RNA splicing modulates the postharvest physiological deterioration of cassava storage root.

Rapid postharvest physiological deterioration (PPD) of cassava (Manihot esculenta Crantz) storage roots is a major constraint that limits the potential of this plant as a food and industrial crop. Extensive studies have been performed to explore the regulatory mechanisms underlying the PPD processes in cassava to understand their molecular and physiological responses. However, the exceptional functional versatility of alternative splicing (AS) remains to be explored during the PPD process in cassava. Here, we identified several aberrantly spliced genes during the early PPD stage. An in-depth analysis of AS revealed that the abscisic acid (ABA) biosynthesis pathway might serve as an additional molecular layer in attenuating the onset of PPD. Exogenous ABA application alleviated PPD symptoms through maintaining ROS generation and scavenging. Interestingly, the intron retention transcript of MeABA1 (ABA DEFICIENT 1) was highly correlated with PPD symptoms in cassava storage roots. RNA yeast three-hybrid and RNA immunoprecipitation assays showed that the serine/arginine-rich protein MeSCL33 (SC35-like splicing factor 33) binds to the precursor mRNA of MeABA1. Importantly, overexpressing MeSCL33 in cassava conferred improved PPD resistance by manipulating the AS and expression levels of MeABA1 and then modulating the endogenous ABA levels in cassava storage roots. Our results uncovered the pivotal role of the ABA biosynthesis pathway and RNA splicing in regulating cassava PPD resistance and proposed the essential roles of MeSCL33 for conferring PPD resistance, broadening our understanding of SR proteins in cassava development and stress responses.

Mitochondrial dynamics, quality control and mtDNA in Alcohol-associated liver disease and liver cancer.

Mitochondria are intracellular organelles responsible for energy production, glucose and lipid metabolism, cell death, cell proliferation, and innate immune response. Mitochondria are highly dynamic organelles that constantly undergo fission, fusion, and intracellular trafficking, as well as degradation and biogenesis. Mitochondrial dysfunction has been implicated in a variety of chronic liver diseases including alcohol-associated liver disease (ALD), metabolic dysfunction-associated steatohepatitis (MASH), and hepatocellular carcinoma (HCC). In this review, we provide a detailed overview of mitochondrial dynamics, mitophagy, and mtDNA-mediated innate immune response, and how dysregulation of these mitochondrial processes affects the pathogenesis of ALD and HCC. Mitochondrial dynamics and mtDNA-mediated innate immune response may thereby represent an attractive therapeutic target for ameliorating ALD and alcohol-associated HCC.

TMEM120B strengthens breast cancer cell stemness and accelerates chemotherapy resistance via ß1-integrin/FAK-TAZ-mTOR signaling axis by binding to MYH9.

BACKGROUND: Breast cancer stem cell (CSC) expansion results in tumor progression and chemoresistance; however, the modulation of CSC pluripotency remains unexplored. Transmembrane protein 120B (TMEM120B) is a newly discovered protein expressed in human tissues, especially in malignant tissues; however, its role in CSC expansion has not been studied. This study aimed to determine the role of TMEM120B in transcriptional coactivator with PDZ-binding motif (TAZ)-mediated CSC expansion and chemotherapy resistance. METHODS: Both bioinformatics analysis and immunohistochemistry assays were performed to examine expression patterns of TMEM120B in lung, breast, gastric, colon, and ovarian cancers. Clinicopathological factors and overall survival were also evaluated. Next, colony formation assay, MTT assay, EdU assay, transwell assay, wound healing assay, flow cytometric analysis, sphere formation assay, western blotting analysis, mouse xenograft model analysis, RNA-sequencing assay, immunofluorescence assay, and reverse transcriptase-polymerase chain reaction were performed to investigate the effect of TMEM120B interaction on proliferation, invasion, stemness, chemotherapy sensitivity, and integrin/FAK/TAZ/mTOR activation. Further, liquid chromatography-tandem mass spectrometry analysis, GST pull-down assay, and immunoprecipitation assays were performed to evaluate the interactions between TMEM120B, myosin heavy chain 9 (MYH9), and CUL9. RESULTS: TMEM120B expression was elevated in lung, breast, gastric, colon, and ovarian cancers. TMEM120B expression positively correlated with advanced TNM stage, lymph node metastasis, and poor prognosis. Overexpression of TMEM120B promoted breast cancer cell proliferation, invasion, and stemness by activating TAZ-mTOR signaling. TMEM120B directly bound to the coil-coil domain of MYH9, which accelerated the assembly of focal adhesions (FAs) and facilitated the translocation of TAZ. Furthermore, TMEM120B stabilized MYH9 by preventing its degradation by CUL9 in a ubiquitin-dependent manner. Overexpression of TMEM120B enhanced resistance to docetaxel and doxorubicin. Conversely, overexpression of TMEM120B-∆CCD delayed the formation of FAs, suppressed TAZ-mTOR signaling, and abrogated chemotherapy resistance. TMEM120B expression was elevated in breast cancer patients with poor treatment outcomes (Miller/Payne grades 1-2) than in those with better outcomes (Miller/Payne grades 3-5). CONCLUSIONS: Our study reveals that TMEM120B bound to and stabilized MYH9 by preventing its degradation. This interaction activated the ß1-integrin/FAK-TAZ-mTOR signaling axis, maintaining stemness and accelerating chemotherapy resistance.

Late-Life Alcohol Exposure Does Not Exacerbate Age-Dependent Reductions in Mouse Spatial Memory and Brain TFEB Activity.

Alcohol consumption is believed to affect Alzheimer's disease (AD) risk, but the contributing mechanisms are not well understood. A potential mediator of the proposed alcohol-AD connection is autophagy, a degradation pathway that maintains organelle and protein homeostasis. Autophagy is in turn regulated through the activity of Transcription factor EB (TFEB), which promotes lysosome and autophagy-related gene expression. To explore the effect of alcohol on brain TFEB and autophagy, we exposed young (3-month old) and aged (23-month old) mice to two alcohol-feeding paradigms and assessed biochemical, transcriptome, histology, and behavioral endpoints. In young mice, alcohol decreased hippocampal nuclear TFEB staining but increased SQSTM1/p62, LC3-II, ubiquitinated proteins, and phosphorylated Tau. Hippocampal TFEB activity was lower in aged mice than it was in young mice, and Gao-binge alcohol feeding did not worsen the age-related reduction in TFEB activity. To better assess the impact of chronic alcohol exposure, we fed young and aged mice alcohol for four weeks before completing Morris Water and Barnes Maze spatial memory testing. The aged mice showed worse spatial memory on both tests. While alcohol feeding slightly impaired spatial memory in the young mice, it had little effect or even slightly improved spatial memory in the aged mice. These findings suggest that aging is a far more important driver of spatial memory impairment and reduced autophagy flux than alcohol consumption.

Perioperative management of kidney transplantation in China: A national survey in 2021.

Perioperative anaesthesia management has an important significance for kidney transplantation; however, the related consensus remains limited. An electronic survey with 44 questions was developed and sent to the chief anaesthesiologist at 115 non-military medical centres performing kidney transplantation in China through WeChat. A response rate of 81.7% was achieved from 94 of 115 non-military medical centres, where 94.4% of kidney transplants (10404 /11026) were completed in 2021. The result showed an overview of perioperative practice for kidney transplantations in China, identify the heterogeneity, and provide evidence for improving perioperative management of kidney transplantation. Some controversial therapy, such as hydroxyethyl starch, are still widely used, while some recommended methods are not widely available. More efforts on fluid management, hemodynamical monitoring, perioperative anaesthetics, and postoperative pain control are needed to improve the outcomes. Evidence-based guidelines for standardizing clinical practice are needed.

High-throughput screening of novel TFEB agonists in protecting against acetaminophen-induced liver injury in mice.

Macroautophagy (referred to as autophagy hereafter) is a major intracellular lysosomal degradation pathway that is responsible for the degradation of misfolded/damaged proteins and organelles. Previous studies showed that autophagy protects against acetaminophen (APAP)-induced injury (AILI) via selective removal of damaged mitochondria and APAP protein adducts. The lysosome is a critical organelle sitting at the end stage of autophagy for autophagic degradation via fusion with autophagosomes. In the present study, we showed that transcription factor EB (TFEB), a master transcription factor for lysosomal biogenesis, was impaired by APAP resulting in decreased lysosomal biogenesis in mouse livers. Genetic loss-of and gain-of function of hepatic TFEB exacerbated or protected against AILI, respectively. Mechanistically, overexpression of TFEB increased clearance of APAP protein adducts and mitochondria biogenesis as well as SQSTM1/p62-dependent non-canonical nuclear factor erythroid 2-related factor 2 (NRF2) activation to protect against AILI. We also performed an unbiased cell-based imaging high-throughput chemical screening on TFEB and identified a group of TFEB agonists. Among these agonists, salinomycin, an anticoccidial and antibacterial agent, activated TFEB and protected against AILI in mice. In conclusion, genetic and pharmacological activating TFEB may be a promising approach for protecting against AILI.

Components of the tumor immune microenvironment based on m-IHC correlate with prognosis and subtype of triple-negative breast cancer.

BACKGROUND AND AIM: The spatial distribution and interactions of cells in the tumor immune microenvironment (TIME) might be related to the different responses of triple-negative breast cancer (TNBC) to immunomodulators. The potential of multiplex IHC (m-IHC) in evaluating the TIME has been reported, but the efficacy is insufficient. We aimed to research whether m-IHC results could be used to reflect the TIME, and thus to predict prognosis and complement the TNBC subtyping system. METHODS: The clinical, imaging, and prognosis data for 86 TNBC patients were retrospectively reviewed. CD3, CD4, CD8, Foxp3, PD-L1, and Pan-CK markers were stained by m-IHC. Particular cell spatial distributions and interactions in the TIME were evaluated with the HALO multispectral analysis platform. Then, we calculated the prognostic value of components of the TIME and their correlations with TNBC transcriptomic subtypes and MRI radiomic features reflecting TNBC subtypes. RESULTS: The components of the TIME score were established by m-IHC and demonstrated positive prognostic value for TNBC (p = 0.0047, 0.039, <0.0001 for DMFS, RFS, and OS). The score was calculated from several indicators, including Treg% in the tumor core (TC) or stromal area (SA), PD-L1+ cell% in the SA, CD3 + cell% in the TC, and PD-L1+ /CD8+ cells in the invasive margin and SA. According to the TNBC subtyping system, a few TIME indicators were significantly different in different subtypes and significantly correlated with MRI radiomic features reflecting TNBC subtypes. CONCLUSION: We demonstrated that the m-IHC-based quantitative score and indicators related to the spatial distribution and interactions of cells in the TIME can aid in the accurate diagnosis of TNBC in terms of prognosis and classification.

Hybrid deep multi-task learning radiomics approach for predicting EGFR mutation status of non-small cell lung cancer in CT images.

Objective.Epidermal growth factor receptor (EGFR) mutation genotyping plays a pivotal role in targeted therapy for non-small cell lung cancer (NSCLC). We aimed to develop a computed tomography (CT) image-based hybrid deep radiomics model to predict EGFR mutation status in NSCLC and investigate the correlations between deep image and quantitative radiomics features.Approach.First, we retrospectively enrolled 818 patients from our centre and 131 patients from The Cancer Imaging Archive database to establish a training cohort (N= 654), an independent internal validation cohort (N= 164) and an external validation cohort (N= 131). Second, to predict EGFR mutation status, we developed three CT image-based models, namely, a multi-task deep neural network (DNN), a radiomics model and a feature fusion model. Third, we proposed a hybrid loss function to train the DNN model. Finally, to evaluate the model performance, we computed the areas under the receiver operating characteristic curves (AUCs) and decision curve analysis curves of the models.Main results.For the two validation cohorts, the feature fusion model achieved AUC values of 0.86 ± 0.03 and 0.80 ± 0.05, which were significantly higher than those of the single-task DNN and radiomics models (allP< 0.05). There was no significant difference between the feature fusion and the multi-task DNN models (P> 0.8). The binary prediction scores showed excellent prognostic value in predicting disease-free survival (P= 0.02) and overall survival (P< 0.005) for validation cohort 2.Significance.The results demonstrate that (1) the feature fusion and multi-task DNN models achieve significantly higher performance than that of the conventional radiomics and single-task DNN models, (2) the feature fusion model can decode the imaging phenotypes representing NSCLC heterogeneity related to both EGFR mutation and patient NSCLC prognosis, and (3) high correlations exist between some deep image and radiomics features.

Research on a New Intelligent and Rapid Screening Method for Depression Risk in Young People Based on Eye Tracking Technology.

Depression is a prevalent mental disorder, with young people being particularly vulnerable to it. Therefore, we propose a new intelligent and rapid screening method for depression risk in young people based on eye tracking technology. We hypothesized that the "emotional perception of eye movement" could characterize defects in emotional perception, recognition, processing, and regulation in young people at high risk for depression. Based on this hypothesis, we designed the "eye movement emotional perception evaluation paradigm" and extracted digital biomarkers that could objectively and accurately evaluate "facial feature perception" and "facial emotional perception" characteristics of young people at high risk of depression. Using stepwise regression analysis, we identified seven digital biomarkers that could characterize emotional perception, recognition, processing, and regulation deficiencies in young people at high risk for depression. The combined effectiveness of an early warning can reach 0.974. Our proposed technique for rapid screening has significant advantages, including high speed, high early warning efficiency, low cost, and high intelligence. This new method provides a new approach to help effectively screen high-risk individuals for depression.

The Current Situation of Anaesthesia for Hysteroscopy in Mainland China: A National Survey.

Purpose: The need for anaesthesia or analgesia for performing hysteroscopy remains debatable. This study aimed to conduct an overview of the situation of anaesthesia for hysteroscopy in mainland China. Methods: Two questionnaires were separately designed for anaesthesiologists and gynaecologists and distributed to every medical institution that performed hysteroscopic procedures on patients with infertility in mainland China. Electronic questionnaires were distributed via WeChat, and data on anaesthesia regimen, monitoring parameters, procedure number, and other information were collected. Results: Reproductive technology is conducted by 536 institutions in mainland China. The survey received 491 responses from anaesthetists (91.6%) and 436 from gynaecologists (81.3%). In 2021, 552,225 hysteroscopies were conducted in 268 medical centres. The average percentage of hysteroscopy under anaesthesia is 63.8% in 2021, wherein 47.3% of institutions have an anaesthesia percentage of >75%. Propofol and opioid analgesics, such as fentanyl and sufentanil, were the most commonly used intravenous anaesthetics. All sedations were performed by anaesthesiologists. Monitoring parameters included pulse oxygen saturation (98.9%), electrocardiogram (91.6%) and noninvasive blood pressure (91.3%). An anaesthesiologist-to-operating room ratio of <1 was observed in 31.3% of medical institutions. Surprisingly, 52.4% of medical institutions performing hysteroscopy had no postanaesthesia care unit (PACU). Most institutions with PACU were equipped with independent oxygen sources, suction and monitors. Both rigid and flexible hysteroscopes (rigid hysteroscope, 45.1%; flexible hysteroscope, 4.5%; both types, 50.4%) were used, and the hysteroscopic diameter was ≤5 mm in 60.3% of medical centres. Conclusions: China performs a large number of hysteroscopies, and sedation is the most frequently used anesthesia regimen. However, issues such as inadequate emergency support devices, insufficient personnel and weak resuscitation management after anaesthesia, have been observed.

Mitochondria-lysosome-related organelles mediate mitochondrial clearance during cellular dedifferentiation.

Dysfunctional mitochondria are removed via multiple pathways, such as mitophagy, a selective autophagy process. Here, we identify an intracellular hybrid mitochondria-lysosome organelle (termed the mitochondria-lysosome-related organelle [MLRO]), which regulates mitochondrial homeostasis independent of canonical mitophagy during hepatocyte dedifferentiation. The MLRO is an electron-dense organelle that has either a single or double membrane with both mitochondria and lysosome markers. Mechanistically, the MLRO is likely formed from the fusion of mitochondria-derived vesicles (MDVs) with lysosomes through a PARKIN-, ATG5-, and DRP1-independent process, which is negatively regulated by transcription factor EB (TFEB) and associated with mitochondrial protein degradation and hepatocyte dedifferentiation. The MLRO, which is galectin-3 positive, is reminiscent of damaged lysosome and could be cleared by overexpression of TFEB, resulting in attenuation of hepatocyte dedifferentiation. Together, results from this study suggest that the MLRO may act as an alternative mechanism for mitochondrial quality control independent of canonical autophagy/mitophagy involved in cell dedifferentiation.

ZNF500 abolishes breast cancer proliferation and sensitizes chemotherapy by stabilizing P53 via competing with MDM2.

Zinc finger protein 500 (ZNF500) has an unknown expression pattern and biological function in human tissues. Our study revealed that the ZNF500 mRNA and protein levels were higher in breast cancer tissues than those in their normal counterparts. However, ZNF500 expression was negatively correlated with advanced TNM stage (p = 0.018), positive lymph node metastasis (p = 0.014), and a poor prognosis (p < 0.001). ZNF500 overexpression abolished in vivo and in vitro breast cancer cell proliferation by activating the p53-p21-E2F4 signaling axis and directly interacting with p53 via its C2H2 domain. This may prevent ubiquitination of p53 in a manner that is competitive to MDM2, thus stabilizing p53. When ZNF500-∆C2H2 was overexpressed, the suppressed proliferation of breast cancer cells was neutralized in vitro and in vivo. In human breast cancer tissues, ZNF500 expression was positively correlated with p53 (p = 0.022) and E2F4 (p = 0.004) expression. ZNF500 expression was significantly lower in patients with Miller/Payne Grade 1-2 than in those with Miller/Payne Grade 3-5 (p = 0.012). ZNF500 suppresses breast cancer cell proliferation and sensitizes cells to chemotherapy.

Ufmylation on UFBP1 alleviates non-alcoholic fatty liver disease by modulating hepatic endoplasmic reticulum stress.

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease characterized by lipid accumulation and endoplasmic reticulum (ER) stress, while effective therapies targeting the specific characteristics of NAFLD are limited. Ufmylation is a newly found post-translational modification process that involves the attachment of the Ubiquitin-fold modifier 1 (UFM1) protein to its substrates via ufmylation modification system. Ufmylation regulates ER stress via modifying UFM1 binding protein 1 (UFBP1), suggesting a potential role for ufmylation in NAFLD pathogenesis. However, the precise role of ufmylation in NAFLD remains unclear. Herein, we aim to elucidate the impact of ufmylation on UFBP1 in NAFLD and explore the underlying mechanisms involved. We observed increased expression of UFM1-conjugated proteins and ufmylation modification system components in livers with steatosis derived from NAFLD patients and NAFLD models. Upregulation of ufmylation on hepatic proteins appeared to be an adaptive response to hepatic ER stress in NAFLD. In vitro, knocking down UFBP1 resulted in increased lipid accumulation and lipogenesis in hepatocytes treated with free fatty acids (FFA), which could be rescued by wild-type UFBP1 (WT UFBP1) but not by a mutant form of UFBP1 lacking the main ufmylation site lys267 (UFBP1 K267R). In vivo, ufmylation on UFBP1 ameliorated obesity, hepatic steatosis, hepatic lipogenesis, dyslipidemia, insulin resistance and liver damage in mice with NAFLD induced by a high fat diet (HFD). We also demonstrated that the downregulation of UFBP1 induced ER stress, whereas the reintroduction or overexpression of UFBP1 alleviated ER stress in a manner dependent on ufmylation in NAFLD. This mechanism could be responsible for the amelioration of aberrant hepatic lipogenesis and insulin resistance in NAFLD. Our data reveal a protective role of ufmylation on UFBP1 against NAFLD and offer a specific target for NAFLD treatment.

A new early warning method for mild cognitive impairment due to Alzheimer's disease based on dynamic evaluation of the "spatial executive process".

Objective: Mild cognitive impairment (MCI) due to Alzheimer's disease (AD), as an early stage of AD, is an important point for early warning of AD. Neuropathological studies have shown that AD pathology in pre-dementia patients involves the hippocampus and caudate nucleus, which are responsible for controlling cognitive mechanisms such as the spatial executive process (SEP). The aim of this study is to design a new method for early warning of MCI due to AD by dynamically evaluating SEP. Methods: We designed fingertip interaction handwriting digital evaluation paradigms and analyzed the dynamic trajectory of fingertip interaction and image data during "clock drawing" and "repetitive writing" tasks. Extracted fingertip interaction digital biomarkers were used to assess participants' SEP disorders, ultimately enabling intelligent diagnosis of MCI due to AD. A cross-sectional study demonstrated the predictive performance of this new method. Results: We enrolled 30 normal cognitive (NC) elderly and 30 MCI due to AD patients, and clinical research results showed that there may be neurobehavioral differences between the two groups in digital biomarkers captured during SEP. The early warning performance for MCI due to AD of this new method (areas under the curve (AUC) = 0.880) is better than that of the Minimum Mental State Examination (MMSE) neuropsychological scale (AUC = 0.856) assessed by physicians. Conclusion: Patients with MCI due to AD may have SEP disorders, and this new method based on dynamic evaluation of SEP will provide a novel human-computer interaction and intelligent early warning method for home and community screening of MCI due to AD.

Independent prognostic value of the congestion and renal index in patients with acute heart failure.

BACKGROUND: Clinical outcomes are poor if patients with acute heart failure (AHF) are discharged with residual congestion in the presence of renal dysfunction. However, there is no single indication to reflect the combined effects of the two related pathophysiological processes. We, therefore, proposed an indicator, congestion and renal index (CRI), and examined the associations between the CRI and one-year outcomes and the incremental prognostic value of CRI compared with the established scoring systems in a multicenter prospective cohort of AHF. METHODS: We enrolled AHF patients and calculated the ratio of thoracic fluid content index divided by estimated glomerular filtration rate before discharge, as CRI. Then we examined the associations between CRI and one-year outcomes. RESULTS: A total of 944 patients were included in the analysis (mean age 63.3 ± 13.8 years, 39.3% women). Compared with patients with CRI ≤ 0.59 mL/min per kΩ, those with CRI > 0.59 mL/min per kΩ had higher risks of cardiovascular death or HF hospitalization (HR = 1.56 [1.13-2.15]) and all-cause death or all-cause hospitalization (HR = 1.33 [1.01-1.74]). CRI had an incremental prognostic value compared with the established scoring system. CONCLUSIONS: In patients with AHF, CRI is independently associated with the risk of death or hospitalization within one year, and improves the risk stratification of the established risk models.

An automated method for stem diameter measurement based on laser module and deep learning.

BACKGROUND: Measuring stem diameter (SD) is a crucial foundation for forest resource management, but current methods require expert personnel and are time-consuming and costly. In this study, we proposed a novel device and method for automatic SD measurement using an image sensor and a laser module. Firstly, the laser module generated a spot on the tree stem that could be used as reference information for measuring SD. Secondly, an end-to-end model was performed to identify the trunk contour in the panchromatic image from the image sensor. Finally, SD was calculated from the linear relationship between the trunk contour and the spot diameter in pixels. RESULTS: We conducted SD measurements in three natural scenarios with different land cover types: transitional woodland/shrub, mixed forest, and green urban area. The SD values varied from 2.00 cm to 89.00 cm across these scenarios. Compared with the field tape measurements, the SD data measured by our method showed high consistency in different natural scenarios. The absolute mean error was 0.36 cm and the root mean square error was 0.45 cm. Our integrated device is low cost, portable, and without the assistance of a tripod. Compared to most studies, our method demonstrated better versatility and exhibited higher performance. CONCLUSION: Our method achieved the automatic, efficient and accurate measurement of SD in natural scenarios. In the future, the device will be further explored to be integrated into autonomous mobile robots for more scenarios.

The hidden inequality: the disparities in the quality of daily use masks associated with family economic status.

Wearing high-quality masks plays a critical role in reducing COVID-19 transmission. However, no study has investigated socioeconomic inequality in the quality of masks. Addressing this gap, this paper explored the relationships between mask's quality and family economic status. The cross-sectional survey was conducted in two Chinese universities by distributing structured questionnaires to assess participants' characteristics including family economic status, and meanwhile collecting their masks to evaluate the quality by measuring particle filtration efficiency. The valid responses were obtained from 912 students with mean age of 19.556 ± 1.453 years and were analyzed by using fractional or binary logistic regression. Three main findings were presented. First, inequality existed in the quality of masks. 36.07% of students were using unqualified masks with average filtration efficiency of 0.795 ± 0.119, which was much lower than China's national standard (0.9). Of those masks with identified production date, 11.43% were manufactured during COVID-19 outbreak when market was flooded with counterfeit production, and thus were of poor quality with average filtration efficiency of 0.819 ± 0.152. Second, better family economic status was associated with better masks' filtration efficiency and greater probability of using qualified masks. Third, students with better family economic status tend to use masks with individual packaging, and unique patterns and special designs, which may lead to inequality on a psychological level. Our analysis reveals the hidden socioeconomic inequality that exist behind cheap masks. In facing the challenges of future emerging infectious diseases, it is important to address the inequity to ensure equal access to affordable qualified personal protection equipment.

Concurrent Dual-Contrast Enhancement Using Fe3O4 Nanoparticles to Achieve a CEST Signal Controllability.

Traditional T2 magnetic resonance imaging (MRI) contrast agents have defects inherent to negative contrast agents, while chemical exchange saturation transfer (CEST) contrast agents can quantify substances at trace concentrations. After reaching a certain concentration, iron-based contrast agents can "shut down" CEST signals. The application range of T2 contrast agents can be widened through a combination of CEST and T2 contrast agents, which has promising application prospects. The purpose of this study is to develop a T2 MRI negative contrast agent with a controllable size and to explore the feasibility of dual contrast enhancement by combining T2 with CEST contrast agents. The study was carried out in vitro with HCT-116 human colon cancer cells. A GE SIGNA Pioneer 3.0 T medical MRI scanner was used to acquire CEST images with different saturation radio-frequency powers (1.25/2.5/3.75/5 µT) by 2D spin echo-echo planar imaging (SE-EPI). Magnetic resonance image compilation (MAGiC) was acquired by a multidynamic multiecho 2D fast spin-echo sequence. The feasibility of this dual-contrast enhancement method was assessed by scanning electron microscopy, transmission electron microscopy, Fourier transform infrared spectroscopy, dynamic light scattering, ζ potential analysis, inductively coupled plasma, X-ray photoelectron spectroscopy, X-ray powder diffraction, vibrating-sample magnetometry, MRI, and a Cell Counting Kit-8 assay. The association between the transverse relaxation rate r2 and the pH of the iron-based contrast agents was analyzed by linear fitting, and the linear relationship between the CEST effect in different B1 fields and pH was analyzed by the ratio method. Fe3O4 nanoparticles (NPs) with a mean particle size of 82.6 ± 22.4 nm were prepared by a classical process, and their surface was successfully modified with -OH active functional groups. They exhibited self-aggregation in an acidic environment. The CEST effect was enhanced as the B1 field increased, and an in vitro pH map was successfully plotted using the ratio method. Fe3O4 NPs could stably serve as reference agents at different pH values. At a concentration of 30 µg/mL, Fe3O4 NPs "shut down" the CEST signals, but when the concentration of Fe3O4 NPs was less than 10 µg/mL, the two contrast agents coexisted. The prepared Fe3O4 NPs had almost no toxicity, and when their concentration rose to 200 µg/mL at pH 6.5 or 7.4, they did not reach the half-maximum inhibitory concentration (IC50). Fe3O4 magnetic NPs with a controllable size and no toxicity were successfully synthesized. By combining Fe3O4 NPs with a CEST contrast agent, the two contrast agents could be imaged simultaneously; at higher concentrations, the iron-based contrast agent "shut down" the CEST signal. An in vitro pH map was successfully plotted by the ratio method. CEST signal inhibition can be used to realize the pH mapping of solid tumors and the identification of tumor active components, thus providing a new imaging method for tumor efficacy evaluation.