Transcription factor FoxM1 promotes cyst growth in PKD1 mutant ADPKD.

Autosomal dominant polycystic kidney disease (ADPKD) is driven by mutations in the PKD1 and PKD2 genes, and it is characterized by renal cyst formation, inflammation and fibrosis. Forkhead box protein M1 (FoxM1), a transcription factor of the Forkhead box (Fox) protein super family, has been reported to promote tumor formation, inflammation and fibrosis in many organs. However, the role and mechanism of FoxM1 in regulation of ADPKD progression is still poorly understood. Here, we show that FoxM1 is an important regulator of cyst growth in ADPKD. FoxM1 is upregulated in cyst-lining epithelial cells in Pkd1 mutant mouse kidneys and human ADPKD kidneys. FoxM1 promotes cystic renal epithelial cell proliferation by increasing the expression of Akt and Stat3 and the activation of ERK and Rb. FoxM1 also regulates cystic renal epithelial cell apoptosis through NF-κB signaling pathways. In addition, FoxM1 regulates the recruitment and retention of macrophages in Pkd1 mutant mouse kidneys, a process that is associated with FoxM1-mediated upregulation of monocyte chemotactic protein 1. Targeting FoxM1 with its specific inhibitor, FDI-6, delays cyst growth in rapidly progressing and slowly progressing Pkd1 mutant mouse kidneys. This study suggests that FoxM1 is a central and upstream regulator of ADPKD pathogenesis and provides a rationale for targeting FoxM1 as a therapeutic strategy for ADPKD treatment.

The mechanism and clinical application of farnesyl diphosphate farnesyltransferase 1 in cancer metabolism.

Cancer poses a significant risk to human well-being. Among the crucial characteristics of cancer is metabolic reprogramming. To meet the relentless metabolic needs, cancer cells enhance cholesterol metabolism within the adverse tumor microenvironment. Reprograming cholesterol metabolism includes a series of modifications in the synthesis, absorption, esterification, and metabolites associated with cholesterol. These adjustments have a strong correlation with the proliferation, invasion, metastasis, and other characteristics of malignant tumors. FDFT1, also known as farnesyl diphosphate farnesyltransferase 1, is an enzyme crucial in the process of cholesterol biosynthesis. Its significant involvement in tumor metabolism has garnered considerable interest. The significance of FDFT1 in cancer metabolism cannot be overstated, as it actively interacts with cancer cells. This paper aims to analyze and consolidate the mechanism of FDFT1 in cancer metabolism and explore its clinical application. The goal is to contribute new strategies and targets for the prevention and treatment of cancer metabolism.

Discovery of Aurovertin B as a Potent Metastasis Inhibitor against Triple-Negative Breast Cancer: Elucidating the Complex Role of the ATF3-DUSP1 Axis.

Triple-negative breast cancer (TNBC) is characterized by high mortality rates primarily due to its propensity for metastasis. Addressing this challenge necessitates the development of effective antimetastatic therapies. This study aimed to identify natural compounds with potential antimetastatic properties mainly based on the high-throughput phenotypic screening system. This system, utilizing luciferase reporter gene assays combined with scratch wound assays, evaluates compounds based on their influence on the epithelial-mesenchymal transition (EMT) marker E-cadherin. Through this approach, aurovertin B (AVB) was revealed to have significant antimetastatic capability. Notably, AVB exhibited substantial metastasis suppression in many TNBC cell lines, including MDA-MB-231, HCC1937 and 4T1. Also, its remarkable antimetastatic activity was demonstrated in vivo via the orthotopic breast cancer mouse model. Further exploration revealed a pronounced association between AVB-induced upregulation of DUSP1 (dual-specificity phosphatase 1) and its inhibitory effect on TNBC metastasis. Additionally, microarray analysis conducted to elucidate the underlying mechanism of the AVB-DUSP1 interaction identified ATF3 (activating transcription factor 3) as a critical transcription factor instrumental in DUSP1 transcriptional activation. This discovery, coupled with observations of enhanced ATF3-DUSP1 expression and consequent reduction in TNBC metastatic foci in response to AVB, provides novel insights into the molecular mechanisms driving metastasis in TNBC. Significance Statement We construct a high-throughput phenotypic screening system utilizing EMT marker E-cadherin promoter luciferase reporter gene combined with scratch wound assays. Aurovertin B was revealed to possess significant antimetastatic activity through this approach, which was further demonstrated via in vivo and in vitro experiments. The discovery of the regulatory role of the ATF3-DUSP1 pathway enriches our understanding of TNBC metastasis mechanism and suggests the potential of ATF3 and DUSP1 as biomarkers for diagnosing TNBC metastasis.

AURKA Identified as Potential Lung Cancer Marker through Comprehensive Bioinformatic Analysis and Experimental Verification.

Non-small-cell lung cancer (NSCLC) is a malignancy with high overall morbidity and mortality due to a lack of reliable methods for early diagnosis and successful treatment of the condition. We identified genes that would be valuable for the diagnosis and prognosis of lung cancer. Common DEGs (DEGs) in three GEO datasets were selected for KEGG and GO enrichment analysis. A protein-protein interaction (PPI) network was constructed using the STRING database, and molecular complex detection (MCODE) identified hub genes. Gene expression profiling interactive analysis (GEPIA) and the Kaplan-Meier method analyzed hub genes expression and prognostic value. Quantitative PCR and western blotting were used to test for differences in hub gene expression in multiple cell lines. The CCK-8 assay was used to determine the IC50 of the AURKA inhibitor CCT137690 in H1993 cells. Transwell and clonogenic assays validated the function of AURKA in lung cancer, and cell cycle experiments explored its possible mechanism of action. Overall, 239 DEGs were identified from three datasets. AURKA, BIRC5, CCNB1, DLGAP5, KIF11, and KIF15 had shown great potential for lung cancer diagnosis and prognosis. In vitro experiments suggested that AURKA significantly influenced the proliferation and migration of lung cancer cells and activities related to the dysregulation of the cell cycle. AURKA, BIRC5, CCNB1, DLGAP5, KIF11, and KIF15 may be critical genes that influence the occurrence, development, and prognosis of NSCLC. AURKA significantly affects the proliferation and migration of lung cancer cells by disrupting the cell cycle.

Deoxynivalenol (DON)-Triggered Dual-Color Composite Probe Based on Gold Nanoclusters for Simultaneous Imaging of DON and miR-34a in Living Cells.

Deoxynivalenol (DON) is a mycotoxin secreted by Fusarium species, posing great harm to food safety and human health. Therefore, it is of great significance to study its toxic effects and mechanism. miR-34a is a representative biomarker during the process of DON-induced apoptosis. Herein, a DON-triggered dual-color composite probe was constructed for simultaneous imaging of DON and miR-34a in living cells. The aptamer blocks the recognition sequence of miR-34a to realize DON-triggered cell imaging. The specific binding of DON with its aptamer and HCR induced by miR-34a resulted in the recovery of fluorescence of the dual-color Au NCs. Under the optimal conditions, the correlation between the relative fluorescence intensities of dual-color Au NCs showed good linear relationships with the logarithm of DON and miR-34a concentration, respectively. With the increase in DON concentration (0-20 µg/mL) and stimulation time (0-12 h), the fluorescence of dual-color Au NCs gradually recovered. This dual-color Au NCs composite probe can realize simultaneous detection of DON and miR-34a induced by DON, which is significant for verifying the cytotoxic mechanism of DON.

Real-World Experience of PD-1 Inhibitors for Relapsed and Refractory Hodgkin Lymphoma: A Multicenter Retrospective Analysis of Patients in China.

INTRODUCTION: Despite the promising clinical trial data regarding programmed death 1 (PD-1) inhibitors in relapsed/refractory classical Hodgkin lymphoma (R/R cHL), there remains a paucity of studies describing the outcomes of patients in a real-world setting, especially for Asian cohort. METHODS: We present a multicenter retrospective analysis of patients with R/R cHL who had failed ≥2 prior lines of therapies and received sintilimab or tislelizumab developed in China (sintilimab or tislelizumab monotherapy) at 3 medical centers from January 2019 to September 2021. Efficacy was evaluated with progression-free survival (PFS), overall survival, duration of response (DOR), best overall response (BOR) including objective response rate (ORR), complete response rate (CRR). Safety data were also recorded. RESULTS: 74 patients were reviewed. The median age was 38 years (range, 14-85 years). The ORR, CRR, and disease control rate were 78.3%, 52.7%, and 91.9%, respectively. The median duration of follow-up was 22 (4-36) months. Four patients (5.4%) died of disease progression. The median PFS and DOR was 22.1 and 23.5 months. BOR as a new emergent endpoint was found to be the only independent prognostic factor for PFS in our study (HR = 6.234, p = 0.005), suggesting this endpoint carries stronger prognostic value over traditional endpoints in the immunotherapy era. 66 (89.2%) patients reported adverse event (AE) with any grade, with the majority of AEs being grade 1 or 2. CONCLUSION: We presented a unique real-life experience and conducted a relatively long follow-up of PD-1 antibodies developed in China for R/R HL patients which confirmed their promising effectiveness and manageable side effects given in real world in an Asian cohort. Even for those who would usually be excluded in most of clinical trials such as elderly or minor patients, anti-PD-1 monotherapy also showed a significant improvement of outcomes. Furthermore, the depth of response seemed to be a more powerful predictive tool in new era, which might serve as a basis for future immune risk-adapted strategies.

Oxygen-independent alkyl radical nanogenerator enhances breast cancer therapy.

The hypoxic microenvironment of breast cancer substantially reduces oxygen-dependent free radical generation. Overexpression of glutathione (GSH) in tumor cells mitigates the impact of free radical generation. In this study, we designed and developed an oxygen-independent alkyl radical nanogenerator (copper monosulfide/2,2'-azabis(2-imidazoline) dihydrochloride@bovine serum albumin; CuS/AIPH@BSA) with spatiotemporally controlled properties and GSH consumption to enhance breast cancer therapy. We encapsulated the alkyl radical initiator, AIPH, in hollow mesoporous CuS nanoparticles with photothermal conversion effect and enveloped them in BSA. AIPH was released and decomposed to generate alkyl radicals in hypoxic breast cancer with the photothermal conversion effect of CuS under near-infrared laser irradiation. CuS consumed high GSH levels in tumor cells because it could form complex with GSH and thereby enhanced free radical treatment. In vivo and in vitro assays demonstrated the anti-tumor efficacy of the rationally designed free-radical nanogenerator in hypoxic microenvironment of breast cancer without showing systemic toxicity.

Metagenomic insights into the mechanisms of triphenyl phosphate degradation by bioaugmentation with Sphingopyxis sp. GY.

Biodegradation of triphenyl phosphate (TPHP) by Sphingopyxis sp. GY was investigated, and results demonstrated that TPHP could be completely degraded in 36 h with intracellular enzymes playing a leading role. This study, for the first time, systematically explores the effects of the typical brominated flame retardants, organophosphorus flame retardants, and heavy metals on TPHP degradation. Our findings reveal that TCPs, BDE-47, HBCD, Cd and Cu exhibit inhibitory effects on TPHP degradation. The hydrolysis-, hydroxylated-, monoglucosylated-, methylated products and glutathione (GSH) conjugated derivative were identified and new degradation pathway of TPHP mediated by microorganism was proposed. Moreover, toxicity evaluation experiments indicate a significant reduction in toxicity following treatment with Sphingopyxis sp. GY. To evaluate its potential for environmental remediation, we conducted bioaugmentation experiments using Sphingopyxis sp. GY in a TPHP contaminated water-sediment system, which resulted in excellent remediation efficacy. Twelve intermediate products were detected in the water-sediment system, including the observation of the glutathione (GSH) conjugated derivative, monoglucosylated product, (OH)2-DPHP and CH3-O-DPHP for the first time in microorganism-mediated TPHP transformation. We further identify the active microbial members involved in TPHP degradation within the water-sediment system using metagenomic analysis. Notably, most of these members were found to possess genes related to TPHP degradation. These findings highlight the significant reduction of TPHP achieved through beneficial interactions and cooperation established between the introduced Sphingopyxis sp. GY and the indigenous microbial populations stimulated by the introduced bacteria. Thus, our study provides valuable insights into the mechanisms, co-existed pollutants, transformation pathways, and remediation potential associated with TPHP biodegradation, paving the way for future research and applications in environmental remediation strategies.

ZIF-8 base-aptamer "gate-lock" probes enable the visualization of a cascade response between deoxynivalenol and cytochrome c inside living cells.

Zeolitic imidazolate framework (ZIF-8) base-aptamer "gate-lock" biomaterial probes have been synthesized for monitoring intracellular deoxynivalenol (DON) and cytochrome c (cyt c) levels. The aptamer and organic fluorescent dye were regarded as a recognition element and a sensing element, respectively. In the presence of DON, the aptamers of DON and cyt c were specifically bound with the DON and induced cyt c, leading to the dissociation of aptamers from the porous surface of the probes. The gate was subsequently opened to release methylene blue (MB) and Rhodamine 6G (Rh6G), and their fluorescence (emission of MB at 700 nm and Rh6G at 550 nm) significantly recovered within 6 h. Cell imaging successfully monitored the exposure of DON and the biological process of cyt c discharge triggered by the activation of the DON-induced apoptosis pathway. In addition, the response between DON and cyt c was observed during the apoptosis process, which is of high significance for the comprehensive and systematic development of mycotoxins cytotoxicity.

Bioinspired Nanosponge for Salvaging Ischemic Stroke via Free Radical Scavenging and Self-Adapted Oxygen Regulating.

Either hypoxia in an acute ischemic stroke before thrombolysis or the oxygen-boost after thrombolysis cause a high level of free radicals, resulting in successive injuries to neurocytes. To treat an ischemic stroke, it is needed to scavenge free radicals, combining sequentially regulating hypoxia and oxygen-boost microenvironment. Here, we report an engineered nanosponge (Mn3O4@nanoerythrocyte-T7, MNET) that could remodel the microenvironment of a stroke by self-adapted oxygen regulating and free radical scavenging. With a long circulation time in blood due to the stealth effect of the erythrocyte and preferential accumulation in the infarct site by the assisting of T7 peptide, MNET exerts a distinct therapeutic effect in two stages of an ischemic stroke: (i) before thrombolysis, rescue neurocyte via rapid free radical scavenging and timely oxygen supply; (ii) after thrombolysis, suppress oxygen-boost via oxygen storage, as well as scavenge free radical to avoid reperfusion injury. MNET holds an attractive potential for ischemic stroke treatment via phased regulation of pathological microenvironment.

Postnatal leptin surge is critical for the transient induction of the developmental beige adipocytes in mice.

Beige adipocytes have become a promising therapeutic target to combat obesity. Our senior author Dr. B. Xue previously discovered a transient but significant induction of beige adipocytes in mice during early postnatal development, which peaked at postnatal day (P) 20 and then disappeared thereafter. However, the physiological mechanism underlying the transient induction of the developmental beige cells remains mystery. Interestingly, there exists a postnatal surge of leptin in mice at P10 before the appearance of the developmental beige adipocytes. Given the neurotropic effect of leptin during neuronal development and its role in activating the sympathetic nervous system (SNS), we tested the hypothesis that postnatal leptin surge is required for the transient induction of developmental beige adipocytes through sympathetic innervation. Unlike wild-type (WT) mice that were able to acquire the developmentally induced beige adipocytes at P20, ob/ob mice had much less uncoupling protein 1 (UCP1)-positive multilocular cells in inguinal white adipose tissue at the same age. This was consistent with reduced expression of UCP1 mRNA and protein levels in white fat of ob/ob mice. In contrast, daily injection of ob/ob mice with leptin between P8 and P16, mimicking the postnatal leptin surge, largely rescued the ability of these mice to acquire the developmentally induced beige adipocytes at P20, which was associated with enhanced sympathetic nerve innervation assessed by whole mount adipose tissue immunostaining of tyrosine hydroxylase. Our data demonstrate that the postnatal leptin surge is essential for the developmentally induced beige adipocyte formation in mice, possibly through increasing sympathetic nerve innervation.

Aurovertin B exerts potent antitumor activity against triple-negative breast cancer in vivo and in vitro via regulating ATP synthase activity and DUSP1 expression.

Aurovertin B, a natural compound from Calcarisporium arbuscular, exhibits potent antiproliferative activity particularly against triple-negative breast cancer cells (TNBC), while having less cytotoxicity on normal breast cell MCF10A. However, very little is known about the in vivo antitumor activity of aurovertin B and the possible mechanism of the selective effect on triple-negative breast cancer cells. In this study, flow cytometry and DAPI staining analysis showed that aurovertin B treatment in human triple-negative breast cancer cell MDA-MB-231 could induce more apoptotic cells than taxol treatment group. Furthermore, the present study also revealed that aurovertin B induced apoptosis was due to regulation of ATP synthase activity rather than changes in gene expression. Interestingly, the cancer genome atlas (TCGA) data analysis implied that the expression level of DUSP1, a member of the dual-specificity phosphatases, was highly downregulated in breast tissue of TNBC patients compared with their adjacent normal tissues. Real-time PCR and western blot analyses further demonstrated that aurovertin B could dramatically increase mRNA and protein expression levels of DUSP1 in MDA-MB-231 cells but not in MCF10A cells. The potent anti-tumor activity of aurovertin B was further verified in a human MDA-MB-231 xenograft mouse model.

Association between mineral and bone disorder in patients with acute kidney injury following cardiac surgery and adverse outcomes.

BACKGROUND: Numerous studies have evaluated the prevalence and importance of mineral and bone disorders among patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD). However, little is known about dysregulated mineral and bone metabolism in acute kidney injury (AKI). METHODS: We evaluated the association between mineral and bone metabolites and clinical outcomes in 158 patients who underwent cardiac surgery and developed AKI between June 2014 and January 2016. The baseline characteristics of the patients were recorded, and the levels of mineral and bone metabolites, including calcium, phosphate, intact parathyroid hormone (iPTH), 25-hydroxyvitamin D (25D), bone-specific alkaline phosphatase (BAP), tartrate-resistant acid phosphatase 5b (TRACP-5b) and C-terminal fibroblast growth factor 23 (cFGF23) were measured within 12 h after establishing the clinical diagnosis. RESULTS: The serum phosphate, iPTH and cFGF23 levels were significantly associated with the 28-day mortality (phosphate: Hazard Ratio [HR] =2.620, 95% CI: 1.083 to 6.338, p = 0.035; iPTH: HR = 1.044, 95% CI: 1.001 to 1.090, p = 0.046; cFGF23: HR = 1.367, 95% CI: 1.168 to 1.599, p < 0.001). Moreover, higher serum cFGF23 and BAP levels were independently associated with an increased risk of adverse outcomes. Additionally, we found that the serum cFGF23 levels rose most significantly and were associated with the severity of AKI (P < 0.001). CONCLUSIONS: Mineral and bone metabolites are dysregulated and are associated with adverse clinical outcomes among patients with AKI. TRIAL REGISTRATION: www.clinicaltrials.gov NCT00953992. Registered 6 August 2009.

Assessing the Use of GACOS Products for SBAS-InSAR Deformation Monitoring: A Case in Southern California.

The Generic Atmospheric Correction Online Service (GACOS) products for interferometric synthetic aperture radar (InSAR) are widely used near-real-time and global-coverage atmospheric delay products which provide a new approach for the atmospheric correction of repeat-pass InSAR. However, it has not been determined whether these products can improve the accuracy of InSAR deformation monitoring. In this paper, GACOS products were used to correct atmospheric errors in short baseline subset (SBAS)-InSAR. Southern California in the U.S. was selected as the research area, and the effect of GACOS-based SBAS-InSAR was analyzed by comparing with classical SBAS-InSAR results and external global positioning system (GPS) data. The results showed that the accuracy of deformation monitoring was improved in the whole study area after GACOS correction, and the mean square error decreased from 0.34 cm/a to 0.31 cm/a. The improvement of the mid-altitude (15-140 m) point was the most obvious after GACOS correction, and the accuracy was increased by about 23%. The accuracy for low- and high-altitude areas was roughly equal and there was no significant improvement. Additionally, GACOS correction may increase the error for some points, which may be related to the low accuracy of GACOS turbulence data.

The leukotriene B4-leukotriene B4 receptor axis promotes cisplatin-induced acute kidney injury by modulating neutrophil recruitment.

Cisplatin is an effective chemotherapeutic agent and widely used in treatment of various solid organ malignancies, including head and neck, ovarian, and testicular cancers. However, the induction of acute kidney injury (AKI) is one of its main side effects. Leukotriene B4 receptor 1 (BLT1) mediates the majority of physiological effects of leukotriene B4 (LTB4), a potent lipid chemoattractant generated at inflammation sites, but the role of the LTB4-BLT1 axis in cisplatin-induced AKI remains unknown. Here we found upregulated LTB4 synthesis and BLT1 expression in the kidney after cisplatin administration. Cisplatin was found to directly upregulate gene expression of leukotriene A4 hydrolase and stimulate LTB4 production in renal tubular epithelial cells. Reduced kidney structural/functional damage, inflammation, and apoptosis were observed in BLT1-/- mice, as well as in wild-type mice treated with the LTA4H inhibitor SC-57461A and the BLT1 antagonist U-75302. Neutrophils were likely the target of this pathway, as BLT1 absence induced a significant decrease in infiltrating neutrophils in the kidney. Adoptive transfer of neutrophils from wild-type mice restored kidney injury in BLT1-/- mice following cisplatin challenge. Thus, the LTB4-BLT1 axis contributes to cisplatin-induced AKI by mediating kidney recruitment of neutrophils, which induce inflammation and apoptosis in the kidney. Hence, the LTB4-BLT1 axis could be a potential therapeutic target in cisplatin-induced AKI.

[MiR-519 inhibits gastric cancer cell activity through regulation of HuR expression].

OBJECTIVE: To investigate the role of miR-519 in regulating the cell activity of gastric cancer. 
 METHODS: The expression of miR-519 was measured by qPCR. The protein expression of HuR was detected by Western blot. MTT assay was used to detect the cell activity of gastric cancer cells.
 RESULTS: The protein level of HuR in the gastric cancer cells was higher than that in the control cells. Over-expression of HuR resulted in the increase in the cell activity of gastric cancer (P<0.001). Suppression of HuR decreased the cell activity of gastric cancer (P=0.001). The miR-519 level in the gastric cancer cells was lower than that in the control cells (P=0.001). Over-expression of miR-519 decreased the protein level of HuR and the activity of gastric cancer cells.
 CONCLUSION: MiR-may inhibit the gastric cancer cell activity through suppression of HuR expression.

Coherent optomechanical oscillation of a silica microsphere in an aqueous environment.

We report the observation of optomechanical oscillation by immersing a silica microsphere in liquid. Due to the ultra high quality factor of the microsphere in the aqueous environment, sufficient optical force was established to quiver the microsphere at a pump laser power around 1 mW.

Identification of sex-specific biomarkers related to programmed cell death and analysis of immune cells in ankylosing spondylitis.

Ankylosing spondylitis (AS) stands as a persistent inflammatory ailment predominantly impacting the axial skeleton, with the immune system and inflammation intricately entwined in its pathogenesis. This study endeavors to elucidate gender-specific patterns in immune cell infiltration and diverse forms of cell demise within the AS milieu. The aim is to refine the diagnosis and treatment of gender-specific AS patients, thereby advancing patient outcomes. In the pursuit of our investigation, two datasets (GSE25101 and GSE73754) pertinent to ankylosing spondylitis (AS) were meticulously collected and normalized from the GEO database. Employing the CIBERSORT algorithm, we conducted a comprehensive analysis of immune cell infiltration across distinct demographic groups and genders. Subsequently, we discerned differentially expressed genes (DEGs) associated with various cell death modalities in AS patients and their healthy counterparts. Our focus extended specifically to ferroptosis-related DEGs (FRDEGs), cuproptosis-related DEGs (CRDEGs), anoikis-related DEGs (ARDEGs), autophagy-related DEGs (AURDEGs), and pyroptosis-related DEGs (PRDEGs). Further scrutiny involved discerning disparities in these DEGs between AS patients and healthy controls, as well as disparities between male and female patients. Leveraging machine learning (ML) methodologies, we formulated disease prediction models employing cell death-related DEGs (CDRDEGs) and identified biomarkers intertwined with cell death in AS. Relative to healthy controls, a myriad of differentially expressed genes (DEGs) linked to cell death surfaced in AS patients. Among AS patients, 82 FRDEGs, 29 CRDEGs, 54 AURDEGs, 21 ARDEGs, and 74 PRDEGs were identified. In male AS patients, these numbers were 78, 33, 55, 24, and 94, respectively. Female AS patients exhibited 66, 41, 40, 17, and 82 DEGs in the corresponding categories. Additionally, 36 FRDEGs, 14 CRDEGs, 19 AURDEGs, 10 ARDEGs, and 36 PRDEGs exhibited differential expression between male and female AS patients. Employing machine learning techniques, LASSO, RF, and SVM-RFE were employed to discern key DEGs related to cell death (CDRDDEGs). The six pivotal CDRDDEGs in AS patients, healthy controls, were identified as CLIC4, BIRC2, MATK, PKN2, SLC25A5, and EDEM1. For male AS patients, the three crucial CDRDDEGs were EDEM1, MAP3K11, and TRIM21, whereas for female AS patients, COX7B, PEX2, and RHEB took precedence. Furthermore, the trio of DDX3X, CAPNS1, and TMSB4Y emerged as the key CDRDDEGs distinguishing between male and female AS patients. In the realm of immune correlation, the immune infiltration abundance in female patients mirrored that of healthy controls. Notably, key genes exhibited a positive correlation with T-cell CD4 memory activation when comparing male and female patient samples. This study engenders a more profound comprehension of the molecular underpinnings governing immune cell infiltration and cell death in ankylosing spondylitis (AS). Furthermore, the discernment of gender-specific disparities among AS patients underscores the clinical significance of these findings. By identifying DEGs associated with diverse cell death modalities, this study proffers invaluable insights into potential clinical targets for AS patients, taking cognizance of gender-specific nuances. The identification of gender-specific biological targets lays the groundwork for the development of tailored diagnostic and therapeutic strategies, heralding a pivotal step toward personalized care for AS patients.

Global biomarker trends in triple-negative breast cancer research: a bibliometric analysis.

BACKGROUND: Triple-negative breast cancer (TNBC) is defined as breast cancer that is negative for estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER-2) in cancer tissue. The lack of specific biomarkers makes the diagnosis and prognosis of TNBC challenging. METHOD: A comprehensive literature review and bibliometric analysis was performed using CiteSpace, VOSviewer and Scimago Graphica. RESULTS: TNBC biomarker research has been growing rapidly in recent years, reflecting the enormous academic interest in TNBC biomarker research. A total of 127 journals published relevant studies and 1749 authors were involved in the field, with developed countries such as the United States, France, and the United Kingdom contributing greatly to the field. Collaborative network analysis found that the research in this field has not yet formed good communication and interaction, and the partnership should be strengthened in the future in order to promote the in-depth development of TNBC biomarker research. Comprehensive analysis of keywords and co-cited literature, etc. found that TNBC biomarker research mainly focuses on immune checkpoint markers, microenvironment-related markers, circulating tumour DNA, metabolic markers, genomics markers and so on. These research hotspots will help to better understand the molecular characteristics and biological processes of TNBC, and provide more accurate biomarkers for its diagnosis, treatment and prognosis. CONCLUSIONS: The bibliometric analysis highlighted global trends and key directions in TNBC biomarker research. Future developments in TNBC biomarker research are likely to be in the direction of multi-omics integration, meticulous study of the microenvironment, targeted therapeutic biomarkers, application of liquid biopsy, application of machine learning and artificial intelligence, and individualised therapeutic strategies. Young scholars should learn and collaborate across disciplines, pay attention to new technologies and methods, improve their data analysis skills, and continue to follow up on the latest research trends in order to meet the challenges and opportunities in the field of TNBC biomarkers.

Du-moxibustion ameliorates depression-like behavior and neuroinflammation in chronic unpredictable mild stress-induced mice.

BACKGROUND: Neuroinflammation is involved in the advancement of depression. Du-moxibustion can treat depression. Here, we explored whether Du-moxibustion could alleviate neuroglia-associated neuro-inflammatory process in chronic unpredictable mild stress (CUMS) mice. METHODS: C57BL/6J mice were distributed into five groups. Except for the CON group, other four groups underwent CUMS for four consecutive weeks, and Du-moxibustion was given simultaneously after modeling. Behavioral tests were then carried out. Additionally, Western blot was conducted to measure the relative expression levels of high-mobility group box 1 (HMGB1), toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), and nuclear factor-kappa B (NF-κB). Immunofluorescence was employed to evaluate the positive cells of ionized calcium binding adapter molecule 1 (Iba-1) and glial fibrillary acidic protein (GFAP). Furthermore, interleukin-1 beta (IL-1ß) and tumor necrosis factor-alpha (TNF-α) were analyzed using an ELISA assay. RESULTS: We found that CUMS induced depression-like behaviors, such as reduced sucrose preference ratio, decreased locomotor and exploratory activity, decreased the time in open arms and prolonged immobility. Furthermore, versus the CON group, the expression of HMGB1, TLR4, MyD88, NF-κB, positive cells of Iba-1, IL-1ß and TNF-α were increased but positive cells of GFAP were decreased in CUMS group. However, the detrimental effects were ameliorated by treatment with CUMS+FLU and CUMS+DM. LIMITATIONS: A shortage of this study is that only CUMS model of depression were used, while other depression model were not included. CONCLUSIONS: Du-moxibustion alleviates depression-like behaviors in CUMS mice mainly by reducing neuroinflammation, which offers novel insights into the potential treatment of depression.