T-Cell-Based Platform for Functional Screening of T-Cell Receptors Identified in Single-Cell RNA Sequencing Data Sets of Tumor-Infiltrating T-Cells.

The advent of single-cell RNA sequencing (scRNAseq) has enabled in-depth gene expression analysis of several thousand cells isolated from tissues. We recently reported the application of scRNAseq toward the dissection of the tumor-infiltrating T-cell repertoire in human pancreatic cancer samples. In this study, we demonstrated that combined whole transcriptome and T-cell receptor (TCR) sequencing provides an effective way to identify tumor-reactive TCR clonotypes on the basis of gene expression signatures.

Characterization of sub-nanosecond pulse compression based on frequency-detuning SBS.

High-frequency, high-power picosecond lasers have important and wide-ranging applications in laser ranging, optoelectronic countermeasures, and ultrafine industrial processing. Pulse compression based on stimulated Brillouin scattering (SBS) can achieve a highly efficient picosecond laser output, while improving the peak power and beam quality of the laser. In this paper, a generator-amplifier two-cell structure with frequency-detuning was proposed to achieve a pulse output that combines high compression ratio and high energy reflectivity.

Transcriptome-based identification of tumor-reactive and bystander CD8 T cell receptor clonotypes in human pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is generally refractory to immune checkpoint blockade, although patients with genetically unstable tumors can show modest therapeutic benefit. We previously demonstrated the presence of tumor-reactive CD8 T cells in PDAC samples. Here, we charted the tumor-infiltrating T cell repertoire in PDAC by combining single-cell transcriptomics with functional testing of T cell receptors (TCRs) for reactivity against autologous tumor cells.

ROTACs leverage signaling-incompetent R-spondin for targeted protein degradation.

Proteolysis-targeting chimeras (PROTACs) are an emerging technology for therapeutic intervention, but options to target cell surface proteins and receptors remain limited. Here we introduce ROTACs, bispecific WNT- and BMP-signaling-disabled R-spondin (RSPO) chimeras, which leverage the specificity of these stem cell growth factors for ZNRF3/RNF43 E3 transmembrane ligases, to target degradation of transmembrane proteins. As a proof-of-concept, we targeted the immune checkpoint protein, programmed death ligand 1 (PD-L1), a prominent cancer therapeutic target, with a bispecific RSPO2 chimera, R2PD1.

Discovery of a Series of 5-Amide-1-pyrazole-3-carboxyl Derivatives as Potent P2YR Antagonists with Anti-Inflammatory Characters.

UDPG/P2YR signaling pathway has been considered as a potential therapeutic target for innate immune system diseases. Based on the scaffold hopping strategy, a series of pyrazole analogues were designed and synthesized as novel P2YR antagonists with improved physicochemical properties, together with potential anti-inflammatory activities. Additionally, we designed and synthesized a fluorescent probe based on highly selective and potent PPTN to study the affinity of synthesized compounds.

High-repetition-rate, quarter acoustic wave oscillation period pulse compression using transient stimulated Brillouin scattering.

In this work we demonstrate the compression of laser pulses at a high repetition rate, using transient stimulated Brillouin scattering (SBS). Output pulses with pulse durations close to the quarter-acoustic wave oscillation period (τ) was obtained. We find that the primary factors which limit the compression of pulses under high repetition-rate, transient conditions are the inherently low gain in the transient regime, thermal accumulation within the SBS medium and optical breakdown.

Hyperglycemia Enhances Immunosuppression and Aerobic Glycolysis of Pancreatic Cancer Through Upregulating Bmi1-UPF1-HK2 Pathway.

Background & Aims: Accumulating evidence strongly suggests that hyperglycemia promotes the progression of pancreatic cancer (PC). Approximately 80% of patients with PC are intolerant to hyperglycemic conditions. In this study, we define the role of Bmi1, a stemness-related oncogene, in controlling the Warburg effect, and immune suppression under hyperglycemia conditions.

Point Adversarial Self-Mining: A Simple Method for Facial Expression Recognition.

In this article, we propose a simple yet effective approach, called point adversarial self mining (PASM), to improve the recognition accuracy in facial expression recognition (FER). Unlike previous works focusing on designing specific architectures or loss functions to solve this problem, PASM boosts the network capability by simulating human learning processes: providing updated learning materials and guidance from more capable teachers. Specifically, to generate new learning materials, PASM leverages a point adversarial attack method and a trained teacher network to locate the most informative position related to the target task, generating harder learning samples to refine the network.

Design, synthesis and evaluation of 3-amide-5-aryl benzoic acid derivatives as novel P2YR antagonists with potential high efficiency against acute gouty arthritis.

P2Y nucleotide receptor plays important roles in series of physiological and pathologic events especially associated with immune and inflammation. Based on the 3-amide benzoic acid scaffold reported by our group previously, a series of 5-aryl-3-amide benzoic acid derivatives were designed as novel P2Y antagonists with improved pharmacokinetic properties. Among which compound 11m showed most potent P2Y antagonizing activity with an IC value of 2.

Lymph node ratio predicts prognosis in patients with surgically resected invasive pancreatic cystic neoplasms.

Background: In current days, the prevalence of pancreatic cystic neoplasms (PCN) is on the rise. Lymph node ratio (LNR) has emerged as a promising prognostic factor in pancreatic adenocarcinoma (PDAC). However, the prognostic value of LNR in patients with invasive PCN remains unknown.

The mA-Related mRNA Signature Predicts the Prognosis of Pancreatic Cancer Patients.

N-methyladenosine (mA) has an important epitranscriptomic modification that controls cancer self-renewal and cell fate. The addition of mA to mRNA is a reversible modification. The deposition of mA is encoded by a methyltransferase complex involving three homologous factors, jargonized as "writers," "erasers," and "readers.

FBP1 binds to the bromodomain of BRD4 to inhibit pancreatic cancer progression.

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive tumour that is characteristically unresponsive to most chemotherapeutic regimens. Bromodomain and extra terminal domain (BET) inhibitors that specifically repress the function of BET family proteins, such as BRD4, are under evaluation in clinical trials for their activity in repressing cancer growth. However, resistance to BET inhibitors has hindered their further clinical application in pancreatic cancer.

FGD1 promotes tumor progression and regulates tumor immune response in osteosarcoma via inhibiting PTEN activity.

: Mesenchymal cell-derived osteosarcoma is a rare malignant bone tumor affecting children and adolescents. PTEN down-regulation or function-loss mutation is associated with the aggressive of osteosarcoma. Explicating the regulatory mechanism of PTEN might highlight new targets for improving the survival rate of osteosarcoma patients.

Using ESTIMATE algorithm to establish an 8-mRNA signature prognosis prediction system and identify immunocyte infiltration-related genes in Pancreatic adenocarcinoma.

Objective: The tumour microenvironment is one of the significant factors driving the carcinogenesis of Pancreatic adenocarcinoma (PAAD). However, the underlying mechanism of how the tumour microenvironment impacts the prognosis of PAAD is not completely clear.

Results: The transcriptome and clinical data of 182 PAAD program cases were downloaded from the TCGA database.

The aberrant expression of ADAR1 promotes resistance to BET inhibitors in pancreatic cancer by stabilizing c-Myc.

Pancreatic cancer is a malignant tumor with the worst prognosis worldwide. This cancer type requires new insight to help with diagnosis and, eventually, treatment. Adenosine deaminases acting on RNA 1 (ADAR1) is reportedly overexpressed in many types of tumors, such as lung, liver, breast, and esophageal cancers.

Overexpressed ITGA2 promotes malignant tumor aggression by up-regulating PD-L1 expression through the activation of the STAT3 signaling pathway.

Background: Recent studies have reported that Integrin alpha 2 (ITGA2) plays an essential role in tumor cell proliferation, invasion, metastasis, and angiogenesis. An abnormally expressed ITGA2 correlates with unfavorable prognoses in multiple types of cancer. However, the specific mechanism of how ITGA2 contributes to tumorigenesis remains unclear.

Pulmonary papillary squamous cell carcinoma: a population-based analysis of incidence, treatment, and prognosis.

Background: Pulmonary papillary squamous cell carcinoma (PSCC) is a rare variant of pulmonary squamous cell carcinoma (SCC). This study aims to improve relevant understanding and demonstrate the incidence, treatment, and prognosis of pulmonary PSCC using a population-based database.

Methods: The Surveillance, Epidemiology and End Results (SEER) database was used to extract data of cases diagnosed with PSCC from 1973 to 2015 and analyze the incidence, treatment, and prognosis.

Intra-Ampullary Papillary-Tubular Neoplasm: A Population-Based Analysis.

BACKGROUND Intra-ampullary papillary-tubular neoplasm (IAPN) is recognized as a precancerous lesion with a great tendency to evolve into pancreatic cancer. The Surveillance, Epidemiology, and End Results (SEER) database is now large enough to study unusual cancers. Based on pathologic and epidemiologic characteristics of IAPN available in SEER, important clinicopathological correlations can be made.

Design, synthesis and anti-inflammatory evaluation of 3-amide benzoic acid derivatives as novel P2Y receptor antagonists.

The P2Y receptor (P2YR) plays a key role in the modulation of inflammatory process, but very few classes of antagonists have been reported. A series of 3-amide benzoic acid derivatives were identified as novel and potent P2YR antagonists. The most potent antagonist, 16c, showed comparable activity (IC = 1.

Colonic Gastrointestinal Stromal Tumor: A Population-Based Analysis of Incidence and Survival.

Objectives: The incidence of gastrointestinal stromal tumors (GISTs) located in the colon is rare. Current studies mainly focus on case reports for colonic GISTs. Therefore, a population-based analysis was useful to guide the clinical treatment strategy.

Prognostic accuracy of the serum lactate level, the SOFA score and the qSOFA score for mortality among adults with Sepsis.

Background: Sepsis is a common critical condition caused by the body's overwhelming response to certain infective agents. Many biomarkers, including the serum lactate level, have been used for sepsis diagnosis and guiding treatment. Recently, the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) recommended the Sequential Organ Failure Assessment (SOFA) and the quick SOFA (qSOFA) rather than lactate for screening sepsis and assess prognosis.

Tumor location as an indicator of survival in T1 resectable pancreatic ductal adenocarcinoma: a propensity score-matched analysis.

Background: The latest 8th edition of the AJCC staging system emphasizes the importance of tumor size however, the clinical significance of the combination of tumor location with tumor size remains unknown.

Methods: We conducted this study to investigate the prognostic role of tumor location in T1 resectable pancreatic ductal adenocarcinoma (PDAC). Resectable PDAC patients from Surveillance, Epidemiology, and End Results (SEER) database (2004-2014) were selected for the propensity score matching analysis.

Overexpressed histone acetyltransferase 1 regulates cancer immunity by increasing programmed death-ligand 1 expression in pancreatic cancer.

Background: Pancreatic ductal adenocarcinoma is one of the leading causes of cancer-related death worldwide. Immune checkpoint blockade therapy, including anti-PD-1 and anti-PD-L1, is a new therapeutic strategy for cancer treatment but the monotherapy with PD-L1 inhibitors for pancreatic cancer is almost ineffective for pancreatic cancer. Thus, exploring the regulatory mechanism of PD-L1 in cancer cells, especially in pancreatic cancer cells, is one of the key strategies to improving cancer patient response to PD-L1 blockade therapy.