Comparative Study of Treatment Outcome with Tenofovir Alafenamide and Entecavir in Patients with HBV Related Acute on Chronic Liver Failure.

Major causes of acute insult in Hepatitis B virus related acute on chronic liver failure in the Asian region are reactivation of Hepatitis B virus and super infection with hepatitis A and E virus (ACLF). Anti viral therapy should be started as soon as possible in the ACLF patients at presentation while waiting for confirmation by HBV DNA level. This randomized controlled trial was carried out at the Department of Hepatology, BSMMU, Bangladesh from September 2019 to august 2020 with Hepatitis B virus related ACLF patient. This trial was conducted among twenty seven HBV acute on chronic liver failure patient to compare Child Turcotte pugh (CTP) score, Model for end stage liver disease (MELD) score, Asia Pacific Association for study of Liver (APASL) ACLF Research consortium (AARC) score, survival of the patients and HBV DNA level at 3 months with antiviral therapy between tenofovir alafenamide (25mg) and entecavir (0.5mg) group. CTP score, MELD score and AARC score were significantly (p<0.05) decline from baseline to all subsequent follow-up at 1st (at 7 days), 2nd (at 14 days), 3rd (at 30 days) and 4th (at 90 days) in each group but non significant (p>0.05) difference occurred between two group. All twenty seven patients had detectable HBV DNA level at pre-treatment and all survived patients became undectable at 4th, 90 days follow-up. Total 10 patients (37.07%) were survived at 90 days follow-up, out of them seven patients (70.0%) were in tenofovir alafenamide group and three patients (30.0%) were in entecavir group which was statistically significant (p<0.05) in between two group. Hepatic encephalopathy and hepatorenal syndrome were most common causes of death in both groups. Both drugs tenofovir alafenamide and entecavir significantly improves liver functions but the former one is superior regarding survival.

Single episode of moderate to severe traumatic brain injury leads to chronic neurological deficits and Alzheimer's-like pathological dementia.

Traumatic brain injury (TBI) is one of the foremost causes of disability and mortality globally. While the scientific and medical emphasis is to save lives and avoid disability during acute period of injury, a severe health problem can manifest years after injury. For instance, TBI increases the risk of cognitive impairment in the elderly. Remote TBI history was reported to be a cause of the accelerated clinical trajectory of Alzheimer's disease-related dementia (ADRD) resulting in earlier onset of cognitive impairment and increased AD-associated pathological markers like greater amyloid deposition and cortical thinning. It is not well understood whether a single TBI event may increase the risk of dementia. Moreover, the cellular signaling pathways remain elusive for the chronic effects of TBI on cognition. We have hypothesized that a single TBI induces sustained neuroinflammation and disrupts cellular communication in a way that results later in ADRD pathology. To test this, we induced TBI in young adult CD1 mice and assessed the behavioral outcomes after 11 months followed by pathological, histological, transcriptomic, and MRI assessment. On MRI scans, these mice showed significant loss of tissue, reduced CBF, and higher white matter injury compared to sham mice. We found these brains showed progressive atrophy, markers of ADRD, sustained astrogliosis, loss of neuronal plasticity, and growth factors even after 1-year post-TBI. Because of progressive neurodegeneration, these mice had motor deficits, showed cognitive impairments, and wandered randomly in open field. We, therefore, conclude that progressive pathology after adulthood TBI leads to neurodegenerative conditions such as ADRD and impairs neuronal functions.

CRISPR-Cas9 Long-Read Sequencing for Mapping Transgenes in the Mouse Genome.

Microinjected transgenes, both large and small, are known to insert randomly into the mouse genome. Traditional methods of mapping a transgene are challenging, thus complicating breeding strategies and accurate interpretation of phenotypes, particularly when a transgene disrupts critical coding or noncoding sequences. As the vast majority of transgenic mouse lines remain unmapped, we developed CRISPR-Cas9 Long-Read Sequencing (CRISPR-LRS) to ascertain transgene integration loci. This novel approach mapped a wide size range of transgenes and uncovered more complex transgene-induced host genome re-arrangements than previously appreciated. CRISPR-LRS offers a facile, informative approach to establish robust breeding practices and will enable researchers to study a gene without confounding genetic issues. Finally, CRISPR-LRS will find utility in rapidly and accurately interrogating gene/genome editing fidelity in experimental and clinical settings.

Electro-oxidation reconstitution of aluminium copper MOF-derived metal oxyhydroxides for a robust OER process.

It is common knowledge that the O2 evolution reaction (OER) is a crucial half-reaction in the electrolysis of water. However, it is currently difficult to create inexpensive OER electrode materials in a way that is efficient, simple, and environmentally friendly. In this research, metal oxy-hydroxides with numerous oxygen defects (M-OOHv) are created at surface of Cu foam (CF) using a unique, straightforward electro-oxidation reconstitution (ER) process. Different spectroscopic and microscopy methods are used to analyse the electrode characteristics of Al2Cu-MOF@M-OOHv-ER/CF; electrochemical measurements display a lower overpotential (η) of 366 mV @ 10 mA cm-2 and a Tafel slope of 95.2 mV dec-1 in 1.0 M KOH. X-Ray diffraction (XRD), scanning electron microscopy (SEM), and Raman studies confirm the phase transition of the metal-organic framework (MOF) to the M-OOH, which acts as the active site to boost the OER activity. Through spectroscopic and microscopic investigations, it is determined that the efficiency of bimetallic electrode materials and oxygen vacancies in the M-OOHv have an impact on the electron power density. The manufactured electrode material additionally showed good durability for 50 hours. As a result, the newly developed Al2Cu-MOF@M-OOHv-ER/CF nanomaterial has greater potential for both electrolysis of water and other energy storage equipment.

Experimental shielding properties for a novel glassy system.

In the current study, we fabricated a series of boro-tellurite glass samples with a composition 10SrO-10Al2O3-10MoO3-(70-x)B2O3-xTeO2, where (x = 0, 17.5, 35, 52.5, and 70 mol%) via an ordinary melt-quench method. The glass structure was explored by X-ray diffraction (XRD), physical and structural properties. XRD results affirm the existence of two broad peaks, proving the amorphous state of the current glasses. The acquired results exhibit a linear relationship between the density, Poisson's ratio, and the addition of TeO2 amounts. The addition of TeO2 to the glass system shows a rise in glass stability and a reduction in packing density. Additionally, the values of mass attenuation coefficient (MAC) were determined experimentally within five energies (0.184, 0.280, 0.661, 0.710, and 0.810 MeV) from two radiation sources (166Ho and 137Cs). The (MAC)exp results were compared with XCOM values, and the compared values showed excellent compatibility. From the experimental results, many radiation shielding features involving half-value layer (HVL), mean free path (MFP), tenth value layer (TVL), and radiation protection efficiency (RPE) were computed. From the obtained results, it can be concluded that the TeSB4 sample has the highest stability and absorption for radiation, indicating the ability to use it as a radiation shielding substance.

Non-enzymatic glucose sensor with electrodeposited silver/carbon nanotubes composite electrode.

Diabetes mellitus is a debilitating disease that affects each and every organ of human body. Hence it is important to continuously monitor the glucose level throughout the day and night. Glucose sensors are in great demand due to a rapid increase in diabetic community. A strategy has been implemented here to fabricate silver nanoparticles (AgNPs) with the support of functionalized carbon nanotubes (f-CNTs). Silver/carbon nanotubes (Ag/CNTs) nanocomposite electrode have been prepared by electrochemical process on Fluorine doped tin oxide (FTO) glass, by varying silver (Ag) concentrations for non-enzymatic glucose sensor. The variable Ag concentration in the morphology of Ag/CNTs nanocomposite has influenced the electrical conductivity, oxidation and reduction potential and electrochemical activity of glucose. Highest current density and good electrocatalytic activity for electrodes are obtained at 70 mM concentration of silver in Ag/CNTs composite. The present study indicates that the Ag/CNTs electrode is a possible substitute of the expensive glassy carbon electrode for enzyme-free glucose sensors.

Opto-electronic and thermoelectric properties of MgIn2X4 (X = S, Se) spinels via ab-initio calculations.

The structural behavior of MgIn2X4 (X = S, Se) has been elaborated by FP-LAPW + lo method as included in the Wien2k code. The stability of the phase has been confirmed by negative formation energy (-1.24 eV for MgIn2S4 and -0.78 eV for MgIn2Se4). The band gap dependent opto-electronic and thermoelectric properties are realized by modified Becke-Johnson exchange potential. The electronic band gap tuned from ultraviolet to visible (3.1 eV and 1.9 eV) by replacing the S with Se that motivated the studied spinels for photovoltaic and solar applications. Moreover, the attenuation of light, dispersion, transparency, reflection and energy loss when light scattered from material are discussed as function of energy. The thermal conductivity to electrical conductivity ratio, potential gradient and thermal efficiency in the range 0.78-0.80 are elaborated. The comparative study of opto-electronic and thermoelectric properties for energy harvesting increases the potential for optoelectronic than thermoelectric applications.

Interkinetic nuclear migration in the tracheal and esophageal epithelia of the mouse embryo: Possible implications for tracheo-esophageal anomalies.

Interkinetic nuclear migration (INM) is a cell polarity-based phenomenon in which progenitor cell nuclei migrate along the apico-basal axis of the pseudostratified epithelium in synchrony with the cell cycle. INM is suggested to be at least partially cytoskeleton-dependent and to regulate not only the proliferation/differentiation of stem/progenitor cells but also the localized/overall size and shape of organs/tissues. INM occurs in all three of the germ-layer derived epithelia, including the endoderm-derived gut. However, INM has not been documented in the esophagus and respiratory tube arising from the anterior foregut. Esophageal atresia with or without trachea-esophageal fistula (EA/TEF) is a relatively common developmental defect. Transcription factors and signaling molecules have been implicated in EA/TEF, but the etiology of EA/TEF-which has been suggested to involve cell polarity-related mechanisms-remains highly controversial. In the present study, we first examined whether INM exists in the trachea and esophagus of mouse embryos at embryonic day 11.5 (E11.5), just after separation of the two tubes from the anterior foregut. By labeling the DNA-synthesizing stem cell nuclei with 5-ethynyl-2'-deoxyuridine, a nucleotide analogue, and statistically analyzing chronological changes in the distribution pattern of the labeled nuclei by using multidimensional scaling, we showed the existence of INM in both the esophagus and trachea, with differences in the INM magnitude and cycle pattern. We further showed morphological changes from the INM-based pseudostratified single layer to the stratified multilayer in the esophageal epithelium in association with a temporal loss/perturbation of AB polarity, suggesting a possible relation with the pathogenesis of EA/TEF.

OPTIXcell improves the postthaw quality and fertility of buffalo bull sperm.

The present study was conducted to compare the liposome-containing, animal protein-free, commercially available OPTIXcell extender with the Tris-citric-egg yolk extender for postthaw quality and fertility of buffalo semen. Semen was collected from five adult Nili-Ravi buffalo (Bubalus bubalis) bulls of similar age group with an artificial vagina (at 42 °C) for 3 weeks (replicates). Semen ejaculates from each buffalo bull were divided into two aliquots and diluted (at 37 °C having 50 × 10(6) spermatozoa/mL) in the OPTIXcell or Tris-citric-egg yolk (control) extender. Diluted semen was cooled to 4 °C in 2 hours, equilibrated for 4 hours, and filled in 0.5-mL straws. The semen straws were kept over liquid nitrogen vapors (5 cm) for 10 minutes. The straws were then plunged and stored in liquid nitrogen (-196 °C). After 24 hours of storage, the semen straws were thawed at 37 °C for 30 seconds to assess postthaw quality. Percentages of sperm motility, plasma membrane integrity, viability, and acrosomal integrity were improved (P < 0.05) in the OPTIXcell extender compared to the Tris-citric-egg yolk extender. Values for DNA integrity (%) did not differ in the OPTIXcell and Tris-citric-egg yolk extenders. The overall conception rate in buffaloes was improved (P < 0.05) with semen cryopreserved in the OPTIXcell extender (59.5%) compared to semen cryopreserved in the Tris-citric-egg yolk extender (41.5%). It is concluded that the liposome-containing commercially available OPTIXcell extender is more efficient to conserve postthaw quality and resulted in higher fertility rate of buffalo in the field.

Indoleamine 2,3-dioxygenase expression and activity in patients with hepatitis C virus-induced liver cirrhosis.

Indoleamine 2,3-dioxygenase (IDO) is an immunoregulatory enzyme. It plays a key role in various malignancies, infection and autoimmune diseases. IDO induces immunosuppression through the depletion of tryptophan and its downstream metabolites. Hepatitis C virus (HCV) has infected more than 12 million individuals in Pakistan. The aim of the present study was to assess the expression and activity of IDO in HCV-infected patients. The functional enzymatic activity of IDO was measured by colorimetric assay. Serum samples from 100 HCV-infected patients were taken to examine IDO activity and samples from 100 healthy volunteers were used as controls. Liver sections from patients with HCV (n=35) and healthy controls (n=5) were used for immunohistochemical studies. Immunohistochemical analysis revealed that IDO was overexpressed in 28 of 35 (80%) cirrhotic liver samples, whereas 5 of 35 (14.2%) cases presented moderate and 2 of 35 (5.7%) cases presented mild expression of IDO. The enzymatic activity of IDO was significantly higher in the serum samples of HCV-infected patients as compared with those in the control. These data indicate that the expression of IDO correlated with the pathogenesis of disease. In summary, it is suggested that the high expression of IDO in the progressively cirrhotic livers of HCV-infected patients might contribute to the development of hepatocellular carcinoma. IDO may characterize a novel therapeutic target against HCV.

Evaluation of antifreeze protein III for cryopreservation of Nili-Ravi (Bubalus bubalis) buffalo bull sperm.

Lower fertility in buffaloes with frozen-thawed semen is attributed to sperm damage that is believed to be due to formation of ice crystals during freeze/thaw process. It was hypothesized that antifreeze proteins in the extender may improve the post thaw quality of buffalo bull sperm. For this purpose, two separate experiments were conducted to evaluate antifreeze proteins III (AFP III) at 0 (control), 0.1, 1 and 10 µg/mL (Experiment I) and 0 (control), 0.01, 0.1 and 1 µg/mL (Experiment II) for its effect on post thaw quality of buffalo bull semen. Semen was collected from three Nili-Ravi buffalo (Bubalus bubalis) bulls with artificial vagina (42 °C) for three weeks (replicate) per experiment. For each experiment, qualifying ejaculates (6 ejaculates/bull) were divided into four aliquots and diluted (at 37 °C having 50 × 10(6) sperm/mL) in tris-citric acid extender containing above mentioned concentrations of AFP III. Diluted semen was cooled to 4 °C in 2 h, equilibrated for 4 h, filled in 0.5 mL straws, kept over liquid nitrogen vapors for 10 min and plunged in the liquid nitrogen. After 24 h of storage, semen straws were thawed at 37 °C for 30 s to assess sperm progressive motility (SM), plasma membrane integrity (PMI), viability (live sperm with intact acrosome) and normal epical ridge (NAR). In experiment I, improvement (P<0.05) in percentage SM and sperm PMI was recorded in extender containing 0.1 µg/mL AFP III compared to control, the higher concentrations (1 µg/mL and 10 µg/mL) being inefficient. While evaluating the lower concentration (experiment II), 0.01 µg/mL of AFP III in the extender it was found to be ineffective to improve semen quality parameters, while 0.1 µg/mL AFP III in extender was found better in terms of progressive motility and plasma membrane integrity of buffalo bull semen compared to control. Sperm viability and NAR remained similar (P>0.05) in extenders containing different concentrations of AFP III and control in both of experiments. In conclusion addition of AFP III in the extender at 0.1 µg/mL improved the progressive motility and plasma membrane integrity of cryopreserved buffalo bull semen.

Chemically modified diamond-like carbon (DLC) for protein enrichment and profiling by MALDI-MS.

The development of new high throughput methods based on different materials with chemical modifications for protein profiling of complex mixtures leads towards biomarkers; used particularly for early diagnosis of a disease. In this work, diamond-like carbon (DLC) is developed and optimized for serum protein profiling by matrix-assisted laser/desorption ionization mass spectrometry (MALDI-MS). This study is carried out in connection with a material-based approach, termed as material-enhanced laser desorption ionization mass spectrometry. DLC is selected as carrier surface which provides large surface to volume ratio and offers high sensitivity. DLC has a dual role of working as MALDI target while acting as an interface for protein profiling by specifically binding peptides and proteins out of serum samples. Serum constituents are bound through immobilized metal ion affinity chromatography (IMAC) functionality, created through glycidyl methacrylate polymerization under ultraviolet light followed by further derivatization with iminodiacetic acid and copper ion loading. Scanning electron microscopy highlights the morphological characteristics of DLC surface. It could be demonstrated that IMAC functionalized DLC coatings represent a powerful material in trapping biomolecules for their further analysis by MALDI-MS resulting in improved sensitivity, specificity and capacity in comparison to other protein-profiling methods.

Enhanced production of an extracellular beta-D-fructofuranosidase fructohydrolase from a 2-deoxy-D-glucose stabilized mutant of Candida utilis.

The enzyme beta-D-fructofuranosidase fructohydrolase (FFH) cleaves the alpha-1,4 glycosidic linkage between alpha-D-glucose and beta-D: -fructose molecules of sucrose, releasing monosaccharides by hydrolysis. In the present study, FFH production in Candida utilis GC-46, a lipolytic wild yeast strain was improved by exposure to N-methyl N-nitro N-nitroso guanidine (NG) and 2-deoxy-D-glucose (2dg) at various levels. The mutant strain NG-5 was obtained after exposure to 0.06 mg/ml of NG for 20 min. NG-5 offers improved extracellular FFH production (34 +/- 2.6 U/ml/min) when compared to the wild strain (1.15 +/- 0.01 U/ml/min). A 40-fold increase of FFH (45.65 +/- 2.0 U/ml/min) was achieved when the process parameters, including incubation period (48 h), sucrose concentration (5.0 g/l), initial pH (6.0), inoculum size (2.0% v/v, 16 h old), and urea concentration (0.2%, w/v) were identified using Plackett-Burman design. The kinetic parameters viz. Q (p) (0.723 U/g/h), Y (p/s) (2.036 U/g), and q (p) (0.091 U/g yeast cells/h) indicate that NG-5 is a hyperproducer of extracellular FFH with a concomitant increase in growth rate. The volumetric productivity of NG-5 was over sixfold improved over the parental strain. The enzyme production improvement is highly significant (HS, LSD 0.042, p < or = 0.05), indicating commercial utility.

Kinetics of an extracellular exo-inulinase production from a 5-flourocytosine resistant mutant of Geotrichum candidum using two-factorial design.

In the present study, eight different strains of Geotrichum candidum were isolated and screened for an extracellular exo-inulinase production using chemically enriched sucrose-mineral media. The isolate (Zool-3i) with a better enzyme activity (1.38 IU/ml) was subjected to induced mutagenesis using methyl methane sulphonate (MMS) and a mutant with an enzyme activity of 32.06 IU/ml was obtained. Further exposure to ethyl methane sulphonate (EMS) and ultraviolet (UV) radiations yielded a mutant exhibiting an improved activity of 39.34 IU/ml. The potential mutant was cultured overnight and plated on 5fc-YPR agar medium and thus made resistant against 5-flourocytocine. Over 50-fold enhancement in enzyme production (71.85 IU/ml) was achieved when the process parameters including incubation period (48 h), sucrose concentration (5.0 g/L), pH (6.0), inoculum size (2.0%, 16 h old) and urea (0.2%) were identified using Plackett-Burman design. On the basis of kinetic variables, notably Q(p) (0.723 U/g/h), Y(p/s) (2.036U/g) and q(p) (0.091U/g cells/h), the mutant MEU-5fc-6 was found to be a hyper producer of exo-inulinase (HS, LSD 0.045, p< or =0.05).