Electrical aligned polyurethane nerve guidance conduit modulates macrophage polarization and facilitates immunoregulatory peripheral nerve regeneration.

Biomaterials can modulate the local immune microenvironments to promote peripheral nerve regeneration. Inspired by the spatial orderly distribution and endogenous electric field of nerve fibers, we aimed to investigate the synergistic effects of electrical and topological cues on immune microenvironments of peripheral nerve regeneration. Nerve guidance conduits (NGCs) with aligned electrospun nanofibers were fabricated using a polyurethane copolymer containing a conductive aniline trimer and degradable L-lysine (PUAT). In vitro experiments showed that the aligned PUAT (A-PUAT) membranes promoted the recruitment of macrophages and induced their polarization towards the pro-healing M2 phenotype, which subsequently facilitated the migration and myelination of Schwann cells. Furthermore, NGCs fabricated from A-PUAT increased the proportion of pro-healing macrophages and improved peripheral nerve regeneration in a rat model of sciatic nerve injury. In conclusion, this study demonstrated the potential application of NGCs in peripheral nerve regeneration from an immunomodulatory perspective and revealed A-PUAT as a clinically-actionable strategy for peripheral nerve injury.

Prominent Intrinsic Proton Conduction in Two Robust Zr/Hf Metal-Organic Frameworks Assembled by Bithiophene Dicarboxylate.

To date, developing crystalline proton-conductive metal-organic frameworks (MOFs) with an inherent excellent proton-conducting ability and structural stability has been a critical priority in addressing the technologies required for sustainable development and energy storage. Bearing this in mind, a multifunctional organic ligand, 3,4-dimethylthiophene[2,3-b]thiophene-2,5-dicarboxylic acid (H2DTD), was employed to generate two exceptionally stable three-dimensional porous Zr/Hf MOFs, [Zr6O4(OH)4(DTD)6]·5DMF·H2O (Zr-DTD) and [Hf6O4(OH)4(DTD)6]·4DMF·H2O (Hf-DTD), using solvothermal means. The presence of Zr6 or Hf6 nodes, strong Zr/Hf-O bonds, the electrical influence of the methyl group, and the steric effect of the thiophene unit all contribute to their structural stability throughout a wide pH range as well as in water. Their proton conductivity was fully examined at various relative humidities (RHs) and temperatures. Creating intricate and rich H-bonded networks between the guest water molecules, coordination solvent molecules, thiophene-S, -COOH, and -OH units within the framework assisted proton transfer. As a result, both MOFs manifest the maximum proton conductivity of 0.67 × 10-2 and 4.85 × 10-3 S·cm-1 under 98% RH/100 °C, making them the top-performing proton-conductive Zr/Hf-MOFs. Finally, by combining structural characteristics and activation energies, potential proton conduction pathways for the two MOFs were identified.

The role of coagulopathy and subdural hematoma thickness at admission in predicting the prognoses of patients with severe traumatic brain injury: A multicenter retrospective cohort study from China.

BACKGROUND: Traumatic brain injury (TBI) is one of the diseases with high disability and mortality worldwide. Recent studies have shown that TBI-related factors may change the complex balance between bleeding and thrombosis, leading to coagulation disorders. The aim of this retrospective study was to investigate the prediction of coagulopathy and subdural hematoma thickness at admission using the Glasgow Outcome Scale (GOS) in patients with severe TBI at 6 months after discharge. METHODS: In this retrospective cohort study, a total of 1,006 patients with severe TBI in large medical centers in three different provinces of China from June 2015 to June 2021 were enrolled after the exclusion criteria, and 800 patients who met the enrollment criteria were included. A receiver operating characteristic (ROC) curve was used to determine the best cut-off values of platelet (PLT), international normalized ratio (INR), activated partial thromboplastin time (APTT), and subdural hematoma (SDH) thickness. The ROC curve, nomogram, calibration curve, and the decision curve were used to evaluate the predictive effect of the coagulopathy and Coagulopathy-SDH(X1) models on the prognoses of patients with severe TBI, and the importance of predictive indicators was ranked by machine learning. RESULTS: Among the patients with severe TBI on admission, 576/800 (72%) had coagulopathy, 494/800 (61%) had SDH thickness ≥14.05 mm, and 385/800 (48%) had coagulopathy combined with SDH thickness ≥14.05 mm. Multivariate logistic regression analyses showed that age, pupil, brain herniation, WBC, CRP, SDH, coagulopathy, and X1 were independent prognostic factors for GOS after severe TBI. Compared with other single indicators, X1 as a predictor of the prognosis of severe TBI was more accurate. The GOS of patients with coagulopathy and thick SDH (X1, 1 point) at 6 months after discharge was significantly worse than that of patients with coagulopathy and thin SDH (X1, 2 points), patients without coagulopathy and thick SDH (X1, 3 point), and patients without coagulopathy and thin SDH (X1, 4 points). In the training group, the C-index based on the coagulopathy nomogram was 0.900. The C-index of the X1-based nomogram was 0.912. In the validation group, the C-index based on the coagulopathy nomogram was 0.858. The C-index of the X1-based nomogram was 0.877. Decision curve analysis also confirmed that the X1-based model had a higher clinical net benefit of GOS at 6 months after discharge than the coagulopathy-based model in most cases, both in the training and validation groups. In addition, compared with the calibration curve based on the coagulopathy model, the prediction of the X1 model-based calibration curve for the probability of GOS at 6 months after discharge showed better agreement with actual observations. Machine learning compared the importance of each independent influencing factor in the evaluation of GOS prediction after TBI, with results showing that the importance of X1 was better than that of coagulopathy alone. CONCLUSION: Coagulopathy combined with SDH thickness could be used as a new, accurate, and objective clinical predictor, and X1, based on combining coagulopathy with SDH thickness could be used to improve the accuracy of GOS prediction in patients with TBI, 6 months after discharge.

A sequential macrophage activation strategy for bone regeneration: A micro/nano strontium-releasing composite scaffold loaded with lipopolysaccharide.

Effective tissue repair relies on the orchestration of different macrophage phenotypes, both the M2 phenotype (promotes tissue repair) and M1 phenotype (pro-inflammatory) deserve attention. In this study, we propose a sequential immune activation strategy to mediate bone regeneration, by loading lipopolysaccharide (LPS) onto the surface of a strontium (Sr) ions -contained composite scaffold, which was fabricated by combining Sr-doped micro/nano-hydroxyapatite (HA) and dual degradable matrices of polycaprolactone (PCL) and poly (lactic-co-glycolic acid) (PLGA). Our strategy involves the sequential release of LPS to promote macrophage homing and induce the expression of the pro-inflammatory M1 phenotype, followed by the release of Sr ions to suppress inflammation. In vitro and in vivo experiments demonstrated that, the appropriate pro-inflammatory effects at the initial stage of implantation, along with the anti-inflammatory effects at the later stage, as well as the structural stability of the scaffolds conferred by the composition, can synergistically promote the regeneration and repair of bone defects.

Effectiveness of WeChat-assisted preoperative education to reduce perioperative anxiety in breast cancer patients: a prospective randomized controlled study protocol.

BACKGROUND: Breast cancer is the most prevalent cancer among women globally, and surgical procedures continue to be the primary treatment. However, over 50% of patients experience preoperative anxiety due to the unknown and fear associated with surgery. Although drug therapy is commonly used to address this anxiety, its side effects have led to a heated debate regarding its effectiveness. Consequently, non-pharmacological therapies, such as preoperative education, have emerged as an alternative approach to alleviate anxiety. WeChat, a widely popular social media platform, offers a public platform that can potentially be utilized for effective preoperative education. This study aims to evaluate the use of WeChat public platform as a tool for preoperative education in patients undergoing breast surgery. METHODS: This is a prospective, randomized, and controlled trial will involve 392 adult women scheduled for breast cancer resection. Participants will be randomly assigned to either the WeChat education group or the regular group. In addition to regular preoperative visits, the WeChat education group will also watch science videos through the WeChat public platform. The regular group will only receive education from ward nurses during preoperative visits. The primary outcome measure will be the incidence of preoperative anxiety, defined by scores of the State Anxiety Inventory (SAI) exceeding 40 points. Secondary outcome measures include the incidence of severe anxiety (SAI > 44) on the day before surgery, incidence of anxiety 72 h after surgery, incidence of severe anxiety 72 h after surgery, NRS scores for pain at rest and during activity 24, 48, and 72 h after surgery, incidence of nausea and vomiting within 24 h after surgery, subjective sleep score at 1 week postoperatively, quality of life QoR-15 scores at 1 and 3 months postoperatively, incidence of chronic pain at 3 months postoperatively, bowel function recovery, length of hospital stay, and hospitalization expenses. DISCUSSION: This is the first clinical trial to investigate the use of WeChat public platform for delivering preoperative education on perioperative anxiety in breast cancer patients. By utilizing the renowned WeChat public platform, our study aims to improve patient outcomes by providing video education that explains the disease, surgery, and anesthesia in a more accessible manner, thereby reducing the incidence of perioperative anxiety. If our hypothesis is confirmed, this non-pharmacological approach can be universally acknowledged as a cost-effective and practical method in clinical care. Its application can also be extended to other medical fields beyond breast cancer. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05291494. Registered on 29 December 2021.

The biophysical function of pulmonary surfactant.

The type II pneumocytes of the lungs secrete a mixture of lipids and proteins that together acts as a surfactant. The material forms a thin film on the surface of the liquid layer that lines the alveolar air sacks. When compressed by the decreasing alveolar surface area during exhalation, the films reduce surface tension to exceptionally low levels. Pulmonary surfactant is essential for preserving the integrity of the barrier between alveolar air and capillary blood during normal breathing. This review focuses on the major biophysical processes by which endogenous pulmonary surfactant achieves its function and the mechanisms involved in those processes. Vesicles of pulmonary surfactant adsorb rapidly from the alveolar liquid to form the interfacial film. Interfacial insertion, which requires the hydrophobic surfactant protein SP-B, proceeds by a process analogous to the fusion of two vesicles. When compressed, the adsorbed film desorbs slowly. Constituents remain at the surface at high interfacial concentrations that reduce surface tensions well below equilibrium levels. We review the models proposed to explain how pulmonary surfactant achieves both the rapid adsorption and slow desorption characteristic of a functional film.

Syntheses, crystal structures and intermolecular interactions of six novel pyrimidin-2-yl-substituted triaryltriazoles.

Six new pyrimidin-2-yl-substituted triaryltriazoles, namely, 4-(4-R-phenyl)-3-(pyridin-2-yl)-5-(pyrimidin-2-yl)-1,2,4-triazoles [L1: R = methoxy (OCH3); L2: R = methyl (CH3); L3: R = nil (H); L4: R = bromo (Br); L5: R = chloro (Cl); L6: R = fluoro (F)] have been successfully synthesized with yields in the range 68.3-81.7%. Compounds L1-6 have been characterized by UV-Vis, FT-IR, 1H NMR and ESI-MS spectroscopy, and elemental analysis. In addition, the structures of L2-6 and the ethanol monosolvate of L2 (L2·C2H5OH) have been determined by single-crystal X-ray diffraction. A combination of intermolecular O-H...N, C-H...O, C-H...N and C-H...π hydrogen bonds connects the components of L2·C2H5OH into a three-dimensional (3D) framework. A combination of three intermolecular C-H...N hydrogen bonds links the molecules of L2 or L3 into two different 3D networks. Both L4 and L5 show a similar 3D net structure through two intermolecular C-H...N hydrogen bonds and one kind of C-H...π interaction. However, L6 displays a more complicated 3D net structure via three intermolecular C-H...N hydrogen bonds and one kind of C-H...π interaction. Notably, an interaction between the π-electrons and the lone-pair p-electrons of a halogen atom (Br, Cl and F) is observed in L4-6, which will further stabilize the 3D networks. The intermolecular interactions in L2·C2H5OH and L2-6 were further investigated by 3D Hirshfeld surface analyses and 2D fingerprint plots to show that the prominent interactions are H...H, N...H/H...N and C...H/H...C contacts.

The Idesia polycarpa genome provides insights into its evolution and oil biosynthesis.

The deciduous tree Idesia polycarpa can provide premium edible oil with high polyunsaturated fatty acid contents. Here, we generate its high-quality reference genome, which is ∼1.21 Gb, comprising 21 pseudochromosomes and 42,086 protein-coding genes. Phylogenetic and genomic synteny analyses show that it diverged with Populus trichocarpa about 16.28 million years ago. Notably, most fatty acid biosynthesis genes are not only increased in number in its genome but are also highly expressed in the fruits. Moreover, we identify, through genome-wide association analysis and RNA sequencing, the I. polycarpa SUGAR TRANSPORTER 5 (IpSTP5) gene as a positive regulator of high oil accumulation in the fruits. Silencing of IpSTP5 by virus-induced gene silencing causes a significant reduction of oil content in the fruits, suggesting it has the potential to be used as a molecular marker to breed the high-oil-content cultivars. Our results collectively lay the foundation for breeding the elite cultivars of I. polycarpa.

End-to-end model-based trajectory prediction for ro-ro ship route using dual-attention mechanism.

With the rapid increase of economic globalization, the significant expansion of shipping volume has resulted in shipping route congestion, causing the necessity of trajectory prediction for effective service and efficient management. While trajectory prediction can achieve a relatively high level of accuracy, the performance and generalization of prediction models remain critical bottlenecks. Therefore, this article proposes a dual-attention (DA) based end-to-end (E2E) neural network (DAE2ENet) for trajectory prediction. In the E2E structure, long short-term memory (LSTM) units are included for the task of pursuing sequential trajectory data from the encoder layer to the decoder layer. In DA mechanisms, global attention is introduced between the encoder and decoder layers to facilitate interactions between input and output trajectory sequences, and multi-head self-attention is utilized to extract sequential features from the input trajectory. In experiments, we use a ro-ro ship with a fixed navigation route as a case study. Compared with baseline models and benchmark neural networks, DAE2ENet can obtain higher performance on trajectory prediction, and better validation of environmental factors on ship navigation.

Ultralow-loss optical interconnect enabled by topological unidirectional guided resonance.

Grating couplers that interconnect photonic chips to off-chip components are crucial for various optoelectronics applications. Despite numerous efforts in past decades, the existing grating couplers are still far from optimal in energy efficiency and thus hinder photonic integration toward a larger scale. Here, we propose a strategy to achieve ultralow-loss grating couplers by using unidirectional guided resonances (UGRs), suppressing the useless downward radiation with no mirror on the bottom. By engineering the dispersion and apodizing the geometry of grating, we experimentally realize a grating coupler with a record-low loss of -0.34 dB and 1-dB bandwidth exceeding 30 nm at the telecom wavelength of 1550 nm and further demonstrate an optic via with a loss of only -0.94 dB. Given that UGRs ubiquitously exist in a variety of grating geometries, our work sheds light on a systematic method to achieve energy-efficient optical interconnect and paves the way to large-scale photonic integration.

Translational modulator ISRIB alleviates synaptic and behavioral phenotypes in Fragile X syndrome.

Fragile X syndrome (FXS) is caused by the loss of fragile X messenger ribonucleoprotein (FMRP), a translational regulator that binds the transcripts of proteins involved in synaptic function and plasticity. Dysregulated protein synthesis is a central effect of FMRP loss, however, direct translational modulation has not been leveraged in the treatment of FXS. Thus, we examined the effect of the translational modulator integrated stress response inhibitor (ISRIB) in treating synaptic and behavioral symptoms of FXS. We show that FMRP loss dysregulates synaptic protein abundance, stabilizing dendritic spines through increased PSD-95 levels while preventing spine maturation through reduced glutamate receptor accumulation, thus leading to the formation of dense, immature dendritic spines, characteristic of FXS patients and Fmr1 knockout (KO) mice. ISRIB rescues these deficits and improves social recognition in Fmr1 KO mice. These findings highlight the therapeutic potential of targeting core translational mechanisms in FXS and neurodevelopmental disorders more broadly.

Hybridization-based discovery of novel quinazoline-2-indolinone derivatives as potent and selective PI3Kα inhibitors.

INTRODUCTION: Phosphatidylinositol 3-kinases (PI3Ks) overexpression can elicit cellular homeostatic dysregulation, which further contributes to tumorigenesis, with PI3Kα emerging as the most prevalent mutant isoform kinase among PI3Ks. Therefore, selective inhibitors targeting PI3Kα have attracted considerable interest in recent years. Molecular hybridization, with the advantage of simplified pharmacokinetics and drug-drug interactions, emerged as one of the important avenues for discovering potential drugs. OBJECTIVES: This study aimed to construct PI3Kα inhibitors by hybridization and investigate their antitumor activity and mechanism. METHODS: 26 quinazoline-2-indolinone derivatives were obtained by molecular hybridization, and their structure-activity relationship was analyzed by MTT, in vitro kinase activity and molecular docking. The biological evaluation of compound 8 was performed by transwell, flow cytometry, laser scanning confocal microscopy, Western blot, CTESA and immunohistochemistry. RESULTS: Here, we employed molecular hybridization methods to construct a series of quinazoline-2-indolinone derivatives as PI3Kα selective inhibitors. Encouragingly, representative compound 8 exhibited a PI3Kα enzymatic IC50 value of 9.11 nM and 10.41/16.99/37.53-fold relative to the biochemical selectivity for PI3Kß/γ/δ, respectively. Moreover, compound 8 effectively suppressed the viability of B16, HCT116, MCF-7, H22, PC-3, and A549 cells (IC50 values: 0.2 µM âˆ¼ 0.98 µM), and dramatically inhibited the proliferation and migration of NSCLC cells, as well as induced mitochondrial apoptosis through the PI3K/Akt/mTOR pathway. Importantly, compound 8 demonstrated potent in vivo anti-tumor activity in non-small cell lung cancer mouse models without visible toxicity. CONCLUSIONS: This study presented a new avenue for the development of PI3Kα inhibitors and provided a solid foundation for novel QHIDs as potential future therapies for the treatment of NSCLC.

Engineering vascularized skin-mimetic phantom for non-invasive Raman spectroscopy.

Recent advances in Raman spectroscopy have shown great potential for non-invasive analyte sensing, but the lack of a standardized optical phantom for these measurements has hindered further progress. While many research groups have developed optical phantoms that mimic bulk optical absorption and scattering, these materials typically have strong Raman scattering, making it difficult to distinguish metabolite signals. As a result, solid tissue phantoms for spectroscopy have been limited to highly scattering tissues such as bones and calcifications, and metabolite sensing has been primarily performed using liquid tissue phantoms. To address this issue, we have developed a layered skin-mimetic phantom that can support metabolite sensing through Raman spectroscopy. Our approach incorporates millifluidic vasculature that mimics blood vessels to allow for diffusion akin to metabolite diffusion in the skin. Furthermore, our skin phantoms are mechanically mimetic, providing an ideal model for development of minimally invasive optical techniques. By providing a standardized platform for measuring metabolites, our approach has the potential to facilitate critical developments in spectroscopic techniques and improve our understanding of metabolite dynamics in vivo.

Cytoplasmic accumulation and plasma membrane association of anillin and Ect2 promote confined migration and invasion.

Cells migrating in confinement experience mechanical challenges whose consequences on cell migration machinery remain only partially understood. Here, we demonstrate that a pool of the cytokinesis regulatory protein anillin is retained during interphase in the cytoplasm of different cell types. Confinement induces recruitment of cytoplasmic anillin to plasma membrane at the poles of migrating cells, which is further enhanced upon nuclear envelope (NE) rupture(s). Rupture events also enable the cytoplasmic egress of predominantly nuclear RhoGEF Ect2. Anillin and Ect2 redistributions scale with microenvironmental stiffness and confinement, and are observed in confined cells in vitro and in invading tumor cells in vivo. Anillin, which binds actomyosin at the cell poles, and Ect2, which activates RhoA, cooperate additively to promote myosin II contractility, and promote efficient invasion and extravasation. Overall, our work provides a mechanistic understanding of how cytokinesis regulators mediate RhoA/ROCK/myosin II-dependent mechanoadaptation during confined migration and invasive cancer progression.

Biodegradable Polyurethane Scaffolds in Regeneration Therapy: Characterization and In Vivo Real-Time Degradation Monitoring by Grafted Fluorescent Tracer.

There is an urgent need to assess material degradation in situ and in real time for their promising application in regeneration therapy. However, traditional monitoring methods in vitro cannot always profile the complicated behavior in vivo. This study designed and synthesized a new biodegradable polyurethane (PU-P) scaffold with polycaprolactone glycol, isophorone diisocyanate, and l-lysine ethyl ester dihydrochloride. To monitor the degradation process of PU-P, calcein was introduced into the backbone (PU-5) as a chromophore tracing in different sites of the body and undegradable fluorescent scaffold (CPU-5) as the control group. Both PU-P and PU-5 can be enzymatically degraded, and the degradation products are molecularly small and biosafe. Meanwhile, by virtue of calcein anchoring with urethane, polymer chains of PU-5 have maintained the conformational stability and extended the system conjugation, raising a structure-induced emission effect that successfully achieved a significant enhancement in the fluorescence intensity better than pristine calcein. Evidently, unlike the weak fluorescent response of CPU-5, PU-5 and its degradation can be clearly imaged and monitored in real time after implantation in the subcutaneous tissue of nude mice. Meanwhile, the in situ osteogeneration has also been promoted after the two degradable scaffolds have been implanted in the rabbit femoral condyles and degraded with time. To sum up, the strategy of underpinning tracers into degradable polymer chains provides a possible and effective way for real-time monitoring of the degradation process of implants in vivo.

Novel sulfonyl-substituted tetrandrine derivatives for colon cancer treatment by inducing mitochondrial apoptosis and inhibiting PI3K/AKT/mTOR pathway.

Tetrandrine (TET) possesses multiple pharmacological activities and could suppress tumor proliferation via PI3K pathway inhibition. However, inferior antitumor activity and potential toxicity limit its clinical application. In the present study, a series of 14-sulfonamide and sulfonate TET derivatives were designed, synthesized, and evaluated for biological activities. Through structural-activity relationship studies, compound 3c with α, ß-unsaturated carbonyl group exhibited the most potent activity against all tested tumor cell lines (including Hela, HCT116, HepG2, MCF-7, and SHSY5Y), as well as negligible toxicity against normal cell lines LO2 and HEK293. Additionally, compound 3c effectively inhibited HCT116 and CT26 cell proliferation in vitro with increased cell proportion in the G2/M phase, activated the mitochondrial apoptosis pathway, and induced colon cancer cell apoptosis by suppressing the PI3K/AKT/mTOR pathway. The further molecular docking results confirmed that compound 3c is potentially bound to multiple residues in PI3K with a stronger binding affinity than TET. Ultimately, compound 3c dramatically suppressed tumor growth in the CT26 xenograft tumor model, without noticeable visceral toxicity detected in the high-dose group. In summary, compound 3c might present new insights for designing new PI3K inhibitors and be a potential candidate for colon cancer treatment.

Emerging trends and hotspots of Nuclear factor erythroid 2-related factor 2 in nervous system diseases.

BACKGROUND: The Nuclear factor erythroid 2-related factor 2 (NRF2) transcription factor has attracted much attention in the context of neurological diseases. However, none of the studies have systematically clarified this field's research hotspots and evolution rules. AIM: To investigate the research hotspots, evolution patterns, and future research trends in this field in recent years. METHODS: We conducted a comprehensive literature search in the Web of Science Core Collection database using the following methods: (((((TS=(NFE2 L2)) OR TS=(Nfe2 L2 protein, mouse)) OR TS=(NF-E2-Related Factor 2)) OR TS=(NRF2)) OR TS=(NFE2L2)) OR TS=(Nuclear factor erythroid2-related factor 2) AND (((((((TS=(neurological diseases)) OR TS=(neurological disorder)) OR TS=(brain disorder)) OR TS=(brain injury)) OR TS=(central nervous system disease)) OR TS=(CNS disease)) OR TS=(central nervous system disorder)) OR TS=(CNS disorder) AND Language = English from 2010 to 2022. There are just two forms of literature available: Articles and reviews. Data were processed with the software Cite-Space (version 6.1. R6). RESULTS: We analyzed 1884 articles from 200 schools in 72 countries/regions. Since 2015, the number of publications in this field has increased rapidly. China has the largest number of publications, but the articles published in the United States have better centrality and H-index. Among the top ten authors with the most published papers, five of them are from China, and the author with the most published papers is Wang Handong. The institution with the most articles was Nanjing University. To their credit, three of the top 10 most cited articles were written by Chinese scholars. The keyword co-occurrence map showed that "oxidative stress", "NRF2", "activation", "expression" and "brain" were the five most frequently used keywords. CONCLUSION: Research on the role of NRF2 in neurological diseases continues unabated. Researchers in developed countries published more influential papers, while Chinese scholars provided the largest number of articles. There have been numerous studies on the mechanism of NRF2 transcription factor in neurological diseases. NRF2 is also emerging as a potentially effective target for the treatment of neurological diseases. However, despite decades of research, our knowledge of NRF2 transcription factor in nervous system diseases is still limited. Further studies are needed in the future.

Microplastics and Nanoplastics Impair the Biophysical Function of Pulmonary Surfactant by Forming Heteroaggregates at the Alveolar-Capillary Interface.

Microplastics (MPs) are ubiquitous environmental pollutants produced through the degradation of plastic products. Nanoplastics (NPs), commonly coexisting with MPs in the environment, are submicrometer debris incidentally produced from fragmentation of MPs. We studied the biophysical impacts of MPs/NPs derived from commonly used commercial plastic products on a natural pulmonary surfactant extracted from calf lung lavage. It was found that in comparison to MPs/NPs derived from lunch boxes made of polypropylene or from drinking water bottles made of poly(ethylene terephthalate), the MP/NP derived from foam packaging boxes made of polystyrene showed the highest adverse impact on the biophysical function of the pulmonary surfactant. Accordingly, intranasal exposure of MP/NP derived from the foam boxes also induced the most serious proinflammatory responses and lung injury in mice. Atomic force microscopy revealed that NP particles were adsorbed on the air-water surface and heteroaggregated with the pulmonary surfactant film. These results indicate that although the incidentally formed NPs only make up a small mass fraction, they likely play a predominant role in determining the nano-bio interactions and the lung toxicity of MPs/NPs by forming heteroaggregates at the alveolar-capillary interface. These findings may provide novel insights into understanding the health impact of MPs and NPs on the respiratory system.

Clinical risk factors and blood protein biomarkers of 10-year pneumonia risk.

Background: Chronic inflammation may increase susceptibility to pneumonia. Research Question: To explore associations between clinical comorbidities, serum protein immunoassays, and long-term pneumonia risk. Methods: Framingham Heart Study Offspring Cohort participants ≥65 years were linked to their Centers for Medicare Services claims data. Clinical data and 88 serum protein immunoassays were evaluated for associations with 10-year incident pneumonia risk using Fine-Gray models for competing risks of death and least absolute shrinkage and selection operators for covariate selection. Results: We identified 1,370 participants with immunoassays and linkage to Medicare data. During 10 years of follow up, 428 (31%) participants had a pneumonia diagnosis. Chronic pulmonary disease [subdistribution hazard ratio (SHR) 1.87; 95% confidence interval (CI), 1.33-2.61], current smoking (SHR 1.79, CI 1.31-2.45), heart failure (SHR 1.74, CI 1.10-2.74), atrial fibrillation/flutter (SHR 1.43, CI 1.06-1.93), diabetes (SHR 1.36, CI 1.05-1.75), hospitalization within one year (SHR 1.34, CI 1.09-1.65), and age (SHR 1.06 per year, CI 1.04-1.08) were associated with pneumonia. Three baseline serum protein measurements were associated with pneumonia risk independent of measured clinical factors: growth differentiation factor 15 (SHR 1.32; CI 1.02-1.69), C-reactive protein (SHR 1.16, CI 1.06-1.27) and matrix metallopeptidase 8 (SHR 1.14, CI 1.01-1.30). Addition of C-reactive protein to the clinical model improved prediction (Akaike information criterion 4950 from 4960; C-statistic of 0.64 from 0.62). Conclusions: Clinical comorbidities and serum immunoassays were predictive of pneumonia risk. C-reactive protein, a routinely-available measure of inflammation, modestly improved pneumonia risk prediction over clinical factors. Our findings support the hypothesis that prior inflammation may increase the risk of pneumonia.

The Circadian Clock Coordinates the Tradeoff between Adaptation to Abiotic Stresses and Yield in Crops.

Plants have evolved a circadian clock to adapt to ever-changing diel and seasonal environmental conditions. The circadian clock is generally considered an internal system that has evolved to adapt to cyclic environmental cues, especially diel light and temperature changes, which is essential for higher plants as they are sessile organisms. This system receives environmental signals as input pathways which are integrated by circadian core oscillators to synchronize numerous output pathways, such as photosynthesis, the abiotic stress response, metabolism, and development. Extreme temperatures, salinity, and drought stresses cause huge crop losses worldwide, imposing severe pressure on areas of agricultural land. In crop production, the circadian system plays a significant role in determining flowering time and responding to external abiotic stresses. Extensive studies over the last two decades have revealed that the circadian clock can help balance the tradeoff between crop yield-related agronomic traits and adaptation to stress. Herein, we focus on summarizing how the circadian clock coordinates abiotic stress responses and crop yield. We also propose that there might be an urgent need to better utilize circadian biology in the future design of crop breeding to achieve high yields under stress conditions.