TRIM21 Promotes Tumor Growth and Gemcitabine Resistance in Pancreatic Cancer by Inhibiting EPHX1-Mediated Arachidonic Acid Metabolism.

Pancreatic cancer (PC) progresses rapidly, and gemcitabine-based chemotherapy has brought only limited efficacy. Identifying key drivers and therapeutic targets holds significant clinical value. In this study, through comprehensive analysis of multiple PC databases, this work identifies TRIM21 as a promising driver mediator.

Nab-paclitaxel plus S-1 followed by gemcitabine-oxaliplatin as first-line alternating sequential treatment of pancreatic ductal adenocarcinoma.

Background: Alternating sequential administration of drugs may be a promising approach to overcome chemotherapy resistance in advanced pancreatic ductal adenocarcinoma (PDAC).

Methods: This study was an open-label, single-arm, and prospective trial included patients with untreated advanced PDAC. They received 2 cycles of NS regimen (nab-paclitaxel:125 mg/m2, intravenously injected on days 1 and 8, plus S-1:40-60 mg, orally twice per day for 1-14 days) followed by 2 cycles of GemOx regimen (gemcitabine, intravenously injected on days 1 and 8, and oxaliplatin: 130 mg/m2, intravenously injected on day 1).

Electrochemical C-H Mono-/Multi-Bromination Regulation of -Sulfonylanilines on a Cost-Effective Carbon Fiber Electrode and Its Prospective Electroactive Molecule Screening.

Electrochemical C-H mono/multi-bromination regulation of -sulfonylanilines on the cost-effective CF electrode is described. This reaction proceeds smoothly under mild conditions with a broad substrate scope, affording diverse mono/multi-brominated anilines in moderate to good yields. Mechanism study reveals that this transformation involves anodic oxidation, aromatic electrophilic substitution, and deprotonation.

Clinical Manifestation, Risk Factors, and Immune Checkpoint Inhibitor Rechallenge of Checkpoint Inhibitor-Associated Pneumonitis in Patients With Lung Cancer.

Immune-related adverse effects can lead to damage to various systems of the body, checkpoint inhibitor-associated pneumonitis (CIP) is one of the potentially lethal immune-related adverse effects. However, evidence regarding the risk factors associated with CIP is limited. To timely and accurate identification and prompt treatment of CIP, understanding the risk factors for multimorbidity among diverse study populations becomes crucial.

VDR promotes pancreatic cancer progression in vivo by activating CCL20-mediated M2 polarization of tumor associated macrophage.

Background: Activation of VDR pathway was a promising anti-tumor therapy strategy. However, numerous clinical studies have demonstrated the effect of activating VDR is limited, which indicates that VDR plays a complex role in vivos.

Methods: We analyzed the TCGA database to examine the association between VDR expression and immune cell infiltration in pancreatic adenocarcinoma (PAAD).

The rare-earth yttrium induces cell apoptosis and autophagy in the male reproductive system through ROS-Ca-CamkII/Ampk axis.

China has the world's largest reserves of rare earth elements (REEs), but widespread mining and application of REEs has led to an increased risk of potential pollution. Yttrium (Y), the first heavy REEs to be discovered, poses a substantial threat to human health. Unfortunately, little attention has been given to the impact of Y on human reproductive health.

Effects of indoor temperature on office workers' performance: an experimental study based on subjective assessments, neurobehavioral tests, and physiological measurements.

Indoor temperature has a critical impact on the performance of office workers. This study aimed to evaluate the effect of indoor temperature on work performance through subjective assessments, neurobehavioral tests, and physiological measurements. The experiment was conducted in a controlled office environment.

New abietane and tigliane diterpenoids from the roots of and their cytotoxic activities.

Three new abietane and two new tigliane diterpenoids were isolated from the roots Their structures were elucidated by spectroscopic methods and quantum chemical calculation. Compounds and exhibited the inhibitory activities against human cancer cells HeLa and HepG2, with IC ranging from 3.54 to 11.

Effects of magnetic resonance imaging (MRI)-detected extramural vascular invasion (mrEMVI) and tumor deposits (TDs) on distant metastasis and long-term survival after surgery for stage III rectal cancer: a retrospective study grouped based on the relationship between the bottom of the tumor and peritoneal reflection.

Background: To evaluate the effect of magnetic resonance imaging (MRI)-detected extramural vascular invasion (mrEMVI) and tumor deposits (TDs) on distant metastasis and long-term survival after surgery for stage III rectal cancer based on the relationship between the bottom of the tumor and peritoneal reflection.

Methods: A retrospective study was performed on 694 patients who underwent radical resection for rectal cancer at the Harbin Medical University Tumor Hospital from October 2016 to October 2021. According to the surgical records, a new group was established based on the relationship between the lower end of the tumor and peritoneal reflection.

Chronic exposure to yttrium induced cell apoptosis in the testis by mediating Ca/IP3R1/CaMKII signaling.

Introduction: Environmental pollutants, such as rare earth elements, affect human health and particularly induce reproductive system injury. Yttrium (Y), one of the most widely used heavy rare earth elements, has been reported the cytotoxicity. However, the biological effects of Y in the human body are largely unknown.

DCLK1 Suppresses Tumor-Specific Cytotoxic T Lymphocyte Function Through Recruitment of MDSCs via the CXCL1-CXCR2 Axis.

Background & Aims: Gastrointestinal cancer stem cell marker doublecortin-like kinase (DCLK1) is strongly associated with poor outcomes in colorectal cancer (CRC). Although DCLK1's regulatory effect on the tumor immune microenvironment has been hypothesized, its mode of action has not been shown previously in vivo, which hampers the potential intervention based on this molecule for clinical practice.

Methods: To define the immunomodulatory mechanisms of DCLK1 in vivo, we generated DCLK1 tumor cells by Clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9 (Cas9) and developed subcutaneous and intestinal orthotopic transplantation tumor models.

A targetable MYBL2-ATAD2 axis governs cell proliferation in ovarian cancer.

The chromatin-modifying enzyme ATAD2 confers oncogenic competence and proliferative advantage in malignances. We previously identified ATAD2 as a marker and driver of cell proliferation in ovarian cancer (OC); however, the mechanisms whereby ATAD2 is regulated and involved in cell proliferation are still unclear. Here, we disclose that ATAD2 displays a classical G2/M gene signature, functioning to facilitate mitotic progression.

Prediction scores of postoperative liver metastasis and long-term survival of pancreatic head cancer based on the distance between the mesenteric vessels and tumor, preoperative serum carbohydrate antigen 19-9 level, and lymph node metastasis rate.

Background: The shortest distance between the superior mesenteric artery (SMA) or superior mesenteric vein (SMV) and the tumor margin was combined with preoperative serum carbohydrate antigen (CA) 19-9 and lymph node ratio (LNR) to evaluate joint effects on long-term survival and liver metastasis in patients with pancreatic head cancer after radical surgery.

Methods: This retrospective study included 149 patients who underwent pancreaticoduodenectomy for pancreatic head cancer at Harbin Medical University Tumor Hospital from May 2011 to March 2021. The preoperative serum CA 19-9 level and LNR were combined with the SMA or SMV distance.

Facile purification of active recombinant mouse cytosolic carboxypeptidase 6 from Escherichia coli.

CCP6 is a member of cytosolic carboxypeptidases (CCPs) family, an eraser of a reversible protein posttranslational modification - polyglutamylation, and represents a potential therapeutic target. Currently, production of CCPs mainly depends on eukaryotic expression system, which is time-consuming and costly. Here, we reported that mouse origin full-length CCP6 can be successfully expressed in the soluble fraction of bacteria ArcticExpress (DE3) strain.

Valorization of Cattle Slaughtering Industry By-Products: Modification of the Functional Properties and Structural Characteristics of Cowhide Gelatin Induced by High Hydrostatic Pressure.

This study investigates the effects of different pressures (200, 250, 300, 350, and 400 MPa) and durations (5, 10, 15, 20, and 25 min) on the functional properties, secondary structure, and intermolecular forces of cowhide gelatin. Our results show that high hydrostatic pressure significantly affected the two, three, and four-level structures of gelatin and caused the contents of the α-helix and β-turn to decrease by 68.86% and 78.

Structural Basis of the Main Proteases of Coronavirus Bound to Drug Candidate PF-07321332.

The high mutation rate of COVID-19 and the prevalence of multiple variants strongly support the need for pharmacological options to complement vaccine strategies. One region that appears highly conserved among different genera of coronaviruses is the substrate-binding site of the main protease (M or 3CL), making it an attractive target for the development of broad-spectrum drugs for multiple coronaviruses. PF-07321332, developed by Pfizer, is the first orally administered inhibitor targeting the main protease of SARS-CoV-2, which also has shown potency against other coronaviruses.

Inhibition of DCLK1 sensitizes resistant lung adenocarcinomas to EGFR-TKI through suppression of Wnt/β-Catenin activity and cancer stemness.

Lung adenocarcinoma is the most common form of lung cancer, accounting for 60% of non-small cell lung cancer (NSCLC) cases in Asian patients. Importantly, nearly half of these patients have epithelial growth factor receptor (EGFR) mutations. Though EGFR-tyrosine kinase inhibitors (EGFR-TKIs) are recommended as the first-line therapy for NSCLC patients, the development of resistance reduces their efficiency and limits their application.

Inhibition of DCLK1 kinase reverses epithelial-mesenchymal transition and restores T-cell activity in pancreatic ductal adenocarcinoma.

Immunotherapy has recently become a promising cancer therapy with extensive applications of immune checkpoint inhibitors (ICIs). However, pancreatic ductal adenocarcinoma (PDAC) appears to be unresponsive to immunotherapy due to the immunosuppressive microenvironment. Recent studies showed that cancer stem cell marker DCLK1 promoted the initiation and development of PDAC.

Development and Validation of a Prognostic Gene Signature Correlated With M2 Macrophage Infiltration in Esophageal Squamous Cell Carcinoma.

Background: Esophageal squamous cell carcinoma (ESCC) is the most common type of esophageal cancer and the seventh most prevalent cause of cancer-related death worldwide. Tumor microenvironment (TME) has been confirmed to play an crucial role in ESCC progression, prognosis, and the response to immunotherapy. There is a need for predictive biomarkers of TME-related processes to better prognosticate ESCC outcomes.

Combination of anlotinib and gemcitabine promotes the G0/G1 cell cycle arrest and apoptosis of intrahepatic cholangiocarcinoma in vitro.

Background: Intrahepatic cholangiocarcinoma (ICC) is a malignant carcinoma with high rate of mortality. The current treatment is ineffective with poor survival time. Therefore, there is an urgent need for effective therapeutic drug regimens.

Comparison of the Efficacy of S-1 Plus Oxaliplatin or Capecitabine Plus Oxaliplatin for Six and Eight Chemotherapy Cycles as Adjuvant Chemotherapy in Patients With Stage II-III Gastric Cancer After D2 Resection.

Objective: To compare the efficacy of adjuvant chemotherapy with six or eight cycles of S-1 plus oxaliplatin (SOX) or Capecitabine plus oxaliplatin (XELOX) after D2 resection of GC.

Design And Participants: We collected 470 cases of patients with TNM stage II and III GC who underwent D2 gastrectomy in the Harbin Medical University Cancer Hospital from January 2007 to December 2017 and received six or eight cycles of SOX or XELOX regimen. This study was designed to evaluate the prognosis of patients receiving six or eight cycles of SOX or XELOX chemotherapy and identify the appropriate number of chemotherapy cycles.

Inflammatory Markers Predict Survival in Patients With Advanced Gastric and Colorectal Cancers Receiving Anti-PD-1 Therapy.

There is a lack of useful biomarkers for predicting the efficacy of anti-programmed death-1 (PD-1) therapy for advanced gastric and colorectal cancer. To address this issue, in this study we investigated the correlation between inflammatory marker expression and survival in patients with advanced gastric and colorectal cancer. Data for 111 patients with advanced gastric and colorectal cancer treated with anti-PD-1 regimens were retrospectively analyzed.

Recent Development in Liquid Metal Materials.

Liquid metals (LM) have shown a very broad development prospect over the past decades. This review article focuses on the latest research dedicated to liquid metal materials and their applications in five significant areas: stretchable conductive composite, intelligent sensing electronic skin, catalysis, 3D printing material, and driving machines. The fabrication, specific properties and application of stretchable liquid metal-polymer composites that can be used as self-healing materials have been summarized.

Research Progress of Sirtuin4 in Cancer.

Sirtuins (SIRTs) are members of the silent information regulator-2 family. They are a conserved family of nicotinamide adenine dinucleotide-dependent protein lysine deacylases. SIRTS are involved in intricate cellular processes.