BACE1 inhibitors:A promising therapeutic approach for the management of Alzheimer’s disease

Alzheimer’s disease is a neurological disorder marked by the accumulation of amyloid beta(Aβ)aggregates,resulting from mutations in the amyloid precursor protein.The enzymeβ-secretase,also known asβ-site amyloid precursor protein cleaving enzyme 1(BACE1),plays a crucial role in generating Aβpeptides.With no targeted therapy available for Alzheimer’s disease,inhibiting BACE1 aspartic protease has emerged as a primary treatment target.Since 1999,compounds demonstrating potential binding to the BACE1 receptor have advanced to human trials.Structural optimization of synthetically derived compounds,coupled with computational approaches,has offered valuable insights for developing highly selective leads with drug-like properties.This review highlights pivotal studies on the design and development of BACE1 inhibitors as anti-Alzheimer’s disease agents.It summarizes computational methods employed in facilitating drug discovery for potential BACE1 inhibitors and provides an update on their clinical status,indicating future directions for novel BACE1 inhibitors.The promising clinical results of Elenbecestat(E-2609)catalyze the development of effective,selective BACE1 inhibitors in the future.

Tailored nutritional interventions: A precision approach to managing gestational diabetes mellitus

Gestational diabetes mellitus(GDM)is a risk to maternal-fetal health due to uncertain diagnostic criteria and treatment options.Luo's study demonstrated the efficacy of customized nutritional therapies in controlling GDM.Tailored strategies led to significant body weight loss,improved glucolipid metabolism,and fewer prenatal and newborn problems.This holistic approach,which emphasizes the notion of’chrononutrition’,takes into account optimal meal timing that is in sync with circadian rhythms,as well as enhanced sleep hygiene.Implementing tailored dietary therapy,managing meal timing,and ensuring appropriate sleep may improve results for women with GDM,opening up a possible avenue for multi-center trials.

Emerging perspectives on RNA virus-mediated infections:from pathogenesis to therapeutic interventions

RNA viruses continue to pose significant threats to global public health,necessitating a profound understanding of their pathogenic mechanisms and the development of effective therapeutic interventions.This manuscript provides a comprehensive overview of emerging perspectives on RNA virus-mediated infections,spanning from the intricate intricacies of viral pathogenesis to the forefront of innovative therapeutic strategies.A critical exploration of antiviral drugs sets the stage,highlighting the diverse classes of compounds that target various stages of the viral life cycle,underscoring the ongoing efforts to combat viral infections.Central to this discussion is the exploration of RNA-based therapeutics,with a spotlight on messenger RNA(mRNA)-based approaches that have revolutionized the landscape of antiviral interventions.Furthermore,the manuscript delves into the intricate world of delivery systems,exploring innovative technologies designed to enhance the efficiency and safety of mRNA vaccines.By analyzing the challenges and advancements in delivery mechanisms,this review offers a roadmap for future research and development in this critical area.Beyond conventional infectious diseases,the document explores the expanding applications of mRNA vaccines,including their promising roles in cancer immunotherapy and personalized medicine approaches.This manuscript serves as a valuable resource for researchers,clinicians,and policymakers alike,offering a nuanced perspective on RNA virus pathogenesis and the cutting-edge therapeutic interventions.By synthesizing the latest advancements and challenges,this review contributes significantly to the ongoing discourse in the field,driving the development of novel strategies to combat RNA virus-mediated infections effectively.

Current understanding of the impact of COVID-19 on gastrointestinal disease:Challenges and openings

The novel coronavirus disease-2019(COVID-19)is caused by a positive-sense single-stranded RNA virus which belongs to the Coronaviridae family.In March 2019 the World Health Organization declared that COVID-19 was a pandemic.COVID-19 patients typically have a fever,dry cough,dyspnea,fatigue,and anosmia.Some patients also report gastrointestinal(GI)symptoms,including diarrhea,nausea,vomiting,and abdominal pain,as well as liver enzyme abnormalities.Surprisingly,many studies have found severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)viral RNA in rectal swabs and stool specimens of asymptomatic COVID-19 patients.In addition,viral receptor angiotensin-converting enzyme 2 and transmembrane protease serine-type 2,were also found to be highly expressed in gastrointestinal epithelial cells of the intestinal mucosa.Furthermore,SARS-CoV-2 can dynamically infect and replicate in both GI and liver cells.Taken together these results indicate that the GI tract is a potential target of SARS-CoV-2.Therefore,the present review summarizes the vital information available to date on COVID-19 and its impact on GI aspects.

Gender differences in the relationship between alcohol consumption and gastric cancer risk are uncertain and not well-delineated

The role of alcoholic and other beverage consumption in the etiology of gastric cancer is unknown.Several studies have summarized and established a significant association between heavy alcohol consumption and gastric cancer risk,but evidence on alcohol-related cancer risk is conflicting.

Effect of Buchanania lanzan Spreng.bark extract on cyclophosphamide induced genotoxicity and oxidative stress in mice

Objective:To elucidate the effect of ethanolic extract of Buchanania lanzan Spreng.(B.lanan) bark against cyclophosphamide induced genotoxicity and oxidative stress in mice.Methods: The prevalence of micronuclei in bone marrow,the extent of lipid peroxidation,reduced glutathione and the status of the antioxidant enzymes,superoxide dismutase and catalase in liver of mice were used as intermediate biomarkers for chemoprolection.Lipid peroxidation and associated compromised antioxidant defenses in cyclophosphamide treated mice were observed in the liver.Results:Pre-treatment with B.lanzan 250,500 and 1 000 mg/ kg,p.o.,daily for 7 days significantly reduced the chromosomal damage and lipid peroxidation with concomitant changes in antioxidants and detoxification systems.Conclusions:These results point out the presence of chemopreventive phytoconstituents in the crude extract offering protection against cyclophosphamide induced genotoxicity and oxidative stress in mice.

Effect of Substrate on CuS/PVA Nanocomposite Thin Films Deposited on Glass and Silicon Substrate

Transition metal chalcogenide nanocomposite thin films deposited by chemical routes are currently attracting wide attention being inexpensive, simple and have utility for large area applications. The role of substrate becomes very important in film deposition as well as in controlling their properties due to strain induced properties modification and lattice mismatch. CuS/PVA nanocomposite thin films were successfully deposited on glass and silicon substrates using sol-gel technique. Thin films were characterized by X-ray diffraction (XRD), atomic force microscopy (AFM), UV-visible (UV-VIS) and Raman spectroscopy. Structural data confirm the amorphous nature of as grown films which transform into crystalline films after annealing at 200°C. The degree of crystallinity seems to be better in film deposited on silicon substrate in comparison to those grown over glass substrate with average crystallite sizes ≅?4.00 nm and 7.00 nm for films deposited on glass and silicon substrate respectively. Atomic force microscopy (AFM) images in dynamic as well as contact modes display nanoparticles embedded in polymer network. The films surface roughness parameters quantitatively estimated from AFM micrographs are compared. Raman spectra show a sharp peak at ≅474 cm¯1 assigned to S-S stretching mode of S2 ions in films grown on both substrates and associated as due to presence of hexagonal (covellite) crystal structure. Optical band gaps of thin film on glass and silicon substrate are 2.10 eV and 2.02 eV respectively. The effect of substrate on the measured properties is discussed.

Biochemical composition and photosynthetic activity of Pongamia pinnata（L.） Pierre in response to acute 60Co γ-irradiation

To elucidate the potential and sensitivity of cirradiation in Pongamia pinnata,the present study has been done by irradiating the air-dried seeds to differentγ-irradiation doses(100 Gy,200 Gy,400 Gy and 600 Gy),using 60Co source.Significant increase(p≤0.05)in the germination,growth,and vigor was recorded under the100 Gy treatment than the control set.The chlorophylla and total chlorophyll content(mgg-1 FW)in the leaves of P.pinnata showed a significant decrease under the higher irradiation treatments(200 Gy,400 Gy and 600 Gy).In contrast,chlorophyllb showed a radio-resistance up to 200 Gy dose,and above which its concentration declined significantly(p≤0.05).Photosynthetic rate,stomatal conductance,intercellular CO2 concentration,and transpiration rate were stimulated by 100 Gy irradiation treatment and the higher doses inhibited these parameters.Antioxidant activity in the leaves of P.pinnata tended to increase after irradiation in a dose-dependent manner.All the plants under different treatments ofγ-irradiation showed stimulation in production of proline,flavonoid,and phenolic content in comparision to the control.The findings of the present study showed thatγ-irradiation treatment stimulates the secondary metabolite production(proline,flavonoid and phenolic)and favours faster growth of P.pinnata.

SARS-CoV-2 infection in people with pre-existing liver disease:Further research is warranted

Patients with severe liver disease who have been infected with severe acute respiratory syndrome coronavirus-2(coronavirus disease 2019)frequently develop acute respiratory distress syndrome and multiple organ failure,with a high mortality rate,as a result of the hyper-proinflammatory state known as the cytokine storm.Clinicians must recognize cytokine storms earlier to avoid intensive care admission and multi-organ damage,a critical life-threatening condition with prognostic and therapeutic implications.

Effect of types of reinforcement on plastic hinge rotation parameters of RC beams under pushover and cyclic loading

Experimental evaluation of reinforced concrete beam specimens with different characteristics of reinforcement subjected to pushover and cyclic loading is presented.Plastic hinge rotation parameters are determined based on the idealization of pushover and hysteresis curves of reinforced concrete beam specimens constructed in two percentage of reinforcement(0.471%and 0.71%) with different ductile characteristics.The experimental test results provide a clear demarcation of the effect of types of loading and the types of reinforcement on the nonlinear performance characteristics of beam specimens.These results are helpful to update the nonlinear modeling parameters of beam components for the specific type of reinforcement used in the construction of a structure.The updated non-linear modeling parameters of beam components in lumped plasticity model are compared with the values of ASCE/SEI 41-06(2007) used for the performance based design of structures.

Viral hepatitis: A global burden needs future directions for the management

Viral hepatitis is an acute or chronic liver disease due to the infection from Hepatitis A,B,C,D and E viruses.It can cause severe liver damage such as cirrhosis,liver failure and liver cancer.To avoid such fatal complications,hepatitis patients must be diagnosed,pathologized and treated as soon as possible.Furthermore,these hepatitis viruses infect through different routes,resulting in distinct disease pathologies,severity and even the need for specific treatment strategies to combat the infection.

Fabrication, characterization, numerical simulation and compact modeling of P3HT based organic thin film transistors

This paper presents the fabrication,characterization and numerical simulation of poly-3-hexylthiophene(P3HT)-based bottom-gate bottom-contact(BGBC)organic thin film transistors(OTFTs).The simulation is based on a drift diffusion charge transport model and density of defect states(DOS)for the traps in the band gap of the P3HT based channel.It combines two mobility models,a hopping mobility model and the Poole-Frenkel mobility model.It also describes the defect density of states(DOS)for both tail and deep states.The model takes into account all the operating regions of the OTFT and includes sub-threshold and above threshold characteristics of OTFTs.The model has been verified by comparing the numerically simulated results with the experimental results.This model is also used to simulate different structure in four configurations of OTFT e.g.bottom-gate bottom-contact(BGBC),bottom-gate top-contact(BGTC),top-gate bottom-contact(TGBC)and top-gate top-contact(TGTC)configurations of the OTFTs.We also present the compact modeling and model parameter extraction of the P3HT-based OTFTs.The extracted compact model has been further applied in a p-channel OTFT-based inverter and three stage ring oscillator circuit simulation.

Exposure to Hypobaric Hypoxia and Reoxygenation Induces Transient Anxiety-Like Behavior in Rat

Chronic exposure to hypobaric hypoxia (HH) causes memory impairment and prolonged state of mental confusion. However, effect of high altitude exposure on mood state and its underlying mechanisms have been poorly studied.? Present study was undertaken to investigate the mood state alteration following chronic exposure to HH. Male Sprague Dawley rats were divided into five groups and exposed to hypoxia for 3, 7, 14 and 21 days in an animal decompression chamber at an altitude of 25,000ft. Anxiety-and depression-like behaviors were assessed by using various mazes along with changes in serotonin and glutamate level. Our study revealed a decrease in exploratory, grooming and rearing behavior in open field test following initial exposure to HH for 7 days without affecting the locomotory behavior. Initial exposure to HH-decreased time spent in open arm of elevated plus maze indicating induction of anxiety-like behavior which normalized on prolonged hypoxic exposure for 21 days. Hypoxic exposure for 7 days induced anhedonia and increased despair behavior in rat while there was steady improvement in these behaviors when exposed for 21 days. Decrease in serotonin level was noted in hippocampus along with elevated corticosterone and glutamate level which gradually decreased on prolonged exposure to HH. These findings suggest that initial exposure to HH increases transient anxiety-like behavior in rats followed by gradual improvement in mood state on prolonged exposure. Further, the study also indicates the involvement of serotonergic system in mood state alteration at high altitude following chronic exposure and reoxygenation.

Detection of Behavioral Patterns Employing a Hybrid Approach of Computational Techniques

As far as the present state is concerned in detecting the behavioral pattern of humans(subject)using morphological image processing,a considerable portion of the study has been conducted utilizing frontal vision data of human faces.The present research work had used a side vision of human-face data to develop a theoretical framework via a hybrid analytical model approach.In this example,hybridization includes an artificial neural network(ANN)with a genetic algorithm(GA).We researched the geometrical properties extracted from side-vision human-face data.An additional study was conducted to determine the ideal number of geometrical characteristics to pick while clustering.The close vicinity ofminimum distance measurements is done for these clusters,mapped for proper classification and decision process of behavioral pattern.To identify the data acquired,support vector machines and artificial neural networks are utilized.A method known as an adaptiveunidirectional associative memory(AUTAM)was used to map one side of a human face to the other side of the same subject.The behavioral pattern has been detected based on two-class problem classification,and the decision process has been done using a genetic algorithm with best-fit measurements.The developed algorithm in the present work has been tested by considering a dataset of 100 subjects and tested using standard databases like FERET,Multi-PIE,Yale Face database,RTR,CASIA,etc.The complexity measures have also been calculated under worst-case and best-case situations.

Structural and Raman Spectroscopic Study of Antimony Doped Bi<SUB>0.5</SUB>Na<SUB>0.5</SUB>TiO<SUB>3</SUB>Electroceramic

Pure and Antimony (Sb, x = 0.01%, 0.02% and 0.03%) doped Bi0.5Na0.5TiO3 electro ceramics were successfully synthesized by a conventional solid state reaction route. X-ray diffraction analysis showed that a distinct 002/200 peak splitting appears when doping percentage changes from 0.02 to 0.03, referring to a hexagonal symmetry. The data show the Lorentzian deconvolution of the 002 and 200 peaks of the tetragonal phase and the 202 peak of the rhombohedral phase. There is no significant change in the Raman spectra for the prepared compositions while some additional peaks around 151, 281, 585 and 853 cm-1 compared to the peaks observed in BNT. It may be possible that a morphotrophic phase boundary (MPB) exists around x = 0.03. Analysis of peak positions, widths and intensities of Raman spectroscopy study also confirmed the existence of structural change around x = 0.03 composition.

Synthesis, Characterization, Optical and Transport Properties of BaSnO<SUB>3</SUB>Synthesized by Wet Chemical Route

Alkaline earth stannates have renewed attention as potential materials for gas sensing, transparent conducting oxides and ceramic capacitor applications. A noble wet chemical route is chosen to synthesize BaSnO3 powders having micron size grains. Problems related to uneven grains and poor densification in conventional solid state route have been overcome in the present method. X-ray diffraction data confirms the single phase formation without any secondary phase having cubic perovskite structure (S.G. Pm-3m). The estimated lattice parameter is ≈4.11933&Aring;and percentage density is ≈90%. The microstructure probed by scanning electron micrograph reveals almost homogeneously distributed particles having random shape with some porosity. Phonon modes in FT-IR and Raman spectra confirm the local symmetry distortion. The DC conductivity at 200&deg;C approaches almost 2 × 10-2 (Ω-cm)-1, which is almost of the same order as that observed in perovskite based electronic conductors. DC and a.c. electrical conductivity of the material follow Mott’s variable range hopping at low temperature and Arrhenius type thermally activated process at elevated temperatures. Evidence of small polar on formation is also verified. Optical band gap estimated from absorption data is ≈2.94 very close to the reported value. Composition prepared through the noble wet chemical route has high electrical conduction and suitable for gas sensing applications.

Conclusive Growth of CdTe Nanorods by Solvothermal Decomposition Using Single Source Precursors

CdTe nanorods are synthesized by solvothermal decomposition, using single source molecular precursors (SSMP) cadmium (II), complex of bis-(aminopropyl telluride) (SSMP-I) and cadmium (II) bis-(isopropyl telluro) propane (SSMP-II) and quinoline as solvent at relatively low temperature (210°C). As synthesized nanomaterials are structurally characterized by XRD and SEM, SEM micrographs revealed formation of rod shapes structures whose dimensions change with the source precursor molecule. The average crystallite size estimated from XRD data is 29.78 and 28.94 nm respectively using Precursors I and II. The average size of nanorods is 1.237 μm and 0.15μm respectively, estimated from SEM micrographs. These are much larger than the average crystallite size estimated from XRD data. This is attributed to the agglomeration of nanocrystallites as quinoline is not a good capping agent.

Management of SARS-CoV-2 infection is a major challenge in patients with lymphoid malignancies: Warrants a clear therapeutic strategy

Patients with lymphoid malignancies are at a higher risk of coronavirus disease 2019(COVID-19)infection due to their immunocompromised state and results in higher mortality rates in these patients.Anti-CD 20 therapy is one of the leading causes of immunosuppression that worsens in COVID-19 cases.COVID-19 vaccines,on the other hand,appear to be less beneficial to these patients.Appropriate treatment and recommendations are required for these COVID-19 patients with lymphoid malignancies.

Bacterial and fungal co-infection is a major barrier in COVID-19 patients:A specific management and therapeutic strategy is required

Microbial co-infections are another primary concern in patients with coronavirus disease 2019(COVID-19),yet it is an untouched area among researchers.Preliminary data and systematic reviews only show the type of pathogens responsible for that,but its pathophysiology is still unknown.Studies show that these microbial co-infections are hospital-acquired/nosocomial infections,and patients admitted to intensive care units with invasive mechanical ventilation are highly susceptible to it.Patients with COVID-19 had elevated inflammatory cytokines and a weakened cell-mediated immune response,with lower CD4+T and CD8+T cell counts,indicating vulnerability to various co-infections.Despite this,there are only a few studies that recommend the management of coinfections.

Oncofertility:Treatment options from bench to bedside

In recent years,there has been continuous improvement in the treatment and diagnosis of cancer,which has led to a significant improvement in the survival rate of cancer patients.Treatments that include chemotherapy,radiotherapy,surgery,or combined therapy have several side effects that may lead to premature ovarian insufficiency in females or substantial male germ cell loss.Reproductive biologists recommend that all patients who are diagnosed with a malignant tumor must undergo a consultation for fertility protection and preservation.In this review,we discuss the background knowledge,methods,and options for fertility preservation and how these new strategies help oncologists,surgeons,pediatricians,and hematologists,conserve fertility and be aware of the concepts,methods,and importance of fertility guards.This review may aid in the advancement of novel personalized methods for fertility preservation according to patients’conditions.