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Inflammatory bowel disease (IBD) is a chronic inflammatory condition of gastrointestinal (GI) tract with dysregulated mucosal immune functions and disturbed commensal ecosystem of the intestinal lumen. IBD is categorized into two major subsets: Crohn’s disease (CD) and ulcerative colitis (UC). Though advent of biologics has shifted the treatment with relatively longer remission compared to small molecule pharmaceuticals, patients still suffer from long-term complications. Since gut-microbiome is now accepted as another human organ holding potential for long-lasting human health, probiotics, and its engineering hold great promises to treat several previously untreatable chronic inflammatory conditions including IBD. Several emerging biological engineering tools have unlimited potential to manipulate probiotic bacterial system. These can produce useful therapeutic biologics with a goal to either ameliorate and/or treat previously untreatable chronic inflammatory conditions. As gut-microbiome is diverse and vary in different ethnic, geographic, and cultural human population, it will be important to develop vision for personalized probiotic treatment and develop the technology thereof to make personalized probiotic options a reality. The aim of this review paper is to present an overview of the current knowledge on both pharmacological and nonpharmacological IBD treatment modalities with a special emphasis on probiotic strains that are developed through the probiotic engineering. These engineered probiotics contain the most anti-inflammatory cytokines found within the human immune response and are currently being used to treat the intestinal inflammation in IBD for the IBD treatment.

The JAK family, particularly JAK3, plays a crucial role in immune signaling and inflammatory responses. Dysregulated JAK3 activation in SARS-CoV-2 infections has been associated with severe inflammation and respiratory complications, making JAK inhibitors a viable therapeutic option. However, their use raises concerns regarding immunosuppression, which could increase susceptibility to secondary infections. While long-term adverse effects are less of a concern in acute COVID-19 treatment, patient selection and monitoring remain critical. Furthermore, adverse effects associated with oral JAK3 inhibitors necessitate the exploration of alternative strategies to optimize therapeutic efficacy while minimizing risks. This review highlights the role of JAK3 in immune and epithelial cells, examines the adverse effects of oral JAK3 inhibitors in COVID-19 and other treatments, and discusses alternative therapeutic strategies for improving patient outcomes.

Janus kinases (Jaks) are a family of nonreceptor tyrosine kinase that include four different members, viz., Jak1, Jak2, Jak3, and Tyk2. Jaks play critical roles in immune cells functions; however, recent studies suggest they also play essential roles in nonimmune cell physiology. This review highlights the significance of epithelial Jaks in understanding the molecular basis of some of the diseases through regulation of epithelial-mesenchymal transition, cell survival, cell growth, development, and differentiation. Growth factors and cytokines produced by the cells of hematopoietic origin use Jak kinases for signal transduction in both immune and nonimmune cells. Among Jaks, Jak3 is widely expressed in both immune cells and in intestinal epithelial cells (IECs) of both humans and mice. Mutations that abrogate Jak3 functions cause an autosomal severe combined immunodeficiency disease (SCID) while activating Jak3 mutations lead to the development of hematologic and epithelial cancers. A selective Jak3 inhibitor CP-690550 (Xeljanz) approved by the FDA for certain chronic inflammatory conditions demonstrates immunosuppressive activity in rheumatoid arthritis, psoriasis, and organ transplant rejection. Here, we also focus on the consequences of Jak3-directed drugs on adverse effects in light of recent discoveries in mucosal epithelial functions of Jak3 with some information on other Jaks. Lastly, we brief on structural implications of Jak3 domains beyond the immune cells. As information about the roles of Jak3 in gastrointestinal functions and associated diseases are only just emerging, in the review, we summarize its implications in gastrointestinal wound repair, inflammatory bowel disease, obesity-associated metabolic syndrome, and epithelial cancers. Lastly, we shed lights on identifying potential novel targets in developing therapeutic interventions of diseases associated with dysfunctional IEC.

Fewest switches surface hopping (FSSH) is a well benchmarked dynamical method for simulating nonadiabatic systems. In particular, the literature shows that for the spin-Boson model Hamiltonian, FSSH with appropriate corrections usually captures the detailed balance well and obtains rate constants within a factor of 2 compared to numerically exact results. In this study, we show that in the deep inverted Marcus regime, the augmented-FSSH (AFSSH, one version that includes decoherence) yields reasonably accurate rate constants but incorrect thermal populations over a broad range of parameters. We present an analytical derivation to understand the AFSSH behavior, and therefore, show that AFSSH obtains correct rate constants owing to the resonance of the time derivative coupling with the exothermicity, but obtains an incorrect thermal population owing to the self-consistency issue. The presented derivation provides an analytical expression for the quantum correction factor for AFSSH simulations in the Marcus inverted regime.

The presented paper introduces a design for a phase-locked loop (PLL) that is utilized in frequency synthesis and modulation-demodulation within communication systems and in VLSI applications. The CMOS PLL is designed using 180 nm Fabrication Technology on Cadence Virtuoso Tool with a supply voltage of 1.8 V. The performance is evaluated through simulations and measurements, which demonstrate its ability to track and lock onto the input frequency. The PLL is a frequency synthesizer implemented to generate 2.4 GHz frequency. The input reference clock from a crystal oscillator is 150 MHz square wave. Negative feedback is given by divide-by-16 frequency divider, ensuring the phase and frequency synchronization between the divided signal and the reference signal. The design has essential components such as a phase frequency detector, charge pump, loop filter, current-starved voltage-controlled oscillator (CSVCO), and frequency divider. Through their collaborative operation, the system generates an output frequency that is 16 times the input frequency. The centre frequency of the 3-stage CSVCO is 3.208 GHz at 900 mV input voltage. With an input voltage ranging from 0.4 V to 1.8 V, the VCO offers a tuning range that spans from 1.066 GHz to 3.731 GHz.PLL demonstrates a lock-in range spanning from 70.4 MHz to 173 MHz, with an output frequency range of 1.12 GHz to 2.78 GHz. It achieves a lock time of 260.03 ns and consumes a maximum power of 5.15 mW at 2.4 GHz.

This paper presents AI Guide Dog (AIGD), a lightweight egocentric (first-person) navigation system for visually impaired users, designed for real-time deployment on smartphones. AIGD employs a vision-only multi-label classification approach to predict directional commands, ensuring safe navigation across diverse environments. We introduce a novel technique for goal-based outdoor navigation by integrating GPS signals and high-level directions, while also handling uncertain multi-path predictions for destination-free indoor navigation. As the first navigation assistance system to handle both goal-oriented and exploratory navigation across indoor and outdoor settings, AIGD establishes a new benchmark in blind navigation. We present methods, datasets, evaluations, and deployment insights to encourage further innovations in assistive navigation systems.

The study describes a novel and environment friendly route of biosynthesis of nanohydroxyapatite (nHAP). Bacillus licheniformis mediated synthesis of nHAP has been carried out with different phosphate concentrations (2%, 5%, 10% and 20% w/v ) of potassium dihydrogen orthophosphate monobasic (K 2 HPO 4 ). The synthesis is supported by a two-step mechanism – (i) solubilization of P by organic acids extracellularly secreted by the bacterial strain and (ii) gelation of P and Ca. The nHAP particles were characterized using electron microscopy and XRD analysis. Powdered crystalline particles with a size range of 30 ± 5 nm were obtained with shape and size dependent on phosphate concentrations. The particles showed no adverse effect on plant growth-promoting bacteria. Evaluation of nHAP prepared by this route with 2% P source provides scope for a wide range of applications, especially as a nano-fertilizer.

The present study uses both carbon dioxide emission and ecological footprints as proxies for environmental degradation to examine the environmental Kuznets curve hypothesis for the top three emitters from Asia, i.e., China, India, and Japan. To this end, the autoregressive distributed lag model for time series and panel estimation is used for a period spanning over 1980–2016. For carbon dioxide emission, China presents an inverted-U shape of the environmental Kuznets curve, while a U-shape relationship is found for India and Japan. Similarly, when the hypothesis is tested with the ecological footprint, Japan offers an inverted U-shape and U-shaped association is detected for China and India. The panel analysis indicates the existence of the environmental Kuznets curve with both proxies of environmental degradation. Besides, human capital and renewable energy promote environmental sustainability, while non-renewable energy use hinders environmental quality. The findings of this study suggest that in order to meet the combined goals of economic growth and environmental protection, the three economies, i.e., China, India, and Japan, should employ renewable energy–enabled technology. Graphical abstract