A 2.5 V In-Plane Flexi-Pseudocapacitor with Unprecedented Energy and Cycling Efficiency for All-Weather Applications.

As electronic devices for aviation, space, and satellite applications become more sophisticated, built-in energy storage devices also require a wider temperature spectrum. Herein, an all-climate operational, energy and power-dense, flexible, in-plane symmetric pseudocapacitor is demonstrated with utmost operational safety and long cycle life. The device is constructed with interdigital-patterned laser-scribed carbon-supported electrodeposited V5O12·6H2O as a binder-free electrode and a novel high-voltage anti-freezing water-in-salt-hybrid electrolyte. The anti-freezing electrolyte can operate over a wide temperature range of -40-60 °C while offering a stable potential window of ≈2.5 V. The device undergoes rigorous testing under diverse environmental conditions, including rapid and regular temperature and mechanical transition over multiple cycles. Additionally, detailed theoretical simulation studies are performed to understand the interfacial interactions with the active material as well as the local behavior of the anti-freeze electrolyte at different temperatures. As a result, the all-weather pseudocapacitor at 1 A g-1 shows a high areal capacitance of 234.7 mF cm-2 at room temperature and maintains a high capacitance of 129.8 mF cm-2 even at -40 °C. Besides, the cell operates very reliably for over 80 950 cycles with a capacitance of 25.7 mF cm-2 at 10 A g-1 and exhibits excellent flexibility and bendability under different stress conditions.

Designer tryptophan-rich peptide modulates structural dynamics of HIF-1α DNA i-motif DNA.

Cytosine-rich DNA sequences can fold into intercalated motifs known as i-motifs, through noncanonical hydrogen bonding interactions. Molecular probes can provide valuable insights into the conformational stability and potential cellular functions of i-motifs. W5K5, a decapeptide composed of alternating tryptophan (W) and lysine (K) units, has been identified as a lead candidate to modulate the structural dynamics of the hypoxia-inducible factor 1-alpha (HIF-1α) DNA i-motif. This finding is expected to facilitate the rational design of peptide-based probes for studying the structure and functional dynamics of i-motifs.

Time traveling through the floodscape: assessing the spatial and temporal probability of floods and susceptibility zones in the Lower Damodar Basin.

The flood of Damodar river is a well-known fact which is used to the whole riverine society of the basin as well as to the eastern India. The study aims to estimate the spatio-temporal probability of floods and identify susceptible zones in the Lower Damodar Basin (LDB). A flood frequency analysis around 90 years hydrological series is performed using the Log-Pearson Type III model. The frequency ratio model has also been applied to determine the spatial context of flood. This reveals the extent to which the LDB could be inundated in response to peak discharge conditions, especially during the monsoon season. The findings indicate that 36.64% of the LDB falls under high to very high flood susceptibility categories, revealing an increasing downstream flood vulnerability trend. Hydro-geomorphic factors substantially contribute to the susceptibility of the LDB to high magnitude floods. A significant shift in flood recurrence intervals, from biennial occurrences in the pre-dam period to decadal or vicennial occurrences in the post-dam period, is observed. Despite a reduction in high-magnitude flood incidents due to dam and barrage construction, irregular flood events persist. The effect of flood in the LDB region is considered to be either positive as well as negative in terms of wholistic sense and impact. The analytical results of this research could serve to identify flood-prone zones and guide the development of flood resilience policies, thereby promoting sustainability within the LDB floodplain.

Modeling Approaches to Reimagine Stability (MARS) for Enabling Earlier Access to Critical Drugs for Patients with Unmet Medical Needs.

FDA's experience to date has shown that completion of stability data requirements is one of the most observed challenges for applicants of New Drug Applications (NDAs) with an expedited review designation. Since NDAs submitted under these expedited pathways often have limited available real-time stability data from the primary batches, Modeling Approaches to Reimagine Stability (MARS) have been proposed to support establishment of tentative retest periods of the drug substance and/or expiration dating period (shelf-life) of the drug product. MARS incorporate statistical principles and available tools as a part of the predictive models. In this study, a data mining exercise has been conducted with regulatory submissions of Investigational New Drug (IND) Applications, NDAs, and Abbreviated New Drug Applications (ANDAs) containing MARS data. The case studies presented herein demonstrate how MARS data has been applied to regulatory scenarios involving prediction of retest and/or shelf-life, bridging major development changes, and confirming that no degradation has been observed or predicted. Using the assumption of a linear time trend for those cases that do not display sufficient degradation to conduct MARS for projection of an expiration date, an analysis of covariance (ANCOVA) model is developed and described herein to test the hypothesis of zero slope by a p-value method. Our results show that the application of MARS adequately supported establishment of a tentative commercially viable retest date/shelf-life, thus enabling earlier access to critical drugs for patients with unmet medical needs.

Rural child health in India: the persistent nature of deprivation, undernutrition and the 2030 Agenda.

The 2030 Agenda for sustainable development was launched to achieve Sustainable Development Goals (SDGs) across the globe. This paper is based on the primary database to assess the nutritional status of 5-10 years children and the incidence of deprivation in their households of a backward district (Purulia), India in the context of the first two SDGs, e.g., no poverty and zero hunger. We conclude that around 74% of children are undernourished. The proportion of households multidimensionally deprived is 90%, and the majority of them live on less than $1.25 a day. Results reveal that the BMI of mother and the education of father are the two most statistically significant predictors of child malnutrition. Purulia has long been witnessing the persistent nature of deprivation, which is well reflected in the child's health. The district is quite far from the national targets in achieving the SDGs. Government, private sector, and civil society must come together to accelerate the progress of SDGs.

Impact of Atomic Rearrangement and Single Atom Stabilization on MoSe2 @NiCo2 Se4 Heterostructure Catalyst for Efficient Overall Water Splitting.

High overpotentials required to cross the energy barriers of both hydrogen and oxygen evolution reactions (HER and OER) limit the overall efficiency of hydrogen production by electrolysis of water. The rational design of heterostructures and anchoring single-atom catalysts (SAC) are the two successful strategies to lower these overpotentials, but realization of such advanced nanostructures with adequate electronic control is challenging. Here, the heterostructure of edge-oriented molybdenum selenide (MoSe2 ) and nickel-cobalt-selenide (NiCo2 Se4 ) realized through selenization of mixed metal oxide/hydroxide is presented. The as-developed sheet-on-sheet heterostructure shows excellent HER performance, requiring an overpotential of 89 mV to get a current density 10 mA cm-2 and a Tafel slope of 65 mV dec-1 . Further, resultant MoSe2 @NiCo2 Se4 is photochemically decorated with single-atom iridium, which on electrochemical surface reconstruction displays outstanding OER activity, requiring only 200 and 313 mV overpotentials for 10 and 500 mA cm-2 current densities, respectively. A full cell electrolyzer comprising of MoSe2 @NiCo2 Se4 as cathode and its SAC-Ir decorated counterpart as anode requires only 1.51 V to attain 10 mA cm-2 current density. Density functional theory calculation reveals the importance of rational heterostructure design and synergistic electronic coupling of single atom iridium in HER and OER processes, respectively.

Developing High-Performance In-Plane Flexible Aqueous Zinc-Ion Batteries with Laser-Scribed Carbon-Supported All Electrodeposited Electrodes.

Developing high-performance, safer, and affordable flexible batteries is of urgent need to power the fast-growing flexible electronics market. In this respect, zinc-ion chemistry employing aqueous-based electrolytes represents a promising combination considering the safety, cost efficiency, and both high energy and high-power output. Herein, we represent a high-performance flexible in-plane aqueous zinc-ion miniaturized battery constructed with all electrodeposited electrodes, i.e., MnO2 cathode and zinc anode with polyimide-derived interdigital patterned laser-scribed carbon (LSC) as the current collector as well as the template for electrodeposition. The LSC possesses a cross-linked network of graphitic carbon sheet, which offers large surface area over low footprint and ensures active materials loading with a robust conductive network. The LSC with high zincophilic characteristic also offers dendrite-free zinc deposition with very low Zn2+ plating stripping overpotential. Benefitting from the Zn//MnO2-rich redox chemistry, the ability of the 3D LSC network to uniformly distribute reaction sites, and the architectural merits of in-plane interdigitated electrode configuration, we report very high capacity values of ∼549 mAh/g (or ∼523 µAh/cm2) and 148 mAh/g (or 140 µAh/cm2) at 0.1 A/g (0.095 mA/cm2) and 2 A/g (1.9 mA/cm2) currents, respectively. The device was also able to maintain a high capacity of 196 mAh/g (areal capacity of 76.19 µAh/cm2) at 1 A/g (0.95 mA/cm2) current after 1350 cycles. The flexibility of the device was demonstrated in polyacryl amide (PAM) gel polymer soaked with a 2 M ZnSO4 and 0.2 M MnSO4 electrolyte, which exhibited a comparable specific capacity of ∼102-110 mAh/g in flat condition and different bending (100° or 160° bending) conditions. The device does not use any conventional current collector, separator, and conductive or polymer additives. The overall process is highly scalable and can be completed in less than a couple of hours.

DNA Minor Groove-Induced cis-trans Isomerization of a Near-Infrared Fluorescent Probe.

The discovery of small molecules that exhibit turn-on far-red or near-infrared (NIR) fluorescence upon DNA binding and understanding how they bind DNA are important for imaging and bioanalytical applications. Here we report the DNA-bound structure and the DNA binding mechanism of quinone cyanine dithiazole (QCy-DT), a recently reported AT-specific turn-on NIR fluorescent probe for double-stranded DNA. The nuclear magnetic resonance (NMR)-derived structure showed minor groove binding but no specific ligand-DNA interactions, consistent with an endothermic and entropy-driven binding mechanism deduced from isothermal titration calorimetry. Minor groove binding is typically fast because it minimally perturbs the DNA structure. However, QCy-DT exhibited unusually slow DNA binding. The cyanine-based probe is capable of cis-trans isomerization due to overlapping methine bridges, with 16 possible slowly interconverting cis/trans isomers. Using NMR, density functional theory, and free energy calculations, we show that the DNA-free and DNA-bound environments of QCy-DT prefer distinctly different isomers, indicating that the origin of the slow kinetics is a cis-trans isomerization and that the minor groove preferentially selects an otherwise unstable cis/trans isomer of QCy-DT. Flux analysis showed the conformational selection pathway to be the dominating DNA binding mechanism at low DNA concentrations, which switches to the induced fit pathway at high DNA concentrations. This report of cis/trans isomerization of a ligand, upon binding the DNA minor groove, expands the prevailing understanding of unique discriminatory powers of the minor groove and has an important bearing on using polymethine cyanine dyes to probe the kinetics of molecular interactions.

Solid State Flexible Asymmetric Supercapacitor Based on Carbon Fiber Supported Hierarchical Co(OH)xCO3 and Ni(OH)2.

Conducting flexible carbon fiber (CF) cloth was used as a substrate for the hydrothermal growth of nickel hydroxide (Ni(OH)2) and cobalt hydroxy carbonate [Co(OH)xCO3] with unique hierarchical flowery architecture and then was used as a flexible supercapacitor electrode. In a three-electrode configuration in 6 M KOH aqueous electrolyte, the CF-Ni(OH)2 and CF-Co(OH)xCO3 electrode showed the maximum specific capacitance of 789 F/g and 550 F/g, respectively, at 2A/g current accompanied by outstanding cycle stability by retaining 99.9% and 99.5% specific capacitance over 1500 consecutive charge-discharge cycles at 5 A/g. However, the low cell voltage (0.4 V) restricted the respective specific energy to 4.38 and 3.05 Wh/kg at a specific power of 100 W/kg. To overcome the issue, two solid state flexible asymmetric supercapacitors were fabricated using the CF-Ni(OH)2 and CF-Co(OH)xCO3 as the anode and sonochemically deposited CNT over carbon fiber as the cathode material in PVA-KOH gel electrolyte. The as-fabricated flexible supercapacitors CF-Ni(OH)2//CF-CNT and CF-Co(OH)xCO3//CF-CNT were able to deliver high specific energy of 41.1 and 33.48 Wh/kg, respectively, at high specific power of 1.4 kW/kg accompanied by excellent cycle stability (retaining 98% and 97.6% specific capacitance, respectively, over 3000 charge-discharge cycle at 5 A/g).

U.S. Food and Drug Administration approval summary: omacetaxine mepesuccinate as treatment for chronic myeloid leukemia.

On October 26, 2012, the U.S. Food and Drug Administration (FDA) granted accelerated approval to omacetaxine mepesuccinate (Synribo; Teva Pharmaceuticals USA, Inc., North Wales, PA, http://www.tevausa.com) for the treatment of adult patients with chronic phase (CP) or accelerated phase (AP) chronic myeloid leukemia (CML) with resistance and/or intolerance to two or more tyrosine kinase inhibitors (TKIs). The approval was based on the FDA review of data from 111 patients with CML in CP or in AP who had received two or more prior TKIs, including imatinib. Major cytogenetic response was achieved in 18% of patients with CP, with a median response duration of 12.5 months. Major hematologic response was achieved in 14% of patients with AP, with a median response duration of 4.7 months. The FDA safety evaluation was based on submitted data from 163 patients with CP or AP CML who had received at least one dose of omacetaxine mepesuccinate. The safety evaluation was limited by the single-arm design of the clinical trials as conducted in a small number of previously treated patients. The most common (≥20%) adverse reactions of any grade in enrolled patients included thrombocytopenia, anemia, neutropenia, diarrhea, nausea, fatigue, asthenia, injection site reaction, pyrexia, and infection. The FDA concluded that omacetaxine mepesuccinate has shown activity and a favorable benefit-to-risk profile for the studied population of adult patients with CML (CP or AP) with resistance and/or intolerance to two or more TKIs. Further evidence of response durability to verify clinical benefit is pending.

Cooperative dissolution of peptidomimetic vesicles and amyloid ß fibrils.

The aggregation of amyloid proteins in the brain is a significant neurotoxic event that contributes to neurodegenerative disorders. The aggregation of amyloid beta (Aß), particularly Aß42 monomers, into various forms such as oligomers, protofibrils, fibrils, and amyloid plaques is a key pathological feature in Alzheimer's disease. As a result, Aß42 is a primary target and the development of molecular strategies for the dissolution of Aß42 aggregates is considered a promising approach to mitigating Alzheimer's disease pathology. A set of pyrene-conjugated peptidomimetics derived from Aß14-23 (AkdcPy, AkdmPy, and AkdnPy) by incorporating an unnatural amino acid [kd: cyclo(Lys-Asp)] were studied for their ability to modulate Aß42 aggregation. AkdcPy and AkdmPy formed vesicular structures in aqueous media. The vesicles of AkdmPy loaded with the neuroprotective compound berberine (Ber), dissipated mutually in the presence of preformed Aß42 fibrils. During this process, the active drug Ber was released. This work is expected to inspire the development of drug-loaded peptidomimetic-based therapeutic formulations to modulate disorders associated with amyloid toxicity.

Cost-effective remedial to microfiber pollution from wash effluent in Kolkata and Ranaghat.

The microfibers generated from Polyester and Nylon based materials during washing cause serious environmental pollution by both contaminating the aquatic environment and the livelihood of the underwater creatures as well. This study aims at investigating the microfiber-pollution in wash effluents collected from different regions of Kolkata which is believed to be one of the microfiber-polluted cities in the South-east Asia in recent times. In this work, packed bed microfiltration (PBMF) was adopted in an economic and eco-friendly manner to arrest adequate amounts of microfibers and non-biodegradable matters present in the water samples collected from different regions of Kolkata and its surrounding areas. Moreover, effective parameters such as packed bed height to diameter ratio (H/D), mess size of the adopted filtration unit were varied from 0.71 to 2.85 and 60 to 100, respectively to understand the efficacy of the approach and to justify the potential of such alternative in order to alleviate the concern as well. The present study reveals that the microfiltration efficiency of the proposed PBMF unit was achieved maximum 93.5% for sample A and 92.2% for sample D respectively to reduce the microfiber count from 7614 to 543 in an hour operation at a flow rate of 60 L h-1. Besides, the cost of such system was found to be promising as much as 5 US$ on a yearly basis.

Nanoclusters with specific DNA overhangs: modifying configurability, engineering contrary logic pairs and the parity generator/checker for error detection.

The most promising alternative for next-generation molecular computers is biocomputing, which uses DNAs as its primary building blocks to perform a Boolean operation. DNA nanoclusters (NCs) have emerged as promising candidates for biosensing applications due to their unique self-assembly properties and programmability. It has been demonstrated that adding DNA overhangs to DNA NCs improves their adaptability in identifying specific biomolecular interactions. A recent proposal in DNA computing is the concept of "contrary logic pairs (CLPs)" executed by employing a DNA hybrid architecture as a universal platform. We have designed thymine overhang-modified DNA-templated NCs (T-Au/Ag NCs). These NCs serve as a chemosensing ensemble platform, where the presence of HgII ions mediates the formation of M-Au/Ag NCs. The resulting NCs exhibit the capability to drive elementary CLPs (YES, NOT, OR, NOR, INH and IMP) as well as complex logic operations (XOR and XNOR). Additionally, they can be utilized for advanced non-arithmetic DNA logic devices like a parity generator (pG) and a parity checker (pC) for "error detection". Bit errors are an unavoidable and common occurrence during any computing. A cascade of XOR operations was used to evaluate these errors by introducing the pG and pC at the transmitting (TX) and receiving (RX) ends in binary transmission, respectively, which has devastating implications for reliable logic circuits, especially in advanced logic computation. Moreover, an even/odd natural number from 0 to 9 distinguishable pC was designed based on a dual-source responsive computing platform. This work offers inspiring avenues for a cost-effective strategy to construct highly-intelligent DNA computing devices by enhancing the multi-input responsive single DNA platform concept.

Practical Recommendations for the Use of Angiotensin Receptor-Neprilysin Inhibitors (ARNI) in Heart Failure: Insights from Indian Cardiologists.

Heart failure is a significant public health concern characterized by notable rates of morbidity and mortality. Despite the presence of guideline-directed medical therapy (GDMT), its utilization remains inadequate. This practical recommendation paper focuses on the utilization of angiotensin receptor-neprilysin inhibitor (ARNI) as a pivotal treatment for heart failure with reduced ejection fraction (HFrEF), heart failure with preserved ejection fraction (HFpEF), and heart failure with improved ejection fraction (HFimpEF). The recommendations presented in this paper have been developed by a group of cardiologists in India who convened six advisory board meetings to discuss the utilization of ARNI in the management of heart failure. The paper emphasizes the importance of accurate biomarkers for diagnosing heart failure, particularly N-terminal pro-B-type natriuretic peptide (NT-proBNP) and B-type natriuretic peptide (BNP), which are commonly used. Additionally, the paper advocates the use of imaging, specifically echocardiography, in diagnosing and monitoring heart failure patients. Moreover, the paper highlights the role of ARNI in heart failure management, with numerous clinical trials that have demonstrated its effectiveness in reducing cardiovascular death or heart failure hospitalization, enhancing quality of life, and diminishing the risk of ventricular arrhythmias. This practical recommendation paper offers valuable insights into the utilization of ARNI in the management of heart failure, aiming to enhance the implementation of GDMT and ultimately alleviate the burden of heart failure on society.

Drug Dissolution in Oral Drug Absorption: Workshop Report.

The in-person workshop "Drug Dissolution in Oral Drug Absorption" was held on May 23-24, 2023, in Baltimore, MD, USA. The workshop was organized into lectures and breakout sessions. Three common topics that were re-visited by various lecturers were amorphous solid dispersions (ASDs), dissolution/permeation interplay, and in vitro methods to predict in vivo biopharmaceutics performance and risk. Topics that repeatedly surfaced across breakout sessions were the following: (1) meaning and assessment of "dissolved drug," particularly of poorly water soluble drug in colloidal environments (e.g., fed conditions, ASDs); (2) potential limitations of a test that employs sink conditions for a poorly water soluble drug; (3) non-compendial methods (e.g., two-stage or multi-stage method, dissolution/permeation methods); (4) non-compendial conditions (e.g., apex vessels, non-sink conditions); and (5) potential benefit of having both a quality control method for batch release and a biopredictive/biorelevant method for biowaiver or bridging scenarios. An identified obstacle to non-compendial methods is the uncertainty of global regulatory acceptance of such methods.

A randomized double-blind placebo-controlled clinical study on the effects of gabapentin premedication on hemodynamic stability during laparoscopic cholecystectomy.

BACKGROUND: Carbon dioxide pneumoperitoneum for laparoscopic surgery increases arterial pressures, heart rate, and systemic vascular resistance. In this randomized double-blind placebo-controlled clinical study, we investigated the efficacy of gabapentin premedication to provide perioperative hemodynamic stability in patients undergoing laparoscopic cholecystectomy. MATERIALS AND METHODS: Sixty patients, of either sex (18-65 years of age) undergoing elective laparoscopic cholecystectomy were randomly allocated to two groups of 30 patients each. Patients of group G received oral gabapentin 900 mg 2 h before induction of anesthesia, while patients in group P received placebo at the same time. RESULTS: Mean arterial pressure in patients of group G were significantly lower (P < 0.05) after tracheal intubation and pneumoperitoneum and remained lower, as compared to group P, throughout the pneumoperitoneum. Similarly, heart rate in group G was significantly lower (P < 0.05) after tracheal intubation and pneumoperitoneum and remained lower, in comparison to group P, throughout the peumoperitoneum. Intravenous labetalol was required, to control intraoperative hypertension, in 33.3% (10 out of 30) patients in group P. There was no significant difference in the incidence of adverse effects between the two groups. CONCLUSION: Gabapentin premedication provided perioperative hemodynamic stability during laparoscopic surgery.

Combating amyloid-induced cellular toxicity and stiffness by designer peptidomimetics.

Amyloid beta (Aß) aggregation species-associated cellular stress instigates cytotoxicity and adverse cellular stiffness in neuronal cells. The study and modulation of these adverse effects demand immediate attention to tackle Alzheimer's disease (AD). We present a de novo design, synthesis and evaluation of Aß14-23 peptidomimetics with cyclic dipeptide (CDP) units at defined positions. Our study identified AkdNMC with CDP units at the middle, N- and C-termini as a potent candidate to understand and ameliorate Aß aggregation-induced cellular toxicity and adverse stiffness.

Differential copper-guided architectures of amyloid ß peptidomimetics modulate oxidation states and catalysis.

Orchestration of differential architectures of designer peptidomimetics that modulate metal oxidation states to perform multiple chemical transformations remains a challenge. Cu-chelation and self-assembly properties of amyloid ß (Aß14-23) peptide were tuned by the incorporation of cyclic dipeptide (CDP) and pyrene (Py) as the assembly directing and reporting units, respectively. We explore the molecular architectonics of Aß14-23 derived peptidomimetics (AkdNMCPy) to form differential architectures that stabilize distinct Cu oxidation states. The fibrillar self-assembly of AkdNMCPy is modulated to form nanosheets by the one-off addition of CuII. Notably, the serial addition of CuII resulted in the formation of micelle-like core-shell architectures. The micelle-like and nanosheet architectures were found to differentially stabilize CuII and CuI states and catalyze tandem oxidative-hydrolysis and alkyne-azide cycloaddition reactions, respectively.

Mercury mediated DNA-Au/Ag nanocluster ensembles to generate a gray code encoder for biocomputing.

Boolean operations utilizing DNA as a platform for biocomputing have become a promising tool for next-generation bio-molecular computers. In the whole process of any binary data transmission, bit errors are unavoidable and commonly occur. Cascades of exclusive-OR (XOR) operations show the great potential to evaluate these errors by introducing a parity generator (pG) and a parity checker (pC). Herein, we constructed a DNA hybrid architecture platform employing a chemosensing ensemble of mercury-mediated DNA-Au/Ag nanoclusters (M-Au/Ag NCs) to operate unconventional pG/pC for "error detection". Taking advantage of pG/pC, the transmitted and received data is converted to secure information using a binary to gray code encoder. To the best of our knowledge, this is the first molecular gray code encoder for biocomputing, which discovers an exciting avenue to protect information security through sophisticated logic circuits.