The mediating role of systemic inflammation in the association between bedroom light at night and new-onset depressive symptoms among Chinese young adults: A prospective cohort study.

BACKGROUND: The detrimental effects of exposure to light at night (LAN) have received increasing attention. However, the effects of LAN exposure on depressive symptoms and underlying mechanism are less explored. OBJECTIVES: To investigate the association between LAN exposure with new-onset and trajectories of depressive symptoms, and the potential mediating role of systemic inflammation. METHODS: Baseline bedroom LAN exposure was monitored every minute for 2 consecutive nights using a portable illuminance meter. Fasting blood samples were collected at the 1-year follow-up to determine high sensitivity C-reactive protein (hs-CRP). Depressive symptoms were assessed at baseline, 1- and 2-year follow-up using the Mood and Feelings Questionnaire (MFQ). RESULTS: At baseline, the mean age of the 347 participants was 18.7 ± 0.8 years, and 35.2 % were men. At 2-year follow-up, the new-onset depressive symptoms were 14.7 %. Compared with low-LANavg (average light intensity from bedtime to rising time) intensity group (LANavg < 3 lx), those with high-LANavg intensity (LANavg ≥ 3 lx) were associated with an 125 % increase in risk for depressive symptoms (HR = 2.25; 95 % CI: 1.27, 4.00); Compared with short-LAN5 (duration of nighttime light intensity ≥5 lx) duration group (LAN5 < 45 min), those with long-LAN5 duration (LAN5 ≥ 45 min) were associated with an 119 % increase in risk for depressive symptoms (HR = 2.19; 95 % CI: 1.18, 4.06). Participants were classified into 3 trajectory groups: consistently low, slow or rapid increase depressive symptoms; both intensity and duration of LAN exposure were associated with higher likelihood of slow or rapid increase depressive symptoms. Additionally, hs-CRP partially mediated the relationship between intensity (mediation proportion: 7.1 %) and duration (mediation proportion: 10.6 %) of LAN exposure with depressive symptoms. CONCLUSION: Excessive bedroom LAN exposure is associated with increased risk of depressive symptoms among young adults, and systemic inflammation may be a partial mediator in the LAN-depressive symptoms association.

Isolicoflavonol ameliorates acute liver injury via inhibiting NLRP3 inflammasome activation through boosting Nrf2 signaling in vitro and in vivo.

BACKGROUND: NOD like receptor pyrin domain containing 3 (NLRP3) inflammasome is involved in innate immunity, and related to liver injury. However, no inflammasome inhibitors are clinically available until now. Our previous research suggests that isolicoflavonol (ILF), isolated from Macaranga indica, is a potent NLRP3 inflammasome inhibitor, but its mechanism is unclear. METHODS: Fluorescent imaging and Western blot assay were used to ascertain the effects of ILF on pyroptosis and NLRP3 inflammasome activation in macrophages. Next, Nrf2 signal pathway, its downstream gene transcription and expression were further investigated. ML385, a Nrf2 inhibitor, was used to verify whether ILF targets Nrf2 signaling. A carbon tetrachloride induced liver injury model was introduced to evaluate the liver protection activity of ILF in mice. RESULTS: This work revealed that ILF inhibited macrophage LDH release and IL-1ß secretion in a dose-dependent manner. ILF had no significant cytotoxic effect on macrophage, it reduced pyroptosis and Gasdermin D N-terminal fragment formation. Moreover, ILF inhibited IL-1ß maturation and Caspase-1 cleavage, but did not affect NLRP3, pro-Caspase-1, pro-IL-1ß and ASC expression. ILF decreased ASC speck rate and reduced ASC oligomer formation. ILF decreased aggregated JC-1 formation restoring mitochondria membrane potential. In addition, ILF increased Nrf2 expression, extended Nrf2 lifespan and upregulated Nrf2 signaling pathway in macrophages whether the NLRP3 inflammasome was activated or not. Besides, ILF increased Nrf2 nuclear translocation, maintained a high proportion of Nrf2 in the nucleus, and upregulated ARE-related gene transcription and expression. Furthermore, Nrf2 signal inhibition attenuated compound ILF-mediated inhibition of pyroptosis, inflammasome activation and upregulation of Nrf2 signaling. ILF in a liver injury mouse model inhibited NLRP3 inflammasome activation and enhanced Nrf2 signaling. CONCLUSION: Our study verified that ILF ameliorates liver injury via inhibiting NLRP3 inflammasome activation through boosting Nrf2 signaling, and highlighted that ILF is a potent anti-inflammatory drug for inflammasome-related liver diseases.

Lifestyle-specific association between adversity dimensions with group-based mental health trajectories.

BACKGROUND: Childhood adversity (CA) has a substantial correlation with mental health problems. Keeping a healthy lifestyle is essential for mental health interventions; it is unclear, however, how healthy lifestyle affect the relationship between CA and persistent mental health problems. METHODS: This longitudinal study (n = 1112, 54.5 % male) collected the data on CA (measured through three dimensions: threat, deprivation and unpredictability), mental health problems, and lifestyle factors. Group-based multi-trajectory modeling (GBMTM) was utilized to estimate trajectories for three mental health problems (i.e., depression, ADHD and overanxiety). Close friendships, regular physical activity, appropriate sleep duration, shorter screen time, and healthy eating were combined to establish a healthy lifestyle score (which ranges from 0 to 5). Higher scores indicated a healthier lifestyle. RESULTS: Three trajectories of mental health problems were identified: persistently low risk (24.9 %), persistently medium-high risk (50.0 %), and persistently high risk (25.1 %). Multinomial logistic regression showed that high adversity (high-threat: ß = 2.01, P < 0.001; high-deprivation: ß = 1.03, P < 0.001; high-unpredictability: ß = 0.83, P = 0.001; high-overall adversity: ß = 1.64, P < 0.001) resulted in a persistently high risk of mental health problems; these outcomes were maintained after robust control for covariates. Further lifestyle stratification, null associations were observed among children with a healthy lifestyle, irrespective of their gender; however, after controlling for covariates, the above associations remained relatively stable only among boys. LIMITATIONS: The generalizability of our findings is restricted by 1) limited racial diversity and 2) missing data. CONCLUSIONS: This finding underscores the benefits of promoting a healthy lifestyle in children to prevent persistent mental health problems caused by CA.

Nuclear NME1 enhances the malignant behavior of A549 cells and impacts lung adenocarcinoma patient prognosis.

NME1 is a metastatic suppressor inconsistently reported to have multiple roles as both a promoter and inhibitor of cancer metastasis. Nevertheless, the specific mechanism behind these results is still unclear. We observed that A549 cells with stable transfer of NME1 into the nucleus (A549-nNm23-H1) exhibited significantly increased migration and invasion activity compared to vector control cells, which was further enhanced by over-expressing CYP24A1 (p < 0.001). NME1 demonstrated the ability to safely attach to and amplify the transcription activation of JUN, consequently leading to the up-regulation of CYP24A1. Analysis of clinical data showed a positive relationship between nuclear NME1 levels and CYP24A1 expression. Furthermore, they were positively associated with postoperative distant metastasis and negatively correlated with prognosis in those with early stage lung adenocarcinoma. In conclusion, the data presented provides a new understanding of the probable pathways by which nuclear NME1 facilitates tumor metastasis, establishing the groundwork for future prediction and treatment of tumor metastasis.

High-throughput single-molecule long-read RNA sequencing analysis of tissue-specific genes and isoforms in lettuce (Lactuca sativa L.).

Lettuce is one of the most widely cultivated and consumed dicotyledonous vegetables globally. Despite the availability of its reference genome sequence, lettuce gene annotation remains incomplete, impeding comprehensive research and the broad application of genomic resources. Long-read RNA isoform sequencing (Iso-Seq) offers substantial advantages for analyzing RNA alternative splicing and aiding gene annotation, yet it faces throughput limitations. We present the HIT-ISOseq method tailored for bulk sample analysis, significantly enhancing RNA sequencing throughput on the PacBio platform by concatenating cDNA. Here we show, HIT-ISOseq generates 3-4 cDNA molecules per CCS read in lettuce, yielding 15.7 million long reads per PacBio Sequel II SMRT Cell 8 M. We validate its effectiveness in analyzing six lettuce tissue samples, including roots, stems, and leaves, revealing tissue-specific gene expression patterns and RNA isoforms. Leveraging diverse tissue long-read RNA sequencing, we refine the transcript annotation of the lettuce reference genome, expanding its GO and KEGG annotation repertoire. Collectively, this study serves as a foundational reference for genome annotation and the analysis of multi-sample isoform expression, utilizing high-throughput long-read transcriptome sequencing.

Study on the Prediction of Liver Injury in Acute Pancreatitis Patients by Radiomic Model Based on Contrast-Enhanced Computed Tomography.

OBJECTIVES: to predict liver injury in acute pancreatitis (AP) patients by establishing a radiomics model based on contrast-enhanced computed tomography (CECT). METHODS: a total of 1223 radiomic features were extracted from late arterial-phase pancreatic CECT images of 209 AP patients (146 in the training cohort and 63 in the test cohort), and the optimal radiomic features retained after dimensionality reduction by least absolute shrinkage and selection operator (LASSO) were used to construct a radiomic model through logistic regression analysis. In addition, clinical features were collected to develop a clinical model, and a joint model was established by combining the best radiomic features and clinical features to evaluate the practicality and application value of the radiomic models, clinical model and combined model. RESULTS: four potential features were selected from the pancreatic parenchyma to construct the radiomic model, and the area under the receiver operating characteristic curve (AUC) of the radiomic model was significantly greater than that of the clinical model for both the training cohort (0.993 vs. 0.653, p = 0.000) and test cohort (0.910 vs. 0.574, p = 0.000). The joint model had a greater AUC than the radiomics model for both the training cohort (0.997 vs. 0.993, p = 0.357) and test cohort (0.925 vs. 0.910, p = 0.302). CONCLUSIONS: the radiomic model based on CECT has good performance in predicting liver injury in AP patients and can guide clinical decision-making and improve the prognosis of patients with AP.

Altered executive control network and default model network topology are linked to acute electronic cigarette use: A resting-state fNIRS study.

In recent years, electronic cigarettes (e-cigs) have gained popularity as stylish, safe, and effective smoking cessation aids, leading to widespread consumer acceptance. Although previous research has explored the acute effects of combustible cigarettes or nicotine replacement therapy on brain functional activities, studies on e-cigs have been limited. Using fNIRS, we conducted graph theory analysis on the resting-state functional connectivity of 61 male abstinent smokers both before and after vaping e-cigs. And we performed Pearson correlation analysis to investigate the relationship between alterations in network metrics and changes in craving. E-cig use resulted in increased degree centrality, nodal efficiency, and local efficiency within the executive control network (ECN), while causing a decrease in these properties within the default model network (DMN). These alterations were found to be correlated with reductions in craving, indicating a relationship between differing network topologies in the ECN and DMN and decreased craving. These findings suggest that the impact of e-cig usage on network topologies observed in male smokers resembles the effects observed with traditional cigarettes and other forms of nicotine delivery, providing valuable insights into their addictive potential and effectiveness as aids for smoking cessation.

Aerodynamic Simulation of Small Airway Resistance: A New Imaging Biomarker for Chronic Obstructive Pulmonary Disease.

Purpose: To develop a novel method for calculating small airway resistance using computational fluid dynamics (CFD) based on CT data and evaluate its value to identify COPD. Patients and Methods: 24 subjects who underwent chest CT scans and pulmonary function tests between August 2020 and December 2020 were enrolled retrospectively. Subjects were divided into three groups: normal (10), high-risk (6), and COPD (8). The airway from the trachea down to the sixth generation of bronchioles was reconstructed by a 3D slicer. The small airway resistance (RSA) and RSA as a percentage of total airway resistance (RSA%) were calculated by CFD combined with airway resistance and FEV1 measured by pulmonary function test. A correlation analysis was conducted between RSA and pulmonary function parameters, including FEV1/FVC, FEV1% predicted, MEF50% predicted, MEF75% predicted and MMEF75/25% predicted. Results: The RSA and RSA% were significantly different among the three groups (p<0.05) and related to FEV1/FVC (r = -0.70, p < 0.001; r = -0.67, p < 0.001), FEV1% predicted (r = -0.60, p = 0.002; r = -0.57, p = 0.004), MEF50% predicted (r = -0.64, p = 0.001; r = -0.64, p = 0.001), MEF75% predicted (r = -0.71, p < 0.001; r = -0.60, p = 0.002) and MMEF 75/25% predicted (r = -0.64, p = 0.001; r = -0.64, p = 0.001). Conclusion: Airway CFD is a valuable method for estimating the small airway resistance, where the derived RSA will aid in the early diagnosis of COPD.

Real-ambient bedroom light at night increases systemic inflammation and disrupts circadian rhythm of inflammatory markers.

BACKGROUND: Exposure to light at night (LAN) has been associated with multiple adverse health outcomes. However, evidence is limited regarding the impacts of LAN exposure on human inflammation. OBJECTIVES: To examine the association between real-ambient bedroom LAN exposure with systemic inflammation and circadian rhythm of inflammatory markers. METHODS: Using data from a prospective cohort study of Chinese young adults. At baseline, bedroom LAN exposure was measured with a portable illuminance meter; fasting blood sample for high-sensitivity C-reactive protein (hs-CRP) assay was collected. At 3-year follow-up, 20 healthy young adults (10 LANavg < 5 lx, 10 LANavg ≥ 5 lx) were recruited from the same cohort; time-series venous blood samples were sampled every 4 h over a 24 h-cycle for the detection of 8 inflammatory markers. Circadian rhythm of inflammatory markers was assessed using cosinor analysis. RESULTS: At baseline, the average age of the 276 participants was 18.7 years, and 33.3 % were male. Higher levels of bedroom LAN exposure were significantly associated with increased hs-CRP levels. The association between bedroom LAN exposure and systemic inflammation was only significant in the inactive group (MVPA < 2 h/d) but not in the physically active group (MVPA ≥ 2 h/d). In addition, exposure to higher levels of nighttime light (LANavg ≥ 5 lx) disrupted circadian rhythms (including rhythmic expression, circadian amplitude and circadian phase) of some inflammatory cytokines and inflammatory balance indicators. CONCLUSION: Exposure to bedroom nighttime light increases systemic inflammation and disrupts circadian rhythm of inflammatory markers. Keep bedroom darkness at night may represent important strategies for the prevention of chronic inflammation. Additionally, for people living a community with higher nighttime light pollution, regular physical activity may be a viable option to counteract the negative impacts of LAN exposure on chronic inflammation.

Association of sleep fragmentation with general and abdominal obesity: a population-based longitudinal study.

OBJECTIVE: To evaluate the causal relationship between sleep fragmentation (SF) parameters with general and abdominal obesity in free-living conditions. METHODS: SF parameters were assessed by ActiGraph accelerometers for 7 consecutive days. Obesity was measured at baseline and 1-year follow-up with InBody S10 body composition analyzer. RESULTS: At baseline, the mean age of the study population was 18.7 years old (SD = 0.9) and 139 (35.7%) were male. Each 1-unit increase of baseline sleep fragmentation index (SFI) was associated with 0.08 kg/m2-increase of body mass index (BMI) (95% CI: 0.03, 0.14), 0.20%-increase of percentage of body fat (PBF) (95% CI: 0.07, 0.32), 0.15 kg-increase of fat mass (FM) (95% CI: 0.03, 0.27), 0.15 cm-increase of waist circumference (WC) (95% CI: 0.03, 0.26) and 0.91 cm2-increase of visceral fat area (VFA) (95% CI: 0.36, 1.46) at the 1-year follow-up. In addition, each 1-unit increase of baseline SFI was associated with 15% increased risk of general obesity (OR = 1.15, 95% CI = 1.04-1.28; p = 0.006) and 7% increased risk of abdominal obesity (OR = 1.07, 95% CI = 1.01-1.13; p = 0.021) in the following year. CONCLUSIONS: Fragmented sleep is independently associated with an increased risk of both general and abdominal obesity. The result highlights SF as a modifiable risk factor for the prevention and treatment of obesity.

Enhancing polycyclic aromatic hydrocarbon soil remediation in cold climates using immobilized low-temperature-resistant mixed microorganisms.

Polycyclic aromatic hydrocarbons (PAHs), widespread organic pollutants, significantly impact human health and environmental integrity. Recent approaches to ameliorate PAH-contaminated soils, particularly in cold environments, have been insufficient. This study investigates the use of immobilized low-temperature-resistant mixed microorganisms (LTRMM) for enhancing the degradation of PAHs in soils from coke plants and the Shenfu irrigation area. Our results demonstrate that treatment with immobilized mixed microorganisms (MC-HS) is more effective than treatments with free bacteria (H-S) and control (CK). Specifically, the degradation rates in the MC-HS1 treatment were 10.10 %-41.13 % higher than those in the coking plant soil treated with CK1 and H-S1. Similarly, in the Shenfu irrigation area soil, MC-HS2 showed improvements of 6.00 % to 52.56 % over CK2 and H-S2. A kinetic model was used to analyze the enhanced degradation capabilities, revealing that the half-life of PAHs under the immobilized mixed microorganism treatment (T3) was significantly shorter compared to the free bacteria (T2) and control treatments (T1). These findings suggest that employing immobilized LTRMM could significantly improve the remediation efficiency of PAH-contaminated soils in cold climates.

[Status of outcome measures in randomized controlled trials of kidney-tonifying and blood-activating method in treatment of knee osteoarthritis].

This study assesses the status of outcome measures in the randomized controlled trial(RCT) involving the kidney-tonif-ying and blood-activating method for treating knee osteoarthritis(KOA), aiming to establish a theoretical foundation for the development of a core set of outcome measures in traditional Chinese medicine(TCM) treatment of KOA. The relevant articles were retrieved from CNKI, Wanfang, VIP, SinoMed, PubMed, EMbase, Cochrane Library, and Web of Science, in addition to ClinicalTrials.gov and the China Clinical Trial Registration Center, with the time interval from inception to August 2023. The RCT of treating KOA with the kidney-tonifying and blood-activating method was included. Two assessors independently conducted literature screening, data collection, and qualitative analysis to compile the outcome measure results. A total of 350 RCTs were included, involving 165 outcome measures with the total frequency of 1 462. These outcome measures were categorized into six domains: symptom and sign measures(23) with the frequency of 718(49.1%), TCM symptom and syndrome measures(3) with the frequency of 53(3.6%), physical examination measures(130) with the frequency of 506(34.6%), quality of life measures(4) with the frequency of 20(1.3%), long-term efficacy measures(2) with the frequency of 6(0.4%), and safety measures(3) with the frequency of 159(10.9%). Additionally, 53 studies used TCM syndrome and symptom scores as indicators of efficacy, employing eight distinct measurement tools. The RCTs involving the kidney-tonifying and blood-activating method for treating KOA had a variety of problems, such as unclear prio-ritization of outcome measures, diversity in measurement tools, absence of standardized assessment criteria for specific measures, and non-standardized usage. These problems affected the research quality and reliability. Hence, it is advisable to draw upon international expertise, improve research design, and merge TCM efficacy characteristics with clinical research to establish a core set of KOA outcome measures aligned with TCM principles.

[Simultaneous determination of seven artemisinin-related compounds in Artemisia annua by UPLC-QQQ-MS/MS].

A variety of compounds in Artemisia annua were simultaneously determined to evaluate the quality of A. annua from multiple perspectives. A method based on ultra-high performance liquid chromatography-triple quadrupole tandem mass spectrometry(UPLC-QQQ-MS/MS) was established for the simultaneous determination of seven compounds: amorpha-4,11-diene, artemisinic aldehyde, dihydroartemisinic acid, artemisinic acid, artemisinin B, artemisitene, and artemisinin, in A. annua. The content of the seven compounds in different tissues(roots, stems, leaves, and lateral branches) of A. annua were compared. The roots, stems, leaves, and lateral branches of four-month-old A. annua were collected and the content of seven artemisinin-related compounds in different tissues was determined. A multi-reaction monitoring(MRM) acquisition mode of UPLC-QQQ-MS/MS was used, with a positive ion mode of atmospheric pressure chemical ion source(APCI). Chromatographic separation was achieved on an Eclipse Plus RRHD C_(18) column(2.1 mm×50 mm, 1.8 µm). The gradient elution was performed with the mobile phase consisted of formic acid(0.1%)-ammonium formate(5 mmol·L~(-1))(A) and the methanol(B) gradient program of 0-8 min, 55%-100% B, 8-11 min, 100% B, and equilibrium for 3 min, the flow rate of 0.6 mL·min~(-1), the column temperature of 40 ℃, the injection volume of 5 µL, and the detection time of 8 min. Through methodological investigation, a method based on UPLC-QQQ-MS/MS was established for the simultaneous quantitative determination of seven representative compounds involved in the biosynthesis of artemisinin. The content of artemisinin in A. annua was higher than that of artemisinin B, and the content of artemisinin and dihydroartemisinic acid were high in all the tissues of A. annua. The content of the seven compounds varied considerably in different tissues, with the highest levels in the leaves and neither artemisinene nor artemisinic aldehyde was detected in the roots. In this study, a quantitative method based on UPLC-QQQ-MS/MS for the simultaneous determination of seven representative compounds involved in the biosynthesis of artemisinin was established, which was accurate, sensitive, and highly efficient, and can be used for determining the content of artemisinin-related compounds in A. annua, breeding new varieties, and controlling the quality of Chinese medicinal materials.

Exposure to real-ambient bedroom light at night delayed circadian rhythm in healthy Chinese young adults: A cross-sectional study.

BACKGROUND: Light at night (LAN) have attracted increased research attention on account of its widespread health hazards. However, the underlying mechanism remains unknown. The objective of this study was to investigate the effects of real-ambient bedroom LAN exposure on circadian rhythm among young adults and potential sex differences. METHODS: Bedroom LAN exposure was measured at 60-s intervals for 2 consecutive days using a portable illuminance meter. Circadian phase was determined by the dim light melatonin onset (DLMO) time in 7 time-series saliva samples. RESULTS: The mean age of the 142 participants was 20.7 ± 0.8 years, and 59.9% were women. The average DLMO time was 21:00 ± 1:11 h, with men (21:19 ± 1:12 h) later than women (20:48 ± 1:07 h). Higher level of LAN intensity (LANavg ≥ 3lx vs. LANavg < 3lx) was associated with an 81.0-min later in DLMO time (95% CI: 0.99, 1.72), and longer duration of nighttime light intensity ≥ 5lx (LAN5; LAN5 ≥ 45 min vs. LAN5 < 45 min) was associated with a 51.6-min later in DLMO time (95% CI: 0.46, 1.26). In addition, the delayed effect of LAN exposure on circadian phase was more pronounced in men than in women (all P-values <0.05). CONCLUSIONS: Overall, bedroom LAN exposure was significantly associated with delayed circadian rhythm. Additionally, the delayed effect is more significant in men. Keeping bedroom dark at night may be a practicable option to prevent circadian disruption and associated health implications. Future studies with more advanced light measurement instrument and consensus methodology for DLMO assessment are warranted.

Advances in disilylation reactions to access cis/trans-1,2-disilylated and gem-disilylated alkenes.

Organosilane compounds are widely used in both organic synthesis and materials science. Particularly, 1,2-disilylated and gem-disilylated alkenes, characterized by a carbon-carbon double bond and multiple silyl groups, exhibit significant potential for subsequently diverse transformations. The versatility of these compounds renders them highly promising for applications in materials, enabling them to be valuable and versatile building blocks in organic synthesis. This review provides a comprehensive summary of methods for the preparation of cis/trans-1,2-disilylated and gem-disilylated alkenes. Despite notable advancements in this field, certain limitations persist, including challenges related to regioselectivity in the incorporation and chemoselectivity in the transformation of two nearly identical silyl groups. The primary objective of this review is to outline synthetic methodologies for the generation of these alkenes through disilylation reactions, employing silicon reagents, specifically disilanes, hydrosilanes, and silylborane reagents. The review places particular emphasis on investigating the practical applications of the C-Si bond of disilylalkenes and delves into an in-depth discussion of reaction mechanisms, particularly those reactions involving the activation of Si-Si, Si-H, and Si-B bonds, as well as the C-Si bond formation.

MRI-guided photothermal/photodynamic immune activation combined with PD-1 inhibitor for the multimodal combination therapy of melanoma and metastases.

Non-invasive image-guided precise photothermal/photodynamic therapy (PTT/PDT) has been proven to be an effective local treatment modality but incompetent against metastases. Hence, the combination of local PTT/PDT and systemic immunotherapy would be a promising strategy for tumor eradication. Herein, a magnetic resonance imaging (MRI)-visualized PTT/PDT agent (SIDP NMs) was constructed, and the efficacy of its multimodal combination with a programmed cell death 1 (PD-1) inhibitor in the treatment of melanoma and metastases was studied. Due to the hydrophobic encapsulation of indocyanine green within the micellar core, SIDP NMs exhibited excellent photothermal/photodynamic properties and stability under an 808 nm near-infrared laser. In vitro cell experiments showed that SIDP NMs had a good killing effect. After incubating with B16-F10 cells for 24 h and irradiating with an 808-nm laser for 10 min, cell viability decreased significantly. Magnetic resonance imaging experiments in melanoma-bearing mice have shown that the dynamic distribution of SIDP NMs in tumor tissue could be monitored by T2WI and T2-MAP non-invasively due to the presence of superparamagnetic iron oxide nanocrystal in SIDP NMs. When the 808 nm laser was irradiated at the maximum focusing time point shown by MRI, the temperature of the tumor area rapidly increased from 32°C to 60.7°C in 5 min. In mouse melanoma ablation and distant tumor immunotherapy studies, SIDP NMs provided excellent MRI-guided PTT/PDT results and, when combined with PD-1 inhibitor, have great potential to cure primary tumors and eradicate metastases.

FTO attenuates TNF-α-induced damage of proximal tubular epithelial cells in acute pancreatitis-induced acute kidney injury via targeting AQP3 in an N6-methyladenosine-dependent manner.

BACKGROUND: Acute kidney injury (AKI) is a frequent complication of severe acute pancreatitis (SAP). Previous investigations have revealed the involvement of FTO alpha-ketoglutarate-dependent dioxygenase (FTO) and aquaporin 3 (AQP3) in AKI. Therefore, the aim of this study is to explore the association of FTO and AQP3 on proximal tubular epithelial cell damage in SAP-induced AKI. METHODS: An in-vitro AKI model was established in human proximal tubular epithelial cells (PTECs) HK-2 via tumor necrosis factor-α (TNF-α) induction (20 ng/mL), after which FTO and AQP3 expression was manipulated and quantified by quantitative real-time PCR and Western blotting. The viability and apoptosis of PTECs under various conditions, and reactive oxygen species (ROS), superoxide dismutase (SOD), and malonaldehyde (MDA) levels within these cells were measured using commercial assay kits and flow cytometry. Methylated RNA immunoprecipitation and mRNA stability assays were performed to elucidate the mechanism of FTO-mediated N6-methyladenosine (m6A) modification. Western blotting was performed to quantify ß-catenin protein levels in the PTECs. RESULTS: FTO overexpression attenuated the TNF-α-induced decrease in viability and SOD levels, elevated apoptosis, increased levels of ROS and MDA, and diminished TNF-α-induced AQP3 expression and reduced ß-catenin expression, but its silencing led to contradictory results. FTO negatively modulates AQP3 levels in RTECs in an m6A-depednent manner and compromises AQP3 stability. In addition, all FTO overexpression-induced effects in TNF-α-induced PTECs were neutralized following AQP3 upregulation. CONCLUSION: FTO alleviates TNF-α-induced damage to PTECs in vitro by targeting AQP3 in an m6A-dependent manner.

Vertical Distribution Mapping for Methane Fugitive Emissions Using Laser Path-Integral Sensing in Non-Cooperative Open Paths.

Observing the vertical diffusion distribution of methane fugitive emissions from oil/gas facilities is significant for predicting the pollutant's spatiotemporal transport and quantifying the random emission sources. A method is proposed for methane's vertical distribution mapping by combining the laser path-integral sensing in non-non-cooperative open paths and the computer-assisted tomography (CAT) techniques. It uses a vertical-plume-mapping optical path configuration and adapts the developed dynamic relaxation and simultaneous algebraic reconstruction technique (DR-SART) into methane-emission-distribution reconstruction. A self-made miniaturized TDLAS telemetry sensor provides a reliable path to integral concentration information in non-non-cooperative open paths, with Allan variance analysis yielding a 3.59 ppm·m sensitivity. We employed a six-indexes system for the reconstruction performance analysis of four potential optical path-projection configurations and conducted the corresponding validation experiment. The results have shown that that of multiple fan-beams combined with parallel-beam modes (MFPM) is better than the other optical path-projection configurations, and its reconstruction similarity coefficient (ε) is at least 22.4% higher. For the different methane gas bag-layout schemes, the reconstruction errors of maximum concentration (γm) are consistently around 0.05, with the positional errors of maximum concentration (δ) falling within the range of 0.01 to 0.025. Moreover, considering the trade-off between scanning duration and reconstruction accuracy, it is recommended to appropriately extend the sensor measurement time on a single optical path to mitigate the impact of mechanical vibrations induced by scanning motion.

Quantitative Assessment Characteristics of Small Pulmonary Vessel Remodelling in Populations at High Risk for COPD and Smokers Using Low-Dose CT.

Purpose: To explore the morphological alterations in small pulmonary vessels in populations at high risk for chronic obstructive pulmonary disease (COPD) and smokers based on multiple computed tomography (CT) quantitative parameters. Patients and Methods: A total of 1969 Three Major Chest Diseases Screening Study participants with available demographic data and smoking history who underwent low-dose chest CT from 2018 to 2020 were included. All subjects were divided into normal, high risk for COPD, and COPD groups according to their pulmonary function test (PFT) results. Furthermore, the three groups were further subdivided into never-smokers, current smokers, and former smokers subgroups according to their smoking history. Quantitative parameters, such as the number, area at 6 mm~24 mm subpleura and volume of small pulmonary vessels, were extracted by computer software. Differences in small pulmonary vessel parameters among the groups were compared using two-way ANOVA. Results: The number, area at 6 mm~24 mm subpleura and volume of small pulmonary vessels in the group at high risk for COPD were lower than those in the normal group (P<0.05). The number, area at 6 mm~24 mm subpleura and volume of small pulmonary vessels in the COPD group were higher than those in the normal group (P<0.05). The number, area of small pulmonary vessels at 6 mm~12 mm subpleura in current smokers with high risk for COPD were higher than those in former smokers with high risk for COPD (P<0.05). Conclusion: The number, area, and volume of small pulmonary vessels in populations at high risk for COPD were decreased. Smoking cessation may impede structural changes in small pulmonary vessels in populations at high risk for COPD.

Efficacy and Safety of Huashi Baidu Granules in Treating Patients with SARS-CoV-2 Omicron Variant: A Single-Center Retrospective Cohort Study.

OBJECTIVE: To evaluate the efficacy and safety of Huashi Baidu Granules (HSBD) in treating patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant. METHODS: A single-center retrospective cohort study was conducted during COVID-19 Omicron epidemic in the Mobile Cabin Hospital of Shanghai New International Expo Center from April 1st to May 23rd, 2022. All COVID-19 patients with asymptomatic or mild infection were assigned to the treatment group (HSBD users) and the control group (non-HSBD users). After propensity score matching in a 1:1 ratio, 496 HSBD users of treatment group were matched by propensity score to 496 non-HSBD users. Patients in the treatment group were administrated HSBD (5 g/bag) orally for 1 bag twice a day for 7 consecutive days. Patients in the control group received standard care and routine treatment. The primary outcomes were the negative conversion time of nucleic acid and negative conversion rate at day 7. Secondary outcomes included the hospitalized days, the time of the first nucleic acid negative conversion, and new-onset symptoms in asymptomatic patients. Adverse events (AEs) that occurred during the study were recorded. Further subgroup analysis was conducted in vaccinated (378 HSBD users and 390 non-HSBD users) and unvaccinated patients (118 HSBD users and 106 non-HSBD users). RESULTS: The median negative conversion time of nucleic acid in the treatment group was significantly shortened than the control group [3 days (IQR: 2-5 days) vs. 5 days (IQR: 4-6 days); P<0.01]. The negative conversion rate of nucleic acid in the treatment group were significantly higher than those in the control group at day 7 (91.73% vs. 86.90%, P=0.014). Compared with the control group, the hospitalized days in the treatment group were significantly reduced [10 days (IQR: 8-11 days) vs. 11 days (IQR: 10.25-12 days); P<0.01]. The time of the first nucleic acid negative conversion had significant differences between the treatment and control groups [3 days (IQR: 2-4 days) vs. 5 days (IQR: 4-6 days); P<0.01]. The incidence of new-onset symptoms including cough, pharyngalgia, expectoration and fever in the treatment group were lower than the control group (P<0.05 or P<0.01). In the vaccinated patients, the median negative conversion time and hospitalized days were significantly shorter than the control group after HSDB treatment [3 days (IQR: 2-5 days) vs. 5 days (IQR: 4-6 days), P<0.01; 10 days (IQR: 8-11 days) vs. 11 days (IQR: 10-12 days), P<0.01]. In the unvaccinated patients, HSBD treatment efficiently shorten the median negative conversion time and hospitalized days [4 days (IQR: 2-6 days) vs. 5 days (IQR: 4-7 days), P<0.01; 10.5 days (IQR: 8.75-11 days) vs. 11.0 days (IQR: 10.75-13 days); P<0.01]. No serious AEs were reported during the study. CONCLUSION: HSBD treatment significantly shortened the negative conversion time of nuclear acid, the length of hospitalization, and the time of the first nucleic acid negative conversion in patients infected with SARS-COV-2 Omicron variant (Trial registry No. ChiCTR2200060472).