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Neuropeptides are ubiquitous in the nervous system. Research into neuropeptides has been limited by a lack of experimental tools that allow for the precise dissection of their complex and diverse dynamics in a circuit-specific manner. Opioid peptides modulate pain, reward and aversion and as such have high clinical relevance. To illuminate the spatiotemporal dynamics of endogenous opioid signaling in the brain, we developed a class of genetically encoded fluorescence sensors based on kappa, delta and mu opioid receptors: κLight, δLight and µLight, respectively. We characterized the pharmacological profiles of these sensors in mammalian cells and in dissociated neurons. We used κLight to identify electrical stimulation parameters that trigger endogenous opioid release and the spatiotemporal scale of dynorphin volume transmission in brain slices. Using in vivo fiber photometry in mice, we demonstrated the utility of these sensors in detecting optogenetically driven opioid release and observed differential opioid release dynamics in response to fearful and rewarding conditions.

Background: Synaptic plasticity is an essential process encoding fine-tuned brain functions, but models to study this process in adult human systems are lacking. Objective: We aim to test whether ex vivo organotypic culture of post-mortem adult brain explants (OPABs) retain synaptic plasticity. Methods: OPABs were seeded on 3D microelectrode arrays to measure local field potential (LFP). Paired stimulation of distant electrodes was performed over three days to investigate our capacity to modulate specific neuronal connections. Results: Long-term potentiation (LTP) or depression (LTD) did not occur within a single day. In contrast, after two and three days of training, OPABs showed a significant modulation of the paired electrodes’ response compared to the non-paired electrodes from the same array. This response was alleviated upon treatment with dopamine. Conclusion: Our work highlights that adult human brain explants retain synaptic plasticity, offering novel approaches to neural circuitry in animal-free models.

Abstract Motor contagions refer to implicit effects induced by the observation of actions made by others on one’s own actions. A plethora of studies conducted over the last two decades have demonstrated that both observed and predicted actions can induce various kinds of motor contagions in a human observer. However, motor contagions have always been investigated with regard to different features of an observed action, and it remains unclear whether the background environment in which an observed action takes place modulates motor contagions as well. Here, we investigated participant movements in an empirical hand steering task during which the participants were required to move a cursor through a visual channel after being presented with videos of an actor performing the same task. We manipulated the congruency between the actions shown in the video and the background channels and examined whether and how they affected the participants’ own movements. We observed a clear interaction between the observed action and its background. The movement time of the participants’ actions tended to increase or decrease depending on whether they observed a faster or slower movement, respectively, and these changes were amplified if the background was not congruent with the action contained within it. These results suggest that background information can modulate motor contagions in humans.

Acute Urinary Retention (UR) is a common perioperative complication with incidences between 5-70%. Orthopaedic patients tend to have this complication at a comparatively higher incidence rate (8-55%) than any other surgeries. Acute UR is multifactorial and can occur irrespective of any pre-existing urological condition. Acute distension due to UR is sometimes associated with comparatively rare manifestations of cardiovascular morbidity in the form of rhythm disturbances and massive haemodynamic alterations. In this case, a 62-year-old, 50 kg female with no co-morbidities was scheduled for open reduction of a fractured right forearm under General Anaesthesia (GA) in the supine position. Towards the end of the surgery, there was an abrupt change in the patient’s haemodynamics, starting from hypertension with tachycardia to hypotension with tachycardia followed by extreme bradycardia. A quick inspection revealed bladder overdistension due to the blockade of the urinary catheter. After saline flushing and decompression of the bladder, the haemodynamics returned to normal within five minutes. Acute bladder overdistension is a relatively benign complication that may prove fatal if not addressed promptly.

Abstract Viral neuroinfections represent a major health burden for which the development of antivirals is needed. Antiviral compounds that target the consequences of a brain infection (symptomatic treatment) rather than the cause (direct-acting antivirals) constitute a promising mitigation strategy that requires to be investigated in relevant models. However, physiological surrogates mimicking an adult human cortex are lacking, limiting our understanding of the mechanisms associated with viro-induced neurological disorders. Here, we optimized the Organotypic culture of Post-mortem Adult human cortical Brain explants (OPAB) as a preclinical platform for Artificial Intelligence (AI)-driven antiviral studies. OPAB shows robust viability over weeks, well-preserved 3D cytoarchitecture, viral permissiveness, and spontaneous local field potential (LFP). Using LFP as a surrogate for neurohealth, we developed a machine learning framework to predict with high confidence the infection status of OPAB. As a proof-of-concept, we showed that antiviral-treated OPAB could partially restore LFP-based electrical activity of infected OPAB in a donor-dependent manner. Together, we propose OPAB as a physiologically relevant and versatile model to study neuroinfections and beyond, providing a platform for preclinical drug discovery.

Aluminium–Silicon (Al-Si) eutectic alloy matrix composites are widely used in engineering application. However, it is a well-known fact that this material is not heat-treatable. In order to take advantage of the improvement in the mechanical properties due to the heat treatment, it is essential to find a way to make the Al-Si composite heat treatable. The dissolution of magnesium in the matrix, makes the composite age-hardenable, showing improvements in hardness and tensile strength properties according to changes in aging kinetics. This study analyses the peak aging kinetics on the hardness-related property improvement according to the magnesium dissolution content in the matrix. Hence, this research focuses on the role of aging treatment on the mechanical properties, especially the hardness of stir-cast Al-Si matrix Silicon Carbide (SiC) composites with up to 1.5 wt. % Mg intentionally dissolved in base alloy. Two aging temperatures (100 and 200 °C) were pitched into the target peak hardness and peak-aged condition. A minor quantity of Mg dissolution in the Al-Si matrix SiC composite has resulted in the improvement of hardness up to 24%, and age-hardening conditions contributeed up to a 40% increase in peak hardness. Similarly, the peak aged condition tensile strength shows an increase of up to 45% during age hardening compared to the Mg-free as-cast composite.

Austempered ductile iron is an innovative material obtained by subjecting it to an austempering heat treatment. The wide application of this material is because its properties are comparable to those of steel, which has a much lower weight. However, the machinability of this material is always a difficult task owing to its high hardness. This problem becomes more complex when a considerable amount of Mn is added. In this study, a novel two-step austempering heat treatment was performed on spheroidal graphite iron containing different amounts of manganese. Although the novel heat treatment method helps to obtain a superior combination of hardness and impact, its effect on machinability must be determined. This study provides the results of machinability tests carried out on austempered ductile iron with various manganese contents produced using the novel method. Scanning electron microscope images of the microstructures revealed a typical ausferrite structure with no segregation of manganese at the grain boundary. This is evident from the good tool life obtained in the machinability tests. Regression equations are fitted to determine the tool life and surface roughness for machining parameters with a range of values considered in this study. The results obtained have shown that till 1 wt% of manganese alloyed austempered ductile iron can be successfully produced using the novel heat treatment method. This helps to obtain the optimum combination of strength and impact properties.

The aim of this work is to investigate the variations in microstructure, hardness, wear and surface roughness between as-cast and heat treated trace elements added A356 alloy. Alloy A was prepared by adding 1 wt.% magnesium to A356 alloy which was used as the base material for the preparation of alloys with zinc (Zn) and copper (Cu) particles as alloying elements. Other set of samples was fabricated where Cu-coated Zn and Cu were added as reinforcements to base matrix A. The microstructural analysis indicated that the addition of Zn to A356 as an alloying element had a limited effect on controlling the grain size during solidification compared to Cu. The addition of Cu as reinforcement resulted in a higher proportion of pro eutectic α-Al phase, leading to finer grain boundaries. Micro-polishing test was conducted on the alloys and composites by determining the surface roughness (Ra) value using profilometer to study the changes in surface roughness under individual load conditions of 20 and 40 N. In the as-cast condition, the addition of Cu increased the hardness by 39% and 58% over the base alloy, respectively. Age-hardening treatment significantly enhanced the wear resistance properties of unreinforced alloys and composites at both aging temperatures, especially at 100 °C. Composite samples exhibited excellent surface finish (lower surface roughness) compared to alloy samples, attributed to the presence of hard reinforcement particles.

Among the various types of recently released composite materials, particle-reinforced metal matrix composites (MMCs), in particular aluminum as the matrix material, have been shown to provide substantial industrial benefits in the automotive and aerospace sectors. The current research focused on the corrosion behavior of an Al7075 hybrid composite in 0.1 M hydrochloric acid (HCl) and 3.5% NaCl media at different temperatures. Electrochemical techniques, such as Tafel polarization (TP) and electrochemical impedance spectroscopy (EIS), were employed to study the corrosion behavior in the respective solutions. The results showed that the corrosion rate of the studied specimen increased from 31.77 to 47.61 mmy−1 in 0.1 M HCl and from 0.26 to 1.28 mmy−1 in 3.5% NaCl with increasing temperature. The corrosion current density of the Al7075 hybrid composite in 0.1 M HCl is on the order of 10−3 Acm2, and that in 3.5% NaCl is on the order of 10−5 Acm2. This confirms the increased rate of composite corrosion in the 0.1 M HCl medium compared to that in the 3.5% NaCl medium. A suitable mechanism was proposed for the corrosion of the Al7075 hybrid composite in both media.

Precision machine tool structures require enhanced stability with higher static stiffness and increased damping. Granite epoxy (G-E) composite offers improved damping properties and is a promising alternative material. This study evaluates the mechanical strength and damping of G-E hybrid polymer composites with varying percentages of cast iron (CI) filler. Experimental and finite element (FE) analyses were conducted on hybrid composite samples incorporating 5, 10 and 15 wt% CI filler particles. Results show that a 70:30 ratio of G-E with 10% CI filler enhances compressive strength. Tensile and flexural behaviors are influenced by epoxy content, with minimal effects from CI filler. Both experimental and numerical simulations show significant improvement in stiffness and damping properties with higher quantities of granite particulates (80 wt%) and 5 wt% CI filler. Modal analysis confirms higher natural frequencies in all modes. This hybrid composite configuration presents a viable alternative for machine tool structures, offering increased structural damping.

AbstractThis study employed a two-stage stir-casting technique to fabricate experimental alloys and composites using A356 + 1 wt.% Mg as the base alloy and trace copper/zinc as alloying elements and reinforcements. Peak aging conditions were applied through a solutionizing process at 520 °C and subsequent aging at 100 °C and 200 °C. A wear test was conducted using a pin-on-disk tribometer under dry sliding conditions to measure wear and frictional force. The ANSYS software simulated the wear, demonstrating a close approximation to the experimental values. The study emphasized the influence of material hardness and coefficient of friction on the wear coefficient accuracy. A higher hardness yielded closer simulated experimental values, whereas lower friction coefficients enhanced convergence. The increased contact pressure and frictional stress were accompanied by higher applied loads. The study suggests future exploration of thermal changes in frictional contact regions and incorporation of surface irregularities in realistic simulations, requiring advanced computing tools.

AbstractFiber-reinforced polymer composites (FRPs) experience exposure to diverse environments throughout their intended design life. Investigating the aging process of FRPs immersed in water is crucial for enhancing the material’s durability. In this study, glass fiber, bamboo fiber, nanoclay and epoxy composites are produced using the hand lay-up process. Tensile and flexural tests are performed in adherence to ASTM standards. The water uptake percentage of soaked specimens is computed, and a comparison is drawn between the results of dry and water-immersed composite specimens. Water-soaking condition negatively affects all the composites. Water-soaked specimens exhibit lesser tensile and flexural strengths than dry specimens by 7.4–14.8% and 7–13.6%, respectively. The addition of nanoclay further improves the tensile and flexural strengths of epoxy and all composites by 6–11%. Water uptake (%) and water-soaking effects on the strength of composites decline when nanoclay is added. The addition of nanoclay declines the percentage of reduction of tensile strength from 8.6–14.8% to 7.4–12%. Similarly, the percentage of flexural strength reduction declines from 8–13.6% to 7–11%. The dry and water-soaked specimens’ fracture surfaces (Scanning Electron Microscope [SEM] images) show significant variations.

The long-term bond degradation and strength retention of flexural bond prisms strengthened with carbon fiber-reinforced polymer (CFRP) composite and galvanized steel mesh (GSM) systems, bonded to concrete using epoxy adhesives and cement-based mortar under aggressive conditioning regimes are compared in this paper. Notched prisms strengthened using low-cord density steel mesh (LSM) with epoxy (SME-strengthened) and cement mortar (SMM-strengthened), and CFRP-epoxy systems were weathered under saline water and direct sunlight for a period of 28 and 540 days. The results of the study were analyzed based on experimentally obtained ultimate load (Pu) values and empirically calculated average bond shear stress (τavg) and prism strength retention (Rp) values. The bond strength degraded by 39 and 34 % in CFRP strengthened, 2.9 and 33 % in SME strengthened, and 2.8 and 10.8 % in SMM-strengthened specimens following the 540-day exposure to saline water and direct sunlight, respectively. The average prism retention ratio was calculated to be 0.61 and 0.66 for CFRP-strengthened, 0.97 and 0.67 for SME-strengthened, and 0.97 and 0.89 for SMM-strengthened specimens after 540 days of saline water and direct sunlight exposure. Flexural prism environment strength reduction factors (CE) were proposed as 0.60, 0.95, and 0.95 for CFRP, SME, and SMM-strengthened specimens under saline water exposures and 0.65, 0.65, and 0.85 for CFRP, SME, and SMM strengthened specimens under direct sunlight exposures. Saline water exposure was observed to be most critical to all strengthening systems. Although CFRP-strengthened specimens showed minimum degradation in load-carrying capacity under both conditioning regimes, they showed maximum bond strength reduction in contrast to SMM-strengthened specimens. It was observed that the choice of bonding agent significantly influenced the extent of bond strength degradation under extreme exposure regimes, like those that prevail in the UAE and the Persian Gulf.

Abstract Objectives To establish audiological and other outcomes following cochlear implantation in humans and animals with eluting electrodes. Methods Systematic review and narrative synthesis. Databases searched (April 2023): MEDLINE, EMBASE, CENTRAL, ClinicalTrials.gov, and Web of Science. Studies reporting outcomes in either humans or animals following cochlear implantation with a drug‐eluting electrode were included. No limits were placed on language or year of publication. Risk of bias assessment was performed on all included studies using either the Brazzelli or Systematic Review Centre for Laboratory animal Experimentation (SYRCLE) assessment tools. The review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) 2020 statement. Results Searches identified 146 abstracts and 108 full texts. Of these, 18 studies met the inclusion criteria, reporting outcomes in 523 animals (17 studies) and 24 humans (1 study). Eluting electrodes included dexamethasone (16 studies), aracytine (1 study), nicotinamide adenine dinucleotide (1 study), the growth factors insulin‐like growth factor 1 (IGF1) and hepatocyte growth factor (HGF) (1 study), and neurotrophin‐3 (1 study). All included studies compare outcomes following implantation with an eluting electrode with a control non‐eluting electrode. In the majority of studies, audiological outcomes (e.g., auditory brainstem response threshold) were superior following implantation with an eluting electrode compared with a standard electrode. Most studies which investigated post‐implantation impedance reported lower impedance following implantation with an eluting electrode. The influence of eluting electrodes on other reported outcomes (including post‐implantation cochlear fibrosis and the survival of hair cells and spiral ganglion neurons) was more varied across the included studies. Conclusions Eluting electrodes have shown promise in animal studies in preserving residual hearing following cochlear implantation and in reducing impedance, though data from human studies remain lacking. Further in‐human studies will be required to determine the clinical usefulness of drug‐eluting cochlear implants as a future treatment for sensorineural hearing loss.

The infrastructure of a country depends significantly on cement concrete as the primary construction material. The aggregate comprises a significant proportion of the overall volume of concrete. However, the ongoing extraction of granite rock to obtain coarse aggregate contributes to the escalating need for natural resources among future generations. Due to its high carbon dioxide (CO2) footprint, the cement industry is a significant contributor to global warming. An appropriate reduction in the amount of cement in concrete without affecting its key properties can result in economical and sustainable development of the construction industry. In this investigation, agricultural waste coconut shell is considered as a substitute for conventional aggregate in concrete to produce lightweight coconut shell concrete. The alccofine-1203 contains ultrafine particles with a distinctive composition that enhances the pozzolanic and hydration process in concrete. Alccofine ranging from 5 % to 15 % were added to cement. The results demonstrated that the 10 % alccofine enhanced the fresh and mechanical properties of the lightweight coconut shell concrete. Using a combination of coconut shell and alccofine in concrete would be the most environmentally sustainable option in the construction industry.

Background: Endometrial cancer is one of the most commonly diagnosed cancers in women worldwide. Aim and Objectives: To study the expression of estrogen receptor (ER), progesterone receptor (PR) and p53 immunohistochemistry (IHC) markers in subtyping endometrial carcinoma. Materials and Methods: A total of 100 cases of carcinoma endometrium submitted during January 2016 to October 2018 were included in our study. The ER, PR and p53 expressions were scored as per the adopted scoring system. Agreement between ER, PR and p53 IHC expression and the consensus HE diagnosis, FIGO grading and tumour staging were assessed using Chi square tests. Results: There was a statistical association between ER, PR and p53 status and tumour histologic type with a P value < 0.01. There was no statistical significance observed between ER and PR expressions and different FIGO grades. Statistical significance (P = 0.036) between p53 and different FIGO grades seen. No statistical significance was observed between ER, PR and p53 expressions and different tumour stages and tumour invasiveness. There was a statistical association between ER and PR status and lymph node metastasis. p53 did not show a statistical significance. Conclusion: Combination of ER, PR and p53 IHC markers can be used to distinguish type 1 and type 2 endometrial cancers. PR expression is more specific than ER in endometrioid carcinomas. p53 expression is more specific in serous carcinoma, however, p53 IHC alone cannot be used to distinguish different grades of endometrioid carcinomas as there is variability of staining in endometrioid carcinomas.

AbstractA nasopalatine duct cyst (NPDC) is the most common type of non-odontogenic cyst in the maxillary region and oral cavity. Recently, a novel transnasal endoscopic approach has been described to allow marsupialization of NPDCs, with good outcomes. However, one common complication appears to be paresthesia of the palate around the upper incisors, which is thought to occur due to damage to the nasopalatine nerve following the septal incision. In this case report, we introduce a variant of this endoscopic technique that attempts to minimize damage to this nerve by adopting a septum-sparing flap. We report no complications, including no paresthesia, at the 3-month follow-up. We also report a novel ‘Mickey Mouse’ sign on MRI imaging associated with this NPDC.

This comprehensive review paper delves into the utilization of Glass Fiber-Reinforced Polymer (GFRP) composites within the realm of concrete column reinforcement, spotlighting the surge in structural engineering applications that leverage GFRP instead of traditional steel to circumvent the latter’s corrosion issues. Despite a significant corpus of research on GFRP-reinforced structural members, questions about their compression behavior persist, making it a focal area of this review. This study evaluates the properties of GFRP bars and their impact on the structural behavior of concrete columns, addressing variables such as concrete type and strength, cross-sectional geometry, slenderness ratio, and reinforcement specifics under varied loading protocols. With a dataset spanning over 250 publications from 1988 to 2024, our findings reveal a marked increase in research interest, particularly in regions like China, Canada, and the United States, highlighting GFRP’s potential as a cost-effective and durable alternative to steel. However, gaps in current knowledge, especially concerning Ultra-High-Performance Concrete (UHPC) reinforced with GFRP, underscore the necessity for targeted research. Additionally, the contribution of GFRP rebars to compressive column capacity ranges from 5% to 40%, but current design codes and standards underestimate this, necessitating new models and design provisions that accurately reflect GFRP’s compressive behavior. Moreover, this review identifies other critical areas for future exploration, including the influence of cross-sectional geometry on structural behavior, the application of GFRP in seismic resistance, and the evaluation of the size effect on column strength. Furthermore, the paper calls for advanced studies on the long-term durability of GFRP-reinforced structures under various environmental conditions, environmental and economic impacts of GFRP usage, and the potential of Artificial Intelligence (AI) and Machine Learning (ML) in predicting the performance of GFRP-reinforced columns. Addressing these research gaps is crucial for developing more resilient and sustainable concrete structures, particularly in seismic zones and harsh environmental conditions, and fostering advancements in structural engineering through the adoption of innovative, efficient construction practices.

Global increase in recurrence of bacterial vaginosis (BV) and worrisome rise in antimicrobial resistance pose an urgent call for new/novel antibacterial agents. In light of the circumstance, the present study demonstrates the in vitro and in vivo antibacterial activity of a phytochemical citral, with a particular emphasis to elucidate its mechanistic action against Gardnerella vaginalis –a potential cause of BV. Out of 21 phytochemicals screened initially against G. vaginalis, citral was envisaged to be a phenomenal antibacterial agent showing MIC and MBC at 128 μg/mL. Citral's rapid killing ability was revealed by a time-killing kinetics assay supported by CFU, signifying that it completely killed the given inoculum of planktonic G. vaginalis cells within 60 min. Further, citral was found to exhibit 1 min contact-killing efficacy together with mature-biofilm disintegrating ability at increasing MICs. To further understand the molecular action of citral, in vitro investigations such as ROS estimation, PI staining and intracellular protein release assay were performed, which demonstrated that citral deteriorated the membrane integrity of G. vaginalis. Galleria mellonella, a simple invertebrate model used to evaluate citral's non-toxic and antibacterial activity in vivo, demonstrates that citral completely restored the larvae from G. vaginalis infection. The metabolite level investigation using LC-MS revealed that citral had negative impact on biotin metabolism (via., biotin), spermidine metabolism (via., 5′-methylthioadenosine and spermidine) and nucleotide metabolism (via., guanine, adenine and uridine). Since that biotin is associated with seven different metabolic pathways, it is conceivable that citral could target biotin biosynthesis or its metabolism and as a result, disrupt other metabolic pathways, such as lipid and fatty acid synthesis, which is essential for the creation of cell membranes. Thus, the current study is the first of its kind to delineate the promising in vitro and in vivo antibacterial efficacy of citral and decipher its plausible antibacterial action mechanism through metabolomic approach, which concomitantly emphasizes citral as a viable natural therapeutic alternative to manage and control BV.

Abstract The present study explores the avenue of phage therapy as an alternative antimicrobial therapeutic approach to counter multidrug-resistant (MDR) Pseudomonas aeruginosa infection. Our study investigated two novel virulent phages PSPa and APPa, specific to P. aeruginosa, in which in vitro evaluations were carried out to assess the therapeutic potential of phages. Both the identified phages exhibited host specificity by showing antagonistic activity of about 96.43% (27/28) and 92.85% (26/28) towards the 28 MDR clinical isolates of P. aeruginosa. The PSPa phage was found to have linear dsDNA with a sequence length of 66,368 bp and 92 ORFs, of which 32 were encoded for known functions of the phage life cycle and the remaining 60 were hypothetical functions. The APPa phage was found to have linear dsDNA with 59,591 bp of genome length and 79 ORFs, of which 15 were found to have known phage functions and the remaining 64 were found to be hypothetical proteins. Notably, the genome of both the phages lacks genes coding for tRNA, rRNA, and tmRNA. The phylogenetic analysis revealed that PSPa and APPa share > 95% sequence similarity with previously sequenced Pseudomonas viruses of their respective families. Further, the in vivo efficacy evaluation using the zebrafish model revealed that the treatment with PSPa and APPa has remarkably improved the survival rate of bacterial-infected zebrafish, reinforcing the anti-infective potential of the isolated phages PSPa and APPa against P. aeruginosa infection.

Abstract Chimeric antigen receptor (CAR) T cell therapy is effective in treating B cell malignancies, but factors influencing the persistence of functional CAR+ T cells, such as product composition, patients’ lymphodepletion, and immune reconstitution, are not well understood. To shed light on this issue, here we conduct a single-cell multi-omics analysis of transcriptional, clonal, and phenotypic profiles from pre- to 1-month post-infusion of CAR+ and CAR− T cells from patients from a CARTELL study (ACTRN12617001579381) who received a donor-derived 4-1BB CAR product targeting CD19. Following infusion, CAR+ T cells and CAR− T cells shows similar differentiation profiles with clonally expanded populations across heterogeneous phenotypes, demonstrating clonal lineages and phenotypic plasticity. We validate these findings in 31 patients with large B cell lymphoma treated with CD19 CAR T therapy. For these patients, we identify using longitudinal mass-cytometry data an association between NK-like subsets and clinical outcomes at 6 months with both CAR+ and CAR− T cells. These results suggest that non-CAR-derived signals can provide information about patients’ immune recovery and be used as correlate of clinically relevant parameters.

This technical paper presents the successful reinforcement of nickel (Ni) coated duralumin powder in an Al7075 matrix using the liquid stir casting technique and property stability obtained by heat treatment. Ni coating is performed by electroless nickel plating technique where 8 μm coating thickness was observed to be the minimum required to prevent dissolution of the reinforcements (duralumin powder) in the matrix (Al7075). During stir casting it was observed to uniformly disperse the coated duralumin powder up to 7 wt.%. Al7075 alloy and composites were artificially aged with solution heat treatment (SHT) performed at 450 °C for 4 h, water quenched and then aged at 120, 150 and 180 °C. Al7075 alloy and composites were naturally aged for 24 weeks in atmospheric temperature after peak aging. Composites aged at 120 °C exhibited superior results and considered as optimum aging temperature compared to those aged at 150 and 180 °C. Peak hardness values in 7075-7Dp+8T composite improved by 108% and 7075-7Dp+10T composite improved by 110% when compared to peak aged (at 120 °C) Al7075 alloy. Moreover, composites with coated reinforcement displayed a higher resistance to natural aging, with reductions of 53.5 and 54.4% in natural aging tendency compared to the naturally aged Al7075 alloy for 7075-7Dp+8T and 7075-7Dp+10T composites respectively. However, an increase in Ni coating thickness beyond the optimal 8 μm did not significantly improve as cast and peak hardness or natural aging resistance. XRD analysis confirmed that there is presence of CuAl2, CuAl2Mg, Mg2Si, and MgZn2 phases in peak-aged (120 °C) 7075-7Dp+8T sample. Considering the limited impact on property enhancement and the financial burden associated with thicker coatings, a coating thickness of 8 μm is recommended as compared to 10 μm.

Introduction Focal and segmental glomerulosclerosis (FSGS) is a leading cause of nephrotic syndrome in both adults and children. The “Columbia classification of FSGS” includes five variants; not otherwise specified (NOS), tip, perihilar, cellular, and collapsing variants that may have different prognostic and therapeutic implications.

Bacterial infections continue to represent a significant healthcare burden worldwide, causing considerable mortality and morbidity every year. The emergence of multidrug-resistant bacterial strains continues to rise, posing serious risks to controlling global disease outbreaks. To develop novel and more effective treatment and vaccination programs, there is a need for clinically relevant small animal models. Since multiple bacterial species have human-specific tropism for numerous virulence factors and toxins, conventional mouse models do not fully represent human disease. Several human disease characteristic phenotypes, such as lung granulomas in the case of Mycobacterium tuberculosis infections, are absent in standard mouse models. Alternatively, certain pathogens, such as Salmonella enterica serovar typhi and Staphylococcus aureus, can be well tolerated in mice and cleared quickly. To address this, multiple groups have developed humanized mouse models and observed enhanced susceptibility to infection and a more faithful recapitulation of human disease. In the last two decades, multiple humanized mouse models have been developed to attempt to recapitulate the human immune system in a small animal model. In this review, we first discuss the history of immunodeficient mice that has enabled the engraftment of human tissue and the engraftment methods currently used in the field. We then highlight how humanized mouse models successfully uncovered critical human immune responses to various bacterial infections, including Salmonella enterica serovar Typhi, Mycobacterium tuberculosis, and Staphylococcus aureus.