Damage Mechanism of Cu6Sn5 Intermetallics Due to Cyclic Polymorphic Transitions.

The formation of high-melting-point Cu6Sn5 interconnections is crucial to overcome the collapse of Sn-based micro-bumps and to produce reliable intermetallic interconnections in three-dimensional (3D) packages. However, because of multiple reflows in 3D package manufacturing, Cu6Sn5 interconnections will experience cyclic polymorphic transitions in the solid state. The repeated and abrupt changes in the Cu6Sn5 lattice due to the cyclic polymorphic transitions can cause extreme strain oscillations, producing damage at the surface and in the interior of the Cu6Sn5 matrix. Moreover, because of the polymorphic transition-induced grain splitting and superstructure phase formation, the reliability of Cu6Sn5 interconnections will thus face great challenges in 3D packages. In addition, the Cu6Sn5 polymorphic transition is structure-dependent, and the η ’↔ η polymorphic transition will occur at the surface while the η ’↔ ηs ↔ η polymorphic transition will occur in the deep matrix. This study can provide in-depth understanding of the structural evolution and damage mechanism of Cu6Sn5 interconnections in real 3D package manufacturing

Methylene blue-photodynamic therapy for Microsporum canis infection: investigating a dual mechanism of fungicidal action and neutrophil homeostasis restoration

BackgroundMicrosporum canis is an increasingly common cause of tinea capitis. Conventional antifungal therapies are limited by toxicity and resistance, creating a need for novel treatments. Antimicrobial photodynamic therapy (aPDT) is a promising alternative. We investigated the efficacy and dual mechanism of methylene blue-photodynamic therapy (MB-PDT) against M. canis, focusing on its effects on the host innate immune response.MethodsThe in vitro susceptibility of clinical M. canis isolates was determined by broth microdilution. Fungal ultrastructural changes were examined using transmission electron microscopy. In vivo efficacy was assessed in a murine dermatophytosis model and compared to topical terbinafine. Systemic immunomodulatory effects were evaluated by flow cytometric analysis of peripheral blood neutrophil phenotypes (Dectin-1, Dectin-2) and functional markers (MPO, NOX2).ResultsIn vitro, MB-PDT demonstrated potent fungicidal activity (Geometric Mean MIC at 80 J/cm2: 0.367 μg/mL; 95% CI: 0.295–0.439 μg/mL). It induced severe ultrastructural damage, including mitochondrial collapse and cell wall disruption. In the murine model, MB-PDT achieved an 80% mycological cure rate, significantly outperforming topical terbinafine (20% cure rate). Mechanistically, M. canis infection induced systemic neutrophil dysfunction, evidenced by a population shift and suppressed MPO and NOX2 expression. MB-PDT treatment reversed this immune dysfunction, restoring neutrophil homeostasis and the expression of key functional markers (MPO, NOX2).ConclusionMB-PDT is a highly effective treatment for M. canis infection. Its efficacy is based on a dual mechanism: direct fungicidal action through oxidative damage and restoration of host neutrophil function

Common Reservoirs for Penicillium marneffei Infection in Humans and Rodents, China

Human penicilliosis marneffei is an emerging infectious disease caused by the fungus Penicillium marneffei. High prevalence of infection among bamboo rats of the genera Rhizomys and Cannomys suggest that these rodents are a key facet of the P. marneffei life cycle. We trapped bamboo rats during June 2004–July 2005 across Guangxi Province, China, and demonstrated 100% prevalence of infection. Multilocus genotypes show that P. marneffei isolates from humans are similar to those infecting rats and are in some cases identical. Comparison of our dataset with genotypes recovered from sites across Southeast Asia shows that the overriding component of genetic structure in P. marneffei is spatial, with humans containing a greater diversity of genotypes than rodents. Humans and bamboo rats are sampling an as-yet undiscovered common reservoir of infection, or bamboo rats are a vector for human infections by acting as amplifiers of infectious dispersal stages

Agarwood extract improves psoriatic-like inflammation in HaCaT cells by regulating NF-κB pathway

Objective To investigate the effect and mechanism of agarwood extract (AE) on tumor necrosis factor-α (TNF-α)-induced psoriatic-like inflammation model of keratinocytes (HaCaT). Methods The psoriatic-like inflammation model of HaCaT cells was induced by 40 ng/mL TNF-α, and then the cells were treated with AE at concentrations of 16 μg/mL (low concentration), 24 μg/mL (medium concentration), 32 μg/mL (high concentration). Cell counting kit-8 (CCK-8) assay was used to detect the viability of HaCaT cells. Flow cytometry was applied to detect the apoptosis of HaCaT cells. Reverse transcription-quantitative polymerase chain reaction (RTqPCR) and enzyme-linked immunosorbent assay (ELISA) were used to detect the mRNA expression and secretion levels of various inflammatory mediators, as well as that of inhibitor kappa B alpha (IκBα). Western blotting was used to detect the expression of key proteins in the NF-κB pathway. Results After 40 ng/mL TNF-α stimulation, the viability of HaCaT cells was increased (P < 0.01), the early apoptosis rate and IκBα mRNA level were decreased (P < 0.05), and the mRNA expression levels and release of interleukin-6 (IL-6), interleukin-1β (IL-1β), interleukin17A (IL-17A), TNF-α, chemokine ligand 20 (CCL20) in cells were increased (P < 0.05). The expres‐sion level of phosphorylated nuclear factor-κB p65 (p-p65) protein was increased (P < 0.01). After a certain concentration of AE intervention, the viability of HaCaT cells was decreased (P < 0.01). Treatment with low, medium and high concentrations of AE in TNF-α pretreated HaCaT cells increased the early apoptosis rate and the mRNA-expression level of IκBα (P < 0.01). Meanwhile, it decreased the mRNA expression and release of IL-6, IL-1β, IL-17A, TNF-α and CCL20 (P < 0.05), as well as the p-p65 protein level (P < 0.01). Conclusion AE can inhibit the phosphorylation of p65 protein in the NF-κB pathway, thereby reducing the release of inflammatory factors and chemokines in the psoriatic-like inflammatory model of HaCaT cells, inducing apoptosis, and improving the inflammatory response

Novel emerging nano-assisted anti-cancer strategies based on the STING pathway

Activation of simulator of interferon genes (STING), which induces the production of proinflammatory factors and immune effector cell activation, is considered a promising strategy for enhanced anti-cancer intervention. However, several obstacles prevent STING signaling in solid tumors, such as delivered molecules’ rapid degradation, restriction to tumor sites, insufficient intracellular concentrations, and low responsivity. Well-designed, multifunctional nano-formulations have emerged as optimized platforms for STING activation. Recently, a variety of nano-formulations have been developed and used in STING activation, thus facilitating immunotherapy in preclinical and clinical stages. Herein, we summarize recent advances in nanotechnology-based delivery, activation, and application strategies, which have advanced various aspects of immunotherapy. Novel STING agonists and their mechanisms in STING-activation-mediated tumor interventions are highlighted herein, to provide a comprehensive overview and discuss future directions for boosting immunotherapy via STING regulation

Case Report: Anti-interferon-γ autoantibodies in an adolescent with disseminated Talaromyces marneffei and mycobacterial co-infections

BackgroundAnti-interferon-γ autoantibodies (AIGAs) are associated with adult-onset immunodeficiency syndrome, which makes individuals susceptible to intracellular pathogen infections. However, AIGAs are rarely reported in adolescents.Case presentationWe report a 13-year-old Chinese boy who presented with fever, cough, and enlarged cervical lymph nodes. Blood cultures yielded Mycobacterium abscessus, and Talaromyces marneffei (TM) was cultured from pericardial effusion. Whole exome sequencing revealed no pathogenic variants. Notably, high levels of neutralizing AIGAs were detected in the patient's serum. After receiving treatment for Mycobacterium abscessus and antifungal therapy for TM, the patient showed significant improvement. However, at the 19-month follow-up, the patient developed a Mycobacterium asiaticum infection.ConclusionThis case highlights the importance of screening for AIGAs in pediatric patients with disseminated TM or NTM infections. Prolonged treatment and continuous follow-up remains crucial for managing pediatric patients with AIGAs

Damage Mechanism of Cu&lt;sub&gt;6&lt;/sub&gt;Sn&lt;sub&gt;5&lt;/sub&gt; Intermetallics Due to Cyclic Polymorphic Transitions

The formation of high-melting-point Cu6Sn5 interconnections is crucial to overcome the collapse of Sn-based micro-bumps and produce reliable intermetallic interconnections in three-dimensional (3D) package. However, because of the multiple reflows in 3D package manufacturing, Cu6Sn5 interconnections will experience the cyclic polymorphic transitions in the solid state. The repeated and abrupt change in the Cu6Sn5 lattice due to the cyclic polymorphic transitions can cause extreme strain oscillations, producing damages at the surface and in the interior of the Cu6Sn5 matrix. Moreover, because of the polymorphic-transition-induced grain splitting and superstructure phase formation, the reliability of Cu6Sn5 interconnections will thus face great challenges in 3D package. In addition, the Cu6Sn5 polymorphic transition is structure-dependent, and the &amp;eta;&amp;prime;&amp;harr;&amp;eta; polymorphic transition will occur at the surface while the &amp;eta;&amp;prime;&amp;harr;&amp;eta;s&amp;harr;&amp;eta; polymorphic transition will occur in the deep matrix. Our results can provide in-depth understandings of structural evolution and damage mechanism of Cu6Sn5 interconnections in real 3D package manufacturing.</jats:p