Generation and Propagation of Flexoelectricity-Induced Solitons in Nematic Liquid Crystals.

Solitons in nematic liquid crystals facilitate the rapid transport and sensing in microfluidic systems. Little is known about the elementary conditions needed to create solitons in nematic materials. In this study, we apply a combination of theory, computational simulations, and experiments to examine the formation and propagation of solitary waves, or "solitons", in nematic liquid crystals under the influence of an alternating current (AC) electric field. We find that these solitary waves exhibit "butterfly"-like or "bullet"-like structures that travel in the direction perpendicular to the applied electric field. Such structures propagate over long distances without losing their initial shape. The theoretical framework adopted here helps identify several key factors leading to the formation of solitons in the absence of electrostatic interactions. These factors include surface irregularities, flexoelectric polarization, unequal elastic constants, and negative anisotropic dielectric permittivity. The results of simulations are shown to be in good agreement with our own experimental observations, serving to establish the validity of the theoretical concepts and ideas advanced in this work.

Gut Microbiome and Polycystic Ovary Syndrome: Interplay of Associated Microbial-Metabolite Pathways and Therapeutic Strategies.

Polycystic ovary syndrome (PCOS) is a multifaceted disease with an intricate etiology affecting reproductive-aged women. Despite attempts to unravel the pathophysiology, the molecular mechanism of PCOS remains unknown. There are no effective or suitable therapeutic strategies available to ameliorate PCOS; however, the symptoms can be managed. In recent years, a strong association has been found between the gut microbiome and PCOS, leading to the formulation of novel ideas on the genesis and pathological processes of PCOS. Further, gut microbiome dysbiosis involving microbial metabolites may trigger PCOS symptoms via many mechanistic pathways including those associated with carbohydrates, short-chain fatty acids, lipopolysaccharides, bile acids, and gut-brain axis. We present the mechanistic pathways of PCOS-related microbial metabolites and therapeutic opportunities available to treat PCOS, such as prebiotics, probiotics, and fecal microbiota therapy. In addition, the current review highlights the emerging treatment strategies available to alleviate the symptoms of PCOS.

Conformational Sampling over Transition-Metal-Catalyzed Reaction Pathways: Toward Revealing Atroposelectivity.

The Py-Conformational-Sampling (PyCoSa) technique is introduced as a systematic computational means to sample the configurational space of transition-metal-catalyzed stereoselective reactions. When applied to atroposelective Suzuki-Miyaura coupling to create axially chiral biaryl products, the results show a range of mechanistic possibilities that include multiple low-energy channels through which C-C bonds can be formed.

Current updates on metabolites and its interlinked pathways as biomarkers for diabetic kidney disease: A systematic review.

Diabetic kidney disease (DKD) is a major microvascular complication of diabetes mellitus (DM) that poses a serious risk as it can lead to end-stage renal disease (ESRD). DKD is linked to changes in the diversity, composition, and functionality of the microbiota present in the gastrointestinal tract. The interplay between the gut microbiota and the host organism is primarily facilitated by metabolites generated by microbial metabolic processes from both dietary substrates and endogenous host compounds. The production of numerous metabolites by the gut microbiota is a crucial factor in the pathogenesis of DKD. However, a comprehensive understanding of the precise mechanisms by which gut microbiota and its metabolites contribute to the onset and progression of DKD remains incomplete. This review will provide a summary of the current scenario of metabolites in DKD and the impact of these metabolites on DKD progression. We will discuss in detail the primary and gut-derived metabolites in DKD, and the mechanisms of the metabolites involved in DKD progression. Further, we will address the importance of metabolomics in helping identify potential DKD markers. Furthermore, the possible therapeutic interventions and research gaps will be highlighted.

BiVO4-Liquid Junction Photovoltaic Cell with 0.2% Solar Energy Conversion Efficiency.

BiVO4 is an important photoanode material for water oxidation, but its photoelectrochemistry regarding the triiodide/iodide redox couple is not well understood. Here, we use a combination of open circuit potential measurements, photoelectrochemical scans, and liquid surface photovoltage spectroscopy (SPS) to confirm that BiVO4/triiodide/iodide electrolyte contacts produce up to 0.55 V photovoltage under 23 mW/cm-2 illumination from a 470 nm LED. Inspired by these results, we construct FTO/BiVO4/KI(I2)aq/Pt sandwich photoelectrochemical cells from electrochemically grown 0.5 × 0.5 cm2 BiVO4 and Mo-doped BiVO4 films. Under AM 1.5 illumination, the devices have up to 0.22% energy conversion efficiency, 0.32 V photovoltage, and 1.8 mA cm-2 photocurrent. Based on SPS, hole transfer to iodide is sufficiently fast to prevent the competing water oxidation reaction. Mo doping increases the incident photon-to-current efficiency to up to 55% (at 425 nm under front illumination) by improving the BiVO4 conductivity, but this comes at the expense of a lower photovoltage resulting from recombination at the Mo defects and a detrimental Schottky junction at the interface with FTO. Additional photovoltage losses are caused by the offset between the BiVO4 valence band edge and the triiodide/iodide electrochemical potential and by electron back transfer to iodide at the FTO back contact (shunting). Overall, this work provides the first example of a BiVO4-liquid photovoltaic cell and an analysis of its limitations. Even though the larger band gaps of metal oxides constrain their solar energy conversion efficiency, their transparency to visible light and deep valence bands makes them suitable for tandem photovoltaic devices.

Minimal Model of Solitons in Nematic Liquid Crystals.

Solitons in liquid crystals have generated considerable interest. Several hypotheses of varying complexity have been advanced to explain how they arise, but consensus has not emerged yet about the underlying forces responsible for their formation or their structure. In this work, we present a minimal model for solitons in achiral nematic liquid crystals, which reveals the key requirements needed to generate them in the absence of added charges. These include a surface inhomogeneity, consisting of an adsorbed particle capable of producing a twist, flexoelectricity, dielectric contrast, and an applied ac electric field that can couple to the director's orientation. Our proposed model is based on a tensorial representation of a confined liquid crystal, and it predicts the formation of "butterfly" structures, quadrupolar in character, in regions of a slit channel where the director is twisted by the surface imperfection. As the applied electric field is increased, solitons (or "bullets") become detached from the wings of the butterfly, and then propagate rapidly throughout the system. The main observations that emerge from the model, including the formation and structure of butterflies, bullets, and stripes, as well as the role of surface inhomogeneity and the strength of the applied field, are consistent with experimental findings presented here for nematic LCs confined between two chemically treated parallel plates.

Jetting and Droplet Formation Driven by Interfacial Electrohydrodynamic Effects Mediated by Solitons in Liquid Crystals.

Solitons are highly confined, propagating waves that arise from nonlinear feedback in natural (e.g., shallow and confined waters) and engineered systems (e.g., optical wave propagation in fibers). Solitons have recently been observed in thin films of liquid crystals (LCs) in the presence of ac electric fields, where localized LC director distortions arise and propagate due to flexoelectric polarization. Here we report that collisions between LC solitons and interfaces to isotropic fluids can generate a range of interfacial hydrodynamic phenomena. We find that single solitons can either generate single droplets or, alternatively, form jets of LC that subsequently break up into organized assemblies of droplets. We show that the influence of key parameters, such as electric field strength, LC film thickness, and LC-oil interfacial tension, map onto a universal state diagram that characterizes the transduction of soliton flexoelectric energy into droplet interfacial energy. Overall, we reveal that solitons in LCs can be used to focus the energy of nonlocalized electric fields to generate a new class of nonlinear electrohydrodynamic effects at fluid interfaces, including jetting and emulsification.

Oxidative Cross Dehydrogenative Coupling of N-Heterocycles with Aldehydes through C(sp3)-H Functionalization.

Existing methodologies for metal-catalyzed cross-couplings typically rely on preinstallation of reactive functional groups on both reaction partners. In contrast, C-H functionalization approaches offer promise in simplification of the requisite substrates; however, challenges from low reactivity and similar reactivity of various C-H bonds introduce considerable complexity. Herein, the oxidative cross dehydrogenative coupling of α-amino C(sp3)-H bonds and aldehydes to produce ketone derivatives is described using an unusual reaction medium that incorporates the simultaneous use of di-tert-butyl peroxide as an oxidant and zinc metal as a reductant. The method proceeds with a broad substrate scope, representing an attractive approach for accessing α-amino ketones through the formal acylation of C-H bonds α to nitrogen in N-heterocycles. A combination of experimental investigation and computational modeling provides evidence for a mechanistic pathway involving cross-selective nickel-mediated cross-coupling of α-amino radicals and acyl radicals.

Metallocene-coupled cumulenes: a quest for chiral single-molecule magnets.

In this work, we computationally investigated nickelocene and chromocene-coupled linear carbon chains. The designed systems are [Ni]-Cn-Ni], [Cr]-Cn-[Cr] and [Cr]-Cn-[Ni] (n = 3 to 9), where [Ni], [Cr] and Cn represent nickelocene (NiCp2, Cp = cyclopentadienyl), chromocene (CrCp2) and linear carbon chains respectively. The magnetic properties of these systems were computationally investigated by a density functional theory-based method. Ferromagnetic ground states were observed for [Ni]-Cn-[Ni] and [Cr]-Cn-[Cr] complexes for couplers with odd numbers of carbon atoms (n = 3, 5, 7 and 9), whereas antiferromagnetic ground states result for couplers with even numbers of carbon atoms (n = 4, 6 and 8). However, a totally opposite trend is followed by [Cr]-Cn-[Ni] complexes due to the spin polarization inside the chromocene. The calculation and study of magnetic anisotropy for all the ferromagnetic complexes suggest that the [Ni]-Cn-[Ni] complexes with coupler of odd number of carbon atoms will be suitable for the synthesis of single-molecule magnets among the designed complexes.

Molecular mechanisms augmenting resistance to current therapies in clinics among cervical cancer patients.

Cervical cancer (CC) is the fourth leading cause of cancer death (~ 324,000 deaths annually) among women internationally, with 85% of these deaths reported in developing regions, particularly sub-Saharan Africa and Southeast Asia. Human papillomavirus (HPV) is considered the major driver of CC, and with the availability of the prophylactic vaccine, HPV-associated CC is expected to be eliminated soon. However, female patients with advanced-stage cervical cancer demonstrated a high recurrence rate (50-70%) within two years of completing radiochemotherapy. Currently, 90% of failures in chemotherapy are during the invasion and metastasis of cancers related to drug resistance. Although molecular target therapies have shown promising results in the lab, they have had little success in patients due to the tumor heterogeneity fueling resistance to these therapies and bypass the targeted signaling pathway. The last two decades have seen the emergence of immunotherapy, especially immune checkpoint blockade (ICB) therapies, as an effective treatment against metastatic tumors. Unfortunately, only a small subgroup of patients (< 20%) have benefited from this approach, reflecting disease heterogeneity and manifestation with primary or acquired resistance over time. Thus, understanding the mechanisms driving drug resistance in CC could significantly improve the quality of medical care for cancer patients and steer them to accurate, individualized treatment. The rise of artificial intelligence and machine learning has also been a pivotal factor in cancer drug discovery. With the advancement in such technology, cervical cancer screening and diagnosis are expected to become easier. This review will systematically discuss the different tumor-intrinsic and extrinsic mechanisms CC cells to adapt to resist current treatments and scheme novel strategies to overcome cancer drug resistance.

CDK regulators-Cell cycle progression or apoptosis-Scenarios in normal cells and cancerous cells.

Serine/threonine kinases called cyclin-dependent kinases (CDKs) interact with cyclins and CDK inhibitors (CKIs) to control the catalytic activity. CDKs are essential controllers of RNA transcription and cell cycle advancement. The ubiquitous overactivity of the cell cycle CDKs is caused by a number of genetic and epigenetic processes in human cancer, and their suppression can result in both cell cycle arrest and apoptosis. This review focused on CDKs, describing their kinase activity, their role in phosphorylation inhibition, and CDK inhibitory proteins (CIP/KIP, INK 4, RPIC). We next compared the role of different CDKs, mainly p21, p27, p57, p16, p15, p18, and p19, in the cell cycle and apoptosis in cancer cells with respect to normal cells. The current work also draws attention to the use of CDKIs as therapeutics, overcoming the pharmacokinetic barriers of pan-CDK inhibitors, analyze new chemical classes that are effective at attacking the CDKs that control the cell cycle (cdk4/6 or cdk2). It also discusses CDKI's drawbacks and its combination therapy against cancer patients. These findings collectively demonstrate the complexity of cancer cell cycles and the need for targeted therapeutic intervention. In order to slow the progression of the disease or enhance clinical outcomes, new medicines may be discovered by researching the relationship between cell death and cell proliferation.

The impact of human papilloma virus on human reproductive health and the effect on male infertility: An updated review.

It is believed that human papilloma virus infection (HPV), which is caused by the DNA virus, is the most prominent factor contributing to sexually transmitted disease (STD) in the world, with males having a prevalence rate of 3.5%-45% while that women are 2%-44%. Infertility is a rising problem on a global basis, affecting anywhere from 10% to 30% of couples who have reached reproductive age. This study aims to investigate the existing research on HPV, its connection to male infertility, and how it could be a helpful tool for medical professionals managing HPV in the context of reproductive health care. Infection with HPV has been identified as a risk factor for several spontaneous abortions; however, there is a lack of evidence on how HPV influences individuals undergoing assisted reproductive technology (ART) in terms of live births. The significance of the immune response to HPV-infected male reproductive system cells and its effect on embryos, as well as the oxidative stress generated by high-risk HPV DNA damage and genomic instability, is discussed in this review. Further, the association between male individuals infected with HPV and asthenozoospermia should provide a compelling case for vaccinating young people against HPV.

Revisiting the Burden Borne by Fumarase: Enzymatic Hydration of an Olefin.

Fumarate hydratase (FH) is a remarkable catalyst that decreases the free energy of the catalyzed reaction by 30 kcal mol-1, much larger than most exceptional enzymes with extraordinary catalytic rates. Two classes of FH are observed in nature: class-I and class-II, which have different folds, yet catalyze the same reversible hydration/dehydration reaction of the dicarboxylic acids fumarate/malate, with equal efficiencies. Using class-I FH from the hyperthermophilic archaeon Methanocaldococcus jannaschii (Mj) as a model along with comparative analysis with the only other available class-I FH structure from Leishmania major (Lm), we provide insights into the molecular mechanism of catalysis in this class of enzymes. The structure of MjFH apo-protein has been determined, revealing that large intersubunit rearrangements occur across apo- and holo-protein forms, with a largely preorganized active site for substrate binding. Site-directed mutagenesis of active site residues, kinetic analysis, and computational studies, including density functional theory (DFT) and natural population analysis, together show that residues interacting with the carboxylate group of the substrate play a pivotal role in catalysis. Our study establishes that an electrostatic network at the active site of class-I FH polarizes the substrate fumarate through interactions with its carboxylate groups, thereby permitting an easier addition of a water molecule across the olefinic bond. We propose a mechanism of catalysis in FH that occurs through transition-state stabilization involving the distortion of the electronic structure of the substrate olefinic bond mediated by the charge polarization of the bound substrate at the enzyme active site.

Intestinal microbiome diversity of diabetic and non-diabetic kidney disease: Current status and future perspective.

A significant portion of the health burden of diabetic kidney disease (DKD) is caused by both type 1 and type 2 diabetes which leads to morbidity and mortality globally. It is one of the most common diabetic complications characterized by loss of renal function with high prevalence, often leading to acute kidney disease (AKD). Inflammation triggered by gut microbiota is commonly associated with the development of DKD. Interactions between the gut microbiota and the host are correlated in maintaining metabolic and inflammatory homeostasis. However, the fundamental processes through which the gut microbiota affects the onset and progression of DKD are mainly unknown. In this narrative review, we summarised the potential role of the gut microbiome, their pathogenicity between diabetic and non-diabetic kidney disease (NDKD), and their impact on host immunity. A well-established association has already been seen between gut microbiota, diabetes and kidney disease. The gut-kidney interrelationship is confirmed by mounting evidence linking gut dysbiosis to DKD, however, it is still unclear what is the real cause of gut dysbiosis, the development of DKD, and its progression. In addition, we also try to distinguish novel biomarkers for early detection of DKD and the possible therapies that can be used to regulate the gut microbiota and improve the host immune response. This early detection and new therapies will help clinicians for better management of the disease and help improve patient outcomes.

The pathophysiological and immunological background of the monkeypox virus infection: An update.

In addition to the COVID-19 waves, the globe is facing global monkeypox (MPX) outbreak. MPX is an uncommon zoonotic infection characterized by symptoms similar to smallpox. It is caused by the monkeypox virus (MPXV), a double-stranded DNA virus that belongs to the genus Orthopoxvirus (OPXV). MPXV, which causes human disease, has been confined to Africa for many years, with only a few isolated cases in other areas. Outside of Africa, the continuing MPXV outbreak in multiple countries in 2022 is the greatest in recorded history. The current outbreak, with over 10 000 confirmed cases in over 50 countries between May and July 2022, demonstrates that MPXV may travel rapidly among humans and pose a danger to human health worldwide. The rapid spread of such outbreaks in recent times has elevated MPX to the status of a rising zoonotic disease with significant epidemic potential. While the MPXV is not as deadly or contagious as the variola virus that causes smallpox, it poses a threat because it could evolve into a more potent human pathogen. This review assesses the potential threat to the human population and provides a brief overview of what is currently known about this reemerging virus. By analyzing the biological effects of MPXV on human health, its shifting epidemiological footprint, and currently available therapeutic options, this review has presented the most recent insights into the biology of the virus. This study also clarifies the key potential causes that could be to blame for the present MPX outbreak and draw attention to major research questions and promising new avenues for combating the current MPX epidemic.

Two-Dimensional Mechanics of Atomically Thin Solids on Water.

Movement of a three-dimensional solid at an air-water interface is strongly influenced by the extrinsic interactions between the solid and the water. The finite thickness and volume of a moving solid causes capillary interactions and water-induced drag. In this Letter, we report the fabrication and dynamical imaging of freely floating MoS2 solids on water, which minimizes such extrinsic effects. For this, we delaminate a synthesized wafer-scale monolayer MoS2 onto a water surface, which shows negligible height difference across water and MoS2. Subsequently patterning by a laser generates arbitrarily shaped MoS2 with negligible in-plane strain. We introduce photoswitchable surfactants to exert a lateral force to floating MoS2 with a spatiotemporal control. Using this platform, we demonstrate a variety of two-dimensional mechanical systems that show reversible shape changes. Our experiment provides a versatile approach for designing and controlling a large array of atomically thin solids on water for intrinsically two-dimensional dynamics and mechanics.

Using Nanoscopic Solvent Defects for the Spatial and Temporal Manipulation of Single Assemblies of Molecules.

Here we report the use of defects in ordered solvents to form, manipulate, and characterize individual molecular assemblies of either small-molecule amphiphiles or polymers. The approach exploits nanoscopic control of the structure of nematic solvents (achieved by the introduction of topological defects) to trigger the formation of molecular assemblies and the subsequent manipulation of defects using electric fields. We show that molecular assemblies formed in solvent defects slow defect motion in the presence of an electric field and that time-of-flight measurements correlate with assembly size, suggesting methods for the characterization of single assemblies of molecules. Solvent defects are also used to transport single assemblies of molecules between solvent locations that differ in composition, enabling the assembly and disassembly of molecular "nanocontainers". Overall, our results provide new methods for studying molecular self-assembly at the single-assembly level and new principles for integrated nanoscale chemical systems that use solvent defects to transport and position molecular cargo.

Understanding the Regioselectivity of Ion-Pair-Assisted Meta-Selective C(sp2)-H Activation in Conformationally Flexible Arylammonium Salts.

The lack of directionality and the long-range nature of Coulomb interactions have been a bottleneck to achieve chemically precise C-H activation using ion-pairs. Recent report by Phipps and co-workers of the ion-pair-directed regioselective Iridium-catalyzed borylation opens a new direction toward harnessing noncovalent interactions for C-H activation. In this article, the mechanism and specific role of ion-pairing are investigated using density functional theory (DFT). Computational studies reveal that meta C-H activation is kinetically more favorable than the para analogue due to stronger electrostatic interactions between the ion-pairs in closer proximity [d(NMe3+···SO3-)TSP1m = 3.93 Å versus d(NMe3+···SO3-)TSP1p = 4.30 Å]. The electrostatic interactions overwhelm the Pauli repulsion and distortion interactions incurred in bringing the oppositely charged ions in close contact for the rate-limiting meta transition state (TSP1m). Multiple linear regression shows that the free energies of activation correlate well with descriptors like the charge densities on the meta carbon and Ir atom along with that on the cation and anion with R2 = 0.74. Tuned range-separated DFT calculations demonstrate accurately the localization of charge separation in the reactant complex and transition state for the meta selectivity.

Programming Solitons in Liquid Crystals Using Surface Chemistry.

AC electric fields cause three-dimensional orientational fluctuations (solitons) to form and rapidly propagate in confined films of liquid crystals (LCs), offering the basis of a new class of active soft matter (e.g., for accelerating mixing and transport processes in microscale chemical systems). How surface chemistry impacts the formation and trajectories of solitons, however, is not understood. Here, we show that self-assembled monolayers (SAMs) formed from alkanethiols on gold, which permit precise control over surface chemistry, are electrochemically stable over voltage and frequency windows (<100 V; 1 kHz) that lead to soliton formation in achiral nematic films of 4'-butyl-4-heptyl-bicyclohexyl-4-carbonitrile (CCN-47). By comparing soliton formation in LC films confined by SAMs formed from hexadecanethiol (C16SH) or pentadecanethiol (C15SH), we reveal that the electric field required for soliton formation increases with the LC anchoring energy: surfaces patterned with regions of C16SH and C15SH SAMs thus permit spatially controlled creation and annihilation of solitons necessary to generate a net flux of solitons. We also show that solitons propagate in orthogonal directions when confined by obliquely deposited gold films decorated with SAMs formed from C16SH or C15SH and that the azimuthal direction of propagation of solitons within achiral LC films possessing surface-induced twists is not unique but reflects variation in the spatial location of the solitons across the thickness of the twisted LC film. Finally, discontinuous changes in LC orientation induced by patterned surface anchoring lead to a range of new soliton behaviors including refraction, reflection, and splitting of solitons at the domain boundaries. Overall, our results provide new approaches for the controlled generation and programming of solitons with complex and precise trajectories, principles that inform new designs of chemical soft matter.

The ring in the neck-managing paraparesis in cervical intramedullary tuberculoma: Inputs from a neurorehabilitation desk.

Central nervous system (CNS) tuberculosis is a less common entity even in endemic countries like India. Involvement of spine is much less frequent than brain, but concurrent involvement of brain and spine by tuberculoma is rare. A 23-year-old female with paraparesis was diagnosed as having cervical ring enhancing lesion in MRI suggesting intramedullary tuberculoma along with long segment cervicodorsal edema. On brain screening she had multiple intracerebral tuberculomas without any evidence of tuberculosis elsewhere in the body. She was treated with a multidisciplinary approach including neurological management and neurorehabilitation, with remarkable clinical recovery. In presence of acute neurological deficit, early start of rehabilitation along with medical management can give outstanding results in terms of neuro-recovery and improvement of residual neurodeficits. Surgical intervention can be avoided in many cases.