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This roadmap includes the perspectives and visions of leading researchers in the key areas of flexible and printable electronics. The covered topics are broadly organized by the device technologies (sections 1–9), fabrication techniques (sections 10–12), and design and modeling approaches (sections 13 and 14) essential to the future development of new applications leveraging flexible electronics (FE). The interdisciplinary nature of this field involves everything from fundamental scientific discoveries to engineering challenges; from design and synthesis of new materials via novel device design to modelling and digital manufacturing of integrated systems. As such, this roadmap aims to serve as a resource on the current status and future challenges in the areas covered by the roadmap and to highlight the breadth and wide-ranging opportunities made available by FE technologies.

High apolipoprotein B-containing (apoB-containing) low-density lipoproteins (LDLs) and low apoA1-containing high-density lipoproteins (HDLs) are associated with atherosclerotic cardiovascular diseases. In search of a molecular regulator that could simultaneously and reciprocally control both LDL and HDL levels, we screened a microRNA (miR) library using human hepatoma Huh-7 cells. We identified miR-541-3p that both significantly decreases apoB and increases apoA1 expression by inducing mRNA degradation of 2 different transcription factors, Znf101 and Casz1. We found that Znf101 enhances apoB expression, while Casz1 represses apoA1 expression. The hepatic knockdown of Casz1 in mice increased plasma apoA1, HDL, and cholesterol efflux capacity. The hepatic knockdown of Zfp961, an ortholog of Znf101, reduced lipogenesis and production of triglyceride-rich lipoproteins and atherosclerosis, without causing hepatic lipid accumulation. This study identifies hepatic Znf101/Zfp961 and Casz1 as potential therapeutic targets to alter plasma lipoproteins and reduce atherosclerosis without causing liver steatosis.

Lipid processing in the retinal pigment epithelium (RPE) is important for maintaining the health and function of the neural retina and the RPE itself. One mode of en mass lipid transport from the RPE is apolipoprotein B-containing lipoproteins (Blps), the assembly of which is regulated by microsomal triglyceride transfer protein (MTP). To gain an initial understanding of how the loss of MTP and, thereby, Blp secretion alters other lipid processing pathways in the RPE, we measured the expression of proteins associated with β-oxidation and lipid droplets in mice lacking MTP expression in the RPE (RPEΔMttp) and age-matched controls. Expression of perilipin 2, a lipid droplet-associated protein, nearly doubled in the RPE of RPEΔMttp, and its localization with neutral lipids also increased. Meanwhile, expression of CPT1A, which mediates the transport of fatty acids into the mitochondria for β-oxidation, was unaffected. These results suggest that the loss of Blp assembly alters intracellular lipid storage patterns. Future studies will examine the effects of the loss of RPE-specific MTP expression and Blp secretion on additional lipid processing pathways., (© 2025. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

Microsomal triglyceride transfer protein (MTP) plays crucial roles in the assembly and secretion of apolipoprotein B-containing lipoproteins and loss of function MTP variants are associated with abetalipoproteinemia, a disease characterized by the absence of these lipoproteins. MTP is a heterodimeric protein of two subunits, MTP and protein disulfide isomerase (PDI). In this study, we report a proband with abetalipoproteinemia who was monitored annually for 10 years in her third decade and had very low plasma lipids and undetectable apoB-containing lipoproteins. Genetic testing revealed biallelic variants in the MTTP gene. She has a well-documented nonsense mutation Gly865∗ that does not interact with the PDI subunit. She also has a novel missense MTP mutation, Ile344Asn. We show that this mutation abrogates lipid transfer activity in MTP and does not support apolipoprotein B secretion. This residue is present in the central α-helical domain of MTP and the substitution of Ile with Asn at this position disrupts interactions between MTP and PDI subunits. Ile344 is away from the known MTP:PDI interacting sites identified in the crystal structure of MTP suggesting that MTP:PDI interactions are more dynamic than previously envisioned. Identification of more missense mutations will enhance our understanding of the structure-function of MTP and the role of critical residues in these interactions between the two subunits. This knowledge may guide us in developing novel treatment modalities to reduce plasma lipids and atherosclerosis., Competing Interests: Conflicts of Interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Vitamin A is an essential nutrient crucial to ensuring proper mammalian embryonic development. β-Carotene is the most prevalent form of vitamin A in food that, when transferred in its intact form from mother to the developing tissues, can serve as an in situ source of retinoic acid, the active form of vitamin A. We have previously provided evidence that the maternal-fetal transfer of β-carotene across the placenta is mediated by lipoproteins and that β-carotene itself regulates placenta lipoprotein biogenesis by means of its derivatives β-apo-10'-carotenoids and retinoic acid. These metabolites exert antagonistic transcriptional activity on placental microsomal triglyceride transfer protein (MTP) and apolipoprotein B (APOB), two key players of lipoprotein biosynthesis. Here, we analyzed the time-dependency of this regulation over the course of 24 h upon a single maternal administration of β-carotene. We also tested the hypothesis that the transcriptional repressor intestine-specific homeobox (ISX) plays a role in the regulation of Mttp in placenta. We observed that ISX is expressed in placenta of mouse dams and is regulated by β-carotene availability. Furthermore, we demonstrated that the absence of Isx disrupts the β-carotene-mediated regulation of placental MTP. We also showed that this mechanism is organ-specific, as it was not observed in enterocytes of the intestine, a major place of Isx expression. Therefore, we identified ISX as a "master" regulator of a placental β-carotene-dependent transcriptional regulatory cascade that fine-tunes the flux of provitamin A carotenoid towards the developing fetus., 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 © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Flexible electronics are integral in numerous domains such as wearables, healthcare, physiological monitoring, human-machine interface, and environmental sensing, owing to their inherent flexibility, stretchability, lightweight construction, and low profile. These systems seamlessly conform to curvilinear surfaces, including skin, organs, plants, robots, and marine species, facilitating optimal contact. This capability enables flexible electronic systems to enhance or even supplant the utilization of cumbersome instrumentation across a broad range of monitoring and actuation tasks. Consequently, significant progress has been realized in the development of flexible electronic systems. This study begins by examining the key components of standalone flexible electronic systems-sensors, front-end circuitry, data management, power management and actuators. The next section explores different integration strategies for flexible electronic systems as well as their recent advancements. Flexible hybrid electronics, which is currently the most widely used strategy, is first reviewed to assess their characteristics and applications. Subsequently, transformational electronics, which achieves compact and high-density system integration by leveraging heterogeneous integration of bare-die components, is highlighted as the next era of flexible electronic systems. Finally, the study concludes by suggesting future research directions and outlining critical considerations and challenges for developing and miniaturizing fully integrated standalone flexible electronic systems., (© 2024 The Author(s). Advanced Materials published by Wiley‐VCH GmbH.)

Objective: Triglycerides (TGs) associate with apolipoprotein B100 (apoB100) to form very low density lipoproteins (VLDLs) in the liver. The repertoire of factors that facilitate this association is incompletely understood. FITM2, an integral endoplasmic reticulum (ER) protein, was originally discovered as a factor participating in cytosolic lipid droplet (LD) biogenesis in tissues that do not form VLDL. We hypothesized that in the liver, in addition to promoting cytosolic LD formation, FITM2 would also transfer TG from its site of synthesis in the ER membrane to nascent VLDL particles within the ER lumen., Methods: Experiments were conducted using a rat hepatic cell line (McArdle-RH7777, or McA cells), an established model of mammalian lipoprotein metabolism, and mice. FITM2 expression was reduced using siRNA in cells and by liver specific cre-recombinase mediated deletion of the Fitm2 gene in mice. Effects of FITM2 deficiency on VLDL assembly and secretion in vitro and in vivo were measured by multiple methods, including density gradient ultracentrifugation, chromatography, mass spectrometry, stimulated Raman scattering (SRS) microscopy, sub-cellular fractionation, immunoprecipitation, immunofluorescence, and electron microscopy., Main Findings: 1) FITM2-deficient hepatic cells in vitro and in vivo secrete TG-depleted VLDL particles, but the number of particles is unchanged compared to controls; 2) FITM2 deficiency in mice on a high fat diet (HFD) results in decreased plasma TG levels. The number of apoB100-containing lipoproteins remains similar, but shift from VLDL to low density lipoprotein (LDL) density; 3) Both in vitro and in vivo, when TG synthesis is stimulated and FITM2 is deficient, TG accumulates in the ER, and despite its availability this pool is unable to fully lipidate apoB100 particles; 4) FITM2 deficiency disrupts ER morphology and results in ER stress., Conclusion: The results suggest that FITM2 contributes to VLDL lipidation, especially when newly synthesized hepatic TG is in abundance. In addition to its fundamental importance in VLDL assembly, the results also suggest that under dysmetabolic conditions, FITM2 may be an important factor in the partitioning of TG between cytosolic LDs and VLDL particles., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Purpose: Abetalipoproteinemia (ABL, MIM 200,100) is a rare autosomal recessive disorder caused by nonfunctional microsomal triglyceride transfer protein leading to absence of apolipoprotein B-containing lipoproteins in plasma and a retinitis pigmentosa-like fundus. The MTTP gene is expressed in retinal pigment epithelium (RPE) and ganglion cells of the human retina. Understanding ABL pathophysiology would benefit from new cellular-level clinical imaging of affected retinas., Methods: We report multimodal retinal imaging in two patients with ABL. Case 1 (67-year-old woman) exhibited a bilateral decline of vision due to choroidal neovascularization (CNV) associated with angioid streaks and calcified Bruch membrane. Optical coherence tomography were consistent with basal laminar deposits and subretinal drusenoid deposits (SDD)., Results: Case 2 (46-year-old woman) exhibited unusual hyperpigmentation at the right fovea with count-fingers vision and a relatively unremarkable left fundus with 20/30 vision. The left eye exhibited the presence of nodular drusen and SDD and the absence of macular xanthophyll pigments., Conclusion: We propose that mutated MTTP within the retina may contribute to ABL retinopathy in addition to systemic deficiencies of fat-soluble vitamins. This concept is supported by a new mouse model with RPE-specific MTTP deficiency and a retinal degeneration phenotype. The observed range of human pathology, including angioid streaks, underscores the need for continued monitoring in adulthood, especially for CNV, a treatable condition.

Background and Aims: The small intestine plays a central role in lipid metabolism, most notably the uptake of dietary fats that are packaged into chylomicrons and secreted into the circulation for utilisation by peripheral tissues. While microsomal triglyceride transfer protein (MTP) is known to play a key role in this pathway, the intracellular assembly, trafficking, and secretion of chylomicrons is incompletely understood., Methods and Results: Using human transcriptome datasets to find genes co-regulated with MTTP, we identified ERICH4 as a top hit. The gene encodes for glutamate-rich protein 4, a protein of unknown function. REACTOME gene-function prediction tools indicated that ERICH4 is involved in intestinal lipid metabolism. In addition, GWAS data point to a strong relationship between ERICH4 and plasma lipids. To validate ERICH4 as a lipid gene, we generated whole-body Erich4 knockout (Erich4 -/- ) mice. ERICH4 deficiency, however, did not result in changes in body weight and composition, food intake, circulating plasma lipids, energy absorption and excretion, and tissue weights compared to controls. Additionally, there were no morphological abnormalities seen in the small intestine. Challenging mice with a high-fat diet did not give rise to a phenotype either., Conclusions: Despite prediction tools indicating ERICH4 as a strong candidate gene in intestinal lipid metabolism, we here show that ERICH4 does not play a role in intestinal lipid metabolism in mice. It remains to be established whether ERICH4 plays a role in human lipid metabolism., Competing Interests: Declaration of competing interest The other authors have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Plasma lipids are mainly carried in apolipoprotein B (apoB) containing lipoproteins. High levels of these lipoproteins are associated with several metabolic diseases and lowering their plasma levels is associated with reduced incidence of atherosclerotic cardiovascular disease. MicroRNAs (miRs) are small non-coding RNAs that reduce the protein expression of their target mRNAs and are potential therapeutic agents. Here, we identified a novel miR-615-3p that interacts with human 3'-UTR of apoB mRNA, induces post-transcriptional mRNA degradation, and reduces cellular and secreted apoB100 in human hepatoma Huh-7 cells. Reducing cellular miR-615-3p levels by CRISPR-sgRNA increased cellular and secreted apoB100 indicating endogenous miR regulates apoB expression. Overexpression of miR-615-3p along with or without palmitic acid treatment decreased cellular and media apoB and increased cellular triglyceride levels without inducing endoplasmic reticulum stress. These studies have identified miR-615-3p as a negative regulator of apoB expression in human liver-derived cells. It is likely that there are more miRs that regulate apoB-containing lipoprotein assembly and secretion. Discovery of additional miRs may uncover novel mechanisms that control lipoprotein assembly and secretion., Competing Interests: Conflicts of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

With 24 million inhabitants and 6.6 million vehicles on the roads, Karachi, Pakistan ranks among the world's most polluted cities due to high levels of fine particulate matter (PM 2.5 ). This study aims to investigate PM 2.5 mass, seasonal and temporal variability, chemical characterization, source apportionment, and health risk assessment at two urban sites in Karachi. Samples were analyzed using ion chromatography and dual-wavelength optical transmissometer for various inorganic components (anions, cations, and trace elements) and black carbon (BC). Several PM 2.5 pollution episodes were frequently observed, with annual mean concentrations at Kemari (140 ± 179 μg/m 3 ) and Malir (95 ± 40.9 μg/m 3 ) being significantly above the World Health Organization's guidelines of 5 μg/m 3 . Chemical composition at both sites exhibited seasonal variability, with higher pollution levels in winter and fall and lower concentrations in summer. The annual average BC concentrations were 4.86 ± 5.29 μg/m 3 and 4.52 ± 3.68 μg/m 3 , respectively. A Positive Matrix Factorization (PMF) analysis identified 5 factors, crustal, sea salt, vehicular exhaust, fossil-fuel combustion, and industrial emission. The health risk assessment indicated a higher number of deaths in colder seasons (fall and winter) at the Kemari (328,794 and 287,814) and Malir (228,406 and 165,737) sites and potential non-carcinogenic and carcinogenic risks to children from metals. The non-carcinogenic risk of PM 2.5 bound Pb, Fe, Zn, Mn, Cr, Cu and Ni via inhalation exposure were within the acceptable level (<1) for adults. However, potential non-carcinogenic and carcinogenic health risk posed by Pb and Cr through inhalation were observed for children. The findings exhibit critical levels of air pollution that exceed the safe limits in Karachi, posing significant health risks to children and sensitive groups. Our study underscores the urgent need for effective emission control strategies and policy interventions to mitigate these air pollution risks., 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 © 2024. Published by Elsevier B.V.)

The utilization of biowastes for producing biochar to remove potentially toxic elements from water represents an important pathway for aquatic ecosystem decontamination. Here we explored the significance of thiol-functionalization on sugarcane bagasse biochar (Th/SCB-BC) and rice husk biochar (Th/RH-BC) to enhance arsenite (As(III)) removal capacity from water and compared their efficiency with both pristine biochars (SCB-BC and RH-BC). The maximum As(III) sorption was found on Th/SCB-BC and Th/RH-BC (2.88 and 2.51 mg g -1 , respectively) compared to the SCB-BC and RH-BC (1.51 and 1.40 mg g -1 ). Relatively, a greater percentage of As(III) removal was obtained with Th/SCB-BC and Th/RH-BC (92% and 83%, respectively) at a pH 7 compared to pristine SCB-BC and RH-BC (65% and 55%) at 6 mg L -1 initial As(III) concentration, 2 h contact time and 1 g L -1 sorbent dose. Langmuir (R 2  = 0.99) isotherm and pseudo-second-order kinetic (R 2  = 0.99) models provided the best fits to As(III) sorption data. Desorption experiments indicated that the regeneration ability of biochars decreased and it was in the order of Th/SCB-BC (88%) > Th/RH-BC (82%) > SCB-BC (77%) > RH-BC (69%) up to three sorption-desorption cycles. Fourier-transform infrared spectroscopy and X-ray photoelectron spectroscopy results demonstrated that the thiol (-S-H) functional groups were successfully grafted on the surface of two biochars and as such contributed to enhance As(III) removal from water. Spectroscopic data indicated that the surface functional moieties, such as -S-H, - OH, - COOH, and C = O were involved to increase As(III) sorption on thiol-functionalized biochars. This study highlights that thiol-grafting on both biochars, notably on SCB-BC, enhanced their ability to remove As(III) from water, which can be used as an effective technique for the treatment of As from drinking water., (© 2024. The Author(s).)

Background: Free-living amoebae rarely instigate intracranial infections that may resemble neoplastic conditions on imaging. Naegleria fowleri precipitates an acute, swiftly fatal meningoencephalitis, whereas Acanthamoeba and Balamuthia species typically manifest with a less aggressive onset but carry equally dire consequences., Case Description: The case describes a 33-year-old woman with subacute encephalitis caused by Balamuthia mandrillaris . She experienced 2 months of back pain, 1 month of headaches, and 2 weeks of vomiting without fever, recent travel, aquatic activities, or animal exposure. Brain magnetic resonance imaging revealed a sizable, heterogeneous enhancing mass in the right temporal and frontal lobes, accompanied by vasogenic edema and midline shift. Histopathology showed marked inflammation and damage to blood vessels with amoebic trophozoites present. The trophozoites displayed specific characteristics, leading to the diagnosis of amoebic meningoencephalitis. Polymerase chain reaction and Sanger sequencing confirmed B. mandrillaris infection while testing for N. fowleri and Acanthamoeba was negative. Despite antibiotic treatment, the patient's condition deteriorated rapidly, resulting in death within 2 weeks of presentation., Conclusion: This is the first confirmed case of B. mandrillaris central nervous system (CNS) infection from Pakistan. The incidence of this disease is expected to rise due to increasing temperatures due to climate change and the deteriorating quality of the water supply. Balamuthia meningoencephalitis should, therefore be on the differential for non-neoplastic CNS lesions. Furthermore, an atypical histopathologic picture, including the absence of granulomatous inflammation, needs to be recognized., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Surgical Neurology International.)

Introduction  Tandem spinal stenosis (TSS) refers to the narrowing of the spinal canal at two distinct anatomic areas. Symptoms can present due to either cervical myelopathy or lumbar stenosis. Consequently, determining the symptomatic anatomical levels requiring surgery can pose a challenge. We sought to identify the surgical approach associated with better patient-reported outcomes. Materials and Methods  The Information Management System was queried using the International Classification of Diseases Ninth and Tenth Edition codes to identify patients who underwent simultaneous or staged decompression surgery for TSS between 2011 and 2020. Patient records were reviewed to collect data on age, sex, comorbidities, surgical approach, modified Japanese Orthopedic Association (mJOA) score, and complications. The mJOA is a validated composite assessment used to quantify postoperative neurological status. Multivariable regression models were utilized to identify factors associated with better postoperative neurological recovery. Results  Among 42 patients included in the analytical cohort, 33 (78.6%) underwent simultaneous cervical and lumbar decompression, while 9 (21.4%) underwent staged decompression (cervical followed by lumbar). The patient's age, sex, comorbid conditions, and American Society of Anesthesiologists level were similar between the two groups. Furthermore, simultaneous decompression was associated with higher blood loss (676.97 vs. 584.44 mL) and an increased need for transfusion (259.09 vs. 111.11 mL) compared with staged decompression. Moreover, patients who underwent simultaneous decompression experienced a higher number of postoperative complications (10 vs. 1; p  = 0.024). Notably, postoperative mJOA scores improved in both groups; however, the improvement was more pronounced in the staged group (mJOA score: 15.16% [ ± 2.18] vs. 16.56% [ ± 1.59]). On follow-up visits, patients who underwent staged decompression showed better recovery rates (mJOA score: 78.20% [ ± 24.45] vs. 59.75% [ ± 25.05]). Conclusion  The patient's clinical history and examination findings should be the main determinants of surgical decision-making. Our study showed a slightly higher postoperative mJOA score and a recovery rate with fewer complications in staged decompression of TSS., Competing Interests: Conflict of Interest None declared., (Asian Congress of Neurological Surgeons. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

Background: The surge in digital media consumption, coupled with the ensuing consequences of digital addiction, has witnessed a rapid increase, particularly after the initiation of the COVID-19 pandemic. Despite some studies exploring specific technological addictions, such as internet or social media addiction, in Bangladesh, there is a noticeable gap in research focusing on digital addiction in a broader context. Thus, this study aims to investigate digital addiction among students taking the university entrance test, examining its prevalence, contributing factors, and geographical distribution using GIS techniques., Methods: Data from a cross-sectional survey were collected from a total of 2,157 students who were taking the university entrance test at Jahangirnagar University, Bangladesh. A convenience sampling method was applied for data collection using a structured questionnaire. Statistical analyses were performed with SPSS 25 Version and AMOS 23 Version, whereas ArcGIS 10.8 Version was used for the geographical distribution of digital addiction., Results: The prevalence of digital addiction was 33.1% (mean score: 16.05 ± 5.58). Those students who are attempting the test for a second time were more likely to be addicted (42.7% vs. 39.1%), but the difference was not statistically significant. Besides, the potential factors predicted for digital addiction were student status, satisfaction with previous mock tests, average monthly expenditure during the admission test preparation, and depression. No significant difference was found between digital addiction and districts. However, digital addiction was higher in the districts of Manikganj, Rajbari, Shariatpur, and Chittagong Hill Tract areas, including Rangamati, and Bandarban., Conclusions: The study emphasizes the pressing need for collaborative efforts involving educational policymakers, institutions, and parents to address the growing digital addiction among university-bound students. The recommendations focus on promoting alternative activities, enhancing digital literacy, and imposing restrictions on digital device use, which are crucial steps toward fostering a healthier digital environment and balanced relationship with technology for students., (© 2024. The Author(s).)

Infective endocarditis (IE) is a life-threatening infection predominantly affecting the endocardium and heart valves, commonly seen in older patients and those with pre-existing cardiac conditions. Although rare in younger individuals with intact cardiac valves, certain structural heart diseases such as hypertrophic obstructive cardiomyopathy (HOCM) can increase the risk. We present a unique case of a 39-year-old female with a known history of HOCM, a condition characterized by abnormally thickened cardiac muscle primarily affecting the left ventricle. This patient was diagnosed with group B streptococcus infective endocarditis. Notably, this case was complicated by septic emboli to the brain. This case underscores the significant risk of IE in patients with HOCM, a demographic usually less susceptible to IE. It underscores the importance of early recognition and aggressive management of IE, especially in patients with structural heart diseases., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Yetiskul et al.)

Lipid processing by the retinal pigment epithelium (RPE) is necessary to maintain retinal health and function. Dysregulation of retinal lipid homeostasis due to normal aging or age-related disease triggers lipid accumulation within the RPE, on Bruch's membrane (BrM), and in the subretinal space. In its role as a hub for lipid trafficking into and out of the neural retina, the RPE packages a significant amount of lipid into lipid droplets for storage and into apolipoprotein B (APOB)-containing lipoproteins (Blps) for export. Microsomal triglyceride transfer protein (MTP), encoded by the MTTP gene, is essential for Blp assembly. Herein we test the hypothesis that MTP expression in the RPE is essential to maintain lipid balance and retinal function using the newly generated RPEΔMttp mouse model. Using non-invasive ocular imaging, electroretinography, and histochemical and biochemical analyses we show that genetic depletion of Mttp from the RPE results in intracellular lipid accumulation, increased photoreceptor-associated cholesterol deposits, and photoreceptor cell death, and loss of rod but not cone function. RPE-specific reduction in Mttp had no significant effect on plasma lipids and lipoproteins. While APOB was decreased in the RPE, most ocular retinoids remained unchanged, with the exception of the storage form of retinoid, retinyl ester. Thus suggesting that RPE MTP is critical for Blp synthesis and assembly but is not directly involved in plasma lipoprotein metabolism. These studies demonstrate that RPE-specific MTP expression is necessary to establish and maintain retinal lipid homeostasis and visual function., (© 2024 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.)

Vertebrates transport hydrophobic triglycerides through the circulatory system by packaging them within amphipathic particles called Triglyceride-Rich Lipoproteins. Yet, it remains largely unknown how triglycerides are loaded onto these particles. Mutations in Phospholipase A2 group 12B (PLA2G12B) are known to disrupt lipoprotein homeostasis, but its mechanistic role in this process remains unclear. Here we report that PLA2G12B channels lipids within the lumen of the endoplasmic reticulum into nascent lipoproteins. This activity promotes efficient lipid secretion while preventing excess accumulation of intracellular lipids. We characterize the functional domains, subcellular localization, and interacting partners of PLA2G12B, demonstrating that PLA2G12B is calcium-dependent and tightly associated with the membrane of the endoplasmic reticulum. We also detect profound resistance to atherosclerosis in PLA2G12B mutant mice, suggesting an evolutionary tradeoff between triglyceride transport and cardiovascular disease risk. Here we identify PLA2G12B as a key driver of triglyceride incorporation into vertebrate lipoproteins., (© 2024. The Author(s).)

Hyperlipidemia predisposes individuals to cardiometabolic diseases, the most common cause of global mortality. Microsomal triglyceride transfer protein (MTP) transfers multiple lipids and is essential for the assembly of apolipoprotein B-containing lipoproteins. MTP inhibition lowers plasma lipids but causes lipid retention in the liver and intestine. Previous studies suggested two lipid transfer domains in MTP and that specific inhibition of triglyceride (TG) and not phospholipid (PL) transfer can lower plasma lipids without significant tissue lipid accumulation. However, how MTP transfers different lipids and the domains involved in these activities are unknown. Here, we tested a hypothesis that two different β-sandwich domains in MTP transfer TG and PL. Mutagenesis of charged amino acids in β2-sandwich had no effect on PL transfer activity indicating that they are not critical. In contrast, amino acids with bulky hydrophobic side chains in β1-sandwich were critical for both TG and PL transfer activities. Substitutions of these residues with smaller hydrophobic side chains or positive charges reduced, whereas negatively charged side chains severely attenuated MTP lipid transfer activities. These studies point to a common lipid transfer domain for TG and PL in MTP that is enriched with bulky hydrophobic amino acids. Furthermore, we observed a strong correlation in different MTP mutants with respect to loss of both the lipid transfer activities, again implicating a common binding site for TG and PL in MTP. We propose that targeting of areas other than the identified common lipid transfer domain might reduce plasma lipids without causing cellular lipid retention., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Over the past decades, many forests have been converted to monoculture plantations, which might affect the soil microbial communities that are responsible for governing the soil biogeochemical processes. Understanding how reforestation efforts alter soil prokaryotic microbial communities will therefore inform forest management. In this study, the prokaryotic communities were comparatively investigated in a secondary Chinese fir forest (original) and a reforested Chinese fir plantation (reforested from a secondary Chinese fir forest) in Southern China. The results showed that reforestation changed the structure of the prokaryotic community: the relative abundances of important prokaryotic families in soil. This might be caused by the altered soil pH and organic matter content after reforestation. Soil profile layer depth was an important factor as the upper layers had a higher diversity of prokaryotes than the lower ones ( p < 0.05). The composition of the prokaryotic community presented a seasonality characteristic. In addition, the results showed that the dominant phylum was Acidobacteria (58.86%) with Koribacteraceae (15.38%) as the dominant family in the secondary Chinese fir forest and the reforested plantation. Furthermore, soil organic matter, total N, hydrolyzable N, and NH 4 + - N were positively correlated with prokaryotic diversity ( p < 0.05). Also, organic matter and NO 3 - - N were positively correlated to prokaryotic abundance ( p < 0.05). This study demonstrated that re-forest transformation altered soil properties, which lead to the changes in microbial composition. The changes in microbial community might in turn influence biogeochemical processes and the environmental variables. The study could contribute to forest management and policy-making., 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 © 2024 Hou, Qiao, Gu, Liu, Hussain, Du, Zhou, Wang and Li.)

Under paddy soil conditions, rice plants are vulnerable to arsenic (As) accumulation, thus causing potential threat to human health. Here we investigated the influence of foliar-applied phosphorus (P: 10 and 20 mg L -1 ), silicon (Si: 0.6 and 1.5 g L -1 ) and selenium (Se: 5 and 10 mg L -1 ) on As accumulation, morphological and physiological attributes of two contrasting rice genotypes (KSK-133 and Super Basmati) under As stress (25 mg kg -1 as arsenate). Silicon foliar dressing significantly ( p  < 0.05) reduced grain As uptake (up to 67%) and improved rice growth and chlorophyll content (28-66%) in both rice genotypes over their controls. Phosphorus foliar application resulted in a notable decrease (17%) in grain As uptake of coarse rice genotype (KSK-133), while it slightly increased grain As uptake in the fine one (Super Basmati; 6%) compared to controls. However, foliar-applied Se did not show significant effects on rice plants growth attributes and As uptake in both genotypes. Similarly, biochemical and enzymatic attributes ( i.e., lipid peroxidation, electrolyte leakage, peroxidase and catalase) were improved with Si application in rice plants, except for P treatment that was only effective for coarse one. Foliar-applied Si also resulted in reduced cancer risk and hazard quotient (< 0.10) for both rice genotypes. This study advances our understanding on critical role of different foliar-applied nutrients and rice genotypes, which is imperative to develop effective As remediation and management strategies in coarse and fine rice genotypes and protect human health.

Exogenous carbon (C) inputs stimulate soil organic carbon (SOC) decomposition, strongly influencing atmospheric concentrations and climate dynamics. The direction and magnitude of C decomposition depend on the C and nitrogen (N) addition, types and pattern. Despite the importance of decomposition, it remains unclear whether organic C input affects the SOC decomposition under different N-types (Ammonium Nitrate; AN, Urea; U and Ammonium Sulfate; AS). Therefore, we conducted an incubation experiment to assess glucose impact on N-treated soils at various levels (High N; HN: 50 mg/m 2 , Low N; LN: 05 mg/m 2 ). The glucose input increased SOC mineralization by 38% and 35% under HN and LN, respectively. Moreover, it suppressed the concentration of NO 3 - -N by 35% and NH 4 + -N by 15% in response to HN and LN soils, respectively. Results indicated higher respiration in Urea-treated soils and elevated net total nitrogen content (TN) in AS-treated soils. AN-amended soil exhibited no notable rise in C mineralization and TN content compared to other N-type soils. Microbial biomass carbon (MBC) was higher in glucose treated soils under LN conditions than control. This could result that high N suppressed microbial N mining and enhancing SOM stability by directing microbes towards accessible C sources. Our results suggest that glucose accelerated SOC mineralization in urea-added soils and TN contents in AS-amended soils, while HN levels suppressed C release and increased TN contents in all soil types except glucose-treated soils. Thus, different N-types and levels play a key role in modulating the stability of SOC over C input., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Wastewater contamination with heavy metal(loids)s has become a worldwide environmental and public health problem due to their toxic and non-degradable nature. Different methods and technologies have been applied for water/wastewater treatment to mitigate heavy metal(loid)-induced toxicity threat to humans. Among various treatment methods, adsorption is considered the most attractive method because of its high ability and efficiency to remove contaminants from wastewater. Agricultural waste-based adsorbents have gained great attention because of high efficiency to heavy metal(loids)s removal from contaminated water. Chemically modified biosorbents can significantly enhance the stability and adsorption ability of the sorbents. The two mathematical models of sorption, Freundlich and Langmuir isotherm models, have mostly been studied. In kinetic modeling, pseudo-second-order model proved better in most of the studies compared to pseudo-first-order model. The ion exchange and electrostatic attraction are the main mechanisms for adsorption of heavy metal(loid)s on biosorbents. The regeneration has allowed various biosorbents to be recycled and reused up to 4-5 time. Most effective eluents used for regeneration are dilute acids. For practical perspective, biosorbent removal efficiency has been elucidated using various types of wastewater and economic analysis studies. Economic analysis of adsorption process using agricultural waste-based biosorbents proved this approach cheaper compared to traditional commercial adsorbents, such as chemically activated carbon. The review also highlights key research gaps to advance the scope and application of waste peels for the remediation of heavy metal(loid)s-contaminated wastewater.

Glyphosate (Gly) and its formulations are broad-spectrum herbicides globally used for pre- and post-emergent weed control. Glyphosate has been applied to terrestrial and aquatic ecosystems. Critics have claimed that Gly-treated plants have altered mineral nutrition and increased susceptibility to plant pathogens because of Gly ability to chelate divalent metal cations. Still, the complete resistance of Gly indicates that chelation of metal cations does not play a role in herbicidal efficacy or have a substantial impact on mineral nutrition. Due to its extensive and inadequate use, this herbicide has been frequently detected in soil (2 mg kg -1 , European Union) and in stream water (328 µg L -1 , USA), mostly in surface (7.6 µg L -1 , USA) and groundwater (2.5 µg L -1 , Denmark). International Agency for Research on Cancer (IARC) already classified Gly as a category 2 A carcinogen in 2016. Therefore, it is necessary to find the best degradation techniques to remediate soil and aquatic environments polluted with Gly. This review elucidates the effects of Gly on humans, soil microbiota, plants, algae, and water. This review develops deeper insight toward the advances in Gly biodegradation using microbial communities. This review provides a thorough understanding of Gly interaction with mineral elements and its limitations by interfering with the plants biochemical and morphological attributes.

Objectives: Triglyceride (TG) association with apolipoprotein B100 (apoB100) serves to form very low density lipoproteins (VLDL) in the liver. The repertoire of factors that facilitate this association is incompletely defined. FITM2, an integral endoplasmic reticulum (ER) protein, was originally discovered as a factor participating in cytoplasmic lipid droplets (LDs) in tissues that do not form VLDL. We hypothesized that in the liver, in addition to promoting cytosolic LD formation, FITM2 would also transfer TG from its site of synthesis in the ER membrane to nascent VLDL particles within the ER lumen., Methods: Experiments were conducted using a rat hepatic cell line (McArdle-RH7777, or McA cells), an established model of mammalian lipoprotein metabolism, and mice. FITM2 expression was reduced using siRNA in cells and by liver specific cre-recombinase mediated deletion of the Fitm2 gene in mice. Effects of FITM2 deficiency on VLDL assembly and secretion in vitro and in vivo were measured by multiple methods, including density gradient ultracentrifugation, chromatography, mass spectrometry, simulated Raman spectroscopy (SRS) microscopy, sub-cellular fractionation, immunoprecipitation, immunofluorescence, and electron microscopy., Main Findings: 1) FITM2-deficient hepatic cells in vitro and in vivo secrete TG-depleted VLDL particles, but the number of particles is unchanged compared to controls; 2) FITM2 deficiency in mice on a high fat diet (HFD) results in decreased plasma TG levels. The number of apoB100-containing lipoproteins remains similar, but shift from VLDL to LDL density; 3) Both in vitro and in vivo , when TG synthesis is stimulated and FITM2 is deficient, TG accumulates in the ER, and despite its availability this pool is unable to fully lipidate apoB100 particles; 4) FITM2 deficiency disrupts ER morphology and results in ER stress., Principal Conclusions: The results suggest that FITM2 contributes to VLDL lipidation, especially when newly synthesized hepatic TG is in abundance. In addition to its fundamental importance in VLDL assembly, the results also suggest that under dysmetabolic conditions, FITM2 may be a limiting factor that ultimately contributes to non-alcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH).

Lipid processing by the retinal pigment epithelium (RPE) is necessary to maintain retinal health and function. Dysregulation of retinal lipid homeostasis due to normal aging or to age-related disease triggers lipid accumulation within the RPE, on Bruch's membrane (BrM), and in the subretinal space. In its role as a hub for lipid trafficking into and out of the neural retina, the RPE packages a significant amount of lipid into lipid droplets for storage and into apolipoprotein B (apoB)-containing lipoproteins (Blps) for export. Microsomal triglyceride transfer protein (MTP), encoded by the MTTP gene, is essential for Blp assembly. Herein we test the hypothesis that MTP expression in the RPE is essential to maintain lipid balance and retinal function using the newly generated RPEΔMttp mouse model. Using non-invasive ocular imaging, electroretinography, and histochemical and biochemical analyses we show that genetic deletion of Mttp from the RPE results in intracellular lipid accumulation, increased photoreceptor -associated cholesterol deposits and photoreceptor cell death, and loss of rod but not cone function. RPE-specific ablation of Mttp had no significant effect on plasma lipids and lipoproteins. While, apoB was decreased in the RPE, ocular retinoid concentrations remained unchanged. Thus suggesting that RPE MTP is critical for Blp synthesis and assembly but not directly involved in ocular retinoid and plasma lipoprotein metabolism. These studies demonstrate that RPE-specific MTP expression is necessary to establish and maintain retinal lipid homeostasis and visual function., Competing Interests: Conflict of interest statements: The authors have no conflicts of interest

The abuse of antibiotics has led to serious environmental pollution and the emergence of drug-resistant bacteria surpassing the replacement rate of antibiotics. Herein, near-infrared fluorescent carbon dots (NIR-CDs) were developed to meet the requirements for oxytetracycline (OTC) detection in food and water samples (milk, honey, and lake water) with a detection limit of 0.112 μM. These NIR-CDs, possessing excellent water-solubility, deep tissue penetration ability, and tunable optical properties, exhibit maximum emission at 790 nm (NIR-I window). Unlike traditional CDs, this novel NIR-CDs nanoprobe provides a dual response in the presence of OTC (quenching and bathochromic shifting), without obvious interference from other existing biomolecules and metal ions. Additionally, these NIR-CDs exhibit excellent photostability and multi-resistance under UV irradiation, exceptional pH stability (pH 6-12), reliable long-time exposure, and durability in ionic (NaCl) environments. Moreover, NIR-CDs and NIR-CDs@OTC are nontoxic and were successfully utilized for cell-imaging applications in normal (NIH3T3) and cancer cells (HeLa).

Dopamine (DA) is a biomolecule that plays a critical part in the functioning of our brains by promoting motivation, maintaining focus, and altering mood. Excessive or low-level concentrations of DA in the human brain led to a dangerous neurological disorder. It is significantly important to trace the precise amount of DA to prevent such risky brain disease. Recently, heteroatoms-doped carbon dots (H-CDs) have attracted great attention for their capacity to detect biomolecules, metal ions, organic solvents, chemical dyes, etc. In this review, we have provided a comprehensive summary of the emerging trends in the heteroatom functional dopamine-doped carbon dots (DA-CDs), which are based on DA used as starting substances or functionalizing agents. Our analysis encompasses a detailed exploration of the synthetic methods, physical and chemical properties of carbon dots derived from dopamine, as well as their diverse range of applications. Additionally, we have also discussed the application of H-CDs in the dopmine detection by using various fluorescent, colorimetric, and electrochemical techniques., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Blockchain technology finds widespread application across various fields due to its key features such as immutability, reduced costs, decentralization, and transparency. The security of blockchain relies on elements like hashing, digital signatures, and cryptography. However, the emergence of quantum computers and supporting algorithms poses a threat to blockchain security. These quantum algorithms pose a significant threat to both public-key cryptography and hash functions, compelling the redesign of blockchain architectures. This paper investigates the status quo of the post-quantum, quantum-safe, or quantum-resistant cryptosystems within the framework of blockchain. This study starts with a fundamental overview of both blockchain and quantum computing, examining their reciprocal influence and evolution. Subsequently, a comprehensive literature review is conducted focusing on Post-Quantum Distributed Ledger Technology (PQDLT). This research emphasizes the practical implementation of these protocols and algorithms providing extensive comparisons of characteristics and performance. This work will help to foster further research at the intersection of post-quantum cryptography and blockchain systems and give prospective directions for future PQDLT researchers and developers., (© 2023. The Author(s).)

In the modern era, with the emergence of the Internet of Things (IoT), big data applications, cloud computing, and the ever-increasing demand for high-speed internet with the aid of upgraded telecom network resources, users now require virtualization of the network for smart handling of modern-day challenges to obtain better services (in terms of security, reliability, scalability, etc.). These requirements can be fulfilled by using software-defined networking (SDN). This research article emphasizes one of the major aspects of the practical implementation of SDN to enhance the QoS of a virtual network through the load management of network servers. In an SDN-based network, several servers are available to fulfill users' hypertext transfer protocol (HTTP) requests to ensure dynamic routing under the influence of the SDN controller. However, if the number of requests is directed to a specific server, the controller is bound to follow the user-programmed instructions, and the load on that server is increased, which results in (a) an increase in end-to-end user delay, (b) a decrease in the data transfer rate, and (c) a decrease in the available bandwidth of the targeted server. All of the above-mentioned factors will result in the degradation of network QoS. With the implementation of the proposed algorithm, dynamic active sensing server load management (DASLM), on the SDN controller, the load on the server is shared based on QoS control parameters (throughput, response time, round trip time, etc.). The overall delay is reduced, and the bandwidth utilization along with throughput is also increased.

High apoB-containing low-density lipoproteins (LDL) and low apoA1-containing high-density lipoproteins (HDL) are associated with atherosclerosis. In search of a molecular regulator that could simultaneously and reciprocally control both LDL and HDL levels, we screened a microRNA (miR) library using human hepatoma Huh-7 cells. We identified miR-541-3p that both decreases apoB and increases apoA1 expression by inducing mRNA degradation of two different transcription factors, Znf101 and Casz1. Znf101 enhances apoB expression while Casz1 represses apoA1 expression. The hepatic knockdown of orthologous Zfp961 and Casz1 genes in mice altered plasma lipoproteins and reduced atherosclerosis without causing hepatic lipid accumulation, most likely by lowering hepatic triglyceride production, increasing HDL cholesterol efflux capacity, and reducing lipogenesis. Notably, human genetic variants in the MIR541, ZNF101, and CASZ1 loci are significantly associated with plasma lipids and lipoprotein levels. This study identifies miR-541-3p and Znf101/Casz1 as potential therapeutic agent and targets, respectively, to reduce plasma lipoproteins and atherosclerosis without causing liver steatosis.

Background: Molecular genetic testing of patients with hypobetalipoproteinemia may identify a genetic cause that can form the basis for starting proper therapy. Identifying a genetic cause may also provide novel data on the structure-function relationship of the mutant protein., Objective: To identify a genetic cause of hypobetalipoproteinemia in a patient with levels of low density lipoprotein cholesterol at the detection limit of 0.1 mmol/l., Methods: DNA sequencing of the translated exons with flanking intron sequences of the genes adenosine triphosphate-binding cassette transporter 1, angiopoietin-like protein 3, apolipoprotein B, apolipoprotein A1, lecithin-cholesterol acyltransferase, microsomal triglyceride transfer protein and proprotein convertase subtilisin/kexin type 9., Results: The patient was homozygous for mutation Q384K (c.1150C>A) in the apolipoprotein B gene, and this mutation segregated with hypobetalipoproteinemia in the family. Residue Gln 384 is located in the large lipid transfer module of apoB that has been suggested to be important for lipidation of apolipoprotein B through interaction with microsomal triglyceride transfer protein. Based on measurements of serum levels of triglycerides and apolipoprotein B-48 after an oral fat load, we conclude that the patient was able to synthesize apolipoprotein B-48 in the intestine in a seemingly normal fashion., Conclusion: Our data indicate that mutation Q384K severely reduces the secretion of apolipoprotein B-100 in the liver without reducing the secretion of apolipoprotein B-48 in the intestine. Possible mechanisms for the different effects of this and other missense mutations affecting the large lipid transfer module on the two forms of apoB are discussed., (Copyright © 2023. Published by Elsevier Inc.)

Background and Aims: The assembly and secretion of VLDL from the liver, a pathway that affects hepatic and plasma lipids, remains incompletely understood. We set out to identify players in the VLDL biogenesis pathway by identifying genes that are co-expressed with the MTTP gene that encodes for microsomal triglyceride transfer protein, key to the lipidation of apolipoprotein B, the core protein of VLDL. Using human and murine transcriptomic data sets, we identified small leucine-rich protein 1 ( SMLR1 ), encoding for small leucine-rich protein 1, a protein of unknown function that is exclusively expressed in liver and small intestine., Approach and Results: To assess the role of SMLR1 in the liver, we used somatic CRISPR/CRISPR-associated protein 9 gene editing to silence murine Smlr1 in hepatocytes ( Smlr1 -LKO). When fed a chow diet, male and female mice show hepatic steatosis, reduced plasma apolipoprotein B and triglycerides, and reduced VLDL secretion without affecting microsomal triglyceride transfer protein activity. Immunofluorescence studies show that SMLR1 is in the endoplasmic reticulum and Cis-Golgi complex. The loss of hepatic SMLR1 in female mice protects against diet-induced hyperlipidemia and atherosclerosis but causes NASH. On a high-fat, high-cholesterol diet, insulin and glucose tolerance tests did not reveal differences in male Smlr1 -LKO mice versus controls., Conclusions: We propose a role for SMLR1 in the trafficking of VLDL from the endoplasmic reticulum to the Cis-Golgi complex. While this study uncovers SMLR1 as a player in the VLDL assembly, trafficking, and secretion pathway, it also shows that NASH can occur with undisturbed glucose homeostasis and atheroprotection., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

In the maternal circulation, apoB-containing low-density lipoproteins (LDL) and apoA1-containing high-density lipoproteins (HDL) transport lipids. The production of lipoproteins in the placenta has been suggested, but the directionality of release has not been resolved. We compared apolipoprotein concentrations and size-exclusion chromatography elution profiles of lipoproteins in maternal/fetal circulations, and in umbilical arteries/veins; identified placental lipoprotein-producing cells; and studied temporal induction of lipoprotein-synthesizing machinery during pregnancy. We observed that maternal and fetal lipoproteins are different with respect to concentrations and elution profiles. Surprisingly, concentrations and elution profiles of lipoproteins in umbilical arteries and veins were similar indicating their homeostatic control. Human placental cultures synthesized apoB100-containing LDL-sized and apoA1-containing HDL-sized particles. Immunolocalization techniques revealed that ApoA1 was present mainly in syncytiotrophoblasts. MTP, a critical protein for lipoprotein assembly, was in these trophoblasts. ApoB was in the placental stroma indicating that trophoblasts secrete apoB-containing lipoproteins into the stroma. ApoB and MTP expressions increased in placentas from the 2nd trimester to term, whereas apoA1 expression was unchanged. Thus, our studies provide new information regarding the timing of lipoprotein gene induction during gestation, the cells involved in lipoprotein assembly and the gel filtration profiles of human placental lipoproteins. Next, we observed that mouse placenta produces MTP, apoB100, apoB48 and apoA1. The expression of genes gradually increased and peaked in late gestation. This information may be useful in identifying transcription factors regulating the induction of these genes in gestation and the importance of placental lipoprotein assembly in fetal development., Competing Interests: Declaration of competing interest Authors have no conflicts to report., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Apolipoprotein B (apoB)-lipoproteins initiate and promote atherosclerotic cardiovascular disease. Plasma tissue plasminogen activator (tPA) activity is negatively associated with atherogenic apoB-lipoprotein cholesterol levels in humans, but the mechanisms are unknown. We found that tPA, partially through the lysine-binding site on its Kringle 2 domain, binds to the N terminus of apoB, blocking the interaction between apoB and microsomal triglyceride transfer protein (MTP) in hepatocytes, thereby reducing very-low-density lipoprotein (VLDL) assembly and plasma apoB-lipoprotein cholesterol levels. Plasminogen activator inhibitor 1 (PAI-1) sequesters tPA away from apoB and increases VLDL assembly. Humans with PAI-1 deficiency have smaller VLDL particles and lower plasma levels of apoB-lipoprotein cholesterol. These results suggest a mechanism that fine-tunes VLDL assembly by intracellular interactions among tPA, PAI-1, and apoB in hepatocytes.

Human societies depend on marine ecosystems, but their degradation continues. Toward mitigating this decline, new and more effective ways to precisely measure the status and condition of marine environments are needed alongside existing rebuilding strategies. Here, we provide an overview of how sensors and wearable technology developed for humans could be adapted to improve marine monitoring. We describe barriers that have slowed the transition of this technology from land to sea, update on the developments in sensors to advance ocean observation and advocate for more widespread use of wearables on marine organisms in the wild and in aquaculture. We propose that large-scale use of wearables could facilitate the concept of an 'internet of marine life' that might contribute to a more robust and effective observation system for the oceans and commercial aquaculture operations. These observations may aid in rationalizing strategies toward conservation and restoration of marine communities and habitats., (© 2023. Springer Nature America, Inc.)

Cybersecurity guarantees the exchange of information through a public channel in a secure way. That is the data must be protected from unauthorized parties and transmitted to the intended parties with confidentiality and integrity. In this work, we mount an attack on a cryptosystem based on multivariate polynomial trapdoor function over the field of rational numbers Q. The developers claim that the security of their proposed scheme depends on the fact that a polynomial system consisting of 2n (where n is a natural number) equations and 3n unknowns constructed by using quasigroup string transformations, has infinitely many solutions and finding exact solution is not possible. We explain that the proposed trapdoor function is vulnerable to a Gröbner basis attack. Selected polynomials in the corresponding Gröbner basis can be used to recover the plaintext against a given ciphertext without the knowledge of the secret key., Competing Interests: The authors declare that there are no competing interests., (©2023 Ali et al.)

Background: Inflammatory Breast Cancer (IBC) is a rare but aggressive subtype of breast cancer accounting for only 1% to 5% of cases but comprising 7% to 10% of breast cancer deaths. Diagnosis of IBC can be challenging which can lead to delays in diagnosis and treatment. We formed a multidisciplinary IBC program to address the unique challenges of diagnosing and treating patients with IBC., Materials and Methods: We retrospectively identified patients with an IBC CPT code and collected data on the date of the first visit with medical oncology, surgical oncology, or radiation oncology, date of biopsy, and initiation of neoadjuvant chemotherapy. In 2020, as part of the IBC program at The Ohio State University, the decision tree (DT) was revised to help identify potential IBC patients. These patients were prioritized with a multidisciplinary appointment within 3 days., Results: After adjusting the call center DT, there was a significant decline in the median and mean time from initial contact to chemotherapy initiation and an insignificant decrease in the mean time from contact to biopsy (P = .71884). The median time of contact to chemotherapy was 10 days (range 9-14) in 2020, a decrease of 43% compared to 3 prior years (P = .0068). After initiation of the IBC program, 100% of patients underwent trimodality therapy-neoadjuvant systemic therapy, modified radical mastectomy, and post mastectomy radiation therapy., Conclusion: A multidisciplinary IBC program that included scheduling DT with specific questions about IBC symptoms helped identify potential patients and significantly decrease time to treatment and assured completion of trimodality therapy., Competing Interests: Disclosure These authors have the following conflict of interest: Park – Bayer, LLC consultant. No conflict of interest: Hussain, Grimes, Stover, Jhawar, Kerger, Agnese, Beyer, Skoracki., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: Achondroplasia is a genetic disorder known for short stature and skeletal abnormalities., Case Report: We present a case of narrowing of the foramen magnum from a large opisthion extending to the spinal canal., Conclusion: Foramen magnum stenosis and cervicomedullary stenosis are potentially life threatening neurological manifestations of achondroplasia.

Background: Genetic inactivation and pharmacologic inhibition of the microsomal triglyceride transfer protein (MTP; gene name MTTP) inhibits hepatic secretion of VLDL, thereby reducing serum lipids and apoB at the expense of increasing hepatic steatosis., Aim: To examine the effects of missense variants in MTTP on hepatic and circulating lipids., Methods: We analysed the association of MTTP missense variants with metabolic, hepatic and clinical phenotypes in the Penn Medicine Biobank (PMBB; n = 37,960) and the UKBiobank (UKB; n = 451,444)., Results: We analysed 24 missense variants in MTTP in PMBB for association with biopsy-proven hepatic steatosis and found that an isoleucine 128 to threonine variant (I128T: rs3816873-A, frequency 26%) was associated with reduced steatosis (p < 0.001). PMBB subjects with imaging-proven steatosis also revealed significantly fewer carriers of MTTP I128T compared to controls. Analysis in UKB also showed that MTTP I128T was associated with reduced risk of hepatic steatosis. Unexpectedly, MTTP I128T was found to be associated with reduced plasma levels of LDL-cholesterol and apoB (all p < 0.001). Functional studies indicated that MTTP I128T is neither a classic loss nor gain of function allele., Conclusions: MTTP I128T is associated with reduced hepatic steatosis as well as reduced plasma lipids and apoB. This paradoxical profile is not consistent with a simple gain or loss of function in MTP activity and suggests a more complex effect on MTP function. Further investigation of MTTP I128T will provide insight into the structure-function of MTP and potentially new approaches to modulate MTP activity that could both reduce hepatic and circulating lipids., (© 2023 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.)

This study endeavors to investigate the environmental cost of FDI inflows in the Sub-Saharan African (SSA) region over the period of 2006 to 2020. There are two opposing theories about how FDI impacts the environment, namely, the pollution halo hypothesis (PHH) and the pollution haven hypothesis (PH). Given the SSA region's poor environmental performance and potential spatial spillover effects on neighboring nations, the study underlines the necessity to look into the pollution hypotheses in the region. The examination is carried out through non-spatial and spatial panel data econometric approaches. The empirical findings provide evidence that an increase in FDI inflow by 1% in SSA is positively associated with increasing levels of CO2 emissions by 0.03% on average, thus validating the notion of a pollution haven in the region. Furthermore, the study reveals that the environmental spillovers of CO2 emissions are not confined to the host country alone, but also extend to neighboring nations. Other key determinants of CO2 emissions, including GDP, population, and urbanization, were also found to be positively linked to CO2 emissions, whereas the use of renewable energy resources was found to have a mitigating effect. The empirical findings offer valuable insights for policymakers and stakeholders in the SSA region. These insights highlight the importance of the adoption of renewable energy sources and enacting regulatory measures to monitor the environmental cost of FDI, with the aim of mitigating the deleterious consequences of CO2 emissions, not only in the host nation but also in the neighboring nations., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Acute myocardial infarction (AMI) is the top cause of death in Maldives. Our study aims to determine the prehospital delay and its associated factors in AMI patients in Maldives., Methods: A cross-sectional study was conducted with 127 patients, divided into early (≤ 6 h) and delayed (> 6 h) presenters to the hospital. The data collection for the study was carried out by interviewing AMI patients, focusing on their socio-demographic characteristics, coronary artery disease risk factors, clinical symptoms, situational factors, and behavioral and cognitive responses to symptoms., Results: The median onset-to-door time was 230 (IQR 420) minutes. The mean age of AMI patients was 50.9 (SD ± 12.9) years old, and 39.4% of them had delayed presentation to the hospital. Smokers (adj OR = 0.3; 95% CI: 0.1, 0.9; P = 0.047) and those with previous episodes of chest pain or AMI (adj OR = 0.2; 95% CI: 0.03, 0.91; P = 0.038) were significant factors for early presentation to the hospital, while denial of symptoms (adj OR = 29.3; 95% CI: 1.6, 547.2; P = 0.024) and lack of knowledge (adj OR = 7.2; 95% CI: 1.77, 29.43; P = 0.006) led to a delayed decision to seek treatment. Situational factors such as onset at the workplace (adj OR = 5.8; 95% CI: 1.24, 26.83; P = 0.025) had lower odds of delay, whereas referral cases (adj OR = 7.7; 95% CI: 1.9, 30.94; P = 0.004) and use of sea ambulance (adj OR = 11.1; 95% CI: 2.8, 43.8; P = 0.001) were prone to delay in presentation to the hospital., Conclusion: Sea ambulance, referral cases, lack of knowledge, and denial of symptoms are significant factors associated with prehospital delay among patients with AMI. Public awareness about the benefits of early presentation and improvement of the means of transportation between islands is suggested to improve emergency cardiac care in the country., (© 2023. The Author(s).)

Purpose of Review: This review is aimed at providing an overview of new developments in gene editing technology, including examples of how this technology has been used to develop cell models for studying the effects of gene ablation or missense mutations on lipoprotein assembly and secretion., Recent Findings: CRISPR/Cas9-mediated gene editing is superior to other technologies because of its ease, sensitivity, and low off-target effects. This technology has been used to study the importance of microsomal triglyceride transfer protein in the assembly and secretion of apolipoprotein B-containing lipoproteins, as well as to establish causal effects of APOB gene missense mutations on lipoprotein assembly and secretion. CRISPR/Cas9 technology is anticipated to provide unprecedented flexibility in studying protein structure and function in cells and animals and to yield mechanistic insights into variants in the human genome., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Like many urban centers in developing countries, the effect of air pollution in Karachi is understudied. The goal of this study was to determine the chemical characterization, temporal and seasonal variability, sources, and health impacts of fine particulate matter (PM 2.5 ) in Karachi, Pakistan. Daily samples of PM 2.5 were collected using a low-volume air sampler at two different sites (Makro and Karachi University) over the four seasons between October 2009 and August 2010. Samples were analyzed for black carbon (BC), trace metals, and water-soluble ions. Results showed that the annual average concentrations of PM 2.5 at Makro and Karachi University were 114 ± 115 and 71.7 ± 56.4 μg m -3 , respectively, about 22.8 and 14.3-fold higher than the World Health Organization annual guideline of 5 μg m -3 . BC concentrations were 3.39 ± 1.97 and 2.70 ± 2.06 μg m -3 , respectively. The concentrations of PM 2.5 , BC, trace metals, and ions at the two sites showed clear seasonal trends, with higher concentrations in winter and lower concentrations in summer. The trace metals and ionic species with the highest concentrations were Pb, S, Zn, Ca, Si, Cl, Fe, and SO 4 2- . The air quality index in the fall and winter at both sites was about 68 %, which is "unhealthy" for the general population. Positive Matrix Factorization revealed the overall contribution to PM 2.5 at the Makro site came from three major sources - industrial emissions (13.3 %), vehicular emissions (59.1 %), and oil combustion (23.3 %). The estimates of expected number of deaths due to short-term exposure to PM 2.5 were high in the fall and winter at both sites, with an annual mean estimate of 3592 expected number of deaths at the Makro site. Attention should be paid to the reduction of inorganic pollutants from industrial facilities, vehicular traffic, and fossil fuel combustion, due to their extremely high contribution to PM 2.5 mass and health risks., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: The coronavirus disease-19 pandemic has aggravated the already neglected neurosurgical specialty in developing countries with a mounting shortage of specialists, long queues of operative patients, and a lack of adequate critical care units., Methods: We have reviewed the innovative strategies adopted for maintaining an optimal surgical practice while ensuring team safety at the Aga Khan University Hospital, Karachi Pakistan., Results: There is already a scarcity of resources in developing countries. The international guidelines had to be tailored to the context of the developing world. A multimodal strategy that focused on infection control, continuum of care, and the well-being of staff was adopted at Aga Khan University. Patients were screened and seen either in person or through telemedicine, depending on the severity of the disease. All educational activities for residents were shifted online, and this helped in preventing overcrowding., Conclusion: Optimal surgical practice while ensuring team safety can be achieved through a multimodal strategy focusing on infection control, continuum of care, and the well-being of staff., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Surgical Neurology International.)