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Over the past few decades, the state of groundwater has become a pressing concern, significantly impacting human health. Groundwater contamination from various pollutants poses substantial risks to communities worldwide, particularly in areas with limited access to clean water. Addressing these challenges necessitates a comprehensive approach, including source control, water quality monitoring, advanced treatment technologies, policy formulation, education, and community engagement. This review paper aims to raise awareness of the diverse factors contributing to water contamination. Examining studies on water pollution from human activities reveals that pesticides, fertilizers, industrial operations, and mining activities are major sources of contamination. Nitrate, harmful substances, and radioactive elements negatively affect the quality of both surface and groundwater, posing significant health risks, especially to vulnerable populations like children and women. Microplastic contamination, primarily from sewage discharge into oceans, poses additional concerns. Geological sources contribute to groundwater contamination through geochemical processes, with fluoride, nitrate, arsenic, uranium, manganese, and various trace elements identified as contaminants. Pharmaceutical ingredients have also been detected in drinking water and fish, albeit in minimal quantities with negligible health risks. Nonetheless, the cumulative impact of pollution sources on individual well-being and quality of life is considerable. Safeguarding groundwater quality is crucial for protecting public health and requires a combination of regulatory measures, technological advancements, community involvement, and sustainable practices. Consistent monitoring of groundwater quality is recommended to identify pollutant sources and develop effective remedial strategies, ensuring healthier and safer environments for current and future generations. • Groundwater quality issues rise, affecting regions with limited clean water access, and posing health threats. • Comprehensive strategy required for contamination addressing. • Pesticides, fertilizers, industries, and mining contribute, heightening risks. • Combat waterborne diseases, and long-term health consequences. • Aligns with Sustainable Development Goals, promoting holistic sustainability. [ABSTRACT FROM AUTHOR]

Tumor recurrence, which happens as a result of persisting tumor cells and minor lesions after treatments like surgery and chemotherapy, is a major problem in oncology. Herein, a strategy to combat this issue by utilize a theranostic nanovaccine composed of photonic HCuS. This nanovaccine aims to eradicate cancer cells and their traces while also preventing tumor recurrence via optimizing the photothermal immune impact. Successful membrane targeting allows for the introduction of new therapeutic agents into the tumor cells. Together with co-encapsulated Toll-Like Receptors (TLR7/8) agonist R848 for activating T cells and maturing DCs, the combined effects of HCuS and ICG function as photothermal agents that generate heat in the presence of NIR light. Photothermal-mediated immunotherapy with therapeutic modalities proved successful in killing tumor cells. By activating the immune system, this new photonic nanovaccine greatly increases immunogenic cell death (ICD), kills tumor cells, and prevents their recurrence. Photonic agent-mediated for PTT with NIR light that effectively induces tumor immunogenic cell death (ICD), including the immunological component R848. The prepared photonic NC acts as a theranostic agent which includes HCuS and ICG. Under 808 nm NIR irradiation, the NC produced photothermal effects to kill tumor cells. Photothermally ablated cancer cells produced cytokines, that activate the immature DCs to mature DCs along with other immune molecules. NC eliminates the cancer cells and produces immunity to recurrent tumor cells. [Display omitted] • Remodeling of tumor microenvironment modulating strategy is reported using NIR-light activatable hollow nanostructure. • Photonic-activatable nanoplatform precisely induced post-photothermal immunogenic cell death pathways simultaneously. • The therapeutic efficacy is well controlled via photothermal-activation, leading to precise cancer therapy. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Ethanol extracts of C. auriculata L. buds and flowers showed higher in vitro antioxidant potential. • Specific phytochemicals detected in CABE and CAFE through LC ESI/MS analysis. • CABE and CAFE exhibited in vitro antidiabetic activity by inhibition of digestive enzymes. • In vivo antidiabetic studies revealed CABE is more efficient than CAFÉ. • Treatment with CABE500, but not CAFE500 upregulated the IRS2 gene expression in liver. Abstract Type 2 Diabetes Mellitus (T2DM) is very common metabolic disorder affecting people of all age groups. The change in life style and environmental factors are the considerable factors which are involved in the development of the disorder. The different parts of medicinal plants vary in their composition of bioactive compounds. There are reports on antidiabetic activity of C. auriculata L. flower and leaves. Traditionally bud of C. auriculata L. is used to treat diabetes rather than flower. This study aims to explore the antidiabetic efficiency of bud and flower and to identify the differential composition of phycompounds present in bud and flower parts of C. auriculata L. The compounds present in the bud and flower parts were identified using LC-ESI/MS analysis. Antidiabetic activity of C. auriculata L. bud and flower parts was studied in high fat diet (HFD) and streptozotocin (STZ) induced diabetic rats. During which parameters such as feed intake, water intake, and body weight were monitored. After 21 days of the study, blood parameters like insulin, glucose, lipid profile, hepatic function test, renal function test and oxidative stress markers were analysed. Real time PCR was done to monitor the expression of IRS2 and GRIA2 genes. The LC-ESI/MS analysis showed the presence of various phenolics and flavonoid compounds specific to bud and flower parts. The antidiabetic activity results showed that the animal treated with C. auriculata L. bud ethanol extract (CABE500) could better reverse and control the progression of the disease compared to the flower ethanol extract. The gene expression studies revealed that regulation of IRS2 gene occurred in bud but not in flower extract treated animal livers and no differential expression of GRIA2 gene in all the experimental groups. C. auriculata L. bud extract can potentially better control the diabetes compared to the flower extract. [ABSTRACT FROM AUTHOR]

The current research work proposes a novel approach to produce holes with high degree of cylindricity on brittle materials using Micro-Abrasive Jet Machining (μ-AJM) technique. Cylindrical micro holes are used as fluid reservoir in microfluidics application such as lab on chip and organ on chip systems. The shape of the holes produced using μ-AJM is observed to be conical due to its tapered sidewalls. It is difficult to achieve cylindrical holes through the μ-AJM process at present. The novel approach presents a hypothesis that by maintaining nozzle stand-off distance (NSD) constant during machining to a value set at the beginning of machining, the taper angle of the holes can be reduced resulting in holes with higher degree of cylindricity. Geometrical characteristics of the machined holes such as their dimension and form error have been examined using coordinate measuring machine (CMM). The obtained results showed significant reduction of 56% in the taper angle and improvement of 57% in the cylindricity of machined holes. [ABSTRACT FROM AUTHOR]

A library of novel dispiro compounds containing oxindole-pyrrolo-carbazole hybrid frame works has been synthesized in a fully regio- and stereoselective fashion by the three-component 1,3-dipolar cycloaddition of azomethineylides generated in situ from the condensation of isatins and benzylamine with 2-arylidene/heteroarylidene-2,3,4,9-tetrahydro-1 H -carbazole-1-one. The structures of the compounds were established by FT-IR, 1 H NMR, 13 C NMR, X-ray diffraction and elemental analysis. The synthesized dispiro heterocycles have been screened for in vitro cytotoxic activity by MTT assay and displayed enviable growth inhibition on both the cancer cell lines i.e. breast cancer cell line MCF-7 and lung cancer cell line A-549. Morphological changes and apoptosis induction have been studied by inverted light microscopic, fluorescent microscopic techniques and by flow cytometry analyses. The preliminary structure activity relationships were also carried out. Data indicated that among dispiro-carbazole compounds,6-chloro-4'-(thiophen-2-yl)-5′-phenyl-3,4-dihydrodispiro[carbazole-2,3′-pyrrolo-2′,3″-indole]-9( H )-1,2″-dione 7e could be exploited as a significant therapeutic drug against breast cancer as well as lung cancer cell proliferation. [ABSTRACT FROM AUTHOR]

Claisen-Schmidt condensation of 2,3,4,9-tetrahydro-1 H -carbazol-1-one with 3-bromo-4-methoxy benzaldehyde afforded the 2-(3'-bromo-4'-methoxybenzylidene)-2,3,4,9-tetrahydro-1 H -carbazol-1-one 3 . Compound 3 was allowed to react with different organic reactants, hydroxylamine hydrochloride, malononitrile and guanidine nitrate through condensation cum cycloaddition reactions to afford a series of the respective novel hetero annulated carbazoles such as isoxazolo-, pyrido- and pyrimido carbazoles. The structures of the compounds were established by FT-IR, 1 H NMR, 13 C NMR, X-ray diffraction and elemental analysis. The compounds have been screened for in vitro anti-tumor activity by MTT assay and displayed enviable selective growth inhibition on MCF-7 cell line compared to A-549 cell line. Apoptotic morphological changes in MCF-7 and A-549 cells were visualized using fluorescent microscopic technique. The preliminary structure activity relationships were also carried out. Data pointed out that among pyrimido carbazole compounds, 2-amino-4-(3'-bromo-4'-methoxyphenyl)-8-chloro-11 H -pyrimido [4,5- a ]carbazole could be exploited as an excellent therapeutic drug against cancer cell proliferation. [ABSTRACT FROM AUTHOR]

This research has identified the groundwater potential and vulnerability zones in Tiruchirappalli district of Tamil Nadu, India. The Schlumberger electrode array has been used to conduct vertical electrical sounding (VES) at 95 sites with a maximum electrode spacing of 150 m. The study area comprises of hard rock and sedimentary formations. Geographical Information System (GIS) has been used to integrate the geoelectrical data and to prepare spatial variation maps for various parameters. Finally, groundwater potential and vulnerability zones have been demarcated, and these outputs have been validated using water level and nitrate data, respectively. The Dar-Zarrouk parameters such as longitudinal conductance (S), transverse unit resistance (T), and aquifer anisotropy (λ) have been used along with the spatial variation of resistivity and aquifer thickness to find out groundwater potential areas with the support of GIS. The thickness of topsoil, weathered zone and fractured zone are not uniform in the research area. Top soil plus weathered zone acts as a water table (phreatic) aquifer, which extends up to 38 m from the surface. Fractured zone extends up to 45 m, which acts as a kind of confined/semi-confined aquifer. Open and bore wells have been constructed to tap groundwater from the unconfined (water table) and confined/semi-confined aquifers, respectively. High to very high groundwater potential areas are associated with low resistivity, high thickness, low longitudinal conductance, high transverse unit resistance and high aquifer anisotropy areas. Very high groundwater potential areas are mostly confined to flood plain (alluvium) deposits in the central portion of the study area. High potential areas are noticed in the northern part, whereas low potential areas are noticed in the southern part. The areas with high longitudinal conductance indicate low permeable zones with less possibility of external pollution. Since agriculture is an important activity in the study region, this work will be useful to provide water supply for irrigation as well as for domestic needs. [Display omitted] • IPI2Win was used for curve matching to evaluate VES data obtained from 95 locations. • Spatial variations of thickness of top soil, weathered zone and fractured zone were plotted using GIS. • Thickness of weathered zone varied from <10 m to >38 m, which played a major role in groundwater occurrence. • Groundwater potential zones were demarcated using hydrogeophysical investigations. [ABSTRACT FROM AUTHOR]

More electric aircraft initiative has led to Fly-By-Wire (FBW) and Power-By-Wire (PBW) technologies. PBW technology has several advantages and has potential for weight reduction and energy saving compared to conventional hydraulic system. Recent development in aviation technology have combined the electric and hydraulic system and arrived at high performance Electro Hydrostatic Actuator (EHA) system. It is a one of the PBW technology which aims at replacing the centralized hydraulic system by a local self-contained and compact actuator system. It is an emerging technology which combines the benefits of conventional hydraulic system and direct drive actuators, like the high energy efficiency, high dynamic response, high torque to mass ratio and high maintainability. EHA system was initially introduced in aircraft for flight control system. Most of the current research literatures considered the EHA system with symmetric actuator configuration. This is because, most of the aircraft application uses symmetric cylinder. However in case of industrial application, asymmetric actuators are predominantly used. An indigenous experimental setup of EHA system with asymmetric actuator has been developed with sensors and instrumentation. In this paper, the dynamic analysis, position tracking and control of the EHA system by varying the speed of drive motor has been established using a Proportional Integral Derivative (PID) controller. PID tuning has been done using Ziegler Nichols (ZN) method. The response using of Proportional Integral (PI), Proportional Derivative (PD) and PID controllers has been studied and found that the PD controller gives the best response. [ABSTRACT FROM AUTHOR]

Abstract: Flapper–nozzle type Electro Hydraulic Servo Valve (EHSV) operated by conventional torque motor actuators has been used in wide range of industrial applications. As their bandwidths are limited, they are not suitable for high-speed applications. The work presented in this paper deals with the mechatronic approach for the design of a magnetostrictive actuator with flexure amplifier and a magnetically biased magnetostrictive actuator for application in high frequency flapper–nozzle servo valve. A magnetostrictive actuator has been designed, built and integrated into an existing flapper–nozzle servo valve by replacing the torque motor. Incorporating the dynamics of the magnetostrictive actuator, the dynamics of the valve was simulated. Necessary parameters for the actuator have been arrived by finite element model. No load flow characteristics are analyzed and compared with experimental values. Step response has been compared with conventional valve. The results show that the valve has satisfactory static and dynamic characteristics for applications in high-speed actuation systems. [Copyright &y& Elsevier]

A study was undertaken to identify in the irrigational suitability of groundwater in the cuddalore district (coastal part), Tamil Nadu, India. An entire study, 132 shallow and deep groundwater samples was gathered during Pre monsoon period (PRM) year of 2017 and post monsoon (POM) period samples collected year of 2018. Rock water interaction, silicate weathering and domestic waste are dominant sources for the water quality in the study area. The groundwater classification and irrigational suitability of groundwater were performed for both seasons. From the results of Chloro-Alkaline Indices (CAI I), and Chloro-Alkaline Indices (CAI II), during both seasons and classes, the direct ions exchange processes are predominant when compare with reverse ions exchange processes. The r 1 and r 2 results represents that most of the samples found as saline sources as Na+ - SO 4 2− facies and performing with Deep Meteoric Percolation (DMP) than shallow meteoric percolation During PRM season, r 1 represents 65 (98%) samples for Na+ - SO 4 2− facies and 1 (2%) sample represents Na+ - HCO 3 − facies and during POM season, r 1 represents 63 (95%) samples for Na+ - SO 4 2− facies and 3 (5%) samples represent Na+ - HCO 3 − facies respectively. Irrigation water quality parameters like and satisfied the analysed water's irrigation suitability. However, according to MAR parameters, 5% of water samples were unsuitable for irrigation in PRM based on KR parameters, 41% of samples collected in the PRM season only were unsuitable for irrigation. The Wilcox diagram showed that 35% of water samples are suitable for irrigation. Sodium Adsorption Ratio (SAR), Soluble Sodium Percentage (SSP), Magnesium Adsorption Ratio (MAR), Permeability Index (PI), Potential Salinity (PS), and Total Dissolved Solids (TDS) are indicating the irrigational appropriateness of the groundwater samples, which is more suitable in post monsoon season compare to pre monsoon due to enrichment of Na+ by seawater intrusion and other processes. During POM season, the most number of groundwater samples are representing excellent to good categories might be due to an effective rainfall recharge by the monsoonal rain in the study area. The parameters indicated the introduction of geogenic and anthropogenic pollutions. The coastal community's knowledge is crucial to the long conservation of coastal water resources. • The rock water interaction, silicate weathering and domestic effluents mainly control the groundwater chemistry in the study region. • Na+ - SO 4 2- facies mainly confirmed that most of the groundwater samples belong to saline origin. • The enrichment of Na+ concentration is lowered at post monsoon due to dominant processes of dilution and groundwater is suitable for irrigation purpose at post monsoon. [ABSTRACT FROM AUTHOR]

Deterioration of water and soil quality, poor infrastructure facilities and improper maintenance are the major factors that govern aquaculture growth and production in major part of India. In the present study aims to identify the suitable land for aquaculture growth and suggest the sustainable practice to improvise the growth of aquaculture in study region. With use of analytical hierarchy process (AHP) the various significant parameters such as geology, pH, salinity, soil media, slope, geomorphology, land use land cover, distance to water, settlement and road networks were analyzed and based on these characteristics, thematic maps were prepared. The results are revealed that, that 882.13 km2 area was most suitable, 1264.88 km2 area was suitable and 14.00 km2 area was unsuitable for aquaculture in the study region. The study results will helpful to decision makers and to make a design plan for aquaculture growth in the study region. • An integrated technique of GIS-AHP was used to determine suitable sites for aquaculture farms in coastal region. • Ten criteria were evaluated for site selection of the aquaculture. • In present study, 2147.01 km2 area was suitable for aquaculture farms. • The GIS-AHP technique is significant method for assessing suitable site with high accuracy. [ABSTRACT FROM AUTHOR]

• Groundwater of the study region is high to very high saline and low alkaline in nature. • Around 53% of the total area has good quality groundwater for drinking water supply. • Southeast part has poor groundwater quality due to less recharge from surface water bodies. • Nearly 82% of the groundwater samples possess health risks for infants in the study region. The main objective of the present investigation is to estimate groundwater suitability for sustainable drinking water supply and food production in a semi-urban area of south India with a focus on risk assessment for making healthy society. As urbanization and industrialization make the water unfit for water supply and crop rising in most parts of the world this study is very much significant for the fast growing Edappadi region in the southern part of India. A total of sixty-nine groundwater samples were obtained during May 2019 (summer season) and analyzed for Total Dissolved Solids (TDS), Electrical Conductivity (EC), pH, potassium (K+), magnesium (Mg2+), sodium (Na+), calcium (Ca2+), bicarbonate (HCO 3 −), nitrate (NO 3 −), sulphate (SO 4 2-), chloride (Cl−), and fluoride (F−). Fluoride and nitrate ranged from 0.38 to 3.23 mg/L and 12 to 136 mg/L with an average of 1.7 mg/L and 62 mg/L, respectively. About 36 % of samples occupying 80.74 km2 area surpass the allowable limit of fluoride (1.5 mg/L). Similarly, 42 % of samples occupying 98.75 km2 area surpass the allowable limit of nitrate as per WHO and BIS standards (45 mg/L). Correlation studies point out that groundwater contamination is happening due to manmade activities. The Improved Water Quality Index (IWQI) suggested that about 57% of groundwater samples can be used for drinking utility. The alkalinity of groundwater is within the suitable level for crops but groundwater salinity is high to very high in most of the areas. The Total Hazard Index (THI) showed that 72%, 59%, 33% and 29% and 86%, 77%, 51% and 43% of groundwater samples are within the non-carcinogenic health risk category based on fluoride and nitrate contents, respectively, for infants, children, teens, and adults. This study will help the decision and policymakers such as municipal corporation, pollution control board, public works department, water supply and drainage boards, agricultural and public health departments, etc., to use appropriate groundwater resources for providing safe drinking water supply and food production from crops. The findings of this study can aid in the development of appropriate management strategies by the above government departments for ensuring safe water supply and health protection measures for inhabitants. [ABSTRACT FROM AUTHOR]

The present research was attempted to examine the human health risks due to nitrate contamination in the groundwater of Texvalley (Tiruppur region) of southern India. Groundwater samples (n = 40) were picked up from open wells (shallow aquifer) and tube wells (deep aquifer) during January 2020, and laboratory examination was conducted for various major physicochemical constituents. Nitrate concentration varied from 10 to 290 mg/l with a mean of 83.45 mg/l. About 58% (n = 23) of the wells exceeded the recommended limit (>45 mg/l) of World Health Organisation, which spread over an area of 335.16 km2. Among this, 45% of the samples (n = 18) represented shallow aquifers (depth < 15 m), and 13% of them (n = 5) represented deep aquifers (depth > 15 m). Synthetic fertilizers, cow dung and sheep manure, industrial discharge, septic tank leakage and municipal solid waste disposal are the major sources of nitrate pollution in this region. The USEPA health risk assessment model was applied in this study to assess hazard quotients (HQ) according to the NO 3 − exposure in various age groups of inhabitants through two different pathways such as drinking (HQ oral) and skin contact (HQ dermal). Eventually, total hazard index (THI) was obtained for all the groundwater samples for different age groups. According to THI, 87%, 78%, 66%, 60%, 56% and 48% of the samples contain health risks (THI >1) for infants, kids, children, teens, adults and aged people, respectively. The study finally recommended seven environmental friendly actions for the groundwater quality improvements and for the sustainable health management. Image 1 • Nearly 58% of the groundwater samples in Tiruppur region are affected by nitrate pollution. • Shallow aquifers are more polluted (45%) than deep aquifers (13%) due to anthropogenic inputs. • The major sources of nitrate are sewages, fertilizers and municipal solid wastes. • About 87% of the samples possess health risks for infants in Tiruppur region. [ABSTRACT FROM AUTHOR]

Contamination of fluoride in drinking water affects human health, and its reduction is essential for the safe utilization of groundwater for domestic and agricultural uses. Groundwater in the ephemeral (monsoonal) Shanmuganadhi River basin, situated at rain shadow of the Western Ghats (south India), is indiscriminately utilized for rural water supply and agricultural activities. Fluoride contamination in groundwater of the river basin was evaluated using geochemical characteristics of sixty-one groundwater samples collected from the observation wells. Groundwater quality evaluation was attempted by estimating pH, Total Dissolved Solids (TDS), Electrical Conductivity (EC), and concentrations of Ca2+ Mg2+, Na+, K+, HCO3-, Cl-, SO 4 2-, NO3-, PO 4 3- and F-. Multivariate statistical techniques helped to identify the factors responsible for fluoride enrichment. The fluoride ion ranges from 0.01 to 2.5 mg/l with 77 % of the samples having less than 1.5 mg/l. Groundwater samples (23 %) with more than 1.5 mg/l of F- are unsuitable for consumption. Fluoride vulnerable zones were mapped using the Geographical Information System (GIS) in which fourteen villages of the basin are with risk category for dental fluorosis among children. The multivariate statistical techniques (including correlation matrix) highlight the relationship among various geochemical parameters, and the cluster analysis apprehends the sources/processes contributing the chemical variables. Based on this study, it is recommended to adopt natural remediation technique like Managed Aquifer Recharge (MAR) for the enhancement of groundwater quality in this basin. [ABSTRACT FROM AUTHOR]

Background Soft tissue sarcomas belong to a heterogeneous group of malignant tumours of mesenchymal origin which constitutes <1% of adult cancers and 12% of paediatric cancers. This study highlights the clinical spectrum of sarcomas, various histological patterns and survival outcomes. The intent is to study retrospectively the clinicopathologic profile and survival outcomes of soft tissue sarcomas and bone sarcomas treated with radiation therapy at a Regional Cancer Centre from South India. Methods The clinical and treatment details of patients were collected retrospectively for the period 2014 -2017 and were analysed using descriptive statistics. Survival analysis was done using Kaplan-Meir Analysis. Results The median age of presentation was 42 years (Range 2-80). Among the 123 patients studied , 54.5%(n = 67) were males and 45.5%(n = 56) were females. The most common presenting complaint was swelling 69% (n = 85) followed by pain 38.2% (n = 47). The most common site of involvement was extremity 48% (n = 59). Other more commonly involved sites were Genitourinary 7.3%(n = 9) and uterus 4.9% (n = 6). The most common histology was Ewing Sarcoma 14.6%(n = 18) followed by Undifferentiated Pleomorphic Sarcoma 13.8% (n = 17). Around 17.9%(n = 22) had metastatic disease at presentation, of which metastasis to lungs (n = 13) was most common, followed by bone (n = 8) and liver(n = 4). The intent of Radiation Therapy was Adjuvant 54.4%(n = 67), Palliative 32.2%(n = 21), Radical 13.8 (n = 17) and Neoadjuvant 6.5%(n = 8). Only 65.9%(n = 81) completed their intended radiation therapy. 91.9% (n = 113) received External Beam Radiation Therapy and 13% (n = 16) received Brachytherapy. Around 48.8% (n = 60) underwent surgery and 66.6% (n = 82) received some form of chemotherapy. The Mean Overall Survival was 50.4 months (95% CI 44.2-56.5 months). Median OS was not reached. Conclusions As per our study, the most common histology was Ewing Sarcoma, followed by Undifferentiated Pleomorphic sarcoma. Approximately 70% of sarcoma patients referred to Radiation Oncology department were for Curative intent whereas 30% with palliative intent and this has led to Mean OS of 50.4 months. At the same time with limited follow up data and the low number of events, the Median OS was not reached. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest. [ABSTRACT FROM AUTHOR]

• The novel T. ramosus chitosan was derived and employed in diabetic studies. • The high influence on biocompatibility was found in drug combination. • Antioxidant effect variations based on different solvents were revealed. • Structural and functional properties of chitosan/metformin composite was revelled. • Hence, the composite reduce cost, frequent consumption and overdosing effect. Metformin is widely used as a frontline medicine of type-II diabetes. Frequent overdose side-effects and their consequent adversative need to be reduced. The novel source of marine hydrozoa, Thyroscyphus ramosus derived chitosan combined metformin drug was administrated to evaluate the antidiabetic potential on a high-fat diet (HFD) with streptozotocin (STZ) induced diabetic rats. The primary analysis of In vitro antioxidant activity was tested for various solvent dissolved chitosan. Based on their IC 50 dose values, CsnAA was chosen for further experiments. The chitosan was combined with metformin by sonication and confirmed through XRD, FTIR and SEM analysis. The enhanced activity was observed in 100 mg/kg metformin combined with CSN500mg/kg. The level of serum bilirubin, total protein, SGH, liver glycogen, Glucose-6-phosphatase and fructose-1,6- phosphatase values were significantly similar to metformin 300 mg/kg treated group. With this beneficiary, the novel chitosan was recommended to administrate with metformin to improve the drug efficacy and reduction of overdose lethal effects. [ABSTRACT FROM AUTHOR]

A novel series of 1,3,4-thiadiazole-thiazolone hybrids 5a – v were designed, synthesized, characterized, and evaluated against the basal and the microtubule (MT)-stimulated ATPase activity of Eg5. From the evaluated derivatives, 5h displayed the highest inhibition with an IC 50 value of 13.2 µM against the MT-stimulated Eg5 ATPase activity. Similarly, compounds 5f and 5i also presented encouraging inhibition with IC 50 of 17.2 µM and 20.2 µM, respectively. A brief structure–activity relationship (SAR) analysis indicated that 2-chloro and 4-nitro substituents on the phenyl ring of the thiazolone motif contributed significantly to enzyme inhibition. An in silico molecular docking study using the crystal structure of Eg5 further supported the SAR and reasoned the importance of crucial molecular protein–ligand interactions in influencing the inhibition of the ATPase activity of Eg5. The magnitude of the electron-withdrawing functionalities over the hybrids and the critical molecular interactions contributed towards higher in vitro potency of the compounds. The drug-like properties of the synthesized compounds 5a – v were also calculated based on the Lipinski’s rule of five and in silico computation of key pharmacokinetic parameters (ADME). Thus, the present work unveils these hybrid molecules as novel Eg5 inhibitors with promising drug-like properties for future development. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Cassia auriculata (CA) is used as an antidiabetic therapy in Ayurvedic and Siddha practice. This study aimed to understand the mode-of-action of CA via combined cheminformatics and in vivo biological analysis. In particular, the effect of 10 polyphenolic constituents of CA in modulating insulin and immunoprotective pathways were studied. Materials and methods In silico target prediction was first employed to predict the probability of the polyphenols interacting with key protein targets related to insulin signalling, based on a model trained on known bioactivity data and chemical similarity considerations. Next, CA was investigated in in vivo studies where induced type 2 diabetic rats were treated with CA for 28 days and the expression levels of genes regulating insulin signalling pathway, glucose transporters of hepatic ( GLUT2 ) and muscular ( GLUT4 ) tissue, insulin receptor substrate ( IRS ), phosphorylated insulin receptor ( AKT ), gluconeogenesis ( G6PC and PCK-1 ), along with inflammatory mediators genes ( NF-κB , IL-6 , IFN-γ and TNF-α ) and peroxisome proliferators-activated receptor gamma ( PPAR-γ ) were determined by qPCR. Results In silico analysis shows that several of the top 20 enriched targets predicted for the constituents of CA are involved in insulin signalling pathways e.g. PTPN1, PCK- α , AKT2, PI3K- γ . Some of the predictions were supported by scientific literature such as the prediction of PI3K for epigallocatechin gallate. Based on the in silico and in vivo findings, we hypothesized that CA may enhance glucose uptake and glucose transporter expressions via the IRS signalling pathway. This is based on AKT2 and PI3K- γ being listed in the top 20 enriched targets. In vivo analysis shows significant increase in the expression of IRS , AKT , GLUT2 and GLUT4 . CA may also affect the PPAR- γ signalling pathway. This is based on the CA-treated groups showing significant activation of PPAR- γ in the liver compared to control. PPAR- γ was predicted by the in silico target prediction with high normalisation rate although it was not in the top 20 most enriched targets. CA may also be involved in the gluconeogenesis and glycogenolysis in the liver based on the downregulation of G6PC and PCK-1 genes seen in CA-treated groups. In addition, CA-treated groups also showed decreased cholesterol, triglyceride, glucose, CRP and Hb1Ac levels, and increased insulin and C-peptide levels. These findings demonstrate the insulin secretagogue and sensitizer effect of CA. Conclusion Based on both an in silico and in vivo analysis, we propose here that CA mediates glucose/lipid metabolism via the PI3K signalling pathway, and influence AKT thereby causing insulin secretion and insulin sensitivity in peripheral tissues. CA enhances glucose uptake and expression of glucose transporters in particular via the upregulation of GLUT2 and GLUT4 . Thus, based on its ability to modulate immunometabolic pathways, CA appears as an attractive long term therapy for T2DM even at relatively low doses. [ABSTRACT FROM AUTHOR]

Highlights: [•] We report the regulation of 12 genes which are believed to play a role in biofilm formation using RT-qPCR. [•] Simultaneously, the expressions of such genes were compared with the morphological changes using SEM. [•] The main findings were that the delayed expressions of certain genes were significantly higher at 48 h. · We conclude that these genes are considered important for the development of biofilm.{insert the bullet point as per style} [ABSTRACT FROM AUTHOR]

Abstract: Purpose: At our institute, we use high–dose-rate (HDR) intracavitary brachytherapy (ICBT) schedule of 9Gy per fraction for two fractions after external beam radiotherapy (EBRT) in patients with advanced carcinoma of the cervix. But American Brachytherapy Society recommends that individual fraction size should be less than 7Gy per fraction in such patients. We present the results of comparison of our institution standard schedule with biologically equivalent dose of 6.8Gy per fraction for three fractions in terms of local control, disease-free survival, and late toxicity. Methods and Materials: Between October 2003 and August 2007, 104 patients with carcinoma of the uterine cervix (Stages IIB and IIIB) were treated with EBRT and HDR ICBT. After EBRT, patients were randomized to one of the treatment arms. ICBT dose in Control Arm A (n =52) was 9Gy per fraction in two fractions, 1 week apart, and in Study Arm B (n =52), it was 6.8Gy per fraction in 3 fractions, 1 week apart. Results: The median followup was 31.48 months. The 3-year actuarial local control was 81.35% in Arm A and 65.18% in Arm B (p =0.0423), and the 3-year actuarial disease-free survival was 64.97% in Arm A and 49.47% in Arm B (p =0.0393). The 3-year actuarial risk of developing any Grade 3 or worse late toxicity was 7.47% in Arm A and 3.57% in Arm B (p =0.2907). Conclusion: In our setup, HDR brachytherapy at 9Gy per fraction in two fractions is safe and effective with good local control, survival, and manageable normal tissue toxicity. [Copyright &y& Elsevier]

Several methods are explored for the thermal management of highly packed electronic systems. A forced convection setup called micro-blower is an effective solution for the application of heat removal and it consists of a piezoelectric disc (PED), diaphragm, ring and a top plate. A numerical model is developed to study the influence of input voltage on the micro-blower using COMSOL Multiphysics. The size of the micro-blower selected is 20 × 20 × 3 mm3. Structural characteristics such as Eigen frequency, diaphragm displacement and von Mises stress and output characteristic such as velocity at the nozzle exit, the volumetric flow rate of air, density variation in the fluid domain and pressure gradient of air at the nozzle for various voltage inputs (peak-to-peak voltage, V p-p) from 5 to 20 V were estimated. The diaphragm displacement of the blower was estimated with various input voltages. An average nozzle velocity of 21.21 m/s was achieved with an average volumetric flow rate of 10.66 × 10−6 m3/s for the voltage input of 20 V p-p. The von Mises stresses of PED, diaphragm, ring and top plate were 3.38, 6.38, 15.72 and 88.97 MPa and these were within the maximum yield strength of respective components at 20 V and hence the micro-blower design is safe. The proposed Eigen frequency in the ultrasonic range was 21.298 kHz and the proposed input voltage as per the breakdown voltage was 20 V. The results were compared with existing literature data and found promising agreement. • A numerical model of micro-blower was developed to identify the safe working condition. • Eigen frequency study was carried out to find the ultrasonic range frequency. • Structural behaviour such as displacement and von Mises stress were estimated. • The flow characteristics such as velocity, volume flow rate, pressure and density were calculated. • An air velocity of 21.21 m/s was achieved at nozzle exit of the micro-blower. [ABSTRACT FROM AUTHOR]

Background: The contribution of long-chain acyl-CoA dehydrogenase (LCAD) to human fatty acid oxidation is not understood. Results: LCAD localizes to lung alveolar type II cells, which produce pulmonary surfactant; LCAD-deficient mice have surfactant dysfunction. Conclusion: LCAD is important for lung energy metabolism and lung function. Significance: LCAD may play a role in human lung disease and unexplained sudden infant death. Long-chain acyl-CoA dehydrogenase (LCAD) is a mitochondrial fatty acid oxidation enzyme whose expression in humans is low or absent in organs known to utilize fatty acids for energy such as heart, muscle, and liver. This study demonstrates localization of LCAD to human alveolar type II pneumocytes, which synthesize and secrete pulmonary surfactant. The physiological role of LCAD and the fatty acid oxidation pathway in lung was subsequently studied using LCAD knock-out mice. Lung fatty acid oxidation was reduced in LCAD-/- mice. LCAD-/- mice demonstrated reduced pulmonary compliance, but histological examination of lung tissue revealed no obvious signs of inflammation or pathology. The changes in lung mechanics were found to be due to pulmonary surfactant dysfunction. Large aggregate surfactant isolated from LCAD-/- mouse lavage fluid had significantly reduced phospholipid content as well as alterations in the acyl chain composition of phosphatidylcholine and phosphatidylglycerol. LCAD-/- surfactant demonstrated functional abnormalities when subjected to dynamic compression-expansion cycling on a constrained drop surfactometer. Serum albumin, which has been shown to degrade and inactivate pulmonary surfactant, was significantly increased in LCAD-/- lavage fluid, suggesting increased epithelial permeability. Finally, we identified two cases of sudden unexplained infant death where [ABSTRACT FROM AUTHOR]

Abstract: Background and purpose: To evaluate the prognostic significance of response to external beam radiation (EBRT) in predicting the clinical outcomes in stage IIIB cancer cervix and to find out factors affecting response to EBRT. Patients and methods: This retrospective study included 556 patients of cancer cervix stage IIIB treated between 1996 and 2001 with EBRT (46Gy/23fx/4.5 weeks) followed by intracavitary radiotherapy (ICRT). At the end of EBRT, response to EBRT was grouped as ‘no gross residual tumor’(NRT) or ‘gross residual tumor’(GRT). Results: Follow up ranged from 2 to 93 months with a median of 36 months. Median dose to point A was 81Gy. At the end of EBRT, 393 patients (70.7%) attained NRT response. NRT responders had significantly better 5 year pelvic control, disease free survival (DFS) and overall survival (OS) than those who had a GRT response (75.6 vs. 54.6%; 60.6 vs. 31.9% and 62.6 vs. 33.7%, respectively; all P values <0.0001). Apart from response to EBRT, overall treatment time also has emerged as an independent factor to affect all clinical outcomes in multivariate analysis but age had significant impact on pelvic control only. Age was the only factor, which significantly influenced the response to EBRT in univariate as well as multivariate analysis (P=<0.001, OR=1.973, 95% C.I. 1.357–2.868). Patients with age more than 50 years had more NRT response (77%) than patients with age less than 50 years (63.8%). Conclusions: Patients who attain NRT response to EBRT will have an impressive long term pelvic control, DFS and OS in stage IIIB cancer cervix. Older patients (≥50 years) attain significantly higher NRT rates than younger patients. [Copyright &y& Elsevier]

Abstract: Aims: In this retrospective audit, we describe the results of external-beam radiotherapy (EBRT) alone in patients with invasive cancer of the cervix treated at our centre. Material and Methods: We included 146 patients with invasive cancer of the cervix who were treated with EBRT to a total dose of 60–66Gy between January 1996 and December 2001. None of these patients were suitable for intracavitary radiotherapy (ICRT) after a median dose of 46Gy. A boost dose of 14–20Gy was given after a gap of 2–4 weeks. Most patients belonged to stage IIIB (n =124). Results: Follow-up of patients at risk ranged from 19 to 89 months (median 48 months). One hundred and thirty-six patients (93.2%) received EBRT to a dose of 66Gy, and 10 patients (6.8%) received 60Gy. Overall treatment time (OTT) ranged from 56 to 160 days (median 78 days). At completion of 46Gy of EBRT, 63 patients achieved partial response and 83 patients had stable disease. Five-year overall survival, disease-free survival (DFS) and pelvic control were 15.1% (median 9 months), 11.6% (median 5 months) and 21.9% (median 6 months), respectively. Factors found to affect 5-year pelvic control in univariate analysis by Kaplan–Meier method were response to EBRT at 46Gy (partial response 36.5% and stable disease 10.8%), age (≥50 years 28.8% and <50 years 13.6%) and OTT (<90 days 26.5% and ≥90 days 12.5%). For DFS and overall survival, response to EBRT was the only factor that was significant in univariate analysis. In multivariate analysis by Cox''s proportional hazard model, response to EBRT was the only factor to influence pelvic control (P =0.007), DFS (P =0.01) and overall survival (P <0.001). Conclusions: Overall outcome of patients in whom ICRT was not given remains less than satisfactory. Response to EBRT emerged as the most important factor to predict all clinical outcomes. To improve upon the dismal results of EBRT alone, we will have to decrease the OTT and consider concurrent chemo-radiation with cisplatin. [Copyright &y& Elsevier]

Purpose: To evaluate the results of salvage radiotherapy (RT) after inadequate surgery in patients with invasive carcinoma of the cervix. Methods and Materials: Between 1996 and 2001, 105 invasive cervical carcinoma patients were treated at our center with external beam RT with or without intracavitary RT after having undergone total/subtotal hysterectomy at outside institutions. Results: The median follow-up was 34 months. The gap between surgery and RT was 23–198 days (median, 80). Clinically visible residual disease was present in 81 patients (77.1%). Total hysterectomy had been done in 82 patients (78%) and subtotal hysterectomy in 23 patients (22%). The 5-year overall survival, disease-free survival, and pelvic control rates of all patients were 55.2%, 53.3%, and 72.4%, respectively. On univariate analysis, older age, total hysterectomy, hemoglobin level >10 g% before RT, nonsquamous histologic type, use of intracavitary RT, a shorter gap between surgery and RT, and the absence of, or a small volume of, residual disease favorably affected the outcome. The 5-year actuarial rate of late toxicity (Radiation Therapy Oncology Group Criteria) was 19% in the rectum, 4.8% in the bladder, 24.8% in the skin, and 14.3% in the small intestine. Conclusions: Inadequate and inappropriate surgery in invasive cervical cancer with resulting gross residual disease is common in India. Factors such as the use of intracavitary RT, the correction of anemia, and a shorter gap between surgery and RT will enable postoperative RT to achieve acceptable results with minimal morbidity. [Copyright &y& Elsevier]