A Cross-Process Signal Integrity Analysis (CPSIA) Method and Design Optimization for Wafer-on-Wafer Stacked DRAM.

A multi-layer stacked Dynamic Random Access Memory (DRAM) platform is introduced to address the memory wall issue. This platform features high-density vertical interconnects established between DRAM units for high-capacity memory and logic units for computation, utilizing Wafer-on-Wafer (WoW) hybrid bonding and mini Through-Silicon Via (TSV) technologies. This 3DIC architecture includes commercial DRAM, logic, and 3DIC manufacturing processes. Their design documents typically come from different foundries, presenting challenges for signal integrity design and analysis. This paper establishes a lumped circuit based on 3DIC physical structure and calculates all values of the lumped elements in the circuit model with the transmission line model. A Cross-Process Signal Integrity Analysis (CPSIA) method is introduced, which integrates three different manufacturing processes by modeling vertical stacking cells and connecting DRAM and logic netlists in one simulation environment. In combination with the dedicated buffer driving method, the CPSIA method is used to analyze 3DIC impacts. Simulation results show that the timing uncertainty introduced by 3DIC crosstalk ranges from 31 ps to 62 ps. This analysis result explains the stable slight variation in the maximum frequency observed in vertically stacked memory arrays from different DRAM layers in the physical testing results, demonstrating the effectiveness of this CPSIA method.

Length-dependent toxic effects of microplastic fibers on Chlorella pyrenoidosa.

Microplastics (MPs), a pervasive pollutant in aquatic environments, are increasingly recognized for their detrimental effects on aquatic organisms. However, the present understanding of their impact on phytoplankton, particularly freshwater microalgae, remains limited. Furthermore, previous studies have predominantly focused on MP particles, largely overlooking the most prevalent form of MPs in aquatic settings-fibers. In this study, we scrutinized the toxicological implications of microplastic fibers (MFs) spanning four distinct lengths (50 µm, 100 µm, 150 µm, and 200 µm) on the protein-nucleated algae Chlorella pyrenoidosa over a six-day period. The study unequivocally demonstrated that MFs markedly impeded C. pyrenoidosa growth, diminished photosynthetic pigment content, and induced oxidative stress, with all observed effects exhibiting a length-dependent correlation. Electron microscopy further revealed notable damage to algal cell membranes. Cell membrane shrinkage, cytoplasm outflow, and abnormalities in cell division were observed in the 150 µm and 200 µm groups. Furthermore, C. pyrenoidosa clustered around the 200 µm MF were notably denser compared to other groups. The present study demonstrated that MFs had length-dependent toxic effects on C. pyrenoidosa. These findings offer novel insights into the deleterious impact of MFs on aquatic organisms, underscoring the pivotal role of length in influencing their toxicity.

Clinical Analysis of Microvascular Reconstruction Combined With Decompressive Craniectomy in Patients With Malignant Middle Cerebral Artery Infarctions.

PURPOSE: This study aimed to evaluate the safety and efficacy of microvascular reconstruction combined with decompressive craniectomy (DHC) in patients with malignant middle cerebral artery infarctions (MMCA). METHODS: We searched for patients with MMCA and aged＜60 years old, postoperative survival of more than 3 months, consistent with decompression of bone flap removal. Patients were divided into experimental group and control group according to whether they underwent emergency vascular revascularization within 5 days after onset of ischemic stroke. RESULTS: A total of sixpatients were included in the treatment group and 12 patients in the control group. The National Institutes of Health Stroke Scale (NIHSS) score of the treatment group was lower than that of the control group seven days after operation, but the difference was not statistically significant; 3 months after surgery, modified ranking scale (mRs) score in the treatment group was lower than that in the control group, the difference was statistically significant (P = 0.002); mRs scores of the treatment group 3 months after surgery were significantly different from those before surgery (P < 0.05), but no such difference was found in the control group. CONCLUSION: Compared with decompressive craniectomy, open surgical revascularization can improve early cerebral perfusion in MMCA patients, and neurological recovery is better at 3 months after operation. By ensuring that surgeons are properly trained and hospitals are equipped, open surgical revascularization can be a treatment option for patients with MMCA.

Bisphenol A has a sex-dependent disruptive effect on hepatic lipid metabolism in zebrafish.

Bisphenol A (BPA) is an endocrine disruptor that has adverse effects on lipid metabolism. However, most of the current studies on the effects of BPA on lipid metabolism in fish have focused on middle- and short-term exposure tests. The aim of this study was to investigate the effects of long-term BPA exposure on liver lipid metabolism in zebrafish. Post-fertilization embryos were exposed to environmentally relevant concentrations of BPA for 120 days, and the changes in triglyceride (TG), total cholesterol (TC) levels, and gene expression related to liver lipid metabolism were investigated in both male and female fish. The results showed that long-term exposure to BPA led to lipid deposition in liver, and there was a sex difference. In the liver of female fish, there was higher lipid transport and synthesis at low concentration of BPA, while overall metabolic levels were increased at high concentration of BPA. In contrast, BPA showed a dose-dependent effect on the lipid deposition in male fish. The expression of mRNA of TG transport-related and lipid synthesis-related genes was significantly up-regulated and the expression of genes related to lipid catabolism, was significantly down-regulated with increasing BPA dose. Taken together, our results indicate that long-term exposure to BPA can increase lipid deposition in a gender-specific manner. This may be due to the different responses of lipid metabolism related genes to BPA in male and female zebrafish. These results will provide a new reference for a deeper understanding of the ecotoxicological effects of BPA on aquatic animals.

Ultra-Early Treatment for Poor-Grade Aneurysmal Subarachnoid Hemorrhage: A Systematic Review and Meta-Analysis.

BACKGROUND: It remains unknown if ultra-early (within 24 hours after onset) treatment can improve the prognosis in patients with poor-grade aneurysmal subarachnoid hemorrhage (aSAH). We aimed to evaluate the effect of ultra-early treatment on functional outcomes and mortality in patients with poor-grade aSAH via a systematic review and meta-analysis. METHODS: We performed a literature search in the PubMed, MEDLINE, and Web of Science databases. Primary outcomes were death and functional outcome assessed at any time period. Secondary outcomes were the rebleeding rate before an aneurysm occlusion procedure and the incidence of intraoperative technique difficulty (ITD). The results are reported as odds ratio (OR) with 95% confidence interval (CI). RESULTS: A total of 14 articles containing 1111 patients met our inclusion criteria and were included in our analysis. The pooled incidence was 47% (95% CI, 40%-54%) for favorable outcome across 13 studies, 26% (95% CI, 19%-32%) for mortality in 11 studies, 10% (95% CI, 3%-16%) for rebleeding in 5 studies, and 20% (95% CI, 10%-31%) for ITD in 5 studies after ultra-early treatment of poor-grade aSAH. Compared with delayed treatment (>24 hours), the ultra-early treatment failed to improve outcomes (OR, 1.23; 95% CI, 0.75-2.01; P = 0.40) or reduce mortality (OR, 0.84; 95% CI, 0.58-1.22; P = 0.45), but tended to prevent preoperative rebleeding (OR, 0.59; 95% CI, 0.32 to 1.07; P = 0.08) in 6, 4, and 4 case-control studies, respectively. CONCLUSIONS: Our findings show no significant change both in functional outcome and mortality between ultra-early and delayed treatment although ultra-early treatment may be associated with lower rebleeding rate.

Cell cycle-related genes p57kip2, Cdk5 and Spin in the pathogenesis of neural tube defects.

In the field of developmental neurobiology, accurate and ordered regulation of the cell cycle and apoptosis are crucial factors contributing to the normal formation of the neural tube. Preliminary studies identified several genes involved in the development of neural tube defects. In this study, we established a model of developmental neural tube defects by administration of retinoic acid to pregnant rats. Gene chip hybridization analysis showed that genes related to the cell cycle and apoptosis, signal transduction, transcription and translation regulation, energy and metabolism, heat shock, and matrix and cytoskeletal proteins were all involved in the formation of developmental neural tube defects. Among these, cell cycle-related genes were predominant. Retinoic acid ment caused differential expression of three cell cycle-related genes p57kip2, Cdk5 and Spin, the expression levels of which were downregulated by retinoic acid and upregulated during normal neural tube formation. The results of this study indicate that cell cycle-related genes play an important role in the formation of neural tube defects. P57kip2, Cdk5 and Spin may be critical genes in the pathogenesis of neural tube defects.

Aquaporin 4 expression and ultrastructure of the blood-brain barrier following cerebral contusion injury.

This study aimed to investigate aquaporin 4 expression and the ultrastructure of the blood-brain barrier at 2-72 hours following cerebral contusion injury, and correlate these changes to the formation of brain edema. Results revealed that at 2 hours after cerebral contusion and laceration injury, aquaporin 4 expression significantly increased, brain water content and blood-brain barrier permeability increased, and the number of pinocytotic vesicles in cerebral microvascular endothelial cells increased. In addition, the mitochondrial accumulation was observed. As contusion and laceration injury became aggravated, aquaporin 4 expression continued to increase, brain water content and blood-brain barrier permeability gradually increased, brain capillary endothelial cells and astrocytes swelled, and capillary basement membrane injury gradually increased. The above changes were most apparent at 12 hours after injury, after which they gradually attenuated. Aquaporin 4 expression positively correlated with brain water content and the blood-brain barrier index. Our experimental findings indicate that increasing aquaporin 4 expression and blood-brain barrier permeability after cerebral contusion and laceration injury in humans is involved in the formation of brain edema.

Inhibition of all-trans retinoic acid on MDM2 gene expression in astrocytoma cell line SHG-44.

OBJECTIVE: To investigate the impact of all-trans retinoic acid (ATRA) on MDM2 gene expression in astrocytoma cell line SHG-44, and to provide basic data for further research on the progression mechanism and gene therapy of human astrocytoma. METHODS: The differential expressions of MDM2 gene and protein in SHG-44 cells were detected by cDNA microarray and Western blot, respectively, before and after treatment of ATRA. The expressions of MDM2 protein in WHO grade II and grade IV astrocytomas were determined by immunohistochemical streptavidin-peroxidase method. Some differentially expressed genes were selected randomly for Northern blot analysis. RESULTS: The intensity ratio of ATRA-treated to untreated SHG-44 cell was 0.37 in the cDNA microarray, suggesting that the expression of MDM2 gene was down-regulated in SHG-44 cells after treatment with ATRA. Some genes differentially expressed in the microarray were confirmed by Northern blot. Western blot demonstrated that the optical density ratios of MDM2 to beta-actin in ATRA-treated and untreated SHG-44 were 14.02+/-0.35 and 21.40+/-0.58 (t = 24.728, P = 0.000), respectively, suggesting that the expression of MDM2 protein was inhibited in ATRA-treated SHG-44 cells. Moreover, the percentages of MDM2-positive protein were 24.00% (6/25) and 56.52% (13/23) (chi(2) = 5.298, P = 0.021) in WHO grade II and grade IV astrocytomas, respectively, suggesting that the expression of MDM2 protein may increase along with the elevation of astrocytoma malignancy. CONCLUSION: ATRA can inhibit MDM2 gene expression in SHG-44 cells, and MDM2 is related to astrocytoma progression.