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Abstract Objectives To evaluate the diagnostic accuracy of machine learning models incorporating multimodal features for predicting radiation pneumonitis in lung cancer through a systematic review and meta-analysis. Methods Relevant studies were identified through a systematic search of PubMed, Web of Science, Embase, and the Cochrane Library from October 2003 to December 2023. Additional studies were located by reviewing bibliographies and relevant websites. Two independent researchers screened titles, abstracts, and full-text articles according to predefined inclusion and exclusion criteria. Data extraction was performed using standardized forms, and study quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. The primary outcomes, including combined sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the curve (AUC), were calculated using STATA MP-64 software(Stata Corporation LLC, College Station, USA) with a random-effects model. Meta-analysis was conducted to synthesize diagnostic accuracy measures, and analyses of heterogeneity and publication bias were performed. Results A total of 1,406 patients with primary lung cancer were included in this systematic review, drawing data from 9 studies. The pooled analysis revealed a sensitivity of 0.74 [0.58–0.85] and a specificity of 0.91 [0.87–0.95] for machine learning models in diagnosing radiation pneumonitis. The positive likelihood ratio (PLR) was 8.69 [5.21–14.50], the negative likelihood ratio (NLR) was 0.28 [0.16–0.49], and the diagnostic odds ratio (DOR) was 30.73 [11.96–78.97]. The area under the curve (AUC) was 0.93 [0.90–0.95], indicating excellent diagnostic performance. Meta-regression analysis identified that the number of machine learning models, year of publication, and study design contributed to heterogeneity among studies. No evidence of publication bias was found. Overall, machine learning models incorporating multimodal characteristics demonstrated 75% accuracy in predicting moderate to severe radiation pneumonitis. Conclusion In conclusion, by integrating the current machine learning (ML) algorithm's ability in big data mining, a predictive model can be constructed by combining multi-modal features such as genetics, imaging, and cell factors. By selecting multiple machine learning algorithm frameworks and competing for the best combination model based on research goals, the reliability and accuracy of the radiation pneumonitis prediction model can be greatly improved. Trial registration PROSPERO (CRD42024497599).

Abstract The outbreaks of severe acute respiratory syndrome coronavirus (SARS-CoV-1), Middle East respiratory syndrome coronavirus (MERS-CoV), and SARS-CoV-2 highlight the need for countermeasures to prevent future coronavirus pandemics. Given the unpredictable nature of spillover events, preparing antibodies with broad coronavirus-neutralizing activity is an ideal proactive strategy. Here, we investigated whether SARS-CoV-2 infection and vaccination could provide cross-neutralizing antibodies (nAbs) against zoonotic sarbecoviruses. We evaluated the cross-neutralizing profiles of plasma and monoclonal antibodies constructed from B cells from coronavirus disease 2019 (COVID-19) convalescents and vaccine recipients; against sarbecoviruses originating from bats, civets, and pangolins; and against SARS-CoV-1 and SARS-CoV-2. We found that the majority of individuals with natural infection and vaccination elicited broad nAb responses to most tested sarbecoviruses, particularly to clade 1b viruses, but exhibited very low cross-neutralization to SARS-CoV-1 in both natural infection and vaccination, and vaccination boosters significantly augmented the magnitude and breadth of nAbs to sarbecoviruses. Of the nAbs, several exhibited neutralization activity against multiple sarbecoviruses by targeting the spike receptor-binding domain (RBD) and competing with angiotensin-converting enzyme 2 (ACE2) binding. SCM12-61 demonstrated exceptional potency, with half-maximal inhibitory concentration (IC50) values of 0.001–0.091 μg/mL against tested sarbecoviruses; while VSM9-12 exhibited remarkable cross-neutralizing breadth against sarbecoviruses and SARS-CoV-2 Omicron subvariants, highlighting the potential of these two nAbs in combating sarbecoviruses and SARS-CoV-2 Omicron subvariants. Collectively, our findings suggest that vaccination with an ancestral SARS-CoV-2 vaccine, in combination with broad nAbs against sarbecoviruses, may provide a countermeasure for preventing further sarbecovirus outbreaks in humans.

Abstract Diabetic kidney disease (DKD) is a prevalent and debilitating complication of diabetes characterized by progressive renal function decline and a lack of effective treatment options. Here, we investigated the role of the transcription factor CCAAT/enhancer binding protein alpha (C/EBPα) in DKD pathogenesis. Analysis of renal biopsy samples revealed increased C/EBPα expression in patients with DKD. Using RNA sequencing and proteomics, we explored the mechanisms through which the C/EBPα contributes to DKD. Our findings demonstrated that C/EBPα exacerbated tubular injury by promoting acyl-CoA synthetase long-chain family member 4 (ACSL4)-dependent ferroptosis. We identified that C/EBPα upregulated ACSL4 expression by binding to its transcription regulatory sequence (TRS), leading to elevated lipid peroxidation and ferroptosis. Furthermore, inhibition or genetic ablation of C/EBPα attenuated ferroptosis and mitigated tubular injury in DKD. These results highlighted the C/EBPα-ACSL4-ferroptosis pathway as a promising therapeutic target for DKD treatment.

Abstract Immune checkpoint inhibitors (ICIs) have become an important treatment modality for various malignancies. Due to excessive inflammatory and immune responses, immune-related adverse events (irAEs), such as rash, pruritis, pneumonitis, hepatitis, hypothyroidism, hyperthyroidism and fatigue, can occur. Acquired immune thrombocytopenia is a rare irAE that can lead to severe low platelet counts and hemorrhage. A retrospective observational analysis was conducted on data from the United States Food and Drug Administration Adverse Event Reporting System (FAERS). We searched for all reports recorded in the FAERS covering the period from 2011 Q1 to 2023 Q4 for target agents. Signal analysis was performed using the reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN) and multi-item gamma Poisson shrinker (MGPS) algorithm. Nonparametric tests were used to compare the time to onset of thrombocytopenia-associated fractures between different regimens. There were 404 reports of immune thrombocytopenia in the FAERS database. Immune thrombocytopenia was associated with all ICIs except tremelimumab, and signals were detected by all 4 methods. The median time to the onset of immune thrombocytopenia caused by PD-1, PD-L1 and CTLA-4 inhibitors was 47 days (range: 21-139.2), 21 days (range: 13–131) and 9 days (range: 7–27), respectively. The Weibull shape parameter test revealed that pembrolizumab-, durvalumab-, and ipilimumab-induced thrombocytopenia had a random failure-type profile, and nivolumab- and atezolizumab-induced thrombocytopenia were characterized by an early failure-type profile. There was a significant reporting signal of ICI-induced thrombocytopenia associated with most ICIs. Immune thrombocytopenia has a greater incidence in males, elderly individuals and Asian populations, and PD-1 inhibitors were the most common cause. Clinicians should be aware of the signs of potential serious adverse events.

Introduction There needs to be more up-to-date evidence on the prevalence of e-cigarette use among Chinese adults. This study aims to investigate the prevalence and associated factors of e-cigarette use among adults aged 18–44 years in China. Methods Cross-sectional design and convenience sampling were used. The data for this study were obtained from an online survey conducted in mainland China from April to May 2023. The target population was adults aged 18–44 years. Descriptive analysis was employed to report the prevalence of e-cigarette use, while adjusted multivariable logistic regression was performed to examine the association between e-cigarette use and related factors. Results A total of 4256 participants were included in this study; 12.9% were current e-cigarette users, 5.9% were frequent users, and 7.0% were occasional users. The descriptive analysis results indicated that males and cigarette users had a higher prevalence of e-cigarette use. Multivariable analysis showed that e-cigarette use was significantly associated with female gender (AOR=0.76, 95% CI: 0.60–0.96), those aged 25–34 years with monthly income 6000–8999 CNY (AOR=2.01; 95% CI: 1.18–3.41), those aged 25–34 years with monthly income ≥9000 CNY (AOR=2.20; 95% CI: 1.26–3.82), college or undergraduate degree (AOR=1.91; 95% CI: 1.22–3.00), urban residence (AOR=1.72; 95% CI: 1.34–2.20), being a current smoker (AOR=3.32; 95% CI: 2.64–4.16), perception of harm (AOR=0.66; 95% CI: 0.60–0.73), and perception of benefit (AOR=2.31; 95% CI: 2.04–2.61). Conclusions The prevalence of current e-cigarette use among adults in China was 12.9% within our sample. In addition to sociodemographic factors, individuals with a higher perception of the harm associated with e-cigarettes were less likely to engage in e-cigarette consumption. Conversely, individuals who perceive the ‘benefits’ of e-cigarettes more favorably use them. Targeted interventions, such as health education, are recommended to help adults develop a correct understanding of e-cigarettes and lower the prevalence of e-cigarette use.

Abstract Background Idiopathic Pulmonary Fibrosis (IPF) is a progressive fibrotic lung disease. However, the field of quantitative CT scan analysis in conjunction with pulmonary function test for IPF patients remains relatively understudied. In this study, we evaluated the diagnostic value of features derived high-resolution computed tomography (HRCT) for patients with IPF and correlated them with pulmonary function tests. Methods We retrospectively analyzed the chest HRCT images and pulmonary function test results of 52 patients with IPF during the same period (1 week) and selected 52 healthy individuals, matched for sex, age, and body mass index (BMI) and with normal chest HRCT as controls. HRCT scans were performed using a Philips 256-row Brilliance iCT scanner with standardized parameters. Lung function tests were performed using a Jaeger volumetric tracer for forced vital capacity (FVC), total lung capacity (TLC), forced expiratory volume in first second (FEV1), FEV1/FVC, carbon monoxide diffusing capacity (DLCO), and maximum ventilation volume (MVV) metrics. CT quantitative analysis, including tissue segmentation and threshold-based quantification of lung abnormalities, was performed using 3D-Slicer software to calculate the percentage of normal lung areas (NL%), percentage of ground-glass opacity areas (GGO%), percentage of fibrotic area (F%) and abnormal lesion area percentage (AA%). Semi-quantitative analyses were performed by two experienced radiologists to assess disease progression. The aortic-to-sternal distance (ASD) was measured on axial images as a standardized parameter. Spearman or Pearson correlation analysis and multivariate stepwise linear regression were used to analyze the relationship between the data in each group, and the ROC curve was used to determine the optimal quantitative CT metrics for identifying IPF and controls. Results ROC curve analysis showed that F% distinguished the IPF patient group from the control group with the largest area under the curve (AUC) of 0.962 (95% confidence interval: 0.85–0.96). Additionally, with F% = 4.05% as the threshold, the Youden’s J statistic was 0.827, with a sensitivity of 92.3% and a specificity of 90.4%. The ASD was significantly lower in the late stage of progression than in the early stage (t = 5.691, P

Abstract Background Oral cancer is one of the most common cancers in China and seriously threaten life and health of Chinese people. We analysed the trends and disparities of oral cancer mortality rates and the disease burden of oral cancer in China from 2006 to 2021 to provide a reference for its prevention and control. Methods Annual death data for oral cancer was gleaned from the China Death Surveillance Database. The age-standardized mortality rate (ASMR), annual percentage change (APC), and average APC (AAPC) were used to analyze the trend of mortality. Loss of life expectancy (LLE) and years of life lost (YLL) were adopted to assess disease burden. Results From 2006 to 2021, the overall ASMR of oral cancer lightly declined (AAPC: − 0.97%; 95% CI: − 1.89%, − 0.04%), and the similar trend was observed among females (AAPC: − 1.22%; 95% CI: − 1.89%, − 0.55%). The ASMR of males was 2.31–3.16 times higher than that of females per year. The median of LLE for overall, males and females caused by oral cancer from 2006 to 2021 were 0.05, 0.06 and 0.03 years, respectively. There was a decrease of standardized YLL rate from 2006 to 2021 for overall (AAPC: − 1.31%, 95% CI: − 2.24% ~ − 0.37%) and for female (AAPC: − 1.63%, 95% CI: − 2.30% ~ − 0.95%). ASMR in urban areas was 1.02–1.28 times higher than that in rural areas from 2006 to2011, but 0.85–0.97 times lower in urban areas than that in rural areas from 2018 to 2021. The disease burden was higher in urban areas than in rural areas in 2006, whereas the reverse was observed in 2021. Conclusions There are severe health gaps and disparities in trends between sexes and different areas in China. Males and rural populations need to be focused on targeted interventions for the main influencing factors.

Abstract Background Preoperative discrimination between non-muscle-invasive bladder cancer (NMIBC) and the muscle invasive bladder cancer (MIBC) is a determinant of management. The purpose of this research is to employ radiomics to evaluate the diagnostic value in determining muscle invasiveness of compressed sensing (CS) accelerated 3D T2-weighted-SPACE sequence with high resolution and short acquisition time. Methods This prospective study involved 108 participants who underwent preoperative 3D-CS-T2-weighted-SPACE, 3D-T2-weighted-SPACE and T2-weighted sequences. The cohort was divided into training and validation cohorts in a 7:3 ratio. In the training cohort, a Rad-score was constructed based on radiomic features selected by intraclass correlation coefficients, pearson correlation coefficient and least absolute shrinkage and selection operator . Multivariate logistic regression was used to develop a nomogram combined radiomics and clinical indices. In the validation cohort, the performances of the models were evaluated by ROC, calibration, and decision curves. Results In the validation cohort, the area under ROC curve of 3D-CS-T2-weighted-SPACE, 3D-T2-weighted-SPACE and T2-weighted models were 0.87(95% confidence interval (CI):0.73-1.00), 0.79(95%CI:0.63–0.96) and 0.77(95%CI:0.60–0.93), respectively. The differences in signal-to-noise ratio and contrast-to-noise ratio between 3D-CS-T2-weighted-SPACE and 3D-T2-weighted-SPACE sequences were not statistically significant(p > 0.05). While the clinical model composed of three clinical indices was 0.74(95%CI:0.55–0.94) and the radiomics-clinical nomogram model was 0.88(95%CI:0.75-1.00). The calibration curves confirmed high goodness of fit, and the decision curve also showed that the radiomics model and combined nomogram model yielded higher net benefits than the clinical model. Conclusion The radiomics model based on compressed sensing 3D T2WI sequence, which was acquired within a shorter acquisition time, showed superior diagnostic efficacy in muscle invasion of bladder cancer. Additionally, the nomogram model could enhance the diagnostic performance.

Abstract Purpose To investigate the performance of histogram features of non-Gaussian diffusion metrics for diagnosing muscle invasion and histological grade in bladder cancer (BCa). Methods Patients were prospectively allocated to MR scanner1 (training cohort) or MR2 (testing cohort) for conventional diffusion-weighted imaging (DWIconv) and multi-b-value DWI. Metrics of continuous time random walk (CTRW), diffusion kurtosis imaging (DKI), fractional-order calculus (FROC), intravoxel incoherent motion (IVIM), and stretched exponential model (SEM) were simultaneously calculated using multi-b-value DWI. Whole-tumor histogram features were extracted from DWIconv and non-Gaussian diffusion metrics for logistic regression analysis to develop diffusion models diagnosing muscle invasion and histological grade. The models’ performances were quantified by area under the receiver operating characteristic curve (AUC). Results MR1 included 267 pathologically-confirmed BCa patients (median age, 67 years [IQR, 46–82], 222 men) and MR2 included 83 (median age, 65 years [IQR, 31–82], 73 men). For discriminating muscle invasion, CTRW achieved the highest testing AUC of 0.915, higher than DWIconv’s 0.805 (p = 0.014), and similar to the combined diffusion model’s AUC of 0.885 (p = 0.076). For differentiating histological grade of non-muscle-invasion bladder cancer, IVIM outperformed a testing AUC of 0.897, higher than DWIconv’s 0.694 (p = 0.020), and similar to the combined diffusion model’s AUC of 0.917 (p = 0.650). In both tasks, DKI, FROC, and SEM failed to show diagnostic superiority over DWIconv (p > 0.05). Conclusion CTRW and IVIM are two potential non-Gaussian diffusion models to improve the MRI application in assessing muscle invasion and histological grade of BCa, respectively. Critical relevance statement Our study validates non-Gaussian diffusion imaging as a reliable, non-invasive technique for early assessment of muscle invasion and histological grade in BCa, enhancing accuracy in diagnosis and improving MRI application in BCa diagnostic procedures. Key Points Muscular invasion largely determines bladder salvageability in bladder cancer patients. Evaluated non-Gaussian diffusion metrics surpassed DWIconv in BCa muscle invasion and histological grade diagnosis. Non-Gaussian diffusion imaging improved MRI application in preoperative diagnosis of BCa. Graphical Abstract

Academic engagement was recognized as a crucial predictor to measure the effectiveness of online teaching of international students. Therefore, this study established a mediating model to explore the mechanism underlying of interaction and information technology accessibility on academic engagement of international students, as well as the impact of learning interest on these mechanisms with the context of online teaching. Using a stratified random sampling method, 1895 international students from 32 Chinese universities were selected. These international students had completed the academic engagement scale, interaction scale, information technology accessibility scale, and learning interest scale. The study variables were analyzed in sequence for reliability and validity, common method biases test, correlation analysis, structural equation model testing, and bias-corrected percentile Bootstrap testing. The results revealed that online interaction positively affected the academic engagement of international students in Chinese universities (β= 0.35, p 0.05); but learning interest played a complete mediating role between information technology accessibility and academic engagement (indirect effect = 0.09, 95 % Boot CI = [0.05, 0.11], p

Radiation-induced lung injury (RILI) is a severe complication arising from thoracic tumor radiotherapy, which constrains the possibility of increasing radiation dosage. Current RILI therapies provide only limited relief and may result in undesirable side effects. Therefore, there is an urgent demand for effective and low-toxicity treatments for RILI. Macrophages play a pivotal role in RILI, promoting inflammation in the initial stages and facilitating fibrosis in the later stages. Sodium clodronate, a bisphosphonate, can induce macrophage apoptosis when encapsulated in liposomes. In this study, we explored the potential of liposomal sodium clodronate (LC) as a specific agent for depleting macrophages to alleviate acute RILI. We assessed the impact of LC on macrophage consumption both in vitro and in vivo. In a mouse model of acute RILI, LC treatment group led to a reduction in alveolar macrophage counts, mitigated lung injury severity, and lowered levels of pro-inflammatory cytokines in both plasma and bronchoalveolar lavage fluid. Additionally, we further elucidated the specific effects and mechanism of LC on macrophages in vitro. Alveolar macrophages MHS cells were subjected to varying concentrations of LC (0, 50, 100, 200 μg/ml), and the results demonstrated its dose-dependent inhibition of cell proliferation and induction of apoptosis. Moreover, LC decreased the secretion of pro-inflammatory cytokines, including IL-1β, IL-6, and TNF-α. Conditioned media from LC-treated macrophages protected alveolar epithelial cells MLE-12 from radiation-induced damage, as demonstrated by reduced apoptosis and DNA damage. These findings imply that LC-mediated macrophage depletion may present a promising therapeutic strategy for alleviating radiation-induced lung injury.

Abstract Ongoing global climate change and conventional forestry have led to a dramatic increase in new forest gaps, predicted to strongly impact litter turnover and nutrient cycling. Here we synthesized 8739 paired observations to quantify the impacts of naturally occurring and artificially created gaps on litterfall, litter decomposition, and the release of carbon and nutrients. Globally, forest gaps decreased annual litterfall by 29.5% and litter remaining carbon and phosphorus by 5.6%, while litter decomposition increased in the 0–20% mass loss interval. Climate and litter quality showed a major contribution to forest gap effects on litter decomposition, with gap characteristics further influencing the release of carbon and nutrients during decomposition. Our results uncovered the potential impact of escalating forest gaps on reducing litter turnover and carbon sequestration, providing support for the inclusion of gaps into global litter dynamic models to improve predictions of ecosystem material cycling responses to ongoing climate change.

Abstract Background Results regarding whether it is essential to incorporate genetic variants into risk prediction models for esophageal cancer (EC) are inconsistent due to the different genetic backgrounds of the populations studied. We aimed to identify single-nucleotide polymorphisms (SNPs) associated with EC among the Chinese population and to evaluate the performance of genetic and non-genetic factors in a risk model for developing EC. Methods A meta-analysis was performed to systematically identify potential SNPs, which were further verified by a case-control study. Three risk models were developed: a genetic model with weighted genetic risk score (wGRS) based on promising SNPs, a non-genetic model with environmental risk factors, and a combined model including both genetic and non-genetic factors. The discrimination ability of the models was compared using the area under the receiver operating characteristic curve (AUC) and the net reclassification index (NRI). The Akaike information criterion (AIC) and Bayesian information criterion (BIC) were used to assess the goodness-of-fit of the models. Results Five promising SNPs were ultimately utilized to calculate the wGRS. Individuals in the highest quartile of the wGRS had a 4.93-fold (95% confidence interval [CI]: 2.59 to 9.38) increased risk of EC compared with those in the lowest quartile. The genetic or non-genetic model identified EC patients with AUCs ranging from 0.618 to 0.650. The combined model had an AUC of 0.707 (95% CI: 0.669 to 0.743) and was the best-fitting model (AIC = 750.55, BIC = 759.34). The NRI improved when the wGRS was added to the risk model with non-genetic factors only (NRI = 0.082, P = 0.037). Conclusions Among the three risk models for EC, the combined model showed optimal predictive performance and can help to identify individuals at risk of EC for tailored preventive measures.

Abstract The design and implementation of virtual museums have evolved over decades, broadening the scope of traditional museum exhibitions and serving as an effective complement to physical museums. However, virtual visual effects have consistently fallen short of replicating the authentic exhibition experience and cannot substitute for physical museums. In this paper, we report a dual-mode mixed visualization system combining computational photography and binocular stereo vision techniques, and introduce an innovative virtual museum for Sanxingdui bronzes. This approach enables visitors to engage with the artifacts in a multifaceted manner-allowing for navigation, interaction, auditory guidance, and the examination of textural details as if handling the artifacts directly. Further analysis of participant responses in terms of visual cognition and aesthetic appreciation across different settings demonstrates that this dual-mode mixed visualization delivers not only a spatiotemporal experience consistent with the real world but also surreal visual effects. This immersive experience allows audiences to experience Sanxingdui art intimately, offering both high-resolution visuals and cost-effectiveness.

Abstract Reversible solid-state hydrogen storage of magnesium hydride, traditionally driven by external heating, is constrained by massive energy input and low systematic energy density. Herein, a single phase of Mg2Ni(Cu) alloy is designed via atomic reconstruction to achieve the ideal integration of photothermal and catalytic effects for stable solar-driven hydrogen storage of MgH2. With the intra/inter-band transitions of Mg2Ni(Cu) and its hydrogenated state, over 85% absorption in the entire spectrum is achieved, resulting in the temperature up to 261.8 °C under 2.6 W cm−2. Moreover, the hydrogen storage reaction of Mg2Ni(Cu) is thermodynamically and kinetically favored, and the imbalanced distribution of the light-induced hot electrons within CuNi and Mg2Ni(Cu) facilitates the weakening of Mg-H bonds of MgH2, enhancing the “hydrogen pump” effect of Mg2Ni(Cu)/Mg2Ni(Cu)H4. The reversible generation of Mg2Ni(Cu) upon repeated dehydrogenation process enables the continuous integration of photothermal and catalytic roles stably, ensuring the direct action of localized heat on the catalytic sites without any heat loss, thereby achieving a 6.1 wt.% H2 reversible capacity with 95% retention under 3.5 W cm−2.

Purpose: To develop and validate deep learning algorithms that can identify and classify angle-closure (AC) mechanisms using anterior segment optical coherence tomography (AS-OCT) images. Methods: This cross-sectional study included participants of the Handan Eye Study aged ≥35 years with AC detected via gonioscopy or on the AS-OCT images. These images were classified by human experts into the following to indicate the predominant AC mechanism (ground truth): pupillary block, plateau iris configuration, or thick peripheral iris roll. A deep learning architecture, known as comprehensive mechanism decision net (CMD-Net), was developed to simulate the identification of image-level AC mechanisms by human experts. Cross-validation was performed to optimize and evaluate the model. Human-machine comparisons were conducted using a held-out and separate test sets to establish generalizability. Results: In total, 11,035 AS-OCT images of 1455 participants (2833 eyes) were included. Among these, 8828 and 2.207 images were included in the cross-validation and held-out test sets, respectively. A separate test was formed comprising 228 images of 35 consecutive patients with AC detected via gonioscopy at our eye center. In the classification of AC mechanisms, CMD-Net achieved a mean area under the receiver operating characteristic curve (AUC) of 0.980, 0.977, and 0.988 in the cross-validation, held-out, and separate test sets, respectively. The best-performing ophthalmologist achieved an AUC of 0.903 and 0.891 in the held-out and separate test sets, respectively. And CMD-Net outperformed glaucoma specialists, achieving an accuracy of 89.9 % and 93.0 % compared to 87.0 % and 86.8 % for the best-performing ophthalmologist in the held-out and separate test sets, respectively. Conclusions: Our study suggests that CMD-Net has the potential to classify AC mechanisms using AS-OCT images, though further validation is needed.

In view of the problems caused by chromium-containing wastewater, such as environmental pollution, biological toxicity, and human health risks. Based on fly ash adsorption and nano-FeS reduction characteristics, fly ash loaded nano-FeS composite (nFeS-FA) was synthesized using mineral supported modification technology and ultrasonic precipitation method. The effect of adsorbent dosage, initial pH, contact time, and initial concentration of the solution on the adsorption of Cr(VI) and total Cr by nFeS-FA was investigated. The characteristics of Cr(VI) and total Cr adsorption by nFeS-FA were studied using adsorption isotherms, adsorption kinetics principles, as well as XRD, TEM, SEM-EDS, and BET analysis. The results demonstrated that under the conditions of nFeS-FA of 8 g/L, initial pH of 4, contact time of 150 min, and initial concentration of the solution at 100 mg/L, nFeS-FA achieved removal efficiency of 87.85 % for Cr(VI) and 71.77 % for total Cr. The adsorption of Cr(VI) and total Cr by nFeS-FA followed the Langmuir model and pseudo-second-order kinetic model, indicating monolayer adsorption with chemical adsorption as the dominant mechanism. XRD, TEM, SEM-EDS, and BET revealed that the flaky nano-FeS was uniformly distributed on the surface of fly ash, exhibiting good dispersion and thereby increasing the specific surface area. During the adsorption experiments, nFeS-FA reacted with Cr(VI), and the generated Fe3+ mainly existed as FeOOH precipitation, while S2− reacted with Cr(III) to produce Cr2S3 precipitation. Therefore, nFeS-FA exhibited excellent adsorption performance towards Cr(VI) and total Cr. It can serve as a technological reference for the remediation of heavy metal chromium pollution in the field of water treatment.

Abstract Hydrogen storage in MgH2 is an ideal solution for realizing the safe storage of hydrogen. High operating temperature, however, is required for hydrogen storage of MgH2 induced by high thermodynamic stability and kinetic barrier. Herein, flower‐like microspheres uniformly constructed by N‐doped TiO2 nanosheets coated with TiN nanoparticles are fabricated to integrate the light absorber and thermo‐chemical catalysts at a nanometer scale for driving hydrogen storage of MgH2 using solar energy. N‐doped TiO2 is in situ transformed into TiNxOy and Ti/TiH2 uniformly distributed inside of TiN matrix during cycling, in which TiN and Ti/TiHx pairs serve as light absorbers that exhibit strong localized surface plasmon resonance effect with full‐spectrum light absorbance capability. On the other hand, it is theoretically and experimentally demonstrated that the intimate interface between TiH2 and MgH2 can not only thermodynamically and kinetically promote H2 desorption from MgH2 but also simultaneously weaken Ti─H bonds and hence in turn improve H2 desorption from the combination of weakened Ti─H and Ti─H bonds. The uniform integration of photothermal and catalytic effect leads to the direct action of localized heat generated from TiN on initiating the catalytic effect in realizing hydrogen storage of MgH2 with a capacity of 6.1 wt.% under 27 sun.

Abstract Adventitious root formation is a key step in vegetative propagation via cuttings. It is crucial for establishing birch plantations and preserve birch varieties. Although previous studies have highlighted role of WOX11 in controlling adventitious root formation, no such study has been conducted in birch. Understanding the mechanism of adventitious root formation is essential for improvement of rooting or survival rate using stem cuttings in birch. In this study, we cloned BpWOX11 and produced BpWOX11 overexpression (OE) transgenic lines using the Agrobacterium-mediated plant transformation. OE lines exhibited early initiated adventitious root formation, leading to increase the rooting rate of stem cuttings plants. RNA sequencing analysis revealed that OE lines induced the gene expression related to expansin and cell division pathway, as well as defense and stress response genes. These may be important factors for the BpWOX11 gene to promote adventitious root formation in birch cuttings. The results of this study will help to further understand the molecular mechanisms controlling the formation of adventitious roots in birch.

Abstract Background The current literature shows a strong relationship between retinal neuronal and vascular alterations in dementia. The purpose of the study was to use NFN+ deep learning models to analyze retinal vessel characteristics for cognitive impairment (CI) recognition. Methods We included 908 participants from a community-based cohort followed for over 15 years (the prospective KaiLuan Study) who underwent brain magnetic resonance imaging (MRI) and fundus photography between 2021 and 2022. The cohort consisted of both cognitively healthy individuals (N = 417) and those with cognitive impairment (N = 491). We employed the NFN+ deep learning framework for retinal vessel segmentation and measurement. Associations between Retinal microvascular parameters (RMPs: central retinal arteriolar / venular equivalents, arteriole to venular ratio, fractal dimension) and CI were assessed by Pearson correlation. P

Background: Radiotherapy has become a standard treatment for chest tumors, but a common complication of radiotherapy is radiation lung injury. Currently, there is still a lack of effective treatment for radiation lung injury. Methods: A mouse model of radioactive lung injury (RILI) was constructed and then treated with different cycles of hydrogen inhalation. Lung function tests were performed to detect changes in lung function.HE staining was used to detect pathological changes in lung tissue. Immunofluorescence staining was used to detect the polarization of macrophages in lung tissue. Immunohistochemistry was used to detect changes in cytokine expression in lung tissues. Western Blot was used to detect the expression of proteins related to the NF-κB signalling pathway. Results: Lung function test results showed that lung function decreased in the model group and improved in the treatment group.HE staining showed that inflammatory response was evident in the model group and decreased in the treatment group. Immunohistochemistry results showed that the expression of pro-inflammatory factors was significantly higher in the model group, and the expression of pro-inflammatory factors was significantly higher in the treatment group. The expression of pro-inflammatory factors in the treatment group was significantly lower than that in the model group, and the expression of anti-inflammatory factors in the treatment group was higher than that in the model group. Immunofluorescence showed that the expression of M1 subtype macrophages was up-regulated in the model group and down-regulated in the treatment group. The expression of M2 subtype macrophages was up-regulated in the treatment group relative to the model group. Western Blot showed that P–NF-κB p65/NF-κB p65 was significantly increased in the model group, and P–NF-κB p65/NF-κB p65 was decreased in the treatment group. Conclusion: Hydrogen therapy promotes macrophage polarization from M1 to M2 subtypes by inhibiting the NF-κB signalling pathway, thereby attenuating the inflammatory response to radiation lung injury.

Abstract BiFeO3 is a rare single‐phase multiferroic which shows coupled ferroelectricity, ferroelasticity and antiferromagnetism at room temperature. Many fantastic properties of BiFeO3 are regulated by its domain structure. While (001) rhombohedral BiFeO3 thin films can possibly develop up‐to eight degenerate states of two‐variant 71° ferroelastic domain stripes, complete selective control of all possible switching paths between these states has not yet been achieved. Here, combining phase field simulations and scanning probe microscopy experiments, we demonstrated such a complete selective control. The tip bias and the built‐in field were shown to affect the volume fraction of the 71°, 109° and 180° switched domains in rhombohedral BiFeO3 thin films under single‐point loading. Meanwhile, tip scanning further broke the symmetry of the nucleated domains, leading to different switched domain patterns. We then grew BiFeO3 thin films with a specific two‐variant 71° ferroelastic domain state and showed that such a state could be deterministically switched into the other seven two‐variant domain states by collaborative controlling tip scanning and tip bias in scanning probe microscopy experiments. These results should deepen our current understanding on the domain switching kinetics in BiFeO3 thin films and indicate they are promising platforms for developing configurable electronic and spintronic devices.

The aim of this study was to investigate the effect of interactive immediacy on online learning satisfaction, and the mediating effect of learning interest and academic engagement on the relationship between interactive immediacy and online learning satisfaction. 2221 international students in Chinese universities participated in the questionnaire survey. The coefficient omega (ω) and the confirmatory factor analysis (CFA) were used to test the reliability and validity. Structural equation modeling (SEM) was used to analyze interactive immediacy, learning interest, and academic engagement on online learning satisfaction of international students in Chinese universities, as well as the mediating effect of learning interest and academic engagement. The results showed that interactive immediacy did not directly influence the online learning satisfaction of international students in Chinese universities. Learning interest and academic engagement played a complete mediating role between interactive immediacy and online learning satisfaction. Meanwhile, interactive immediacy not only affected online learning satisfaction of international students in Chinese universities through learning interest and academic engagement respectively, but also indirectly affected online learning satisfaction through the chain mediating effect of learning interest and academic engagement. The results of Bootstrap showed that the mediating effects in the model were significant. The findings of this study explored the underlying mechanism of international students' online learning satisfaction in Chinese universities, which provided an empirical basis for universities and teachers to improve the effect of online teaching, and integrate online teaching and traditional classroom teaching.

Abstract Introduction This study aimed to investigate the associations of comorbidities with knee symptoms and radiographic abnormalities of osteoarthritis (OA). Methods Participants were from the Osteoarthritis Initiative. Comorbidities were identified at baseline using the modified Charlson Comorbidity Index. For both knees, symptoms were assessed annually from baseline to 48 months using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain and function scores (rescaled range 0–100), and radiographic abnormalities using the Kellgren–Lawrence (KL, 0–4) grades. The presence of significant pain and functional disability was defined as a WOMAC score of ≥ 25 and ≥ 22, respectively, and radiographic OA (ROA) as KL ≥ 2. An increase of ≥ 9 in WOMAC scores and ≥ 1 in KL grades were defined as symptomatic and radiographic progression, respectively. Results Of 3337 participants, 28% and 9% had one and ≥ 2 comorbidities, respectively. The number of comorbidities was associated with the presence of significant functional disability (odds ratios [ORs] 1.15; 1.46) and predicted the progression of both knee pain and functional disability (ORs 1.11; 1.51). For the type of comorbidities, non-OA musculoskeletal diseases were associated with the presence of ROA and significant functional disability (ORs 1.63; 1.82) and showed a trend to predict incident ROA (OR 1.84, 95% confidence interval 1.00–3.38 p = 0.051). Diabetes and kidney diseases were associated with symptomatic progression of OA (ORs 1.38; 2.72). Conclusions Having more comorbidities, especially diabetes and kidney diseases, is associated with symptomatic progression of knee OA. Moreover, non-OA musculoskeletal diseases may be associated with the presence and onset of ROA.

Abstract Objectives Sedentary behaviour (SB) and physical activity (PA) have been shown to be associated with depression. However, behaviours, such as PA, occupy a portion of an individual’s 24-h day. Thus, an increase in time for one behaviour takes away time from another. Previous evidence suggests that it would be more appropriate to shift the focus to the importance of reallocating time spent in sedentary behaviour to time spent in physical activity. The aim of this study was to analyse the mutual replacement effect of different health behaviours on depressive tendencies by isotemporal substitution modelling (ISM) under the objective condition of considering a limited 24-h day. Second, we aimed to further explore the potential association between excessive or insufficient sleep duration and depressive symptoms. Methods A total of 10656 employees from 79 companies in four provinces of China participated in this survey. The Center for Epidemiological Studies Depression Scale (CES-D) was used to measure workers’ depressive tendencies. The duration of various types of physical activity was self-reported by workers based on the International Physical Activity Questionnaire (IPAQ). ISM was used to assess the associations of time spent in different activities on displacement of equivalent time spent on other activities with depression risk. Results A total of 10656 participants (89.5% of the sample) were included in the analysis. The ISM found that a 30-min unit of SB replaced with walking (OR, 95% CI: 0.83, 0.77–0.88), sleep (≤ 8 h) (OR, 95% CI: 0.77, 0.74–0.79), moderate physical activity (MPA) (OR, 95% CI: 0.87, 0.81–0.93) and vigorous physical activity (VPA) (OR, 95% CI: 0.91, 0.84–0.99) was significantly and negatively associated with the risk of depressive tendencies. When sleep duration was less than 8 h, each additional half hour of sleep time was significantly associated with a lower risk of depressive tendencies, and this association was no longer significant after 8 h. Conclusion Prolonged SB is common in the current workplace in China. Replacing an average of 30 min per day of SB with VPA and MPA, even walking is associated with less depression among workers. In addition, insufficient daily sleep is also an important risk factor for workers' depressive tendencies. These findings provide valuable evidence to promote mental health among occupational groups and support the development of healthy workplaces.

Abstract N 6-methyladenosine (m6A) modification is a dynamic, reversible process and is the most prevalent internal modification of RNA. This modification is regulated by three protein groups: methyltransferases (“writers”), demethylases (“erasers”), and m6A-binding proteins (“readers”). m6A modification and related enzymes could represent an optimal strategy to deepen the epigenetic mechanism. Numerous reports have suggested that aberrant modifications of m6A lead to aberrant expression of important viral genes. Here, we review the role of m6A modifications in viral replication and virus–host interactions. In particular, we focus on DNA and RNA viruses associated with human diseases, such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), human immunodeficiency virus (HIV)-1, Epstein–Barr virus (EBV), and Kaposi’s sarcoma-associated herpesvirus (KSHV). These findings will contribute to the understanding of the mechanisms of virus–host interactions and the design of future therapeutic targets for treatment of tumors associated with viral infections.

The present study aimed to optimize the ultrasonic wave and cellulase synergistic extraction technology of total flavonoids from Bambusae Caulis in Taeniam and evaluate their antioxidant capacity in vitro. Taking yield of total flavonoids as the metric, the appropriate amount of cellulase added, pH of extraction solvents, ethanol concentration, ultrasonic power, ultrasonic temperature, material-liquid ratio and ultrasonic time were scouted by single-factor experiments, and the optimal conditions for the extraction of total flavonoids from Bambusae Caulis in Taeniam were optimized by response surface methodology (RSM). Meanwhile, the antioxidant capacity was investigated in vitro using scavenging 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2'-azino-bis-3-ethylbenzothiaz-oline-6-sulfonic acid (ABTS) free radicals and iron ion reduction method (FRAP). As the result showed that the optimum extraction parameters were the amount of cellulase added: 5%, pH of extraction solvents: 4.7, ethanol concentration: 61%, ultrasonic power: 240 W, ultrasonic temperature: 60 ℃, material-liquid ratio: 1:30 (g/mL), ultrasonic time: 30 min. The total flavonoids yield of Bambusae Caulis in Taeniam was 0.83%±0.02% under these conditions, and the content of total flavonoids in Bambusae Caulis in Taeniam extract was 16.21%±0.42%. The results of antioxidant experiments showed that the total flavonoids could scavenge DPPH and ABTS+ radicals with IC50 values of 150.1 and 44.6 μg/mL, respectively, which were 1.22 and 1.27 times greater than VC. The ferric ion reducing ability of total flavonoids from Bambusae Caulis in Taeniam was slightly higher than that of VC. This optimized extraction process is simple and feasible, and the extracted total flavonoids shows strong antioxidant effects in vitro, which provides scientific evidence for the further study and exploit of flavonoids from Bambusae Caulis in Taeniam.

The loop closure detection (LCD) methods in Unmanned Aerial Vehicle (UAV) Visual Inertial Navigation System (VINS) are often affected by issues such as insufficient image texture information and limited observational perspectives, resulting in constrained UAV positioning accuracy and reduced capability to perform complex tasks. This study proposes a Bag-of-Words (BoW) LCD method based on Neural Radiance Field (NeRF), which estimates camera poses from existing images and achieves rapid scene reconstruction through NeRF. A method is designed to select virtual viewpoints and render images along the flight trajectory using a specific sampling approach to expand the limited observational angles, mitigating the impact of image blur and insufficient texture information at specific viewpoints while enlarging the loop closure candidate frames to improve the accuracy and success rate of LCD. Additionally, a BoW vector construction method that incorporates the importance of similar visual words and an adapted virtual image filtering and comprehensive scoring calculation method are designed to determine loop closures. Applied to VINS-Mono and ORB-SLAM3, and compared with the advanced BoW model LCDs of the two systems, results indicate that the NeRF-based BoW LCD method can detect more than 48% additional accurate loop closures, while the system’s navigation positioning error mean is reduced by over 46%, validating the effectiveness and superiority of the proposed method and demonstrating its significant importance for improving the navigation accuracy of VINS.

Radiotherapy is widely used in the management of advanced colorectal cancer (CRC). However, the clinical efficacy is limited by the safe irradiated dose. Sensitizing tumor cells to radiotherapy via interrupting DNA repair is a promising approach to conquering the limitation. The BRCA1–BARD1 complex has been demonstrated to play a critical role in homologous recombination (HR) DSB repair, and its functions may be affected by HERC2 or BAP1. Accumulated evidence illustrates that the ubiquitination–deubiquitination balance is involved in these processes; however, the precise mechanism for the cross-talk among these proteins in HR repair following radiation hasn't been defined. Through activity-based profiling, we identified PT33 as an active entity for HR repair suppression. Subsequently, we revealed that BAP1 serves as a novel molecular target of PT33 via a CRISPR-based deubiquitinase screen. Mechanistically, pharmacological covalent inhibition of BAP1 with PT33 recruits HERC2 to compete with BARD1 for BRCA1 interaction, interrupting HR repair. Consequently, PT33 treatment can substantially enhance the sensitivity of CRC cells to radiotherapy in vitro and in vivo. Overall, these findings provide a mechanistic basis for PT33-induced HR suppression and may guide an effective strategy to improve therapeutic gain.

Abstract Background Limited published data suggests that absence of uplifts (minor pleasant events) is associated with clinical worsening in patients with chronic fatigue syndrome (CFS). The current study aimed to assess the relation of illness worsening to the trajectories of social and non-social uplifts and hassles in a six-month prospective study in CFS. Methods Participants were primarily in their 40s, female, white, and ill for over a decade. All participants (N = 128) met criteria for CFS. The interview-based global impression of change rating was used to classify individual outcomes as improved, unchanged, or worsened at six- month follow-up. Uplifts and hassles, both social and non-social, were assessed with the Combined Hassles and Uplifts Scale (CHUS). The CHUS was administered weekly in online diaries over six months. Linear mixed effect models were utilized to examine linear trends for hassles and uplifts. Results No significant differences were found between the three global outcome groups for age, sex, or illness duration; however, work status was significantly lower for the non-improved groups (p

Abstract Background Chylothorax is a condition that can be challenging to diagnose due to its nonspecific clinical presentation. Several biochemical parameters of chylous pleural effusion have been identified as important indicators for the diagnosis of chylothorax. Lymphoscintigraphy is utilized to assess chylothorax and determine the location of chyle leakage. The present study aimed to evaluate the correlation between the biochemical parameters of chylous pleural effusion and 99mTc-dextran (99mTc-DX) lymphoscintigraphy in diagnosing chylothorax. Material and methods A total of 120 patients were enrolled in the study, 83 of the patients with unilateral chylothorax, and 37 with bilateral chylothorax. All patients underwent both 99mTc-DX lymphoscintigraphy and pleural effusion laboratory analysis. The 99mTc-DX lymphoscintigraphy images were categorized as positive or negative groups based on the presence or absence of abnormal radioactive tracer accumulation in the thorax, respectively. The biochemical parameters of the two groups were subsequently compared. Results Among these patients, 101 (84.17%) had exudative effusions, while 19 (15.83%) had transudative effusions, as determined by the levels of pleural effusion protein, lactate dehydrogenase and cholesterol. Abnormal tracer accumulation in thorax was observed in 82 patients (68.33%). Our findings indicated that lymphoscintigraphy results were not associated with exudative and transudative chylothorax (P = 0.597). The lymphoscintigraphy positive group displayed significantly higher levels of pleural effusion triglyceride and pleural effusion triglyceride/serum triglyceride ratio in all biochemical parameters, compared to the negative group (P = 0.000 and P = 0.005). We identified cutoff values of 2.870 mmol/L for pleural effusion triglycerides and 4.625 for pleural effusion triglyceride/serum triglyceride ratio, respectively, which can facilitate differentiating the positive and negative cases on lymphoscintigraphy. Conclusion Lymphoscintigraphy technique is a dependable diagnostic tool for the qualitative assessment of chylous pleural effusion. Higher pleural effusion triglyceride level and pleural effusion triglyceride/serum triglyceride ratio indicate a positive result in patients with chylothorax on lymphoscintigraphy, with the cutoff values of 2.870 mmol/L and 4.625 aiding in the diagnosis.

Abstract Background Lung adenocarcinoma (LUAD) is a common subtype of non‐small cell lung cancer with high morbidity and mortality rates and is usually detected at advanced stages because of the early onset of metastasis. Adenosine deaminase RNA‐specific 1 (ADAR1) is an RNA editing enzyme that catalyzes the important physiological process of adenosine‐to‐inosine editing and has been shown to participate in the progression of LUAD. Increasing evidence has suggested that immune infiltration of the tumor immune microenvironment has prognostic value for most human solid organ malignancies; however, much is unknown about the functions of ADAR1. Methods The expression of ADAR1 was analyzed in The Cancer Genome Atlas ‐LUAD database and validated in our LUAD cohort. To assess the prognostic value of ADAR1, Kaplan‐Meier survival analyses and Cox regression analyses were carried out in LUAD cohorts. The association between ADAR1 and LUAD immune infiltrates via analyses of cell‐type identification by estimating relative subsets of known RNA transcripts. Furthermore, multiplex immunohistochemistry was used to confirm the relationship between ADAR1 expression and immune cells in the present cohort of patients with LUAD. Results ADAR1 was highly expressed in LUAD tissues and closely correlated with lymph node metastasis (LNM) (p

Background: Repurposing antifungal drugs in cancer therapy has attracted unprecedented attention in both preclinical and clinical research due to specific advantages, such as safety, high-cost effectiveness and time savings compared with cancer drug discovery. The surprising and encouraging efficacy of antifungal drugs in cancer therapy, mechanistically, is attributed to the overlapping targets or molecular pathways between fungal and cancer pathogenesis. Advancements in omics, informatics and analytical technology have led to the discovery of increasing “off-site“ targets from antifungal drugs involved in cancerogenesis, such as smoothened (D477G) inhibition from itraconazole in basal cell carcinoma. Aim of review: This review illustrates several antifungal drugs repurposed for cancer therapy and reveals the underlying mechanism based on their original target and “off-site” target. Furthermore, the challenges and perspectives for the future development and clinical applications of antifungal drugs for cancer therapy are also discussed, providing a refresh understanding of drug repurposing. Key scientific concepts of review: This review may provide a basic understanding of repurposed antifungal drugs for clinical cancer management, thereby helping antifungal drugs broaden new indications and promote clinical translation.

BackgroundLow-grade fibromyxoid sarcoma (LGFMS) is a rare type of soft tissue sarcoma that often involves the deep soft tissue of the extremities and trunk in young and middle-aged adults. It is uncommon in the elderly. Here we discuss a case of LGFMS in an elderly patient who had recurrence and metastasis within 2 years of resection of the primary tumor.Case reportA 71-year-old LGFMS patient was presented with a mass in the left forearm accompanied by pain and numbness from the left upper arm to fingers. The patient subsequently underwent 3 surgical resections, although she had 3 recurrences within 6 months after the initial diagnosis. Considering the malignant biological behavior of the tumor, an amputation at 5 cm above the elbow was eventually performed. However, recurrence in the extremity of the stump and chest wall metastasis were observed 2 years after amputation. Then resection of the metastases, radiotherapy and particle implantation therapy were performed. The patient is currently undergoing follow-up and has no evidence of recurrence.ConclusionIn our case, multiple early postoperative recurrences may be associated with a positive margin at initial operation. The patient underwent a total of 5 operations including local resection of the primary tumor, twice wide resections, amputation and metastatic surgery with 4 early postoperative recurrences and metastases within 4 years, suggesting that LGFMS may have highly invasive biological behavior. Our case demonstrated that early aggressive surgical treatment is recommended for LGFMS patients with a positive margin at initial operation and patients who had recurrence even after wide resection rather than local resection. Further research is needed to develop more effective treatment options for rapidly progress and highly aggressive LGFMS.

Abstract Radiation pneumonitis (RP) affects both patients and physicians during radiation therapy for lung cancer. To date, there are no effective drugs for improving the clinical outcomes of RP. The activation of angiotensin-converting enzyme 2 (ACE2) improves experimental acute lung injury caused by severe acute respiratory syndrome coronavirus, acid inhalation, and sepsis. However, the effects and underlying mechanisms of ACE2 in RP remain unclear. Therefore, this study aimed to investigate the effects of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers on RP and ACE2/angiotensin-(1–7)/Mas receptor pathway activation. We found that radiotherapy decreased the expression of ACE2 and that overexpression of ACE2 alleviated lung injury in an RP mouse model. Moreover, captopril and valsartan restored ACE2 activation; attenuated P38, ERK, and p65 phosphorylation; and effectively mitigated RP in the mouse model. Further systematic retrospective analysis illustrated that the incidence of RP in patients using renin-angiotensin system inhibitors (RASis) was lower than that in patients not using RASis (18.2% vs. 35.8% at 3 months, p = 0.0497). In conclusion, the current findings demonstrate that ACE2 plays a critical role in RP and suggest that RASis may be useful potential therapeutic drugs for RP.

Abstract To assess biobehavioral sex differences in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) utilizing a low burden exercise protocol, 22 females and 15 males with ME/CFS and 14 healthy controls underwent two six-min walk tests. Fifteen daily assessments were scheduled for fatigue and function ratings and heart monitoring. Six-min walk tests were conducted on days 8 and 9. The ME/CFS group showed high self-report fatigue and impaired physical function, whereas healthy controls did not show fatigue or function abnormalities. In patients, no significant post-exercise changes were found for heart rate variability (HRV); however, heart rate decreased in ME/CFS males from Day 14 to Day 15 (p = 0.046). Female patients showed increased fatigue (p = 0.006) after the initial walk test, but a downward slope (p = 0.008) in fatigue following the second walk test. Male patients showed a decrease in self-report work limitation in the days after exercise (p = 0.046). The healthy control group evidenced a decrease in HRV after the walk tests from Day 9–14 (p = 0.038). This pilot study did not confirm hypotheses that females as compared to males would show slower exercise recovery on autonomic or self-report (e.g. fatigue) measures. A more exertion-sensitive test may be required to document prolonged post-exertional abnormalities in ME/CFS. Trial registration: NCT NCT03331419.

As a novel antioxidant, a growing body of studies has documented the diverse biological effects of molecular hydrogen (H2) in a wide range of organisms, spanning animals, plants, and microorganisms. Although several possible mechanisms have been proposed, they cannot fully explain the extensive biological effects of H2. Mitochondria, known for ATP production, also play crucial roles in diverse cellular functions, including Ca2+ signaling, regulation of reactive oxygen species (ROS) generation, apoptosis, proliferation, and lipid transport, while their dysfunction is implicated in a broad spectrum of diseases, including cardiovascular disorders, neurodegenerative conditions, metabolic disorders, and cancer. This review aims to 1) summarize the experimental evidence on the impact of H2 on mitochondrial function; 2) provide an overview of the mitochondrial pathways underlying the biological effects of H2, and 3) discuss H2 metabolism in eukaryotic organisms and its relationship with mitochondria. Moreover, based on previous findings, this review proposes that H2 may regulate mitochondrial quality control through diverse pathways in response to varying degrees of mitochondrial damage. By combining the existing research evidence with an evolutionary perspective, this review emphasizes the potential hydrogenase activity in mitochondria of higher plants and animals. Finally, this review also addresses potential issues in the current mechanistic study and offers insights into future research directions, aiming to provide a reference for future studies on the mechanisms underlying the action of H2.

Best management practices (BMPs) have wide application in non-point source (NPS) pollution abatement in agricultural watersheds. Multivariate analysis of BMPs reduction effects taking their randomness and correlations into account is significant to spatial optimization of BMPs configuration. However, quantifying the correlations among high-dimensional random variables of BMPs effects is challenging and remains unexplored thoroughly. This study coupled the SWAT with the Vine Copula model to conduct multivariate analysis of BMPs reduction effects considering their randomness caused by hydro-meteorological variability along with correlations among different indicators (ammonium nitrogen, NH3-N; and total phosphorus, TP) and BMPs. The coupled model was applied to evaluate the multi-indicator effect of individual BMP and combined effect of various BMPs in the upper Boyang River basin, China. Results showed that bivariate copulas and three-dimensional vine copulas can efficaciously describe the dependence of BMPs effects. Simulation results indicate 43–100% probabilities of 45% NH3-N loads reduction, while 0–79% probabilities of 45% TP loads reduction for combined BMPs scenarios. Besides, the joint probabilities of different indicators in combined BMPs scenarios are generally lower than separate probabilities with 0–21% decrease, which is similar to individual BMP. Generally, joint probabilities using copulas can provide more accurate and factual knowledge of the risk and dependability of implementation of BMPs than univariate variables. The proposed model can conduct multivariate analysis of BMPs reduction effects and has great prospect in the future risk-based decision-making of NPS pollution management.

Abstract Objectives Emerging evidence have demonstrated that oligometastatic non-small cell lung cancer (NSCLC) can achieve clinical benefit from local consolidative therapy. Bone oligometastasis is common in advanced lung cancer, but little is known about its molecular features. The purpose of our study aimed to investigate the genomic landscape bone oligometastatic NSCLC. Methods We collected paired blood and tissue samples from 31 bone oligometastatic NSCLC patients to make a comprehensive analysis of mutations by performing next-generation sequencing. Results A total of 186 genomic mutations were detected from 105 distinct cancer-relevant genes, with a median number of 6 alterations per tumor. The most frequently mutated genes were EGFR (58%) and TP53 (55%), followed by KRAS (16%), CDKN2A (13%) and MET (13%). The signatures related to smoking, aging, homologous recombination deficiency and APOBEC were identified as the most important mutational processes in bone oligometastasis. The median tumor mutation burden was 4.4 mutations/Mb. Altogether, genetic alterations of bone oligometastasis are highly targetable that 74.19% of patients had at least one actionable alteration that was recommended for targeted therapy based on the OncoKB evidence. Of these patients, 16.13% had two actionable alterations that could potentially benefit from a different combination of targeted drugs to achieve better outcomes. Conclusion Our research comprehensively elucidates the genomic features of bone oligometastatic NSCLC patients, which may optimize individualized cancer treatment in the era of precision medicine.

Root and foliar litter inputs are the primary sources of carbon and nutrients for soil fauna and microorganisms, yet we still lack a quantitative assessment to evaluate the effects of root and foliar litter on various groups of soil organisms across terrestrial ecosystems. Here, we compiled 978 paired observations from 68 experimental sites to assess the directions and magnitudes of adding and removing foliar and root litter on the soil faunal density and microbial biomass that was evaluated by phospholipid fatty acids (PLFAs) across forests and grasslands worldwide. We found that litter addition had only a marginal effect on soil faunal density but significantly increased the soil total microbial-, fungal- and bacterial-PLFAs by 13%, 14%, and 10%, respectively, across ecosystems, suggesting that the soil microbial community is more sensitive to carbon source addition than soil fauna, particularly in soils with low carbon to nitrogen ratios. In contrast, removing litter significantly decreased the soil faunal density by 17% but had few effects on soil microorganisms. Compared with foliar litter, root litter input had a more positive effect on the development of soil fungal taxa. The effect of both litter addition and removal on soil faunal density and microbial biomass did not differ between humid and arid regions, but a greater influence was observed in grasslands than in forests for soil microbial community. Our results highlight that the increasing litter production under a global greening scenario would stimulate microbial activity in grasslands more than in forests, and this stimulation would be greater for soil microbes than soil fauna.

Key points Quantification of BMAT valuable information for the clinical diagnosis and treatment of OP. DECT can accurately quantify the BMAT of vertebrae. DECT has the same applicability as MRI in the study of OP.

The use of radiotherapy for hypopharyngeal cancer (HC) treatment is increasing, and it is currently the primary treatment option for this cancer. However, radioresistance occurs in a proportion of patients. Here, we found that radiation increased proteasomal gene expression and that proteasome assembly was dependent on the induction of transcription factor NRF1 in HC. Through screening assays, we identified a mechanism by which proteasome-mediated degradation of DEP domain-containing mTOR-interacting protein (DEPTOR) contributes to the elevation of mTORC1 signaling after radiation. Therefore, after treatment with proteasome inhibitors (PIs), stabilization of DEPTOR inhibited mTORC1 signaling elevated by radiation and ultimately sensitized HC to radiotherapy. Mechanically, PIs not only interrupted the deubiquitination and degradation of DEPTOR but also suppressed the ubiquitination of DEPTOR mediated by β-TrCP. Clinically, the high levels of DEPTOR in HC cells were associated with sensitivity to radiotherapy and favorable prognosis. Stabilizing DEPTOR through targeting proteasome-mediated degradation is a potential strategy for sensitizing HC to radiotherapy.

Abstract Objectives To evaluate the usefulness of Contrast-enhanced ultrasound (CEUS) in the diagnosis and differential diagnosis of Polypoid lesions of gallbladder (PLGs) ≥ 1 cm. Methods A prospective analysis was performed on 180 patients with PLGs ≥ 1 cm. 175 cases were confirmed by pathological diagnosis and the remaining were confirmed by other imaging findings. The characteristics of lesions on conventional Ultrasonography (US) and CEUS were recorded. Results Significant differences were observed in enhancement patterns between benign and malignant PLGs during both arterial (P

Abstract Sepsis-associated encephalopathy (SAE) is characterized by brain dysfunction during sepsis, without central nervous system infection. Here, we explored the molecular basis of brain injury in preterm infants with SAE. From Jan 2016 to Dec 2019, a total of 20 preterm infants were hospitalized in the neonatal intensive care unit (NICU) of our hospital, including 10 preterm infants with SAE (SAE group) and 10 preterm infants without encephalopathy after sepsis (no SAE group). Among the 20 premature infants, there were 12 males and 8 females, with mean gestational age 31.0 ± 2.46 weeks, 7 cases with birth weight ≤ 1500 g and 13 cases with birth weight 1500–2500 g. Blood cultures were negative in 6 cases and positive in 14 cases, including 10 cases of Gram-negative and 4 cases of Gram-positive bacteria, respectively. Expression levels of messenger RNA (mRNA) and MicroRNA (miRNA) were analyzed in peripheral blood samples from both groups during sepsis. There were 1858 upregulated and 2226 downregulated mRNAs [fold-change (FC) > |2|, p |2|, p

The high disease burden of type 2 diabetes seriously affects the quality of life of patients, and with the deep integration of the Internet and healthcare, the application of electronic tools and information technology to has become a trend for disease management. The aim of this study was to evaluate the effectiveness of different forms and durations of E-health interventions in achieving glycemic control in type 2 diabetes patients. PubMed, Embase, Cochrane, and Clinical Trials.gov were searched for randomized controlled trials reporting different forms of E-health intervention for glycemic control in type 2 diabetes patients, including comprehensive measures (CM), smartphone applications (SA), phone calls (PC), short message service (SMS), websites (W), wearable devices (WD), and usual care. The inclusion criteria were as follows: (1) adults (age≥18) with type 2 diabetes mellitus; (2) intervention period ≥1 month; (3) outcome HbA1c (%); and (4) randomized control of E-health based approaches. Cochrane tools were used to assess the risk of bias. R 4.1.2 was used to conduct the Bayesian network meta-analysis. A total of 88 studies with 13,972 type 2 diabetes patients were included. Compared to the usual care group, the SMS-based intervention was superior in reducing HbA1c levels (mean difference (MD)-0.56, 95% confidence interval (CI): -0.82 to -0.31), followed by SA (MD-0.45, 95% CI: -0.61 to -0.30), CM (MD-0.41, 95% CI: -0.57 to -0.25), W (MD-0.39, 95% CI: -0.60 to -0.18) and PC (MD-0.32, 95% CI: -0.50 to -0.14) (p < 0.05). Subgroup analysis revealed that intervention durations of ≤6 months were most effective. All type of E-health based approaches can improve glycemic control in patients with type 2 diabetes. SMS is a high-frequency, low-barrier technology that achieves the best effect in lowering HbA1c, with ≤6 months being the optimal intervention duration.Systematic review registrationhttps://www.crd.york.ac.uk/prospero, identifier CRD42022299896.

IntroductionDepression is a prevalent mental disorder that has an irreversible impact on people’s health status. Unhealthy lifestyles are modifiable and influence mental health significantly. The purpose of this study was to explore the impact of different unhealthy lifestyles and their patterns on depressive symptoms.MethodsThe data for this study were obtained from the 2017 Community Diagnostic survey in Daxing District, Beijing. It was a cross-sectional study that included 6,252 samples. The Patient Health Questionnaire version 9 was used to measure depressive symptoms, and the self-administered questionaires were used to investigate five unhealthy lifestyles, including sleep deprivation, the inadequate intake of fruits and vegetables, physical inactivity, smoking, and excessive alcohol consumption. Respondents were assigned 1 point for each of their unhealthy lifestyles, and their overall unhealthy lifestyle scores were calculated. The total scores of unhealthy lifestyles ranged from 0 to 5. Descriptive analyses and Firth’s logistic regression model were used to analyze the relationship between unhealthy lifestyle and depression symptoms.ResultsIt was found that 12.1% of the participants had depressive symptoms. The respondents whose unhealthy lifestyle scores were 2 (OR1.45, 95%CI:1.01 to 2.12), 3 (OR2.29, 95%CI:1.57 to 3.42), 4 (OR 3.04, 95%CI:1.96 to 4.76), or 5 (OR4.08, 95%CI:2.09 to 7.78) were more likely to experience depressive symptoms in comparison with those whose unhealthy lifestyle scores were 0, and the OR increased with the unhealthy lifestyle scores. When the participants had 3 or more unhealthy lifestyles at the same time, different combination patterns of unhealthy lifestyles showed a different effect on depression. The OR was 3.01 (95%CI:1.45 to 5.95) for the combination of sleep deprivation—insufficient intake of fruit and vegetables—excessive alcohol consumption, and was 2.89 (95%CI:1.52 to 5.25) for the combination of sleep deprivation—insufficient intake of fruit and vegetables—physical inactivity—excessive alcohol consumption.DiscussionThe co-existence of multiple unhealthy behavioral lifestyles are associated with depressive symptoms. Among the five unhealthy lifestyles, sleep deprivation and the inadequate intake of fruits and vegetables may have a greater impact on depression.

Baculovirus expression vector system (BEVS) is a powerful and versatile platform for recombinant protein production in insect cells. As the most frequently used baculovirus, Autographa californica multiple nucleopolyhedrovirus (AcMNPV) encodes 155 open reading frames (ORFs), including a considerable number of non-essential genes for the virus replication in cell culture. Studies have shown that protein production in BEVS can be improved by removing some viral dispensable genes, and these AcMNPV vectors also offer the possibility of accommodating larger exogenous gene fragments. In this study, we, respectively, deleted 14 DNA fragments from AcMNPV genome, each of them containing at least two contiguous genes that were known nonessential for viral replication in cell culture or functionally unknown. The effects of these fragment-deletions on virus replication and exogenous protein production were examined. The results showed that 11 of the 14 fragments, containing 43 genes, were dispensable for the virus replication in cultured cells. By detecting the expression of intracellularly expressed and secreted reporter proteins, we demonstrated that nine of the fragment-deletions benefited protein production in Sf9 cells and/or in High Five cells. After combining the deletion of some dispensable fragments, we obtained two AcMNPV vectors shortened by more than 10 kb but displayed an improved capacity for recombinant protein production. The deletion strategies used in this study has the potential to further improve the BEVS.

BackgroundMental health problems are prevalent among men who have sex with men (MSM). Social capital and perceived stress may affect the mental health of MSM. The purpose of this study was to understand the current status of mental health, social capital, and perceived stress among MSM and to explore which variables are influential factors of mental health.MethodsThis study adopted a convenience sampling method and posted recruitment information through online social platforms (Blued, QQ, and WeChat) from January 2022 to June 2022 to recruit participants. The questionnaire included a demographic questionnaire, Social Capital Questionnaire (SCQ), Perceived Stress Scale (PSS), and Self-Reporting Questionnaire 20 (SRQ-20). Descriptive analyses of demographic characteristics, social capital, perceived stress, and mental health were conducted using percentages, median, interquartile range, means, and standard deviations. One-way ANOVA and independent-samples t-test were used to test the relationship between demographic characteristics and mental health, and multiple linear regression was used to analyze which variables were influencing factors of mental health. SPSS 24.0 was used for data analysis, and significant differences were found at p

Cancer treatment is hampered by resistance to conventional therapeutic strategies, including chemotherapy, immunotherapy, and targeted therapy. Redox homeostasis manipulation is one of the most effective innovative treatment techniques for overcoming drug resistance. Reactive oxygen species (ROS), previously considered intracellular byproducts of aerobic metabolism, are now known to regulate multiple signaling pathways as second messengers. Cancer cells cope with elevated amounts of ROS during therapy by upregulating the antioxidant system, enabling tumor therapeutic resistance via a variety of mechanisms. In this review, we aim to shed light on redox modification and signaling pathways that may contribute to therapeutic resistance. We summarized the molecular mechanisms by which redox signaling-regulated drug resistance, including altered drug efflux, action targets and metabolism, enhanced DNA damage repair, maintained stemness, and reshaped tumor microenvironment. A comprehensive understanding of these interrelationships should improve treatment efficacy from a fundamental and clinical research point of view.