Scrub Typhus Presenting as Bilateral Sixth Nerve Palsy.

Scrub typhus, a tropical rickettsial infection, can have various neurological manifestations. Here, we present the case of an otherwise healthy 19-year-old female who presented to the emergency department with fever, headache, and diplopia. On examination, she was found to have bilateral sixth nerve palsy and bilateral papilledema. Initial unenhanced CT of the brain and CT venogram were unremarkable. The cerebrospinal fluid study was normal. Later, bloodwork revealed high titers of Orientia tsutsugamushi antibody. A thorough physical examination revealed no evidence of any eschar. She was treated with doxycycline and had significant clinical improvement with partial recovery of bilateral lateral rectus function. We want to highlight the importance of maintaining a high index of suspicion for atypical neurological presentations of scrub typhus.

Hypomagnesemia with Secondary Hypoparathyroidism and Hypocalcemia due to Novel Variants in the Transient Receptor Potential Cation Channel Subfamily M Member 6 ( TRPM6 ) Gene.

HOMG1 (hypomagnesemia 1, intestinal) or hypomagnesemia with secondary hypocalcemia is a rare autosomal recessive disorder of magnesium metabolism, characterized by impaired magnesium absorption. This disorder may mimic other conditions presenting with neonatal seizures. Here, we report an infant diagnosed to have hypomagnesemia with secondary hypocalcemia due to novel variants in TRPM6 gene.

The photodynamic approach to the molecular-level origin of metal-guided photochromism and ultrafast absorption spectroscopy.

Metal-guided photochromic material (photochromic complex) is one of the latest versions of photo-responsive materials due to their smart behaviour and promising real-world applications. The present work explores the molecular-level origin of metal-guided photochromism using a photodynamic approach and ultrafast absorption spectroscopy, to address all existing lacunas. Here, rhodamine B (RhB) dye containing the Schiff base zinc complex is considered a representative photochromic complex for both theoretical treatment and experimental observations. Detailed theoretical studies, including geometry optimization, frontier molecular orbital (FMO) analysis, transition state (TS) identification, and natural bond orbital (NBO) analysis, along with spectral studies, are employed to investigate the photodynamic equilibrium (enol-form keto-form). This equilibrium is regulated by the interplay of intrinsic factors (push-pull effect) and extrinsic factors (such as UV-light, the phenolic-OH group, metal ions, and solvents). The potential energy surface (PES) of the photo-conversion (enol →enol*→keto*→ meta-stable keto) is evaluated. While, the PES of the reversion (meta-stable keto →enol) is constructed based on the studies of thermo-reversion and photo-reversion. Finally, the theoretical findings related to the photodynamic equilibrium are validated by direct experimental evidence obtained through femtosecond transient absorption (fs-TA) spectroscopy.

Insights into colistin-mediated fluorescence labelling of bacterial LPS.

Gram-negative bacterial infections are becoming untreatable due to their ability to mutate, and the gradual development of their resistance to the available antimicrobials. In recent times colistin, a drug of last resort, started losing its efficacy towards multidrug-resistant bacterial infections. Colistin targets bacterial endotoxin lipopolysaccharides (LPS) and destabilises the cytoplasmic membrane by disrupting the outer LPS membrane. In this study, we have tried to label the bacterial LPS, the main constituent of the cytoplasmic membrane of bacterial cells, to try to understand the interaction mechanism of LPS with colistin. The chemosensor, naphthaldehyde appended furfural (NAF) that selectively recognises colistin can label LPS, by showing its fluorescence signals. The computationally derived three-dimensional structure of LPS has been introduced to speculate on the possible binding mode of colistin with LPS, and this was also thoroughly studied with the help of quantum mechanics and molecular dynamics energy minimisation. Fluorescence microscopy and FE-SEM microscopic studies were also used to observe the change in the structural morphology of colistin-sensitive and resistant Salmonella typhi in different experimental conditions.

LncRTPred: Predicting RNA-RNA mode of interaction mediated by lncRNA.

Long non-coding RNAs (lncRNAs) play a significant role in various biological processes. Hence, it is utmost important to elucidate their functions in order to understand the molecular mechanism of a complex biological system. This versatile RNA molecule has diverse modes of interaction, one of which constitutes lncRNA-mRNA interaction. Hence, identifying its target mRNA is essential to understand the function of an lncRNA explicitly. Existing lncRNA target prediction tools mainly adopt thermodynamics approach. Large execution time and inability to perform real-time prediction limit their usage. Further, lack of negative training dataset has been a hindrance in the path of developing machine learning (ML) based lncRNA target prediction tools. In this work, we have developed a ML-based lncRNA-mRNA target prediction model- 'LncRTPred'. Here we have addressed the existing problems by generating reliable negative dataset and creating robust ML models. We have identified the non-interacting lncRNA and mRNAs from the unlabelled dataset using BLAT. It is further filtered to get a reliable set of outliers. LncRTPred provides a cumulative_model_score as the final output against each query. In terms of prediction accuracy, LncRTPred outperforms other popular target prediction protocols like LncTar. Further, we have tested its performance against experimentally validated disease-specific lncRNA-mRNA interactions. Overall, performance of LncRTPred is heavily dependent on the size of the training dataset, which is highly reflected by the difference in its performance for human and mouse species. Its performance for human species shows better as compared to that for mouse when applied on an unknown data due to smaller size of the training dataset in case of mouse compared to that of human. Availability of increased number of lncRNA-mRNA interaction data for mouse will improve the performance of LncRTPred in future. Both webserver and standalone versions of LncRTPred are available. Web server link: http://bicresources.jcbose.ac.in/zhumur/lncrtpred/index.html. Github Link: https://github.com/zglabDIB/LncRTPred.

Correction: A biomass-derived dual crosslinked DNA-nanoparticle hydrogel for visible light-induced photodynamic bacterial inactivation.

Correction for 'A biomass-derived dual crosslinked DNA-nanoparticle hydrogel for visible light-induced photodynamic bacterial inactivation' by Gourab Das et al., Soft Matter, 2023, https://doi.org/10.1039/D3SM01400B.

A biomass-derived dual crosslinked DNA-nanoparticle hydrogel for visible light-induced photodynamic bacterial inactivation.

Sustainability in developing novel nanomaterials (NPs) from biomass sources is a challenging proposition mainly due to the difficulty of infusing or retaining desired chemical functionalities in the biomass substrate. In this study, we demonstrate the synthesis of DNA-nanoparticles (DNA-NP) from onion genomic DNA as a plant biomass source through controlled hydrothermal pyrolysis to retain functional groups in the NPs for predictable downstream chemical transformations. A dual crosslinking scheme was introduced that involves the DNA-NP to form a hydrogel. Chemical crosslinking was achieved through the formation of a Schiff base between the -CHO groups of glutaraldehyde and the amine functionality present on the DNA-NP surface as well as in the nucleobases of the dangling DNA strands of DNA-NP. Simultaneous physical entanglement was attained through hybridization-mediated self-assembly of the dangling DNA strands of the DNA-NP with untransformed onion genomic DNA. As a corollary of the dual crosslinking, the resulting hydrogel not only displayed remarkable mechanical strength but also showed self-healing properties. The ability of the DNA-NP to generate reactive oxygen species (ROS) with visible light irradiation is translated to the hydrogel, making the system potent for biofilm destruction. The high loading efficiency of the model drug ampicillin sodium (Amp) in the hydrogel was achieved which was released in four days. This hints towards the application of the hydrogel through combination antibiotic-antibacterial photodynamic treatment (APDT) as demonstrated here with both Gram-positive and Gram-negative bacteria.

Controlling the Morphological Features, Aspect Ratio and Emission Patterns of Supramolecular Copolymers by Restricted Dimensional Growth.

One of the bottlenecks associated with supramolecular polymerization of functional π-systems is the spontaneous assembly of monomers leading to one- or two-dimensional (1D or 2D) polymers without control over chain length and optical properties. In the case of supramolecular copolymerization of monomers that are structurally too diverse, preferential self-sorting occurs unless they are closely interacting donor-acceptor pairs. Herein, it is established that the spontaneous 1D polymerization of a phenyleneethynylene (PE) derivative and the 2D polymerization of a Bodipy derivative (BODIPY) can be controlled by copolymerizing them in different ratios, leading to unusual spindle-shaped structures with controlled aspect ratio, as evident by scanning electron microscopy (SEM), transmission electron microscopy (TEM) and confocal laser scanning microscopy (CLSM) studies. For example, when the content of BODIPY is 50 % in the BODIPY-PE mixture, the 1D polymerization of PE is significantly restricted to form elongated spindle-like structures having an aspect ratio of 4-6. The addition of 75 % of BODIPY to PE resulted in circular spindles having an aspect ratio of 1-2.5, thereby completely restricting the 1D polymerization of PE monomers. Moreover, the resultant supramolecular copolymers exhibited morphology and aspect ratio dependent emission features as observed by the time-resolved emission studies.

TarpiD, a database of putative and validated targets of piRNAs.

Piwi-interacting RNAs (piRNAs) are a novel class of 18-36 nts long small non-coding single-stranded RNAs that play crucial roles in a wide array of critical biological activities besides maintaining genome integrity by transposon silencing. piRNAs influence biological processes and pathways by regulating gene expression at transcriptional and post-transcriptional level. Studies have reported that piRNAs silence various endogenous genes post-transcriptionally by binding to respective mRNAs through interaction with the PIWI proteins. Several thousands of piRNAs have been discovered in animals, but their functions remain largely undiscovered owing to a lack of proper guiding principles of piRNA targeting or diversity in targeting patterns amongst piRNAs from the same or different species. Identification of piRNA targets is essential for deciphering their functions. There are a few tools and databases on piRNAs, but there are no systematic and exclusive repositories to obtain information on target genes regulated by piRNAs and other related information. Hence, we developed a user-friendly database named TarpiD (Targets of piRNA Database) that offers comprehensive information on piRNA and its targets, including their expression, methodologies (high-throughput or low-throughput) for target identification/validation, cells/tissue types, diseases, target gene regulation types, target binding regions, and key functions driven by piRNAs through target gene interactions. The contents of TarpiD are curated from the published literature and enable users to search and download the targets of a particular piRNA or the piRNAs that target a specific gene for use in their research. This database harbours 28 682 entries of piRNA-target interactions supported by 15 methodologies reported in hundreds of cell types/tissues from 9 species. TarpiD will be a valuable resource for a better understanding of the functions and gene-regulatory mechanisms mediated by piRNAs. TarpiD is freely accessible for academic use at https://tarpid.nitrkl.ac.in/tarpid_db/.

MicroRNA mediated gene regulatory circuits leads to machine learning based preliminary detection of acute myeloid leukemia.

Acute Myeloid Leukemia (AML) can be detected based on morphology, cytochemistry, immunological markers, and cytogenetics. MicroRNAs (miRNAs) influence key biological pathways in multiple haematological malignancies including AML. In this work, we have analysed the miRNome and the transcriptome of normal and AML samples and have identified the significant set of miRNA-target mRNA pairs present within AML- Peripheral Blood and AML- Bone Marrow samples from both tissue and cell lines. The miRNA target genes are further filtered based on their functional significance in AML system. These filtered genes constitute the set of selected miRNA target features, which have been finally used for developing machine learning based prediction tool, 'TbAMLPred' for preliminary detection of AML. This model implements both unsupervised clustering and supervised classification algorithms that would increase the reliability of prediction. Our results show that the selected miRNA target-based features can separate the control and disease samples linearly. Overall, we put forward 'TbAMLPred' for a non-invasive mode of preliminary AML diagnosis in future. Github link for accessing TbAMLPred: https://github.com/zglabDIB/TbAMLPred.

Mechanistic insight highlights the key steps and significance of metal in Ir(III)-catalysed C-H activated chromones generation.

A mild C-H activation reaction catalysed by an Ir(III)-complex to generate chromones from salicylaldehydes at room temperature has been studied theoretically to explore the reaction mechanism. The DFT study reveals that the key point of the catalytic cycle is cyclometallation, more precisely it is in the C-H metallation step where the significance of the metal becomes obvious. The favourable pathway includes several steps, namely, coordination of the substrate with the metal catalyst, O-H metallation, C-H metallation, denitrogenation, migration insertion, proton transfer, and demetallation. On removal of one pivalic acid, the metal is activated and the C-H metallation proceeds via oxidative addition followed by reductive elimination. The DFT study clearly indicated that, although there are two possibilities for cyclometallation, it only proceeds via O-H metallation followed by stepwise C-H metallation. The effect of substituents on the mechanism was also been studied. The low energetic span obtained for this catalytic cycle implies that the reaction can proceed at room temperature, and this is consistent with the experimental result.

Acetic Acid-Catalyzed Regioselective C(sp2)-H Bond Functionalization of Indolizines: Concomitant Involvement of Synthetic and Theoretical Studies.

An atom economical and environmentally benign protocol has been developed for the regioselective C(sp2)-H bond functionalization of indolizines. The acetic acid-catalyzed cross-coupling reaction proceeds under metal-free conditions, producing a wide range of synthetically useful indolizine derivatives. The present protocol showed good functional group tolerance and broad substrate scope in good to excellent yields. Quantum mechanical investigation using density functional theory (DFT) has played a crucial role in understanding that acetic acid is the key player in determining the actual pathway as the catalyst and its ultrafast nature. Different pathways involving inter- and intramolecular proton transfer, with or without acetic acid, were investigated. Calculated results revealed that a proton shuttle mechanism is involved for the least energetic, most favorable acetic acid-catalyzed pathway. Furthermore, regioselectivity has also been explained theoretically.

Tweaking a BODIPY Spherical Self-Assembly to 2D Supramolecular Polymers Facilitates Excited-State Cascade Energy Transfer.

Excited state properties such as emission, exciton transport, electron transfer, etc., are strongly dependent on the shape, size and molecular arrangement of chromophore based supramolecular architectures. Herein, we demonstrate creation and control of distinct supramolecular energy landscapes for the reversible control of the excited-state emission processes through cascade energy transfer in chromophore assemblies, facilitated by an unprecedented solvent effect. In methylcyclohexane, a tailor-made Y-shaped BODIPY derivative self-assembles to form an unusual spherical architecture of 400-1200 nm size, which exhibits a single emission at 540 nm upon 475 nm excitation through a normal excitation deactivation process. However, in n-decane, the same BODIPY derivative forms two-dimensional supramolecular sheets, exhibiting multiple emission peaks at 540, 610, 650, 725 and 790 nm with 475 nm excitation due to cascade energy transfer. Further control on the morphology and excitation energy transfer is possible with variable solvent composition and ultrasound stimulation, resulting in enhanced near-infrared emission with an overall pseudo Stokes shift of 7105 cm-1 .

Closure of oroantral fistula: Comparison between buccal fat pad and buccal advancement flap: A clinical study.

BACKGROUND: The oro antral fistula (OAF) is an unnatural epithelialized communication between oral cavity and maxillary sinus. It may heal spontaneously but a larger fistula requires surgical intervention. OAF causes excruciating pain, escape of fluids from nose, escape of air from mouth into nose, epistaxis, change in voice due to resonance, purulent discharge in case of chronic OAF, post nasal discharge, popping out of antral polyp into oral cavity and sinusitis. Closure of OAF is strenuous, technique sensitive and challenging. AIMS AND OBJECTIVES: To compare and evaluate the efficacy of buccal fat pad and buccal advancement pad for closure of oroantral fistula. MATERIALS AND METHODS: Twenty patients of age ranging from 24-64 years with complaint of OAF were included in this prospective, comparative analytic study. In group I, OAF was treated with a buccal advancement flap and in group II, BFP was sutured over the defect. All patients were called for follow up on 1st, 7th, 14th and 21st day post operatively. Pain, mouth opening, edema, infection and wound dehiscence were evaluated on each visit. RESULT: The mean age of selected patients in both the treatment groups was comparable. The mean age of patients in group I was 45.00 ± 13.33 years whereas in group II the mean age was 44.00 ± 13.13 years. Pain, edema was less in Group I. Mouth opening was less in group II. We did not encountered infection and wound dehiscence in any case. CONCLUSION: Various techniques can be utilized for the closure; regardless of the technique used, success of the surgical procedure depends on effective removal of fistulous tract and complete extermination of any sinus pathology and/or infection. The major factors determining the type of surgery for closure of OAF are dimension and location of the defect. The other decisive factors could be the adequacy and health of adjoining tissue. We observed buccal fat pad to be better option for closure of OAF, despite of its more morbidity; as all the complications were of some time period and when evaluated for long term.

Repurposed drugs and nutraceuticals targeting envelope protein: A possible therapeutic strategy against COVID-19.

COVID-19 pandemic caused by SARS-CoV-2 has already claimed millions of lives worldwide due to the absence of a suitable anti-viral therapy. The CoV envelope (E) protein, which has not received much attention so far, is a 75 amino acid long integral membrane protein involved in assembly and release of the virus inside the host. Here we have used artificial intelligence (AI) and pattern recognition techniques for initial screening of FDA approved pharmaceuticals and nutraceuticals to target this E protein. Subsequently, molecular docking simulations have been performed between the ligands and target protein to screen a set of 9 ligand molecules. Finally, we have provided detailed insight into their mechanisms of action related to the varied symptoms of infected patients.

A Zn(II)-Coordination Polymer for the Instantaneous Cleavage of Csp3-Csp3 Bond and Simultaneous Reduction of Ketone to Alcohol.

Two coordination polymers of Zn(II) and Cu(II) with n-butylmalonic acid have been achieved in this work. The crystallographic structural descriptions along with the sedimentary rock-type microstructural morphology of these two coordination polymers (CPs) have been explored. The reactivity of ß-hydroxy ketones with these two CPs has also been investigated. The Zn(II)-CP shows a specific reactivity with ß-hydroxy ketone at room temperature and in open air conditions. Through a microcolumn-based filtration technique, the Zn(II)-CP shows the capability to break the Csp3-Csp3 σ bonds of ß-hydroxy ketone and simultaneously reduce the associated ketone to alcohol. Such conversion has been progressed without the use of any additional external reducing agent and any chemical workup or column chromatographic purification protocol. Other similar type CPs of Cu(II) and Mn(II) with n-butylmalonic acid completely failed to show similar reactivity with ß-hydroxy ketone. On the basis of much experimental evidence, the most possible mechanistic pathway of the reactivity between ß-hydroxy ketone and Zn(II)-CP has also been proposed through this work.

A semiconducting supramolecular Co(ii)-metallohydrogel: an efficient catalyst for single-pot aryl-S bond formation at room temperature.

A novel mechanically stable supramolecular Co(ii)-metallohydrogel has been synthesized. Cobalt(ii) nitrate hexahydrate and monoethanolamine, as a low molecular weight organic gelator, are used to get the gel. The mechanical stability of the supramolecular hydrogel was analyzed. The morphology of the supramolecular metallohydrogel was scrutinized. The semiconducting features of the metallohydrogel were studied. The conducting properties of the Co(ii)-metallohydrogel establish a Schottky barrier diode type nature. The catalytic nature of the Co(ii)-metallohydrogel based room temperature single pot aryl-S coupling reaction was explored. Most interestingly, the Co(ii)-metallohydrogel based catalytic aryl-S coupling reaction does not require any column-chromatographic purification protocol to get pure aryl-thioethers. Thus, through this work a semiconducting Schottky barrier diode application and catalytic role in the room temperature single pot aryl-S coupling reaction of a supramolecular Co(ii)-metallohydrogel have been explored.

Collagen Membrane Over Buccal Fat Pad Versus Buccal Fat Pad in Management of Oral Submucous Fibrosis: A Comparative Prospective Study.

OBJECTIVE: The objective of this study was to assess the effectiveness of collagen membrane as biological dressing over buccal fat pad (BFP) during crucial postoperative healing phase in the surgical management of oral submucous fibrosis (OSMF). STUDY DESIGN: The study comprised of 40 patients of OSMF of group IVa (Khanna and Andrade). Patients were randomly divided in two groups (20 patients in each group). Group I patients were treated using buccal fat pad only, whereas collagen membrane was used as a covering over harvested BFP in group II patients. Postoperative follow-up was done at 1 week, 3 weeks, 6 months and 1 year. RESULT: Mean postoperative mouth opening achieved in both the groups was comparable at every follow-up visit. Infection was evident in four patients of group I at 1-week follow-up, whereas none of the group II patients developed infection. Pain score was lesser in group II patients as compared to group I. Relapse was seen in two patients in group I and one patient in group II. Time taken for epithelialization was 2-3 weeks in both the groups. CONCLUSION: Although intraoperative time was increased in group II application of collagen membrane reduced infection when compared with group I. Also, the chances of damage to BFP are reduced during the hygiene maintenance at surgical site and jaw-opening exercise. Reduction in pain scores during postoperative period in group II patients was an additional advantage.

Stepwise control of host-guest interaction using a coordination polymer gel.

Precise control of host-guest interaction as seen in biological processes is difficult to achieve with artificial systems. Herein we have exploited the thermodynamic benefits of a system in equilibrium to achieve controlled stepwise release and capture of cyclodextrin (guest) using a coordination polymer (Mg-CP) as the host and temperature as the stimulus. Since temperature is not a precision stimulus for artificial host-guest interaction, the present system is a distinct prototype that manifests temperature-controlled natural host-guest interaction. The described coordination polymeric host system, when incorporated into a hydrogel matrix, provides a microenvironment that facilitates the stepwise release of α-CD in response to temperature variation within a quasi-solid state. The work demonstrated here may pave the way towards thermally controlled delivery and monitoring of otherwise spectroscopically silent molecules such as cyclodextrins.

Au-Catalyzed Hexannulation and Pt-Catalyzed Pentannulation of Propargylic Ester Bearing a 2-Alkynyl-phenyl Substituent: A Comparative DFT Study.

The mechanistic pathways of metal-catalyzed pentannulation and hexannulation of aromatic enediyne were studied quantum mechanically with Pt and Au salts. In agreement with the experimental facts, our result shows that the pentannulation favors over the hexannulation under Pt-catalyzed conditions and the reverse possibility favors when the Pt salt is replaced with an Au one. The Pt-catalyzed reaction involves a long-range acyl migration that follows the cyclization step. Our study reveals that such migration takes place under the assistance of a ligand of the metal atom. Moreover, the variation of aromaticity (probed by the change of the nucleus-independent chemical shift (0) value) in the cyclization steps shows that both processes maintain the development of the aromatic character of the generated intermediate during the progress of the reaction.