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Introduction: Surgeries involving bowel resection and anastomosis are quite common. Fluid overload, leading to tissue edema and impaired tissue perfusion, may contribute to anastomotic leak, which is one of the most dreaded complication. Methods: In our current study, CT scan, done on postoperative day-4, was used to assess visceral edema, and its effect on development of complications post bowel anastomosis and increase in value of cross section of body trunk area ≥20% was taken as an independent risk factor of severe complication. Results: Twenty three patients were enrolled in the study, 7 of them developed complications. The most common complication observed was wound infection (Clavein Dindo grade II). Only 2 patients (28.57%) had an increase in CT area >20%. Among patients who developed complications, 33.3% had an increase in CT area and 28.6% did not. Various other factors – preoperative albumin level, timing of surgery, duration of surgery – also lead to development of complications. Statistically, no significant association could be derived between the increase in CT area and development of complications. Conclusion: As per the findings of the current study, higher fluid balance was not reflected by an increase in body surface area on CT Scan. Hence, use of CT scan as a tool to assess visceral edema needs further evaluation.

Abstract The ability to scale two-dimensional (2D) material thickness down to a single monolayer presents a promising opportunity to realize high-speed energy-efficient memristors. Here, we report an ultra-fast memristor fabricated using atomically thin sheets of 2D hexagonal Boron Nitride, exhibiting the shortest observed switching speed (120 ps) among 2D memristors and low switching energy (2pJ). Furthermore, we study the switching dynamics of these memristors using ultra-short (120ps-3ns) voltage pulses, a frequency range that is highly relevant in the context of modern complementary metal oxide semiconductor (CMOS) circuits. We employ statistical analysis of transient characteristics to gain insights into the memristor switching mechanism. Cycling endurance data confirms the ultra-fast switching capability of these memristors, making them attractive for next generation computing, storage, and Radio-Frequency (RF) circuit applications.

A systematic investigation of isospin dependence of nuclear level density (NLD) is performed for the Zn isotopes. Experimental level densities of 67Zn and 61Zn have been determined by analyzing the spectra of evaporated neutrons emitted from the excited 68Zn and 62Zn nuclei populated via 4He + 64Ni and 4He + 58Ni reactions, respectively. At the low excitation energies, the neutron spectra are predominantly contributed by the first-chance decay, leading to 67Zn and 61Zn as daughters for the two cases. A comparison of the present experimental data along with previously measured NLDs of 66Zn, 64Zn, and 60Zn is performed with state-of-the-art microscopic calculations. While the experimental NLDs of stable isotopes (i.e., 67Zn, 66Zn, and 64Zn) align excellently with theoretical predictions, a compelling contrast emerges for the unstable isotopes 61Zn and 60Zn, exhibiting NLDs an order of magnitude lower than predicted. The possible origins of the observed suppression of NLDs for the N ≈ Z isotopes are discussed. A significant reduction of level density for nuclei situated away from the stability line could have critical implications for the calculation of astrophysical reaction rates pertinent to heavy-element nucleosynthesis.

Summary: Skin/soft tissue infections (SSTIs) caused by methicillin-resistant Staphylococcus aureus (MRSA) pose a major healthcare burden. Distinct inflammatory and resolution phases comprise the host immune response to SSTIs. Resolution is a myeloid PPARγ-dependent anti-inflammatory phase that is essential for the clearance of MRSA. However, the signals activating PPARγ to induce resolution remain unknown. Here, we demonstrate that myeloid glucose transporter 1 (GLUT-1) is essential for the onset of resolution. MRSA-challenged macrophages are unsuccessful in generating an oxidative burst or immune radicals in the absence of GLUT-1 due to a reduction in the cellular NADPH pool. This translates in vivo as a significant reduction in lipid peroxidation products required for the activation of PPARγ in MRSA-infected mice lacking myeloid GLUT-1. Chemical induction of PPARγ during infection circumvents this GLUT-1 requirement and improves resolution. Thus, GLUT-1-dependent oxidative burst is essential for the activation of PPARγ and subsequent resolution of SSTIs.

Bacterial infections at wound sites require more time for a fast and efficient wound-healing process. Antibacterial methyl cellulose-based hydrogel wound dressing can be an excellent option because it can show antibacterial action, absorb wound exudates, and have a cooling and soothing effect on the wound bed. The ultraviolet (UV) ray-assisted semi-solid extrusion 3D printing technique was used to prepare 3D printed construct into a high surface area mesh-like structure utilizing UV radiation for photocrosslinking of hydrogel matrix in the presence of Poly (ethylene glycol) Diacrylate. The prepared hydrogel was characterized for contact angle, and rheological analysis before semi-solid extrusion-based 3D printing. After optimization of printing parameters, the 3D printed mesh was subjected to physicochemical characterizations like dimensional analysis, swelling study, drug content, in vitro drug release, and in vitro antimicrobial activity study. A rheological analysis confirmed the viscosity, thixotropy, and viscoelastic nature of prepared hydrogel. Drug release study showed approximately 50 % release in 4 h, and >80 % drug release in 24 h. After optimization of one batch, hydrogel polymerization was done by functional group analysis followed by validation of thread thickness by electron microscopy images and mechanical property assessment. The 3D-printed mesh was further evaluated for its in-vitro antibacterial performance against Escherichia coli and Staphylococcus aureus. The area of inhibition was one-fold more in Staphylococcus aureus and two-fold in E. coli, ensuring diffusion of the drug from 3D printed mesh and killing of bacteria. The work reported herein represents a universal platform to generate multifunctional and customized hydrogels with various functional substances for wound dressing applications.

Understanding the flow instabilities encountered by the turbocharger compressor is an important step toward improving its overall design for performance and efficiency. While an experimental study using Particle Image Velocimetry was previously conducted to examine the flow field at the inlet of the turbocharger compressor, the present work complements that effort by analyzing the flow structures leading to stall instability within the same impeller. Experimentally validated three-dimensional computational fluid dynamics predictions are carried out at three discrete mass flow rates, including 77 g/s (stable, maximum flow condition), 57 g/s (near peak efficiency), and 30 g/s (with strong reverse flow from the impeller) at a fixed rotational speed of 80,000 rpm. Large stationary stall cells were observed deep within the impeller at 30 g/s, occupying a significant portion of the blade passage near the shroud between the suction surface of the main blades and the pressure surface of the splitter blades. These stall cells are mainly created when a substantial portion of the inlet core flow is unable to follow the impeller’s axial to radial bend against the adverse pressure gradient and becomes entrained by the reverse flow and the tip leakage flow, giving rise to a region of low-momentum fluid in its wake. This phenomenon was observed to a lesser extent at 57 g/s and was completely absent at 77 g/s. On the other hand, the inducer rotating stall was found to be most dominant at 57 g/s. The entrainment of the tip leakage flow by the core flow moving into the impeller, leading to the generation of an unstable, wavy shear layer at the inducer plane, was instrumental in the generation of rotating stall. The present analyses provide a detailed characterization of both stationary and rotating stall cells and demonstrate the physics behind their formation, as well as their effect on compressor efficiency. The study also characterizes the entropy generation within the impeller under different operating conditions. While at 77 g/s, the entropy generation is mostly concentrated near the shroud of the impeller with the core flow being almost isentropic, at 30 g/s, there is a significant increase in the area within the blade passage that shows elevated entropy production. The tip leakage flow, its interaction with the blades and the core forward flow, and the reverse flow within the impeller are found to be the major sources of irreversibilities.

Abstract Down syndrome regression disorder (DSRD) is a clinical symptom cluster consisting of neuropsychiatric regression without an identifiable cause. This study evaluated the clinical effectiveness of IVIg and evaluated clinical characteristics associated with relapse after therapy discontinuation. A prospective, multi-center, non-randomized, observational study was performed. Patients met criteria for DSRD and were treated with IVIg. All patients underwent a standardized wean-off therapy after 9–12 months of treatment. Baseline, on-therapy, and relapse scores of the Neuropsychiatric Inventory Total Score (NPITS), Clinical Global Impression-Severity (CGI-S), and the Bush–Francis Catatonia Rating Scale (BFCRS) were used to track clinical symptoms. Eighty-two individuals were enrolled in this study. Patients had lower BFCRS (MD: −6.68; 95% CI: −8.23, −5.14), CGI-S (MD: −1.27; 95% CI: −1.73, −0.81), and NPITS scores (MD: −6.50; 95% CI: −7.53, −5.47) while they were on therapy compared to baseline. Approximately 46% of the patients (n = 38) experienced neurologic relapse with wean of IVIg. Patients with neurologic relapse were more likely to have any abnormal neurodiagnostic study (χ 2 = 11.82, P = 0.001), abnormal MRI (χ 2 = 7.78, P = 0.005), and abnormal LP (χ 2 = 5.45, P = 0.02), and a personal history of autoimmunity (OR: 6.11, P

Summary: Non-alcoholic fatty liver disease (NAFLD) is an emerging global health problem and a potential risk factor for metabolic diseases. The bidirectional interactions between liver and gut made dysbiotic gut microbiome one of the key risk factors for NAFLD. In this study, we reported an increased abundance of Collinsella aerofaciens in the gut of obese and NASH patients living in India. We isolated C. aerofaciens from the fecal samples of biopsy-proven NASH patients and observed that their genome is enriched with carbohydrate metabolism, fatty acid biosynthesis, and pro-inflammatory functions and have the potency to increase ethanol level in blood. An animal study indicated that mice supplemented with C. aerofaciens had increased levels of circulatory ethanol, high levels of hepatic hydroxyproline, triglyceride, and inflammation in the liver. The present findings indicate that perturbation in the gut microbiome composition is a key risk factor for NAFLD.

Therapeutic options for managing Pancreatic ductal adenocarcinoma (PDAC), one of the deadliest types of aggressive malignancies, are limited and disappointing. Therefore, despite suboptimal clinical effects, gemcitabine (GEM) remains the first-line chemotherapeutic drug in the clinic for PDAC treatment. The therapeutic limitations of GEM are primarily due to poor bioavailability and the development of chemoresistance resulting from the addiction of mutant-K-RAS/AKT/ERK signaling-mediated desmoplastic barriers with a hypoxic microenvironment. Several new therapeutic approaches, including nanoparticle-assisted drug delivery, are being investigated by us and others. This study used pH-responsive nanoparticles encapsulated ERK inhibitor (SCH772984) and surface functionalized with tumor-penetrating peptide, iRGD, to target PDAC tumors. We used a small molecule, SCH772984, to target ERK1 and ERK2 in PDAC and other cancer cells. This nanocarrier efficiently released ERKi in hypoxic and low-pH environments. We also found that the free-GEM, which is functionally weak when combined with nanoencapsulated ERKi, led to significant synergistic treatment outcomes in vitro and in vivo. In particular, the combination approaches significantly enhanced the GEM effect in PDAC growth inhibition and prolonged survival of the animals in a genetically engineered KPC (LSL-KrasG12D/+/LSL-Trp53R172H/+/Pdx-1-Cre) pancreatic cancer mouse model, which is not observed in a single therapy. Mechanistically, we anticipate that the GEM efficacy was increased as ERKi blocks desmoplasia by impairing the production of desmoplastic regulatory factors in PDAC cells and KPC mouse tumors. Therefore, 2nd generation ERKi (SCH 772984)-iRGD-pHNPs are vital for the cellular response to GEM and denote a promising therapeutic target in PDAC with mutant K-RAS.

ABSTRACTStaphylococcus aureus is a major human pathogen that causes a variety of illnesses, ranging from minor skin and soft tissue infections to more severe systemic infections. Although the primary host immune response can typically clear bacterial infections, S. aureus is uniquely resistant to inflammation. For instance, our laboratory has determined that S. aureus is highly resistant to nitric oxide (NO⋅), an important component of the innate immune response that plays a role in both immunomodulatory and antibacterial processes. Additionally, NO⋅ and its derivatives can cause damage to S. aureus DNA, more specifically, deamination and/or oxidation of DNA bases; however, regulation and repair mechanisms of DNA in S. aureus are understudied. Thus, we hypothesize that several DNA repair mechanisms may account for the replication fidelity of S. aureus and may contribute to fitness in the presence of NO⋅. Here, we show the role of several DNA repair mechanisms in S. aureus. More specifically, we found that recombinational repair genes recJ, recG, and polA may play a role in the repair of NO⋅-induced replication fork collapses. We also show the role of the base excision repair pathway protein, MutY, in reducing NO⋅-mediated mutagenesis. Overall, our results suggest that NO⋅ leads to DNA damage, which subsequently induces the activity of several DNA repair pathways, contributing to the replication fidelity and fitness of S. aureus.IMPORTANCEPathogenic bacteria must evolve various mechanisms in order to evade the host immune response that they are infecting. One aspect of the primary host immune response to an infection is the production of an inflammatory effector component, nitric oxide (NO⋅). Staphylococcus aureus has uniquely evolved a diverse array of strategies to circumvent the inhibitory activity of nitric oxide. One such mechanism by which S. aureus has evolved allows the pathogen to survive and maintain its genomic integrity in this environment. For instance, here, our results suggest that S. aureus employs several DNA repair pathways to ensure replicative fitness and fidelity under NO⋅ stress. Thus, our study presents evidence of an additional strategy that allows S. aureus to evade the cytotoxic effects of host NO⋅.

ABSTRACTStaphylococcus aureus is a major human pathogen capable of causing a variety of diseases ranging from skin and soft tissue infections to systemic presentations such as sepsis, endocarditis, and osteomyelitis. For S. aureus to persist as a pathogen in these environments, it must be able to resist the host immune response, including the production of reactive oxygen and nitrogen species (e.g., nitric oxide, NO·). Extensive work from our lab has shown that S. aureus is highly resistant to NO·, especially in the presence of glucose. RNA-seq performed on S. aureus exposed to NO· in the presence and absence of glucose showed a new system important for NO· resistance—phosphate transport. The phosphate transport systems pstSCAB and nptA are both upregulated upon NO·-exposure, particularly in the presence of glucose. Both are key for phosphate transport at an alkaline pH, which the cytosol of S. aureus becomes under NO· stress. Accordingly, the ΔpstSΔnptA mutant is attenuated under NO stress in vitro as well as in macrophage and murine infection models. This work defines a new role in infection for two phosphate transporters in S. aureus and provides insight into the complex system that is NO· resistance in S. aureus.IMPORTANCEStaphylococcus aureus is a bacterial pathogen capable of causing a wide variety of disease in humans. S. aureus is unique in its ability to resist the host immune response, including the antibacterial compound known as nitric oxide (NO·). We used an RNA-sequencing approach to better understand the impact of NO· on S. aureus in different environments. We discovered that inorganic phosphate transport is induced by the presence of NO·. Phosphate is important for the generation of energy from glucose, a carbon source favored by S. aureus. We show that the absence of these phosphate transporters causes lowered energy levels in S. aureus. We find that these phosphate transporters are essential for S. aureus to grow in the presence of NO· and to cause infection. Our work here contributes significantly to our understanding of S. aureus NO· resistance and provides a new context in which S. aureus phosphate transporters are essential.

Abstract Servo press forming machines are advanced forming systems that are capable of imparting interrupted punch motion, resulting in enhanced room temperature formability. The exact mechanism of the formability improvement is not yet established. The contribution of interrupted motion in the ductility improvement has been studied through stress relaxation phenomena in uniaxial tensile (UT) tests. However, the reason for improved formability observed when employing servo press is complicated due to the additional contribution from frictional effects. In the present work, an attempt is made to decouple the friction effect on formability improvement numerically. The improved formability is studied using a hole expansion test (HET). The limit of forming during hole expansion is modeled using the Hosford-Coulomb (HC) damage criteria, which is implemented as a user subroutine in a commercial explicit finite element (FE) software. Only the contribution of stress relaxation is accounted for in the evolution of the damage variable during interrupted loading. Therefore, the difference between simulation and experimental hole expansion ratio (HER) can be used to decouple the friction effect from the overall formability improvement during hole expansion. The improvement in HER due to stress relaxation and friction effect is different. The study showed that the model effectively captures the hole expansion deformation process in both monotonic and interrupted loading conditions. Compared to stress relaxation, friction effect played a major role during interrupted HET.

This work focuses on understanding the electronic properties of materials to enhance the performance of Tunnel Field Effect Transistor (TFET) through Density Functional Theory (DFT) simulations. Material selection prefers a p-type material with in-plane high density of state (DOS) (and low out-of-plane effective mass, m*, where defined for many layer systems), and high valence band maxima (VBM) energy stacked with an n-type material with low conduction band minimum (CBM) energy (large electron affinity (EA)) that creates a broken or nearly broken band alignment and has low lattice mismatch. SnSe2 is well-suited for an n-type 2D material due to high EA, while WSe2, Black phosphorous (BP) and SnSe are explored for p-type materials. Bilayers consisting of monolayers of WSe2 and SnSe2 show a staggered but nearly broken band alignment (gap of 24 meV) and a high valence band DOS for WSe2. BP-SnSe2 shows a broken band alignment and benefits from a low lattice mismatch. SnSe-SnSe2 shows the highest chemical stability, an optimal performance in terms of DOS of SnSe, tunability with an external field, and high VBM that also leads to a broken band alignment.

The aberrant glycosylation is a hallmark of cancer progression and chemoresistance. It is also an immune therapeutic target for various cancers. Tunicamycin (TM) is one of the potent nucleoside antibiotics and an inhibitor of aberrant glycosylation in various cancer cells, including breast cancer, gastric cancer, and pancreatic cancer, parallel with the inhibition of cancer cell growth and progression of tumors. Like chemotherapies such as doxorubicin (DOX), 5′fluorouracil, etoposide, and cisplatin, TM induces the unfolded protein response (UPR) by blocking aberrant glycosylation. Consequently, stress is induced in the endoplasmic reticulum (ER) that promotes apoptosis. TM can thus be considered a potent antitumor drug in various cancers and may promote chemosensitivity. However, its lack of cell-type-specific cytotoxicity impedes its anticancer efficacy. In this review, we focus on recent advances in our understanding of the benefits and pitfalls of TM therapies in various cancers, including breast, colon, and pancreatic cancers, and discuss the mechanisms identified by which TM functions. Finally, we discuss the potential use of nano-based drug delivery systems to overcome non-specific toxicity and enhance the therapeutic efficacy of TM as a targeted therapy.

A significant number of discoveries in past two decades have established the importance of long-distance signaling in controlling plant growth, development, and biotic and abiotic stress responses. Numerous mobile signals, such as mRNAs, proteins, including RNA-binding proteins, small RNAs, sugars, and phytohormones, are shown to regulate various agronomic traits such as flowering, fruit, seed development, and tuberization. Potato is a classic model tuber crop, and several mobile signals are known to govern tuber development. However, it is unknown if these mobile signals have any synergistic effects on potato crop improvement. Here, we employed a simple innovative strategy to test the cumulative effects of a key mobile RNA, StBEL5, and its RNA-binding proteins, StPTB1, and -6 on tuber productivity of two potato cultivars, Solanum tuberosum cv. Désirée and subspecies andigena, using a multi-gene stacking approach. In this approach, the coding sequences of StBEL5 and StPTB1/6 are driven by their respective native promoters to efficiently achieve targeted expression in phloem for monitoring tuber productivity. We demonstrate that this strategy resulted in earliness for tuberization and enhanced tuber productivity by 2–4 folds under growth chamber, greenhouse, and field conditions. This multi-gene stacking approach could be adopted to other crops, whose agronomic traits are governed by mobile macromolecules, expanding the possibilities to develop crops with improved traits and enhanced yields.

The observation of mass-asymmetric fission in neutron-deficient 180Hg dramatically expanded the region of mass-asymmetric fission found across the nuclide chart, and has led to intense experimental and theoretical investigations into the fission of sub-lead nuclei. In particular, two major questions have been raised: how many fission modes are present in the fission of sub-lead nuclides, and which shells dictate these modes?Notably, investigations of the fission modes of 178Pt have led to contrasting results. To solve this disparity, new high-statistics data have been measured at the lowest excitation energy to-date using the CUBE fission spectrometer at The Australian National University. A new fitting procedure was developed to fit the high-statistics two-dimensional mass-kinetic energy distribution without external constraints.The fission of 178Pt can best be described by three fission modes: one mass-symmetric and two mass-asymmetric. Comparisons to previous analyses highlight the necessity of fitting the two-dimensional mass-kinetic energy distribution, rather than fitting slices of individual one-dimensional projections of the full distribution. Systematic studies of high-statistics measurements, combined with a rigorous statistical analysis offer the best chance to determine the shell effects responsible for multi-modal mass-asymmetric fission in this region of the nuclide chart.

We report the detection of carbon monoxide (CO) and dust, formed under hostile conditions, in recurrent nova V745 Sco about 8.7 days after its 2014 outburst. The formation of molecules or dust has not been recorded previously in the ejecta of a recurrent nova. The mass and temperature of the CO and dust are estimated to be T _CO = 2250 ± 250 K, M _CO = (1–5) × 10 ^−8 M _⊙ , and T _dust = 1000 ± 50 K, M _dust ∼ 10 ^−8 –10 ^−9 M _⊙ , respectively. At the time of their detection, the shocked gas was at a high temperature of ∼10 ^7 K as evidenced by the presence of coronal lines. The ejecta were simultaneously irradiated by a large flux of soft X-ray radiation from the central white dwarf. Molecules and dust are not expected to form and survive in such harsh conditions; they are like snowflakes in a furnace. However, it has been posited in other studies that, as the nova ejecta plow through the red giant's wind, a region exists between the forward and reverse shocks that is cool, dense and clumpy where the dust and CO could likely form. We speculate that this site may also be a region of particle acceleration, thereby contributing to the generation of γ -rays.

V445 Puppis, the only known Galactic helium nova, is a unique test bed to verify supernova (SN) theories in the single-degenerate channel that involve a white dwarf (WD) accreting matter from a helium-rich donor. An estimate of the mass of the helium shell on the WD is crucial to deciding whether or not it will undergo an SN detonation. In this context, this study estimates the dust and ejecta masses in the 2000 November eruption of V445 Pup. Subsequent to its outburst, the star became cocooned in a dust envelope. An analysis of the spectral energy distribution (SED) of the dust using infrared data shows that V445 Pup produced at least 10 ^−3 M _⊙ of dust, which is unprecedented for a classical or recurrent nova. The SED can be explained by a combination of a cold dust component at 105 ± 10 K, mass (1.9 ± 0.8) × 10 ^−3 M _⊙ , and a warm dust component at 255 ± 10 K, mass (2.2 ± 1.2) × 10 ^−5 M _⊙ . For a conservative choice of the gas-to-dust mass ratio in the range 10–100, the mass of the ejecta is 0.01–0.1 M _⊙ . Such a high mass range raises the question: why did V445 Pup not detonate as a Type Ia SN as is predicted in certain double-detonation sub-Chandrasekhar supernovae formalisms? We reexamine the nature of V445 Pup and discuss its role as a potential SN progenitor.

Pregestational diabetes (PGDM) leads to developmental impairment, especially cardiac dysfunction, in their offspring. The hyperglycemic microenvironment inside the uterus alters the cardiac plasticity characterized by electrical and structural remodeling of the heart. The altered expression of several transcription factors due to hyperglycemia during fetal development might be responsible for molecular defects and phenotypic changes in the heart. The molecular mechanism of the developmental defects in the heart due to PGDM remains unclear. To understand the molecular defects in the 2-days old neonatal rats, streptozotocin-induced diabetic female rats were bred with healthy male rats. We collected 2-day-old hearts from the neonates and identified the molecular basis for phenotypic changes. Neonates from diabetic mothers showed altered electrocardiography and echocardiography parameters. Transcriptomic profiling of the RNA-seq data revealed that several altered genes were associated with heart development, myocardial fibrosis, cardiac conduction, and cell proliferation. Histopathology data showed the presence of focal cardiac fibrosis and increased cell proliferation in neonates from diabetic mothers. Thus, our results provide a comprehensive map of the cellular events and molecular pathways perturbed in the neonatal heart during PGDM. All of the molecular and structural changes lead to developmental plasticity in neonatal rat hearts and develop cardiac anomalies in their early life.

Nuclear level density and the level density parameter of 115,119,127Te isotopes are experimentally determined by analyzing the backward angle neutron energy spectra from 4He+112,116,124Sn reactions. Measurements are done in the compound nuclear excitation energy range of 25-42 MeV. Statistical model analysis is performed to test different phenomenological prescriptions of the level density parameter. Our data efficiently scan the explicit dependences of level density on three key factors: nuclear deformation, neutron-proton asymmetry, and the separation from the most stable isobar. It is observed that the experimental data are best described when deviation in atomic number from the corresponding β-stable isobar is explicitly taken into account. Further, nuclear level densities determined from the measured spectra show a reduction for 115,127Te in comparison to that of 119Te, which lies closer to the β-stability line.

Abstract Background Since 2005, India has experienced an impressive 77% reduction in maternal mortality compared to the global average of 43%. What explains this impressive performance in terms of reduction in maternal mortality and improvement in maternal health outcomes? This paper evaluates the effect of household wealth status on maternal mortality in India, and also separates out the performance of the Empowered Action Group (EAG) states and the Southern states of India. The results are discussed in the light of various pro-poor programmes and policies designed to reduce maternal mortality and the existing supply side gaps in the healthcare system of India. Using multiple sources of data, this study aims to understand the trends in maternal mortality (1997–2017) between EAG and non EAG states in India and explore various household, economic and policy factors that may explain reduction in maternal mortality and improvement in maternal health outcomes in India. Methods This study triangulates data from different rounds of Sample Registration Systems to assess the trend in maternal mortality in India. It further analysed the National Family Health Surveys (NFHS). NFHS-4, 2015–16 has gathered information on maternal mortality and pregnancy-related deaths from 601,509 households. Using logistic regression, we estimate the association of various socio-economic variables on maternal deaths in the various states of India. Results On an average, wealth status of the households did not have a statistically significant association with maternal mortality in India. However, our disaggregate analysis reveals, the gains in terms of maternal mortality have been unevenly distributed. Although the rich-poor gap in maternal mortality has reduced in EAG states such as Bihar, Odisha, Assam, Rajasthan, the maternal mortality has remained above the national average for many of these states. The EAG states also experience supply side shortfalls in terms of availability of PHC and PHC doctors; and availability of specialist doctors. Conclusions The novel contribution of the present paper is that the association of household wealth status and place of residence with maternal mortality is statistically not significant implying financial barriers to access maternal health services have been minimised. This result, and India’s impressive performance with respect to maternal health outcomes, can be attributed to the various pro-poor policies and cash incentive schemes successfully launched in recent years. Community-level involvement with pivotal role played by community health workers has been one of the major reasons for the success of many ongoing policies. Policy makers need to prioritise the underperforming states and socio-economic groups within the states by addressing both demand-side and supply-side measures simultaneously mediated by contextual factors.

Abstract In the absence of fit-testing, leakage of aerosolized pathogens through the gaps between the face and N95 respirators could compromise the effectiveness of the device and increase the risk of infection for the exposed population. To address this issue, we have developed a model to estimate the increase in risk of infection resulting from aerosols leaking through gaps between the face and N95 respirators. The gaps between anthropometric face-geometry and N95 respirators were scanned using computed tomography. The gap profiles were subsequently input into CFD models. The amount of aerosol leakage was predicted by the CFD simulations. Leakage levels were validated using experimental data obtained using manikins. The computed amounts of aerosol transmitted to the respiratory system, with and without leaks, were then linked to a risk-assessment model to predict the infection risk for a sample population. An influenza outbreak in which 50% of the population deployed respirators was considered for risk assessment. Our results showed that the leakage predicted by the CFD model matched the experimental data within about 13%. Depending upon the fit between the headform and the respirator, the inward leakage for the aerosols ranged between 30 and 95%. In addition, the non-fit-tested respirator lowered the infection rate from 97% (for no protection) to between 42 and 80%, but not to the same level as the fit-tested respirators (12%). The CFD-based leakage model, combined with the risk-assessment model, can be useful in optimizing protection strategies for a given population exposed to a pathogenic aerosol.

Nod-Like Receptor (NLR) is the largest family of Pathogen Recognition Receptors (PRRs) that patrols the cytosolic environment. NLR engagement drives caspase-1 activation that cleaves pro-IL-1B which then gets secreted. Released IL-1B recruits immune cells to the site of infection/injury. Caspase-1 also cleaves Gasdermin-D (GSDM-D) that forms pores within the plasma membrane driving inflammatory cell death called pyroptosis. NLRP3 is the most extensively studied NLR. The NLRP3 gene is encoded by 9 exons, where exon 1 codes for pyrin domain, exon 3 codes for NACHT domain, and Leucine Rich Repeat (LRR) domain is coded by exon 4-9. Exon 2 codes for a highly disorganized loop that connects the rest of the protein to the pyrin domain and may be involved in NLRP3 regulation. The NLRP3 inflammasome is activated by many structurally divergent agonists of microbial, environmental, and host origin. Activated NLRP3 interacts with an adaptor protein, ASC, that bridges it to pro-Caspase-1 forming a multi-protein complex called inflammasome. Dysregulation of NLRP3 inflammasome activity is a hallmark of pathogenesis in several human diseases, indicating its highly significant clinical relevance. In this review, we summarize the existing knowledge about the mechanism of activation of NLRP3 and its regulation during activation by infectious and sterile triggers.

Electrostatic gating of 2D transistors with ionic liquids presents intrinsic limitations. Here, the authors demonstrate n-type MoS2 and p-type WSe2 transistors on a lithium-ion solid electrolyte substrate, displaying sub-threshold values approaching the ideal limit of 60 mV/dec and complementary amplifier gain of 34 with 1 V supply.

Cardiac hypertrophy is characterized by an increase in the size of the cardiomyocytes which is initially triggered as an adaptive response but ultimately becomes maladaptive with chronic exposure to different hypertrophic stimuli. Prolonged cardiac hypertrophy is often associated with mitochondrial dysfunctions and cardiomyocyte cell death. Peroxisome proliferator activated receptor alpha (PPAR α), which is critical for mitochondrial biogenesis and fatty acid oxidation, is down regulated in hypertrophied cardiomyocytes. Yet, the role of PPAR α in cardiomyocyte death is largely unknown. To assess the role of PPAR α in chronic hypertrophy, isoproterenol, a β-adrenergic receptor agonist was administered in PPAR α knock out (PPAR α−/−) mice for 2 weeks and hypertrophy associated changes in cardiac tissues were observed. Echocardiographic analysis ensured the development of cardiac hypertrophy and compromised hemodynamics in PPAR α−/− mice. Proteomic analysis using high resolution mass spectrometer identified about 1,200 proteins enriched in heart tissue. Proteins were classified according to biological pathway and molecular functions. We observed an unexpected down regulation of apoptotic markers, Annexin V and p53 in hypertrophied heart tissue. Further validation revealed a significant down regulation of apoptosis regulator, PTEN, along with other apoptosis markers like p53, Caspase 9 and c-PARP. The autophagy markers Atg3, Atg5, Atg7, p62, Beclin1 and LC3 A/B were up regulated in PPAR α−/− mice indicating an increase in autophagy. Similar observations were made in a high cholesterol diet fed PPAR α−/−mice. The results were further validated in vitro using NRVMs and H9C2 cell line by blocking PPAR α that resulted in enhanced autophagosome formation upon hypertrophic stimulation. The results demonstrate that in the absence of PPAR α apoptotic pathway is inhibited while autophagy is enhanced. The data suggest that PPAR α signaling might act as a molecular switch between apoptosis and autophagy thereby playing a critical role in adaptive process in cardiac hypertrophy.

ABSTRACT Staphylococcus aureus is the most pathogenic member of the Staphylococcaceae. While it acquired an arsenal of canonical virulence determinants that mediate pathogenicity, it has also metabolically adapted to thrive at sites of inflammation. Notably, it has evolved to grow in the presence of nitric oxide (NO·). To this end, we note that the Rex regulon, composed of genes encoding dehydrogenases, metabolite transporters, and regulators, is much larger in S. aureus than other Staphylococcus species. Here, we demonstrate that this expanded Rex regulon is necessary and sufficient for NO· resistance. Preventing its expression results in NO· sensitivity, and the closely related species, Staphylococcus simiae, also possesses an expanded Rex regulon and exhibits NO· resistance. We hypothesize that the expanded Rex regulon initially evolved to provide efficient anaerobic metabolism but that S. aureus has co-opted this feature to thrive at sites of inflammation where respiration is limited. One distinguishing feature of the Rex regulon in S. aureus is that it contains the srrAB two-component system. Here, we show that Rex blocks the ability of SrrA to auto-induce the operon, thereby preventing maximal SrrAB expression. This results in NO·-responsive srrAB expression in S. aureus but not in other staphylococci. Consequently, higher expression of cytochromes and NO· detoxification are also observed in S. aureus alone, allowing for continued respiration at NO· concentrations beyond that of S. simiae. We therefore contend that the intersection of the Rex and SrrAB regulons represents an evolutionary event that allowed S. aureus to metabolically adapt to host inflammatory radicals during infection. IMPORTANCE Pathogens must evolve virulence potential to improve transmission to new hosts as well as evolve metabolically to thrive within their current host. Staphylococcus aureus has achieved both of these, and here, we show that one such metabolic adaptation was the expansion of the Rex regulon. First, it affords S. aureus with efficient respiration-independent growth critical to surviving the inflammatory environment replete with respiration-inhibiting immune radicals. Second, it includes the srrAB operon encoding a two-component system critical to maximizing respiratory capacity in the face of host nitric oxide (NO·), a potent respiratory inhibitor. This second facet is only apparent in S. aureus and not in other closely related species. Thus, evolutionarily, it must have occurred relatively recently. The intertwining of the Rex and SrrAB regulons represents an important evolutionary event that affords S. aureus the metabolic flexibility required to thrive within inflamed tissue and cause disease.

In this research work, environmental monitoring processes and assessments are carried out by the modeling and analysis of the water quality of the Chambal River in the state of Rajasthan. Various samples were collected from different locations along the course of the river flow. This water is used for different kinds of human, animal, and agriculture corp. activities. Comparative analyses were conducted on the water parameters, viz. biochemical oxygen demand, chemical oxygen demand, dissolved oxygen, total coliform, and conductivity, for the of consecutive years 2020 and 2021. A model was developed with the help of MATLAB Simulink software (Version R2019a) to find the causes of oxygen deficiency and reoxygenation in water with time and distance. The results of two consecutive years help to predict the responsible factors for the degradation of the river’s water quality. The water quality modeling and simulation results conclude that the water quality of the Chambal River flowing through Rajasthan can rejuvenate itself during an alarming oxygen deficit within a short period. According to the results of this study, the concentration of dissolved oxygen in the water of the Chambal River is high enough to support the survival of the endangered species that inhabit the area.

Microstructure-informed design approach is set to revolutionize the design of metals and alloy components for aerospace applications. In this approach, a designer utilizes the influence of individual microstructural features on microscopic deformation to yield desirable macroscopic properties. Therefore, the development of advanced experimental capabilities that enable detailed characterization of microscopic deformation of material test specimens is critical to realize this paradigm shift in practice. However, extracting the complex characteristics of microscopic deformation hidden in raw image data is quite challenging. In this article, we propose an automated data extraction and analysis method based on instance segmentation and tracking of microstructural features using deep learning (DL) and image processing algorithms. The method consists of a trained mask Region-based Convolutional Neural Network (mask R-CNN) DL model combined with a regional instance segmentation approach for the instance segmentation of features, an intersection over union based multi-object tracking method to track segmented instances as they deform, and kinematics models to extract the material characteristics from the geometrical data of the deforming instances. The method is then validated by characterizing the microscopic deformation of an additively manufactured 316L stainless steel coupon specimen under quasi-static tensile loading. Our study presents a general framework for advancing deep learning algorithms to solve complex problems in the field of experimental mechanics.

Measurements of mass and angular distributions have been made for fission-like outcomes in reactions forming isotopes of flerovium (Z=114), using 48Ca, 50Ti, and 54Cr projectiles. The dominant fast quasifission process, which masks the presence of fusion-fission, has minimum yield at the most backward angles, where the sensitivity to fusion-fission is thus highest. In fitting the backward angle mass spectra, only weak evidence for a component of super-asymmetric fission was found, but a near-symmetric fission component was consistently required for the 48Ca + 244Pu reaction, giving upper limit to the fusion probabilities PCN of ∼10−2, ∼5 times lower than previous results. PCN for the 50Ti reaction was lower than 48Ca, whilst no evidence of fusion-fission was found for the 54Cr reaction.

BackgroundThe current pressure-based coronary diagnostic index, fractional flow reserve (FFR), has a limited efficacy in the presence of microvascular disease (MVD). To overcome the limitations of FFR, the objective is to assess the recently introduced pressure drop coefficient (CDP), a fundamental fluid dynamics-based combined pressure–flow index.MethodsWe hypothesize that CDP will result in improved clinical outcomes in comparison to FFR. To test the hypothesis, chi-square test was performed to compare the percent major adverse cardiac events (%MACE) at 5 years between (a) FFR < 0.75 and CDP > 27.9 and (b) FFR < 0.80 and CDP > 25.4 groups using a prospective cohort study. Furthermore, Kaplan–Meier survival curves were compared between the FFR and CDP groups. The results were considered statistically significant for p < 0.05. The outcomes of the CDP arm were presumptive as clinical decision was solely based on the FFR.ResultsFor the complete patient group, the %MACE in the CDP > 27.9 group (10 out of 35, 29%) was lower in comparison to the FFR < 0.75 group (11 out of 20, 55%), and the difference was near significant (p = 0.05). The survival analysis showed a significantly higher survival rate (p = 0.01) in the CDP > 27.9 group (n = 35) when compared to the FFR < 0.75 group (n = 20). The results remained similar for the FFR = 0.80 cutoff. The comparison of the 5-year MACE outcomes with the 1-year outcomes for the complete patient group showed similar trends, with a higher statistical significance for a longer follow-up period of 5 years.ConclusionBased on the MACE and survival analysis outcomes, CDP could possibly be an alternate diagnostic index for decision-making in the cardiac catheterization laboratory.Clinical Trial Registrationwww.ClinicalTrials.gov, identifier NCT01719016.

Precise estimation of the rare direct 3α decay of the Hoyle state of 12C has been made to unveil its unusual α-cluster configurations ranging from linear 3α chain structure to diffuse Bose gas as well as Bose Einstein condensate. The present new high precision, nearly zero background experimental study with 1.6×105 Hoyle events has converged on the upper limit for direct decay at ∼0.019% with 95% confidence limit, which is more than a factor of 2 lower than the limit obtained in the previous studies. Keywords: 3α cluster state, 12C(α, α)3α reaction, Complete kinematics reaction, The Hoyle state decay, Direct versus sequential decay, Inelastic scattering

Abstract Background Coronary artery disease (CAD) is the leading cause of morbidity and mortality in patients with type 2 diabetes mellitus (T2DM). The purpose of the present study was to discriminate the Indian CAD patients with or without T2DM by using multiple pathophysiological biomarkers. Methods Using sensitive multiplex protein assays, we assessed 46 protein markers including cytokines/chemokines, metabolic hormones, adipokines and apolipoproteins for evaluating different pathophysiological conditions of control, T2DM, CAD and T2DM with CAD patients (T2DM_CAD). Network analysis was performed to create protein-protein interaction networks by using significantly (p

The collective rotational enhancement in the nuclear level density (NLD) arising due to nuclear deformation is still not well understood due to sparse experimental findings. To address this issue, angular momentum (J) gated neutron, proton and GDR γ-ray spectra have been measured from two deformed nuclei (169Tm and 185Re) and one near spherical nucleus (201Tl) by populating them around 26 MeV excitation energy. An enhanced yield compared to statistical decay is observed in all the three spectra (p, n, γ) for both the deformed nuclei but only statistical decay for near spherical nucleus. Intriguingly, the relative enhancement factors determined independently from all the spectra are very similar (≈10) for both the deformed nuclei. Moreover, the results indicate that the fadeout of the collective enhancement does not dependent strongly on the nuclear ground state deformation which is in stark contrast to the expectations of the phenomenological as well as microscopic calculations. The possible reasons for this discrepancy are discussed.

Fatty liver is one of the most common metabolic syndrome affecting the global population. Presently, limited treatment modalities with symptomatic approach are available for alleviating fatty liver. Traditional and herbal treatment modalities have shown evidence to improve the disease pathology. In the present research work, evaluation of a selected medicinal plant Lysimachia candida Lindl. was carried out to investigate its beneficial effects on fatty liver disease in rats. Male Sprague Dawley (SD) rats were fed with high-fat high-fructose diet to induce fatty liver phenotypes. After induction for 15 weeks, methanolic extract of Lysimachia candida Lindl. (250 mg/kg b. w. p. o.) was administrated to the rats daily for the next 17 weeks. Blood samples were collected at different time points to analyze fasting blood glucose levels and relevant biochemical parameters important for the assessment of metabolic disease phenotypes. Liquid chromatography-mass spectrometry (LC-MS) based metabolomics was done to study the dynamics of metabolic changes in the serum during disease progression and how the medicinally important plant extract treatment reversed the metabolic diseases. Multivariate data analysis approaches have been employed to understand the metabolome changes and disease pathology. This study has identified the interplay of some metabolic pathways that alter the disease progression and their reversal after administration of the plant extract. Different group of metabolites mainly bile acids, fatty acids, carnitines, and their derivatives were found to be altered in the diseased rats. However, all the metabolites identified between control and disease groups are mainly related to lipid metabolism. The results depict that the treatment with the above-mentioned plant extract improves the regulation of aberrant lipid metabolism, and reverses the metabolic syndrome phenotype. Therefore, the present study reveals the potential mechanism of the herbal extract to prevent metabolic syndrome in rats.

Abstract Epigallocatechin‐3‐gallate (EGCG) has been considered an anticancer agent despite conflicting and discrepant bioavailability views. EGCG impairs the viability and self‐renewal capacity of triple‐negative breast cancer (TNBC) cells and makes them sensitive to estrogen via activating ER‐α. Surprisingly, the mechanism of EGCG’s action on TNBC cells remains unclear. CCN5/WISP‐2 is a gatekeeper gene that regulates viability, ER‐α, and stemness in TNBC and other types of cancers. This study aimed to investigate whether EGCG (free or encapsulated in nanoparticles) interacts with the CCN5 protein by emphasizing its bioavailability and enhancing its anticancer effect. We demonstrate that EGCG activates CCN5 to inhibit in vitro cell viability through apoptosis, the sphere‐forming ability via reversing TNBC cells’ stemness, and suppressing tumor growth in vivo. Moreover, we found EGCG‐loaded nanoparticles to be functionally more active and superior in their tumor‐suppressing ability than free‐EGCG. Together, these studies identify EGCG (free or encapsulated) as a novel activator of CCN5 in TNBC cells and hold promise as a future therapeutic option for TNBC with upregulated CCN5 expression.