From Lab to Home: Ultrasensitive Rapid Detection of SARS-CoV-2 with a Cascade CRISPR/Cas13a-Cas12a System Based Lateral Flow Assay.

Currently, CRISPR/Cas-based molecular diagnostic techniques usually rely on the introduction of nucleic acid amplification to improve their sensitivity, which is usually more time-consuming, susceptible to aerosol contamination, and therefore not suitable for at-home molecular testing. In this research, we developed an advanced CRISPR/Cas13a-Cas12a-based lateral flow assay that facilitated the ultrasensitive and rapid detection of SARS-CoV-2 RNA directly from samples, without the need for nucleic acid amplification. This method was called CRISPR LFA enabling at-home RNA testing (CLEAR). CLEAR used a novel cascade mechanism with specially designed probes that fold into hairpin structures, enabling visual detection of SARS-CoV-2 sequences down to 1 aM sensitivity levels. More importantly, CLEAR had a positive coincidence rate of 100% and a negative coincidence rate of 100% for clinical nasopharyngeal swabs from 16 patients. CLEAR was particularly suitable for at-home molecular testing, providing a low-cost, user-friendly solution that can efficiently distinguish between different SARS-CoV-2 variants. CLEAR overcame the common limitations of high sensitivity and potential contamination associated with traditional PCR-based systems, making it a promising tool for widespread public health application, especially in environments with limited access to laboratory resources.

Research on cognitive impairment and potential risk factors in peritoneal dialysis patients: An observational study.

The objective of this study is to investigate the associated risk factors and their effects on cognitive impairment (CI) in patients undergoing peritoneal dialysis. A retrospective analysis was conducted on the basic information of 268 patients who underwent continuous ambulatory peritoneal dialysis (CAPD) at our hospital from January 2020 to September 2023. Cognitive function was assessed using the Montreal Cognitive Assessment Scale during their subsequent dialysis visits. Participants were categorized into a CI group and a cognitively normal group. Blood and other biological samples were collected for relevant biomarker analysis. Subsequently, we analyzed and compared the factors influencing CI between the 2 groups. The prevalence of CI among CAPD patients was 58.2%. Compared to the cognitively normal group, the CI group had a higher prevalence of alcohol consumption, lower levels of education, and reduced serum uric acid levels (P < .05). There was also a higher incidence of autoimmune diseases such as systemic lupus erythematosus in the CI group (P < .05). In terms of dialysis efficacy, the residual kidney Kt/V and residual kidney Ccr were significantly lower in the CI group compared to the cognitively normal group. In blood parameters, the CI group showed elevated total cholesterol levels and lower serum calcium concentrations (P < .05). Logistic regression analysis identified male gender, older age, lower educational attainment, hypercholesterolemia, and elevated high-sensitivity C-reactive protein levels as independent risk factors for CI in CAPD patients (P < .05). Additionally, in this patient cohort, dialysis duration and residual renal function were protective factors against CI (P < .05). CI is prevalent among PD patients. Elevated high-sensitivity C-reactive protein levels, male gender, older age, lower educational attainment, and hypercholesterolemia constitute an independent risk factor for CI in CAPD patients, whereas residual renal function acts as a protective element.

Water-assisted oxidative redispersion of Cu particles through formation of Cu hydroxide at room temperature.

Sintering of active metal species often happens during catalytic reactions, which requires redispersion in a reactive atmosphere at elevated temperatures to recover the activity. Herein, we report a simple method to redisperse sintered Cu catalysts via O2-H2O treatment at room temperature. In-situ spectroscopic characterizations reveal that H2O induces the formation of hydroxylated Cu species in humid O2, pushing surface diffusion of Cu atoms at room temperature. Further, surface OH groups formed on most hydroxylable support surfaces such as γ-Al2O3, SiO2, and CeO2 in the humid atmosphere help to pull the mobile Cu species and enhance Cu redispersion. Both pushing and pulling effects of gaseous H2O promote the structural transformation of Cu aggregates into highly dispersed Cu species at room temperature, which exhibit enhanced activity in reverse water gas shift and preferential oxidation of carbon monoxide reactions. These findings highlight the important role of H2O in the dynamic structure evolution of supported metal nanocatalysts and lay the foundation for the regeneration of sintered catalysts under mild conditions.

Influence of Social Distance on Foreign Language Effect in Moral Judgment.

Previous research has shown that moral choice depends on language, a phenomenon known as the moral foreign language effect (mFLE). The current study examines the influence of social distance on the mFLE. In Experiment 1, 200 participants were randomly assigned to either close or distant social distance in English or Chinese. In Experiment 2, 188 participants were randomly assigned to either English or Chinese and were presented with eight moral dilemmas, each with five different levels of social distance. After reading the dilemma, participants made a choice on a binary scale (Yes/No) in both Experiments 1 and 2 or on a more sensitive 100-point scale in Experiment 2. The results showed that the mFLE was present in distant social distance but absent in close social distance. Finally, a meta-analysis of the results from both studies confirmed the effect of social distance on the mFLE. These findings demonstrate that social distance might play an important role in moderating the mFLE in moral judgment.

Computer Vision-Based Biomass Estimation for Invasive Plants.

We report on the detailed steps of a method to estimate the biomass of invasive plants based on UAV remote sensing and computer vision. To collect samples from the study area, we prepared a sample square assembly to randomize the sampling points. An unmanned aerial camera system was constructed using a drone and camera to acquire continuous RGB images of the study area through automated navigation. After completing the shooting, the aboveground biomass in the sample frame was collected, and all correspondences were labeled and packaged. The sample data was processed, and the aerial images were segmented into small images of 280 x 280 pixels to create an image dataset. A deep convolutional neural network was used to map the distribution of Mikania micrantha in the study area, and its vegetation index was obtained. The organisms collected were dried, and the dry weight was recorded as the ground truth biomass. The invasive plant biomass regression model was constructed using the K-nearest neighbor regression (KNNR) by extracting the vegetation index from the sample images as an independent variable and integrating it with the ground truth biomass as a dependent variable. The results showed that it was possible to predict the biomass of invasive plants accurately. An accurate spatial distribution map of invasive plant biomass was generated by image traversal, allowing precise identification of high-risk areas affected by invasive plants. In summary, this study demonstrates the potential of combining unmanned aerial vehicle remote sensing with machine learning techniques to estimate invasive plant biomass. It contributes significantly to the research of new technologies and methods for real-time monitoring of invasive plants and provides technical support for intelligent monitoring and hazard assessment at the regional scale.

Integrated phase separation in microliter droplets for ultratrace-enriching biomarker analysis.

Ultratrace-enriching biomarker analysis is an effective method for achieving highly accurate and enhanced sensitive detection. In this study, we have developed an enrichment detection platform by combining a minipillar array with an aqueous two-phase system (ATPS) for ultratrace enriching biomarker analysis. After optimizing the enrichment conditions of ATPS, target miRNAs at ultratrace levels specifically accumulate in the DEX-rich phase, which significantly increases the target miRNA concentration-related fluorescence intensity. Compared to non-enriched miRNA in the single-phase PEG solution, the detection limit of ATPS-enriched miRNA had improved more than 200-fold. The ATPS-based enrichment detection strategy offers a novel and convenient approach for the simultaneous detection of biomarkers with ultratrace.

Foldback-crRNA-Enhanced CRISPR/Cas13a System (FCECas13a) Enables Direct Detection of Ultrashort sncRNA.

The CRISPR/Cas13a system has promising applications in clinical small noncoding RNA (sncRNA) detection because it is free from the interference of genomic DNA. However, detecting ultrashort sncRNAs (less than 20 nucleotides) has been challenging because the Cas13a nuclease requires longer crRNA-target RNA hybrids to be activated. Here, we report the development of a foldback-crRNA-enhanced CRISPR/Cas13a (FCECas13a) system that overcomes the limitations of the current CRISPR/Cas13a system in detecting ultrashort sncRNAs. The FCECas13a system employs a 3'-terminal foldback crRNA that hybridizes with the target ultrashort sncRNA, forming a double strand that "tricks" the Cas13a nuclease into activating the HEPN structural domain and generating trans-cleavage activity. The FCECas13a system can accurately detect miRNA720 (a sncRNA currently known as tRNA-derived small RNA), which is only 17 nucleotides long and has a concentration as low as 15 fM within 20 min. This FCECas13a system opens new avenues for ultrashort sncRNA detection with significant implications for basic biological research, disease prognosis, and molecular diagnosis.

Ultrasound-enhanced catalytic hairpin assembly capable of ultrasensitive microRNA biosensing for the early screening of Alzheimer's disease.

Catalytic hairpin assembly (CHA) is a promising enzyme-free, isothermal signal amplification strategy, but the relatively time-consuming strand replacement limits its application scenarios. Here, we developed an ultrasound-enhanced catalytic hairpin assembly (UECHA) biosensing platform for early screening of Alzheimer's disease by introducing a portable acoustic-drive platform with functionalized microspheres for effective biomarkers enrichment and fluorescence enhancement. By constructing a gradient ultrasonic field in a microcavity, the platform concentrates the functionalized microspheres in a central position, accompanied by an enhanced fluorescence signal with a specific release. In addition, the programmable frequency modulation can also modify the acoustic potential well and effectively promote non-equilibrium chemical reactions such as CHA (25 min). Compared with the conventional catalytic hairpin assembly (CHA), UECHA allows for direct and quantitative measurement of AD miRNAs down to 3.55 × 10-15 M in 1 µL samples. This visual analysis of ultra-trace biomarkers based on acoustic enrichment and promotion provides a new perspective for the rapid and highly sensitive clinical detection of Alzheimer's disease.

RatioCRISPR: A ratiometric biochip based on CRISPR/Cas12a for automated and multiplexed detection of heteroplasmic SNPs in mitochondrial DNA.

Mitochondrial genetic diseases are often characterized by heteroplasmic single nucleotide polymorphisms (SNPs) where both wild-type (WT) and mutant-type (MT) coexist, making detection of accurate SNP abundance critical for diagnosis. Here, we present RatioCRISPR, an automated ratiometric biochip sensor based on the CRISPR/Cas12a system for detecting multiple heteroplasmic SNPs in mitochondrial DNA (mtDNA). The ratiometric sensor output is only influenced by the relative abundance of WT and MT, with minimal impact from sample concentration. Biochips allow the simultaneous detection of multiple SNP sites for more accurate disease diagnosis. RatioCRISPR can accurately detect 8 samples simultaneously within 25 min with a limit of detection (LOD) of 15.7 aM. We successfully detected 13 simulated samples of three mtDNA point mutations (m.3460G>A, m.11778G>A, and m.14484T>C), which lead to Leber's hereditary optic neuropathy (LHON) and set a threshold (60%) of heteroplasmy to evaluate disease risk. This automated and accurate biosensor has broad applications in diagnosing multiple SNPs, especially those with heteroplasmic variations, making it an advanced and convenient tool for mtDNA disease diagnosis.

Metabolic Syndrome and Inflammation from Young to Mid-Adulthood and Subclinical Kidney Damage in Middle-Aged Australians.

Background: Relationships between metabolic syndrome (MetS), inflammation, and chronic kidney disease (CKD) have been reported, but long-term follow-up studies are limited. This study aimed to investigate whether MetS and C-reactive protein (CRP) from young adulthood associated with the risk of subclinical kidney damage (SKD), a surrogate measure for CKD, in mid-adulthood. Materials and Methods: One thousand fifteen participants from the Childhood Determinants of Adult Health study aged 26-36 years at baseline (2004-2006) were followed up at age 36-49 (2014-2019). Log-binomial regression was used to determine whether MetS and high CRP in young adulthood and from young to mid-adulthood predicted the risk of SKD (an estimated glomerular filtration rate [eGFR] of 30-60 mL/min/1.73 m2 or an eGFR >60 mL/min/1.73 m2 with a urine albumin-creatinine ratio ≥2.5 mg/mmol [males] or ≥3.5 mg/mmol [females]) in midlife. Results: Having MetS in young adulthood was associated with an increased risk of SKD in midlife (adjusted relative risk [aRR] = 2.67, 95% confidence interval [CI]: 1.24-5.76). Participants with MetS and high CRP as young adults had a greater risk of having SKD in midlife (aRR = 4.27, 95% CI: 1.61-11.30) compared with those without MetS and high CRP. Furthermore, for participants with persistent MetS, the aRR of SKD in midlife was 4.08 (95% CI: 1.84-9.05) compared with those without MetS from young to mid-adulthood. No significant associations were found between CRP in young adulthood, or change in CRP from young to mid-adulthood, and SKD in midlife. Conclusions: MetS in young adulthood, with and without high CRP, and persistent MetS were associated with an increased risk of SKD in middle midlife.

Investigation of Immune Responses in Giant African Snail, Achatina immaculata, against a Two-Round Lipopolysaccharide Challenge.

As one of the 100 most-threatening invasive alien species, the giant African snail (Achatina immaculata) has successfully invaded and established itself in most areas of southern China. Protection against recurrent pathogen infections is vital to biological invasion. Enhanced immune protection has been previously found in other invertebrates, but not in the unique immune system of the giant African snail. In the present study, the survival rate of the giant African snail was recorded following a second infection with lethal doses of Escherichia coli after a previous first injection using lipopolysaccharide (LPS), and the mechanism of immune enhancement was investigated by examining the cellular and transcriptomic response of the giant African snail after two successive stimuli using LPS. Snails injected first with LPS, sterilized physiologic (0.9%) saline (SPS), phosphate-buffered saline (PBS) or untreated (Blank) were rechallenged at 7d with E. coli (Ec), and were named as LPS + Ec, SPS + Ec, PBS + Ec, Ec, and Blank. The log-rank test shows the survival rate of the LPS + Ec group as significantly higher than that of other control groups after the second injection (p < 0.05). By performing cell counting and BrdU labeling on newly generated circulating hemocytes, we found that the total hemocyte count (THC) and the ratio of BrdU-positive cells to total cells increased significantly after primary stimulation with LPS and that they further increased after the second challenge. Then, caspase-3 of apoptosis protease and two antioxidant enzyme activities (CAT and SOD) increased significantly after infection, and were significantly higher in the second response than they had been in the first round. Moreover, transcriptome analysis results showed that 84 differentially expressed genes (DEGs) were expressed at higher levels in both the resting and activating states after the second immune response compared to the levels observed after the first challenge. Among them, some DEGs, including Toll-like receptor 4 (TLR4) and its downstream signaling molecules, were verified using qRT-PCR and were consistent with the transcriptome assay results. Based on gene expression levels, we proposed that these genes related to the TLR signaling cascade participate in enhanced immune protection. All results provide evidence that enhanced immune protection exists in the giant African snail.

Advancements in artificial micro/nanomotors for nucleic acid biosensing: a review of recent progress.

Artificial micro/nanomotors represent a class of well-designed tools that exhibit dynamic motion and remote-control capabilities, endowing them with the capacity to perform complex tasks at the micro/nanoscale. Their utilization in nucleic acid biosensing has been paid significant attention, owing to their ability to facilitate targeted delivery of detection probes to designated sites and enhance hybridization between detection probes and target nucleic acids, thereby improving the sensitivity and specificity of biosensing. Within this comprehensive overview, we elucidate the advancement of nucleic acid biosensing through the integration of micro/nanomotors over the past decade. In particular, we provide an in-depth exploration of the diverse applications of micro/nanomotors in nucleic acid biosensing, including fluorescence recovery-based biosensing, velocity change-based biosensing, and aggregation-enhanced biosensing. Additionally, we outline the remaining challenges that impede the practical application of artificial micro/nanomotors in nucleic acid detection, and offer personal insights into prospective avenues for future development. By overcoming these obstacles, we anticipate that artificial micro/nanomotors will revolutionize conventional nucleic acid detection methodologies, providing enhanced sensitivity and reduced diagnostic timeframes, thereby facilitating more effective disease diagnosis.

Acetyl-cinobufagin suppresses triple-negative breast cancer progression by inhibiting the STAT3 pathway.

BACKGROUND: The incidence of breast cancer (BC) worldwide has increased substantially in recent years. Epithelial-mesenchymal transition (EMT) refers to a crucial event impacting tumor heterogeneity. Although cinobufagin acts as an effective anticancer agent, the clinical use of cinobufagin is limited due to its strong toxicity. Acetyl-cinobufagin, a pre-drug of cinobufagin, was developed and prepared with greater efficacy and lower toxicity. METHODS: A heterograft mouse model using triple negative breast cancer (TNBC) cell lines, was used to evaluate the potency of acetyl-cinobufagin. Signal transducer and stimulator of transcription 3 (STAT3)/EMT involvement was investigated by gene knockout experiments using siRNA and Western blot analysis. RESULTS: Acetyl-cinobufagin inhibited proliferation, migration, and cell cycle S/G2 transition and promoted apoptosis in TNBC cells in vitro. In general, IL6 triggered the phosphorylation of the transcription factor STAT3 thereby activating the STAT3 pathway and inducing EMT. Mechanistically, acetyl-cinobufagin suppressed the phosphorylation of the transcription factor STAT3 and blocked the interleukin (IL6)-triggered translocation of STAT3 to the cell nucleus. In addition, acetyl-cinobufagin suppressed EMT in TNBC by inhibiting the STAT3 pathway. Experiments in an animal model of breast cancer clearly showed that acetyl-cinobufagin was able to reduce tumor growth. CONCLUSIONS: The findings of this study support the potential clinical use of acetyl-cinobufagin as a STAT3 inhibitor in TNBC adjuvant therapy.

A neural cell adhesion molecule from oyster Crassostrea gigas: Molecular identification and immune functional characterization.

Neural cell adhesion molecules (NCAMs) are large cell-surface glycoproteins playing important roles in cell-cell and cell-extracellular matrix interactions in nervous system. Recent study identified a homologue of NCAM (CgNCAM) from the Pacific oyster Crassostrea gigas. Its ORF was of 2634 bp which encodes a protein (877 amino acids) consisting of five immunoglobulin domains and two fibronectin type III domains. CgNCAM transcripts were broadly distributed in oyster tissues especially in mantle, labial palp and haemolymph. CgNCAM showed up-regulated expression in haemocytes of oysters after Vibrio splendidus and Staphylococcus aureus stimulation. The recombinant CgNCAM protein (rCgNCAM) was able to bind manose, lipopolysaccharide and glucan, as well as different microbes including Gram-negative bacteria and fungi. rCgNCAM displayed bacterial agglutination and hemagglutination activity. CgNCAM improved the phagocytosis of haemocytes towards V. splendidus by regulating the expression of CgIntegrin, CgRho J and CgMAPKK. Moreover, CgNCAM was involved in the extracellular trap establishment of haemocytes after V. splendidus stimulation. The results collectively indicated that CgNCAM acted as a recognition receptor executing multiple immune functions to recognize and eliminate invading microorganisms in innate immunity of oysters.

Research on the Efficacy of Ganpu Vine Tea in Inhibiting Uric Acid Production.

Ganpu vine tea is a new type of health care citrus fruit tea made from citrus shell, Pu-er tea, and vine tea baked as raw materials. In this study, the in vitro uric acid synthase inhibition system and hyperuric acid cell model were constructed to appraise the uric acid lowering efficacy of Ganpu vine tea, traditional Ganpu tea, and vine tea. Results showed that in the uric acid synthase inhibition system, the aqueous extract can inhibite the puric metabolically related enzymes, such as adenosine deaminase (ADA), purine nucleoside phosphorylase (PNP), and xanthine oxidase (XOD). The ability of the aqueous extract to inhibit the above enzyme was as follows: vine tea > Ganpu vine tea > Ganpu tea; all teas had a strong effect on XOD inhibition. The hyperuric acid cell model test showed that the aqueous extract inhibited uric acid production through accumulating inosine and hypoxanthine and hindering xanthine synthesis. The uric acid reductive ability was as follows: Vine tea > Ganpu vine tea > Ganpu tea. The inhibition of enzymes related to uric acid synthesis and the inhibition of uric acid production were significantly enhanced through adding vine tea to Ganpu tea. It also shows that flavonoids are the main factor driving this ability because they are the main active ingredients in these botanical drinks.

Childhood modifiable risk factors and later life chronic kidney disease: a systematic review.

BACKGROUND: Relationships between adulthood modifiable risk factors and chronic kidney disease (CKD) are well-established, but associations with childhood risk factors are unclear. This study systematically assesses the published evidence about childhood modifiable risk factors and adulthood CKD. METHODS: We searched MEDLINE, EMBASE, and Web of Science to 6th May 2022. Articles were included if (1) they were population-based longitudinal studies, (2) exposures were potentially modifiable, for example through pharmacological or lifestyle modifications, including clinical conditions/measures (diabetes, blood pressure, adiposity, and dyslipidaemia); health behaviours (smoking, alcohol consumption, physical activity, fitness, and poor nutrition); and socio-economic factors (socio-economic position), and occurred during childhood (ages 2-19 years), and (3) outcome was CKD or surrogate markers of CKD in adulthood (ages 20 years or older). Three reviewers independently extracted the data. RESULTS: 15,232 articles were identified after deduplication; 17 articles met the inclusion criteria, reporting childhood blood pressure (n = 8), adiposity (n = 4), type 2 diabetes (n = 1), socio-economic position (n = 1), famine (n = 1), cardiorespiratory fitness (n = 1), and a healthy lifestyle score (n = 1). The results suggested positive associations of childhood adiposity, type 2 diabetes, and low socio-economic position and cardiorespiratory fitness in females with CKD in adulthood. Findings were inconsistent on associations between childhood BP and CKD in adulthood. Childhood healthy lifestyle score and exposure to famine were not associated with risk of CKD in adulthood. CONCLUSIONS: The limited evidence suggests childhood factors may contribute to the CKD risk in adulthood, particularly adiposity, type 2 diabetes, and low socio-economic position and cardiorespiratory fitness in females. Further high-quality community-based studies are needed with long-term follow-up and investigation of a broader range of modifiable risk factors.

Metal-oxide interactions modulating the activity of active oxygen species on atomically dispersed silver catalysts.

The activity of active oxygen species on supported Ag atoms can be effectively modulated by metal-support interactions using different oxide supports. The strong interaction between Ag and Al2O3 with more electrons transferred from Ag to Al2O3 leads to the formation of more Ag-O2- (superoxide) species, responsible for the selective oxidation of ethylene to ethylene oxide. The relatively weak interaction between Ag and SiO2 induces the generation of Ag-O (atomic oxygen) and Ag-O22- (peroxide) species, which are more active for complete oxidation of CO and ethylene to CO2. This work is of significance for deep understanding of active surface species in atomically dispersed metal catalysts.

Inhibition of invasive plant Mikania micrantha rapid growth by host-specific rust (Puccinia spegazzinii).

Mikania micrantha Kunth is a fast-growing global invasive weed species that causes severe damage to natural ecosystems and very large economic losses of forest and crop production. Although Puccinia spegazzinii can effectively inhibit the growth of M. micrantha and is used as a biological control strain in many countries, the mechanism of inhibiting the growth of M. micrantha is not clear. Here, we used a combination of phenotypic, enzyme activity, transcriptomic, and metabolomic approaches to study the response of M. micrantha after infection by P. spegazzinii. In the early stages of rust infection, jasmonic acid (JA), jasmonoyl-isoleucine (JA-Ile), and salicylic acid (SA) levels in infected leaves were significantly lower than those in uninfected leaves. In teliospore initial and developed stages of P. spegazzinii, JA and JA-Ile levels substantially increased by more than 6 times, which resulted in a significant decrease in the accumulation of defense hormone SA in infected leaves of M. micrantha. The contents of plant growth-promoting hormones were significantly reduced in the infected plants as a result of substantial downregulation of the expression of key genes related to hormone biosynthesis. Furthermore, rust infection led to high levels of reactive oxygen species in chloroplasts and the destruction of chlorophyll structure, which also led to decreased photosynthetic gene expression, net photosynthetic rate, activity of Rubisco, and levels of important organic acids in the Calvin cycle. We hypothesized that after P. spegazzinii infection, JA or JA-Ile accumulation not only inhibited SA levels to promote rust infection and development, but also impeded the rapid growth of M. micrantha by affecting plant growth hormones, carbon, and nitrogen metabolic pathways.

ß, ß-Dimethylacrylshikonin potentiates paclitaxel activity, suppresses immune evasion and triple negative breast cancer progression via STAT3Y705 phosphorylation inhibition based on network pharmacology and transcriptomics analysis.

BACKGOUND: Triple negative breast cancer (TNBC) is an extremely aggressive and rapidly progressing cancer, wherein existing therapies provide little benefit to patients. ß, ß-Dimethylacrylshikonin (DMAS), an active naphthoquinone derived from comfrey root, has potent anticancer activity. However, the antitumor function of DMAS against TNBC remains to be proved. PURPOSE: Explore effects of DMAS on TNBC and clarify the mechanism. STUDY DESIGN: Network pharmacology, transcriptomics and various cell functional experiments were applied to TNBC cells to explore the effects of DMAS on TNBC. The conclusions were further validated in xenograft animal models. METHODS: MTT, EdU, transwell, scratch tests, flow cytometry, immunofluorescence, and immunoblot were utilized to assess the activity of DMAS on three TNBC cell lines. The anti-TNBC mechanism of DMAS was clarified by overexpression and knockdown of STAT3 in BT-549 cells. In vivo efficacy of DMAS was analysed using a xenograft mouse model. RESULTS: In vitro analysis revealed that DMAS inhibited the G2/M phase transition and suppressed TNBC proliferation. Additionally, DMAS triggered mitochondrial-dependent apoptosis and reduced cell migration by antagonizing epithelial-mesenchymal transition. Mechanistically, DMAS exerted its antitumour effects by inhibiting STAT3Y705 phosphorylation. STAT3 overexpression abolished the inhibitory effect of DMAS. Further studies showed that treatment with DMAS inhibited TNBC growth in a xenograft model. Notably, DMAS potentiated the sensitivity of TNBC to paclitaxel and inhibited immune evasion by downregulating the immune checkpoint PD-L1. CONCLUSIONS: For the first time, our study revealed that DMAS potentiates paclitaxel activity, suppresses immune evasion and TNBC progression by inhibiting STAT3 pathway. It has the potential as a promising agent for TNBC.

The effect of explicit and implicit online self-compassion interventions on sleep quality among Chinese adults: A longitudinal and diary study.

Objective: This study aimed to investigate the effects of explicit and implicit online intervention methods for self-compassion on improving sleep quality among Chinese adults. Methods: A total of 328 adult participants were recruited to complete the Pittsburgh Sleep Quality Questionnaire and Self-compassion Scale, and 168 participants were randomly assigned to one of three different conditions: two self-compassion intervention groups (self-compassion writing intervention asked participants to write several sentences with self-compassion, and self-compassion combination intervention asked participants to combine words into complete sentences with self-compassion) and one control group. After 1 week of online self-compassion intervention with daily sleep quality measured simultaneously, 150 participants completed the posttest of the Pittsburgh Sleep Quality Questionnaire and Self-Compassion Scale. Results: The pretest and posttests results showed that the self-compassion level and sleep quality of the self-compassion writing intervention group were significantly better than those of the control group. However, there was no significant difference between the self-compassion combination intervention group and the control group. For the diary tracking results, sleep quality was significantly better for both the self-compassion writing intervention group and self-compassion combination intervention group than the control group, however, the self-compassion writing intervention group showed great improvements. Conclusion: Both self-compassion writing and combination interventions were effective in improving sleep quality, and the effect of self-compassion writing was more stable.