Impact of Hydrogen Voiding in Chip-to-Chip Electroless All-Copper Interconnections.

Three-dimensional (3D) integration has become a leading approach in chip packaging. The interconnection density and reliability of micro-bumps in chip stacking are often threatened by high bonding temperatures. The method of building chip-to-chip interconnections by electroless deposition of metal has its distinct merit, while the interfacial defect issue, especially that related to voiding during the merging of opposite sides, remains largely unsolved. In this study, to trace the influencing factors in the voiding, the growth characteristics of the electroless all-copper interconnections were examined by carrying out deposition experiments in a microfluidic channel device. The results show that when the gap between the opposite copper bumps to be electrolessly merged is as low as 10 µm, significant voids appear at the inflow side and the top of the copper bumps because the hydrogen cannot be expelled in time. A finite-element flow model of the plating solution between the chips was established, which showed that the flow rate of the plating solution around the copper bumps was much higher than in the merging gap, causing an uneven supply of reactants. Based on these findings, we proposed two potential solutions, one is to improve the flow mode of the plating solution, and the other is to add the reaction inhibitor, 2,2'-bipyridine. Finally, the combination of these two approaches successfully achieved an improved merging quality of the copper joints.

A randomized controlled trial comparison of PTEBL and traditional teaching methods in "Stop the Bleed" training.

BACKGROUND: The Stop the Bleed (STB) training program was launched by the White House to minimize hemorrhagic deaths. Few studies focused on the STB were reported outside the United States. This study aimed to evaluate the effectiveness of a problem-, team- and evidence-based learning (PTEBL) approach to teaching, compared to traditional teaching methods currently employed in STB courses in China. METHODS: This study was a parallel group, unmasked, randomised controlled trial. We included third-year medical students of a five-year training program from the Xiangya School of Medicine, Central South University who voluntarily participated in the trial. One hundred fifty-three medical students were randomized (1:1) into the PTEBL group (n = 77) or traditional group (n = 76). Every group was led by a single instructor. The instructor in the PTEBL group has experienced in educational reform. However, the instructor in the traditional group follows a traditional teaching mode. The teaching courses for both student groups had the same duration of four hours. Questionnaires were conducted to assess teaching quality before and after the course. The trial was registered in the Central South University (No. 2021JY188). RESULTS: In the PTEBL group, students reported mastery in three fundamental STB skills-Direct Finger Compression (61/77, 79.2%), Packing (72/77, 93.8%), and Tourniquet Placement (71/77, 92.2%) respectively, while 76.3% (58/76), 89.5% (68/76), and 88.2% (67/76) of students in the traditional group (P > 0.05 for each pairwise comparison). 96.1% (74/77) of students in the PTEBL group felt prepared to help in an emergency, while 90.8% (69/76) of students in the traditional group (P > 0.05). 94.8% (73/77) of students reported improved teamwork skills after the PTEBL course, in contrast with 81.6% (62/76) of students in the traditional course (P = 0.011). Furthermore, a positive correlation was observed between improved clinical thinking skills and improved teamwork skills (R = 0.82, 95% CI: 0.74-0.88; P < 0.001). CONCLUSIONS: Compared with the traditional teaching method, the PTEBL method was superior in teaching teamwork skills, and has equally effectively taught hemostasis techniques in the emergency setting. The PTEBL method can be introduced to the STB training in China.

X-box binding protein 1 as a key modulator in "healing endothelial cells", a novel EC phenotype promoting angiogenesis after MCAO.

BACKGROUND: Endothelial cells (ECs) play an important role in angiogenesis and vascular reconstruction in the pathophysiology of ischemic stroke. Previous investigations have provided a profound cerebral vascular atlas under physiological conditions, but have failed to identify new disease-related cell subtypes. We aimed to identify new EC subtypes and determine the key modulator genes. METHODS: Two datasets GSE174574 and GSE137482 were included in the study. Seurat was utilized as the standard quality-control pipeline. UCell was used to calculate single-cell scores to validate cellular identity. Monocle3 and CytoTRACE were utilized in aid of pseudo-time differentiation analysis. CellChat was utilized to infer the intercellular communication pathways. The angiogenesis ability of ECs was validated by MTS, Transwell, tube formation, flow cytometry, and immunofluorescence assays in vitro and in vivo. A synchrotron radiation-based propagation contrast imaging was introduced to comprehensively portray cerebral vasculature. RESULTS: We successfully identified a novel subtype of EC named "healing EC" that highly expressed pan-EC marker and pro-angiogenic genes but lowly expressed all the arteriovenous markers identified in the vascular single-cell atlas. Further analyses showed its high stemness to differentiate into other EC subtypes and potential to modulate inflammation and angiogenesis via excretion of signal molecules. We therefore identified X-box binding protein 1 (Xbp1) as a key modulator in the healing EC phenotype. In vitro and in vivo experiments confirmed its pro-angiogenic roles under both physiological and pathological conditions. Synchrotron radiation-based propagation contrast imaging further proved that Xbp1 could promote angiogenesis and recover normal vasculature conformation, especially in the corpus striatum and prefrontal cortex under middle cerebral artery occlusion (MCAO) condition. CONCLUSIONS: Our study identified a novel disease-related EC subtype that showed high stemness to differentiate into other EC subtypes. The predicted molecule Xbp1 was thus confirmed as a key modulator that can promote angiogenesis and recover normal vasculature conformation.

Ferroptosis in Intracerebral Hemorrhage: A Panoramic Perspective of the Metabolism, Mechanism and Theranostics.

Iron is one of the most crucial elements in the human body. In recent years, a kind of programmed, non-apoptotic cell death closely related to iron metabolism-called ferroptosis- has aroused much interest among many scientists. Ferroptosis also interacts with other pathways involved in cell death including iron abnormality, the cystine/glutamate antiporter and lipid peroxidation. Together these pathological pathways exert great impacts on intracerebral hemorrhage (ICH), a lethal cerebrovascular disease with a high incidence rate and mortality rate. Furthermore, the ferroptosis also affects different brain cells (neurons and neuroglial cells) and different organelles (mitochondria and endoplasmic reticulum). Clinical treatments for ferroptosis in ICH have been closely investigated recently. This perspective provides a comprehensive summary of ferroptosis mechanisms after ICH and its interaction with other cell death patterns. Understanding the role of ferroptosis in ICH will open new windows for the future treatments and preventions for ICH and other intracerebral diseases.