Naphthalimide-based new architecture for fluorescence turn-on sensing of Cu2+ and colorimetric detection of F-/CN.

A new molecular structure 1 has been developed on naphthalimide motif. The amine and triazole binding groups have been employed at the 4-position of naphthalimide to explore the sensing behavior of molecule 1. Single crystal x-ray diffraction and other spectroscopic techniques confirm the identity of 1. Compound 1 exhibits high selectivity and sensitivity for Cu2+ ions in CH3CN. The binding of Cu2+ shows âˆ¼ 70-fold enhancement in emission at 520 nm. The binding follows 1:1 interaction and the detection limit is determined to be 6.49 × 10-7 M. The amine-triazole binding site in 1 also corroborates the detection of F- through a colour change in CH3CN. Initially H-bonding and then deprotonation of amine -NH- in the presence of F- are the sequential steps involved in F- recognition with a detection limit of 4.13 × 10-7 M. Compound 1 is also sensible to CN- like F- ion and they are distinguished by Fe3+ ion. Cu2+-ensemble of 1 fluorimetrically recognizes F- among the tested anions and vice-versa. The collaborative effect of amine and triazole motifs in the binding of both Cu2+ and F-/CN- has been explained by DFT calculation.

ApCPS2 contributes to medicinal diterpenoid biosynthesis and defense against insect herbivore in Andrographis paniculata.

Kalmegh (Andrographis paniculata) spatiotemporally produces medicinally-important ent-labdane-related diterpenoids (ent-LRDs); andrographolide (AD), 14-deoxy-11,12-didehydroandrographolide (DDAD), neoandrographolide (NAD). ApCPS1 and ApCPS2, the ent-copalyl pyrophosphate (ent-CPP)-producing class II diterpene synthases (diTPSs) were identified, but their contributions to ent-CPP precursor supply for ent-LRD biosynthesis were not well understood. Here, we characterized ApCPS4, an additional ent-CPP-forming diTPS. Further, we elucidated in planta function of the ent-CPP-producing diTPSs (ApCPS1,2,4) by integrating transcript-metabolite co-profiles, biochemical analysis and gene functional characterization. ApCPS1,2,4 localized to the plastids, where diterpenoid biosynthesis occurs in plants, but ApCPS1,2,4 transcript expression patterns and ent-LRD contents revealed a strong correlation of ApCPS2 expression and ent-LRD accumulation in kalmegh. ApCPS1,2,4 upstream sequences differentially activated ß-glucuronidase (GUS) in Arabidopsis and transiently-transformed kalmegh. Similar to higher expression of ApCPS1 in kalmegh stem, ApCPS1 upstream sequence activated GUS in stem/hypocotyl of Arabidopsis and kalmegh. However, ApCPS2,4 upstream sequences weakly activated GUS expression in Arabidopsis, which was not well correlated with ApCPS2,4 transcript expression in kalmegh tissues. Whereas, ApCPS2,4 upstream sequences could activate GUS expression at a considerable level in kalmegh leaf and roots/calyx, respectively, suggesting the involvement of transcriptional regulator(s) of ApCPS2,4 that might participate in kalmegh-specific diterpenoid pathway. Interestingly, ApCPS2-silenced kalmegh showed a drastic reduction in AD, DDAD and NAD contents and compromised defense against insect herbivore Spodoptera litura. However, ent-LRD contents and herbivore defense in ApCPS1 or ApCPS4-silenced plants remained largely unaltered. Overall, these results suggested an important role of ApCPS2 in producing ent-CPP for medicinal ent-LRD biosynthesis and defense against insect herbivore.

A comprehensive literature scoping review of infection prevention and control methods for viral-mediated gene therapies.

Objective: This comprehensive literature scoping review outlines available infection prevention and control (IPC) methods for viral-mediated gene therapies and provides one IPC strategy for the healthcare setting based on a single-center recommendation. Methods: A team of experts in pharmacy, healthcare epidemiology, and biosafety with experience in viral-mediated gene therapy was assembled within a pediatric hospital to conduct a comprehensive literature scoping review. The comprehensive review included abstracts and full-text articles published since 2009 and utilized prespecified search terms of the five viral vectors of interest: adenovirus (AV), retrovirus (RV), adeno-associated virus (AAV), lentivirus (LV), and herpes simplex virus (HSV). Case reports, randomized controlled trials, and bench research studies were all included, while systematic reviews were excluded. Results: A total of 4473 case reports, randomized control trials, and benchtop research studies were identified using the defined search criteria. Chlorine compounds were found to inactivate AAV and AV, while alcohol-based disinfectants were ineffective. There was a relative paucity of studies investigating surface-based disinfection for HSV, however, alcohol-based disinfectants were effective in one study. Ultraviolent irradiation was also found to inactivate HSV in numerous studies. No studies investigated disinfection for LV and RV vectors. Conclusions: The need to define IPC methods is high due to the rapid emergence of viral-mediated gene therapies to treat rare diseases, but published clinical guidance remains scarce. In the absence of these data, our center recommends a 1:10 sodium hypochlorite solution in clinical and academic environments to ensure complete germicidal activity of viral-mediated gene therapies.

Iodine(III)-promoted oxidative carbotrifluoromethylation of maleimides with imidazopyridines and Langlois' reagent.

A metal-free protocol for oxidative carbotrifluoromethylation of maleimides with imidazopyridines and Langlois' reagent has been developed using (diacetoxyiodo)benzene (PIDA) as an oxidant. This three-component strategy enables one-step construction of 3,4-disubstituted maleimides in good yields with high functional group tolerance. Both experimental and theoretical studies support the proposed radical reaction mechanism.

High-level biosynthesis of enantiopure germacrene D in yeast.

Germacrene D, a sesquiterpenoid compound found mainly in plant essential oils at a low level as (+) and/or (-) enantiomeric forms, is an ingredient for the fragrance industry, but a process for the sustainable supply of enantiopure germacrene D is not yet established. Here, we demonstrate metabolic engineering in yeast (Saccharomyces cerevisiae) achieving biosynthesis of enantiopure germacrene D at a high titer. To boost farnesyl pyrophosphate (FPP) flux for high-level germacrene D biosynthesis, a background yeast chassis (CENses5C) was developed by genomic integration of the expression cassettes for eight ergosterol pathway enzymes that sequentially converted acetyl-CoA to FPP and by replacing squalene synthase promoter with a copper-repressible promoter, which restricted FPP flux to the competing pathway. Galactose-induced expression of codon-optimized plant germacrene D synthases led to 13-30 fold higher titers of (+) or (-)-germacrene D in CENses5C than the parent strain CEN.PK2.1C. Furthermore, genomic integration of germacrene D synthases in GAL80, LPP1 and rDNA loci generated CENses8(+D) and CENses8(-D) strains, which produced 41.36 µg/ml and 728.87 µg/ml of (+) and (-)-germacrene D, respectively, without galactose supplementation. Moreover, coupling of mitochondrial citrate pool to the cytosolic acetyl-CoA, by expressing a codon-optimized ATP-citrate lyase of oleaginous yeast, resulted in 137.71 µg/ml and 815.81 µg/ml of (+) or (-)-germacrene D in CENses8(+D)* and CENses8(-D)* strains, which were 67-120 fold higher titers than in CEN.PK2.1C. In fed-batch fermentation, CENses8(+D)* and CENses8(-D)* produced 290.28 µg/ml and 2519.46 µg/ml (+) and (-)-germacrene D, respectively, the highest titers in shake-flask fermentation achieved so far. KEY POINTS: • Engineered S. cerevisiae produced enantiopure (+) and (-)-germacrene D at high titers • Engineered strain produced up to 120-fold higher germacrene D than the parental strain • Highest titers of enantiopure (+) and (-)-germacrene D achieved so far in shake-flask.

Genetic Underpinnings of Pulmonary Fibrosis: An Overview.

INTRODUCTION: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive disorder, in which genetic and environmental factors are involved in disease onset. Although, by definition, the disease is considered idiopathic in nature, evidence-based studies have indicated familial cases of pulmonary fibrosis, in which genetic factors contribute to IPF pathogenesis. METHODS: Both common as well as rare genetic variants are associated with sporadic as well as familial forms of IPF. Although clinical inferences of the genetic association have still not been explored properly, observation-based studies have found a genotypic influence on disease development and outcome. RESULTS: Based on genetic studies, individuals with a risk of IPF can be easily identified and can be classified more precisely. Identification of genetic variants also helps to develop more effective therapeutic approaches. CONCLUSION: Further comprehensive research is needed to get a blueprint of IPF pathogenesis. The rapidly evolving field of genetic engineering and molecular biology, along with the bioinformatics approach, will possibly explore a new horizon very soon to achieve this goal.

Surface nanocrystallization enhances the biomedical performance of additively manufactured stainless steel.

Additive manufacturing enables the fabrication of patient-specific implants of complex geometries. Although selective laser melting (SLM) of 316L stainless steel (SS) is well established, post-processing is essential to preparing high-performance biomedical implants. The goal of this study was to investigate surface mechanical attrition treatment (SMAT) as a means to enhance the electrochemical, biomechanical, and biological performances of 316L SS fabricated by SLM in devices for the repair of bone tissues. The SMAT conditions were optimized to induce surface nanocrystallization on the additively manufactured samples. SMAT resulted in a thicker oxide layer, which provided corrosion resistance by forming a passive layer. The fretting wear results showed that the rate of wear decreased after SMAT owing to the formation of a harder nanostructured layer. Surface modification of the alloy by SMAT enhanced its ability to support the attachment and proliferation of pre-osteoblasts in vitro. The study of the response in vivo to the additively manufactured alloy in a critical-sized cranial defect murine model revealed enhanced interactions with the cellular components after the alloy was subjected to SMAT without inducing any adverse immune response. Taken together, the results of this work establish SMAT of additively manufactured metallic implants as an effective strategy for engineering next-generation, high-performance medical devices for orthopedics and craniomaxillofacial applications.

A rare presentation of dengue fever: bilateral psoas muscle hematoma, intrahepatic cholestatic hepatitis, pancreatitis and pancytopenia.

Dengue is the foremost cause of arthropod-borne viral disease in the world. It is and commonly found in tropical and subtropical parts of the world. Dengue fever is caused by one of the four distinct serotypes (DENV 1-4) of single-stranded RNA Flavivirus genus and transmitted through Aedes mosquito. Infection caused by one serotype develops lifelong immunity to that serotype, but not to others. Dengue fever (DF) presents with high fever, headache, myalgia, and arthralgia, and rash. Severe dengue, dengue haemorrhagic fever (DHF), and dengue shock syndrome (DSS) are accompanied by thrombocytopenia, vascular leakage, and hypotension. DSS is characterized by shock, which can be fatal with case fatality high as 12% to 44%. There are few atypical manifestations of dengue fever growing with rising disease burden, often missed and sometimes difficult to diagnosis. In this case report, we will discuss atypical manifestations of bilateral psoas muscle hematoma, intrahepatic cholestatic hepatitis, pancreatitis and pancytopenia observed in dengue fever patient.

Unraveling the terpene synthase family and characterization of BsTPS2 contributing to (S)-( +)-linalool biosynthesis in Boswellia.

Boswellia tree bark exudes oleo-gum resin in response to wounding, which is rich in terpene volatiles. But, the molecular and biochemical basis of wound-induced formation of resin volatiles remains poorly understood. Here, we combined RNA-sequencing (RNA-seq) and metabolite analysis to unravel the terpene synthase (TPS) family contributing to wound-induced biosynthesis of resin volatiles in B. serrata, an economically-important Boswellia species. The analysis of large-scale RNA-seq data of bark and leaf samples representing more than 600 million sequencing reads led to the identification of 32 TPSs, which were classified based on phylogenetic relationship into various TPSs families found in angiosperm species such as TPS-a, b, c, e/f, and g. Moreover, RNA-seq analysis of bark samples collected at 0-24 h post-wounding shortlisted 14 BsTPSs that showed wound-induced transcriptional upregulation in bark, suggesting their important role in wound-induced biosynthesis of resin volatiles. Biochemical characterization of a bark preferentially-expressed and wound-inducible TPS (BsTPS2) in vitro and in planta assays revealed its involvement in resin terpene biosynthesis. Bacterially-expressed recombinant BsTPS2 catalyzed the conversion of GPP and FPP into (S)-( +)-linalool and (E)-(-)-nerolidol, respectively, in vitro assays. However, BsTPS2 expression in Nicotiana benthamiana found that BsTPS2 is a plastidial linalool synthase. In contrast, cytosolic expression of BsTPS2 did not form any product. Overall, the present work unraveled a suite of TPSs that potentially contributed to the biosynthesis of resin volatiles in Boswellia and biochemically characterized BsTPS2, which is involved in wound-induced biosynthesis of (S)-( +)-linalool, a monoterpene resin volatile with a known role in plant defense.

Biological evaluation of the novel 3,3'-((4-nitrophenyl)methylene)bis(4-hydroxy-2H-chromen-2-one) derivative as potential anticancer agents via the selective induction of reactive oxygen species-mediated apoptosis.

Selective initiation of programmed cell death in cancer cells than normal cells is reflected as an attractive chemotherapeutic strategy. In the current study, a series of synthetic bis-coumarin derivatives were synthesized possessing reactive oxygen species (ROS) modulating functional groups and examined in four cancerous and two normal cell lines for their cytotoxic ability using MTT assay. Among these compounds, 3 l emerged as the most promising derivative in persuading apoptosis in human renal carcinoma cells (SKRC-45) among diverse cancer cell lines. 3 l causes significantly less cytotoxicity to normal kidney cells compared to cisplatin. This compound was able to induce apoptosis and cell-cycle arrest by modulating the p53 mediated apoptotic pathways via the generation of ROS, decreasing mitochondrial membrane potential, and causing DNA fragmentation. Unlike cisplatin, the 3 l derivative was found to inhibit the nuclear localisation of NF-κB in SKRC-45 cells. It was also found to reduce the proliferation, survival and migration ability of SKRC-45 cells by downregulating COX-2/ PTGES2 cascade and MMP-2. In an in vivo tumor model, 3 l showed an anticancer effect by reducing the mean tumor mass, volume and inducing caspase-3 activation, without affecting kidney function. Further studies are needed to establish 3 l as a promising anti-cancer drug candidate.

Recent advances in triterpenoid pathway elucidation and engineering.

Triterpenoids are among the most assorted class of specialized metabolites found in all the taxa of living organisms. Triterpenoids are the leading active ingredients sourced from plant species and are utilized in pharmaceutical and cosmetic industries. The triterpenoid precursor 2,3-oxidosqualene, which is biosynthesized via the mevalonate (MVA) pathway is structurally diversified by the oxidosqualene cyclases (OSCs) and other scaffold-decorating enzymes such as cytochrome P450 monooxygenases (P450s), UDP-glycosyltransferases (UGTs) and acyltransferases (ATs). A majority of the bioactive triterpenoids are harvested from the native hosts using the traditional methods of extraction and occasionally semi-synthesized. These methods of supply are time-consuming and do not often align with sustainability goals. Recent advancements in metabolic engineering and synthetic biology have shown prospects for the green routes of triterpenoid pathway reconstruction in heterologous hosts such as Escherichia coli, Saccharomyces cerevisiae and Nicotiana benthamiana, which appear to be quite promising and might lead to the development of alternative source of triterpenoids. The present review describes the biotechnological strategies used to elucidate complex biosynthetic pathways and to understand their regulation and also discusses how the advances in triterpenoid pathway engineering might aid in the scale-up of triterpenoid production in engineered hosts.

Visible Light Induced Three-Component 1,2-Dicarbofunctionalization of Alkenes and Alkynes.

Harnessing visible-light in organic synthesis is one of the most effective methods that aligns with green and sustainable chemistry principles and hence skyrocketed in the last two decades. Similarly, three-component 1,2-dicarbofunctionalization of alkenes and alkynes has recently been a great choice to construct complex molecular systems in an easy and rapid manner. Therefore, light-induced reactions can be an excellent alternative to carry out 1,2-dicarbofunctionalization reactions, and very recently, organic chemists across the globe have fascinated us with their interesting articles. In this present review, we have summarized the recent advancements in the area of visible light induced three-component 1,2-dicarbofunctionalization of alkenes and alkynes till March 2023. We have categorized the discussion based on the catalysts used to carry out the transformations for better understanding and different important aspects of these transformations have also been covered.

A combined 3D-atomic/nanoscale comprehension and ab initio computation of iron carbide structures tailored in Q&P steels via Si alloying.

The essences of the quenching and partitioning (Q&P) process are to stabilize the finely divided retained austenite (RA) via carbon (C) partitioning from supersaturated martensite during partitioning. Competitive reactions, i.e., transition carbide precipitation, C segregation, and decomposition of austenite, might take place concurrently during partitioning. In order to maintain the high volume fraction of RA, it is crucial to suppress the carbide precipitation sufficiently. Since silicon (Si) in the cementite θ (Fe3C) is insoluble, alloying Si in adequate concentrations prolongs its precipitation during the partitioning step. Consequently, C partitioning facilitates the desired chemical stabilization of RA. To elucidate the mechanisms of formation of transition η (Fe2C) carbides as well as cementite, θ (Fe3C), besides the transformation of transition carbides to more stable θ during the quenching and partitioning (Q&P) process, samples of 0.4 wt% C steels tailored with different Si contents were extensively characterized for microstructural evolution at different partitioning temperatures (TP) using high resolution transmission electron microscopy (HR-TEM) and three-dimensional atom probe tomography (3D-APT). While 1.5 wt% Si in the steel allowed only the formation of η carbides even at a high TP of 300 °C, reduction in Si content to 0.75 wt% only partially stabilized η carbides, allowing limited η → θ transformation. With 0.25 wt% Si, only θ was present in the microstructure, suggesting a η → θ transition during the early partitioning stage, followed by coarsening due to enhanced growth kinetics at 300 °C. Although η carbides precipitated in martensite under paraequilibrium conditions at 200 °C, θ carbides precipitated under negligible partitioning local equilibrium conditions at 300 °C. Competition with the formation of orthorhombic η and θ precipitation further examined via ab initio (density functional theory, DFT) computation and a similar probability of formation/thermodynamic stability were obtained. With an increase in Si concentration, the cohesive energy decreased when Si atoms occupied C positions, indicating decreasing stability. Overall, the thermodynamic prediction was in accord with the HR-TEM and 3D-APT results.

Redox-neutral carbon-heteroatom bond formation under photoredox catalysis.

Recently, visible-light-mediated photoredox catalysis has been emerging as one of the fastest growing fields in organic chemistry because of its low cost, easy availability and environmental benignness. In the past five years, a new yet challenging trend, visible-light-induced redox-neutral carbon-heteroatom bond formation reaction involving presumed radical intermediates, has been flourishing rapidly. Although mostly transition metal-based photoredox catalysts were reported, a few organophotoredox catalysts have also shown efficacy towards carbon-heteroatom bond formation reactions. This review intends to summarize the recent research progress in redox-neutral carbon-heteroatom bond formations based on active intermediate(s) involved under photoredox catalysis.

Visible-light-induced cascade reaction: a sustainable approach towards molecular complexity.

Photoredox catalysis has demonstrated rapid evolution in the field of synthetic organic chemistry. On the other hand, the splendour of cascade reactions in providing complex molecular architectures renders them a cutting-edge research area. Therefore, the merging of photocatalysis with cascade synthesis brings out a synthetic paradigm with immense potential. The development of photocascade catalysis for a target molecule with a particular molecular skeleton and stereochemical framework presents certain challenges but provides a robust and environmentally benign synthetic alternative. This comprehensive review assembles all the accomplishments and highlights of visible-light-induced cascade reactions with literature coverage up to October 2022.

Enantioselective terpene emission signifies forest climate response mechanism.

Forest vegetation produces terpene enantiomers, but atmospheric emission mechanisms and ecological functions remain poorly understood. In a study on the tropical rainforest ecosystem, Byron et al. noticed distinct diel trends and sources of enantiomer emission, and a striking change in (-)-α-pinene emission under severe drought, which might favor cloud formation.

Recent advances in carbosilylation of alkenes and alkynes.

Alkene and alkyne difunctionalization is a flexible process that allows the construction of two functional groups simultaneously in one step. On the other hand, carbosilylation, an ingenious difunctionalization pathway to concurrently incorporate both a silyl group and an organic functional group (alkyl, (hetero)aryl, alkenyl, alkynyl and allenyl) across a carbon-carbon multiple-bond system, is achieving immense interest in recent days. This review article provides a decade's update on the discoveries and developments in the synthesis of carbosilylated products from two very important carbon-carbon unsaturated substrates, alkenes and alkynes.

pH-responsive and targeted delivery of chrysin via folic acid-functionalized mesoporous silica nanocarrier for breast cancer therapy.

Cancer is a disease of global importance. In order to mitigate conventional chemotherapy-related side effects, phytochemicals with inherent anticancer efficacy have been opted. However, the use of nanotechnology is essential to enhance the bioavailability and therapeutic efficacy of these phytochemicals. Herein, we have formulated folic acid conjugated polyacrylic acid capped mesoporous silica nanoparticles (∼47.6 nm in diameter) for pH-dependent targeted delivery of chrysin to breast cancer (MCF-7) cells. Chrysin loaded mesoporous silica nanoparticles (Chr- mSiO2@PAA/FA) have been noted to induce apoptosis in MCF-7 cells through oxidative insult and mitochondrial dysfunction with subsequent G1 arrest. Further, in tumor bearing mice, intravenous incorporation of Chr-mSiO2@PAA/FA has been noticed to enhance the anti-neoplastic effects of chrysin via tumor site-specific accumulation. Enhanced cytotoxicity of chrysin contributed towards in vivo tumor regression, restoration of normalized tissue architecture and maintenance of healthy body weight. Besides, no serious systemic toxicity was manifested in response to Chr-mSiO2@PAA/FA administration in vivo. Thus, the study evokes about the anticancer potentiality of chrysin and its increased therapeutic activity via incorporation into folic acid conjugated mesoporous silica nanoparticles, which may hold greater impact in field of future biomedical research.