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Abstract Breast cancer ranks as one of the most common malignancies among women, with its prognosis and therapeutic efficacy heavily influenced by factors associated with the tumor cell biology, particularly the tumor microenvironment (TME). The diverse elements of the TME are engaged in dynamic bidirectional signaling interactions with various pathways, which together dictate the growth, invasiveness, and metastatic potential of breast cancer. The Hedgehog (Hh) signaling pathway, first identified in Drosophila, has been established as playing a critical role in human development and disease. Notably, the dysregulation of the Hh pathway is recognized as a major driver in the initiation, progression, and metastasis of breast cancer. Consequently, elucidating the mechanisms by which the Hh pathway interacts with the distinct components of the breast cancer TME is essential for comprehensively evaluating the link between Hh pathway activation and breast cancer risk. This understanding is also imperative for devising novel targeted therapeutic strategies and preventive measures against breast cancer. In this review, we delineate the current understanding of the impact of Hh pathway perturbations on the breast cancer TME, including the intricate and complex network of intersecting signaling cascades. Additionally, we focus on the therapeutic promise and clinical challenges of Hh pathway inhibitors that target the TME, providing insights into their potential clinical utility and the obstacles that must be overcome to harness their full therapeutic potential.

Background Numerous studies have demonstrated that hypothermia in preterm infants correlates with increased morbidity and mortality, especially among those with very low or extremely low birth weights (VLBW/ELBW). An increasing number of healthcare facilities are implementing quality improvement (QI) bundles to lower the incidence of hypothermia at birth in this vulnerable population. However, the effectiveness and safety of these interventions have yet to be fully assessed. A meta-analysis is necessary to evaluate the efficacy and safety of QI bundles in reducing hypothermia at birth among VLBW/ELBW infants. Methods We searched PubMed, Embase, the Cochrane Library and Web of Science through April 22nd, 2024. Study selection, data extraction, quality evaluation and risk bias assessment were performed independently by two investigators. Meta-analysis was performed using Review Manager 5.4.1. Results A total of 18 studies were included for qualitative analysis and 12 for meta-analysis. For VLBW infants, meta-analysis revealed a reduction in hypothermia and an increase in hyperthermia following the introduction of QI bundles (mild hypothermia, OR 0.22, 95% CI [0.13–0.37]; moderate hypothermia, OR 0.18, 95% CI [0.15–0.22]; hyperthermia, OR 2.79, 95% CI [1.53–5.09]). For ELBW infants, meta-analysis showed a decrease in hypothermia but no increase in hyperthermia after implementing QI bundles (mild hypothermia, OR 0.46, 95% CI [0.26–0.81]; moderate hypothermia, OR 0.21, 95% CI [0.08–0.58]; hyperthermia, OR 1.10, 95% CI [0.22–5.43]). Conclusion QI bundles effectively reduce hypothermia in VLBW/ELBW infants, but they may also increase hyperthermia, especially in VLBW infants.

Abstract Background Gut bacteria are related to colorectal cancer (CRC) and its clinicopathologic characteristics. Objective To develop gut bacterial subtypes and explore potential microbial targets for CRC. Methods Stool samples from 914 volunteers (376 CRCs, 363 advanced adenomas, and 175 normal controls) were included for 16S rRNA sequencing. Unsupervised learning was used to generate gut microbial subtypes. Gut bacterial community composition and clustering effects were plotted. Differences of gut bacterial abundance were analyzed. Then, the association of CRC‐associated bacteria with subtypes and the association of gut bacteria with clinical information were assessed. The CatBoost models based on gut differential bacteria were constructed to identify the diseases including CRC and advanced adenoma (AA). Results Four gut microbial subtypes (A, B, C, D) were finally obtained via unsupervised learning. The characteristic bacteria of each subtype were Escherichia‐Shigella in subtype A, Streptococcus in subtype B, Blautia in subtype C, and Bacteroides in subtype D. Clinical information (e.g., free fatty acids and total cholesterol) and CRC pathological information (e.g., tumor depth) varied among gut microbial subtypes. Bacilli, Lactobacillales, etc., were positively correlated with subtype B. Positive correlation of Blautia, Lachnospiraceae, etc., with subtype C and negative correlation of Coriobacteriia, Coriobacteriales, etc., with subtype D were found. Finally, the predictive ability of CatBoost models for CRC identification was improved based on gut microbial subtypes. Conclusion Gut microbial subtypes provide characteristic gut bacteria and are expected to contribute to the diagnosis of CRC.

Abstract Background The circadian clock, also known as the circadian rhythm, is responsible for predicting daily and seasonal changes in the environment, and adjusting various physiological and developmental processes to the appropriate times during plant growth and development. The circadian clock controls the expression of the Lhcb gene, which encodes the chlorophyll a/b binding protein. However, the roles of the Lhcb gene in tea plant remain unclear. Results In this study, a total of 16 CsLhcb genes were identified based on the tea plant genome, which were distributed on 8 chromosomes of the tea plant. The promoter regions of CsLhcb genes have a variety of cis-acting elements including hormonal, abiotic stress responses and light response elements. The CsLhcb family genes are involved in the light response process in tea plant. The photosynthetic parameter of tea leaves showed rhythmic changes during the two photoperiod periods (48 h). Stomata are basically open during the day and closed at night. Real-time quantitative PCR results showed that most of the CsLhcb family genes were highly expressed during the day, but were less expressed at night. Conclusions Results indicated that CsLhcb genes were involved in the circadian clock process of tea plant, it also provided potential references for further understanding of the function of CsLhcb gene family in tea plant.

During tumor development, the tumor itself must continuously generate new blood vessels to meet their growth needs while also allowing for tumor invasion and metastasis. One of the most common features of tumors is hypoxia, which drives the process of tumor angiogenesis by regulating the tumor microenvironment, thus adversely affecting the prognosis of patients. In addition, to overcome unsuitable environments for growth, such as hypoxia, nutrient deficiency, hyperacidity, and immunosuppression, the tumor microenvironment (TME) coordinates angiogenesis in several ways to restore the supply of oxygen and nutrients and to remove metabolic wastes. A growing body of research suggests that tumor angiogenesis and hypoxia interact through a complex interplay of crosstalk, which is inextricably linked to the TME. Here, we review the TME's positive contribution to angiogenesis from an angiogenesis-centric perspective while considering the objective impact of hypoxic phenotypes and the status and limitations of current angiogenic therapies.

With the rapid development of histological techniques and the widespread application of single-cell sequencing in eukaryotes, researchers desire to explore individual microbial genotypes and functional expression, which deepens our understanding of microorganisms. In this review, the history of the development of microbial detection technologies was revealed and the difficulties in the application of single-cell sequencing in microorganisms were dissected as well. Moreover, the characteristics of the currently emerging microbial single-cell sequencing (Microbe-seq) technology were summarized, and the prospects of the application of Microbe-seq in microorganisms were distilled based on the current development status. Despite its mature development, the Microbe-seq technology was still in the optimization stage. A retrospective study was conducted, aiming to promote the widespread application of single-cell sequencing in microorganisms and facilitate further improvement in the technology.

Background: In recent years, there has been a surge in media reports on articles being retracted after publication. This issue has gained significant attention, particularly due to the consecutive large-scale retractions carried out by renowned international publishers, which have aroused widespread concern in the society. Objective: To analyze the data of retracted articles and retraction trends. Methods: The publications were searched through Web of Science Core Collection (WoSCC) database and imported into CiteSpace in plain text format, and visual analysis of countries, institutions, keywords, and subject areas were performed to reveal the trends of retracted articles and the worst areas of retraction. Results: From 1990 to 2022, 21,568 retracted articles were retrieved, among which the number of retracted articles increased year by year. China is the country with the highest number of retracted articles; Islamic Azad University is the institution with the highest number of retracted articles. In the analysis of all retracted articles across different subject areas, the number of retracted articles in the field of oncology was the highest; In the keyword cluster analysis of retracted articles within the field of oncology, the most prominent category of retracted articles were related to pancreatic cancer. Conclusions: Scientific and systematic analysis of retracted articles is conducive to improving the quality of papers, raising the level of human research, and cleaning up the research environment.

Abstract Background The current standard of care for locally advanced gastric cancer (GC) involves neoadjuvant chemotherapy followed by radical surgery. Recently, neoadjuvant treatment for this condition has involved the exploration of immunotherapy plus chemotherapy as a potential approach. However, the efficacy remains uncertain. Methods A single‐arm, phase 2 study was conducted to evaluate the efficacy and tolerability of neoadjuvant camrelizumab combined with mFOLFOX6 and identify potential biomarkers of response through multi‐omics analysis in patients with resectable locally advanced GC. The primary endpoint was the pathological complete response (pCR) rate. Secondary endpoints included the R0 rate, near pCR rate, progression‐free survival (PFS), disease‐free survival (DFS), and overall survival (OS). Multi‐omics analysis was assessed by whole‐exome sequencing, transcriptome sequencing, and multiplex immunofluorescence (mIF) using biopsies pre‐ and post‐neoadjuvant therapy. Results This study involved 60 patients, of which 55 underwent gastrectomy. Among these, five (9.1%) attained a pathological complete response (pCR), and 11 (20.0%) reached near pCR. No unexpected treatment‐emergent adverse events or perioperative mortality were observed, and the regimen presented a manageable safety profile. Molecular changes identified through multi‐omics analysis correlated with treatment response, highlighting associations between HER2‐positive and CTNNB1 mutations with treatment sensitivity and a favourable prognosis. This finding was further supported by immune cell infiltration analysis and mIF. Expression data uncovered a risk model with four genes (RALYL, SCGN, CCKBR, NTS) linked to poor response. Additionally, post‐treatment infiltration of CD8+ T lymphocytes positively correlates with pathological response. Conclusion The findings suggest the combination of PD‐1‐inhibitor and mFOLFOX6 showed efficacy and acceptable toxicity for locally advanced GC. Extended follow‐up is required to determine the duration of the response. This study lays essential groundwork for developing precise neoadjuvant regimens.

Idiopathic multicentric Castleman disease is a rare and complex disease characterized by systemic inflammation, lymphadenopathy, and multiorgan involvement. This case report presents a 66-year-old Chinese man with idiopathic multicenter Castleman disease without significant lymphadenopathy and challenging diagnosis. Patients present with fever, fatigue, loss of appetite, weight loss, and acute kidney injury. Initially, a urinary tract infection was suspected, but despite anti-infective treatment, the patient’s symptoms persisted. Lymph node biopsy, although there is no significant lymphadenopathy, confirms idiopathic multicenter Castleman disease. Treatment includes thalidomide, cyclophosphamide, and dexamethasone, as well as supportive measures and infection control. After 8 months of follow-up, the patient’s clinical symptoms, inflammatory markers and renal function were significantly improved, and there was no symptomatic recurrence. This case underscores the importance of considering idiopathic multicenter Castleman’s disease in patients with persistent fever and systemic inflammation, even in the absence of significant lymphadenopathy. Early identification and accurate diagnosis of idiopathic multicenter Castleman’s disease can lead to the initiation of targeted therapy strategies that ultimately yield favorable outcomes.

Abstract Background Emergence of novel immuno‐therapeutics has shown promising improvement in the clinical outcome of colorectal cancer (CRC). Objective To identify robust immune checkpoints based on expression and immune infiltration profiles of clinical CRC samples. Methods One dataset from The Cancer Genome Atlas database and two from Gene Expression Omnibus were independently employed for the analysis. Genes associated with overall survival were identified, and distribution of each immune checkpoint with respect to different clinical features was determined to explore key immune checkpoints. Multiple staining methods were used to verify the correlation between key immune checkpoint ICOS and clinical pathological features. Differentially expressed mRNA and long non‐coding RNA (lncRNA) were then detected for gene set enrichment analysis and gene set variation analysis to investigate the differentially enriched biological processes between low‐ and high‐expression groups. Significant immune‐related mRNAs and lncRNA were subjected to competing endogenous RNA (ceRNA) network analysis. Correlation of inducible T‐cell costimulator (ICOS) and top 10 genes in ceRNA network were further considered for validation. Results ICOS was identified from 14 immune checkpoints as the most highly correlated gene with survival and clinical features in CRC. The expression of ICOS protein in the poorly differentiated group was lower than that in the moderately differentiated group, and the expression in different pathological stages was significant. In addition, the expressions of ICOS were negatively correlated with Ki67. A conspicuous number of immune‐related pathways were enriched in differentially expressed genes in the ICOS high‐ and low‐expression groups. Integration with immune infiltration data revealed a multitude of differentially expressed immune‐related genes enriched for ceRNA network. Furthermore, expression of top 10 genes investigated from ceRNA network showed high correlation with ICOS. Conclusion ICOS might serve as a robust immune checkpoint for prognosis with several genes being potential targets of ICOS‐directed immunotherapy in CRC.

Exosomes are nanoscale extracellular vesicles that are secreted by a variety of cells in the body. They carry particular miRNA, protein molecules, transcription factors, and other information molecules, and they play a role in the pathophysiological regulation of a number of diseases in the body. Exosomes can persist steadily in biological tissues and bodily fluids. Exosomes have quickly advanced in ophthalmology in recent years due to the extensive studies of exosomes in a variety of fields, such as diabetic retinopathy, age-related macular degeneration, autoimmune uveitis, corneal disease, glaucoma, and other diseases. The number of people who are blind caused by diabetic retinopathy is rising as living standards rise. However, it is still unclear how diabetic retinopathy works. In recent years, many studies have found that exosomes play an important role in diabetic retinopathy. In this paper, the most recent developments in exosome studies as they relate to the pathogenesis and progression of diabetic retinopathy are reviewed.

Abstract Background Aging is one of the factors leading to cancer. Gut microbiota is related to aging and colorectal cancer (CRC). Methods A total of 11 metagenomic data sets related to CRC were collected from the R package curated Metagenomic Data. After batch effect correction, healthy individuals and CRC samples were divided into three age groups. Ggplot2 and Microbiota Process packages were used for visual description of species composition and PCA in healthy individuals and CRC samples. LEfSe analysis was performed for species relative abundance data in healthy/CRC groups according to age. Spearman correlation coefficient of age‐differentiated bacteria in healthy individuals and CRC samples was calculated separately. Finally, the age prediction model and CRC risk prediction model were constructed based on the age‐differentiated bacteria. Results The structure and composition of the gut microbiota were significantly different among the three groups. For example, the abundance of Bacteroides vulgatus in the old group was lower than that in the other two groups, the abundance of Bacteroides fragilis increased with aging. In addition, seven species of bacteria whose abundance increases with aging were screened out. Furthermore, the abundance of pathogenic bacteria (Escherichia_coli, Butyricimonas_virosa, Ruminococcus_bicirculans, Bacteroides_fragilis and Streptococcus_vestibularis) increased with aging in CRCs. The abundance of probiotics (Eubacterium_eligens) decreased with aging in CRCs. The age prediction model for healthy individuals based on the 80 age‐related differential bacteria and model of CRC patients based on the 58 age‐related differential bacteria performed well, with AUC of 0.79 and 0.71, respectively. The AUC of CRC risk prediction model based on 45 disease differential bacteria was 0.83. After removing the intersection between the disease‐differentiated bacteria and the age‐differentiated bacteria from the healthy samples, the AUC of CRC risk prediction model based on remaining 31 bacteria was 0.8. CRC risk prediction models for each of the three age groups showed no significant difference in accuracy (young: AUC=0.82, middle: AUC=0.83, old: AUC=0.85). Conclusion Age as a factor affecting microbial composition should be considered in the application of gut microbiota to predict the risk of CRC.

Tea plants are a perennial crop with significant economic value. Chlorophyll, a key factor in tea leaf color and photosynthetic efficiency, is affected by the photoperiod and usually exhibits diurnal and seasonal variations. In this study, high-throughput transcriptomic analysis was used to study the chlorophyll metabolism, under different photoperiods, of tea plants. We conducted a time-series sampling under a skeleton photoperiod (6L6D) and continuous light conditions (24 L), measuring the chlorophyll and carotenoid content at a photoperiod interval of 3 h (24 h). Transcriptome sequencing was performed at six time points across two light cycles, followed by bioinformatics analysis to identify and annotate the differentially expressed genes (DEGs) involved in chlorophyll metabolism. The results revealed distinct expression patterns of key genes in the chlorophyll biosynthetic pathway. The expression levels of CHLE (magnesium-protoporphyrin IX monomethyl ester cyclase gene), CHLP (geranylgeranyl reductase gene), CLH (chlorophyllase gene), and POR (cytochrome P450 oxidoreductase gene), encoding enzymes in chlorophyll synthesis, were increased under continuous light conditions (24 L). At 6L6D, the expression levels of CHLP1.1, POR1.1, and POR1.2 showed an oscillating trend. The expression levels of CHLP1.2 and CLH1.1 showed the same trend, they both decreased under light treatment and increased under dark treatment. Our findings provide potential insights into the molecular basis of how photoperiods regulate chlorophyll metabolism in tea plants.

Leaf spreading is a key processing step that affects the aroma formation of green tea. The effects of a single-light wavelength on the aroma and taste of tea have been extensively studied. Less attention has been paid to the effect of different complex light intensities on the formation of green tea’s volatile aroma during leaf spreading. The current study was designed to evaluate how leaf spreading under different complex light intensities relates to the quality of green tea. Using headspace solid-phase micro-extraction and gas chromatography-mass spectrometry (HS-SPME/GC-MS), volatile flavor compounds in green tea were analyzed during leaf spreading in five different light conditions. Multivariate statistical analysis and odor activity values (OAVs) were used to classify these samples and identify key odors. Eight distinct groups, including ninety volatile compounds, were detected. The most prevalent volatile compounds found in green tea samples were hydrocarbons and alcohols, which accounted for 29% and 22% of the total volatile compounds, respectively. Fourteen volatile compounds (OAV > 1) were identified as key active differential odorants. The chestnut-like aroma in green tea was mostly derived from 3-methyl-butanal and linalool, which were significantly accumulated in medium-intensity light (ML).

Abstract Triple-negative breast cancer (TNBC), a highly aggressive and heterogeneous subtype of breast cancer, lacks effective treatment options. Sophora flavescens Aiton, a Chinese medicinal plant, is often used in traditional Chinese medicine to treat cancer. Matrine (MAT) is an alkaloid extracted from Sophora flavescens. It has good anticancer effects, and thus can be explored as a new therapeutic agent in TNBC research. We performed bioinformatics analysis to analyze the differentially expressed genes between normal breast tissues and TNBC tissues, and comprehensive network pharmacology analyses. The activity and invasion ability of TNBC cells treated with MAT were analyzed. Apoptosis and cell cycle progression were determined using cytometry. We used Monodansylcadaverine (MDC) staining to determine the condition of autophagosomes. Finally, the expression levels of the key target proteins of the PI3K/AKT pathway were determined using western blotting. The proliferation and invasion ability of MDA-MB-231 and MDA-MB-468 can be effectively inhibited by MAT. The results of flow cytometry indicated that MAT arrested the TNBC cell cycle and induced apoptosis. In addition, we confirmed that MAT inhibited the expression of BCL-2 while up-regulating the expression of cleaved caspase-3. Moreover, enhanced intensity of MDC staining and high LC3-II expression were observed, which confirmed that MAT induced autophagy in TNBC cells. Western blotting showed that MAT inhibited the PI3K/AKT pathway and downregulated the expressions of PI3K, AKT, p-AKT, and PGK1. This study provides feasible methods, which include bioinformatics analysis and in vitro experiments, for the identification of compounds with anti-TNBC properties. MAT inhibited the PI3K/AKT signaling pathway, arrested cell cycle, as well as promoted cell apoptosis and autophagy. These experiments provide evidence for the anti-TNBC effect of MAT and identified potential targets against TNBC.

Abstract Background Implantable Collamer Lens (ICL) surgery has been proven to be a safe, effective, and predictable method for correcting myopia and myopic astigmatism. However, predicting the vault and ideal ICL size remains technically challenging. Despite the growing use of artificial intelligence (AI) in ophthalmology, no AI studies have provided available choices of different instruments and combinations for further vault and size predictions. This study aimed to fill this gap and predict post-operative vault and appropriate ICL size utilizing the comparison of numerous AI algorithms, stacking ensemble learning, and data from various ophthalmic devices and combinations. Results This retrospective and cross-sectional study included 1941 eyes of 1941 patients from Zhongshan Ophthalmic Center. For both vault prediction and ICL size selection, the combination containing Pentacam, Sirius, and UBM demonstrated the best results in test sets [R 2 = 0.499 (95% CI 0.470–0.528), mean absolute error = 130.655 (95% CI 128.949–132.111), accuracy = 0.895 (95% CI 0.883–0.907), AUC = 0.928 (95% CI 0.916–0.941)]. Sulcus-to-sulcus (STS), a parameter from UBM, ranked among the top five significant contributors to both post-operative vault and optimal ICL size prediction, consistently outperforming white-to-white (WTW). Moreover, dual-device combinations or single-device parameters could also effectively predict vault and ideal ICL size, and excellent ICL selection prediction was achievable using only UBM parameters. Conclusions Strategies based on multiple machine learning algorithms for different ophthalmic devices and combinations are applicable for vault predicting and ICL sizing, potentially improving the safety of the ICL implantation. Moreover, our findings emphasize the crucial role of UBM in the perioperative period of ICL surgery, as it provides key STS measurements that outperformed WTW measurements in predicting post-operative vault and optimal ICL size, highlighting its potential to enhance ICL implantation safety and accuracy.

Abstract Background The development of biofuels, especially liquid hydrocarbon fuels, has been widely concerned due to the depletion of fossil resources. In order to obtain fuel precursors, the reaction of C–C bond formation is usually carried out with biomass derived ketones/aldehydes as reactants. Acetoin and 2,3-butanediol are two platform chemicals, which are co-existed in fermentation broth and traditionally separated by distillation, and then acetoin could be use as C4 building block to prepare hydrocarbon fuels. In order to mitigate the process complexity, direct aldol condensation reaction of acetoin in fermentation broth was studied in this work. Results A one-pot process of product separation and acetoin derivative synthesis was proposed based on salting-out extraction (SOE). Aldol condensation reaction of acetoin and 5-methyl furfural in different SOE systems was compared, and the results showed that the synthesis of C10 fuel precursors and separation of C10 products and 2,3-butanediol from fermentation broth were achieved in one-pot with ethanolammonium butyrate (EOAB) and K2HPO4 as SOE reagents and catalysts. The SOE and reaction conditions such as the concentrations of EOAB and K2HPO4, reaction temperature and time were optimized. When the system was composed of 6 wt% EOAB-44 wt% K2HPO4 and the mixture was stirred for 6 h at 200 rpm, 40 ℃, the yield of C10 products was 80.7%, and 95.5% 2,3-butanediol was distributed to the top EOAB-rich phase. The exploration of reaction mechanism showed that an imine intermediate was rapidly formed and the subsequent C10 product formation was the key step for aldol condensation reaction. Conclusions With EOAB and K2HPO4 as SOE reagents and catalysts, one-pot synthesis of fuel precursor from acetoin fermentation broth was achieved without prior purification. A yield of 80.7% for C10 products was obtained which was accumulated at the interface of two aqueous-phase, and 95.5% 2,3-BD was distributed to the top EOAB-rich phase. This work provides a new integration process of product separation and derivative synthesis from fermentation broth based on ionic liquid SOE. Graphical Abstract

The glomerular filtration barrier, comprising the inner layer of capillary fenestrated endothelial cells, outermost podocytes, and the glomerular basement membrane between them, plays a pivotal role in kidney function. Podocytes, terminally differentiated epithelial cells, are challenging to regenerate once injured. They are essential for maintaining the integrity of the glomerular filtration barrier. Damage to podocytes, resulting from intrinsic or extrinsic factors, leads to proteinuria in the early stages and eventually progresses to chronic kidney disease (CKD). Immune-mediated podocyte injury is a primary pathogenic mechanism in proteinuric glomerular diseases, including minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, and lupus nephritis with podocyte involvement. An extensive body of evidence indicates that podocytes not only contribute significantly to the maintenance of the glomerular filtration barrier and serve as targets of immune responses but also exhibit immune cell-like characteristics, participating in both innate and adaptive immunity. They play a pivotal role in mediating glomerular injury and represent potential therapeutic targets for CKD. This review aims to systematically elucidate the mechanisms of podocyte immune injury in various podocyte lesions and provide an overview of recent advances in podocyte immunotherapy. It offers valuable insights for a deeper understanding of the role of podocytes in proteinuric glomerular diseases, and the identification of new therapeutic targets, and has significant implications for the future clinical diagnosis and treatment of podocyte-related disorders.

In Chinese medicine, the Cucurbitaceae family contains many compounds known as cucurbitacins, which have been categorized into 12 classes ranging from A to T and more than 200 derivatives. Cucurbitacins are a class of highly oxidized tetracyclic triterpenoids with potent anticancer properties. The eight components of cucurbitacins with the strongest anticancer activity are cucurbitacins B, D, E, I, IIa, L-glucoside, Q, and R. Cucurbitacins have also been reported to suppress JAK-STAT 3, mTOR, VEGFR, Wnt/β-catenin, and MAPK signaling pathways, all of which are crucial for the survival and demise of cancer cells. In this paper, we review the progress in research on cucurbitacin-induced apoptosis, autophagy, cytoskeleton disruption, cell cycle arrest, inhibition of cell proliferation, inhibition of invasion and migration, inhibition of angiogenesis, epigenetic alterations, and synergistic anticancer effects in tumor cells. Recent studies have identified cucurbitacins as promising molecules for therapeutic innovation with broad versatility in immune response. Thus, cucurbitacin is a promising class of anticancer agents that can be used alone or in combination with chemotherapy and radiotherapy for the treatment of many types of cancer.Therefore, based on the research reports in the past five years at home and abroad, we further summarize and review the structural characteristics, chemical and biological activities, and studies of cucurbitacins based on the previous studies to provide a reference for further development and utilization of cucurbitacins.

Background: Lycopene is a natural red compound with potent antioxidant activity that can be utilized both as pigment and as a raw material in functional food, and so possesses good commercial prospects. The biosynthetic pathway has already been documented, which provides the foundation for lycopene production using biotechnology. Aim of review: Although lycopene production has begun to take shape, there is still an urgent need to alleviate the yield of lycopene. Progress in this area can provide useful reference for metabolic engineering of lycopene production utilizing multiple approaches. Key scientific concepts of review: Using conventional microbial fermentation approaches, biotechnologists have enhanced the yield of lycopene by selecting suitable host strains, utilizing various additives, and optimizing culture conditions. With the development of modern biotechnology, genetic engineering, protein engineering, and metabolic engineering have been applied for lycopene production. Extraction from natural plants is the main way for lycopene production at present. Based on the molecular mechanism of lycopene accumulation, the production of lycopene by plant bioreactor through genetic engineering has a good prospect. Here we summarized common strategies for optimizing lycopene production engineering from a biotechnology perspective, which are mainly carried out by microbial cultivation. We reviewed the challenges and limitations of this approach, summarized the critical aspects, and provided suggestions with the aim of potential future breakthroughs for lycopene production in plants.

Highlights A comprehensive review is presented on the chemical reactions of perovskite films under different environmental conditions and with charge transfer materials and metal electrodes in perovskite solar cells. The influence of chemical reactions on device stability is elucidated. Effective strategies for suppressing the degradation reactions are specified.

Animal models have been indispensable in shaping the understanding of myopia mechanisms, with form-deprivation myopia (FDM) and lens-induced myopia (LIM) being the most utilized. Similar pathological outcomes suggest that these two models are under the control of shared mechanisms. miRNAs play an important role in pathological development. Herein, based on two miRNA datasets (GSE131831 and GSE84220), we aimed to reveal the general miRNA changes involved in myopia development. After a comparison of the differentially expressed miRNAs, miR-671-5p was identified as the common downregulated miRNA in the retina. miR-671-5p is highly conserved and related to 40.78% of the target genes of all downregulated miRNAs. Moreover, 584 target genes of miR-671-5p are related to myopia, from which we further identified 8 hub genes. Pathway analysis showed that these hub genes are enriched in visual learning and extra-nuclear estrogen signaling. Furthermore, two of the hub genes are also targeted by atropine, which strongly supports a key role of miR-671-5p in myopic development. Finally, Tead1 was identified as a possible upstream regulator of miR-671-5p in myopia development. Overall, our study identified the general regulatory role of miR-671-5p in myopia as well as its upstream and downstream mechanisms and provided novel treatment targets, which might inspire future studies.

Celery (Apium graveolens L.) is a kind of green leaf vegetable with a large consumption demand in the food industry. It is a commonly used material in quick-frozen food stuffing such as dumplings and steamed stuffed. Fresh celery leaf blades and petioles are rich in photosynthetic pigments including chlorophyll and carotenoid, their contents are closely related to the quality of celery and its products. In order to explore the effects of freezing and thawing temperature and thawing time on the degradation of photosynthetic pigments in celery leaf blades and petioles, the changes in photosynthetic pigments during thawing storage were measured under different freezing and thawing temperatures. The results showed that lower freezing and thawing temperatures were beneficial to the preservation of photosynthetic pigments in celery leaf blades and petioles, and the loss of photosynthetic pigments enhanced with the increase in thawing temperature and thawing time. Under the cold storage condition of −80 °C, the loss rate of pigment substances can be reduced by nearly 20% compared with that of −18 °C, and −80 °C and 4 °C could be the best temperature combination of freezing and thawing. The content and degradation rate of photosynthetic pigments in celery leaf blades were higher than that in petioles during thawing, with a total chlorophyll loss rate reaching 35% during 6 to 12 h after thawing. The increase in temperature difference between freezing and thawing could aggravate the damage to the cell structure and the degradation of the pigment, as chlorophyll is more sensitive to temperature changes, and the degradation rate is significantly higher than that of carotenoids. From the perspective of delaying the degradation of photosynthetic pigments, the results of this study will provide potential references for the reasonable configuration of freezing and thawing temperatures in the process of storage and transportation of celery products.

BackgroundThe objective of this study was to explore the association between the sarcopenia index and abnormal liver function in adult individuals in the United States.MethodologyThis study employed a rigorous cross-sectional analysis of data derived from the National Health and Nutrition Examination Survey (NHANES) conducted between 2017 and 2018. The primary objective was to investigate the correlation between the sarcopenia index and abnormal liver function. To achieve this, an advanced multivariate regression model was utilized, allowing for comprehensive analysis and meticulous adjustment of relevant variables. To ensure the robustness of the findings, a visually appealing smooth curve was constructed, and a two-stage regression model was applied for validation. Additionally, a detailed gender-stratified analysis was conducted to further explore the association between the sarcopenia index and abnormal liver function within distinct subgroups.ResultsThrough our rigorous participant selection process, a total of 1756 individuals were included in the study. The meticulously adjusted multivariate regression model revealed a significant negative association between the sarcopenia index and abnormal liver function, with an adjusted odds ratio (OR) of 0.73 and a 95% confidence interval (CI) ranging from 0.63 to 0.86. The robustness of this association was further supported by the visually appealing smooth curve plot. Moreover, in the gender-stratified subgroup analysis, after meticulous adjustment for confounding factors, notable differences in this association emerged (males: OR = 0.8, 95% CI: 0.66–0.98; females: OR = 0.61, 95% CI: 0.47–0.79).ConclusionThis cross-sectional study yields robust evidence indicating a negative correlation between the sarcopenia index and abnormal liver function, predominantly observed among females.

The tumor microenvironment (TME), the ''soil'' on which tumor cells grow, has an important role in regulating the proliferation and metastasis of tumor cells as well as their response to treatment. Cancer-associated fibroblasts (CAFs), as the most abundant stromal cells of the TME, can not only directly alter the immunosuppressive effect of the TME through their own metabolism, but also influence the aggregation and function of immune cells by secreting a large number of cytokines and chemokines, reducing the body’s immune surveillance of tumor cells and making them more prone to immune escape. Our study provides a comprehensive review of fibroblast chemotaxis, malignant transformation, metabolic characteristics, and interactions with immune cells. In addition, the current small molecule drugs targeting CAFs have been summarized, including both natural small molecules and targeted drugs for current clinical therapeutic applications. A complete review of the role of fibroblasts in TME from an immune perspective is presented, which has important implications in improving the efficiency of immunotherapy by targeting fibroblasts.

IntroductionAutosomal dominant polycystic kidney disease (ADPKD) is a common genetic disorder. The PKD1 gene is responsible for the majority of ADPKD cases, and the mutations in this gene exhibit high genetic diversity. This study aimed to investigate the association between genotype and phenotype in ADPKD patients with PKD1 gene mutations through pedigree analysis.MethodsEight Chinese pedigrees affected by ADPKD were analyzed using whole-exome sequencing (WES) on peripheral blood DNA. The identified variants were validated using Sanger sequencing, and clinical data from the patients and their families were collected and analyzed.ResultsNine novel mutation sites in PKD1 were discovered across the pedigrees, including c.4247T > G, c.3298_3301delGAGT, c.4798A > G, c.7567G > A, c.11717G > C, c.7703 + 5G > C, c.3296G > A, c.8515_8516insG, and c.5524C > A. These mutations were found to be associated with a range of clinical phenotypes, including chronic kidney disease, hypertension, and polycystic liver. The age of onset and disease progression displayed significant heterogeneity among the pedigrees, with some individuals exhibiting early onset and rapid disease progression, while others remained asymptomatic or had milder disease symptoms. Inheritance patterns supported autosomal dominant inheritance, as affected individuals inherited the mutations from affected parents. However, there were instances of individuals carrying the mutations who remained asymptomatic or exhibited milder disease phenotypes.ConclusionThis study highlights the importance of comprehensive genotype analysis in understanding the progression and prognosis of ADPKD. The identification of novel mutation sites expands our knowledge of PKD1 gene mutations. These findings contribute to a better understanding of the disease and may have implications for personalized therapeutic strategies.

Immunotherapy has transformed treatment for various types of malignancy. However, the benefit of immunotherapy is limited to a minority of patients with mismatch-repair-deficient (dMMR) and microsatellite instability-high (MSI-H) (dMMR-MSI-H) colorectal cancer (CRC). Understanding the complexity and heterogeneity of the tumor immune microenvironment (TIME) and identifying immune-related CRC subtypes will improve antitumor immunotherapy. Here, we review the current status of immunotherapy and typing schemes for CRC. Immune subtypes have been identified based on TIME and prognostic gene signatures that can both partially explain clinical responses to immune checkpoint inhibitors and the prognosis of patients with CRC. Identifying immune subtypes will improve understanding of complex CRC tumor heterogeneity and refine current immunotherapeutic strategies.

The Wnt/β-catenin pathway is abnormally activated in most lung cancer tissues and considered to be an accelerator of carcinogenesis and lung cancer progression, which is closely related to increased morbidity rates, malignant progression, and treatment resistance. Although targeting the canonical Wnt/β-catenin pathway shows significant potential for lung cancer therapy, it still faces challenges owing to its complexity, tumor heterogeneity and wide physiological activity. Therefore, it is necessary to elucidate the role of the abnormal activation of the Wnt/β-catenin pathway in lung cancer progression. Moreover, Wnt inhibitors used in lung cancer clinical trials are expected to break existing therapeutic patterns, although their adverse effects limit the treatment window. This is the first study to summarize the research progress on various compounds, including natural products and derivatives, that target the canonical Wnt pathway in lung cancer to develop safer and more targeted drugs or alternatives. Various natural products have been found to inhibit Wnt/β-catenin in various ways, such as through upstream and downstream intervention pathways, and have shown encouraging preclinical anti-tumor efficacy. Their diversity and low toxicity make them a popular research topic, laying the foundation for further combination therapies and drug development.

Background. Chronic hepatitis B virus (HBV) infection is the main pathogen of hepatocellular carcinoma. However, the mechanisms of HBV-related hepatocellular carcinoma (HCC) progression are practically unknown. Materials and Methods. The results of RNA-sequence and clinical data for GSE121248 and GSE17548 were accessed from the Gene Expression Omnibus data library. We screened Sangerbox 3.0 for differentially expressed genes (DEGs). The weighted gene co-expression network analysis (WGCNA) was employed to select core modules and hub genes, and protein-protein interaction network module analysis also played a significant part in it. Validation was performed using RNA-sequence data of cancer and normal tissues of HBV-related HCC patients in the cancer genome atlas-liver hepatocellular cancer database (TCGA-LIHC). Results. 787 DEGs were identified from GSE121248 and 772 DEGs were identified from GSE17548. WGCNA analysis indicated that black modules (99 genes) and grey modules (105 genes) were significantly associated with HBV-related HCC. Gene ontology analysis found that there is a direct correlation between DEGs and the regulation of cell movement and adhesion; the internal components and external packaging structure of plasma membrane; signaling receptor binding, calcium ion binding, etc. Kyoto Encyclopedia of Genes and Genomes pathway analysis found out the association between cytokine receptors, cytokine-cytokine receptor interactions, and viral protein interactions with cytokines were important and HBV-related HCC. Finally, we further validated 6 key genes including C7, EGR1, EGR3, FOS, FOSB, and prostaglandin-endoperoxide synthase 2 by using the TCGALIHC. Conclusions. We identified 6 hub genes as candidate biomarkers for HBV-related HCC. These hub genes may act as an essential part of HBV-related HCC progression.

Abstract Background The occurrence and development of gastric cancer are related to microorganisms, which can be used as potential biomarkers of gastric cancer. Objective To screen the microbiological markers of gastric cancer from the microorganisms of gastric juice. Methods Gastric juice samples were collected from 61 healthy people and 78 patients with gastric cancer (48 cases of early gastric cancer and 30 cases of advanced gastric cancer). The bacterial 16 S rRNA V1-V4 region of gastric juice samples was sequenced. The Shannon index, Simpson index, Ace index and Chao index were used to analyze the diversity of gastric juice samples. The RDP classifier Bayesian algorithm was used to analyze the community structure of 97% OTU representative sequences with similar levels. Linear discriminant analysis and ST-test were used to analyze the differences. Six machine learning algorithms, including the logistic regression algorithm, random forest algorithm, neural network algorithm, support vector machine algorithm, Catboost algorithm and gradient lifting tree algorithm, were used to construct risk prediction models for gastric cancer and advanced gastric cancer. Results The microbiota diversity and the abundance of bacteria was different in the healthy group, early gastric cancer and advanced gastric cancer (P

AIM: To investigate the behaviors of smartphone usage and parental knowledge of vision health among primary students in the rural areas of China. METHODS: In this school-based, cross-sectional study, a total of 52 606 parents of students from 30 primary schools in the Xingguo County were investigated through an online questionnaire from July 2020 to August 2020. The self-designed questionnaire contained three parts: the demographic factors of both children and parents, parental knowledge and attitude toward myopia, and the preventive treatment of myopia. RESULTS: A total of 52 485 appropriately answered questionnaires were received, showing an effective response rate of 95.1%. The average age of the primary students was 10.1±0.98y and the prevalence of myopia among the primary students was 40.3%. The age of myopia occurrence in elementary students was significantly correlated with the parents' educational level (95%CI: 0.82-0.98, P=0.013), children's gender (95%CI: 1.08-1.20, P

Cell mediated immune escape, a microenvironment factor, induces tumorigenesis and metastasis. The purpose of this study was to display the characteristics of T cell populations in immune microenvironments for colorectal cancer (CRC) metastasis. Unsupervised cluster analysis was conducted to identify functionally distinct T cell clusters from 3,003 cells in peripheral blood and 4,656 cells in tissues. Subsequently, a total of 8 and 4 distinct T cell population clusters were identified from tumor tissue and peripheral blood, respectively. High levels of CD8+TEX, CD4+TRM, TH1-like T cells, CD8+TEM, tumor-Treg from tissues, and CD4+TN from peripheral blood are essential components of immune microenvironment for the prediction of CRC metastasis. Moreover, exhausted T cells are characterized by higher expression of multiple inhibitory receptors, including PDCD1 and LAG3. Some genes such as PFKFB3, GNLY, circDCUN1D4, TXNIP and NR4A2 in T cells of cluster were statistically different between CRC metastasis and non-metastasis. The ligand-receptor interactions identified between different cluster cells and metastases-related DEGs identified from each cluster revealed that the communications of cells, alterations of functions, and numbers of T subsets may contribute to the metastasis of CRC. The mutation frequency of KiAA1551, ATP8B4 and LNPEP in T cells from tissues and SOR1 from peripheral blood were higher in metastatic CRC than that in non-metastatic CRC. In conclusion, the discovery of differential genes in T cells may provide potential targets for immunotherapy of CRC metastasis and relevant insights into the clinical prediction and prognosis of CRC metastasis.

The circadian clock refers to the formation of a certain rule in the long-term evolution of an organism, which is an invisible ‘clock’ in the body of an organism. As one of the largest TF families in higher plants, the MYB transcription factor is involved in plant growth and development. MYB is also inextricably correlated with the circadian rhythm. In this study, the transcriptome data of the tea plant ‘Baiyeyihao’ were measured at a photoperiod interval of 4 h (24 h). A total of 25,306 unigenes were obtained, including 14,615 unigenes that were annotated across 20 functional categories within the GO classification. Additionally, 10,443 single-gene clusters were annotated to 11 sublevels of metabolic pathways using KEGG. Based on the results of gene annotation and differential gene transcript analysis, 22 genes encoding MYB transcription factors were identified. The G10 group in the phylogenetic tree had 13 members, of which 5 were related to the circadian rhythm, accounting for 39%. The G1, G2, G8, G9, G15, G16, G18, G19, G20, G21 and G23 groups had no members associated with the circadian rhythm. Among the 22 differentially expressed MYB transcription factors, 3 members of LHY, RVE1 and RVE8 were core circadian rhythm genes belonging to the G10, G12 and G10 groups, respectively. Real-time fluorescence quantitative PCR was used to detect and validate the expression of the gene transcripts encoding MYB transcription factors associated with the circadian rhythm.

Triple-negative breast cancer (TNBC) presented as high heterogeneous immunogenicity that lacks useful clinical signatures to risk-stratify immune-benefit subtypes. We hypothesized that molecular-based phenotypic characterization of TNBC tumors and their immunity may overcome these challenges. We enrolled 1,145 patients with TNBC for analysis. Through combining algorithm integration analysis and TNBC datasets, a tumor immune risk score (TIRS) panel consisting of 8 potential biomarkers was identified. The TIRS panel represented excellent effectiveness as an independent predictor. High- and low risk stratification of patients was further achieved by TIRS, and significant survival and immune-infiltration pattern differences were found in each cohort, both at the transcriptome and protein levels. Non-negative matrix factorization clustering further identified four different tumor immune microenvironment types (TIMTs), among which TIMT-II was associated with the best prognosis and immune status, whereas TIMT-IV had the opposite effect, TIMT-III was associated with highly unstable genomes, and TIMT-I displayed stem-cell-related characteristics along with high stromal scores and may have extensive enrichment of tumor-associated fibroblasts and vascular cells. In conclusion, our TIRS panel could serve as a robust prognostic signature and provide therapeutic benefits for immunotherapy. Additionally, coordinating four TIMTs may be helpful for clinical decision-making in TNBC patients.

Understanding how plant pathogenic fungi adapt to their hosts is of critical importance to securing optimal crop productivity. In response to pathogenic attack, plants produce reactive oxygen species (ROS) as part of a multipronged defense response. Pathogens, in turn, have evolved ROS scavenging mechanisms to undermine host defense. Thioredoxins (Trx) are highly conserved oxidoreductase enzymes with a dithiol-disulfide active site, and function as antioxidants to protect cells against free radicals, such as ROS. However, the roles of thioredoxins in Verticillium dahliae, an important vascular pathogen, are not clear. Through proteomics analyses, we identified a putative thioredoxin (VdTrx1) lacking a signal peptide. VdTrx1 was present in the exoproteome of V. dahliae cultured in the presence of host tissues, a finding that suggested that it plays a role in host-pathogen interactions. We constructed a VdTrx1 deletion mutant ΔVdTrx1 that exhibited significantly higher sensitivity to ROS stress, H2O2, and tert-butyl hydroperoxide (t-BOOH). In vivo assays by live-cell imaging and in vitro assays by western blotting revealed that while VdTrx1 lacking the signal peptide can be localized within V. dahliae cells, VdTrx1 can also be secreted unconventionally depending on VdVps36, a member of the ESCRT-II protein complex. The ΔVdTrx1 strain was unable to scavenge host-generated extracellular ROS fully during host invasion. Deletion of VdTrx1 resulted in higher intracellular ROS levels of V. dahliae mycelium, displayed impaired conidial production, and showed significantly reduced virulence on Gossypium hirsutum, and model plants, Arabidopsis thaliana and Nicotiana benthamiana. Thus, we conclude that VdTrx1 acts as a virulence factor in V. dahliae.

The synthesis of tea fatty acids plays a crucial role in determining the oil content of tea seeds and selecting tea tree varieties suitable for harvesting both leaves and fruits. However, there is limited research on fatty acid synthesis in tea trees, and the precise mechanisms influencing tea seed oil content remain elusive. To reveal the fatty acid biosynthesis mechanism, we conducted a photosynthetic characteristic and targeted metabolomics analysis in comparison between Jincha 2 and Wuniuzao cultivars. Our findings revealed that Jincha 2 exhibited significantly higher net photosynthetic rates (Pn), stomatal conductance (Gs), and transpiration rate (Tr) compared with Wuniuzao, indicating the superior photosynthetic capabilities of Jincha 2. Totally, we identified 94 metabolites with significant changes, including key hormone regulators such as gibberellin A1 (GA1) and indole 3-acetic acid (IAA). Additionally, linolenic acid, methyl dihydrojasmonate, and methylthiobutyric acid, precursors required for fatty acid synthesis, were significantly more abundant in Jincha 2 compared with Wuniuzao. In summary, our research suggests that photosynthetic rates and metabolites contribute to the increased yield, fatty acid synthesis, and oil content observed in Jincha 2 when compared with Wuniuzao.

ABSTRACT The occurrence and development of colorectal cancer (CRC) and advanced adenoma (AA) are closely related to the gut microbiome, and AA has a high cancerization progression rate to CRC. Current studies have revealed that bacteriological analysis cannot identify CRC from AA. The objective was to explore microbial targets that could identify CRC and AA from a microecological perspective and to figure out the best way to identify CRC based on fecal microbes. The metagenomic sequencing data were used to describe the gut microbiome profile and analyze the differences between microbial abundance and microbial single nucleotide polymorphism (SNP) characteristics in AA and CRC patients. It was found that there were no significant differences in the diversity between the two groups. The abundance of bacteria (e.g., Firmicutes, Clostridia, and Blautia), fungi (Hypocreales), archaea (Methanosarcina, Methanoculleus, and Methanolacinia), and viruses (Alphacoronavirus, Sinsheimervirus, and Gammaretrovirus) differed between AA and CRC patients. Multiple machine-learning algorithms were used to establish prediction models, aiming to identify CRC and AA. The accuracy of the random forest (RF) model based on the gut microbiome was 86.54%. Nevertheless, the accuracy of SNP was 92.31% in identifying CRC from AA. In conclusion, using microbial SNP was the best method to identify CRC, it was superior to using the gut microbiome, and it could provide new targets for CRC screening. IMPORTANCE There are differences in characteristic microorganisms between AA and CRC. However, current studies have indicated that bacteriological analysis cannot identify CC from AA, and thus, we wondered if there were some other targets that could be used to identify CRC from AA in the gut microbiome. The differences of SNPs in the gut microbiota of intraindividuals were significantly smaller than those of interindividuals. In addition, compared with intestinal microbes, SNP was less affected by time with certain stability. It was discovered that microbial SNP was better than the gut microbiome for identifying CRC from AA. Therefore, screening characteristic microbial SNP could provide a new research direction for identifying CRC from AA.

Polyphenol compounds are natural antioxidants, which are rich in anti-inflammatory and antioxidant components. They have a wide range of medicinal benefits that are believed to improve human health across various aspects; especially its anticancer effect has been gradually confirmed. The anticancer effect of polyphenols is mainly based on their strong antioxidant and immunomodulatory effects. The innate and adaptive immune responses as well as the development and maintenance of cells and tissues of the immune system are regulated by the NF-κB family of transcription factors. Dysregulation of NF-κB can lead to autoimmune diseases, chronic inflammation, and even cancer. Polyphenol compounds can exert antioxidant and immunomodulatory effects by targeting NF-κB, thus hindering the occurrence and development of tumors.Polyphenol compounds have unique advantages over conventional anticancer therapies such as chemotherapy because they have few side effects and do not cause toxicity to healthy cells. Additionally, they can attenuate the toxic effects of current anticancer therapies. Based on these characteristics, polyphenols have great potential in the prevention and treatment of cancer. This article systematically summarizes the mechanism of NF-κB in tumor genesis, progression, metastasis, angiogenesis, and drug resistance. In addition, we present the anticancer effect of polyphenol compounds by targeting NF-κB during the different stages of tumorigenesis.

Minimal change disease (MCD) is one of the common causes of idiopathic nephrotic syndrome (INS), accounting for 10–20% of INS in adults. Glucocorticoids are the most commonly used and effective drugs in the treatment of MCD, but there is still a proportion of adult patients with MCD who are characterized by glucocorticoid resistance, glucocorticoid dependence, and frequent relapse, which are defined as refractory nephrotic syndrome. Glucocorticoid combination with immunosuppressants is frequently used in patients with refractory nephrotic syndrome, and patients concerned about adverse effects caused by long-term high-dose glucocorticoid therapy. Recent studies have suggested that Rituximab (RTX), a chimeric monoclonal antibody targeted against the pan-B-cell marker CD20, combined with a small or medium dose of glucocorticoid has a beneficial effect with less adverse effects on adult patients with refractory MCD. β-thalassemia is an inherited hemoglobulin disorder caused by the mutation of genes that encode β-globin and results in ineffective erythropoiesis. We here report a case of an adult patient with refractory MCD complicated with β-thalassemia minor accompanied by autoimmune hemolytic anemia (AIHA). MCD relapsed several times despite treatment using glucocorticoid combined with or without different immunosuppressive agent regimens. The β-thalassemia minor was caused by heterozygosity for a 4-base deletion mutation [codons 41/42 (−TTCT) BETA0] of the β-globin gene. After the administration of RTX, MCD achieved clinical complete remission, and the anemia due to mild β-thalassemia recovered to normal as well. The disease situation remained stable during 36 months of follow-up. These findings suggest that RTX may contribute to the improvement of refractory MCD and anemia in β-thalassemia minor accompanied by AIHA.

Harnessing the broad immunostimulatory capabilities of chemotherapy in combination with immune checkpoint inhibitors has improved immunotherapy outcomes in patients with cancer. Certain chemotherapeutic agents can extensively modify the tumor microenvironment (TME), resulting in the reprogramming of local immune responses. Although chemotherapeutic agents with an enhanced generation of potent anti-tumor immune responses have been tested in preclinical animal models and clinical trials, this strategy has not yet shown substantial therapeutic efficacy in selected difficult-to-treat cancer types. In addition, the efficacy of chemotherapeutic agent-based monotherapy in eliciting a long-term anti-tumor immune response is restricted by the immunosuppressive TME. To enhance the immunomodulatory effect of chemotherapy, researchers have made many attempts, mainly focusing on improving the targeted distribution of chemotherapeutic agents and designing combination therapies. Here, we focused on the mechanisms of the anti-tumor immune response to chemotherapeutic agents and enumerated the attempts to advance the use of chemo-immunotherapy. Furthermore, we have listed the important considerations in designing combinations of these drugs to maximize efficacy and improve treatment response rates in patients with cancer.

High-throughput next-generation sequencing (NGS) provides insights into genome-wide mutations and can be used to identify biomarkers for the prediction of immune and targeted responses. A deeper understanding of the molecular biological significance of genetic variation and effective interventions is required and ultimately needs to be associated with clinical benefits. We conducted a retrospective observational study of patients in two cancer cohorts who underwent NGS in a “real-world” setting. The association between differences in tumor mutational burden (TMB) and clinical presentation was evaluated. We aimed to identify several key mutation targets and describe their biological characteristics and potential clinical value. A pan-cancer dataset was downloaded as a verification set for further analysis and summary. Natural product screening for the targeted intervention of key markers was also achieved. The majority of tumor patients were younger adult males with advanced cancer. The gene identified with the highest mutation rate was TP53, followed by PIK3CA, EGFR, and LRP1B. The association of TMB (0–103.7 muts/Mb) with various clinical subgroups was determined. More frequent mutations, such as in LRP1B, as well as higher levels of ferritin and neuron-specific enolase, led to higher TMB levels. Further analysis of the key targets, LRP1B and APC, was performed, and mutations in LRP1B led to better immune benefits compared to APC. APC, one of the most frequently mutated genes in gastrointestinal tumors, was further investigated, and the potential interventions by cochinchinone B and rottlerin were clarified. In summary, based on the analysis of the characteristics of gene mutations in the “real world,” we obtained the potential association indicators of TMB, found the key signatures LRP1B and APC, and further described their biological significance and potential interventions.

Tumor-associated macrophages (TAMs) are important immune cells in the tumor microenvironment, and their invasion in tumors is closely related to poor prognosis. Although TAMs are recognized as therapeutic targets, their heterogeneity makes studying tumor mechanism and developing drugs targeting TAMs difficult. The study of TAMs heterogeneity can be used to analyze the mechanism of tumor progression and drug resistance, and may provide possible treatment strategies for cancer patients. Single-cell RNA sequencing (scRNA-seq) can reveal the RNA expression profile for each TAM to distinguish heterogeneity, thereby providing a more efficient detection method and more accurate information for TAM-related studies. In this review, by summarizing the research progress in macrophage heterogeneity and other aspects of scRNA-seq over the past five years, we introduced the development of scRNA-seq technology and its application status in solid tumors, analyzed the advantages and selections of scRNA-seq in TAMs, and summarized the detailed specific research fields. To explore the mechanism of tumor progression and drug intervention from single cell level will provide new perspective for personalized treatment strategies targeting macrophages.

Green tea is a popular non-alcoholic beverage consumed worldwide and has been shown to be beneficial for human health. However, further exploration is needed to fully understand its function in reducing obesity and regulating gut microbes. Here, we investigated the modulatory effects of green tea and its functional components on high-fat diet (HF)-induced metabolic alterations and gut microbiota in obese mice. Our results showed that 1%, 2%, and 4% of green tea promotes weight loss, with the 2% and 4% groups exhibiting distinct gut microflora clusters compared to the HF group. These results were comparable to those observed in the tea polyphenols (TPP)-treated group, suggesting the TPP in green tea plays a crucial role in body weight control and gut microbiota regulation. Additionally, 32 bacteria were identified as potential obesity markers via 16S rRNA gene sequencing. The 16SrDNA gene is a chromosomal gene present in all bacterial species, highly conserved in structure and function, that can reflect the differences between different taxa. The 16S rRNA-based analysis revealed that Akkermansia, a gut-beneficial bacteria, significantly increased in the TPP group.

Abstract Exosomes derived from tumor cells play a key role in tumor development. In the present study, we identified the bioactivity of exosomes released from WERI-Rb1 retinoblastoma cells in tumor angiogenesis, as well as the underlying mechanism, through biochemical methods and animal experiments. Our in vitro data showed that exosomes could be engulfed by human vesicle endothelial cells (HUVECs), significantly promote cell viability and induce an inflammatory response in HUVECs by increasing the expression of a series of related genes, such as IL-1, IL-6, IL-8, MCP-1, VCAM1, and ICAM1. Significant increases in migration and tube formation were also observed in the HUVECs incubated with exosomes. Moreover, experiments with a nude mouse xenotransplantation model showed that exosomes injected near tumors could be strongly absorbed by tumor cells. The numbers of endothelial cells and blood vessels were significantly increased in tumor tissues treated with exosomes compared to control tissues. Furthermore, to reveal the mechanism underlying exosome-mediated angiogenesis in retinoblastoma, we analyzed the levels of 12 microRNAs in the exosomes. Specifically, our data showed that miR-92a-3p was enriched in RB exosomes. Accordingly, miR-92a-3p was increased in the HUVECs incubated with these exosomes. After treatment with a miR-92a-3p inhibitor, the promoting effect of exosomes on the migration and tube formation of HUVECs was significantly abrogated. The expression of the angiogenesis-related genes mentioned above was markedly decreased in HUVECs. Similarly, treatment with a microRNA mimic also demonstrated that miR-92a-3p was involved in the angiogenesis of HUVECs. More importantly, bioinformatics analysis predicted that Krüppel-like factor 2 (KLF2), a member of the KLF family of zinc-finger transcription factors, might be an active target of miR-92a-3p. Notably, this prediction was confirmed both in vitro and in vivo. Thus, our work suggests that exosomal miR-92a-3p is involved in tumor angiogenesis and might be a promising therapeutic candidate for retinoblastoma.

Purpose: Models for predicting postoperative overall survival of patients with metaplastic breast cancer have not yet been discovered. The purpose of this study is to establish a model for predicting postoperative overall survival of metaplastic breast cancer patients.Methods: Patients in the Surveillance, Epidemiology, and End Results database diagnosed with MBC from 2010 to 2015 were selected and randomized into a SEER training cohort and an internal validation cohort. We identified independent prognostic factors after MBC surgery based on multivariate Cox regression analysis to construct nomograms. The discriminative and predictive power of the nomogram was assessed using Harrell’s consistency index (C-index) and calibration plots. The decision curve analysis (DCA) was used to evaluate the clinical usefulness of the model. We verify the performance of the prediction model with a Chinese multi-center data set.Results: Multifactorial analysis showed that age at diagnosis, T stage, N stage, M stage, tumor size, radiotherapy, and chemotherapy were important prognostic factors affecting OS. The C-index of nomogram was higher than the eighth edition of the AJCC TNM grading system in the SEER training set and validation set. The calibration chart showed that the survival rate predicted by the nomogram is close to the actual survival rate. It has also been verified in the SEER internal verification set and the Chinese multi-center data set.Conclusion: The prognostic model can accurately predict the post-surgical OS rate of patients with MBC and can provide a reference for doctors and patients to establish treatment plans.

Abstract Long non-coding RNAs (lncRNAs) are a group of non-protein coding RNAs with a length of more than 200 bp. The lncRNA taurine up-regulated gene 1 (TUG1) is abnormally expressed in many human malignant cancers, where it acts as a competitive endogenous RNA (ceRNA), regulating gene expression by specifically sponging its corresponding microRNAs. In the present review, we summarised the current understanding of the role of lncRNA TUG1 in cancer cell proliferation, metastasis, angiogenesis, chemotherapeutic drug resistance, radiosensitivity, cell regulation, and cell glycolysis, as well as highlighting its potential application as a clinical biomarker or therapeutic target for malignant cancer. This review provides the basis for new research directions for lncRNA TUG1 in cancer prevention, diagnosis, and treatment.

Glycogen synthase kinase-3β (GSK-3β) has been shown to attenuate DNA damage in nerve cells, thereby enhancing neuronal survival under pathological conditions; however, the underlying mechanism remains unclear. An in vitro serum-starvation retinal neuron model and in vivo ischemia/reperfusion retina injury rat model were established and treated with SB216763, a GSK-3β inhibitor. SB21673 decreased the formation of γ-H2A histone family member X foci and enhanced the viability of ischemic retinal neurons. In addition, SB216763 upregulated expression of phosphorylated-CREB1, a ligase IV transcription factor, and significantly increased the transcriptional activity of ligase IV in ischemic retinal neurons. These results were confirmed in rat retinas following ischemia/reperfusion injury. Furthermore, we found that unlike lithium chlorine (a well-known direct inhibitor of GSK-3β), SB216763 inhibited GSK-3β activity by suppressing its phosphorylation. Taken together, our results suggest that GSK-3β inhibition enhances repair of DNA double-strand breaks by upregulating ligase IV expression in ischemic retinal neurons. This study was approved by the Institutional Animal Care and Use Committee of Zhongshan Ophthalmic Center on February 18, 2018.

Human epidermal growth factor receptor 2 (HER2)-positive breast cancer and triple-negative breast cancer have their own genetic, epigenetic, and protein expression profiles. In the present study, based on bioinformatics techniques, we explored the prognostic targets of HER2-positive breast cancer from metabonomics perspective and developed a new risk score system to evaluate the prognosis of patients. By identifying the differences between HER2 positive and normal control tissues, and between triple negative breast cancer and normal control tissues, we found a large number of differentially expressed metabolic genes in patients with HER2-positive breast cancer and triple-negative breast cancer. Importantly, in HER2-positive breast cancer, decreased expression of metabolism-related genes ATIC, HPRT1, ASNS, SULT1A2, and HAL was associated with increased survival. Interestingly, these five metabolism-related genes can be used to construct a risk score system to predict overall survival (OS) in HER2-positive patients. The time-dependent receiver operating characteristic (ROC) curve analysis showed that the predictive sensitivity of the risk scoring system was higher than that of other clinical factors, including age, stage, and tumor node metastasis (TNM) stage. This work shows that specific transcriptional changes in metabolic genes can be used as biomarkers to predict the prognosis of patients, which is helpful in implementing personalized treatment and evaluating patient prognosis.