Circular economy life cycle cost for kerbside waste material looping process.

Rapid expansion in urban areas has engendered a superfluity of municipal solid waste (MSW) stemming from contemporary civilization, encompassing commercial sectors and human undertakings. Kerbside waste, a type of MSW, has the potential for recycling and reuse at the end of its first life cycle, but is often limited to a linear cycle. This study aimed to assess the life cycle costs of different separation and recycling methods for handling kerbside waste. A new life cycle cost model, drawing from the circular economy's value retention process (VRP) model, has been created and applied to assess the continuous recycling of kerbside glass. The study investigates two key separation techniques, kerbside recycling mixed bin recycling (KRMB) kerbside glass recycling separate bin (KGRSB) and analyses their impact on the life cycle cost of the recycling process. Additionally, the research explores two approaches of recycling and downcycling: closed-loop recycling, which pertains to the recycling of glass containers, and open-looped recycling, which involves the use of recycled glass in asphalt. The results showed when use annually collected waste as the functional unit, the KRMB model incurred lower costs compared to the KGRSB model due to its lower production output. However, when evaluated over a 1-ton production of glass container and asphalt, the KGRSB method demonstrated superior cost performance with a 40-50% reduction compared to the KRMB method. The open-loop recycling method (asphalt) incurred a higher cost compared to the closed-loop recycling method due to its larger production volume over a 21-year period.

Airborne pollen exposure and risk of hospital admission for allergic rhinitis in Beijing: A time-stratified case-crossover study.

BACKGROUND: Airborne pollen is a crucial risk factor in allergic rhinitis (AR). The severity of AR symptoms can vary based on pollen type and concentration. This study aimed to estimate the association between exposure to different pollen types and AR risk. METHODS: We obtained data from patients admitted to the Beijing Tongren Hospital for AR, and data on pollen concentration, meteorological factors, and fine particulate matter (PM2.5) from 13 districts in Beijing from 2016 to 2019. We used a time-stratified case-crossover study design and calculated odds ratios (ORs) related to the risk of AR associated with a 10 grain/1000 mm2 increase in total pollen concentrations for specific pollen types. A stratified analysis was conducted to assess whether the associations were varied by age and sex. RESULTS: The OR of AR associated with a 10 grain/1000 mm2 increase in the 7-day average pollen concentration was 1.014 (95% CI: 1.014, 1.015), 1.076 (95% CI: 1.070, 1.082), 1.024 (95% CI: 1.023, 1.025), 1.042 (95% CI: 1.039, 1.045), 1.142 (95% CI: 1.137, 1.147), 1.092 (95% CI: 1.088, 1.097), 1.046 (95% CI: 1.035, 1.058), and 1.026 (95% CI: 1.024, 1.028) for total pollen, Ulmus, Cupressaceae, Populus, Fraxinus, Pinus, Betula, and Artemisia, respectively. Both tree pollen (Ulmus, Cupressaceae, Populus, Fraxinus, Betula, and Pinus) and weed pollen (Artemisia, Chenopodium, and Humulus) were correlated with an increased risk of AR. These associations remained consistent across distinct subgroups defined by both age and sex. CONCLUSION: Exposure to pollen from trees and weeds might be associated with an increased risk of AR. This research provides valuable scientific support for both clinical practitioners and patients with AR regarding the hazards of pollen exposure.

The Structure Characteristics and Function of Non B Cell-Derived Immunoglobulin.

According to classical immunology theory, immunoglobulin (Ig) is exclusively produced by differentiated B lymphocytes, which exhibit a typical tetrapeptide chain structure and are predominantly present on the surface of B cells and in bodily fluids. B-Ig is one of the critical effector molecules for humoral immune responses specifically recognising antigens and eliminating them. However, mounting evidence has demonstrated that Ig is widely expressed in non B lineage cells, especially malignant ones (referred to as non B-Ig). Interestingly, non B-Ig mainly resides in the cytoplasm and secretion, but to some extent on the cell surface. Furthermore non B-Ig not only displays a tetrapeptide chain structure but also shows free heavy chains and free light chains (FLCs). Additionally, Ig derived from non B cancer cell typically displays unique glycosylation modifications. Functionally, non B-Ig demonstrated diversity and versatility, showing antibody activity and cellular biological activity, such as promoting cell proliferation and survival, and it is implicated in cancer progression and some immune-related diseases, such as renal diseases.

Advancing NSCLC pathological subtype prediction with interpretable machine learning: a comprehensive radiomics-based approach.

Objective: This research aims to develop and assess the performance of interpretable machine learning models for diagnosing three histological subtypes of non-small cell lung cancer (NSCLC) utilizing CT imaging data. Methods: A retrospective cohort of 317 patients diagnosed with NSCLC was included in the study. These individuals were randomly segregated into two groups: a training set comprising 222 patients and a validation set with 95 patients, adhering to a 7:3 ratio. A comprehensive extraction yielded 1,834 radiomic features. For feature selection, statistical methodologies such as the Mann-Whitney U test, Spearman's rank correlation, and one-way logistic regression were employed. To address data imbalance, the Synthetic Minority Over-sampling Technique (SMOTE) was utilized. The study designed three distinct models to predict adenocarcinoma (ADC), squamous cell carcinoma (SCC), and large cell carcinoma (LCC). Six different classifiers, namely Logistic Regression, Support Vector Machine, Decision Tree, Random Forest, eXtreme Gradient Boosting (XGB), and LightGBM, were deployed for model training. Model performance was gauged through accuracy metrics and the area under the receiver operating characteristic (ROC) curves (AUC). To interpret the diagnostic process, the Shapley Additive Explanations (SHAP) approach was applied. Results: For the ADC, SCC, and LCC groups, 9, 12, and 8 key radiomic features were selected, respectively. In terms of model performance, the XGB model demonstrated superior performance in predicting SCC and LCC, with AUC values of 0.789 and 0.848, respectively. For ADC prediction, the Random Forest model excelled, showcasing an AUC of 0.748. Conclusion: The constructed machine learning models, leveraging CT imaging, exhibited robust predictive capabilities for SCC, LCC, and ADC subtypes of NSCLC. These interpretable models serve as substantial support for clinical decision-making processes.

A simplified reliability-based design method for multiple design variables considering different limit states.

A generalized reliability model comprising the objective, constraint, and judgment functions is established for the reliability index approach (RIA), taking parameters' properties of engineering practice and negative reliability index into consideration. Based on this, the reliability-based design (RBD) problem with multiple design variables is translated into the solution to the nonlinear equations, and a simplified method consisting of a simple variant of the Newton iteration method and the finite difference method (FDM) is proposed. Numerical examples are presented to verify the efficiency of the proposed reliability approach and to determine the incremental step size for FDM. RBD of a simply supported beam is illustrated and the variabilities of design variables are investigated considering the uncertainties in the manufacturing process and practical operations. Results reveal that the variations of the design variables should not be ignored. Moreover, analysis results show that the design value might not intuitively increase with the increase of its coefficient of variation (CoV), and it might not increase with the increasing reliability requirement for problems involving multiple variables. The reasons for this phenomenon are very complicated, and it is a systematic problem. One should be aware of this phenomenon, and specific analysis is required for specific problems.

Diagnostic value of contrast-enhanced ultrasonography for patent foramen ovale detection.

Background: Patent foramen ovale (PFO) has been associated with migraine, cryptogenic stroke (CS), and hypoxemia. However, which examination method is most reliable remains controversial. This study sought to investigate the diagnostic value of contrast-enhanced ultrasonography (cU), including contrast-enhanced transcranial Doppler (cTCD), contrast transthoracic echocardiography (cTTE), and contrast transesophageal echocardiography (cTEE), for PFO; and to determine the best diagnostic strategy. Methods: This retrospective observational study included a total of 147 consecutive patients suspected PFO at The First Hospital of Shanxi Medical University between October 2019 and January 2022. The patients also underwent cTCD, cTTE, and cTEE examinations. The standard for the diagnosis of PFO was confirmation of the presence of PFO by color Doppler flow signals or contrast microbubbles (MBs) passing through the foramen ovale. Results: A total of 123 patients were diagnosed with PFO and 24 patients without PFO during the study period. The detectable rates of cTCD, cTTE, and cTEE were 120 (97.56%), 110 (89.43%), and 121 (98.37%), respectively. The sensitivity between cTCD and cTEE for PFO were comparable [97.56%, 95% confidence interval (CI): 92.5% to 99.4% vs. 98.37%, 95% CI: 93.7% to 99.7%; P>0.99], and the sensitivity of both were higher than that of cTTE (89.43%, 95% CI: 82.3% to 94.0%; P=0.02 and P=0.001, respectively). In addition, the specificity of cTEE for PFO was significantly higher than that of cTCD (100%, 95% CI: 82.3% to 100.0% vs. 75.00%, 95% CI: 53.0% to 89.4%; P<0.001) and cTTE (100%, 95% CI: 82.3% to 100.0% vs. 75.00%, 95% CI: 53.0% to 89.4%; P<0.001). Further, the semi-quantitative classification ability of cTCD for PFO with right-to-left shunt (RLS) was significantly higher than that of cTTE and cTEE (P=0.02 and P<0.001, respectively), and that of cTTE was significantly higher than that of cTEE (P=0.01). The Spearman analysis showed that the degree of RLS was positively correlated with the inner diameter of the PFO (r=0.695, P<0.001). Conclusions: The combination of cTCD and cTEE may provide a favorable strategy for the diagnosis of PFO.

Cholesterol sulfate-mediated ion-pairing facilitates the self-nanoassembly of hydrophilic cationic mitoxantrone.

HYPOTHESIS: Hydrophilic cationic drugs such as mitoxantrone hydrochloride (MTO) pose a significant delivery challenge to the development of nanodrug systems. Herein, we report the use of a hydrophobic ion-pairing strategy to enhance the nano-assembly of MTO. EXPERIMENTS: We employed biocompatible sodium cholesteryl sulfate (SCS) as a modification module to form stable ion pairs with MTO, which balanced the intermolecular forces and facilitated nano-assembly. PEGylated MTO-SCS nanoassemblies (pMS NAs) were prepared via nanoprecipitation. We systematically evaluated the effect of the ratio of the drug module (MTO) to the modification module (SCS) on the nanoassemblies. FINDINGS: The increased lipophilicity of MTO-SCS ion pair could significantly improve the encapsulation efficiency (∼97 %) and cellular uptake efficiency of MTO. The pMS NAs showed prolonged blood circulation, maintained the same level of tumor antiproliferative activity, and exhibited reduced toxicity compared with the free MTO solution. It is noteworthy that the stability, cellular uptake, cytotoxicity, and in vivo pharmacokinetic behavior of the pMS NAs increased in proportion to the molar ratio of SCS to MTO. This study presents a self-assembly strategy mediated by ion pairing to overcome the challenges commonly associated with the poor assembly ability of hydrophilic cationic drugs.

Exploring the role of myeloperoxidase in the atherosclerotic process in hypoxic mice based on the MAPK signaling pathway.

Atherosclerosis (AS) is the common pathophysiological basis of various cardiovascular diseases and the leading cause of death from cardiovascular disease worldwide. When the body is in a hypoxic environment, enhanced oxidative stress and significant accumulation of reactive oxygen species (ROS) in tissue cells exacerbate the inflammatory response, resulting in increased release of myeloperoxidase (MPO), catalyzing the formation of large quantities of hypochlorous acid (HOCl), further oxidative modification of low-density lipoprotein (LDL), and exacerbating the formation and progression of atherosclerotic plaques. The MAPK signaling pathway is important in oxidative stress-mediated promotion of atherogenesis. MPO -/- mice were used in this study to establish a hypoxia model simulating 5000 m altitude and a Western high-fat diet-induced atherosclerosis model for 12 weeks. Exploring the role of MPO in the atherosclerotic process in hypoxic mice by observing the MAPK signaling pathway to provide a therapeutic target for the prevention and treatment of hypoxic atherosclerotic disease in the plateau. We found that hypoxia promotes the formation of atherosclerosis in mice, and the mechanism may be that increased MPO in vivo promotes an inflammatory response, which plays a crucial role in the formation of atherosclerosis. In addition, hypoxia further exacerbates plaque instability by activating the MAPK signaling pathway to upregulate vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP9), which in turn promotes angiogenesis within the plaque. Therefore, a potential target for preventing and treating hypoxic atherosclerotic disease is the inhibition of MPO.

Noise characterization of an ultra-stable laser for optical clocks.

We report on the development and performance evaluation of an ultra-stable laser for an 27Al+ optical clock. After a series of noise suppressions, especially the vibrational and temperature fluctuation noise, the 30 cm long cavity stabilized laser obtains a frequency instability of 1.3 × 10-16 @1 s. This result is predicted by noise summation and confirmed by the three-cornered hat method. The 27Al+ optical clock transition is also used to characterize the laser frequency noise, and consistent results are yielded. This is the first reported instance of using single ion optical clocks to measure the frequency noise of ultra-stable lasers, as far as we know. With the implementation of the ultra-stable clock laser, an ultra-narrow linewidth clock transition of 2.8 Hz is obtained.

Nickel-Catalyzed Three-Component Unsymmetrical Bis-Allylation of Alkynes with Alkenes: A Density Functional Theory Study.

Density functional theory (DFT) characterizations were employed to resolve the structural and energetic aspects and product selectivities along the mechanistic reaction paths of the nickel-catalyzed three-component unsymmetrical bis-allylation of alkynes with alkenes. Our putative mechanism initiated with the in situ generation of the active catalytic species [Ni(0)L2] (L = NHC) from its precursors [Ni(COD)2, NHC·HCl] to activate the alkyne and alkene substrates to form the final skipped trienes. This proceeds via the following five sequential steps: oxidative addition (OA), ß-F elimination, ring-opening complexation, C-B cleavage and reductive elimination (RE). Both the OA and RE steps (with respective free energy barriers of 24.2 and 24.8 kcal·mol-1) contribute to the observed reaction rates, with the former being the selectivity-controlling step of the entire chemical transformation. Electrophilic/nucleophilic properties of selected substrates were accurately predicted through dual descriptors (based on Hirshfeld charges), with the chemo- and regio-selectivities being reasonably predicted and explained. Further distortion/interaction and interaction region indicator (IRI) analyses for key stationary points along reaction profiles indicate that the participation of the third component olefin (allylboronate) and tBuOK additive played a crucial role in facilitating the reaction and regenerating the active catalyst, ensuring smooth formation of the skipped triene product under a favorably low dosage of the Ni(COD)2 catalyst (5 mol%).

Palladium-Catalyzed Sequential Cross-Coupling/Annulation of ortho-Vinyl Bromobenzene with Aryl Bromide: Bimetallic Pathway versus Pd(II)-Pd(IV) Pathway: A DFT Investigation.

The palladium-catalyzed sequential cross-coupling/annulation of ortho-vinyl bromobenzenes with aryl bromides generating phenanthrenes was characterized by density functional theory (DFT). The Pd(II)-Pd(IV) pathway (Path V) is shown to be less probable than the bimetallic pathway (Path I), the latter proceeding via the following six steps: oxidative addition, vinyl-C(sp2)-H activation, Pd(II)-Pd(II) transmetalation, C-C coupling, aryl-C(sp2)-H activation, and reductive elimination. The aryl-C(sp2)-H activation process acts as the rate-determining step (RDS) of the entire chemical transformation, with an activation free energy barrier of ca. 27.4-28.8 kcal·mol-1, in good agreement with the corresponding experimental data (phenanthrenes' yields of ca. 65-90% at 130 °C after 5 h of reaction). The K2CO3 additive effectively reduces the activation free energy barrier of the RDS through direct participation in the reaction while preferentially modulating the charge distributions and increasing the stability of corresponding intermediates and complexes along the reaction path. Furthermore, bonding and electronic structure analyses of the key structures indicate that the chemo- and regioselectivities of the reaction are strongly influenced by both electronic effects and steric hindrance.

Metal-Centered Boron-Wheel Cluster of Y©B112- with Rare D11h Symmetry.

Molecules with high point-group symmetry are interesting prototype species in the textbook. As transition metal-centered boron clusters tend to have highly symmetric structures to fulfill multicenter bonding and high stability, new boron clusters with rare point-group symmetry may be viable. Through in-depth scrutiny over the structures of experimentally already observed transition metal-centered boron-wheel complexes, geometric and electronic design principles are summarized, based on which we studied M©B11k- (M = Y, La; Zr, Hf; k = 1, 2) clusters and found that a Y©B112- boron-wheel complex has an unprecedented D11h point-group symmetry. The remarkable stability of the planar Y©B112- complex is illustrated via extensive global-minimum structural search as well as comprehensive chemical bonding analyses. Similar to other boron-wheel complexes, the Y©B112- complex is shown to possess σ and π double aromaticity, indeed following the electronic design principle previously summarized. This new compound is expected to be experimentally identified, which will extend the currently known largest possible planar molecular symmetry and enrich the metal-centered boron-wheel class.

Dataset on the effects of psychological care on depression and suicide ideation in underrepresented children.

Massive increases in the risks of depressive disorders and the ensuing suicide have become the overarching menace for children/adolescents. Despite global consensus to instigate psychological healthcare policy for these children/adolescents, their effects remain largely unclear neither from a small amount of official data nor from small-scale scientific studies. More importantly, in underprivileged children/adolescents in lower-middle-economic-status countries/areas, the data collection may not be as equally accessible as in developed countries/areas, thus resulting in underrepresented observations. To address these challenges, we released a large-scale and multi-center cohort dataset (n = 249,772) showing the effects of primary psychological healthcare on decreasing depression and suicidal ideation in these children/adolescents who were underrepresented in previous studies or current healthcare systems, including unattended children/adolescents, orphans, children/adolescents in especially difficult circumstances, and "left-behind" and "single-parenting" children/adolescents. We provided all individual data recording the depressive symptoms and suicide ideation that had been collected at baseline (Oct 2022) and half-year follow-up (May 2023) from practicing this psychological healthcare system.

A control study on pain characteristics and influencing factors in patients with depressive disorders-based on a 5-year follow-up report from the epidemiological survey of mental disorders in Shandong Province, China.

BACKGROUND: This study extends from the 2015 Shandong Province Epidemiological Survey of Mental Disorders in adults aged 18 and above. Over five years, it investigates pain characteristics and influencing factors in individuals with depressive disorders in Shandong Province. METHODS: The study encompasses 871 individuals who met DSM-IV criteria for depressive disorders in 2015. Using 1:1:1 matching by gender, age, and residence, 825 non-afflicted individuals were selected as high-risk controls, and 825 screening-negative individuals became low-risk controls. A follow-up study in 2020 involved 1848 participants. Survey tools included a general information questionnaire, General Health Questionnaire-12 (GHQ-12), SCID-I/P, Global Pain Scale (GPS), Quality of Life Questionnaire (QLQ), PSQI, MoCA, and clinical data questionnaire. RESULTS: GPS scores in the current depressive group were higher than in non-current depressive group (Z = 14.36, P < 0.01). GPS scores in study group exceeded those in high-risk and low-risk control groups (H = 93.71, P < 0.01). GPS scores in non-remission group were higher than in the remission group (Z = 8.90, P < 0.01). Regression analysis revealed positive correlations between GPS scores and physical illnesses, current depression, incumbency, GHQ-12 total score, and PSQI total score. Negative correlations were observed with QLQ total score and MoCA total score. LIMITATIONS: The study could not assess pain during the 2015 survey, limiting controlled pain analysis before and after five years. CONCLUSION: Depression sufferers may experience prolonged heightened pain, potentially relieved when depression subsides. Individual pain is influenced by depression, physical illnesses, sleep quality, quality of life, cognitive function, gender, residence, and occupation.

Association between high or low-quality carbohydrate with depressive symptoms and socioeconomic-dietary factors model based on XGboost algorithm: From NHANES 2007-2018.

BACKGROUND: Depressive symptoms are a serious public mental health problem, and dietary intake is often considered to be associated with depressive symptoms. However, the relationship between the quality of dietary carbohydrates and depressive symptoms remains unclear. Therefore, this study aimed to investigate the relationship between high and low-quality carbohydrates and depressive symptoms and to attempt to construct an integrated model using machine learning to predict depressive symptoms. METHODS: A total of 4982 samples from the National Health and Nutrition Examination Survey (NHANES) were included in this study. Carbohydrate intake was assessed by a 24-h dietary review, and depressive symptoms were assessed using the Patient Health Questionnaire-9 (PHQ9). Variance inflation factor (VIF) and Relief-F algorithms were used for variable feature selection. RESULTS: The results of multivariate linear regression showed a negative association between high-quality carbohydrates and depressive symptoms (ß: -0.147, 95 % CI: -0.239, -0.056, p = 0.002) and a positive association between low-quality carbohydrates and depressive symptoms (ß: 0.018, 95 % CI: 0.007, 0.280, p = 0.001). Subsequently, we used the XGboost model to produce a comprehensive depressive symptom evaluation model and developed a corresponding online tool (http://8.130.128.194:5000/) to evaluate depressive symptoms clinically. LIMITATIONS: The cross-sectional study could not yield any conclusions regarding causality, and the model has not been validated with external data. CONCLUSIONS: Carbohydrate quality is associated with depressive symptoms, and machine learning models that combine diet with socioeconomic factors can be a tool for predicting depression severity.

Assessing the mediation pathways: How decent work affects turnover intention through job satisfaction and burnout in nursing.

AIM: This study aimed to assess the potential mediating roles of nurses' job satisfaction and burnout in the association between decent work and turnover intention. BACKGROUND: There is a global challenge of nursing shortages in healthcare systems worldwide. Decent work is crucial for safeguarding the rights and professional development outcomes of nurses. However, there is currently limited research on decent work among nurses, and there is a lack of studies exploring the relationships between nurses' decent work, job satisfaction, burnout, and turnover intention. METHODS: A cross-sectional survey design was employed with a sample of 460 nurses from three hospitals: The Affiliated Hospital of Hangzhou Normal University, Hangzhou Third People's Hospital, and Hangzhou Red Cross Hospital. The STROBE checklist was used. Mediation analysis using the PROCESS Macro was used to examine the relationships between decent work, job satisfaction, burnout, and turnover intention. RESULTS: The results showed that nurses' perception of decent work directly influences their turnover intention. Additionally, these findings strongly support the role of job satisfaction and burnout as mediating factors in the relationship between decent work and turnover intention. CONCLUSIONS: Decent work reduces nurse burnout and turnover intention of enhancing their job satisfaction. IMPLICATIONS FOR NURSING AND HEALTH POLICY: This study's findings have important implications for healthcare organizations and policymakers. Recognizing the pivotal role of decent work in nurses' job satisfaction and well-being can guide the development of strategies to improve working conditions and reduce turnover rates. It is imperative for healthcare institutions to prioritize creating safe, supportive, and equitable work conditions for nurses, as this can contribute to higher job satisfaction and, subsequently, lower turnover rates.

Decent work, work engagement, and turnover intention among registered nurses: a cross-sectional study.

BACKGROUND: Nurses face substantial career challenges arising from global pandemics, economic crises, and their roles in conflict-ridden areas. In this context, the rights of nurses pertaining to decent work, such as freedom, fairness, safety, and dignity, are not adequately safeguarded. This study examines decent work status among Chinese nurses and its links to demographics, work engagement, and turnover intention. METHODS: A cross-sectional study design was used following STROBE guidelines. Through a convenient sampling method, a total of 476 nurses were surveyed. These participants were drawn from three esteemed tertiary Grade A hospitals in Hangzhou, with data collection spanning from June to August in 2023. We used a comprehensive set of assessment instruments, encompassing an evaluation of demographic characteristics, the Decent Work Perceptions Scale (DWPS), the Utrecht Work Engagement Scale (UEWS), and turnover intention questionnaire. Bootstrapping procedures were used to ensure the robustness and reliability of the model. RESULTS: The study revealed that nurses' perceptions of decent work significantly impacted work engagement (ß = 0.603, p < 0.001) and turnover intention (ß = -0.275, p < 0.001). Work engagement operated as a mediator between decent work and turnover intention, decreasing the likelihood of nurses leaving their positions (ß = -0.062, p < 0.001). Factors such as age, years of working experience, professional title, job category, and attendance at professional conferences significantly influenced nurses' perceptions of decent work (all p < 0.05). CONCLUSIONS: This study examines factors affecting decent work among nurses and explores its connection with work engagement and the intention to leave. Despite limitations (sample, social desirability bias), the study offers valuable insights for nursing practice. This suggests managers improve decent work for young nurses through rational shift schedules and continuous education. Policymakers should consider adjusting nursing policies for better employment conditions.

Enzymatic Synthesis of Noncanonical α-Amino Acids Containing γ-Tertiary Alcohols.

Noncanonical amino acids (ncAAs) containing tertiary alcohols are valuable as precursors of natural products and active pharmaceutical ingredients. However, the assembly of such ncAA scaffolds from simple material by C-C bond formation remains a challenging task due to the presence of multiple stereocenters and large steric hindrance. In this study, we present a novel solution to this problem through highly selective enzymatic decarboxylative aldol addition. This method allows for the streamlined assembly of multifunctionalized ncAAs with γ-tertiary alcohols from readily available materials, such as L -aspartatic acid and isatins, vicinal diones and keto esters. The modularity of electrophiles furnished four classes of ncAAs with decent efficiency as well as excellent site and stereocontrol. Computational modeling was employed to gain detailed insight into the catalytic mechanism and to provide a rationale for the observed selectivities. The method offers a single-step approach to producing multifunctionalized ncAAs, which can be directly utilized in peptide synthesis and bioactivity assessment.

Subcutaneously Engineered Decalcified Bone Matrix Xenografts Promote Bone Repair by Regulating the Immune Microenvironment, Prevascularization, and Stem Cell Homing.

Immunoregulatory and vascularized microenvironments play an important role in bone regeneration; however, the precise regulation for vascularization and inflammatory reactions remains elusive during bone repair. In this study, by means of subcutaneous preimplantation, we successfully constructed demineralized bone matrix (DBM) grafts with immunoregulatory and vascularized microenvironments. According to the current results, at the early time points (days 1 and 3), subcutaneously implanted DBM grafts recruited a large number of pro-inflammatory M1 macrophages with positive expression of CD68 and iNOS, while at the later time points (days 7 and 14), these inflammatory cells gradually subsided, accompanying increased presence of anti-inflammatory M2 macrophages with positive expression of CD206 and Arg-1, indicating a gradually enhanced anti-inflammatory microenvironment. At the same time, the gradually increased angiogenesis was observed in the DBM grafts with implantation time. In addition, the positive cells of CD105, CD73, and CD90 were observed in the inner region of the DBM grafts, implying the homing of mesenchymal stem cells. The repair results of cranial bone defects in a rat model further confirmed that the subcutaneous DBM xenografts at 7 days significantly improved bone regeneration. In summary, we developed a simple and novel strategy for bone regeneration mediated by anti-inflammatory microenvironment, prevascularization, and endogenous stem cell homing.

Hypoxia exacerbates intestinal injury and inflammatory response mediated by myeloperoxidase during Salmonella Typhimurium infection in mice.

BACKGROUND: High-altitude exposure can cause oxidative stress damage in the intestine, which leads to increased intestinal permeability and bacterial translocation, resulting in local and systemic inflammation. Control of infection is critically dependent on the host's ability to kill pathogens with reactive oxygen species (ROS). Myeloperoxidase (MPO) targets ROS in pathogens. This study aimed to investigate the effects of hypoxia on the colonic mucosal barrier and myeloperoxidase (MPO)-mediated innate immune response in the colon. METHODS AND RESULTS: Genetically engineered mice were exposed to a hypobaric oxygen chamber for 3 days and an inflammation model was established using Salmonella Typhimurium infection. We found that hypoxic exposure caused the development of exacerbated bacterial colitis and enhanced bacterial dissemination in MPO-deficient mice. Infection and disease severity were associated with significantly increased Ly6G+ neutrophil and F4/80+ macrophage counts in infected tissues, which is consistent with elevated proinflammatory cytokines and chemoattractant molecules. Hypoxia restrained antioxidant ability and MPO deficiency aggravated the respiratory burst in the colon. CONCLUSION: Hypoxia can damage the colonic mucosa. MPO mediates the innate immune response and regulates the mucosal and systemic inflammatory responses to Salmonella infection during hypoxia.