Knowledge domain and emerging trends in sacubitril/valsartan study from 2008 to 2023 - a visualized conclusive analysis based on novel scientometric tools.

OBJECTIVE: This study aimed to determine the evolution of sacubitril-valsartan research and analyze the publications quantitatively and qualitatively. MATERIALS AND METHODS: We used the bibliometric method and a combination of CiteSpace_6.1.6 and VOSviewer_1.6.18 to identify top authors, countries, institutions, co-cited articles, co-cited journals, keywords, and trends. This study prioritized key aspects in the existing global research on Entresto (Sacubitril/Valsartan) to assess our depth of knowledge in this field and identify potential insights. The objective was to generate a reference for the utilization of the "angiotensin receptor-neprilysin inhibitor" (ARNI). RESULTS: From 2008 to 2022, citations of sacubitril-valsartan showed an upward trend. VOSviewer keyword analysis of 3,408 publications identified 624 keywords and divided them into seven different clusters. The clustered network was constructed based on 1,191 references cited by 3,408 publications that met the terms, where the clustered network of sacubitril-valsartan was presented. These publications can be regarded as fundamental to Entresto's research. Analysis of co-cited reference clusters showed that other than Entresto's novel application in other diseases, the new combination with other medication or mechanical assistance therapies against heart failure was Entresto's latest focus. Analysis of citation bursts showed that the rank of the top 25 keywords, according to the chronological sequence, marked Entresto's research entering a new era of exploring the extended application in other diseases and novel combinations with other diverse therapies. CONCLUSIONS: We found that emerging new mechanisms in sacubitril-valsartan therapy intended for more targets in the pathogenesis of specific diseases will be the focus of further studies.

[Clinical observation of botulinum toxin A injection in the treatment of acute comitant esotropia: a retrospective cohort study].

Objective: To observe the efficacy and safety of botulinum toxin A (BTA) injection in the treatment of acute comitant esotropia (ACE) with different doses. Methods: This retrospective cohort study included data from patients with ACE who received BTA injection treatment at the First Affiliated Hospital of Zhengzhou University from June 2019 to June 2022. All patients underwent routine ophthalmic examinations, including best-corrected visual acuity (BCVA), spherical equivalent (SE), as well as specialized examinations for strabismus, including the degree of esotropia, eye movement status, and binocular visual function. Patients were categorized into small esotropia [≤60 prism diopters (PD)] and large esotropia (>60 PD) groups based on the pre-treatment degree of esotropia. Each group was further divided into 2.5 U and 5.0 U dose subgroups. Monocular injections were administered to the non-dominant eye. The esotropia degree was recorded and compared at 1, 2, 3, and 6 months of follow-up. The proportion of effectively treated patients in each group was documented. The number of cases with various levels of visual functions (including simultaneous vision, near stereopsis, and distance stereopsis) at 6 months post-treatment was compared, and complications during the follow-up period were observed. Statistical analyses were conducted using t-tests, Mann-Whitney U tests, and χ2 tests. Results: A total of 70 patients were included in the study, comprising 46 males and 24 females, with a median age of 5.0 (4.0, 8.3) years. Among them, 37 patients had small esotropia, with 25 in the 2.5 U group and 12 in the 5.0 U group. Thirty-three patients had large esotropia, with 18 in the 2.5 U group and 15 in the 5.0 U group. There were no statistically significant differences in baseline data, including age, duration of the condition, pre-treatment esotropia degree, BCVA and SE, between the two dose groups in both small and large esotropia patients (all P>0.05). In small esotropia patients, at 1 and 2 months post-treatment, the esotropia degree in the 5.0 U group was -20.00 (-37.50, -7.00) and 0.00 (0.00, 0.00) PD, respectively, which was significantly lower than the 0.00 (-10.00, 4.50) and 5.00 (0.00, 6.50) PD in the 2.5 U group (all P<0.05). At 3 and 6 months post-treatment, the esotropia degree in the 2.5 U group was 5.00 (0.00, 15.00) and 2.00 (0.00, 6.00) PD, respectively, while in the 5.0 U group, it was 0.00 (0.00, 4.50) and 0.00 (0.00, 3.75) PD, with no statistically significant differences between the two groups (all P>0.05). In the 2.5 U group, 20 cases were effectively treated, accounting for 80.0%, while in the 5.0 U group, 10 cases were effective, accounting for 10/12, with no significant difference between the two groups (P>0.05). In the 2.5 U group and the 5.0 U group, the proportions of cases with various levels of visual functions were as follows: simultaneous vision, 76.0% (19/25) and 10/12; near stereopsis, 48.0% (12/25) and 7/12; distance stereopsis, 44.0% (11/25) and 7/12, respectively. No statistically significant differences were observed in these proportions (all P>0.05). In patients with large esotropia, the esotropia degrees in the 5.0 U group at various follow-up times were -5.00 (-25.00, 5.00), 0.00 (0.00, 7.00), 2.00 (0.00, 10.00), and 5.00 (0.00, 7.00) PD, respectively. For the 2.5 U group, the corresponding values were 5.00 (2.75, 27.75), 10.00 (3.75, 24.75), 12.00 (3.75, 38.75), and 14.00 (3.50, 54.00) PD, respectively. The esotropia degrees in the 5.0 U group were consistently lower than those in the 2.5 U group (all P<0.05). The proportion of effective treatment in the 5.0 U group (13/15) was higher than that in the 2.5 U group (9/18), and the proportion of cases with distance stereopsis in the 5.0 U group (9/15) was higher than that in the 2.5 U group (4/18), both showing statistically significant differences (all P<0.05). The number of cases with simultaneous vision and near stereopsis showed no significant differences between the two groups (all P>0.05). The proportion of complications in the 2.5 U and 5.0 U groups in both large and small esotropia patients was 9/18, 13/15, 80.0% (20/25), and 10/12, respectively, with no statistically significant differences (all P>0.05). All complications spontaneously resolved within 3 months post-treatment. Conclusions: BTA injection is effective in the treatment of ACE, and for ACE patients with esotropia degrees greater than 60 PD, increasing the injection dose to 5.0 U can achieve better therapeutic outcomes.

Matrix-bound nanovesicle-associated IL-33 supports functional recovery after skeletal muscle injury by initiating a pro-regenerative macrophage phenotypic transition.

Injuries to skeletal muscle are among the most common injuries in civilian and military populations, accounting for nearly 60% of extremity injuries. The standard of care for severe extremity injury has been focused upon limb salvage procedures and the utilization of tissue grafts or orthotics in conjunction with rehabilitation to avoid amputation. Nonetheless, many patients have persistent strength and functional deficits that permanently impact their quality of life. Preclinical and clinical studies have shown that partial restoration of functional skeletal muscle tissue following injury can be achieved by the implantation of a biologic scaffold composed of extracellular matrix (ECM). These favorable outcomes are mediated, at least in part, through local immunomodulation. The mechanisms underlying this immunomodulatory effect, however, are poorly understood. The present study investigates a potential mechanistic driver of the immunomodulatory effects; specifically, the effect of selected ECM components upon inflammation resolution and repair. Results show that the host response to skeletal muscle injury is profoundly altered and functional recovery decreased in il33-/- mice compared to age- and sex-matched wildtype counterparts by 14 days post-injury. Results also show that IL-33, contained within matrix-bound nanovesicles (MBV), supports skeletal muscle regeneration by regulating local macrophage activation toward a pro-remodeling phenotype via canonical and non-canonical pathways to improve functional recovery from injury compared to untreated il33-/- counterparts. Taken together, these data suggest that MBV and their associated IL-33 cargo represent a novel homeostatic signaling mechanism that contributes to skeletal muscle repair.

Unsupervised approach to decomposing neural tuning variability.

Neural representation is often described by the tuning curves of individual neurons with respect to certain stimulus variables. Despite this tradition, it has become increasingly clear that neural tuning can vary substantially in accordance with a collection of internal and external factors. A challenge we are facing is the lack of appropriate methods to accurately capture the moment-to-moment tuning variability directly from the noisy neural responses. Here we introduce an unsupervised statistical approach, Poisson functional principal component analysis (Pf-PCA), which identifies different sources of systematic tuning fluctuations, moreover encompassing several current models (e.g.,multiplicative gain models) as special cases. Applying this method to neural data recorded from macaque primary visual cortex- a paradigmatic case for which the tuning curve approach has been scientifically essential- we discovered a simple relationship governing the variability of orientation tuning, which unifies different types of gain changes proposed previously. By decomposing the neural tuning variability into interpretable components, our method enables discovery of unexpected structure of the neural code, capturing the influence of the external stimulus drive and internal states simultaneously.

Potential Environmental and Health Implications from the Scaled-Up Production and Disposal of Nanomaterials Used in Biosensors.

Biosensors often combine biological recognition elements with nanomaterials of varying compositions and dimensions to facilitate or enhance the operating mechanism of the device. While incorporating nanomaterials is beneficial to developing high-performance biosensors, at the stages of scale-up and disposal, it may lead to the unmanaged release of toxic nanomaterials. Here we attempt to foster connections between the domains of biosensors development and human and environmental toxicology to encourage a holistic approach to the development and scale-up of biosensors. We begin by exploring the toxicity of nanomaterials commonly used in biosensor design. From our analysis, we introduce five factors with a role in nanotoxicity that should be considered at the biosensor development stages to better manage toxicity. Finally, we contextualize the discussion by presenting the relevant stages and routes of exposure in the biosensor life cycle. Our review found little consensus on how the factors presented govern nanomaterial toxicity, especially in composite and alloyed nanomaterials. To bridge the current gap in understanding and mitigate the risks of uncontrolled nanomaterial release, we advocate for greater collaboration through a precautionary One Health approach to future development and a movement towards a circular approach to biosensor use and disposal.

Bioanalytical approaches for the detection, characterization, and risk assessment of micro/nanoplastics in agriculture and food systems.

This review discusses the most recent literature (mostly since 2019) on the presence and impact of microplastics (MPs, particle size of 1 µm to 5 mm) and nanoplastics (NPs, particle size of 1 to 1000 nm) throughout the agricultural and food supply chain, focusing on the methods and technologies for the detection and characterization of these materials at key entry points. Methods for the detection of M/NPs include electron and atomic force microscopy, vibrational spectroscopy (FTIR and Raman), hyperspectral (bright field and dark field) and fluorescence imaging, and pyrolysis-gas chromatography coupled to mass spectrometry. Microfluidic biosensors and risk assessment assays of MP/NP for in vitro, in vivo, and in silico models have also been used. Advantages and limitations of each method or approach in specific application scenarios are discussed to highlight the scientific and technological obstacles to be overcome in future research. Although progress in recent years has increased our understanding of the mechanisms and the extent to which MP/NP affects health and the environment, many challenges remain largely due to the lack of standardized and reliable detection and characterization methods. Most of the methods available today are low-throughput, which limits their practical application to food and agricultural samples. Development of rapid and high-throughput field-deployable methods for onsite screening of MP/NPs is therefore a high priority. Based on the current literature, we conclude that detecting the presence and understanding the impact of MP/NP throughout the agricultural and food supply chain require the development of novel deployable analytical methods and sensors, the combination of high-precision lab analysis with rapid onsite screening, and a data hub(s) that hosts and curates data for future analysis.

Polyphenol effects on CuO-nanoparticle-mediated DNA damage, reactive oxygen species generation, and fibroblast cell death.

The ability of ten polyphenolic antioxidants to prevent CuO nanoparticle (NPCuO) and H2O2-mediated DNA damage and cytotoxicity was investigated. Five of the polyphenols (MEPCA, PREGA, MEGA, ECG, and EGCG) prevent NPCuO/H2O2-mediated DNA damage (IC50 values of 7.5-800 µM), three have no effect (PCA, VA, and EC), and two (GA and EGC) result in increased DNA damage. Most polyphenols had similar antioxidant/prooxidant activity in the presence of NPCuO or free copper ions. Electron paramagnetic resonance (EPR) spectroscopy of reactive oxygen species (ROS) generated by NPCuO/H2O2 in the presence of representative polyphenols correlate with results of DNA damage studies: in the presence of NPCuO/H2O2, MEPCA prevents ROS formation, VA has no effect on ROS levels, and EGC increases ROS levels. EPR results with CuO nanoparticles washed to remove dissolved copper in solution (wCuO) in the presence of H2O2/ascorbate suggest that MEPCA prevents ROS formation on the nanoparticle surface in addition to preventing ROS formation from dissolved copper. In mouse fibroblast (L929) cells, combining NPCuO with H2O2 results in significantly greater cytotoxicity than observed for either component alone. After 3 h incubation with MEPCA or MEGA, the viability loss in L929 cells induced by NPCuO/H2O2 challenge was significantly rescued at physiologically relevant polyphenol levels (1 µM). These studies show that polyphenols can protect DNA and inhibit cytotoxicity generated by NPCuO under oxidative stress conditions.

Feasibility of Self-Guided Online Cognitive Behavioral Therapy for University Students During COVID-19.

Objective: This study aimed to test the feasibility and efficacy of a self-guided online cognitive behaviour therapy (iCBT) for university students in Hong Kong during COVID-19. Method: One group pre-post-test design with convenient sampling was adopted in this study, involving 84 university students who received a newly developed iCBT within an 8 week intervention period. The iCBT offered eight online modules for students to learn the skills of CBT at home through an online platform which was accessible any time anywhere anonymously with technical support only. Standardized assessment tools were used for outcomes assessment at the pre- and post-intervention periods. Results: Three quarters of participants completed all iCBT modules. The results of paired t-tests showed that, after completing the iCBT, participants showed reduction in anxiety, depression, and perceived stress. Conclusion: This study provides preliminary evidences to support the feasibility and efficacy of the self-guided iCBT for university students during COVID-19.

IL-1ß induces changes in expression of core circadian clock components PER2 and BMAL1 in primary human chondrocytes through the NMDA receptor/CREB and NF-κB signalling pathways.

The circadian clock is a specialised cell signalling circuit present in almost all cells. It controls the timing of key cell activities such as proliferation and differentiation. In osteoarthritis, expression of two components of the circadian clock, BMAL1 and PER2 is altered in chondrocytes and this change has been causally linked with the increase in proliferation and altered chondrocyte differentiation in disease. IL-1ß, an inflammatory cytokine abundant in OA joints, has previously been shown to induce changes in BMAL1 and PER2 expression in chondrocytes. The purpose of this study is to identify the mechanism involved. We found IL-1ß treatment of primary human chondrocytes led to activation of NMDA receptors as evidenced by an increase in phosphorylation of GluN1 and an increase in intracellular calcium which was blocked by the NMDAR antagonist MK801. Levels of phosphorylated CREB were also elevated in IL-1ß treated cells and this effect was blocked by co-treatment of cells with IL-1ß and the NMDAR antagonist MK-801. Knockdown of CREB or inhibition of CREB activity prevented the IL-1ß induced increase in PER2 expression in chondrocytes but had no effect on BMAL1. Phosphorylated p65 levels were elevated in IL-1ß treated chondrocytes indicating increased NF-κB activation. Inhibition of NF-κB activity prevented the IL-1ß induced reduction in BMAL1 expression and partially mitigated the IL-1ß induced increase in PER2 expression in chondrocytes. These data indicate that the NMDAR/CREB and NF-κB signalling pathways regulate the core circadian clock components PER2 and BMAL1 in chondrocytes. Given that changes in expression of these clock components have been observed in a wide range of diseases, these findings may be broadly relevant for understanding the mechanism leading to circadian clock changes in pathology.

[Establishment and validation of a new predictive equation with multiple risk factors for the development of cardiorenal syndrome type 1 in patients with acute myocardial infarction].

Objective: To investigate the independent risk factors of cardiorenal syndrome type 1 (CRS1) in patients with acute myocardial infarction (AMI) and to build a predictive equation for the development of CRS1 in these patients. Method: Consecutive inpatients with AMI, who hospitalized from January 2017 to December 2018 in the Hunan Provincial People's Hospital, were enrolled in this case-control study. Patients were divided into CRS1 group and non-CRS1 group according to the presence or absence of CRS1.The clinical data were collected through the electronic medical record system of Hunan Provincial People's Hospital. The matching process was conducted with a minimum-distance scoring method and a 1∶1 match between the CRS1 group and the no-CRS1 group, the propensity score was calculated through the logistic regression model. Factors with statistically significant differences in univariate analysis were included in the multivariate logistic regression model to analyze the risk factors of AMI patients with CRS1, then the independent risk factors were used to establish a predicting equation for CRS1 by logistic regression function for model building. Area under the curve (AUC) value and the best cut-off value of the combined predictors was determined according to the ROC curve. Python 3.8 software was used to perform 10-fold cross-validation on modeling samples. Results: A total of 942 patients were included, there were 113 cases in CRS1 group and 829 cases in non-CRS1 group. Ultimately, 99 CRS1 patients were successfully matched to 99 non-CRS1 patient using 1∶1 matching. After propensity score matching, the baseline age and sex along with heart rate, mean arterial pressure, percentage of people with a history of diabetes, hypertension, ST-segment elevation myocardial infarction, myocardial ischemia time, angiotensin converting enzyme inhibitors or angiotensin Ⅱ receptor blockers use, and ß receptor blocker use were similar between the two groups(all P>0.05). The contrast agent dosage was also similar between the two groups (P=0.266). The peak cardiac troponin I (cTnI), N-terminal pro-brain natriuretic peptide(NT-proBNP), white blood cell count, base estimated glomerular filtration rate (eGFR), albumin and hemoglobin levels were statistically significant between the two groups (all P<0.05). Multivariate logistic regression analysis showed that decreased baseline eGFR, increased NT-proBNP, peak cTnI concentrations and white blood cell count were independent risk factors of CRS1 in AMI patients (all P<0.01).The predicting equation of the combined predictor was established by transforming the logistic model equation, L=0.031×cTnI+0.000 2×NT-proBNP-0.024×eGFR+0.254×white blood cell count, where L represented the combined predictor. ROC curve analysis indicated that the AUC of the peak cTnI, NT-proBNP, baseline eGFR, white blood cell count, and combined predictor were 0.76, 0.85, 0.79, 0.81, and 0.92 respectively (all P<0.05), and the cutoff value of combined predictor was 2.6. The AUC of ROC curve after the model's ten-fold cross validation was 0.89. Conclusions: Decreased baseline eGFR, increased NT-proBNP, peak cTnI concentrations and white blood cell count are the independent risk factors for CRS1 in AMI patients. The combined predictor equation based on the above 4 biomarkers presents a good predictive value for CRS1 in AMI patients.

Effects of Dietary Inclusion of Dry Hydrastis canadensis on Laying Performance, Egg Quality, Serum Biochemical Parameters and Cecal Microbiota in Laying Hens.

Alternative growth promoters are able to not only effectively replace the traditional use of antibiotics but also provide additional health benefits for livestock and reduce food safety concerns. This study investigated the effects of dry Hydrastis canadensis on the laying performance and fecal microbial community of laying hens. Twenty-four Lohmann (LSL, white layer strain) hens were reared from 40 to 48 weeks of age and randomly allotted to four dietary treatments (six birds/treatment). The dietary treatments comprised a basal diet with no treatment as control, a basal diet plus 0.6% powder of dry Hydrastis canadensis roots (R) or leaves (L), and a basal diet plus 0.6% powder of a mixture of dry Hydrastis canadensis roots and leaves (1:1, LR). No mortality was observed in the whole experimental period. The results indicated that albumen height in the LR group was significantly greater than that in the control group. The diet supplemented with Hydrastis canadensis had no significant effects on egg production rate, egg weight, eggshell strength, eggshell thickness, Haugh unit, or yolk height during the whole experimental phase. However, principal coordinate analysis, comparative heat map analysis, and cluster dendrogram analysis of cecal microbiota showed distinct clusters among the groups treated with Hydrastis canadensis and the control group. Regarding blood biochemical parameters, serum cholesterol levels were significantly lower in all Hydrastis canadensis-treated groups compared with those in the control group. Moreover, serum low-density lipoprotein levels were lower in hens supplemented with the leaf of Hydrastis canadensis. The abundances of the phyla Fusobacteria and Kiritimatiellaeota were increased (p < 0.05) in laying hens fed with 0.6% Hydrastis canadensis leaves, whereas the abundance of the phylum Firmicutes in cecum digesta decreased in response to treatment with Hydrastis canadensis roots and leaves. The relative abundance of the Fusobacterium genus was higher in the LR group compared with that in the control. On the contrary, we found a different trend in the Synergistes genus. The potential influences of these microbiota on the performance of laying hens were discussed. The results demonstrate that Hydrastis canadensis can improve the egg albumen height and modulate the cecum digesta microbiota composition of laying hens.

Conformal Coating of Orthopedic Plates with X-ray Scintillators and pH Indicators for X-ray Excited Luminescence Chemical Imaging through Tissue.

We describe a pH-indicating material that can be directly implanted or coated on orthopedic implant surfaces to provide high-spatial-resolution pH mapping through tissue by X-ray excited luminescence chemical imaging (XELCI). This is especially useful for detecting local pH changes during treatment of implant-associated infections. The material has two layers: an X-ray scintillator layer with Gd2O2S:Eu in epoxy, which emits 620 and 700 nm light when irradiated with X-rays, and a pH indicator dye layer, which absorbs some of the 620 nm light in a pH-dependent fashion. To acquire each pixel in the image, a focused X-ray beam irradiates a small region of scintillators and the ratio of 620 to 700 nm light is acquired through the tissue. Scanning the X-ray beam across the implant surface generates high-spatial-resolution chemical measurements. Two associated challenges are (1) to make robust sensors that can be implanted in tissue to measure local chemical concentrations specifically for metal orthopedic implants and (2) to conformally coat the implant surface with scintillators and pH indicator dyes in order to make measurements over a large area. Previously, we have physically pressed or glued a pH-sensitive hydrogel sensor onto the surface of an implant, but this is impractical for imaging over large irregular device areas such as an orthopedic plate with holes and edges. Herein, we describe a chemically sensitive and biocompatible XELCI sensor material that can conformally coat the implant surface. A two-part commercial-grade epoxy resin was mixed with Gd2O2S:Eu and adhered to the titanium surface. Sugar and salt particles were added to the surface of the epoxy as it cured to create a roughened surface and increase the surface area. On this roughened surface, a secondary layer of diacrylated polyethylene glycol (PEG) hydrogel, containing a pH sensitive dye, was polymerized. This combination of epoxy-PEG layers was found to adhere well to the metal implant unlike other previously tested polymer surfaces, which delaminated when exposed to water or humidity. The focused X-ray beam enabled 0.5 mm spatial resolution through 1 cm-thick tissue. The pH sensor-coated orthopedic plate was imaged with XELCI, through tissue, with different pH levels to acquire a calibration curve. The plates were also imaged through tissue, with a low pH region on one section due to growth of a Staphylococcus aureus biofilm. A pH sensor-coated stainless-steel rod with two distinct pH regions was inserted in a rabbit tibia specimen, and the pH was imaged through both bone and soft tissue. These studies demonstrate the use of pH sensor-coated orthopedic plates and rods for mapping the local pH through tissue during biofilm formation by XELCI.

SNARE protein SEC22B regulates early embryonic development.

The highly conserved SNARE protein SEC22B mediates diverse and critical functions, including phagocytosis, cell growth, autophagy, and protein secretion. However, these characterizations have thus far been limited to in vitro work. Here, we expand our understanding of the role Sec22b plays in vivo. We utilized Cre-Lox mice to delete Sec22b in three tissue compartments. With a germline deletion of Sec22b, we observed embryonic death at E8.5. Hematopoietic/endothelial cell deletion of Sec22b also resulted in in utero death. Notably, mice with Sec22b deletion in CD11c-expressing cells of the hematopoietic system survive to adulthood. These data demonstrate Sec22b contributes to early embryogenesis through activity both in hematopoietic/endothelial tissues as well as in other tissues yet to be defined.

An implanted pH sensor read using radiography.

A biomedical sensor was developed to measure local pH near orthopedic implants to detect and study implant-associated infection. The sensor is read using plain radiography, a technique which is noninvasive, inexpensive, ubiquitously available in medical facilities, and routinely used in diagnosis and follow-up. The sensor comprises a radiopaque tungsten indicator pin embedded within a chemically responsive hydrogel that exhibits a pH-dependent swelling. A stainless steel well holds this hydrogel and attaches to an orthopedic plate. The local pH may be determined from the extent of hydrogel swelling by radiographically measuring the indicator position relative to the well. We calibrated the sensor in a series of standard pH buffers and tested it during bacterial growth in culture. The sensor was robust: its response was negligibly affected by changes in temperature, ionic strength within the normal physiological range, or long-term incubation with reactive oxygen species generated from hydrogen peroxide and copper. Pooled data from several sensors fabricated at different times and tested in different conditions had a root-mean-square deviation from a pH electrode reading of 0.24 pH units. Radiographic measurements were also performed in cadaveric tissue with the sensor attached to an orthopedic plate fixed to a tibia. Pin position readings varied by 100 µm between observers surveying the same radiographs, corresponding to 0.065 pH units precision in the range pH 4-8. The sensor was designed to augment standard radiographs of tissue, bony anatomy, and hardware by also indicating local chemical concentrations.

Spatial distribution of marker gene activity in the mouse lung during alveolarization.

This data is a curated collection of visual images of gene expression patterns from the pre- and post-natal mouse lung, accompanied by associated mRNA probe sequences and RNA-Seq expression profiles. Mammalian lungs undergo significant growth and cellular differentiation before and after the transition to breathing air. Documenting normal lung development is an important step in understanding abnormal lung development, as well as the challenges faced during a preterm birth. Images in this dataset indicate the spatial distribution of mRNA transcripts for over 500 different genes that are active during lung development, as initially determined via RNA-Seq. Images were systematically acquired using high-throughput in situ hybridization with non-radioactive digoxigenin-labeled mRNA probes across mouse lungs from developmental time points E16.5, E18.5, P7, and P28. The dataset was produced as part of The Molecular Atlas of Lung Development Program (LungMAP) and is hosted at https://lungmap.net. This manuscript describes the nature of the data and the protocols for generating the dataset.

Obesity, osteoarthritis and genetic risk: The rs182052 polymorphism in the ADIPOQ gene is potentially associated with risk of knee osteoarthritis.

OBJECTIVES: Given the function of adiponectin (ADIPOQ) on the inflammatory condition of obesity and osteoarthritis (OA), we hypothesized that the ADIPOQ gene might be a candidate gene for a marker of susceptibility to OA. METHODS: We systematically screened three tagging polymorphisms (rs182052, rs2082940 and rs6773957) in the ADIPOQ gene, and evaluated the association between the genetic variants and OA risk in a case-controlled study that included 196 OA patients and 442 controls in a northern Chinese population. Genotyping was performed using the Sequenom MassARRAY iPLEX platform. RESULTS: The single nucleotide polymorphism (SNP) rs182052 was found to be potentially associated with knee OA risk (additive model: odds ratio = 1.38; 95% confidence interval 1.07 to 1.76; p = 0.012). Furthermore, a non-significant association was observed for rs182052 and body mass index with regard to OA risk in interaction analyses (p = 0.063). Similarly, no significant interaction was detected for rs182052 and age with regard to OA risk (p = 0.614). CONCLUSION: These findings suggest that the SNP rs182052 in the ADIPOQ gene may potentially modify individual susceptibility to knee OA in the Chinese population. Further studies are warranted to investigate our findings in more depth.Cite this article: L. Jiang, X. Zhu, J. Rong, B. Xing, S. Wang, A. Liu, M. Chu, G. Huang. Obesity, osteoarthritis and genetic risk: The rs182052 polymorphism in the ADIPOQ gene is potentially associated with risk of knee osteoarthritis. Bone Joint Res 2018;7:494-500. DOI: 10.1302/2046-3758.77.BJR-2017-0274.R1.

Altered N-methyl D-aspartate receptor subunit expression causes changes to the circadian clock and cell phenotype in osteoarthritic chondrocytes.

The chondrocyte circadian clock is altered in osteoarthritis. This change is implicated in the disease-associated changes in chondrocyte phenotype and cartilage loss. Why the clock is changed is unknown. N-methyl-D-aspartate receptors (NMDAR) are critical for regulating the hypothalamic clock. Chondrocytes also express NMDAR and the type of NMDAR subunits expressed changes in osteoarthritis. OBJECTIVE: To determine if NMDAR regulate the chondrocyte clock and phenotype. DESIGN: Chondrocytes isolated from macroscopically-normal (MN) and osteoarthritic human cartilage were treated with NMDAR antagonists or transfected with GRIN2A or GRIN2B-targetting siRNA. H5 chondrocytes were transfected with GluN2B-expression plasmids. Clock genes and chondrocyte phenotypic markers were measured by RT-qPCR. RESULTS: PER2 amplitude was higher and BMAL1 amplitude lower in osteoarthritic compared to MN chondrocytes. In osteoarthritic chondrocytes, NMDAR inhibition restored PER2 and BMAL1 expression to levels similar to MN chondrocytes, and resulted in reduced MMP13 and COL10A1. Paradoxically, NMDAR inhibition in MN chondrocytes resulted in increased PER2, decreased BMAL1 and increased MMP13 and COL10A1. Osteoarthritic, but not MN chondrocytes expressed GluN2B NMDAR subunits. GluN2B knockdown in osteoarthritic chondrocytes restored expression of circadian clock components and phenotypic markers to levels similar to MN chondrocytes. Ectopic expression of GluN2B resulted in reduced BMAL1, increased PER2 and altered SOX9, RUNX2 and MMP13 expression. Knockdown of PER2 mitigated the effects of GluN2B on SOX9 and MMP13. CONCLUSIONS: NMDAR regulate the chondrocyte clock and phenotype suggesting NMDAR may also regulate clocks in other peripheral tissues. GluN2B expression in osteoarthritis may contribute to pathology by altering the chondrocyte clock.

X-ray excited luminescent chemical imaging (XELCI) for non-invasive imaging of implant infections.

X-ray excited luminescent chemical imaging (XELCI) uses a combination of X-ray excitation to provide high resolution and optical detection to provide chemical sensing. A key application is to detect and study implant-associated infection. The implant is coated with a layer of X-ray scintillators which generate visible near infrared light when irradiated with an X-ray beam. This light first passes through a pH indicator dye-loaded film placed over the scintillator film in order to modulate the luminescence spectrum according to pH. The light then passes through tissue is collected and the spectral ratio measured to determine pH. A focused X-ray beam irradiates a point in the scintillator film, and a pH image is formed point-by-point by scanning the beam across the sample. The sensor and scanning system are described along with preliminary results showing images in rabbit models.