Engineering exosomes to reshape the immune microenvironment in breast cancer: Molecular insights and therapeutic opportunities.

BACKGROUND: Breast cancer remains a global health challenge, necessitating innovative therapeutic approaches. Immunomodulation and immunotherapy have emerged as promising strategies for breast cancer treatment. Engineered exosomes are the sort of exosomes modified with surface decoration and internal therapeutic molecules. Through suitable modifications, engineered exosomes exhibit the capability to overcome the limitations associated with traditional therapeutic approaches. This ability opens up novel avenues for the development of more effective, personalized, and minimally invasive interventions. MAIN BODY: In this comprehensive review, we explore the molecular insights and therapeutic potential of engineered exosomes in breast cancer. We discuss the strategies employed for exosome engineering and delve into their molecular mechanisms in reshaping the immune microenvironment of breast cancer. CONCLUSIONS: By elucidating the contribution of engineered exosomes to breast cancer immunomodulation, this review underscores the transformative potential of this emerging field for improving breast cancer therapy. HIGHLIGHTS: Surface modification of exosomes can improve the targeting specificity. The engineered exosome-loaded immunomodulatory cargo regulates the tumour immune microenvironment. Engineered exosomes are involved in the immune regulation of breast cancer.

Influence of experiencing SARS-CoV-2 infection on anxiety levels in Chinese patients undergoing third molar surgery.

Background: In China, most of the citizens experienced SARS-CoV-2 infection since the end of 2022. The Coronavirus disease 2019 (COVID-19) pandemic affected people's physical health and also had a significant impact on mental well-being. The present study aims to discover if the experience of SARS-CoV-2 infection influences patients' anxiety toward third molar surgery in the Chinese population. Materials and methods: The present study took the form of a questionnaire survey. From January 1, 2023, to June 30, 2023, patients who went to the Stomatology Center of China-Japan Friendship Hospital (Beijing, China) for the third molar extraction were included according to the inclusion criteria. The information on COVID-19 infection and the Modified Dental Anxiety Scale (MDAS) was collected. The software SPSS 22.0 was used for the statistical analyses. Results: A total of 574 survey results were harvested in the present study. The infection rate of COVID-19 was 86.6% (p > 0.05). The Average MDAS scores between patients who had been infected with COVID-19 and patients who were never infected were not significantly different (11.65 ± 4.41 vs. 11.42 ± 4.41, p > 0.05). The subgroup analysis was conducted according to the length of time after the recovery of COVID-19 (Model 1), and the highest temperature during the infection (Model 2). In Model 1 and Model 2, the one-way ANOVA test did not find statistical significance between the groups (Model 1 p = 0.114; Model 2 p = 0.481). The MDAS scores in female patients were significantly higher than in male patients (12.29 ± 4.53 vs. 9.91 ± 3.80, p < 0.001). Patients who extracted double teeth got significantly higher MDAS scores than those who extracted single teeth before the surgery (12.03 ± 4.74 vs. 11.24 ± 4.18, p = 0.037). Conclusion: The present study did not establish a significant impact of SARS-CoV-2 infection on the anxiety levels associated with third molar surgery among Chinese patients. The potential long-term biopsychological effects of the virus warrant further investigation.

TIN2-mediated reduction of mitophagy induces RPE senescence under high glucose.

The telomere-associated protein TIN2 localizes to both telomeres and mitochondria. Nevertheless, the impact of TIN2 on retinal pigment epithelial (RPE) cells in diabetic retinopathy (DR) remains unclear. This research aims to examine the role of TIN2 in the senescence of RPE and its potential as a therapeutic target. Western blotting and immunofluorescence staining were utilized to identify TIN2 expression and mitophagy. RT-qPCR was employed to identify senescent associated secretory phenotype (SASP) in ARPE-19 cells infected with TIN2 overexpression. To examine mitochondria and the cellular senescence of RPE, TEM, SA-ß-gal staining, and cell cycle analysis were used. The impact of TIN2 was examined using OCT and immunohistochemistry in mice. DHE staining and ZO-1 immunofluorescence were applied to detect RPE oxidative stress and tight junctions. Our research revealed that increased mitochondria-localized TIN2 aggravated the cellular senescence of RPE cells both in vivo and in vitro under hyperglycemia. TIN2 overexpression stimulated the mTOR signaling pathway in ARPE-19 cells and exacerbated the inhibition of mitophagy levels under high glucose, which can be remedied through the mTOR inhibitor, rapamycin. Knockdown of TIN2 significantly reduced senescence and mitochondrial oxidative stress in ARPE-19 cells under high glucose and restored retinal thickness and RPE cell tight junctions in DR mice. Our study indicates that increased mitochondria-localized TIN2 induced cellular senescence in RPE via compromised mitophagy and activated mTOR signaling. These results propose that targeting TIN2 could potentially serve as a therapeutic strategy in the treatment of DR.

Development of a zinc chloride-based chemo-mechanical system for potential minimally invasive dental caries removal system.

Background/purpose: The chemo-mechanical caries-removal technique is known to offer advantages of selective dentin caries treatment while leaving healthy dental tissues intact. However, current sodium hypochlorite based reagents usually excessively damage dentin collagen. Therefore, the purpose of this study was to develop a novel chemo-mechanical caries-removal system to preserve the collagen network for subsequent prosthetic restorations. Materials and methods: The calfskin-derived collagen was chosen as a model system to investigate the dissolution behavior of collagen under different operating conditions of chemical-ultrasonic treatment systems. The molecular weight, triple-helix structure, the morphology, and functional group of collagen after treatment were investigated. Results: Various concentrations of sodium hypochlorite or zinc chloride together with ultrasonic machinery were chosen to investigate. The outcomes of circular dichroism (CD) spectra demonstrated stability of the triple-helix structure after treatment of a zinc chloride solution. In addition, two apparent bands at molecular weights (MWs) of 130 and 121 kDa evidenced the stability of collagen network. The positive 222 nm and 195 nm negative CD absorption band indicated the existence of a triple-helix structure for type I collagen. The preservation of the morphology and functional group of the collagen network on the etched dentin surface were investigated by in vitro dentin decalcification model. Conclusion: Unlike NaOCl, the 5 wt% zinc chloride solution combined with ultra-sonication showed dissolution rather than denature as well as degradation of the dentin collagen network. Additional in vivo evaluations are needed to verify its usefulness in clinical applications.

Establishing a novel deep learning model for detecting peri-implantitis.

BACKGROUND/PURPOSE: The diagnosis of peri-implantitis using periapical radiographs is crucial. Recently, artificial intelligence may apply in radiographic image analysis effectively. The aim of this study was to differentiate the degree of marginal bone loss of an implant, and also to classify the severity of peri-implantitis using a deep learning model. MATERIALS AND METHODS: A dataset of 800 periapical radiographic images were divided into training (n = 600), validation (n = 100), and test (n = 100) datasets with implants used for deep learning. An object detection algorithm (YOLOv7) was used to identify peri-implantitis. The classification performance of this model was evaluated using metrics, including the specificity, precision, recall, and F1 score. RESULTS: Considering the classification performance, the specificity was 100%, precision was 100%, recall was 94.44%, and F1 score was 97.10%. CONCLUSION: Results of this study suggested that implants can be identified from periapical radiographic images using deep learning-based object detection. This identification system could help dentists and patients suffering from implant problems. However, more images of other implant systems are needed to increase the learning performance to apply this system in clinical practice.

Transcriptome analysis reveals the potential lncRNA-mRNA modules involved in genetic male sterility and fertility of Chinese cabbage (brassica rapa L. ssp. pekinensis).

BACKGROUND: Long non-coding RNAs (lncRNAs) play a crucial role in regulating gene expression vital for the growth and development of plants. Despite this, the role of lncRNAs in Chinese cabbage (Brassica rapa L. ssp. pekinensis) pollen development and male fertility remains poorly understood. RESULTS: In this study, we characterized a recessive genic male sterile mutant (366-2 S), where the delayed degradation of tapetum and the failure of tetrad separation primarily led to the inability to form single microspores, resulting in male sterility. To analyze the role of lncRNAs in pollen development, we conducted a comparative lncRNA sequencing using anthers from the male sterile mutant line (366-2 S) and the wild-type male fertile line (366-2 F). We identified 385 differentially expressed lncRNAs between the 366-2 F and 366-2 S lines, with 172 of them potentially associated with target genes. To further understand the alterations in mRNA expression and explore potential lncRNA-target genes (mRNAs), we performed comparative mRNA transcriptome analysis in the anthers of 366-2 S and 366-2 F at two stages. We identified 1,176 differentially expressed mRNAs. Remarkably, GO analysis revealed significant enrichment in five GO terms, most notably involving mRNAs annotated as pectinesterase and polygalacturonase, which play roles in cell wall degradation. The considerable downregulation of these genes might contribute to the delayed degradation of tapetum in 366-2 S. Furthermore, we identified 15 lncRNA-mRNA modules through Venn diagram analysis. Among them, MSTRG.9997-BraA04g004630.3 C (ß-1,3-glucanase) is associated with callose degradation and tetrad separation. Additionally, MSTRG.5212-BraA02g040020.3 C (pectinesterase) and MSTRG.13,532-BraA05g030320.3 C (pectinesterase) are associated with cell wall degradation of the tapetum, indicating that these three candidate lncRNA-mRNA modules potentially regulate pollen development. CONCLUSION: This study lays the foundation for understanding the roles of lncRNAs in pollen development and for elucidating their molecular mechanisms in regulating male sterility in Chinese cabbage.

Clinical Implications of Estimating Glomerular Filtration Rate with Different Equations in Heart Failure Patients with Preserved Ejection Fraction.

INTRODUCTION: The prognostic values of estimated glomerular filtration rate (eGFR) calculated by different formulas have not been adequately compared in patients with heart failure with preserved ejection fraction (HFpEF). AIM: We compared the predictive values of serum creatinine-based eGFRs calculated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) 2009 equation, Modification of Diet in Renal Disease Study (MDRD) formula, and full-age-spectrum creatinine (FAS Cr) equation in 1751 HFpEF patients. METHODS: The area under the receiver-operating characteristic curve (AUC), integrated discrimination improvement (IDI) and net reclassification improvement (NRI) were employed. RESULTS: eGFR values were lowest calculated with FAS Cr equation (p < 0.001). When patients were classified into 4 subgroups (eGFR ≥ 90, 89-60, 59-30, and  < 30 ml/min/1.73 m2) or only 2 subgroups (≥ 60 or  < 60 ml/min/1.73 m2), the 3 formulas correlated significantly, with the best correlation found between the MDRD and CKD-EPI formulas (kappa = 0.871 and 0.963, respectively). The 3 formulas conveyed independent prognostic information. After adjusting for potential cofounders, risk prediction for all-cause mortality was more accurate (p = 0.001) using the CKD-EPI equation than MDRD formula as assessed by AUC. Compared with MDRD formula, CKD-EPI equation exhibited superior predictive ability assessed by IDI and NRI of 0.32% (p < 0.001)/10.4% (p = 0.010) for primary endpoint and 0.37% (p = 0.010)/10.8% (p = 0.010) for HF hospitalization. The risk prediction for deterioration of renal function was more accurate (p ≤ 0.040) using the CKD-EPI equation than FAS Cr equation as assessed by AUC, IDI, and NRI. CONCLUSION: The CKD-EPI formula might be the preferred creatinine-based equation in clinical risk stratification in HFpEF patients.

Distinctive profile of monomeric and polymeric anti-SSA/Ro52 immunoglobulin A1 isoforms in saliva of patients with primary Sjögren's syndrome and Sicca.

OBJECTIVE: Primary Sjögren's syndrome (pSS) is the second most common chronic autoimmune connective tissue disease. Autoantibodies, immunoglobulin (IgG) anti-SSA/Ro, in serum is a key diagnostic feature of pSS. Since pSS is a disease of the salivary gland, we investigated anti-SSA/Ro52 in saliva. METHODS: Using a novel electrochemical detection platform, Electric Field-Induced Release and Measurement, we measured IgG/M/A, IgG, IgA, IgA isotypes (IgA1 and IgA2) and IgA1 subclasses (polymeric and monomeric IgA1) to anti-SSA/Ro52 in saliva supernatant of 34 pSS, 35 dry eyes and dry mouth (patients with Sicca) and 41 health controls. RESULTS: Saliva IgG/M/A, IgG, IgA, IgA isotypes and IgA1 subclasses to anti-SSA/Ro52 differed significantly between pSS, non-pSS Sicca and healthy subjects. Elevated monomeric IgA1 was observed in patients with non-pSS Sicca while elevated polymeric IgA1 (pIgA1) was observed in patients with pSS. Salivary polymeric but not monomeric IgA1 (mIgA1) isoform correlated with focus score (r2=0.467, p=0.001) CONCLUSIONS: Salivary anti-Ro52 polymeric IgA1 isoform is associated with glandular inflammation in pSS, while salivary monomeric IgA1 is associated with Sicca. Whether IgA1 isotope switching plays a role in the progression of the Sicca to pSS warrants further investigation.

Lipase-Catalyzed Preparation and Optimization of Structured Phosphatidylcholine Containing Nervonic Acid.

This study investigated the incorporation of nervonic acid into the chemical structure of phosphatidylcholine via a lipase-catalyzed acidolysis reaction to obtain a functional phospholipid. Lipase immobilization was conducted, and Amberlite XAD7-HP was selected as a carrier to immobilize phospholipase A1 (PLA1) for subsequent experiments. The main acidolysis reaction parameters, including enzyme load, substrate ratio, temperature, and water content, were studied against the reaction time. The optimum reaction conditions obtained were enzyme load, 20%; reaction temperature, 55 °C; water content, 1%; and reaction time, 9 h. The maximum incorporation of nervonic acid into phosphatidylcholine was 48 mol%, with PC recovery at 61.6 mol%. The positional distribution of structured phosphatidylcholine shows that nervonic acid was found in the sn-1 position due to enzyme specificity and in the sn-2 position, possibly due to acyl migration.

Seronegative patients with primary Sjögren's syndrome and non-pSS sicca test positive for anti-SSA/Ro52 and -Ro60 in saliva.

OBJECTIVES: Testing for anti-SSA/Ro antibodies in serum is essential in the diagnostic work-up for primary Sjögren's syndrome (pSS). In this study, we aimed to validate our previous assay for detection of salivary anti-SSA/Ro52, and to develop assays for detection of salivary anti-SSA/Ro60 and for detection of anti-Ro52 and -Ro60 in plasma using the electric field-induced release and measurement (EFIRM) platform. METHODS: Whole saliva samples from two independent Danish cohorts (DN1 and DN2) including 49 patients with pSS, 73 patients with sicca symptoms, but not fulfilling the classification criteria for pSS (non-pSS sicca), and 51 healthy controls (HC), as well as plasma samples from the DN1 cohort were analyzed using EFIRM to detect anti-SSA/Ro52 and -Ro60. RESULTS: In the DN1 cohort, 100 % in the pSS group and 16 % in the non-pSS sicca group were serum anti-SSA/Ro positive by ELISA. EFIRM detected anti-SSA (Ro52 and/or -Ro60) in plasma and saliva in 100 % and 96 % patients with pSS, and 16 % and 29 % with non-pSS sicca. In the DN2 cohort, 80 % patients with pSS and 26 % with non-pSS sicca were serum anti-SSA/Ro positive. Salivary anti-SSA discriminated patients with pSS from HC and non-pSS sicca with an AUC range of 0.74-0.96 in the DN1 and DN2 cohorts. EFIRM discriminated pSS from non-pSS sicca with an AUC of 0.98 in plasma. CONCLUSION: Our findings suggest that salivary anti-SSA/Ro antibodies are potential discriminatory biomarkers for pSS, which may also identify seronegative patients, addressing the unmet clinical need of early detection and stratification of pSS.

Endocrine disrupting effects of parabens in zebrafish (Danio rerio): New insights from transcriptomics, metabolomics, and molecular dynamics simulation.

Parabens (PBs), a group of widely used synthetic preservatives with potential endocrine disrupting activity, have been detected with increasing frequency in organisms and environmental matrices. This study assessed the hormone interference effects of four typical PBs, namely methylparaben (MeP), ethylparaben (EtP), propylparaben (PrP), and butylparaben (BuP), in zebrafish and elucidated the probable underlying mechanisms. Transcriptomic and metabolomic analyses showed that the differentially expressed genes and metabolites were associated with the tyrosine metabolism, arachidonate metabolism, and glycerophospholipid metabolism, indicating they were essential precursors of steroid hormone biosynthesis and metabolism. Histopathological analysis revealed impaired gonad development in the zebrafish exposed to PBs, as evidenced by the significantly increased vitellogenin (VTG) and estradiol (E2) levels. Furthermore, molecular dynamics simulation suggested that the four PBs could preferentially activate the zebrafish estrogen receptor, zfERß2, to regulate the downstream pathways. Disruption of the amino acid metabolism and lipid metabolism, and activation of zfERß2 signaling pathway were found to be the key mechanisms for the endocrine disrupting effects of PBs. The hormone interference effects of PBs were apparently dependent on the shared oxybenzene on their structures, with the degree of interference determined largely by the length of their alkyl chains. These findings provide new insights into the endocrine disrupting effects of PBs and could help better assess their risk to human health.

[Brain Fog: A Concept Analysis].

Brain fog is a symptom that has gained increasing attention worldwide since the start of the COVID-19 pandemic, as patients affected by COVID-19 may experience cognitive dysfunction, colloquially known as brain fog, for a period of time after recovery. Brain fog affects activities of daily living and work performance and has the potential to negatively impact society and the economy. However, a clear definition and concept analysis of brain fog is lacking in the literature. In this article, a concept analysis of brain fog is conducted using Walker and Avant's concept analysis steps to verify the source and definition of brain fog, clarify related concepts similar to brain fog, and establish the defining attributes, antecedents, and consequences of this condition. Model, borderline, contrary, and related cases are listed to illustrate and provide related empirical references in the literature. The authors hope this article will provide a clearer understanding of brain fog, which then may be applied in nursing clinical practice and future research to develop strategies and care methods for improving brain fog symptoms.

Right ventricular dyssynchrony for the prediction of prognosis in patients with systemic lupus erythematosus-aaociated pulmonary arterial hypertension: a study with two-dimensional speckle tracking.

Pulmonary arterial hypertension (PAH) is a common complication of systemic lupus erythematosus (SLE), and PAH can cause right ventricle (RV) remodel and dyssynchrony. The aim of this study was to explore the value of RV dyssynchrony in predicting adverse clinical events in patients with systemic lupus erythematosus-aaociated pulmonary arterial hypertension (SLE-PAH) using two-dimensional speckle tracking echocardiography (2D-STE). A total of 53 patients with SLE-PAH were enrolled in this study. The dyssynchrony of the RV (RV-SD6) was evaluated by 2D-STE. The clinical data of all participants were collected, and routine cardiac function parameters were measured by two-dimensional echocardiography, and analyzed for their correlation with RV-SD6. The predictive value of RV-SD6 in clinical adverse event was evaluated. RV-SD6 was negatively correlated with RV-FLS, RV-FAC, and TAPSE (r = - 0.788, r = - 0.363 and r = - 0.325, respectively, all P < 0.01), while the correlation with RV-FLS was the strongest. linear regression analysis showed that RV-FLS was an independent risk factor for RV-SD6 (ß = - 1.40, 95% CI - 1.65 ~ - 1.14, P < 0.001). Cox regression analysis showed that RV-SD6 was a predictor with clinical adverse events (HR = 1.03, 95% CI 1 ~ 1.06, P < 0.05). RV-SD6 was highly discriminative in predicting clinical adverse events (AUC = 0.764), at a cutoff of 51.10 ms with a sensitivity of 83.3% and specificity of 68.3%. RV-FLS was negatively correlated with RV-SD6 and was an independent risk factor for it. RV-SD6 can serve as an indicator for predicting the occurrence of adverse clinical events in SLE-PAH patients, with high sensitivity and specificity.

Intermittent fasting shifts the diurnal transcriptome atlas of transcription factors.

Intermittent fasting remains a safe and effective strategy to ameliorate various age-related diseases, but its specific mechanisms are not fully understood. Considering that transcription factors (TFs) determine the response to environmental signals, here, we profiled the diurnal expression of 600 samples across four metabolic tissues sampled every 4 over 24 h from mice placed on five different feeding regimens to provide an atlas of TFs in biological space, time, and feeding regimen. Results showed that 1218 TFs exhibited tissue-specific and temporal expression profiles in ad libitum mice, of which 974 displayed significant oscillations at least in one tissue. Intermittent fasting triggered more than 90% (1161 in 1234) of TFs to oscillate somewhere in the body and repartitioned their tissue-specific expression. A single round of fasting generally promoted TF expression, especially in skeletal muscle and adipose tissues, while intermittent fasting mainly suppressed TF expression. Intermittent fasting down-regulated aging pathway and upregulated the pathway responsible for the inhibition of mammalian target of rapamycin (mTOR). Intermittent fasting shifts the diurnal transcriptome atlas of TFs, and mTOR inhibition may orchestrate intermittent fasting-induced health improvements. This atlas offers a reference and resource to understand how TFs and intermittent fasting may contribute to diurnal rhythm oscillation and bring about specific health benefits.

Effectiveness of health education and counseling on stages of change, decisional balance, and smoking cessation self-efficacy: A prospective self-control study.

OBJECTIVE: To examine the effectiveness of health education and counseling on the stages of change, decisional balance, and smoking cessations elf-efficacy in smokers with no intention of quitting. METHODS: A prospective self-controlled design was conducted between December 2020 and December 2022. The research period was divided into a control stage (first to fourth weeks) and an experimental stage (fifth to eighth weeks). Patients with coronary artery disease (CAD) and habitually smoked were recruited. Pearson correlation and a one-factor repeated-measurement analysis were performed to assess the effectiveness of the intervention. RESULTS: In total, 108 male CAD patients with a mean age of 58.1 years were recruited. After 4 weeks of the intervention, 55 (51%) exhibited behavior change (X 2 = 18.03, p = .001). The decisional balance and smoking cessation self-efficacy scores significantly improved in the experimental stage. No significant differences were observed in the control stage. CONCLUSIONS: Four weeks of health education and counseling could effectively improve participants' stage of change, decisional balance, and smoking cessation self-efficacy. PRACTICE IMPLICATION: Healthcare professionals can play key roles in helping CAD patients successfully quit smoking through individual education and counseling.

Mortality and Cardiovascular End Points In Relation to the Aortic Pulse Wave Components: An Individual-Participant Meta-Analysis.

BACKGROUND: Wave separation analysis enables individualized evaluation of the aortic pulse wave components. Previous studies focused on the pressure height with overall positive but differing results. In the present analysis, we assessed the associations of the pressure of forward and backward (Pfor and Pref) pulse waves with prospective cardiovascular end points, with extended analysis for time to pressure peak (Tfor and Tref). METHODS: Participants in 3 IDCARS (International Database of Central Arterial Properties for Risk Stratification) cohorts (Argentina, Belgium, and Finland) aged ≥20 years with valid pulse wave analysis and follow-up data were included. Pulse wave analysis was done using the SphygmoCor device, and pulse wave separation was done using the triangular method. The primary end points consisted of cardiovascular mortality and nonfatal cardiovascular and cerebrovascular events. Multivariable-adjusted Cox regression was used to calculate hazard ratios. RESULTS: A total of 2206 participants (mean age, 57.0 years; 55.0% women) were analyzed. Mean±SDs for Pfor, Pref, Tfor, and Tfor/Tref were 31.0±9.1 mm Hg, 20.8±8.4 mm Hg, 130.8±35.5, and 0.51±0.11, respectively. Over a median follow-up of 4.4 years, 146 (6.6%) participants experienced a primary end point. Every 1 SD increment in Pfor, Tfor, and Tfor/Tref was associated with 27% (95% CI, 1.07-1.49), 25% (95% CI, 1.07-1.45), and 32% (95% CI, 1.12-1.56) higher risk, respectively. Adding Tfor and Tfor/Tref to existing risk models improved model prediction (∆Uno's C, 0.020; P<0.01). CONCLUSIONS: Pulse wave components were predictive of composite cardiovascular end points, with Tfor/Tref showing significant improvement in risk prediction. Pending further confirmation, the ratio of time to forward and backward pressure peak may be useful to evaluate increased afterload and signify increased cardiovascular risk.

Transport behavior of microplastics in soil‒water environments and its dependence on soil components.

Microplastic (MP) pollution has become a global concern, and the transport behavior of MPs in soil-water systems is vital in determining their distribution and potential risks to the subsurface environment. To reveal the role of various soil components on MP migration, the downward transport behavior of polystyrene (PS) MPs were explored in this study via column experiments with mono or multi-soil components as porous media. Compared with the selected soil mineral volcanic rock (VR) and fine river sand (RS), condensed soil organic matter (SOM) resulted in higher transport efficiencies for PS microparticles, with greater than 90% total mass recovery under the experimental conditions. The more surface charges of SOM than minerals contribute to the high migration efficiency of PS MPs, and electrostatic repulsion is assumed a significant driving mechanism in the migration of negatively charged PS particles in soils. The ionic strength of porewater influenced the PS migration behaviors by altering the electrostatic interactions between the MPs and soil grains. The uniform mixing of SOM with mineral grains significantly enhanced the transport efficiency of PS MPs in the columns. The results provide supports for the prediction and prevention of the risks of MPs to the subsurface environment.

ThermomiR-377-3p-induced suppression of Cirbp expression is required for effective elimination of cancer cells and cancer stem-like cells by hyperthermia.

BACKGROUND: In recent years, the development of adjunctive therapeutic hyperthermia for cancer therapy has received considerable attention. However, the mechanisms underlying hyperthermia resistance are still poorly understood. In this study, we investigated the roles of cold­inducible RNA binding protein (Cirbp) in regulating hyperthermia resistance and underlying mechanisms in nasopharyngeal carcinoma (NPC). METHODS: CCK-8 assay, colony formation assay, tumor sphere formation assay, qRT-PCR, Western blot were employed to examine the effects of hyperthermia (HT), HT + oridonin(Ori) or HT + radiotherapy (RT) on the proliferation and stemness of NPC cells. RNA sequencing was applied to gain differentially expressed genes upon hyperthermia. Gain-of-function and loss-of-function experiments were used to evaluate the effects of RNAi-mediated Cirbp silencing or Cirbp overexpression on the sensitivity or resistance of NPC cells and cancer stem-like cells to hyperthermia by CCK-8 assay, colony formation assay, tumorsphere formation assay and apoptosis assay, and in subcutaneous xenograft animal model. miRNA transient transfection and luciferase reporter assay were used to demonstrate that Cirbp is a direct target of miR-377-3p. The phosphorylation levels of key members in ATM-Chk2 and ATR-Chk1 pathways were detected by Western blot. RESULTS: Our results firstly revealed that hyperthermia significantly attenuated the stemness of NPC cells, while combination treatment of hyperthermia and oridonin dramatically increased the killing effect on NPC cells and cancer stem cell (CSC)­like population. Moreover, hyperthermia substantially improved the sensitivity of radiation­resistant NPC cells and CSC­like cells to radiotherapy. Hyperthermia noticeably suppressed Cirbp expression in NPC cells and xenograft tumor tissues. Furthermore, Cirbp inhibition remarkably boosted anti­tumor­killing activity of hyperthermia against NPC cells and CSC­like cells, whereas ectopic expression of Cirbp compromised tumor­killing effect of hyperthermia on these cells, indicating that Cirbp overexpression induces hyperthermia resistance. ThermomiR-377-3p improved the sensitivity of NPC cells and CSC­like cells to hyperthermia in vitro by directly suppressing Cirbp expression. More importantly, our results displayed the significantly boosted sensitization of tumor xenografts to hyperthermia by Cirbp silencing in vivo, but ectopic expression of Cirbp almost completely counteracted hyperthermia-mediated tumor cell-killing effect against tumor xenografts in vivo. Mechanistically, Cirbp silencing-induced inhibition of DNA damage repair by inactivating ATM-Chk2 and ATR-Chk1 pathways, decrease in stemness and increase in cell death contributed to hyperthermic sensitization; conversely, Cirbp overexpression-induced promotion of DNA damage repair, increase in stemness and decrease in cell apoptosis contributed to hyperthermia resistance. CONCLUSION: Taken together, these findings reveal a previously unrecognized role for Cirbp in positively regulating hyperthermia resistance and suggest that thermomiR-377-3p and its target gene Cirbp represent promising targets for therapeutic hyperthermia.

Performance of the walking trail making test in older adults with white matter hyperintensities.

BACKGROUND: Several studies have reported that the walking trail making test (WTMT) completion time is significantly higher in patients with developmental coordination disorders and mild cognitive impairments. We hypothesized that WTMT performance would be altered in older adults with white matter hyperintensities (WMH). AIM: To explore the performance in the WTMT in older people with WMH. METHODS: In this single-center, observational study, 25 elderly WMH patients admitted to our hospital from June 2019 to June 2020 served as the WMH group and 20 participants matched for age, gender, and educational level who were undergoing physical examination in our hospital during the same period served as the control group. The participants completed the WTMT-A and WTMT-B to obtain their gait parameters, including WTMT-A completion time, WTMT-B completion time, speed, step length, cadence, and stance phase percent. White matter lesions were scored according to the Fazekas scale. Multiple neuropsychological assessments were carried out to assess cognitive function. The relationships between WTMT performance and cognition and motion in elderly patients with WMH were analyzed by partial Pearson correlation analysis. RESULTS: Patients with WMH performed significantly worse on the choice reaction test (CRT) (0.51 ± 0.09 s vs 0.44 ± 0.06 s, P = 0.007), verbal fluency test (VFT, 14.2 ± 2.75 vs 16.65 ± 3.54, P = 0.012), and digit symbol substitution test (16.00 ± 2.75 vs 18.40 ± 3.27, P = 0.010) than participants in the control group. The WMH group also required significantly more time to complete the WTMT-A (93.00 ± 10.76 s vs 70.55 ± 11.28 s, P < 0.001) and WTMT-B (109.72 ± 12.26 s vs 82.85 ± 7.90 s, P < 0.001). WTMT-A completion time was positively correlated with CRT time (r = 0.460, P = 0.001), while WTMT-B completion time was negatively correlated with VFT (r = -0.391, P = 0.008). On the WTMT-A, only speed was found to statistically differ between the WMH and control groups (0.803 ± 0.096 vs 0.975 ± 0.050 m/s, P < 0.001), whereas on the WTMT-B, the WMH group exhibited a significantly lower speed (0.778 ± 0.111 vs 0.970 ± 0.053 m/s, P < 0.001) and cadence (82.600 ± 4.140 vs 85.500 ± 5.020 steps/m, P = 0.039), as well as a higher stance phase percentage (65.061 ± 1.813% vs 63.513 ± 2.465%, P = 0.019) relative to controls. CONCLUSION: Older adults with WMH showed obviously poorer WTMT performance. WTMT could be a potential indicator for cognitive and motor deficits in patients with WMH.

PFKFB3 in neovascular eye disease: unraveling mechanisms and exploring therapeutic strategies.

BACKGROUND: Neovascular eye disease is characterized by pathological neovascularization, with clinical manifestations such as intraocular exudation, bleeding, and scar formation, ultimately leading to blindness in millions of individuals worldwide. Pathologic ocular angiogenesis often occurs in common fundus diseases including proliferative diabetic retinopathy (PDR), age-related macular degeneration (AMD), and retinopathy of prematurity (ROP). Anti-vascular endothelial growth factor (VEGF) targets the core pathology of ocular angiogenesis. MAIN BODY: In recent years, therapies targeting metabolism to prevent angiogenesis have also rapidly developed, offering assistance to patients with a poor prognosis while receiving anti-VEGF therapy and reducing the side effects associated with long-term VEGF usage. Phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3), a key enzyme in targeted metabolism, has been shown to have great potential, with antiangiogenic effects and multiple protective effects in the treatment of neovascular eye disease. In this review, we summarize the mechanisms of common types of neovascular eye diseases; discuss the protective effect and potential mechanism of targeting PFKFB3, including the related inhibitors of PFKFB3; and look forward to the future exploration directions and therapeutic prospects of PFKFB3 in neovascular eye disease. CONCLUSION: Neovascular eye disease, the most common and severely debilitating retinal disease, is largely incurable, necessitating the exploration of new treatment methods. PFKFB3 has been shown to possess various potential protective mechanisms in treating neovascular eye disease. With the development of several drugs targeting PFKFB3 and their gradual entry into clinical research, targeting PFKFB3-mediated glycolysis has emerged as a promising therapeutic approach for the future of neovascular eye disease.