Effect of Pore Size on the Biodegradation Rate of Silk Fibroin Scaffolds

Controlling the degradation rate of silk fibroin-based biomaterial is an important capability for the fabrication of silk-based tissue engineering scaffolds. In this study, scaffolds with different pore sizes were prepared by controlling the freezing temperature and the silk fibroin concentration. In vitro degradation results showed that the internal pore walls of the scaffolds with a larger pore size collapsed upon exposure to collagenase IA for times ranging from 6 to 12 days, and the silk scaffolds exhibited a faster rate of weight loss. The morphological and structural features of the silk scaffolds with a smaller pore size maintained structural integrity after incubation in the protease solution for 18 days, and the rate of weight loss was relatively slow. Scaffolds with a smaller pore size or a higher pore density degraded more slowly than scaffolds with a larger pore size or lower pore density. These results demonstrate that the pore size of silk biomaterials is crucial in controlling the degradation rate of tissue engineering scaffolds

In-Vessel Co-Composting of Food Waste Employing Enriched Bacterial Consortium

Svrha je ovoga rada bila pripremiti odgovarajuću smjesu za kompostiranje s pomoću kulture bakterija i 2 % vapna za učinkovitu obradu otpada od hrane u posudi zapremnine 60 litara. U pokusu, koji je trajao 42 dana, otpaci su od hrane prvo pomiješani s piljevinom i 2 % (suhe tvari) vapna, zatim je u jedan reaktor dodana obogaćena kultura bakterija, dok se u drugom reaktoru nalazio kontrolni uzorak. Rezultati pokazuju da se inokuliranjem smjese za kompostiranje bakterijskom kulturom može uspješno riješiti problem zasićenosti uljem te poboljšati mineralizacija. Osim toga, parametri kao što su: emisija ugljičnog dioksida od (0,81±0,2) g/(kg·dan), indeks klijanja od (105±3) %, maseni udjel ekstraktibilnog amonijaka od 305,78 mg/kg, omjer ugljika i dušika od 16,18, pH=7,6 i električna vodljivost od 3,12 mS/cm potvrđuju zrelost komposta, koji je zadovoljio standarde kompostiranja. U kontrolnom je uzorku opaženo kašnjenje termofilne faze, pa kompost nije sazrio ni nakon 42 dana. Stoga je zaključeno da su dobro pripremljena smjesa za kompostiranje i bakterijska kultura s odgovarajućim svojstvima za razgradnju ulja nužni za uspješan sustav kompostiranja otpada od hrane.The aim of the present study is to develop a good initial composting mix using a bacterial consortium and 2 % lime for effective co-composting of food waste in a 60-litre in-vessel composter. In the experiment that lasted for 42 days, the food waste was first mixed with sawdust and 2 % lime (by dry mass), then one of the reactors was inoculated with an enriched bacterial consortium, while the other served as control. The results show that inoculation of the enriched natural bacterial consortium effectively overcame the oil-laden co-composting mass in the composter and increased the rate of mineralization. In addition, CO2 evolution rate of (0.81±0.2) g/(kg·day), seed germination index of (105±3) %, extractable ammonium mass fraction of 305.78 mg/kg, C/N ratio of 16.18, pH=7.6 and electrical conductivity of 3.12 mS/cm clearly indicate that the compost was well matured and met the composting standard requirements. In contrast, control treatment exhibited a delayed thermophilic phase and did not mature after 42 days, as evidenced by the maturity parameters. Therefore, a good composting mix and potential bacterial inoculum to degrade the oil are essential for food waste co-composting systems

Research on performance evaluation and optimization theory for thermal microscope imaging systems

Infrared imaging theory is an important theoretical basis for the design of infrared imaging systems, but there is no research on infrared imaging theory for designing thermal microscope imaging systems. Therefore, we studied the performance evaluation and optimization theory of thermal microscope imaging systems. In this paper, we analyzed the difference in spectral radiant flux between thermal microscope imaging and telephoto thermal imaging. The expression of signal-to-noise ratio of the output image of the thermal microscope imaging systems was derived, based on the analysis of the characteristics of thermal microscope imaging. We studied the performance evaluation model of thermal microscope imaging systems based on the minimum resolvable temperature difference and the minimum detectable temperature difference. Simulation and analysis of different detectors (ideal photon detector and ideal thermal detector) were also carried out. Finally, based on the conclusion of theoretical research, we carried out a system design and image acquisition experiment. The results show that the theoretical study of thermal microscope imaging systems in this paper can provide reference for the performance evaluation and optimization of thermal microscope imaging systems

Impact of continuous pharmaceutical care led by clinical pharmacists during transitions of care on medication adherence and clinical outcomes for patients with coronary heart disease: a prospective cohort study

Objectives: The study aimed to explore the impact of a continuous pharmaceutical care (CPC) program during care transitions on medication adherence and clinical outcomes for patients with coronary heart disease (CHD).Methods: A prospective cohort study was conducted from April 2020 to February 2021. Patients diagnosed with CHD were selected and divided into intervention (CPC) and usual care (UC) groups by nurses at equal intervals based on admission time. The intervention group received CPC services provided by clinical pharmacists (including medication reconciliation, disease education, medication guidance, lifestyle counseling, and follow-up services) and usual care. The UC group received only routine medical care. The study compared medication adherence, clinical indicators (low-density lipoprotein cholesterol [LDL-C], blood pressure [BP], glycated hemoglobin [HbA1c] control rates), the incidence of adverse drug reactions (ADRs), and readmission rates (overall, major adverse cardiovascular events [MACEs]-related, and CHD risk factors-related) at admission and 1, 3, and 6 months after discharge between the two groups.Results: A total of 228 patients with CHD completed the study, including 113 patients in the CPC group and 115 patients in the UC group. There were no significant differences (p > 0.05) in both groups in demographic and clinical characteristics at baseline. A total of 101 drug-related problems were identified in the CPC group (an average of 0.89 per person). The CPC group showed significantly higher medication adherence at 1, 3, and 6 months after discharge than the UC group (p < 0.05). At 3 and 6 months after discharge, the intervention group had significantly higher control rates of LDL-C (61.11% vs. 44.64% at 3 months, 78.18% vs. 51.43% at 6 months), and BP (91.15% vs. 77.39% at 3 months, 88.50% vs. 77.19% at 6 months). The CPC group had higher HbA1c control rates (53.85% vs. 34.21% at 3 months, 54.05% vs. 38.46% at 6 months) than the UC group. However, the differences were not statistically significant. The incidence of ADRs 6 months after discharge was significantly lower in the CPC group than in the UC group (5.13% vs. 12.17%, p < 0.05). The CPC group had a lower overall readmission rate (13.27% vs. 20.00%), MACE-related readmission rate (5.31% vs. 12.17%), and readmission rate related to CHD risk factors (0.88% vs. 2.61%) 6 months after discharge compared to the UC group. However, these differences were not statistically significant (p > 0.05).Conclusion: CPC led by clinical pharmacists during care transitions effectively improved medication adherence, safety, and risk factor control in patients with CHD

Critical Roles of STAT3 in β-Adrenergic Functions in the Heart

BACKGROUND: β-Adrenergic receptors (βARs) play paradoxical roles in the heart. On one hand, βARs augment cardiac performance to fulfill the physiological demands, but on the other hand, prolonged activations of βARs exert deleterious effects that result in heart failure. The signal transducer and activator of transcription 3 (STAT3) plays a dynamic role in integrating multiple cytokine signaling pathways in a number of tissues. Altered activation of STAT3 has been observed in failing hearts in both human patients and animal models. Our objective is to determine the potential regulatory roles of STAT3 in cardiac βAR-mediated signaling and function. METHODS AND RESULTS: We observed that STAT3 can be directly activated in cardiomyocytes by β-adrenergic agonists. To follow up this finding, we analyzed βAR function in cardiomyocyte-restricted STAT3 knockouts and discovered that the conditional loss of STAT3 in cardiomyocytes markedly reduced the cardiac contractile response to acute βAR stimulation, and caused disengagement of calcium coupling and muscle contraction. Under chronic β-adrenergic stimulation, Stat3cKO hearts exhibited pronounced cardiomyocyte hypertrophy, cell death, and subsequent cardiac fibrosis. Biochemical and genetic data supported that Gαs and Src kinases are required for βAR-mediated activation of STAT3. Finally, we demonstrated that STAT3 transcriptionally regulates several key components of βAR pathway, including β1AR, protein kinase A, and T-type Ca(2+) channels. CONCLUSIONS: Our data demonstrate for the first time that STAT3 has a fundamental role in βAR signaling and functions in the heart. STAT3 serves as a critical transcriptional regulator for βAR-mediated cardiac stress adaption, pathological remodeling, and heart failure

Adaptive position calibration technique for an optical micro-scanning thermal microscope imaging system

In order to improve the spatial resolution of an optical micro-scanning thermal microscope system, the micro-scanning position must be accurately calibrated. An adaptive calibration method based on image registration and plane coordinate system is proposed. The meaning of calibration is given, and the principle and method of point calibration are introduced in detail and experiments using the real system were done. Different reconstruction methods were applied to reconstruct the visible light image and the real thermal microscope image, and the evaluation scores are given. Results of simulation and real thermal imaging processing show that the method can successfully calibrate the micro-scanning position. The method can significantly improve the oversampled reconstructed image quality, thus enhancing the spatial resolution of the system. This method can also be used in other electro-optical imaging systems

Multiplexed RNAi therapy against brain tumor-initiating cells via lipopolymeric nanoparticle infusion delays glioblastoma progression

Brain tumor-initiating cells (BTICs) have been identified as key contributors to therapy resistance, recurrence, and progression of diffuse gliomas, particularly glioblastoma (GBM). BTICs are elusive therapeutic targets that reside across the blood–brain barrier, underscoring the urgent need to develop novel therapeutic strategies. Additionally, intratumoral heterogeneity and adaptations to therapeutic pressure by BTICs impede the discovery of effective anti-BTIC therapies and limit the efficacy of individual gene targeting. Recent discoveries in the genetic and epigenetic determinants of BTIC tumorigenesis offer novel opportunities for RNAi-mediated targeting of BTICs. Here we show that BTIC growth arrest in vitro and in vivo is accomplished via concurrent siRNA knockdown of four transcription factors (SOX2, OLIG2, SALL2, and POU3F2) that drive the proneural BTIC phenotype delivered by multiplexed siRNA encapsulation in the lipopolymeric nanoparticle 7C1. Importantly, we demonstrate that 7C1 nano-encapsulation of multiplexed RNAi is a viable BTIC-targeting strategy when delivered directly in vivo in an established mouse brain tumor. Therapeutic potential was most evident via a convection-enhanced delivery method, which shows significant extension of median survival in two patient-derived BTIC xenograft mouse models of GBM. Our study suggests that there is potential advantage in multiplexed targeting strategies for BTICs and establishes a flexible nonviral gene therapy platform with the capacity to channel multiplexed RNAi schemes to address the challenges posed by tumor heterogeneity. Keywords: siRNA; lipopolymeric nanoparticle; glioblastoma transcription factor; brain tumor-initiating; cells; convection-enhanced deliver

CCL2 produced by the glioma microenvironment is essential for the recruitment of regulatory T cells and myeloid-derived suppressor cells

In many aggressive cancers, such as glioblastoma multiforme (GBM), progression is enabled by local immunosuppression driven by the accumulation of regulatory T cells (Treg) and myeloid-derived suppressor cells (MDSC). However, the mechanistic details of how Treg and MDSC are recruited in various tumors is not yet well understood. Here we report that macrophages and microglia within the glioma microenvironment produce CCL2, a chemokine that is critical for recruiting both CCR4+ Treg and CCR2+Ly-6C+ monocytic MDSC in this disease setting. In murine gliomas, we established novel roles for tumor-derived CCL20 and osteoprotegerin in inducing CCL2 production from macrophages and microglia. Tumors grown in CCL2 deficient mice failed to maximally accrue Treg and monocytic MDSC. In mixed-bone marrow chimera assays, we found that CCR4-deficient Treg and CCR2-deficient monocytic MDSC were defective in glioma accumulation. Further, administration of a small molecule antagonist of CCR4 improved median survival in the model. In clinical specimens of GBM, elevated levels of CCL2 expression correlated with reduced overall survival of patients. Lastly, we found that CD163-positive infiltrating macrophages were a major source of CCL2 in GBM patients. Collectively, our findings show how glioma cells influence the tumor microenvironment to recruit potent effectors of immunosuppression that drive progression

One for Multiple: Physics-informed Synthetic Data Boosts Generalizable Deep Learning for Fast MRI Reconstruction

Magnetic resonance imaging (MRI) is a principal radiological modality that provides radiation-free, abundant, and diverse information about the whole human body for medical diagnosis, but suffers from prolonged scan time. The scan time can be significantly reduced through k-space undersampling but the introduced artifacts need to be removed in image reconstruction. Although deep learning (DL) has emerged as a powerful tool for image reconstruction in fast MRI, its potential in multiple imaging scenarios remains largely untapped. This is because not only collecting large-scale and diverse realistic training data is generally costly and privacy-restricted, but also existing DL methods are hard to handle the practically inevitable mismatch between training and target data. Here, we present a Physics-Informed Synthetic data learning framework for Fast MRI, called PISF, which is the first to enable generalizable DL for multi-scenario MRI reconstruction using solely one trained model. For a 2D image, the reconstruction is separated into many 1D basic problems and starts with the 1D data synthesis, to facilitate generalization. We demonstrate that training DL models on synthetic data, integrated with enhanced learning techniques, can achieve comparable or even better in vivo MRI reconstruction compared to models trained on a matched realistic dataset, reducing the demand for real-world MRI data by up to 96%. Moreover, our PISF shows impressive generalizability in multi-vendor multi-center imaging. Its excellent adaptability to patients has been verified through 10 experienced doctors' evaluations. PISF provides a feasible and cost-effective way to markedly boost the widespread usage of DL in various fast MRI applications, while freeing from the intractable ethical and practical considerations of in vivo human data acquisitions.Comment: 22 pages, 9 figures, 1 tabl