Plant Compounds Inhibit the Growth of W12 Cervical Precancer Cells Containing Episomal or Integrant HPV DNA; Tanshinone IIA Synergizes with Curcumin in Cervical Cancer Cells.

This study explores the effects of plant compounds on human papillomavirus (HPV)-induced W12 cervical precancer cells and bioelectric signaling. The aim is to identify effective phytochemicals, both individually and in combination, that can prevent and treat HPV infection and HPV associated cervical cancer. Phytochemicals were tested using growth inhibition, combination, gene expression, RT PCR, and molecular docking assays.

High-Performance Edge-Contact Monolayer Molybdenum Disulfide Transistors.

Edge contact is essential for achieving the ultimate device pitch scaling of stacked nanosheet transistors with monolayer 2-dimensional (2D) channels. However, due to large edge-contact resistance between 2D channels and contact metal, there is currently a lack of high-performance edge-contact device technology for 2D material channels. Here, we report high-performance edge-contact monolayer molybdenum disulfide (MoS) field-effect transistors (FETs) utilizing well-controlled plasma etching techniques.

Liquid-infused nanostructured composite as a high-performance thermal interface material for effective cooling.

Effective heat dissipation remains a grand challenge for energy-dense devices and systems. As heterogeneous integration becomes increasingly inevitable in electronics, thermal resistance at interfaces has emerged as a critical bottleneck for thermal management. However, existing thermal interface solutions are constrained by either high thermal resistance or poor reliability.

Chimeric antigen receptor macrophages (CAR-M) sensitize HER2+ solid tumors to PD1 blockade in pre-clinical models.

We previously developed human CAR macrophages (CAR-M) and demonstrated redirection of macrophage anti-tumor function leading to tumor control in immunodeficient xenograft models. Here, we develop clinically relevant fully immunocompetent syngeneic models to evaluate the potential for CAR-M to remodel the tumor microenvironment (TME), induce T cell anti-tumor immunity, and sensitize solid tumors to PD1/PDL1 checkpoint inhibition. In vivo, anti-HER2 CAR-M significantly reduce tumor burden, prolong survival, remodel the TME, increase intratumoral T cell and natural killer (NK) cell infiltration, and induce antigen spreading.

Survival with Trastuzumab Emtansine in Residual HER2-Positive Breast Cancer.

Background: Patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer with residual invasive disease after neoadjuvant systemic therapy have a high risk of recurrence and death. The primary analysis of KATHERINE, a phase 3, open-label trial, showed that the risk of invasive breast cancer or death was 50% lower with adjuvant trastuzumab emtansine (T-DM1) than with trastuzumab alone.

Methods: We randomly assigned patients with HER2-positive early breast cancer with residual invasive disease in the breast or axilla after neoadjuvant systemic treatment with taxane-based chemotherapy and trastuzumab to receive T-DM1 or trastuzumab for 14 cycles.

Tracking hydrothermal infiltration within light oil reservoirs using organic geochemical proxies in the Shunbei area of Tarim Basin in China.

Deep oil reservoirs are becoming increasingly significant fields of hydrocarbon exploration in recent decades. Hydrothermal fluid flow is deemed as a potentially crucial factor affecting the occurrence of deep oil reservoirs, such as enhancing porosity/permeability of reservoirs, accelerating oil generation and thermal cracking, and modifying organic properties of crude oils. Understanding the interplay between hydrothermal fluids and crude oils would provide useful constraints for reconstructing hydrocarbon accumulation processes and predicting the distribution patterns of crude oils.

Iron-carbon micro-electrolysis coupled to heterotrophic nitrification aerobic denitrification treating low carbon/nitrogen mariculture wastewater.

Considering the unsatisfied nitrogen (N) and phosphorus (P) treatment performance of mariculture wastewater caused by low carbon/nitrogen (C/N), a novel iron-carbon (Fe-C) micro-electrolysis coupled to heterotrophic nitrification aerobic denitrification (HNAD) process was proposed to enhance the N and P elimination. Results revealed that total nitrogen (TN) removal and total phosphorus (TP) removal efficiencies in Fe-C filter with HNAD (R-Fe) increased by 76.1% and 113.

Vps4a Mediates a Unified Membrane Repair Machinery to Attenuate Ischemia/Reperfusion Injury.

Background: Cardiac ischemia/reperfusion disrupts plasma membrane integrity and induces various types of programmed cell death. The ESCRT (endosomal sorting complex required for transport) proteins, particularly AAA-ATPase Vps4a (vacuolar protein sorting 4a), play an essential role in the surveillance of membrane integrity. However, the role of ESCRT proteins in the context of cardiac injury remains unclear.

Experimental Study on the Size Effect of Compression-Shear Fracture Characteristics of Rock-like Materials Containing Open Cracks.

Understanding fracture mechanics in rock-like materials under compression-shear condition is critical for predicting failure mechanisms in various engineering applications, such as mining and civil infrastructure. This study conducted uniaxial compression tests on cubic gypsum specimens of varying sizes (side lengths of 75 mm, 100 mm, 125 mm, and 150 mm) and crack inclination angles (ranging from 0° to 90°) to assess the size effect on fracture behavior. The effects of specimen size and crack inclination on fracture characteristics, including strength, failure mode, and crack initiation angle, were analyzed based on the maximum tangential stress (MTS) criterion and the generalized maximum tangential stress (GMTS) criterion, with relative critical size (α) and relative openness ().

The ClinGen Syndromic Disorders Gene Curation Expert Panel: Assessing the Clinical Validity of 111 Gene-Disease Relationships.

Purpose: The Clinical Genome Resource (ClinGen) Gene Curation Expert Panels (GCEPs) have historically focused on specific organ systems or phenotypes; thus, the ClinGen Syndromic Disorders GCEP (SD-GCEP) was formed to address an unmet need.

Methods: The SD-GCEP applied ClinGen's framework to evaluate the clinical validity of genes associated with rare syndromic disorders. 111 Gene-Disease Relationships (GDRs) associated with 100 genes spanning the clinical spectrum of syndromic disorders were curated.

Prediction of the impact of tobacco waste hydrothermal products on compost microbial growth using hyperspectral imaging combined with machine learning.

The insufficient understanding of the impact of hydrothermal products on the growth characteristics of compost microorganisms presents a significant challenge to the broader implementation of hydrothermal coupled composting for tobacco waste. Traditional biochemical detection methods are labor-intensive and time-consuming, highlighting the need for faster and more accurate alternatives. This study investigated the effects of hydrothermal treatment on tobacco straw products and their influence on compost microorganism growth, using hyperspectral imaging (HSI) technology and machine learning algorithms.

Oncogenic EML4-ALK assemblies suppress growth factor perception and modulate drug tolerance.

Drug resistance remains a challenge for targeted therapy of cancers driven by EML4-ALK and related fusion oncogenes. EML4-ALK forms cytoplasmic protein condensates, which result from networks of interactions between oncogene and adapter protein multimers. While these assemblies are associated with oncogenic signaling, their role in drug response is unclear.

Clinical correlates of dopamine transporter availability in cross-sectional and longitudinal studies with [F]FE-PE2I PET: independent validation with new insights.

[F]FE-PE2I PET is a promising alternative to single positron emission computed tomography-based dopamine transporter (DAT) imaging in Parkinson's disease. While the excellent discriminative power of [F]FE-PE2I PET has been established, so far only one study has reported meaningful associations between motor severity scores and DAT availability. In this study, we use high-resolution (∼3 mm isotropic) PET to provide an independent validation for the clinical correlates of [F]FE-PE2I imaging in separate cross-sectional (28 participants with Parkinson's disease, Hoehn-Yahr: 2 and 14 healthy individuals) and longitudinal (initial results from 6 participants with Parkinson's disease with 2-year follow-up) cohorts.

Agreement between a new fully automatic ocular biometer based on optical low-coherence reflectometry and an optical biometer based on Scheimpflug imaging combined with partial coherence interferometry.

Background: To analyze the difference and agreement between measurements obtained by a new fully automatic optical biometer, the SW-9000 μm Plus, based on optical low-coherence reflectometry (OLCR) and a commonly used optical biometer (Pentacam AXL) based on Scheimpflug imaging with partial coherence interferometry (PCI).

Methods: The central corneal thickness (CCT), anterior chamber depth (ACD, from epithelium to anterior lens surface), lens thickness (LT), mean keratometry (K), corneal astigmatism, corneal diameter (CD), pupil diameter (PD), and axial length (AL) of 74 eyes (from 74 healthy subjects) were measured using the SW-9000 μm Plus and the Pentacam AXL to determine the agreement. Double angle plots were used for astigmatism vector analysis.

Bone and periosteum protein analysis via tandem mass tag quantitative proteomics in pediatric patients with osteomyelitis.

Bone healing is crucial in managing osteomyelitis after fracture fixation. Understanding the mechanism of extensive callus formation in pediatric osteomyelitis is highly important. This study aims to analyze bone and periosteum samples from pediatric patients to elucidate the essential processes involved in callus formation during osteomyelitis.

Fusobacterium Nucleatum Promotes Microsatellite Instability in Colorectal Carcinoma Through Up-regulation of miRNA-155-5p-Targeted Inhibition of MSH6 via the TLR4/NF-κB Signaling Pathway.

Fusobacterium nucleatum (Fn) is significantly associated with poor prognosis in colorectal carcinoma (CRC), however, mechanisms of Fn in DNA mismatch repair (MMR) and microsatellite instability (MSI) in CRC have not been fully elucidated. Clinical samples are collected to analyze the relationship between Fn abundance and microsatellite stability. Tumor cells are treated with Fn to detect the expression of proteins related to toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (Myd88), mutS homolog 6 (MSH6), and nuclear factor-κB (NF-κB) signaling pathways, respectively.

Rapid and Highly Selective Fe(IV) Generation by Fe(II)-Peroxyacid Advanced Oxidation Processes: Mechanistic Investigation via Kinetics and Density Functional Theory.

High-valent iron (Fe(IV/V/VI)) has been widely applied in water decontamination. However, common Fe(II)-activating oxidants including hydrogen peroxide (HO) and persulfate react slowly with Fe(II) and exhibit low selectivity for Fe(IV) production due to the cogeneration of radicals. Herein, we report peroxyacids (POAs; R-C(O)OOH) that can react with Fe(II) more than 3 orders of magnitude faster than HO, with high selectivity for Fe(IV) generation.

In vivo dendritic cell reprogramming for cancer immunotherapy.

Immunotherapy can lead to long-term survival for some cancer patients, yet generalized success has been hampered by insufficient antigen presentation and exclusion of immunogenic cells from the tumor microenvironment. Here, we developed an approach to reprogram tumor cells in vivo by adenoviral delivery of the transcription factors PU.1, IRF8, and BATF3, which enabled them to present antigens as type 1 conventional dendritic cells.

E3 ubiquitin ligase BTBD3 inhibits tumorigenesis of colorectal cancer by regulating the TYRO3/Wnt/β-catenin signaling axis.

Clinical trials and studies have implicated that E3 ubiquitin ligase BTBD3 (BTB Domain Containing 3) is a cancer-associated gene. However, the role and underlying mechanism of BTBD3 in colorectal cancer (CRC) is not fully understood yet. Herein, our study demonstrated that the mRNA and protein levels of BTBD3 were decreased in CRC tissues and associated with TYPO3 and Wnt/β-catenin pathway.

Specific multivalent molecules boost CRISPR-mediated transcriptional activation.

CRISPR/Cas-based transcriptional activators can be enhanced by intrinsically disordered regions (IDRs). However, the underlying mechanisms are still debatable. Here, we examine 12 well-known IDRs by fusing them to the dCas9-VP64 activator, of which only seven can augment activation, albeit independently of their phase separation capabilities.

LAG-3 and PD-1 synergize on CD8 T cells to drive T cell exhaustion and hinder autocrine IFN-γ-dependent anti-tumor immunity.

Overcoming immune-mediated resistance to PD-1 blockade remains a major clinical challenge. Enhanced efficacy has been demonstrated in melanoma patients with combined nivolumab (anti-PD-1) and relatlimab (anti-LAG-3) treatment, the first in its class to be FDA approved. However, how these two inhibitory receptors synergize to hinder anti-tumor immunity remains unknown.

Comparison of clinical efficacy between modified Kamikawa anastomosis in laparoscopic proximal gastrectomy and Roux-en-Y anastomosis in laparoscopic total gastrectomy.

To investigate the short-term clinical efficacy of laparoscopic proximal gastrectomy with modified Kamikawa anastomosis and laparoscopic total gastrectomy with Roux-en-Y anastomosis. Retrospective cohort study was conducted. The clinicopathological data of 268 patients who underwent laparoscopic proximal gastrectomy for adenocarcinoma of esophagogastric junction and upper gastric adenocarcinoma from January 2016 to October 2022 were collected.