Micropeptide MPM regulates cardiomyocyte proliferation and heart growth via the AKT pathway.

The role of micropeptide in cardiomyocyte proliferation remains unknown. We found that MPM (micropeptide in mitochondria) was highly expressed in cardiomyocytes. Compared to MPM+/+ mice, MPM knockout (MPM-/-) mice exhibited reduction in left ventricular (LV) mass, myocardial thickness and LV fractional shortening. RNA-sequencing analysis in H9c2, a rat cardiomyocyte cell line, identified downregulation of cell cycle-promoting genes as the most significant alteration in MPM-silencing cells. Consistently, gain- and loss-of-function analyses in H9c2 cells revealed that cardiomyocyte proliferation was repressed by silencing MPM but was promoted by overexpressing MPM. Moreover, the cardiomyocytes in the hearts of MPM-/- mice displayed reduced proliferation rates. Mechanism investigations disclosed that MPM is crucial for AKT activation in cardiomyocytes. We also identified an interaction between MPM and PTPMT1, and found that silencing PTPMT1 attenuated the effect of MPM in activating the AKT pathway, whereas inhibition of the AKT pathway abrogated the role of MPM in promoting cardiomyocyte proliferation. Collectively, these results indicate that MPM may promote cardiomyocyte proliferation and thus heart growth by interacting with PTPMT1 to activate the AKT pathway. Our findings identify the novel function and regulatory network of MPM and highlight the importance of micropeptides in cardiomyocyte proliferation and heart growth.

Precise and Omnidirectional Opto-Thermo-Elastic Actuation in Van Der Waals Contacting Systems.

Actuation of micro-objects along unconstrained trajectories in van der Waals contacting systems-in the same capacity as optical tweezers to manipulate particles in fluidic environments-remains a formidable challenge due to the lack of effective methods to overcome and exploit surface friction. Herein, a technique that aims to resolve this difficulty is proposed. This study shows that, by utilizing a moderate power beam of light, micro-objects adhered on planar solid substrates can be precisely guided to move in arbitrary directions, realizing sub-nanometer resolution across extended surfaces. The underlying mechanism is the interplay between surface friction and pulsed opto-thermo-elastic deformations, and to render a biased motion with off-centroid light illumination. This technique enables high-precision assembly, separation control of nanogaps, regulation of rotation angles in various material-substrate systems, whose capability is further tested in reconfigurable construction of optoelectronic devices. With simple set-up and theoretical generality, opto-thermo-elastic actuation opens up an avenue for versatile optical manipulation in the solid domain.

Parental vaccine hesitancy and influenza vaccine type preferences during and after the COVID-19 Pandemic.

BACKGROUND: Seasonal influenza vaccine (SIV) greatly reduces disease burden among school-aged children, yet parental vaccine hesitancy remains a persistent challenge. Two types of SIV are available for children in Hong Kong and other locations: inactivated influenza vaccine (IIV), administered through intramuscular injection, and live attenuated influenza vaccine (LAIV), administered via nasal spray. We aimed to understand how vaccine hesitancy shaped parental preference for LAIV versus IIV, particularly amidst important public health events, such as the COVID-19 pandemic and the massive rollout of COVID-19 vaccination campaigns. METHODS: We employed a concurrent mixed-methods design. The quantitative part involves longitudinal surveys spanning three years, from pre-pandemic to post-pandemic periods, tracking parental vaccine hesitancy and preference for SIV types. The qualitative part involves 48 in-depth interviews, providing insights into parental preference for SIV types, underlying reasons, and related values. RESULTS: Our quantitative analyses show an overall increase in parental vaccine hesitancy and preference for LAIV over IIV after the onset of the COVID-19 pandemic and especially after the rollout of the COVID-19 vaccination campaign. Further logistic regression modelling based on the cohort data shows that higher vaccine hesitancy, coupled with the COVID-19 vaccination campaign rollout, predicts a greater preference for LAIV over IIV. The qualitative analysis complements these results, highlighting that LAIV's non-invasive nature aligns with parental values of prioritizing natural immunity and concerns about overmedication, leading to a more acceptable attitude towards LAIV. CONCLUSIONS: Leveraging the higher acceptability of LAIV compared to IIV among parents with high vaccine hesitancy could promote childhood vaccination uptake.

We examined how parents' concerns about vaccines and major public health events affected their preference for different types of seasonal influenza vaccines for children. Currently, children can receive either an injected vaccine or a nasal-spray vaccine. We tracked parental vaccine hesitancy and their preferences for different types of vaccines over three years covering a period before the COVID-19 pandemic and a period during the pandemic. Parents became more hesitant about seasonal influenza vaccines for children after the start of the COVID-19 pandemic and the rollout of COVID-19 vaccines. Higher vaccine hesitancy and the rollout of COVID-19 vaccines predicted a greater preference for nasal-spray vaccines for children among parents. Parents preferred the non-invasive nature of the nasal-spray vaccines and were concerned about overmedication, particularly vaccines that were administered via injection. We suggest that the nasal-spray vaccines could be one option offered to address high parental vaccine hesitancy.

Highly Potent and Intestine Specific P-Glycoprotein Inhibitor to Enable Oral Delivery of Taxol.

Taxol is widely used in cancer chemotherapy; however, the oral absorption of Taxol remains a formidable challenge. Since the intestinal p-glycoprotein (P-gp) mediated drug efflux is one of the primary causes, the development of P-gp inhibitor is emerging as a promising strategy to realize Taxol's oral delivery. Because P-gp exists in many tissues, the non-selective P-gp inhibitors would lead to toxicity. Correspondingly, a potent and intestine specific P-gp inhibitor would be an ideal solution to boost the oral absorption of Taxol and avoid exogenous toxicity. Herein, we would like to report a highly potent and intestine specific P-gp inhibitor to enable oral delivery of Taxol in high efficiency. Through a multicomponent reaction and post-modification, various benzofuran-fused-piperidine derivatives were achieved and the biological evaluation identified 16c with potent P-gp inhibitory activity. Notably, 16c was intestine specific and showed almost none absorption (F = 0.82%), but possessing higher efficacy than Encequidar to improve the oral absorption of Taxol. In MDA-MB-231 xenograft model, the oral administration of Taxol and 16c showed high therapeutic efficiency and low toxicity, thus providing a valuable chemotherapy strategy.

Effects of physical activity and self-control on mobile phone addiction in college students: a cross-lagged study in China.

Purpose: This study aims to investigate the impact of physical activity and self-control on college students' mobile phone addiction through cross-lagged longitudinal surveys, addressing the limitations of previous cross-sectional studies. Patients and methods: A total of 414 college students were tracked three times during a 12-month period using the Physical Activity Rating Scale-3 (PARS-3), the Mobile Phone Addiction Tendency Scale (MPATS), and the Brief Self-Control Scale (BSCS). AMOS25.0 software was used to construct the cross-lagged relationship model, and the maximum likelihood approach was employed to investigate the model fitting. The asynchronous correlation between variables was investigated from the time series through the cross-lagged path coefficient. Results: The fitting indexes of the cross-lagged model showed x 2/df = 5.098, GFI = 0.977, NFI = 0.969, IFI = 0.975, CFI = 0.974; RMSEA = 0.100, and SRMR = 0.030. The calculation conducted by combining the path coefficient of the model shows that PA and SC are the antecedent variables of MPA, and PA is the antecedent variable of SC. In addition, SC serves as a mediator in the path of PA, affecting MPA. Conclusion: (1) physical activity can positively affect subsequent self-control; (2) physical activity can negatively influence subsequent mobile phone addiction; (3) self-control can negatively affect subsequent mobile phone addiction; and (4) physical activity can indirectly influence subsequent mobile phone addiction through self-control.

Mechanically induced M2 macrophages are involved in bone remodeling of the midpalatal suture during palatal expansion.

BACKGROUND: Palatal expansion is a common way of treating maxillary transverse deficiency. Under mechanical force, the midpalatal suture is expanded, causing local immune responses. This study aimed to determine whether macrophages participate in bone remodeling of the midpalatal suture during palatal expansion and the effects on bone remodeling. METHODS: Palatal expansion model and macrophage depletion model were established. Micro-CT, histological staining, and immunohistochemical staining were used to investigate the changes in the number and phenotype of macrophages during palatal expansion as well as the effects on bone remodeling of the midpalatal suture. Additionally, the effect of mechanically induced M2 macrophages on palatal osteoblasts was also elucidated in vitro. RESULTS: The number of macrophages increased significantly and polarized toward M2 phenotype with the increase of the expansion time, which was consistent with the trend of bone remodeling. After macrophage depletion, the function of osteoblasts and bone formation at the midpalatal suture were impaired during palatal expansion. In vitro, conditioned medium derived from M2 macrophages facilitated osteogenic differentiation of osteoblasts and decreased the RANKL/OPG ratio. CONCLUSIONS: Macrophages through polarizing toward M2 phenotype participated in midpalatal suture bone remodeling during palatal expansion, which may provide a new idea for promoting bone remodeling from the perspective of regulating macrophage polarization.

TMK4-mediated FIP37 phosphorylation regulates auxin-triggered N6-methyladenosine modification of auxin biosynthetic genes in Arabidopsis.

The dynamics of N6-methyladenosine (m6A) mRNA modification are tightly controlled by the m6A methyltransferase complex and demethylases. Here, we find that auxin treatment alters m6A modification on auxin-responsive genes. Mechanically, TRANSMEMBRANE KINASE 4 (TMK4), a component of the auxin signaling pathway, interacts with and phosphorylates FKBP12-INTERACTING PROTEIN 37 (FIP37), a core component of the m6A methyltransferase complex, in an auxin-dependent manner. Phosphorylation of FIP37 enhances its interaction with RNA, thereby increasing m6A modification on its target genes, such as NITRILASE 1 (NIT1), a gene involved in indole-3-acetic acid (IAA) biosynthesis. 1-Naphthalacetic acid (NAA) treatment accelerates the mRNA decay of NIT1, in a TMK4- and FIP37-dependent manner, which leads to inhibition of auxin biosynthesis. Our findings identify a regulatory mechanism by which auxin modulates m6A modification through the phosphorylation of FIP37, ultimately affecting mRNA stability and auxin biosynthesis in plants.

Aerosol inhalation of total ginsenosides repairs acute lung injury and inhibits pulmonary fibrosis through SMAD2 signaling-mediated mechanism.

BACKGROUND: Pulmonary fibrosis (PF) is a progressive lung disease caused by previous acute lung injury (ALI), but there is currently no satisfactory therapy available. Aerosol inhalation of medicine is an effective way for treating PF. Total ginsenosides (TG) shows potential for the treatment of ALI and PF, but the effects of inhaled TG remain unclear. PURPOSE: To determine the therapeutic effects of TG in ALI and PF, to assess the superiority of the inhaled form of TG over the routine form, and to clarify the mechanism of action of inhaled TG. METHODS: Ultrahigh-performance liquid chromatography coupled with Q-Exactive Orbitrap mass spectrometry (UPLC-QE-MS) was applied to determine the chemoprofile of TG. A mouse model of ALI and PF was established to evaluate the effects of inhaled TG by using bronchoalveolar lavage fluid (BALF) analysis, histopathological observation, hydroxyproline assay, and immunohistochemical analysis. Primary mouse lung fibroblasts (MLF) and human lung fibroblast cell line (HFL1) were applied to determine the in vitro effects and mechanism of TG by using cell viability assay, quantitative real time PCR (qPCR) assay, and western blot (WB) analysis. RESULTS: The UPLC-QE-MS results revealed the main types of ginsenosides in TG, including Re (14.15 ± 0.42%), Rd (8.42 ± 0.49%), Rg1 (6.22 ± 0.42%), Rb3 (3.28 ± 0.01%), Rb2 (3.09 ± 0.00%), Rc (2.33 ± 0.01%), Rg2 (2.09 ± 0.04%), Rb1 (1.43 ± 0.24%), and Rf (0.13 ± 0.06%). Inhaled TG, at dosages of 10, 20, and 30 mg/kg significantly alleviated both ALI and PF in mice. Analyses of BALF and HE staining revealed that TG modulated the levels of IFN-γ, IL-1ß, and TGF-ß1, reduced inflammatory cell infiltration, and restored the alveolar architecture of the lung tissues. Furthermore, HE and Masson's trichrome staining demonstrated that TG markedly decreased fibroblastic foci and collagen fiber deposition, evidenced by the reduction of blue-stained collagen fibers. Hydroxyproline assay and immunohistochemical analyses indicated that TG significantly decreased hydroxyproline level and down-regulated the expression of Col1a1, Col3a1, and α-sma. The inhaled administration of TG demonstrated enhanced efficacy over the oral route when comparable doses were used. Additionally, inhaled TG showed superior safety and therapeutic profiles compared to pirfenidone, as evidenced by a CCK8 assay, which confirmed that TG concentrations ranging from 20 to 120 µg/ml were non-cytotoxic. qPCR and WB analyses revealed that TG, at concentrations of 25, 50, and 100 µg/ml, significantly suppressed the phosphorylation of smad2 induced by TGF-ß1 and down-regulated the expression of fibrotic genes and proteins, including α-sma, Col1a1, Col3a1, and FN1, suggesting an anti-fibrotic mechanism mediated by the smad2 signaling pathway. In vitro, TG's safety and efficacy were also found to be superior to those of pirfenidone. CONCLUSIONS: This study demonstrates, for the first time, the therapeutic efficacy of inhaled TG in treating ALI and PF. Inhaled TG effectively inhibits inflammation and reduces collagen deposition, with a particular emphasis on its role in modulating the Smad2 signaling pathway, which is implicated in the anti-fibrotic mechanism of TG. The study also highlights the superiority of inhaled TG over the oral route and its favorable safety profile in comparison to pirfenidone, positioning it as an ideal alternative for ALI and PF therapy.

[Genome-wide screening and bioinformatics analysis of Cannabis sativa LecRLK gene family].

Lectin receptor-like kinase(LecRLK) is a class of phytokinase with lectin conserved domain, which plays an important role in plant resistance to biological and abiotic stresses, as well as plant growth and development. Cannabis sativa is an important multi-purpose plant, widely used in food, textile, medicine, and other fields. Genome-wide screening and expression analysis of the LecRLK family of C. sativa were performed in this paper, so as to provide scientific reference for functional analysis of the LecRLK family of C. sativa. Based on BLAST and HMM methods, 93 LecRLKs were identified in the whole genome of C. sativa, including 69 G types, 23 L types, and one C types. Subsequently, a series of bioinformatics analyses were performed on the LecRLK family members, and the physicochemical properties of the protein of the LecRLK family members were initially revealed. The prediction of cis-acting elements of promoters in family members showed that family members were regulated by hormones and stress response. The expression analysis showed that some family members were highly expressed in the roots, which may participate in the process of stress resistance. Several members were highly expressed in female flowers and may be involved in female flower development. This study provides a theoretical basis for further study of LecRLK gene function. Meanwhile, the expression analysis screens candidate LecRLK members who may participate in the resistance of C. sativa, which provides a theoretical basis for the subsequent selection of C. sativa varieties against resistance.

Concurrent and legacy effects of sheep trampling on soil organic carbon stocks in a typical steppe, China.

Grazing plays a key role in ecosystem biogeochemistry, particularly soil carbon (C) pools. The non-trophic interactions between herbivores and soil processes through herbivore trampling have recently attracted extensive attention. However, their concurrent and legacy effects on the ecosystem properties and processes are still not clear, due to their effects being hard to separate via field experiments. In this study, we conducted a 2-year simulated-sheep-trampling experiment with four trampling intensity treatments (i.e., T0, T40, T80, and T120 for 0, 40, 80, and 120 hoofprints m-2, respectively) in a typical steppe to explore the concurrent and legacy effects of trampling on grassland ecosystem properties and processing. In 2017 (trampling treatment year), we found that trampling decreased aboveground biomass (AGB) of plant community and community-weighted mean shoot C concentration (CWM C), soil available nitrogen (N) and available phosphorus (P), but did not affect plant species diversity and belowground biomass (BGB). We show that compared with T0, trampling increased soil bulk density (BD) at T80, and decreased soil organic carbon (SOC) stocks. After the cessation of trampling for two years (i.e., in 2019), previous trampling increased plant diversity and BGB, reaching the highest values at T80, but decreased soil available N and available P. Compared with T0, previous trampling significantly increased soil BD at T120, while significantly decreased CWM C at T80 and T120, and reduced SOC stocks at T80. Compared with 2017, the trampling negative legacy effects amplified at T80 but weakened at T40 and T120. We also show that trampling-induced decreases in soil available N, AGB of Fabaceae and CWM C were the main predictors of decreasing SOC stocks in 2017, while previous trampling-induced legacy effects on soil available P, AGB of Poaceae and CWM C contributed to the variations of SOC stocks in 2019. Taken together, short-term trampling with low intensity could maintain most plant functions, while previous trampling with low intensity was beneficial to most plant and soil functions. The results of this study show that T40 caused by sheep managed at a stocking rate of 2.7 sheep ha-1 is most suitable for grassland adaptive management in the typical steppe. The ecosystem functions can be maintained under a high stocking rate through the process of providing enough time to rebuild sufficient vegetation cover and restore soil through measures such as regional rotational grazing and seasonal grazing.

Ameliorating lung fibrosis and pulmonary function in diabetic mice: Therapeutic potential of mesenchymal stem cell.

This study aimed to investigate the potential of mesenchymal stem cells (MSCs) in alleviating diabetic lung injury by decreasing inflammation, fibrosis and recovering tissue macrophage homeostasis. To induce pulmonary injuries in an in vivo murine model, we utilized a streptozotocin (STZ), and high-fat diet (HFD) induced diabetic C57 mouse model. Subsequently, human umbilical cord-derived MSCs (hUC-MSCs) were administered through the tail vein on a weekly basis for a duration of 4 weeks. In addition, in vitro experiments involved co-culturing of isolated primary abdominal macrophages from diabetic mice and high glucose-stimulated MLE-12 cells with hUC-MSCs. The objective was to evaluate if hUC-MSCs co-culturing could effectively mitigate cell inflammation and fibrosis. Following hUC-MSCs injection, diabetic mice displayed enhanced pulmonary functional parameters, reduced pulmonary fibrosis, and diminished inflammation. Notably, the dynamic equilibrium of lung macrophages shifted from the M1 phenotype to the M2 phenotype, accompanied by a notable reduction in various indicators associated with inflammation and fibrosis. Results from cell co-culturing experiments further supported this trend, demonstrating a reduction in inflammatory and fibrotic indicators. In conclusion, our findings suggest that hUC-MSCs treatment holds promise in mitigating diabetic pulmonary injury by significantly reducing inflammation, fibrosis and maintain tissue macrophage homeostasis within the lungs. This study sheds light on the therapeutic potential of hUC-MSCs in managing diabetic complications affecting the pulmonary system.

Silicon Waveguide-Integrated Platinum Telluride Midinfrared Photodetector with High Responsivity and High Speed.

The detection of mid-infrared light, covering a variety of molecular vibrational spectra, is critical for both civil and military purposes. Recent studies have highlighted the potential of two-dimensional topological semimetals for mid-infrared detection due to their advantages, including van der Waals (vdW) stacking and gapless electronic structures. Among them, mid-infrared photodetectors based on type-II Dirac semimetals have been less studied. In this paper, we present a silicon waveguide integrated type-II Dirac semimetal platinum telluride (PtTe2) mid-infrared photodetector, and further improve detection performance by using PtTe2-graphene heterostructure. For the fabricated silicon waveguide-integrated PtTe2 photodetector, with an external bias voltage of -10 mV and an input optical power of 86 nW, the measured responsivity is 2.7 A/W at 2004 nm and a 3 dB bandwidth of 0.6 MHz is realized. For the fabricated silicon waveguide-integrated PtTe2-graphene photodetector, as the external bias voltage and input optical power are 0.5 V and 0.13 µW, a responsivity of 5.5 A/W at 2004 nm and a 3 dB bandwidth of 35 MHz are obtained. An external quantum efficiency of 119% can be achieved at an input optical power of 0.376 µW.

Protein - carbohydrate interaction studies using domestic animals as role models support the search of new glycomimetic molecules.

The structural dynamics of the interactions between defensins or lysozymes and various saccharide chains that are covalently linked to lipids or proteins were analyzed in relation to the sub-molecular architecture of the carbohydrate binding sites of lectins. Using tissue materials from rare and endangered domestic animals as well as from dogs it was possible to compare these results with data obtained from a human glioblastoma tissue. The binding mechanisms were analyzed on a cellular and a sub-molecular size level using biophysical techniques (e.g. NMR, AFM, MS) which are supported by molecular modeling tools. This leads to characteristic structural patterns being helpful to understand glyco-biochemical pathways in which galectins, defensins or lysozymes are involved. Carbohydrate chains have a distinct impact on cell differentiation, cell migration and immunological processes. The absence or the presence of sialic acids and the conformational dynamics in glycans are often correlated with zoonoses such as influenza- and coronavirus-infections. Receptor-sensitive glycomimetics could be a solution. The new findings concerning the function of galectin-3 in the nucleus in relation to differentiation processes can be understood when the binding specificity of neuroleptic molecules as well as the interactions between proteins and nucleic acids are describable on a sub-molecular size level.

Infection and biogeographical characteristics of Paragonimus westermani and P. skrjabini in humans and animal hosts in China: A systematic review and meta-analysis.

BACKGROUND: Paragonimiasis, primarily caused by Paragonimus westermani and P. skrjabini in China, is a common food-borne parasitic zoonosis. However, the national distribution of Paragonimus spp. infection and its associated environmental determinants remain poorly understood. In this paper, we summarize the infection of P. westermani and P. skrjabini and describe key biogeographical characteristics of the endemic areas in China. METHODS: Data on Paragonimus infection in humans and animal hosts were extracted from eight electronic databases, including CNKI, CWFD, Chongqing VIP, SinoMed, Medline, Embase, PubMed, and Web of Science. A random-effects meta-analysis model was used to estimate the pooled prevalence. All survey locations were georeferenced and plotted on China map, and scatter plots were used to illustrate the biogeographical characteristics of regions reporting Paragonimus infection. RESULTS: A total of 28,948 cases of human paragonimiasis have been documented, with 2,401 cases reported after 2010. Among the 11,443 cases with reported ages, 88.05% were children or adolescents. The pooled prevalence of P. skrjabini is 0.45% (95% CI: 0.27-0.66%) in snails, 31.10% (95% CI: 24.77-37.80%) in the second intermediate host, and 20.31% (95% CI: 9.69-33.38%) in animal reservoirs. For P. westermani, the pooled prevalence is 0.06% (95% CI: 0.01-0.13%) in snails, 52.07% (95% CI: 43.56-60.52%) in the second intermediate host, and 21.40% (95% CI: 7.82-38.99%) in animal reservoirs. Paragonimus are primarily distributed in regions with low altitude, high temperature, and high precipitation. In northeastern China, only P. westermani infections have been documented, while in more southern areas, infections of both P. westermani and P. skrjabini have been reported. CONCLUSIONS: Paragonimiasis remains prevalent in China, particularly among children and adolescents. Variations exist in the intermediate hosts and geographical distribution of P. westermani and P. skrjabini. Additionally, altitude, temperature, and precipitation may influence the distribution of Paragonimus.

Characteristics of astigmatism in school-age children aged 5 to 13 years in northeast Sichuan: a cross-sectional school-based study.

Background: Astigmatism is closely associated with myopia progression, vision loss, eye fatigue and amblyopia, which seriously endangers children's eye health. This study aims to investigate the prevalence and characteristic distribution of astigmatism in children in Langzhong City, providing valuable insights for allocating resources and develop prevention and control strategies. Methods: A cross-sectional study and random sampling survey were conducted. Between January and November 2021, 21,415 students aged 5 to 13 years from 14 primary schools in Langzhong City underwent non-cycloplegic refractive testing using autorefraction. The data on myopia were analyzed using SPSS (Statistical Package for the Social Sciences) version 23.0. Results: The inclusion criterion was set at an absolute astigmatism value of ≥0.50D. Among the 21,415 children studied, 61.70% were found to have astigmatism. The prevalence of astigmatism varied significantly across different grades (χ2=501.414, P<0.001). The predominant types of astigmatism were mild astigmatism (0.50-1.00D) and with-the-rule astigmatism. Mixed astigmatism was primarily observed in children in grades 1 and 2, while compound myopic astigmatism was more common in children in grades 3 to 6. These differences were statistically significant. As the degree of astigmatism increased, the proportions of against-the-rule astigmatism, oblique astigmatism, compound myopic astigmatism, and simple hyperopic astigmatism decreased, whereas the proportions of with-the-rule astigmatism, mixed astigmatism, and compound hyperopic astigmatism increased. Conclusions: The prevalence of astigmatism among school-age children aged 5 to 13 years in northeast Sichuan is notably high, with compound myopic astigmatism and with-the-rule astigmatism being the most common types. Regular refractive examinations are crucial for the early detection and management of astigmatism.

Performance of Impulse Oscillometry in Identifying Restrictive Lung Defects in a Veteran Cohort.

Background: Impulse oscillometry (IOs) is a technique used to evaluate lung function that uses sound waves imposed over tidal breathing to characterize the airways and lung parenchyma. IOs has been particularly useful in the identification of obstructive lung defects. The present analysis seeks to explore the use of IOs in the identification of restrictive lung physiology among a group of Gulf War I veterans exposed to depleted uranium (DU). Methods: A total of 36 out of a dynamic 85-veteran cohort attended in-person surveillance visits in 2019 and completed both IOs and PFTs. Performance on IOs was evaluated in a cross-sectional analysis of the group overall and in those identified as having restrictive lung defects defined by either spirometry (FEV1/FVC ≥ LLN and FVC < LLN) or lung volumes (TLC < LLN). Results: A total of 6 individuals were identified as having restriction (4 based on spirometry alone and an additional 2 by lung volumes). When restriction was present, IOs values of both resistance and reactance were significantly more abnormal. Conclusion: In the assessment of lung function, IOs may be advantageous over PFTs because it is faster to perform and effort-independent. Although little is known about the utility of IOs in identifying restrictive lung physiology, our results support its use.

SENP1-Mediated HSP90ab1 DeSUMOylation in Cardiomyocytes Prevents Myocardial Fibrosis by Paracrine Signaling.

Myocardial infarction (MI) triggers a poor ventricular remodeling response, but the underlying mechanisms remain unclear. Here, the authors show that sentrin-specific protease 1 (SENP1) is downregulated in post-MI mice and in patients with severe heart failure. By generating cardiomyocyte-specific SENP1 knockout and overexpression mice to assess cardiac function and ventricular remodeling responses under physiological and pathological conditions. Increased cardiac fibrosis in the cardiomyocyte-specific SENP1 deletion mice, associated with increased fibronectin (Fn) expression and secretion in cardiomyocytes, promotes fibroblast activation in response to myocardial injury. Mechanistically, SENP1 deletion in mouse cardiomyocytes increases heat shock protein 90 alpha family class B member 1 (HSP90ab1) SUMOylation with (STAT3) activation and Fn secretion after ventricular remodeling initiated. Overexpression of SENP1 or mutation of the HSP90ab1 Lys72 ameliorates adverse ventricular remodeling and dysfunction after MI. Taken together, this study identifies SENP1 as a positive regulator of cardiac repair and a potential drug target for the treatment of MI. Inhibition of HSP90ab1 SUMOylation stabilizes STAT3 to inhibit the adverse ventricular remodeling response.

SHAP based predictive modeling for 1 year all-cause readmission risk in elderly heart failure patients: feature selection and model interpretation.

Heart failure (HF) is a significant global public health concern with a high readmission rate, posing a serious threat to the health of the elderly population. While several studies have used machine learning (ML) to develop all-cause readmission risk prediction models for elderly patients with HF, few have integrated ML-selected features with those chosen by human experts to assess HF patients readmission. A retrospective analysis of 8396 elderly HF patients hospitalized at the Affiliated Hospital of North Sichuan Medical College from January 1, 2018 to December 31, 2021 was conducted. Variables selected by XGBoost, LASSO regression, and random forest constituted the machine group, while the human expert group comprised variables chosen by two experienced cardiovascular professors. The variables selected by both groups were combined to form a human-machine collaboration group. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC). The SHapley Additive exPlanations (SHAP) method was used to elucidate the importance of each predictive feature, explain the impact of individual features on the model, and provide visual representation. A total of 73 features were included for model development. The human-machine collaboration model, utilizing CatBoost, achieved an AUC of 0.83617, an F1-score of 0.73521, and a Brier score of 0.16536 on the validation set. This model demonstrated superior predictive performance compared to those created solely by human experts or machine. The SHAP plot was then used to visually display the feature analysis of the human-machine collaboration model, revealing HGB, NT-proBNP, smoking history, NYHA classification, and LVEF as the 5 most important features. This study indicate that the human-machine collaboration model outperforms those relying solely on human expert selection or machine algorithm at predicting all-cause readmission in elderly HF patients. The application of the SHAP method enhanced the interpretability of the model outcomes, aiding clinicians in accurately pinpointing risk factors associated with HF readmission. This advancement enables the formulation of tailored treatment strategies, offering a more personalized approach to patient care.