Effects of major air pollutants on angina hospitalizations: a correlation study.

BACKGROUND: Angina is a crucial risk signal for cardiovascular disease. However, few studies have evaluated the effects of ambient air pollution exposure on angina. OBJECTIVE: We aimed to explore the short-term effects of air pollution on hospitalization for angina and its lag effects. METHODS: We collected data on air pollutant concentrations and angina hospitalizations from 2013 to 2020. Distributed lag nonlinear model (DLNM) was used to evaluate the short-term effects of air pollutants on angina hospitalization under different lag structures. Stratified analysis by sex, age and season was obtained. RESULTS: A total of 39,110 cases of angina hospitalization were included in the study. The results showed a significant positive correlation between PM2.5, SO2, NO2, and CO and angina hospitalization. Their maximum harmful effects were observed at lag0-7 (RR = 1.042; 95% CI: 1.017, 1.068), lag0-3 (RR = 1.067; 95% CI: 1.005, 1.133), lag0-6 (RR = 1.078; 95% CI: 1.041, 1.117), and lag0-6 (RR = 1.244; 95% CI: 1.109, 1.397), respectively. PM10 did not have an overall risk effect on angina hospitalization, but it did have a risk effect on women and the elderly. O3 was significantly negatively correlated with angina hospitalization, with the most pronounced effect observed at lag0-6 (RR = 0.960; 95% CI: 0.940, 0.982). Stratified analysis results showed that women and the elderly were more susceptible to pollutants, and the adverse effects of pollutants were stronger in the cold season. CONCLUSION: Short-term exposure to PM2.5, SO2, NO2, and CO increases the risk of hospitalization for angina.

A Theoretical Investigation into the Oligomer Structure of Carbon Dots Formed from Small-Molecule Precursors.

In-depth insights into the oligomers of carbon dots (CDs) prepared from small-molecule precursors are important in the study of the carbonization mechanism of CDs and for our knowledge of their complex structure. Herein, citric acid (CA) and ethylenediamine (EDA) were used as small-molecule precursors to prepare CDs in an aqueous solution. The structure of oligomers acquired from CA and EDA in different molar ratios and their formation process were first studied using density functional theory, including the dispersion correction (DFT-D3) method. The results showed that the energy barrier of dimer cyclization was higher than that of its linear polymerization, but the free energy of the cyclized product was much lower than that of its reactant, and IPCA (5-oxo-1,-2,3,5-tetrahydroimidazo [1,2-a]pyridine-7-carboxylic acid) could therefore be obtained under certain conditions. The oligomers obtained from different molar ratios of EDA and CA were molecular clusters formed by short polyamide chains through intermolecular forces; with the exception of when the molar ratio of EDA to CA was 0.5, excessive CA did not undergo an amidation reaction but rather attained molecular clusters directly through intermolecular forces. These oligomers exhibited significant differences in their surface functional groups, which would affect the carbonization process and the surface structure of CDs.

Mollisol Erosion-Driven Efflux of Energetic Organic Carbon and Microflora Increases Greenhouse Gas Emissions from Cold-Region Rivers.

Massive soil erosion occurs in the world's Mollisol regions due to land use change and climate warming. The migration of Mollisol organic matter to river systems and subsequent changes in carbon biogeochemical flow and greenhouse gas fluxes are of global importance but little understood. By employing comparative mesocosm experiments simulating varying erosion intensity in Mollisol regions of northeastern China, this research highlights that erosion-driven export and biomineralization of terrestrial organic matter facilitates CO2 and CH4 emission from receiving rivers. Stronger Mollisol erosion, as represented by a higher soil-to-water ratio in suspensions, increased CO2 efflux, particularly for the paddy Mollisols. This is mechanistically attributable to increased bioavailability of soluble organic carbon in river water that is sourced back to destabilized organic matter, especially from the cultivated Mollisols. Concurrent changes in microbial community structure have enhanced both aerobic and anaerobic processes as reflected by the coemission of CO2 and CH4. Higher greenhouse gas effluxes from paddy Mollisol suspensions suggest that agricultural land use by supplying more nitrogen-containing, higher-free-energy organic components may have enhanced microbial respiration. These new findings highlight that Mollisol erosion is a hidden significant contributor to greenhouse gas emissions from river water, given that the world's four major Mollisol belts are all experiencing intensive cultivation.

Spatiotemporal variations of ecosystem services in the Aral Sea basin under different CMIP6 projections.

The Aral Sea, located in Central Asia, has undergone significant reduction in surface area owing to the combined impacts of climate change and human activities. This reduction has led to a regional ecological crisis and profound repercussions on ecosystem services. Investigating the spatiotemporal variations and synergistic trade-offs of ESs in the Aral Sea basin is crucial for fostering the integrated development of the region's socioeconomic ecology. This study utilizes the Future Land-Use Simulation and InVEST models to analyze future land-use scenarios, integrating CMIP6 projections to assess the quality of four key ecosystem services: water production, soil conservation, carbon storage, and habitat quality over two timeframes: the historical period (1995-2020) and the projected future (2021-2100). Employing Spearman correlation, the study explores the trade-offs and synergies among these ecosystem services. Findings reveal that the primary forms of land-use change in the Aral Sea basin are the reduction in water area (- 49.59%) and the rapid expansion of urban areas (+ 504.65%). Temporally, habitat quality exhibits a declining trend, while carbon storage shows an increasing trend, and water production and soil retention fluctuate initially decreasing and then increasing. Spatially, water production and carbon storage demonstrate an increasing trend from the northwest to the southeast. Habitat quality exhibits a higher spatial pattern in the southeast and south, contrasting with lower spatial patterns in the north and west. Low-level soil conservation is predominantly distributed in the northwest, while medium to low-level soil conservation is prevalent in the east of the basin. The trade-off and synergy analysis indicates that between 1995 and 2020, a trade-off relationship existed between carbon storage and habitat quality and water production, whereas synergies were observed between soil conservation and carbon storage, water production and habitat quality, and soil conservation. The correlation between water production and soil conservation emerges as the strongest, whereas the correlation between carbon storage and habitat quality appears to be the weakest. The dynamic spatiotemporal changes, trade-offs, and collaborative relationships of ESs constitute major aspects of ecosystem service research, holding substantial implications for the effective management of the regional ecological environment.

A ternary nucleotide-lanthanide coordination nanoprobe for ratiometric fluorescence detection of ciprofloxacin.

Ciprofloxacin (CIP) is a widely used broad-spectrum antibiotic and has been associated with various side effects, making its accurate detection crucial for patient safety, drug quality compliance, and environmental and food safety. This study presents the development of a ternary nucleotide-lanthanide coordination nanoprobe, GMP-Tb-BDC (GMP: guanosine 5'-monophosphate, BDC: 2-amino-1,4-benzenedicarboxylic acid), for the sensitive and ratiometric detection of CIP. The GMP-Tb-BDC nanoprobe was constructed by incorporating the blue-emissive ligand BDC into the Tb/GMP coordination polymers. Upon the addition of CIP, the fluorescence of terbium ion (Tb3+ ) was significantly enhanced due to the coordination and fluorescence sensitization properties of CIP, while the emission of the BDC ligand remained unchanged. The nanoprobe demonstrated good linearity in the concentration range of 0-10 µM CIP. By leveraging mobile phone software to analyze the color signals, rapid on-site analysis of CIP was achieved. Furthermore, the nanoprobe exhibited accurate analysis of CIP in actual drug and milk samples. This study showcases the potential of the GMP-Tb-BDC nanoprobe for practical applications in CIP detection.

LncRNA LY6E-DT and its encoded metastatic-related protein play oncogenic roles via different pathways and promote breast cancer progression.

Abnormal long noncoding RNA (lncRNA) expression plays an important role in tumor invasion and metastasis. Here, we show that lncRNA LY6E divergent transcript (LY6E-DT) levels are increased in breast cancer (BC) tissues. Transcription factor SP3 binds directly to the LY6E-DT promoter, activating its transcription. Moreover, LY6E-DT N6-methyladenosine modification by methyltransferase-like protein 14 (METTL14) promotes its expression, dependent on the "reader" insulin-like growth factor 2 mRNA binding protein 1(IGF2BP1)-dependent pathway. Notably, we discovered that the lncRNA LY6E-DT encodes a conserved 153-aa protein, "Metastatic-Related Protein" (MRP). Both LY6E-DT and MRP promote BC invasion and metastasis, and MRP expression could distinguish BC patients with lymph node metastasis from those without. Mechanistically, MRP binds heterogeneous nuclear ribonucleoproteins C1/C2 (HNRNPC), enhancing the interaction between HNRNPC and epidermal growth factor receptor (EGFR) mRNA, increasing EGFR mRNA stability and protein expression and subsequently activating the phosphatidylinositol 3­kinase/protein kinase B signaling (PI3K) pathway. LncRNA LY6E-DT promotes the interaction between Y box binding protein 1 (YBX1) and importin α1 and increases YBX1 protein entry into the nucleus, where it transcriptionally activates zinc finger E-box-binding homeobox 1(ZEB1). Our findings uncover a novel regulatory mechanism underlying BC invasion orchestrated by LY6E-DT and its encoded MRP.

[Effect of Neodymium-Doped Yttrium Aluminum Garnet Laser Combined With Desensitizing Toothpaste on Dentinal Tubule Occlusion Against Acid Challenge].

Objective To assess the effects of different application sequences of neodymium-doped yttrium aluminum garnet(Nd∶YAG)laser and the desensitizing toothpaste containing stannous fluoride on dentinal tubule occlusion.Methods Twelve intact third molars freshly extracted from human were selected and prepared into dentin slices with a thickness of 0.8 mm.Each dentin slice was subdivided into four small slices,three of which were etched with 6% citric acid and randomly assigned to the following three groups(n=12):(1)control group:no treatment;(2)Nd∶YAG+toothbrushing(TB)group:first irradiated with Nd∶YAG laser and then brushed with desensitizing toothpaste;(3)TB+Nd∶YAG group:first brushed with desensitizing toothpaste and then irradiated with Nd∶YAG laser.The Nd∶YAG laser irradiation were carried out at 1 W,15 pulses/s,and the pulse width of 150 µs for 10 s(for a total of 6 cycles).After the above treatment,the 12 dentin slices from the Nd∶YAG+TB and TB+Nd∶YAG groups were randomly assigned to four subgroups(n=3)and subjected to acid etching in the Coca-Cola solution for 0,5,10,and 15 min.A scanning electron microscope was used to observe and photograph the dentin slices in each group,and eight single-blinded examiners scored the slices according to uniform criteria.The analysis of variance was carried out to compared the scores between groups.Results Before acid etching,the dentin tubule occlusion scores of the Nd∶YAG+TB and TB+Nd∶YAG groups were(4.83±0.09) scores and(3.85±0.66) scores,respectively,which had no significant difference between each other(P=0.0590)and were higher than that[(0.10±0.07)scores]of the control group(both P<0.0001).The dentin tubule occlusion scores of the Nd∶YAG+TB group after acid etching for 5,10,and 15 min were(4.33±0.60)scores,(4.27±0.24)scores,and(3.63±0.07)scores,respectively,which were not significantly different from those[(4.04±0.10)scores,(3.76±0.59)scores,and(3.17±0.29)scores,respectively]of the TB+Nd∶YAG group(all P>0.05).In the Nd∶YAG+TB subgroup,the dentin tubule occlusion score after acid etching for 15 min was significantly lower than that before acid etching(P=0.0011).In the TB+Nd∶YAG group,there was no statistically significant difference in the score between before and after acid etching(P>0.05).Conclusions Nd∶YAG laser irradiation with appropriate parameters combined with the use of desensitizing toothpaste could produce an excellent occluding effect on dentinal tubules regardless of the sequence.However,brushing with desensitizing toothpaste followed by Nd∶YAG laser irradiation produced more consistent dentin sealing after acid etching.

Clinical characterization of PLAG1- related Silver-Russell syndrome：A clinical report.

BACKGROUND: Silver-Russell syndrome (SRS) is a rare genetic disorder that is mainly associated with prenatal and postnatal growth retardation. Loss of methylation on chromosome 11p15 and maternal uniparental disomy on chromosome 7 (upd(7)mat) are two common causes, accounting for approximately 50% and 10% of all patients, respectively. Pathogenic variants of genes, such as HMGA2, IGF2, CDKN1C, and PLAG1, have also been detected in patients with SRS. So far, SRS caused by PLAG1 alterations have only been described in two sporadic cases and three families. PATIENT PRESENTATION: The genetic and clinical manifestations of SRS in a patient carrying a novel variant of PLAG1 were reported and these results were compared with those of five previously reported cases. Trio-based whole-exome sequencing revealed a heterozygous variation in PLAG1 (NM_002655.3: c.131del; p.(Asn44Thrfs*6)) in an infant girl with clinical suspicion of SRS. Familial studies confirmed that the mutation was inherited from her father. As seen in previously reported cases, the patient presented with prenatal and postnatal growth retardation, relative macrocephaly at birth, prominent forehead during infancy, and triangular face. However, no clinical characteristics such as feeding difficulties, hypothyroidism, or psychomotor and speech delay. CONCLUSIONS: This study identified the sixth documented case of PLAG1 variants leading to SRS and expanded our knowledge of the molecular spectrum of SRS phenotypes.

CAP2 promotes gastric cancer metastasis by mediating the interaction between tumor cells and tumor-associated macrophages.

The metastasis of cancer cells is the main cause of death in patients with gastric cancer (GC). Mounting evidence has demonstrated the vital importance of tumor-associated macrophages in promoting tumor invasion and metastasis; however, the interaction between tumor cells and macrophages in GC is largely unknown. In this study, we demonstrated that cyclase-associated protein 2 (CAP2) was upregulated in GC, especially in cases with lymph node metastasis, and was correlated with a poorer prognosis. The transcription factor JUN directly bound to the promoter region of CAP2 and activated CAP2 transcription. The N-terminal domain of CAP2 bound to the WD5 to WD7 domains of receptor for activated C kinase 1 (RACK1) and induced M2 macrophage polarization by activating the SRC/focal adhesion kinase (FAK)/ERK signaling pathway, which resulted in IL-4 and IL-10 secretion. Polarized M2 macrophages induced premetastatic niche formation and promoted GC metastasis by secreting TGFB1, which created a TGFB1/JUN/CAP2 positive-feedback loop to activate CAP2 expression continuously. Furthermore, we identified salvianolic acid B as an inhibitor of CAP2, which effectively inhibited GC cell invasion capabilities by suppressing the SRC/FAK/ERK signaling pathway. Our data suggest that CAP2, a key molecule mediating the interaction between GC cells and tumor-associated macrophages, may be a promising therapeutic target for suppressing tumor metastasis in GC.

Intravaginal estrogen management in postmenopausal patients with vaginal squamous intraepithelial lesions along with CO2 laser ablation: A retrospective study.

This study aims to investigate the influence of topical estrogen management in postmenopausal patients who had undergone CO2 laser ablation for vaginal squamous intraepithelial lesions (SILs). The clinical data of 211 postmenopausal women with vaginal SILs were reviewed. Patients were divided into two groups by 2-month different management: Group 1 (intervention group): patients were treated with estrogen cream 0.5 g every other day and Group 2 (control group): no topical agent was used for the treatment of patients. In low-grade squamous intraepithelial lesions (LSILs), the response rates for patients in the intervention group and the control group were 49.1% (27/55) and 54.2% (16/48), respectively; human papillomavirus (HPV) status turned negative in 12 (12/38, 31.6%) patients of the intervention group and in 15 (15/35, 42.9%) patients of the control group. In high-grade squamous intraepithelial lesions (HSILs), the response rates for patients in the intervention group and the control group were 72.4% (42/58) and 78.0% (39/50), respectively, nearly 1.5 times higher than those of the LSIL patients; 22 (22/54, 40.7%) patients of the intervention groups and 12 (12/46, 26.1%) patients of the control group cleared the HPV infection. In postmenopausal patients, local use of estrogen cream improves the recognition of lesions and is conducive to precision medicine.

Optimization of pig manure-derived biochar for ammonium and phosphate simultaneous recovery from livestock wastewater.

Livestock wastewater has led to serious eco-environmental issues. To effectively treat livestock wastewater and realize the resource utilization of livestock solid waste, manure waste has been widely used to prepare biochar for the recovery of nitrogen and phosphorus. However, fresh biochar has a poor ability to adsorb phosphate due to its negative charge. To overcome the defect, the proportion of biochar samples prepared at 400 °C and 700 °C was optimized under a mass ratio of 2:3 to obtain mixed biochar PM 4-7, achieving the purpose of enhanced ammonium and phosphate recovery in livestock wastewater simultaneously without any modification. The effects of pyrolysis temperature, dosage, and pH were studied, different adsorption models were used to explore the adsorption mechanism, and the effect of biochar loaded with nutrient elements on seed was verified through a seed germination experiment. It was revealed that the maximum removal rates of phosphate and ammonium were 33.88 % and 41.50 %, respectively, endorsing that mixed biochar PM 4-7 can recover nutrients from livestock wastewater, and could be used as a slow-release fertilizer to promote seed germination and growth. This method provides a new potential way for the efficient resource utilization of pig manure and the recovery of nutrients from breeding wastewater.

Enhanced energy recovery from landfill leachate by linking light and dark bio-reactions: Underlying synergistic effects of dual microalgal interaction.

Bioconversion of nutrients and energy from landfill leachate (LL) to biohydrogen and volatile fatty acids (VFAs) using dark fermentation (DF) is a promising technique for developing a sustainable ecosystem. However, poor performance of DF caused by vulnerable fermentative bacteria vitality and strong LL toxicity significantly hinder its commercialization. Herein, an integrated technique linking microalgae photosynthesis and DF was proposed, in which mixed microalgae were applied to robustly reclaim nutrients and chemical oxygen demand (COD) from LL. Then, microalgae biomass was fermented into biohydrogen and VFAs using the DF process. Underlying synergistic mechanisms of the interaction of Scenedesmus obliquus and Chlorella vulgaris resulting from the functioning of extracellular polymeric substances (EPS) were discussed in detail. For better absorption of nutrients from LL, the mixed microalgae secreted obviously more EPS than pure microalgae, which played vital roles in the assimilation of cellular nutrients by forming more negative zeta potential and secreting more tyrosine-/tryptophan-family proteins in EPS. Besides, mixed microalgae produced more intracellular proteins and carbohydrates than the pure microalgae, thereby providing more feedstock for DF and achieving higher energy yield of 10.80 kJ/L than 6.64 kJ/L that was obtained when pure microalgae were used. Moreover, the energy conversion efficiency of 7.75% was higher for mixed microalgae than 4.77% that was obtained for pure microalgae. This work may inspire efficient disposal of LL and production of bioenergy, together with filling the knowledge gaps of synergistic mechanisms of dual microalgal interactions.

Climate change adaptation responses among riparian settlements: A case study from Bangladesh.

As transition areas between aquatic ecosystems and the adjacent terrestrial ones, riparian regions are highly exposed to coastal climate hazards. This article describes how climate change and extreme weather impact vulnerable riparian communities and settlements. The analysis is done by reviewing past research and empirical case studies from riparian rural communities of the impact zone of the Sundarbans in Bangladesh, the world's most extensive mangrove forest. The article discusses the climate-related impacts on households through a Severity Index of Vulnerability and assesses the adaptation responses they may pursue. The principal climate-related vulnerabilities and impacts due to increases in temperature, storm surges, sea flooding, and sea-level rise are seawater intrusion and riverbank erosion. Many households have adopted several autonomous reactive adaptation strategies rather than planned ones, to cope with these impacts. However, government organisations and NGOs provide less than optimal technical and financial support to households for planned and anticipatory adaptive responses. The main barriers to adaptation were the high cost of improved crop varieties, inadequate agricultural extension services, and a lack of knowledge on effective climate adaptation. The restoration of the mangrove ecosystem may increase its resilience and, among other things, make local communities less exposed. The article also presents some adaptation measures proper to reduce the climate-related vulnerability of riparian settlements.

Comprehensive analysis of the potential role and prognostic value of sine oculis homeobox homolog family in colorectal cancer.

BACKGROUND: Several genes, important for development, are reduced or silenced in adulthood, and their abnormal expression has been related to the occurrence and development of malignant tumors. Human sine oculis homeobox homolog (SIX) proteins belong to the homeobox family and play important roles in the development of different organs. Importantly, SIXs are predicted to have chromatin-binding and DNA-binding transcription factor activity with reported roles in cancers. However, a comprehensive analysis of SIXs in colorectal cancers (CRCs) has not been performed. AIM: To explore the expression pattern of six SIX proteins in CRCs and their relationship with the clinicopathological parameters of CRC patients as well as investigate the potential utilization of SIXs as novel prognostic indicators in CRCs. METHODS: The expression level of SIXs in normal tissues of different organs and related cancerous tissues was analyzed in the Human Protein Atlas. Kaplan-Meier Plotter and GEPIA2 were used to analyze the prognostic values of SIXs. To analyze the potential signaling pathways with SIX family involvement, LinkedOmics was used to perform Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses of SIX4-related genes. Subsequently, immunohistochemical experiments were performed on CRC tissues and adjacent normal tissues, and we examined the SIX4 expression level in 87 pairs of patients with tissue microarray. The relationship between SIX4 and clinicopathological parameters in CRC patients was tested using the χ 2 test and Fisher's exact probability to verify the results of the database analysis. RESULTS: The RNA levels of SIX1-4 and SIX6 were relatively low in normal human tissues, while SIX5 was highly expressed at both the RNA and protein levels. However, the protein level of SIX4 was found to be elevated in various malignancies. In CRC tissues, SIX1, SIX2 and SIX4 were elevated in cancer tissues compared with adjacent normal tissue. Among all SIXs, a high level of SIX4 was found to be associated with poor overall and disease-free survival in patients with CRC. For different clinicopathological parameters, increased SIX4 expression was positively correlated with advanced CRC. The top 50 SIX4-related genes were involved with oxidative phosphorylation and the respiratory chain signaling pathways. CONCLUSION: The current results provided a comprehensive analysis of the expression and prognostic values of SIX family members in CRC. Among different SIXs, SIX4 plays an oncogenic role in CRC to promote the development of malignancy. In CRC, SIX4 mRNA and protein expression is higher than that in normal tissues and associated with shorter CRC patient survival, suggesting that SIX4 may be a potential therapeutic target for treatment of CRC patients.

Potential of six-transmembrane epithelial antigen of the prostate 4 as a prognostic marker for colorectal cancer.

BACKGROUND: Immune cells play a role in the regulation of tumor cell behavior, and accumulating evidence supports their significance in predicting outcomes and therapeutic efficacy in colorectal cancers (CRC). Human six-transmembrane epithelial antigen of the prostate (STEAP) proteins have been recognized and utilized as promising targets for cell- and antibody-based immunotherapy. One STEAP family member, STEAP4, is expected to be an attractive biomarker for the immunotherapy of prostate and breast cancer. However, the immunotherapeutic role of STEAP4 for colorectal carcinomas has not been demonstrated. AIM: To explore the expression pattern of STEAPs in CRC and their relationship with immune infiltration, and investigate the potential utilization of STEAPs as novel prognostic indicators in colorectal carcinomas. METHODS: The expression level of STEAPs in CRC was evaluated using various open-resource databases and online tools to explore the expression characteristics and prognostic significance of STEAPs, as well as their correlation with immune-related biomarkers, such as immune infiltration. Immunohistochemical (IHC) experiments were subsequently performed to verify the database conclusions. RESULTS: The levels of STEAPs in CRC were inconsistent. The expression of STEAPs 1-3 in CRC was not significantly different from that in normal tissues. However, STEAP4 mRNA levels were significantly lower in CRC than in normal tissue and were positively correlated with immune-related biomarkers, such as immune cell infiltration, immune stimulation, major histocompatibility complex levels, and chemokines. Interestingly, the expression of STEAP4 in microsatellite instability-high CRC subtype was higher than that in microsatellite stability subtype. IHC staining was performed on colon cancer tissue samples and showed that high expression of STEAP4 in adjacent tissues positively correlated with immune-related biomarkers, including MLH1, MLH6, and PMS2, but negatively correlated with programmed death ligand 1, to varying degrees. CONCLUSION: Our results provide an analysis of the expression of STEAP family members in CRC. Among different STEAP family members, STEAP4 plays a different role in CRC compared to STEAPs 1-3. In CRC, STEAP4 expression is not only lower than that in normal tissues, but it is also positively correlated with immune infiltration and immune-related biomarkers. These findings suggest that STEAP4 may be a potential biomarker for predicting CRC immune infiltration status.

Repurposed itraconazole for use in the treatment of malignancies as a promising therapeutic strategy.

Understanding cancer biology and the development of novel agents for cancer treatment has always been the goal of cancer researchers. However, the research and development of new drugs is hindered by its long development time, exorbitant cost, high regulatory hurdles, and staggering failure rates. Given the challenges involved drug development for cancer therapies, alternative strategies, in particular the repurposing of 'old' drugs that have been approved for other indications, are attractive. Itraconazole is an FDA-approved anti-fungal drug of the triazole class, and has been used clinically for more than 30 years. Recent drug repurposing screens revealed itraconazole exerts anti-cancer activity via inhibiting angiogenesis and multiple oncogenic signaling pathways. To explore the potential utilization of itraconazole in different types of malignancies, we retrieved the published literature relating to itraconazole in cancer and reviewed the mechanisms of itraconazole in preclinical and clinical cancer studies. Current research predicts the hedgehog signaling pathway as the main target by which itraconazole inhibits a variety of solid and hematological cancers. As clinical trial results become available, itraconazole could emerge as a new antitumor drug that can be used in combination with first-line antitumor drugs.

Induced Cell Cycle Arrest in Triple-Negative Breast Cancer by Combined Treatment of Itraconazole and Rapamycin.

Triple-negative breast cancer (TNBC) is the aggressive molecular type of breast carcinoma, with a high metastasis/relapse incidence and cancer-related death rate, due to lack of specific therapeutic targets in the clinic. Exploring potential therapeutic targets or developing novel therapeutic strategies are the focus of intense research to improve the survival and life quality of patients with TNBC. The current study focused on drugs targeting the mTOR signaling pathway by investigating the potential utilization of itraconazole (ITZ) combined with rapamycin in the treatment of TNBC. CCK-8, colony formation and transwell assays were conducted to evaluate the effect of ITZ with rapamycin in combination on MDA-MB-231 and BT-549 TNBC cells. Synergistic inhibition was found in terms of proliferation and motility of TNBC cells. However, apoptosis was not enhanced by the combined treatment of ITZ and rapamycin. Flow cytometry analysis showed that ITZ and/or rapamycin arrested cells in G0/G1 phase and prevented G1/S phase transition. Reduced cyclin D1 protein levels were consistent with G0/G1 phase arrest, especially when resulting from the combination of ITZ with rapamycin. In conclusion, the combination of ITZ with rapamycin is a promising therapeutic strategy for patients with TNBC through synergistically arresting cells in the G0/G1 phase of the cell cycle, rather than inducing apoptosis.

Target-Induced In Situ Formation of Organic Photosensitizer: A New Strategy for Photoelectrochemical Sensing.

Small-molecule photosensitizers have great application prospects in photoelectrochemical (PEC) sensing due to their defined composition, diversified structure, and adjustable photophysical properties. Herein, we propose a new strategy for PEC analysis based on the target-induced in situ formation of the organic photosensitizer. Taking thiophenol (PhSH) as a model analyte, we designed and synthesized a 2,4-dinitrophenyl (DNP)-caged coumarin precursor (Dye-PhSH), which was then covalently coupled onto the TiO2 nanoarray substrate to obtain the working photoanode. Due to the intramolecular photoinduced electron transfer process, Dye-PhSH has only a very weak photoelectric response. Upon reacting with the target, Dye-PhSH undergoes a tandem reaction of the detachment of the DNP moiety and the intramolecular cyclization process, which leads to a coumarin dye with a pronounced photoelectric effect, thus achieving a highly selective turn-on PEC response to PhSH. For the first time, this study was to construct a PEC sensor by exploiting specific organic reactions for the in situ generation of small molecule-based photoactive material. It can be anticipated that the proposed strategy will expand the paradigm of PEC sensing and holds great potential for detecting various other analytes.

Influences of Climate Change and Variability on Estuarine Ecosystems: An Impact Study in Selected European, South American and Asian Countries.

It is well-known that climate change significantly impacts ecosystems (at the macro-level) and individual species (at the micro-level). Among the former, estuaries are the most vulnerable and affected ecosystems. However, despite the strong relations between climate change and estuaries, there is a gap in the literature regarding international studies across different regions investigating the impacts of climate change and variability on estuaries in different geographical zones. This paper addresses this need and reviews the impacts of climate change, variability and extreme weather on estuaries. It emphasises the following: (i) a set of climate parameters governing estuarine hydrology and processes; and (ii) a sample of countries in Asia (Bangladesh), Europe (Portugal) and South America (Uruguay). We reviewed the influences of the climatic drivers of the estuarine hydrology, ecological processes and specific species in estuarine communities across the selected geographical regions, along with an analysis of their long-term implications. The key results from the three estuaries are as following: (i) Hilsa fish, of which the catches contribute to 10% of the total earnings of the fishery sector (1% of GDP), are affected by climate-forced hydrological and productivity changes in the Meghna; (ii) extreme droughts and short-term severe precipitation have driven the long-term abundance and spatial distribution of both fish larvae and juveniles/adults in the Mondego; and (iii) the river inflow and fluctuations increases since the early 1970s have contributed to variations in the salinity, the stratification, the oxygen, nutrient and trophic levels and the spatial pattern for the life stages of planktonic species, fish biomass and captures in the Rio de la Plata. The results suggested that immediate action is needed to reduce the vulnerability of estuaries to climate stressors, mainly the changing river flows, storms and sea-level rise. As a contribution to addressing current problems, we described a set of adaptation strategies to foster climate resilience and adaptive capacity (e.g., early-warning systems, dam management to prevent overflows and adaptive fisheries management). The implications of this paper are two-fold. Firstly, it showcases a variety of problems that estuaries face from changing climate conditions. Secondly, the paper outlines the need for suitable adaptive management strategies to safeguard the integrity of such vital ecosystems.

Diverse roles of FOXO family members in gastric cancer.

Gastric cancer (GC) is the fifth most diagnosed cancer and the third leading cause of cancer-related death worldwide. Although progress has been made in diagnosis, surgical resection, systemic chemotherapy, and immunotherapy, patients with GC still have a poor prognosis. The overall 5-year survival rate in patients with advanced GC is less than 5%. The FOXO subfamily, of the forkhead box family of transcription factors, consists of four members, FOXO1, FOXO3, FOXO4, and FOXO6. This subfamily plays an important role in many cellular processes, such as cell cycle, cell growth, apoptosis, autophagy, stress resistance, protection from aggregate toxicity, DNA repair, tumor suppression, and metabolism, in both normal tissue and malignant tumors. Various studies support a role for FOXOs as tumor suppressors based on their ability to inhibit angiogenesis and metastasis, and promote apoptosis, yet several other studies have shown that FOXOs might also promote tumor progression in certain circumstances. To elucidate the diverse roles of FOXOs in GC, this article systematically reviews the cellular functions of FOXOs in GC to determine potential therapeutic targets and treatment strategies for patients with GC.