Balancing aquaculture and estuarine ecosystems: machine learning-based water quality indices for effective management.

This study delves into the environmental impact of inland aquaculture on estuarine ecosystems by examining the water quality of four estuarine streams within the key inland aquaculture zone of South India. In this region, extensive and intensive aquaculture practices are common, posing potential challenges to estuarine health. The research explores the predictive capabilities of the Gaussian elimination method (GEM) and machine learning techniques, specifically multi-linear regression (MLR) and support vector regressor (SVR), in forecasting the water quality index of these streams. Through comprehensive evaluation using performance metrics such as coefficient of determination (R2) and average mean absolute percentage error (MAPE), MLR and SVR demonstrate higher prediction efficiency. Notably, employing key water parameters as inputs in machine learning models is also more effective. Biochemical oxygen demand (BOD) emerges as a critical water parameter, identified by both MLR and SVR, exhibiting high specificity in predicting water quality. This suggests that MLR and SVR, incorporating key water parameters, should be prioritized for future water quality monitoring in intensive aquaculture zones, facilitating timely warnings and interventions to safeguard water quality.

Effective image fusion strategies in scientific signal processing disciplines: Application to cancer and carcinoma treatment planning.

Multimodal medical image fusion is a perennially prominent research topic that can obtain informative medical images and aid radiologists in diagnosing and treating disease more effectively. However, the recent state-of-the-art methods extract and fuse features by subjectively defining constraints, which easily distort the exclusive information of source images. To overcome these problems and get a better fusion method, this study proposes a 2D data fusion method that uses salient structure extraction (SSE) and a swift algorithm via normalized convolution to fuse different types of medical images. First, salient structure extraction (SSE) is used to attenuate the effect of noise and irrelevant data in the source images by preserving the significant structures. The salient structure extraction is performed to ensure that the pixels with a higher gradient magnitude impact the choices of their neighbors and further provide a way to restore the sharply altered pixels to their neighbors. In addition, a Swift algorithm is used to overcome the excessive pixel values and modify the contrast of the source images. Furthermore, the method proposes an efficient method for performing edge-preserving filtering using normalized convolution. In the end,the fused image are obtained through linear combination of the processed image and the input images based on the properties of the filters. A quantitative function composed of structural loss and region mutual data loss is designed to produce restrictions for preserving data at feature level and the structural level. Extensive experiments on CT-MRI images demonstrate that the proposed algorithm exhibits superior performance when compared to some of the state-of-the-art methods in terms of providing detailed information, edge contour, and overall contrasts.

Apigenin-6-C-glucoside ameliorates MASLD in rodent models via selective agonism of adiponectin receptor 2.

Adiponectin plays key roles in energy metabolism and ameliorates inflammation, oxidative stress, and mitochondrial dysfunction via its primary receptors, adiponectin receptors -1 and 2 (AdipoR1 and AdipoR2). Systemic depletion of adiponectin causes various metabolic disorders, including MASLD; however adiponectin supplementation is not yet achievable owing to its large size and oligomerization-associated complexities. Small-molecule AdipoR agonists, thus, may provide viable therapeutic options against metabolic disorders. Using a novel luciferase reporter-based assay here, we have identified Apigenin-6-C-glucoside (ACG), but not apigenin, as a specific agonist for the liver-rich AdipoR isoform, AdipoR2 (EC50: 384 pM) with >10000X preference over AdipoR1. Immunoblot analysis in HEK-293 overexpressing AdipoR2 or HepG2 and PLC/PRF/5 liver cell lines revealed rapid AMPK, p38 activation and induction of typical AdipoR targets PGC-1α and PPARα by ACG at a pharmacologically relevant concentration of 100 nM (reported cMax in mouse; 297 nM). ACG-mediated AdipoR2 activation culminated in a favorable modulation of key metabolic events, including decreased inflammation, oxidative stress, mitochondrial dysfunction, de novo lipogenesis, and increased fatty acid ß-oxidation as determined by immunoblotting, QRT-PCR and extracellular flux analysis. AdipoR2 depletion or AMPK/p38 inhibition dampened these effects. The in vitro results were recapitulated in two different murine models of MASLD, where ACG at 10 mg/kg body weight robustly reduced hepatic steatosis, fibrosis, proinflammatory macrophage numbers, and increased hepatic glycogen content. Together, using in vitro experiments and rodent models, we demonstrate a proof-of-concept for AdipoR2 as a therapeutic target for MASLD and provide novel chemicobiological insights for the generation of translation-worthy pharmacological agents.

Air pollution mitigation and suspended particulate matter retention potential of selected plant species across seasonal variation in the urban area.

Air pollution is a pressing environmental concern in urban areas, especially in densely populated cities like Delhi, India. However, plant species can effectively capture airborne suspended pollutants. Given this, the present study aimed to investigate the seasonal variations (pre- and post-monsoon) in the pollution-mitigating potential, biochemical characteristics, and suspended particulate matter (SPM) capturing capacities of select plant species in Delhi. Also, using biochemical parameters, plant morphology, and socioeconomic factors, the study computed tolerance indices such as the Air Pollution Tolerance Index (APTI) and Anticipated Performance Index (API). Ficus religiosa L. exhibited the highest APTI value of 11.94, while Polyalthia longifolia (Sonn.) Thwaites displayed the lowest 7.99 APTI value during the pre-monsoon. Ficus benghalensis L. showed the maximum SPM adhesion on the leaves, with a deposition of 1305.46 µg/cm2, whereas F. religiosa exhibited the lowest SPM deposition of 56.62 µg/cm2. Moreover, the statistical analysis indicated a positive correlation between ascorbic acid and chlorophyll content (R2 > 0.6) with APTI. Also, F. religiosa demonstrated a significant Pearson's correlation (P < 0.05) between chlorophyll content and SPM deposition during the pre-monsoon. The study highlighted the dynamic nature of plant-based air pollution mitigation. It offered valuable insights into the potential of green infrastructure as a sustainable solution for addressing air quality concerns in urban environments. The results emphasized the significance of selecting adequate plant species and considering seasonal variations in developing urban greening strategies to combat air pollution.

ALDH5A1/miR-210 axis plays a key role in reprogramming cellular metabolism and has a significant correlation with glioblastoma patient survival.

BACKGROUND: Glioblastoma (GBM) is the most aggressive among the tumors of the central nervous system (CNS), and has a dismal prognosis. Altered metabolism, especially the increased rate of aerobic glycolysis promotes rapid proliferation of GBM cells. Here, we investigated the role of aldehyde dehydrogenase 5 family member A1 (ALDH5A1), a mitochondrial enzyme in the aspect of GBM metabolism. We also studied the regulatory mechanisms of altered ALDH5A1 expression in GBM. APPROACH AND RESULTS: We show that ALDH5A1 is significantly downregulated in GBM patients in a grade dependent manner as compared to control brain and its low expression is associated with poor prognosis. It is significantly downregulated under hypoxia and is a direct target of the hypoxia induced microRNA: miR-210. Ectopic overexpression of ALDH5A1 in GBM cell lines U-87 MG and T98G markedly reduced their proliferation, 3D spheroid forming ability, and formation of reactive oxygen species (ROS). ALDH5A1 upregulation increased the oxygen consumption rate (OCR), and reduced the extracellular acidification rate (ECAR) of GBM cells while miR-210 overexpression showed the opposite. A significant downregulation in the transcript levels of LDHA, PDK1, and SLC2A1; coupled with lower glucose uptake and lactate production upon ALDH5A1 overexpression reveals that ALDH5A1 significantly reduces the glycolytic capacity of GBM cells. Total ATP generated in 24 h was more when miR-210 was overexpressed, while a slight decrease in ATP formation was observed upon ALDH5A1 upregulation. Interestingly, we also observed that ALDH5A1 expression is elevated and miR-210 levels are downregulated in IDH-mutant glioma as compared to its wild-type form. CONCLUSION: Overall, our findings suggest that miR-210 mediated downregulation of ALDH5A1 plays a critical role in tumor metabolism and helps maintaining a high glycolytic phenotype in GBM.

Time-Dependent Multireference Coupled-Cluster Method (TDMRCCM) for the Bath-Dynamics in System-Bath Approach to Nonadiabatic Dynamics.

The time-dependent multireference coupled-cluster method (TDMRCCM) fits well in the scheme of the system-bath separation used to study the nonadiabatic dynamics. In TDMRCCM, a projection operator is defined as one that projects the full Hilbert space onto the space spanned by the collection of system degrees of freedom, called the model space. The inverse of this projection operator is a wave operator that acts on the model space and takes its projection back to the full wave function. This wave operator is defined as an exponential of the excitation terms and, hence, can be expanded into a Taylor series, which we have truncated in this work at the second-order of excitations. The attraction of using TDMRCCM for describing the bath dynamics is due to the exponential nature of the ansatz used in the method, which makes it possible for the higher-order excitations to be absorbed by the lower-order terms, even upon truncating the series. This improves the accuracy of the numerical calculations using TDMRCCM as an approximation for the bath-mode dynamics in the system-bath framework for nonadiabatic dynamics. We present the theoretical details of TDMRCCM and the numerical results for implementing this method to study the dynamics in the butatriene cation.

A standardized combination of Terminalia chebula and Withania somnifera extracts enhances immune function in adults: a pilot randomized, double-blind, placebo-controlled clinical study.

Background: The use of botanical medicine has been demonstrated as a potential strategy to manage or treat a variety of health issues. Terminalia chebula (Retz) fruit and Withania somnifera (L.) Dunal roots are important medicinal herbs described in Ayurveda and traditional therapy for diverse health benefits. Objective: This pilot study aimed to evaluate the immune function-enhancing potential of a unique blend of T. chebula fruit and W. somnifera root extracts, LN20189, in healthy men and women. Methods: Forty healthy volunteers (age: 35-60 years) were randomized into two groups receiving either LN20189 (500 mg per day) or a matched placebo over 28 consecutive days. The total T-cell population was the primary efficacy measure in this study. The secondary efficacy measures included counts of CD4, CD8, natural killer (NK) cells, serum levels of interleukin-2 (IL-2), interferon-gamma (IFN-γ), total immunoglobulin-G (IgG), and Immune Function Questionnaire (IFQ) scores. Safety parameter assessments were also conducted. Results: Post-trial, in LN20189-supplemented subjects, T cells, CD4, NK cells count, and the CD4:CD8 ratio were increased by 9.32, 10.10, 19.91, and 17.43%, respectively, as compared to baseline. LN20189 supplementation increased serum IFN-γ and IgG levels by 14.57 and 27.09% from baseline and by 13.98 and 21.99%, compared to placebo, respectively. Also, the IFQ scores in the LN20189 group were 84.68% (vs. baseline) and 69.44% (vs. placebo) lower at the end of the trial. LN20189 improved the study volunteers' cellular and humoral immune functions. Conclusion: In summary, LN20189 supplementation was found tolerable and improved the key cellular and humoral factors of the immune system and helped improve immune function of the trial volunteers.

Assessment of metals and metalloids agglutinated to airborne suspended particulate matter in selected plant species during the pre-and post-monsoon in the urban area.

The elemental accumulation has emerged as a major environmental concern due to various anthropogenic sources such as vehicles, road dust, and industrial activities, contributing to the agglutination of elements to airborne Suspended Particulate Matter (SPM). SPM-bound elements accumulate on plant surfaces impact air quality and human health due to their noxiousness. Therefore, plants' ability to capture and mitigate air pollutants plays a crucial role in urban areas. This study aimed to investigate the levels and distribution of twenty-six elements, comprised of heavy metals (Cd, Pb, Cr, Cu Zn, Co, Ni, Fe, Mn, Ag, Mo, V, Ga, and Bi), light metals (B, As, Te, and Se), and metalloids (Al, Li, Sr, K, Mg, Na, Ca, and Ba) accumulated on the surface and inside the leaves of dominant plant species during the pre-and post-monsoon at six categorized (commercial, traffic-prone, residential, educational, greenbelt and industrial areas) locations in Delhi, India. In addition, the Metal Accumulation Index (MAI) was determined, and the statistical analysis was conducted using two-way ANOVA, Principal Component Analysis (PCA), and Hierarchical Cluster Analysis (HCA). In the pre-and post-monsoon, two-way ANOVA revealed significant differences (P < 0.05) in metal concentrations. During the pre-monsoon plants exhibited the highest metal accumulation (∼21%) at the Anand Vihar (commercial) in Delhi, with the maximum average concentrations of Cr (118.25 mg/kg), Cu (204.38 mg/kg), Zn (293.27 mg/kg), and Fe (2721.17 mg/kg). Ficus benghalensis L exhibited the maximum 213.73 MAI at the Anand Vihar in the pre-monsoon. Ni and Cr indicated the highest correlation (P < 0.05, r = 0.82) in the PCA test. HCA test revealed similarity (∼87.7%) at ITO (traffic-prone) and Okhla Phase-2 (industrial) in F. religiosa regarding metal concentration patterns. Findings highlighted seasonal elemental pollutants uptake dynamics of plant species and explored species-specific metal accumulation, revealing potential implications of metal-tolerant plants for urban greenbelt.

A facile green synthesis of gold nanoparticles using Canthium parviflorum extract sustainable and energy efficient photocatalytic degradation of organic pollutants for environmental remediation.

Organic dye and nitrophenol pollution from textiles and other industries present a substantial risk to people and aquatic life. One of the most essential remediation techniques is photocatalysis, which uses the strength of visible light to decolorize water. The present study reports Canthium Parviflorum (CNP) leaf extract utilization as an effective bio-reductant for green synthesis of Au NPs. A simple, eco-friendly process with low reaction time and temperature was adopted to synthesize CNP extract-mediated Au-NPs (CNP-AuNPs). The prepared AuNPs characterization involving X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FT-IR), energy-dispersive X-ray spectroscopy (EDX), scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray photoelectron microscopy (XPS) surface area analysis, ultraviolet-visible spectroscopy (UV-Vis). XRD results showed that the cubic-structured AuNPs had a crystallite size of 14.12 nm. Assessment of organic dyes performance in degrading brilliant green (BTG) and amido black 10B (AMB) under visible light irradiation highlights an impressive 83.25% and 86% degradation efficiency within 120 min, accompanied by a kinetic rate constant dyes was found to be 0.0828 min⁻1, BTG, and 0.0123 min⁻1, Furthermore, the reduction of 4-nitrophenol by NaBH4 using CNP-AuNPs as a catalyst demonstrated good catalytic performance and rapid degradation at 89.4%. and rate constant 0.099 min-1 followed pseudo-first-order. The LC-MS analysis identified various intermediates during the degradation of the CR dye. Radical trapping experiments suggest that photogenerated free electrons and hydroxyl radicals are crucial for degrading the amido black 10B dye The AuNPs influenced the significant factors responsible for the photocatalytic activity, such as the increase in range of absorbance, increased e- and h+ pair separation, improvement in the charge transfer process, and active site formation, which significantly enhanced the process of degradation. We found that the CNP-AuNPs could effectively remove dyes and nitrophenol from industrial wastewater.

Anti-fouling rotating polymer-based heat exchanger for zero liquid discharge humidification-dehumidification desalination.

The objective of this investigation is to assess the performance of various heat exchangers for application in a novel solar-powered zero liquid discharge humidification-dehumidification desalination system. In this study four heat exchangers (HX) having two different flow configurations namely counter flow (cf), cross flow (cr) made up of three different materials namely high-density polyethylene (HDPE), aluminum (Al), and Polypropelyne (PP) were compared in terms of their effectiveness and overall heat transfer coefficient under varying salinity levels (up to 10%) and mixing ratios (0.22-0.45). At a mixing ratio of 0.22 and 0% salinity, PP-HXcr and Al-HXcf exhibited similar effectiveness (∼85%), surpassing that of HDPE-HXcf (∼65%). Despite PP-HXcr's lower thermal conductivity in comparison to Al-HXcf, comparable effectiveness was achieved due to the superior flow distribution in PP-HXcr. Further investigations focused on the impact of salinity on heat exchanger performance. At 3.5% salinity, all heat exchangers experienced a decline in effectiveness and heat transfer coefficient (HTC), with Al-HXcf experiencing a more pronounced decrease compared to PP-HXcr. The higher thermal conductivity of Al-HXcf led to greater salt accumulation, while PP-HXcr demonstrated minimal fouling. As the experiment progressed, fouling increased for all heat exchangers, with the Al-HXcf being practically ineffective at 10% salinity with an effectiveness below 10%. To address the issue of fouling, a rotating cross-flow heat exchanger (RPP-HXcr) was introduced. While the effectiveness of the PP-HXcr drops from 85% to approximately 60% with increasing salinity from 0% to 10%, the RPP-HXcr demonstrates only a marginal decline in effectiveness with increasing salinity. For instance, at mixing ratio of 0.22 when the salinity is increased from 0% to 10%, the effectiveness of RPP-HXcr only drops from 83% to 77%. This exceptional performance was attributed to the continuous contact between the rotating tubes and the incoming feed, effectively preventing fouling and ensuring sustained efficiency. Rotating cross-flow heat exchanger (RPP-HXcr) is introduced and validated as a potentially reliable solution for mitigating fouling, as it demonstrates sustained efficiency and minimal performance degradation across different salinity conditions.

Synthesis of 2,2-dimethyl-chroman-based stereochemically flexible and constrained anti-breast cancer agents.

Receptors are proteinous macromolecules which remain in the apo form under normal/unliganded conditions. As the ligand approaches, there are specific stereo-chemical changes in the apo form of the receptor as per the stereochemistry of a ligand. Accordingly, a series of substituted dimethyl-chroman-based stereochemically flexible and constrained Tamoxifen analogs were synthesized as anti-breast cancer agents. The synthesized compounds 19a-e, 20a-e, 21, and 22a-e, showed significant antiproliferative activity against estrogen receptor-positive (ER+, MCF-7) and negative (ER-, MDA MB-231) cells within IC50 value 8.5-25.0 µM. Amongst all, four potential molecules viz 19b, 19e, 22a, and 22c, were evaluated for their effect on the cell division cycle and apoptosis of ER+ and ER- cancer cells (MCF-7 & MDA MB-231cells), which showed that these compounds possessed antiproliferative activity through triggering apoptosis. In-silico docking experiments elucidated the possible affinity of compounds with estrogen receptors-α and -ß.

Perceived social support and professional quality of life of health professionals during COVID-19 pandemic in Nepal: a cross-sectional study.

OBJECTIVE: To assess the perceived social support and professional quality of life (ProQOL) among healthcare professionals during COVID-19 pandemic in Nepal, encompassing both positive (compassion satisfaction) and negative (compassion fatigue) dimensions as well as the factors associated with them. DESIGN: A cross-sectional web-based study. SETTING: Nepal PARTICIPANTS: We carried out a convenience sampling technique to enrol 313 health professionals aged 18-60 years old. OUTCOME MEASURES: We employed the ProQOL V.5 questionnaire (comparing 30 self-report items) and the Multidimensional Scale of Perceived Social Support with 12 items to assess the ProQOL and social support, respectively. A χ2 test was performed to determine associated factors of different dimensions of ProQOL. RESULTS: The study included a total of 313 participants, mostly consisting of frontline health workers. More than one-third of the participants worked in places where precautionary measures were insufficient. However, the majority of them (73.8%) had high social support. Concerning the ProQOL, the percentage of health professionals that had moderate compassion satisfaction (CS), moderate Burnout (BO) and moderate secondary traumatic stress (STS) were 57.5%, 58.2% and 75.4%, respectively. Factors like sex, marital status, profession, work-shift, type of health institution and status of precautionary measures at the workplace were associated with the different dimensions of ProQOL at the significance level of 0.05. CONCLUSION: This study findings revealed a considerable proportion of BO and STS among health professionals during COVID-19 pandemic in Nepal. Implementation of appropriate interventions and support systems are needed to enhance CS, alleviate BO and mitigate STS among health professionals to combat future health emergencies.

Tiny Organs, Big Impact: How Microfluidic Organ-on-Chip Technology Is Revolutionizing Mucosal Tissues and Vasculature.

Organ-on-chip (OOC) technology has gained importance for biomedical studies and drug development. This technology involves microfluidic devices that mimic the structure and function of specific human organs or tissues. OOCs are a promising alternative to traditional cell-based models and animals, as they provide a more representative experimental model of human physiology. By creating a microenvironment that closely resembles in vivo conditions, OOC platforms enable the study of intricate interactions between different cells as well as a better understanding of the underlying mechanisms pertaining to diseases. OOCs can be integrated with other technologies, such as sensors and imaging systems to monitor real-time responses and gather extensive data on tissue behavior. Despite these advances, OOCs for many organs are in their initial stages of development, with several challenges yet to be overcome. These include improving the complexity and maturity of these cellular models, enhancing their reproducibility, standardization, and scaling them up for high-throughput uses. Nonetheless, OOCs hold great promise in advancing biomedical research, drug discovery, and personalized medicine, benefiting human health and well-being. Here, we review several recent OOCs that attempt to overcome some of these challenges. These OOCs with unique applications can be engineered to model organ systems such as the stomach, cornea, blood vessels, and mouth, allowing for analyses and investigations under more realistic conditions. With this, these models can lead to the discovery of potential therapeutic interventions. In this review, we express the significance of the relationship between mucosal tissues and vasculature in organ-on-chip (OOC) systems. This interconnection mirrors the intricate physiological interactions observed in the human body, making it crucial for achieving accurate and meaningful representations of biological processes within OOC models. Vasculature delivers essential nutrients and oxygen to mucosal tissues, ensuring their proper function and survival. This exchange is critical for maintaining the health and integrity of mucosal barriers. This review will discuss the OOCs used to represent the mucosal architecture and vasculature, and it can encourage us to think of ways in which the integration of both can better mimic the complexities of biological systems and gain deeper insights into various physiological and pathological processes. This will help to facilitate the development of more accurate predictive models, which are invaluable for advancing our understanding of disease mechanisms and developing novel therapeutic interventions.

Carcinogenicity and non-carcinogenicity health risks due to PM2.5 bound trace metals at a sub urban site in Northwest Indo-Gangetic Plain.

This study investigates the PM2.5 bound metals using yearlong measurements at a regionally representative suburban site in the Northwest Indo-Gangetic Plain (NWIGP). The order of the measured annual average concentrations of PM2.5 bound metals is Fe > Zn > Ba > Sn > Pb > Cd > Ni > Mn > Cr > Li. Lithium bound to airborne PM2.5 has been reported for the first time in NWIGP. Ni (72.4 ng m-3) and Cd (36.9 ng m-3) have exceeded the acceptable limits set by NAAQS, India. Estimated the hazard quotient (HQ > 1) of Mn and hazard index (HI > 1) of measured metals exceeded the threshold limits indicating the potential non-carcinogenic health risk due to inhalation exposure of PM2.5 bound trace metals. Further, excessive lifetime cancer risk due to inhalation exposure to Cd, Ni and Cr was estimated and found to exceed the threshold limit set by the USEPA for adults and children.

Short term biodistribution and in vivo toxicity assessment of intravenously injected pristine graphene oxide nanoflakes in SD rats.

The present study aimed to elucidate the short term biodistribution of nano sized graphene oxide (GO) along with the toxicological assessment under in-vivo condition with an intent to analyse the toxic effects of sudden accidental exposure of GO The synthesised GO was characterized using UV-Visible spectroscopy, XRD, FTIR, Raman spectroscopy, TGA and DLS. The morphological imaging was performed using SEM, TEM and AFM. With a lateral size of less than 300 nm, these nanoparticles exhibit significant organ barrier permeability of up to 20%. Upon acute exposure to 10 mg/kg dose of ICG-tagged GO nanoflakes through intravenous route, various organs such as kidney, spleen and liver were observed, and the nanoparticles predominantly accumulated in the liver upon 24 h of exposure. Upon confirming the accumulation of these particles in liver through IVIS imaging, our next attempt was to analyse various biochemical and serum parameters. An elevation in various serum parameters such as ALT, AST, Creatinine and Bilirubin was observed. Similarly, in the case of biochemical parameters tested in liver homogenates, an increase in NO, Catalase, GSH, SOD, ROS, LPO, GR, GPx, and GST was observed. This study highlights the potential toxicological risk associated with GO exposure which must be taken into account for any risk analysis associated with GO based consumer products and the occupational hazards.

Strain-enabled radical spirocyclization cascades: rapid access to spirocyclobutyl lactones and - lactams.

Spirocyclobutane derivatives have gained significant attention in drug discovery programs due to their broad spectrum of biological activities and clinical applications. Ring-strain in organic molecules is a powerful tool to promote reactivity by releasing strain energy, allowing the construction of complex molecules selectively and efficiently. Herein, we report the first strain-enabled radical spirocyclization cascades for the synthesis of functionalized spirocyclobutyl lactones and - lactams, which are finding increasing applications in medicinal chemistry. The reaction of interelement compounds with bicyclobutane (BCB) allyl esters and - amides proceeds with high chemoselectivity under simple, catalyst-free conditions using blue light irradiation. The reaction has been successfully extended to synthesize bis-spirocycles. To introduce a more diverse set of functional groups, we have developed a dual photoredox/nickel catalytic system capable of mediating the carbosulfonylation of BCB allyl amides. The reaction shows broad applicability across various (hetero)aryl halides, aryl sulfinates, and BCB allyl amides, operates under mild conditions and demonstrates excellent functional group compatibility. The functional groups introduced during the cascade reactions served as versatile handles for further synthetic elaboration.

ProTect: a hybrid deep learning model for proactive detection of cyberbullying on social media.

The emergence of social media has given rise to a variety of networking and communication opportunities, as well as the well-known issue of cyberbullying, which is continuously on the rise in the current world. Researchers have been actively addressing cyberbullying for a long time by applying machine learning and deep learning techniques. However, although these algorithms have performed well on artificial datasets, they do not provide similar results when applied to real-time datasets with high levels of noise and imbalance. Consequently, finding generic algorithms that can work on dynamic data available across several platforms is critical. This study used a unique hybrid random forest-based CNN model for text classification, combining the strengths of both approaches. Real-time datasets from Twitter and Instagram were collected and annotated to demonstrate the effectiveness of the proposed technique. The performance of various ML and DL algorithms was compared, and the RF-based CNN model outperformed them in accuracy and execution speed. This is particularly important for timely detection of bullying episodes and providing assistance to victims. The model achieved an accuracy of 96% and delivered results 3.4 seconds faster than standard CNN models.

Estimating phenotypic stability for relevant yield and quality traits in French bean (Phaseolus vulgaris L.) using AMMI analysis.

The presence of strong G x E (genotype by environment interaction) is a major hurdle for selecting superior genotypes when genotypes are placed into new and unfamiliar production systems. Genotype or cultivar (s) with high yield potential and having less adaptability and stability to particular environment is never a suitable choice for a breeder and farmer particularly. Purposefully, four successive seasons were chosen to enumerate the phenotypic stability of 27 French bean genotypes for yield and quality traits by involving modern statistical tools like AMMI (Additive Main Effect and Multiplicative Interaction), GGE [G + (G x E)] and cluster analysis. AMMI analysis of variance witnessed magnitude of G, E and G x E was 81.94%, 11.58% and 6.48% of the total variation respectively. The IPCA I (Interaction Principal Component Axes) was contributed with 55.44%, 73.60%, 71.81%, 81.69% and 72.16% G x E variations of days to 50% flowering, pod length, number of pods per plant, average pod weight and pod yield respectively. For qualitative traits i.e., protein content (mg/100g FW), total soluble solids (%) and total phenol content (mg GAE/g FW) the involvement of IPCA I to total genotype by environment interaction variations were 89.55%, 96.07% and 66.52% respectively. The AMMI biplot revealed French bean genotypes viz., IC632961, Arka Sukomal, IIHR-PV-29, IIHR-PV-30 having low AMMI stability value and higher mean value for relevant yield and quality traits in both late kharif and rabi as two mega-environments. Multivariate analysis demonstrated significant higher contribution of pod yield associated traits towards total variations and positive correlation between them. The 27 French bean genotypes formed five groups as per Euclidean distance and the clustering revealed the nature of diversity of French bean genotypes viz., IC 632961, IIHR-B-PV-24, Arka Sukomal, Arka Arjun, Ayoka and Phalguni in response to changing environments and can be utilized in future breeding programme. The study revealed pole type French bean genotypes viz., IC 632961, Arka Sukomal and bush type French bean genotypes viz., IIHR-B-PV-29, IIHR-B-PV-30 could be promising for utilization in future breeding programmes for the concerned traits.

Cancer testis antigen burden (CTAB): a novel biomarker of tumor-associated antigens in lung cancer.

BACKGROUND: Cancer-testis antigens (CTAs) are tumor antigens that are normally expressed in the testes but are aberrantly expressed in several cancers. CTA overexpression drives the metastasis and progression of lung cancer, and is associated with poor prognosis. To improve lung cancer diagnosis, prognostic prediction, and drug discovery, robust CTA identification and quantitation is needed. In this study, we examined and quantified the co-expression of CTAs in lung cancer to derive cancer testis antigen burden (CTAB), a novel biomarker of immunotherapy response. METHODS: Formalin fixed paraffin embedded (FFPE) tumor samples in discovery cohort (n = 5250) and immunotherapy and combination therapy treated non-small cell lung cancer (NSCLC) retrospective (n = 250) cohorts were tested by comprehensive genomic and immune profiling (CGIP), including tumor mutational burden (TMB) and the mRNA expression of 17 CTAs. PD-L1 expression was evaluated by IHC. CTA expression was summed to derive the CTAB score. The median CTAB score for the discovery cohort of 170 was applied to the retrospective cohort as cutoff for CTAB "high" and "low". Biomarker and gene expression correlation was measured by Spearman correlation. Kaplan-Meier survival analyses were used to detect overall survival (OS) differences, and objective response rate (ORR) based on RECIST criteria was compared using Fisher's exact test. RESULTS: The CTAs were highly co-expressed (p < 0.05) in the discovery cohort. There was no correlation between CTAB and PD-L1 expression (R = 0.011, p = 0.45) but some correlation with TMB (R = 0.11, p = 9.2 × 10-14). Kaplan-Meier survival analysis of the immunotherapy-treated NSCLC cohort revealed better OS for the pembrolizumab monotherapy treated patients with high CTAB (p = 0.027). The combination group demonstrated improved OS compared to pembrolizumab monotherapy group (p = 0.04). The pembrolizumab monotherapy patients with high CTAB had a greater ORR than the combination therapy group (p = 0.02). CONCLUSIONS: CTA co-expression can be reliably measured using CGIP in solid tumors. As a biomarker, CTAB appears to be independent from PD-L1 expression, suggesting that CTAB represents aspects of tumor immunogenicity not measured by current standard of care testing. Improved OS and ORR for high CTAB NSCLC patients treated with pembrolizumab monotherapy suggests a unique underlying aspect of immune response to these tumor antigens that needs further investigation.

Efficacy and safety of fixed dose combination of Sitagliptin, metformin, and pioglitazone in type 2 Diabetes (IMPACT study): a randomized controlled trial.

BACKGROUND: Due to the progressive decline in ß-cell function, it is often necessary to utilize multiple agents with complementary mechanisms of action to address various facets and achieve glycemic control. Thus, this study aimed to evaluate the efficacy and safety of a fixed-dose combination (FDC) of metformin/sitagliptin/pioglitazone (MSP) therapy vs. metformin/sitagliptin (MS) in type 2 diabetes mellitus (T2DM). METHODS: In this phase 3, multicenter, double-blind study, patients with T2DM who exhibited inadequate glycemic control with HbA1c of 8.0-11.0% while taking ≥1500 mg/day metformin for at least 6 weeks were randomized to receive either FDC of MSP (1000/100/15 mg) or MS (1000/100 mg) per day for 24 weeks. The primary outcome measure was the change in HbA1c, and secondary outcomes included changes in fasting plasma glucose (FPG), postprandial plasma glucose (PPG), and body weight from baseline to 24 weeks along with safety and tolerability. RESULTS: Among the 236 patients randomized, 207 (87.71%) successfully completed the study. All baseline characteristics were comparable between the FDC of MSP and MS groups. There was a subsequent significant reduction of HbA1c in FDC of MSP (- 1.64) vs. MS (- 1.32); between groups was [- 0.32% (95% CI, - 0.59, - 0.05)], P = 0.0208. Similar reductions were found in FPG [- 13.2 mg/dL (95% CI, - 22.86, - 3.71)], P = 0.0068, and PPG [- 20.83 mg/dL (95% CI, - 34.11, - 7.55)], P = 0.0023. There were no significant changes in body weight. A total of 27 adverse effects (AEs) and one severe AE were reported, none of which were related to the study drug. CONCLUSION: The FDC of MSP demonstrated significant efficacy in managing glycemic indices and could serve as a valuable tool for physicians in the management of Indian patients with T2DM. TRIAL REGISTRATION: Clinical Trials Registry of India, CTRI/2021/10/037461.