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.

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.

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.

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.

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.

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.

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.

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.

Aging-Responsive Phase Transition of VOOH to V10O24·nH2O vs Zn2+ Storage Performance as a Rechargeable Aqueous Zn-Ion Battery Cathode.

Vanadium oxyhydroxide has been recently investigated as a starting material to synthesize different phases of vanadium oxides by electrochemical or thermal conversion and has been used as an aqueous zinc-ion battery (AZIB) cathode. However, the low-valent vanadium oxides have poor phase stability under ambient conditions. So far, there is no study on understanding the phase evolution of such low-valent vanadium oxides and their effect on the electrochemical performance toward hosting the Zn2+ ions. The primary goal of the work is to develop a high-performance AZIB cathode, and the highlight of the current work is the insight into the auto-oxidation-induced phase transition of VOOH to V10O24·nH2O under ambient conditions and Zn2+ intercalation behavior thereon as an aqueous zinc-ion battery cathode. Herein, we demonstrate that hydrothermally synthesized VOOH undergoes a phase transition to V10O24·nH2O during both the electrochemical cycling and aerial aging over 38-45 days. However, continued aging till 150 days at room temperature in an open atmosphere exhibited an increased interlayer water content in the V10O24·nH2O, which was associated with a morphological change with different surface area/porosity characteristics and notably reduced charge transfer/diffusion resistance as an aqueous zinc-ion battery cathode. Although the fresh VOOH cathode had impressive specific capacity at rate performance, (326 mAh/g capacity at 0.1 A/g current and 104 mAh/g capacity at 4 A/g current) the cathode suffered from a continuous capacity decay. Interestingly, the aged VOOH electrodes showed gradually decreasing specific capacity with aging at low current and however followed the reverse order at high current. At a comparable specific power of ∼64-66 W/kg, the fresh VOOH and aged VOOH after 60, 120, and 150 days of aging showed the respective energy densities of 208.3, 281.2, 269.2, and 240.6 Wh/kg. Among all the VOOH materials, the 150 day-aged VOOH cathode exhibited the highest energy density at a power density beyond 1000 W/kg. Thanks to the improved kinetics, the 150 day-aged VOOH cathode delivered a considerable energy density of 39.7 Wh/kg with a high specific power of 4466 W/kg. Also, it showed excellent cycling performance with only 0.002% capacity loss per cycle over 20 300 cycles at 10 A/g.

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.

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.

Expert Opinion on the Use of Novel Oral Anticoagulants for Stroke Prevention in Non-valvular Atrial Fibrillation for the Primary Care Setting in India: A Literature Review.

Atrial fibrillation (AF), the most prevalent cardiac arrhythmia encountered in clinical practice, is linked with substantial morbidity and mortality due to accompanying risk of stroke and thromboembolism. Patients with AF are at a five-fold higher risk of suffering from a stroke. Anticoagulation therapy, with either vitamin K antagonists or novel oral anticoagulants (NOACs), is a standard approach to reduce the risk. Consultant physicians (CPs) in India are the primary point of contact for the majority of patients before they approach a specialist. The CPs may face challenges in screening and diagnosing AF patients. The apprehensions associated with managing AF patients with anticoagulants, further add to the challenges of a CP. This review aimed to identify the key decision points for the CPs to diagnose AF and initiate anticoagulation in patients with non-valvular AF (NVAF) and bring to the table a simplified recommendation supported by expert opinion and guidelines for stroke prevention in NVAF patients.

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.

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.

Nucleic Acid Architectonics for pH-Responsive DNA Systems and Devices.

Nucleic acid-based architectures have opened up numerous opportunities for basic and applied research in the field of DNA nanotechnology. The scheme of molecular architectonics of nucleic acids exploits conventional and unconventional base pairing interactions to integrate molecular partners in constructing functional molecular architectures and devices. The pH-responsive functional nucleic acid systems and devices have gained interest in diagnostics and therapeutics because of their biocompatibility and structural programmability. In this Mini-Review, we discuss recent advancements in the area of nucleic acid architectonics with a special emphasis on pH-driven molecular systems including molecular and nanoarchitectures, templated architectures and nanoclusters, nanomachines, hydrogels, targeted bioimaging, and drug delivery architectures. Finally, the Mini-Review is concluded by highlighting the challenges and opportunities for future developments.