Prognostic value of FGFR2 alterations in patients with iCCA undergoing surgery or systemic treatments: A meta-analysis.

BACKGROUND: Over recent years, there has been a notable rise in the incidence of intrahepatic cholangiocarcinoma (iCCA), which presents a significant challenge in treatment due to its complex disease characteristics and prognosis. Notably, the identification of fibroblast growth factor receptor 2 (FGFR2) fusion/rearrangement, a potential oncogenic driver primarily observed in iCCA, raises questions about its impact on the prognostic outcomes of patients undergoing surgical intervention or other therapeutic approaches. METHODS: A comprehensive search from inception to July 2023 was conducted across PubMed, Embase, Web of Science, and the Cochrane Library databases. The objective was to identify relevant publications comparing the prognosis of FGFR2 alterations and no FGFR2 alterations groups among patients with iCCA undergoing surgical resection or other systemic therapies. The primary outcome indicators, specifically Overall Survival (OS) and Disease-Free Survival (DFS), were estimated using Hazard Ratios (HRs) with 95% confidence intervals (CIs), and statistical significance was defined as p < .05. Study quality was assessed using the Newcastle-Ottawa Quality Assessment Scale. Statistical analyses were performed using Review Manager 5.4 software and Stata, version 12.0. RESULTS: Six studies, involving 1314 patients (FGFR2 alterations group n = 173 and no FGFR2 alterations group n = 1141), were included in the meta-analysis. The analysis revealed that the FGFR2 alterations group exhibited a significantly better OS prognosis compared to the no FGFR2 alterations group, with a fixed-effects combined effect size HR = 1.31, 95%CI = 1.001-1.715, p = .049. Furthermore, meta-regression and subgroup analysis showed that the length of the follow-up period did not introduce heterogeneity into the results. This finding indicates the stability and reliability of the study outcomes. CONCLUSION: The current study provides compelling evidence that FGFR2 alterations are frequently associated with improved survival outcomes for patients with iCCA undergoing surgical resection or other systemic treatments. Additionally, the study suggests that FGFR2 holds promise as a safe and dependable therapeutic target for managing metastatic, locally advanced or unresectable iCCA. This study offers a novel perspective in the realm of targeted therapy for iCCA, presenting a new and innovative approach to its treatment.

Ferritin Light Chain (FTL) competes with long noncoding RNA Linc00467 for miR-133b binding site to regulate chemoresistance and metastasis of colorectal cancer.

Although the colorectal cancer (CRC) mortality rates are decreasing in virtue of CRC screening and improved therapeutic methods, CRC is still a leading cause of cancer deaths. One of the main causes is chemoresistance occurrence in CRC. Understanding of the molecular mechanisms of chemoresistance benefits to CRC diagnosis and treatment. In this study, gene expression was determined by western blot and qRT-PCR. The biological functions of genes in CRC cells were studied by knocking down or overexpressing the gene in CRC cells and then analyzing cell sensitivity to 5-Fu by the MTT assay and the flow cytometry, and analyzing cell migration and invasion by transwell assays. The luciferase reporter assay was used to examine microRNA regulation of target gene expression, and biotin pull-down assay was performed to detect interaction between RNA molecules. This study found that ferritin light chain (FTL) and long intergenic noncoding RNA Linc00467 were both upregulated in CRC tissues and cell lines, and inversely correlated to CRC patient survival. FTL and Linc00467 promoted CRC cells abilities to resistance against 5-fluor-ouracil (5-Fu), migration and invasion. These effects were compromised by miR-133b which targeted both FTL and Linc00467. miR-133b interacted with Linc00467 and miR-133b inhibitor prevented Linc00467 knockdown-induced alternations of FTL expression and biological functions. Both FTL and Linc00467 are oncogenes in CRC. FTL expression upregulated in CRC via Linc00467/ miR-133b axis, and leads to CRC cell resistance against 5-FU treatment and promotes CRC metastasis. FTL expression upregulated in CRC via Linc00467/miR-133b axis, and leads to CRC cell resistance to 5-FU treatment and promotes CRC metastasis.

Highly sensitive, label-free and real-time detection of alpha-fetoprotein using a silicon nanowire biosensor.

Alpha-fetoprotein (AFP) is a tumor-associated fetal protein that can be expressed in large amounts in adult tumor cells, serving as a useful clinical tumor-marker. Silicon nanowire (SiNW) biosensors have emerged as a powerful tool in detecting protein biomarkers, due to their ultrahigh sensitivity, real-time response and label-free detection. We fabricated a SiNW-based field-effect transistor (FET) according to "top-down" methodology. First, anti-AFP antibodies were immobilized onto the surface of the SiNW-FET. A polydimethylsiloxane (PDMS) microchannel was then integrated to the modified SiNW-FET. Various concentrations of AFP were then pumped through the sensing area. We observed a current change that corresponded to binding of AFP onto the surface of our anti-AFP functionalized SiNW-FET biosensor. Concentrations of AFP as low as 0.1 ng/mL were detected. The results implicate our SiNW biosensor as an effective AFP biomarker detector with promising potential in clinical applications.

Simultaneous Detection of α-Fetoprotein and Carcinoembryonic Antigen Based on Si Nanowire Field-Effect Transistors.

Primary hepatic carcinoma (PHC) is one of the most common malignancies worldwide, resulting in death within six to 20 months. The survival rate can be improved by effective treatments when diagnosed at an early stage. The α-fetoprotein (AFP) and carcinoembryonic antigen (CEA) have been identified as markers that are expressed at higher levels in PHC patients. In this study, we employed silicon nanowire field-effect transistors (SiNW-FETs) with polydimethylsiloxane (PDMS) microfluidic channels to simultaneously detect AFP and CEA in desalted human serum. Dual-channel PDMS was first utilized for the selective modification of AFP and CEA antibodies on SiNWs, while single-channel PDMS offers faster and more sensitive detection of AFP and CEA in serum. During the SiNW modification process, 0.1% BSA was utilized to minimize nonspecific protein binding from serum. The linear dynamic ranges for the AFP and CEA detection were measured to be 500 fg/mL to 50 ng/mL and 50 fg/mL to 10 ng/mL, respectively. Our work demonstrates the promising potential of fabricated SiNW-FETs as a direct detection kit for multiple tumor markers in serum; therefore, it provides a chance for early stage diagnose and, hence, more effective treatments for PHC patients.

Effect of indocyanine green near-infrared light imaging technique guided lymph node dissection on short-term clinical efficacy of minimally invasive radical gastric cancer surgery: a meta-analysis.

Objective: In recent years, the utilization of indocyanine green near-infrared (ICG NIR) light imaging-guided lymph node dissection in the context of minimally invasive radical gastric cancer has emerged as a novel avenue for investigation. The objective of this study was to assess the influence of employing this technique for guiding lymph node dissection on the short-term clinical outcomes of minimally invasive radical gastric cancer surgery. Methods: The present study conducted a comprehensive search for short-term clinical outcomes, comparing the group undergoing ICG NIR light imaging-guided lymph node dissection with the control group, by thoroughly examining relevant literature from the inception to July 2023 in renowned databases such as PubMed, Embase, Web of Science, and Cochrane Library. The primary endpoints encompassed postoperative complications, including abdominal infection, abdominal bleeding, pneumonia, anastomotic fistula, and overall incidence of complications (defined as any morbidity categorized as Clavien-Dindo class I or higher within 30 days post-surgery or during hospitalization). Additionally, secondary outcome measures consisted of the time interval until the initiation of postoperative gas and food intake, as well as various other parameters, namely postoperative hospital stay, operative time, intraoperative blood loss, total number of harvested lymph nodes, and the number of harvested metastatic lymph nodes. To ensure methodological rigor, the Cochrane Collaboration Risk of Bias Tool and the Newcastle-Ottawa Scale (NOS) were employed to assess the quality of the included studies, while statistical analyses were performed using Review Manager 5.4 software and Stata, version 12.0 software. Results: A total of 19 studies including 3103 patients were ultimately included (n=1276 in the ICG group and n=1827 in the non-ICG group). In this meta-analysis, the application of ICG near-infrared light imaging in minimally invasive radical gastric cancer surgery effectively improved the occurrence of postoperative Clavien-Dindo grade II or higher complications in patients (RR=0.72, 95% CI 0.52 to 1.00) with a statistically significant P=0.05; in reducing intraoperative blood loss and shortening While reducing intraoperative blood loss and shortening postoperative hospital stay, it could ensure the thoroughness of lymph node dissection in minimally invasive radical gastric cancer surgery (MD=5.575, 95% CI 3.677-7.473) with significant effect size (Z=5.76, p<0.00001). Conclusion: The utilization of indocyanine green near-infrared light imaging technology in the context of minimally invasive radical gastric cancer surgery demonstrates notable efficacy in mitigating the occurrence of postoperative complications surpassing Clavien-Dindo grade II, while concurrently augmenting both the overall quantity of lymph node dissections and the identification of positive lymph nodes, all the while ensuring the preservation of surgical safety. Furthermore, the implementation of this technique proves particularly advantageous in the realm of robotic-assisted radical gastric cancer surgery, thus bearing significance for enhancing the short-term prognostic outcomes of patients.

Inhibition of indoleamine 2,3-dioxygenase 1 synergizes with oxaliplatin for efficient colorectal cancer therapy.

We investigated the immunogenic cell death provoked by oxaliplatin (OXA) and the involvement of OXA-induced immunosuppression in colorectal cancer. Immune-proficient or -deficient mice were employed to evaluate the therapeutic effects of OXA. Immunogenic cell death was characterized by cell-surface calreticulin, cytosol-translocated high migration rate group protein B1 (HMGB1), and secretory ATP content. Bone marrow-derived dendritic cell (BMDC) maturation and CD8+ T cell expansion were measured by flow cytometry. Expression of immunosuppressive genes was quantified by both RT-PCR and western blots. The proliferative and apoptotic indexes of xenograft tumors were evaluated by immunohistochemistry and TUNEL assays, respectively. The secretory cytokines were measured with ELISA. OXA induced immunogenic cell death of murine colorectal cancer, which greatly depended on the host immune response. OXA-pretreated CT26 cells promoted BMDC maturation and CD8+ T cell expansion. OXA significantly upregulated indoleamine 2,3-dioxygenase 1 (IDO1) in patient-derived colorectal cancer cells and in combination with the IDO1-specific inhibitor, NLG919, suppressed tumor progression. Simultaneous administration with both OXA and NLG919 greatly promoted CD8+ T cell infiltration and decreased immunosuppressive cytokine transforming growth factor ß (TGF-ß) production, whereas increased immunostimulatory cytokines interleukin (IL)-12p70 and interferon (IFN)-γ. We demonstrated the upregulation of IDO1 by OXA, which combined with the IDO1 inhibitor, tremendously potentiated therapeutic effects of OXA against colorectal cancer.

Long Non-coding RNA SENP3-EIF4A1 Functions as a Sponge of miR-195-5p to Drive Triple-Negative Breast Cancer Progress by Overexpressing CCNE1.

Triple-negative breast cancer (TNBC) has high malignancy and limited treatment, so novel molecular therapeutic targets are urgently needed. Cyclin E1 (CCNE1) promotes progression in breast cancer, but its role and inherent mechanisms in TNBC are yet to be elucidated. Competing endogenous RNA (ceRNA) may be a potential mechanism. CCNE1 was selected though bioinformatics and clinical samples, and cell lines were utilized to verify CCNE1 expression by qRT-PCR and western blot. Predicting tools provided potential miR-195-5p and SENP3-EIF4A1 and tested from multilevel. Functional experiments were conducted in vitro and in vivo. Luciferase reporter assay and RNA immunoprecipitation experiments were implemented to ensure the interaction between miR-195-5p and SENP3-EIF4A1/CCNE1 in TNBC. Bioinformatics found DNA hypermethylation of miR-195-5p and preliminarily verified. Mechanistically, SENP3-EIF4A1-miR-195-5p-associated ceRNA could drive TNBC progress though regulating CCNE1. DNA hypermethylation of miR-195-5p might be another reason. In summary, SENP3-EIF4A1-miR-195-5p-CCNE1 axis promotes TNBC progress and may contribute to the novel diagnosis and treatment of TNBC.

Correction: High-throughput cell focusing and separation via acoustofluidic tweezers.

Correction for 'High-throughput cell focusing and separation via acoustofluidic tweezers' by Mengxi Wu et al., Lab Chip, 2018, 18, 3003-3010, DOI: .

Circ-SMARCA5 suppresses colorectal cancer progression via downregulating miR-39-3p and upregulating ARID4B.

BACKGROUND: Circular RNAs are crucial in tumorigenesis. However, little is known about their functions in colorectal cancer (CRC). Circ-SMARCA5 was found to be an oncogene or tumor suppresser in different types of cancers, but its exact role in CRC remains unknown. Here, we aim to identify the role of circ-SMARCA5 in CRC development. METHODS: Circ-SMARCA5 expression was determined by qRT-PCR. CRC cell proliferation, migration, and invasion were detected by CCK-8, wound healing, and Transwell assays, respectively. Bioinformatics analysis was performed to predict target genes. The interaction of microRNA (miR) with circ-SMARCA5 or target genes was detected using luciferase reporter assay. Xenograft model was established to determine the effect of circ-SMARCA5 on CRC tumor growth in vivo. RESULTS: Circ-SMARCA5 expression was dramatically decreased in CRC cell lines and tissues. Circ-SMARCA5 overexpression inhibited CRC cell proliferation, migration and invasion. MiR-93-3p was predicted as a target of circ-SMARCA5 and its overexpression attenuated the anti-tumor effect of circ-SMARCA5 on CRC cells. Furthermore, we predicted AT-rich interaction domain 4B (ARID4B) as the target of miR-39-3p. Functional analysis showed that circ-SMARCA5 upregulated ARID4B expression via miR-39-3p. Additionally, in vivo studies demonstrated that circ-SMARCA5 suppressed CRC tumor progression. CONCLUSION: Circ-SMARCA5 functions as a tumor suppressor by upregulating ARID4B expression via sponging miR-39-3p, and thereby inhibited CRC progression.

MiR-4319 suppresses colorectal cancer progression by targeting ABTB1.

Background: Colorectal cancer is one of the highly malignant cancers with a poor prognosis. The exact mechanism of colorectal cancer progression is not completely known. Recently, microRNAs (miRNAs, miRs) were suggested to participate in the regulation of multiple cancer development, including colorectal cancer. Methods: MiR-4319 expression in colorectal cancer patient samples was detected by real-time polymerase chain reaction. MiR-4319 was knocked down in the colorectal cancer cells by siRNA transfection to study the role of miR-4319 in the cell cycle and proliferation of colorectal cancer cells. Results: MiR-4319 expression was found to be inverse correlated with survival in colorectal cancer patients. Overexpression of miR-4319 markedly reduced the proliferation of colorectal cancer cells and altered cell cycle distribution. A further experiment showed that ABTB1 is the target gene of miR-4319. MiR-4319 was regulated by PLZF. Conclusion: Our studies indicated that reduced expression of miR-4319 was correlated with poor prognosis in colorectal cancer patients; miR-4319 also suppressed colorectal cancer cell proliferation by targeting ABTB1. ABTB1 might become an excellent therapeutic target for colorectal cancer treatment.

A new biosensor detection system to overcome the Debye screening effect: dialysis-silicon nanowire field effect transistor.

Background: A silicon nanowire field effect transistor biosensor has four advantages in the detection of small biomolecules. It is mark-free, immediately responsive, highly sensitive, and specific. However, because of environments with a high salt concentration, the Debye screening effect has been a major issue in biological detection. Objective: To overcome Debye screening effect, realize the clinical application of silicon nanowire field effect transistor and verify its specificity and sensitivity. Materials and methods: The test solution was desalted by miniature blood dialyzer, and then the tumor markers were detected by silicon nanowire field effect transistor. Results: Tumor markers in serum were detected successfully and their sensitivity and specificity were verified. Conclusion: This method was found to effectively promote the development of semiconductor materials in biological solution detection.

High-throughput cell focusing and separation via acoustofluidic tweezers.

Separation of particles and cells is an important function in many biological and biomedical protocols. Although a variety of microfluidic-based techniques have been developed so far, there is clearly still a demand for a precise, fast, and biocompatible method for separation of microparticles and cells. By combining acoustics and hydrodynamics, we have developed a method which we integrated into three-dimensional acoustofluidic tweezers (3D-AFT) to rapidly and efficiently separate microparticles and cells into multiple high-purity fractions. Compared with other acoustophoresis methods, this 3D-AFT method significantly increases the throughput by an order of magnitude, is label-free and gently handles the sorted cells. We demonstrate not only the separation of 10, 12, and 15 micron particles at a throughput up to 500 µl min-1 using this 3D-AFT method, but also the separation of erythrocytes, leukocytes, and cancer cells. This 3D-AFT method is able to meet various separation demands thus offering a viable alternative with potential for clinical applications.

Change of precipitation characteristics in the water-wind erosion crisscross region on the Loess Plateau, China, from 1958 to 2015.

Precipitation plays an important and crucial role in processes in the water-wind erosion crisscross region of the Loess Plateau than in other parts of the region. We analyzed precipitation data and standardized precipitation index (SPI) at 14 representative synoptic stations from 1958 to 2015 used trend-free prewhitening, linear trend estimation, Spearman's rho test, the Mann-Kendall trend test, the Mann-Kendall abrupt change test and rescaled range analysis. The following conclusions were drawn. First, the analysis of monthly precipitation at all stations suggested that precipitation during the rainy season (July, August, September), especially rain in July and August, exhibited a general decreasing trend, while both increasing and decreasing trends were observed in other months. Moreover, the annual precipitation of all stations continued to exhibit decreasing trends except Wuzhai. Erosive rainfall frequency in the rainy season and the annual scale was weakly reduced but erosive force of single rainfall has been enhanced. Second, the SPI exhibited different increasing degrees in winter, while decreasing trends were observed in other seasons. Additionally, the annual-scale SPI at most stations exhibited a stable and sustained downward trend. Therefore, this region is currently associated with a drought trend, and the drought degree will likely continue to increase.

Nonlocal Effects and Slip Heat Flow in Nanolayers.

Guyer-Krumhansl (G-K) equation is a promising macroscopic model to explore heat transport in nanoscale. In the present work, a new nonlocal characteristic length is proposed by considering the effects of heat carriers-boundaries interactions to modify the nonlocal term in G-K equation, and a slip heat flux boundary condition is developed based on the local mean free path of heat carriers. Then an analytical solution for heat flux across 2-D nanolayers and an in-plane thermal conductivity model are obtained based on the modified G-K equation and the slip heat flux boundary. The predictions of the present work are in good agreement with our numerical results of direct simulation Monte Carlo (DSMC) for argon gas nanolayer and the available experimental data for silicon thin layers. The results of this work may provide theoretical support for actual applications of G-K equation in predicting the thermal transport properties of nanolayers.

Climatic and drought characteristics in the loess hilly-gully region of China from 1957 to 2014.

The loess hilly-gully region is a focus region of the "Grain for Green" program in China. Drought is the main problem in the study region. Precipitation and temperature are two indicators that directly characterize climatic drought. A thorough analysis of the precipitation, temperature and drought characteristics of the loess hilly-gully region can clarify the current water and heat conditions in the region to improve regional water resource management and provide a reliable reference for effectively improving water use efficiency. In this study, we fully analyzed the precipitation and temperature characteristics at 11 representative synoptic stations in the loess hilly-gully region over the period from 1957 to 2014 using a combination of trend-free pre-whitening, linear trend estimation, Spearman's rho test, the Mann-Kendall (M-K) trend and abrupt change tests and wavelet analysis. The standardized precipitation evapotranspiration index was calculated and analyzed on different time scales. The following conclusions were drawn: (1) There were significant spatial differences and inter-annual variations in precipitation at the 11 synoptic stations in the study area between 1957 and 2014; the precipitation consistently decreased with fluctuations, and the extent of the decrease varied from a maximum of 17.74 mm/decade to a minimum of 2.92 mm/decade. Except for the downward trends of the autumn and winter mean temperatures at Hequ, the seasonal and annual mean temperatures at the stations showed upward trends, including highly significant upward trends. (2) Alternating drought and wetness occurred in the study area; the wet period mainly appeared in the 1960s, and the main dry period lasted from the late 20th century to 2012. There were fewer dry and wet years than normal years; however, the study area still showed a drying trend, and the severity of the drought was increasing. (3) The annual precipitation and annual mean temperature showed marked cyclical fluctuations at each synoptic station, and the first primary cycle was approximately 28 years. The seasonal precipitation and seasonal temperature showed different cycle lengths; the seasonal cycles of precipitation for spring, summer, autumn and winter were 10, 28, 10 and 26 years long, respectively, and the cycles of the temperature fluctuations for all four seasons were approximately 28 years long.

Obese donor mice splenocytes aggravated the pathogenesis of acute graft-versus-host disease via regulating differentiation of Tregs and CD4+ T cell induced-type I inflammation.

Acute graft-versus-host disease (aGVHD) remains one of the most severe complications in organ and bone marrow transplantation, leading to much morbidity and mortality. Obesity has been associated with increased risk of development of various inflammatory diseases. Here, we investigated the in vitro and in vivo effects of obese donor splenocytes on the development of acute graft-versus-host disease (aGVHD). In this study, mixed lymphocyte reactions (MLR) in vitro showed that obese donor mouse CD4+ T cell promoted the production of interleukin-2 (IL-2), interferon (IFN)-γ and tumor necrosis factor (TNF)-α. Meanwhile, the inducible Tregs population decreased greatly in obese donor mouse CD4+ T cells' induction group, compared with normal group. Then in the murine aGVHD model, we found that obese donor splenocytes dramatically increased the severity of aGVHD through down-regulating immune tolerance while enhancing systemic and local immunity. Moreover, we showed that aGVHD induced by obese donors resulted in massive expansion of donor CD3+ T cells, release of Th1-related cytokines, interleukin-17 (IL-17) and chemokines, significant increase of Th17 cells and inhibition of CD4+CD25+Foxp3+ regulatory T cells (Tregs) and impaired suppressive ability of donor Tregs. Expression of sphingosine-1-phosphate receptor 1 (S1PR1), phosphorylated Akt, mammalian target of rapamycin (mTOR) and Raptor increased, while the phosphorylation level of SMAD3 was decreased in the skin, intestine, lung and liver from obese donor splenocytes-treated aGVHD mice. Furthermore, at mRNA and protein levels, we defined several molecules that may account for the enhanced ability of obese donor splenocytes to migrate into target organs, such as IL-2, IL-17, IFN-γ, TNF-α, CXCR3, CXCL9, CXCL10, CXCL11 and CCL3. Therefore, these results imply that obese donor cells may be related to the risk of aGVHD and helping obese donor individuals lose weight represent a compulsory clinical strategy before implementing transplantation to control aGVHD of recipients.

Chitinase 3-Like-1-Deficient Splenocytes Deteriorated the Pathogenesis of Acute Graft-Versus-Host Disease via Regulating Differentiation of Tfh Cells.

Acute graft-versus-host disease (aGVHD) is an intractable complication in transplant patients, limiting the efficacy of this therapy. Chitinase 3-like-1 (CHI3L1), a member of the glycosyl hydrolase 18 family that lacks chitinase activity, plays a critical role in a variety of inflammatory diseases. Here, we investigated the in vitro and in vivo effects of CHI3L1 on the development of aGVHD. In this study, mixed lymphocyte reactions (MLR) in vitro showed that CHI3L1 deficiency in CD4+ T cell promoted the production of interferon (IFN)-γ and T follicular helper (Tfh)-related cytokines such as interleukin-6 (IL-6) and interleukin-21 (IL-21). Meanwhile, the inducible Tfh cell population increased remarkably in CHI3L1-KO CD4+ T cells' induction group, compared with WT group. Then, in the murine acute GVHD model, we found that CHI3L1 deficiency in donor splenocytes dramatically increased the severity of aGVHD through enhancing Tfh cell differentiation. Moreover, at mRNA and protein levels, we defined several molecules that may account for the enhanced ability of CHI3L1-KO splenocytes to migrate into target organs and produce IFN-γ and Tfh-related cytokines and chemokines, such as IL-6, IL-21, and CXCL13. Expression of inducible co-stimulator (ICOS) and B cell lymphoma 6 (Bcl6) increased in the skin, the intestine, the lung, and the liver from CHI3L1-KO splenocyte-treated aGVHD mice. Therefore, these results strongly imply that CHI3L1 levels in donor cells may be related to the risk of aGVHD and targeting CHI3L1 represents a novel therapeutic strategy for controlling aGVHD progression.

Top-down nanofabrication of silicon nanoribbon field effect transistor (Si-NR FET) for carcinoembryonic antigen detection.

Sensitive and quantitative detection of tumor markers is highly required in the clinic for cancer diagnosis and consequent treatment. A field-effect transistor-based (FET-based) nanobiosensor emerges with characteristics of being label-free, real-time, having high sensitivity, and providing direct electrical readout for detection of biomarkers. In this paper, a top-down approach is proposed and implemented to fulfill a novel silicon nano-ribbon FET, which acts as biomarker sensor for future clinical application. Compared with the bottom-up approach, a top-down fabrication approach can confine width and length of the silicon FET precisely to control its electrical properties. The silicon nanoribbon (Si-NR) transistor is fabricated on a Silicon-on-Insulator (SOI) substrate by a top-down approach with complementary metal oxide semiconductor (CMOS)-compatible technology. After the preparation, the surface of Si-NR is functionalized with 3-aminopropyltriethoxysilane (APTES). Glutaraldehyde is utilized to bind the amino terminals of APTES and antibody on the surface. Finally, a microfluidic channel is integrated on the top of the device, acting as a flowing channel for the carcinoembryonic antigen (CEA) solution. The Si-NR FET is 120 nm in width and 25 nm in height, with ambipolar electrical characteristics. A logarithmic relationship between the changing ratio of the current and the CEA concentration is measured in the range of 0.1-100 ng/mL. The sensitivity of detection is measured as 10 pg/mL. The top-down fabricated biochip shows feasibility in direct detecting of CEA with the benefits of real-time, low cost, and high sensitivity as a promising biosensor for tumor early diagnosis.

Chitinase 3-like-1 deficient donor splenocytes accentuated the pathogenesis of acute graft-versus-host diseases through regulating T cell expansion and type I inflammation.

Acute graft-versus-host disease (aGVHD) is a major complication following transplantation, limiting the success of this therapy. Chitinase 3-like-1 (CHI3L1), a member of the glycosyl hydrolase 18 family, plays a critical role in bacterial infections, allergic disease and a variety of malignancies. Here, we investigated whether CHI3L1 could affect the pathogenesis of aGVHD in a mouse allo-HCT model. In this study, we show that CHI3L1 deficiency in donor T cells increased the severity of aGVHD through enhancing systemic and local inflammation. In addition, we found that aGVHD induced by CHI3L1-knockout (CHI3L1-KO) donors resulted in massive expansion of donor CD3+ T cells, release of Th1-related cytokines and chemokines, and significant inhibition of CD4+CD25+Foxp3+ regulatory T cells (Tregs) without changing the suppressive ability of donor Tregs remarkably. Expression of PERK1/2 and PAkt increased both in the skin and intestine from CHI3L1-KO splenocytes-treated aGVHD mice. Moreover, at mRNA and protein levels, we defined several molecules that may account for the enhanced ability of CHI3L1-KO splenocytes to migrate into target organs and produce Th1-related cytokines and chemokines, such as CXCL9, CXCL11, IFN-γ and TNF-α. Therefore, these results imply that CHI3L1 levels in donor cells may be related to the risk of aGVHD and targeting CHI3L1 may be a promising clinical strategy to control aGVHD.

Study on Unit Cell Models and the Effective Thermal Conductivities of Silica Aerogel.

In this paper, two modified unit cell models, truncated octahedron and cubic array of intersecting square rods with 45-degree rotation, are developed in consideration of the tortuous path of heat conduction in solid skeleton of silica aerogel. The heat conduction is analyzed for each model and the expressions of effective thermal conductivity of the modified unit cell models are derived. Considering the random microstructure of silica aerogel, the probability model is presented. We also discuss the effect of the thermal conductivity of aerogel backbone. The effective thermal conductivities calculated by the proposed probability model are in good agreement with available experimental data when the density of the aerogel is 110 kg/m3.