Search Results (35)

The phosphatidylinositol-3-kinase (PI3K)/Akt signaling pathway is a central regulator of cellular metabolism, survival, and proliferation and is frequently dysregulated in cancer. Since the identification of protein kinase B (Akt) in 1996, extensive research has established its critical role in tumor initiation, progression, and therapeutic resistance, making Akt an attractive target for anticancer drug development. Although numerous inhibitors targeting the PI3K/Akt pathway have been developed, their clinical success has been limited due to inadequate isoform specificity and unfavorable toxicity profiles. These limitations have prompted increasing interest in identifying Akt-selective inhibitors from natural sources, particularly microbial metabolites. Recent in vitro and in vivo studies demonstrate that several microbial-derived compounds effectively modulate PI3K/Akt signaling and suppress key cancer hallmarks, including proliferation, angiogenesis, and metastatic potential. Nevertheless, further studies are required to define Akt isoform specificity, evaluate selectivity against closely related kinases, and validate therapeutic efficacy in relevant preclinical models, including patient-derived xenografts. In addition, the development of robust purification and optimization strategies remains essential to enable the reliable isolation and translational advancement of these bioactive metabolites. This review summarizes Akt structure, function, and key regulatory motifs relevant to pharmacological targeting and critically examines microbial-derived inhibitors of the PI3K/Akt pathway and their mechanisms of action. Representative compounds discussed include Bostrycin, Anthracycline analogs, Wentilactone A, Thiocoraline, Iturin A, SZ-685C, Isebromoamide B, Xyloketal B, and Demethoxyfumitremorgin C. Collectively, this review highlights the therapeutic potential of microbial natural products while outlining current challenges and future directions for developing selective Akt-targeted anticancer therapies. Full article

The mineralogical, geochemical, and statistical characteristics of recent fluvial deposits from the Brahmaputra–Jamuna River, Bangladesh, were examined to determine their provenance, transport dynamics, and depositional environment. Sediments were analyzed using X-ray diffraction (XRD), wavelength dispersive X-ray fluorescence (WD-XRF), field emission scanning electron microscopy (FE-SEM), and electron probe microanalysis (EPMA). Grain size analysis revealed a predominance of medium-to-fine sand (mean grain size 1.77–3.43 ϕ), with moderately well-sorted textures (sorting: 0.33–0.77 ϕ), mesokurtic to leptokurtic distributions, and skewness values ranging from −0.21 to +0.30. Mineralogical results show a high quartz content with minor feldspar, mica, zircon, rutile, and iron-bearing minerals. Geochemical data indicates high SiO₂ (63.39%–70.94%) and Al₂O₃ (12.25%–14.20%) concentrations and calculated chemical index of alteration (CIA) values ranging from 60.90 to 66.82. The microstructural study revealed angular to sub-angular grains with conchoidal fractures and stepped microcracks, indicating brittle deformation under high-energy conditions, which is consistent with short transport distances, limited sedimentary recycling, and a derivation from mechanically weathered source rocks. Multivariate analyses (PCA and K-means clustering) of grain size parameters reveal two distinct sedimentary regimes, namely Cluster 1 as finer-grained (2.36 ϕ), poorly sorted sediments, and Cluster 2 as coarser (2.98 ϕ), well-sorted deposits. Discriminant function values (Y₂: 78.82–119.12; Y₃: −6.01 to −2.56; V₁: 1.457–2.442; V₂: 1.409–2.323) highlight shallow water, fluvial/deltaic aspects, and turbidite depositional environments. These findings advance the understanding of sedimentary dynamics within large, braided river basins and support future investigations into the sustainable management of fluvial depositional environments. Full article

This study uses a sample of pegmatite (LS-1) from the Longquanping deposit in Lushi County, Henan Province, to evaluate its potential as a valuable source of HPQ. This investigation uses various analytical techniques to assess the quality of quartz and its suitability for industrial applications. The methods used in this study include optical microscopy, scanning electron microscopy (SEM), Raman spectroscopy, X-ray fluorescence spectrometry (XRF), laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS), and inductively coupled plasma mass spectrometry (ICP-MS) to analyze the petrographic, mineralogical, and trace element characteristics of quartz before and after purification and comprehensively evaluate the potential of quartz in these rocks as an HPQ raw material ore. The optical and scanning electron microscopic observations reveal several impurities and associated minerals in quartz, including feldspar, biotite, magnetite, sphene, and large number of fluid inclusions composed of both gas and liquid phases. The content of trace element in raw quartz ore in the LS-1 sample as determined by LA-ICP-MS analysis ranges from 41.61 to 256.13 ppm, with the main impurity elements being Al, Ti, Li, Na, K, and Ca. After purification, the SiO₂ contents and total trace elements contents of the LS-1 refined quartz sand was 99.997 wt.% and 29.29 ppm, respectively, with Al (13.29 ppm), Ti (4.20 ppm), Li (1.15 ppm), and Na (10.32 ppm). The major trace element contents of Al and Ti in the quartz concentrates were lower than the upper limit of the HPQ standard and thus belonged to the high-end products (4N8). Results of this study show that quartz from a pegmatite in the Lushi region has the potential to be purified HPQ. This study underscores the importance of thorough mineralogical and elemental analyses in assessing the suitability of quartz raw material deposits for HPQ production. Full article

Sandbars are an integral part of the alluvial river’s geophysical system due to these rivers’ wide sediment availability and varied transport capacity. The sandbars’ evolution and translation considerably influence the stability of the riverbank. However, while designing the riverbank protection structures (RBPS), the impact of such sandbars is often overlooked, as the evolution of such bars is quite uncertain in terms of location, amplitude, and translation. This study evaluates the localized impact of sandbars on bank protection structures in two types of alluvial rivers: meandering (Ganges) and braided (Brahmaputra-Jamuna), utilizing time series satellite images, hydraulic characteristics, and numerical modeling. We found that sandbar development initiates width adjustment in both meandering and braided rivers when the ratio of width to depth surpasses 90. In the case of meandering rivers, riverbank erosion mostly occurs as a result of the presence of alternate bars or point bars. Sandbars in a meandering river (Ganges) can lead to an approximate 18% increase in flow depth. The depth-averaged velocity is anticipated to rise by approximately 29%, and the tractive force may increase by a factor of 1.6. On the other hand, the braided river (the Brahmaputra-Jamuna) underwent significant bank erosion due to the presence of both free unit and hybrid types of bars. In such rivers, the depth of the flow may experience a notable increase of 18%, while the depth-averaged velocity undergoes an approximate increase of 50%, and the tractive force has the potential to grow by a factor of 5.3. Consequently, we recommend allowing the natural evolution of sandbars while preserving the riverbank (where needed only) through RBPS, considering these additional loads. Full article

This study investigated riverbank protection strategies along the dynamic Jamuna River in Bangladesh, a braided river prone to erosion and sedimentation. It reviews past countermeasures and emphasizes the effectiveness of groyne-type structures in redirecting flow and preventing erosion. Notably, the left bank exhibited greater stability than the right bank, emphasizing the need for effective groyne installations. A systematic methodology utilizing numerical modeling using International River Interface Cooperation (iRIC Nays2DH) ensured accuracy in assessing morphological impacts. This research presents novel countermeasures incorporating groyne installations along the right bank of the Jamuna River. Simulations are undertaken to assess the effectiveness of these measures under a range of flood scenarios, identifying a zone highly prone to erosion that exhibits the utmost vulnerability. The simulation scenarios comprised a base condition without groynes, two series of groynes separately placed in two selected zones, and a combined approach for both areas. Analysis of the four simulation cases, each encompassing three flood conditions, revealed that implementing two ‘I’-shaped perpendicular groynes in series within the erosion-prone area effectively diverted oblique flow. This approach proved optimal, mitigating erosion risk by redirecting flow and shaping sandbars along the Jamuna River’s riverbank. This study enhances Jamuna River protection, emphasizing groyne-type structures’ importance and promoting a holistic understanding of morphological dynamics for future river management and effective countermeasures. Full article

Breast cancer (BC) continues to be one of the major causes of cancer deaths in women. Progress has been made in targeting hormone and growth factor receptor-positive BCs with clinical efficacy and success. However, little progress has been made to develop a clinically viable treatment for the triple-negative BC cases (TNBCs). The current study aims to identify potent agents that can target TNBCs. Extracts from microbial sources have been reported to contain pharmacological agents that can selectively inhibit cancer cell growth. We have screened and identified pigmented microbial extracts (PMBs) that can inhibit BC cell proliferation by targeting legumain (LGMN). LGMN is an oncogenic protein expressed not only in malignant cells but also in tumor microenvironment cells, including tumor-associated macrophages. An LGMN inhibition assay was performed, and microbial extracts were evaluated for in vitro anticancer activity in BC cell lines, angiogenesis assay with chick chorioallantoic membrane (CAM), and tumor xenograft models in Swiss albino mice. We have identified that PMB from the Exiguobacterium (PMB1), inhibits BC growth more potently than PMB2, from the Bacillus subtilis strain. The analysis of PMB1 by GC-MS showed the presence of a variety of fatty acids and fatty-acid derivatives, small molecule phenolics, and aldehydes. PMB1 inhibited the activity of oncogenic legumain in BC cells and induced cell cycle arrest and apoptosis. PMB1 reduced the angiogenesis and inhibited BC cell migration. In mice, intraperitoneal administration of PMB1 retarded the growth of xenografted Ehrlich ascites mammary tumors and mitigated the proliferation of tumor cells in the peritoneal cavity in vivo. In summary, our findings demonstrate the high antitumor potential of PMB1. Full article

The blood–brain barrier (BBB) is the specialised microvasculature system that shields the central nervous system (CNS) from potentially toxic agents. Attempts to develop therapeutic agents targeting the CNS have been hindered by the lack of predictive models of BBB crossing. In vitro models mimicking the human BBB are of great interest, and advances in induced pluripotent stem cell (iPSC) technologies and the availability of reproducible differentiation protocols have facilitated progress. In this study, we present the efficient differentiation of three different wild-type iPSC lines into brain microvascular endothelial cells (BMECs). Once differentiated, cells displayed several features of BMECs and exhibited significant barrier tightness as measured by trans-endothelial electrical resistance (TEER), ranging from 1500 to >6000 Ωcm². To assess the functionality of our BBB models, we analysed the crossing efficiency of adeno-associated virus (AAV) vectors and peptide-conjugated antisense oligonucleotides, both currently used in genetic approaches for the treatment of rare diseases. We demonstrated superior barrier crossing by AAV serotype 9 compared to serotype 8, and no crossing by a cell-penetrating peptide-conjugated antisense oligonucleotide. In conclusion, our study shows that iPSC-based models of the human BBB display robust phenotypes and could be used to screen drugs for CNS penetration in culture. Full article

Agricultural crop production was affected worldwide due to the variability of weather causing floods or droughts. In climate change impacts, flood becomes the most devastating in deltaic regions due to the inundation of crops within a short period of time. Therefore, the aim of this study was to propose climate-adaptive crops that are suitable for the flood inundation in risk-prone areas of Bangladesh. The research area included two districts adjacent to the Jamuna River in Bangladesh, covering an area of 5489 km², and these districts were classified as highly to moderately vulnerable due to inundation by flood water during the seasonal monsoon time. In this study, first, an inundation vulnerability map was prepared from the multicriteria analysis by applying a fuzzy expert system in the GIS environment using satellite remote sensing datasets. Among the analyzed area, 42.3% was found to be highly to moderately vulnerable, 42.1% was marginally vulnerable and 15.6% was not vulnerable to inundation. Second, the most vulnerable areas for flooding were identified from the previous major flood events and cropping practices based on the crop calendar. Based on the crop adaptation suitability analysis, two cash crops, sugarcane and jute, were recommended for cultivation during major flooding durations. Finally, a land suitability analysis was conducted through multicriteria analysis applying a fuzzy expert system. According to our analysis, 28.6% of the land was highly suitable, 27.9% was moderately suitable, 19.7% was marginally suitable and 23.6% of the land was not suitable for sugarcane and jute cultivation in the vulnerable areas. The inundation vulnerability and suitability analysis proposed two crops, sugarcane and jute, as potential candidates for climate-adaptive selection in risk-prone areas. Full article

The effectiveness of current antifungal therapies is hampered by the emergence of drug resistance strains, highlighting an urgent need for new alternatives such as adjuvant antifungal treatments. This study aims to examine the synergism between propranolol and antifungal drugs, based on the premise that propranolol is known to inhibit fungal hyphae. In vitro studies demonstrate that propranolol potentiates the antifungal activity of azoles and that the effect is more pronounced for propranolol–itraconazole combination. Using an in vivo murine systemic candidemia model, we show that propranolol–itraconazole combination treatment resulted in a lower rate of body weight loss, decreased kidney fungal bioburden and renal inflammation when compared to propranolol and azole treatment alone or untreated control. Altogether, our findings suggest that propranolol increases the efficacy of azoles against C. albicans, offering a new therapeutic strategy against invasive fungal infections. Full article

Green corrosion inhibitors are of great interest due to their exciting and environmentally friendly behavior in mild steel corrosion control during and after the acid cleaning process. Herein, alkaloids were extracted from the stem of Ageratina adenophora and were ensured by qualitative chemical tests as well as spectroscopic test methods. The corrosion inhibition efficacy of the alkaloids against mild steel corrosion was evaluated by gravimetric, electrochemical and EIS measurement methods. In addition, the adsorption isotherm, free energy of adsorption and thermodynamic parameters of the process were evaluated. The investigations indicated the most promising inhibition efficacy of the alkaloids for mild steel corrosion. The adsorption isotherm study revealed that the adsorption of inhibitor molecules on the MS interface was manifested by dominant physisorption followed by chemisorption. Free energy and thermodynamic parameters are well suited to endothermic processes. Full article

Klebsiella pneumoniae (K. pneumoniae) colonizes the human gut and is a causative factor of pyogenic liver abscess (PLA). Retrospective studies conducted on K. pneumoniae PLA patients revealed subsequent CRC development in later years of their life with increasing prevalence of these strains harbouring polyketide synthase (PKS) genes. To our knowledge there are no known studies directly implicating K. pneumoniae with CRC to date. Our aims are to characterize K. pneumoniae isolates from CRC patients and investigate its effects on cell proliferation in vitro. K. pneumoniae isolates were characterized by screening virulence genes including polyketide synthase (PKS), biofilm assay, antibiotic susceptibility, and string test to determine hypervirulent (hvKp) strains. Solubilised antigens of selected K. pneumoniae isolates were co-cultured with primary colon cell lines and CRC cell lines (Stage I-IV) for 48 h. The enhancement of proliferation was measured through MTT and ECIS assay. Twenty-five percent of K. pneumoniae isolates were PKS-positive out of which 50% were hvKp strains. The majority of the isolates were from the more virulent serotype of K1 (30%) and K2 (50%). PKS-positive K. pneumoniae isolates did not possess genes to confer carbapenem resistance but instead were more highly associated with siderophore genes (aerobactin, enterobactin, and yersiniabactin) and allantoin metabolism genes (allS, allS2). Cell proliferation in primary colon, SW1116 (Stage I), and SW480 (Stage II) CRC cell lines were enhanced when co-cultured with PKS-positive K. pneumoniae antigens. ECIS revealed enhanced cell proliferation upon recurrent antigen exposure. This demonstrates the possible role that PKS-positive K. pneumoniae has in exacerbating CRC progression. Full article

Melioidosis, also known as Whitmore’s disease, is a potentially fatal infection caused by the Gram-negative bacteria Burkholderia pseudomallei with a mortality rate of 10–50%. The condition is a “glanders-like” illness prevalent in Southeast Asian and Northern Australian regions and can affect humans, animals, and sometimes plants. Melioidosis received the epithet “the great mimicker” owing to its vast spectrum of non-specific clinical manifestations, such as localised abscesses, septicaemia, pneumonia, septic arthritis, osteomyelitis, and encephalomyelitis, which often lead to misdiagnosis and ineffective treatment. To date, antibiotics remain the backbone of melioidosis treatment, which includes intravenous therapy with ceftazidime or meropenem, followed by oral therapy with TMP-SMX or amoxicillin/clavulanic acid and supported by adjunctive treatment. However, bacteria have developed resistance to a series of antibiotics, including clinically significant ones, during treatment. Therefore, phage therapy has gained unprecedented interest and has been proposed as an alternative treatment. Although no effective phage therapy has been published, the findings of experimental phage therapies suggest that the concept could be feasible. This article reviews the benefits and limitations of antibiotics and phage therapy in terms of established regimens, bacterial resistance, host specificity, and biofilm degradation. Full article

The residual ions of the acid cleaning processes induce the further corrosion of the metals, and this could be minimized using green inhibitors. Alkaloids extracted from plant parts could be cost effective and efficient inhibitors. In this work, alkaloids from Solanum xanthocarpum stem were successfully extracted, and they were characterized by qualitative chemical tests and spectroscopic measurements. As-extracted alkaloids were employed as green corrosion inhibitors for mild steel. The effectiveness of the inhibitor was determined by the weight loss and electrochemical measurement methods. From the weight loss measurement, the maximum inhibition efficiency of 93.14% was achieved. The temperature effect study revealed that the inhibitor can work up to a temperature of 58 °C. This could be one of the highest working temperatures among the reported green inhibitors. The electrochemical measurement reveals that the alkaloids could inhibit effectively up to 98.14% of the corrosion and serve as a mixed-type green inhibitor. A study on the kinetic parameters reflects that the inhibitor forms a potential barrier for the protection of a mild steel surface against corrosion. The values obtained from the thermodynamic parameters study reflect that the process is a spontaneous endothermic process. Based on the findings, it is revealed that the alkaloids extracted from S. xanthocarpum can serve as an excellent, eco-friendly and a promising green inhibitor against mild steel corrosion. Full article

Using natural plant extracts on metallic substances is the most frequently studied green corrosion inhibition approach in corrosion science. In this work, Coriaria nepalensis Stem Alkaloid (CNSA) has been successfully extracted and characterized by qualitative chemical (Mayer’s and Dragendroff’s) test and spectroscopic (UV and FTIR) measurement. CNSA has been employed as a green inhibitor for Mild Steel (MS) corrosion subjected to 1 M H₂SO₄ solution. The corrosion inhibition efficacy has been assessed by weight loss and polarization measurement methods. The effect of inhibitor concentration, immersion period, and temperature on the inhibition efficiency for the MS immersed in both acid and inhibitor solutions of different concentrations have been investigated. The maximum inhibition effect observed for CNSA is 96.4% for MS immersed in 1000 ppm inhibitor solution for 6 h at 18 °C by the weight loss measurement method. Similarly, the polarization measurement method observed a 97.03% inhibition efficiency for MS immersed for 3 h. The adsorption of inhibitor molecules on the MS surface aligns with the Langmuir model. The free energy of adsorption obtained is −28.75 kJ/mol indicating physical adsorption dominance over chemical adsorption. These findings suggested that CNSA has greater potential as an efficient green inhibitor. Full article

Climate change is expected to raise river discharge and sea level in the future, and these near-term changes could alter the river flow regime and sedimentation pattern of future floods. Present hazard assessment studies have limitations in considering such morpho-dynamic responses in evaluating flood hazards or risks. Here, we present a multi-model-based approach to quantify such potential hazard parameters influenced by climate change for the most vulnerable communities living on river bars and islands of the Brahmaputra–Jamuna River. River flood-flow and flood wave propagation characteristics are predicted to be affected by changing temporal distribution patterns of precipitation as a result of enhanced global warming. Increased incidences of large multi-peak floods or uncommon floods resulting in long-duration floods driven by sea-level rise may happen as a result of this. To assess it, we have set up a hydromorphic model, Delft3D, for the Brahmaputra–Jamuna River forced by upstream flow, generated from a hydrological model SWAT, over the Brahmaputra basin. The simulations cover moderate, wettest, and driest conditions of the RCP8.5 scenario, and the results reflect the flooding consequences of the near-future, mid-century, and end-century. Floods in the Brahmaputra–Jamuna River are becoming more severe, frequent, and long-lasting, as a result of climate change, and are expected to last until the end of November rather than the current September timeline. While assessing the hazard, we found that the pattern and timing of the flood are as equally important as the peak of the flood, as the river continuously adjusts its cross-sectional area with the flow. The study also demonstrates that, depending on their location/position, climate-induced hazards can affect sand bars/islands disproportionally. The high flood depth, duration, and sedimentation have a significant impact on the sand bars downstream of the river, making them more vulnerable. Full article