Additive Manufacturing of Micro-Architected Copper based on an Ion-Exchangeable Hydrogel.

Additive manufacturing (AM) of copper through laser-based processes poses challenges, primarily attributed to the high thermal conductivity and low laser absorptivity of copper powder or wire as the feedstock. Although the use of copper salts in vat photopolymerization-based AM techniques has garnered recent attention, achieving micro-architected copper with high conductivity and density has remained elusive. In this study, we present a facile and efficient process to create complex 3D micro-architected copper structures with superior electrical conductivity and hardness. The process entails the formulation of an ion-exchangeable photoresin, followed by the utilization of digital light processing (DLP) printing to sculpt 3D hydrogel scaffolds, which were transformed into Cu2+-chelated polymer frameworks (Cu-CPFs) with a high loading of Cu2+ ions through ion exchange, followed by debinding and sintering, results in the transformation of Cu-CPFs into miniaturized copper architectures. This methodology represents an efficient pathway for the creation of intricate micro-architected 3D metal structures.

[Expert knowledge-based strategies for ventilator parameter setting and stepless adaptive adjustment].

The setting and adjustment of ventilator parameters need to rely on a large amount of clinical data and rich experience. This paper explored the problem of difficult decision-making of ventilator parameters due to the time-varying and sudden changes of clinical patient's state, and proposed an expert knowledge-based strategies for ventilator parameter setting and stepless adaptive adjustment based on fuzzy control rule and neural network. Based on the method and the real-time physiological state of clinical patients, we generated a mechanical ventilation decision-making solution set with continuity and smoothness, and automatically provided explicit parameter adjustment suggestions to medical personnel. This method can solve the problems of low control precision and poor dynamic quality of the ventilator's stepwise adjustment, handle multi-input control decision problems more rationally, and improve ventilation comfort for patients.

Computational investigation of flow characteristics and particle deposition patterns in a realistic human airway model under different breathing conditions.

Airborne particle pollution causes a range of respiratory and cardiovascular disorders by entering the human respiratory system through the breathing process. The administration of pharmaceutical particles by inhalation is another effective way to treat pulmonary illnesses. Studying particle deposition in the respiratory system during human breathing is crucial to maintaining human health. This necessity served as the impetus for this work, which aims to investigate how the airflow and particles' deposition are influenced by constant inhalation and circulatory breathing, particle diameter, and changes in airflow rate. The focus of this paper is to compare the particle deposition results of circulatory respiration with constant respiration. Based on computed tomography (CT) scan pictures, a precise human airway model from the mouth cavity to the fifth-generation bronchi was created. Flow fields and particle deposition inside the respiratory tract were examined at varied breathing rates (30, 60, and 90 L/min of constant and circulatory breathing) and varying haled particle sizes (5 and 10 µm). The results showed that the oropharyngeal area is often where the majority of particles are deposited. The particle distribution fraction is more significant in the bronchial area than the oropharyngeal region due to lower inhalation velocities and smaller particle sizes. For particles with a diameter of 5 µm, constant respiration and circulatory respiration have virtually identical particle distribution fractions in each region. For particles with a diameter of 10 µm, the particle distribution fraction for circulatory respiration is slightly higher than for constant respiration in the bronchial region as the flow rate increases. For both constant and circulatory respiration, particles are deposited more in the right lung and less in the left. These results contribute to further research on respiratory diseases caused by inhaled particles and guide inhalation therapy for better treatment outcomes.

The impact of an integrated PBL curriculum on clinical thinking in undergraduate medical students prior to clinical practice.

BACKGROUND: Problem-based learning (PBL) is a widely adopted educational approach in medical education that aims to promote critical thinking and problem-solving in authentic learning situations. However, the impact of PBL educational mode on undergraduate medical students' clinical thinking ability has been limitedly investigated. This study aimed to assess the influence of an integrated PBL curriculum on clinical thinking ability of medical students prior to clinical practice. METHODS: Two hundred and sixty-seven third-year undergraduate medical students at Nantong University were recruited in this study and were independently assigned to either the PBL or control group. The Chinese version of the Clinical Thinking Ability Evaluation Scale was used to assess clinical thinking ability, and the students' performance in the PBL tutorials was assessed by tutors. All participants in both groups were required to complete the pre-test and post-test questionnaires to self-report their clinical thinking ability. A paired sample t-test, independent sample t-test and one-way analysis of variance test (ANOVA) were used to compare the difference in clinical thinking scores among different groups. Multiple linear regression was conducted to analyze the influencing factors correlated with clinical thinking ability. RESULTS: The clinical thinking ability of most third-year undergraduate medical students at Nantong University was at a high level. The PBL group had a higher proportion of students with high-level clinical thinking ability in the post-test compared to the control group. The pre-test scores of clinical thinking ability were similar between the PBL and control groups, but the post-test scores of clinical thinking ability in the PBL group were significantly higher than those in the control group. Additionally, there was a significant difference in clinical thinking ability between the pre-test and post-test in the PBL group. The post-test scores of sub-scales of critical thinking ability were significantly higher than the pre-test in the PBL group. Furthermore, the frequency of reading literature, time of PBL self-directed learning, and PBL performance score ranking were influencing factors on the clinical thinking ability of medical students in the PBL group. Moreover, there was a positive correlation between clinical thinking ability and the frequency of reading literature, as well as the scores of the PBL performance. CONCLUSIONS: The integrated PBL curriculum model has an active impact on improving undergraduate medical students' clinical thinking ability. This improvement in clinical thinking ability may be correlated with the frequency of reading literature, as well as the performance of the PBL curriculum.

General anesthetic action profile on the human prefrontal cortex cells through comprehensive single-cell RNA-seq analysis.

The cellular and molecular actions of general anesthetics to induce anesthesia state and also cellular signaling changes for subsequent potential "long term" effects remain largely elusive. General anesthetics were reported to act on voltage-gated ion channels and ligand-gated ion channels. Here we used single-cell RNA-sequencing complemented with whole-cell patch clamp and calcium transient techniques to examine the gene transcriptome and ion channels profiling of sevoflurane and propofol, both commonly used clinically, on the human fetal prefrontal cortex (PFC) mixed cell cultures. Both propofol and sevoflurane at clinically relevant dose/concentration promoted "microgliosis" but only sevoflurane decreased microglia transcriptional similarity. Propofol and sevoflurane each extensively but transiently (<2 h) altered transcriptome profiling across microglia, excitatory neurons, interneurons, astrocytes and oligodendrocyte progenitor cells. Utilizing scRNA-seq as a robust and high-through put tool, our work may provide a comprehensive blueprint for future mechanistic studies of general anesthetics in clinically relevant settings.

Evaluation of Feature Selection for Alzheimer's Disease Diagnosis.

Accurate recognition of patients with Alzheimer's disease (AD) or mild cognitive impairment (MCI) is important for the subsequent treatment and rehabilitation. Recently, with the fast development of artificial intelligence (AI), AI-assisted diagnosis has been widely used. Feature selection as a key component is very important in AI-assisted diagnosis. So far, many feature selection methods have been developed. However, few studies consider the stability of a feature selection method. Therefore, in this study, we introduce a frequency-based criterion to evaluate the stability of feature selection and design a pipeline to select feature selection methods considering both stability and discriminability. There are two main contributions of this study: (1) It designs a bootstrap sampling-based workflow to simulate real-world scenario of feature selection. (2) It develops a decision graph to determine the optimal combination of supervised and unsupervised feature selection both considering feature stability and discriminability. Experimental results on the ADNI dataset have demonstrated the feasibility of our method.

Interpretable Recognition for Dementia Using Brain Images.

Machine learning-based models are widely used for neuroimage-based dementia recognition and achieve great success. However, most models omit the interpretability that is a very important factor regarding the confidence of a model. Takagi-Sugeno-Kang (TSK) fuzzy classifiers as the high interpretability and promising classification performance have widely used in many scenarios. TSK fuzzy classifier can generate interpretable fuzzy rules showing the reasoning process. However, when facing high-dimensional data, the antecedent become complex which may reduce the interpretability. In this study, to keep the antecedent of fuzzy rule concise, we introduce the subspace clustering technique and use it for antecedent learning. Experimental results show that the used model can generate promising recognition performance as well as concise fuzzy rules.

Porous structure design and mechanical behavior analysis based on TPMS for customized root analogue implant.

Compared with the traditional dental implant with screw structure, the root analogue implant (RAI) is customized to fit with the wall of the alveolar bone, which helps to accelerate the clinical implantation process. However, a solid RAI made of Ti6Al4V material has a much higher Young's modulus than the surrounding bone tissue, which can cause a stress shielding effect and thereby lead to implant failure. Also, a solid RAI is not conducive to the growth of osteoblasts. To overcome these problems, a porous structure design and optimization method for customized RAIs is proposed. A triply periodic minimal surface (TPMS) offers a smooth surface with pore interconnectivity, which can satisfy the biological/mechanical implantation requirements and efficiently construct many complex bone scaffolds. P and G structures with four degrees of porosity (30%, 40%, 50%, and 60%) were designed and prepared as cubic samples. The Young's modulus, Poisson's ratio, and yield strength of each sample were measured through compression experiments. Additionally, the stress distribution at the interface between the customized RAI and surrounding bone tissue under different pore structures and porosities was evaluated by finite element analysis (FEA). It was found that the quantitative relationships between the Young's modulus/Poisson's ratio and porosity of the P and G structures were consistent with the rules of the percolation model. The yield strengths of the P and G structures with four different porosities were all greater than the yield strength of cortical bone, which satisfies the implantation conditions. Furthermore, the P and G structures with 30% and 40% porosity were proved by FEA to have no stress shielding effect, promote the growth of surrounding bone tissue, and form long-term and stable osseointegration. It can be concluded that the porous RAI constructed with a TPMS can reduce the stress shielding effect, which is beneficial for accelerating the clinical implantation process.

Biological and mechanical property analysis for designed heterogeneous porous scaffolds based on the refined TPMS.

For tissue engineering (TE), triply periodic minimal surfaces (TPMSs) have received widespread application, as they produce smooth surfaces and pore interconnectivity, which can satisfy the biological/mechanical requirements and efficiently construct many complex bone scaffolds. To control the microstructure of the scaffold and mimic the anisotropy of native tissue, a design approach for heterogeneous porous scaffolds is proposed in this paper. It is carried out by discretizing the original model using the conformal refinement of an all-hexahedral mesh and mapping the TPMS units to the mesh elements with the help of a shape function. Another aim of this work is to assess the impact on the biologic/mechanical properties of the model, as it is discretized with different mesh patterns. It is found that the mesh pattern has a non-obvious effect on the surface curvature distribution that is a crucial factor to osteoblast proliferation in the TPMS scaffold. Nevertheless, the comparison presents that the mechanical properties of the refined scaffolds model exhibited anisotropy and improvements in elasticity, strengths, and especially energy absorption. With the help of conformal remeshing, the local density of architecture can be conveniently controlled and the elastic modulus of scaffold can be designed to the appropriate range in a specified area in order to mimic the actual cancellous bone.

Interleukin-6 reduces NMDAR-mediated cytosolic Ca²âº overload and neuronal death via JAK/CaN signaling.

Cytosolic Ca(2+) overload induced by N-methyl-D-aspartate (NMDA) is one of the major causes for neuronal cell death during cerebral ischemic insult and neurodegenerative disorders. Previously, we have reported that the cytokine interleukin-6 (IL-6) reduces NMDA-induced cytosolic Ca(2+) overload by inhibiting both L-type voltage-gated calcium channel (L-VGCC) activity and intracellular Ca(2+) store release in cultured cerebellar granule neurons (CGNs). Here we aimed to show that NMDA-gated receptor channels (i.e., NMDA receptors, NMDARs) are an inhibitory target of IL-6 via a mediation of calcineurin (CaN) signaling. As expected, IL-6 decreased NMDAR-mediated cytosolic Ca(2+) overload and inward current in cultured CGNs. The NMDAR subunits, NR1, NR2A, NR2B and NR2C, were expressed in CGNs. Blocking either of NR2A, NR2B and NR2C with respective antagonist reduced NMDA-induced extracellular Ca(2+) influx and neuronal death. Importantly, the reduced percentages in extracellular Ca(2+) influx and neuronal death by either NR2B or NR2C antagonist were weaker in the presence of IL-6 than in the absence of IL-6, while the reduced percentage by NR2A antagonist was not significantly different between the presence and the absence of IL-6. AG490, an inhibitor of Janus kinase (JAK), abolished IL-6 protection against extracellular Ca(2+) influx, mitochondrial membrane depolarization, neuronal death, and CaN activity impairment induced by NMDA. The CaN inhibitor FK506 reduced these IL-6 neuroprotective properties. Collectively, these results suggest that IL-6 exerts neuroprotection by inhibiting activities of the NMDAR subunits NR2B and NR2C (but not NR2A) via the intermediation of JAK/CaN signaling.

Interleukin-6 inhibits L-type calcium channel activity of cultured cerebellar granule neurons.

Our previous work has shown that interleukin-6 (IL-6) implements its neuroprotective effect by inhibiting the intracellular Ca(2+) overload in neurons. Here, we examined whether regulation of L-type calcium channels (LCCs) activities is involved in the neuroprotective action of IL-6. In cultured cerebellar granule neurons (CGNs), patch-clamp recording showed that the whole-cell Ca(2+) current and LCC current were significantly reduced by IL-6 pretreatment (120 ng/ml, for 24 h). Calcium imaging data indicated that IL-6 significantly suppressed high K(+)-induced intracellular Ca(2+) overload and LCC Ca(2+) influx. Moreover, expression of the LCC subunit, Ca(v)1.2, was remarkably downregulated by IL-6 in cultured CGNs. These findings suggest that IL-6 exerts a neurotrophic effect by preventing Ca(2+) overload, at least partly through inhibition of LCC activity in cultured CGNs.

Histamine evokes excitatory response of neurons in the cerebellar dentate nucleus via H2 receptors.

Previous studies have shown an excitatory effect of histamine on neurons in two cerebellar nuclei, the fastigial nucleus and the interposed nucleus. Here we investigated action of histamine on the dentate nucleus (DN), another nucleus of the cerebellum, and provided more evidence for motor control by histamine via the cerebellum. Spontaneous unitary discharge of neurons in the DN was extracellularly recorded by use of cerebellar slice preparations. In total 79-recorded neurons, which were from 53 cerebellar slices, 67 neurons (84.8%) had an excitatory response to histamine stimulation, and the rest (15.2%) were not reactive. The histamine-induced excitation of the DN neurons was not blocked by low-Ca(2+)/high-Mg(2+) medium, demonstrating that this effect of histamine was postsynaptic. Triprolidine, an antagonist of histamine H(1) receptors, did not block the excitatory effect of histamine, but ranitidine, an antagonist for H(2) receptors, blocked the excitatory response to histamine in a concentration-dependent manner. Further, histamine H(1) receptor agonist 2-pyridylethylamine did not elicit any response of DN neurons, but H(2) receptor agonist dimaprit had an excitatory action on the DN cells and this action was blocked by ranitidine. These results indicate that histamine excites cerebellar DN neurons via histamine H(2) receptors. Since the DN receives hypothalamocerebellar histaminergic projections and plays a role in initiation and planning of somatic movement, the postsynaptic excitation of the DN neurons by histamine suggests the possibility that the initiation and planning of movement may be modulated by the histaminergic projections.

Neuroprotection of interleukin-6 against NMDA-induced apoptosis and its signal-transduction mechanisms.

We have previously shown that interleukin-6 (IL-6)-protected neurons against the suppression of neuronal vitality and overload of intracellular Ca(2+) induced by glutamate or N-methyl-D: -aspartate (NMDA). Herein we provide further evidence for IL-6 neuroprotection against NMDA-induced apoptosis and explore the signal-transduction mechanisms underlying the anti-apoptotic action of IL-6. Cerebellar granule neurons (CGNs) from postnatal 8-day infant rats were chronically exposed to IL-6 (40 or 120 ng/ml) for 8 days, and stimulated with NMDA (100 µM) for 30 min. To observe the signaling pathways, we employed AG490 (5 or 10 µM), an inhibitor of Janus kinases (JAKs), or LY294002 (5 or 10 µM), an inhibitor of phosphatidylinositol 3-kinase (PI3K), to pretreat the CGNS together with IL-6. The levels of phosphorylation for the downstream effectors of JAKs and PI3K, i.e., phosphorylated STAT3 and Akt, were quantified by Western blot assay. In the cultured CGNs with various drug exposures, the expressions of Bcl-2, Bax, and caspase-3 were measured by real-time PCR and Western blot, and the percentage of apoptotic nuclei was tested by Hoechst 33342 staining. After the CGNs were chronically exposed to IL-6, NMDA stimulation led to an increase in the expression of Bcl-2 mRNA and a decrease in the expression of Bax and caspase-3 mRNAs and proteins when compared with those neurons lacking IL-6 exposure. IL-6 pretreatment of the neurons without NMDA stimulation concentration-dependently enhanced the expressions of Bcl-2 mRNA and protein while attenuating the expressions of Bax and caspase-3 mRNAs and proteins in comparison with control lacking any treatment. Furthermore, IL-6 prevented the increase in the percentage of apoptotic neurons induced by NMDA. The combined pretreatment of the CGNs with AG490 and IL-6 or with LY294002 and IL-6 reduced these anti-apoptotic effects of IL-6. Neither AG490 nor LY294002 exposure alone altered the expressions of Bcl-2, Bax, and cleaved caspase-3 proteins. IL-6 up-regulated the levels of phosphorylated STAT3 and Akt, and this was blocked by AG490 and LY294002, respectively. These results suggest that IL-6 protects neurons against NMDA-induced apoptosis, and that the IL-6 neuroprotection is jointly mediated by JAK-STAT3 and PI3K-Akt signaling pathways.