Optimizing graphene content in scaffolds for evenly distributed crumpled MoS2paper wads as anodes for high-performance Li-ion batteries.

Lithium-ion batteries (LIBs) have revolutionized portable electronics, yet their conventional graphite anodes face capacity limitations. Integrating graphene and 3D molybdenum disulfide (MoS2) offers a promising solution. Ensuring a uniform distribution of 3D MoS2nanostructures within a graphene matrix is crucial for optimizing battery performance and preventing issues like agglomeration and capacity degradation. This study focuses on synthesizing a uniformly distributed paper wad structure by optimizing a composite of reduced graphene oxide RGO@MoS2through structural and morphological analyses. Three composites with varying graphene content were synthesized, revealing that the optimized sample containing 30 mg RGO demonstrates beneficial synergy between MoS2and RGO. The interconnected RGO network enhances reactivity and conductivity, addressing MoS2aggregation. Experimental results exhibit an initially superior capacity of 911 mAh g-1, retained at 851 mAh g-1even after 100 cycles at 0.1 A g-1current density, showcasing improved rate efficiency and long-term stability. This research underscores the pivotal role of graphene content in customizing RGO@MoS2composites for enhanced LIB performance.

PdSe2/MoSe2: a promising van der Waals heterostructure for field effect transistor application.

The field-effect transistor (FET) is a fundamental component of semiconductors and the electronic industry. High on-current and mobility with layer-dependent features are required for outstanding FET channel material. Two-dimensional materials are advantageous over bulk materials owing to their higher mobility, high ON/OFF ratio, low tunneling current, and leakage problems. Moreover, two-dimensional heterostructures provide a better way to tune electrical properties. In this work, the two distinct possibilities of PdSe2/MoSe2heterostructure have been employed through mechanical exfoliation and analyzed their electrical response. These diffe approaches to heterostructure formation serve as crucial components of our investigation, allowing us to explore and evaluate the unique electronic properties arising from each design. This work demonstrates that the heterostructure possesses a better ON/OFF ratio of ∼5.78 × 105, essential in switching characteristics. Moreover, MoSe2provides a defect-free interface to PdSe2, resulting in a higher ON current of ∼10µA and mobility of ∼63.7 cm2V-1s-1, necessary for transistor applications. In addition, comprehending the process of charge transfer occurring at the interface between transition metal dichalcogenides is fundamental for advancing next-generation technologies. This work provides insights into the interface formed between the PdSe2and MoSe2that can be harnessed in transistor applications.

Tungsten Disulfide Decorated Screen-Printed Electrodes for Sensing of Glycated Hemoglobin.

Diabetes is a global menace, and its severity results in various disorders including cardiovascular, retinopathy, neuropathy, and nephropathy. Recently, diabetic conditions are diagnosed through the level of glycated hemoglobin. The level of glycated hemoglobin is determined with enzymatic methodology. Although the system is sensitive, it has various restrictions such as long processing times, expensive equipment required for testing, and complex steps involved in sample preparation. These limitations are a hindrance to faster results. The limitations of the developed methods can be eliminated through biosensors. In this work, an electrochemical platform was fabricated that facilitates the identification of glycated hemoglobin protein in diabetic patients. The working electrode on the integrated circuit was modified with molecularly imprinted polymer decorated with tungsten disulfide nanoparticles to enhance its analytical properties. The analytical properties of the biosensor were studied using electrochemical techniques. The obtained detection limit of the nanoelectronic sensor was 0.01 pM. The calculated sensitivity of the biosensor was observed to be 0.27 µA/pM. Also, the sensor promises to operate in a dynamic working concentration range and provide instant results.

Ruddlesden-Popper 2D perovskites of type (C6H9C2H4NH3)2(CH3NH3)n-1PbnI3n+1 (n = 1-4) for optoelectronic applications.

Ruddlesden-Popper (RP) phase metal halide organo perovskites are being extensively studied due to their quasi-two dimensional (2D) nature which makes them an excellent material for several optoelectronic device applications such as solar cells, photo-detectors, light emitting diodes (LEDs), lasers etc. While most of reports show use of linear carbon chain based organic moiety, such as n-Butylamine, as organic spacer in RP perovskite crystal structure, here we report a new series of quasi 2D perovskites with a ring type cyclic carbon group as organic spacer forming RP perovskite of type (CH)2(MA)n-1PbnI3n+1; CH = 2-(1-Cyclohexenyl)ethylamine; MA = Methylamine). This work highlights the synthesis, structural, thermal, optical and optoelectronic characterizations for the new RP perovskite series n = 1-4. The demonstrated RP perovskite of type for n = 1-4 have shown formation of highly crystalline thin films with alternate stacking of organic and inorganic layers, where the order of PbI6 octahedron layering are controlled by n-value, and shown uniform direct bandgap tunable from 2.51 eV (n = 1) to 1.92 eV (n = 4). The PL lifetime measurements supported the fact that lifetime of charge carriers increase with n-value of RP perovskites [154 ps (n = 1) to 336 ps (n = 4)]. Thermogravimetric analysis (TGA) showed highly stable nature of reported RP perovskites with linear increase in phase transition temperatures from 257 °C (n = 1) to 270 °C (n = 4). Scanning electron microscopy (SEM) and energy dispersive X-ray analysis (EDAX) are used to investigate the surface morphology and elemental compositions of thin films. In addition, the photodetectors fabricated for the series using (CH)2(MA)n-1PbnI3n+1 RP perovskite as active absorbing layer and without any charge transport layers, shown sharp photocurrent response from 17 nA/cm2 for n = 1 to 70 nA/cm2 for n = 4, under zero bias and low power illumination conditions (470 nm LED, 1.5 mW/cm2). Furthermore, for lowest bandgap RP perovskite n = 4, (CH)2MA3Pb4I13 the photodetector showed maximum photocurrent density of ~ 508 nA/cm2 at 3 V under similar illumination condition, thus giving fairly large responsivity (46.65 mA/W). Our investigations show that 2-(1-Cyclohexenyl)ethylamine based RP perovskites can be potential solution processed semiconducting materials for optoelectronic applications such as photo-detectors, solar cells, LEDs, photobatteries etc.

Influence of Parental Factors on Tobacco Smoking among Male Adolescents.

In Bangladesh, more than one-fifth (20.5 percent) of the total population, that is 30.68 million is adolescents. Most of the adult smokers initiate smoking in their adolescent period. This study aimed to investigate parental influencing factors for the initiation of tobacco smoking in adolescence period among 15-19 years old college students of Dhaka city, Bangladesh. This was an unmatched case-control study. The information was collected from 91 ever-smokers in the case group and 91 never-smokers in the control group. The respondents were 11th and 12th-grade male college students selected from two colleges of Dhaka city, Bangladesh. The results were analysed using univariate, bivariate and multivariate analysis. Parental control variable was categorized by using Likert Scale. Around 68.7 percent (n=57) respondents were 18-19 years old who were ever-smoker and about 44 percent (n=40) ever-smokers initiated smoking at or below the age of 16. Father's smoking status was found significant (p value <0.05) in bivariate analysis. In binary logistic regression, respondents who received intermediate to low control from their father compared to high control (OR 3.35, 95% CI 1.08-10.38, p value 0.035), respondents who received intermediate to low control from their mother compared to high control (OR 3.73, 95% CI 1.07-13.05, p value 0.039), and presence of any smoking member in their family compared to who did not have (OR 6.23, 95% CI 2.57-15.12, p value 0.001) found significantly higher odds of being ever-smoker. Respondents whose mother passed up to 8 hours in a day with them compared to mothers who gave limited time (less than 1 hour) in a day was found significantly lower odds (OR 0.07, 95% CI 0.01-0.65, p value 0.019) which was a protective factor of being ever-smoker. The result of the study concludes that parental influencing factors had a significant role in tobacco smoking of college-going male adolescents. Parent focused tobacco prevention program may be effective to reduce tobacco smoking prevalence. Further interventional studies are required.

Reversible synthesis of GO: Role of differential bond structure transformation in fine-tuning photodetector response.

The controlled modification of graphene's electronic band structure poses serious challenges. In the present work, we study the effect of sp 2 cluster size variation on the electronic band gap and photoconductive properties of reduced graphene oxide (RGO). This is achieved by performing reversible functionalization of RGO with oxygen species. The reversible functionalization of RGO results in its partial transformation to graphene oxide (GO) so that the size of the sp 2 clusters within the sp 3 matrix varies, thereby affecting the π-π* band structure and photoconductive properties. The study reveals: (1) incremental creation/elimination of oxygenated surface bonds' related energy states within the π-π* band; (2) customized tuning of the sp 2/sp 3 ratio; (3) the presence/absence of oxygenated states impacts the optical transition processes both from band-to-band and oxygenated states; and (4) the incremental addition/depletion of surface states in a tunable manner directly influences the carrier transport in the photoconductive device. Experiments show a two-stage transformation of RGO electronic properties with changing oxygen functionalities: oxidation (Stage I) and decomposition or erosion (Stage II). Sp 2 cluster size variation induced bandgap change was analyzed by Raman and photoluminescence studies, indicating the possibility for photodetection in a specific band encompassing NIR to UV, depending on the sp 2/sp 3 ratio. Energy-dispersive x-ray spectroscopy and Fourier transform infrared studies confirm the surface oxygenation/de-oxygenation during plasma treatment, and XRD confirms partial transformation of RGO to GO and its amorphization at higher plasma exposure times. In addition, the photodetector performance is optimized in terms of carrier generation-recombination and carrier-lattice scattering. Thus, manipulating better photoconductive response is possible through suitable handling of the parameters involved in the plasma treatment process. This is the first study on the influence of the sp 2/sp 3 ratio-induced lattice structure evolution on photodetection.

WS2 Quantum Dots on e-Textile as a Wearable UV Photodetector: How Well Reduced Graphene Oxide Can Serve as a Carrier Transport Medium?

We document the fabrication and investigations of a novel photodetector based on a WS2 quantum dots and reduced graphene oxide (RGO) (WS2-QDs/RGO) heterostructure. The proposed photodetector is simple, scalable, cost-effective, and flexible and works in an ambient environment. An enhanced photodetection efficiency is observed due to the superior electronic properties of WS2-QDs and excellent electrical as well as thermal properties of the carrier transportation medium, RGO. For device fabrication, GO and WS2-QDs were separately synthesized via different chemistry followed by decorating WS2-QDs on RGO coated cotton textile. Characterization studies confirm the transformation of exfoliated WS2-2D flakes into WS2-0D quantum dots and graphene oxide (GO) to RGO. The optimized photodetection performance of WS2-QDs/RGO demonstrates its photoresponsivity of 5.22 mA W-1 at 1.4 mW mm-2 power density of a 405 nm illumination source. Other sensor parameters such as photosensitivity (∼20.2%), resolution (∼0.031 mW mm-2 µA-1), response time (1.57 s), recovery time (1.83 s), and specific detectivity (∼1.6 × 106 jones) are found for WS2-QDs/RGO sensor, and a few of these parameters are comparable and even superior to some of the devices as reported. Photosensing mechanism is explained in terms of charge transfer caused by appropriate band alignment across the interface between WS2-QDs and RGO, where dimensionality and quantum confinement of nanostructures synergistically enhance the overall performance of the heterostructure. The device flexibility is examined through bending, stretching, and twisting experiments and successfully demonstrated its potentiality. Sensor performance even after being soaked in water and subsequent drying shows the possibility of reuse. The attributes of flexibility, high sensitivity and responsivity, superior resolution, and cost-effectiveness of our novel flexible photodetector indicate its promising potential for flexible and wearable optical detectors operating in UV band. Although negative photoconductance of the WS2-QDs/RGO sensor is a major cause for not allowing the sensor to show its best performance, a trade-off is made with improved device design to qualify the expectations of being a competitive device, and this has been demonstrated with experimental facts.

Avenue to Large-Scale Production of Graphene Quantum Dots from High-Purity Graphene Sheets Using Laboratory-Grade Graphite Electrodes.

Graphene has unprecedented physical, chemical, and electronic properties, but need of the hour is to develop low-dimensional nanomaterials, such as graphene quantum dots (GQDs), that could be incorporated into nanoscale devices. This article depicts the production of GQDs from ultrafine, thin (0.8-1 nm), bilayer graphene sheets (GSs) possessing large micron-sized lateral dimension, low defect density (I D/I G: 0.1), and oxidation degree (C/O ratio: 27) of lowest level, in contrast to many other techniques where synthesis of GSs was done using analytical-grade expensive graphite electrodes. This low-cost manufacturing of GSs for industrial-scale applications was achieved by utilizing only 99%-purity graphite electrodes. The variants of such graphite electrodes (graphite rod, film, pencil) are etched in different pH electrolytes (H2SO4, NaCl, NaOH) via prompt electrochemical exfoliation, each giving more than 50% yield. Nowadays, semiconductor quantum dots (QDs) are utilized in smart device production industries, but their toxicity is a major issue of concern. Therefore, the dimension of this two-dimensional (2D) material is reduced to <10 nm to generate GQDs. A facile and highly reproducible approach has been reported for the large-scale generation of GQDs (size ca. 6-10 nm) with minimal surface defects. The protocol followed in this article to synthesize GQDs involves the use of ethylenediamine (en), which passivates the surface and reduces defects, thereby enhancing the optical properties. We demonstrate the correlation of the electrochemical and hydrothermal parameters with the growth mechanism and morphological, structural, chemical, and optical properties of the graphene nanomaterials. Raman spectroscopy and X-ray diffraction (XRD) reveal the structural configurations of GSs and GQDs to investigate the nature of defects. Field emission scanning electron microscopy (FESEM) confirms the morphological characteristics of the as-prepared GSs and GQDs with energy-dispersive X-ray (EDX) analysis determining the C/O ratio. The optical properties like UV-visible absorption and fluorescence assays show the quantum confinement effect phenomenon in GQDs. The obtained GSs and GQDs display enhanced solution stability in DI water and other solvents due to controllable oxidation degree as elucidated through Fourier transform infrared (FTIR) analysis.

New Concept in Humidity Sensing: Role of Molecular Brownian Energy and Probabilistic Mean Free Path to differentiate RH- and Trace Level Detection.

A break in the traditional pore morphology approach in anodic alumina is presented here to see its niche merit over the conventional sensors for water vapor detection. The cylindrical pore structure was replaced with a normal cone for trace-level and inverse cone for RH-level detection. The normal conical pore was fabricated by sheer manipulation of the reaction rates of electrolytes, anodic polarization, rate and time; the procedure was reversed in the case of the inverse cone structure. A sensor with a normal cone geometry exhibits excellent response at the ppm level and slightly extended to low RH level with a detection range of 120 ppm-30% RH, having response and recovery times of 6 and 255 s, measured at 120 ppm. Lowering of the minimum detection limit further requires alteration of the conical geometric parameters, in tandem with the molecular dynamics of water vapor molecules within the pore. In contrast, a sensor developed from an inverse conical structure shows response only at the RH level, from 20% RH to 90% RH with response and recovery times of less than 60 s over the entire range. Limitations such as nonlinear response, large response-recovery time, and high hysteresis as observed in conventional anodic alumina-based humidity sensors have been removed. The sensor response in conical and inverse conical pore morphologies is compared with that of standard sensors having a cylindrical pore morphology, with a top pore diameter identical with that of the reported sensors. The standard sensors were found to detect in the RH range only, with response and recovery times below 20s. The sensing mechanisms in both structures have been suitably demonstrated and ratified with experimental data. Trace level detection is interpreted with the statistical probabilistic approach in the light of the kinetic theory of gases and Brownian energy. A correlation between top surface pore diameter (through which water molecules enter) and the optimized mean free path of vapor molecule is established, and its effectiveness has been demonstrated for humidity detection at a trace level. The results are encouraging, and the same concept may be tried for the detection of other gaseous stimuli, including organic vapors.

Inter-dependency between surface morphology and sensitive low RH detection: exploration of an intricate mechanism to extend the lower detection limit.

The water vapor molecular dynamics inside a pore structure control both molecular adsorption and desorption processes and the limit of minimum detection (LOD). Pore morphology design, and a higher concentration of electrolyte-driven anions, in accordance with the kinetics of water vapor molecules, is reported here, as the ultimate answer to extremely low relative humidity (RH) detection. In this report, a series of samples were prepared by anodization in different voltage windows, related to specific electrolyte solutions. The sensing attributes comprised: (i) a LOD of ∼3 RH%, (ii) excellent response time (6 s) and recovery time (54 s), and (iii) a hysteresis loss of ∼0.36%, with sustained stability over the period of one year; all these occurring in a sample with a pore diameter ∼5 nm ±3 nm. Interestingly, the LOD extend towards a lower RH% with a decrease in pore diameter; and a suitable explanation is given for the entire range of humidity level, in terms of the molecular mean free path, loss of kinetic energy due to scattering inside the pores, and subsequent overall loss of Brownian energy of the molecules. It is inferred from the sensing response characteristics that pore morphology and lower detection limit are interrelated; therefore, a further extension in LOD from extremely low RH% to trace levels, needs careful engineering of the pore morphology and parameters related to molecular kinetics.

Evaluation of Fixation for Distal Humeral Diaphyseal Fracture by Locking Compression Plate.

Treatment of extra-articular distal humeral shaft fractures with plating techniques is often difficult. The recent development of LCP has improved the surgical treatment of fractures by overcoming the few drawbacks of older fixators. The aim of this prospective observational study was to assess the effectiveness of osteosynthesis of extra-articular diaphyseal fractures of the distal third of the humerus using a single locking compression plate (LCP) and was conducted from July 2016 to June 2018 at the National Institute of Traumatology and Orthopedic Rehabilitation (NITOR), Dhaka, Bangladesh. Thirty (30) patients with closed fracture distal 3rd extra-articular humeral shaft fractures were treated by open reduction and internal fixation by locking compression plate. Two cases were excluded from the evaluation of final outcome due to their discontinued follow up. Detailed clinical conditions of all patients, technical difficulty with the implant, postoperative hospital stay period were recorded. Patients were followed up at 2nd week, 4th week, then 4 weekly upto 6 months. The patients were evaluated clinically and radiologically for outcomes. The progresses of healing as well as occurrence of complications were recorded. The range of motion of the shoulder and elbow were evaluated according to the criteria by Rommens grading. Functional evaluation was made according to the criteria by Modified Constant and Murley Scoring System. Union was achieved in all the patients after a mean of 15 weeks (range 12-20 weeks). There were no complications like deep infection, nonunion, malunion, implant failure, or nerve injury occurs in any of the patients. Two patients had transient radial nerve palsy. Two patients developed superficial infection. All patients were relieved pain postoperatively. Functional outcome were excellent in 10 patients, good in 15 patients which constituted 89% satisfactory results. The study has shown that the LCP is an effective, dependable solution for the management of distal third diaphyseal fractures of the humerus.

Influence of growth temperature on titanium sulphide nanostructures: from trisulphide nanosheets and nanoribbons to disulphide nanodiscs.

We report the fabrication and characterization of titanium sulphide nanostructures using a chemical vapour transport (CVT) method. In CVT, reactions occur between titanium and sulphur powder in the vapor phase for TiS x nanostructure growth. Systematic studies on the effect of temperature, consequent structural evolution and optical properties were investigated by various characterization techniques. A series of experiments were performed by maintaining a fixed compositional ratio (1 : 3) of Ti and S within a temperature range from 400 °C to 650 °C. On increasing the temperature from 400 °C to 650 °C; a gradual change in morphology was obtained from nanosheets (NS) to mixed phase nanoribbons and nanosheets (NS: NR), nanoribbons (NR), and nanodiscs (ND) of titanium sulphide, which was confirmed using SEM/TEM analysis. Then, the composition of titanium sulphides was studied using XRD, EDX and Raman spectroscopic techniques and it is observed that NS, NR and NS: NR have the composition ratio of TiS3 whereas ND has a ratio of TiS2. The phenomenon of decomposition of TiS3 into TiS2 at elevated temperatures was explained using thermogravimetric analysis (TGA) and differential thermal analysis (DTA) along with pictorial representations. The optical properties of the prepared TiS3/TiS2 nanostructures were studied using UV-vis and photoluminescence spectroscopy. It is concluded that composition ratio of Ti and S as well as the temperature variation plays a crucial role in the formation of different Ti-S nanostructures with unique optical, electronic and thermal properties.

An ultrafast quantum thermometer from graphene quantum dots.

We report an ultra-sensitive temperature sensor derived from graphene quantum dots (GQDs) embedded in a self-standing reduced graphene oxide (RGO) film. The GQDs are obtained as a natural derivative during synthesis of GO to RGO. A fundamental study on low temperature transport mechanisms reveals the applicability of temperature zone specific 'variable range hopping (VRH)' conduction models, i.e. Mott-VRH, Efros-Shklovskii-VRH and activation energy supported VRH. On the basis of transport behavior and confirmed by characterization analyses, the RGO film is modeled as GQD arrays where graphitic (sp2) domains behave as QDs and oxygenated (sp3) domains between interdots act as tunneling barriers. Temperature dependent resistance and current-voltage (I-V) characteristics indicate high sensitivity where sensor resistance changes by almost six orders of magnitude as the temperature is varied between 300 and 12 K. In convection mode, the developed temperature sensor shows a temperature coefficient of resistance (TCR) of ∼-1999% K-1 in the 300-77 K temperature range, which is much higher than the TCR values reported so far. Additionally, the sensor exhibits an extremely fast response (∼0.3 s) and recovery (0.8 s) time; and such high TCR leads to ultra high resolution of ∼ µK. The sensor shows excellent repeatability with negligible drift over several cycles. These studies are crucial for modern day thermal management and sensitive cryogenic applications.

Single-wall carbon nanotube based electrochemical immunoassay for leukemia detection.

A label-free electrochemical immunosensor is fabricated using high quality single-walled carbon nanotube for early detection of leukemia cells. It is based on P-glycoprotein (P-gp) expression level detection; by effective surface immune-complex formation with the monoclonal anti-P-glycoprotein antibodies bound to an epoxy modified nanotube surface. The expression level of P-gp on the leukemia cell surface detected by cyclic voltammetry is in good agreement with immunofluorescence microscopy studies. The proposed biosensor could be used for the detection of P-gp expressing cells within a linear range of 1.5 × 103 cells/mL - 1.5 × 107 cells/mL where lowest detection limit is found to be 19 cells/mL. A calibration plot of peak current v/s the logarithm of concentration of leukemia K562 cells is found linear with a regression coefficient of 0.935. This strategy promises high sensitivity, low-cost, fast, and repeatable recognition of cancer cells. The immunosensor was stable for three weeks and showed good precision with the relative standard deviation (RSD) of 3.57% and 2.12% assayed at the cell concentrations of 1.5 × 103 and 1.5 × 105 cells mL-1 respectively. The proposed single-wall carbon nanotube based immunosensor showed better analytical performance in comparison to similar leukemia electrochemical sensors reported.

Reduced graphene oxide (rGO) based wideband optical sensor and the role of Temperature, Defect States and Quantum Efficiency.

We report a facile and cost-effective approach to develop self-standing reduced Graphene Oxide (rGO) film based optical sensor and its low-temperature performance analysis where midgap defect states play a key role in tuning the crucial sensor parameters. Graphite oxide (GO) is produced by modified Hummers' method and reduced thermally at 250 °C for 1 h in Argon atmosphere to obtain rGO. Self-standing rGO film is prepared via vacuum filtration. The developed film is characterized by HRTEM, FESEM, Raman, and XRD techniques. The developed sensor exhibits highest sensitivity towards 635 nm illumination wavelength, irrespective of the operating temperature. For a given excitation wavelength, photoresponse study at low temperature (123K-303K) reveals inverse relationship between sensitivity and operating temperature. Highest sensitivity of 49.2% is obtained at 123 K for 635 nm laser at power density of 1.4 mW/mm2. Unlike sensitivity, response- and recovery-time demonstrate directly proportional dependence with operating temperature. Power dependent studies establish linear relation between power-density and sensitivity, and a safe limit beyond which sample heating prolongs the recovery time. Wavelength-dependent studies shows that proposed sensor can efficiently operate from visible to near NIR region. To the best of our knowledge such rGO based optical sensor performance at low temperature had not been reported earlier.

Serum sonic hedgehog (SHH) and interleukin-(IL-6) as dual prognostic biomarkers in progressive metastatic breast cancer.

Serum from one hundred and ten breast cancer patients and thirty healthy female volunteers, were prospectively collected and evaluated for serum levels of Shh and IL-6 using human Shh and IL-6 specific enzyme-linked immunoassays. All patients were regularly monitored for event free survival (EFS) and overall survival (OS). Overall outcome analysis was based on serum Shh and IL-6 levels. In patients with progressive metastatic BC, both serum Shh and IL-6 concentrations were elevated in 44% (29 of 65) and 63% (41 of 65) of patients, respectively, at a statistically significant level [Shh (p = 0.0001) and IL-6 (p = 0.0001)] compared to the low levels in healthy volunteers. Serum levels tended to increase with metastatic progression and lymph node positivity. High serum Shh and IL-6 levels were associated with poor EFS and OS opposite to the negative or lower levels in serum Shh and IL-6. The elevated levels of both serum Shh and IL-6 were mainly observed in BC patients who had a significantly higher risk of early recurrence and bone metastasis, and associated with a worse survival for patients with progressive metastatic BC. Further studies are warranted for validating these biomarkers as prognostic tools in a larger patient cohort and in a longer follow-up study.

Overexpression of sonic hedgehog in the triple negative breast cancer: clinicopathological characteristics of high burden breast cancer patients from Bangladesh.

Dysregulation of Hedgehog (Hh) signaling pathway has been documented in mammary gland development and breast cancer (BC) progression. Despite the remarkable progress in therapeutic interventions, BC related mortality in Bangladesh increased in the last decade. Triple negative breast cancer (TNBC) still presents a critical therapeutic challenge. Thus effective targeted therapy is urgently needed. In this study, we report the clinicopathological characteristics and prognosis of BC patients from Bangladesh. Routine immunohistochemical analysis and high throughput RNA-Seq data from the TCGA library were used to analyze the expression pattern and association of high and low level of Shh expression in a collection of BC patients with a long-term follow-up. High levels of Shh were observed in a subset of BC tumors with poor prognostic pathological features. Higher level of Shh expression correlated with a significantly poorer overall survival of patients compared with patients whose tumors expressed a low level of Shh. These data support the contention that Shh could be a novel biomarker for breast cancer that is involved in mediating the aggressive phenotype of BC. We propose that BC patients exhibiting a higher level of Shh expression, representing a subset of BC patients, would be amenable to Shh targeted therapy.

Simultaneous Targeting of Bladder Tumor Growth, Survival, and Epithelial-to-Mesenchymal Transition with a Novel Therapeutic Combination of Acetazolamide (AZ) and Sulforaphane (SFN).

BACKGROUND: Current chemotherapies for advanced stage metastatic bladder cancer often result in severe side effects, and most patients become drug resistant over time. Thus, there is a need for more effective therapies with minimal side effects. OBJECTIVE: The acid/base balance in tumor cells is essential for tumor cell functioning. We reasoned that simultaneous targeting of pH homeostasis and survival pathways would improve therapeutic efficacy. We evaluated the effectiveness of targeting pH homeostasis with the carbonic anhydrase inhibitor acetazolamide (AZ) in combination with the survival pathway targeting isothiocyanate sulforaphane (SFN) on the HTB-9 and RT112(H) human bladder tumor cell lines. MATERIALS AND METHODS: We assessed viability, proliferation, and survival in vitro and effect on xenografts in vivo. RESULTS: Combination AZ + SFN treatment induced dose-dependent suppression of growth, produced a potent anti-proliferative and anti-clonogenic effect, and induced apoptosis through caspase-3 and PARP activation. The anti-proliferative effect was corroborated by significant reductions in Ki-67, pHH3, cyclin D1, and sustained induction of the cell cycle inhibitors, p21 and p27. Both active p-Akt (Ser473) and p-S6 were significantly downregulated in the AZ + SFN combination treated cells with a concomitant inhibition of Akt kinase activity. The inhibitory effects of the AZ + SFN combination treatment showed similar efficacy as the dual PI3K/mTOR pathway inhibitor NVP-BEZ235, albeit at an expected higher dose. In terms of the effect on the metastatic potential of these bladder cancers, we found downregulated expression of carbonic anhydrase 9 (CA9) concomitant with reductions in both E-cadherin, N-cadherin, and vimentin proteins mitigating the epithelial-to-mesenchymal transition (EMT), suggesting negation of this program. CONCLUSION: We suggest that reductions in these components could be linked with downregulation of the survival mediated Akt pathway and suggested an active role of the Akt pathway in bladder cancer. Altogether, our in vitro and pre-clinical model data support the potential use of an AZ + SFN combination for the treatment of bladder cancer.

Sonic hedgehog (Shh) signaling promotes tumorigenicity and stemness via activation of epithelial-to-mesenchymal transition (EMT) in bladder cancer.

Activation of the sonic hedgehog (Shh) signaling pathway controls tumorigenesis in a variety of cancers. Here, we show a role for Shh signaling in the promotion of epithelial-to-mesenchymal transition (EMT), tumorigenicity, and stemness in the bladder cancer. EMT induction was assessed by the decreased expression of E-cadherin and ZO-1 and increased expression of N-cadherin. The induced EMT was associated with increased cell motility, invasiveness, and clonogenicity. These progression relevant behaviors were attenuated by treatment with Hh inhibitors cyclopamine and GDC-0449, and after knockdown by Shh-siRNA, and led to reversal of the EMT phenotype. The results with HTB-9 were confirmed using a second bladder cancer cell line, BFTC905 (DM). In a xenograft mouse model TGF-ß1 treated HTB-9 cells exhibited enhanced tumor growth. Although normal bladder epithelial cells could also undergo EMT and upregulate Shh with TGF-ß1 they did not exhibit tumorigenicity. The TGF-ß1 treated HTB-9 xenografts showed strong evidence for a switch to a more stem cell like phenotype, with functional activation of CD133, Sox2, Nanog, and Oct4. The bladder cancer specific stem cell markers CK5 and CK14 were upregulated in the TGF-ß1 treated xenograft tumor samples, while CD44 remained unchanged in both treated and untreated tumors. Immunohistochemical analysis of 22 primary human bladder tumors indicated that Shh expression was positively correlated with tumor grade and stage. Elevated expression of Ki-67, Shh, Gli2, and N-cadherin were observed in the high grade and stage human bladder tumor samples, and conversely, the downregulation of these genes were observed in the low grade and stage tumor samples. Collectively, this study indicates that TGF-ß1-induced Shh may regulate EMT and tumorigenicity in bladder cancer. Our studies reveal that the TGF-ß1 induction of EMT and Shh is cell type context dependent. Thus, targeting the Shh pathway could be clinically beneficial in the ability to reverse the EMT phenotype of tumor cells and potentially inhibit bladder cancer progression and metastasis.

Proteinuria is an independent risk factor for ischemic stroke among diabetic patients.

This study was done to assess the relationship between proteinuria and ischemic stroke in subjects with diabetes mellitus, and to determine whether proteinuria is an independent risk factor for stroke. This comparative study was conducted in Mymensingh Medical College Hospital from January 2009 to June 2010. It was done to establish the relationship between proteinuria (Microalbuminuria) and ischemic stroke among diabetic patients. Other risk factors were also assessed. Patients were divided in Group A - diabetic patients with ischemic stroke (n=50) and Group B diabetic patients without stroke (n=50). Mean age of the Group A & B were 60.16±8.33 and 57.19±7.73 years (p=0.068). Mean Blood sugar (2 hours after Break Fast) was 14.68±4.32mmol/L in Group A and 14.75±4.02mmol/L in Group B (p>0.05). Albumin Creatinine ratio was abnormal in 84.0% in Group A and 22.0% in Group A (p=0.001) [Odds ratio (95%CI) = 18.61 (6.78-51.09)]. Logistic regression analysis has also shown that microalbuminuria (ACR) is an independent risk factor for ischemic stroke (p=0.001), [Odds ratio (95%CI) = 19.811(5.915-66.348)]. In diabetic patients increased urinary protein is a risk factor for stroke. Estimation of urinary protein (Microalbuminuria) may be used as a predictor for ischemic stroke in patients with diabetes.