Ferroptosis, a newly discovered mode of cell death, emerges as a new target for atherosclerosis (AS). Long noncoding RNAs (lncRNAs) are involved in the regulation of ferroptosis. In our previous study, lnc-MRGPRF-6:1 was highly expressed in patients with coronary atherosclerotic disease (CAD) and closely associated with macrophage-mediated inflammation in AS. In the present study, we aim to investigate the role of lnc-MRGPRF-6:1 in oxidized-low-density lipoprotein (ox-LDL)-induced macrophage ferroptosis in AS.  Firstly, ox-LDL-treated macrophages were used to simulate macrophage injury in AS. Then, ferroptosis-related biomarkers and mitochondrial morphology were detected and observed in ox-LDL-treated macrophages. Subsequently, we constructed lnc-MRGPRF-6:1 knockdown and overexpression of THP-1-derived macrophages and investigated the role of lnc-MRGPRF-6:1 in ox-LDL-induced ferroptosis. Then human monocytes were isolated successfully and were used to explore the role of lnc-MRGPRF-6:1 in macrophage ferroptosis. Likely, we constructed lnc-MRGPRF-6:1 knockdown and overexpression of human monocyte-derived macrophages and detected the expression levels of ferroptosis-related biomarkers. Then, transcriptome sequencing, literature searching, and following quantitative real-time polymerase chain reaction and western blot were implemented to explore specific signaling pathway in the process. It was demonstrated that lnc-MRGPRF-6:1 may regulate ox-LDL-induced macrophage ferroptosis through glutathione peroxidase 4 (GPX4). Eventually, the correlation between lnc-MRGPRF-6:1 and GPX4 was measured in monocyte-derived macrophages of CAD patients and controls.  The ox-LDL-induced injury in macrophages was involved in ferroptosis. The knockdown of lnc-MRGPRF-6:1 could alleviate ox-LDL-induced ferroptosis in macrophages. Meanwhile, the overexpression of lnc-MRGPRF-6:1 could intensify ox-LDL-induced ferroptosis. Furthermore, the knockdown of lnc-MRGPRF-6:1 could alleviate the decrease of GPX4 induced by RAS-selective lethal compounds 3 (RSL-3). These indicated that lnc-MRGPRF-6:1 may suppress GPX4 to induce macrophage ferroptosis. Eventually, lnc-MRGPRF-6:1 was highly expressed in the monocyte-derived macrophages of CAD patients and was negatively correlated with the expression of GPX4.  lnc-MRGPRF-6:1 can promote ox-LDL-induced macrophage ferroptosis through inhibiting GPX4. As the increasing incidence of coronary atherosclerotic disease (CAD) with high mortality and disability rate, it has attracted great attention. Atherosclerosis (AS), the pathologic basement of CAD, is worth studying in-depth –3. As is−/glutathione peroxidase 4 (GPX4) axis is considered as the central inhibition pathway in ferroptosis [−, which can promote the resistance of ferroptosis [Ferroptosis is the newly discovered and unconventional form of cell death in 2012, which is different from the previously reported cell death modes . Ferroptroptosis –20. Soluroptosis , 22.Studies showed that ferroptosis is closely involved in AS , 23. It Long noncoding RNAs (lncRNAs) are a class of nucleotide sequences with a length of more than 200 bases and no protein-coding potential, which play an important role in biological processes such as cell metabolism, proliferation, differentiation, and apoptosis . It is rLnc-MRGPRF-6:1, the newly discovered lncRNA by our group which is located on the antisense chain of human chromosome 11, hg38 chr11:69303412-69303807. In our previous studies, it was identified that lnc-MRGPRF-6:1 was significantly increased in plasma of CAD patients and was related to macrophage polarization-mediated inflammation in AS closely. However, the ox-LDL-induced macrophage ferroptosis in AS has not been revealed entirely. This study aims to investigate the role of lnc-MRGPRF-6:1 in ox-LDL-induced macrophage ferroptosis.5/well and incubating with 100 ng/mL phorbol 12-myristate 13-acetate  for 48 hr. Then, groups were as follows, control group, ox-LDL, ox-LDL + Fer-1, and Erastin group. Macrophages without special treatment were used as the control group. In ox-LDL group, macrophages were incubated with 50 mg/L ox-LDL  for 24 hr. In ox-LDL + Fer-1 group, macrophages were incubated with 50 mg/L ox-LDL and 5 μmol/L Fer-1  for 24 hr. In Erastin group, macrophages were incubated with 5 μM Erastin  for 24 hr to induce ferroptosis. The mitochondrial morphology of macrophages was observed by transmission electron microscopy (TEM). lnc-MRGPRF-6:1 knockdown, overexpression, and negative control lentiviral vectors were purchased from GENECHEM . THP-1 cells were infected with different lentiviral vectors, respectively, for 16 hr at multiplicity of infection of 30 to construct lnc-MRGPRF-6:1 knockdown, overexpression, and control cells. Then, 2 mg/mL puromycin  was used to screen out uninfected cells for 72 hr. RAS-selective lethal compound 3 (RSL-3) was reported as a GPX4 inhibitor. Macrophages were incubated with 5 μM RSL-3  for 24 hr to inhibit the expression of GPX4. All cells were cultured in incubator at 37°C and 5% CO2.THP-1 cells were purchased from Shanghai Institute of Cell Research  and incubated with RPMI Medium 1640  with 10% fetal bovine serum . THP-1-derived macrophages were obtained by inoculating logarithmic growth phase THP-1 cells in six-well plate at 5 × 10In our study, 20 CAD patients and 20 controls were recruited. The inclusion criteria of CAD patients were that any major coronary artery  had ≥50% stenosis as shown by coronary angiography. Another 20 patients with stenosis <50% indicated by coronary angiography were selected as control group. Patients with congenital heart disease, cardiomyopathy, hepatic and renal insufficiency, hematologic diseases, malignant tumor, and other concomitant diseases were all excluded. Ficoll  was used for the isolation of peripheral blood mononuclear cells (PBMCs) from blood. Then, CD14 microbeads  and magnetic beads conjugated with antibodies against human CD14 were used to separate out monocytes. The identification of human monocytes was performed with CD14  immunofluorescent staining. Subsequently, macrophage colony-stimulating factor (M-CSF)  was used to induce the formation of human monocyte-derived macrophages at the concentration of 50 ng/mL for 7 days.The expression of CD14 was assessed by immunofluorescence staining. Human monocytes were fixed in 4% paraformaldehyde  for 15 min and blocked with 3% bovine serum albumin  at room temperature for 30 min. Subsequently, the primary antibody CD14 was used to incubate cells at 4°C overnight. After washed three times with PBS, cells were incubated with Goat Anti-Rabbit IgG  at room temperature for 50 min. DAPI  was used for cellular nuclei staining. Then, all cells were observed with fluorescent microscope .RIPA lysis buffer  was used to lyse macrophages. Firstly, the protein concentration in cell lysis supernatant was detected by protein assay kit . Then, the MDA assay kit , ROS assay kit , LDH assay kit , GSH assay kit , SOD assay kit , and iron assay kit  were used to detect the relevant expression in macrophages according to product manual.Macrophages were stained with oil red staining kit  and then observed and photographed under the microscope .Macrophages were stained with neutral red staining medium  according to product manual. Then, the optical density (OD) value was detected using a microplate reader at 540 nm.ΔΔCt− was used to analyze the relative expression. All the primers were synthesized by GenScript . Detailed primer sequences are shown in Total RNA from cells was extracted by RNA Isolation Kit . RNA was reverse transcribed to cDNA with HIScript ⅢRT SuperMix . RT-qPCR was performed using ChamQ SYBR qPCR Master Mix  on Step One Plus Real-Time PCR System . GAPDH was used as internal reference. Equation 2Lysis buffer  containing 1% protease inhibitor  was used to extract protein. The protein assay kit  was used to detect protein concentration. The equal amount of protein was separated by 10% SDS-PAGE gel and transferred to polyvinylidene fluoride membranes. The membranes were blocked with blocking reagent  for 1 hr followed by incubation with primary antibody GPX4 , ferritin heavy chain (FTH) , and Tubulin  at 4°C overnight. Then, the membranes were incubated with HRP-labeled goat anti-rabbit IgG secondary antibody  for 1 hr at room temperature. The membranes were observed and photographed by Bio-Rad chemiluminescence imaging system after enhanced chemiluminescence solution  was exposed. The image gray value was analyzed quantitatively by Image J 1.8.μL CCK-8 detection reagent  and incubated for 3 hr in incubator and then detected optical density (OD) at 450 nm on the microplate reader .The cell supernatant was replaced with culture medium containing 10 http://www.bgionline.cn).Total RNA was extracted from lnc-MRGPRF-6:1 knockdown macrophages and control, respectively. Transcriptome sequencing was performed by Beijing Genomics Institute (BGI) . Analysis of sequencing was carried out with BGI Online platform , and χ2 test or Yates' correction for continuity was applied. P < 0.05 was considered statistically significant difference.All data were analyzed with SPSS 26.0  and GraphPad Prism 9.0 . Data were reported as mean ± standard deviation. Quantitative data between the two groups were evaluated using Student's Firstly, we constructed the ox-LDL-treated macrophage model to simulate macrophage injury in AS. Erastin-induced ferroptosis was used as positive control. We measured the expression levels of MDA , ROS Fi, LDH Fi, GSH Fi, IRON F, cell viSupplementary 1).It was proven that ox-LDL could induce ferroptosis in macrophage, and the expression levels of MDA, ROS, and LDH were obviously increased. Meanwhile, the expression of GSH and SOD was downregulated. To verify the role of lnc-MRGPRF-6:1 in macrophage ferroptosis, we established the lnc-MRGPRF-6:1 knockdown and overexpression of THP-1-derived macrophage model Figures . We furtSupplementary 1).Subsequently, we isolated human monocytes and established the human monocyte-derived macrophages. The isolated human monocytes were stained with CD14 . It showSupplementary 2). Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway classification analysis of differential genes shows that multiple metabolic processes including lipid metabolism and amino acid metabolism which are associated with ferroptosis could be sorted out  to transferrin to mediate iron transport. TFRC can accelerate iron uptake and ferritin synthesis [However, how lnc-MRGPRF-6:1 regulates ox-LDL-induced macrophage ferroptosis remained to be investigated. Transcriptome sequencing was applied to lnc-MRGPRF-6:1 knockdown macrophages and control macrophages. Fascinatingly, lnc-MRGPRF-6:1 was associated with lipid metabolism pathway, amino acid metabolism pathway, and ferroptosis pathway through KEGG pathway classification and enrichment analysis of differential genes. Combined transcriptome sequencing results with literature findings, SLC7A11, GPX4, ACSL3, ACSL4, TFRC, FTH, FTL, NCOA4 were screened out for RT-qPCR validation. SLC7A11 is known as a transmembrane amino acid transporter which can transport extracellular cystine to intracellular and transport intracellular glutamate to extracellular , 34, 35.ynthesis , 48. As ynthesis . Nuclearynthesis . FascinaEventually, we also investigated the relationship between lnc-MRGPRF-6:1 and GPX4 in subjects. It was demonstrated that lnc-MRGPRF-6:1 was highly expressed in the monocyte-derived macrophages of CAD patients, while the expression of GPX4 was opposite. Furthermore, lnc-MRGPRF-6:1 showed a significant negative correlation with GPX4 through correlation analysis.In summary, our results clarify that ox-LDL-induced cell damage was involved in ferroptosis. Meanwhile, the ferroptosis inhibitor could alleviate lipid peroxidation and the decrease of cell viability induced by ox-LDL. Furthermore, it is demonstrated that lnc-MRGPRF-6:1 can promote ox-LDL-induced macrophage ferroptosis through inhibiting GPX4. Our findings may contribute to the study of pathophysiology in AS and provide new insights into the treatment of AS.


Cnidarian marine species. We further observed ~12h rhythms of intron retention events of genes involved in MHC class I antigen presentation in all three subjects, synchronized to those of mRNA splicing gene expressions in each individual. Gene regulatory network inference revealed XBP1, GABPA and KLF7 as putative transcriptional regulators of human ~12h rhythms. These results thus establish human ~12h biological rhythms have a primordial evolutionary origin and are likely to have far-reaching implications in human health and disease.While circadian rhythms are entrained to the once daily light-dark cycle of the sun, many marine organisms exhibit ~12h ultradian rhythms corresponding to the twice daily movement of the tides. Although human ancestors emerged from circatidal environment millions of years ago, direct evidence of the existence of ~12h ultradian rhythms in humans are lacking. Here, we performed prospective, temporal transcriptome profiling of peripheral white blood cells and identified robust ~12h transcriptional rhythms from three healthy subjects. Pathway analysis implicated ~12h rhythms effecting RNA and protein metabolism, with strong homology to the circatidal gene programs previously identified in  Biological rhythms are conserved from single-cell organisms to humans. The relevance of biological rhythms is best exemplified by circadian rhythms, which are entrained to a ~24-hour cycle by the rotation of the Earth and daily exposure to sun light. Circadian gene expression programs in turn regulate canonical hormonal systems, vasomotor activity, coagulation, amongst other processes, accounting for predilection of certain disease events at specific times of day . GeneticA. diaphana, exhibit ~12h ultradian rhythms, entrained by the twice daily movements of the tides [Our understanding of biorhythms is now expanded by discoveries of alternative, noncircadian rhythms in lower organisms. Coastal marine organisms, such as the sea anemone he tides . Oscillahe tides . However2. Subjects were admitted for a 1-day acclimatization period prior to the 48 hours of blood sampling at 2-hour sampling interval  and translation (such as MRPL27) among the top enriched processes  . We perfrocesses , A and BTo assess the robustness of the uncovered ~12h gene program, we applied an orthogonal rhythm-identification algorithm, RAIN , which dXBP1, GABPA and KLF7 met a higher level of stringency having been identified by both the eigenvalue and RAIN methods. We then performed an analysis of a recently published XBP1 ChIPmentation dataset in mouse T helper cells [Thoc6, Smu1, Snrnp53, Eny2 and Snrpc, as well as Xbp1 itself, Gabpa and Klf7  events, predicting that if the rhythm of RNA splicing genes’ transcription was functionally relevant, it would temporally correlate with global IR. We applied a recently published algorithm iREAD . Using te.g. HLA-A/C/E and B2M), and whereas the evening intron retention gene sets exhibited greater heterogeneity across the three subjects , again highly enriched in mRNA splicing and protein processing pathways , F. To tIn this study, we discovered a ~12h regulatory network in healthy humans, controlling gene programs related to fundamental processes of mRNA and protein metabolism. Remarkably, we found that conservation of ~12h rhythms in humans extends to specific gene orthologs and functional pathways present in marine animals. Our discovery of one such conserved ~12h pathway, ‘mRNA splicing,’ provided opportunity to establish functional significance through identification of corresponding ~12h rhythms in global intron retention events. Due to the presence of ~12h ultradian rhythms of intron retention rhythms and the synchronization of such rhythms with those of mRNA splicing gene expression in both humans and mice, we hypothesize the existence of ~12h stress fluctuations that negatively impact global mRNA splicing efficiency, a term we coin as “splicing stress”. Just as proteotoxic stress increases unfolded/misfolded proteins and the induction of the unfolded protein response (UPR) and/or the integrated stress response (ISR), we speculate that “splicing stress” accounts for the elevation of unspliced/retained introns. Consequently, this may activate an adaptive stress response (orthologous to URP and ISR) to ameliorate the original stress through increased expression of mRNA processing genes. Future efforts are needed to identify underlying mechanisms of the putative mRNA splicing stress response, and whether the ~12h oscillator may couple both proteotoxic and mRNA splicing stress responses.XBP1, which regulates ~12h gene oscillations in mice [XBP1 not only exhibited ~12h rhythmicity in our human subjects but was also implicated by gene regulatory network inferences as a lead candidate regulator of human ~12h gene programs. What adaptive advantage might ~12h rhythms of gene expression confer? We reason that the ancient ~12h rhythms that evolved in marine species in response to tidal cues have been coopted by humans as an adaptive response to accommodate physiological transitions related to feeding, physical activity, and sleep that are temporally concentrated at dawn and dusk.We further demonstrate conservation of a potential master ~12h transcriptional regulator,  in mice . XBP1 noInterestingly, pathway analyses of rhythmic intron retention suggests that one functional consequence of ~12h rhythms in human white blood cells could be rhythmic antigen presentation by splicing of MHC class I gene transcripts. Antigen presentation by MHC class I molecules depends on the ER and Golgi apparatus  - whose within each subject. The likelihood that rhythms uncovered in our study are functionally relevant is enhanced by the commonality of the putative ~12h pathways across all three human subjects and their conservation in organisms ranging from marine animals to humans. While these data provide evidence in support of a ~12h gene program in humans, larger studies will be needed to determine how variable the ~12h programs are in the human population, the degree to which they are sensitive to aging or environmental stressors as observed for circadian rhythms, and most importantly whether disruption of ~12h rhythms is a causal determinant of disease pathobiology. Aside from the identification of ~12h pathways related to fundamental cellular processes, several pieces of evidence suggest that ~12h rhythms are important for maintenance of homeostasis: (i) the ~12h gene program was similar in magnitude to the circadian program; and (ii) prior human studies suggest ~12h rhythms in physiological metrics of relevance to human health and disease, including heart rate variability, blood pressure, hormone levels, and cognitive function [Similar studies of molecular rhythms in model organisms typically require terminal tissue collection and therefore require inclusion of several animals at each time point , 11, in function , 31. As 2. Subjects were excluded if they admitted to nighttime shift work or other regular nighttime sleep-disrupting activities, if they had any chronic medical conditions, took any medications or recreational drugs, or used tobacco products. Potential subjects presented for a screening visit, inclusive of measurement of body weight, height, BMI, and laboratory studies, including a comprehensive metabolic panel , complete blood count, 25-OH vitamin D, and thyroid stimulating hormone level, to screen for potential subclinical chronic diseases. We excluded subjects with low hemoglobin/hematocrit, abnormal thyroid function and individuals with 25-OH vitamin D < 20 ng/mL.The study protocol was approved by the University of Pittsburgh Institutional Review Board  and written consent was obtained from all study participants. We studied 3 healthy male subjects, who were recruited through online advertisements. Inclusion criteria consisted of individuals 18–35 years of age with a self-reported regular nighttime sleep schedule and a body mass index between 18.5–24.9 kg/mQualifying study participants maintained a food diary, which was used to estimate their daily caloric intake and subsequently presented to the University of Pittsburgh Medical Center (UPMC) Clinical Translational Research Center (CTRC) for a 3-day inpatient visit. On the morning of admission, subjects selected items from a food menu designed to match their standard daily caloric intake with a uniform macronutrient composition of 55% carbohydrates, 25% fat, 20% protein per day. No interventions were performed during the first 24-hour period of acclimatization.On the morning of the second day at 8am, an intravenous (IV) line was placed. Blood samples were then collected every two hours for 48 hours . Nighttime blood collection was performed through a long IV line from outside the room so that the study participant would not be exposed to light or woken up during blood collection. Blood was then immediately processed in the Center for Human Integrative Physiology, two floors above the UPMC CTRC by a rotating study team, all of whom were trained in the processing procedures for this study. Blood was centrifuged (1900 RCF × 10 min) and the buffy coats were collected and immediately snap frozen in liquid nitrogen for storage at −80C.™ RNA BR Assay Kit (Thermo Fisher Scientific) followed by the RNA quality check using Fragment Analyzer (Agilent). For each sample, RNA libraries were prepared from 100ng RNA using the KAPA RNA HyperPrep Kit with RiboErase (Kapa Biosystems) according to manufacturer’s protocol, followed by quality check using Fragment Analyzer (Agilent) and quantification by qPCR  on the LightCycler 480 (Roche). The libraries were normalized and pooled, and then sequenced using NovaSeq6000 platform (Illumina) to an average of 40M 101bp paired end reads per sample. Low-quality reads and adapter sequences were trimmed from the raw sequencing data with Trimmomatic [RNA was isolated from peripheral blood buffy coat samples on the automated Chemagic 360 (Perkin Elmer) instrument according to the manufacturer’s instructions. Extracted RNA was quantitated by Qubitmmomatic . The remmmomatic . Gene commomatic .http://www.bioconductor.org/packages/release/bioc/html/rain.html) with either 48h continuous data or 24h data with biological duplicates as input [Averaged FPKM values at each time were used for cycling transcripts identification. Lowly expressed transcripts were removed by calculating the background expression in each subject using the average expression of a panel of 62 genes known not to be expressed in peripheral blood cells. Temporal transcriptomes were subject to linear detrend prior to identification of oscillations by either the eigenvalue/pencil or RAIN methods. For the eigenvalue/pencil method , 9, a maas input . We inclThe eigenvalue method can detect multiple superimposed oscillations. Therefore, we defined a circadian gene as one that exhibited a circadian rhythm, regardless of its amplitude relative to other superimposed oscillations. Similar criteria were applied to other oscillations. As such, a gene can meet criteria for both a circadian and ~12h gene. By comparison, we define a dominant circadian gene as one in which the superimposed circadian rhythm has the largest amplitude among all oscillations. With this definition, dominant circadian and dominant 12h genes are mutually exclusive.Intron retention events were detected by tool iREAD . Intron https://david.ncifcrf.gov) was used to perform Gene Ontology analyses. Briefly, gene names were first converted to DAVID-recognizable IDs using Gene Accession Conversion Tool. The updated gene list was then subject to GO analysis using all Homo Sapiens as background and with Functional Annotation Chart function. GO_BP_DIRECT, KEGG_PATHWAY or UP_KW_BIOLOGICAL_PROCESS were used as GO categories. Only GO terms with a p value less than 0.05 were included for further analysis.DAVID (Version 2021)  (https:/http://lisa.cistrome.org/).Motif analysis was performed with the SeqPos motif tool (version 0.590) embedded in Galaxy Cistrome using all motifs within the homo sapiens reference genome hg19 as background. LISA analysis was performed using webtool (Supplement 1


The growing interest in augmented reality applications has led to an in-depth look at the performance of head-mounted displays and their testing in numerous domains. Other devices for augmenting the real world with virtual information are presented less frequently and usually focus on the description of the device rather than on its performance analysis. This is the case of projected augmented reality, which, compared to head-worn AR displays, offers the advantages of being simultaneously accessible by multiple users whilst preserving user awareness of the environment and feeling of immersion. This work provides a general evaluation of a custom-made head-mounted projector for the aid of precision manual tasks through an experimental protocol designed for investigating spatial and temporal registration and their combination. The results of the tests show that the accuracy ( In recent years, the potential of Augmented Reality (AR) technology to enhance the real world with auxiliary virtual information has become increasingly prominent. To this end, Head Mounted Displays (HMDs) are by far the most studied devices. Their application has been proposed in various fields ranging from industrial quality control and assembly ,2, educaProjected AR, also called spatial AR, lends itself to preserving the user’s awareness of the environment and the feeling of immersion since it does not require any optical interface interposed between the user’s eyes and the surrounding world. In projected AR, physical and digital information are mixed directly into the real world via visible light projectors. As a result, a single projected AR device can be simultaneously experienced by multiple users. However, such devices are mostly static, as they are installed in a fixed position, hence they inevitably constrain the user’s freedom of movement. With the development of increasingly smaller and lighter projectors, new solutions have been proposed to overcome this problem. Nazarova et al., for instance, mounted a tracking and projection module on a collaborative robot to provide immersive and intuitive robot control to the user . HartmanThe term MTP latency was originally used to denote the average time between the instant when a motion occurs and the instant when the corresponding rendering event gets displayed on the display . MTP latency has been extensively studied for HMDs and literature results reveal their major impact on the system’s usability  since hiMeasure the temporal registration error of the HMP in terms of MTP latency.Measure the static spatial registration error in terms of accuracy by evaluating the distance between the actual position of the virtual content and the desired position for perfect alignment in static conditions.Measure how these two errors combine when a user wears the device and uses it to augment a tracked structure in real time.In this work, we propose an HMP built by assembling commercial devices, and we provide a detailed description of the assessment of its spatial and temporal registration together with their influence on the usability of the worn system . The spaAll measurements were taken within the working area accessible to a user who intends to perform manual tasks while wearing the HMP. This area is between 350 mm and 600 mm from the user’s head, with an average value of 475 mm .First, we present the hardware specifics of the HMP together with a brief explanation of the software framework that implements the tracking and the rendering. Then, the experimental protocol employed to evaluate the spatial and temporal registration accuracy and the combined effect of MTP latency and virtual-to-real static registration is described during a user test.The custom-made HMP includes a Leopard Imaging OV580 stereo camera rig and an Anybeam laser mini-projector. The adopted camera configuration is 2560 × 720 @ 60 fps, which corresponds to an angular resolution of about 3.6 arcmin/px. The AnyBeam projector offers the advantage of no need for focus adjustment, as this is ensured by the MEMS laser technology. Projector resolution and brightness are, respectively, 720p @ 60 fps and 150 lumens. The stereo rig and the projector are calibrated to estimate both their intrinsic and extrinsic parameters ,22. The The software, originally conceived for the deployment of AR applications on video see-through (VST) and optical see-through (OST) display interfaces, is capable also of supporting the deployment of AR applications on different typologies of AR projectors. The software features a non-distributed architecture, which makes it also compatible with embedded computing units.The software framework is based on Compute Unified Device Architecture (CUDA by Nvidia) to leverage parallel computing over the multi-core GPU card.The software supports in situ visualization of 3D structures, thanks to the employment of the open-source library VTK for 3D computer graphics, modeling, and volume rendering.The software framework is highly configurable in terms of rendering and tracking capabilities.The software features a robust inside-out video-based tracking algorithm based on OpenCV API 3.4.1,The software framework that controls the HMP was thoroughly described in . Here, wThe software framework is able to support in situ visualization of medical imaging data; the key function of the software, under projector AR modality, is to process the images grabbed by the stereo pair of RGB cameras. The grabbed frames of the real scene are processed to perform marker-based optical tracking, which requires the identification of the 3D position of the markers both in the target reference frame and camera reference frame. The projected AR device needs a dedicated calibration between the world-facing tracking cameras and the projector. For this purpose, the projector is considered as an inverse camera according to the procedure exposed in . Such caThe experimental protocol relies on an external device for the evaluation of spatial and temporal registration accuracy. We selected a GoPro Hero 5 Black camera that features either a 4000 × 3000 photo resolution or a frame rate of up to 240 fps for videos at a 1280 × 720 resolution. As shown in We evaluated the AR spatial registration accuracy as the on-image distance between the location of a real point and its virtual counterpart . For this purpose, we adopted a spatial registration evaluation tool consisting of three spherical markers fixed on a plane featuring two elevated points. The tool was modeled using Creo Parametric 3.0 and printed by rapid prototyping with a 600 dpi X-Y resolution, 1600 dpi Z resolution, and 0.1 mm precision. The two target points were dyed in red to be easily identified in the images as they are the reference points for AR alignment error assessment. The experimental set-up is shown in For the evaluation of MTP latency, we chose to adopt the protocol proposed in . SpecifiTo evaluate how the spatial and temporal registration errors combine whilst the HMP is worn by a user, we adopted the dummy presented in . The dumThe spatial registration error within the working area was 6±0.1 mm . These sFor the temporal registration, the number of frames elapsed between the motion of the evaluation tool and the update of the virtual information is 13±12 ms  This valWe recorded a 25 s clip during the user tests which corresponds to about 6000 frames. Each frame was processed to estimate the centreline of the real and the projected cutting lines. Their Hausdorff distance is plotted in 9±0.2 mm . The regIn terms of perceived user comfort and ergonomics, weight distribution in head-worn displays and projectors is one of the main limiting factors that hinder the widespread adoption of mobile AR devices in the healthcare sector and specifically in image-guided neurosurgery ,31. By wWe proposed a device for projected AR, which can be worn by the user to guide the execution of precision manual tasks while preserving mobility in the working area. Compared to HMDs, our HMP offers the advantages of being simultaneously accessible by multiple users, without altering their awareness of the environment and feeling of immersion. We evaluated the performance of our HMP in terms of spatial and temporal registration along with their mutual interaction in a user test. The latency of 113 ms is a positive result, especially considering that the HMP is not equipped with an IMU sensor, nor with predictive slam algorithms or fast-rendering engines such as the ones adopted in the HoloLens. Specifically, the HMP meets the specifications proposed in  for HMDsTo the best of the authors’ knowledge, our evaluation of spatial and temporal registration, together with their mutual interaction in a user test constitutes the first overall assessment of an HMP for precision manual tasks. We hope that this will provide a reference for further investigation of this and other AR HMPs and HMDs contributing to providing a standard for their performance assessment.


Klebsiella pneumoniae AR 0047 from the CDC and FDA Antibiotic Resistance Isolate Bank is resistant to cefiderocol, a siderophore-conjugated cephalosporin. Genomics analysis and genetic complementation revealed that a frameshift mutation in ompK35 contributed to cefiderocol resistance. Heterologous expression of blaSHV-5 or blaSHV-12 in Escherichia coli increased the host resistance to cefiderocol. Moreover, avibactam, a β-lactamase inhibitor, enhanced cefiderocol activity against the resistant strain. Therefore, cefiderocol resistance is linked to SHV and the loss of ompK35.IMPORTANCE Understanding cefiderocol resistance mechanisms is essential for providing solutions to treat infections and to prevent resistance development. Cefiderocol resistance in Klebsiella pneumoniae AR 0047 is linked to SHV β-lactamase activities and functional loss of outer membrane porin. The cefiderocol-avibactam combination represents an opportunity to increase potency against cefiderocol-resistant pathogens. Enterobacterales are recognized as a threat to public health , as determined by multilocus sequence typing using MLST 2.0 (https://cge.food.dtu.dk/services/MLST/). Antimicrobial resistance genes in K. pneumoniae AR 0047 were identified using the Resistance Gene Identifier (RGI). The resistance genes included blaSHV-5, blaSHV-12, blaSHV-11, blaTEM-1, aac(6′)-Ib10, tet(D), mphA, sul1, aadA2, dfrA12, catI, fosA6, and several antibiotic efflux genes. Genomics analysis revealed that no deletions or early terminations were found in the well-characterized siderophore uptake genes  in K. pneumoniae AR 0047 compared to the reference strain K. pneumoniae ATCC 43816  and truncation in OmpK35. It has been reported that OmpK35 truncation occurred ubiquitously in K. pneumoniae ST258  were identified in the genome of K. pneumoniae AR 0047. However, the contribution of individual β-lactamases to cefiderocol resistance is unknown. Multidrug resistance to commonly used antibiotic selection markers in K. pneumoniae AR 0047 makes it difficult to inactivate multiple β-lactamase genes for functional analysis. Alternatively, we compared the impact of individual β-lactamase genes on cefiderocol susceptibility by heterologous expression in Escherichia coli. E. coli cells carrying the extended-spectrum β-lactamases blaSHV-5 or blaSHV-12 showed an increase in cefiderocol MIC compared to the control strain E. coli TOP10 (blaSHV-5 and blaSHV-12) may contribute to the baseline cefiderocol nonsusceptibility in K. pneumoniae AR 0047.Four β-lactamase genes  and avibactam (4 μg/mL) eradicated almost all bacterial cells . The PCR products were cloned into the pCR-Blunt II-TOPO vector, followed by transformation into chemically competent One Shot TOP10 E. coli cells. The plasmid carrying the wild-type ompK35 was then transferred into K. pneumoniae AR 0047 by electroporation, followed by selection at 50 μg/mL Zeocin. The cefiderocol MICs of confirmed transformants carrying the wild-type ompK35 gene were determined and compared to the MIC of K. pneumoniae AR 0047 without complementation.A point mutation in the outer membrane porin gene K. pneumoniae AR 0047 were identified using the Resistance Gene Identifier (RGI) . There are four β-lactamase genes  in the genome of K. pneumoniae AR 0047. The coding region of blaSHV-5 was amplified from K. pneumoniae AR 0047 using Platinum SuperFi II DNA polymerase and cloned into a pCR-Blunt II-TOPO vector, followed by transformation into chemically competent One Shot TOP10 E. coli cells. The transformants were selected on kanamycin plates. The other three β-lactamase genes, blaSHV-12 from K. pneumoniae AR 0043 and blaSHV-11 and blaTEM-1 from K. pneumoniae AR 0097  was supplemented with the β-lactamase inhibitor avibactam (20 μg). Then, a cefiderocol disk and a cefiderocol-avibactam disk were plated onto Mueller-Hinton agar inoculated with the test strain, followed by incubation at 35°C for 18 h . An incrK. pneumoniae AR 0047 was determined in the presence of avibactam at a fixed concentration of 4 μg/mL. Cefiderocol was used at concentrations from 2 to 32 μg/mL. After 24 h of incubation at 35°C, the bacterial populations were enumerated.The bactericidal activity of cefiderocol against K. pneumoniae AR 0047 is available publicly under accession number GCF_002180085.1.The genome of


Sensors published the most papers. The top keywords included rehabilitation, stroke, and recovery. The clusters of keywords comprised machine learning, specific neurological conditions, and sensor-based rehabilitation technologies. Conclusions: This study provides a comprehensive overview of the current state of sensor-based rehabilitation research in neurological diseases, highlighting the most influential authors, journals, and research themes. The findings can help researchers and practitioners to identify emerging trends and opportunities for collaboration and can inform the development of future research directions in this field.Background: As the field of sensor-based rehabilitation continues to expand, it is important to gain a comprehensive understanding of its current research landscape. This study aimed to conduct a bibliometric analysis to identify the most influential authors, institutions, journals, and research areas in this field. Methods: A search of the Web of Science Core Collection was performed using keywords related to sensor-based rehabilitation in neurological diseases. The search results were analyzed with CiteSpace software using bibliometric techniques, including co-authorship analysis, citation analysis, and keyword co-occurrence analysis. Results: Between 2002 and 2022, 1103 papers were published on the topic, with slow growth from 2002 to 2017, followed by a rapid increase from 2018 to 2022. The United States was the most active country, while the Swiss Federal Institute of Technology had the highest number of publications among institutions.  Neurological diseases, such as stroke, traumatic brain injury, spinal cord injury, Parkinson’s disease, and multiple sclerosis, are major public health concerns. Their global burden is significant, with neurological disorders being the leading cause of disability worldwide according to the World Health Organization and affecting over one billion people ,2.Contributing 11.6% of the global DALYs (disability-adjusted life years) and 16.5% of the deaths from all causes, neurological disorders remain the leading group cause of DALYs and the second leading group cause of deaths in the world . In addiGovernments will have to deal with an increase in the demand for treatment, rehabilitation, and support services for neurological illnesses, as populations are aging, and significantly disabling neurological conditions are more common as people age. Care for these conditions relies heavily on rehabilitation, which aids patients in regaining lost function, enhancing their quality of life, and resuming work and other regular activities.Despite the significant burden of these disorders, there are currently no established or distinct risk factors to focus on for prevention and treatment, emphasizing the need for additional studies and comprehension to create effective strategies . In receSensors are devices that can detect and respond to physical changes, such as changes in temperature, pressure, or movement . They caThe use of sensors in medicine has evolved significantly over the last few decades. Initially, sensors were used primarily to monitor vital signs such as heart rate, blood pressure, and body temperature . HoweverHowever, the use of sensors can also pose significant challenges in terms of data processing and analysis. The large amount of data generated by sensors can be difficult to analyze, especially when dealing with high-dimensional data sets. This can make it difficult to identify patterns and trends in the data and can also make it difficult to visualize the data in a meaningful way.Bibliometrics is a quantitative method for analyzing and measuring the scientific literature. It provides a systematic approach to evaluating research outputs and impacts, identifying emerging trends, and mapping the intellectual structure of a specific field . CiteSpaIn this study, we conducted a bibliometric analysis on sensor-based rehabilitation in neurological diseases, exploring emerging trends, research collaborations, and the intellectual structure. The aim of this study was to identify the current state of the literature on sensor-based neurorehabilitation, explore the trends and patterns in the research, and find potential areas for future research. This bibliometric study used the Web of Science Core Collection (WoSCC) as the source database for data retrieval. The complete data retrieval strategy is illustrated in A total of 1788 original English articles published between 1 January 2002 and 31 December 2022 were screened. The analysis was conducted on 31 December 2022. In the study, the document types that were analyzed and included in the sample consisted of two categories, namely, “article” and “review”. The inclusion of both types of documents allowed for a comprehensive analysis of the current state of knowledge and understanding in the field. Excluded from the analysis were proceedings papers, book chapters, and articles available only as early access. To obtain data for the analysis, the complete details of each article, such as publication outputs, research categories, authors/co-cited authors, countries/institutions, journals/co-cited journals, co-cited references, and keywords, were obtained from the WoSCC database. The bibliometric analysis procedure was conducted in accordance with best practices and guidelines [2 trend analysis.CiteSpace 6.1.R6  was usedCo-occurrence analysis was used to identify the relationships between words in the documents and measure the frequency of their occurrence to reveal the underlying themes. Co-citation analysis was also used to detect the intellectual structure and emerging sensor-based technology among rehabilitation topics from the selected bibliographic data ,24. To evaluate the structural quality of the networks and the clustering organization, three structural metrics were used: the average silhouette score , the modCluster labeling was conducted automatically using two algorithms, the Log-Likelihood Ratio (LLR) and the Latent Semantic Indexing (LSI)  functionWe found 1103 papers on the topic of sensor-based rehabilitation in neurological diseases. The publications included 1003 articles and 100 reviews. As shown in p-value < 0.001). Overall, the exponential growth of publications demonstrated an increasing interest in this field of sensor-based rehabilitation.The linear regression analysis showed that the number of publications increased significantly in the examined decades , accounting for 11.69% of all papers. The highest-ranking journal was the Journal of Neuroengineering and Rehabilitation with 65 publications and an impact factor of 5.208, the only journal in the top 10 with an impact factor greater than 5.000. Six journals had an IF between 5.000 and 3.000, while three journals had an IF < 3.000 (minimum 2.356). A total of 348 journals published papers related to sensor-based rehabilitation in neurological diseases between 2002 and 2022. The top 10 most active journals are shown in Archives of Physical Medicine and Rehabilitation, Journal of Neuroengineering and Rehabilitation, and IEEE Transactions on Neural Systems and Rehabilitation Engineering are the three most co-cited journals.The journals A total of 4777 authors published papers on sensor-based rehabilitation in neurological diseases. A total of 822 references were cited during the 20 years between 2002 and 2022. The 10 top references with the most citations are presented in Journal of Neuroengineering and Rehabilitation published by Patel et al. [The top 20 co-cited references with the strongest citation burst can be observed in l et al.  in 2012.The co-citation cluster map a revealeKeywords may reflect current topics and anticipate forthcoming research boundaries that are more engaging. As shown in In addition, the keywords could be divided in 11 clusters; a list of the clusters with the main keywords are reported in The present study aimed to conduct a bibliometric analysis of the research on sensor-based rehabilitation in neurological diseases published over the past 20 years. The results showed a steady increase in the number of publications over the years, with a significant increase in the last five years, indicating a growing interest in this field. The exponential growth of publications suggests the potential of this area of research to address the challenges of neurological diseases.The subject categories extracted from the Web of Science and mapped with CiteSpace showed that the field of study involves 90 categories. Rehabilitation, biomedical engineering, and electrical engineering were the most frequent categories, indicating the interdisciplinary nature of this field. Other categories, such as neuroscience, clinical neurology, and analytical chemistry, also made significant contributions. This diversity in subject categories suggests that research in this area is not only complex but also requires collaboration and interdisciplinary efforts from experts with a wide range of knowledge and skills, highlighting the interdisciplinary nature of the field. It is crucial for researchers to recognize the importance of collaboration and the exchange of knowledge across different fields to address the challenges and improve the outcomes of sensor-based rehabilitation interventions. The analysis of the countries with the highest number of publications showed that the United States, Italy, and China were the most active countries. This indicates that research on sensor-based rehabilitation in neurological diseases is a global concern, with active participation from multiple countries. The visual network map of collaborations demonstrated a moderate degree of cooperation among the countries.The institutions with the highest number of publications included the Swiss Federal Institute of Technology in Switzerland, Oregon Health & Science University in the USA, and Universitat Zurich in Switzerland. It is noteworthy that the number of institutions involved in sensor-based rehabilitation research in neurological diseases is growing, indicating the increasing interest in and recognition of this field. The inclusion of new institutions in this research area can contribute to the development of new ideas and approaches, as well as promote the dissemination of knowledge and collaboration between different research groups. Thus, it is important to continue tracking the trends and changes in the institutional landscape of this field in order to better understand its evolution and potential future directions.The main active authors identified in this study were from the United States and Italy. This suggests the significant contributions made by these authors to the field of sensor-based rehabilitation in neurological diseases. The fact that the number of publications per author in this discipline was very modest is also significant to notice because it suggests that there are not any dominant or extraordinarily prolific authors in this field. This highlights the need for continued collaboration and interdisciplinary research efforts to advance the field of sensor-based rehabilitation in neurological diseases. The lack of a few standout authors also suggests that progress in this field is the result of the collective efforts of numerous researchers, rather than the work of a small group of individuals. Moreover, the analysis of author and institutional collaborations in this study has revealed a notable lack of strong research groups within the network. According to this result, there is a lot that can be done to create more coherent research groups that span several disciplines. It may be required to prioritize multidisciplinary collaboration and bring together academics with various backgrounds and skill sets in order to form more productive research groups. This can entail dismantling conventional disciplinary boundaries, encouraging interdisciplinary cooperation, and establishing a climate of open communication and knowledge sharing. Additionally, it could be crucial to set up specific research goals and objectives as well as to make sure that everyone in the group is on the same page with regard to the research’s approach and overall vision.Sensors published the most papers, while the Journal of Neuroengineering and Rehabilitation had the highest impact factor. The analysis also identified the three most co-cited journals, namely, Archives of Physical Medicine and Rehabilitation, Journal of Neuroengineering and Rehabilitation, and IEEE Transactions on Neural Systems and Rehabilitation Engineering.The analysis of journals publishing papers related to sensor-based rehabilitation in neurological diseases showed that A stronger knowledge of the trends in a particular study discipline is provided through references with citation bursts. We chose to analyze the references with the strongest citation bursts because they are indicative of publications that have garnered significant attention within the scientific community. These publications are likely to contain groundbreaking research or ideas that have had a significant impact on the field of sensor-based rehabilitation in neurological diseases. A review of wearable sensors and systems with application in rehabilitation, published in the Journal of Neuroengineering Rehabilitation in 2012 [The paper by Patel et al. revealed the strongest burst, lasting 4 years: the paper  in 2012 , is a reQuantifying Real-World Upper-Limb Activity in Nondisabled Adults and Adults with Chronic Stroke, published in Neurorehabilitation and Neural Repair in 2015 [Baily et al. revealed the second-strongest citation burst with the paper  in 2015 . The stuWearable Movement Sensors for Rehabilitation: A Focused Review of Technological and Clinical Advances by Porciuncula et al. [On the other hand, we also chose to examine the references with the most recent bursts because they are indicative of emerging trends or current areas of active research in the field. By analyzing these references, we can gain insights into the most recent advancements and directions of research within sensor-based rehabilitation for neurological diseases. a et al.  is a revA remote quantitative Fugl-Meyer assessment framework for stroke patients based on wearable sensor networks by Yu et al. [Exploring the Role of Accelerometers in the Measurement of Real World Upper-Limb Use After Stroke by Hayward et al. [The other two papers focus on the use of wearable sensor networks for stroke patients. The first paper, u et al. , proposed et al. , exploreSubsequently, we analyzed the 20 references exhibiting the highest citation bursts. Based on our analysis, we found that the majority of references with the strongest citation bursts (13 out of 20) were related to stroke rehabilitation. This suggests that sensor-based rehabilitation is a highly researched area in stroke rehabilitation, with a significant amount of literature available on the topic. Furthermore, 50% (10 out of 20) of the references specifically focused on upper-limb rehabilitation, indicating a strong emphasis on upper-limb rehabilitation after stroke. Finally, we found that 7 out of 20 were review or systematic review papers, highlighting the importance of synthesizing and summarizing the existing literature in this area. An important theme that emerged from the analysis of the references with the strongest citation bursts is the use of Kinect technology in sensor-based rehabilitation ,40,42. TThe analysis of keywords in the bibliometric study of sensor-based technology in rehabilitation for neurological diseases revealed several themes and trends in this field. The most commonly used terms were related to the core concept of rehabilitation, stroke, and recovery, indicating the strong focus on the use of technology to aid in the recovery process of individuals with neurological conditions. Other terms, such as Parkinson’s disease, spinal cord injury, cerebral palsy, multiple sclerosis, and traumatic brain injury, demonstrated the wide scope of neurological diseases being investigated in this field. The importance of walking and gait analysis was also highly prioritized, reflecting the need for accurate and precise measurements in this area of research. The presence of keywords such as “wearable sensors,” “virtual reality,” and “exoskeleton” indicates a growing interest in using technology to monitor and improve mobility and physical activity. Machine learning: Machine learning techniques have become increasingly essential in the analysis and interpretation of data acquired through sensors. These techniques enable the identification of patterns and relationships within the data, which may be difficult or impossible for humans to discern. As a result, machine learning has become a crucial tool in many areas of research, including wearable sensor technology, virtual reality, rehabilitation robotics, and clinical trials, among others . The appTask analysis: Task analysis is a critical aspect of rehabilitation that involves breaking down a specific activity or task into its individual components to understand the physical requirements and limitations of the patient. This analysis helps therapists design personalized therapy programs that target the patient’s specific needs and goals . The appRobot sensing system: A robot sensing system is a set of sensors integrated into a robot to collect data about the robot’s environment and the physical parameters related to its operation. These sensors can include cameras, microphones, force sensors, accelerometers, and others, depending on the specific application of the robot. The data collected by the sensors is used to control the robot’s movements, adjust its behavior, and make decisions based on the information gathered. A well-designed robot sensing system can significantly improve the robot’s functionality, safety, and performance in various applications, such as manufacturing, healthcare, and exploration ,61,62,63Brain–computer interface (BCI): BCI is a technology that allows direct communication between the brain’s electrical activity and an external device, most commonly a computer . BCIs caThe top burst keywords showed emerging topics such as “machine learning”, “deep learning”, “task analysis”, “robot sensing system”, and “brain computer interface”, suggesting that these areas are rapidly evolving and likely to drive new advances in the field and may lead to improved rehabilitation strategies and outcomes for patients and respond to changes in the environment. In particular:The clustering of keywords in this analysis also suggests that there are specific areas of focus within the field, such as Parkinson’s disease, spinal cord injury, and stroke. The largest cluster is focused on machine learning, which is a promising area of research in rehabilitation, as it can be used to identify patterns and trends in patient data and provide personalized feedback to improve outcomes. The continued growth and advancement of machine learning techniques are expected to contribute significantly to the development of new and innovative solutions in the field of biomedical engineering. Human–computer interaction and learning algorithms suggest that researchers are exploring ways to improve the interaction between users and sensor-based systems. These clusters are important because they emphasize the need to design systems that are intuitive and user-friendly for patients affected by neurological disorders.This study has certain limitations that are inherent to bibliometric analysis. First, the data were collected only from the WoSCC database, which may have missed some relevant studies that are present in other databases. Second, only studies in English were included. Third, some recent high-quality works may not have received enough citations, which could lead to an underestimation of their influence. Although the WoSCC database is regularly updated and citation-specific parameters are subject to temporal changes, the influence of time on citation trends is limited.Moreover, the data presented in this paper have limitations that preclude their use for some purposes. The metrics we employed only measure the frequency and performance, not their quality or impact. For example, articles may receive numerous citations for negative reasons, such as being refuted or criticized. Additionally, metrics may distort research by incentivizing researchers to produce papers that are more likely to be cited, rather than those that advance knowledge. Finally, we acknowledge that a bibliometric analysis has its limitations and cannot account for all the nuances and emerging areas of a scientific field. Therefore, our results should be interpreted with caution and not as a definitive representation of the state of the art in the field. Rather, we suggest that our results provide a useful overview of the main trends and topics in the literature, as well as some insights into the gaps and challenges that need further investigation. To overcome some of the limitations of bibliometric analysis, we recommend that future studies complement our approach with other methods, such as the qualitative analysis of the content and context of selected publications, expert interviews to elicit opinions, and perspectives from key stakeholders.The present study provides a comprehensive overview of the research on sensor-based rehabilitation in neurological diseases in the last 20 years. The analysis of journals publishing related papers and references with citation bursts provided insights into the most impactful and groundbreaking research in the field. Overall, this study sheds light on the evolution and potential future directions of the field of sensor-based rehabilitation in neurological diseases. This article contributes to advancing the field of sensor-based rehabilitation and helps to pave the way for future research in this area.Sensor-based rehabilitation is not only a promising research area but also a rapidly growing market that attracts many established and emerging technologies. According to a recent report by Grand View Research, the global wearable medical device (including sensors) market size was valued at USD 21.3 billion in 2021 and is expected to grow at a compound annual growth rate (CAGR) of 28.1% from 2022 to 2030 . Some ofIn the context of targeted neural rehabilitation , we can


Rallus elegans) is a wetland dependent species of conservation concern. Our objective was to gain a better understanding of the breeding habitat associations of King Rails in the Midwestern United States and the relationship of this species to other obligate marsh birds using occupancy and MaxEnt models. To collect data pertaining to occupancy, we placed trail cameras at 50 random points in coastal wetlands in the western Lake Erie basin where calls of King Rails were continuously broadcast at night. Data pertaining to other marsh bird species were collected via call‐broadcast surveys and camera surveys at each sample point. For MaxEnt modeling, we obtained presence data for King Rails and other obligate marsh birds from eBird and habitat data from GIS databases. Trail cameras and call‐broadcast surveys captured 10 detections of King Rails at nine sites, an 18% naive occupancy rate. King Rail occupancy was positively related to amount of interspersion, average water depth, and percent cover of emergent vegetation at local scales within a 5‐m radius. Our MaxEnt models indicated that, at a broader scale, the presence of other rail species such as the Sora (Porzana carolina) may be more important for predicting King Rail presence than other marsh birds or coarse wetland categories such as “emergent vegetation.” Our results could help wetland managers to predict where King Rails occur and to adapt management plans to incorporate King Rail conservation.The King Rail ( Our study is unique in that it builds occupancy and MaxEnt habitat models for King Rails at multiple spatial scales and incorporates data on the presence of other marsh‐obligate birds. We found that King Rail occupancy was associated with local wetland habitat factors and presence of other rails. At a broader spatial scale, our MaxEnt models indicated presence of other rail species was most important for predicting King Rail presence compared to coarse wetland classification categories. Populations around the Gulf of Mexico and southern Atlantic Coast are mainly resident, while the migratory population breeds further inland, extending into the Midwestern United States  and Virginia Rail  are often found in the same wetlands as King Rails . The system was placed on top of a 33‐cm‐tall milk crate to prevent water damage. Speakers were set to play at 80 db when measured from 1 m away . Random points occurred within wetland habitat that was managed in a fashion that could potentially support King Rails and were separated by at least 260 m based on average daily movement of adult King Rails. Points were also temporally separated such that points being simultaneously sampled were separated by 2000 m based on maximum seasonal movement observed in adult King Rails. Movement values came from studies in North Carolina , American Coot (Fulica americana), Common Gallinule , King Rail, Least Bittern (Ixobrychus exilis), Marsh Wren , Pied‐billed Grebe (Podilymbus podiceps), Sora, and Virginia Rail. These surveys, which were included among the repeat visits for occupancy modeling, followed the standard operating procedures outlined by the Great Lakes Coastal Wetland Monitoring Program  variables were used together in models. We first built models that focused on only one group of variables . We then examined and compared these models to gain information about variable importance. Following this, we built and compared models that combined the most important variables from different groups . We built models with a maximum of five habitat covariates in order to maintain degrees of freedom within the bounds of n/K  for each model  using the package unmarked  for modeling. Uncorrelated variables included: proportion of forested wetland within 250 m; proportion of shrub‐dominated wetland within 250 m; proportion of open water within 250 m; proportion of emergent wetland within 250 m; and presence/absence of American Bittern, American Coot, Common Gallinule, Least Bittern, Marsh Wren, Pied‐Billed Grebe, Sora, and Virginia Rail, within 250 m. Following the recommendations of Merow et al. , to compare our models  had constant detection probability and four local‐scale variables informing occupancy . The fitted probability for detection was 16.6%, and the fitted probability of occupancy varied by site , which suggests that King Rails may select for structural attributes of habitat more than an individual plant species. Dense vegetation has been previously associated with King Rail habitat use in our study area  in our top occupancy models and therefore our results should be interpreted with caution  distribution in New Mexico  habitat selection at low population densities ; data curation ; formal analysis ; investigation ; methodology ; project administration ; writing – original draft ; writing – review and editing . Dustin E. Brewer: Supervision ; visualization ; writing – review and editing . Thomas M. Gehring: Conceptualization ; formal analysis ; funding acquisition ; investigation ; methodology ; project administration ; resources ; supervision ; writing – review and editing . Brendan T. Shirkey: Conceptualization ; data curation ; funding acquisition ; investigation ; methodology ; project administration ; resources ; supervision ; writing – review and editing . Kevin L. Pangle: Writing – review and editing . Donald G. Uzarski: Writing – review and editing . Michael A. Picciuto: Data curation . John W. Simpson: Conceptualization ; funding acquisition ; investigation ; resources ; writing – review and editing .We had no competing interests.All applicable ethical guidelines for the use of birds in research have been followed, including those presented in the Ornithological Council's “Guidelines to the Use of Wild Birds in Research” (Fair et al., Figure S1.Click here for additional data file.Table S1.Click here for additional data file.Data S1.Click here for additional data file.Data S2.Click here for additional data file.Data S3.Click here for additional data file.


Natural fibers have some advantages in comparison to synthetic fibers, especially because they are more environmentally friendly. For this reason, using them as a reinforcement for polymeric matrices is growing exponentially. However, they present the disadvantage of having the hydrophilic nature, which strongly reduces the interface interaction. Sedge fibers have been investigated when reinforcing an epoxy matrix in terms of ballistic properties and mechanical performance. Aiming to enhance the fiber−matrix interface, an alkali treatment was proposed. The group conditions were divided into three NaOH concentrations , as well as the three periods of immersion . Therefore, nine different conditions were investigated in terms of their thermal behaviors, chemical structures, physical structures, and morphological aspects. Based on TGA curves, it could be noticed that treatments related to 3% NaOH for 24 h and 48 h exhibited better thermal stability properties. For the time of 48 h, better thermal stability with for a decay of the thermal DSC curve was shown for all treatment conditions. The FTIR spectra has shown a reduction of waxes for higher NaOH concentrations. The XRD diffractogram exhibited an increase in the crystallinity index only for 5% NaOH and an immersion time of 48 h. The morphological aspects of fibers treated with 5% and 10% of NaOH have shown that the treatments have damaged the fiber, which highlighted the crystallinity index reductions. The processing of polymeric matrices reinforced by synthetic fibers requires a great amount of energy. It also displays a harmful effect on the environment generated by pollution. The concern associated with the disadvantages and negative impacts of using these materials has increased. As a consequence, researchers focused their efforts on the past decades to apply natural lignocellulosic fibers (NLFs) as a reinforcement. The reason was due to the distinct characteristics they present. Among the advantages presented by these biological materials over synthetic fibers, it is worth mentioning the easiness of processing, non-toxicity, less abrasiveness, and full biodegradation can reduce the carbon foot of the composite materials and possess relatively high specific mechanical properties ,2,3,4. ATherefore, the employment of NLFs as a reinforcement for thermoplastic or thermoset polymeric resins has become relevant in building ,8, automA strong interaction on the interface of composites is critical for them to disclose higher mechanical properties ,19. A poThis treatment consists of immersing fibers in an aqueous NaOH solution, previously establishing the concentration and the immersion time. Nevertheless, a high alkaline concentration or period of exposure excessively increases NLFs delignification, which leads to weaker or damaged fibers, as well as diminishing their mechanical performance . For thiLuffa cylindrica which was immersed in a 2% NaOH alkaline solution or even the sisal [Several studies have related that chemical treatments, including alkaline, induce a decrease in the tensile strength of fibers. This might be assigned to damage present on the cell wall and the exceeding removal of lignin and hemicellulose that act as a matrix phase in NLFs structures ,28,29. Nhe sisal . It alsohe sisal . Thus, ihe sisal ,33.Cyperus malaccensis) or sedge for short discloses a relatively good Izod impact energy when applied as a reinforcement for an epoxy matrix [The seven-islands-sedge  was performed to verify if a reduction of the moisture absorption and a thermal stability enhancement occurred. Furthermore, morphological analysis was conducted by scanning electron microscopy (SEM) to confirm if the surface roughness increased partial removal of the structural components. The Fourier-transform infrared spectroscopy (FTIR) analysis allowed checking the absence of the components in the chemical structure and possible interaction with Na. At last, an investigation of the fiber structure has been performed by the X-ray diffraction (XRD), where the crystallinity index, novel peaks related to cellulose, and the crystallite size were evaluated.CM sedge fibers were extracted from as-received stalks acquired by a company known as Artevale in São Paulo, Brazil. The stalks were manually cleaned and then immersed in deionized water for 24 h, to provide greater flexibility and easier defibration. The manual extraction of fibers was performed using a sharp stiletto to carefully separate them from the stalks, which were originally obtained by the commercial supplier from the plant stem. The fiber bundle was cut to approximately 900 mm in length and dried in an oven at 70 °C for 24 h. These fibers were not subjected to any chemical treatment. Before the coating processing, the fiber bundle was cut to 150 mm.w/v) NaOH were prepared with distilled water. At first, the clean and dried sedge fibers were soaked and immersed in an alkali solution at room temperature for the proposed times without stirring. After 24, 48, or 72 h, the sedge fibers were then washed several times with distilled water to neutralize the remaining NaOH on the surface of the fibers and then dried at 80 °C in an oven for 24 h.Furthermore, the sedge fibers were subjected to NaOH alkaline treatment in different conditions, as shown in TGA was conducted to supplement previous results without NaOH treatment . The sedDSC analyses of the composites were also performed to supplement previous results without NaOH treatment. The fibers were comminuted and placed in a platinum crucible. A model DTG-60H  was used, with a heating rate of 10 °C/min starting at 30 up to 600 °C, on a nitrogen atmosphere with a gas flow of 50 mL/min.−1. Fourier-transform infrared spectroscopy (FTIR) analysis was performed on a model IRPrestige-21 . The sedge fibers were grounded in the required powder condition to produce the KBr sample tablets. Then, they were scanned from 4000 to 400 cmIc) and the crystallite size (CS) of the sedge fibers were calculated from the diffractogram obtained by X-ray diffraction (XRD). To calculate the fiber Ic, the proposed method by Segal et al. [The crystallinity index , scanning from 5° to 75°, a current of 40 mA, and a voltage of 40 kV. For the calculation of the CS, the method used was established by Scherer’s relations as expressed by the equation below [K is the constant (0.89); λ corresponds to the intensity of radiation; β denotes the full-width at half-maximum (FWHM); and θ is the Bragg’s angle.A PANalytical X’pert Pro MRD diffractometer, with a cobalt anode (0.1789 nm), was used with the following parameters to obtain the diffractogram: a scan rate of 0.05 . The equipment operated with a secondary electron detector at an acceleration voltage between 9 and 10 kV. The fiber was platinum-coated in the equipment in order to create an electron current, so that images illustrating the mechanisms of failure could be observed with a higher resolution and few artifacts.It could be observed that the fiber mass losses for all treatments at temperatures up to 200 °C were around ~12%, due to the evaporation of the moisture content on the surface of the fibers. The untreated sedge fibers have shown a mass loss of 13.23% , which wonset values found for 24, 48 and 72 h of the sedge-treated fibers were slightly lower when compared to those of the untreated fibers. As for the maximum rate, all treatments presented to be slightly higher, indicating higher thermal stability at higher temperatures. Furthermore, it could be observed that in all treated fiber concentrations the hemicellulose content was decomposed within a range of 240–360 °C. This behavior is in accordance with other reports in the literature [The Tterature .onset region resulted in mass losses around ~58% for all NaOH concentrations of 3%, 5%, and 10%. The untreated sedge fiber showed a slightly higher mass loss, indicating that the treated fibers presented better thermal stability at higher temperatures. The third stage ranged from 300 to 590 °C for all the treated sedge fibers and resulted in a total mass loss around ~95% for the 3%, 5%, and 10% NaOH concentrations. The final mass loss occurred at higher temperatures for the treated fibers when compared to that found for the untreated sedge fibers at 496 °C. Further, after this range, no degradation and mass loss occurred until the end of the test at 600 °C, due to the ash content present.The sudden mass drop starting at the TIt is extensively known that the final stage of degradation is directly associated with the elimination of lignin, within a range of 560–580 °C for all conditions. Observing all the treatments for different durations of time, it can be noted that the treatments related to 3% NaOH for 24 h and 48 h exhibited better thermal stability properties. Furthermore, the group treated with 3% NaOH for 48 h showed that the lignin present did not fully decompose. For this reason, it can be selected for its use as a reinforcement for composites. Furthermore, previous results incorporating untreated sedge as a reinforcement for an epoxy matrix showed that the composites disclose poor thermal stability when compared to the neat epoxy . This reDSC plots of treated sedge fibers shown in The endothermic peak noticed ranging from 81 to 92 °C in The endothermic peak noticed ranging from 69 to 72 °C in Comparing all the tests, the sedge fibers treated with NaOH at a concentration of 3% obtained low values of the thermal curves when compared with those treated with 5% and 10% NaOH. In addition, the untreated fibers showed lower values than those with the 3% NaOH treatment . Under t−1. The region at 3453−3489 cm−1 indicates bands of O-H functional groups in cellulose. The band at 2915−2915 cm−1 is identified as the C-H stretching of cellulose [−1 is assigned to the bond between organic molecules and wax compounds in the fiber surface [−1 is related to C=O aromatic groups in the lignin component present in the sedge fibers [−1 can be related to the CH3 symmetric bending according to [−1 is associated with C-O stretching vibrations, and the band at 674 cm−1 is related to C-C stretching. It could be stated that the treatment in the conditions investigated was not enough to reduce the content of hemicellulose and lignin, although the peak related to wax content was absent at the 10% NaOH treatment. surface . The come fibers . The banrding to . The ban−1 indicated bands of O-H functional groups in cellulose. The band at 2361−2367 cm−1 is assigned to the bond between organic molecules and wax compounds in the fiber surface, which is almost absent for the 5% NaOH condition [−1 is related to C=O aromatic groups in lignin and hemicellulose components present in the sedge fibers [−1 can be related to the CH3 symmetric bending according to [−1 is associated with C-O stretching vibrations, and the band at 664−955 cm−1 is related to the C-C stretching. It could be stated that the treatment in the conditions investigated was not enough to reduce the content of hemicellulose and lignin, although the conditions of 24 h presented stronger peaks related to the C=O aromatic groups.In ondition . The peae fibers . It can rding to . The ban−1 indicated bands of O-H functional groups in cellulose. The band at 2921−2927 cm−1 is identified as the C-H stretching of cellulose [−1 is assigned to the bond between organic molecules and wax compounds in the fiber surface [−1 is related to C=O aromatic groups in lignin and hemicellulose components present in the sedge fibers [−1 can be related to the CH3 symmetric bending according to [−1 and 1034 cm−1 are associated with C-O stretching vibrations, and the band at 664−955 cm−1 is related to the C-C stretching. It could be stated that the treatment in the conditions investigated was not enough to reduce the content of hemicellulose and lignin, although the conditions of 24 h presented stronger peaks related to the C=O aromatic groups.In ellulose , and the surface . The peae fibers . It can rding to . The ban−1 band stood out in comparison with the untreated fiber [For all treatments of different percentages and times, the disappearance of the 1731 cmed fiber . This baed fiber .SEM images for the alkali-treated fibers are shown in The work evaluated the effect of chemical treatment with NaOH on natural sedge fibers. Different concentrations of immersion with 3%, 5%, and 10% of NaOH with different times of 24, 48, and 72 h presented parameters that can be applied for obtaining better properties of the sedge fiber in polymeric composites.TGA/DTG analysis revealed mass loss type results up to 200 °C, at the end of the second stage, and up to 600 °C, in addition to the initial degradation and the maximum degradation rate. Comparing all the tests, the sedge fibers treated with NaOH at a concentration of 3% obtained the lower values of the thermal curves when compared with those under 5% and 10% NaOH treatments. In addition, the untreated fibers showed lower values than those with the 3% NaOH treatment. Under the time of 48 h, better thermal stability with a decay of the thermal curves was shown for all treatment conditions.−1 band stood out in comparison with the untreated fiber. This band is associated to the stretching of ester and carboxyl groups (C-O compound) present in hemicellulose. The increase in crystallite size favored resistance to moisture absorption and chemical reactivity of sedge fibers; a higher concentration of NaOH could lower the content of α cellulose, since strong degradation occurred by intracrystalline swelling.DSC analysis showed the endothermic and exothermic peaks that better clarified the degradation of cellulose and hemicellulose and volatilization of lignin and wax present in the structure of the sedge fiber. For all treatments of different concentrations and times, the disappearance of the 1731 cmSEM images for the fibers treated with alkali showed that there was not as much presence of hemicellulose, wax, impurities, and lignin as shown for the fibers treated with 3% NaOH in different periods of time. Under conditions of 5% and 10% NaOH, damages on the surface of the fiber and greater extension of voids were present. For this reason, the lowest (3%) NaOH concentration has the potential to enhance composites reinforced by this fiber.


Despite well-defined clinical phenotypes of chronic rhinitis, the underlying in-depth pathophysiological mechanism, particularly with reference to the involvement of immune mediators, genetic, and environmental factors, are still not fully understood. Therefore, our aim was to give updated information on the pathogenesis of allergic rhinitis (AR), with an emphasis on the role of cytokines in adults aged 18 years and above. Additionally, we investigated the impact of genetic and environmental factors in the pathogenesis of AR.A search in various databases identified 1,178 records, and 18 studies were ultimately selected from January 2018 to April 2023. The total sample size in our studies was 4,317, with 2,186 in the experimental and 2,131 in control groups, respectively. The mean age was 33.4 years, with 43% were male, while 57% were female. According to the selected studies, various factors, including immune mediators, particularly cytokines, genetic, and environmental factors, were identified in the development of AR.The selected studies presented findings on different factors and sub-factors in the pathogenesis of AR, making it a challenge for us to compare their results. However, based on our findings, researchers can link our identified factors to potential therapies for AR. UnfortuThe pathogenesis of chronic rhinitis is linked to immune mediators, environmental, genetic, and epigenetic factors. However, the available data is insufficient to draw definitive conclusions about the involvement of these factors particularly in AR . The avaThe prevalence of AR varies among studies due to the lack of an acceptable definition for both conditions , 9. A reHowever, despite well-defined clinical phenotypes of chronic rhinitis, the underlying pathophysiological mechanism, particularly with reference to the involvement of cytokines, genetic, and environmental factors, is still not fully understood . The sig2.On May 02, 2023, a literature search was conducted based on PRISMA  guidelines. The search included relevant articles published between 2018 and 2023 in PubMed, Scopus, Wiley online library, and Google Scholar. Keywords such as Rhinitis, Chronic rhinitis, Allergic rhinitis, Non-Allergic Rhinitis, Pathophysiology, Etiology, Mechanism, Environmental factors, Epigenetic factors, Inflammatory Mediators, Inflammatory Biomarkers, Cytokines, Interleukin, Interferon, Chemokines, and Immune mediators were used in various combinations. The searches were conducted separately for each primary database using Boolean operators (AND) and (OR) in combination with Medical Subject Subheadings (MeSH) terms and key text words.Our inclusion criteria include controlled trials that investigated the role of cytokines, genetic factors, and environmental factors in the pathogenesis of AR. Experimental or animal studies, non-English language studies, non-peer-reviewed studies, conference abstracts, papers, letters, and unpublished manuscripts were excluded. Likewise, studies that investigated the pathogenesis for coexistence of AR with other diseases were also excluded.The potential studies were initially screened based on their abstracts and article titles. Subsequently, full-text articles of potential studies were evaluated by two independent researchers. Any discrepancies were discussed until a consensus was reached to ensure the accuracy of the research. We utilized descriptive statistics, such as mean and median, to obtain summary measures.3.3.1.A search was conducted in databases as well as other sources like relevant journals and bibliographic searches, resulting in the identification of 1,178 records. After a screening process based on titles, abstracts, and full-text articles, 103 articles were screened. Out of the 103 articles, 85 were excluded for not meeting the inclusion criteria, such as not being a controlled trial, involving patients under 18 years of age, studied only the correlation of different factors in the pathogenesis of AR with drugs, or was centered on the pathogenesis non-allergic rhinitis or mixed rhinitis. In the end, 14 studies from January 2018 to April 2023 were ultimately selected. These studies were chosen based on their relevance to immune mediators i.e., cytokines, genetic factors, and environmental factors in the pathogenesis of AR. The PRISMA flow chart in 3.2.The studies selected for analysis comprised of seven conducted in China, three in Iran, and one each in Turkey, Malaysia, Romania, and Australia. Out of the 14 selected studies, four were cross-sectional, five were case-control, two were comparative studies, and three were genome-wide association studies (GWAS). The total sample size for these studies was 4,317, with 2,186 in the experimental and 2,131 in the control groups, respectively. The mean age was 33.4 years with 43% were male, while 57% were female. Various diagnostic criteria were used for the diagnosis of AR, including clinical examination, allergic rhinitis and its impact on asthma (ARIA) guidelines , and ski3.3.Due to the heterogeneity in the outcomes of the selected studies, we divided the analysis into three subheadings to ensure a comprehensive evaluation as.3.3.1.While various immune mediators have been reported to play a role in the pathogenesis of AR, it is not feasible to cover all of them in a single study. Though we mainly focused on essential mediators of cytokines, along with subtypes for our analysis. However, we also considered other relevant mediators in our study if considered important. We identified five studies from 2018 to 2023 that focused on these immune mediators in the pathogenesis of AR.The outcomes of these five studies on the pathogenesis of AR indicate that patients with AR had higher serum levels of CCL3, RvE1, and LTB4, but a lower ratio of RvE1 and RvD1 to LTB4, IL-10, and TGF-β cytokines. Additionally, AR patients had more CD4+ T cells and higher levels of IL-10, IL-6, and IFN-γ, but lower levels of Th1 and Th17 subsets with chemokine receptors. There were no significant differences in IL-25 and IL-33 levels between fungal and non-fungal AR. Furthermore, IL-17, IL-22, and TGF-β levels were higher in patients with AR, while IFN-γ levels were lower compared to the control group –17. The 3.3.2.There were ten studies that focused on the genetic pathogenesis of AR. Due to the wide range of genetic and epigenetic factors studied, it was not possible to draw a single conclusion for any particular factor in the pathogenesis of AR. The research showed a link between the IL1RL1 gene markers rs72823628, rs950881, and rs3771175, and a lower likelihood of AR. In the AR group, genes connected to allergies were more active in nasal tissue, with 113 genes exhibiting differential expression in peripheral blood samples and 14 genes in nasal lysate samples. Long non-coding RNA GAS5 (lnc-GAS5) showed an inverse relationship with its targets (miR-21 and miR-140) in AR, all of which correlated with disease risk, symptom severity, and Th1/Th2 imbalance. The AA genotype of rs1965708 was associated with a heightened AR risk. The expression of CST1, TFF3, ITLN1, and rs754466 in DLG5 were linked to lower susceptibility to house dust mite-induced AR. T-B cell interaction, bridged by CD23 expression, was involved in AR progression. However, no significant association was found between the IL-13 rs20541 polymorphism and AR . The out3.3.3.We identified only one study that examined the impact of environmental factors in relation to AR. This study assessed the mRNA expression levels of various tight junctions, including occludin (OCLN), claudin-3 and −7 (CLDN3 and CLDN7), desmoglein 3 (DSG3), and thymic stromal lymphopoietin (TSLP) in 30 individuals with Allergic Rhinitis (AR) and 30 non-allergic controls. The research found a significantly lower expression of OCLN, CLDN3, and CLDN7 transcripts in AR sufferers compared to the non-allergic control group. However, no noticeable variances were seen in the DSG3 or TSLP transcript expression between the two groups. The study also revealed an association between urban areas and decreased OCLN expression, and a correlation between second-hand smoke exposure and lower CLDN7 expression in AR patients. Ultimately, the conclusion was drawn that decreased expression of OCLN and CLDN7, connected to urban settings and second-hand smoke exposure, may be contributing to the impaired nasal epithelial barrier seen in AR patients, supporting recent studies positing air pollution as a possible cause of AR .4.Chronic rhinitis, and AR in particular, is a major global health concern that affects approximately 400 million people worldwide. The prevalence of AR has been on the rise due to increased urbanization and exposure to environmental pollutants, which are believed to be among the leading causes of the disease. Developing effective therapies for chronic rhinitis requires a thorough understanding of its complex pathophysiology, including various contributing factors . TherefoAlthough literature reviews on AR are available, many of them are focused on either single pathology or based on a single pathogenic factor only , 30, 31.In our study, we have identified several cytokines that were reported in the included studies for their involvement in the pathogenesis of AR. The findings from the studies indicate that individuals with AR tend to have elevated levels of certain immune mediators such as CCL3, RvE1, LTB4, CD4+ T cells, IL-10, IL-6, IL-17, IL-22, and TGF-β, but reduced levels of the RvE1 and RvD1 ratio to LTB4, Th1 and Th17 subsets with chemokine receptors, and IFN-γ –17.The role of Cytokines and Chemokines was described in various previous studies. AR is categorized as a type 2 inflammation mediated disease. The pathology of AR involves interleukins 4, 5, and 13, which play significant roles . The typFurthermore, there are indications that the pathophysiology of AR may encompass other pathways, specifically involving the regulation of Th2 cytokine responses by cytokines expressed in the epithelial cells. These cytokines include thymic stromal lymphopoietin, IL-25, and IL-33 . We haveChemokine (C-C motif) ligand 3 (CCL3), also known as macrophage inflammatory protein 1-alpha , is a protein that in humans is encoded by the CCL3 gene and plays a role in inflammatory responses through binding to the receptors CCR1, CCR4 and CCR5 . CCL3 stEndogenous lipid mediators known as Resolvins, specifically Resolvin E1 (RvE1) and Resolvin D1 (RvD1), are identified for their positive influence on resolving inflammation . RvE1 haSimilar to the focus on cytokines, most of our studies also concentrated on examining the role of genetic factors, specifically in AR. The findings indicated an increase in the expression of allergy-related genes in the nasal mucosa, CD23 expression during T-B cell interaction, and TNF-induced HDAC11 expression. However, the IL1RL1 gene variants, namely rs72823628, rs950881, and rs3771175, were associated with a lower risk of developing AR –26. A reOur review has some limitations that should be addressed in future research. Firstly, the studies included in our review varied in terms of their objectives, methodology, and findings. Similarly, the studies focused on different sub-factors, making it difficult to compare their results. Therefore, future studies should focus on one aspect at a time to obtain more conclusive results. Furthermore, based on our findings, researchers should link these mechanisms to potential therapies for AR and mixed rhinitis.5.Various factors, including immune mediators particularly cytokines, genetic, and environmental factors, are involved in the development of AR. However, the studies presented findings on different factors and sub-factors, making it challenging for us to compare their results. Therefore, future studies should focus on one aspect at a time to obtain more conclusive results. Additionally, researchers should connect these mechanisms to potential treatments for AR and mixed rhinitis based on our findings.