Tumor-infiltrating mast cells stimulate ICOS+ regulatory T cells through an IL-33 and IL-2 axis to promote gastric cancer progression.

INTRODUCTION: In solid tumors, regulatory T cell (Treg) and mast cell perform different roles depending on the microenvironment. Nevertheless, mast cell and Treg-mediated interactions in gastric cancer (GC) are unclear, as are their regulation, function, and clinical significance. OBJECTIVE: The present study demonstrated the mechanism of tumor-infiltrating mast cells stimulating ICOS+ regulatory T cells via the IL-33/IL-2 axis to promote the growth of gastric cancer. METHODS: Analyses of 98 patients with GC were conducted to examine mast cell counts, ICOS+ Tregs, and the levels of IL-33 or IL-2. Isolated ICOS+ Treg and CD8+ T cell were stimulated, cultured and tested for their functional abilities in vitro and in vivo. RESULTS: GC patients exhibited a significantly more production of IL-33 in tumors. Mast cell stimulated by tumor-derived IL-33 exhibited a prolonged lifespan through IL-33 mediated inhibition of apoptosis. Moreover, mast cells stimulated by tumor-derived IL-33 secreted IL-2, which induced Treg expansion. These inducible Tregs displayed an activated immunosuppressive phenotype with positive expression for the inducible T cell co-stimulator (ICOS). In vitro, IL-2 from IL to 33-stimulated mast cells induced increased numbers of ICOS+ Tregs with increased immunosuppressive activity against proliferation and effector function of CD8+ T cell. In vivo, ICOS+ Tregs were treated with anti-IL-2 neutralizing antibody followed by co-injection with CD8+ T cells in GC mouse model, which showed an increased CD8+ T cell infiltration and effector molecules production, meanwhile tumor growth and progression were inhibited. Besides, reduction in GC patient survival was associated with tumor-derived ICOS+ Tregs. CONCLUSION: Our results highlight a crosstalk between GC-infiltrating mast cells and ICOS+ Tregs and provide a novel mechanism describing ICOS+ Treg expansion and induction by an IL-33/mast cell/IL-2 signaling axis in GC, and also provide functional evidence that the modulation of this immunosuppressive pathway can attenuate GC-mediated immune tolerance.

A simple fragility fracture risk score for type 2 diabetes patients: a derivation, validation, comparison, and risk stratification study.

OBJECTIVES: The aims of this study were to develop and validate 2 simple scores for stratification of the risks of (1) any fragility (AF) and (2) major osteoporotic fracture (MOF) in type 2 diabetes (T2D) patients; we also compared the performance of these scores with that of the Fracture Risk Assessment Tool (FRAX) and its adjustments. DESIGN AND METHODS: In this longitudinal cohort study, 1855 patients with T2D were enrolled from January 2015 to August 2019. Cox proportional hazard regression was used to model the 5-year risk of AF and MOF. These scores were internally validated using a bootstrap resampling method of 1000. RESULTS: During a median follow-up of 5 years, 119 (6.42%) cases of AF and 92 (4.96%) cases of MOFs were identified. Both the concordance index (C-index) and calibration plots indicated improved identification performance using the newly established scores. Furthermore, these scores also showed improved outcomes regarding the decision curve analysis (DCA) and area under the curve (AUC) compared to the widely used FRAX and its derivatives. More importantly, these scores successfully separated T2D patients into risk groups according to significant differences in fracture incidence. CONCLUSIONS: These novel scores enable simple and reliable fracture risk stratification in T2D patients. Future work is needed to validate these findings in external cohort(s).

Protein Nucleation and Crystallization Process with Process Analytical Technologies in a Batch Crystallizer.

Protein crystallization has drawn great attention to replacing the traditional downstream processing for protein-based pharmaceuticals due to its advantages in stability, storage, and delivery. Limited understanding of the protein crystallization processes requires essential information based on real-time tracking during the crystallization process. A batch crystallizer of 100 mL fitted with a focused beam reflectance measurement (FBRM) probe and a thermocouple was designed for in situ monitoring of the protein crystallization process, with simutaneously record of off-line concentrations and crystal images. Three stages in the protein batch crystallization process were identified: long-period slow nucleation, rapid crystallization, and slow growth and breakage. The induction time was estimated by FBRM, i.e., increasing numbers of particles in the solution, which could be half of the time required for detecting the decrease of the concentration, by offline measurement. The induction time decreased with an increase in supersaturation within the same salt concentration. The interfacial energy for nucleation was analyzed based on each experimental group with equal salt concentration and different concentrations of lysozyme. The interfacial energy reduced with an increase in salt concentration in the solution. The yield of the experiments was significantly affected by the protein and salt concentrations and could achieve up to 99% yield with a 26.5 µm median crystal size upon stabilized concentration readings.

Tubulointerstitial nephritis antigen-like 1 is a novel matricellular protein that promotes gastric bacterial colonization and gastritis in the setting of Helicobacter pylori infection.

The interaction between the gastric epithelium and immune cells plays key roles in H. pylori-associated pathology. Here, we demonstrate a procolonization and proinflammatory role of tubulointerstitial nephritis antigen-like 1 (TINAGL1), a newly discovered matricellular protein, in H. pylori infection. Increased TINAGL1 production by gastric epithelial cells (GECs) in the infected gastric mucosa was synergistically induced by H. pylori and IL-1ß via the ERK-SP1 pathway in a cagA-dependent manner. Elevated human gastric TINAGL1 correlated with H. pylori colonization and the severity of gastritis, and mouse TINAGL1 derived from non-bone marrow-derived cells promoted bacterial colonization and inflammation. Importantly, H. pylori colonization and inflammation were attenuated in Tinagl1-/- and Tinagl1ΔGEC mice and were increased in mice injected with mouse TINAGL1. Mechanistically, TINAGL1 suppressed CCL21 expression and promoted CCL2 production in GECs by directly binding to integrin α5ß1 to inhibit ERK and activate the NF-κB pathway, respectively, which not only led to decreased gastric influx of moDCs via CCL21-CCR7-dependent migration and, as a direct consequence, reduced the bacterial clearance capacity of the H. pylori-specific Th1 response, thereby promoting H. pylori colonization, but also resulted in increased gastric influx of Ly6Chigh monocytes via CCL2-CCR2-dependent migration. In turn, TINAGL1 induced the production of the proinflammatory protein S100A11 by Ly6Chigh monocytes, promoting H. pylori-associated gastritis. In summary, we identified a model in which TINAGL1 collectively ensures H. pylori persistence and promotes gastritis.

Comparing the prognostic value of the old and new sarcopenia criteria from the Asian Working Group on Sarcopenia in older adults with type 2 diabetes: Which set is more appropriate?

BACKGROUND: This study aimed to compare the prevalence of sarcopenia according to the old and new Asian Working Group on Sarcopenia (AWGS) operational criteria and explore the effects of sarcopenia on adverse outcomes in older adults with type 2 diabetes (T2D). METHODS: A total of 386 patients with T2D aged ≥ 60 years were recruited in retrospective cohort study. Sarcopenia was assessed with different versions of the AWGS consensus, including the AWGS2014, AWGS2019H (muscle mass adjusted for height), and AWGS2019B (muscle mass adjusted for body mass index). The median follow-up period was 47 months. The composite primary endpoint was the first occurrence of cardiovascular disease (CVD), fragility fracture, and all-cause mortality and the secondary outcomes included the three separate components of the primary outcome. RESULTS: In this study, the prevalence of sarcopenia under different criteria was significantly different, with AWGS2019H having the highest prevalence of 31.3%. The agreement among sarcopenia criteria was unsatisfactory. By Cox regression analysis, all three AWGS definitions of sarcopenia were associated with the composite outcome of all-cause mortality, fracture and CVD (hazard ratio [HR], 2.69 vs. HR, 2.63; vs. HR, 2.23; model 3). Further exploratory analysis, sarcopenia defined by the AWGS2019H criteria was an independent risk factor for death, incident CVD, and fractures. While AWGS2014 criteria was an increased risk factor of death and CVD. The AWGS2019B criteria were only associated with incident fractures. CONCLUSION: All three AWGS definitions of sarcopenia were associated the composite primary endpoint. Additionally, the AWGS2019H criteria may be a better independent risk factor for negative health outcomes.

An investigation of the relationships between suicidal ideation, psychache, and meaning in life using network analysis.

BACKGROUND: Previous studies have investigated the relationships between psychache or meaning in life and suicidal ideation based on sum score of corresponding scale. However, this practice has hampered the fine-grained understanding of their relationships. This network analysis study aimed to conduct a dimension-level analysis of these constructs and the relationships among them in a joint framework, and identify potential intervention targets to address suicidal ideation. METHODS: Suicidal ideation, psychache, and meaning in life were measured using self-rating scales among 738 adults. A network of suicidal ideation, psychache, and meaning in life was constructed to investigate the connections between dimensions and calculate the expected influence and bridge expected influence of each node. RESULTS: "Psychache" was positively linked to "sleep" and "despair", while "presence of meaning in life" had negative associations with "psychache", "despair", and "pessimism". The most important central nodes were "sleep" and "despair", and the critical bridge nodes were "presence of meaning in life" and "psychache". CONCLUSION: These preliminary findings uncover the pathological pathways underlying the relationships between psychache, meaning in life, and suicidal ideation. The central nodes and bridge nodes identified may be potential targets for effectively preventing and intervening against the development and maintenance of suicidal ideation.

How are patterned movements stored in working memory?

Introduction: In this study, the change detection paradigm was used to study the working memory of patterned movements and the relationship of this type of memory with the visuospatial sketchpad in three experiments. Methods: Experiment 1 measured participants' working memory capacity for patterned movements and explored the influence of stimulus type with indicators such as response time and accuracy rate. Experiments 2 and 3 explored the relationship between patterned movements and the visual and spatial subsystems, respectively. Results: The results of Experiment 1 indicated that individuals can store 3-4 patterned movements in working memory; however, a change in stimulus format or an increase in memory load may decrease the speed and efficiency of working memory processing. The results of Experiment 2 showed that working memory and visual working memory are independent when processing patterned movements. The results of Experiment 3 showed that the working memory of patterned movements was affected by spatial working memory. Discussion: Changes in stimulus type and memory load exerted different effects on the working memory capacity of participants. These results provide behavioral evidence that the storage of patterned movement information is independent of the visual subsystem but requires the spatial subsystem of the visuospatial sketchpad.

Effects of plastisphere on phosphorus availability in freshwater system: Critical roles of polymer type and colonizing habitat.

Biofilm covered microplastics (BMPs) can act as vectors for the transport of exogenous microbial groups to aquatic ecosystem. However, a consensus regarding the formation and development of BMPs and their effect on phosphorus (P) availability has not been reached. Herein, plastic particles made of fuel-based (PET) and biobased polymers (PLA) were deployed in water and hyporheic zones of an urban river for biofilm colonization. Then, BMPs were transferred to lab incubation to study their effects on the P availability. The results showed that different microplastic biofilms had various bacteria and phytoplankton compositions. Additionally, BMPs induced a shift in the microbial co-occurrence patterns co-differentiated by polymer type and colonizing habitats. Network analyses revealed that the structure of PLA BMPs was more robust, while PET colonized in the hyporheic zone reduced network complexity with looser connections between species, and stronger negatively correlated interactions. However, PET formed denser biofilms by the excretion of extracellular polymeric substances from microalgae, which contributed to the better capacity of P utilization. PET colonized in the water/hyporheic zone significantly decreased soluble reactive phosphate by 42.5 % and 30.8 %, respectively. The abovementioned results indicated that BMPs have the potential to disrupt nutrient availability. This study broadens our perspectives for the ecological effects of BMPs in the aquatic environment.

The Relationships Between Suicidal Ideation, Meaning in Life, and Affect: a Network Analysis.

Transitioning from holistic analysis to a fine-grained level analysis may provide further understanding of psychopathology. This study aimed to explore dimension-level relationships between suicidal ideation, meaning in life, and affect in a joint framework using network analysis and to identify potential prevention and intervention targets to address suicidal ideation. A total of 852 healthy adults aged 18-35 years completed self-report scales to assess suicidal ideation, meaning in life, and affect. A regularized partial correlation network was then built to examine the links between these dimensions. Expected influence and bridge expected influence values were calculated for each node. The prevalence of suicidal ideation was 4.2%. The search for and presence of meaning in life and positive and negative affect exhibited distinct and complex links to the three dimensions of suicidal ideation (pessimism, sleep, and despair). The important central nodes were search for meaning in life, sleep, despair, and positive affect, while the critical bridge nodes were positive affect, negative affect, and presence of meaning in life. These findings provide further understanding of the specific roles of meaning in life and affect in suicidal ideation. The identified nodes may be promising targets for prevention and intervention for suicidal ideation.

Sarcopenic obesity predicts negative health outcomes among older patients with type 2 diabetes: The Ageing and Body Composition of Diabetes (ABCD) cohort study.

BACKGROUND AND AIMS: The definition of and diagnostic criteria for sarcopenic obesity (SO) remain unclear, hindering the assessment of its prevalence as well as its clinical relevance to negative health outcomes, especially in diabetic patients, who are more prone to body composition changes. The aim of this study was to investigate the prevalence of SO and its impact on negative health outcomes among elderly patients with type 2 diabetes (T2DM) from the Ageing and Body Composition of Diabetes (ABCD) cohort. METHODS: This retrospective cohort study included 386 elderly patients with T2DM (177 males and 209 females, mean age of 67.91 ± 6.10 years). SO was defined as the coexistence of sarcopenia defined by the 2019 Asian Working Group for Sarcopenia up-to-date consensus and obesity identified by five alternative measurements as follows: body mass index (BMI)≥28 kg/m2 (BMI28), BMI≥25 kg/m2 (BMI25), body fat percentage (BF%)≥25% for men or 35% for women, visceral fat area (VFA)≥100 cm2, or android fat mass (AF) higher than the sex-specific median. The primary endpoint was all-cause death or fragility fracture, and the secondary endpoint was a composite of cardiovascular diseases (CVDs). Cox proportional hazards regression analysis was used to estimate the association between SO and negative health outcomes. RESULTS: The prevalence of SO was 0.2% (BMI28), 2.5% (BMI25), 9.8% (AF), and 18.7% (BF% or VFA) among elderly patients with T2DM, according to the different obesity surrogate markers. During a mean follow-up period of 3.46 ± 1.15 years, 50 patients reached the primary endpoint, and 33 patients had incident CVD. SO classified using BF% was significantly associated with the primary endpoint [hazard ratio (HR) = 2.94, 95% CI = 1.25-6.92] and incident CVD (HR = 6.02, 95% CI = 1.56-23.15), even after comprehensive adjustment for bone-, comorbidity-, and diabetes-specific confounding variables. When SO was classified using BMI25, VFA and AF, similar results were found for adverse outcomes. However, SO classified using BMI25 resulted in misclassification of SO for 61 participants, 19 of whom experienced adverse events during follow-up, and SO classified using VFA or AF was not significantly associated with incident CVD. CONCLUSIONS: SO is not uncommon in geriatric patients with T2DM, and its prevalence varies widely depending on the diverse surrogate indices of body fat excess. Furthermore, SO may be a better independent risk factor for negative health outcomes when classified using BF%.

Effects of Audiovisual Interactions on Working Memory Task Performance-Interference or Facilitation.

(1) Background: The combined n-back + Go/NoGo paradigm was used to investigate whether audiovisual interactions interfere with or facilitate WM. (2) Methods: College students were randomly assigned to perform the working memory task based on either a single (visual or auditory) or dual (audiovisual) stimulus. Reaction times, accuracy, and WM performance were compared across the two groups to investigate effects of audiovisual interactions. (3) Results: With low cognitive load (2-back), auditory stimuli had no effect on visual working memory, whereas visual stimuli had a small effect on auditory working memory. With high cognitive load (3-back), auditory stimuli interfered (large effect size) with visual WM, and visual stimuli interfered (medium effect size) with auditory WM. (4) Conclusions: Audiovisual effects on WM follow the resource competition theory, and the cognitive load of a visual stimulus is dominated by competition; vision always interferes with audition, and audition conditionally interferes with vision. With increased visual cognitive load, competitive effects of audiovisual interactions were more obvious than those with auditory stimuli. Compared with visual stimuli, audiovisual stimuli showed significant interference only when visual cognitive load was high. With low visual cognitive load, the two stimulus components neither facilitated nor interfered with the other in accordance with a speed-accuracy trade-off.

Cryogenic Coaxial Printing for 3D Shell/Core Tissue Engineering Scaffold with Polymeric Shell and Drug-Loaded Core.

For decades, coaxial printing has been widely applied in 3D tissue engineering scaffold fabrication. However, there are few reports regarding polymeric materials application in shell production due to fabrication constraints. In this study, a combination of cryogenic printing and coaxial printing aims to approach the challenge. Polycaprolactone (PCL) and sodium alginate (SA) were selected as the representative shell and core materials to test the feasibility of the coaxial cryogenic printing by optimizing key parameters, including working temperature, air pressure, PCL, and SA concentration. According to the optical and SEM images, the SA core contracts a string inside the PCL shell, illustrating the shell/core structure of the 3D coaxial PCL/SA scaffolds. Besides, the shell/core 3D scaffold possesses a 38.39 MPa Young's modulus in mechanical tests; the PCL shell could retain at least 8 h in 5 mol/L HCl solution, leading to a fabricated drug-loaded PCL/SA shell/core "responsive" to acidic pH. In summary, coaxial cryogenic printing was developed to fabricate 3D scaffolds with a PCL/SA shell/core scaffold, broadening the material range of coaxial printing and providing promising applications in drug release.

Self-Assembly of Ultrafine Fibers with Micropores via Cryogenic Electrospinning and Its Potential Application in Esophagus Repair.

Electrospinning (e-spinning) has been widely applied to fabricate flat films accumulated by microfibers for tissue engineering. In order to acquire an uneven surface morphology, two methods have been applied traditionally. The first uses a designed receiving substrate, which is stable, but suppresses the flexibility. The second uses dual solvents to achieve bimodal distribution of the fiber diameter. However, the bimodal fiber diameter causes inhomogeneity. To solve these challenges, cryogenic electrospinning, using a flat substrate and a single solvent, was performed in this study to obtain uneven films. By applying a low temperature to the flat receiving substrate, uneven e-spun films with wall-like structures were achieved through the self-assembly of uniform filaments. In addition, the wall-like structures enhanced the mechanical properties of the e-spun films. Moreover, the cryogenic e-spinning produced micropores on the fiber surface, which have the potential to promote esophageal epithelial cell adhesion, proliferation and differentiation.

Working Memory Capacity of Biological Motion's Basic Unit: Decomposing Biological Motion From the Perspective of Systematic Anatomy.

Many studies have shown that about three biological motions (BMs) can be maintained in working memory. However, no study has yet analyzed the difficulties of experiment materials used, which partially affect the ecological validity of the experiment results. We use the perspective of system anatomy to decompose BM, and thoroughly explore the influencing factors of difficulties of BMs, including presentation duration, joints to execute motions, limbs to execute motions, type of articulation interference tasks, and number of joints and planes involved in the BM. We apply the change detection paradigm supplemented by the articulation interference task to measure the BM working memory capacity (WMC) of participants. Findings show the following: the shorter the presentation duration, the less participants remembered; the more their wrist moved, the less accurate their memory was; repeating verbs provided better results than did repeating numerals to suppress verbal encoding; the more complex the BM, the less participants remembered; and whether the action was executed by the handed limbs did not affect the WMC. These results indicate that there are many factors that can be used to adjust BM memory load. These factors can help sports psychology professionals to better evaluate the difficulty of BMs, and can also partially explain the differences in estimations of BM WMC in previous studies.

Down-regulated TINAGL1 in fibroblasts impairs wound healing in diabetes.

Matricellular proteins, a group of extracellular matrix (ECM) proteins, are key regulators of skin repair and their dysregulation impairs wound healing in diabetes. Tubulointerstitial nephritis antigen like 1 (TINAGL1) is a new member of matricellular protein family, and the understanding of its functional role is still relatively limited. In the current study, we detected the expression of TINAGL1 in diabetic skin wound tissues through RT-PCR, ELISA and Western blot analysis, investigated the contribution of TINAGL1 to wound healing through cutaneous administration of recombinant TINAGL1 protein, and characterized its regulation by hyperglycemia through RNA-seq and signal pathway inhibition assay. We showed that TINAGL1 expression has dynamic change and reaching a peak on day-9 after wound during the wound healing process in wild-type (WT) mice. Interestingly, decreased TINAGL1 expression is detected in skin tissues of diabetic patients and mice after wound. Then, we found that high glucose (HG), an important factor that impairs wound healing, reduces the expression of TINAGL1 in fibroblasts through JNK pathway. Notably, the histology analysis, Masson trichrome assay and IHC assay showed that exogenous TINAGL1 promotes wound healing in diabetic mice by accelerating the formation of granulation tissues. Our study provides evidence that TINAGL1 has an essential role in diabetic wound healing, and meanwhile, indicates that manipulation of TINAGL1 might be a possible therapeutic approach.

FasL+ PD-L2+ Identifies a Novel Immunosuppressive Neutrophil Population in Human Gastric Cancer That Promotes Disease Progression.

Neutrophils constitute abundant cellular components in human gastric cancer (GC) tissues, but their protumorigenic subset in pathogenesis of GC progression is unclear. Here, it is found that patients with GC show significantly higher neutrophil infiltration in tumors that is regulated by CXCL12-CXCR4 chemotaxis. These tumor-infiltrating neutrophils express high level immunosuppressive molecules FasL and PD-L2, and this FasL+ PD-L2+ neutrophil subset with a unique phenotype constitutes at least 20% of all neutrophils in advanced GC and predicts poor patient survival. Tumor induces neutrophils to express FasL and PD-L2 proteins with similar phenotype to those in GC tumors in both time-dependent and dose-dependent manners. Mechanistically, Th17 cell-derived IL-17A and tumor cell-derived G-CSF can significantly induce neutrophil FasL and PD-L2 expression via activating ERK-NF-κB and JAK-STAT3 signaling pathway, respectively. Importantly, upon over-expressing FasL and PD-L2, neutrophils acquire immunosuppressive functions on tumor-specific CD8+ T-cells and promote the growth and progression of human GC tumors in vitro and in vivo, which can be reversed by blocking FasL and PD-L2 on these neutrophils. Thus, the work identifies a novel protumorigenic FasL+ PD-L2+ neutrophil subset in GC and provides new insights for human cancer immunosuppression and anti-cancer therapies targeting these pathogenic cells.

Helicobacter pylori-induced REDD1 modulates Th17 cell responses that contribute to gastritis.

OBJECTIVE: Regulated in development and DNA damage responses-1 (REDD1) is a conserved and ubiquitous protein, which is induced in response to multiple stimuli. However, the regulation, function and clinical relevance of REDD1 in Helicobacter pylori-associated gastritis are presently unknown. APPROACH: Immunohistochemistry, real-time PCR and Western blot analyses were performed to examine the levels of REDD1 in gastric samples from H. pylori-infected patients and mice. Gastric tissues from Redd1-/- and wildtype (WT, control) mice were examined for inflammation. Gastric epithelial cells (GECs), monocytes and T cells were isolated, stimulated and/or cultured for REDD1 regulation and functional assays. RESULTS: REDD1 was increased in gastric mucosa of H. pylori-infected patients and mice. H. pylori induced GECs to express REDD1 via the phosphorylated cytotoxin associated gene A (cagA) that activated MAPKp38 pathway to mediate NF-κB directly binding to REDD1 promoter. Human gastric REDD1 increased with the severity of gastritis, and mouse REDD1 from non-marrow chimera-derived cells promoted gastric inflammation that was characterized by the influx of MHCII+ monocytes. Importantly, gastric inflammation, MHCII+ monocyte infiltration, IL-23 and IL-17A were attenuated in Redd1-/- mice. Mechanistically, REDD1 in GECs regulated CXCL1 production, which attracted MHCII+ monocytes migration by CXCL1-CXCR2 axis. Then H. pylori induced MHCII+ monocytes to secrete IL-23, which favored IL-17A-producing CD4+ cell (Th17 cell) polarization, thereby contributing to the development of H. pylori-associated gastritis. CONCLUSIONS: The present study identifies a novel regulatory network involving REDD1, which collectively exert a pro-inflammatory effect within gastric microenvironment. Efforts to inhibit this REDD1-dependent pathway may prove valuable strategies in treating of H. pylori-associated gastritis.

In situ bone regeneration with sequential delivery of aptamer and BMP2 from an ECM-based scaffold fabricated by cryogenic free-form extrusion.

In situ tissue engineering is a powerful strategy for the treatment of bone defects. It could overcome the limitations of traditional bone tissue engineering, which typically involves extensive cell expansion steps, low cell survival rates upon transplantation, and a risk of immuno-rejection. Here, a porous scaffold polycaprolactone (PCL)/decellularized small intestine submucosa (SIS) was fabricated via cryogenic free-form extrusion, followed by surface modification with aptamer and PlGF-2123-144*-fused BMP2 (pBMP2). The two bioactive molecules were delivered sequentially. The aptamer Apt19s, which exhibited binding affinity to bone marrow-derived mesenchymal stem cells (BMSCs), was quickly released, facilitating the mobilization and recruitment of host BMSCs. BMP2 fused with a PlGF-2123-144 peptide, which showed "super-affinity" to the ECM matrix, was released in a slow and sustained manner, inducing BMSC osteogenic differentiation. In vitro results showed that the sequential release of PCL/SIS-pBMP2-Apt19s promoted cell migration, proliferation, alkaline phosphatase activity, and mRNA expression of osteogenesis-related genes. The in vivo results demonstrated that the sequential release system of PCL/SIS-pBMP2-Apt19s evidently increased bone formation in rat calvarial critical-sized defects compared to the sequential release system of PCL/SIS-BMP2-Apt19s. Thus, the novel delivery system shows potential as an ideal alternative for achieving cell-free scaffold-based bone regeneration in situ.

[Application of Iron and Sulfate-Modified Biochar in Phosphorus Removal from Water].

The excessive discharge of phosphate into natural water has caused serious environmental problems. Adsorption is an efficient technology for phosphorus removal from water. In this study, a novel biochar modified by chitosan, ferrous sulfate, and sodium sulfide was synthesized and performed well in phosphorus adsorption. The results of batch experiments showed that the optimum synthesized composite could adsorb 49.32 mg·g-1 of phosphate at 298 K. Meanwhile, the simulation results showed better fitting with the pseudo-second-order model and Langmuir model. The adsorption rate was dominated by three-dimensional diffusion within the inner pores. The adsorption process was defined as physic/chemisorption, while the adsorption mechanism was concluded to be electrostatic adsorption, porous filling, surface chemical precipitation, hydrogen binding, and the ligand effect. This study showed that the composite is effective in phosphorus removal from water, and we anticipate that our research will offer guidelines for adsorbent design and reveal the adsorption mechanism.

How and When Job Crafting Relates to Employee Creativity: The Important Roles of Work Engagement and Perceived Work Group Status Diversity.

Creative employees are treasured assets for organizations. However, relatively little is known about what specific actions employees can take to manage their own creative process. Taking a motivational perspective, this study examined how job crafting behaviors positively link to employee creative performance through work engagement, and whether perceived work group status diversity moderates this relationship. We conducted a weekly diary study in which 55 employees from a Chinese energy company were asked to fill in diaries over four consecutive weeks (176 observations in total). Results of the multilevel analyses showed that weekly job crafting behaviors were positively related to weekly creative performance through increasing weekly work engagement. In contrast to our expectation, we found that weekly job crafting behaviors were more positively related to weekly creative performance when perceived work group status diversity was high. In summary, our study suggests that job crafting behaviors are effective actions employees can take to manage their creative processes through increasing work engagement. In addition, we stress that status diversity in existing work environments is an important contextual factor that shapes the job crafting process.