T7-assisted special rolling circular amplification platform for point-of-care cervical cancer screening.

Cervical cancer, primarily caused by high-risk human papillomavirus (HPV) infections, remains a leading cause of mortality among women in underdeveloped and developing countries. Conventional screening methods, necessitating professional equipment and trained personnel, are impractical in resource-limited settings, underscoring the need for a point-of-care (POC) detection platform. Isothermal nucleic acid amplification techniques (NAATs) are widely used in POC applications due to their cost-effectiveness and instrument-free nature.

PRODH2-Mediated Metabolism in the Bone Microenvironment Promotes Breast Cancer Metastasis.

Breast cancer (BC) frequently metastasizes to the bone, but treatment options for bone metastatic breast cancer are limited. Amino acid metabolism is reprogrammed in the bone metastatic microenvironment, suggesting that it could represent a therapeutic vulnerability. In this study, we focused on metabolism of hydroxyproline (Hyp), a key amino acid resulting from bone collagen degradation, which serves as a critical biomarker for bone metastases.

POLRMT enhances lenvatinib resistance in hepatocellular carcinoma cells by maintaining mitochondrial ATP production.

Lenvatinib is one of first-line therapeutic agents for advanced hepatocellular carcinoma (HCC), yet lenvatinib resistance of tumor resulting in a weak response on many patients. Mitochondrial energy metabolism is environmentally adaptable and has been shown to play a crucial role in tumor resistance to therapy. Therefore, identification of the key regulator of mitochondrial energy metabolism during lenvatinib resistance provides a novel target for drug-resistant HCC.

KRAS/ABHD17C/ALOX15B Axis Promotes Pancreatic Cancer Progression via Ferroptosis Evasion.

Understanding the mechanisms underlying Kirsten rat sarcoma (KRAS) mutation-driven development and progression of pancreatic ductal adenocarcinoma (PDAC) may facilitate the discovery of novel strategies for KRAS-mutant PDAC (KRAS-PDAC) treatment. Here, it is reported that downregulation of arachidonate 15-lipoxygenase (ALOX15B) significantly correlated with poor outcomes in patients with KRAS-PDAC. Mechanistically, KRAS/ERK1-elicited phosphorylation of ABHD17C promotes depalmitoylation and membrane-to-cytoplasm translocation of ALOX15B, facilitating proteasome-dependent degradation of ALOX15B via interaction with the E3 ligase complex CUL4/DDB1/DCAF10.

Exploration of choroidal vascular changes in juveniles with different degrees of myopia: The application of swept-source optical coherence tomography angiography.

Objective: To investigate the vascular characteristic changes in the macular retina and choriocapillaris, as well as the choroidal vascularization of eyes with different degrees of myopia in juveniles using Swept-source Optical Coherence Tomography (SS-OCT), aiming to understand the pathophysiological characteristics of myopic eyes further.

Methods: We conducted a retrospective case-control study involving 103 patients (198 eyes) aged 6-17 years who had undergone SS-OCT examination. Based on equivalent spherical power, they were divided into four groups: emmetropia group, low myopia group, moderate myopia group, and high myopia group.

Supplementing sialic acid analogs overcomes radiotherapy resistance in triple-negative breast cancer by exacerbating ER stress.

Radiotherapy is a cornerstone treatment for triple-negative breast cancer (TNBC), and its incorporation has significantly delayed tumor recurrence. However, the emergence of radiotherapy resistance remains a major clinical challenge, substantially compromising treatment efficacy. Sialylation play a pivotal role in tumor therapeutic resistance which refers to the covalent linkage of sialic acids at the terminal ends of glycoproteins, a process catalyzed by a family of sialyltransferases.

Glass fiber-interfaced CRISPR/Cas biosensing adaptable for diverse biomarker detection.

Developing a generic sensitive platform for detecting diverse biomarkers is essential for a comprehensive understanding of disease states, guiding precision medicine. Herein, we introduce a versatile platform based on glass fiber interfaced CRISPR/Cas with a universal reagent setting (g-CURS), which used a fixed pair of CRISPR RNA (crRNA) and a single-stranded DNA (ssDNA) activator to enable detection of multiple nucleic acids or proteins with ultrahigh sensitivity. The fixed ssDNA activator was labeled on multiple specific ligation products or detection antibodies conjugated on glass fiber to initiate CRISPR/Cas12a-assisted rapid and exponential cascade amplification through circular reporters (CRs), generating fluorescence signals readable by a portable detector.

CRISPR/Cas on Microfluidic Paper-Based Analytical Devices for Point-of-Care Screening of Cervical Cancer.

Highly sensitive point-of-care early screening for high-risk human papillomavirus (HPV) infections is urgently needed, particularly in resource-limited settings. Nucleic acid amplification methods, especially CRISPR/Cas-based biosensors, have emerged as promising tools for sensitive HPV detection; however, current approaches typically rely on tedious tube-based formats coupled with lateral flow assays for signal readout in point-of-care testing (POCT). Here, we developed customized microfluidic paper-based analytical devices (μPADs) with valves that seamlessly integrated recombinase polymerase amplification (RPA) with CRISPR/Cas12a biosensing (RPA-CRISPR/Cas12a) on the filter paper substrate.

Chemotherapy-induced macrophage CXCL7 expression drives tumor chemoresistance via the STAT1/PHGDH-serine metabolism axis and SAM paracrine feedback to M2 polarization.

Chemotherapy resistance in colorectal cancer (CRC) remains a major obstacle in clinical oncology. Analysis of clinical specimens from chemotherapy-resistant patients revealed elevated CXCL7 expression in tumor-associated macrophages (TAMs). Through integrated in vitro and in vivo studies, we demonstrated that chemotherapy induces tumor cell-macrophage crosstalk, leading to CXCL7 upregulation in TAMs.

RNF31 induces paclitaxel resistance by sustaining ALYREF cytoplasmic-nuclear shuttling in human triple-negative breast cancer.

Background: Resistance to paclitaxel-based chemotherapy is the major obstacle in triple-negative breast cancer (TNBC) treatment. However, overcoming paclitaxel resistance remains an unsolved problem. The present study aimed to determine whether paclitaxel treatment impairs Aly/REF export factor (ALYREF) cytoplasmic-nuclear shuttling, its mechanism, and the role of ubiquitinated ALYREF in paclitaxel resistance.

Targeting the SPC25/RIOK1/MYH9 Axis to Overcome Tumor Stemness and Platinum Resistance in Epithelial Ovarian Cancer.

In epithelial ovarian cancer (EOC), platinum resistance, potentially mediated by cancer stem cells (CSCs), often leads to relapse and treatment failure. Here, the role of spindle pole body component 25 (SPC25) as a key determinant promoting stemness and platinum resistance in EOC cells, with its expression being correlated with adverse clinical outcomes is delineated. Mechanistically, SPC25 acts as a scaffolding platform, orchestrating the assembly of an SPC25/RIOK1/MYH9 trimeric complex, triggering RIOK1-mediated phosphorylation of MYH9 at Ser1943.

Dynamic structural remodeling of LINC01956 enhances temozolomide resistance in -methylated glioblastoma.

The mechanisms underlying stimuli-induced dynamic structural remodeling of RNAs for the maintenance of cellular physiological function and survival remain unclear. Here, we showed that in promoter-methylated glioblastoma (GBM), the RNA helicase DEAD-box helicase 46 (DDX46) is phosphorylated by temozolomide (TMZ)-activated checkpoint kinase 1 (CHK1), resulting in a dense-to-loose conformational change and an increase in DDX46 helicase activity. DDX46-mediated tertiary structural remodeling of LINC01956 exposes the binding motifs of LINC01956 to the 3' untranslated region of O-methylguanine DNA methyltransferase ().

MANF facilitates breast cancer cell survival under glucose-starvation conditions via PRKN-mediated mitophagy regulation.

During tumor expansion, breast cancer (BC) cells often experience reactive oxygen species accumulation and mitochondrial damage because of glucose shortage. However, the mechanism by which BC cells deal with the glucose-shortage-induced oxidative stress remains unclear. Here, we showed that MANF (mesencephalic astrocyte derived neurotrophic factor)-mediated mitophagy facilitates BC cell survival under glucose-starvation conditions.

Portable Device with Nicking Enzyme Enhanced Special RCA on μPADs toward Sensitive Detection of High-Risk HPV Infection.

Development of an accurate, rapid, and cost-effective portable device is in high demand for point-of-care molecular diagnosis toward disease screening. Here we report a one-pot homogeneous isothermal assay that leverages nicking endonuclease and minimum secondary structured rolling circle amplification (N-MSSRCA) for fast and sensitive quantification of nucleic acids on distance microfluidic paper-based analytical devices (dμPAD) by a portable custom-made fluorescence detector. Human papillomavirus (HPV) oncogenic E7 mRNA as the biomarker for cervical cancer was used as the model analyte.

LPCAT1-mediated membrane phospholipid remodelling promotes ferroptosis evasion and tumour growth.

The mechanisms underlying the dynamic remodelling of cellular membrane phospholipids to prevent phospholipid peroxidation-induced membrane damage and evade ferroptosis, a non-apoptotic form of cell death driven by iron-dependent lipid peroxidation, remain poorly understood. Here we show that lysophosphatidylcholine acyltransferase 1 (LPCAT1) plays a critical role in ferroptosis resistance by increasing membrane phospholipid saturation via the Lands cycle, thereby reducing membrane levels of polyunsaturated fatty acids, protecting cells from phospholipid peroxidation-induced membrane damage and inhibiting ferroptosis. Furthermore, the enhanced in vivo tumour-forming capability of tumour cells is closely associated with the upregulation of LPCAT1 and emergence of a ferroptosis-resistant state.

Infiltrative Vessel Co-optive Growth Pattern Induced by IQGAP3 Overexpression Promotes Microvascular Invasion in Hepatocellular Carcinoma.

Purpose: Microvascular invasion (MVI) is a major unfavorable prognostic factor for intrahepatic metastasis and postoperative recurrence of hepatocellular carcinoma (HCC). However, the intervention and preoperative prediction for MVI remain clinical challenges due to the absent precise mechanism and molecular marker(s). Herein, we aimed to investigate the mechanisms underlying vascular invasion that can be applied to clinical intervention for MVI in HCC.

Multi-objective optimization of saline water irrigation in arid oasis regions: Integrating water-saving, salinity control, yield enhancement, and CO emission reduction for sustainable cotton production.

Brackish water stands as a promising alternative to mitigate freshwater scarcity in arid regions. However, its application poses potential threats to agricultural sustainability. There is a need to establish a clear understanding of the economic and ecological benefits.

SHC4 orchestrates β-catenin pathway-mediated metastasis in triple-negative breast cancer by promoting Src kinase autophosphorylation.

Triple-negative breast cancer (TNBC) is highly aggressive and metastatic, and has the poorest prognosis among all breast cancer subtypes. Activated β-catenin is enriched in TNBC and involved in Wnt signaling-independent metastasis. However, the underlying mechanisms of β-catenin activation in TNBC remain unknown.

CircMMP2(6,7) Cooperates with β-Catenin and PRMT5 to Disrupt Bone Homeostasis and Promote Breast Cancer Bone Metastasis.

Unlabelled: The bone is the most common site of distant metastasis of breast cancer, which leads to serious skeletal complications and mortality. Understanding the mechanisms underlying breast cancer bone metastasis would provide potential strategies for the prevention and treatment of breast cancer bone metastasis. In this study, we identified a circular RNA that we named circMMP2(6,7) that was significantly upregulated in bone metastatic breast cancer tissues and correlated with breast cancer-bone metastasis.

Lysosomal cyst(e)ine storage potentiates tolerance to oxidative stress in cancer cells.

Cyst(e)ine is a key precursor for the synthesis of glutathione (GSH), which protects cancer cells from oxidative stress. Cyst(e)ine is stored in lysosomes, but its role in redox regulation is unclear. Here, we show that breast cancer cells upregulate major facilitator superfamily domain containing 12 (MFSD12) to increase lysosomal cyst(e)ine storage, which is released by cystinosin (CTNS) to maintain GSH levels and buffer oxidative stress.

Inhibition of DPAGT1 suppresses HER2 shedding and trastuzumab resistance in human breast cancer.

Human epidermal growth factor receptor 2-targeted (HER2-targeted) therapy is the mainstay of treatment for HER2+ breast cancer. However, the proteolytic cleavage of HER2, or HER2 shedding, induces the release of the target epitope at the ectodomain (ECD) and the generation of a constitutively active intracellular fragment (p95HER2), impeding the effectiveness of anti-HER2 therapy. Therefore, identifying key regulators in HER2 shedding might provide promising targetable vulnerabilities against resistance.

A Wnt-induced lncRNA-DGCR5 splicing switch drives tumor-promoting inflammation in esophageal squamous cell carcinoma.

Alternative splicing (AS) is a critical mechanism for the aberrant biogenesis of long non-coding RNA (lncRNA). Although the role of Wnt signaling in AS has been implicated, it remains unclear how it mediates lncRNA splicing during cancer progression. Herein, we identify that Wnt3a induces a splicing switch of lncRNA-DGCR5 to generate a short variant (DGCR5-S) that correlates with poor prognosis in esophageal squamous cell carcinoma (ESCC).

Timing and water temperature of drip irrigation regulate cotton growth and yield under film mulching in arid areas of Xinjiang.

Background: Cotton (Gossypium hirsutum L.) is the fiber crop most widely cultivated globally and one of the most important commercial crops in China, irrigation is closely related to the growth of cotton. A water temperature for irrigation that is too low or too high inhibits cotton growth.

Downregulation of BASP1 Promotes Temozolomide Resistance in Gliomas via Epigenetic Activation of the FBXO32/NF-κB/MGMT Axis.

Unlabelled: The chemoresistance of temozolomide-based therapy is a serious limitation for lasting effective treatment of gliomas, while the underlying mechanisms remain unclear. In this study, we showed that downregulation of BASP1 correlated negatively with the response to temozolomide therapy and disease-free survival (DFS) of patients with gliomas. Silencing BASP1 significantly enhanced the temozolomide resistance of glioma cells both in vitro and in vivo through repair of temozolomide-induced DNA damage via activation of the FBXO32/NF-κB/MGMT axis in both MGMT-methylated and -unmethylated gliomas.