Large Orientation Angle Buried Substrate Enables Efficient Flexible Perovskite Solar Cells and Modules.

Flexible perovskite solar cells (f-PSCs) have emerged as potential candidates for specific mechanical applications owing to their high foldability, efficiency, and portability. However, the power conversion efficiency (PCE) of f-PSC remains limited by the inferior contact between perovskite and flexible buried substrate. Here, an asymmetric π-extended self-assembled monolayer (SAM) (4-(9H-dibenzo[a,c]carbazol-9-yl)butyl)phosphonic acid (A-4PADCB) is reported as a buried substrate for efficient inverted f-PSCs. Employing this design strategy, A-4PADCB exhibits a significant orientation angle away from the surface normal, homogenizing the distribution of contact potentials. This enhancement improves the SAM/perovskite interface quality, controlling the growth of favorable perovskite films with low defect density and slight tensile stress. Integration of A-4PADCB into small-area f-PSCs and large-area flexible perovskite solar modules with an aperture area of 20.84 cm2 achieves impressive PCEs of up to 25.05% and 20.64% (certified 19.51%), respectively. Moreover, these optimized A-4PADCB-based f-PSCs possess enhanced light, thermal, and mechanical stability. This research paves a promising avenue toward the design of SAM-buried substrates with a large orientation angle, regulating perovskite growth, and promoting the commercialization of large-area flexible perovskite photovoltaics.

Vegetation increases global climate vulnerability risk by shifting climate zones in response to rising atmospheric CO2.

Global climate zones are experiencing widespread shifts with ongoing rise in atmospheric CO2, influencing vegetation growth and shifting its distributions to challenge ecosystem structure and function, posing threats on ecological and societal safety. However, how rising atmospheric CO2 affects the pace of global climate zone shifts is highly uncertain. More attentions are urgently required to understand the underlying mechanisms and quantifications of regional climate vulnerability in response to rising CO2. In this study, we employ nine Earth system models from CMIP6 to investigate global climate zone shifts with rising CO2, unravel the effects of vegetation physiological response (PHY), and categorize climate vulnerable regions depending on the extent of climate zone shifts. We find that climate zone shifts over half of the global land area, 16.8% of which is contributed by PHY at 4 × CO2. Intriguingly, besides warming, PHY-induced precipitation changes and their interactions with warming dominate about two-fifths of PHY-forced shifts, providing potential direction for model improvement in future predictions of climate zone shifts. Aided with PHY effects, 4 × CO2 imposes substantial climate zone shifts over about one-fifth of the global land area, suggesting substantial changes in local climate and ecosystem structure and functions. Hence, those regions would experience strong climate vulnerability, and face high risk of climate extremes, water scarcity and food production. Our results quantitatively identify the vulnerable regions and unravel the underlying drivers, providing scientific insights to prioritize conservation and restoration efforts to ensure ecological and social safety globally.

Phosphorus desorption regulates phosphorus fraction dynamics in soil aggregates of revegetated ecosystems.

To elucidate the mechanisms and effects of phosphorus (P) desorption on P fractions in soil aggregates of revegetated ecosystems is fundamental for regulating the P supply and biogeochemical cycle. We selected four aggregate sizes (1-5, 0.5-1, 0.25-0.5, and <0.25 mm) from a desert revegetation chronosequence (11, 31, 40, 57, and 65 years) as our study targets and used the Freundlich model to reveal the dynamics of P desorption and changes in P fractions. The results showed that the calibrated model [Formula: see text] for different size aggregates in seven deserts (two natural and five revegetated) described the P desorption characteristics well. In soil aggregates of revegetated deserts, smaller aggregates with higher specific surface area did not desorb more P, nor did older aggregates after revegetation. The natural P desorption process in aggregates resulted in significant changes in Ca2-P, Ca8-P, Al-P and Fe-P fractions (p < 0.05), and revegetation years also affected P fraction dynamics significantly (p < 0.05). This study highlights that the calibrated kinetic model in the revegetated soil aggregates elucidated the P desorption characteristics, and that the P desorption process drove P fraction changes.

Using phlebotomy to remove a difficult peripherally inserted central catheter insertion and removal in very low birth weight infants: case report of a rare complication.

Background: A peripherally inserted central catheter (PICC) is an important way to supply long-term intravenous infusion or parenteral nutrition for premature infants, especially very low birth weight (VLBW) infants. PICC removal difficulties occur mostly during use. It is rare to have difficulty removing a PICC due to reverse folding during catheterization. We presented a case to explore the nursing experience of caring for a VLBW infant with difficult PICC removal. Case Description: A 30-week, 1,240-g infant, suffered a difficult PICC removal during the catheterization adjustment process. The X-ray images showed that the tip of the catheter was bent at the elbow joint and formed three abnormal bends in the blood vessel. The result was that the catheter was removed by a multidisciplinary team, and the reasons for the difficulty were analyzed. We used multidisciplinary team collaboration to solve a clinical problem. First, we analyzed the possible causes of a difficult removal by consulting PICC nurses, vascular interventional surgeons, and venous specialist nurses. Second, we used nonsurgical treatment methods to try to solve the problem. Finally, the catheter was completely removed using phlebotomy. Healing of wound and the growth of blood vessel are both well. Conclusions: In neonates, PICC may have obstacles in insertion and removal, methods such as posture changes, wet and hot compresses, and local massage can help. Multidisciplinary cooperation can improve the success rate of removal with minimal trauma. Individualized analysis of causes and measures are key steps to solve the difficulty of PICC insertion and removal.

Iguratimod, an allosteric inhibitor of macrophage migration inhibitory factor (MIF), prevents mortality and oxidative stress in a murine model of acetaminophen overdose.

BACKGROUND: Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine that has been implicated in multiple inflammatory and non-inflammatory diseases, including liver injury induced by acetaminophen (APAP) overdose. Multiple small molecule inhibitors of MIF have been described, including the clinically available anti-rheumatic drug T-614 (iguratimod); however, this drug's mode of inhibition has not been fully investigated. METHODS: We conducted in vitro testing including kinetic analysis and protein crystallography to elucidate the interactions between MIF and T-614. We also performed in vivo experiments testing the efficacy of T-614 in a murine model of acetaminophen toxicity. We analyzed survival in lethal APAP overdose with and without T-614 and using two different dosing schedules of T-614. We also examined MIF and MIF inhibition effects on hepatic hydrogen peroxide (H2O2) as a surrogate of oxidative stress in non-lethal APAP overdose. RESULTS: Kinetic analysis was consistent with a non-competitive type of inhibition and an inhibition constant (Ki) value of 16 µM. Crystallographic analysis revealed that T-614 binds outside of the tautomerase active site of the MIF trimer, with only the mesyl group of the molecule entering the active site pocket. T-614 improved survival in lethal APAP overdose when given prophylactically, but this protection was not observed when the drug was administered late (6 h after APAP). T-614 also decreased hepatic hydrogen peroxide concentrations during non-lethal APAP overdose in a MIF-dependent fashion. CONCLUSIONS: T-614 is an allosteric inhibitor of MIF that prevented death and decreased hepatic hydrogen peroxide concentrations when given prophylactically in a murine model of acetaminophen overdose. Further studies are needed to elucidate the mechanistic role of MIF in APAP toxicity.

Efficient and Stable Perovskite Solar Modules Enabled by Inhibited Escape of Volatile Species.

The intrinsically weak bonding structure in halide perovskite materials makes components in the thin films volatile, leading to the decomposition of halide perovskite materials. The reactions within the perovskite film are reversible provided that components do not escape the thin films. Here, a holistic approach is reported to improve the efficiency and stability of PSMs by preventing the effusion of volatile components. Specifically, a method for in situ generation of channel barrier layers for perovskite photovoltaic modules is developed. The resulting PSMs attain a certified aperture PCE of 21.37%, and possess remarkable continuous operation stability for maximum power point tracking (MPPT) of T90 > 1100 h in ambient air, and damp heat (DH) tracking of T93 > 1400 h.

Impact of nitrogen application and crop stage on epiphytic microbial communities on silage maize leaf surfaces.

This study aimed to examine the impact of nitrogen (N) fertilization on phyllosphere microorganisms in silage maize (Zea mays) to enhance the production of high-quality silage. The effects of different N application rates (160, 240, and 320 kg ha-1) and maturity stages (flowering and dough stages) on microbial diversity, abundance and physiochemical properties of the leaf surfaces were evaluated in a field experiment. The results showed that N application rates did not significantly impact the abundance of lactic acid bacteria (LAB), aerobic bacteria (AB), yeasts, or molds on the leaf surfaces. However, these microbes were more abundant during the flowering stage compared to the dough stage. Furthermore, the N application rate had no significant impact on inorganic phosphorus, soluble sugar, free amino acids, total phenolic content, and soluble protein concentrations, or pH levels on the leaf surfaces. Notably, these chemical indices were lower during the dough stage. The abundance of Pantoea decreased with higher N application rates, while that of other microorganisms did not changes significantly. The abundance of AB, LAB, yeasts, and molds were positively correlated with soluble sugar, soluble protein, inorganic phosphorus, free amino acids, and total phenolic concentrations on leaf surfaces. Moreover, water loss was negatively correlated with the abundance of AB, LAB, yeasts, and molds, whereas water retention capacity and stomatal density were positively correlated with microbial abundance. We recommend applying an optimal N rate of 160 kg ha-1 to silage maize and harvesting at the flowering stage is recommended.

Microplastic transport during desertification in drylands: Abundance and characterization of soil microplastics in the Amu Darya-Aral Sea basin, Central Asia.

Desertification and microplastic pollution are major environmental issues that impact the function of the ecosystem and human well-being of drylands. Land desertification may influence soil microplastics' abundance, transport, and distribution, but their distribution in the dryland deserts of Central Asia's Amu Darya-Aral Sea basin is unknown. Here, we investigated the abundance and distribution of microplastics in dryland desert soils from the Amu Darya River to the Aral Sea basin in Central Asia at a spatial scale of 1000 km and soil depths ranging from 0 to 50 cm. Microplastics were found in soils from all sample locations, with abundances ranging from 182 to 17841 items kg-1 and a median of 3369. Twenty-four polymers were identified, with polyurethane (PU, 37.3%), silicone resin (SR, 17.0%), and chlorinated polyethylene (CPE, 9.8%) accounting for 64.1% of all polymer types. The abundance of microplastics was significantly higher in deep (20-50 cm) soils than in surface (0-5, 5-20 cm) soils. The main morphological characteristics of the observed microplastics were small size (20-50 µm) and irregular particles with no round edges (mean eccentricity 0.65). The abundance was significantly and positively related to soil EC and TP. According to the findings, desertification processes increase the abundance of microplastic particles in soils and promote migration to deeper soil layers. Human activities, mainly grazing, may be the region's primary cause of desertification and microplastic pollution. Our findings provide new information on the diffusion of microplastics in drylands during desertification; these findings are critical for understanding and promoting dryland plastic pollution prevention and control.

Multi-Drug Cocktail Therapy Improves Survival and Neurological Function after Asphyxial Cardiac Arrest in Rodents.

BACKGROUND: Cardiac arrest (CA) can lead to neuronal degeneration and death through various pathways, including oxidative, inflammatory, and metabolic stress. However, current neuroprotective drug therapies will typically target only one of these pathways, and most single drug attempts to correct the multiple dysregulated metabolic pathways elicited following cardiac arrest have failed to demonstrate clear benefit. Many scientists have opined on the need for novel, multidimensional approaches to the multiple metabolic disturbances after cardiac arrest. In the current study, we have developed a therapeutic cocktail that includes ten drugs capable of targeting multiple pathways of ischemia-reperfusion injury after CA. We then evaluated its effectiveness in improving neurologically favorable survival through a randomized, blind, and placebo-controlled study in rats subjected to 12 min of asphyxial CA, a severe injury model. RESULTS: 14 rats were given the cocktail and 14 received the vehicle after resuscitation. At 72 h post-resuscitation, the survival rate was 78.6% among cocktail-treated rats, which was significantly higher than the 28.6% survival rate among vehicle-treated rats (log-rank test; p = 0.006). Moreover, in cocktail-treated rats, neurological deficit scores were also improved. These survival and neurological function data suggest that our multi-drug cocktail may be a potential post-CA therapy that deserves clinical translation. CONCLUSIONS: Our findings demonstrate that, with its ability to target multiple damaging pathways, a multi-drug therapeutic cocktail offers promise both as a conceptual advance and as a specific multi-drug formulation capable of combatting neuronal degeneration and death following cardiac arrest. Clinical implementation of this therapy may improve neurologically favorable survival rates and neurological deficits in patients suffering from cardiac arrest.

Occlusal contact and clearance of posterior implant-supported single crowns designed by two different methods: a self-controlled study.

BACKGROUND: Precise occlusal design of implant-supported fixed prostheses is difficult to achieve by the conventional wax-up method, often requiring chairside adjustments. The computer-aided design (CAD) method is promising. This study aims to compare the occlusal contacts and clearance of posterior implant-supported single crowns designed by the CAD and conventional methods. METHODS: Sample size calculation indicated fourteen samples per group. Two sets of type-IV plaster casts with a single implant analog inserted in the posterior teeth region were mounted as master casts in a mechanical articulator in maximal intercuspal position (MIP). Seven working cast sets were obtained from each master cast by a closed tray technique, and mounted in MIP. Two implant-supported single crowns were designed with an occlusal clearance to achieve light occlusal contact in each working cast set by CAD and conventional method, separately. For the CAD group, the crown was designed in digital models obtained by scanning the working casts. For the conventional group, wax-up of the crown was prepared on the working casts and scanned to generate a STL file. In the working and master casts, mean and minimum occlusal clearances in the designed occlusal contact area of the both finished prostheses were calculated using the occlusal clearance (OC) and occlusal record (OR) method. The prostheses' occlusion was evaluated in master casts. RESULTS: For the evaluation in the working casts, both design methods had similar mean occlusal clearances by the OC method (195.4 ± 43.8 vs. 179.8 ± 41.8 µm; P = 0.300), while CAD group resulted in a significantly larger minimum occlusal clearance in the designed occlusal contact area (139.5 ± 52.3 vs. 99.8 ± 43.8 µm; P = 0.043). Both design methods had similar mean and minimum occlusal clearances by the OR method (P > 0.05). For the evaluation in the master casts, both design techniques had similar mean and minimum occlusal clearances, number and distribution of occlusal contacts, and lateral interference ratios (P > 0.05). CONCLUSION: Occlusal contact and clearance of posterior implant-supported single crowns designed by the CAD method can be at least as good as those designed by the conventional wax-up method.

Atmospheric dryness thresholds of grassland productivity decline in China.

Atmospheric dryness events are bound to have a broad and profound impact on the functions and structures of grassland ecosystems. Current research has confirmed that atmospheric dryness is a key moisture constraint that inhibits grassland productivity, yet the risk threshold for atmospheric dryness to initiate ecosystem productivity loss has not been explored. Based on this, we used four terrestrial ecosystem models to simulate gross primary productivity (GPP) data, analyzed the role of vapor pressure deficit (VPD) in regulating interannual variability in Chinese grasslands by focusing on the dependence structure of VPD and GPP, and then constructed a bivariate linkage function to calculate the conditional probability of ecosystem GPP loss under atmospheric dryness, and further analyzed the risk threshold of ecosystem GPP loss triggered by atmospheric dryness. The main results are as follows: we found that (1) the observed and modeled VPD of Chinese grasslands increases rapidly in both historical and future periods. VPD has a strongly negative regulation on ecosystem GPP, and atmospheric dryness is an important moisture constraint that causes deficit and even death to ecosystem GPP. (2) The probability of the enhanced atmospheric dryness that induced GPP decline in Chinese grasslands in the future period increases significantly. (3) When the VPD is higher than 40.07 and 27.65 percentile of the past and future time series, respectively, the risk threshold of slight ecosystem GPP loss can be easily initiated by atmospheric dryness. (4) When the VPD is higher than 82.57 and 65.09 percentile, respectively, the threshold of moderate ecosystem GPP loss can be exceeded by the benchmark probability. (5) The risk threshold of severe ecosystem GPP loss is not initiated by atmospheric dryness in the historical period, and the threshold of severe ecosystem GPP loss can be initiated when the future VPD is higher than 91.92 percentile. In total, a slight atmospheric dryness event is required to initiate a slight ecosystem GPP loss threshold, and a stronger atmospheric dryness event is required to initiate a severe ecosystem GPP loss. Our study enhances the understandings of past and future atmospheric dryness on grassland ecosystems, and strongly suggests that more attention be invested in improving next-generation models of vegetation dynamics processes with respect to the response of mechanisms of ecosystem to atmospheric dryness.

Effect of a novel interocclusal recording method on occlusal accuracy of implant-supported fixed prostheses: A randomized clinical trial.

OBJECTIVES: To investigate the effect of a novel interocclusal recording method on the occlusal accuracy of implant-supported fixed prostheses for partially dentate patients with distal extension. MATERIALS AND METHODS: Twenty patients with two or more adjacent teeth missing in the distal extension and scheduled to receive implant-supported fixed prostheses were enrolled. Two interocclusal recording methods were used: placing polyvinyl siloxane (PVS) on the interocclusal recording caps (test), and placing PVS on healing abutments (control). The intraoral occlusal contacts in maximal intercuspal position (MIP) were compared with those in the mounted casts to calculate sensitivity and positive predictive value (PPV). Then, patients were randomly allocated into two groups to determine which interocclusal record would be used. The implant prostheses' evaluations mainly included occlusal adjustment height, volume, and time, occlusal contact score based on articulating paper examination. Paired-samples t-test, Mann-Whitney U test, and least squares regression analyzed the statistic differences. RESULTS: The test method had higher sensitivity to detect intraoral occlusal contacts than the control method (p = .002), but similar PPV (p = .10). During the prostheses' evaluations, the occlusal adjustment height in the test group was significantly lower than that in the control group [99.4 (53.2, 134.2) vs. 159.0 (82.3, 247.8) µm, p = .03], while the occlusal contact score before adjustment was higher (p = .006). The groups had similar occlusal adjustment volume and time. CONCLUSIONS: The novel interocclusal recording method for implant-supported fixed prostheses was more accurate and could reduce the occlusal adjustment.

Thiocarbazate building blocks enable the construction of azapeptides for rapid development of therapeutic candidates.

Peptides, polymers of amino acids, comprise a vital and expanding therapeutic approach. Their rapid degradation by proteases, however, represents a major limitation to their therapeutic utility and chemical modifications to native peptides have been employed to mitigate this weakness. Herein, we describe functionalized thiocarbazate scaffolds as precursors of aza-amino acids, that, upon activation, can be integrated in a peptide sequence to generate azapeptides using conventional peptide synthetic methods. This methodology facilitates peptide editing-replacing targeted amino acid(s) with aza-amino acid(s) within a peptide-to form azapeptides with preferred therapeutic characteristics (extending half-life/bioavailability, while at the same time typically preserving structural features and biological activities). We demonstrate the convenience of this azapeptide synthesis platform in two well-studied peptides with short half-lives: FSSE/P5779, a tetrapeptide inhibitor of HMGB1/MD-2/TLR4 complex formation, and bradykinin, a nine-residue vasoactive peptide. This bench-stable thiocarbazate platform offers a robust and universal approach to optimize peptide-based therapeutics.

Dynamics of soil organic carbon and nitrogen and their relations to hydrothermal variability in dryland.

Carbon (C) and nitrogen (N) cycles of terrestrial ecosystems play key roles in global climate change and ecosystem sustainability. In recent decades, climate change has threatened the nutrient balance of dryland ecosystems. However, its impact on soil organic carbon (SOC) and soil total nitrogen (STN) in drylands of China are still unclear. In this study, the structural equation model (SEM) was used to explain the relationship between environmental variables used by the best model and SOC or STN. Then Adaptive Boosting Regressor (AdaBoost), Gradient Boosting Regression (GBRT), Extreme gradient boosting Regression (XGBoost) and Random Forest Regression (RF) were used to establish the prediction model of SOC and STN based on soil samples along with environmental variables. The performance of these models was assessed based on a 10-fold cross-validation method using three statistical indicators. Finally, we predicted the SOC and STN of soil samples from 2000 to 2019 based on the best model. Overall, the RF model performed better at predicting SOC and STN in drylands than the other three prediction models (AdaBoost, GBRT, XGBoost). Climate factors were the main factors affecting SOC and STN in the study area. In the Alashan, a dryland in northern China, the precipitation in the growing season increased from 2000 to 2019, at a rate of 12.9 mm/decade. During the same period, the annual sunshine duration significantly decreased by 66 h/decade. Along with interannual hydrothermal variability, SOC showed a fluctuating upward trend at a rate of 0.04 g/kg/decade, while STN exhibited a fluctuating downward trend at 0.003 g/kg/decade from 2000 to 2019. Due to the effects of climate change, dryland were considered as potential sites for carbon sequestration. However, due to the annual hydrothermal variance causing dynamic annual changes, it was deemed unstable. Moreover, it would cause STN loss, which might reduce soil fertility. More attention should be paid to STN monitoring in dryland in the future.

Azapeptides -A History of Synthetic Milestones and Key Examples.

For over 50 years of azapeptide synthetic techniques, developments have renewed the field of peptidomimetic therapeutics. Azapeptides are close surrogates of natural peptides: they contain a substitution of the amino acid α-carbon by a nitrogen atom. Goserelin (1989) and Atazanavir (2003) are two well-known, FDA-approved azapeptide-based drugs for the treatment of cancers and HIV infection, providing evidence for the successful clinical implementation of this class of therapeutic. This review highlights the azapeptides in recent medicinal chemistry applications and synthetic milestones. We describe the current techniques for azapeptide bond formation by introducing azapeptide coupling reagents and chain elongation methods both in solution and solid-phase strategies.

Determination of catechin and glutathione using copper aspartate nanofibers with multiple enzyme-like activities.

Copper aspartate nanofibers were facilely prepared based on aspartic acid and copper (CuAsp nanofibers). It is found that the prepared CuAsp nanofibers have catalytic activities of five enzymes, including peroxidase, laccase, catalase, ascorbate oxidase, and superoxide dismutase mimetic activities. The kinetic and catalytic properties of CuAsp nanofibers were systematically investigated, showing their high catalytic activity, excellent stability, and reusability. The laccase mimetic activity of nanofibers could be used to detect catechin in the range 20-1200 µM with a detection limit of 5.88 µM. In addition, a sensing platform for glutathione with a detection limit of 0.25 µM and a detection range of 1-50 µM was established based on CuAsp nanofibers which have the peroxidase-mimicking activity. The sensor had good selectivity and could detect glutathione in actual samples of human serum. Therefore, CuAsp nanofibers with multi-enzyme activity have broad application prospects such as biosensing, environmental management, and disease diagnosis.

HMGB1-mediated restriction of EPO signaling contributes to anemia of inflammation.

Anemia of inflammation, also known as anemia of chronic disease, is refractory to erythropoietin (EPO) treatment, but the mechanisms underlying the EPO refractory state are unclear. Here, we demonstrate that high mobility group box-1 protein (HMGB1), a damage-associated molecular pattern molecule recently implicated in anemia development during sepsis, leads to reduced expansion and increased death of EPO-sensitive erythroid precursors in human models of erythropoiesis. HMGB1 significantly attenuates EPO-mediated phosphorylation of the Janus kinase 2/STAT5 and mTOR signaling pathways. Genetic ablation of receptor for advanced glycation end products, the only known HMGB1 receptor expressed by erythroid precursors, does not rescue the deleterious effects of HMGB1 on EPO signaling, either in human or murine precursors. Furthermore, surface plasmon resonance studies highlight the ability of HMGB1 to interfere with the binding between EPO and the EPOR. Administration of a monoclonal anti-HMGB1 antibody after sepsis onset in mice partially restores EPO signaling in vivo. Thus, HMGB1-mediated restriction of EPO signaling contributes to the chronic phase of anemia of inflammation.

The Accuracy of Transferring Casts in Maximal Intercuspal Position to a Virtual Articulator.

PURPOSE: To analyze the accuracy of transferring casts in maximal intercuspal position to a virtual articulator by using transfer plates in the laboratory scanner before and after occlusal optimization. MATERIAL AND METHODS: Five sets of standard dental casts were mounted on a mechanical articulator in maximal intercuspal position. The number and position of occlusal contacts were determined with 12-µm articulating foil. After a calibration process according to the manufacturer's instructions, the mountings were transferred to a virtual articulator using the transfer plates in a laboratory scanner. The occlusion of the digital casts was determined before and after the occlusal optimization process. Then, the sensitivity and positive predictive value were determined by comparing the occlusal contact points in the virtual articulator with those in the mechanical articulator. To evaluate trueness, the occlusal surface of the maxillary teeth in the mechanical articulator was recorded by polyvinyl siloxane occlusal record in maximal intercuspal position and retained on the mandibular arch. The trueness was calculated as the deviation between the occlusal surface of the maxillary teeth in the mechanical articulator and the virtual articulator. To evaluate precision, one set of the casts was scanned 10 times. And the deviation of the interarch position of the maxillary arches when superimposing the mandibular arches of every 2 different scans was calculated. RESULTS: The sensitivity before occlusal optimization (0.14 ± 0.15) was significantly lower than that after occlusal optimization (0.82 ± 0.10) (p = 0.003). However, there was no significant difference between the positive predictive value before (0.80 ± 0.45) and after (0.81 ± 0.09) occlusal optimization (p = 0.952). The trueness before (91.0 ± 10.7 µm) and after (75.4 ± 25.2 µm) occlusal optimization had no significant difference (p = 0.249). The precision before occlusal optimization (11.6 ± 3.8 µm) was significantly superior to that after occlusal optimization (75.6 ± 39.2 µm ) (p < 0.001). CONCLUSIONS: The accuracy of transferring casts in maximal intercuspal position to a virtual articulator using transfer plates in the laboratory scanner could be improved after occlusal optimization and can meet the clinical needs for occlusal design and analysis of prostheses.

Human Dermcidin Protects Mice Against Hepatic Ischemia-Reperfusion-Induced Local and Remote Inflammatory Injury.

Background: Hepatic ischemia and reperfusion (I/R) injury is commonly associated with surgical liver resection or transplantation, and represents a major cause of liver damage and graft failure. Currently, there are no effective therapies to prevent hepatic I/R injury other than ischemic preconditioning and some preventative strategies. Previously, we have revealed the anti-inflammatory activity of a sweat gland-derived peptide, dermcidin (DCD), in macrophage/monocyte cultures. Here, we sought to explore its therapeutic potential and protective mechanisms in a murine model of hepatic I/R. Methods: Male C57BL/6 mice were subjected to hepatic ischemia by clamping the hepatic artery and portal vein for 60 min, which was then removed to initiate reperfusion. At the beginning of reperfusion, 0.2 ml saline control or solution of DCD (0.5 mg/kg BW) or DCD-C34S analog (0.25 or 0.5 mg/kg BW) containing a Cys (C)→Ser (S) substitution at residue 34 was injected via the internal jugular vein. For survival experiments, mice were subjected to additional resection to remove non-ischemic liver lobes, and animal survival was monitored for 10 days. For mechanistic studies, blood and tissue samples were collected at 24 h after the onset of reperfusion, and subjected to measurements of various markers of inflammation and tissue injury by real-time RT-PCR, immunoassays, and histological analysis. Results: Recombinant DCD or DCD-C34S analog conferred a significant protection against lethal hepatic I/R when given intravenously at the beginning of reperfusion. This protection was associated with a significant reduction in hepatic injury, neutrophilic CXC chemokine (Mip-2) expression, neutrophil infiltration, and associated inflammation. Furthermore, the administration of DCD also resulted in a significant attenuation of remote lung inflammatory injury. Mechanistically, DCD interacted with epidermal growth factor receptor (EGFR), a key regulator of liver inflammation, and significantly inhibited hepatic I/R-induced phosphorylation of EGFR as well as a downstream signaling molecule, protein kinase B (AKT). The suppression of EGFR expression by transducing Egfr-specific shRNA plasmid into macrophages abrogated the DCD-mediated inhibition of nitric oxide (NO) production induced by a damage-associated molecular pattern (DAMP), cold-inducible RNA-binding protein, CIRP. Conclusions: The present study suggests that human DCD and its analog may be developed as novel therapeutics to attenuate hepatic I/R-induced inflammatory injury possibly by impairing EGFR signaling.

Inhibition of IRF5 hyperactivation protects from lupus onset and severity.

The transcription factor IFN regulatory factor 5 (IRF5) is a central mediator of innate and adaptive immunity. Genetic variations within IRF5 are associated with a risk of systemic lupus erythematosus (SLE), and mice lacking Irf5 are protected from lupus onset and severity, but how IRF5 functions in the context of SLE disease progression remains unclear. Using the NZB/W F1 model of murine lupus, we show that murine IRF5 becomes hyperactivated before clinical onset. In patients with SLE, IRF5 hyperactivation correlated with dsDNA titers. To test whether IRF5 hyperactivation is a targetable function, we developed inhibitors that are cell permeable, nontoxic, and selectively bind to the inactive IRF5 monomer. Preclinical treatment of NZB/W F1 mice with an inhibitor attenuated lupus pathology by reducing serum antinuclear autoantibodies, dsDNA titers, and the number of circulating plasma cells, which alleviated kidney pathology and improved survival. Clinical treatment of MRL/lpr and pristane-induced lupus mice with an inhibitor led to significant reductions in dsDNA levels and improved survival. In ex vivo human studies, the inhibitor blocked SLE serum-induced IRF5 activation and reversed basal IRF5 hyperactivation in SLE immune cells. We believe this study provides the first in vivo clinical support for treating patients with SLE with an IRF5 inhibitor.