas; while soil conservation and water yield service shows significant changes in places other than the DLA. (3) From 2000 to 2020, land use transition dynamics, population density, GDP density, night lighting and transition intensity had mainly negative effects on ecosystem services. Only the Normalized Vegetation Index (NDVI) showed a positive effect on ecosystem services. The results of the research will provide valuable references for the development and implementation of spatial ecological restoration planning and land use policies in the national territory.

Integrated crop-livestock production (ILP) is an interesting alternative for more sustainable soil use. However, more studies are needed to analyze soil pore properties under ILP at the micrometer scale. Thus, this study proposes a detailed analysis of soil pore architecture at the micrometer scale in three dimensions. For this purpose, samples of an Oxisol under ILP subjected to minimum tillage (MT) and no-tillage (NT) with ryegrass as cover crop (C) and silage (S) were investigated. The soil micromorphological properties of the soil were analyzed using X-ray microtomography. The MT(C) system showed the highest values of porosity (c. 20.4%), connectivity (c. 32.8×103), volume (c. 26%), and number of pores (c. 32%) in a rod-like shape. On the other hand, the MT(S), NT(C), and NT(S) systems showed higher tortuosities (c. 2.2, c. 2.0, and c. 2.1) and lower pore connectivities (c. 8.3×103, c. 6.9×103, and c. 6.2×103), especially in S use. Ellipsoidal and rod-shaped pores predominated over spheroidal and disc-shaped pores in all treatments. The results of this study show that the use of ryegrass as a cover crop improves soil physical properties, especially in MT. For S use, the type of soil management (MT or NT) did not show any differences.

Respiratory syncytial virus (RSV) infection is a major cause of severe respiratory disease in infants and young children worldwide. Two vaccines targeting the elderly and pregnant women have been recently approved employing the prefusion form of the RSV-fusion protein (F). However, there are currently no vaccines for infants. Studies have shown a fusion-inactive prefusogenic F form is significantly more immunogenic and produces higher antibody titers to both the prefusion and postfusion structures of the F protein. Here we have developed RSV virus-like particles (RSV-VLPs) consisting of prefusogenic F, RSV glycoprotein and matrix proteins, produced them using the baculovirus expression system, and studied their protective efficacy in Balb/c mice. Morphology and successful assembly of VLPs were confirmed by transmission electron microscopy and western blot. Mice immunized with VLPs developed high levels of serum IgG and neutralizing antibodies as compared with mice immunized with inactivated virus. The VLP vaccine also induced higher levels of IFNγ and IL4, elicited limited proliferation of CD4+ and CD8+ T cells but higher cytotoxic-T-lymphocyte responses. VLP immunization abolished lung pathology in the mice after RSV challenge. Overall, our results indicate that RSV-VLPs consisting of prefusogenic F, glycoprotein and matrix proteins are a potential vaccine candidate against RSV.

The Mara River basin (MRB) has a world-famous ecosystem, but the vegetation has been damaged due to economic development in recent years, and there is little known about the area that will experience severe vegetation damage in the future. Based on the vegetation vulnerability system, principal component analysis, and three CMIP6 scenarios (SSP1-2.6, SSP2-4.5, SSP5-8.5), vegetation vulnerability was calculated in the base period (2010-2019), near-term period (2020-2059) and long-term period (2060-2099) in the MRB. The spatial cluster of vegetation vulnerability was revealed by spatial correlation analysis, and the transition of vegetation vulnerability of different periods was analyzed by stochastic matrix. The results showed that in all periods, the vulnerability showed a high-high cluster in the east, and a low-low cluster midstream and downstream. From the stochastic matrix, the area of high vulnerability increased the least under the SSP1-2.6, while it increased the most under the SSP5-8.5. The vegetation vulnerability upstream increased the most from the base period to the near-term period and long-term period in the MRB. By comparing the vegetation vulnerability under different scenarios, and pointing out the areas with the highest vulnerability increase, this study can better provide comprehensive decision-making for vegetation protection in the MRB.

Our study explores the role of cancer-derived extracellular exosomes (EXs), particularly focusing on collagen alpha-3 (VI; COL6A3), in facilitating tumor dissemination and metastasis in epithelial ovarian cancer (EOC). We found that COL6A3 is expressed in aggressive ES2 derivatives, SKOV3 overexpressing COL6A3 (SKOV3/COL6A3), and mesenchymal-type ovarian carcinoma stromal progenitor cells (MSC-OCSPCs), as well as their EXs, but not in less aggressive SKOV3 cells or ES2 cells with COL6A3 knockdown (ES2/shCOL6A3). High COL6A3 expression correlates with worse overall survival in EOC patients, as evidenced by TCGA and GEO data analysis. In vitro experiments showed that EXs from MSC-OCSPCs or SKOV3/COL6A3 cells significantly enhance invasion ability in ES2 or SKOV3/COL6A3 cells, respectively (both, P &lt;0.001). In contrast, ES2 cells with ES2/shCOL6A3 EXs exhibit reduced invasion ability (p&lt;0.001). In vivo, the average disseminated tumor numbers in the peritoneal cavity were significantly greater in mice receiving intraperitoneally injected SKOV3/COL6A3 cells than in SKOV3 cells (p&lt;0.001). Furthermore, mice intravenously (IV) injected with SKOV3/COL6A3 cells and SKOV3/COL6A3-EXs showed increased lung colonization compared to mice injected with SKOV3 cells and PBS (p=0.007) or SKOV3/COL6A3 cells and PBS (p=0.039). Knockdown of COL6A3 or treatment with EXs inhibitor GW4869 or rapamycin-abolished COL6A3-EXs may suppress the aggressiveness in EOC.

Ecological Society is based on socioeconomic systems directed to the equilibrium of inter-relationships between environment, climate, production systems, technologies and human communities to promote the overall well-being of people and the Earth planet. It has a main goal for supporting sustainable development and equitable societies and achieving optimal health outcomes recognizing the interconnection between people, technologies, animals, plants, and their shared environment for the one health. Using data of scientific publications and patents until the year 2024, this study shows new technologies that can support the energy transition with the shift from fossil fuels to renewable energy sources in an effort to reduce CO₂ emissions for an ecological society having, whenever possible, zero-carbon economies to reduce environmental pollution and climate change and foster health and wellbeing of people. Results reveal that sustainable technologies supporting the transformation of the energy sector, economies and societies, and having a rapid growth, are blue hydrogen, floating photovoltaic systems, carbon capture and utilization, green hydrogen and liquid metal batteries. These findings can guide decisions of policymakers and stakeholders towards fruitful investments driving the transition from fossil-based to zero-carbon socioeconomic systems to have a long-run sustainable development of overall world system that has to direct towards an ecological society associated with one health.

This research analyzes the phenomenon of the reduction of urban green spaces in the post-socialist city. Belgrade was selected as a post-socialist city of the former Yugoslavia. The article analyses the views of urban planners on the reasons for the reduction of urban green areas in the post-socialist city based on semi-structured interviews with representative samples for urban areas. This result research confirms the hypothesis that post-socialist city planning reduces urban green areas due to the lack of new mechanisms in documents for the planning of urban green space. The concept of sustainability should connect and balance the skills of urban planners and focus on how urban planners develop and apply standards and protect them in market-democratic systems. In other words, a new mechanism of post-socialist city planning implies a balance between the private and public sectors. In the planning document, urban planners should find a common denominator between the public interest, citizens, investors, and spheres determined by the sustainable principles of the development. City institutions should provide opportunities for the application of those standards. With the new approach, planning would imply work in the service of citizens in the concepts of a sustainable and green city.

In this paper, a regression model between neutron star crust-core pressure and the symmetry energy characteristics was estimated using the Akaike information criterion and the adjusted coefficient of determination Radj2. Based on the obtained regression function, the most probable value of the transition density, which should characterize the crust-core environment of the sought physical neutron star model, was determined. An anti-correlation was found between this transition density and the main characteristic of the symmetry energy, i.e., its slope L.

Malassezia is a lipid-dependent genus of yeasts known for being an important part of the skin mycobiota. These yeasts have been associated in the development of skin disorders and cataloged as a causal agent of systemic infections under specific conditions, making them opportunistic pathogens. Little is known about the host-microbe interaction of Malassezia spp., and unraveling this implies the implementation of infection models. In this mini review we present different models that have been implemented in the fungal infections study with greater attention in Malassezia spp. infections. These models range from in vitro (cell cultures and ex vivo tissue), to in vivo (murine models, rabbits, guinea pigs, insects, nematodes, and amoebas). We additionally highlight the alternative models that reduce the use of mammals as model organisms, which have been gaining importance in the study of fungal host-microbe interactions. This is due to the fact that these systems have shown to have reliable results, which correlate with those obtained from mammalian models. Example of alternative models are Caenorhabditis elegans, Drosophila melanogaster, Tenebrio molitor, and Galleria mellonella. These are invertebrates that have been implemented in the study of Malassezia spp. infections in order to identify differences in virulence between Malassezia species.

Cigarette smoke (CS) exposure results in lung damage and inflammation through mitochondrial dysfunction. Mitochondria quality control is sustained by Miro1 (Rhot1), a calcium-binding membrane-anchored GTPase by its interaction with PINK1/Parkin during mitophagy. However, the exact mechanism that operates this interaction of mitophagy machinery in Miro1 degradation and CS-induced mitochondrial dysfunction that results in lung inflammation remains unclear. We hypothesized that mitochondrial Miro1 plays an important role in regulating mitophagy machinery and resulting lung inflammation by CS in mouse lung. We showed a role of Miro1 in CS-induced mitochondrial dysfunction and quality control mechanisms. The Rhot1Fl/Fl (WT) and lung epithelial cell-specific Rhot1 KO were exposed to mainstream CS for 3 days (acute) and 4 months (chronic). The cellular infiltration, cytokines, and lung histopathology were studied for the inflammatory response in the lungs. Acute CS exposure showed a notable increase in the total inflammatory cells, macrophages, and neutrophils associated with inflammatory mediators and Miro1 associated mitochondrial quality control proteins Parkin and OPA1. Chronic exposure showed an increase infiltration of total inflammatory cells and neutrophils versus air controls. Histopathological changes, such as pulmonary macrophages and neutrophils were increased in CS exposed mice. The epithelial Miro1 ablation led to augmentation of inflammatory cell infiltration with alteration in the levels of pro-inflammatory cytokines and histopathological changes. Thus, CS induces disruption of mitochondrial quality control mechanisms, and Rhot1/Miro1 mediates the process of CS-induced mitochondrial dysfunction ensuing lung inflammatory responses.

Migraine is a common condition that affects children as they develop into adults. Transition of care from pediatric to adult care has becoming an increasingly popular topic in the medical literature. It has been suggested that discussions between patients, their families and providers should be initiated as early as age 13. Patients who are un or underprepared have poorer outcomes due to increased morbidity and worsening of their medical condition. Many children continue to have migraine into adulthood and if efforts are taken to ensure patients receive appropriate transfer of care, the results can significantly decrease the economic burden of this disease.

The 70/30 copper–nickel alloy is mainly used in critical parts with more demanding conditions in marine settings. There is a need for innovative methods that offer fast production and cost-effectiveness to supplement current copper–nickel alloy manufacturing processes. In this study, we employ wire-arc additive manufacturing (WAAM) to fabricate the 70/30 copper–nickel alloy. The as-built microstructure is characterized by columnar grains with prominent dendrites and chemical segregation in the inter-dendritic area. The aspect ratio of the columnar grain increases with increasing travel speed (TS) at the same wire feed speed (WFS). This is in contrast to an equiaxed grain structure with a more random orientation of conventional sample. The sample built with a WFS of 8 m/min, TS of 1000 mm/min, and a track distance of 3.85 mm exhibits superior corrosion properties in the 3.5 wt% NaCl solution compared to the conventional one, as evidenced by a higher film resistance and breakdown potential, along with a lower passive current density of the WAAM sample. The corrosion morphology reveals the critical roles played by the nickel element unevenly distributed between the dendrite core and inter-dendritic area.

Objective To explore the endoscopic anatomical structures of lumbar surgery. Methods A total of 290 patients who underwent lumbar endoscopic surgery due to lumbar intervertebral disc (IVD) herniation from September 2020 to September 2022 were retrospectively reviewed in our hospital,179 patients had complete surgical video recordings, including 108 males and 71 females, aged from 19 to 65 years, with an average age of 41±16 years. The endoscopic structures through the intervertebral foramen and interlaminar space were independently identified by 3 doctors with more than 3 years of related surgery experience. When there were differences of opinions, the three doctors would discuss and come to a consensus. The probability, location, and neighboring structures of each specific structures were statistically analyzed. Results The anatomical structures observed through the lumbar foramen under endoscopy include muscles and ligaments attached to the superior articular process (SAP), main blood vessels inside the intervertebral foramen, blood vessels on the surface of IVD, and blood vessels on the surface of the dural sac and nerve root. The major anatomical structures observed through interlaminar space are multifidus, the conjugated ligament of ligament flavum and capsule ligament (capsule part of flavum ligaments), edges of the lamina, specific vessel bundle to facet with exit nerve root. Conclusion The anatomical structures under spinal endoscopy have certain characteristics, which are grossly different from those under open surgery. Familiarity with these anatomical structures has important clinical significance.

Abstract — Game development using technology was started in 1950 around the first video game created Tennis for Two by Higginbotham as a fun diversion, to show the power of technology. The advanced development of Artificial intelligence (AI), has turned out to be the heart of game development technology and AI has revolutionized gaming and brought so many features to life.in reality, it isn't easy to give a definition and meaning to it even though games are becoming a part of human survival. It is difficult to define the real meaning of a game but it is part of human survival as it usually refers to the cleverness of the way the human being involvement in the characters of the game. As a part of game development, many technologies were used to create a game for the players with creativity, complex design, variety of levels, and aspects for the player to use choices effectively and efficiently to interact with the character in the game and enhance the experience to the next levels. This paper initially gives the importance of game development and need for the technology usage to enhance the current state of games. Then analyzes the history and present state of Artificial intelligence in game development. Finally, it explains the highlights of potential changes in game development and the impact and influence of artificial intelligence and machine learning models in the future development of games.

Mortality in children accounts for 15% of all AIDS-related deaths globally, with a higher burden among Cameroonian children (25%), likely due to poor virological response. We sought to evaluate viral suppression (VS) and its determinants in a nationally representative paediatric and young adult population receiving antiretroviral therapy (ART). A cross-sectional and multicentric study was conducted among Cameroonian children (

Ab initio density functional theory molecular dynamics extensive calculations were used for the first time to evaluate stability conditions for relevant phases of InN. In particular, thermal decomposition of InN with formation of N2 molecules and pressure induced wurtzite – rocksalt solid-solid phase transition were established. The results consistent with available experimental data allowed a critical evaluation of potential and limitations of the proposed simulation method. The ab initio molecular dynamics as an efficient tool for simulations of phase transformations of InN including solid-solid structural transition and thermal decomposition with formation of N2 molecules has been demonstrated. It is of high interest because InN being important component of epitaxial quantum structures has still not been obtained as a bulk single crystal making difficult a determination of its basic physical properties and designing new applications.

It is widely believed that the dramatic transformation of the spherical outflows of AGB stars into the extreme aspherical geometries seen during the planetary nebula (PN) phase is linked to binarity and driven by the associated production of fast jets and central disks/torii. The key to understanding the engines that produce these jets and the jet-shaping mechanisms lies in the study of objects in transition between the AGB and PN phases. I discuss the results of our recent studies with high-angular-resolution (with ALMA & HST) and at high-energies (with GALEX, XMM-Newton & Chandra) of several such objects, which reveal new details of close binary interactions and high-speed outflows. These include two PPNe (the Boomerang Nebula and IRAS16342-3814), and the late carbon star, V Hya. The Boomerang is notable for a massive, high-speed outflow that has cooled below the microwave background temperature, making it the coldest object in the Universe. IRAS16342 is the prime example of the class of water-fountain PPNe (very young PPNe with high-velocity H₂O masers) and shows the signature of a precessing jet. V Hya ejects high-speed bullets every 8.5 years associated with the periastron passage of a companion in an eccentric orbit. I discuss our work on AGB stars with strongly-variable high-energy (FUV, X-ray) emission, suggesting that these objects are in the early stages of binary interactions that result in the formation of accretion disks and jets.

Nanostructured transition metal nitrides (TMNs) have been considered a promising substitute for precious metal catalysts toward ORR due to their multi-electron orbitals, metallic properties, and low cost. To design TMNs catalysts with high catalytic activity toward ORR, the intrinsic features of the influencing factor on the catalytic activity toward ORR of nanostructured TMNs need to be investigated. In the paper, titanium nitride (TiN), zirconium nitride (ZrN), and hafnium nitride (HfN) nanoparticles (NPs) are high-efficiency and one-step synthesized by the direct current arc plasma. TiN, ZrN, and HfN NPs with an oxidation layer are applied as the catalysts of hybrid sodium-air batteries (HSABs). The effect of composition and structure attributes of TMNs on ORR catalysis is defined as follows. (ⅰ) Composition effect. With the increase of the oxygen content, the catalytic ORR capability of TMNs decreases progressively due to the reduction of oxygen adsorption capacity; (ⅱ) Structure effect. The redistribution of the density of states (DOS) of ZrN indicates higher ORR activity than TiN and HfN. HSABs with ZrN exhibit an excellent cyclic stability up to 137 cycles (about 140 h), an outstanding rate performance, and a specific capacity of 2817 mAh·g−1 at 1.0 mA·cm−2.

The economy is a complex system, and the interactions between different agents are still not easy to quickly see-through. This complexity should reflect in a spatial dimension; in this way, tracking the tradeoffs opens a new window to the nexus of place and flow. Due to the fact, the economic systems often go through transitions and end up in another state, and this evolution is embedded in cities as the new motor of paradigm shift. To adequately represent and study these dynamics, we aim to develop an integrated method based on network analysis science and geographic economy synthesis to detect a multiscale navigator to track the transition from regional to the local level. This paper seeks to explore the specialization of regional clusters and their innovative behaviour in a particular lagging region, hence unfolding the innovation ecosystem to the smallest granularity then simulating the emergence phase of this complex system. First, our findings reveal that the local scale is relevant to start a bottom-up planning approach on policy implementation. Second, the global challenges could be addressed on a regional scale if we investigate the local complexity to unfold the innovation flow over its complex ecosystem and lead the knowledge as a critical element for inclusive transition, most probably into cities. Finally, the innovation network is an existing fact which can translate as a host for prosperity; In this line of reasoning, we intend to spatialize the track of the innovation flow to achieve transition hotspots and respond adequately to upcoming world concerns.

ELTD1 is expressed in endothelial and vascular smooth muscle cells and has a role in angiogenesis. It has been classified as an adhesion GPCR, but as yet, no ligand has been identified and its function remains unknown. To establish its role, ELTD1 was overexpressed in endothelial cells. Expression and consequently ligand independent activation of ELTD1 results in EndMT with a loss of cell-cell contact, formation of stress fibres and mature focal adhesions and an increased expression of smooth muscle actin. The effect was pro-angiogenic, increasing Matrigel network formation and endothelial sprouting. RNA-Seq analysis after the cells had undergone EndMT revealed large increases in chemokines and cytokines involved in regulating immune response. Gene set enrichment analysis of the data identified a number of pathways involved in myofibroblast biology suggesting that the endothelial cells had undergone a type II EMT. This type of EMT is involved in wound repair and is closely associated with inflammation implicating ELTD1 in these processes.

Candida albicans is a major fungal pathogen of humans, accounting for 15% of nosocomial infections with an estimated attributable mortality of 47%. C. albicans is usually a benign member of the human microbiome in healthy people. Under constant exposure to highly dynamic environmental cues in diverse host niches, C. albicans has successfully evolved to adapt to both commensal and pathogenic lifestyles. The ability of C. albicans to undergo a reversible morphological transition from yeast to filamentous forms is a well-established virulent trait. Over the past few decades, a significant amount of research has been carried out to understand the underlying regulatory mechanisms, signaling pathways, and transcription factors that govern the C. albicans yeast-to-hyphal transition. This review will summarize our current understanding of well-elucidated signal transduction pathways that activate C. albicans hyphal morphogenesis in response to various environmental cues and the cell cycle machinery involved in the subsequent regulation and maintenance of hyphal morphogenesis.

The food system, the most important driver of planetary transformation, is in a deep crisis. Therefore, seeking a sustainable and socially-fair transition pathway becomes an issue of utmost priority for our own survival. The consideration of food as a commodity, a social construct that played a central role in driving this crisis, remains the uncontested narrative to lead the different transition pathways what seems rather contradictory. By exploring the normative values in the transition landscape, this paper seeks to understand how relevant is the hegemonic narrative of “food as commodity” and its alternative of “food as commons” to determine transition trajectories and food policy beliefs. Applying the Multi-level Perspective framework and developing the ill-studied “agency in transition”, this research enquired food-related professionals that belong to an online community of practice (N=95) on valuation of food dimensions and agency in food transitions to check whether the valuation of food is relevant to explain personal stances in transition. Results suggest the socially-constructed view of food as commodity is positively correlated to the gradual reforming attitude, whereas food as commons is positively correlated to the counter-hegemonic transformers regardless the self-defined position in the transition landscape (regime or niches). At personal level, there are multiple loci of resistance with counter-hegemonic attitudes in varied institutions of the regime and the innovative niches, many of them holding this discourse of food as commons. Conversely, alter-hegemonic attitudes are not positively correlated to this alternative discourse and they may inadvertently or purportedly reinforce the ‘‘neoliberal narrative’’. Food as commons, a different narrative whose rationale is explained in the paper, seems to be a relevant framework that could enrich the multiple transformative constituencies that challenge the industrial food system and therefore facilitate the convergence of movements that reject the commodification of food.

In kidney, epithelial barrier has diverse functions in body fluid and electrolyte homeostasis, and urine production. Maintaining epithelial integrity fundamentally builds up physiological functionality of the renal epithelial barrier (REB). Specially, the REB) states regularly in osmotic dynamics. The osmotic dynamics gives rise of osmotic pressure that is a physical force. Overloading of osmotic pressure can crack epithelial integrity and damage REB. How REB endures the osmotic pressure force yet remains enigmatic. LMO7 (LIM domain only 7) is a protein associated with cell-cell junctional complex and cortical F-actin. LMO7 upregulation was observed in cells cultured in hypertonic condition. In kidney, LMO7 predominantly distributes in epithelial cells in renal tubules. Hypertonic stimulation leads to assembly of LMO7 and F-actin in cortical stress fibers in renal epithelial cells. Hypertonic-isotonic alternation as pressure force pushing plasma membrane inward/outward was set as osmotic disturbance and was applied to test FAK signaling and LMO7 functioning in maintaining junctional integrity. Along with junctional integrity, LMO7 depleted cells resulted in loss of junctional integrity in the epithelial sheet cultured hypertonic medium or hypertonic-isotonic alternation. On the other hand, FAK inhibited by PF-573228 leads to failure in robust cortical F-actin assembly and association of LMO7 with cortical F-actin in epithelial cells responding upon hypertonic stress. Epithelial integrity in context of osmotic stress, LMO7 and FAK signaling both involves in assembling robust cortical F-actin and maintaining junctional integrity. The LMO7 elaborately manages FAK activation in renal epithelial cells, which was evidently demonstrated in NRK-52E cells who have excessive FAK activation and lost epithelial integrity when cells with LMO7 depletion exposed to hypertonic environment. Our data suggests that LOM7 manages FAK activation and is responsible for maintaining REB under osmotic disturbance.

Biosolids from stabilized sludge presents a high fertilization potential due to its rich content of nutrients and organic matter. Three formulas of organo-mineral fertilizers based on biosolids were manufactured having at least 2 % N, 2 % P2O5, and 2 % K2O and characterized by classical and advanced methods. The content of N and P in the final formula was measured using specific reactants combined with VIS-nearIR spectroscopy. Additionally, all three formulas were characterized by advanced 1H NMR relaxometry, double-quantum and FT-IR spectroscopy. Structural characterization was performed using SEM, EDX and X-ray diffraction. Four dynamical components were identified in the T2-distribution showing that the rigid component is into a percentage larger than 90 %. In order to evaluate the release properties of organo-mineral fertilizers dynamic measurements of electric conductivity and pH were performed, by placing 0.25 g of formulas (V1, V2 and V3) in 200 ml of distillate water. It was found that V3 present the smallest release velocity, but release the largest amount of fertilizers. Two release mechanisms were also observed.

This paper explores Ghana's two-decade journey in developing a digital land information system (LIS), exemplified by Ghana Enterprise Land Information System (GELIS) and Enterprise Land Information System (ELIS). Despite advancements by Ghana’s Lands Commission, manual processes persist and coexist with digital ones. Our study uses a qualitative approach to assess the effectiveness of the LIS implemented in Accra. The study found that Accra’s LIS is highly aligned with clear institutional mandates, roles, and responsibilities as well as the availability of laws and policies to support analogue to digital conversion. Furthermore, a robust approach for protecting data, operating system and software underpins the system. Subsequently, the integration of a digital LIS has enhanced service delivery and accountability. Nonetheless, Accra’s LIS is still at the beginning of a comprehensive learning and development curve. To sustain the LIS requires furtherance in the implementation plan, funding, law implementation, ICT strategy, divisional integration, work processes, data quality, and communication strategy. These findings will inform the next steps of improvement for Accra's LIS and guide its nationwide scaling, contributing to discussions on technology acceptance dynamics in predominantly analogue environments.

On a rotating disk, two particles bounce at the vertices of a regular polygon in opposite directions. On the return to the entry point, a clock measures the time difference, called Sagnac effect. Due to Coriolis effects, the counterclockwise and clockwise paths are different. The particular case of the slow disk where the two trajectories are very close and almost polygonal is studied. The existence of a transition between a classical and a relativistic regime is proved. An experimental verification is proposed. Although the two Sagnac effects seem analogous, in detail their behavior is quite different.

This article explores the pressing need for a paradigm shift in economics, challenging the dominance of classical economic theories and models that have long held sway. We delve into the limitations of traditional economic paradigms, which often rely on unrealistic assumptions and fail to capture the complexities of human behavior and the modern global economy. Drawing from insights in behavioral economics, environmental economics, and complexity theory, we argue for a more nuanced and multidisciplinary approach to economic analysis. Our discussion addresses the challenges of breaking away from deeply entrenched academic norms and the resistance to change within the economics profession. We highlight strategies for individuals and groups to advocate for the incorporation of modern economic theories in education and research. By fostering interdisciplinary collaboration, encouraging critical thinking, and engaging with policymakers and the public, we aim to catalyze a shift toward economics that is better equipped to address the intricate challenges of the 21st century. This article serves as a call to action for economists and educators alike to embrace a more dynamic and responsive approach to understanding human behavior and decision-making in the modern world.

On June 8 and June 9, 2017, we gave two invited lectures at the Zelinsky Institute of Organic Chemistry (ZIOC) of the Russian Academy of Sciences, Moscow. The first lecture, “Sol-Gel Catalysts: Making Green Chemistry Possible”, focused on the practical outcomes of 25 years of research on sol-gel entrapped catalysts. The second, “Chemistry for the Bioeconomy: From Discussion to Action”, offered a critical insight to the forthcoming bioeconomy. Both lectures aroused much interest in the audience and ended with a vigorous discussion lasting about one hour. An outlook is provided herein.

Pregnancy at advanced maternal age (AMA) is a condition of potential risk for the development of maternal-fetal complications with possible repercussions even in the long-term. Here, we analyzed the changes of plasma redox balance and the effects of plasma on human umbilical cord mesenchymal cells (hUMSCs) in AMA pregnant women (patients) at various timing of pregnancy. One hundred patients and twenty pregnant women younger than 40 years (controls) were recruited, and evaluated at various timings during pregnancy until after delivery. Plasma samples were used to measure the thiobarbituric acid reactive substances (TBARS), glutathione and nitric oxide (NO). In addition, plasma was used to stimulate the hUMSCs, which were tested for cell viability, reactive oxygen species (ROS) and NO release. The obtained results showed that throughout pregnancy until after delivery in patients the levels of plasma glutathione and NO were lower than those of controls, while those of TBARS were higher. Moreover, plasma of patients reduced cell viability and NO release, and increased ROS release in hUMSCs. Our results highlighted alterations in the redox balance and the presence of potentially harmful circulating factors in plasma of patients They could have clinical relevance for the prevention of complications related to AMA pregnancy.

Gastroparesis (GP) is associated with depletion of interstitial cells of Cajal (ICC) and enteric neurons, which leads to pyloric dysfunction followed by severe nausea, vomiting and delayed gastric-emptying. Regenerating these fundamental structures with stem cell therapy, would be helpful to restore gastric function in GP. Mesenchymal stem cells (MSC) have been successfully used in animal models of other gastrointestinal (GI) diseases including colitis. However, no study has been performed with these cells on GP animals. In this study, we explored if mouse MSC can be delivered from a hydrogel-scaffold to the luminal surfaces of GP mice stomach. Mouse MSC was seeded atop alginate-gelatin, coated with poly-L-lysine. These cell-gel constructs were placed atop stomach explants facing the luminal side. MSC grew uniformly all across the gel surface within 48 hr. When placed atop the lumen of the stomach, MSC migrated from the gels to the tissues as confirmed by positive staining with Vimentin and N-cadherin. The feasibility of transplanting a cell-gel construct to deliver stem cells in the stomach wall was successfully shown in a mice GP model, thereby making a significant advance towards envisioning the transplantation of an entire tissue-engineered ‘gastric patch’ or ‘microgels’ with stem cells, and growth factors.

The European mink (Mustela lutreola) is one of Europe's most endangered species, and it is on the brink of extinction in the Iberian Peninsula. The species' precarious situation requires the application of new ex-situ conservation methodologies that complement the existing ex-situ and in-situ conservation measures. Here, we report for the first time the establishment of a biobank of European mink mesenchymal stem cells (emMSC) and oocytes from specimens found dead in the Iberian Peninsula, either free or in captivity. New emMSC lines were isolated from different tissues: bone marrow (emBM-MSC), oral mucosa (emOM-MSc), dermal skin (emDS-MSC), oviduct (emO-MSc), endometrium (emE-MSC), testicular (emT-MSC), and adipose tissue from two different adipose depots: subcutaneous (emSCA-MSC) and ovarian (emOA-MSC). All the eight emMSC lines showed plastic adhesion, detectable expression of characteristic markers of MSCs and, when cultured under osteogenic and adipogenic conditions, differentiation capacity to these lineages. Additionally, we were able to keep 227 Cumulus-oocyte complexes (COCs) in the biobank, 97 of which are grade I or II. The European mink MSC and oocyte biobank will allow for the conservation of the species' genetic variability, the application of assisted reproduction techniques, and the development of in vitro models for studying the molecular mechanisms of infectious diseases that threaten the species' precarious situation.

Pneumonia remains a major cause of morbidity and mortality worldwide, especially during COVID-19 pandemic. With the significant global health burden that pneumonia poses, it is es-sential to improve therapeutic and management strategies. The increasing emergence of antibiotic resistant bacterial strains limits options for effective antibiotic use. New antibiotics for treatment of pneumonia may address deficits in current antimicrobial drugs, with an ability to cover both typical, atypical, and resistance pathogen. Several of these newer drugs also have structural characteristics that allow for a decreased propensity in development of bacterial resistance. Po-tential use of stem cell therapies in place of corticosteroid treatments may also offer an im-provement in patient outcomes. Human mesenchymal stem cell treatments have shown efficacy and safety in treating COVID-19 induced pneumonia. Combined treatment with both stem cells and antibiotics in pneumonia in a rabbit model has also shown significantly increased efficacy in comparison to antibiotic treatment alone, presenting yet another possible route for a novel strategy in treating pneumonia, though additional future studies are necessary before clinical implementation. While pneumonia remains a major disease of concern, having newer approved antibiotics as well as novel therapies such as stem cell treatments in the pipeline offers clinicians more options in effectively treating pneumonia.

This research investigates entrepreneurial attitudes among 415 students in the academic sports domain. Utilizing a 15-item questionnaire, participants were categorized into four groups based on their sports background: individual and team sports with competitive history, amateur athletes, and non-practitioners. The questionnaire exhibited good internal consistency (Cronbach's alpha coefficient = 0.755). Statistical analysis using the Chi-Square Test of Homogeneity across criteria such as gender, competitive sports involvement, type of competitive sports, and engagement in amateur sports revealed significant differences in nine out of 60 comparisons. Furthermore, this study employs an explanatory approach to elucidate the distinctions among athletes, amateur, and non-athlete students in academic sports programs regarding assumption of responsibilities, proactive initiative, determination to establish their own businesses, perception of the comfort zone, and the perception of post-sports career adaptation. Additionally, a gender comparison is conducted concerning the perception of business risk, comfort and security in a stable workplace, and the applicability of sports-oriented approaches in business. These results provide valuable insights into how sports backgrounds shape entrepreneurial perspectives, thereby contributing to the development of customized entrepreneurial programs. Moreover, the study seeks to offer a nuanced comprehension of the diverse factors influencing the entrepreneurial attitudes and perceptions of students in sports academic programs.

Breast cancer develops upon sequential acquisition of driver mutations in mammary epithelial cells; however how these mutations collaborate to transform normal cells remains unclear in most cases. We aimed to reconstitute this process in a particular case. To this end, we combined the activated form of the PI 3-kinase harboring the H1047R mutation with the inactivation of the histone lysine methyl-transferase KMT2D in the non-tumorigenic human mammary epithelial cell line MCF10A. We found that PI 3-kinase activation promoted cell cycle progression, especially when growth signals were limiting, as well as cell migration, both in a collective monolayer and as single cells. Furthermore, we showed that KMT2D inactivation had relatively little influence on these processes, except for single cell migration that KMT2D inactivation promoted in synergy with PI 3-kinase activation. Combination of these two genetic alterations induced expression of the ARPC5L gene that encodes a subunit of the Arp2/3 complex. ARPC5L depletion fully abolished the enhanced migration persistence exhibited by double-mutant cells. Our reconstitution approach in MCF10A has thus revealed both the cell function, single cell migration, and the underlying Arp2/3-dependent mechanism, which are synergistically regulated when KMT2D inactivation is combined with the activation of the PI 3-kinase.

Stem cells can be used to treat diabetic mellitus and complications. ω3-docosahexaenoic acid (DHA) derived lipid mediators are inflammation-resolving and protective. This study found novel DHA-derived 7S,14R-dihydroxy-4Z,8E,10Z,12E,16Z,19Z-docosahexaenoic acid (7S,14R-diHDHA), a maresin-1 stereoisomer biosynthesized by leukocytes and related enzymes. Moreover, 7S,14R-diHDHA can enhance mesenchymal stem cell (MSC) functions in the amelioration of diabetic mellitus and retinal pericyte loss in diabetic db/db mice. MSCs treated with 7S,14R-diHDHA were delivered into db/db mice i.v. every 5 days for 35 days. Blood glucose levels in diabetic mice were lowered by 7S,14R-diHDHA-treated MSCs compared to control and untreated MSC groups, accompanied by improved glucose tolerance and higher blood insulin levels. 7S,14R-diHDHA-treated MSCs increased insulin+ β-cell ratio and decreased glucogan+ α-cell ratio in islets, as well as reduced macrophages in pancreas. 7S,14R-diHDHA induced MSC functions in promoting MIN6 β-cell viability and insulin secretion. 7S,14R-diHDHA induced MSC paracrine functions by increasing the generation of hepatocyte growth factor and vascular endothelial growth factor. Furthermore, 7S,14R-diHDHA enhanced MSC functions to ameliorate diabetes-caused pericyte loss in diabetic retinopathy by increasing their density in retina in db/db mice. Our findings provide a novel strategy for improving therapy for diabetes and diabetic retinopathy using 7S,14R-diHDHA-primed MSCs.