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Maya S Nair,1 Ullas Mony,1 Deepthy Menon,1 Manzoor Koyakutty,1 Neeraj Sidharthan,2 Keechilat Pavithran,2 Shantikumar V Nair,1 Krishnakumar N Menon11Amrita Centre for Nanosciences and Molecular Medicine, 2Department of Oncology, Amrita Institute of Medical Sciences and Research Centre, Amrita Vishwa Vidyapeetham University, Kerala, IndiaAbstract: Standard in vitro drug testing employs 2-D tissue culture plate systems to test anti-leukemic drugs against cell adhesion-mediated drug-resistant leukemic cells that harbor in 3-D bone marrow microenvironments. This drawback necessitates the fabrication of 3-D scaffolds that have cell adhesion-mediated drug-resistant properties similar to in vivo niches. We therefore aimed at exploiting the known property of polyurethane (PU)/poly-L-lactic acid (PLLA) in forming a micro-nanofibrous structure to fabricate unique, not presented before, as far as we are aware, 3-D micro-nanofibrous scaffold composites using a thermally induced phase separation technique. Among the different combinations of PU/PLLA composites generated, the unique PU/PLLA 60:40 composite displayed micro-nanofibrous morphology similar to decellularized bone marrow with increased protein and fibronectin adsorption. Culturing of acute myeloid leukemia (AML) KG1a cells in FN-coated PU/PLLA 60:40 shows increased cell adhesion and cell adhesion-mediated drug resistance to the drugs cytarabine and daunorubicin without changing the original CD34+/CD38-/CD33- phenotype for 168 hours compared to fibronectin tissue culture plate systems. Molecularly, as seen in vivo, increased chemoresistance is associated with the upregulation of anti-apoptotic Bcl2 and the cell cycle regulatory protein p27Kip1leading to cell growth arrest. Abrogation of Bcl2 activity by the Bcl2-specific inhibitor ABT 737 led to cell death in the presence of both cytarabine and daunorubicin, demonstrating that the cell adhesion-mediated drug resistance induced by Bcl2 and p27Kip1in the scaffold was similar to that seen in vivo. These results thus show the utility of a platform technology, wherein drug testing can be performed before administering to patients without the necessity for stromal cells.Keywords: daunorubicin, cytarabine, Bcl2, p27Kip1, cell adhesion-mediated drug resistance

Chronic stress results in long-term dynamic changes at multiple levels of the hypothalamic-pituitary-adrenal (HPA) axis resulting in stress axis dysregulation with long-term impacts on human and animal health. However, the underlying mechanisms and dynamics of altered of HPA axis function, in particular at the level of pituitary corticotrophs, during a period of chronic stress and in the weeks after its cessation (defined as "recovery") are very poorly understood. Here, we address the fundamental question of how a period of chronic stress results in altered anterior pituitary corticotroph function and whether this persists in recovery, as well as the transcriptomic changes underlying this. We demonstrate that, in mice, spontaneous and corticotrophin-releasing hormone-stimulated electrical excitability of corticotrophs, essential for ACTH secretion, is suppressed for weeks to months of recovery following a period of chronic stress. Surprisingly, there are only modest changes in the corticotroph transcriptome during the period of stress, but major alterations occur in recovery. Importantly, although transcriptional changes for a large proportion of mRNAs follow the time course suppression of corticotroph excitability, many other genes display highly dynamic transcriptional changes with distinct time courses throughout recovery. Taken together, this suggests that chronic stress results in complex dynamic transcriptional and functional changes in corticotroph physiology, which are highly dynamic for weeks following cessation of chronic stress. These insights provide a fundamental new framework to further understand underlying molecular mechanisms as well approaches to both diagnosis and treatment of stress-related dysfunction of the HPA axis., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)

Remarkable progress has been made in the field of genome engineering after the discovery of CRISPR/Cas9 in 2012 by Jennifer Doudna and Emmanuelle Charpentier. Compared to any other gene-editing tools, CRISPR/Cas9 attracted the attention of the scientific community because of its simplicity, specificity, and multiplex editing possibilities for which the inventors were awarded the Nobel prize for chemistry in 2020. CRISPR/Cas9 allows targeted alteration of the genomic sequence, gene regulation, and epigenetic modifications using an RNA-guided site-specific endonuclease. Though the impact of CRISPR/Cas9 was undisputed, some of its limitations led to key modifications including the use of miniature-Cas proteins, Cas9 Retron precise Parallel Editing via homologY (CRISPEY), Cas-Clover, or development of alternative methods including retron-recombineering, Obligate Mobile Element Guided Activity(OMEGA), Fanzor, and Argonaute proteins. As cancer is caused by genetic and epigenetic alterations, gene-editing was found to be highly useful for knocking out oncogenes, editing mutations to regain the normal functioning of tumor suppressor genes, knock-out immune checkpoint blockade in CAR-T cells, producing 'off-the-shelf' CAR-T cells, identify novel tumorigenic genes and functional analysis of multiple pathways in cancer, etc. Advancements in nanoparticle-based delivery of guide-RNA and Cas9 complex to the human body further enhanced the potential of CRISPR/Cas9 for clinical translation. Several studies are reported for developing novel delivery methods to enhance the tumor-specific application of CRISPR/Cas9 for anticancer therapy. In this review, we discuss new developments in novel gene editing techniques and recent progress in nanoparticle-based CRISPR/Cas9 delivery specific to cancer applications., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Shantikumar Nair reports was provided by Amrita Vishwa Vidyapeetham Amrita Centre for Nanosciences and Molecular Medicine. Shantikumar Nair reports a relationship with Amrita Vishwa Vidyapeetham Amrita Centre for Nanosciences and Molecular Medicine that includes: employment. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Amrita Vishwa Vidyapeetham Kochi.)

Artificial intelligence (AI) has been extensively researched in medicine, but its practical application remains limited. Meanwhile, there are various disparities in existing AI-enabled clinical studies, which pose a challenge to global health equity. In this study, we conducted an in-depth analysis of the geo-economic distribution of 159 AI-enabled clinical studies, as well as the gender disparities among these studies. We aim to reveal these disparities from a global literature perspective, thus highlighting the need for equitable access to medical AI technologies., (© 2024. The Author(s).)

Hybrid bioprinting uses sequential printing of melt-extruded biodegradable thermoplastic polymer and cell-encapsulated bioink in a predesigned manner using high- and low-temperature print heads for the fabrication of robust three-dimensional (3D) biological constructs. However, the high-temperature print head and melt-extruded polymer cause irreversible thermal damage to the bioprinted cells, and it affects viability and functionality of 3D bioprinted biological constructs. Thus, there is an urgent need to develop innovative approaches to protect the bioprinted cells, coming into contact or at close proximities to the melt-extruded thermoplastic polymer and the high-temperature print head during hybrid bioprinting. Therefore, this study investigated the potential of iterating the structural architecture pattern (SAP) of melt-printed thermoplastic layers and the cell printing pattern (CPP) to protect the cells from temperature-associated damage during hybrid bioprinting. A novel SAP for printing the thermoplastic polymer and an associated CPP for minimizing thermal damage to the 3D bioprinted construct have been developed. The newly developed SAP- and CPP-based hybrid bioprinted biological constructs showed significantly low thermal damage compared to conventionally hybrid bioprinted biological constructs. The results from this study suggest that the newly developed SAP and CPP can be an improved hybrid bioprinting strategy for developing living constructs at the human scale.

Objective: The 2x2 factorial design is an effective method that allows for multiple comparisons, especially in the context of interactions between different interventions, without substantially increasing the required sample size. In view of the considerable preclinical evidence for Curcumin and Metformin in preventing the development and progression of head and neck squamous cell carcinoma (HNSCC), this study describes the protocol of the clinical trial towards applying the drug combination in prevention of second primary tumors., Methods: We have applied the trial design to a large phase IIB/III double-blind, multi-centric, placebo-controlled, randomized clinical trial to determine the safety and efficacy of Metformin and Curcumin in the prevention of second primary tumours (SPT) of the aerodigestive tract following treatment of HNSCC (n=1,500) [Clinical Registry of India, CTRI/2018/03/012274]. Patients recruited in this trial will receive Metformin (with placebo), Curcumin (with placebo), Metformin, and Curcumin or placebo alone for a period of 36 months. The primary endpoint of this trial is the development of SPT, while the secondary endpoints are toxicities associated with the agents, incidence of recurrence, and identifying potential biomarkers. In this article, we discuss the 2x2 factorial design and how it applies to the head and neck cancer chemoprevention trial., Conclusion: 2x2 factorial design is an effective trial design for chemoprevention clinical trials where the effectiveness of multiple interventions needs to be tested parallelly.

The inheritable impact of exposure to graphene oxide nanoparticles (GO NPs) on vertebrate germline during critical windows of gamete development remain undetermined to date. Here, we analyzed the transgenerational effects of exposure to nano-graphene oxide particles (nGO) synthesized in house with lateral dimensions 300-600 nm and surface charge of -36.8 mV on different developmental stages of germ cells (GCs): (1) during GCs undergoing early development and differentiation, and (2) during GCs undergoing gametogenesis and maturation in adulthood. Biocompatibility analyses in Japanese medaka embryos showed lethality above 1 µg/ml and also an aberrant increase in germ cell count of both males and females at doses below the lethal dose. However, no lethality or anomalies were evident in adults up to 45 µg/ml. Long term exposure of embryos and adults for 21 days resulted in reduced fecundity. This effect was transmitted to subsequent generations, F1 and F2. Importantly, the inheritable effects of nGO in adults were pronounced at a high dose of 10 µg/ml, while 1 µg/ml showed no impact on the germline indicating lower doses used in this study to be safe. Further, expressions of selected genes that adversely affected oocyte maturation were enhanced in F1 and F2 individuals. Interestingly, the inheritance patterns differed corresponding to the stage at which the fish received the exposure.

Bioengineered 3D models that can mimic patient-specific pathologies in vitro are valuable tools for developing and validating anticancer therapeutics. In this study, microfibrillar matrices with unique structural and functional properties were fabricated as 3D spherical and disc-shaped scaffolds with highly interconnected pores and the potential of the newly developed scaffolds for developing prostate cancer model has been investigated. The newly developed scaffolds showed improved cell retention upon seeding with cancer cells compared to conventional electrospun scaffolds. They facilitated rapid growth and deposition of cancer-specific extracellular matrix through-the-thickness of the scaffold. Compared to the prostate cancer cells grown in 2D culture, the newly developed prostate cancer model showed increased resistance to the chemodrug Docetaxel regardless of the drug concentration or the treatment frequency. A significant reduction in the cell number was observed within one week after the drug treatment in the 2D culture for both PC3 and patient-derived cells. Interestingly, almost 20%-30% of the cancer cells in the newly developed 3D model survived the drug treatment, and the patient-derived cells were more resistant than the tested cell line PC3. The results from this study indicate the potential of the newly developed prostate cancer model for in vitro drug testing., (© 2023 IOP Publishing Ltd.)

Food 3D printing is a computer-aided additive manufacturing technology that can transform foods into intricate customized forms. In the past decade, this field has phenomenally advanced and one pressing need is the development of strategies to support process optimization. Among different approaches, a range of modeling methods have been explored to simulate 3D printing processes. This review details the concepts of various modeling techniques considered for simulating 3D printing processes and their application range. Most modeling studies majorly focus on predicting the mechanical behavior of the material supply, modifying the internal texture of printed constructs, and assessing the post-printing stability. The approach can also be used to simulate the dynamics of 3D printing processes, in turn, assisting the design of 3D printers based on material composition, properties, and printing conditions. While most existing works are associated with extrusion-based 3D printing, this article presents scope for expanding avenues with prominent research and commercial interest. The article concludes with challenges and research needs, emphasizing opportunities for computational and data-driven dynamic simulation approaches for multi-faceted applications.

Biomedical implants possessing the structural and functional characteristics of extracellular matrix (ECM) are pivotal for vascular applications. This study investigated the potential of recreating a natural ECM-like structural and functional environment on the surface of biodegradable polymeric nanotextiles for vascular implants. Human adipose-derived mesenchymal stem cells (MSCs) were grown on a suitably engineered polycaprolactone (PCL) nanofibrous textile and were allowed to modify its surface through the deposition of MSC-specific ECM. This surface-modified nanotextile showed mechanical characteristics and functionality appropriate for vascular patch material. The uniformity of ECM coating significantly improved the viability, proliferation, and migration of human endothelial cells compared to bare and xenogeneic collagen-coated PCL nanotextile patches. Thus, a polymeric nanotextile, which is surface modified using MSC-driven ECM, provided a rapid and improved endothelialization, thereby suggesting its potential for vascular patch applications.

Stress-related illness represents a major burden on health and society. Sex differences in stress-related disorders are well documented, with women having twice the lifetime rate of depression compared to men and most anxiety disorders. Anterior pituitary corticotrophs are central components of the hypothalamic-pituitary-adrenal (HPA) axis, receiving input from hypothalamic neuropeptides corticotrophin-releasing hormone (CRH) and arginine vasopressin (AVP), while regulating glucocorticoid output from the adrenal cortex. The dynamic control of electrical excitability by CRH/AVP and glucocorticoids is critical for corticotroph function; however, whether corticotrophs contribute to sexually differential responses of the HPA axis, which might underlie differences in stress-related disorders, is very poorly understood. Using perforated patch clamp electrophysiology in corticotrophs from mice expressing green fluorescent protein under the control of the Pomc promoter, we characterized basal and secretagogue-evoked excitability. Both male and female corticotrophs show predominantly single-spike action potentials under basal conditions; however, males predominantly display spikes with small-amplitude (<20 mV) afterhyperpolarizations (B-type), whereas females displayed a mixture of B-type spikes and spikes with a large-amplitude (>25 mV) afterhyperpolarization (A-type). In response to CRH, or CRH/AVP, male cells almost exclusively transition to a predominantly pseudo-plateau bursting, whereas only female B-type cells display bursting in response to CRH±AVP. Treatment of male or female corticotrophs with 1 nM estradiol (E2) for 24-72 h has no effect on the proportion of cells with A- or B-type spikes in either sex. However, E2 results in the cessation of CRH-induced bursting in both male and female corticotrophs, which can be partially reversed by adding a BK current using a dynamic clamp. RNA-seq analysis of purified corticotrophs reveals extensive differential gene expression at the transcriptional level, including more than 71 mRNAs encoding ion channel subunits. Interestingly, there is a two-fold lower level ( p < 0.01) of BK channel pore-forming subunit (Kcnma1) expression in females compared to males, which may partially explain the decrease in CRH-induced bursting. This study identified sex differences at the level of the anterior pituitary corticotroph ion channel landscape and control of both spontaneous and CRH-evoked excitability. Determining the mechanisms of sex differences of corticotroph and HPA activity at the cellular level could be an important step for better understanding, diagnosing, and treating stress-related disorders., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Duncan, Romanò, Nair, Murray, Le Tissier and Shipston.)

Tumor microenvironment (TME) is a heterogeneous system consisting of both cellular and acellular components. The growth and progression of tumors rely greatly on the nature of TME, marking it as an important target in cancer immunotherapy. Lewis Lung Carcinoma (LLC) is an established murine lung cancer model representing immunologically 'cold' tumors characterized by very few infiltrated cytotoxic T-cells, high levels of Myeloid-Derived Suppressor Cells (MDSCs) and Tumor-Associated Macrophages (TAMs). Here, we report various strategies we applied to reverse the non-immunogenic character of this cold tumor by imparting: a) immunogenic cell death using Hypericin nanoparticle-based photodynamic therapy (PDT), b) repolarising TAM using a TLR7/8 agonist, resiquimod, c) immune checkpoint inhibition using anti-PD-L1 and d) depleting MDSCs using low-dose 5-fluorouracil (5-FU) chemotherapy. Interestingly, the nano-PDT, resiquimod or anti-PD-L1 treatment had no major impact on tumor growth, whereas low-dose 5-FU-mediated depletion of MDSCs showed significant anti-tumor effect, primarily caused by the increased infiltration of CD8 + cytotoxic T-cells (∼96%). Though we have tested combining PDT with resiquimod or 5-FU for any synergistic effect, low-dose 5-FU alone showed better response than combinations. In effect, we show that depletion of MDSCs using low-dose 5-FU was one of the best methods to augment infiltration of CD8 + cytotoxic T-cells into a cold tumor, which is resistant to conventional therapies including immune checkpoint inhibitors., 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. Published by Elsevier B.V.)

We have conducted this study to understand the impact of poor differentiation (PD), as a sole poor prognostic factor, in early oral cancers. This was a retrospective analysis of a prospectively maintained database of clinically node-negative early T stage OSCC patients operated between 2012 and 2014. Impact of PD on the survival and role of adjuvant therapy in these patients was noted. Out of 1172 patients screened, 280 patients were found to be eligible for the study. 11.4% patients had PDSCC. It was found to be associated with tongue cancers and peri-neural invasion. It had a significant impact on OS and DFS (48.7 months vs 81.4 months, p < 0.00 and 44.6 months vs 73.5 months, p < 0.00 respectively. Hazard ratio for DFS: 4.08. Although patients with PDSCC had better survival with radiotherapy, but this was not statistically significant. Poor differentiation as a stand-alone factor impacts survival in patients with early oral cancer. It may be seen more often in patients with tongue cancer and may have associated PNI. The role of adjuvant therapy in such patients is not clear., Competing Interests: Conflict of InterestThe authors declare no competing interests., (© The Author(s), under exclusive licence to Indian Association of Surgical Oncology 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

The voyage of semiconductor industry to decrease the size of transistors to achieve superior device performance seems to near its physical dimensional limitations. The quest is on to explore emerging material systems that offer dimensional scaling to match the silicon- based technologies. The discovery of atomic flat two-dimensional materials has opened up a completely new avenue to fabricate transistors at sub-10 nanometer level which has the potential to compete with modern silicon-based semiconductor devices. Molybdenum disulfide (MoS 2 ) is a two-dimensional layered material with novel semiconducting properties at atomic level seems like a promising candidate that can possibly meet the expectation of Moore's law. This review discusses the various ' fabrication challenges ' in making MoS 2 based electronic devices from start to finish. The review outlines the intricate challenges of substrate selection and various synthesis methods of mono layer and few-layer MoS 2 . The review focuses on the various techniques and methods to minimize interface defect density at substrate/MoS 2 interface for optimum MoS 2 -based device performance. The tunable band-gap of MoS 2 with varying thickness presents a unique opportunity for contact engineering to mitigate the contact resistance issue using different elemental metals. In this work, we present a comprehensive overview of different types of contact materials with myriad geometries that show a profound impact on device performance. The choice of different insulating/dielectric gate oxides on MoS 2 in co-planar and vertical geometry is critically reviewed and the physical feasibility of the same is discussed. The experimental constraints of different encapsulation techniques on MoS 2 and its effect on structural and electronic properties are extensively discussed., (© 2023 IOP Publishing Ltd.)

Glioblastoma Multiforme (GBM) is one of the challenging tumors to treat as it recurs, almost 100%, even after surgery, radiation, and chemotherapy. In many cases, recurrence happens within 2-3cm depth of the resected tumor margin, indicating the inefficacy of current anti-glioma drugs to penetrate deep into the brain tissue. Here, we report an injectable nanoparticle-gel system, capable of providing deep brain penetration of drug up to 4 cm, releasing in a sustained manner up to >15 days. The system consists of ∼222 nm sized PLGA nanoparticles (NP-222) loaded with an anti-glioma drug, Carmustine (BCNU), and coated with a thick layer of polyethylene glycol (PEG). Upon release of the drug from PLGA core, it will interact with the outer PEG-layer leading to the formation of PEG-BCNU nanocomplexes of size ∼33 nm (BCNU-NC-33), which could penetrate >4 cm deep into the brain tissue compared to the free drug (< 5 mm). In vitro drug release showed sustained release of drug for 15 days by BCNU-NP gel, and enhanced cytotoxicity by BCNU-NC-33 drug-nanocomplexes in glioma cell lines. Ex vivo goat-brain phantom studies showed drug diffusion up to 4 cm in tissue and in vivo brain-diffusion studies showed almost complete coverage within the rat brain (∼1.2 cm), with ∼55% drug retained in the tissue by day-15, compared to only ∼5% for free BCNU. Rat orthotopic glioma studies showed excellent anti-tumor efficacy by BCNU-NP gel compared to free drug, indicating the potential of the gel-system for anti-glioma therapy. In effect, we demonstrate a unique method of sustained release of drug in the brain using larger PLGA nanoparticles acting as a reservoir while deep-penetration of the released drug was achieved by in situ formation of drug-nanocomplexes of size <50 nm which is less than the native pore size of brain tissue (> 100 nm). This method will have a major impact on a challenging field of brain drug delivery., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier B.V. All rights reserved.)

A simple yet efficient assay for the quantitation of proteins ranging from plasma proteins to purified proteins from whole cell lysate, based on the bioconjugation reaction between protein and Meldrum's acid Activated Furan (MAF) is described. This easy to use, sensitive method is based on the conjugation of amine functionalities present on the protein with MAF to form the corresponding Donor Acceptor Stenhouse Adducts (DASAs) with characteristic absorption in the visible region. The reaction is rapid as well as reproducible and shows a proportionate increase in color change over a broad range of protein concentration. The assay was found to be sensitive up to 0.125 mg/mL concentration of the protein and was compatible with most of the commonly employed detergents and isolation protocols which makes it ideal for the estimation of protein samples containing detergents. Another striking feature of this protocol is its tolerance towards other major interference contributors such as chelating agents, reducing agents, carbohydrates and protease inhibitors., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background Chronic stress is commonly thought to have a net negative effect on the efficacy of the immune response, leading to an imbalance between host and parasite and consequently resulting in a periodontal breakdown. Aim To identify the prevalence of chronic periodontitis and chronic stress as well as a comparative evaluation of clinical, demographic, and psychoanalytical parameters among the South Indian population. Materials and methods A total of 500 subjects between the ages of 30 and 60 were chosen from the Trivandrum district, Kerala, using multistage random sampling. Subjects were evaluated based on psychoanalytical parameters as well as periodontal examination. Psychoanalytical parameters were measured by the questionnaire method using the perceived stress scale. Periodontal parameters examined were the probing depth, clinical attachment loss, bleeding on probing, simplified oral hygiene index, and community periodontal index (loss of attachment). Statistical Analysis Categorical and quantitative variables were expressed as frequency (percentage) and mean ± SD respectively. Logistic regression analysis was used to analyze the association between the periodontal variables and psychoanalytical variables. All the statistical analysis was performed using IBM Statistical Package for Social Sciences (SPSS) Statistics for Windows (IBM Corp., USA). Results A total of 500 subjects, of whom 308 (61.6%) were female and 192 (38.1%) were male, participated in this study. The overall prevalence of periodontitis among all the subjects was found to be 42.4%, and the proportion of periodontitis among the stressed participants was found to be 46.2%, which is 10% higher compared to the non-stressed (36.1%) participants. Conclusion Our study showed an increased frequency of periodontitis among the stressed subjects as compared to the non-stressed subjects. These findings suggest that there is a positive association between chronic stress and chronic periodontitis, but further prospective studies are required to establish the extent of the effect chronic stress has on chronic periodontitis and vice versa., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Varma et al.)

Orally delivered molecularly targeted small-molecule drugs play a significant role in managing cancer as a chronic disease. However, due to the poor oral bioavailability of some of these molecules, high-dose administration is required leading to dose-limiting toxicity especially when delivered daily for a long duration. Here, we report an oral nanoformulation for small-molecule multi-kinase inhibitor, sorafenib tosylate, showing nearly two fold enhancement in the oral bioavailability and enhanced therapeutic efficacy with a better safety profile compared to the current clinical formulation. Using a scalable process involving high-pressure homogenization, sorafenib was loaded into an albumin nanocarrier at ~ 50 w/w%. Repeated preparation of gram-scale batches (n = 7) showed an average particle size of 180 ± 9 nm, encapsulation efficiency of 95 [Formula: see text] 2%, and drug-loading efficiency of 48 [Formula: see text] 0.7%. Further, surface engineering with a mucoadhesive layer on nanoparticles (referred to as ABSORF) resulted in the final size of 299 ± 38 nm and surface charge of -54 ± 8 mV. Single-dose and multidose pharmacokinetic studies showed two fold enhancement in the plasma concentration of sorafenib compared to current clinically used tablets. Antitumor efficacy studies in the orthotopic rat liver tumor model showed significant tumor regression (p value = 0.0037) even at half dose (eqv. to 200 mg of human equivalent dose) of ABSORF compared to clinical control (eqv. to 400 mg). The biodistribution of sorafenib from ABSORF was higher in the liver; however, liver and kidney function test parameters were comparable with that of the 2 × dose of clinical control. No abnormalities and signs of toxicity were seen in the histopathological analysis for ABSORF-treated animals. In summary, we demonstrate a scalable preparation of small-molecule drug-loaded nanoformulation with approximately two fold enhancement in oral bioavailability, improved antitumor efficacy, and acceptable toxicity profile., (© 2022. Controlled Release Society.)

Recent advances in coronary stents have all been distinctively focused towards directing re-endothelialization with minimal in-stent restenosis, potentially via alterations in surface topographical cues, for augmenting the efficacy of vascular implants. This perspective was proven by our group utilizing a simple and easily scalable nanosurface modification strategy on metallic stents devoid of any drugs or polymers. In the present work, we explore the impact of surface characteristics in modulating this cell response in-vitro and in-vivo, using titania coated cobalt-chromium (CC) stents, with and without nanotopography, in comparison to commercial controls. Interestingly, titania nanotopography facilitated a preferential cell response in-vitro as against the titania coated and bare CC surfaces, which can be attributed to surface topography, hydrophilicity, and roughness. This in turn altered the cellular adhesion, proliferation and focal contact formations of endothelial and smooth muscle cells. We also demonstrate that titania nanotexturing plays a pivotal role in fostering rapid re-endothelialization with minimal neointimal hyperplasia, leading to excellent in-vivo patency of CC stents post 8 weeks implantation in rabbit iliac arteries, in comparison to bare CC, nano-less titania coated CC, and commercial drug-eluting stents (CC DES), without administering antiplatelet agents. This exciting result for the drug and polymer-free titania nanotextured stents, in the absence of platelet therapy, reveals the possibility of proposing an alternative to clinical DES for coronary stenting., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2022. Published by Elsevier B.V.)

The osteopontin (OPN) released from mesenchymal stem cells (MSCs) undergoing lineage differentiation can negatively influence the expansion of hematopoietic stem cells (HSCs) in coculture systems developed for expanding HSCs. Therefore, minimizing the amount of OPN in the coculture system is important for the successful ex vivo expansion of HSCs. Toward this goal, a bioengineered three dimensional (3D) microfibrous-matrix that can maintain MSCs in less OPN-releasing conditions has been developed, and its influence on the expansion of HSCs has been studied. The newly developed 3D matrix significantly decreased the release of OPN, depending on the MSC culture conditions used during the priming period before HSC seeding. The culture system with the lowest amount of OPN facilitated a more than 24-fold increase in HSC number in 1 week time period. Interestingly, the viability of expanded cells and the CD34 +   pure population of HSCs were found to be the highest in the low OPN-containing system. Therefore, bioengineered microfibrous 3D matrices seeded with MSCs, primed under suitable culture conditions, can be an improved ex vivo expansion system for HSC culture., (© 2022 Wiley Periodicals LLC.)

Soybeans play a key role in global food security. U.S. soybean yields, which comprise [Formula: see text] of the total soybeans planted in the world, continue to experience unprecedented grain loss due to the soybean cyst nematode (SCN) plant pathogen. SCN remains one of the primary disruptive pests despite the existence of advanced management techniques such as crop rotation and SCN-resistant varieties. SCN detection is a key step in managing this disease; however, early detection is challenging because soybeans do not show any above ground symptoms unless they  are significantly damaged. Direct soil sampling remains the most common method for SCN detection, however, this method has several problems. For example, the threshold damage methods-adopted by most of the laboratories to make recommendations-is not reliable as it does not consider soil pH, N, P, and K values and relies solely on the egg count instead of assessment of the root infection. To overcome the challenges of manual soil sampling methods, deep learning and hyperspectral imaging are important current topics in precision agriculture for plant disease detection and have been proposed as cost-effective and efficient detection methods that can work at scale. We have reviewed more than 150 research papers focusing on soybean cyst nematodes with an emphasis on deep learning techniques for detection and management. First: we describe soybean vegetation and reproduction stages, SCN life cycles, and factors influencing this disease. Second: we highlight the impact of SCN on soybean yield loss and the challenges associated with its detection. Third: we describe direct sampling methods in which the soil samples are procured and analyzed to evaluate SCN egg counts. Fourth: we highlight the advantages and limitations of these direct methods, then review computer vision- and remote sensing-based detection methods: data collection using ground, aerial, and satellite approaches followed by a review of machine learning methods for image analysis-based soybean cyst nematode detection. We highlight the evaluation approaches and the advantages of overall detection workflow in high-performance and big data environments. Lastly, we discuss various management approaches, such as crop rotation, fertilization, SCN resistant varieties such as PI 88788, and SCN's increasing resistance to these strategies. We review machine learning approaches for soybean crop yield forecasting as well as the influence of pesticides, herbicides, and fertilizers on SCN infestation reduction. We provide recommendations for soybean research using deep learning and hyperspectral imaging to accommodate the lack of the ground truth data and training and testing methodologies, such as data augmentation and transfer learning, to achieve a high level of detection accuracy while keeping costs as low as possible., (© 2022. The Author(s).)

Introduction: HIV-1 viral Load (VL) testing is recommended for the monitoring of antiretroviral treatment. Dried Blood Spots (DBS) are an effective sample type in resource limited settings, where safe phlebotomy and reliable shipping are hard to guarantee. In HIV high burden countries, high throughput assays can improve access to testing services. The Hologic Aptima HIV-1 Quant Dx Assay (Aptima Assay) is a high throughput assay that runs on the CE-IVD approved Panther platform. The objectives of this study were to assess the performance characteristics of Aptima for VL monitoring using plasma and venous DBS specimens and to determine the stability of HIV-1 RNA in DBS., Materials and Methods: This was a cross-sectional study of 2227 HIV infected adults visiting health facilities in Nairobi and Busia, Kenya. Each provided a venous blood sample; plasma was prepared from 1312 samples while paired DBS samples and plasma were prepared from the remaining 915 samples. The agreement between the Aptima assay and the Abbott RealTime HIV-1 Assay (Abbott RT) was analysed by comparing the HIV-1 VL in both assays at the medical decision point of 1000 copies/mL. To assess stability of HIV-1 RNA in DBS, VL in DBS spotted on day 0 were compared with that from the same DBS card after 21 days of storage at room temperature., Results: Overall, 436 plasma samples had quantifiable results in both Aptima and Abbott RT. The agreement between the two assays at 1000 copies/mL was 97.48% with a Pearson's correlation coefficient (r) of 0.9589 and gave a mean bias of 0.33 log copies/mL on Bland-Altman analysis. For fresh DBS, the agreement in both assays was 94.64% at 1000 copies/mL, with an r of 0.8692 and a mean bias of 0.35 log copies/mL. The overall agreement between DBS tested in Aptima on day 0 versus day 21 was 95.71%, with a mean bias of -0.154., Conclusion: The Aptima HIV-1 Quant Dx assay is an accurate test for VL monitoring of HIV-1 using DBS and plasma sample types in Kenya., Competing Interests: Hologic, Inc. provided the funds and materials for the study. Sangeetha Nair and Sven Schaffer were employees of Hologic, Inc at the time of the study. The rest of the authors are employees of the Kenya Medical Research Institute and declare no conflict of interest. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

The role of neurogenic inflammation in various systemic diseases has been well established, but there is a dearth of studies and evidence regarding its role in periodontitis. This study aimed to systematically review the evidence in establishing the role of neurogenic inflammation in chronic periodontitis. Databases such as PubMed, Scopus, and Google Scholar were reviewed. We analyzed studies of any design that compared and evaluated the presence of neuropeptides such as substance P, calcitonin gene-related peptide, neurokinin A, neuropeptide Y, and vasoactive intestinal polypeptide in systemically healthy patients with and without periodontitis. We screened 2,495 articles and abstracts electronically and manually, which yielded 191 articles relevant to our study. Full-text examination of these 191 articles led to the final inclusion of 14 publications. Most studies here confirmed an association between various neuropeptides and periodontitis, but there is a high heterogeneity between the studies, making it necessary to clarify the mechanism between these two. Although most studies included in this review found a positive association between neurogenic inflammation and periodontitis, the evidence is of moderate to low quality., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Varma et al.)

Globally, millions of patients are affected by myocardial infarction or lower limb gangrene/amputation due to atherosclerosis. Available surgical treatment based on vein and synthetic grafts provides sub-optimal benefits. We engineered a highly flexible and mechanically robust nanotextile-based vascular graft (NanoGraft) by interweaving nanofibrous threads of poly-L-lactic acid to address the unmet need. The NanoGrafts were rendered impervious with selective fibrin deposition in the micropores by pre-clotting. The pre-clotted NanoGrafts (4 mm diameter) and ePTFE were implanted in a porcine carotid artery replacement model. The fibrin-laden porous milieu facilitated rapid endothelization by the transmural angiogenesis in the NanoGraft. In-vivo patency of NanoGrafts was 100% at 2- and 4-weeks, with no changes over time in lumen size, flow velocities, and minimal foreign-body inflammatory reaction. However, the patency of ePTFE at 2-week was 66% and showed marked infiltration, neointimal thickening, and poor host tissue integration. The study demonstrates the in-vivo feasibility and safety of a thin-layered vascular prosthesis, viz., NanoGraft, and its potential superiority over the commercial ePTFE., (© 2022. The Author(s).)

Mandible reconstruction and dental rehabilitation after trauma or tumor resection represent a serious challenge for maxillofacial surgeons. This study aimed to investigate the bone formation potential of nanocomposite fibrous scaffold (silica-nanohydroxyapatite-gelatin reinforced with poly L-lactic acid yarns - CSF) for delayed Titanium (Ti) implantation, which was compared to autograft (AG) taken from the iliac crest. The grafts were placed in critical-sized mandibular defects in an adult pig model for 6 months followed by dental implant placement for another 3 months. There was complete union and vascularised lamellar bone formation within 6 months. Moreover, the biological processes associated with angiogenesis, bone maturation and remodelling were seen in CSF, which was comparable to AG. Later, when Ti dental implant was placed on newly formed bone, CSF group demonstrated better osseointegration. In short, nanocomposite fibrous scaffold promoted quality bone formation in mandible defect that leads to successful osseointegration, suggesting as a potential candidate for implant-based rehabilitation in clinics in future., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Tolerance induction is central to the suppression of autoimmunity. Here, we engineered the preferential uptake of nano-conjugated autoantigens by spleen-resident macrophages to re-introduce self-tolerance and suppress autoimmunity. The brain autoantigen, myelin oligodendrocyte glycoprotein (MOG), was conjugated to 200 or 500 nm silica nanoparticles (SNP) and delivered to the spleen and liver-resident macrophages of experimental autoimmune encephalomyelitis (EAE) mice, used as a model of multiple sclerosis. MOG-SNP conjugates significantly reduced signs of EAE at a very low dose (50 μg) compared to the higher dose (>800 μg) of free-MOG. This was associated with reduced proliferation of splenocytes and pro-inflammatory cytokines secretion, decreased spinal cord inflammation, demyelination and axonal damage. Notably, biodegradable porous SNP showed an enhanced disease suppression assisted by elevated levels of regulatory T cells and programmed-death ligands (PD-L1/2) in splenic and lymph node cells. Our results demonstrate that targeting nano-conjugated autoantigens to tissue-resident macrophages in lymphoid organs can effectively suppress autoimmunity., (Copyright © 2021. Published by Elsevier Inc.)

This study investigated the adverse effects of 200 nm zinc oxide particles (nZnO) on sexual behavior and reproduction in Japanese medaka in comparison with ZnSO 4 and correlated the consequences with the bioaccumulation pattern of the particles in associated organs. nZnO exposure impaired sexual and territorial behaviors and affected fertility by altering sperm viability and motility in males through reactive oxygen species (ROS) induction. Conversely, none of these effects other than behavior loss was seen in males exposed to ZnSO 4 . nZnO exposure to females induced ROS in ovaries, causing follicular growth arrest, atresia, and subfertility. Further, sex-steroid levels were altered by both nZnO and ZnSO 4 in males and by nZnO but not ZnSO 4 in females. Biodistribution studies revealed the deposition of nZnO as particulate matter in the brain, gills, gut, kidney, and ovary. Particle accumulation in the brain was sex specific, as the particles were found in the brain of males but not that of females. A similar trend was seen for zinc levels in males and females exposed to ZnSO 4 . Importantly, the female sex hormone, 17β-estradiol was found to prevent nZnO accumulation in the female brain, emphasizing the need for biodistribution profiling of nanoparticle-based drug delivery vehicles separately in males and females before they are commercialized. This study has demonstrated that the toxic effects of nZnO on the reproductive system were mainly caused by ROS induction, while zinc ions were predominantly responsible for the adverse impact of ZnSO 4 .

Objective: In this article, we provide a gestalt idea about NGS technologies and their applications in cancer research and molecular diagnosis., Background: Next-generation sequencing (NGS) advancements like DNA sequencing and RNA sequencing allow uncovering of genomic, transcriptomic, and epigenomic scenes of individual malignant growths. An assortment of genomic abnormalities can be screened at the same time, for example common and uncommon variations, auxiliary variations like insertions and deletions, copy-number variation, and fusion transcripts., Conclusion: NGS innovations together with bioinformatics investigation, which extend our insight, are progressively used to analyze multiple genes in a cost-effective way and have been applied in examining clinical cancer samples and offering NGS-based molecular diagnosis., Application: NGS is progressively significant as a device for the diagnosis of cancers., (© The Association of Oral and Maxillofacial Surgeons of India 2020.)

Background: Patients on maintenance haemodialysis (MHD) often complain of fatigue and tiredness following haemodialysis sessions leading to poor compliance with the dialysis schedule. There is limited Indian data on dialysis recovery time (DRT). The present study was designed to assess the factors affecting DRT in our haemodialysis population., Methods: We recorded self-reported patient recovery times of 120 patients who satisfied the inclusion criteria, over three consecutive dialysis sessions by asking the question, 'How long does it take to recover from a dialysis session'? Data recorded included patient factors like age, sex, co-morbidities, Charlson comorbidity index score (CCI), dialysis vintage, duration of kidney disease, interdialytic weight gain (IDWG), treatment factors like ultrafiltration rate (UFR), SpKt/V, blood pump speed, dialysate sodium, session length, pre and post HD blood pressure and laboratory parameters. Health-related quality of life (HRQoL) was assessed with the KDQOL-SF v. 1.3 questionnaire. Results from the SF-36 score were summarised into the physical composite score (PCS), mental composite score (MCS) and kidney disease composite score (KDCS)., Results: The mean age of the study population was 50.6 ± 12.6 years. Among the 120 patients, 77 (64.2%) were males. Thirty-nine patients (32.5%) were diabetic and 95 (79.1%) patients were hypertensive. The mean dialysis vintage of the study population was 26.1 ± 18.6 months, 41 (34.2%) patients reported DRT <2 h; 48 (40%) reported DRT between 2-6 h and 31 (25.8%) reported DRT >6 h. On multivariate regression analysis, higher IDWG, CCI score and UFR were associated with prolonged DRT. Reported DRT also inversely correlated with PCS (r = - 0.66), MCS (r = - 0.65) and KDCS (r = - 0.59) scores which was statistically significant., Conclusion: The present study showed that higher CCI scores, IDWG and UFR were associated with prolonged DRT in Indian haemodialysis patients and patients with longer recovery time had poor HRQoL. Interventions to reduce DRT need to be assessed in further trials in Indian MHD patients., Competing Interests: Nil, (Copyright: © 2021 Indian Journal of Nephrology.)

Background: Nanoparticle siRNA-conjugates are promising clinical therapeutics as indicated by recent US-FDA approval. In glioma stem cells (GSC), multiple stemness associated genes were found aberrant. We report intracranially injectable, multi-gene-targeted siRNA nanoparticle gel (NPG) for the combinatorial silencing of 3 aberrant genes, thus inhibiting the tumorogenic potential of GSCs., Methods: NPG loaded with siRNAs targeted against FAK, NOTCH-1, and SOX-2 were prepared by the self-assembly of siRNAs with protamine-hyaluronic acid combination. Electron microscopy, DLS, and agarose gel electrophoresis were used for the physicochemical characterization. Cell transfection and gene-silencing efficiency were studied using human mesenchymal stem cells and rat C6 glioma-derived GSCs. Neurosphere inhibition was tested in vitro using GSCs derived from C6 cell line and glioma patient samples. Patient-derived xenograft model and orthotopic rat glioma model were used to test the effect of NPG on in vivo tumorigenicity., Results: The siRNA nanoparticles with an average size ~ 250 nm and ~ 95% loading efficiency showed cellular uptake in ~95.5% GSCs. Simultaneous gene silencing of FAK, NOTCH-1, and SOX-2 led to the inhibition of neurosphere formation by GSCs, whereas normal stem cells remained unaffected and retained neuronal differentiation capability. GBM PDX models manifested significant impairment in the tumorigenic potential of NPG treated GSCs. Intracranial injection of NPG inhibited tumor growth in orthotopic rat brain tumor model., Conclusion: Intracranially injectable n-siRNA NPG targeted to multiple stem-cell signaling impairs glioma initiation capabilities of GSCs and inhibited tumor growth in vivo., (© The Author(s) 2021. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.)

Introduction: Depth of invasion (DOI) has been incorporated into oral cancer staging. Increasing DOI is known to be associated with an increased propensity to neck metastasis and adverse tumor factors and hence may not be an independent prognosticator but a surrogate for a biologically aggressive tumor., Methods: 570 patients, median follow up 79.01 months from a previously reported randomized trial (NCT00193765) designed to establish appropriate neck treatment [elective neck dissection (END) vs therapeutic neck dissection (TND)] in clinically node-negative early oral cancers were restaged (nT) according to AJCC TNM 8th edition. Overall survival (OS) was estimated for the entire cohort, END, and TND arms. Multivariate analysis performed for stratification and prognostic factors, and interaction term between revised T-stage and neck treatment, for tumours with DOI≤10mm. Presence of adverse factors was compared between nT3 (DOI>10 mm) and those with DOI≤10 mm., Results: Stage migration occurred in 44.38% of patients. 5-Year OS was nT1-79%, nT2-69.4% and nT3-53.8%, (p < 0.001). In TND arm 5-year OS was nT1-81.1% versus nT2-65%,p = 0.004, while that in END arm was nT1 -76.9% versus nT2 -73.7%,p = 0.73. There was a significant interaction between T stage and neck treatment (p = 0.03). T3 tumors (>10 mm) were associated with a higher proportion of adverse factors (occult nodal metastasis, p = 0.035; LVE/PNI, p = 0.001)., Conclusion: Elective neck treatment negates the prognostic impact of DOI for early oral cancers (T1/T2 DOI≤10 mm). T3 tumors with DOI>10 mm have a higher association with other adverse risk factors resulting in poorer outcomes in spite of elective neck dissection., Competing Interests: Declaration of competing interest None of the authors have any conflict of interest with respect to this manuscript., (Copyright © 2021 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Coronary in-stent restenosis and late stent thrombosis are the two major inadequacies of vascular stents that limit its long-term efficacy. Although restenosis has been successfully inhibited through the use of the current clinical drug-eluting stent which releases antiproliferative drugs, problems of late-stent thrombosis remain a concern due to polymer hypersensitivity and delayed re-endothelialization. Thus, the field of coronary stenting demands devices having enhanced compatibility and effectiveness to endothelial cells. Nanotechnology allows for efficient modulation of surface roughness, chemistry, feature size, and drug/biologics loading, to attain the desired biological response. Hence, surface topographical modification at the nanoscale is a plausible strategy to improve stent performance by utilizing novel design schemes that incorporate nanofeatures via the use of nanostructures, particles, or fibers, with or without the use of drugs/biologics. The main intent of this review is to deliberate on the impact of nanotechnology approaches for stent design and development and the recent advancements in this field on vascular stent performance., (© 2021 Author(s).)

Aim: To develop a method for making total serum nanoparticles (TSN) loaded with cytotoxic chemodrugs for cancer therapy. Materials & methods: TSN loaded with paclitaxel (PTX) or piperlongumine (PL) were prepared using high-pressure homogenization and tested for immunogenicity in healthy animals and antitumor properties in pancreatic cancer xenograft models. Results: TSN-PL nanoparticles of average size 104 nm and encapsulation efficiency approximately 50% showed enhanced dose-dependent cytotoxicity compared with TSN-PTX or clinically used combination of gemcitabine and nano-PTX in two pancreatic cell lines. Significant antitumor efficacy was also established in the pancreatic xenograft model. Conclusion: We developed a unique method of converting total blood serum into chemo drug-loaded nanoparticles and demonstrated its efficacy in vitro and in vivo.

Quantification of HIV-1 RNA is essential for clinical management of HIV patients. The limited throughput and significant hands-on time required by most HIV Viral load (VL) tests makes it challenging for laboratories with high test volume, to turn around patient results quickly. The Hologic Aptima HIV-1 Quant Dx Assay (Aptima), has the potential to alleviate this burden as it is high throughput and fully automated. This assay is validated for both plasma and dried blood spots (DBS), which are commonly used in resource limited settings. The objective of this study was to compare the performance of Aptima to Abbott RealTime HIV-1 Assay (Abbott RT), which was used as reference. This was a cross-sectional prospective study where HIV VL in finger stick (FS) DBS, venous blood (VB) DBS and plasma, collected from 258 consenting adults visiting 5 medical facilities in Kenya, Africa were tested in Aptima. The results were compared to plasma VL in Abbott RT at the medical decision point (MDP) of 1000 copies/mL and across Aptima assay range. The total agreement at MDP between plasma HIV VL in Abbott RT and plasma, FS and VB DBS tested in Aptima were 97.7%, 92.2% and 95.3% respectively with kappa statistic of 0.95, 0.84 and 0.90. The positive and negative agreement for all 3 sample types were >92%. Regression analysis between VL in Abbott RT plasma and various sample types tested in Aptima had a Pearson's correlation coefficient ≥0.91 with systematic bias of < 0.20 log copies/mL on Bland-Altman analysis. The high level of agreement in Aptima HIV VL results for all 3 sample types with Abbott RT plasma VL along with the high throughput, complete automation, and ease of use of the Panther platform makes Aptima a good option for HIV VL monitoring for busy laboratories with high volume of testing., Competing Interests: Hologic Inc. provided support in the form of salaries for authors SN, AW and JF. This does not alter our adherence to PLOS ONE policies on sharing data and materials. The rest of the authors, based at Kenya Medical Research Institute, declare no conflict of interest.

Background: High dialysate sodium is a significant contributor to intradialytic hypertension (IDH) in maintenance hemodialysis patients. In this study, we aimed to study the effect of low dialysate sodium on IDH in Indian hemodialysis patients., Materials and Methods: Fifty patients on maintenance hemodialysis for atleast 3 months with episodes of IDH were enrolled in this study. The study was performed in two different stages. In the first phase, patients were dialyzed with standard dialysate sodium (140 mEq/L) for eight consecutive sessions and in the second phase, they were dialyzed with low sodium dialysate (136 mEq/L) for eight consecutive sessions. Differences in pre, intradialytic, and post-HD blood pressure, interdialytic weight gain, mean serum sodium, intradialytic adverse events, and number of IDH episodes requiring intervention between the two phases were assessed., Results: The mean age of the study population was 52 years (36 males,14 females). The mean post-HD systolic and diastolic BP was 163.26 ± 9.58 mmHg and 88.60 ± 5.27 mmHg in the standard dialysate phase and 142.38 ± 14.09 mmHg and 84.58 ± 4.276 mmHg, respectively, in the low dialysate phase (p < 0.01). Interdialytic weight gain was 3.34 ± 0.9 and 3.11 ± 0.86 in the standard and low sodium dialysate phases, respectively (p = 0.19).The mean pre-HD plasma sodium level was 138.48 ± 3.69 and 135.80 ± 1.35 mEq/dl, respectively, in standard and low dialysate phases (p = 0.01). There was significant reduction in number of IDH episodes requiring intervention. There was no difference in hypotensive episodes, adverse events between the two phases., Conclusion: In patients with intradialytic hypertension, low dialysate sodium significantly reduces the post-HD blood pressure and intradialytic hypertensive episodes, when compared with standard sodium dialysate., (© 2021 International Society for Hemodialysis.)

Co-therapy with herbal extracts along with current clinical drugs is being increasingly recognized as a useful complementary treatment for cancer. The anti-cancer property of the phyto-derivative acetyl-11 keto β boswellic acid (AKBA) has been studied in many cancers, including prostate cancer. However, the whole extract of the gum resin Boswellia serrata (BS) and anti-androgen enzalutamide has not been explored in prostate cancer to date. We hypothesized that the BS extract containing 30% (AKBA) with enzalutamide acted synergistically in the early phase of cancer, especially in LNCaP cells, by inhibiting androgen receptor (AR) and by reducing cell proliferation, and further, that the extract would be superior to the action of the active ingredient AKBA when used alone or in combination with enzalutamide. To test our hypothesis, we treated LNCaP cells with BS extract or AKBA and enzalutamide both individually and in combination to analyze cell viability under different levels of dihydrotestosterone (DHT). The inhibition of androgen receptor (AR) followed by the expression of prostate-specific antigen (PSA) and the efflux mechanism of the cells were analyzed to determine the effect of the combination on the cellular mechanism. Cells derived from prostate cancer patients were also tested with the combination. Only 6 µM enzalutamide along with BS in the range of 4.1 µg/ml to 16.4 µg/ml gave the best synergistic results with nearly 50% cell killing even though standard enzalutamide doses were as high as 48 µM. Cell killing was most effective at intermediate DHT concentrations of approximately 1 nM, which corresponds to normal physiological serum levels of DHT. The Pgp expression level and the androgen receptor expression levels were reduced under the combination treatment; the former helping to minimize drug efflux and the latter by reducing the sensitivity to hormonal changes. Furthermore, the combination reduced the PSA level secreted by the cells. In contrast, AKBA could not achieve the needed synergism for adequate cell killing at equivalent concentrations. The combination of enzalutamide and BS extract containing 30% AKBA because of their synergistic interaction is an attractive therapeutic option for treating early stage (hormone-dependent) prostate cancer and is superior to the use of AKBA alone.

The main intent of this investigation was to retain the strength and superabsorbency of natural and non-toxic biodegradable polymers using an innovative combination of cross-linkers for application as the absorbent core of sanitary napkins. For this, sodium carboxymethyl cellulose (NaCMC) and starch were blend to form membranes by phase inversion and lyophilisation, using an optimized cross-linker combination of sodium trimetaphosphate (STMP) and aluminium sulphate (AlS). Optimal cross-linking of NaCMC and starch hampered membrane dissolution and disintegration, yielding a microtextured surface morphology. The membranes were biodegradable and yet possessed the requisite flexibility and mechanical strength for the proposed application, without compromise of superabsorbency. Lyophilised membranes possessed higher immediate water and blood sorption with ∼50% water retention capabilities when compared to the phase inversion technology. The results suggest that the developed membranes can be a cost-effective degradable alternative to the commercial polyacrylate-based nonbiodegradable sanitary products., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Competing Interests: There are no conflicts of interest.

We implemented gas-phase (argon plasma) and wet-chemical (HNO 3 ) surface treatments on close space sublimated (CSS) Cadmium Telluride (CdTe) thin films exhibiting morphologies of (i) vertically aligned walls on copper (Cu) and stainless steel (SS) substrates, (ii) valley-hills on aluminum (Al) substrates and (iii) micro-granules on nickel (Ni). As all the growth conditions (temperature, pressure, duration and source/substrate distance) were exactly the same in the CSS process to coat CdTe films, it is asserted that the various microstructures were raised only on Cu, Al, Ni and SS substrates. Plasma and HNO 3 surface treatments on metal substrates did not affect the CdTe morphologies in terms of specific structures but it was observed that structural, optical and electrical charge transport characteristics were highly tunable by the two surface treatments. Thus, substrate driven morphological evaluation followed by surface treatments was enabled. The present study demonstrated various microstructures of CdTe films on metallic thin foil substrates to attempt the establishment of flexible opto-electronics based on CdTe., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Bare metal stents (BMSs) of stainless steel (SS) were surface engineered to develop nanoscale titania topography using a combination of physical vapor deposition and thermochemical processing. The nanoleafy architecture formed on the stent surface remained stable and adherent upon repeated crimping and expansion, as well as under flow. This titania nanoengineered stent showed a preferential proliferation of endothelial cells over smooth muscle cells in vitro, which is an essential requirement for improving the in vivo endothelialization, with concurrent reduction of intimal hyperplasia. The efficacy of this surface-modified stent was assessed after implantation in rabbit iliac arteries for 8 weeks. Significant reduction in neointimal thickening and thereby in-stent restenosis with complete endothelial coverage was observed for the nanotextured stents, compared to BMSs, even without the use of any antiproliferative agents or polymers as in drug-eluting stents. Nanotexturing of stents did not induce any inflammatory response, akin to BMSs. This study thus indicates the effectiveness of a facile titania nanotopography on SS stents for coronary applications and the possibility of bringing this low-priced material back to clinics., Competing Interests: The authors declare no competing financial interest., (Copyright © 2020 American Chemical Society.)

Lysosomal exocytosis and resealing of damaged plasma membrane are essential for cellular homeostasis and tumor invasion. However, very little is known of the molecular machinery that regulates these physiological processes. Moreover, no mutations in any of the known regulators of lysosomal exocytosis in primary tumors of patients have been characterized. Here we demonstrate that RNF167-a, a lysosomal-associated ubiquitin ligase, negatively regulates lysosomal exocytosis by inducing perinuclear clustering of lysosomes. Importantly, we also characterized a set of novel natural mutations in RNF167-a, which are commonly found in diverse tumor types. We found that RNF167-a-K97N mutant, unlike the wild type, localizes in the cytoplasm and does not promote perinuclear lysosomal clustering. Furthermore, cells expressing RNF167-a-K97N exhibit dispersed lysosomes, increased exocytosis and enhanced plasma membrane repair. Interestingly, these functional features of RNF167-a-K97N were shared with a naturally occurring short version of RNF167 (isoform RNF167-b). In brief, the results presented here reveal a novel role of RNF167-a, as well as its natural variants RNF167-a-K97N and RNF167-b, as an upstream regulator of lysosomal exocytosis and plasma membrane resealing., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2020. Published by The Company of Biologists Ltd.)