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Brown fat is known to provide non-shivering thermogenesis through mitochondrial uncoupling mediated by uncoupling protein 1 (UCP1). Non-shivering is not dependent on UCP2, UCP4, and BMCP1/UCP5 genes, which are distinct from UCP1 in a way that they are not constitutive uncouplers. Although they are susceptible to free fatty acid and free radical activation, their functioning has a significant impact on the performance of neurons. Using subject-specific keywords (Adipose tissue; Adipocytes; Mitochondria; Obesity; Thermogenesis; UCP's in Neurodegeneration; Alzheimer's disease; Parkinson's disease), research articles and reviews were retrieved from Web of Science, ScienceDirect, Google Scholar, and PubMed. This article includespublications published between 2018 and 2023. The drugs that upregulate UCP1 are included in the study while the drugs that do not impact UCP1 are were not included. Neuronal UCPs have a direct impact on synaptic plasticity, neurodegenerative processes, and neurotransmission, by modulating calcium flux, mitochondrial biogenesis, local temperature, and free radical generation. Numerous significant advances in the study of neuronal UCPs and neuroprotection are still to be made. Identification of the tissue-dependent effects of UCPs is essential first. Pharmacologically targeting neuronal UCPs is a key strategy for preventing both neurodegenerative diseases and physiological aging. Given that UCP2 has activities that are tissue-specific, it will be essential to develop treatments without harmful side effects. The triggering of UCPs by CoQ, an essential cofactor, produces nigral mitochondrial uncoupling, reduces MPTP-induced toxicity, and may even decrease the course of Parkinson's disease, according to early indications. Herein, we explore the potential of UCP1 as a therapeutic target for treating obesity, neurodegenerative diseases as well as a potential activator of both synthetic and natural drugs. A deeper knowledge of synaptic signaling and neurodegeneration may pave the way to new discoveries regarding the functioning and controlling of these genes. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is a neurodegenerative condition characterized by the progressive loss of dopaminergic neurons within the substantia nigra. Neuroinflammation plays a pivotal role in the pathogenesis of PD, involving the activation of microglia cells, heightened production of proinflammatory cytokines, and perturbations in the composition of the gut microbiota. Rubusoside (Ru), the principal steviol bisglucoside present in Rubus chingii var. suavissimus (S.K.Lee) L.T.Lu (Rosaceae), has been documented for its anti-inflammatory properties in diverse disease models. Nonetheless, there is an imperative need to comprehensively assess and elucidate the protective and anti-inflammatory attributes of Ru concerning PD, as well as to uncover the underlying mechanism involved. The aim of this study is to evaluate the neuroprotective and anti-inflammatory effects of Ru on PD and investigate its potential mechanisms associated with microbes. We pre-treated mice and cell lines with Ru in order to simulate the progression of PD and the neuroinflammatory state. The mouse model was induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), SN4741 cells were induced by 1-methyl-4-phenylpyridine (mpp+), and BV-2 cells were induced by lipopolysaccharide (LPS). We assessed the impact of Ru on motor function, neuroinflammation, neuron apoptosis, the composition of gut microbes, and their metabolites. Ru treatment reduces the release of pro-inflammatory mediators by inhibiting microglia activation. It also prevents neuronal apoptosis, thereby safeguarding dopaminergic neurons and ameliorating motor dysfunction. Furthermore, it induces alterations in the fecal microbiota composition and metabolites profile in PD mice. In vitro experiments have demonstrated that Ru inhibits neuronal apoptosis in SN4741 cells induced by mpp+, suppresses the production of pro-inflammatory mediators, and activates the c-Jun N-terminal kinase (JNK), mitogen-activated protein kinase (p38 MAPK), and nuclear factor kappa-B (NF-κB) signaling pathways. Ru exhibits inhibitory effects on the MPTP-induced PD model by mitigating neuroinflammation and neuronal apoptosis while also inducing changes in the gut microbiota and metabolite composition. [Display omitted] [ABSTRACT FROM AUTHOR]

Nearly half of the malnourished population of the world lives in South Asia, and agriculture is the main source of livelihood of the people in this region. Many review exercises have analysed the available evidences to understand the ways in which agriculture can be leveraged to enhance nutritional status; however, very few of them have employed a systematic approach ensuring internal and external validity. The present paper seeks to fill this gap for strengthening the policy recommendations. It demonstrates an association between agricultural interventions and nutritional outcomes; and it shows that the production of targeted nutrition-rich crops, homestead gardens, and diversification of the agricultural production system towards fruits and vegetables and aquaculture can potentially improve nutrient intake and nutritional outcomes. The empowerment of women and nutrition knowledge play a crucial role in establishing linkage between agriculture and nutritional outcomes. [ABSTRACT FROM AUTHOR]

Indian agriculture is experiencing under-performance despite increased attention given to it in the recent past. This paper analyzes the disparities in agricultural growth across Indian states and explores the determinants of agricultural growth, using Panel Corrected Standard Error approach. Analysis using beta convergence shows that the disparities across the state's agricultural growth are narrowing down for the period 1980–1981 to 2011–2012. However, to stimulate growth in the states where agriculture is lagging behind, a higher emphasis on increasing the area under irrigation, expenditure on agricultural research, area under fruits and vegetables, number of regulated markets, length of roads, cold storage facilities and institutional credit for investment purposes is needed. Private sector should be involved in public–private-partnership mode for improving the infrastructure in this sector. [ABSTRACT FROM AUTHOR]

Highlights: [•] A graft copolymer (CMG-g-HMA) was synthesized via free radical polymerization. [•] TGA data show that the grafted polymer is more thermally stable than pure CMG. [•] The synthesized graft copolymer can be used as superabsorbent and flocculants. [Copyright &y& Elsevier]

Highlights: [•] A graft copolymer (CgOH-g-HMAAm) was synthesized via free radical polymerization. [•] TGA data show that the grafted polymer is more thermally stable than pure CgOH. [•] The synthesized graft copolymer can be used as superabsorbent and flocculants. [ABSTRACT FROM AUTHOR]

The graft copolymerization of N,N′-dimethylacrylamide onto guar gum initiated by potassium peroxymonosulphate/glycolic acid redox pair in an aqueous medium was studied gravimetrically under a nitrogen atmosphere. Grafting ratio, grafting efficiency and add on increase on increasing the concentration of potassium peroxymonosulphate (8.0×10−3 to 24.0×10−3 moldm−3) and glycolic acid concentration (4.4×10−3 to 7.6×10−3 moldm−3). On increasing the hydrogen ion concentration from 4×10−3 to 12.0×10−3 moldm−3, grafting ratio, efficiency, add on and conversion were increased. Maximum grafting was obtained when guar gum and N,N′-dimethylacrylamide concentration were 1.0×10−2 gdm−3 and 14.0×10−2 moldm−3, respectively. An increase in temperature from 25°C to 45°C, the grafting ratio increases but conversion and homopolymer decrease. The optimum time period for graft copolymerization was 2h. The graft copolymers were characterized by IR spectroscopy and thermogravimetric analysis. [ABSTRACT FROM AUTHOR]

Abstract: Energy is essential to attain the quality of life and economic prosperity in a society. In the rural areas of India, cooking dominates the aggregate consumption of energy. This energy demand is mostly met by biomass fuels, which have many associated inherent disadvantages. Hence, it is important to understand the decision making process in rural households regarding the choice of cooking fuels. For this purpose, household information using the 61st round of National Sample Survey is analyzed for the rural parts of India. The logistic regression model is used to explain the determinants of clean fuel use for cooking purposes. The study shows that number of educated females between 10 and 50 years of age, average household education index, regular salary, and monthly per capita consumption expenditure have a positive and significant impact on probability of using clean cooking fuels, whereas possessing a Below Poverty Line ration card, belonging to reserved caste categories, family size and size of farm land have a significant negative linkage. [Copyright &y& Elsevier]

The immunosuppressive tumour microenvironment (TME) plays a critical role in cancer progression and relapse by significantly influencing cancer pathogenesis through autocrine and paracrine signalling. Trefoil factor 3 (TFF3), a secreted protein, has been implicated in modulating the TME to promote cancer advancement. Herein, we investigated the potential association between TFF3 and key immunosuppressive TME components to distinguish a co-targetable oncotherapeutic strategy. The TFF3-PVRL2 association were identified and investigated by integrating multiple bioinformatic-tools. The virtual compound screening for PVRL2 inhibitors was done with EasyVS. The TFF3-PVRL2 protein-level correlation was validated by immunoblotting, and the effectiveness of co-inhibiting TFF3 and PVRL2 was assessed using siRNA and AMPC (a TFF3 inhibitor). Analysis of the TISIDB database revealed a positive correlation between TFF3 and PVRL2 mRNA levels across multiple cancer types. This correlation was confirmed at the protein level through immunoblot analysis. Further evaluation using TCGA pan-cancer datasets demonstrated that TFF3 and PVRL2 interact to establish an immunosuppressive TME, promoting cancer progression in BRCA, LUAD, PAAD, PRAD, and STAD. Enrichment analyses of positively correlated genes, PPI network hub proteins, and ceRNA networks involving TFF3 and PVRL2, conducted using LinkedOmics, STRING, and Cytoscape, provided insights into their potential co-functions in cancer. A cell-based assay was performed to evaluate the combined therapeutic efficacy of targeting both, TFF3 and PVRL2 and virtual screening identified potential drugs for inhibiting PVRL2. PVRL2 has emerged as a promising immunoinhibitory target with significant associations with TFF3 and represents a key co-targetable molecule for effective oncotherapeutic strategies. [Display omitted] • Elevated TFF3 expression is positively correlated with changes in immunosuppressive TME, thereby progressing tumour. • TFF3 and PVRL2 both contribute to an immunosuppressive TME and disease progression. • In vitro analyses confirmed a positive association between TFF3 and PVRL2 in multiple cancers. • Co-targeting TFF3 and PVRL2 has emerged as an effective and promising strategy for cancer treatment [ABSTRACT FROM AUTHOR]

Abstract: A graft copolymer of κ-carrageenan and 2-acrylamidoglycolic acid (CgOH-g-AGA) was synthesized via free radical polymerization initiated by potassium peroxymonosulphate/malonic acid redox pair. For affording maximum percentage of grafting, optimum conditions were determined by varying the concentrations of κ-carrageenan, 2-acrylamidoglycolic acid, potassium peroxymonosulphate, malonic acid, hydrogen ion, time and temperature. The swelling, metal ion uptake and flocculation studies were investigated with water, three metals (Ni2+, Pb2+ and Zn2+) solutions, coal (coking and non-coking) suspensions, respectively. Both, polymer backbone and its corresponding graft copolymer samples were characterized by Fourier transform infrared spectroscopy and thermogravimetric analysis. [Copyright &y& Elsevier]

Triple Negative Breast Cancer (TNBC) is the most aggressive type of breast cancer (BC). Despite advances in the clinical management of TNBC, recurrence-related mortality remains a challenge. The stem-like phenotype of TNBC plays a significant role in the persistence of minimal disease residue after therapy. Individuals exhibiting stem-like characteristics are particularly prone to inducing malignant relapse accompanied by strong resistance. Therefore, stem-like traits have been broadly proposed as therapeutic vulnerabilities to treat TNBC and reduce recurrence. However, heterogeneity within TNBC often generally restricts the stability of the therapeutic efficacy. To understand the heterogeneity and manage TNBC more precisely, multiple TNBC subtyping categories have been reported, providing the basis for profile-according therapeutic regimens. To provide more insight into targeting stem-like traits to ablate TNBC and reduce recurrence in the context of heterogeneity, this paper reviewed the molecular subtyping of TNBC, identified the consensus subtypes with distinct stem-like phenotypes, characterized the stemness hierarchy of TNBC, outlined the biological models for stem-like TNBC subtypes, summarized the therapeutic vulnerabilities in stem-like traits of the subtypes, and proposed potential therapeutic regimens targeting stem-like characteristics to improve TNBC prognosis. [Display omitted] • Comparing different subtyping categories of TNBC. • Proposing stemness hierarchy within TNBC subtypes. • Outlining biological models of TNBC subtypes with enriched stemness. • Stem-like traits as therapeutic vulnerabilities to treat TNBC in context of TNBC subtyping. [ABSTRACT FROM AUTHOR]

Vascular endothelial growth factor (VEGF) and its receptor (VEGFR) is essential for physiological functions of tissues and neovasculature. VEGFR signaling is associated with the progression of pathological angiogenesis in various types of malignancies, making it an attractive therapeutic target in cancer treatment. In the present work, we report the synthesis of 1,4-disubstituted 1,2,3-triazoles and 1,2,4-triazolo[1, 5- a ]pyrimidine derivatives via copper (I)-catalyzed azide-alkyne cycloaddition (CuAAC) reaction and screened for their anticancer activity against MCF7 cells. We identified 1-(2′-ethoxy-4′-fluoro-[1,1′-biphenyl]-4-yl)-4-phenyl-1H-1,2,3-triazole (EFT) as lead cytotoxic agent against MCF7 cell lines with an IC 50 value of 1.69 µM. Further evaluation revealed that EFT induces cytotoxicity on Ishikawa, MDA-MB-231 and BT474 cells with IC 50 values of 1.97, 4.81 and 4.08 µM respectively. However, EFT did not induce cytotoxicity in normal lung epithelial (BEAS-2B) cells. Previous reports suggested that 1,2,3-triazoles are the inhibitors of VEGFR1 and therefore, we evaluated the effect of EFT on the expression of VEGFR1. The results demonstrated that EFT downregulates the expression of VEGFR1 in MCF7 cells. In summary, we identified a potent cytotoxic agent that imparts its antiproliferative activity by targeting VEGFR1 in breast cancer cells. The novel compound could serve as a lead structure in developing VEGFR1 inhibitors. [ABSTRACT FROM AUTHOR]

Signal transducer and activator of transcription 3 (STAT3) is a transcription factor that regulates genes involved in cell growth, proliferation, and survival, and given its association with many types of cancers, it has recently emerged as a promising target for therapy. In this work, we present the synthesis of N-substituted azaspirane derivatives and their biological evaluation against hepatocellular carcinoma (HCC) cells (IC50 = 7.3 µM), thereby identifying 2-(1-(4-(2-cyanophenyl)1-benzyl-1H-indol-3-yl)-5-(4-methoxy-phenyl)-1-oxa-3-azaspiro(5,5) undecane (CIMO) as a potent inhibitor of the JAK-STAT pathway with selectivity over normal LO2 cells (IC50 >100µM). The lead compound, CIMO, suppresses proliferation of HCC cells and achieves this effect by reducing both constitutive and inducible phosphorylation of JAK1, JAK2, and STAT3. Interestingly, CIMO displayed inhibition of Tyr-705 phosphorylation, which is required for nuclear translocation of STAT3, but it has no effect on Ser-727 phosphorylation. CIMO accumulates cancer cells in the sub-G1 phase and decreases STAT3 in the nucleus and thereby causes down-regulation of genes regulated via STAT3. Suppression of STAT3 phosphorylation by CIMO and knockdown of STAT3 mRNA using siRNA transfection displayed a similar effect on the viability of HCC cells. Furthermore, CIMO significantly decreased the tumor development in an orthotopic HCC mouse model through the modulation of phospho-STAT3, Ki-67, and cleaved caspase-3 in tumor tissues. Thus, CIMO represents a chemically novel and biologically in vitro and in vivo validated compound, which targets the JAKSTAT pathway as a potential cancer treatment. [ABSTRACT FROM AUTHOR]

In this work, a miniaturized multiple-input-multiple-output (MIMO) antenna with frequency agility is designed and developed for 1.8 GHz, 2.4 GHz, and 3.5 GHz application bands. The prospective antenna element comprised of a modified ground surface and a microstrip-line-fed slotted radiator (SR) loaded with a modified-electric inductive capacitive (m-ELC) meta-resonator. In order to achieve frequency reconfigurability, a PIN diode is integrated between the SR and the m-ELC resonator. The size of the antenna element is 0.19 λ 0 × 0.18 λ 0 , and the size of the MIMO antenna is 0.39 λ 0 × 0.36 λ 0 , where λ 0 is the smallest resonating frequency. In the proposed MIMO antenna, only four PIN diodes are required to provide frequency reconfigurability, and it does not require an additional impedance matching network. [ABSTRACT FROM AUTHOR]