Quantitative determination of C-polysaccharide in Streptococcus pneumoniae capsular polysaccharides by enzyme-linked immunosorbent assay.

Capsular polysaccharides of Streptococcus pneumoniae are used in pneumococcal polysaccharide and protein-conjugate vaccines. Cell-wall polysaccharide (C-Ps) is a critical impurity that must be kept at low levels in purified polysaccharide preparations. Hence, accurate and precise methods for determining C-Ps are needed. Currently available methods include nuclear magnetic resonance (NMR) spectroscopy and high-performance anion-exchange chromatography with pulsed amperometric detection (HPAEC-PAD). Both these methods suffer from their own limitations; therefore, we developed a simple and efficient enzyme-linked immunosorbent assay (ELISA) for accurate and precise quantification of C-Ps in samples of any serotype of pneumococcal capsular polysaccharide without interference. We quantified C-Ps in preparations of 14 serotype polysaccharides using newly developed ELISA method and compared the results with C-Ps values obtained using two previously reported methods, 1H NMR and HPAEC-PAD. The C-Ps value determined using 1H NMR for serotype 5 was 21.08%, whereas the values obtained using HPAEC-PAD and ELISA were 2.38% and 2.89% respectively, indicating some interference in 1H NMR method. The sensitivity of the ELISA method is higher because the sample is used directly unlike HPAEC-PAD method where sample is subjected to harsh treatment, such as acid digestion and quantify C-Ps based on peak area of ribitol or AAT. Furthermore, 1H NMR and HPAEC-PAD are expensive and laborious methods. Our work, underscores the simple and efficient ELISA that can be used for quantification of C-Ps in pneumococcal polysaccharide preparations.

A Cross-Sectional Study on Patient Preferences for Selecting Surgeons for Joint Replacement Surgery in India.

Introduction This study aims to investigate the complex decision-making process of patients in India when choosing surgeons for joint replacement surgery, with a focus on both clinical and non-clinical factors influencing their preferences. Methods This was a cross-sectional observational study conducted at the KIMS-Sunshine Hospitals, Hyderabad, a high-volume tertiary care institute in India, in which patients with end-stage osteoarthritis requiring primary total knee arthroplasty were evaluated using a self-administered questionnaire, which assessed both patient-related and surgeon-related factors in choosing their joint replacement surgeon. Results A total of 210 participants were surveyed among whom the majority were females with an average age of 60.2 years with the majority belonging to the upper-middle-class socioeconomic status (48.6%, N=102). Fifty-nine percent preferred surgeons with over 20 years of experience, and 63.8% were willing to travel out-of-state for recognized expertise. Family recommendations (33.8%) and surgeon reputation (24.3%) were primary factors in surgeon selection. A vast majority (73.3%) preferred surgeons who were skilled in robotic surgery and had foreign training (32.9%). However, the majority (67.6%) did not express any gender preference. The survey highlighted a broad range of informational sources affecting decisions, including financial consideration (63.8%), personal referrals, and online platforms (17.1%). Preferences were also shaped by hospital reputation and insurance options (10.5%), illustrating a nuanced interplay of quality, cost, and personal connections in the selection process. Conclusion The findings of this survey illuminate the intricate and diverse preferences exhibited by patients when selecting a surgeon for joint replacement surgery. A significant rise in patient expectations is evident, underscoring a demand for more personalized, contemporary, and high-quality healthcare services. Importantly, geographical proximity appears to be a diminishing concern in their decision-making process. This trend presents an opportunity for centers of excellence to extend their influence and attract patients on both a regional and national level.

Purtscher's like retinopathy - A rare ocular complication of acute pancreatitis.

INTRODUCTION AND IMPORTANCE: Purtscher retinopathy is the rare form of occlusive microvasculopathy, characterized by multiple retinal white areas around the optic nerve head and fovea with paravascular clearing and may be related to intraretinal hemorrhages. Acute Pancreatitis (AP) is one of the most common gastrointestinal reasons for hospital admissions globally. The complications of Acute Pancreatitis may include Purtscher's-like retinopathy, which has a low incidence rate of less than 0.24 instances per million cases. This case report highlights the value of thorough medical history taking and examination, and it apprises the consideration of ophthalmological manifestation in patients of Acute Pancreatitis. CASE PRESENTATION: A 34-year-old female came to the emergency room due to intense abdominal pain associated with nausea and vomiting, which worsened over the last 24 h. The pain was described as continuous, sharp, and cramping-like in the upper abdomen, radiating to the back. Lab tests revealed elevated serum amylase and lipase levels, indicating pancreatitis, along with slight leukocytosis. A contrast-enhanced CT scan confirmed acute pancreatitis with mild inflammation and enlargement of the pancreas. Two days after admission, the patient experienced a sudden and painless loss of central vision in both eyes. There was no history of trauma or any other significant relevant history, other than pancreatitis. The ophthalmologist's examination found reduced visual acuity (6/60 in the right eye, 3/60 in the left eye), normal corneas, and anterior chambers. DISCUSSION: Inkeles and Walsh established the first link between acute pancreatitis and Purtscher-like retinopathy when they reported three cases of the distinctive retinal appearance in individuals with acute pancreatitis in 1975. CONCLUSION: The recovery and prognosis in cases of Purtscher-like retinopathy is variable and further research is required to ascertain the usage of corticosteroids and pentoxifylline in improving the course of a patient's with Purtscher's-like retinopathy.

O-phthalaldehyde based quantification of polysaccharide modification in conjugate vaccines.

Polysaccharide-based vaccines cannot stimulate long-lasting immune response in infants due to their inability to elicit a T-cell-dependent immune response. This has been addressed using conjugation technology, where conjugates were produced by coupling a carrier protein to polysaccharides using different conjugation chemistries, such as cyanylation, reductive amination, ethylene diamine reaction, and others. Many glycoconjugate vaccines that are manufactured using different conjugation technologies are already in the market for neonates, infants and young children (e.g., Haemophilus influenzae type-b, Streptococcus pneumoniae and Neisseria meningitidis vaccines), and all of them elicit a T-cell dependent immune response. To manufacture glycoconjugate vaccines, the capsular polysaccharide is first activated by converting its hydroxyl groups to aldehyde-, cyanyl-, or cyanate ester groups, depending on the conjugation chemistry selected. The oxidized and reduced aldehyde functional groups of the polysaccharides are subsequently reacted with the amino groups of carrier protein by reductive amination to form a stable amide bond. In CDAP-based conjugation, the polysaccharide -OH groups are activated to form cyanyl-, or cyanate ester groups to react with the amino groups of carrier protein and forms an isourea bond. Understanding the extent of polysaccharide activation/modification is essential since it directly influences the molar mass of the conjugate, its stability, and the immunogenicity of the product. Reported methods are available to estimate the aldehyde groups of polysaccharides generated by reductive amination. However, no method is available to quantify the cyanyl or cyanate ester (-OCN) groups generated by cyanylation with 1-cyano-4-dimethylaminopyridinium tetrafluoroborate (CDAP). We report a novel strategy using an O-phthalaldehyde (OPA) derivatization process followed by size-exclusion chromatography (SEC) high-performance liquid chromatography (HPLC) separation and UV detection. The cyanate ester groups on the activated polysaccharide directly reveal the extent of polysaccharide activation/modification and the residual activated groups in the purified conjugates. This method would be useful for conjugate vaccine manufacturing using CDAP chemistry.

Decompression of Paralabral Cyst near Axillary Nerve: A Case Report.

Introduction: Paralabral cyst is benign fluid-filled lesion that occurs adjacent to glenoid labrum. Origin of the cyst can be traumatic or atraumatic. This cystic lesion can compress nearby axillary nerve or suprascapular nerve, resulting in shoulder pain and numbness. In this case report, we will discuss about anteroinferior paralabral cyst with axillary neuropathy in atraumatic condition. Case Report: A 35-year-old male was admitted in our institute with complaining of numbness in the mid-part of the lateral arm and pain in the posterior aspect in the left shoulder for 2 weeks. The patient has on-and-off pain in the left shoulder on lifting weight. He had no history of trauma. X-ray was normal. On examination, tenderness presents over the dorsal aspect of shoulder and reduced sensations over deltoid muscle (regimen badge sign). Deltoid atrophy was noted. Range of motion was normal. On examination, cervical spine was normal, and reduced sensation over the lateral aspect of arm and deltoid atrophy was present. Magnetic resonance imaging (MRI) shows large multiloculated paralabral cyst caudal to inferior glenoid rim. The diagnosis was compressive axillary neuropathy which was confirmed by nerve condition study. Conclusion: According to this case report, accurate early clinical examination and MRI evaluation are crucial in patients with atraumatic shoulder pain associated with neurological symptoms. On identification, cyst can be successfully decompressed by shoulder arthroscopy which can prevent axillary nerve damage, muscle denervation, and also recurrence of cyst can be avoided.

Multi epitope vaccine candidate design against Streptococcus pneumonia.

Streptococcus pneumonia, the causative agent of sepsis, meningitis and pneumonia, is held responsible for causing invasive diseases predominantly in children along with adults from both developing and developed countries. The available vaccines coverage in the context of different serotypes is limited and emergence of non-vaccine serotypes could further emerge as a threat in future. Advanced immunoinformatics tools have been used for developing a multi epitope subunit vaccine. In the current study we have subjected these four surface antigenic proteins Ply, PsaA, PspA and PspK to construct vaccine designs. We have predicted different B-cell and T-cell epitopes by using NetCTL 1.2, IEDB (Immune Epitope Databases) and ABCpred. An adjuvant (griselimycin) has been added to the vaccine construct sequence in order to improve its immunogenicity. The vaccine construct has been evaluated for its antigenicity, allergenicity, toxicity and different physio-chemical properties. The bioinformatic tools have been used for prediction, refinement and validation of the 3 D structure. Further, the vaccine structure has been docked with a toll-like receptor (TLR-4) by ClusPro 2.0. In conclusion, the proposed multi-epitope vaccine designs could potentially activate both humoral and cellular immune responses and has a potential to be a vaccine candidate against S.pneumoniae, and requires experimental validation for ensuring immunogenicity and safety profile.Communicated by Ramaswamy H. Sarma.

Vitamin C and its therapeutic potential in the management of COVID19.

COVID19 has emerged as one of the worst pandemics in the history of mankind. Several vaccines have been approved by different government agencies worldwide, but data on their efficacy and safety are limited, and distribution remains a massive challenge. As per WHO, personal immunity is vital for protection against COVID19. Earlier, Vitamin C-mediated pathways have been shown to play critical role in boosting immunity attributed to its antioxidant properties. Recently, the involvement of such pathways in protection against COVID19 has been suggested. The controlled doses of Vitamin C administered through intravenous (IV) injections are being studied for determining its role in the prognosis of COVID19. In this article, we have discussed the potential role of Vitamin C in the management in COVID19 patients and presented recent clinical trials data. Additionally, we have elaborated the possibility of administering Vitamin C through inhalers in order to achieve local high concentration and the challenges of such approach.

High-Performance Anion-Exchange chromatography with conductivity detection method for simultaneous determination of nitrogen and phosphorus in polysaccharides.

Capsular polysaccharides of Streptococcus pneumoniae contain a characteristic mix of monosaccharides in their structure resulting in immunologically distinct serotypes. Pneumococcal capsular polysaccharides include sugars such as hexoses, uronic acids, hexosamines, methyl pentoses, other functional groups are attached to the sugars are N and O-acetyl groups, nitrogen and phosphorus. Most of these components can be quantified using different colorimetric methods. However, available methods for quantifying nitrogen and phosphorus are not sensitive enough and laborious. We report a highly sensitive high-performance anion-exchange chromatography-conductivity detector (HPAEC-CD) method for quantifying nitrogen and phosphorus present in pneumococcal capsular polysaccharides. The method is reliable, robust and reproducible with no interference. The LOQ for nitrogen and phosphorus of 3.125 and 62.5 ng/mL, respectively, is highly critical for estimating low levels of total nitrogen and total phosphorus. We have implemented this method to quantify total nitrogen in Typhoid Vi polysaccharide and phosphorus in Haemophilus influenzae type-b polysaccharide. This method has greater application for quantification of nitrogen and phosphorus present in low concentrations in polysaccharide vaccines/biologicals.

Arthroscopic Anterior Capsule Reconstruction Using Fascia Lata Autograft and Knotless Fibretak: A Case Report.

Introduction: Shoulder has multidirectional mobility with capsule and rotator cuff as stabilizers. Irreparable subscapularis tears are relatively uncommon. Anterior capsule reconstruction (ACR) is one of the different modalities of treatment for irreparable subscapularis tears. Anterior capsular reconstruction can be performed using hamstring autograft, tibialis anterior allograft, and human dermal allograft. Procedures using hamstring autograft and tibialis anterior allograft reported severe capsular deficiency, recurrent dislocation, and subluxations. Dermal allograft is routinely used for ACR anterior capsule reconstruction. But However, there are no reports of Fascia lata autograft being used for ACR anterior capsule reconstruction. As fascia lata is an autograft, it may have a better chance of healing than dermal allograft. Case Report: A 60-year year-old male patient came with history of slip and fall at home 3 months ago and injured his left shoulder. Magnetic resonance imaging MRI is showing subscapularis tear retracted medial to glenoid and anterior supraspinatus tear with minimal retraction. The aim of this case report is to describe in detail the arthroscopic technique of ACR anterior capsule reconstruction using fascia lata autograft using the new knotless all suture anchors (fibereTak) on glenoid. Conclusion: Fascia lata being an autograft may have better healing potential, but its superiority over dermal allografts in the setting of ACR anterior capsule reconstruction needs further studies.

The extended (p)ppGpp family: New dimensions in Stress response.

Second messenger (p)ppGpp mediated stress response plays a crucial role in bacterial persistence and multiple drug resistance. In E. coli, (p)ppGpp binds to RNA polymerase and upregulates the transcription of genes essential for stress response while concurrently downregulating the expression of genes critical for growth and metabolism. Recently, the family of alarmone molecules has expanded to pppGpp, ppGpp, pGpp & (pp)pApp as distinct members. These molecules may help in fine-tuning stress responses in different hostile conditions. Do all of these molecules bind to RNA polymerase? Do they compete with each other or complement each other's functions is still not clear. Earlier, others and we have synthesized artificial analogs of (p)ppGpp that inhibited (p)ppGpp synthesis and long-term survival in M. smegmatis and in B. subtilis suggesting that analogs could compete with each other. Understanding the interplay of these molecules will allow deciphering novel pathways that can be potentially subjected to the therapeutic intervention. In this article, we have reviewed newly characterized second messengers and discussed their mode of action. We have also documented the progress made to-date in understanding the molecular basis of regulation of transcription by second messenger ppGpp, pppGpp, and pGpp.

Growth Mechanism of Micro/Nano Metal Dendrites and Cumulative Strategies for Countering Its Impacts in Metal Ion Batteries: A Review.

Metal-ion batteries are capable of delivering high energy density with a longer lifespan. However, they are subject to several issues limiting their utilization. One critical impediment is the budding and extension of solid protuberances on the anodic surface, which hinders the cell functionalities. These protuberances expand continuously during the cyclic processes, extending through the separator sheath and leading to electrical shorting. The progression of a protrusion relies on a number of in situ and ex situ factors that can be evaluated theoretically through modeling or via laboratory experimentation. However, it is essential to identify the dynamics and mechanism of protrusion outgrowth. This review article explores recent advances in alleviating metal dendrites in battery systems, specifically alkali metals. In detail, we address the challenges associated with battery breakdown, including the underlying mechanism of dendrite generation and swelling. We discuss the feasible solutions to mitigate the dendrites, as well as their pros and cons, highlighting future research directions. It is of great importance to analyze dendrite suppression within a pragmatic framework with synergy in order to discover a unique solution to ensure the viability of present (Li) and future-generation batteries (Na and K) for commercial use.

Cause and Mitigation of Lithium-Ion Battery Failure-A Review.

Lithium-ion batteries (LiBs) are seen as a viable option to meet the rising demand for energy storage. To meet this requirement, substantial research is being accomplished in battery materials as well as operational safety. LiBs are delicate and may fail if not handled properly. The failure modes and mechanisms for any system can be derived using different methodologies like failure mode effects analysis (FMEA) and failure mode methods effects analysis (FMMEA). FMMEA is used in this paper as it helps to identify the reliability of a system at the component level focusing on the physics causing the observed failures and should thus be superior to the more data-driven FMEA approach. Mitigation strategies in LiBs to overcome the failure modes can be categorized as intrinsic safety, additional protection devices, and fire inhibition and ventilation. Intrinsic safety involves modifications of materials in anode, cathode, and electrolyte. Additives added to the electrolyte enhance the properties assisting in the improvement of solid-electrolyte interphase and stability. Protection devices include vents, circuit breakers, fuses, current interrupt devices, and positive temperature coefficient devices. Battery thermal management is also a protection method to maintain the temperature below the threshold level, it includes air, liquid, and phase change material-based cooling. Fire identification at the preliminary stage and introducing fire suppressive additives is very critical. This review paper provides a brief overview of advancements in battery chemistries, relevant modes, methods, and mechanisms of potential failures, and finally the required mitigation strategies to overcome these failures.

Simultaneous CK2/TNIK/DYRK1 inhibition by 108600 suppresses triple negative breast cancer stem cells and chemotherapy-resistant disease.

Triple negative breast cancer (TNBC) remains challenging because of heterogeneous responses to chemotherapy. Incomplete response is associated with a greater risk of metastatic progression. Therefore, treatments that target chemotherapy-resistant TNBC and enhance chemosensitivity would improve outcomes for these high-risk patients. Breast cancer stem cell-like cells (BCSCs) have been proposed to represent a chemotherapy-resistant subpopulation responsible for tumor initiation, progression and metastases. Targeting this population could lead to improved TNBC disease control. Here, we describe a novel multi-kinase inhibitor, 108600, that targets the TNBC BCSC population. 108600 treatment suppresses growth, colony and mammosphere forming capacity of BCSCs and induces G2M arrest and apoptosis of TNBC cells. In vivo, 108600 treatment of mice bearing triple negative tumors results in the induction of apoptosis and overcomes chemotherapy resistance. Finally, treatment with 108600 and chemotherapy suppresses growth of pre-established TNBC metastases, providing additional support for the clinical translation of this agent to clinical trials.

In-vitro evaluation of antioxidant and anticholinesterase activities of novel pyridine, quinoxaline and s-triazine derivatives.

Cholinesterase enzymes such as acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) cause hydrolysis of acetylcholine (ACh), a neurotransmitter responsible for the cognitive functions of the brain such as acquiring knowledge and comprehension. Therefore, inhibition of these enzymes is an effective process to curb the progressive and fatal neurological Alzheimer's disease (AD). Herein, we explored the potential inhibitory activities of various pyridine, quinoxaline, and triazine derivatives (3a-k, 6a-j and 11a-h) against AChE and BuChE enzymes by following the modified Ellman's method. Further, anti-oxidant property of these libraries was monitored using DPPH (2,2'-diphenyl-1-picryl-hydrazylhydrate) radical scavenging analysis. From the studies, we identified that compounds 6e, 6f, 11b and 11f behaved as selective AChE inhibitors with IC50 values ranging from 7.23 to 10.35 µM. Further studies revealed good anti-oxidant activity by these compounds with IC50 values in the range of 14.80-27.22 µM. The kinetic studies of the active analogues demonstrated mixed-type of inhibition due to their interaction with both the catalytic active sites (CAS) and peripheral anionic sites (PAS) of the AChE. Additionally, molecular simulation in association with fluorescence and circular dichroism (CD) spectroscopic analyses explained strong affinities of inhibitors to bind with AChE enzyme at the physiological pH of 7.2. Binding constant values of 5.4 × 104, 4.3 × 104, 3.2 × 104 and 4.9 × 104 M-1 corresponding to free energy changes -5.593, -6.799, -6.605 and -8.104 KcalM-1 were obtained at 25 °C from fluorescence emission spectroscopic studies of 6e, 6f, 11b and 11f, respectively. Besides, CD spectroscopy deliberately explained the secondary structure of AChE partly unfolded upon binding with these dynamic molecules. Excellent in vitro profiles of distinct quinoxaline and triazine compounds highlighted them as the potential leads compared to pyridine derivatives, suggesting a path towards developing preventive or therapeutic targets to treat the Alzheimer's disease.

Custom 3D Printed Jigs in Salvage Reverse Shoulder Arthroplasty for Failed Four-Part Proximal Humerus Fracture Fixation: A Case Report.

INTRODUCTION: Complications of open reduction and internal fixation (ORIF) in four-part proximal humerus fractures (PHFs) include non-union, malunion, avascular necrosis of humeral head, and glenoid defect due to implant failure. Reverse total shoulder arthroplasty is a salvage procedure for cases of failed fixation. In cases with significant abnormal glenoid anatomy, custom-made patient-specific 3D printed jigs play a major role in pre-operative planning and accurate positioning of the glenoid component, thereby improving the final outcome. We report a case of salvage reverse shoulder arthroplasty done using the patient-specific custom-made 3D printed jig. CASE REPORT: A 58-year-old female sustained bilateral PHF due to electrocution and was treated with bilateral ORIF in single stage in February 2018.At 4 months from the time of surgery, the fracture on the left side had united, but there was non-union on the right side with screw penetration eroding the glenoid. Reverse shoulder arthroplasty was planned as a salvage procedure. Intraoperative, the glenoid was found to be small (2.7cm × 1.72cm) and there was a posterior glenoid defect due to screw penetration. During drilling for central peg, an iatrogenic glenoid fracture occurred. The procedure was deferred. After 4 months of conservative treatment, the glenoid fracture had united and then a definitive procedure with the reverse shoulder prosthesis was planned. 3D glenoid bone model was made based on the computed tomography scan and custom-made jigs are designed and 3D printed, which are specific for the patient. Reverse shoulder arthroplasty was done, and surgery went uneventful. The patient achieved active forward elevation of 110°, lateral elevation of 90°, and an external rotation of 10° at 1-year follow-up. CONCLUSION: Reverse shoulder arthroplasty can be considered as a salvage procedure for failed fixation of PHF with predictable outcomes. Custom-made patient-specific 3D printed jigs in reverse shoulder arthroplasty are useful in assessing the position and direction of central peg in case of small glenoid and glenoid bone defects. 3D bone models are useful in implant selection also.

A Contaminant Impurity, Not Rigosertib, Is a Tubulin Binding Agent.

Rigosertib is a styryl benzyl sulfone that inhibits growth of tumor cells and acts as a RAS mimetic by binding to Ras binding domains of RAS effectors. A recent study attributed rigosertib's mechanism of action to microtubule binding. In that study, rigosertib was obtained from a commercial vendor. We compared the purity of clinical-grade and commercially sourced rigosertib and found that commercially sourced rigosertib contains approximately 5% ON01500, a potent inhibitor of tubulin polymerization. Clinical-grade rigosertib, which is free of this impurity, does not exhibit tubulin-binding activity. Cell lines expressing mutant ß-tubulin have also been reported to be resistant to rigosertib. However, our study showed that these cells failed to proliferate in the presence of rigosertib at concentrations that are lethal to wild-type cells. Rigosertib induced a senescence-like phenotype in the small percentage of surviving cells, which could be incorrectly scored as resistant using short-term cultures.

2-Phenoxyethanol: A novel reagent for improved sensitivity of carbohydrate quantification.

Anthrone is a routinely used reagent for estimating carbohydrates (Polysaccharides) in research, development and pharmaceutical applications. In presence of sulphuric acid, the polysaccharide gets hydrolyzed to monosaccharides in the form of hydroxymethyl furfural or furfural. The furfural then reacts with anthrone to form a green color complex with a maximum absorbance at 625 nm. Though anthrone reacts well with polysaccharides containing hexoses (such as glucose and galactose) and rhamnose, it is less reactive with uronic acids (such as glucuronic acid and galacturonic acid) and hexosamines (such as fucosamine, glucosamine, galactosamine, mannosamine, pneumosamine). Here, we report a novel reagent, 2-Phenoxyethanol, which reacts with furfural or hydroxymethyl furfural resulting in higher absorptivity. This method is rapid, sensitive, simple and direct, and can be used for quantitative determination of any type of carbohydrate that contains neutral sugars and uronic acids. For these saccharides, the sensitivity of the assay using 2-Phenoxyethanol (2-PE) is twice over anthrone method. Uronic acids show improved sensitivity using 2-PE over Phenol and it is more than twice with glucuronic acid. 2-PE reagent method has greater application for quantification of carbohydrates when present in low concentration in vaccines/biologicals.

Rigosertib ameliorates the effects of oncogenic KRAS signaling in a murine model of myeloproliferative neoplasia.

Aberrant signaling triggered by oncogenic or hyperactive RAS proteins contributes to the malignant phenotypes in a significant percentage of myeloid malignancies. Of these, juvenile myelomonocytic leukemia (JMML), an aggressive childhood cancer, is largely driven by mutations in RAS genes and those that encode regulators of these proteins. The Mx1-cre kras+/G12D mouse model mirrors several key features of this disease and has been used extensively to determine the utility and mechanism of small molecule therapeutics in the context of RAS-driven myeloproliferative disorders. Treatment of disease-bearing KRASG12D mice with rigosertib (RGS), a small molecule RAS mimetic that is in phase II and III clinical trials for MDS and AML, decreased the severity of leukocytosis and splenomegaly and extended their survival. RGS also increased the frequency of HSCs and rebalanced the ratios of myeloid progenitors. Further analysis of KRASG12D HSPCs in vitro revealed that RGS suppressed hyperproliferation in response to GM-CSF and inhibited the phosphorylation of key RAS effectors. Together, these data suggest that RGS might be of clinical benefit in RAS-driven myeloid disorders.

NiO decorated CeO2 nanostructures as room temperature isopropanol gas sensors.

Heterostructures developed using CeO2 show promising peculiarities in the field of metal oxide gas sensors due to the great variations in the resistance during the adsorption and desorption processes. NiO decorated CeO2 nanostructures (NiO/CeO2) were synthesized via a facile two-step process. High resolution transmission electron microscopy (HRTEM) results revealed the perfect decoration of NiO on the CeO2 surface. The porous nature of the NiO/CeO2 sensor surface was confirmed from scanning electron microscopy (SEM) analysis. Gas sensing studies of pristine CeO2 and NiO/CeO2 sensors were performed under room conditions and enhanced gas sensing properties for the NiO/CeO2 sensor towards isopropanol were observed. Decoration of NiO on the CeO2 surface develops a built-in potential at the interface of NiO and CeO2 which played a vital role in the superior sensing performance of the NiO/CeO2 sensor. Sharp response and recovery times (15 s/19 s) were observed for the NiO/CeO2 sensor towards 100 ppm isopropanol at room temperature. Long-term stability of the NiO/CeO2 sensor was also studied and discussed. From all the results it is concluded that the decoration of NiO on the CeO2 surface could significantly enhance the sensing performance and it has great advantages in designing best performing isopropanol gas sensors.

Effect of vanadium pentoxide concentration in ZnO/V2O5 nanostructured composite thin films for toluene detection.

ZnO/V2O5 nanocomposite thin films were synthesised by the spray pyrolysis technique with optimised deposition parameters by varying the concentration of vanadium pentoxide. The X-ray diffraction results showed that the ZnO/V2O5 nanocomposite thin films have a Wurtzite-type hexagonal ZnO structure. We attained crystal phases at all concentrations. These results indicated that the two crystal phases of pure zinc oxide and vanadium pentoxide exist together within the composite thin film matrix. The morphology was investigated with field emission scanning electron microscopy and transmission electron microscopy (TEM). The microstructures of the deposited thin films were confirmed by Raman spectroscopy. The optical characterizations of the prepared samples were investigated by using a UV-vis spectrophotometer. X-ray photoelectron spectroscopy (XPS) was carried out to confirm the oxidation states of the elements existing on the surface of the composite thin films. The gas-sensing properties of the composite thin films towards toluene gas were studied at the temperature of 27 °C. The sensing mechanism for toluene gas was reported; the response and recovery times were determined from the transient response curve and were found to be 24 s and 28 s, respectively, for the optimised composite film.