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Performance of an optical wireless link is adversely affected due to attenuation caused by the presence of weather conditions as well as atmospheric turbulence. In this paper, average channel capacity of an optical wireless link is evaluated under the combined effect of attenuation due to weather conditions and atmospheric turbulence modeled by lognormal distribution using a simple closed form expression. Capacity of optical wireless link with aperture averaging is also computed. Further, the feasibility of aperture averaging as a mitigation technique for various weather conditions such as clear air, haze, rain and fog is also investigated. Our study reveals that aperture averaging significantly increases the capacity in presence of clear air and haze. However, for rain and fog, a high value of signal to noise ratio is required at the receiver to enhance the capacity by using aperture averaging. [ABSTRACT FROM AUTHOR]

Understanding the origin of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been a highly debatable and unresolved issue for scientific communities all over the world. Understanding the mechanism of virus entry to the host cells is crucial to deciphering the susceptibility profiles of animal species to SARS-CoV-2. The interaction of SARS-CoV-2 ligands (receptor-binding domain on spike protein) with its host cell receptor, angiotensin-converting enzyme 2 (ACE2), is a critical determinant of host range and cross-species transmission. In this study, we developed and implemented a rigorous computational approach for predicting binding affinity between 299 ACE2 orthologs from diverse vertebrate species and the SARS-CoV-2 spike protein. The findings show that the SARS-CoV-2 spike protein can bind to a wide range of vertebrate species carrying evolutionary divergent ACE2, implying a broad host range at the virus entry level, which may contribute to cross-species transmission and further viral evolution. Furthermore, the current study facilitated the identification of genetic determinants that may differentiate susceptible from resistant host species based on the conservation of ACE2-spike protein interacting residues in vertebrate host species known to facilitate SARS-CoV-2 infection; however, these genetic determinants warrant in vivo experimental confirmation. The molecular interactions associated with varied binding affinity of distinct ACE2 isoforms in a specific bat species were identified using protein structure analysis, implying the existence of diversified bat species' susceptibility to SARS-CoV-2. The current study's findings highlight the importance of intensive surveillance programmes aimed at identifying susceptible hosts, especially those with the potential to transmit zoonotic pathogens, in order to prevent future outbreaks. [ABSTRACT FROM AUTHOR]

Rapid advance of computer technologies in data processing, collection, and storage has provided unparalleled opportunities to expand capabilities in production, services, communications, and research. However, immense quantities of high-dimensional data renew the challenges to the state-of-the-art data mining techniques. Artificial Bee Colony (ABC) is a popular meta-heuristic search algorithm used in solving numerous combinatorial optimization problems. Feature Selection (FS) helps to speed up the process of classification by extracting the relevant and useful information from the dataset. FS is seen as an optimization problem because selecting the appropriate feature subset is very important. Classifier Ensemble is the best solution for the pitfall of accuracy lag in a single classifier. We first briefly introduce the concept of data mining and key components of feature selection. This paper proposed a hybrid approach for the feature selection by using artificial bee colony and particular swarm optimization. The proposed technique is simulated using the WEKA and results show the better performance of the proposed technique. [ABSTRACT FROM AUTHOR]

Neurotrypsin (NT) is a neuronal trypsin-like serine protease whose mutations cause severe mental retardation in humans. NT is activated in vitro by Hebbian-like conjunction of pre- and postsynaptic activities, which promotes the formation of dendritic filopodia via proteolytic cleavage of the proteoglycan agrin. Here, we investigated the functional importance of this mechanism for synaptic plasticity, learning, and extinction of memory. We report that juvenile neurotrypsin-deficient (NT−/−) mice exhibit impaired long-term potentiation induced by a spaced stimulation protocol designed to probe the generation of new filopodia and their conversion into functional synapses. Behaviorally, juvenile NT−/− mice show impaired contextual fear memory and have a sociability deficit. The latter persists in aged NT−/− mice, which, unlike juvenile mice, show normal recall but impaired extinction of contextual fear memories. Structurally, juvenile mutants exhibit reduced spine density in the CA1 region, fewer thin spines, and no modulation in the density of dendritic spines following fear conditioning and extinction in contrast to wild-type littermates. The head width of thin spines is reduced in both juvenile and aged NT−/− mice. In vivo delivery of adeno-associated virus expressing an NT-generated fragment of agrin, agrin-22, but not a shorter agrin-15, elevates the spine density in NT−/− mice. Moreover, agrin-22 co-aggregates with pre- and postsynaptic markers and increases the density and size of presynaptic boutons and presynaptic puncta, corroborating the view that agrin-22 supports the synaptic growth. [ABSTRACT FROM AUTHOR]

Many viruses that cause serious diseases in humans and animals, including the betacoronaviruses (beta-CoVs), such as SARS-CoV, MERS-CoV, and the recently identified SARS-CoV-2, have natural reservoirs in bats. Because these viruses rely entirely on the host cellular machinery for survival, their evolution is likely to be guided by the link between the codon usage of the virus and that of its host. As a result, specific cellular microenvironments of the diverse hosts and/or host tissues imprint peculiar molecular signatures in virus genomes. Our study is aimed at deciphering some of these signatures. Using a variety of genetic methods we demonstrated that trends in codon usage across chiroptera-hosted CoVs are collaboratively driven by geographically different host-species and temporal-spatial distribution. We not only found that chiroptera-hosted CoVs are the ancestors of SARS-CoV-2, but we also revealed that SARS-CoV-2 has the codon usage characteristics similar to those seen in CoVs infecting the Rhinolophus sp. Surprisingly, the envelope gene of beta-CoVs infecting Rhinolophus sp., including SARS-CoV-2, had extremely high CpG levels, which appears to be an evolutionarily conserved trait. The dissection of the furin cleavage site of various CoVs infecting hosts revealed host-specific preferences for arginine codons; however, arginine is encoded by a wider variety of synonymous codons in the murine CoV (MHV-A59) furin cleavage site. Our findings also highlight the latent diversity of CoVs in mammals that has yet to be fully explored. [ABSTRACT FROM AUTHOR]

The extracellular matrix (ECM) plays a key role in synaptogenesis and the regulation of synaptic functions in the central nervous system. Recent studies revealed that in addition to dopaminergic and serotoninergic neuromodulatory systems, microglia also contribute to the regulation of ECM remodeling. In the present work, we investigated the physiological role of microglia in the remodeling of perineuronal nets (PNNs), predominantly associated with parvalbumin-immunopositive (PV+) interneurons, and the perisynaptic ECM around pyramidal neurons in the hippocampus. Adult mice were treated with PLX3397 (pexidartinib), as the inhibitor of colony-stimulating factor 1 receptor (CSF1-R), to deplete microglia. Then, confocal analysis of the ECM and synapses was performed. Although the elimination of microglia did not alter the overall number or intensity of PNNs in the CA1 region of the hippocampus, it decreased the size of PNN holes and elevated the expression of the surrounding ECM. In the neuropil area in the CA1 str. radiatum, the depletion of microglia increased the expression of perisynaptic ECM proteoglycan brevican, which was accompanied by the elevated expression of presynaptic marker vGluT1 and the increased density of dendritic spines. Thus, microglia regulate the homeostasis of pre- and postsynaptic excitatory terminals and the surrounding perisynaptic ECM as well as the fine structure of PNNs enveloping perisomatic—predominantly GABAergic—synapses. [ABSTRACT FROM AUTHOR]

This paper reports the results of structural, morphological, and optical analysis of Cu core Ag shell (Cu c Ag s) nanoparticles (NPs) and Cu c Ag s polyvinyl alcohol (PVA) nanocomposite (NC) films. Further their application for colorimetric cyanide (CN‾) sensing has been demonstrated. High resolution transmission electron microscopy (HRTEM) confirmed the growth of Cu c Ag s NPs. Morphological investigations have been performed using field-emission scanning electron microscopy (FE-SEM). Cu c Ag s NPs and Cu c Ag s PVA NC films have been used for colorimetric CN‾ sensing in water. Cu c Ag s NPs show good sensitivity and selectivity for CN‾ ion among other related anions with a limit of detection (LOD) of 0.15 μM. The potential application of Cu c Ag s NPs for the detection of CN‾ in apricot seed extract has also been explored. Further, UV–visible analysis reveals that NC containing 1.6 wt% Cu c Ag s NPs completely blocks the UV region of electromagnetic spectrum. Image 1 • Cu c Ag s NPs and Cu c Ag s PVA NC have been used for colorimetric sensing of toxic CN‾ ion. • The Cu c Ag s NPs showed good sensitivity for CN‾ with LOD of 0.15 μM. • Applicability of Cu c Ag s NPs for detection of CN‾ in apricot seeds extract with LOD of 0.19 μM has been demonstrated. • NC films with 1.6 wt% Cu c Ag s NPs block UV radiations, thus can be used as UV blocker. [ABSTRACT FROM AUTHOR]

• A Multianalyte sensor for detecting different classes of chemicals that barely interfere in the real samples has been reported. • Low detection limits for moisture (0.0032 w/w % for DMSO and 0.0014 w/w% for THF) and Phosgene (23 nM). • Naked eye detection and discriminate between Cu2+ and Fe3+. • Time gated colorimetric phosgene gas detection. • A practical application using a smartphone as a portable analytical device was also explored. An organic molecule-based sensor 4-((4-(dimethylamino)phenyl)diazenyl)-N-(quinolin-8-yl)benzenesulfonamide(MASP)able to detect multiple analytes such as moisture, warfare reagent (phosgene), divalent (Cu2+), and trivalent (Fe3+) has been reported. These analytes belong to the different classes of chemicals and barely interfere in the real sample. Fluorescence emission of MASP was observed due to the ESIPT mechanism, but it was inhibited by water. This phenomenon was utilized for moisture detection in DMSO and THF with the detection limit of 0.0032 % w/w and 0.0014 % w/w, respectively. The MASP was also employed for the colorimetric sensing (yellow to red) of phosgene in solution and gas with good selectivity and high sensitivity (LOD = 23 nM). The naked eye detection of MASP was incorporated with RGB color value to make use of MASP for the practical application using a smartphone as a portable analytical device. The distinct color change of divalent Cu2+ (yellow to colorless) and trivalent Fe3+ (yellow to red) observed with MASP also helps discriminate Cu2+ and Fe3+ among various cations. [ABSTRACT FROM AUTHOR]

• Dhanvantari is a comprehensive automatic drug design software suite. • It would help in discovering new potential drug targets from genomic/proteomic data. • Dhanvantari screens different molecular libraries to find novel hits. • Tested on 111 FDA approved drugs against 33 diseases with ~90% accuracy. • Entire protocol proposed in Dhanvantari requires ~6–12 h. Big data generation through sequencing of genomes and proteomes has led to over thousands of whole genomes and millions of protein sequences. However, utilization of this data to generate drug-like molecules for curing diseases remains a challenge. We propose here, Dhanvantari , a comprehensive software suite which automates the journey from genomes to hit molecules via its various modules such as i) gene finding, ii) computational structural study of target proteins and iii) virtual screening/identification of hit molecules for computer aided drug discovery. The pipeline has five possible entry points. Validation of the protocol is performed on 10 major life-threatening diseases reported by WHO covering 33 different protein targets and 111 FDA approved drugs. Three complete case studies from genomes to hits are also performed using the pipeline where the reported FDA drugs against the pathogen have been successfully recovered. The proposed software suite promises to deliver some new opportunities and insights into "genome-based" drug discovery along with the classical structure-based approaches to discover novel potential drug-like molecules. The entire protocol requires ~6–12 h. Individual steps, however, get completed within a few minutes. The pipeline can be freely accessed at http://www.scfbio-iitd.res.in/software/dhanvantari_new/Home.html. [ABSTRACT FROM AUTHOR]

The undesired research results of triazole synthesis were successfully utilized as a simpler, sensitive and selective turn-on fluorescent probe 2 namely chloro-acetic acid 2-benzothiazol-2-yl-phenyl ester (HBT-AcCl) which was synthesized by simple chloroacylation of 2-hydroxyphenyl benzothiazole (HBT). Only one simple chloroacetate, a trigger unit as the reaction site of probe 2 makes it more simple, sensitive and selective for Cys and Hcy over other Amino Acids. The presented probe HBT-AcCl conserves simple structure, reduces the use of extra chloroacetate and improves %atom economy as compare to similar reported probes. Paper strip tests were carried out to explore the potential application for naked-eye detection of Cys under UV lamp. The selectivity of the HBT-AcCl probe for Cys and Hcy is supported by the results of absorbance and emission spectroscopy experiments and theoretical DFT calculations. A new simpler, sensitive, selective turn-on fluorescent probe chloro-acetic acid 2-benzothiazol-2-yl-phenyl ester (HBT-AcCl) was developed from the negative research results of some other scheme. The probe selectively detected Cys & Hcy from other amino acids. The presented probe considered as a green probe that conserves complexity, reduces use of extra chloroacetate and has improved %atom economy. Image 1 • A new simpler, sensitive, selective turn-on ESIPT-based fluorescent probe chloro-acetic acid 2-benzothiazol-2-yl-phenyl ester (HBT-AcCl) developed from the negative research results of some other scheme. • The HBT-AcCl probe was efficiently utilized for selective detection of Cys and Hcy over other Amino Acids. • The %atom economy of the presented probe was found better than other similar but complex reported probes. • Paper strip tests were carried out to explore the potenitial application for naked eye detection of Cys under UV lamp. • Selectivity of HBT-AcCl probe for Cys and Hcy is supported by theoritical DFT calculations. [ABSTRACT FROM AUTHOR]

The dedicator of cytokinesis (DOCK)/engulfment and cell motility (ELMO) complex serves as a guanine nucleotide exchange factor (GEF) for the GTPase Rac. RhoG, another GTPase, activates the ELMO-DOCK-Rac pathway during engulfment and migration. Recent cryo-EMstructures of theDOCK2/ELMO1 and DOCK2/ELMO1/Rac1 complexes have identified closed and open conformations that are key to understanding the autoinhibition mechanism. Nevertheless, the structural details of RhoG-mediated activation of the DOCK/ELMO complex remain elusive. Herein, we present cryo-EM structures of DOCK5/ELMO1 alone and in complex with RhoGand Rac1. TheDOCK5/ELMO1 structure exhibits a closed conformation similar to that of DOCK2/ELMO1, suggesting a shared regulatory mechanism of the autoinhibitory state across DOCK-A/B subfamilies (DOCK1-5). Conversely, the RhoG/DOCK5/ELMO1/Rac1 complex adopts an open conformation that differs from that of the DOCK2/ELMO1/Rac1 complex, with RhoG binding to both ELMO1 and DOCK5. The alignment of the DOCK5 phosphatidylinositol (3,4,5)-trisphosphate binding site with the RhoG Cterminal lipidation site suggests simultaneous binding of RhoG and DOCK5/ELMO1 to the plasma membrane. Structural comparison of the apo and RhoG-bound states revealed that RhoG facilitates a closed-to-open state conformational change of DOCK5/ELMO1. Biochemical and surface plasmon resonance (SPR) assays confirm that RhoG enhances the Rac GEF activity of DOCK5/ELMO1 and increases its binding affinity for Rac1. Further analysis of structural variability underscored the conformational flexibility of the DOCK5/ELMO1/Rac1 complex core, potentially facilitating the proximity of the DOCK5 GEF domain to the plasma membrane. These findings elucidate the structural mechanism underlying the RhoG-induced allosteric activation andmembrane binding of the DOCK/ELMO complex. [ABSTRACT FROM AUTHOR]

• Collagen XVIII deficiency induces blood-brain-barrier leakage. • It also induces other pathological changes typical of early CSVD. • Expression of basement membrane ECM molecules was upregulated. • ECM of perineuronal nets around interneurons was impaired. • Perisynaptic ECM proteins and C1q at excitatory synapses were upregulated. Collagen type XVIII (COL18) is an abundant heparan sulfate proteoglycan in vascular basement membranes. Here, we asked (i) if the loss of COL18 would result in blood-brain barrier (BBB) breakdown, pathological alterations of small arteries and capillaries and neuroinflammation as found in cerebral small vessel disease (CSVD) and (ii) if such changes may be associated with remodeling of synapses and neural extracellular matrix (ECM). We found that 5-month-old Col18a1−/− mice had elevated BBB permeability for mouse IgG in the deep gray matter, and intravascular erythrocyte accumulations were observed brain-wide in capillaries and arterioles. BBB permeability increased with age and affected cortical regions and the hippocampus in 12-month-old Col18a1−/− mice. None of the Col18a1−/− mice displayed hallmarks of advanced CSVD, such as hemorrhages, and did not show perivascular space enlargement. Col18a1 deficiency-induced BBB leakage was accompanied by activation of microglia and astrocytes, a loss of aggrecan in the ECM of perineuronal nets associated with fast-spiking inhibitory interneurons and accumulation of the perisynaptic ECM proteoglycan brevican and the microglial complement protein C1q at excitatory synapses. As the pathway underlying these regulations, we found increased signaling through the TGF-ß1/Smad3/TIMP-3 cascade. We verified the pivotal role of COL18 for small vessel wall structure in CSVD by demonstrating the protein's involvement in vascular remodeling in autopsy brains from patients with cerebral hypertensive arteriopathy. Our study highlights an association between the alterations of perivascular ECM, extracellular proteolysis, and perineuronal/perisynaptic ECM, as a possible substrate of synaptic and cognitive alterations in CSVD. [ABSTRACT FROM AUTHOR]

The pharmaceutical industry plays a pivotal role in public health by providing essential medications. However, flawed medications can have severe consequences for patients and healthcare systems. This article provides a thorough examination of the process and implications of recalling flawed medications. It delves into the various challenges faced by pharmaceutical companies, regulators, and healthcare professionals in identifying and addressing medication flaws. The article also discusses the significant consequences of medication recalls, including potential harm to patients, financial burdens, and damage to a company's reputation. Furthermore, it explores innovative solutions and strategies to minimize the occurrence of medication recalls and streamline the recall process when necessary. By shedding light on this critical aspect of the healthcare industry, this article aims to contribute to a safer and more effective medication supply chain, ultimately ensuring the well-being of patients and the integrity of the pharmaceutical sector. [ABSTRACT FROM AUTHOR]

The ability to form precise, episodic memories develops with age, with young children only able to form gist-like memories that lack precision. The cellular and molecular events in the developing hippocampus that underlie the emergence of precise, episodic-like memory are unclear. In mice, the absence of a competitive neuronal engram allocation process in the immature hippocampus precluded the formation of sparse engrams and precise memories until the fourth postnatal week, when inhibitory circuits in the hippocampus mature. This age-dependent shift in precision of episodic-like memories involved the functional maturation of parvalbumin-expressing interneurons in subfield CA1 through assembly of extracellular perineuronal nets, which is necessary and sufficient for the onset of competitive neuronal allocation, sparse engram formation, and memory precision. [ABSTRACT FROM AUTHOR]

Simple Summary: Memory is a fundamental cognitive function we need for everyday life. Since we process so much information each day, it is believed that our memory system selects only relevant information to encode in order to avoid overload. In this work, we study the molecular mechanism supporting this selective memory encoding. It is believed that memory encoding occurs mainly when we encounter a new unexpected condition: a novel context. In a novel context, the hippocampus, which is crucial for memory function, intensifies a specific rhythmic activity called beta oscillations. While these beta oscillations are believed to support memory encoding, the molecular mechanisms underlying this increase in beta oscillations are not yet understood. We demonstrate that a specific type of membrane ionic channel called transient receptor potential canonical 4 (TRPC4) supports the modulation of beta oscillation in the hippocampus, indicating that TRPC4 channels play a role in novelty-related memory encoding. Hippocampal local field potentials (LFP) are highly related to behavior and memory functions. It has been shown that beta band LFP oscillations are correlated with contextual novelty and mnemonic performance. Evidence suggests that changes in neuromodulators, such as acetylcholine and dopamine, during exploration in a novel environment underlie changes in LFP. However, potential downstream mechanisms through which neuromodulators may alter the beta band oscillation in vivo remain to be fully understood. In this paper, we study the role of the membrane cationic channel TRPC4, which is modulated by various neuromodulators through G-protein-coupled receptors, by combining shRNA-mediated TRPC4 knockdown (KD) with LFP measurements in the CA1 region of the hippocampus in behaving mice. We demonstrate that the increased beta oscillation power seen in the control group mice in a novel environment is absent in the TRPC4 KD group. A similar loss of modulation was also seen in the low-gamma band oscillations in the TRPC4 KD group. These results demonstrate that TRPC4 channels are involved in the novelty-induced modulation of beta and low-gamma oscillations in the CA1 region. [ABSTRACT FROM AUTHOR]

Solvent extracts of Cinnamomum tamala (CT) leaves were screened for phytochemicals, and the flavonoid and phenolic contents were estimated. The two standard marker compounds quercetin and eugenol were also quantified using high-performance thin-layer chromatography (HPTLC). The total flavonoid and phenolic contents were determined using aluminum chloride and Folin–Ciocalteu colorimetric methods, respectively. The ethanolic extracts had the highest total flavonoid and phenolic contents with 141.31 ± 0.053 mg QE g−1 and 178.96 ± 0.62 mg GAE g−1, respectively. The HPTLC method was used to detect spots for quercetin and eugenol (Rf value of 0.63 and 0.59, respectively). The amounts of eugenol and quercetin were 452.6 µg and 705.6 µg in 100 mg of the ethanolic extract of CT leaves, respectively. [ABSTRACT FROM AUTHOR]

Our previous studies demonstrated that enzymatic removal of highly sulfated heparan sulfates with heparinase 1 impaired axonal excitability and reduced expression of ankyrin G at the axon initial segments in the CA1 region of the hippocampus ex vivo, impaired context discrimination in vivo, and increased Ca2+/calmodulin-dependent protein kinase II (CaMKII) activity in vitro. Here, we show that in vivo delivery of heparinase 1 in the CA1 region of the hippocampus elevated autophosphorylation of CaMKII 24 h after injection in mice. Patch clamp recording in CA1 neurons revealed no significant heparinase effects on the amplitude or frequency of miniature excitatory and inhibitory postsynaptic currents, while the threshold for action potential generation was increased and fewer spikes were generated in response to current injection. Delivery of heparinase on the next day after contextual fear conditioning induced context overgeneralization 24 h after injection. Co-administration of heparinase with the CaMKII inhibitor (autocamtide-2-related inhibitory peptide) rescued neuronal excitability and expression of ankyrin G at the axon initial segment. It also restored context discrimination, suggesting the key role of CaMKII in neuronal signaling downstream of heparan sulfate proteoglycans and highlighting a link between impaired CA1 pyramidal cell excitability and context generalization during recall of contextual memories. [ABSTRACT FROM AUTHOR]

Synaptic dysfunction caused by soluble β‐amyloid peptide (Aβ) is a hallmark of early‐stage Alzheimer's disease (AD), and is tightly linked to cognitive decline. By yet unknown mechanisms, Aβ suppresses the transcriptional activity of cAMP‐responsive element‐binding protein (CREB), a master regulator of cell survival and plasticity‐related gene expression. Here, we report that Aβ elicits nucleocytoplasmic trafficking of Jacob, a protein that connects a NMDA‐receptor‐derived signalosome to CREB, in AD patient brains and mouse hippocampal neurons. Aβ‐regulated trafficking of Jacob induces transcriptional inactivation of CREB leading to impairment and loss of synapses in mouse models of AD. The small chemical compound Nitarsone selectively hinders the assembly of a Jacob/LIM‐only 4 (LMO4)/ Protein phosphatase 1 (PP1) signalosome and thereby restores CREB transcriptional activity. Nitarsone prevents impairment of synaptic plasticity as well as cognitive decline in mouse models of AD. Collectively, the data suggest targeting Jacob protein‐induced CREB shutoff as a therapeutic avenue against early synaptic dysfunction in AD. Synopsis: The synapto‐nuclear shuttling protein Jacob assembles and docks a signalosome to the transcriptional regulator CREB to promote CREB de‐phosphorylation and neuronal cell death. Here, β‐amyloid peptide (Aβ) is found to cause Alzheimer‐associated synapse loss by regulating nuclear translocation of Jacob, providing a potential target for therapeutic intervention. Aβ promotes nuclear translocation of Jacob in Alzheimer's disease (AD) patient brains and mouse hippocampal neurons.Aβ‐regulated trafficking of Jacob induces transcriptional inactivation of cAMP‐responsive element‐binding protein (CREB), leading to synapse impairment and loss in an AD mouse model.The small‐molecular compound Nitarsone selectively prevents the assembly of the Jacob/LMO4/PP1 signalosome to promote CREB transcriptional activity.Nitarsone prevents synaptic plasticity impairment and cognitive decline in mouse models of AD. [ABSTRACT FROM AUTHOR]

• Recent M. pneumoniae outbreaks show evolving dynamics with public health implications. • Advocating integration of advanced technologies, genomics, and clinical strategies. • Antibiotic resistance in M. pneumoniae underscores the need for antimicrobial stewardship. • AI provides important tools to assist in the diagnosis and treatment of M. pneumoniae. • Assessing current treatments amid evolving resistance highlights the need for novel strategies. Mycoplasma pneumoniae (M. pneumoniae) continues to pose a significant disease burden on global public health as a respiratory pathogen. The antimicrobial resistance among M. pneumoniae strains has complicated the outbreak control efforts, emphasizing the need for robust surveillance systems and effective antimicrobial stewardship programs. This review comprehensively investigates studies stemming from previous outbreaks to emphasize the multifaceted nature of M. pneumoniae infections, encompassing epidemiological dynamics, diagnostic innovations, antibiotic resistance, and therapeutic challenges. We explored the spectrum of clinical manifestations associated with M. pneumoniae infections, emphasizing the continuum of disease severity and the challenges in gradating it accurately. Artificial intelligence and machine learning have emerged as promising tools in M. pneumoniae diagnostics, offering enhanced accuracy and efficiency in identifying infections. However, their integration into clinical practice presents hurdles that need to be addressed. Further, we elucidate the pivotal role of pharmacological interventions in controlling and treating M. pneumoniae infections as the efficacy of existing therapies is jeopardized by evolving resistance mechanisms. Lessons learned from previous outbreaks underscore the importance of adaptive treatment strategies and proactive management approaches. Addressing these complexities demands a holistic approach integrating advanced technologies, genomic surveillance, and adaptive clinical strategies to effectively combat this pathogen. [ABSTRACT FROM AUTHOR]

Understanding changes in the expression of genes involved in regulating various components of the neural extracellular matrix (ECM) during aging can provide an insight into aging-associated decline in synaptic and cognitive functions. Hence, in this study, we compared the expression levels of ECM-related genes in the hippocampus of young, aged and very aged mice. ECM gene expression was downregulated, despite the accumulation of ECM proteoglycans during aging. The most robustly downregulated gene was carbohydrate sulfotransferase 3 (Chst3), the enzyme responsible for the chondroitin 6-sulfation (C6S) of proteoglycans. Further analysis of epigenetic mechanisms revealed a decrease in H3K4me3, three methyl groups at the lysine 4 on the histone H3 proteins, associated with the promoter region of the Chst3 gene, resulting in the downregulation of Chst3 expression in non-neuronal cells. Cluster analysis revealed that the expression of lecticans—substrates of CHST3—is tightly co-regulated with this enzyme. These changes in ECM-related genes were accompanied by an age-confounded decline in cognitive performance. Despite the co-directional impairment in cognitive function and average Chst3 expression in the studied age groups, at the individual level we found a negative correlation between mRNA levels of Chst3 and cognitive performance within the very aged group. An analysis of correlations between the expression of ECM-related genes and cognitive performance in novel object versus novel location recognition tasks revealed an apparent trade-off in the positive gene effects in one task at the expense of another. Further analysis revealed that, despite the reduction in the Chst3 mRNA, the expression of CHST3 protein is increased in glial cells but not in neurons, which, however, does not lead to changes in the absolute level of C6S and even results in the decrease in C6S in perineuronal, perisynaptic and periaxonal ECM relative to the elevated expression of its protein carrier versican. [ABSTRACT FROM AUTHOR]

Achieving the desired final protein formulation using ultrafiltration/diafiltration (UF/DF) operations is an essential component of many protein purification processes. It is well documented that differences in the excipient and buffer concentrations exist between the DF and retentate solutions when they have achieved equilibrium. Several publications have proposed ways to calculate these differences. However, the accuracy of these methods has been limited by the use of an estimated protein charge value. In this article, a small-scale system is described, which can accurately determine the protein charge by making buffer and excipient concentration measurements and applying the determined values to the Donnan and volume exclusion equations. This information can be utilized to generate a standard curve, which in turn can be applied to at-scale UF/DF operations. For 2 different antibodies, the standard curve generated by the small-scale system yielded buffer concentrations and pH values that agreed well with those generated after UF/DF operations, whereas using the theoretical protein charge caused a departure from the measured results. This model also provides good estimates as to how the final formulation pH and buffer concentration vary as a function of the pH and buffer concentration in the DF buffer. This information is of important utility for the accurate formulation of high-concentration protein solutions (>100 mg/mL) where the coconcentration of buffers and the volume exclusion of certain excipients are amplified. The low material requirements of the small-scale system are a major benefit for early phase formulation and process development when sufficient time and material may not be available, in particular to ensure successful UF/DF operations for the development of high protein concentration formulations. [ABSTRACT FROM AUTHOR]

Acne is a common skin condition that affects people of all ages and can lead to significant physical and psychological distress. The first line of action against acne is topical products, though the most effective are topical antibiotics. In such a scenario, the development of effective and safe herbal formulations for the treatment of acne is of great importance. Rubia cordifolia , Aloe barbadensis , and Allium cepa extracts are rich sources of bioactive metabolites and are safe compared with antibiotics, in addition to being cost effective, sustainable, and eco-friendly. Also, their combination has not been studied for treating acne, and their potential benefits need to be investigated. The present study aimed to develop an effective polyherbal gel formulation of R. cordifolia , A. barbadensis , and A. cepa combined extract for treating acne and validate its effect with reference to conventional antibiotics. Plant materials were extracted in water by the reflux method, and phytochemical analysis was done for flavonoid, anthraquinone, and phenolic contents. The combined extract ( R. cordifolia , A. barbadensis , and A. cepa extracts) was formulated in gel. The selected polyherbal gel was evaluated for in vitro antibacterial activity using agar well diffusion against Cutibacterium acnes ( P. acnes) culture. Phytochemical analysis of the composite extract revealed the rich presence of flavonoids, phenolics, and anthraquinones. The polyherbal gels showed good physicochemical properties; however, FCEG-4 was selected for further studies. It was found to be effective against C. acnes (MTCC 1951) in agar well diffusion, as it showed a similar zone of inhibition as that of standard. Also, during in vivo studies, FCEG-4 showed comparable efficacy with clindamycin gel. It was concluded from the study that composite extracts incorporated in an aqueous-based gel system were effective in topical therapy of mild acne vulgaris, showing similar efficacy to that of clindamycin cream.

Due to the its high abundance, iron ion contamination and toxicity is one of the most challenging issue for living beings. Although, iron is extremenly important for several body functions, excess amount of iron in the body can also be fatal. In last century, rapid industrialization, iron extraction and mismanagement of industrial waste disposal leads to iron contamination in water bodies. Therefore, versatile iron sensors needs to be develop which can be employed for detection in biological as well as real water samples. 8-hydroxyquinoline is well-known for its strong affinity towards transition metals including Fe 3+ . In this regard, we have synthesised benzothiazole-quinoline derived 1,2,3- triazole (4HBTHQTz), in which 4-(benzo[d]thiazol-2-yl)phenolic (4-HBT) group acts as a fluorophore. 4HBTHQTz showed high fluorescence and induced a selective decrease in fluorescence with Fe 3+ at 380 nm (λ ex.  = 320 nm). The detection limit of 4HBTHQTz with Fe 3+ is calculated as 0.64 μM, which is lower than the WHO recommended limit in drinking water. 4HBTHQTz works over the 5-8 pH range and has shown promising results for quantitative detection of Fe 3+ in water samples collected from tap, river and seawater. 4HBTHQTz can also detect the Fe 3+ in biological samples which is confirmed by fluorescence cell imaging using L929 mouse fibroblast cells. Overall, 4HBTHQTz showed advantages such as high selectivity, quick detection, and good limit of detection (LOD) for Fe 3+ ., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The dedicator of cytokinesis (DOCK)/engulfment and cell motility (ELMO) complex serves as a guanine nucleotide exchange factor (GEF) for the GTPase Rac. RhoG, another GTPase, activates the ELMO-DOCK-Rac pathway during engulfment and migration. Recent cryo-EM structures of the DOCK2/ELMO1 and DOCK2/ELMO1/Rac1 complexes have identified closed and open conformations that are key to understanding the autoinhibition mechanism. Nevertheless, the structural details of RhoG-mediated activation of the DOCK/ELMO complex remain elusive. Herein, we present cryo-EM structures of DOCK5/ELMO1 alone and in complex with RhoG and Rac1. The DOCK5/ELMO1 structure exhibits a closed conformation similar to that of DOCK2/ELMO1, suggesting a shared regulatory mechanism of the autoinhibitory state across DOCK-A/B subfamilies (DOCK1-5). Conversely, the RhoG/DOCK5/ELMO1/Rac1 complex adopts an open conformation that differs from that of the DOCK2/ELMO1/Rac1 complex, with RhoG binding to both ELMO1 and DOCK5. The alignment of the DOCK5 phosphatidylinositol (3,4,5)-trisphosphate binding site with the RhoG C-terminal lipidation site suggests simultaneous binding of RhoG and DOCK5/ELMO1 to the plasma membrane. Structural comparison of the apo and RhoG-bound states revealed that RhoG facilitates a closed-to-open state conformational change of DOCK5/ELMO1. Biochemical and surface plasmon resonance (SPR) assays confirm that RhoG enhances the Rac GEF activity of DOCK5/ELMO1 and increases its binding affinity for Rac1. Further analysis of structural variability underscored the conformational flexibility of the DOCK5/ELMO1/Rac1 complex core, potentially facilitating the proximity of the DOCK5 GEF domain to the plasma membrane. These findings elucidate the structural mechanism underlying the RhoG-induced allosteric activation and membrane binding of the DOCK/ELMO complex., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

A highly divergent bovine calicivirus was identified in an Indian calf with enteritis. The whole genome of this virus was sequenced, revealing distinct amino acid motifs in the polyprotein encoded by open reading frame 1 (ORF1) that are unique to caliciviruses. Phylogenetic analysis showed that it was related to members of the genus Nebovirus of the family Caliciviridae. Although it showed only 33.7-34.2% sequence identity in the VP1 protein to the nebovirus prototype strains, it showed 90.6% identity in VP1 to Kirklareli virus, a nebovirus detected in calves with enteritis in Turkey in 2012. An in-house-designed and optimized reverse transcription polymerase chain reaction (RT-PCR) assay was used to screen 120 archived bovine diarrhoeic fecal samples, 40 each from the Indian states of Uttar Pradesh, Haryana, and Himachal Pradesh, revealing frequent circulation of these divergent caliciviruses in the bovine population, with an overall positivity rate of 64.17% (77/120). This underscores the importance of conducting a comprehensive investigation of the prevalence of these divergent caliciviruses and assessing their associations with other pathogens responsible for enteritis in India., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

An explosive is a container that is filled with material that will explode when it is thrown or dropped, or when a device inside it makes it explode. Many materials can be used in making up of a bomb individually or when mixed with some other chemical. The type of explosive that gets misused most commonly are those used in manufacturing and other commercial applications due to their easy accessibility to public. Improper handling and inattentive behavior toward the explosives can lead to disastrous circumstances. Here we report such a case in which a 30-year-old male took rocks of potassium sulphate (called Gandhak Potash in the local vernacular language) and struck them with a metallic pestle, which triggered an explosion. The distal phalanges of both hands were found traumatically amputated. Stippling effect due to unburnt powdered explosive substance were present over the head, face, chest, and anteromedial aspect of legs. He died within few hours after the blast. Different type of mechanical injuries and injuries to the internal organs can be sustained over the body due to effects of explosion as we've seen in our case, that is, abrasion, contusion, lacerations, fractures, burn injury and such pattern of injury, and specific injuries sustained due to pressure effect like blast lung along with circumstantial evidence helps in deciding the manner of death., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© 2024 The Author(s).)

Neboviruses (NeVs) from the Caliciviridae family have been linked to enteric diseases in bovines and have been detected worldwide. As viruses rely entirely on the cellular machinery of the host for replication, their ability to thrive in a specific host is greatly impacted by the specific codon usage preferences. Here, we systematically analyzed the codon usage bias in NeVs to explore the genetic and evolutionary patterns. Relative Synonymous Codon Usage and Effective Number of Codon analyses indicated a marginally lower codon usage bias in NeVs, predominantly influenced by the nucleotide compositional constraints. Nonetheless, NeVs showed a higher codon usage bias for codons containing G/C at the third codon position. The neutrality plot analysis revealed natural selection as the primary factor that shaped the codon usage bias in both the VP1 (82%) and VP2 (57%) genes of NeVs. Furthermore, the NeVs showed a highly comparable codon usage pattern to bovines, as reflected through Codon Adaptation Index and Relative Codon Deoptimization Index analyses. Notably, yak NeVs showed considerably different nucleotide compositional constraints and mutational pressure compared to bovine NeVs, which appear to be predominantly host-driven. This study sheds light on the genetic mechanism driving NeVs' adaptability, evolution, and fitness to their host species.

The article has been withdrawn at the request of the authors of the journal "Central Nervous System Agents in Medicinal Chemistry" as a conflict has arisen among the authors in adding another author at the later stage of publication, Bentham Science apologizes to the readers of the journal for any inconvenience this may have caused., The Bentham Editorial Policy on Article Withdrawal can be found at https://benthamscience.com/editorial-policies-main.php, Bentham Science Disclaimer: It is a condition of publication that manuscripts submitted to this journal have not been published and will not be simultaneously submitted or published elsewhere. Furthermore, any data, illustration, structure or table that has been published elsewhere must be reported, and copyright permission for reproduction must be obtained. Plagiarism is strictly forbidden, and by submitting the article for publication the authors agree that the publishers have the legal right to take appropriate action against the authors, if plagiarism or fabricated information is discovered. By submitting a manuscript the authors agree that the copyright of their article is transferred to the publishers if and when the article is accepted for publication., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Diabetes mellitus remains a global health challenge, demanding innovative therapeutic strategies. Herbal remedies have garnered attention for their potential in diabetes management, and recent advancements in nanotechnology have enabled the development of herbal nanoformulations with enhanced efficacy and bioavailability., Objective: This review aimed to comprehensively analyze the mechanisms, formulations, and clinical impact of herbal nanoformulations in managing diabetes mellitus., Method: A systematic literature search was conducted to identify relevant studies exploring the mechanisms of action, various formulations, and clinical outcomes of herbal nanoformulations in diabetes management., Result: Herbal nanoformulations exert their anti-diabetic effects through multiple mechanisms, including enhanced bioavailability, improved tissue targeting, and potentiation of insulin signaling pathways. Various herbal ingredients, such as bitter melon, fenugreek, and Gymnema sylvestre, have been encapsulated into nanocarriers, like liposomes, polymeric nanoparticles, and solid lipid nanoparticles, to enhance their therapeutic potential. Clinical studies have demonstrated promising results, showing improvements in glycemic control, lipid profile, and antioxidant status with minimal adverse effects., Conclusion: Herbal nanoformulations represent a promising avenue for the management of diabetes mellitus, offering improved therapeutic outcomes compared to conventional herbal preparations. Further research is warranted to optimize formulation strategies, elucidate long-term safety profiles, and explore the potential synergistic effects of herbal nanoformulations in combination therapies for diabetes management., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

After the emergence of the COVID-19 pandemic in late 2019, the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has undergone a dynamic evolution driven by the acquisition of genetic modifications, resulting in several variants that are further classified as variants of interest (VOIs), variants under monitoring (VUM) and variants of concern (VOC) by World Health Organization (WHO). Currently, there are five SARS-CoV-2 VOCs (Alpha, Beta, Delta, Gamma and Omicron), two VOIs (Lambda and Mu) and several other VOIs that have been reported globally. In this study, we report a natural compound, Curcumin, as the potential inhibitor to the interactions between receptor binding domain (RBD(S1)) and human angiotensin-converting enzyme 2 (hACE2) domains and showcased its inhibitory potential for the Delta and Omicron variants through a computational approach by implementing state of the art methods. The study for the first time revealed a higher efficiency of Curcumin , especially for hindering the interaction between RBD(S1) and hACE-2 domains of Delta and Omicron variants as compared to other lead compounds. We investigated that the mutations in the RBD(S1) of VOC especially Delta and Omicron variants affect its structure compared to that of the wild type and other variants and therefore altered its binding to the hACE2 receptor. Molecular docking and molecular dynamics (MD) simulation analyses substantially supported the findings in terms of the stability of the docked complexes. This study offers compelling evidence, warranting a more in-depth exploration into the impact of these alterations on the binding of identified drug molecules with the Spike protein. Further investigation into their potential therapeutic effects in vivo is highly recommended.Communicated by Ramaswamy H. Sarma.

Fluorescent and colourimetric probes for small analytes (cations, anions and neutral molecules) have drawn significant attention in recent years. These probes interact with analytes and induce spectral change due to the variations in the photo-physical properties of the fluorophore/chromophore used. Among several photo-physical mechanisms, ESIPT (excited state intramolecular proton transfer) based probes are more advantageous due to their photo-physical properties viz. solvent polarity effect, large spectral shift with multi-channel fluorescence, high quantum yield etc. In recent years, ESIPT-based probes have shown several promising applications, especially monitoring small analytes in biological samples, smartphone app-assisted heavy metal detection in environmental samples, inkless writing, anti-counterfeiting applications etc. Therefore, this review is dedicated to recently reported ESIPT-based probes for small analytes. We have highlighted the organic units responsible for the ESIPT mechanism, their photo-physical parameters, selectivity and sensitivity properties and recent advances in their applications.

Epilepsy is the most general, extensive, and severe neurological disorder, affecting more than 50 million individuals globally. Initially, conventional medicines and simple salts like potassium bromide were employed as antiepileptic medication candidates. Nowadays, many anticonvulsant drugs have been discovered as first-generation and second-generation and newer drugs and are still in development phases. The pharmacophore-based drug design process includes pharmacophore modeling and validation, pharmacophore-based virtual screening, virtual hits profiling, and lead identification with special reference. This comprehensive article reviews recently developed anticonvulsant derivatives on the basis of pharmacophoric approaches. A literature survey was performed using various search engines like Google Scholar, Scopus, Sci Finder, ScienceDirect, Science gate, Scilit, PubMed, NINDS database of NIH, Bentham Sciences, and other online and print journals and scientific databases. The presented review discusses such kinds of newer drugs that are in the market as well as in clinical trial phases. Detailed outcomes of pharmacophoric modeling have been discussed for newly derived derivatives like targets involved in Epilepsy, lead molecules etc., for the treatment of epilepsy. This exhaustive review will assist the researchers in the further development of potential antiepileptic agents., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Multiple severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants continue to evolve carrying flexible amino acid substitutions in the spike protein's receptor binding domain (RBD). These substitutions modify the binding of the SARS-CoV-2 to human angiotensin-converting enzyme 2 (hACE2) receptor and have been implicated in altered host fitness, transmissibility, and efficacy against antibody therapeutics and vaccines. Reliably predicting the binding strength of SARS-CoV-2 variants RBD to hACE2 receptor and neutralizing antibodies (NAbs) can help assessing their fitness, and rapid deployment of effective antibody therapeutics, respectively. Here, we introduced a two-step computational framework with 3-fold validation that first identified dissociation constant as a reliable predictor of binding affinity in hetero- dimeric and trimeric protein complexes. The second step implements dissociation constant as descriptor of the binding strengths of SARS-CoV-2 variants RBD to hACE2 and NAbs. Then, we examined several variants of concerns (VOCs) such as Alpha, Beta, Gamma, Delta, and Omicron and demonstrated that these VOCs RBD bind to the hACE2 with enhanced affinity. Furthermore, the binding affinity of Omicron variant's RBD was reduced with majority of the RBD-directed NAbs, which is highly consistent with the experimental neutralization data. By studying the atomic contacts between RBD and NAbs, we revealed the molecular footprints of four NAbs (GH-12, P2B-1A1, Asarnow_3D11, and C118)-that may likely neutralize the recently emerged Omicron variant-facilitating enhanced binding affinity. Finally, our findings suggest a computational pathway that could aid researchers identify a range of current NAbs that may be effective against emerging SARS-CoV-2 variants., (© 2023 Wiley Periodicals LLC.)

Biothiols (cysteine, homocysteine, and glutathione) are an important class of compounds with a free thiol group. These biothiols plays an important role in several metabolic processes in living bodies when present in optimum concentration. Researchers have developed several probes for the detection and quantification of biothiols that can absorb in UV, visible, and near-infrared (NIR) regions of the electromagnetic spectrum. Among them, NIR organic probes have attracted significant attention due to their application in in vivo and in vitro imaging. In this review, we have summarized probes for these biothiols, which could work in the NIR region, and discussed their sensing mechanism and potential applications. Along with focusing on the pros and cons of the reported probes we have classified them according to the fluorophore used and summarized their photophysical and sensing properties (emission, response time, limit of detection)., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)