Water-Ice Microstructures and Hydration States of Acridinium Iodide Studied by Phosphorescence Spectroscopy.

Ice has been suggested to have played a significant role in the origin of life partly owing to its ability to concentrate organic molecules and promote reaction efficiency. However, the techniques for studying organic molecules in ice are absorption-based, which limits the sensitivity of measurements. Here we introduce an emission-based method to study organic molecules in water ice: the phosphorescence displays high sensitivity depending on the hydration state of an organic salt probe, acridinium iodide (ADI). The designed ADI aqueous system exhibits phosphorescence that can be severely perturbed when the temperature is higher than 110 K at a concentration of the order of 10-5M, indicating changes in hydration for ADI. Using the ADI phosphorescent probe, it is found that the microstructures of water ice, i.e., crystalline vs. glassy, can be strongly dictated by a trace amount (as low as 10-5M) of water-soluble organic molecules. Consistent with cryoSEM images and temperature-dependent Raman spectral data, the ADI is dehydrated in more crystalline ice and hydrated in more glassy ice. The current investigation serves as a starting point for using more sensitive spectroscopic techniques for studying water-organics interactions at a much lower concentration and wider temperature range.

SIRT5-related lysine demalonylation of GSTP1 contributes to cardiomyocyte pyroptosis suppression in diabetic cardiomyopathy.

Sirtuin 5 (SIRT5), localized in the mitochondria, has been identified as a protein desuccinylase and demalonylase in the mitochondria since the depletion of SIRT5 boosted the global succinylation and malonylation of mitochondrial proteins. We investigated the role of SIRT5 in diabetic cardiomyopathy (DCM) and identified the mechanism regarding lysine demalonylation in this process. Wild-type and SIRT5 knockout mice were induced with DCM, and primary cardiomyocytes and cardiac fibroblasts extracted from wild-type and SIRT5 knockout mice were subjected to high glucose (HG). SIRT5 deficiency exacerbated myocardial injury in DCM mice, aggravated HG-induced oxidative stress and mitochondrial dysfunction in cardiomyocytes, and intensified cardiomyocyte senescence, pyroptosis, and DNA damage. DCM-induced SIRT5 loss diminished glutathione S-transferase P (GSTP1) protein stability, represented by significantly increased lysine malonylation (Mal-Lys) modification of GSTP1. SIRT5 overexpression alleviated DCM-related myocardial injury, which was reversed by GSTP1 knockdown. Reduced SIRT5 transcription in DCM resulted from the downregulation of SPI1. SPI1 promoted the transcription of SIRT5, thereby ameliorating DCM-associated myocardial injury. However, SIRT5 deletion resulted in a significant reversal of the protective effect of SPI1. These observations suggest that SPI1 activates SIRT5 transcriptionally to mediate GSTP1 Mal-Lys modification and protein stability, thus ameliorating DCM-associated myocardial injury.

Engineering Semicarbazide-Bearing Polypeptide Conjugates for Efficient Tumor Chemotherapy and Imaging of Tumor Metastasis.

Polypeptide materials offer scalability, biocompatibility, and biodegradability, rendering them an ideal platform for biomedical applications. However, the preparation of polypeptides with specific functional groups, such as semicarbazide moieties, remains challenging. This work reports, for the first time, the straightforward synthesis of well-defined methoxy-terminated poly(ethylene glycol)-b-polypeptide hybrid block copolymers (HBCPs) containing semicarbazide moieties. This synthesis involves implementing the direct polymerization of environment-stable N-phenoxycarbonyl-functionalized α-amino acid (NPCA) precursors, thereby avoiding the handling of labile N-carboxyanhydride (NCA) monomers. The resulting HBCPs containing semicarbazide moieties enable facile functionalization with aldehyde/ketone derivatives, forming pH-cleavable semicarbazone linkages for tailored drug release. Particularly, the intracellular pH-triggered hydrolysis of semicarbazone moieties restores the initial semicarbazide residues, facilitating endo-lysosomal escape and thus improving therapeutic outcomes. Furthermore, the integration of the hypoxic probe (Ir(btpna)(bpy)2 ) into the pH-responsive nanomedicines allows sequential responses to acidic and hypoxic tumor microenvironments, enabling precise detection of metastatic tumors. The innovative approach for designing bespoke functional polypeptides holds promise for advanced drug delivery and precision therapeutics.

The AT-hook protein AHL29 promotes Bacillus subtilis colonization by suppressing SWEET2-mediated sugar retrieval in Arabidopsis roots.

Beneficial Bacillus subtilis (BS) symbiosis could combat root pathogenesis, but it relies on root-secreted sugars. Understanding the molecular control of sugar flux during colonization would benefit biocontrol applications. The SWEET (Sugar Will Eventually Be Exported Transporter) uniporter regulates microbe-induced sugar secretion from roots; thus, its homologs may modulate sugar distribution upon BS colonization. Quantitative polymerase chain reaction revealed that gene transcripts of SWEET2, but not SWEET16 and 17, were significantly induced in seedling roots after 12 h of BS inoculation. Particularly, SWEET2-ß-glucuronidase fusion proteins accumulated in the apical mature zone where BS abundantly colonized. Yet, enhanced BS colonization in sweet2 mutant roots suggested a specific role for SWEET2 to constrain BS propagation, probably by limiting hexose secretion. By employing yeast one-hybrid screening and ectopic expression in Arabidopsis protoplasts, the transcription factor AHL29 was identified to function as a repressor of SWEET2 expression through the AT-hook motif. Repression occurred despite immunity signals. Additionally, enhanced SWEET2 expression and reduced colonies were specifically detected in roots of BS-colonized ahl29 mutant. Taken together, we propose that BS colonization may activate repression of AHL29 on SWEET2 transcription that would be enhanced by immunity signals, thereby maintaining adequate sugar secretion for a beneficial Bacillus association.

IL-38 alleviates airway remodeling in chronic asthma via blocking the profibrotic effect of IL-36γ.

Airway remodeling is a major feature of asthma. Interleukin (IL)-36γ is significantly upregulated and promotes airway hyper-responsiveness (AHR) in asthma, but its role in airway remodeling is unknown. Here, we aimed to investigate the role of IL-36γ in airway remodeling, and whether IL-38 can alleviate airway remodeling in chronic asthma by blocking the effects of IL-36γ. IL-36γ was quantified in mice inhaled with house dust mite (HDM). Extracellular matrix (ECM) deposition in lung tissues and AHR were assessed following IL-36γ administration to mice. Airway inflammation, AHR, and remodeling were evaluated after IL-38 or blocking IL-36 receptor (IL-36R) treatment in asthmatic mice. The effects of lung fibroblasts stimulated with IL-36γ and IL-38 were quantified in vitro. Increased expression of IL-36γ was detected in lung tissues of HDM-induced asthmatic mice. The intratracheal instillation of IL-36γ to mice significantly enhanced the ECM deposition, AHR, and the number of activated lung fibroblasts around the airways. IL-38 or blocking IL-36R treated asthmatic mice showed a significant alleviation in the airway inflammation, AHR, airway remodeling, and number of activated fibroblasts around airways as compared with the HDM group. In vitro, IL-36γ promoted the activation and migration of human lung fibroblasts (HFL-1). The administration of IL-38 can counteract these biological processes induced by IL-36γ in HFL-1cells. The results indicated that IL-38 can mitigate airway remodeling by blocking the profibrotic effects of IL-36γ in chronic asthma. IL-36γ may be a new therapeutic target, and IL-38 is a potential candidate agent for inhibiting airway remodeling in asthma.

Targeting Labile Iron-Mediated Ferroptosis Provides a Potential Therapeutic Strategy for Rhabdomyolysis-Induced Acute Kidney Injury.

Acute kidney injury (AKI) is a global health problem that occurs in a variety of clinical settings. Despite some advances in supportive clinical care, no medicinal intervention has been demonstrated to reliably prevent AKI thus far. Therefore, it is highly necessary to investigate the pathophysiology and mechanisms involved in AKI for the discovery of therapeutics. In the current study, a robust change in the level of renal malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE) and elevated renal iron levels were observed in murine rhabdomyolysis-induced AKI (RM-AKI), which supports a pathogenic role of labile iron-mediated ferroptosis and provides a chance to utilize iron chelation for RM-AKI prevention. Given that the existing small molecule-based iron chelators did not show promising preventative effects against RM-AKI, we further designed and synthesized a new hydroxypyridinone-based iron chelator to potently inhibit labile iron-mediated ferroptosis. Lead compound AKI-02 was identified, which remarkably protected renal proximal tubular epithelial cells from ferroptosis as well as showed excellent iron chelation ability. Moreover, administration of AKI-02 led to renal function recovery, a result that was substantiated by the decreased contents of BUN and creatinine, as well as the reduced labile iron level and improved histopathology. Thus, our studies highlighted that targeting labile iron-mediated ferroptosis could provide therapeutic benefits against RM-AKI.

A Methodology for Quantitation of Dictamnine and Fraxinellone and its Application to Study Pharmacokinetics and Bioavailability in Rats Via Oral and Intravenous Administration.

The pharmacological activities of dictamnine and fraxinellone have been well reported; however, only a few studies have focused on the pharmacokinetics and bioavailability of concomitant delivery of these drugs in vivo. To shed light on this neglected area, we developed a rapid and sensitive UPLC-MS/MS method that quantified the levels of dictamnine and fraxinellone simultaneously in rat plasma. This method was initiated by a one-step protein precipitation strategy to purify plasma samples collected from rats treated with either oral or intravenous administration of dictamnine and fraxinellone. The mobile phase contained acetonitrile and 0.1% formic acid at a steady flow rate of 0.6 mL/min. As a result, an excellent analyte peak resolution was achieved, and the entire process took only 3 min per sample. The results were indicative of the desired linearity (r2 ≥ 0.999), precision (RSD% was within 15%), accuracy (RE% was within 15%), recoveries (≥80.66 and 68.15% for dictamnine and fraxinellone, respectively) and matrix effects (≥94.66 and 91.37% for dictamnine and fraxinellone, respectively). Additionally, the detectable limits of these two compounds were both low even when they reached 5 ng/mL. Taken together, these findings contribute to a better understanding of the pharmacokinetics and bioavailability properties of concomitant delivery of dictamnine and fraxinellone.

Digital micelles of encoded polymeric amphiphiles for direct sequence reading and ex vivo label-free quantification.

Identification and quantification of synthetic polymers in complex biological milieu are crucial for delivery, sensing and scaffolding functions, but conventional techniques based on imaging probe labellings only afford qualitative results. Here we report modular construction of precise sequence-defined amphiphilic polymers that self-assemble into digital micelles with contour lengths strictly regulated by oligourethane sequences. Direct sequence reading is accomplished with matrix-assisted laser desorption/ionization (MALDI) tandem mass spectrometry, facilitated by high-affinity binding of alkali metal ions with poly(ethylene glycol) dendrons and selective cleavage of benzyl-carbamate linkages. A mixture of four types of digital micelles could be identified, sequence-decoded and quantified by MALDI and MALDI imaging at cellular, organ and tissue slice levels upon in vivo administration, enabling direct comparison of biological properties for each type of digital micelle in the same animal. The concept of digital micelles and encoded amphiphiles capable of direct sequencing and high-throughput label-free quantification could be exploited for next-generation precision nanomedicine designs (such as digital lipids) and protein corona studies.

Advice for smokers in smoking cessation clinic: a review.

Background: Tobacco dependence has become a global public health concern. We chose to investigate the modifiable factors and motivations during the period of smoking cessation based on the mechanism of nicotine addiction. Methods: We selected emotion, sleep, alcohol, caffeine beverages, mental activities after dinner, exercise and CYP2A6 genotype as influencing factors, and provided corresponding recommendations for smokers based on these factors. Based on these characteristics, we reviewed literature and summarized the relationship between these factors and nicotine dependence or smoking. Results: Different emotion, sleep deficiency, caffeine intake, alcohol consumption, mental activities after dinner, physical exercises and CYP2A6 genotype have an effect on daily smoking and nicotine dependence. Conclusion: These suggestions related literature-derived factors may increase the success rate of smoking cessation.

Assessing the efficacy of myopia control in monocular orthokeratology treated unilateral myopic children.

PURPOSE: To investigate the efficacy of myopia control by comparing the orthokeratology (Ortho-K) treated eyes and the emmetropic contralateral eyes in unilateral myopic children, and to identify the inter-individual influence factors. METHOD: In this retrospective study, 1566 medical records of children wearing Ortho-K lens were reviewed, and 62 children who received monocular Ortho-K lens for more than 1 year were analyzed. The change in axial length (AL) of the Ortho-K eyes and the emmetropic contralateral eyes was recorded. To evaluate the absolute and relative efficacy of myopia control, the intra-bilateral absolute reduction in AL growth (ibARAL) and the intra-bilateral relative reduction in AL growth (ibRRAL) were calculated as main outcomes. Association of the AL elongation, ibARAL and ibRRAL with age, sex and ocular parameters was analyzed by correlation analysis and generalized estimating equation (GEE) analysis. RESULT: The average initial wearing age was 10.76 ± 1.45 (ranged 8.5 to 15.8). The average baseline SER was - 2.15 ± 1.03 (ranged - 5.25 to -1.00) D in the Ortho-K eyes and - 0.01 ± 0.40 (ranged - 0.75 to 0.75) D in the contralateral eyes. At the 1-year follow-up, the average increased AL was significantly less in the Ortho-K eyes (0.07 ± 0.18 mm) than in the fellow eyes (0.48 ± 0.24 mm) (p < 0.001). The mean ibARAL was 0.41 ± 0.30 mm, and the mean ibRRAL was 83.4%±56.3%. In the GEE model, the AL change in Ortho-K eyes (ß = 0.051, p = 0.009, 95%CI: 0.012 to 0.090), the ibARAL (ß= -0.153, p = 0.000, 95%CI: -0.228 to -0.078) and the ibRRAL (ß= -0.196, p = 0.020, 95%CI: -0.361 to -0.030) were independently associated with the spherical equivalent refraction (SER) of the Ortho-K eyes, after adjusting for age, sex, and keratometry. CONCLUSION: In our study, the Ortho-K treatment was efficacious in controlling axial length growth in the monocular orthokeratology treated unilateral myopic eyes. The efficacy increased when the myopia was more severe. In the children from 8 to 16 years old, the effectiveness was independent of age and sex.

Hsa_circRNA_0008028 Deficiency Ameliorates High Glucose-Induced Proliferation, Calcification, and Autophagy of Vascular Smooth Muscle Cells via miR-182-5p/TRIB3 Axis.

Background: It is well-known that dysfunctions of vascular smooth muscle cells (VSMCs) act an essential part in vascular complications of diabetes. Studies have shown that circular RNAs (circRNAs) and microRNAs (miRNAs) play a crucial role in regulating cell functions. However, their influence on the proliferation, calcification, and autophagy of VSMCs remains to be further explored. Therefore, this study elucidates the role and mechanism of hsa_circRNA_0008028 in high glucose- (HG-, 30 mM) treated VSMCs in vitro. Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) was chosen to detect the levels of hsa_circRNA_0008028, miR-182-5p, and tribble 3 (TRIB3). Then, dual-luciferase reporter and RNA immunoprecipitation (RIP) assays were used to predict and verify the binding relationship between miR-182-5p and hsa_circRNA_0008028 or TRIB3. Cell counting kit-8 assay, 5-ethynyl-2'-deoxyuridine (EdU) staining, corresponding commercial kits, and western blotting were used to measure indexes reflecting cell viability, proliferation, calcification, and autophagy of VSMCs, respectively. Results: In HG-induced VSMCs, hsa_circRNA_0008028 and TRIB3 were highly expressed, whereas miR-182-5p decreased. Meanwhile, cell proliferation, calcification, and autophagy could be repressed by silencing of hsa_circRNA_0008028. However, these effects can be eliminated by miR-182-5p inhibition. Furthermore, it was demonstrated that hsa_circRNA_0008028 could promote the expression of TRIB3, a target of miR-182-5p, by directly sponging miR-182-5p. The expression of TRIB3 was suppressed by hsa_circRNA_0008028 knockout, which was rescued by miR-182-5p inhibition. Conclusion: This study reveals that hsa_circRNA_0008028 can act as a sponge of miR-182-5p and promote HG-induced proliferation, calcification, and autophagy of VSMCs partly by regulating TRIB3.

Study on the effects of combined tea drinking and mental activity after dinner on smokers in China.

INTRODUCTION: Cigarette and tobacco use is a leading cause of chronic obstructive pulmonary disease, lung cancer, and other malignant tumors. In China, people prefer to engage in mental activities (gambling, overtime work, playing video games, or other mental activities) on the weekends or during spare time, especially in the evening before they prepare for bed. In China, smokers frequently consume tea while smoking. The relationship between smokers who consume tea, engage in mental activities after dinner, or both (drinking tea and engaging in cognitive activities after dinner together), and daily cigarette smoking or nicotine addiction must be clarified. METHODS: A total of 438 smokers were included in the study. Age, gender, body mass index (BMI), smoking habits, Fagerström test for nicotine dependence scores, and behaviors, were recorded. The study excluded smokers with a Fagerström score <1 or with a mental disorder diagnosis. The smokers were divided into four groups based on their behaviors: those who did not drink tea, did not engage in mental activities after dinner, those who drank tea only, those who engaged in mental activities only, and those who engaged in both. RESULTS: Only drinking tea or doing mental activities after dinner cannot increase cigarettes per day (22.20 ± 10.143 vs 23.49 ± 11.966, p=0.362; 22.20 ± 10.143 vs 22.66 ± 1.192, p=0.750) or FTND scores [6.0 (4.0; 7.0) vs 6.0 (4.0; 7.75), p=0.941; 6.0 (4.0; 7.0) vs 6.0 (4.25; 7.75), p=0.980]. People who drink tea and engage in mental activities after dinner smoke more (22.20 ± 10.143 vs 30.75 ± 17.264, p<0.0001) and have higher nicotine dependence levels [6.0 (4.0; 7.0) vs 7.0 (5.0; 8.0), p=0.015]. CONCLUSIONS: The consumption of tea or a mental activity after dinner is not associated with daily smoking or nicotine dependence. There is an association between the combined behaviors (tea drinking and mental activity after dinner) and the daily consumption of cigarettes, and the degree of nicotine dependence.

Fluorinated Copolypeptide-Stabilized Microbubbles with Maleimide-Decorated Surfaces as Long-Term Ultrasound Contrast Agents.

Gas-filled microbubbles (MBs) have been clinically used as ultrasound (US) contrast agents for disease diagnosis and treatment. However, it remains a great challenge to resolve the dilemma of stability and contrast enhancement of MBs. Herein, amphiphilic copolypeptides bearing fluorinated blocks are synthesized to stabilize perfluorocarbon (PFC)-filled MBs, exhibiting unique stability under both long-term storage and US imaging conditions. The fluorinated inner layer reduces the internal Laplace pressure and greatly improves the stability of MBs, which can be further reinforced by crosslinking of the dipropargyl-containing middle blocks. To overcome the suppressed nonlinear oscillation of polymer shells, maleimide groups are introduced onto the surface of MBs, enabling in situ reaction with plasma proteins to enhance second harmonic signals without compromising the stability of MBs, conferring better US imaging performance than that of SonoVueTM MBs.

Toxin-Enabled "On-Demand" Liposomes for Enhanced Phototherapy to Treat and Protect against Methicillin-Resistant Staphylococcus aureus Infection.

An effective therapeutic strategy against methicillin-resistant Staphylococcus aureus (MRSA) that does not promote further drug resistance is highly desirable. While phototherapies have demonstrated considerable promise, their application toward bacterial infections can be limited by negative off-target effects to healthy cells. Here, a smart targeted nanoformulation consisting of a liquid perfluorocarbon core stabilized by a lipid membrane coating is developed. Using vancomycin as a targeting agent, the platform is capable of specifically delivering an encapsulated photosensitizer along with oxygen to sites of MRSA infection, where high concentrations of pore-forming toxins trigger on-demand payload release. Upon subsequent near-infrared irradiation, local increases in temperature and reactive oxygen species effectively kill the bacteria. Additionally, the secreted toxins that are captured by the nanoformulation can be processed by resident immune cells to promote multiantigenic immunity that protects against secondary MRSA infections. Overall, the reported approach for the on-demand release of phototherapeutic agents into sites of infection could be applied against a wide range of high-priority pathogens.

[Utilization of UiO-66-NH2@cellulose hybrid aerogel for solid-phase extraction of sildenafil in health products].

Sildenafil is a prescription drug used to treat pulmonary hypertension and erectile dysfunction. However, the illegal addition of sildenafil to health supplements may be hazardous to human health. Therefore, it is imperative to develop a method for the detection of sildenafil in health products. Solid-phase extraction (SPE) is typically used for the separation, purification, and enrichment of samples, with the aim of reducing the matrix interference of the samples and improving the detection sensitivity. SPE is widely employed in the detection of trace compounds in complex samples. Metal-organic frameworks (MOFs) are hybrid crystalline materials composed of metal ions and organic ligands. MOFs offer the advantages of a large specific surface area, permanent nanopores, good stability, and pore controllability. Owing to their advantages, researchers have attempted to use MOFs for SPE; however, it is difficult to collect MOFs in the powder form when they are directly used in SPE, necessitating the use of a substrate material to fix the MOFs. Hence, this study proposes a novel SPE method with high sensitivity that employs a UiO-66-NH2@cellulose hybrid aerogel, for the detection of sildenafil in health products. First, UiO-66-NH2 was synthesized by a hydrothermal method. Cellulose nanocrystal (CNC) was modified with an aldehyde group to obtain CNC-CHO, and carboxymethyl cellulose (CMC) was modified with a hydrazide group to obtain CMC-NHNH2. Subsequently, UiO-66-NH2 was added to the CNC-CHO solution, mixed with the CMC-NHNH2 solution, and then crosslinked to load UiO-66-NH2 and form a hybrid aerogel as a bulk adsorbent. This bulk hybrid aerogel could be collected easily without extra force for use in SPE. The synthesized hybrid aerogel was characterized by X-ray powder diffraction, scanning electron microscopy, Fourier transform-infrared (FT-IR) spectroscopy, and nitrogen gas adsorption/desorption. The results showed that UiO-66-NH2 was successfully loaded on the pore surface of the hybrid aerogel, which made the pore of aerogel become more regular and a larger surface area. Investigation of the loading amount of UiO-66-NH2 in the hybrid aerogel revealed that a higher amount of UiO-66-NH2 could yield better extraction efficiency. The highest amount of UiO-66-NH2 that could be loaded in the hybrid aerogel was 50%. The experimental conditions affecting the enrichment of sildenafil were optimized, and determined to be the following: pH of the sample, 9.0; extraction time, 60 min; eluent, acetonitrile; elution time, 40 min; elution volume, 3×2 mL; salt ion concentration, 0. Separation was performed on an Agilent Zorbax Eclipse Plus C18 column (150 mm×4.6 mm, 5 µm) with a phosphate solution containing 0.1 mol/L triethylamine (pH=6.50)-acetonitrile (30∶70, v/v) as the mobile phase. The detection wavelength was set at 292 nm. Under the optimal conditions, the UiO-66-NH2@cellulose hybrid aerogel was used as an adsorbent to extract sildenafil in different concentrations. The peak area was proportional to the sildenafil concentration in the range of 10-2000 ng/mL, with limit of detection (LOD, S/N=3) of 2.85 ng/mL and enrichment factor of 59.17. The correlation coefficient (R2) was 0.9950. Compared to previous preconcentration methods for sildenafil, this method offered a wider linear range. Five batches of hybrid aerogels were simultaneously prepared under the same conditions and used to extract sildenafil; the relative standard deviation (RSD, n=3) was 1.71%, indicating that the prepared hybrid aerogels offered good reproducibility. The used composite aerogels were freeze-dried again and reused to extract sildenafil; the recovery was still maintained at 85.23% after five extraction cycles, indicating that the UiO-66-NH2@cellulose hybrid aerogel had good regeneration ability. The feasibility of the developed method was verified by analyzing five health products. The results demonstrated the presence of 3.01 µg/g sildenafil in one of the products and no sildenafil in the others. The recoveries of this SPE method ranged from 74.93% to 89.12%, with RSDs in the range of 2.8%-5.3%, proving the feasibility of this analytical method.

Oscillating the local milieu of polymersome interiors via single input-regulated bilayer crosslinking and permeability tuning.

The unique permselectivity of cellular membranes is of crucial importance to maintain intracellular homeostasis while adapting to microenvironmental changes. Although liposomes and polymersomes have been widely engineered to mimic microstructures and functions of cells, it still remains a considerable challenge to synergize the stability and permeability of artificial cells and to imitate local milieu fluctuations. Herein, we report concurrent crosslinking and permeabilizing of pH-responsive polymersomes containing Schiff base moieties within bilayer membranes via enzyme-catalyzed acid production. Notably, this synergistic crosslinking and permeabilizing strategy allows tuning of the mesh sizes of the crosslinked bilayers with subnanometer precision, showing discriminative permeability toward maltooligosaccharides with molecular sizes of ~1.4-2.6 nm. The permselectivity of bilayer membranes enables intravesicular pH oscillation, fueled by a single input of glucose. This intravesicular pH oscillation can further drive the dissipative self-assembly of pH-sensitive dipeptides. Moreover, the permeabilization of polymersomes can be regulated by intracellular pH gradient as well, enabling the controlled release of encapsulated payloads.

Comparison of peak expiratory Flow(PEF) and COPD assessment test (CAT) to assess COPD exacerbation requiring hospitalization: A prospective observational study.

BACKGROUND: Acute exacerbation of chronic obstructive pulmonary disease (COPD) resulting in hospitalization is significantly associated with the increased morbidity and mortality, but there is a lack of an effective method to assess it. This study aimed to compare the ability of peak expiratory flow (PEF) and COPD assessment test (CAT) to assess COPD exacerbations requiring hospitalization. METHODS: A cohort of 110 patients with moderate to severe COPD was studied over a period of 12 months, and their daily morning PEFs and CAT scores were recorded throughout the study. RESULTS: After 12 months of follow-up, 72 patients experienced 156 COPD exacerbations, 74 (47%) that resulted in hospitalization and 82 (53%) that did not result in hospitalization. Change in CAT score from baseline to exacerbation was significantly related to change in PEF and Spearman's rho =0.375 (95% CI, 0.227 to 0.506; p < .001). Change in PEF and CAT score from baseline to hospitalized exacerbation was significantly larger than that from baseline to non-hospitalized exacerbation (p < .05). Multivariable analysis indicated that ΔPEF (OR 1.11, 95% CI 1.06-1.16, p < .001) and ΔCAT (OR 1.64 95% CI 1.18-2.27, p = .003) were independently associated with risk of hospitalized exacerbation. ROC analysis indicated that the optimal cutoff value of ΔPEF for identifying hospitalized exacerbation was 49 L/min (27% from baseline), with a sensitivity and specificity of 82.7% and 76.7% (area under the curve [AUC] = 0.872 (95% CI 0.80-0.944, p < .05). The optimal cutoff value of ΔCAT score for identifying hospitalized exacerbation was 10.5 (63% from baseline), with a sensitivity and specificity of 67.3% and 77.4% [AUC]=0.763 (95% CI 0.67-0.857, p < .05). The AUC of ΔPEF and ΔCAT combined for the identification of hospitalized exacerbation was 0.900 (95% CI 0.841-0.959, p < .05), which was larger than that of ΔCAT or ΔPEF. CONCLUSIONS: ΔPEF and ΔCAT were independently associated with risk of hospitalized exacerbation. Compared with CAT, PEF was superior to identify hospitalized exacerbation. Identification via PEF and CAT combined is more effective than using PEF or CAT alone. These results help to assess the severity of COPD exacerbation and provide valuable information for clinical decision-making.

Synthesis of Polypeptides with High-Fidelity Terminal Functionalities under NCA Monomer-Starved Conditions.

Controlled polypeptide synthesis via α-amino acid N-carboxylic anhydride (NCA) polymerization using conventional primary amine initiators encounters two major obstacles: (i) normal amine mechanism (NAM) and activated monomer mechanism (AMM) coexist due to amine basicity and nucleophilicity and (ii) NCA is notoriously sensitive towards moisture and heat and unstable upon storage. We serendipitously discover that N-phenoxycarbonyl-functionalized α-amino acid (NPCA), a latent NCA precursor, could be polymerized solely based on NAM with high initiating efficiency by using primary amine hydrochloride as an initiator. The polymerization affords well-defined polypeptides with narrow polydispersity and high-fidelity terminal functionalities, as revealed by the clean set of MALDI-TOF MS patterns. We further demonstrate successful syntheses of random and block copolypeptides, even under open-vessel conditions. Overall, the integration of moisture-insensitive and air-tolerant NPCA precursors with stable primary amine hydrochloride initiators represents a general strategy for controlled synthesis of high-fidelity polypeptides with sophisticated functions.

THE Impact of Disruption on the Relationship Between Exploitation, Exploration, and Organizational Adaptation.

Firms should deploy exploration and exploitation to foster organizational adaptation. Previous research on exploration and exploitation lacked a focus on disruption implications in different contexts. This study aims to empirically test a moderation model including disruption events, exploration, exploitation, and organizational adaptation and enable a deeper understanding of organizational learning and innovation theory to yield competitive advantage and sustainability of innovative firms. Our results reveal that exploration is more effective during outside disruption events. The results do not support the concept that exploitation is more effective during inside disruptions. Disruptions also moderate the combined effect of exploration and exploitation. Although they are generally complementary in facilitating organizational adaptation, a singular focus on either exploration or exploitation is as effective as is combining exploration and exploitation during inside and outside disruption events. The results of an event study using seven Chinese international firms, including Alibaba, Meituan, Dianping, Baidu, Beibei, TP-link, and Maxio, provided 132 completed and usable questionnaires that supported our hypotheses. Our study contributes to a better understanding of disruption, exploration, exploitation, and related performance implications.

[The Surgical Effects of Medial Rectus Recession on Divergence Insufficiency Esotropia].

OBJECTIVE: To study the surgical effects of medial rectus recession (MRR) on divergence insufficiency esotropia (DIE). METHODS: Nine DIE patients who were admitted to and had MRR at Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University between December 2017 and June 2020 were included in this retrospective study. All patients were followed up for 1 year at least. The postoperative esodeviation, near-distant disparity (NDD) and visual function were observed and compared. RESULTS: The mean age of the 9 patients was 28.8 years old (10-49 yr.), including 3 adolescent patients (≤18 yr.). The mean preoperative esodeviation was (19.8±13.2) PD for near and (32.6±15.3) PD at distance, while, the mean postoperative esodeviation 1 year after MMR was (-0.2±3.5) PD for near and (6.0±2.2) PD at distance, showing significant improvement over the mean preoperative esodeviation ( P=0.012, P=0.007). NDD dropped from (12.8±2.4) PD before the surgery to (6.0±2.2) PD 1 year after the surgery, showing significant improvement ( P=0.008), and remained stable 1 year after the surgery ( F=0.075, P=0.900). There was no significant improvement of near stereopsis ( P=0.306). Binocular function at distance was significantly improved after surgery (Worth 4 dots test : P=0.017; Bagolini striated glasses: P=0.035). The patients were divided into two groups, the adolescent group (age≤18 yr., n=3) and the adult group (age>18 yr., n=6). Prior to the operation, the mean spherical diopter of the adolescent group (OD -1.75 D, OS -1.92 D) was lower than that of the adult group (OD -6.17 D, OS -6.04 D) ( P=0.012). The average value of preoperative AC/A of the adolescent group was 4.33. It was 2.33 in the adult group, which was lower than the normal value, and significantly lower than that of the adolescent group ( P=0.12). There was no significant difference in esodeviation or NDD between the adolescent group and the adult group before and after operation. CONCLUSIONS: Medial rectus muscle recession can effectively improve the NDD and the binocular function at distance of patients with divergence insufficiency esotropia. Postoperative esodeviations both for near and at distance tend to regress after the surgery. Therefore, it is recommended that the amount of MRR be increased in the treatment of DIE.