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Backgrounds The inflammatory biomarker “C-reactive protein to albumin ratio (CAR)” has been reported to significantly correlate to a variety of human cancers. However, there are conflicting results regarding the prognostic value of CAR in colorectal cancer. Previous studies mainly assessed patients in Eastern countries, so their findings may not be applicable to the Western population. Therefore, this updated meta-analysis aimed to investigate the prognostic value of pre-treatment CAR and outcomes of patients with colorectal cancer. Methods We conducted a systematic search for eligible literature until October 31, 2020, using PubMed and Embase databases. Studies assessing pre-treatment CAR and outcomes of colorectal cancer were included. Outcome measures included overall survival, disease-free survival, progression-free survival, and clinicopathological features. The pooled hazard ratios (HR) with 95% confidence intervals (CI) were used as effective values. Results A total of 15 studies involving 6329 patients were included in this study. The pooled results indicated that a high pre-treatment CAR was associated with poor overall survival (HR 2.028, 95% CI 1.808−2.275, p < 0.001) and poor disease-free survival/progression-free survival (HR 1.768, 95% CI 1.321–2.365, p < 0.001). Subgroup analysis revealed a constant prognostic value of the pre-treatment CAR despite different study regions, sample size, cancer stage, treatment methods, or the cut-off value used. We also noted a correlation between high pre-treatment CAR and old age, male sex, colon cancer, advanced stage (III/IV), large tumor size, poor differentiation, elevated carcinoembryonic antigen levels, neutrophil-to-lymphocyte ratio, and the modified Glasgow prognostic score. Conclusions High pre-treatment CAR was associated with poor overall survival, disease-free survival, and progression-free survival in colorectal cancer. It can serve as a prognostic marker for colorectal cancer in clinical practice.

Being aware of global pandemics, this research focused on the potential infection routes in building drainage systems. Case studies have found that dysfunctional building drainage systems not only failed to block contaminants but also potentially became a route for the spreading of viruses. Several fluid simulations in pipelines were conducted in this research using COMSOL Multiphysics. In particular, virus transmission from one patient’s room to other uninfected residential units through pipelines was visualized. A 12-story building, which is commonly seen in the local area, was designed as a simulation model to visualize the transmission and analyze its hazards. Furthermore, five environmental factors were filtered out for discussion: distance, time span, pressure, initial concentration, and environment temperature. By manipulating these factors, the relationship between the factors and the behavior of the contaminant could be explored. In addition, a simulation with a different pipeline arrangement was included to observe the virus diffusion behavior under different scenarios. The visualized simulation concluded that the contaminant would spread through the drainage system and arrive at the neighboring four floors within an hour under the circumstances of a 12-story building with broken seals and constant pressure and contaminant supply on the seventh floor. Meanwhile, the whole building would be exposed to infection risks by the continuous virus spreading through a drainage system. Distance, time span, and pressure were considered critical factors that affected indoor contamination in the system. On the other hand, initial concentration and environmental temperature did not have significant roles. Visualizing the behavior of viruses provides a glimpse of what happens behind walls, paving the way for recognizing the importance of maintaining functional drainage systems for individuals’ health.

Immune checkpoint blockade therapy has revolutionized non-small cell lung cancer treatment. However, not all patients respond to this therapy. Assessing the tumor expression of immune checkpoint molecules, including programmed death-ligand 1 (PD-L1), is the current standard in predicting treatment response. However, the correlation between PD-L1 expression and anti-PD-1/PD-L1 treatment response is not perfect. This is partly caused by tumor heterogeneity and the common practice of assessing PD-L1 expression based on limited biopsy material. To overcome this problem, we developed a novel method that can make formalin-fixed, paraffin-embedded tissue translucent, allowing three-dimensional (3D) imaging. Our protocol can process tissues up to 150 μm in thickness, allowing anti-PD-L1 staining of the entire tissue and producing high resolution 3D images. Compared to a traditional 4 μm section, our 3D image provides 30 times more coverage of the specimen, assessing PD-L1 expression of approximately 10 times more cells. We further developed a computer-assisted PD-L1 quantitation method to analyze these images, and we found marked variation of PD-L1 expression in 3D. In 5 of 33 needle-biopsy-sized specimens (15.2%), the PD-L1 tumor proportion score (TPS) varied by greater than 10% at different depth levels. In 14 cases (42.4%), the TPS at different depth levels fell into different categories (< 1%, 1–49%, or ≥ 50%), which can potentially influence treatment decisions. Importantly, our technology permits recovery of the processed tissue for subsequent analysis, including histology examination, immunohistochemistry, and mutation analysis. In conclusion, our novel method has the potential to increase the accuracy of tumor PD-L1 expression assessment and enable precise deployment of cancer immunotherapy.

Unlike most ancient microRNAs, which conservatively target homologous genes across species, microRNA827 (miR827) targets two different types of SPX (SYG1/PHO81/XPR1)-domain-containing genes, NITROGEN LIMITATION ADAPTATION (NLA) and PHOSPHATE TRANSPORTER 5 (PHT5), in Arabidopsis thaliana and Oryza sativa to regulate phosphate (Pi) transport and storage, respectively. However, how miR827 shifted its target preference and its evolutionary history are unknown. Based on target prediction analysis, we found that in most angiosperms, miR827 conservatively targets PHT5 homologs, but in Brassicaceae and Cleomaceae it preferentially targets NLA homologs, and we provide evidence for the transition of target preference during Brassicales evolution. Intriguingly, we found a lineage-specific loss of the miR827-regulatory module in legumes. Analysis of miR827-mediated cleavage efficiency and the expression of PHT5 in A. thaliana indicated that accumulation of mutations in the target site and the exclusion of the target site by alternative transcriptional initiation eliminated PHT5 targeting by miR827. Here, we identified a transition of miR827 target preference during plant evolution and revealed the uniqueness of miR827-mediated regulation among conserved plant miRNAs. Despite the change in its target preference, upregulation of miR827 by Pi starvation and its role in regulating cellular Pi homeostasis were retained.

Background Early-stage colorectal cancer had excellent outcomes after curative resection, typically. However, a perplexing survival paradox between stage II and stage III was noted. This paradox could be influenced by the administration of routine postoperative adjuvant chemotherapy and the presence of high-risk factors in stage II CRC. The objective of the study was to investigate the influence of high-risk factors on patients with stage II CRC and assess the efficacy of oral tegafur/uracil (UFT) plus leucovorin as adjuvant chemotherapy for stage II CRC patients. Methods A retrospective study was conducted using propensity score matching at a single medical institution. A total of 1544 patients with stage II colorectal cancer who underwent radical surgery between January 2004 and January 2009 were included. The intervention used was tegafur/uracil plus leucovorin as adjuvant chemotherapy. The main outcome measures were disease-free survival and overall survival. Results After propensity score matching, 261 patients were included in three groups: no-treatment, half-year treatment, and one-year treatment. The clinical characteristics of each group tended to be more consistent. The Cox proportional hazard models showed that tegafur/uracil treatment or not was a significant independent factor for oncological outcome. Kaplan–Meier analysis also showed significantly better disease-free survival and overall survival. Further investigation revealed that tegafur/uracil duration was an independent factor for oncological outcome. While the survival curve did not reach statistical significance, the one-year UFT treatment group demonstrated the best treatment trend. Conclusions This study suggests that tegafur/uracil plus leucovorin is a feasible adjuvant chemotherapy regimen for patients with stage II colorectal cancer after curative surgical treatment. Prolonged tegafur/uracil plus leucovorin treatment for 12 months showed a trend towards better outcomes in patients with stage II colorectal cancer.

Two disastrous earthquakes, the M L 6.6 Guanshan and M L 6.8 Chihshang earthquakes, called the 0917 and 0918 events, respectively, occurred in the southern longitudinal valley (LV) of eastern Taiwan within a 17-h interval in 2022. In the present study, we document the observed strong ground motions and damage distributions and analyze the source properties of both events via broadband (0.2 ~ 10 Hz), near-field, strong-motion seismic records. The results of Empirical Green’s function (EGF) analysis reveal that the 0917 event ruptured to the south in a single strong-motion generation area (SMGA), with a size of 47.04 km 2 , and that the 0918 event ruptured to the north through two SMGAs, with a combined size of 80.16 km 2 . The SMGA models explain the observed velocity pulses that caused severe damage well. Using the source-scanning algorithm technique, we obtain the centroid locations of both events on the west-dipping Central Range Fault (CNF), indicating that the 0917 and 0918 events had southward directivity and northward directivity, respectively, which are consistent with the results from the EGF method. We summarize that the velocity pulses of both events could be attributed to rupture directivity, high stress drops, and shallow ruptures from the obtained SMGA(s). Combined with the findings of previous studies of moderate-to-large earthquakes occurring in the LV, seismic hazard assessment and mitigation are important because of the interaction between the west-dipping CNF and the east-dipping LV fault, especially for the shallow part above a depth of 10 km. Graphical Abstract

This study examined the relationship between radon ( 222 Rn) concentrations in seawater and crustal activity in the Yatsushiro Sea by investigating the submarine fault zone situated at the southern end of the Futagawa–Hinagu fault zone, activated by the 2016 Kumamoto earthquake (M7.3). We conducted an analysis of 222 Rn concentration in samples of bottom water just above the seafloor and pore water in sediments, utilizing multiple and piston cores from the Hakuho Maru Expedition KH18-3. The findings revealed significantly elevated 222 Rn concentrations in the central sites of the Yatsushiro Sea, coinciding with a high-stress field exhibiting dense active faults. Seismicity analysis revealed heightened moment release and a low b-value post the 2016 Kumamoto earthquake, indicative of increased seismic activity and the potential for substantial earthquakes in the Yatsushiro Sea vicinity. Our results indicate that heightened concentrations of 222 Rn in seawater can serve as an effective tracer for identifying and estimating submarine fault activities. Moreover, our research highlights the utility of 222 Rn concentrations in detecting active submarine faults and assessing their activity. It contributes to a comprehensive understanding of the potential for significant earthquakes in the Yatsushiro Sea in the future.

Patients with microsatellite instability‐high (MSI‐H) colorectal cancer (CRC) have high tumor mutation burden and tumor immunogenicity, exhibiting a higher response rate to immunotherapy and better survival. However, a portion of MSI‐H CRC patients still experience adverse disease outcomes. We aimed to identify the tumor‐autonomous regulators determining these heterogeneous clinical outcomes. The Cancer Genome Atlas (TCGA) dataset was used to identify regulators in MSI‐H CRC patients with unfavorable outcomes. Stable CRC tumor clones expressing targeted regulators were established to evaluate migratory and stemness properties, immune cell vulnerability, and cell‐in‐cell (CIC) structure formation. RNA‐sequencing (RNA‐seq) was used to identify enriched biological pathways in stable CRC tumor clones. Clinicopathological characterization of formalin‐fixed paraffin‐embedded (FFPE) MSI‐H CRC specimens was performed to explore the underlying mechanisms involved. We showed that cancer/testis antigen family 45 member A1 (CT45A1) expression was upregulated in MSI‐H CRC patients with poor survival outcomes. CT45A1‐expressing microsatellite stable (MSS) CRC cells showed enhanced migratory ability. However, CT45A1‐expressing MSI‐H CRC cells, but not MSS CRC cells, showed higher resistance to natural killer (NK) cell cytotoxicity and served as outer cells in homotypic CIC structures, preventing exogenous or therapeutic antibody access to inner CRC cells. Inactivating RHO‐ROCK/MLCK‐MLC2 signaling with small‐molecule inhibitors or short‐hairpin RNAs (shRNAs) targeting myosin light chain kinase (MYLK) abolished NK cell resistance and reduced the outer cell fate of CT45A1‐expressing MSI‐H CRC cells. In MSI‐H CRC patients, CT45A1‐positive tumors exhibited increased MLC2 phosphorylation, increased outer cell fate, and decreased survival. We demonstrated that CT45A1 potentiates the advanced progression of MSI‐H CRC, and targeting MLC2 phosphorylation may enhance immunotherapy efficacy in CT45A1‐positive MSI‐H CRC patients. CT45A1, a vital driver of the RHO‐ROCK/MLCK‐MLC2 signaling, is found to enhance cancer cell resistance to natural killer (NK) cell killing and generate a protective cell‐in‐cell (CIC) structure in microsatellite instability‐high (MSI‐H) colorectal cancer (CRC) cells. This structure shields the inner CT45A1 (Low) cancer cells from targeted antibody therapy and potentially subsequent antitumor immunity, thereby driving aggressive MSI‐H CRC outcomes.

Integrating two-dimensional (2D) layered materials with wide bandgap β-Ga 2 O 3 has unveiled impressive opportunities for exploring novel physics and device concepts. This study presents the epitaxial growth of 2D β-In 2 Se 3 /3D β-Ga 2 O 3 heterostructures on c-Sapphire substrates by plasma-assisted molecular beam epitaxy. Firstly, we employed a temperature-dependent two-step growth process to deposit Ga 2 O 3 and obtained a phase-pure ( 2 ¯ 01 ) β-Ga 2 O 3 film on c-Sapphire. Interestingly, the in-situ reflective high-energy electron diffraction (RHEED) patterns observed from this heterostructure revealed the in-plane ‘b’ lattice constant of β-Ga 2 O 3  ~ 3.038Å. In the next stage, for the first time, 2D In 2 Se 3 layers were epitaxially realized on 3D β-Ga 2 O 3 under varying substrate temperatures (T sub ) and Se/In flux ratios (R VI/III ). The deposited layers exhibited (00 l ) oriented β-In 2 Se 3 on ( 2 ¯ 01 ) β-Ga 2 O 3 /c-Sapphire with the epitaxial relationship of [ 11 2 ¯ 0 ] β-In 2 Se 3 || [010] β-Ga 2 O 3 and [ 10 1 ¯ 0 ] β-In 2 Se 3 || [102] β-Ga 2 O 3 as observed from the RHEED patterns. Also, the in-plane ‘a’ lattice constant of β-In 2 Se 3 was determined to be ~ 4.027Å. The single-phase β-In 2 Se 3 layers with improved structural and surface quality were achieved at a T sub  ~ 280 °C and R VI/III  ~ 18. The microstructural and detailed elemental analysis further confirmed the epitaxy of 2D layered β-In 2 Se 3 on 3D β-Ga 2 O 3 , a consequence of the quasi-van der Waals epitaxy. Furthermore, the β-Ga 2 O 3 with an optical bandgap (E g ) of ~ 5.04 eV (deep ultraviolet) when integrated with 2D β-In 2 Se 3 , E g  ~ 1.43eV (near infra-red) can reveal potential applications in the optoelectronic field.

Background: Titanium is commonly used for fracture fixation and is considered inert, but hypersensitivity reactions to titanium alloy still occur and are difficult to diagnose due to a lack of a universally accepted standard in post-orthopedic surgical patients, and other common diagnoses need to be differentiated. Case Presentation: This case report describes three patients with manifestations of allergic reactions to titanium-alloy implants after Open Reduction and Internal Fixation (ORIF) with Ti-6Al-4V plates. Three patients mainly presented with persistent localized dermatitis. During follow-up, radiographs confirmed bone unions, and there were no signs of purulent drainage, abscess formation, or systemic infection. Taken together, these findings reduce the possibility of fracture-related infection (FRI) and other etiologies. Conservative treatment was ineffective, and the patch test and histopathology in two patients respectively supported hypersensitivity reactions. After the implants were surgically removed, there were significant improvements in symptoms. Conclusion: Three cases of suspected titanium-alloy hypersensitivity were diagnosed by exclusion based on clinical history, laboratory results, and additional testing. The findings showed the importance of clinical history and the identification of signs and symptoms of allergic reactions, emphasizing the need for a standardized diagnostic process.