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This study uses Julia Roy Raffel's Dinner Depression, a book that was totally produced by artificial intelligence, to investigate AI-generated fiction. The study emphasizes how AI transforms creativity, authorship, and narrative coherence in the posthuman world by concentrating on the semantic structures found in the novel. The book provides insights into how non-human authorship challenges conventional narrative assumptions and demonstrates the complex ways AI interacts with storytelling. The article contextualizes the blurring lines between human and machine creativity by first exploring posthuman ideas. Through attentive reading and semantic analysis, it examines Dinner Depression's characters, coherence, and meaning, exposing the unique narrative patterns of literature produced by artificial intelligence. The study demonstrates AI's ability to produce emotionally compelling narratives by analyzing the text's semantic richness and coherence. The results highlight AI's capacity to create complex stories that captivate readers and point to a revolution in writing. This study raises questions about creative collaboration between humans and machines and suggests a future in which artificial intelligence (AI) reimagines authorship and storytelling. In the end, it offers a thorough examination of AI's developing involvement in literary production, stimulating more research into the changing dynamics of tales produced by machines and humans. [ABSTRACT FROM AUTHOR]

Hyaluronic acid also called as Hyaluronan, Sodium Hyaluronate (SA), sodium salt form of Hyaluronic acid is a biodegradable, biocompatible, and viscoelastic linear polysaccharide of a wide molecular weight range (1000 to 10,000,000 Da). In this project, described a method for preparing HA microspheres at different pH conditions by adapting a non-toxic and aqueous based crosslinking chemistry for sustained drug delivery of drugs. The derivatization chemistry of HA utilizing adipic dihydrazide has been used to construct hydrogels, applied for microsphere preparation. ADH was coupled efficiently to carbodimide-activated glucoronic acid residues of hyluronans. These ADH modified hyaluronan can be loaded with drug molecules and then cross linked into hydrogel. The drug was present in the bulk of hydrogel droplets which are present in liquid paraffin are precipitated by IPA. Formulating HA microspheres with this method have several advantages. Preliminary studies were conducted to confirm the better ratio of HA and ADH to show maximum entrapment efficiency and drug release. Then microspheres were prepared at different pH conditions and formulations were subjected to evaluation of various parameters like percentage yield, particle size, drug entrapment efficiency, porosity and bulk density, surface morphology, in vitro drug release among which F2B was optimized as best formulation which showed 74.6% entrapment efficiency and above 90% of drug release in 12 hours indicating Hyaluronic acid microspheres can be used as good carriers for sustained drug delivery of drugs.

Petrochemical plastics have become a basic requisite in today's world. Their production has increased dramatically since the last few decades owing to the increase in their demand. Sustainable green plastics produced from polylactic acid have proven to be an alternative to conventional plastics pertaining to their tendency of biodegradability; they are disintegrated by microorganisms and are utilized as carbon sources by plants and other primitive organisms. Rhizopus species is appropriate for the biosynthesis of lactic acid, which is the basic raw material of polylactic acid could be obtained from lignocellulosic biomass since the fungus has the ability to grow on and ferment various carbon sources like cellulose, starch and so on. This research paper deals with the effective biosynthesis of lactic acid from Paper Sludge (PS) through the method of simultaneous saccharification and fermentation (SSF), along with the optimization of various parameters like temperature, pH and initial substrate concentration. An economical and an alternative methodology was opted to prepare cellulase enzyme necessary for the fermentation process, considering the fact that commercially available cellulase are exorbitant. Various combinations of the above enzymes were tested to determine the optimal cellulase cocktail suitable for these conditions. Finally, lactic acid productivity of 27 g/L was achieved when using a blended cellulase cocktail at 50:50 proportion of commercial and fabricate cellulase using a feed concentration of 75 g/L at 40 °C and 6 pH after144 hr by SSF. [ABSTRACT FROM AUTHOR]

Traumatic and inherited cataract spiking blindness is caused by accumulated deposition of mutant eye lens protein or lens microarchitecture alteration. A traumatic cataract is a clouding of the eye's natural lens that occurs as a result of physical trauma to the eye. This trauma can be caused by various incidents such as blunt force injury, penetration by a foreign object, or a significant impact on the eye area. Inheritance cataracts or hereditary cataracts are cataracts that are genetically inherited from one or both parents. Complications following cataract surgery encompass various adverse outcomes such as inflammation, infection, bleeding, swelling, drooping eyelid, glaucoma, secondary cataracts, and complete loss of vision. The main purpose of the review is to highlight common pathophysiology associated with traumatic and inherited cataracts. Also, the review discusses diagnosis and treatment strategies for such cataract types by targeting their key pathological hallmarks. γD-crystallin plays a crucial role in maintaining the optical properties of the lens during the life span of an individual. Carbamazepine, Resveratrol, and Myricetin (CRM) are effectively bound at the γD-crystallin binding site and thereby could minimize misfolding and aggregation of γD-crystallin. miR-202, miR-193b, miR-135a, miR365, and miR-376a had the highest levels of abundance in the aqueous humor of individuals diagnosed with cataracts. The validation of these miRs will provide more insights into their functional roles and may be used for diagnostic purposes. The effective CRM combination as a multidrug formulation may postpone both traumatic and inherited cataracts and protect the eye from blindness., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The Kisspeptin1 (KISS1)/neurokinin B (NKB)/Dynorphin (Dyn) [KNDy] neurons in the hypothalamus regulate the reproduction stage in human beings and rodents. KNDy neurons co-expressed all KISS1, NKB, and Dyn peptides, and hence commonly regarded as KISS1 neurons. KNDy neurons contribute to the "GnRH pulse generator" and are implicated in the regulation of pulsatile GnRH release. The estradiol (E2)-estrogen receptor (ER) interactions over GnRH neurons in the hypothalamus cause nitric oxide (NO) discharge, in addition to presynaptic GABA and glutamate discharge from respective neurons. The released GABA and glutamate facilitate the activity of GnRH neurons via GABAA-R and AMPA/kainate-R. The KISS1 stimulates MAPK/ERK1/2 signaling and cause the release of Ca 2+ from intracellular store, which contribute to neuroendocrine function, increase apoptosis and decrease cell proliferation and metastasis. The ageing in women deteriorates KISS1/KISS1R interaction in the hypothalamus which causes lower levels of GnRH. Because examining the human brain is so challenging, decades of clinical research have failed to find the causes of KNDy/GnRH dysfunction. The KISS1/KISS1R interactions in the brain have a neuroprotective effect against Alzheimer's disease (AD). These findings modulate the pathophysiological role of the KNDy/GnRH neural network in polycystic ovarian syndrome (PCOS) associated with ageing and, its protective role in cancer and AD. This review concludes with protecting effect of the steroid-derived acute regulatory enzyme (StAR) against neurotoxicity in the hippocampus, and hypothalamus, and these measures are fundamental for delaying ageing with PCOS. StAR could serve as novel diagnostic marker and therapeutic target for the most prevalent hormone-sensitive breast cancers (BCs)., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Neolamarckia cadamba (Roxb.) Bosser, a member of the Rubiaceae family, is a botanical species with recognized therapeutic properties. It is commonly used in traditional medicine to treat cardiac ailments and other disorders. However, the precise active constituents and the potential mechanisms by which they manage cardiovascular disorders remain unclear. Therefore, this study aimed to ascertain the bioactive components and investigate their underlying mechanisms of action. N . cadamba is used to treat cardiovascular disorders using the integrated metabolomic methodology. An HPLC-QTOF-MS/MS analysis determined the potential chemicals in the N. cadamba leaf ethanol extract (NCEE). A thorough investigation of the NCEE samples used in this study led to the identification of 32 phytoconstituents. Of the 32 compounds, 19 obeyed Lipinski's rule of five (RO5). A molecular docking study directed towards HMG-CoA reductase used 19 molecules. The reference drug atorvastatin indicated a binding energy of -3.9 kcal/mol, while the other substances, Cinchonain Ib and Dukunolide B, revealed binding energies of -5.7 and -5.3 kcal/mol, respectively. Both phytocompounds showed no toxicity and exhibited favorable pharmacokinetic properties. In vivo study results concluded that treatment with NCEE significantly reduced the cardiac myocardial infarction (MI) marker CK-MB and atherogenic risk indices, such as the atherogenic index plasma (AIP), cardiac risk ratio (CRR), and atherogenic coefficient (AC) in isoproterenol-induced MI rats. In MI rats, NCEE therapy significantly improved the antioxidant system of the heart tissue, as evidenced by the increased levels of GSH and SOD, lower levels of the oxidative stress marker MDA, and significantly decreased HMG-CoA activity. Additionally, electrocardiogram (ECG) signals from rats treated with NCEE resembled those treated with traditional atorvastatin to treat myocardial infarction. This study used H&E staining to show that administering NCEE before treatment reduced cardiac myocyte degeneration in rats with myocardial infarction, increased the presence of intact nuclei, and increased myocardial fiber strength. The potential cardioprotective effect observed in myocardial infarction (MI) rats treated with NCEE can be extrapolated from computational data to be caused by Cinchonain Ib.

Neuronal necroptosis (programmed necrosis) in the CNS naturally occurs through a caspase-independent way and, especially in neurodegenerative diseases (NDDs) such as Alzheimer's disease (AD), Parknson's disease (PD), Amyotrophic Lateral Sclerosis (ALS) and viral infections. Understanding necroptosis pathways (death receptor-dependent and independent), and its connections with other cell death pathways could lead to new insights into treatment. Receptor-interacting protein kinase (RIPK) mediates necroptosis via mixed-lineage kinase-like (MLKL) proteins. RIPK/MLKL necrosome contains FADD, procaspase-8-cellular FLICE-inhibitory proteins (cFLIPs), RIPK1/RIPK3, and MLKL. The necrotic stimuli cause phosphorylation of MLKL and translocate to the plasma membrane, causing an influx of Ca 2+ and Na + ions and, the immediate opening of mitochondrial permeability transition pore (mPTP) with the release of inflammatory cell damage-associated molecular patterns (DAMPs) like mitochondrial DNA (mtDNA), high-mobility group box1 (HMGB1), and interleukin1 (IL-1). The MLKL translocates to the nucleus to induce transcription of the NLRP3 inflammasome complex elements. MLKL-induced NLRP3 activity causes caspase-1 cleavage and, IL-1 activation which promotes neuroinflammation. RIPK1-dependent transcription increases illness-associated microglial and lysosomal abnormalities to facilitate amyloid plaque (Aβ) aggregation in AD. Recent research has linked neuroinflammation and mitochondrial fission with necroptosis. MicroRNAs (miRs) such as miR512-3p, miR874, miR499, miR155, and miR128a regulate neuronal necroptosis by targeting key components of necroptotic pathways. Necroptosis inhibitors act by inhibiting the membrane translocation of MLKL and RIPK1 activity. This review insights into the RIPK/MLKL necrosome-NLRP3 inflammasome interactions during death receptor-dependent and independent neuronal necroptosis, and clinical intervention by miRs to protect the brain from NDDs., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The goal of this review is to increase public knowledge of the etiopathogenesis of diabetic eye diseases (DEDs), such as diabetic retinopathy (DR) and ocular angiosarcoma (ASO), and the likelihood of blindness among elderly widows. A widow's life in North India, in general, is fraught with peril because of the economic and social isolation it brings, as well as the increased risk of death from heart disease, hypertension, diabetes, depression, and dementia. Neovascularization, neuroinflammation, and edema in the ocular tissue are hallmarks of the ASO, a rare form of malignant tumor. When diabetes, hypertension, and aging all contribute to increased oxidative stress, the DR can proceed to ASO. Microglia in the retina of the optic nerve head are responsible for causing inflammation, discomfort, and neurodegeneration. Those that come into contact with them will get blind as a result of this. Advanced glycation end products (AGE), vascular endothelial growth factor (VEGF), protein kinase C (PKC), poly-ADP-ribose polymerase (PARP), metalloproteinase9 (MMP9), nuclear factor kappaB (NFkB), program death ligand1 (PDL-1), factor VIII (FVIII), and von Willebrand factor (VWF) are potent agents for ocular neovascularisation (ONV), neuroinflammation and edema in the ocular tissue. AGE/VEGF, DAG/PKC, PARP/NFkB, RAS/VEGF, PDL-1/PD-1, VWF/FVIII/VEGF, and RAS/VEGF are all linked to the pathophysiology of DEDs. The interaction between ONV and ASO is mostly determined by the VWF/FVIII/VEGF and PDL-1/PD-1 axis. This study focused on retinoprotective medications that can pass the blood-retinal barrier and cure DEDs, as well as the factors that influence the etiology of neovascularization and neuroinflammation in the eye., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Introduction: The mixed flavonoid supplement (MFS) [Trimethoxy Flavones (TMF) + epigallocatechin-3-gallate (EGCG)] can be used to suppress inflammatory ulcers as an ethical medicine in Ayurveda. The inflammation of the rectum and anal regions is mostly attributed to nuclear factor kappa beta (NF-κB) signaling. NF-κB stimulates the expression of matrix metalloproteinase (MMP9), inflammatory cytokines tumor necrosis factor (TNF-α), and interleukin-1β (IL-1β). Although much research targeted the NF-κB and MMP9 signaling pathways, a subsequent investigation of target mediators in the inflammatory ulcer healing and NF-κB pathway has not been done. Methods: The docking studies of compounds TMF and EGCG were performed by applying PyRx and available software to understand ligand binding properties with the target proteins. The synergistic ulcer healing and anti-arthritic effects of MFS were elucidated using dextran sulfate sodium (DSS)-induced colon ulcer in Swiss albino rats. The colon mucosal injury was analyzed by colon ulcer index (CUI) and anorectic tissue microscopy. The IL-1β, tumor necrosis factor (TNF-α), and the pERK, MMP9, and NF-κB expressions in the colon tissue were determined by ELISA and Western blotting. RT-PCR determined the mRNA expression for inflammatory marker enzymes. Results: The docking studies revealed that EGCG and TMF had a good binding affinity with MMP9 (i.e., -6.8 and -6.0 Kcal/mol) and NF-kB (-9.4 and 8.3 kcal/mol). The high dose MFS better suppressed ulcerative colitis (UC) and associated arthritis with marked low-density pERK, MMP9, and NF-κB proteins. The CUI score and inflammatory mediator levels were suppressed with endogenous antioxidant levels in MFS treated rats. Conclusion: The MFS effectively unraveled anorectic tissue inflammation and associated arthritis by suppressing NF-κB-mediated MMP9 and cytokines., (© 2023 The Author(s).)

Parkinsonism is a complex neurodegenerative disease that is difficult to differentiate because of its idiopathic and unknown origins. The hereditary parkinsonism known as autosomal recessive-juvenile parkinsonism (AR-JP) is marked by tremors, dyskinesias, dystonic characteristics, and manifestations that improve sleep but do not include dementia. This was caused by deletions and point mutations in PARK2 (chromosome 6q25.2-27). Diminished or unusual sensations (paresthesias), loss of neuron strength both in the CNS and peripheral nerves, and lack of motor coordination are the hallmarks of neuropathy in parkinsonism. The incidence of parkinsonism during oxidative stress and ageing is associated with parkinopathy. Parkinopathy is hypothesized to be triggered by mutation of the parkin (PRKN) gene and loss of normal physiological functions of PRKN proteins, which triggers their pathogenic aggregation due to conformational changes. Two important genes that control mitochondrial health are PRKN and phosphatase and tensin homologue deleted on chromosome 10-induced putative kinase 1 (PINK1). Overexpression of TAR DNA-binding protein-43 (TDP-43) increases the aggregation of insoluble PRKN proteins in OMM. Foreign α-synuclein (ASN) promotes parkinopathy via S-nitrosylation and hence has a neurotoxic effect on dopaminergic nerves. Miro1 (Miro GTPase1), a member of the RAS superfamily, is expressed in nerve cells. Due to PINK1/PRKN and Miro1's functional relationship, an excess of mitochondrial calcium culminates in the destruction of dopaminergic neurons. An interlinked understanding of TDP-43, PINK1/PRKN, ASN, and Miro1 signalling in the communication among astrocytes, microglia, neurons, and immune cells within the brain explored the pathway of neuronal death and shed light on novel strategies for the diagnosis and treatment of parkinsonism., Competing Interests: Conflict of interest No conflict of interest between authors., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Microgravity or the condition of apparent weightlessness causes bone, muscular and immune system dysfunctions in astronauts following spaceflights. These organ and system-level dysfunctions correlate with changes induced at the single cell level both by simulated microgravity on earth as well as microgravity conditions in outer space (as in the international space station). Reported changes in single bone cells, muscle cells and white blood cells include structural/morphological abnormalities, changes in gene expression, protein expression, metabolic pathways and signaling pathways, suggesting that cells mount some response or adjustment to microgravity. However, the implications of such adjustments on many cellular functions and responses are not clear largely because the primary mechanism of gravity sensing in animal cells is unknown. Here, we used a rotary cell culture system developed by NASA to subject leukemic and erythroleukemic cancer cells to microgravity for 48 h and then quantified their innate immune response to common anti-cancer drugs using biophysical parameters and our recently developed quantum-dot-based fluorescence spectroscopy. We found that leukemic cancer cells treated with daunorubicin show increased chemotactic migration ( p < 0.01) following simulated microgravity ( µg ) compared to normal gravity on earth (1 g ). However, cells treated with doxorubicin showed enhanced migration both in 1 g and following µg . Our results show that microgravity modulates cancer cell response to chemotherapy in a drug-dependent manner. These results suggest using simulated microgravity as an immunomodulatory tool for the development of new immunotherapies for both space and terrestrial medicine.

Objectives: This research aimed to evaluate the antiangiogenic activity of isolated flavonoid 4a,5,8,8a-tetrahydro-5-hydroxy-3,7,8-trimethoxy-2-(3,4-dimethoxyphenyl) chromen-4-one (TMF) from Tabebuia chrysantha. STAT3-MMP9 signalling is a signal transduction mechanism that promotes angiogenesis in various cancers., Methods: The tumour xenografting chicken embryo chorioallantoic membrane (CAM) model-based ex vivo assay was used to evaluate the activity of TMF. The Western blot, densitometric analysis and quantitative real-time polymerase chain reaction (qRT-PCR) were performed to evaluate the activity of the MMP9. Zebrafish embryos were used to evaluate embryotoxicity, and in vitro free radical scavenging activity of flavonoid was also elucidated., Key Findings: This research assessed the high level of STAT3, p-ERK, VEGF-R and MMP9 in the tissue extract of the control group, and also, the suppression of angiogenesis in the treatment groups was due to scavenged ROS and RNS, dephosphorylation of STAT3 and ERK, and suppression of MMP9 gene expression., Conclusion: The isolated flavonoid named TMF from T. chrysantha functions as specific regulators of target proteins of angiosarcoma. The STAT3-MMP9 signalling may be used as an effective prognostic marker of angiosarcoma., (© 2020 Royal Pharmaceutical Society.)