Subanesthetic propofol alleviates chronic stress-induced anxiety by enhancing VTADA neurons' activity.

Anxiety, a common mental disorder, imposes significant clinical and economic burdens. Previous studies indicate that propofol has anxiolytic effects at anesthetic doses. However, the risks associated with general anesthesia limit its application in anxiety treatment.

Clinical and biomarker analyses of SHR-1701 combined with famitinib in patients with previously treated advanced biliary tract cancer or pancreatic ductal adenocarcinoma: a phase II trial.

Advanced biliary tract cancer (BTC) and pancreatic ductal adenocarcinoma (PDAC) have poor prognoses and limited treatment options. Here, we conducted this first-in-class phase II study to evaluate the efficacy and safety of SHR-1701, a bifunctional fusion protein targeting programmed death-ligand 1 (PD-L1) and transforming growth factor-beta (TGF-β), combined with famitinib, a multi-targeted receptor tyrosine kinase inhibitor, in patients with advanced BTC or PDAC who failed previous standard treatment (trial registration: ChiCTR2000037927). Among 51 enrolled patients, the BTC cohort showed an objective response rate (ORR) of 28% (including 2 complete responses) and a disease control rate (DCR) of 80%, with a median progression-free survival (mPFS) of 5.

Granular metamaterials with dynamic bond reconfiguration.

Biological materials dynamically reconfigure their underlying structures in response to stimuli, achieving adaptability and multifunctionality. Conversely, mechanical metamaterials have fixed interunit connections that restrict adaptability and reconfiguration. This study introduces granular metamaterials composed of discrete bimaterial structured particles that transition between assembled and unassembled states through mechanical compression and thermal stimuli.

Self-contact snapping metamaterial for tensile energy dissipation.

Mechanical metamaterials for energy dissipation have received significant attention for vibration and impact mitigation. However, existing designs often neglect energy dissipation in the tensile direction, which is crucial for attenuating tensile load and controlling falling descent. Importantly, current energy-dissipating mechanisms including plastic deformation and friction mechanisms, suffer from drawbacks such as reversibility and self-recovery, restricting their effectiveness under tension.

Digital subtraction angiography-guided pancreatic arterial infusion of GEMOX chemotherapy in advanced pancreatic adenocarcinoma: a phase II, open-label, randomized controlled trial comparing with intravenous chemotherapy.

Background: Advanced pancreatic adenocarcinoma lacks effective treatment options, and systemic gemcitabine-based chemotherapy offers only marginal survival benefits at the cost of significant toxicities and adverse events. New therapeutic options with better drug availability are warranted. This study aims to evaluate the safety and efficacy of digital subtraction angiography (DSA)-guided pancreatic arterial infusion (PAI) versus intravenous chemotherapy (IVC) using the gemcitabine and oxaliplatin (GEMOX) regimen in unresectable locally advanced or metastatic pancreatic cancer (PC) patients.

Zona incerta mediates early life isoflurane-induced fear memory deficits.

The potential long-term effects of anesthesia on cognitive development, especially in neonates and infants, have raised concerns. However, our understanding of its underlying mechanisms and effective treatments is still limited. In this study, we found that early exposure to isoflurane (ISO) impaired fear memory retrieval, which was reversed by dexmedetomidine (DEX) pre-treatment.

Microplastic exposure disturbs sleep structure, reduces lifespan, and decreases ovary size in .

The organ-specific toxicity resulting from microplastic (MP) exposure has been extensively explored, particularly concerning the gut, liver, testis, and lung. However, under natural conditions, these effects are not restricted to specific organs or tissues. Investigating whether MP exposure presents a systemic threat to an entire organism, impacting factors such as lifespan, sleep, and fecundity, is essential.

The neoantigens derived from transposable elements - A hidden treasure for cancer immunotherapy.

Neoantigen-based therapy is a promising approach that selectively activates the immune system of the host to recognize and eradicate cancer cells. Preliminary clinical trials have validated the feasibility, safety, and immunogenicity of personalized neoantigen-directed vaccines, enhancing their effectiveness and broad applicability in immunotherapy. While many ongoing oncological trials concentrate on neoantigens derived from mutations, these targets do not consistently provoke an immune response in all patients harboring the mutations.

Metabolic self-feeding in HBV-associated hepatocarcinoma centered on feedback between circulation lipids and the cellular MAPK/mTOR axis.

Introduction: Hepatitis B Virus (HBV) is widely recognized as a "metabolic virus" that disrupts hepatic metabolic homeostasis, rendering it one of the foremost risk factors for hepatocellular carcinoma (HCC). Except for antiviral therapy, the fundamental principles underlying HBV and HBV HCC have remained unchanged, limiting HCC treatment options.

Objectives: In this study, we aim to identify the distinctive metabolic profile of HBV-associated HCC, with the promise of identifying novel metabolic targets that confer survival advantages and ultimately impede cancer progression.

Oncolytic adenovirus in treating malignant ascites: A phase II trial and longitudinal single-cell study.

Malignant ascites is a common complication resulting from the peritoneal spread of malignancies, and currently lacks effective treatments. We conducted a phase II trial (NCT04771676) to investigate the efficacy and safety of oncolytic adenovirus H101 and virotherapy-induced immune response in 25 patients with malignant ascites. Oncolytic virotherapy achieved an increased median time to repeat paracentesis of 45 days (95% confidence interval 16.

Ultrastiff metamaterials generated through a multilayer strategy and topology optimization.

Metamaterials composed of different geometrical primitives have different properties. Corresponding to the fundamental geometrical forms of line, plane, and surface, beam-, plate-, and shell-based lattice metamaterials enjoy many advantages in many aspects, respectively. To fully exploit the advantages of each structural archetype, we propose a multilayer strategy and topology optimization technique to design lattice metamaterial in this study.

Exploring the efficacy and safety of drug-eluting beads transarterial chemoembolization in pancreatic cancer liver metastasis.

Objectives: Drug-eluting beads transarterial chemoembolization (DEB-TACE) has shown promise as a treatment modality for primary liver cancer and colorectal cancer liver metastasis. However, its role in pancreatic cancer liver metastasis (PCLM) remains uncertain. This study aimed to investigate the efficacy and safety of DEB-TACE in PCLM patients.

Long-lasting complete response to SHR-1701 plus famitinib in refractory advanced gallbladder cancer: A case report.

Biliary tract cancer (BTC) is an aggressive malignancy with few options for advanced-stage treatment. The combination of PD-1/PD-L1 inhibitors with famitinib, a receptor tyrosine kinase (RTK) inhibitor, has demonstrated improved clinical outcomes in several clinical trials. We herein reported a case of a gallbladder cancer (GBC) patient with liver metastases, previously resistant to traditional chemotherapy.

Potent induction of antitumor immunity by combining cryo-thermal ablation with immune checkpoint inhibitors in hepatocellular carcinoma.

Background: The low response rate of immune checkpoint inhibitors (ICIs) prompts the exploration of novel combination therapies for patients with hepatocellular carcinoma (HCC). Here, we aimed to examine the efficiency and potential mechanism of cryo-thermal ablation (Cryo-A) combined with anti-programmed death protein 1 (αPD1) and/or cytotoxic T-lymphocyte antigen 4 (αCTLA4) inhibitors in a murine hepatoma model.

Method: Immunocompetent C57BL/6 mice inoculated with unilateral or bilateral H22 hepatic tumour cells were treated with Cryo-A and/or ICIs (αPD1 and/or αCTLA4).

Brief disruption of activity in a subset of dopaminergic neurons during consolidation impairs long-term memory by fragmenting sleep.

Sleep disturbances are associated with poor long-term memory (LTM) formation, yet the underlying cell types and neural circuits involved have not been fully decoded. Dopamine neurons (DANs) are involved in memory processing at multiple stages. Here, using both male and female flies, , we show that, during the first few hours of memory consolidation, disruption of basal activity of a small subset of protocerebral anterior medial DANs (PAM-DANs), by either brief activation or inhibition of the two dorsal posterior medial (DPM) neurons, impairs 24 h LTM.

Sequential high-intensity focused ultrasound treatment combined with chemotherapy for inoperable pancreatic cancer: a retrospective analysis for prognostic factors and survival outcomes.

Objective: To evaluate the effect of HIFU (High-Intensity Focused Ultrasound) therapy on the survival and prognosis of patients with inoperable pancreatic cancer, and the clinical application of serological prognostic indicators.

Methods: We retrospectively analyzed the clinicopathological features, laboratory tests and follow-ups of 192 patients. Among the patients, 57 were treated with HIFU prior to chemotherapy (HIFU-priority), and 135 patients received chemotherapy followed by HIFU (HIFU-second).

Case Report: Overcoming challenges in pancreatic cancer with liver metastases: a personalized therapeutic odyssey of TACE, ablation, and immunotherapy.

Pancreatic cancer represents a malignant neoplasm originating from pancreatic cells. The optimal approach to cancer treatment remains uncertain, lacking a definitive consensus. Here, we present a compelling case of a 49-year-old female with pancreatic head cancer with liver metastases, as identified by CT and confirmed by biopsy.

Vitamin D-binding protein in plasma microglia-derived extracellular vesicles as a potential biomarker for major depressive disorder.

No well-established biomarkers are available for the clinical diagnosis of major depressive disorder (MDD). Vitamin D-binding protein (VDBP) is altered in plasma and postmortem dorsolateral prefrontal cortex (DLPFC) tissues of MDD patients. Thereby, the role of VDBP as a potential biomarker of MDD diagnosis was further assessed.