Combination of fruquintinib with venetoclax for the treatment of colorectal cancer.

Background: As a novel blocker of vascular endothelial growth factor receptor (VEGFR), fruquintinib has been approved for treating colorectal cancer (CRC). However, its dosage and therapeutic efficacy are limited by its widespread adverse reactions. Venetoclax, recognized as the initial inhibitor of B-cell lymphoma protein 2 (BCL2), has shown potential in boosting the effectiveness of immunotherapy against CRC.

Multidimensional screen exposure and its impact on psychological well-being in toddlers.

Objective: Previous studies have indicated a link between screen exposure and children's mental health, but with the emergence of new screen media and a rise in screen content, uncertainties have grown. Our aim was to investigate the impact of screen use on psychological issues in 2- to 3-year-old children, considering screen time and types of screen media and content.

Methods: This cross-sectional study included participants from Shanghai, China, from February to July 2023.

Peptide amphiphiles alleviate myocardial endoplasmic reticulum stress to enhance cardiomyocyte-macrophage communication and promote macrophage M2 polarization.

Myocardial ischemia-reperfusion (I/R) injury represents a significant clinical challenge with limited therapeutic options. Single-cell RNA sequencing and bioinformatics analyses have revealed complex cellular interactions within cardiac tissue, highlighting the crucial role of cardiomyocytes in intercellular communication. During I/R injury, cardiomyocytes experience severe endoplasmic reticulum (ER) stress, leading to detrimental intercellular communication that affects surrounding cells, particularly promoting the transformation of macrophages toward a pro-inflammatory phenotype.

Early detection of colorectal cancer using aberrant circulating cell-free mitochondrial DNA fragmentomics.

Background: Early detection of colorectal cancer (CRC) is crucial for improving the survival rates of patients.

Objective: We aimed to develop a novel strategy for early CRC detection using the fragmentomic features of circulating cell-free mitochondrial DNA (ccf-mtDNA).

Design: Here, a total of 1147 participants, including 478 healthy controls (HCs), 112 patients with advanced adenomas (AAs) and 557 patients with CRC, were enrolled from five hospitals and plasma samples were collected for capture-based ccf-mtDNA sequencing.

Polydatin-Mediated Inhibition of HSP90α Disrupts NLRP3 Complexes and Alleviates Acute Pancreatitis.

The NLRP3 inflammasome plays a critical role in various inflammatory conditions. However, despite extensive research in targeted drug development for NLRP3, including MCC950, clinical success remains elusive. Here, we discovered that the activated NLRP3 inflammasome complex (disc-NLRP3) and the activating mutation L351P exhibited resistance to MCC950.

Experimental demonstration of an on-chip spatial light receiver based on inverse design in free-space optical communication.

We propose and demonstrate an experiment to explore the optical reception performance of an on-chip spatial optical receiver based on an inverse design under three distinct turbulent conditions. Experimental results demonstrate that the receiver achieved a maximum emission efficiency of 81% at 1530 nm, with fluctuations of less than 2 dB over the wavelength range from 1530 to 1568 nm. Moreover, the measured mode purity for the generated HG mode varied from 89.

Repairing effect of magnesium oxychloride cement modified by γ-polyglutamic acid and chitosan in osteoporotic bone defect.

Magnesium oxychloride cement (MOC) has the advantage of high early strength. However, it has the defect of poor water resistance. Considering this performance, we use γ-polyglutamic acid (γ-PGA) and chitosan (CS) to modify MOC.

Aberrant fragmentomic features of circulating cell-free mitochondrial DNA as novel biomarkers for multi-cancer detection.

Fragmentomic features of circulating cell free mitochondrial DNA (ccf-mtDNA) including fragmentation profile, 5' end base preference and motif diversity are poorly understood. Here, we generated ccf-mtDNA sequencing data of 1607 plasma samples using capture-based next generation sequencing. We firstly found that fragmentomic features of ccf-mtDNA were remarkably different from those of circulating cell free nuclear DNA.

Effects of different microplastic types on soil physicochemical properties, enzyme activities, and bacterial communities.

Global concern continues to mount regarding the accumulation of microplastics (MPs) in soil. However, little is known about how various types of MPs influence the properties of soil ecosystems. Here, we evaluated the effects of six different types of MPs, including low-density polyethylene (LDPE), polyamide (PA), polystyrene (PS), polyhydroxy-alkanoates (PHA), polybutadiene styrene (PBS), and polylactide (PLA), on soil physicochemical properties, enzyme activities, and microbial communities.

Aberrant fragmentomic features of circulating cell-free mitochondrial DNA enable early detection and prognosis prediction of hepatocellular carcinoma.

Background: Early detection and effective prognosis prediction in patients with hepatocellular carcinoma (HCC) provides an avenue for survival improvement, yet more effective approaches are greatly needed. We sought to develop the detection and prognosis models with ultra-sensitivity and low cost based on fragmentomic features of circulating cell free mtDNA (ccf-mtDNA).

Participants And Methods: Capture-based mtDNA sequencing was carried out in plasma cell-free DNA samples from 1168 participants, including 571 patients with HCC, 301 patients with chronic hepatitis B or liver cirrhosis (CHB/LC) and 296 healthy controls (HC).

Revealing synergistic mechanisms of biochar-assisted microbial electrolysis cells in enhancing the anaerobic digestion performance of waste activated sludge: Extracellular polymeric substances characterization, enzyme activity assay, and multi-omics analysis.

Although biochar (BC)-assisted microbial electrolysis cells (MEC) has been shown to improve anaerobic digestion (AD) performance of waste activated sludge (WAS), the underlying mechanisms remain unclear. This study conducted an in-depth investigation into the mechanism based on analyses of extracellular polymeric substances (EPS) characteristics, enzyme activities and multi-omics. The results showed that compared with the control group, methane production improved by 16.

Datasets of fungal diversity and pseudo-chromosomal genomes of mangrove rhizosphere soil in China.

With climate change and anthropic influence on the coastal ecosystems, mangrove ecosystems are disappearing at an alarming rate. Accordingly, it becomes important to track, study, record and store the mangrove microbial community considering their ecological importance and potential for biotechnological applications. Here, we provide information on mangrove fungal community composition and diversity in mangrove ecosystems with different plant species and from various locations differing in relation to anthropic influences.

Transcriptome analysis unveiled the genetic basis of rapid seed germination strategies in alpine plant Rheum pumilum.

Rheum pumilum stands as both a quintessential alpine plant and a significant traditional Chinese and Tibetan medicinal herb. Unraveling the molecular intricacies of seed germination in Rh. pumilum not only unveils the genetic foundations of plant seed germination strategies in high-altitude environments but also offers insights for cultivating Rh.

Research and application discussion of cranial bone model preparation method based on three-dimensional reconstruction and 3D printing technology.

Purpose: The aim of this study was to find an alternative method to meet traditional human anatomy teaching and clinical needs in order to solve the problem of cranial specimen attrition and specimen resource shortage due to long-term use.

Methods: We performed a computed tomography (CT) scan of a well-preserved male cranial specimen and used Mimics 19.0 software for 3D reconstruction and cranial block separation.

TCR-like bispecific antibodies toward eliminating infected hepatocytes in HBV mouse models.

Therapeutics for eradicating hepatitis B virus (HBV) infection are still limited and current nucleos(t)ide analogs (NAs) and interferon are effective in controlling viral replication and improving liver health, but they cannot completely eradicate the hepatitis B virus and only a very small number of patients are cured of it. The TCR-like antibodies recognizing viral peptides presented on human leukocyte antigens (HLA) provide possible tools for targeting and eliminating HBV-infected hepatocytes. Here, we generated three TCR-like antibodies targeting three different HLA-A2.

Allosterically activating SHP2 by oleanolic acid inhibits STAT3-Th17 axis for ameliorating colitis.

Src homology 2 domain-containing tyrosine phosphatase 2 (SHP2) is an essential tyrosine phosphatase that is pivotal in regulating various cellular signaling pathways such as cell growth, differentiation, and survival. The activation of SHP2 has been shown to have a therapeutic effect in colitis and Parkinson's disease. Thus, the identification of SHP2 activators and a complete understanding of their mechanism is required.

Hit-to-Lead Optimization of the Natural Product Oridonin as Novel NLRP3 Inflammasome Inhibitors with Potent Anti-Inflammation Activity.

Targeting NLRP3 inflammasome with inhibitors is a novel strategy for NLRP3-driven diseases. Herein, hit compound possessing an attractive skeleton was identified from our in-house database of oridonin, and then a potential lead compound was obtained by optimization of , displaying two-digit nanomolar inhibition on NLRP3. Moreover, compound showed enhanced safety index (SI) relative to oridonin (IC = 77.

Development of a time-resolved immunochromatographic test strip for rapid and quantitative determination of retinol-binding protein 4 in urine.

Urine retinol-binding protein 4 (RBP4) has recently been reported as a novel earlier biomarker of chronic kidney disease (CKD) which is a global public health problem with high morbidity and mortality. Accurate and rapid detection of urine RBP4 is essential for early monitor of impaired kidney function and prevention of CKD progression. In the present study, we developed a time-resolved fluorescence immunochromatographic test strip (TRFIS) for the quantitative and rapid detection of urine RBP4.

Salvianolic acid A prevents UV-induced skin damage by inhibiting the cGAS-STING pathway.

DNA damage resulting from UV irradiation on the skin has been extensively documented in numerous studies. In our prior investigations, we demonstrated that UVB-induced DNA breakage from keratinocytes can activate the cGAS-STING pathway in macrophages. The cGAS-STING signaling pathway serves as the principal effector for detecting and responding to abnormal double-stranded DNA in the cytoplasm.

Allosteric SHP2 inhibition enhances regorafenib's effectiveness in colorectal cancer treatment.

Colorectal cancer (CRC) is the third most common cancer globally. Regorafenib, a multi-target kinase inhibitor, has been approved for treating metastatic colorectal cancer patients who have undergone at least two prior standard anti-cancer therapies. However, regorafenib efficacy as a single agent remains suboptimal.

IDO1 Inhibition Promotes Activation of Tumor-intrinsic STAT3 Pathway and Induces Adverse Tumor-protective Effects.

Pharmacological inhibition of IDO1 exhibits great promise as a strategy in cancer therapy. However, the failure of phase III clinical trials has raised the pressing need to understand the underlying reasons for this outcome. To gain comprehensive insights into the reasons behind the clinical failure of IDO1 inhibitors, it is essential to investigate the entire tumor microenvironment rather than focusing solely on individual cells or relying on knockout techniques.