Advances in Regulating Cellular Behavior Using Micropatterns.

Micropatterns, characterized as distinct physical microstructures or chemical adhesion matrices on substance surfaces, have emerged as a powerful tool for manipulating cellular activity. By creating specific extracellular matrix microenvironments, micropatterns can influence various cell behaviors, including orientation, proliferation, migration, and differentiation. This review provides a comprehensive overview of the latest advancements in the use of micropatterns for cell behavior regulation. It discusses the influence of micropattern morphology and coating on cell behavior and the underlying mechanisms. It also highlights future research directions in this field, aiming to inspire new investigations in materials medicine, regenerative medicine, and tissue engineering. The review underscores the potential of micropatterns as a novel approach for controlling cell behavior, which could pave the way for breakthroughs in various biomedical applications.

Flavonoids regulate tumor-associated macrophages - From structure-activity relationship to clinical potential (Review).

In recent years, the strategy for tumor therapy has changed from focusing on the direct killing effect of different types of therapeutic agents on cancer cells to the new mainstream of multi-mode and -pathway combined interventions in the microenvironment of the developing tumor. Flavonoids, with unique tricyclic structures, have diverse and extensive immunomodulatory and anti-cancer activities in the tumor microenvironment (TME). Tumor-associated macrophages (TAMs) are the most abundant immunosuppressive cells in the TME. The regulation of macrophages to fight cancer is a promising immunotherapeutic strategy. This study covers the most comprehensive cognition of flavonoids in regulating TAMs so far. Far more than a simple list of studies, we try to dig out evidence of crosstalk at the molecular level between flavonoids and TAMs from literature, in order to discuss the most relevant chemical structure and its possible relationship with the multimodal pharmacological activity, as well as systematically build a structure-activity relationship between flavonoids and TAMs. Additionally, we point out the advantages of the macro-control of flavonoids in the TME and discuss the potential clinical implications as well as areas for future research of flavonoids in regulating TAMs. These results will provide hopeful directions for the research of antitumor drugs, while providing new ideas for the pharmaceutical industry to develop more effective forms of flavonoids.

Comparative transcriptomic and metabolomic analyses of carotenoid biosynthesis reveal the basis of white petal color in Brassica napus.

MAIN CONCLUSION: The molecular mechanism underlying white petal color in Brassica napus was revealed by transcriptomic and metabolomic analyses. Rapeseed (Brassica napus L.) is one of the most important oilseed crops worldwide, but the mechanisms underlying flower color in this crop are known less. Here, we performed metabolomic and transcriptomic analyses of the yellow-flowered rapeseed cultivar 'Zhongshuang 11' (ZS11) and the white-flowered inbred line 'White Petal' (WP). The total carotenoid contents were 1.778-fold and 1.969-fold higher in ZS11 vs. WP petals at stages S2 and S4, respectively. Our findings suggest that white petal color in WP flowers is primarily due to decreased lutein and zeaxanthin contents. Transcriptome analysis revealed 10,116 differentially expressed genes with a fourfold or greater change in expression (P-value less than 0.001) in WP vs. ZS11 petals, including 1,209 genes that were differentially expressed at four different stages and 20 genes in the carotenoid metabolism pathway. BnNCED4b, encoding a protein involved in carotenoid degradation, was expressed at abnormally high levels in WP petals, suggesting it might play a key role in white petal formation. The results of qRT-PCR were consistent with the transcriptome data. The results of this study provide important insights into the molecular mechanisms of the carotenoid metabolic pathway in rapeseed petals, and the candidate genes identified in this study provide a resource for the creation of new B. napus germplasms with different petal colors.

The plasmid-borne quinolone resistance protein QnrB, a novel DnaA-binding protein, increases the bacterial mutation rate by triggering DNA replication stress.

Bacterial antibiotic resistance, a global health threat, is caused by plasmid transfer or genetic mutations. Quinolones are important antibiotics, partially because they are fully synthetic and resistance genes are unlikely to exist in nature; nonetheless, quinolone resistance proteins have been identified. The mechanism by which plasmid-borne quinolone resistance proteins promotes the selection of quinolone-resistant mutants is unclear. Here, we show that QnrB increases the bacterial mutation rate. Transcriptomic and genome sequencing analyses showed that QnrB promoted gene abundance near the origin of replication (oriC). In addition, the QnrB expression level correlated with the replication origin to terminus (oriC/ter) ratio, indicating QnrB-induced DNA replication stress. Our results also show that QnrB is a DnaA-binding protein that may act as an activator of DNA replication initiation. Interaction of QnrB with DnaA promoted the formation of the DnaA-oriC open complex, which leads to DNA replication over-initiation. Our data indicate that plasmid-borne QnrB increases bacterial mutation rates and that genetic changes can alleviate the fitness cost imposed by transmitted plasmids. Derivative mutations may impair antibiotic efficacy and threaten the value of antibiotic treatments. Enhanced understanding of how bacteria adapt to the antibiotic environment will lead to new therapeutic strategies for antibiotic-resistant infections.

The potato transcription factor StbZIP61 regulates dynamic biosynthesis of salicylic acid in defense against Phytophthora infestans infection.

Salicylic acid (SA) signalling plays an essential role in plant innate immunity. In this study, we identified a component in the SA signaling pathway in potato (Solanum tuberosum), the transcription factor StbZIP61, and characterized its function in defence against Phytophthora infestans. Expression of StbZIP61 was induced upon P. infestans infection and following exposure to the defense signaling hormones SA, ethylene and jasmonic acid. Overexpression of StbZIP61 increased the tolerance of potato plants to P. infestans while RNA interference (RNAi) increased susceptibility. Yeast two-hybrid and pull down experiments revealed that StbZIP61 could interact with an NPR3-like protein (StNPR3L) that inhibited its DNA-binding and transcriptional activation activities. Moreover, StNPR3L interacted with StbZIP61 in an SA-dependent manner. Among candidate genes involved in SA-regulated defense responses, StbZIP61 had a significant impact on expression of StICS1, which encodes a key enzyme for SA biosynthesis. StICS1 transcription was induced upon P. infestans infection and this responsive expression to the pathogen was reduced in StbZIP61 RNAi plants. Accordingly, StICS1 expression was remarkably enhanced in StbZIP61-overexpressing plants. Together, our data demonstrate that StbZIP61 functions in concert with StNPR3L to regulate the temporal activation of SA biosynthesis, which contributes to SA-mediated immunity against P. infestans infection in potato.

[Real-time three dimensional echocardiography-based evaluation of left ventricular function in children with Kawasaki disease].

OBJECTIVE: To evaluate the clinical significance of full volume real-time three-dimensional echocardiography (RT-3DE) in the assessment of general and local systolic functions of the left ventricle in children with Kawasaki disease (KD). METHODS: A total of 73 KD children (40 with and 33 without coronary artery lesions) and 35 healthy control children were recruited. Left ventricular ejection fraction (LVEF) was measured by M-mode ultrasound and full volume RT-3DE imaging. A left ventricular volume-time curve and a segmental speed-time curve were generated. Differences between control subjects and patients with and without coronary artery lesions were analyzed. RESULTS: The M-mode ultrasound measurements of LVEF in KD patients with coronary artery lesions were significantly lower than in KD patients without coronary artery lesions and control children (P<0.05), while there was no significant difference between KD patients without coronary artery lesions and control children. RT-3DE measurements of LVEF were significantly different between the three groups analyzed (P<0.05): coronary artery lesion group < no coronary artery lesion group < control group. RT-3DE-based segmental ventricular wall analysis revealed that Tmsv16-SD and Tmsv12-SD in KD patients with coronary artery lesions were significantly higher than other two groups and Tmsv6-SD was also significantly higher than in the normal control group (P<0.05) and that Tmsv16-SD in KD patients without coronary artery lesions increased significantly compared with the normal control group (P<0.05). CONCLUSIONS: RT-3DE can be used in the quantitative evaluation of the left ventricular function and therefore has significant clinical implications.

Network pharmacology and bioinformatics approach to unravel the mechanism of Xiao-chai-hu-tang herbal formula in tinnitus treatment.

Background: Tinnitus treatment remains a global challenge, and current therapeutic approaches are still controversial. This study aims to elucidate the potential mechanisms of Xiao-Chai-Hu-Tang (XCHT) in treating tinnitus through the analysis of network pharmacology, mendelian randomization and molecular docking, and molecular dynamics simulation analysis. We hope to contribute to the research on the target of action of traditional Chinese medicine and exploration of the mechanism of tinnitus. Methods: We utilized network pharmacology to screen potential targets of action of XCHT on tinnitus. Mendelian randomization was employed to determine the causal relationship between potential targets of action and tinnitus. Finally, molecular docking and molecular dynamics simulation with clear targets and the combination of the active ingredient in effectiveness. Results: Through network pharmacology, we identified 38 potential targets of action. Mendelian randomization analysis revealed that HIF1A (OR [95 % CI] = 0.78 [0.65, 0.94], P = 0.008) and CCND1 (OR [95 % CI] = 1.22 [1.00, 1.49], P = 0.04) exhibited significant results with tinnitus. Molecular docking and molecular dynamics simulation of HIF1A and active ingredients demonstrated good binding efficacy. Conclusion: HIF1A may play a key role in the treatment of tinnitus by XCHT, which may play a certain protective role in tinnitus patients and may inhibit the occurrence and development of tinnitus. However, the specific mechanism and effect need to be further studied and verified.

Low-dose deoxynivalenol exposure triggers hepatic excessive ferritinophagy and mitophagy mitigated by hesperidin modulated O-GlcNAcylation.

The level and breadth of deoxynivalenol (DON) contamination in foods made with cereals have increased due to global warming. Consumption of DON-contaminated food and feed poses significant risks to human health and animal production. However, the mechanism by which prolonged exposure to low-dose DON leads to liver damage in animals and effective treatments remain unclear. Our investigation focused on the impact of varying DON exposure times on AML12 cells as well as the long-term liver damage caused by low-dose DON exposure in mice. In addition, this article investigated the unique role of hesperidin in mitigating hepatic ferroptosis induced by low-dose DON exposure. Our results imply that DON's suppression of O-GlcNAcylation exacerbated mitophagy by encouraging ferritinophagy and causing labile iron to aggregate within mitochondria. Furthermore, DON could increase NCOA4-mediated ferritinophagy by De-O-GlcNAcylation FTH to trigger ferroptosis-associated liver injury in mice. Notably, hesperidin alleviated the susceptibility to ferroptosis by increasing O-GlcNAcylation levels and effectively attenuated the liver injury induced by low-dose DON exposure. This finding provides a new strategy for dealing with liver injury caused by low-dose DON exposure.

18ß-Glycyrrhetinic acid protects against deoxynivalenol-induced liver injury via modulating ferritinophagy and mitochondrial quality control.

Deoxynivalenol (DON), a widespread mycotoxin, represents a substantial public health hazard due to its propensity to contaminate agricultural produce, leading to both acute and chronic health issues in humans and animals upon consumption. The role of ferroptosis in DON-induced hepatic damage remains largely unexplored. This study investigates the impact of 18ß-glycyrrhetinic acid (GA), a prominent constituent of glycyrrhiza, on DON hepatotoxicity and elucidates the underlying mechanisms. Our results indicate that GA effectively attenuates liver injury inflicted by DON. This was achieved by inhibiting nuclear receptor coactivator 4 (NCOA4)-mediated ferritinophagy and ferroptosis, as well as by adjusting mitochondrial quality control (MQC). Specifically, GA curtails ferritinophagy by diminishing NCOA4 expression without affecting the autophagic flux. At a molecular level, GA binds to and stabilizes programmed cell death protein 4 (PDCD4), thereby inhibiting its ubiquitination and subsequent degradation. This stabilization of PDCD4 leads to the downregulation of NCOA4 via the JNK-Jun-NCOA4 axis. Knockdown of PDCD4 weakened GA's protective action against DON exposure. Furthermore, GA improved mitochondrial function and limited excessive mitophagy and mitochondrial division induced by DON. Disrupting GA's modulation of MQC nullified its anti-ferroptosis effects. Overall, GA offers protection against DON-induced ferroptosis by blocking ferritinophagy and managing MQC. ENVIRONMENTAL IMPLICATION: Food contamination from mycotoxins, is a problem for agricultural and food industries worldwide. Deoxynivalenol (DON), the most common mycotoxins in cereal commodities. A survey in 2023 showed that the positivity rate for DON contamination in food reached more than 70% globally. DON can damage the health of humans whether exposed to high doses for short periods of time or low doses for long periods of time. We have discovered 18ß-Glycyrrhetinic acid (GA), a prominent constituent of glycyrrhiza. Liver damage caused by low-dose DON can be successfully treated with GA. This study will support the means of DON control, including antidotes.

Genetic prediction of the causal relationship between schizophrenia and tumors: a Mendelian randomized study.

Background: Patients with schizophrenia are at a higher risk of developing cancer. However, the causal relationship between schizophrenia and different tumor types remains unclear. Methods: Using a two-sample, two-way Mendelian randomization method, we used publicly available genome-wide association analysis (GWAS) aggregate data to study the causal relationship between schizophrenia and different cancer risk factors. These tumors included lung adenocarcinoma, lung squamous cell carcinoma, small-cell lung cancer, gastric cancer, alcohol-related hepatocellular cancer, tumors involving the lungs, breast, thyroid gland, pancreas, prostate, ovaries and cervix, endometrium, colon and colorectum, and bladder. We used the inverse variance weighting (IVW) method to determine the causal relationship between schizophrenia and different tumor risk factors. In addition, we conducted a sensitivity test to evaluate the effectiveness of the causality. Results: After adjusting for heterogeneity, evidence of a causal relationship between schizophrenia and lung cancer risk was observed (odds ratio [OR]=1.001, 95% confidence interval [CI], 1.000-1.001; P=0.0155). In the sensitivity analysis, the causal effect of schizophrenia on the risk of lung cancer was consistent in both direction and degree. However, no evidence of causality or reverse causality between schizophrenia and other tumors was found. Conclusion: This study elucidated a causal relationship between the genetic predictors of schizophrenia and the risk of lung cancer, thereby providing a basis for the prevention, pathogenesis, and treatment of schizophrenia in patients with lung cancer.

Exploring risk factors for autoimmune diseases complicated by non-hodgkin lymphoma through regulatory T cell immune-related traits: a Mendelian randomization study.

Background: The effect of immune cells on autoimmune diseases (ADs) complicated by non-Hodgkin lymphoma (NHL) has been widely recognized, but a causal relationship between regulatory T cell (Treg) immune traits and ADs complicated by NHL remains debated. Methods: Aggregate data for 84 Treg-related immune traits were downloaded from the Genome-Wide Association Study (GWAS) catalog, and GWAS data for diffuse large B-cell lymphoma (DLBCL; n=315243), follicular lymphoma (FL; n=325831), sjögren's syndrome (SS; n=402090), rheumatoid arthritis (RA; n=276465), dermatopolymyositis (DM; n=311640), psoriasis (n=407876), atopic dermatitis (AD; n=382254), ulcerative colitis (UC; n=411317), crohn's disease(CD; n=411973) and systemic lupus erythematosus (SLE; n=307587) were downloaded from the FinnGen database. The inverse variance weighting (IVW) method was mainly used to infer any causal association between Treg-related immune traits and DLBCL, FL, SS, DM, RA, Psoriasis, AD, UC, CD and SLE, supplemented by MR-Egger, weighted median, simple mode, and weighted mode. Moreover, we performed sensitivity analyses to assess the validity of the causal relationships. Results: There was a potential genetic predisposition association identified between CD39+ CD8br AC, CD39+ CD8br % T cell, and the risk of DLBCL (OR=1.51, p<0.001; OR=1.25, p=0.001) (adjusted FDR<0.1). Genetic prediction revealed potential associations between CD25++ CD8br AC, CD28- CD25++ CD8br % T cell, CD39+ CD8br % CD8br, and the risk of FL (OR=1.13, p=0.022; OR=1.28, p=0.042; OR=0.90, p=0.016) (adjusted FDR>0.1). Furthermore, SLE and CD exhibited a genetically predicted potential association with the CD39+ CD8+ Tregs subset. SS and DM were possibly associated with an increase in the quantity of the CD4+ Tregs subset; RA may have reduced the quantity of the CD39+ CD8+ Tregs subset, although no causal relationship was identified. Sensitivity analyses supported the robustness of our findings. Conclusions: There existed a genetically predicted potential association between the CD39+ CD8+ Tregs subset and the risk of DLBCL, while SLE and CD were genetically predicted to be potentially associated with the CD39+ CD8+ Tregs subset. The CD39+ CD8+ Tregs subset potentially aided in the clinical diagnosis and treatment of SLE or CD complicated by DLBCL.

Osteogenic differentiation of bone mesenchymal stem cells on linearly aligned triangular micropatterns.

Mesenchymal stem cells (MSCs) hold promise for regenerative medicine, particularly for bone tissue engineering. However, directing MSC differentiation towards specific lineages, such as osteogenic, while minimizing undesired phenotypes remains a challenge. Here, we investigate the influence of micropatterns on the behavior and lineage commitment of rat bone marrow-derived MSCs (rBMSCs), focusing on osteogenic differentiation. Linearly aligned triangular micropatterns (TPs) and circular micropatterns (CPs) coated with fibronectin were fabricated to study their effects on rBMSC morphology and differentiation and the underlying mechanobiological mechanisms. TPs, especially TP15 (15 µm), induced the cell elongation and thinning, while CPs also promoted the cell stretching, as evidenced by the decreased circularity and increased aspect ratio. TP15 significantly promoted osteogenic differentiation, with increased expression of osteogenic genes (Runx2, Spp1, Alpl, Bglap, Col1a1) and decreased expression of adipogenic genes (Pparg, Cebpa, Fabp4). Conversely, CPs inhibited both osteogenic and adipogenic differentiation. Mechanistically, TP15 increased Piezo1 activity, cytoskeletal remodeling including the aggregates of F-actin and myosin filaments at the cell periphery, YAP1 nuclear translocation, and integrin upregulation. Piezo1 inhibition suppressed the osteogenic genes expression, myosin remodeling, and YAP1 nuclear translocation, indicating Piezo1-mediated the mechanotransduction in rBMSCs on TPs. TP15 also induced osteogenic differentiation of BMSCs from aging rats, with upregulated Piezo1 and nuclear translocation of YAP1. Therefore, triangular micropatterns, particularly TP15, promote osteogenesis and inhibit adipogenesis of rBMSCs through Piezo1-mediated myosin and YAP1 pathways. Our study provides novel insights into the mechanobiological mechanisms governing MSC behaviors on micropatterns, offering new strategies for tissue engineering and regenerative medicine.

DLM-GelMA/tumor slice sandwich structured tumor on a chip for drug efficacy testing.

The in vitro recapitulation of tumor microenvironment is of great interest to preclinical screening of drugs. Compared with culture of cell lines, tumor organ slices can better preserve the complex tumor architecture and phenotypic activity of native cells, but are limited by their exposure to fluid shear and gradual degradation under perfusion culture. Here, we established a decellularized liver matrix (DLM)-GelMA "sandwich" structure and a perfusion-based microfluidic platform to support long-term culture of tumor slices with excellent structural integrity and cell viability over 7 days. The DLM-GelMA was able to secrete cytokines and growth factors while providing shear protection to the tumor slice via the sandwich structure, leading to the preservation of the tumor microenvironment where immune cells (CD3, CD8, CD68), tumor-associated fibroblasts (α-SMA), and extracellular matrix components (collagen I, fibronectin) were well maintained. Furthermore, this chip presented anti-tumor efficacy at cisplatin (20 µM) on tumor patients, demonstrating our platform's efficacy to design patient-specific treatment regimens. Taken together, the successful development of this DLM-GelMA sandwich structure on the chip could faithfully reflect the tumor microenvironment and immune response, accelerating the screening process of drug molecules and providing insights for practical medicine.

Single-cell and spatial proteo-transcriptomic profiling reveals immune infiltration heterogeneity associated with neuroendocrine features in small cell lung cancer.

Small cell lung cancer (SCLC) is an aggressive pulmonary neuroendocrine malignancy featured by cold tumor immune microenvironment (TIME), limited benefit from immunotherapy, and poor survival. The spatial heterogeneity of TIME significantly associated with anti-tumor immunity has not been systemically studied in SCLC. We performed ultra-high-plex Digital Spatial Profiling on 132 tissue microarray cores from 44 treatment-naive limited-stage SCLC tumors. Incorporating single-cell RNA-sequencing data from a local cohort and published SCLC data, we established a spatial proteo-transcriptomic landscape covering over 18,000 genes and 60 key immuno-oncology proteins that participate in signaling pathways affecting tumorigenesis, immune regulation, and cancer metabolism across 3 pathologically defined spatial compartments (pan-CK-positive tumor nest; CD45/CD3-positive tumor stroma; para-tumor). Our study depicted the spatial transcriptomic and proteomic TIME architecture of SCLC, indicating clear intra-tumor heterogeneity dictated via canonical neuroendocrine subtyping markers; revealed the enrichment of innate immune cells and functionally impaired B cells in tumor nest and suggested potentially important immunoregulatory roles of monocytes/macrophages. We identified RE1 silencing factor (REST) as a potential biomarker for SCLC associated with low neuroendocrine features, more active anti-tumor immunity, and prolonged survival.

Potential of natural flavonoids to target breast cancer angiogenesis (review).

Angiogenesis is the process by which new blood vessels form and is required for tumour growth and metastasis. It helps in supplying oxygen and nutrients to tumour cells and plays a crucial role in the local progression and distant metastasis of, and development of treatment resistance in, breast cancer. Tumour angiogenesis is currently regarded as a critical therapeutic target; however, anti-angiogenic therapy for breast cancer fails to produce satisfactory results, owing to issues such as inconsistent efficacy and significant adverse reactions. As a result, new anti-angiogenic drugs are urgently needed. Flavonoids, a class of natural compounds found in many foods, are inexpensive, widely available, and exhibit a broad range of biological activities, low toxicity, and favourable safety profiles. Several studies find that various flavonoids inhibit angiogenesis in breast cancer, indicating great therapeutic potential. In this review, we summarize the role of angiogenesis in breast cancer and the potential of natural flavonoids as anti-angiogenic agents for breast cancer treatment. We discuss the value and significance of nanotechnology for improving flavonoid absorption and utilization and anti-angiogenic effects, as well as the challenges of using natural flavonoids as drugs.

Advances of new drugs bedaquiline and delamanid in the treatment of multi-drug resistant tuberculosis in children.

Tuberculosis (TB) is a major public health problem, with nearly 10 million new cases and millions of deaths each year. Around 10% of these cases are in children, but only a fraction receive proper diagnosis and treatment. The spread of drug-resistant (DR) strain of TB has made it difficult to control, with only 60% of patients responding to treatment. Multi-drug resistant TB (MDR-TB) is often undiagnosed in children due to lack of awareness or under-diagnosis, and the target for children's DR-TB treatment has only been met in 15% of goals. New medications such as bedaquiline and delamanid have been approved for treating DR-TB. However, due to age and weight differences, adults and children require different dosages. The availability of child-friendly formulations is limited by a lack of clinical data in children. This paper reviews the development history of these drugs, their mechanism of action, efficacy, safety potential problems and current use in treating DR-TB in children.

Exosomal ncRNAs facilitate interactive 'dialogue' between tumor cells and tumor-associated macrophages.

As a biological carrier, exosomes participate in the communication between various kinds of cells, and can mediate the interactive 'dialogue' between tumor cells and tumor-associated macrophages (TAMs). TAMs are the most abundant cell population in the tumor stroma and are an important part of the tumor immune microenvironment. Various stimulating factors in the tumor microenvironment influence the polarization of TAMs into multiple phenotypes, such as M1 and M2. It plays a dual role in tumor immunity by both promoting and inhibiting tumor growth. Exosome-encapsulated non-coding RNAs (ncRNAs) participate in the interactive 'dialogue' between exosome-mediated TAMs and tumor cells. Tumor-derived exosomal ncRNAs can promote macrophage polarization, whereas exosomal ncRNAs derived from TAMs can affect tumor proliferation, metastasis, angiogenesis, and chemotherapy resistance. The present review summarizes the dual effects of exosomal ncRNAs on tumor cells and TAMs, and discusses the application of exosomal ncRNAs as a potential diagnostic or prognostic marker and drug delivery system, to provide a new perspective and potential therapeutic drugs on targeting exosomes and macrophages in the treatment of tumors.

MYB pathways that regulate UV-B-induced anthocyanin biosynthesis in blueberry (Vaccinium corymbosum).

Ultraviolet-B (UV-B) promotes anthocyanin accumulation and improves fruit quality in plants. To explore the underlying network of MYB transcription factors that regulates UV-B-induced anthocyanin biosynthesis in blueberry (Vaccinium corymbosum), we analyzed the response of MYB transcription factor genes to UV-B treatment. Transcriptome sequencing analysis revealed that VcMYBA2 and VcMYB114 expression were upregulated and were positively correlated with the expression of anthocyanin structural genes under UV-B radiation according to weighted gene co-expression network analysis (WGCNA) data. The VcUVR8-VcCOP1-VcHY5 pathway perceives UV-B signals and promotes the expression of anthocyanin structural genes by upregulating VcMYBA2 and VcMYB114 or by regulating the VcBBXs-VcMYB pathway, ultimately promoting anthocyanin accumulation. By contrast, VcMYB4a and VcUSP1 were downregulated under UV-B treatment, and VcMYB4a expression was negatively correlated with that of anthocyanin biosynthesis genes in response to UV-B. Analysis of VcMYB4a-overexpressing and wild-type blueberry calli exposed to UV-B radiation revealed that VcMYB4a represses UV-B-induced anthocyanin accumulation. Yeast one-hybrid and dual luciferase assays showed that the universal stress protein VcUSP1 directly bound to the promoter of VcMYB4a. These results suggest that the VcUSP1-VcMYB4a pathway negatively regulates UV-B-induced anthocyanin biosynthesis and provide insight into UV-B-induced anthocyanin biosynthesis.

Trends and challenges of multi-drug resistance in childhood tuberculosis.

Drug-resistant tuberculosis (DR-TB) in children is a growing global health concern, This review provides an overview of the current epidemiology of childhood TB and DR-TB, including prevalence, incidence, and mortality. We discuss the challenges in diagnosing TB and DR-TB in children and the limitations of current diagnostic tools. We summarize the challenges associated with treating multi-drug resistance TB in childhood, including limitations of current treatment options, drug adverse effects, prolonged regimens, and managing and monitoring during treatment. We highlight the urgent need for improved diagnosis and treatment of DR-TB in children. The treatment of children with multidrug-resistant tuberculosis will be expanded to include the evaluation of new drugs or new combinations of drugs. Basic research is needed to support the technological development of biomarkers to assess the phase of therapy, as well as the urgent need for improved diagnostic and treatment options.

ncRNA-mediated ceRNA regulatory network: Transcriptomic insights into breast cancer progression and treatment strategies.

With the rapid development of next-generation sequencing technology, several studies have shown that ncRNAs can act as competitive endogenous RNAs (ceRNAs) and are involved in various biological processes, such as proliferation, differentiation, apoptosis, and migration of breast cancer (BC) cells, and plays an important role in BC progression as a molecular target for its diagnosis, treatment, prognosis, and differentiation of subtypes and age groups of BC patients. Based on the description of ceRNA-related biological functions, this study screened and sorted the sequencing analysis and experimental verification conclusions of BC-related ceRNAs and found that the ncRNAs mediated ceRNA networks can promote the development of BC by promoting the expression of genes related to BC proliferation, drug resistance, and apoptosis, inducing the production of epithelial-mesenchymal transition (EMT) to promote metastasis and activating cancer-related signaling pathways.