The findings suggested that the aforementioned compound has a strong binding affinity to interact with DNA residues DT8, DC9, DG12, DG16, DA17, and DA18 through the intermolecular hydrogen bonds. Also the performed in silico ADMET analysis was the prediction of the synthesized molecule’s pharmacokinetic and toxicity profile expressing good oral drug like actions and non-toxic nature. The complex has been shown to have the possibility to become a model molecule for drug development processes.Communicated by Ramaswamy H. Sarma.Background. Mesenchymal stem cell (MSC)-derived exosomes play a critical role in regenerative medicine. Objective. To determine the dose- and time-dependent efficacy of exosomes for treatment of traumatic brain injury (TBI). Methods. Male rats were subjected to a unilateral moderate cortical contusion. Sodium valproate In the dose-response study, animals received a single intravenous injection of exosomes (50, 100, 200 µg per rat) or vehicle, with treatment initiated at 1 day after injury. In the therapeutic window study, animals received a single intravenous injection of 100 µg exosomes or vehicle starting at 1, 4, or 7 days after injury. Neurological functional tests were performed weekly after TBI for 5 weeks. Spatial learning was measured on days 31 to 35 after TBI using the Morris water maze test. Results. Compared with the vehicle, regardless of the dose and delay in treatment, exosome treatment significantly improved sensorimotor and cognitive function, reduced hippocampal neuronal cell loss, promoted angiogenesis and neurogenesis, and reduced neuroinflammation. Exosome treatment at 100 µg per rat exhibited a significant therapeutic effect compared with the 50- or 200-µg exosome groups. The time-dependent exosome treatment data demonstrated that exosome treatment starting at 1 day post-TBI provided a significantly greater improvement in functional and histological outcomes than exosome treatments at the other 2 delayed treatments. Conclusions. These results indicate that exosomes have a wide range of effective doses for treatment of TBI with a therapeutic window of at least 7 days postinjury. Exosomes may provide a novel therapeutic intervention in TBI.Background In chronic obstructive pulmonary disease (COPD), both the time needed for patients to gain symptom improvement with long-acting bronchodilator therapy and whether an early response is predictive of a sustained response is unknown. This study aimed to investigate how quickly meaningful symptom responses are seen in patients with COPD with bronchodilator therapy and whether these responses are sustained. Methods Early MAXimisation of bronchodilation for improving COPD stability (EMAX) was a 24-week, double-blind, double-dummy, parallel-group trial that randomised patients to umeclidinium/vilanterol (UMEC/VI), umeclidinium or salmeterol. Daily Evaluating Respiratory Symptoms in COPD (E-RSCOPD) score and rescue salbutamol use were captured via an electronic diary and analysed initially in 4-weekly periods. Post hoc analyses assessed change from baseline in daily E-RSCOPD score and rescue medication use weekly (Weeks 1-8), and association between E-RSCOPD responder status at Weeks 1-4 and later time poiNCT03034915, 2016-002513-22 (EudraCT Number). The reviews of this paper are available via the supplemental material section.The rusticyanin protein, a blue monomeric copper protein type-1, is one of the main components in the iron-electron transfer chain of the Acidithiobacillus ferrooxidans, and is the product of the rus gene expression. Herein, first the bacterial DNA of Acidithiobacillus sp. FJ2 was extracted. Then, the rus gene sequence and the sequence amino acid rusticyanin protein were determined. The Met148Leu mutation increased the oxidase activity of the rusticyanin protein, thereby enhancing the efficiency of the bioleaching process by bacteria Acidithiobacillus ferroxidans. Met148Leu mutation was created in the rusticyanin protein, then molecular dynamics (MD) simulations and structural analysis were performed. The MD analysis of the wild-type and mutant protein demonstrated a slight instability in the mutant protein and significant instability in the active site of the mutant protein. The usefulness of this study is the genetic manipulation of the native Acidithiobacillus sp. FJ2 bacterium, which can boost the bioleaching efficiency of the bacterium to some extent, and investigating its effects on the structure of a mutant protein using computational methods. Communicated by Ramaswamy H. Sarma.Background There are few studies reporting the clinical characteristics and outcomes of interstitial lung disease (ILD) patients with acute respiratory failure (ARF). The goal of this study is to investigate the clinical features, management, mortality, and associated factors in ILD patients with ARF requiring mechanical ventilation (MV). Methods This was a retrospective, observational study conducted in a 24-bed intensive care unit (ICU) of a medical center in Taiwan during a 3-year period. link2 Patients admitted to the ICU with a diagnosis of ILD with ARF needing MV were included for analysis. Patient characteristics, including demographics, critical-illness factors, and outcome data, were collected and analyzed. Results A total of 82 patients with ILD who developed ARF were admitted to the ICU during the study period. At the onset of ARF, 38 patients received invasive MV, while 44 patients were treated with noninvasive MV. Overall in-hospital mortality was 65.9%, and 90-day and 1-year mortality were 69.5% and 76.8%, respectively. The independent risk factors for in-hospital mortality were worse oxygenation on days 5 and 7 after the onset of ARF. Invasive MV patients had significantly lower albumin levels, had higher Acute Physiology and Chronic Health Evaluation (APACHE) II scores at the onset of ARF, and received more vasopressors, sedatives, and corticosteroid pulse therapy during hospitalization compared with noninvasive MV patients. Conclusion High in-hospital and long-term mortality rates were observed in ILD patients with ARF requiring MV. Poor oxygenation during hospitalization could serve as a predictive factor of poor prognosis. The reviews of this paper are available via the supplemental material section.In this study, nine compounds were isolated, eight of them were isolated for the first time from Cystoseira trinodis. The biological activity of the extract, fractions and pure compounds was evaluated. The antimicrobial activity was investigated against 3 fungi species, 3 gram + ve and 3 gram -ve bacteria. The crude extract and fractions showed moderate inhibition against some of the tested microorganisms, especially the butanol fraction exhibited the maximum inhibition zone against Salmonella typhimurium (16 ± 0.60 mm). Cytotoxicity was evaluated against HepG-2 and MCF-7 cell lines. Hexane fraction exhibited the highest cytotoxic effect against HepG-2 and MCF-7 cell lines with an IC50 value of 14.3 ± 0.8 and 19.2 ± 0.7 µg/ml, respectively with compared to other fractions. The isolates were identified as octacosanoic acid (1), glyceryl trilinoleate (2), oleic acid (3), and the epimeric mixture of saringosterols (4, 5), β-sitosterol (6), glycoglycerolipid (7) and a mixture of kjellmanianone and loliolide (8, 9) by spectroscopic analysis. Among the all tested compounds kjellmanianone and loliolide mixture exhibited significant cytotoxic activity with an IC50 value of 7.27 µg/ml against HepG-2 cells. The major and minor constituents of the extract and fractions were identified using GC-MS analysis. Molecular docking analysis confirmed that most of the studied compounds especially compounds 8 and 9 strongly interact with TPK and VEGFR-2 with highest binding energies supported that the high cytotoxicity of these compounds against human hepatocellular cancer in the experimental part. The energetic, geometric and topological properties of compounds 8 and 9 binding with cytosine base were computed by DFT methods. Molecular properties descriptors, bioactivity score and ADMET analysis confirmed that most of the studied compounds especially compounds 8 and 9 exhibit significant biological activities and have a better chance to be developed as drug leads. Communicated by Ramaswamy H. Sarma.Clinical neuroimaging has largely been limited to examining the neurophysiological outcomes of treatments for psychiatric conditions rather than the neurocognitive mechanisms by which these outcomes are brought about as a function of clinical strategies, and the cognitive neuroscientific research aiming to investigate these mechanisms in nonclinical and clinical populations has been ecologically challenged by the extent to which tasks represent and generalize to intervention strategies. However, recent technological and methodological advancements to neuroimaging techniques such as functional near-infrared spectroscopy and functional near-infrared spectroscopy-based hyperscanning provide novel opportunities to investigate the mechanisms of change in more naturalistic and interactive settings, representing a unique prospect for improving our understanding of the intra- and interbrain systems supporting the recogitation of dysfunctional cognitive operations.γ-aminobutyric acid aminotransferase (GABA-AT) is a pyridoxal 5′-phosphate (PLP)-dependent enzyme which degrades γ-aminobutyric (GABA) in the brain. GABA is an important inhibitory neurotransmitter that plays important neurological roles in the brain. Therefore, GABA-AT is an important drug target which regulates the GABA level. Novel and potent drug development to inhibit GABA-AT is still very challenging task. In this study, we aimed to devise novel and potent inhibitors against GABA-AT using computer-aided drug design (CADD) tools. However, the human GABA-AT crystal structure is not available yet, and we built the 3D structure of human GABA-AT based on the crystal structure of pig’s liver (Sus Scrofa) enzyme as a template. The generated model was validated with numerous tools such as ProSA and PROCHECK. A set of selected well-known inhibitors have been tested against the modeled GABA-AT. Molecular docking studies have been accomplished via application of Genetic Optimization for Ligand Docking (GOLD), Vina and Autodock 4.2 software to search for potent inhibitors. The best two candidate inhibitors have been computationally examined for absorption, distribution, metabolism, elimination and toxicity descriptors (ADMET) and Lipinski’s rule of 5. Lastly, molecular dynamics (MD) simulations were carried out to inspect the ligands’ binding mode and stability of the active site of human GABA-AT over time. The top ranked ligands exhibited reliable stability throughout the MD simulation. The selected compounds are promising candidates and might be tested experimentally for the inhibition of human GABA-AT enzyme. Communicated by Ramaswamy H. Sarma.Xanthene derivatives have become a group of molecules of great importance in discovering of new anticancer drugs. link3 Recent studies of our group performed on xanthen-3-one and xanthen-1,8-dione derivatives have shown their antiproliferative activity on HeLa cervical cell lines. Obtained IC50 values together with calculated molecular descriptors were subjected to Quantitative Structure-Activity Relationship (QSAR) study in order to identify the most relevant molecular features responsible for the observed antiproliferative activity of compounds. Partial least square statistical method and the same training and test set were used to obtain statistical parameters for internal and external validation in 2D- and 3D-QSAR study. The obtained QSAR models have shown next results 2D-QSAR R2 = 0.741, Q2 = 0.792, R2pred = 0.875 and 3D-QSAR R2 = 0.951, Q2 = 0.830, R2pred = 0.769. Based on the performed QSAR analysis and calculated ADMET properties, novel xanthene derivatives with enhanced antiproliferative activity were designed.