Proline metabolic reprogramming modulates cardiac remodeling induced by pressure overload in the heart.

Metabolic reprogramming is critical in the onset of pressure overload-induced cardiac remodeling. Our study reveals that proline dehydrogenase (PRODH), the key enzyme in proline metabolism, reprograms cardiomyocyte metabolism to protect against cardiac remodeling. We induced cardiac remodeling using transverse aortic constriction (TAC) in both cardiac-specific PRODH knockout and overexpression mice. Our results indicate that PRODH expression is suppressed after TAC. Cardiac-specific PRODH knockout mice exhibited worsened cardiac dysfunction, while mice with PRODH overexpression demonstrated a protective effect. In addition, we simulated cardiomyocyte hypertrophy in vitro using neonatal rat ventricular myocytes treated with phenylephrine. Through RNA sequencing, metabolomics, and metabolic flux analysis, we elucidated that PRODH overexpression in cardiomyocytes redirects proline catabolism to replenish tricarboxylic acid cycle intermediates, enhance energy production, and restore glutathione redox balance. Our findings suggest PRODH as a modulator of cardiac bioenergetics and redox homeostasis during cardiac remodeling induced by pressure overload. This highlights the potential of PRODH as a therapeutic target for cardiac remodeling.

Dynamic Profiling and Prediction of Antibody Response to SARS-CoV-2 Booster-Inactivated Vaccines by Microsample-Driven Biosensor and Machine Learning.

Knowledge of the antibody response to the third dose of inactivated SARS-CoV-2 vaccines is crucial because it is the subject of one of the largest global vaccination programs. This study integrated microsampling with optical biosensors to profile neutralizing antibodies (NAbs) in fifteen vaccinated healthy donors, followed by the application of machine learning to predict antibody response at given timepoints. Over a nine-month duration, microsampling and venipuncture were conducted at seven individual timepoints. A refined iteration of a fiber optic biolayer interferometry (FO-BLI) biosensor was designed, enabling rapid multiplexed biosensing of the NAbs of both wild-type and Omicron SARS-CoV-2 variants in minutes. Findings revealed a strong correlation (Pearson r of 0.919, specificity of 100%) between wild-type variant NAb levels in microsamples and sera. Following the third dose, sera NAb levels of the wild-type variant increased 2.9-fold after seven days and 3.3-fold within a month, subsequently waning and becoming undetectable after three months. Considerable but incomplete evasion of the latest Omicron subvariants from booster vaccine-elicited NAbs was confirmed, although a higher number of binding antibodies (BAbs) was identified by another rapid FO-BLI biosensor in minutes. Significantly, FO-BLI highly correlated with a pseudovirus neutralization assay in identifying neutralizing capacities (Pearson r of 0.983). Additionally, machine learning demonstrated exceptional accuracy in predicting antibody levels, with an error level of <5% for both NAbs and BAbs across multiple timepoints. Microsample-driven biosensing enables individuals to access their results within hours of self-collection, while precise models could guide personalized vaccination strategies. The technology's innate adaptability means it has the potential for effective translation in disease prevention and vaccine development.

The Effect of Intervention Program based on Interaction Model of Client Health Behavior on Patients of Pressure Injury.

Objective: To investigate the effect of the intervention program based on the Interaction Model of Client Health Behavior (IMCHB) in patients with pressure injury (PI). Methods: The First Affiliated Hospital of Qiqihar Medical University received thirty patients suspected of having pressure injuries from June to December 2022. These patients were selected as the control group. Another thirty patients suspected of having pressure injuries were received by the hospital from January to June 2023 and were selected as the experimental group. The experimental group received a usual care protocol, while the trial group received the IMCHB model intervention for three months. The study compared the knowledge of pressure injuries, quality of life, incidence of pressure injuries, and patient satisfaction of high-risk patients between the two groups. Results: After the intervention, the PI awareness score of caregivers in the experimental group was (31.90 ± 5.24). It is higher than the control group (26.37 ± 6.85). The point of social function, physical function and material function of experimental group were (57.03 ± 5.32), (33.47 ± 3.52) and (58.53 ± 6.93). Respectively, it was higher than the experimental group (48.63 ± 4.80), (27.17 ± 3.04), (46.13 ± 6.72). The incidence of high-risk PI in the experimental group was 3.33%. The point of the control group was 26.67%. The total satisfaction of the experimental group was (8.27 ± 0.78) points, higher than the control group (7.30 ± 0.65). The difference was of statistical significance (P < .05). Conclusion: The intervention program based on IMCHB can significantly improve cognitive ability and thus promote health behavior.

Combining wireless radar sleep monitoring device with deep machine learning techniques to assess obstructive sleep apnea severity.

STUDY OBJECTIVES: The gold standard for diagnosing obstructive sleep apnea (OSA) is polysomnography (PSG). However, PSG is a time-consuming method with clinical limitations. This study aimed to create a wireless radar framework to screen the likelihood of two levels of OSA severity (i.e., moderate-to-severe and severe OSA) in accordance with clinical practice standards. METHODS: We conducted a prospective, simultaneous study using the wireless radar system and PSG in a Northern Taiwan sleep center, involving 196 patients. The wireless radar sleep monitor, incorporating hybrid models such as deep neural decision trees, estimated the respiratory disturbance index relative to the total sleep time established by PSG (RDIPSG_TST), by analyzing continuous-wave signals indicative of breathing patterns. Analyses were performed to examine the correlation and agreement between the RDIPSG_TST and apnea-hypopnea index (AHI), results obtained through PSG. Cut-off thresholds for RDIPSG_TST were determined using Youden's index, and multiclass classification was performed, after which the results were compared. RESULTS: A strong correlation (ρ = 0.91) and agreement (average difference of 0.59 events/h) between AHI and RDIPSG_TST were identified. In terms of the agreement between the two devices, the average difference between PSG-based AHI and radar-based RDIPSG_TST was 0.59 events/h, while 187 out of 196 cases (95.41%) fell within the 95% confidence interval of differences. A moderate-to-severe OSA model achieved an accuracy of 90.3% (cut-off threshold for RDIPSG_TST: 19.2 events/h). A severe OSA model achieved an accuracy of 92.4% (cut-off threshold for RDIPSG_TST: 28.86 events/h). The mean accuracy of multiclass classification performance using these cut-off thresholds was 83.7%. CONCLUSIONS: The wireless-radar-based sleep monitoring device, with cut-off thresholds, can provide rapid OSA screening with acceptable accuracy, and also alleviate the burden on PSG capacity. However, to independently apply this framework, the function of determining the radar-based total sleep time requires further optimizations and verification in future work.

Sulfur dioxide in the mid-infrared transmission spectrum of WASP-39b.

The recent inference of sulfur dioxide (SO2) in the atmosphere of the hot (approximately 1,100 K), Saturn-mass exoplanet WASP-39b from near-infrared JWST observations1-3 suggests that photochemistry is a key process in high-temperature exoplanet atmospheres4. This is because of the low (<1 ppb) abundance of SO2 under thermochemical equilibrium compared with that produced from the photochemistry of H2O and H2S (1-10 ppm)4-9. However, the SO2 inference was made from a single, small molecular feature in the transmission spectrum of WASP-39b at 4.05 µm and, therefore, the detection of other SO2 absorption bands at different wavelengths is needed to better constrain the SO2 abundance. Here we report the detection of SO2 spectral features at 7.7 and 8.5 µm in the 5-12-µm transmission spectrum of WASP-39b measured by the JWST Mid-Infrared Instrument (MIRI) Low Resolution Spectrometer (LRS)10. Our observations suggest an abundance of SO2 of 0.5-25 ppm (1σ range), consistent with previous findings4. As well as SO2, we find broad water-vapour absorption features, as well as an unexplained decrease in the transit depth at wavelengths longer than 10 µm. Fitting the spectrum with a grid of atmospheric forward models, we derive an atmospheric heavy-element content (metallicity) for WASP-39b of approximately 7.1-8.0 times solar and demonstrate that photochemistry shapes the spectra of WASP-39b across a broad wavelength range.

Immediate Effects of Vergence Exercises Using Automatic Dual Rotational Risley Prisms on Accommodative Lag and Facility.

INTRODUCTION: This study evaluated novel automatic dual rotational Risley prisms (ADRRPs) as a vergence exercise tool for patients with myopia to improve accommodative lag and accommodative facility. METHODS: Participants with myopia aged 20-24 years were recruited. After vergence exercises with prisms (treatment group) or plano lenses (control group) using ADRRPs for 10 min, measurements were taken using an open-field autorefractor (Grand Seiko WAM-5500) at viewing distances of 0.4 m and 6.0 m. We measured accommodative facility using a ± 2.00 D accommodative flipper. RESULTS: A total of 56 participants (treatment group, 39; control group, 17) performed vergence exercises using ADRRPs. Participants in the treatment group showed improvements in accommodative lag at a 0.4 m viewing distance, with measurements of 0.57 D (right eye; OD) and 0.53 D (left eye; OS) and 0.21 D (OD) and 0.27 D (OS) before and after the exercises, respectively (p < 0.001). Over-refractions using an open-field autorefractor with spherical equivalent contact lenses at a 6.0 m viewing distance were - 0.01 ± 0.30 D (OD) and 0.03 ± 0.34 D (OS) and 0.15 ± 0.32 D (OD) and 0.19 ± 0.28 D (OS) before and after the exercises, respectively (difference + 0.16 D; p < 0.001). Accommodative facility values before and after exercises were 14.88 ± 3.36 and 15.59 ± 3.60 cpm, respectively (p < 0.01). No significant differences in accommodative lag, relaxation, and accommodative facility before and after exercise were observed in the control group. CONCLUSIONS: Using ADRRPs in vergence exercises can improve accommodative lag, accommodative facility, and accommodative relaxation in adults with myopia. Further research to evaluate persistent and long-term effects is needed.

KDM5 Lysine Demethylases in Pathogenesis, from Basic Science Discovery to the Clinic.

The histone lysine demethylase 5 (KDM5) family proteins are Fe2+ and α-ketoglutarate-dependent dioxygenases, with jumonji C (JmjC) domain as their catalytic core and several plant homeodomains (PHDs) to bind different histone methylation marks. These enzymes are capable of demethylating tri-, di- and mono-methylated lysine 4 in histone H3 (H3K4me3/2/1), the key epigenetic marks for active chromatin. Thus, this H3K4 demethylase family plays critical roles in cell fate determination during development as well as malignant transformation. KDM5 demethylases have both oncogenic and tumor suppressive functions in a cancer type-dependent manner. In solid tumors, KDM5A/B are generally oncogenic, whereas KDM5C/D have tumor suppressive roles. Their involvement in de-differentiation, cancer metastasis, drug resistance, and tumor immunoevasion indicated that KDM5 family proteins are promising drug targets for cancer therapy. Significant efforts from both academia and industry have led to the development of potent and selective KDM5 inhibitors for preclinical experiments and phase I clinical trials. However, a better understanding of the roles of KDM5 demethylases in different physiological and pathological conditions is critical for further developing KDM5 modulators for clinical applications.

Predictive factors of endometrial lesions in patients with abnormal uterine bleeding.

PURPOSE: To explore the risk factors of endometrial lesions in patients with abnormal uterine bleeding(AUB) and establish prediction models which can discriminate between different endometrial etiologies of AUB. MATERIAL AND METHODS: We conducted this cross-sectional study in consecutive 778 women with AUB who received ultrasound examination and endometrial histopathological examination. Models were developed to distinguish between normal endometrium and (1) endometrial lesions, (2) endometrial polyps, (3) endometrial hyperplasia without atypia, (4) endometrial atypical hyperplasia and endometrial carcinoma. RESULTS: 274 (35.2%) women had normal endometrium; 504 (64.8%) had endometrial lesions, including 337(43.3%) endometrial polyps, 139(17.9%) endometrial hyperplasia without atypia, 28(3.6%) endometrial atypical hyperplasia and endometrial carcinoma. Age (OR = 1.122, 95%CI 1.002-1.257, P < 0.001), ET (endometrial thickness, OR = 2.702, 95%CI 1.629-4.402, P < 0.001), and CA125(U/ml) (OR = 1.007, 95%CI 1.003-1.021, P < 0.001) are independent risk factors of endometrial lesions in women with AUB. BMI(OR = 1.109, 95%CI 1.067-1.433,P = 0.038), ET(OR = 20.741, 95%CI 16.136-98.842, P < 0.001), age(OR = 1.182, 95%CI1.031-1.433,P = 0.016)、CA125(U/ml) (OR = 1.690, 95%CI 1.506-1.929,P = 0.001), prevalence of hypertension(OR = 1.350, 95%CI 1.051-67.82, P = 0.014) and diabetes(OR = 1.108, 95%CI 1.008-20.194,P = 0.001) were independent risk factors for atypical hyperplasia and endometrial carcinoma in patients with AUB. The model we built could predict atypical hyperplasia and endometrial carcinoma with the sensitivity of 87.5%, specificity of 80.7% and the AUC of 0.921. CONCLUSION: In women with AUB, the new-built model based on age, BMI, endometrial thickness, hypertension, diabetes and CA125 could discriminate reliable between atypical hyperplasia, endometrial carcinoma and normal women. The model may be useful for management of AUB.

Endothelial mechanobiology in atherosclerosis.

Cardiovascular disease (CVD) is a serious health challenge, causing more deaths worldwide than cancer. The vascular endothelium, which forms the inner lining of blood vessels, plays a central role in maintaining vascular integrity and homeostasis and is in direct contact with the blood flow. Research over the past century has shown that mechanical perturbations of the vascular wall contribute to the formation and progression of atherosclerosis. While the straight part of the artery is exposed to sustained laminar flow and physiological high shear stress, flow near branch points or in curved vessels can exhibit 'disturbed' flow. Clinical studies as well as carefully controlled in vitro analyses have confirmed that these regions of disturbed flow, which can include low shear stress, recirculation, oscillation, or lateral flow, are preferential sites of atherosclerotic lesion formation. Because of their critical role in blood flow homeostasis, vascular endothelial cells (ECs) have mechanosensory mechanisms that allow them to react rapidly to changes in mechanical forces, and to execute context-specific adaptive responses to modulate EC functions. This review summarizes the current understanding of endothelial mechanobiology, which can guide the identification of new therapeutic targets to slow or reverse the progression of atherosclerosis.

Photochemically produced SO2 in the atmosphere of WASP-39b.

Photochemistry is a fundamental process of planetary atmospheres that regulates the atmospheric composition and stability1. However, no unambiguous photochemical products have been detected in exoplanet atmospheres so far. Recent observations from the JWST Transiting Exoplanet Community Early Release Science Program2,3 found a spectral absorption feature at 4.05 µm arising from sulfur dioxide (SO2) in the atmosphere of WASP-39b. WASP-39b is a 1.27-Jupiter-radii, Saturn-mass (0.28 MJ) gas giant exoplanet orbiting a Sun-like star with an equilibrium temperature of around 1,100 K (ref. 4). The most plausible way of generating SO2 in such an atmosphere is through photochemical processes5,6. Here we show that the SO2 distribution computed by a suite of photochemical models robustly explains the 4.05-µm spectral feature identified by JWST transmission observations7 with NIRSpec PRISM (2.7σ)8 and G395H (4.5σ)9. SO2 is produced by successive oxidation of sulfur radicals freed when hydrogen sulfide (H2S) is destroyed. The sensitivity of the SO2 feature to the enrichment of the atmosphere by heavy elements (metallicity) suggests that it can be used as a tracer of atmospheric properties, with WASP-39b exhibiting an inferred metallicity of about 10× solar. We further point out that SO2 also shows observable features at ultraviolet and thermal infrared wavelengths not available from the existing observations.

High atmospheric metal enrichment for a Saturn-mass planet.

Atmospheric metal enrichment (that is, elements heavier than helium, also called 'metallicity') is a key diagnostic of the formation of giant planets1-3. The giant planets of the Solar System show an inverse relationship between mass and both their bulk metallicities and atmospheric metallicities. Extrasolar giant planets also display an inverse relationship between mass and bulk metallicity4. However, there is significant scatter in the relationship and it is not known how atmospheric metallicity correlates with either planet mass or bulk metallicity. Here we show that the Saturn-mass exoplanet HD 149026b (refs. 5-9) has an atmospheric metallicity 59-276 times solar (at 1σ), which is greater than Saturn's atmospheric metallicity of roughly 7.5 times solar10 at more than 4σ confidence. This result is based on modelling CO2 and H2O absorption features in the thermal emission spectrum of the planet measured by the James Webb Space Telescope. HD 149026b is the most metal-rich giant planet known, with an estimated bulk heavy element abundance of 66 ± 2% by mass11,12. We find that the atmospheric metallicities of both HD 149026b and the Solar System giant planets are more correlated with bulk metallicity than planet mass.

Preparation of a Non-Cardiomyocyte Cell Suspension for Single-Cell RNA Sequencing from a Post-Myocardial Infarction Adult Mouse Heart.

Myocardial infarction (MI) is one of the most common cardiovascular diseases, with increasing mortality worldwide. Non-cardiomyocytes account for more than half of the total cardiac cell population, and they contribute to adaptive compensations upon myocardial injury, including inflammatory responses, tissue repair, and scar formation. To study the post-MI cardiac microenvironment, single-cell RNA sequencing (scRNA-seq) is widely used to identify different cardiac cell types and intercellular communications. Among the procedures of scRNA-seq sample preparation, preparing the cell suspension is one of the most critical steps, because the cell viability can affect the quality of the scRNA-seq results. Therefore, we designed an experimental protocol for preparing a non-cardiomyocyte cell suspension from post-MI mouse hearts with an extra focus on improving the cell viability by choosing mild digestive enzymes, controlling the digestion time, and applying fluorescence-activated cell sorting (FACS). Finally, we isolated CD45+ cells from the non-cardiomyocyte cell suspension obtained through this protocol, and then we performed scRNA-seq.

Approximating defense mechanisms in a national study of adults: prevalence and correlates with functioning.

Despite the clinical relevance of defense mechanisms, there are no published studies in nationally representative samples of their prevalence, correlates, and association with psychosocial functioning. We sought to estimate the prevalence and correlates of 12 defense mechanisms in the general adult population by approximating from items used to assess personality traits in the National Epidemiological Survey on Alcohol and Related Conditions (NESARC), a representative sample of US adults (N = 36,653). We examined the associations between sociodemographic characteristics and prevalence of 3 types of defenses mechanisms (pathological, immature, and neurotic). For each defense mechanism, we used the Short-Form 12 to compare psychosocial functioning among 3 groups: those who (1) endorsed the mechanism with self-recognized impairment, (2) endorsed the mechanism without self-recognized impairment, and (3) did not endorse the defense mechanism. The prevalence of defense mechanisms ranged from 13.2% (splitting) to 44.5% (obsessive/controlling behavior). Pathological defenses were more strongly associated with immature defenses (OR = 5.4, 95% CI = 5.2-5.6) than with neurotic defenses (OR = 2.0, 95% CI = 1.9-2.0), whereas the association between immature and neurotic defenses had an intermediate value between the other two (OR = 2.2, 95% CI = 2.1-2.2). Pathological and immature defenses were associated with younger age, having been never married, lower educational attainment, and lower income. After adjusting the crude results for age and sex, individuals who did not endorse a given defense generally had higher scores on the mental health component of the SF-12 than those who endorsed the defense without self-recognized impairment who, in turn, had on average higher scores than those with self-recognized impairment. These results suggest that neurotic, immature, and pathological defense mechanisms are prevalent in the general population and associated with psychosocial impairment. Recognizing defense mechanisms may be important in clinical practice regardless of treatment modality.

Early Release Science of the exoplanet WASP-39b with JWST NIRCam.

Measuring the metallicity and carbon-to-oxygen (C/O) ratio in exoplanet atmospheres is a fundamental step towards constraining the dominant chemical processes at work and, if in equilibrium, revealing planet formation histories. Transmission spectroscopy (for example, refs. 1,2) provides the necessary means by constraining the abundances of oxygen- and carbon-bearing species; however, this requires broad wavelength coverage, moderate spectral resolution and high precision, which, together, are not achievable with previous observatories. Now that JWST has commenced science operations, we are able to observe exoplanets at previously uncharted wavelengths and spectral resolutions. Here we report time-series observations of the transiting exoplanet WASP-39b using JWST's Near InfraRed Camera (NIRCam). The long-wavelength spectroscopic and short-wavelength photometric light curves span 2.0-4.0 micrometres, exhibit minimal systematics and reveal well defined molecular absorption features in the planet's spectrum. Specifically, we detect gaseous water in the atmosphere and place an upper limit on the abundance of methane. The otherwise prominent carbon dioxide feature at 2.8 micrometres is largely masked by water. The best-fit chemical equilibrium models favour an atmospheric metallicity of 1-100-times solar (that is, an enrichment of elements heavier than helium relative to the Sun) and a substellar C/O ratio. The inferred high metallicity and low C/O ratio may indicate significant accretion of solid materials during planet formation (for example, refs. 3,4,) or disequilibrium processes in the upper atmosphere (for example, refs. 5,6).

Efficacy and Cost over 12 Hospitalization Weeks of Postacute Care for Stroke.

Few studies have investigated changes in functional outcomes and economic burden in patients in the postacute care cerebrovascular disease (PAC-CVD) program. We, for the first time, retrospectively investigated changes in functional performance and the national health insurance (NHI) cost over 12 PAC-CVD hospitalization weeks and evaluated the therapeutic effects of the PAC-CVD program on the NHI cost. Specifically, the functional outcomes and NHI cost of 263 stroke patients in the PAC-CVD program were analyzed. The repeated measures t test was used to compare functional performance over 0-3 weeks, and a one-way repeated measures multivariate analysis of variance was used to compare functional performance and NHI costs during weeks 0-6 and 0-9. The Wilcoxon signed-rank test was used to compare functional performance over weeks 9-12. Hierarchical multiple regression was used to estimate the effects of functional performance on NHI costs during weeks 3, 6, and 9. Over weeks 0-12, all functional performance measures demonstrated significant improvements. Changes in NHI costs varied depending on whether hospitalization was extended. At any time point, functional performance did not have a significant impact on NHI cost. Therefore, the PAC-CVD program may aid patients with stroke in sustainably regaining functional performance and effectively controlling economic burden.

Removal of virus aerosols by the combination of filtration and UV-C irradiation.

The COVID-19 pandemic remains ever prevalent and afflicting-partially because one of its transmission pathways is aerosol. With the widely used central air conditioning systems worldwide, indoor virus aerosols can rapidly migrate, thus resulting in rapid infection transmission. It is therefore important to install microbial aerosol treatment units in the air conditioning systems, and we herein investigated the possibility of combining such filtration with UV irradiation to address virus aerosols. Results showed that the removal efficiency of filtration towards f2 and MS2 phages depended on the type of commercial filter material and the filtration speed, with an optimal velocity of 5 cm/s for virus removal. Additionally, it was found that UV irradiation had a significant effect on inactivating viruses enriched on the surfaces of filter materials; MS2 phages had greater resistance to UV-C irradiation than f2 phages. The optimal inactivation time for UV-C irradiation was 30 min, with higher irradiation times presenting no substantial increase in inactivation rate. Moreover, excessive virus enrichment on the filters decreased the inactivation effect. Timely inactivation is therefore recommended. In general, the combined system involving filtration with UV-C irradiation demonstrated a significant removal effect on virus aerosols. Moreover, the system is simple and economical, making it convenient for widespread implementation in air-conditioning systems.

Early pregnancy vitamin D insufficiency and gestational diabetes mellitus.

OBJECTIVES: To test the hypothesis that a link existed between vitamin D levels in the first trimester and gestational diabetes mellitus (GDM). METHODS: The 25-hydroxyvitamin D3 levels were tested in the first trimester and pregnant outcomes were followed up in 1726 women. RESULTS: Only 5.9% of pregnant women have sufficient 25(OH)D3 . More women with GDM are in the status of 25(OH)D3 insufficiency than women with normal glucose tolerance (NGT) (p < 0.05). Age (odds ratio [OR]: 1.047, 95% confidence interval [CI]: 1.014-1.081), pre-pregnancy body mass index (BMI) (OR: 1.132, 95%CI: 1.092-1.173) were risk factors of GDM while 25-(OH) D3 (OR: 0.979, 95%CI: 0.960-0.999) was a protective factor. After adjusted for maternal age and pre-pregnancy BMI, 25(OH)D3 insufficiency (<30 ng/mL) is an independent predictor of GDM (OR: 2.122, 95%CI: 1.084-4.155); 25(OH)D3 level correlated with fasting blood glucose in the first trimester negatively. CONCLUSION: Vitamin D insufficiency in early pregnancy was significantly associated with an increased risk for GDM in Chinese women.

Transcriptome analysis uncovers the autophagy-mediated regulatory patterns of the immune microenvironment in dilated cardiomyopathy.

The relationship between autophagy and immunity has been well studied. However, little is known about the role of autophagy in the immune microenvironment during the progression of dilated cardiomyopathy (DCM). Therefore, this study aims to uncover the effect of autophagy on the immune microenvironment in the context of DCM. By investigating the autophagy gene expression differences between healthy donors and DCM samples, 23 dysregulated autophagy genes were identified. Using a series of bioinformatics methods, 13 DCM-related autophagy genes were screened and used to construct a risk prediction model, which can well distinguish DCM and healthy samples. Then, the connections between autophagy and immune responses including infiltrated immunocytes, immune reaction gene-sets and human leukocyte antigen (HLA) genes were systematically evaluated. In addition, two autophagy-mediated expression patterns in DCM were determined via the unsupervised consensus clustering analysis, and the immune characteristics of different patterns were revealed. In conclusion, our study revealed the strong effect of autophagy on the DCM immune microenvironment and provided new insights to understand the pathogenesis and treatment of DCM.

The Association of Nutritional Risk Screening 2002 With 1-Year Re-hospitalization and the Length of Initial Hospital Stay in Patients With Heart Failure.

Backgrounds and Aims: Nutritional Risk Screening 2002 (NRS-2002) has been widely recommended for identifying the nutritional risk. However, the association between NRS-2002 and the prognosis of heart failure has not been fully addressed. This study aimed to explore the association of NRS-2002 with 1-year re-hospitalization and the length of initial hospital stay in heart failure patients. Methods: This retrospective study included 2,830 heart failure patients. The primary endpoint was 1-year re-hospitalization for heart failure. The secondary endpoint was the length of initial hospital stay. The Log-binomial regression analysis was performed to determine the association between NRS-2002 and re-hospitalization. The Cox regression model was fitted to estimate hazard of discharge. The cumulative incidence curves of discharge were plotted using Kaplan-Meier method and log-rank test was performed. Exploratory analysis was also conducted according to the classification of heart failure and the level of N-terminal pro-B-type natriuretic peptide (NT-proBNP) fold-elevation. Results: Among 2,830 heart failure patients, the mean age was 64.3 years and 66.4% were male. A total of 122 (4.3%) patients were considered at high nutritional risk. Log-binomial regression analysis demonstrated that higher NRS-2002 score was an independent risk factor of re-hospitalization ([1 vs. 0]: relative risks [RR] = 1.383, 95% CI = 1.152 to 1.660; [2 vs. 0]: RR = 1.425, 95% CI = 1.108 to 1.832; [3-7 vs. 0]: RR = 1.770, 95% CI = 1.310 to 2.393). Kaplan-Meier curve showed that the cumulative incidence of discharge was lower in high nutritional risk group (Log rank p < 0.001). Cox regression analysis also found that higher NRS-2002 score (2 or ≥3) was strongly associated with longer length of initial hospital stay ([2 vs. 0]: Hazard ratios [HR] = 0.854, 95% CI = 0.748 to 0.976; [3-7 vs. 0]: HR = 0.609, 95% CI = 0.503 to 0.737). Exploratory analysis showed that such association still remained irrespective of NT-proBNP fold-elevation, but only existed in patients with heart failure with preserved ejection fraction (HFpEF). Conclusion: In patients with heart failure, high NRS-2002 score was strongly and independently associated with the incidence of 1-year re-hospitalization and the length of initial hospital stay.

Two-dimensional metal-organic frameworks: from synthesis to bioapplications.

As a typical class of crystalline porous materials, metal-organic framework possesses unique features including versatile functionality, structural and compositional tunability. After being reduced to two-dimension, ultrathin metal-organic framework layers possess more external excellent properties favoring various technological applications. In this review article, the unique structural properties of the ultrathin metal-organic framework nanosheets benefiting from the planar topography were highlighted, involving light transmittance, and electrical conductivity. Moreover, the design strategy and versatile fabrication methodology were summarized covering discussions on their applicability and accessibility, especially for porphyritic metal-organic framework nanosheet. The current achievements in the bioapplications of two-dimensional metal-organic frameworks were presented comprising biocatalysis, biosensor, and theranostic, with an emphasis on reactive oxygen species-based nanomedicine for oncology treatment. Furthermore, current challenges confronting the utilization of two-dimensional metal-organic frameworks and future opportunities in emerging research frontiers were presented.