Neuropathic pain indicates pain caused by damage to the somatosensory system and is difficult to manage and treat. A new treatment strategy urgently needs to be developed. Both autophagy and ...apoptosis are critical adaptive mechanisms when neurons encounter stress or damage. Recent studies have shown that, after nerve damage, both autophagic and apoptotic activities in the injured nerve, dorsal root ganglia, and spinal dorsal horn change over time. Many studies have shown that upregulated autophagic activities may help myelin clearance, promote nerve regeneration, and attenuate pain behavior. On the other hand, there is no direct evidence that the inhibition of apoptotic activities in the injured neurons can attenuate pain behavior. Most studies have only shown that agents can simultaneously attenuate pain behavior and inhibit apoptotic activities in the injured dorsal root ganglia. Autophagy and apoptosis can crosstalk with each other through various proteins and proinflammatory cytokine expressions. Proinflammatory cytokines can promote both autophagic/apoptotic activities and neuropathic pain formation, whereas autophagy can inhibit proinflammatory cytokine activities and further attenuate pain behaviors. Thus, agents that can enhance autophagic activities but suppress apoptotic activities on the injured nerve and dorsal root ganglia can treat neuropathic pain. Here, we summarized the evolving changes in apoptotic and autophagic activities in the injured nerve, dorsal root ganglia, spinal cord, and brain after nerve damage. This review may help in further understanding the treatment strategy for neuropathic pain during nerve injury by modulating apoptotic/autophagic activities and proinflammatory cytokines in the nervous system.
Progressive immune dysfunction associated with aging is known as immunosenescence. The age-related deterioration of immune function is accompanied by chronic inflammation and microenvironment ...changes. Immunosenescence can affect both innate and acquired immunity. Sepsis is a systemic inflammatory response that affects parenchymal organs, such as the respiratory system, cardiovascular system, liver, urinary system, and central nervous system, according to the sequential organ failure assessment (SOFA). The initial immune response is characterized by an excess release of inflammatory factors, followed by persistent immune paralysis. Moreover, immunosenescence was found to complement the severity of the immune disorder following sepsis. Furthermore, the immune characteristics associated with sepsis include lymphocytopenia, thymus degeneration, and immunosuppressive cell proliferation, which are very similar to the characteristics of immunosenescence. Therefore, an in-depth understanding of immunosenescence after sepsis and its subsequent effects on the organs may contribute to the development of promising therapeutic strategies. This paper focuses on the characteristics of immunosenescence after sepsis and rigorously analyzes the possible underlying mechanism of action. Based on several recent studies, we summarized the relationship between immunosenescence and sepsis-related organs. We believe that the association between immunosenescence and parenchymal organs might be able to explain the delayed consequences associated with sepsis.
Abstract
Background
Insomnia and suicidal thoughts are two of the negative impacts that have been caused by the COVID-19 pandemic. Identifying the factors that contribute to these psychological ...problems may help develop strategies to sustain the mental health of the public. The present study examined the psychosocial impacts caused by the COVID-19 pandemic among different populations in Taiwan, and investigated the relationships between these psychosocial variables, insomnia, and suicidal thoughts.
Methods
Between September 2020 and May 2021, online questionnaires including psychometrically validated scales were distributed to a convenience sample of outpatients (
n
= 205), healthcare workers (HCWs) (
n
= 500), and individuals in the general population (
n
= 1200) in Taiwan to collect data regarding their insomnia severity, suicidal thoughts, fear of COVID-19, trust of information, and resilience. Multivariate logistic regression methods were used to identify variables associated with suicidal thoughts and insomnia.
Results
Greater fear of COVID-19 was significantly associated with suicidal thoughts: odds ratios (ORs) with 95% confidence interval (CI) = 1.155 (1.002–1.330) for outpatients; 1.127 (1.035–1.228) for HCWs; and 1.100 (1.130–1.222) for those in the general population. Higher resilience was significantly associated with lower insomnia: OR (95% CI) = 0.819 (0.725–0.926) for outpatients; 0.803 (0.728–0.887), for HCWs; 0.829 (0.785–0.875), and for those in the general population. In addition, there was a statistically significant association between insomnia diagnosis and greater fear of COVID-19 among HCWs (OR 95% CI = 1.102 1.062–1.144) and those in the general population (OR 95% CI = 1.079 1.053–1.106). Among outpatients, there was a statistically significant association between suicidal thoughts and lower trust of information (OR 95% CI = 0.794 0.646–0.976), while among those in the general population there was a statistically significant association between suicidal thoughts and higher insomnia severity (OR 95% CI = 1.175 1.13–1.222). A statistically significant association was also found between insomnia diagnosis and higher suicidal thoughts among those in the general population (OR 95% CI = 3.455 2.338–5.106).
Conclusions
Trust of information, fear, and resilience were important factors for suppressing suicidal thoughts and insomnia among the three study populations. Health policies that monitor psychological status and build resiliency of the public are recommended to help develop tailored strategies for different populations affected by the COVID-19 pandemic.
Nanosilver sintering is expected to overcome the limitation of relatively high production cost and become widely available for the die bonding of power electronics. A potential application of ...nanosilver sintering is bare copper bonding, where replacing substrates with auxiliary silver or other plating that can damage bonding would be advantageous. Here, we introduce a novel multiscale silver paste containing both nanoparticles (20–100nm) and microparticles (1–5μm) for the bonding of high-power chips on a bare copper substrate by pressure-free sintering in air. The energy potential difference generated in the surface force field was critical in the formation of sintering necks between the nano and microparticles, which, together with other microparticles, formed the high-density sintered structure. Despite the development of a copper oxide film, the interfacial bonding was comparable to or higher than the sintering force due to the high surface energy of porous sintered structure and easy diffusion of nanoparticles occurred. A processing temperature of 265°C was considered optimal for bare copper joint (shear strength: 53MPa, transient thermal impedance: 0.132°C/W) considering the trade-off between achieving excellent mechanical and thermal properties while minimizing oxidation.
Display omitted
•A novel multiscale silver paste for die bonding on bare copper by pressure-free sintering in air is proposed.•The mechanism of bonding is revealed to rely on the presence of copper oxides.•The thin copper oxides do not significantly degrade mechanical and thermal properties of the joint.•Nanoparticles contribute to the formation of chemical bonds between silver and copper oxides.•Nanoparticles serve as bridges between microparticles during sintering.
Die attachment by pressureless silver sintering at <200 °C is significant for power electronic packaging because it can relieve residual thermo-mechanical stress and avoid chip damage. In this ...letter, we developed a trimodal-silver paste capable of pressureless sintering at as low as 180 °C due to the usage of trimodal-system and 170 °C removable organics agents. The bondline could be densified by neck-formation as expected. Thanks to the high packing density of the trimodal system, a high bonding strength of 35 MPa was achieved. Moreover, IGBT modules were demonstrated using the 180 °C sinterable sintered-Ag die attachment. The output I-V characteristics and the thermal resistance of the IGBT modules were discussed.
The mismatch of coefficients of thermal expansion (CTE) causes tremendous thermomechanical stress in die attachment of double-sided bidirectional modules (BMs), thus reducing the reliability of the ...module. The thermomechanical reliability of a double-sided power module is the most critical issue, which needs to be addressed. People have proposed a number of ways to improve the reliability by reducing the CTE mismatches using such as Moly spacer instead of copper or junction temperature rise using high conductive spacer. This work first proposed a composite buffer, namely copper-wire-spacer (CWS), with low elastic modulus, capable of reducing thermomechanical stress by >50%. The lifetime of the double-sided BM with the CWS buffer is 40.0% and 42.9% longer than that with the conventional solid copper buffer, and is only 6.67% and 6.25% shorter than that with the moly buffer under the thermal shocking tests and the power cycling tests, respectively. The novel method of reducing the elastic modulus of the spacer could be a novel and good concept to reduce the thermomechanical stresses as well as improving the reliability of double-sided power modules. It can provide new guidance to design and packaging reliable double-sided power modules.
Operation temperature of typical wire-bonded power modules, especially for harder silicon carbide (SiC) power chips, keeps increasing. The thermo-mechanical reliability of aluminum (Al) wire-bonds ...which suffer from the mismatch of coefficient of thermal expansion (CTE) between chip and bonding wires reduces significantly. In this letter, a novel laminated Al/copper (Cu) soft stress buffer was proposed between SiC chip and bonding wires, capable of reducing thermo-mechanical stress of the wires and using soft Al wires with low ultrasonic bonding energy instead sophisticated Cu wires. Lifetime of Al wire bonding on the proposed 10- μ m Al/40- μ m Cu buffer was 5.14 times longer than that on a SiC chip directly under power cycling with constant Δ T j = 110 °C. In the end, a lifetime prediction model was established to guide the laminated buffer design for enhancing the reliability of Al wire-bonded Si diodes.
This paper proposed a new approach to attach power devices on nonmetallized direct bonding copper (DBC) substrates by pressureless sintering of nanosilver paste in poor-oxygen sintering atmosphere ...and formic acid reduction atmosphere. The average shear strength of die-attach joints could reach 25 MPa, and the copper oxidation issue of the nonmetallized DBC substrates was avoided. Based on the pressureless sintering approach of nanosilver paste, insulated-gate bipolar transistor (IGBT) modules were prototyped to verify the feasibility of this approach for mass production of power modules. The electrical and thermal characteristics of the IGBT modules bonded with sintered nanosilver were then compared with those of the commercialized ones using Pb92.5Sn5Ag2.5 solder alloy. This approach could extend the applications to bonding power devices on nonmetallized DBC substrates by nanosilver paste, and guide fabricating power modules in a mass productive, low facility costs, and high-yield way.
A 2D multiscale numerical strategy is presented in this paper. It allows to generate a representative elementary volume (REV) with a spherulitic microstructure used to predict the elastic properties ...of PET using a 2-scale numerical homogenization scheme. Because of the rapid crystallization kinetics of PET, DSC and optical microscopy were combined with empirical laws to estimate the crystallization kinetic parameters used to generate the REVs. Our framework allows estimating the elastic properties identified by tensile tests for several specimens crystallized at different temperatures. In addition, the comparison with mean-field models from the literature confirms that the Young's modulus of PET does not only depend on the crystallinity volume ratio but also on the crystal organization in the spherulites. The main advantage of this study is to provide a strategy for estimating the elastic properties that can be transposed to many semi-crystalline polymers with a spherulitic microstructure. Nevertheless, the numerical framework presented in the article is limited to semicrystalline polymers with a spherulitic microstructure, which crystallize under isothermal condition.
Display omitted
•Identification of crystallization kinetic parameter of PET.•2D framework for numerical homogenization of spherulitic microstructure.•Estimation of elastic properties of PET versus crystallization temperature.•Comparison with tensile test results and mean-field homogenization models.
Comparative analysis of primate genomes within a phylogenetic context is essential for understanding the evolution of human genetic architecture and primate diversity. We present such a study of 50 ...primate species spanning 38 genera and 14 families, including 27 genomes first reported here, with many from previously less well represented groups, the New World monkeys and the Strepsirrhini. Our analyses reveal heterogeneous rates of genomic rearrangement and gene evolution across primate lineages. Thousands of genes under positive selection in different lineages play roles in the nervous, skeletal, and digestive systems and may have contributed to primate innovations and adaptations. Our study reveals that many key genomic innovations occurred in the Simiiformes ancestral node and may have had an impact on the adaptive radiation of the Simiiformes and human evolution.
PDF
