OTULIN allies with LUBAC to govern angiogenesis by editing ALK1 linear polyubiquitin.

OTULIN coordinates with LUBAC to edit linear polyubiquitin chains in embryonic development, autoimmunity, and inflammatory diseases. However, the mechanism by which angiogenesis, especially that of endothelial cells (ECs), is regulated by linear ubiquitination remains unclear. Here, we reveal that constitutive or EC-specific deletion of Otulin resulted in arteriovenous malformations and embryonic lethality. LUBAC conjugates linear ubiquitin chains onto Activin receptor-like kinase 1 (ALK1), which is responsible for angiogenesis defects, inhibiting ALK1 enzyme activity and Smad1/5 activation. Conversely, OTULIN deubiquitinates ALK1 to promote Smad1/5 activation. Consistently, embryonic survival of Otulin-deficient mice was prolonged by BMP9 pretreatment or EC-specific ALK1Q200D (constitutively active) knockin. Moreover, mutant ALK1 from type 2 hereditary hemorrhagic telangiectasia (HHT2) patients exhibited excessive linear ubiquitination and increased HOIP binding. As such, a HOIP inhibitor restricted the excessive angiogenesis of ECs derived from ALK1G309S-expressing HHT2 patients. These results show that OTULIN and LUBAC govern ALK1 activity to balance EC angiogenesis.

Acetylation-mediated proteasomal degradation of core histones during DNA repair and spermatogenesis.

Histone acetylation plays critical roles in chromatin remodeling, DNA repair, and epigenetic regulation of gene expression, but the underlying mechanisms are unclear. Proteasomes usually catalyze ATP- and polyubiquitin-dependent proteolysis. Here, we show that the proteasomes containing the activator PA200 catalyze the polyubiquitin-independent degradation of histones. Most proteasomes in mammalian testes ("spermatoproteasomes") contain a spermatid/sperm-specific α subunit α4 s/PSMA8 and/or the catalytic ß subunits of immunoproteasomes in addition to PA200. Deletion of PA200 in mice abolishes acetylation-dependent degradation of somatic core histones during DNA double-strand breaks and delays core histone disappearance in elongated spermatids. Purified PA200 greatly promotes ATP-independent proteasomal degradation of the acetylated core histones, but not polyubiquitinated proteins. Furthermore, acetylation on histones is required for their binding to the bromodomain-like regions in PA200 and its yeast ortholog, Blm10. Thus, PA200/Blm10 specifically targets the core histones for acetylation-mediated degradation by proteasomes, providing mechanisms by which acetylation regulates histone degradation, DNA repair, and spermatogenesis.

Mycobacterium tuberculosis suppresses innate immunity by coopting the host ubiquitin system.

Mycobacterium tuberculosis PtpA, a secreted tyrosine phosphatase essential for tuberculosis pathogenicity, could be an ideal target for a drug against tuberculosis, but its active-site inhibitors lack selectivity over human phosphatases. Here we found that PtpA suppressed innate immunity dependent on pathways of the kinases Jnk and p38 and the transcription factor NF-κB by exploiting host ubiquitin. Binding of PtpA to ubiquitin via a region with no homology to human proteins activated it to dephosphorylate phosphorylated Jnk and p38, leading to suppression of innate immunity. Furthermore, the host adaptor TAB3 mediated NF-κB signaling by sensing ubiquitin chains, and PtpA blocked this process by competitively binding the ubiquitin-interacting domain of TAB3. Our findings reveal how pathogens subvert innate immunity by coopting host ubiquitin and suggest a potential tuberculosis treatment via targeting of ubiquitin-PtpA interfaces.

Pyroptosis modulation by bacterial effector proteins.

Pyroptosis is a proinflammatory form of programmed cell death featured with membrane pore formation that causes cellular swelling and allows the release of intracellular inflammatory mediators. This cell death process is elicited by the activation of the pore-forming proteins named gasdermins, and is intricately orchestrated by diverse regulatory factors in mammalian hosts to exert a prompt immune response against infections. However, growing evidence suggests that bacterial pathogens have evolved to regulate host pyroptosis for evading immune clearance and establishing progressive infection. In this review, we highlight current understandings of the functional role and regulatory network of pyroptosis in host antibacterial immunity. Thereafter, we further discuss the latest advances elucidating the mechanisms by which bacterial pathogens modulate pyroptosis through adopting their effector proteins to drive infections. A better understanding of regulatory mechanisms underlying pyroptosis at the interface of host-bacterial interactions will shed new light on the pathogenesis of infectious diseases and contribute to the development of promising therapeutic strategies against bacterial pathogens.

Crotonylation of NAE1 Modulates Cardiac Hypertrophy via Gelsolin Neddylation.

BACKGROUND: Cardiac hypertrophy and its associated remodeling are among the leading causes of heart failure. Lysine crotonylation is a recently discovered posttranslational modification whose role in cardiac hypertrophy remains largely unknown. NAE1 (NEDD8-activating enzyme E1 regulatory subunit) is mainly involved in the neddylation modification of protein targets. However, the function of crotonylated NAE1 has not been defined. This study aims to elucidate the effects and mechanisms of NAE1 crotonylation on cardiac hypertrophy. METHODS: Crotonylation levels were detected in both human and mouse subjects with cardiac hypertrophy through immunoprecipitation and Western blot assays. TMT-labeled quantitative lysine crotonylome analysis was performed to identify the crotonylated proteins in a mouse cardiac hypertrophic model induced by transverse aortic constriction. We generated NAE1 knock-in mice carrying a crotonylation-defective lysine to arginine K238R (lysine to arginine mutation at site 238) mutation (NAE1 K238R) and NAE1 knock-in mice expressing a crotonylation-mimicking lysine to glutamine K238Q (lysine to glutamine mutation at site 238) mutation (NAE1 K238Q) to assess the functional role of crotonylation of NAE1 at K238 in pathological cardiac hypertrophy. Furthermore, we combined coimmunoprecipitation, mass spectrometry, and dot blot analysis that was followed by multiple molecular biological methodologies to identify the target GSN (gelsolin) and corresponding molecular events contributing to the function of NAE1 K238 crotonylation. RESULTS: The crotonylation level of NAE1 was increased in mice and patients with cardiac hypertrophy. Quantitative crotonylomics analysis revealed that K238 was the main crotonylation site of NAE1. Loss of K238 crotonylation in NAE1 K238R knock-in mice attenuated cardiac hypertrophy and restored the heart function, while hypercrotonylation mimic in NAE1 K238Q knock-in mice significantly enhanced transverse aortic constriction-induced pathological hypertrophic response, leading to impaired cardiac structure and function. The recombinant adenoviral vector carrying NAE1 K238R mutant attenuated, while the K238Q mutant aggravated Ang II (angiotensin II)-induced hypertrophy. Mechanistically, we identified GSN as a direct target of NAE1. K238 crotonylation of NAE1 promoted GSN neddylation and, thus, enhanced its protein stability and expression. NAE1 crotonylation-dependent increase of GSN promoted actin-severing activity, which resulted in adverse cytoskeletal remodeling and progression of pathological hypertrophy. CONCLUSIONS: Our findings provide new insights into the previously unrecognized role of crotonylation on nonhistone proteins during cardiac hypertrophy. We found that K238 crotonylation of NAE1 plays an essential role in mediating cardiac hypertrophy through GSN neddylation, which provides potential novel therapeutic targets for pathological hypertrophy and cardiac remodeling.

REME: an integrated platform for reaction enzyme mining and evaluation.

A key challenge in pathway design is finding proper enzymes that can be engineered to catalyze a non-natural reaction. Although existing tools can identify potential enzymes based on similar reactions, these tools encounter several issues. Firstly, the calculated similar reactions may not even have the same reaction type. Secondly, the associated enzymes are often numerous and identifying the most promising candidate enzymes is difficult due to the lack of data for evaluation. Thirdly, existing web tools do not provide interactive functions that enable users to fine-tune results based on their expertise. Here, we present REME (https://reme.biodesign.ac.cn/), the first integrated web platform for reaction enzyme mining and evaluation. Combining atom-to-atom mapping, atom type change identification, and reaction similarity calculation enables quick ranking and visualization of reactions similar to an objective non-natural reaction. Additional functionality enables users to filter similar reactions by their specified functional groups and candidate enzymes can be further filtered (e.g. by organisms) or expanded by Enzyme Commission number (EC) or sequence homology. Afterward, enzyme attributes (such as kcat, Km, optimal temperature and pH) can be assessed with deep learning-based methods, facilitating the swift identification of potential enzymes that can catalyze the non-natural reaction.

Two C-terminal isoforms of Aplysia tachykinin-related peptide receptors exhibit phosphorylation-dependent and phosphorylation-independent desensitization mechanisms.

Diversity, a hallmark of G protein-coupled receptor (GPCR) signaling, partly stems from alternative splicing of a single gene generating more than one isoform for a receptor. Additionally, receptor responses to ligands can be attenuated by desensitization upon prolonged or repeated ligand exposure. Both phenomena have been demonstrated and exemplified by the deuterostome tachykinin signaling system, although the role of phosphorylation in desensitization remains a subject of debate. Here, we describe the signaling system for tachykinin-related peptides (TKRPs) in a protostome, mollusk Aplysia. We cloned the Aplysia TKRP precursor, which encodes three TKRPs (apTKRP-1, apTKRP-2a, and apTKRP-2b) containing the FXGXR-amide motif. In situ hybridization and immunohistochemistry showed predominant expression of TKRP mRNA and peptide in the cerebral ganglia. TKRPs and their posttranslational modifications were observed in extracts of central nervous system ganglia using mass spectrometry. We identified two Aplysia TKRP receptors (apTKRPRs), named apTKRPR-A and apTKRPR-B. These receptors are two isoforms generated through alternative splicing of the same gene and differ only in their intracellular C termini. Structure-activity relationship analysis of apTKRP-2b revealed that both C-terminal amidation and conserved residues of the ligand are critical for receptor activation. C-terminal truncates and mutants of apTKRPRs suggested that there is a C-terminal phosphorylation-independent desensitization for both receptors. Moreover, apTKRPR-B also exhibits phosphorylation-dependent desensitization through the phosphorylation of C-terminal Ser/Thr residues. This comprehensive characterization of the Aplysia TKRP signaling system underscores the evolutionary conservation of the TKRP and TK signaling systems, while highlighting the intricacies of receptor regulation through alternative splicing and differential desensitization mechanisms.

Genome-wide analysis and expression profiling of the HD-ZIP gene family in kiwifruit.

The homeodomain-leucine zipper (HD-Zip) gene family plays a pivotal role in plant development and stress responses. Nevertheless, a comprehensive characterization of the HD-Zip gene family in kiwifruit has been lacking. In this study, we have systematically identified 70 HD-Zip genes in the Actinidia chinensis (Ac) genome and 55 in the Actinidia eriantha (Ae) genome. These genes have been categorized into four subfamilies (HD-Zip I, II, III, and IV) through rigorous phylogenetic analysis. Analysis of synteny patterns and selection pressures has provided insights into how whole-genome duplication (WGD) or segmental may have contributed to the divergence in gene numbers between these two kiwifruit species, with duplicated gene pairs undergoing purifying selection. Furthermore, our study has unveiled tissue-specific expression patterns among kiwifruit HD-Zip genes, with some genes identified as key regulators of kiwifruit responses to bacterial canker disease and postharvest processes. These findings not only offer valuable insights into the evolutionary and functional characteristics of kiwifruit HD-Zips but also shed light on their potential roles in plant growth and development.

The functional divergence of homologous GPAT9 genes contributes to the erucic acid content of Brassica napus seeds.

BACKGROUND: The early allopolyploid Brassica napus was a hybrid of two Brassica species, that had undergone a whole genome duplication event followed by genome restructuring, including deletions and small scale duplications. A large number of homologous genes appeared functional divergence during species domestication. Due to the high conservation of de novo glycerolipid biosynthesis, multiple homologues of glycerol-3-phosphate acyltransferases (GPATs) have been found in B. napus. Moreover, the functional variances among these homologous GPAT-encoding genes are unclear. RESULTS: In this study, four B. napus homologous genes encoding glycerol-3-phosphate acyltransferase 9 (BnaGPAT9) were characterized. Although a bioinformatics analysis indicated high protein sequence similarity, the homologues demonstrated tissue-specific expression patterns and functional divergence. Yeast genetic complementation assays revealed that BnaGPAT9-A1/C1 homologues but not BnaGPAT9-A10/C9 homologues encoded functional GPAT enzymes. Furthermore, a single nucleotide polymorphism of BnaGPAT9-C1 that occurred during the domestication process was associated with enzyme activity and contributed to the fatty acid composition. The seed-specific expression of BnGPAT9-C11124A increased the erucic acid content in the transformant seeds. CONCLUSIONS: This study revealed that BnaGPAT9 gene homologues evolved into functionally divergent forms with important roles in erucic acid biosynthesis.

Actin-bundling protein fimbrin serves as a new auxin biosynthesis orchestrator in Arabidopsis root tips.

Plants delicately regulate endogenous auxin levels through the coordination of transport, biosynthesis, and inactivation, which is crucial for growth and development. While it is well-established that the actin cytoskeleton can regulate auxin levels by affecting polar transport, its potential role in auxin biosynthesis has remained largely unexplored. Using LC-MS/MS-based methods combined with fluorescent auxin marker detection, we observed a significant increase in root auxin levels upon deletion of the actin bundling proteins AtFIM4 and AtFIM5. Fluorescent observation, immunoblotting analysis, and biochemical approaches revealed that AtFIM4 and AtFIM5 affect the protein abundance of the key auxin synthesis enzyme YUC8 in roots. AtFIM4 and AtFIM5 regulate the auxin synthesis enzyme YUC8 at the protein level, with its degradation mediated by the 26S proteasome. This regulation modulates auxin synthesis and endogenous auxin levels in roots, consequently impacting root development. Based on these findings, we propose a molecular pathway centered on the 'actin cytoskeleton-26S proteasome-YUC8-auxin' axis that controls auxin levels. Our findings shed light on a new pathway through which plants regulate auxin synthesis. Moreover, this study illuminates a newfound role of the actin cytoskeleton in regulating plant growth and development, particularly through its involvement in maintaining protein homeostasis via the 26S proteasome.

Tetraazaisoindigos:Serpentine Syntheses and Their Expected and Unexpected Photophysical and Electronic Properties.

Isoindigo, an electron-withdrawing building block for polymeric field-effect transistors, has long been considered to be non-fluorescent. Moreover, using electron-deficient heterocycle to replace the phenyl ring in the isoindigo core for better electron transport behaviour is synthetically challenging. Here we report the syntheses of a series of tetraazaisoindigos, including pyrazinoisoindigo (PyrII), pyrimidoisoindigo (PymII) and their hybrid (PyrPymII), and the investigation on their photophysical and electric properties. Proper flanking groups need to be chosen to stabilize these highly electron-deficient bislactams. Both PyrII and PymII derivatives show lower LUMO energy levels than that of naphthalene bisimide (NDI). Interestingly, PyrII is instinctively unstable and can be easily reduced, while both PymII derivatives are stable. More surprisingly, PymII derivatives are highly fluorescent and their photoluminescence quantum yields are around 40%, 133 times higher than that of reported isoindigo derivatives. UV-vis spectroscopic results and theoretical calculations show that strong intramolecular hydrogen-bond exists in PymII, which prohibits it from non-radiative decay and accounts for its fluorescent behaviour.  PymII deriviatives are n-type semiconductors, while Ph-PyrII and the hybrid show balanced ambipolar charge transport behaviour, all among the best isoindigo derivatives. Our study not only discloses the structure-property relationship of tetraazaisoindigos, but also provides electron-deficient monomers for conjugated polymers.

Genetic and prognostic analysis of blastoid and pleomorphic mantle cell lymphoma: a multicenter analysis in China.

Blastoid or pleomorphic mantle cell lymphoma (B/P-MCL) is characterized by high invasiveness and unfavorable outcomes, which is still a challenge for treating MCL. This retrospective study was performed to comprehensively analyze the clinical, genomic characteristics and treatment options of patients with B/PMCL from multicenter in China. Data were obtained from 693 patients with B/PMCL from three centers in China between April 1999 and December 2019. Seventy-four patients with BMCL (n = 43) or PMCL (n = 31) were included in the analysis. The median age of the cohort was 60.0 years with a male-to-female ratio of 2.89:1. The 3-year progression-free survival (PFS) and overall survival (OS) rates were 44.1% and 46.0%, respectively. Mutations of TP53, ATM, NOTCH1, NOTCH2, NSD2, SMARCA4, CREBBP, KMT2D, FAT1, and TRAF2 genes were the most common genetic changes in B/P-MCL. Progression of disease within 12 months (POD12) could independently predict the poor prognosis of patients with blastoid and pleomorphic variants. Patients with POD12 carried a distinct mutation profile (TP53, SMARCA4, NSD2, NOTCH2, KMT2D, PTPRD, CREBBP, and CDKN2A mutations) compared to patients with non-POD12. First-line high-dose cytosine arabinoside exposure obtained survival benefits in these populations, and BTKi combination therapy as the front-line treatment had somewhat improvement in survival with no significant difference in the statistic. In conclusion, B/P-MCL had inferior outcomes and a distinct genomic profile. Patients with POD12 displayed a distinct mutation profile and a poor prognosis. New therapeutic drugs and clinical trials for B/P-MCL need to be further explored.

The function and therapeutic potential of transfer RNA-derived small RNAs in cardiovascular diseases: A review.

Transfer RNA-derived small RNAs (tsRNAs) are a class of small non-coding RNA (sncRNA) molecules derived from tRNA, including tRNA derived fragments (tRFs) and tRNA halfs (tiRNAs). tsRNAs can affect cell functions by participating in gene expression regulation, translation regulation, intercellular signal transduction, and immune response. They have been shown to play an important role in various human diseases, including cardiovascular diseases (CVDs). Targeted regulation of tsRNAs expression can affect the progression of CVDs. The tsRNAs induced by pathological conditions can be detected when released into the extracellular, giving them enormous potential as disease biomarkers. Here, we review the biogenesis, degradation process and related functional mechanisms of tsRNAs, and discuss the research progress and application prospects of tsRNAs in different CVDs, to provide a new perspective on the treatment of CVDs.

Activation of polyimide by oxygen plasma for atomic layer deposition of highly compact titanium oxide coating.

Titanium oxide (TiO2) coated polyimide has broad application prospects under extreme conditions. In order to obtain a high-quality ultra-thin TiO2coating on polyimide by atomic layer deposition (ALD), the polyimide was activated byin situoxygen plasma. It was found that a large number of polar oxygen functional groups, such as carboxyl, were generated on the surface of the activated polyimide, which can significantly promote the preparation of TiO2coating by ALD. The nucleation and growth of TiO2were studied by x-ray photoelectron spectroscopy monitoring and scanning electron microscopy observation. On the polyimide activated by oxygen plasma, the size of TiO2nuclei decreased and the quantity of TiO2nuclei increased, resulting in the growth of a highly uniform and dense TiO2coating. This coating exhibited excellent resistance to atomic oxygen. When exposed to 3.5 × 1021atom cm-2atomic oxygen flux, the erosion yield of the polyimide coated with 100 ALD cycles of TiO2was as low as 3.0 × 10-25cm3/atom, which is one order less than that of the standard POLYIMIDE-ref Kapton®film.

Ultrathin Al2O3film modification on waterborne epoxy coatings by atomic layer deposition for augmenting the corrosion resistance.

The polar channels formed by the curing of waterborne anticorrosive coatings compromise their water resistance, leading to coating degradation and metal corrosion. To enhance the anticorrosive performance of waterborne coatings, this study proposed a novel method of depositing ultrathin Al2O3films on the surface of waterborne epoxy coatings by atomic layer deposition, a technique that can modify the surface properties of polymer materials by depositing functional films. The Al2O3-modified coatings exhibited improved sealing and barrier properties by closing the polar channels and surface defects and cracks. The surface structure and morphology of the modified coatings were characterized by x-ray photoelectron spectroscopy and scanning electron microscopy. The hydrophilicity and corrosion resistance of the modified coatings were evaluated by water contact angle measurement, Tafel polarization curve, and electrochemical impedance spectroscopy. The results indicated that the water contact angle of the Al2O3-modified coating increased by 48° compared to the unmodified coating, and the protection efficiency of the modified coating reached 99.81%. The Al2O3-modified coating demonstrated high anticorrosive efficiency and potential applications for metal anticorrosion in harsh marine environments.

Integrating carbon dots and gold/silver core-shell nanoparticles to achieve sensitive detection of dopamine with fluorometric/colorimetric dual signal.

Dopamine (DA) is a potent neuromodulator in the brain that affects a wide range of motivated behaviors. Abnormal concentration of DA is related to a variety of diseases. Hence, it is imperative to establish a rapid and precise method for quantifying DA. In this work, we integrate orange-yellow emissive carbon dots (CDs) with target-induced silver deposition on gold nanoparticles (Au NPs), forming gold/silver core-shell nanoparticles (Au@Ag NPs), to construct a fluorometric and colorimetric dual-signal sensor for sensitive detection of DA. Au NPs and silver ions (Ag+) have minimal effect on the fluorescence of CDs. DA can reduce the silver ions to Ag(0) on the surface of the Au NPs to form a silver shell, resulting in the blue-shift of the absorbance peak from 520 to 416 nm, which overlaps with the excitation spectrum of CDs. As a result, the system color turns from pink to orange-yellow, and the fluorescence of CDs is quenched due to the strong inner filter effect. The linear range of the colorimetry is 0.5-18 µM with a limit of detection (LOD) of 0.41 µM, while the linear range for the fluorometry method is 0.5-14 µM with a LOD of 0.021 µM. This method demonstrates notable advantages including a low detection limit, rapid response time, and straightforward operation in practical samples, showing great potential in biomedical analysis.

Dipole-multipole plasmonic coupling between gold nanorods and titanium nitride nanoparticles for enhanced photothermal conversion.

The plasmonic photothermal conversion efficiency can be enhanced by coupling among plasmonic atoms or plasmonic molecules due to the amplified local electric field and extinction cross-section. Recently, it has been theoretically proved that hybridization between dipolar modes and higher order modes can provide higher enhancement than that among dipolar modes in terms of both near- and far-field, which may lead to a higher photothermal conversion rate. In this work, we systematically investigated the photothermal conversion enhancement of plasmonic coupling between a dipolar mode of a titanium nitride nanoparticle (TiN NP) and a higher order mode of a gold nanorod (Au NR), which was compared to that of coupling among TiN NPs' dipolar modes. We evaluated the photothermal conversion efficiency of dipole-dipole coupling and dipole-multipole coupling in the nanocluster under the illumination of a monochromatic laser of 808 nm wavelength and simulated solar light, respectively. Both experimental tests and numerical simulations suggested that the plasmonic dipole-multipole coupling exhibited higher enhancement in photothermal conversion than dipole-dipole plasmonic coupling.

ABRO1 arrests cardiomyocyte proliferation and myocardial repair by suppressing PSPH.

The role of Abraxas 2 (ABRO1 or KIAA0157), a component of the lysine63-linked deubiquitinating system, in the cardiomyocyte proliferation and myocardial regeneration is unknown. Here, we found that ABRO1 regulates cardiomyocyte proliferation and cardiac regeneration in the postnatal heart by targeting METTL3-mediated m6A methylation of Psph mRNA. The deletion of ABRO1 increased cardiomyocyte proliferation in hearts and restored the heart function after myocardial injury. On the contrary, ABRO1 overexpression significantly inhibited the neonatal cardiomyocyte proliferation and cardiac regeneration in mouse hearts. The mechanism by which ABRO1 regulates cardiomyocyte proliferation mainly involved METTL3-mediated Psph mRNA methylation and CDK2 phosphorylation. In the early postnatal period, METTL3-dependent m6A methylation promotes cardiomyocyte proliferation by hypermethylation of Psph mRNA and upregulating PSPH expression. PSPH dephosphorylates cyclin-dependent kinase 2 (CDK2), a positive regulator of cell cycle, at Thr14/Tyr15 and increases its activity. Upregulation of ABRO1 restricts METTL3 activity and halts the cardiomyocyte proliferation in the postnatal hearts. Thus, our study reveals that ABRO1 is an essential contributor in the cell cycle withdrawal and attenuation of proliferative response in the postnatal cardiomyocytes and could act as a potential target to accelerate cardiomyocyte proliferation and cardiac repair in the adult heart.

Hyperglycemia affects axial signs in patients with Parkinson's disease through mechanisms of insulin resistance or non-insulin resistance.

OBJECTIVE: To investigate the influence of hyperglycemia on motor symptoms, especially axial signs, and potential mechanisms related to insulin resistance (IR) in patients with Parkinson's disease (PWP). METHODS: According to glycated hemoglobin (HbA1c) level, PWP were divided into the low-HbA1c and the high-HbA1c groups. Demographic information, glucose metabolism-related variables, Hoehn-Yahr stage, and motor function were compared between the two groups. Correlations between levels of HbA1c and the homeostatic model assessment (HOMA)-IR and motor function in PWP were further analyzed. RESULTS: HbA1c level was significantly and positively correlated with the Movement Disorder Society Unified Parkinson's Disease Rating Scale Part III score, axial signs subscore, the Timed Get Up and Go test time, the center of pressure displacement of standing with eyes open and closed, and significantly and negatively correlated with the 10-m walk test comfortable gait speed. HOMA-IR level was significantly and negatively correlated with 10-m walk test comfortable gait speed, but not with others. CONCLUSIONS: PWP with high HbA1c showed worse axial symptoms, including dysfunction of automatic walking, dynamic balance, and postural control than those with low HbA1c. In PWP, the effects of hyperglycemia on automatic walking speed may be associated with the IR-related mechanisms, and the effects on dynamic balance and postural control may be related to mechanisms other than IR.

A Study of Elderly Patients' Preference for "Internet + Nursing Service" Based on Discrete Choice Experiments.

Objective: To investigate the preference of elderly patients for "Internet + Nursing Service", so as to provide reference for accurately matching their service needs. Methods: Based on discrete choice experiments, the elderly patients' "Internet + Nursing Service" choice preference questionnaire was prepared, and 410 elderly patients were interviewed face-to-face. The Conditional Logit Model was used for quantitative analysis of the experimental data. Results: The six attributes included in the study had a significant impact on the elderly patients' preference for "Internet + Nursing Service" (P < .05). Among non-economic attributes, "medical insurance reimbursement ratio -70%" has the highest utility (.263, P < .001), with "hospital size - larger (.205, P < .05)" and "medical insurance reimbursement ratio -50%" (.188, P < .05) ranking second and third, respectively. The relative importance of the attribute of medical insurance reimbursement proportion is the highest (26.44%), and the relative importance of service content is the lowest (9.78%). If the proportion of medical insurance reimbursement increases from 30% to 70%, patients are willing to pay 202.9 yuan, and the probability of choosing "Internet + Nursing Service" increases by 6.1%. Conclusion: Patients prefer to choose a higher proportion of medical insurance reimbursement, a larger medical institution, a higher level of nurses, low single service costs, a basic package, and "Internet + Nursing Service" led by the government and hospitals. Improvement of the price and medical insurance payment policy is recommended, along with the enhancement of the ability of primary nursing services, strengthening of the management of Internet enterprise platforms, and scientific assessment of the needs of patients for personalized nursing services.