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Abstract The monocyte-to-Apolipoprotein A1 ratio (MAR) emerges as a potentially valuable inflammatory biomarker indicative of metabolic dysfunction-associated fatty liver disease (MASLD). Accordingly, this investigation primarily aims to assess the correlation between MAR and MASLD risk. A cohort comprising 957 individuals diagnosed with type 2 diabetes mellitus (T2DM) participated in this study. The relationship between MAR and MASLD was analyzed through binomial logistic regression analysis and restricted cubic splines (RCS). Furthermore, a comparative assessment of MAR and monocyte to high-density lipoprotein ratio (MHR) in identifying MASLD efficacy was conducted using receiver operating characteristic curve analysis. Remarkably, even after adjusting for metabolic parameters and hepatic functional markers, MAR stood out as an independent predictor for MASLD (OR 1.58, 95% CI 1.36–1.84; P

Abstract Modern facial surgical planning and therapeutic strategies rely heavily on the precise segmentation of the nasal cavity and paranasal sinuses from computed tomography (CT) images for quantitative analysis. Nevertheless, manual segmentation is labor-intensive and prone to inconsistencies, highlighting the need for automatic segmentation methods. A significant challenge in this field is the lack of publicly available clinical datasets for research. To address this issue, we introduce NagalSeg, the first large-scale, publicly available dataset for nasal cavity and paranasal sinus segmentation. In comparison to existing nasal structure segmentation datasets, which are either private or small-scale, NagalSeg stands out as the first publicly accessible dataset. It provides an order of magnitude more labeled data, consisting of 130 3D CT scans with pixel-wise annotations of five anatomical structures: the left nasal cavity, right nasal cavity, nasopharynx, left maxillary sinus, and right maxillary sinus. The NagalSeg dataset serves as an open-access resource to facilitate the development and evaluation of segmentation algorithms and promote future in-depth research towards the clinical application of artificial intelligence methods.

Abstract Thyroid cancer is the most common type of endocrine cancer, and most patients have a good prognosis. However, the thyroid cancer differentiation status strongly affects patient response to conventional treatment and prognosis. Therefore, exploring the molecular mechanisms that influence the differentiation of thyroid cancer is very important for understanding the progression of this disease and improving therapeutic options. In this study, SETMAR as a key gene that affects thyroid cancer differentiation is identified. SETMAR significantly regulates the proliferation, epithelial‐mesenchymal transformation (EMT), thyroid differentiation‐related gene expression, radioactive iodine uptake, and sensitivity to MAPK inhibitor‐based redifferentiation therapies of thyroid cancer cells. Mechanistically, SETMAR methylates dimethylated H3K36 in the SMARCA2 promoter region to promote SMARCA2 transcription. SMARCA2 can bind to enhancers of the thyroid differentiation transcription factors (TTFs) PAX8, and FOXE1 to promote their expression by enhancing chromatin accessibility. Moreover, METTL3‐mediated m6A methylation of SETAMR mRNA is observed and showed that this medication can affect SETMAR expression in an IGF2BP3‐dependent manner. Finally, the METTL3‐14‐WTAP activator effectively facilitates the redifferentiation of thyroid cancer cells via the SETMAR‐SMARCA2‐TTF axis utilized. The research provides novel insights into the molecular mechanisms underlying thyroid cancer dedifferentiation and provides a new approach for therapeutically promoting redifferentiation.

Abstract Idiopathic pulmonary fibrosis (IPF) is a progressive disease characterized by severe lung fibrosis and a poor prognosis. Although the biomolecules related to IPF have been extensively studied, molecular mechanisms of the pathogenesis and their association with serum biomarkers and clinical findings have not been fully elucidated. We constructed a Bayesian network using multimodal data consisting of a proteome dataset from serum extracellular vesicles, laboratory examinations, and clinical findings from 206 patients with IPF and 36 controls. Differential protein expression analysis was also performed by edgeR and incorporated into the constructed network. We have successfully visualized the relationship between biomolecules and clinical findings with this approach. The IPF-specific network included modules associated with TGF-β signaling (TGFB1 and LRC32), fibrosis-related (A2MG and PZP), myofibroblast and inflammation (LRP1 and ITIH4), complement-related (SAA1 and SAA2), as well as serum markers, and clinical symptoms (KL-6, SP-D and fine crackles). Notably, it identified SAA2 associated with lymphocyte counts and PSPB connected with the serum markers KL-6 and SP-D, along with fine crackles as clinical manifestations. These results contribute to the elucidation of the pathogenesis of IPF and potential therapeutic targets.

Abstract Multiple evidence indicates that perinatal factors make impact on immune development and affect offspring allergic rhinitis (AR) risk. In this systematic review and meta-analysis, we examined available published studies to clarify the relationship between cesarean section (C-section) and offspring AR in children. To explore the relationship between C-section, especially the special attention was paid to different cesarean delivery mode, and the risk of AR in children. Articles were searched using PubMed, Web of Science, EMBASE, Cochrane Library, China knowledge Network, Wanfang, and China Science and Technology Journal databases. A meta-analysis of 22 studies published before August 1, 2022, which included 1,464,868 participants, was conducted for statistical analysis with RevMan5.4. The correlation strength between C-section and offspring AR was determined by combining odds ratio (OR) and 95% confidence interval (95% CI). Meta-regression and subgroup analyses were used to explore potential sources of heterogeneity. Publication bias was detected using the funnel chart and Egger tests. Meta-analysis revealed that there was a significant correlation between C-section and children AR (OR = 1.19, 95% CI: 1.12–1.27, P

Abstract The generation of functional β-cells from human pluripotent stem cells (hPSCs) for cell replacement therapy and disease modeling of diabetes is being investigated by many groups. We have developed a protocol to harvest and aggregate hPSC-derived pancreatic progenitors generated using a commercially available kit into near uniform spheroids and to further differentiate the cells toward an endocrine cell fate in suspension culture. Using a static suspension culture platform, we could generate a high percentage of insulin-expressing, glucose-responsive cells. We identified FGF7 as a soluble factor promoting aggregate survival with no inhibitory effect on endocrine gene expression. Notch inhibition of pancreatic progenitor cells during aggregation improved endocrine cell induction in vitro and improved graft function following implantation and further differentiation in mice. Thus we provide an approach to promote endocrine formation from kit-derived pancreatic progenitors, either through extended culture or post implant.

Abstract Multidrug-resistant Pseudomonas aeruginosa (MDRP) is one of the most important pathogens in clinical practice. To clarify the mechanisms contributing to its emergence, we isolated MDRPs using the P. aeruginosa PAO1, the whole genome sequence of which has already been elucidated. Mutant strains resistant to carbapenems, aminoglycosides, and new quinolones, which are used to treat P. aeruginosa infections, were isolated; however, none met the criteria for MDRPs. Then, PAO1 strains were exposed to these antimicrobial agents in various orders and the appearance rate of MDRP varied depending on the order of exposure; MDRPs more frequently appeared when gentamicin was applied before ciprofloxacin, but were rarely isolated when ciprofloxacin was applied first. Exposure to ciprofloxacin followed by gentamicin increased the expression of MexCD-OprJ, an RND-type multidrug efflux pump, due to the NfxB mutation. In contrast, exposure to gentamicin followed by ciprofloxacin resulted in more mutations in DNA gyrase. These results suggest that the type of quinolone resistance mechanism is related to the frequency of MDRP and that the risk of MDRP incidence is highly dependent on the order of exposure to gentamicin and ciprofloxacin.

Abstract Patients with multiple myeloma, an incurable malignancy of plasma cells, frequently develop osteolytic bone lesions that severely impact quality of life and clinical outcomes. Eliglustat, a U.S. Food and Drug Administration-approved glucosylceramide synthase inhibitor, reduced osteoclast-driven bone loss in preclinical in vivo models of myeloma. In combination with zoledronic acid, a bisphosphonate that treats myeloma bone disease, eliglustat provided further protection from bone loss. Autophagic degradation of TRAF3, a key step for osteoclast differentiation, was inhibited by eliglustat as evidenced by TRAF3 lysosomal and cytoplasmic accumulation. Eliglustat blocked autophagy by altering glycosphingolipid composition whilst restoration of missing glycosphingolipids rescued autophagy markers and TRAF3 degradation thus restoring osteoclastogenesis in bone marrow cells from myeloma patients. This work delineates both the mechanism by which glucosylceramide synthase inhibition prevents autophagic degradation of TRAF3 to reduce osteoclastogenesis as well as highlighting the clinical translational potential of eliglustat for the treatment of myeloma bone disease.

In recent decades, global seismic observations have identified increasingly complex anisotropy of the Earth’s inner core. Numerous seismic studies have confirmed hemispherical variations in the inner core’s anisotropy. Here, based on ab initio molecular dynamics calculations, we report how the anisotropy of hexagonal close-packed (hcp)-iron, under inner core conditions, could be altered when alloyed with light elements. We find that light elements in binary allows with iron — hcp-Fe-X (X = C, O, Si, and S) — could have significant effects on density, sound velocities, and anisotropy, compared with the behavior of pure hcp-iron; the anisotropy of these binary alloys depends on combined effects of temperature and the particular alloying light element. Furthermore, the change in anisotropy strength with increasing temperature can be charted for each alloy. Alloying pure iron with some light elements such as C or O actually does not increase but decreases core anisotropy at high temperatures. But the light element S can significantly enhance the elastic anisotropy strength of hcp-Fe.

Abstract In vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) is associated with an increased risk of preterm (33rd–37th gestational week) and early preterm birth (20th–32nd gestational week). The underlying general and procedure related risk factors are not well understood so far. 4328 infertile women undergoing IVF/ICSI were entered into this study. The study population was divided into three groups: (a) early preterm birth group (n = 66), (b) preterm birth group (n = 675) and (c) full-term birth group (n = 3653). Odds for preterm birth were calculated by stepwise multivariate logistic regression analysis. We identified seven independent risk factors for preterm birth and four independent risk factors for early preterm birth. Older (> 39) or younger (

Abstract Antibody‐based therapies could be led astray when target receptors are expressed on nontarget sites, and the on‐target toxicity poses critical challenges to clinical applications. Here, a biomimetic indirect active targeting (INTACT) strategy is proposed based on receptor expression disparities between nontarget sites and the targets. By prebinding the antibodies using cell membrane vesicles with appropriate receptor expressions, the INTACT strategy could filter out the interactions on nontarget sites due to their inferior receptor expression, whereas ensure on‐demand release at the targets by competitive binding. The strategy is verified on CD47 antibody, realizing drastic alleviation of its clinically concerned hematotoxicity on a series of animal models including humanized patient‐derived xenograft platforms, accompanied by preferable therapeutic effects. Furthermore, the INTACT strategy proves extensive applicability for various systems including antibody, antibody–drug conjugate, and targeted delivery systems, providing a potential platform refining the specificity for frontier antibody‐related therapies.

BackgroundCOVID-19 and influenza A can cause severe respiratory illness. Differentiating between the two diseases and identifying critically ill patients in times of epidemics become a challenge for frontline medical staff. We sought to investigate whether both diseases and their severity could be recognized by routine blood parameters.MethodsOur retrospective study analysed the clinical data and first-time routine blood parameters of 80 influenza A patients and 123 COVID-19 patients. COVID-19 patients were divided into three groups according to treatment modalities and outcomes: outpatient group, inpatient without invasive mechanical ventilation (IMV) group, and inpatient with IMV group. We used the Mann-Whitney and Kruskal-Wallis tests to analyze the differences in routine blood parameters between the two or three groups. Receiver operating characteristic (ROC) curve analysis and area under the curve (AUC) were used to assess the diagnostic accuracy.ResultsCompared with outpatient influenza A patients, outpatient COVID-19 patients had a higher neutrophil to lymphocyte ratio (NLR) (6.63 vs 3.55). ROC analysis showed that the NLR had a high diagnostic value for differentiating COVID-19 from influenza A (AUC = 0.739). The best cut-off point of the NLR was 6.48, the diagnostic sensitivity was 0.523, and the specificity was 0.925. The median platelet (PLT) count in the different COVID-19 groups was as follows: outpatient group (189×109/L), inpatient without IMV group (161×109/L), and inpatient with IMV group (94×109/L). Multivariate logistic regression analysis found a significant association between PLT and treatment modality and outcome in COVID-19 patients (pConclusionsNLR can be used as a potential biological indicator to distinguish COVID-19 and influenza A. Decreased PLT predicts the critical condition of COVID-19 patients and helps stratify the treatment of COVID-19 patients.

Most applications of aggregation-induced emission luminogens (AIEgens) have been limited in small animal models. Here, the authors show the versatility of AIEgens-based imaging-guided surgical operation from small animals to rhesus macaque, in support of the clinical translation of AIEgens.

Abstract This study took shear wave elastography (SWE) technology to measure the shear wave velocity (SWV) of peripheral nerve in healthy population, which represents the stiffness of the peripheral nerves, and research whether these parameters (location, age, sex, body mass index (BMI), the thickness and cross-sectional area(CSA) of the nerve) would affect the stiffness of the peripheral nerves. 105 healthy volunteers were enrolled in this study. We recorded the genders and ages of these volunteers, measured height and weight, calculated BMI, measured nerve thickness and CSA using high-frequency ultrasound (HFUS), and then, we measured and compared the SWV of the right median nerve at the middle of the forearm and at the proximal entrance of the carpal tunnel. The SWV of the median nerve of the left side was measured to explore whether there exist differences of SWV in bilateral median nerve. Additionally, we also measured the SWV of the right tibial nerve at the ankle canal to test whether there is any difference in shear wave velocity between different peripheral nerves. This study found that there existed significant differences of SWV between different sites in one nerve and between different peripheral nerves. No significant difference was found in SWV between bilateral median nerves. Additionally, the SWV of peripheral nerves was associated with gender, while not associated with age or BMI. The mean SWV of the studied male volunteers in median nerve were significantly higher than those of female (p

The emergence of microneedle arrays (MNAs) as a novel, simple, and minimally invasive administration approach largely addresses the challenges of traditional drug delivery. In particular, the dissolvable MNAs act as a promising, multifarious, and well-controlled platform for micro-nanotransport in medical research and cosmetic formulation applications. The effective delivery mostly depends on the behavior of the MNAs penetrated into the body, and accurate assessment is urgently needed. Advanced imaging technologies offer high sensitivity and resolution visualization of cross-scale, multidimensional, and multiparameter information, which can be used as an important aid for the evaluation and development of new MNAs. The combination of MNA technology and imaging can generate considerable new knowledge in a cost-effective manner with regards to the pharmacokinetics and bioavailability of active substances for the treatment of various diseases. In addition, noninvasive imaging techniques allow rapid, receptive assessment of transdermal penetration and drug deposition in various tissues, which could greatly facilitate the translation of experimental MNAs into clinical application. Relying on the recent promising development of bioimaging, this review is aimed at summarizing the current status, challenges, and future perspective on in vivo assessment of MNA drug delivery by various imaging technologies.

The human kinome comprises 538 kinases playing essential functions by catalyzing protein phosphorylation. Annotation of subcellular distribution of the kinome greatly facilitates investigation of normal and disease mechanisms. Here, we present Kinome Atlas (KA), an image-based map of the kinome annotated to 10 cellular compartments. 456 epitope-tagged kinases, representing 85% of the human kinome, were expressed in HeLa cells and imaged by immunofluorescent microscopy under a similar condition. KA revealed kinase family-enriched subcellular localizations and discovered a collection of new kinase localizations at mitochondria, plasma membrane, extracellular space, and other structures. Furthermore, KA demonstrated the role of liquid-liquid phase separation in formation of kinase condensates. Identification of MOK as a mitochondrial kinase revealed its function in cristae dynamics, respiration, and oxidative stress response. Although limited by possible mislocalization due to overexpression or epitope tagging, this subcellular map of the kinome can be used to refine regulatory mechanisms involving protein phosphorylation.

Functional proprioceptive information is required to allow an individual to interact with the environment effectively for everyday activities such as locomotion and object manipulation. Specifically, research suggests that application of compression garments could improve proprioceptive regulation of action by enhancing sensorimotor system noise in individuals of different ages and capacities. However, limited research has been conducted with samples of elderly people thus far. This study aimed to examine acute effects of wearing knee-length socks (KLS) of various compression levels on ankle joint position sense in community-dwelling, older adults. A total of 26 participants (12 male and 14 female), aged between 65 and 84 years, were randomly recruited from local senior activity centres in Singapore. A repeated-measures design was used to determine effects on joint position awareness of three different treatments-wearing clinical compression socks (20-30 mmHg); wearing non-clinical compression socks (< 20 mmHg); wearing normal socks, and one control condition (barefoot). Participants were required to use the dominant foot to indicate 8 levels of steepness (2.5°, 5°, 7.5°, 10°, 12.5°, 15°, 17.5°, and 20°), while standing on a modified slope box, in a plantar flexion position. Findings showed that wearing clinical compression KLS significantly reduced the mean absolute errors compared to the barefoot condition. However, there were no significant differences observed between other KLS and barefoot conditions. Among the KLS of various compression levels, results suggested that only wearing clinical compression KLS (20-30 mmHg) improved the precision of estimation of ankle joint plantar flexion movement, by reducing absolute performance errors in elderly people. It is concluded that wearing clinical compression KLS could potentially provide an affordable strategy to ameliorate negative effects of ageing on the proprioception system to enhance balance and postural control in community-dwelling individuals.

Designing and synthesizing protein mimetic molecules to form crystalline structures can be a challenge. Here the authors show lattice self-assembly of cyclodextrin complexes into a variety of capsid like structures, such as, lamellae, helical tubes and hollow rhombic dodecahedra.

Precise assembly of undecorated colloids demands a clever approach. Here, the authors draw unlikely inspiration from vector graphics to direct colloids into 2D structures, pinning the ends and corners of assembled patterns with optical tweezers and manipulating the segments like vectors.

To ascertain if etoricoxib increases the risk of gastrointestinal adverse events (GAEs) compared with placebo, diclofenac, and naproxen in the treatment of patients with osteoarthritis (OA) or rheumatoid arthritis (RA).Studies were searched in MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials from inception to August 2017. Randomized Clinical Trials (RCTs) that compared etoricoxib with placebo and other active drug for patients with OA or RA and reported data on gastrointestinal safety (which is of interest to patients and clinicians) were included. The follow-up time window for GAEs was defined as within 28 days subsequent to the last dose of study medication. A meta-analysis was conducted using a fixed-effect model. Risk ratios (RRs) and 95% confidence intervals (CIs) were measured.We found nine randomized clinical trials (RCTs) that included information on gastrointestinal safety during follow-up time. Among them, five RCTs compared etoricoxib with placebo, four RCTs compared etoricoxib with diclofenac, and three RCTs compared etoricoxib with naproxen. Etoricoxib did not increase the risk of GAEs compared with placebo. Compared with diclofenac and naproxen, etoricoxib reduced the GAE risk (RR, 0.67; 95% CI, 0.59-0.76; p < 0.00001; 0.59; 0.48-0.72; < 0.00001) during follow-up time.In patients with OA or RA, etoricoxib did not increase the GAE risk compared with placebo, but reduced the GAE risk effectively compared with diclofenac and naproxen during follow-up time.

Systematic reviews of balance control have tended to only focus on the effects of single lower-limb stimulation strategies, and a current limitation is the lack of comparison between different relevant stimulation strategies. The aim of this systematic review and meta-analysis was to examine evidence of effects of different lower-limb sensory stimulation strategies on postural regulation and stability. Moderate- to high- pooled effect sizes (Unbiased (Hedges' g) standardized mean differences (SMD) = 0.31-0.66) were observed with the addition of noise in a Stochastic Resonance Stimulation Strategy (SRSS), in three populations (i.e., healthy young adults, older adults, and individuals with lower-limb injuries), and under different task constraints (i.e., unipedal, bipedal, and eyes open). A Textured Material Stimulation Strategy (TMSS) enhanced postural control in the most challenging condition-eyes-closed on a stable surface (SMD = 0.61), and in older adults (SMD = 0.30). The Wearable Garments Stimulation Strategy (WGSS) showed no or adverse effects (SMD = -0.68-0.05) under all task constraints and in all populations, except in individuals with lower-limb injuries (SMD = 0.20). Results of our systematic review and meta-analysis revealed that future research could consider combining two or more stimulation strategies in intervention treatments for postural regulation and balance problems, depending on individual needs.

A novel visualization scheme for permutation entropy is presented in this paper. The proposed scheme is based on non-uniform attractor embedding of the investigated time series. A single digital image of permutation entropy is produced by averaging all possible plain projections of the permutation entropy measure in the multi-dimensional delay coordinate space. Computational experiments with artificially-generated and real-world time series are used to demonstrate the advantages of the proposed visualization scheme.

LNK is an adapter protein negatively regulating the JAK/STAT cell signaling pathway. In this study, we observed the correlation between variation in LNK gene and the clinical type of myeloproliferative neoplasms (MPN).A total of 285 MPN cases were recruited, including essential thrombocythemia (ET) 154 cases, polycythemia vera (PV) 76 cases, primary myelofibrosis (PMF) 19 cases, and chronic myeloid leukemia (CML) 36 cases. Ninety-three healthy individuals were used as normal controls. V617F mutation in JAK2 was identified by allele-specific PCR method, RT-PCR was used for the detection of BCR/ABL1 fusion gene, and mutations and variations in coding exons and their flanking sequences of LNK gene were examined by PCR-sequencing.Missense mutations of A300V, V402M, and R415H in LNK were found in 8 patients including ET (4 cases, all combined with JAK2-V617F mutation), PV (2 cases, one combined with JAK2-V617F mutation), PMF (one case, combined with JAK2-V617F mutation) and CML (one case, combined with BCR/ABL1 fusion gene). The genotype and allele frequencies of the three SNPs (rs3184504, rs111340708 and rs78894077) in LNK were significantly different between MPN patients and controls. For rs3184504 (T/C, in exon2), the T allele (p.262W) and TT genotype were frequently seen in ET, PV and PMF (P

OBJECTIVES: HIV-1 viral quantitation is essential for treatment monitoring. An in-house assay would decrease financial barriers to access. MATERIALS AND METHODS: A real-time competitive RT-PCR in house assay (Sing-IH) was developed in Singapore. Using HXB2 as reference, the assay's primers and probes were designed to generate a 183-bp product that overlaps a portion of the LTR region and gag region. A competitive internal control (IC) was included in each assay to monitor false negative results due to inhibition or human error. Clinical evaluation was performed on 249 HIV-1 positive patient samples in comparison with the commercially available Generic HIV Viral Load assay. Correlation and agreement of results were assessed for plasma HIV-1 quantification with both assays. RESULTS: The assay has a lower limit of detection equivalent to 126 copies/mL of HIV-1 RNA and a linear range of detection from 100-1000000 copies/mL. Comparative analysis with reference to the Generic assay demonstrated good agreement between both assays with a mean difference of 0.22 log10 copies/mL and 98.8% of values within 1 log10 copies/mL range. Furthermore, the Sing-IH assay can quantify HIV-1 group M subtypes A-H and group N isolates adequately, making it highly suitable for our region, where subtype B and CRF01_AE predominate. CONCLUSIONS: With a significantly lower running cost compared to commercially available assays, the broadly sensitive Sing-IH assay could help to overcome the cost barriers and serve as a useful addition to the currently limited HIV viral load assay options for resource-limited settings.

HIV-1 subtype B and CRF01_AE are the predominant infecting subtypes among men who have sex with men (MSM) in Singapore. The genetic history, population dynamics and pattern of transmission networks of these genotypes remain largely unknown. We delineated the phylodynamic profiles of HIV-1 subtype B, CRF01_AE and the recently characterized CRF51_01B strains circulating among the MSM population in Singapore. A total of 105 (49.5%) newly-diagnosed treatment-naïve MSM were recruited between February 2008 and August 2009. Phylogenetic reconstructions of the protease gene (HXB2: 2239 - 2629), gp120 (HXB2: 6942 - 7577) and gp41 (HXB2: 7803 - 8276) of the env gene uncovered five monophyletic transmission networks (two each within subtype B and CRF01_AE and one within CRF51_01B lineages) of different sizes (involving 3 - 23 MSM subjects, supported by posterior probability measure of 1.0). Bayesian coalescent analysis estimated that the emergence and dissemination of multiple sub-epidemic networks occurred between 1995 and 2005, driven largely by subtype B and later followed by CRF01_AE. Exponential increase in effective population size for both subtype B and CRF01_AE occurred between 2002 to 2007 and 2005 to 2007, respectively. Genealogical estimates suggested that the novel CRF51_01B lineages were probably generated through series of recombination events involving CRF01_AE and multiple subtype B ancestors. Our study provides the first insight on the phylodynamic profiles of HIV-1 subtype B, CRF01_AE and CRF51_01B viral strains circulating among MSM in Singapore.

The transducin GTPase-accelerating protein complex, which determines the photoresponse duration of photoreceptors, is composed of RGS9-1, Gβ5L and R9AP. Here we report that RGS9-1 and Gβ5L change their distribution in rods during light/dark adaptation. Upon prolonged dark adaptation, RGS9-1 and Gβ5L are primarily located in rod inner segments. But very dim-light exposure quickly translocates them to the outer segments. In contrast, their anchor protein R9AP remains in the outer segment at all times. In the dark, Gβ5L's interaction with R9AP decreases significantly and RGS9-1 is phosphorylated at S(475) to a significant degree. Dim light exposure leads to quick de-phosphorylation of RGS9-1. Furthermore, after prolonged dark adaptation, RGS9-1 and transducin Gα are located in different cellular compartments. These results suggest a previously unappreciated mechanism by which prolonged dark adaptation leads to increased light sensitivity in rods by dissociating RGS9-1 from R9AP and redistributing it to rod inner segments.

The peanut (Arachis hypogaea) is an important oil crop. Breeding for high oil content is becoming increasingly important. Wild Arachis species have been reported to harbor genes for many valuable traits that may enable the improvement of cultivated Arachis hypogaea, such as resistance to pests and disease. However, only limited information is available on variation in oil content. In the present study, a collection of 72 wild Arachis accessions representing 19 species and 3 cultivated peanut accessions were genotyped using 136 genome-wide SSR markers and phenotyped for oil content over three growing seasons. The wild Arachis accessions showed abundant diversity across the 19 species. A. duranensis exhibited the highest diversity, with a Shannon-Weaver diversity index of 0.35. A total of 129 unique alleles were detected in the species studied. A. rigonii exhibited the largest number of unique alleles (75), indicating that this species is highly differentiated. AMOVA and genetic distance analyses confirmed the genetic differentiation between the wild Arachis species. The majority of SSR alleles were detected exclusively in the wild species and not in A. hypogaea, indicating that directional selection or the hitchhiking effect has played an important role in the domestication of the cultivated peanut. The 75 accessions were grouped into three clusters based on population structure and phylogenic analysis, consistent with their taxonomic sections, species and genome types. A. villosa and A. batizocoi were grouped with A. hypogaea, suggesting the close relationship between these two diploid wild species and the cultivated peanut. Considerable phenotypic variation in oil content was observed among different sections and species. Nine alleles were identified as associated with oil content based on association analysis, of these, three alleles were associated with higher oil content but were absent in the cultivated peanut. The results demonstrated that there is great potential to increase the oil content in A. hypogaea by using the wild Arachis germplasm.

The long-term fate of stem cells after intramyocardial delivery is unknown. We used noninvasive, repetitive PET/CT imaging with [(18)F]FEAU to monitor the long-term (up to 5 months) spatial-temporal dynamics of MSCs retrovirally transduced with the sr39HSV1-tk gene (sr39HSV1-tk-MSC) and implanted intramyocardially in pigs with induced acute myocardial infarction. Repetitive [(18)F]FEAU PET/CT revealed a biphasic pattern of sr39HSV1-tk-MSC dynamics; cell proliferation peaked at 33-35 days after injection, in periinfarct regions and the major cardiac lymphatic vessels and lymph nodes. The sr39HSV1-tk-MSC-associated [(18)F]FEAU signals gradually decreased thereafter. Cardiac lymphography studies using PG-Gd-NIRF813 contrast for MRI and near-infrared fluorescence imaging showed rapid clearance of the contrast from the site of intramyocardial injection through the subepicardial lymphatic network into the lymphatic vessels and periaortic lymph nodes. Immunohistochemical analysis of cardiac tissue obtained at 35 and 150 days demonstrated several types of sr39HSV1-tk expressing cells, including fibro-myoblasts, lymphovascular cells, and microvascular and arterial endothelium. In summary, this study demonstrated the feasibility and sensitivity of [(18)F]FEAU PET/CT imaging for long-term, in-vivo monitoring (up to 5 months) of the fate of intramyocardially injected sr39HSV1-tk-MSC cells. Intramyocardially transplanted MSCs appear to integrate into the lymphatic endothelium and may help improve myocardial lymphatic system function after MI.