Gas-Liquid Interface Route to Hybrid Copper Bromine Perovskite Single-Crystal Membrane with Dielectric Transitions and Ferromagnetic Exchanges.

Single-crystal membranes (SCMs) show great promise in the fields of sensors, light-emitting diodes, and photodetection. However, the growth of a large-area single-crystal membranes is challenging. We report a new organic-inorganic SCMs [HCMA]2CuBr4 (HCMA = cyclohexanemethylamine) crystallized at the gas-liquid interface. It also has low-temperature ferromagnetic order, high-temperature dielectric anomalies, and narrow band gap indirect semiconductor properties. Specifically, the reversible phase transition of the compound occurs at 350/341 K on cooling/heating and exhibits dielectric anomalies and stable switching performance near the phase transition temperature. The ferromagnetic exchange interaction in the inorganic octahedra and the organic layer enables ferromagnetic ordering at low-temperature 10 K. Finally, the single crystal exhibits an indirect semiconducting property with a narrow band gap of 0.99 eV. Such rich multichannel physical properties make it a potential application in photodetection, information storage and sensors.

Manifold-based denoising for Ferumoxytol-enhanced 3D cardiac cine MRI.

The two-dimensional (2D) cine cardiovascular magnetic resonance (CMR) technique is the reference standard for assessing cardiac function. However, one challenge with 2D cine is that the acquisition time for the whole cine stack is long and requires multiple breath holds, which may not be feasible for pediatric or ill patients. Though single breath-hold multi-slice cine may address the issue, it can only acquire low-resolution images, and hence, affect the accuracy of cardiac function assessment. To address these challenges, a Ferumoxytol-enhanced, free breathing, isotropic high-resolution 3D cine technique was developed. The method produces high-contrast cine images with short acquisition times by using compressed sensing together with a manifold-based method for image denoising. This study included fifteen patients (9.1 $ \pm $ 5.6 yrs.) who were referred for clinical cardiovascular magnetic resonance imaging (MRI) with Ferumoxytol contrast and were prescribed the 3D cine sequence. The data was acquired on a 1.5T scanner. Statistical analysis shows that the manifold-based denoised 3D cine can accurately measure ventricular function with no significant differences when compared to the conventional 2D breath-hold (BH) cine. The multiplanar reconstructed images of the proposed 3D cine method are visually comparable to the golden standard 2D BH cine method in terms of clarity, contrast, and anatomical precision. The proposed method eliminated the need for breath holds, reduced scan times, enabled multiplanar reconstruction within an isotropic data set, and has the potential to be used as an effective tool to access cardiovascular conditions.

HPPO-Derived Meroterpenoids from the Marine-Derived Fungus Penicillium sp. SCSIO 41691.

Seven new 4-hydroxy-6-phenyl-2H-pyran-2-one (HPPO) derived meroterpenoids, 1-methyl-12a,12b-epoxyarisugacin M (1), 1-methyl-4a,12b-epoxyarisugacin M (2), 2,3-dihydroxy-3,4a-epoxy-12a-dehydroxyisoterreulactone A (3), 2-hydroxy-12a-dehydroxyisoterreulactone A (4), 3'-demethoxyterritrems B' (5), 4a-hydroxyarisugacin P (6), and 1-epi-arisugacin H (7), together with two known analogues (8 and 9), were isolated from the marine-derived fungal strain Penicillium sp. SCSIO 41691. Their structures were elucidated by spectroscopic methods, and the absolute configurations of compounds 1 and 3 were determined by single-crystal X-ray diffraction. Among them, 1 and 2 had a unique methyl migration in the basic meroterpenoid skeleton with a 12a,12b-epoxy or 4a,12b-epoxy group, and 3 was a highly oxygenated HPPO-derived meroterpenoid featuring a rare 6/5/6/6/6/6 hexacyclic system with a 3,4a-epoxy group. Biologically, 5 exhibited inhibitory activity against lipopolysaccharide-induced nitric oxide production in RAW 264.7 cells with an IC50 value of 21 µM, more potent than the positive control indomethacin.

Motion-resolved 3D Pulmonary MRI Reconstruction using Sinusoidal Representation Networks.

BACKGROUND: Deep learning reconstruction for free-breathing pulmonary MRI. OBJECTIVE: To propose a motion-resolved 3D pulmonary MRI reconstruction scheme using the sinusoidal representation network (SIREN). METHODS: The proposed scheme learns the registration maps using SIREN to register an averaging image to get the final reconstructions. The learning of the network relies only on the undersampled data from the specific subject. The usage of the network for outputting the registration maps enables a memory-efficient algorithm, as outputting registration maps instead of images only requires small networks. The training of the network based on only undersampled data enables an unsupervised learning scheme, which makes the proposed scheme useful in cases in which fully sampled data is not available. RESULTS: We compare the proposed SIREN-based motion-resolved reconstruction with two state-of-the-art methods for ten datasets. Both visual and quantitative comparison indicates the better performance of the proposed method. CONCLUSION: In conclusion, the use of SIREN for 3D pulmonary MRI reconstruction allows for the efficient and accurate reconstruction of data that has been undersampled.

Inflammation mediates the relationship between diet quality assessed by healthy eating index-2015 and metabolic syndrome.

Background: Metabolic syndrome is a cluster of metabolic disorders, including obesity, hypertension, hyperglycemia, and abnormal lipid levels. However, researches on the association between overall dietary quality measured by the Healthy Eating Index-2015 (HEI-2015) and the risk of metabolic syndrome is still lacking. Methods: This study utilized data from four cycles (2011-2018) of the National Health and Nutrition Examination Survey (NHANES) database, including 17,582 participants. Logistic regression analysis was employed to explore the correlation between HEI and the risk of metabolic syndrome. Additionally, mediation analysis was conducted to examine the effects of Systemic Immune-Inflammation Index (SII) and serum uric acid as potential mediators between HEI and metabolic syndrome risk. Weighted quantile sum (WQS) regression evaluated the composite exposure impact of the 13 components of the HEI on metabolic syndrome, as well as the proportion of their weights. Results: Higher dietary quality measured by HEI-2015 (at the 75th percentile) was negatively correlated with the risk of metabolic syndrome (OR=0.80, 95%CI=0.72-0.89, P=0.003). Higher SII and serum uric acid levels were identified as risk factors for metabolic syndrome (P for trend<0.001). Approximately 37.5% of the effect of HEI on metabolic syndrome occurrence was mediated by SII (Indirect effect=-0.002, 95%CI (-0.003,-0.001), Direct effect=-0.022, 95%CI (-0.0273,-0.015)). Additionally, 25% of the effect of HEI on metabolic syndrome occurrence was mediated by serum uric acid levels (Indirect effect=-0.006, 95%CI (-0.010,-0.012), Direct effect=-0.024, 95%CI (-0.041,-0.009)). WQS regression analysis revealed the highest weighted proportions for seafood and plant proteins (25.20%) and sodium (17.79%), while the weight for whole fruit was the lowest (0.25%). Conclusion: Better dietary quality measured by HEI-2015 was associated with a lower likelihood of metabolic syndrome. Higher SII and serum uric acid levels were identified as risk factors for metabolic syndrome and potential mediators.

Differential pathogenic and molecular features in neurological infection of SARS-CoV-2 Omicron BA.5.2 and BA.2.75 and Delta.

The Coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains a global threat, exacerbated by the emergence of viral variants. Two variants of SARS-CoV-2, Omicron BA.2.75 and BA.5, led to global infection peaks between May 2022 and May 2023, yet their precise characteristics in pathogenesis are not well understood. In this study, we compared these two Omicron sublineages with the previously dominant Delta variant using a human angiotensin-converting enzyme 2 knock-in mouse model. As expected, Delta exhibited higher viral replication in the lung and brain than both Omicron sublineages which induced less severe lung damage and immune activation. In contrast, the Omicron variants especially BA.5.2 showed a propensity for cellular proliferation and developmental pathways. Both Delta and BA.5.2 variants, but not BA.2.75, led to decreased pulmonary lymphocytes, indicating differential adaptive immune response. Neuroinvasiveness was shared with all strains, accompanied by vascular abnormalities, synaptic injury, and loss of astrocytes. However, Immunostaining assays and transcriptomic analysis showed that BA.5.2 displayed stronger immune suppression and neurodegeneration, while BA.2.75 exhibited more similar characteristics to Delta in the cortex. Such differentially infectious features could be partially attributed to the weakened interaction between Omicron Spike protein and host proteomes decoded via co-immunoprecipitation followed by mass spectrometry in neuronal cells. Our present study supports attenuated replication and pathogenicity of Omicron variants but also highlights their newly infectious characteristics in the lung and brain, especially with BA.5.2 demonstrating enhanced immune evasion and neural damage that could exacerbate neurological sequelae.

Epigallocatechin gallate prevents cardiomyocytes from pyroptosis through lncRNA MEG3/TAF15/AIM2 axis in myocardial infarction.

BACKGROUND: ( -)-Epigallocatechin-3-gallate (EGCG), a bioactive polyphenol isolated from green tea, has recently garnered attention for its potential protective role against acute myocardial infarction (MI) via inhibiting inflammation. Herein, we tested whether EGCG participates in modulating cardiac ischemia reperfusion-induced injury and elucidate its potential mechanisms. METHODS: To induce MI in mice, we employed coronary artery ligation, while cell models utilized oxygen glucose deprivation/re-oxygenation (OGD/R)-treated HL-1 cells. TTC, HE and Massion staining evaluated the pathological changes of heart tissues. Besides, RNA-pull down and RIP assays analyzed the interactions of MEG3/TAF15 and AIM2 mRNA/TAF15. FISH associated with immunofiuorescence (IF) double staining was conducted to measure the co-localization of MEG3 and TAF15. RESULTS: In vitro and in vivo evidence supported that EGCG treatment improved cardiomyocytes viability while inhibiting the expressions of AIM2, C-caspase-1, ASC, GSDMD-N, IL-18 and IL-1ß. Knockdown of MEG3 intensified EGCG's therapeutic effects both in vitro and in vivo. LncRNA MEG3 and AIM2 mRNA interacted with TAF15, and MEG3, in turn, promoted the stability of AIM2 mRNA through regulating TAF15. Overexpression of TAF15 reversed the promoting effect of EGCG and MEG3 knockdown on cell viability, and the inhibiting effect on cell pyroptosis. CONCLUSION: EGCG protected cardiomyocytes from pyroptosis by the MEG3/TAF15/AIM2 axis, indicating EGCG as a potential novel therapeutic strategy for managing MI.

Time-Resolved 3D cardiopulmonary MRI reconstruction using spatial transformer network.

The accurate visualization and assessment of the complex cardiac and pulmonary structures in 3D is critical for the diagnosis and treatment of cardiovascular and respiratory disorders. Conventional 3D cardiac magnetic resonance imaging (MRI) techniques suffer from long acquisition times, motion artifacts, and limited spatiotemporal resolution. This study proposes a novel time-resolved 3D cardiopulmonary MRI reconstruction method based on spatial transformer networks (STNs) to reconstruct the 3D cardiopulmonary MRI acquired using 3D center-out radial ultra-short echo time (UTE) sequences. The proposed reconstruction method employed an STN-based deep learning framework, which used a combination of data-processing, grid generator, and sampler. The reconstructed 3D images were compared against the start-of-the-art time-resolved reconstruction method. The results showed that the proposed time-resolved 3D cardiopulmonary MRI reconstruction using STNs offers a robust and efficient approach to obtain high-quality images. This method effectively overcomes the limitations of conventional 3D cardiac MRI techniques and has the potential to improve the diagnosis and treatment planning of cardiopulmonary disorders.

Zero-dimensional organic-inorganic hybrid manganese bromide with coexistence of dielectric-thermal double switches and efficient photoluminescence.

Zero-dimensional (0D) hybrid metal halides have attracted much attention due to their rich composition, excellent optical stability, large exciton binding energy, etc. Photoelectric switchable multifunctional materials can integrate multiple physical properties (e.g., ferroelectricity, photoluminescence, magnetic, etc.) into one device and are widely used in many fields such as smart switches, sensors, etc. However, multifunctional materials with thermal energy storage, stimulant dielectric response, and light-emitting properties are rarely reported. Here, we synthesized a new organic-inorganic hybrid metal halide single crystal [TEMA]2MnBr4 (1) (TEMA+ = triethylmethylammonium). Compound 1 undergoes a reversible phase transition at a high temperature of 344/316 K, having a large thermal hysteresis of 28 K and exhibits high stability dielectric switching characteristics near the phase transition temperature. The single crystal exhibits green emission at 513 nm under UV excitation, originating from the 4T1g(G) → 6A1g(S) transition of Mn2+ ions. Excitingly, this single crystal's photoluminescence quantum yield (PLQY) is as high as 80.78%. This work provides a strategy for the development of organic-inorganic hybrid optoelectronic multifunctional materials with high-efficient light emission and switchable dielectric properties.

Preparation of chitosan/retinoic acid @ nanocapsules/TiO2 self-cleaning one-dimensional photonic crystals and the study of the visual detection of acute promyelocytic leukemia.

Sample exposure to air during optical detection leads to the widespread dispersal of microorganisms in the air, posing a health threat to patients and healthcare workers and potentially causing numerous nosocomial infections. In this study, a TiO2/CS-nanocapsules-Va visualization sensor was developed by alternatively spin-coating TiO2, CS and nanocapsules-Va. The uniformly distributed TiO2 can endow the visualization sensor with good photocatalytic performance, and the nanocapsules-Va can bind specifically to the antigen and change its volume. The research results showed that the visualization sensor cannot only detect acute promyelocytic leukemia conveniently, quickly and accurately, but also kill bacteria, decompose organic residues in blood samples under the influence of sunlight, and have an extensive application prospect in substance detection and disease diagnosis.

Circulating tumor cells dynamics during chemotherapy predict survival and response in advanced non-small-cell lung cancer patients.

Background: Circulating tumor cells (CTCs) are prognostic biomarker in non-small-cell lung cancer (NSCLC). CTCs could also be used as predictor of efficacy of systemic treatments in advanced NSCLC. Objectives: We described the dynamic changes of CTCs during first-line platinum-based chemotherapy in advanced NSCLC and clarified the correlation between CTC counts and efficacy of chemotherapy. Design: Chemotherapy is administered and blood specimens are collected at four time points from baseline to disease progression for CTC detection. Methods: This multicenter prospective study enrolled patients with previously untreated stage III or IV NSCLC fit for standard platinum-based chemotherapy. Bloods were sampled as per standard operating procedures at baseline, cycle 1 and cycle 4 of chemotherapy, and at disease progression for CTC analysis using the CellSearch system. Results: Among 150 patients enrolled, median overall survival (OS) was 13.8, 8.4, and 7.9 months in patients with CTC-, KIT-CTC, and KIT+CTC at baseline (p = 0.002). Patients with persistent negative CTC (46.0%) had longer progression-free survival [5.7 months, 95% confidence interval (CI): 5.0-6.5 versus 3.0 months, 0.6-5.4; hazard ratio (HR): 0.34, 95% CI: 0.18-0.67) and OS (13.1 months, 10.9-15.3 versus 5.6 months, 4.1-7.1; HR: 0.17, 0.08-0.36) compared with patients with persistent positive CTC (10.7%), which was not impacted by chemotherapy. Chemotherapy decreased CTC from 36.0% (54/150) to 13.7% (13/95). Conclusions: CTC persistent presence during treatment represents poor prognosis and resistance to chemotherapy in advanced NSCLC. Chemotherapy could effectively eliminate CTCs. Molecular characterization and the functionalization of CTC will be warranted for further intensive investigation. Trial registration: NCT01740804.

Comparison and Optimization of Cardiovascular Risk Scores in Predicting the 4-Year Outcome of Patients with Obstructive Coronary Arteries Disease.

Objective: How well cardiovascular risk models perform in selected atherosclerosis patients for predicting outcomes is unknown. We sought to compare the performance of cardiovascular risk models (Framingham, Globorisk, SCORE2 & SCORE2-OP, and an updated new model) in predicting the 4-year outcome of patients with obstructive coronary artery disease (CAD). Methods: Patients with suspected CAD who underwent coronary computed tomography angiography (CCTA) were recruited. Obstructive CAD was defined from CCTA as ≥ 50% stenosis. Computed tomography images, the scores of the cardiovascular risk models, and 4-year composite endpoints were assessed. Whether the patients underwent revascularization within 60 days after CCTA was also recorded. Multivariate regression analysis and receiver operating characteristics (ROC) curve analysis were performed. Results: A total of 95 patients (mean age: 69.5 ± 10.33 years; 69 males) with obstructive CAD were included in this study. After the ROC analysis, the Framingham, Globorisk, SCORE2 & SCORE2-OP risk score showed prediction values with AUC 0.628 (95% CI: 0.532-0.725), 0.647 (95% CI: 0.542-0.742), 0.684 (95% CI: 0.581-0.776), respectively. Multivariate regression analysis showed that, among the three risk models, only SCORE2 & SCORE2-OP risk score was associated with composite endpoints (hazard ratio: 1.050; 95% CI: 1.021-1.079; p = 0.001) after adjusting for confounding factors. The AUC of the new risk model by combing SCORE2 & SCORE2-OP risk score with revascularization and the number of obstructive vessels in predicting composite endpoints reached 0.898 (95% CI: 0.819-0.951). Conclusion: The SCORE2 & SCORE2-OP risk score combined with the number of obstructive vessels and revascularization is predictive for adverse outcomes in patients with obstructive CAD.

Joint Cardiac T1 Mapping and Cardiac Cine Using Manifold Modeling.

The main focus of this work is to introduce a single free-breathing and ungated imaging protocol to jointly estimate cardiac function and myocardial T1 maps. We reconstruct a time series of images corresponding to k-space data from a free-breathing and ungated inversion recovery gradient echo sequence using a manifold algorithm. We model each image in the time series as a non-linear function of three variables: cardiac and respiratory phases and inversion time. The non-linear function is realized using a convolutional neural networks (CNN) generator, while the CNN parameters, as well as the phase information, are estimated from the measured k-t space data. We use a dense conditional auto-encoder to estimate the cardiac and respiratory phases from the central multi-channel k-space samples acquired at each frame. The latent vectors of the auto-encoder are constrained to be bandlimited functions with appropriate frequency bands, which enables the disentanglement of the latent vectors into cardiac and respiratory phases, even when the data are acquired with intermittent inversion pulses. Once the phases are estimated, we pose the image recovery as the learning of the parameters of the CNN generator from the measured k-t space data. The learned CNN generator is used to generate synthetic data on demand by feeding it with appropriate latent vectors. The proposed approach capitalizes on the synergies between cine MRI and T1 mapping to reduce the scan time and improve patient comfort. The framework also enables the generation of synthetic breath-held cine movies with different inversion contrasts, which improves the visualization of the myocardium. In addition, the approach also enables the estimation of the T1 maps with specific phases, which is challenging with breath-held approaches.

Effect of transcranial direct current stimulation on postpartum depression: A study protocol for a randomized controlled trial.

Postpartum depression (PPD) is a complex combination of physiological, emotional, and behavioral alterations associated with postpartum chemical, social, and psychological variations. It does harm to the relationship between family members that could potentially last for years. However, standard depression treatments are not ideal for PPD, and the outcomes of these treatments are debatable. Transcranial direct current stimulation (tDCS) is an emerging technology that could provide patients with PPD with a safe and non-pharmacological treatment. tDCS can relieve depression by directly stimulating the prefrontal cortex through the excitatory effect of the anode. It may also ease depression indirectly by promoting the production and release of the neurotransmitter GABA. The mechanism of tDCS makes it an ideal therapeutic approach to treat PPD, although it has not been widely used, and its effect has not been evaluated systematically and effectively. A double-blind, randomized controlled trial will be conducted involving 240 tDCS-naive patients with PPD, who will be randomly divided into two groups. One group will receive routine clinical treatment and care with active tDCS, and the other group will receive routine clinical treatment and care with sham tDCS. Each group of patients will receive a 3-week intervention during which they will receive 20 min of active or sham tDCS 6 days per week. The Montgomery-Åsberg Depression Rating Scale will be administered before the intervention as a baseline and on each weekend throughout the intervention phase. Before and after the intervention, the Perceived Stress Scale and the Positive and Negative Affect Schedule will be evaluated. Side effects and abnormal reactions will be recorded during each treatment. As antidepressants are banned in the study, the results will not be affected by drugs and will therefore be more accurate. Nonetheless, this experiment will be conducted in a single center as a small sample experiment. Therefore, future studies are required to confirm the effectiveness of tDCS in treating PPD.

Non-suicidal self-injury: A bibliometrics study and visualization analysis from 2002 to 2022.

Objective: To overview the research actuality and offer the hotspots and cutting-edge issues in the field of Non-suicidal Self-injury (NSSI) by using bibliometric analysis. Materials and methods: Publications related to NSSI from 2002 to 2022 were extracted from the Web of Science Core Collection (WoSCC) database. CiteSpace V 6.1.R2 and VOSviewer 1.6.18 were used to visually analyzed institutions, countries, journals, authors, references, and keywords in research on NSSI. Results: A total of 799 studies about NSSI were analyzed via CiteSpace and VOSviewer. The number of annual publications related to NSSI is fluctuating growth. The USA and Harvard University are the most productive country and institutions. In the case of journals and co-cited journals, Psychiatry Research are the most productive journal and also ranked highest among co-cited journals. Furthermore, Michael Kaess has published the most publications, and Matthew K. Nock is the most cited author. An article published by Swannell SV et al. shows the highest citation counts. After analysis, the most common keywords are harm, adolescents and prevalence. The gender difference, diagnosis, and dysregulation are frontier areas of NSSI research. Conclusion: This study analyzed the research of NSSI from multiple perspectives, and provides valuable information for researchers to capture the current status, hot spots, and frontier trends of NSSI.

Novel Indole-Containing Hybrids Derived from Millepachine: Synthesis, Biological Evaluation and Antitumor Mechanism Study.

Millepachine, a bioactive natural product isolated from the seeds of Millettia pachycarpa, is reported to display potential antitumor activity. In this study, novel indole-containing hybrids derived from millepachine were designed, synthesized and evaluated for their antitumor activities. Among all the compounds, compound 14b exhibited the most potent cytotoxic activity against five kinds of human cancer cell lines, with IC50 values ranging from 0.022 to 0.074 µM, making it almost 100 times more active than millepachine. Valuable structure-activity relationships (SARs) were obtained. Furthermore, the mechanism studies showed that compound 14b induced cell-cycle arrest at the G2/M phase by inhibiting tubulin polymerization and further induced cell apoptosis through reactive oxygen species (ROS) accumulation and mitochondrial membrane potential (MMP) collapse. In addition, the low cytotoxicity toward normal human cells and equivalent sensitivity towards drug-resistant cells of compound 14b highlighted its potential for the development of antitumor drugs.

ADAMTS7-Mediated Complement Factor H Degradation Potentiates Complement Activation to Contributing to Renal Injuries.

BACKGROUND: The dysfunction of complement factor H (CFH), the main soluble complement negative regulator, potentiates various complement-induced renal injuries. However, insights into the underlying mechanism of CFH dysfunction remain limited. In this study, we investigated whether extracellular protease-mediated degradation accounts for CFH dysfunction in complement-mediated renal injuries. METHODS: An unbiased interactome of lupus mice kidneys identified CFH-binding protease. In vitro cleavage assay clarified CFH degradation. Pristane-induced SLE or renal ischemia-reperfusion (I/R) injury models were used in wild-type and ADAMTS7-/- mice. RESULTS: We identified the metalloprotease ADAMTS7 as a CFH-binding protein in lupus kidneys. Moreover, the upregulation of ADAMTS7 correlated with CFH reduction in both lupus mice and patients. Mechanistically, ADAMTS7 is directly bound to CFH complement control protein (CCP) 1-4 domain and degraded CCP 1-7 domain through multiple cleavages. In mice with lupus nephritis or renal I/R injury, ADAMTS7 deficiency alleviated complement activation and related renal pathologies, but without affecting complement-mediated bactericidal activity. Adeno-associated virus-mediated CFH silencing compromised these protective effects of ADAMTS7 knockout against complement-mediated renal injuries in vivo. CONCLUSION: ADAMTS7-mediated CFH degradation potentiates complement activation and related renal injuries. ADAMTS7 would be a promising anticomplement therapeutic target that does not increase bacterial infection risk.

Exploring the Association between Oxygen Concentration and Life Expectancy in China: A Quantitative Analysis.

The aim of this study was to investigate and quantify the association between oxygen concentration and life expectancy. The data from 34 provinces and 39 municipalities were included in all analyses. Bayesian regression modeling with spatial-specific random effects was used to quantify the impact of oxygen concentration (measured as partial pressure of oxygen) on life expectancy, adjusting for other potential confounding factors. We used hierarchical cluster analysis to group the provinces according to disease burden and analyzed the oxygen levels and the characteristics of causes of death between the clusters. The Bayesian regression analysis showed that the life expectancy at the provincial level increased by 0.15 (95% CI: 0.10-0.19) years, while at the municipal level, it increased by 0.17 (95% CI: 0.12-0.22) years, with each additional unit (mmHg) of oxygen concentration, after controlling for potential confounding factors. Three clusters were identified in the hierarchical cluster analysis, which were characterized by different oxygen concentrations, and the years of life lost from causes potentially related to hypoxia were statistically significantly different between the clusters. A positive correlation was found between oxygen concentration and life expectancy in China. The differences in causes of death and oxygen levels in the provincial clusters suggested that oxygen concentration may be an important factor in life expectancy when mediated by diseases that are potentially related to hypoxia.

miR-138-5p inhibits the progression of colorectal cancer via regulating SP1/LGR5 axis.

Colorectal cancer (CRC) is one of the main malignancies that seriously threaten human health. Considering the high mortality and morbidity associated with this disease, even surgical resection and chemotherapy may not be sufficient in certain cases. This study aimed to explore the molecular mechanisms of miR-138-5p in regulating CRC progression. Quantitative reverse transcriptase polymerase chain reaction and western blot were performed to assess the levels of mRNA and proteins, including miR-138-5p, leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5), SP1, ß-catenin, cyclin D1, and c-myc. The bioactivities of LoVo and HCT116 cells were assessed via MTT assay, flow cytometry, and transwell assay. StarBase was used to identify the downstream targets of genes. Double luciferase reporter and RIP assays revealed the direct binding of miR-138-5p to SP1 and of SP1 to LGR5. Our results illustrated that miR-138-5p was downregulated in CRC and its knockdown accelerated CRC progression. Conversely, SP1 was upregulated in CRC and its knockdown inhibited CRC progression. SP1 is also targeted by miR-138-5p and binds to LGR5. This study showed that miR-138-5p inhibits LoVo and HCT116 cell proliferation, migration, and invasion. Overall, miR-138-5p regulates CRC progression and promotes apoptosis via the SP1/LGR5 axis. This study indicates that miR-138-5p is involved in regulating CRC progression.