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A substantial percentage of international students are placed on academic probation each year. This study explored the challenges and resilience characteristics of Chinese international students placed on academic probation in their first year of college. Semi-structured interviews were conducted with nine probationary Chinese international students, and the data were analyzed using a thematic analysis approach. The results indicated that challenges with daily routine, reduced adult supervision, inadequate academic preparation, and limited participation in the application process were the main factors that contributed to their academic probation. Proactivity, independence, and flexible thinking were important resilience characteristics that may have helped students cope positively with stresses relating to academic probation. Targeted institutional support could be strengthened. Implications, limitations, and suggestions for future research are also discussed.

Abstract Acute ischemic stroke (AIS) is a major global health concern due to its high mortality and disability rates. Hemorrhagic transformation, a common complication of AIS, leads to poor prognosis yet lacks effective treatments. Preclinical studies indicate that hyperbaric oxygen (HBO) treatment within 12 h of AIS onset alleviates ischemia/reperfusion injuries, including hemorrhagic transformation. However, clinical trials have yielded conflicting results, suggesting some underlying mechanisms remain unclear. In this study, we confirmed that HBO treatments beginning within 1 h post reperfusion significantly alleviated the haemorrhage and neurological deficits in hyperglycemic transient middle cerebral arterial occlusion (tMCAO) mice, partly due to the inhibition of the NLRP3 inflammasome-mediated pro-inflammatory response in microglia. Notably, reactive oxygen species (ROS) mediate the anti-inflammatory and protective effect of early HBO treatment, as edaravone and N-Acetyl-l-Cysteine (NAC), two commonly used antioxidants, reversed the suppressive effect of HBO treatment on NLRP3 inflammasome-mediated inflammation in microglia. Furthermore, NAC countered the protective effect of early HBO treatment in tMCAO mice with hyperglycemia. These findings support that early HBO treatment is a promising intervention for AIS, however, caution is warranted when combining antioxidants with HBO treatment. Further assessments are needed to clarify the role of antioxidants in HBO therapy for AIS.

Abstract Background Migraine is a neurological disorder characterized by complex, widespread, and sudden attacks with an unclear pathogenesis, particularly in chronic migraine (CM). Specific brain regions, including the insula, amygdala, thalamus, and cingulate, medial prefrontal, and anterior cingulate cortex, are commonly activated by pain stimuli in patients with CM and animal models. This study employs fluorescence microscopy optical sectioning tomography (fMOST) technology and AAV-PHP.eB whole-brain expression to map activation patterns of brain regions in CM mice, thus enhancing the understanding of CM pathogenesis and suggesting potential treatment targets. Methods By repeatedly administering nitroglycerin (NTG) to induce migraine-like pain in mice, a chronic migraine model (CMM) was established. Olcegepant (OLC) was then used as treatment and its effects on mechanical pain hypersensitivity and brain region activation were observed. All mice underwent mechanical withdrawal threshold, light-aversive, and elevated plus maze tests. Viral injections were administered to the mice one month prior to modelling, and brain samples were collected 2 h after the final NTG/vehicle control injection for whole-brain imaging using fMOST. Results In the NTG-induced CMM, mechanical pain threshold decreased, photophobia, and anxiety-like behavior were observed, and OLC was found to improve these manifestations. fMOST whole-brain imaging results suggest that the isocortex-cerebral cortex plate region, including somatomotor areas (MO), somatosensory areas (SS), and main olfactory bulb (MOB), appears to be the most sensitive area of activation in CM (P

Abstract Crizotinib carries an FDA hepatotoxicity warning, yet analysis of the FAERS database suggests that the severity of its hepatotoxicity risks, including progression to hepatitis and liver failure, might be underreported. However, the underlying mechanism remains poorly understood, and effective intervention strategies are lacking. Here, mRNA-sequencing analysis, along with KEGG and GO analyses, revealed that DEGs linked to Crizotinib-induced hepatotoxicity predominantly associate with the ferroptosis pathway which was identified as the principal mechanism behind Crizotinib-induced hepatocyte death. Furthermore, we found that ferroptosis inhibitors, namely Ferrostatin-1 and Deferoxamine mesylate, significantly reduced Crizotinib-induced hepatotoxicity and ferroptosis in both in vivo and in vitro settings. We have also discovered that overexpression of AAV8-mediated Nrf2 could mitigate Crizotinib-induced hepatotoxicity and ferroptosis in vivo by restoring the imbalance in glutathione metabolism, iron homeostasis, and lipid peroxidation. Additionally, both Stat1 deficiency and the Stat1 inhibitor NSC118218 were found to reduce Crizotinib-induced ferroptosis. Mechanistically, Crizotinib induces the phosphorylation of Stat1 at Ser727 but not Tyr701, promoting the transcriptional inhibition of Nrf2 expression after its entry into the nucleus to promote ferroptosis. Meanwhile, we found that MgIG and GA protected against hepatotoxicity to counteract ferroptosis without affecting or compromising the anti-cancer activity of Crizotinib, with a mechanism potentially related to the Stat1/Nrf2 pathway. Overall, our findings identify that the phosphorylation activation of Stat1 Ser727, rather than Tyr701, promotes ferroptosis through transcriptional inhibition of Nrf2, and highlight MgIG and GA as potential therapeutic approaches to enhance the safety of Crizotinib-based cancer therapy.

Abstract Background Community-Acquired Pneumonia (CAP) remains a significant global health concern, with a subset of cases progressing to Severe Community-Acquired Pneumonia (SCAP). This study aims to develop and validate a CT-based radiomics model for the early detection of SCAP to enable timely intervention and improve patient outcomes. Methods A retrospective study was conducted on 115 CAP and SCAP patients at Southern Medical University Shunde Hospital from January to December 2021. Using the Pyradiomics package, 107 radiomic features were extracted from CT scans, refined via intra-class and inter-class correlation coefficients, and narrowed down using the Least Absolute Shrinkage and Selection Operator (LASSO) regression model. The predictive performance of the radiomics-based model was assessed through receiver operating characteristic (ROC) analysis, employing machine learning classifiers such as k-Nearest Neighbors (KNN), Support Vector Machine (SVM), Logistic Regression (LR), and Random Forest (RF), trained and validated on datasets split 7:3, with a training set (n = 80) and a validation set (n = 35). Results The radiomics model exhibited robust predictive performance, with the RF classifier achieving superior precision and accuracy compared to LR, SVM, and KNN classifiers. Specifically, the RF classifier demonstrated a precision of 0.977 (training set) and 0.833 (validation set), as well as an accuracy of 0.925 (training set) and 0.857 (validation set), suggesting its superior performance in both metrics. Decision Curve Analysis (DCA) was utilized to evaluate the clinical efficacy of the RF classifier, demonstrating a favorable net benefit within the threshold ranges of 0.1 to 0.8 for the training set and 0.2 to 0.7 for the validation set. Conclusions The radiomics model developed in this study shows promise for early SCAP detection and can improve clinical decision-making.

Enzyme-assisted ultrasonic extraction was employed to extract polysaccharides from white lilacs. The effects of various experimental conditions on the yield of polysaccharides from white lilacs were systematically analyzed using the response surface methodology (RSM). The crude extract was purified through DEAE-52 cellulose column and Sephadex G-100 gel column chromatography. High-performance gel permeation chromatography (HPGPC), ion chromatography (IC), ultraviolet spectrum analysis, Fourier infrared spectroscopy (FTIR) and scanning electron microscopy (SEM) were utilized for characterization of the polysaccharide structure and its antioxidant activity in vitro was investigated. The results demonstrated that the optimal extraction process for polysaccharides from white lilacs involved ultrasonic power 150 W, ultrasonic time 40 min, ultrasonic temperature 40 ℃, enzyme dosage 2.2%, solid-liquid ratio 1:40 g/mL. Under these conditions, the yield of polysaccharides was 3.03%±0.09%. The polysaccharides were purified using a DEAE-52 cellulose column, and the main component SP-c was collected. Subsequently, SP-c-1 was obtained through a Sephadex G-100 gel column. The monosaccharide composition and molar ratio of SP-c-1 were galacturonic acid, arabinose, galactose, rhamnose, glucose, glucuronic acid, xylose=18.39:11.13:8.96:2.61:1:0.83:0.57, respectively. The weight-average molecular weight (Mw) of SP-c-1 was 14069 Da, and the numerical mean molecular weight (Mn) was 13637 Da. SP-c-1 had the characteristic absorption peak of polysaccharide and contained D-grape pyranose configuration. The half-inhibitory concentration (IC50) of SP-c-1 on DPPH and ABTS+ free radicals was 0.87 and 1.355 mg/mL, respectively. Overall results indicate that SP-c-1 exhibits significant antioxidant activity.

Abstract Quinoa is a full‐nutrition food; however, its poor flavor and small size make it not the best food option for direct consumption. In this study, a quinoa snack (QS, a cake) was developed, and the aroma profile of the products was improved by adding jujube fruit powder (made from dried jujube fruits, from 5% to 30%). Gas chromatography mass spectrum (GC–MS) combined with electronic nose (e‐nose) was applied for characterizing the aroma profiles of QS samples. Results showed a total of 26 aroma compounds were identified in QS samples by GC–MS, and 3‐methylbutanol (from 1525 μg/kg in QS‐30 to 3487 μg/kg in QS‐0), ethanol (from 1126 μg/kg in QS‐0 to 3581 μg/kg in QS‐30), hexanal (from 125.6 μg/kg in QS‐30 to 984.1 μg/kg in QS‐0), and acetaldehyde (from 531.9 μg/kg in QS‐30 to 191.1 μg/kg in QS‐0) were common. The e‐nose response of W1S (sensitive to methane, from 17.50 of QS‐0 to 93.85 of QS‐30) and W1W (sensitive to sulfur‐organic compounds of e‐nose, from 15.57 of QS‐0 to 39.50 of QS‐30) were significantly higher, and significant differences were presented among QS samples. In conclusion, the aroma profile of the QS sample was significantly (p

Background/purpose: Establishing effective irrigation methods is warranted to ensure the predictability of minimally invasive root canal instrumentation. This study aimed to compare the smear layer removal efficacy of different irrigation techniques in root canals instrumented with TruNatomy nickel-titanium rotary instruments. Materials and methods: Experiment 1: Extracted human mandibular incisors were instrumented using TruNatomy Shaping Files up to Small (#20/0.04), Prime (#26/0.04), or Medium (#36/0.03) (n = 17, each) and irrigated with EDTA, NaOCl, and again with EDTA using syringe irrigation (SI). Experiment 2: Extracted mandibular incisors were instrumented using TruNatomy Small and irrigated with EDTA and NaOCl as in Experiment 1, using (1) conventional laser-activated irrigation (LAI) with an erbium-doped yttrium aluminum garnet laser unit at 30 mJ/10 Hz (LAI 30/10) or 70 mJ/20 Hz (LAI 70/20), (2) photon-induced photoacoustic streaming (PIPS) (20 mJ/15 Hz), (3) ultrasonic-activated irrigation, or (4) SI (n = 13 each). Five additional canals served as negative controls (no irrigation). The smear layer on the canal wall was scored under scanning electron microscopy. Results: In Experiment 1, the TruNatomy Small group exhibited significantly higher smear layer scores compared to the other groups in the apical and middle thirds. In Experiment 2, the LAI 70/20 and PIPS groups demonstrated significantly lower smear layer scores compared to the LAI 30/10 and SI groups in the apical third. Conclusion: Conservative instrumentation using the TruNatomy Small reduced the cleaning efficacy of irrigation. However, PIPS performed satisfactory for smear layer removal without injury to the root canal wall.

ABSTRACTMastering the changes in the planting area of crops are critical for formulating sustainable agricultural development strategies. The Landsat 9 satellite provides continuous observational data for crop mapping. It is necessary to evaluate the potential of Landsat 9 images for canola mapping. According to literatures, some canola indices have been proposed in relation to the spectral features of the yellow canola flower, such as the canola ratio index (CRI), normalised difference yellowness index (NDYI), canola index (CI), canola flower index (CFI), normalised difference rapeseed flower index (NRFI) and winter rapeseed index (WRI). However, it is unclear which index has more potential to extract canola based on the Landsat 9 images. Therefore, the potentials of these indices for canola mapping were quantitatively compared by using different classification methods including supervised and unsupervised classification methods. For supervised classification methods and the CFI, the overall accuracy of canola mapping was above 90% and the kappa coefficient was above 0.8. For unsupervised classification methods, CFI also performs best. It was demonstrated that the CFI outperformed the other five indices for canola mapping. It was also confirmed that Landsat 9 images and the CFI exhibit promising potential for canola mapping via quantitative comparison.

Abstract Background The risk of asthma in patients with psoriasis has been identified in previous studies, but the bidirectional association between the two has not been fully explored. Methods We thoroughly searched PubMed, Embase, and the Cochrane Library to find relevant observational studies published from the inception of these databases to October 2023. All the risk and bias assessments were analyzed by STATA 16.0. Where the heterogeneity was less than 50%, the fixed effect model was utilized. While where the level of heterogeneity was more than 50%, the random effect model was applied. Moreover, to identify publication bias, a visual funnel chart, and Egger’s test were applied. Results A total of 12,396,911 participants from 16 studies, published between 2011 and 2023 were included in this meta-analysis. We found that psoriasis patients had a higher risk of developing asthma (OR = 1.48, 95%CI 1.28–1.68). Meanwhile, asthma patients also had a higher overall risk of developing psoriasis (OR = 1.33, 95%CI 1.23–1.44). In the subgroup analysis, we found that the type of study, age, and severity of the psoriasis were significant factors in the survey of asthma risk in psoriasis patients. Conclusions In the present systematic review and meta-analysis, we found a bidirectional association between psoriasis and asthma with significantly increased risk. As a result, clinicians should make patients aware of the connection between the two, particularly adolescents or patients with moderate to severe psoriasis who need to be informed about the rising likelihood of developing asthma. Trial registration Registration number CRD42023390111 .

Abstract Background The inhalational anesthetic isoflurane is commonly utilized in clinical practice, particularly in the field of pediatric anesthesia. Research has demonstrated its capacity to induce neuroinflammation and long-term behavioral disorders; however, the underlying mechanism remains unclear [1]. The cation-chloride cotransporters Na+–K+–2Cl−–1 (NKCC1) and K+–2Cl−–2 (KCC2) play a pivotal role in regulating neuronal responses to gamma-aminobutyric acid (GABA) [2]. Imbalances in NKCC1/KCC2 can disrupt GABA neurotransmission, potentially leading to neural circuit hyperexcitability and reduced inhibition following neonatal exposure to anesthesia [3]. Therefore, this study postulates that anesthetics have the potential to dysregulate NKCC1 and/or KCC2 during brain development. Methods We administered 1.5% isoflurane anesthesia to neonatal rats for a duration of 4 h at postnatal day 7 (PND7). Anxiety levels were assessed using the open field test at PND28, while cognitive function was evaluated using the Morris water maze test between PND31 and PND34. Protein levels of NKCC1, KCC2, BDNF, and phosphorylated ERK (P-ERK) in the hippocampus were measured through Western blotting analysis. Pro-inflammatory cytokines IL-1β, IL-6, and TNF-α were quantified using ELISA. Results We observed a decrease in locomotion trajectories within the central region and a significantly shorter total distance in the ISO group compared to CON pups, indicating that isoflurane induces anxiety-like behavior. In the Morris water maze (MWM) test, rats exposed to isoflurane exhibited prolonged escape latency onto the platform. Additionally, isoflurane administration resulted in reduced time spent crossing in the MWM experiment at PND34, suggesting long-term impairment of memory function. Furthermore, we found that isoflurane triggered activation of pro-inflammatory cytokines IL-1β, IL-6, and TNF-α; downregulated KCC2/BDNF/P-ERK expression; and increased the NKCC1/KCC2 ratio in the hippocampus of PND7 rats. Bumetadine (NKCC1 specific inhibitors) reversed cognitive damage and effective disorder induced by isoflurane in neonatal rats by inhibiting TNF-α activation, normalizing IL-6 and IL-1β levels, restoring KCC2 expression levels as well as BDNF and ERK signaling pathways. Based on these findings, it can be speculated that BDNF, P-ERK, IL-1β, IL-6 and TNF - α may act downstream of the NKCC1/KCC2 pathway. Conclusions Our findings provide evidence that isoflurane administration in neonatal rats leads to persistent cognitive deficits through dysregulation of the Cation-Chloride Cotransporters NKCC1 and KCC2, BDNF, p-ERK proteins, as well as neuroinflammatory processes.

Abstract Organic room-temperature phosphorescence materials have attracted extensive attention, but their development is limited by the stability and processibility. Herein, based on the on-line derivatization strategy, we report the urea-formaldehyde room-temperature phosphorescence materials which are constructed by polycondensation of aromatic diamines with urea and formaldehyde. Excitingly, urea-formaldehyde room-temperature phosphorescence materials achieve phosphor lifetime up to 3326 ms. There may be two ways to enhance phosphorescence performance, one is that the polycondensation of aromatic diamine with urea and formaldehyde promotes spin-orbit coupling, and another is that the imidazole derivatives derived from the condensation of aromatic o-diamine with formaldehyde maintains low levels of energy level difference and spin-orbit coupling, thus achieving ultra-long afterglow. Surprisingly, urea-formaldehyde room-temperature phosphorescence materials exhibit tunable phosphorescence emission in electrostatic field. Accordingly, 1,4-phenylenediamine, urea, and formaldehyde are copolymerized and self-assembled into phosphorescence microspheres with different electrostatic potential strengths. By mixing 1 wt% 1,4-phenylenediamine polycondensation microspheres with 1,4-phenylenediamine free microspheres, phosphor lifetime of the composite could be regulated from 27 ms to 123 ms. Moreover, vulcanization process enables precise shaping of urea-formaldehyde room-temperature phosphorescence materials. This work not only demonstrates that urea-formaldehyde room-temperature phosphorescence materials are promising candidates for organic phosphors, but also exhibits the phenomenon of electrostatically regulated phosphorescence.

Abstract Using photodynamic therapy (PDT) to treat deep-seated cancers is limited due to inefficient delivery of photosensitizers and low tissue penetration of light. Polymeric nanocarriers are widely used for photosensitizer delivery, while the self-quenching of the encapsulated photosensitizers would impair the PDT efficacy. Furthermore, the generated short-lived reactive oxygen spieces (ROS) can hardly diffuse out of nanocarriers, resulting in low PDT efficacy. Therefore, a smart nanocarrier system which can be degraded by light, followed by photosensitizer activation can potentially overcome these limitations and enhance the PDT efficacy. A light-sensitive polymer nanocarrier encapsulating photosensitizer (RB-M) was synthesized. An implantable wireless dual wavelength microLED device which delivers the two light wavelengths sequentially was developed to programmatically control the release and activation of the loaded photosensitizer. Two transmitter coils with matching resonant frequencies allow activation of the connected LEDs to emit different wavelengths independently. Optimal irradiation time, dose, and RB-M concentration were determined using an agent-based digital simulation method. In vitro and in vivo validation experiments in an orthotopic rat liver hepatocellular carcinoma disease model confirmed that the nanocarrier rupture and sequential low dose light irradiation strategy resulted in successful PDT at reduced photosensitizer and irradiation dose, which is a clinically significant event that enhances treatment safety.

Abstract Objectives this study aims to compare the clinical outcomes of traditional and digital crown extension guides in the aesthetic restoration of anterior teeth. Additionally, the study will analyze the differences in the results of various digital crown extension guides in anterior aesthetic restorations. Methods Sixty-two patients who required aesthetic restoration of their anterior teeth were selected for this study. The patients had a total of 230 anterior teeth and were randomly divided into three groups: a control group of 22 cases who received diagnostic wax-up with pressure film, an experimental group 1 of 20 cases who received 3D printed digital models with pressure film, and an experimental group 2 of 20 patients who received digital dual-positioning guides. The control group had a total of 84 anterior teeth, experimental group 1 had 72 anterior teeth, and experimental group 2 had 74 anterior teeth. The study compared three methods for fabricating crown extension guides: the control group used the diagnostic wax-up plus compression film method, while experimental group 1 used compression film on 3D printed models and experimental group 2 used 3D printed digital dual-positioning crown extension guides. After the crown lengthening surgery, the control group patients wore DMG resin temporary crown material for gingival contouring, while the experimental group patients wore 3D printed resin temporary crowns for the same purpose. The patients were followed up in the outpatient clinic after wearing temporary crowns for 1 month, 3 months, and 6 months, respectively. The clinical results were evaluated in terms of marginal fit, red aesthetic index, and white aesthetic index. Results Based on the statistical analysis, the experimental group required significantly fewer follow-up visits and less time for guide design and fabrication compared to the control group. Additionally, the surgical time for the experimental group was significantly shorter than that of the control group. During the postoperative period between the 1st and 3rd month, the PES index scores for the marginal gingival level, proximal, and distal mesiodistal gingival papillae of the experimental group showed a trend of superiority over those of the control group. By the 6th month, the marginal gingival level exhibited a significant difference between the experimental and control groups. The experimental group demonstrated superior results to the control group in terms of shape, contour, and volume of the teeth, color, surface texture, and transparency of the restorations, and features during the 1st and 3rd postoperative months. In the 6th month, the comparative results indicated that the experimental group continued to exhibit superior outcomes to the control group in terms of the shape, color, surface texture, and transparency of the restorations, as well as the characteristics of the teeth. Additionally, the experimental group demonstrated significantly fewer gingival alterations than the control group at 1 month, 3 months, and 6 months post-procedure, with this difference being statistically significant. Furthermore, the combination of 3D printing technology and restorative techniques was utilized, resulting in consistent patient satisfaction. Conclusion Digitalisation plays an important role in anterior aesthetic restorations. The use of digital technology to manage the entire process of anterior cosmetic restorations can improve restorative results, reduce the number of follow-up appointments, shorten consultation time, and achieve better patient satisfaction.

IntroductionHyperarousal has been a significant pathophysiological theory related to insomnia disorder (ID), characterized by excessive cortical activation and abnormal electroencephalogram (EEG) power during daytime or sleep. However, there is currently insufficient attention to the EEG power during rapid eye movement (REM) sleep and different stages of non-rapid eye movement (NREM) sleep. Additionally, whether the abnormal sleep EEG power in ID patients can be restored by repetitive transcranial magnetic stimulation (rTMS) remains unclear.Methods> Data of 26 ID patients and 26 healthy controls (HCs) were included in the current observational study. The comparisons of relative power between patients and HCs at baseline in each band of each sleep stage and the changes in patients before and after rTMS treatment were performed. The correlations between relative power and behavioral measures of the patients were also investigated.ResultsAbnormalities in sleep EEG relative power in the delta, beta and gamma bands of the patients were observed in NREM2, NREM3 and REM sleep. Correlations were identified between relative power and behavioral measures in ID group, primarily encompassing sleep efficiency, sleep onset latency and depression scores. Post-treatment improvements in relative power of the delta and beta band were observed in NREM2 sleep.DiscussionThe relative power of sleep EEG exhibited a significant correlation with sleep measures in ID patients, and demonstrated notable differences from HCs across the delta, beta, and gamma frequency bands. Furthermore, our findings suggest that rTMS treatment may partially ameliorate relative power abnormalities in patients with ID.

Abstract Defensive capability is one of the essential attributes of traditional military settlements. In the Ming dynasty, coastal Wei fort was the one of the most functionally complex and wide-ranging fortifications in the military defense system of China. Because many factors affect their defensive capacities, including three dimensions: individual construction, synergistic links, and regional jurisdiction, it is not easy to compare different settlements’ defensive capacities or to judge the degrees of different factors’ influences. Through principal component analysis, this study determines the weights of each minor factor. It constructs a model for evaluating traditional Chinese military settlements’ defensive capabilities, to quantify the defensive capability. The results show that the synergistic relationship between the settlements, especially settlement accessibility, has the most significant impact on defensive capability, much higher than a single castle's defensive construction. The defensive capability index of the Wei forts in Guangdong is the highest, consistent with the highest rate of victory in the wars fought on the coast during the Ming dynasty. The defensive capacity is directly proportional to the rate of victory, which validates this evaluation model’s soundness. This study not only comprehensively evaluates the coastal Wei forts’ defensive capacity in the Ming Dynasty, but also provides new methods for the quantitative or comparative analysis of military settlements at other temporal and spatial scales.

The rainfall-induced shallow landslides are primarily debris landslides, which features simultaneity with significant hazard, and the hydrological response mechanism of water table and soil moisture content to precipitation of this type of landslide is sophisticated, which makes it difficult to predict the slope stability accurately. To further study the influence of the rainfall-triggered internal hydrological responses on slope-stability, on-site precipitation infiltration monitoring, correlation analysis and mechanical analysis were carried out on the Houshanli landslide in Qingchuan County, Sichuan Province. The relationship between precipitation and water table was proposed based on climate and hydrological monitoring data obtained within three year interval. The response of rainfall infiltration, soil volumetric water content and water table were analyzed. The results indicate that: (1) groundwater exhibits periodic fluctuations throughout the year, characterized by three phases of slow decline, rapid decline, and rapid ascent; a linear negative correlation between precipitation and water table was found, and no significant correlation was observed with the water table increment; (2) through the infinite slope model and the relationship between precipitation and water table, a prediction model for shallow landslide stability was constructed. The precipitation threshold (81.8 mm/d) and water table threshold (0.73 m) were determined which has good agreement with the actual situations. This provides an early warning method for rainfall-induced shallow landslides by monitoring these two factors.

Abstract N6-methyladenosine (m6A) modification, as a common epigenetic modification, has been widely studied in autoimmune diseases. However, the role of m6A in the regulation of the immune microenvironment of ankylosing spondylitis (AS) remains unclear. Therefore, we aimed to investigate the effect of m6A modification on the immune microenvironment of AS. We first evaluated RNA modification patterns mediated by 26 m6A regulators in 52 AS samples and 20 healthy samples. Thereafter, an m6A related classifier composed of seven genes was constructed and could effectively distinguish healthy and AS samples. Then, the correlation between m6A regulators and immune characteristics were investigated, including infiltrating immunocytes, immune reactions activity, and human leukocyte antigen (HLA) genes expression. The results indicated that m6A regulators was closely correlated with immune characteristics. For example, EIF3A was significantly related to infiltrating immunocytes; IGF2BP2 and EIF3A were significant regulators in immune reaction of TGF-β family member, and the expression of HLA-DPA1 and HLA-E were affected by EIF3A and ALKBH5. Next, two distinct m6A expression patterns were identified through unsupervised clustering analysis, and diverse immune characteristics were found between them. A total of 5889 m6A phenotype-related genes were obtained between the two expression patterns, and their biological functions were revealed. Finally, we validated the expression status of m6A modification regulators using two additional datasets. Our findings illustrate that m6A modifications play a critical role in the diversity and complexity of the AS immune microenvironment.

To establish an environmentally friendly and efficient method for extracting polyphenols from Syringa oblata Lindl. flowers and study the antioxidant activity of its polyphenols, this study used ultrasound-assisted deep eutectic solvents (UADESs) to extract polyphenols from Syringa oblata Lindl. flowers. Firstly, the choline chloride-malice acid, at a molar ratio of 1:1.5, and on the basis of the results of single-factor experiments, the extraction temperature, ultrasonic time, solid-liquid ratio and ultrasonic power, were selected as the key factors for optimization, and the extraction amount of polyphenols was used as the response value, and the Box-Behnken response surface method was used to optimize, and the scavenging ability of Syringa oblata Lindl. polyphenols on DPPH radicals and hydroxyl radicals was studied. The results showed that the optimized extraction parameters were extraction temperature of 60 ℃, ultrasonic time of 60 min, solid-liquid ratio 1:30 g/mL and ultrasonic power of 300 W, the polyphenol content could reach 52.19±0.13 mg/g, significantly higher than that of traditional extraction (60% ethanol, methanol) (P

To investigate the efficient method of total flavonoids from Syringa oblata leaves, this paper firstly used cellulase-assisted ultrasound method to extract flavonoids from four Syringa oblata leaves. The effects of cellulase dosage, pH, ultrasound time, ultrasound power, liquid-material ratio, temperature and ethanol volume fraction on the extraction rate of total flavonoids from Syringa pubescens Turcz. leaves were analyzed by single-factor experiments, and the best extraction process was obtained by applying response surface methodology optimization. The scavenging ability of Syringa oblata leaves flavonoids on DPPH and OH radicals was also examined in vitro as an antioxidant. The results showed that, the optimum extraction process was enzyme addition 2%, pH5.5, sonication time 40 min, sonication power 400 W, ethanol volume fraction 63%, temperature 56 ℃, liquid to material ratio 30:1 (mL/g), and under these conditions, the Syringa oblata flavonoids content was 32.21±0.16 mg/g, which was in proximity to the predicted value of 32.57 mg/g from the regression model. The results of antioxidant activity showed that the scavenging ability of the four Syringa oblata leaf flavonoids on DPPH was Syringa pubescens Turcz.>Syringa reticulata var. mamds huricq.>Syringa oblata var. affinis lingdelsh.>Syringa oblata Linal. The scavenging ability on OH was Syringa pubescens Turcz.>Syringa reticulata var. mamds huricq.> Syringa oblata Linal.>Syringa oblata var. affinis lingdelsh. The cellulase-assisted ultrasonication method can efficiently extract flavonoids from Syringa oblata leaves, and the flavonoids of Syringa oblata leaves have good antioxidant properties and have certain potential for development.

Synthetic aperture radar (SAR) and optical sensing are two important means of Earth observation. SAR-to-optical image translation (S2OIT) can integrate the advantages of both and assist SAR image interpretation under all-day and all-weather conditions. The existing S2OIT methods generally follow the generative adversarial networks paradigm, and encounter the problem of mode collapse, making them difficult to train. SAR and optical images have heterogeneous characteristics and large spectral differences, most of the existing methods do not focus on the color correlation between these two image domains, which leads to spectral distortion and detail errors in translation results. To address these issues, we propose a novel diffusion model capable of memorizing color and directly mapping between the SAR and optical image domains for S2OIT called CM-Diffusion. The color attention Brownian bridge diffusion structure is designed to learn the color correlation and translation between the SAR and optical image domains directly through the bidirectional diffusion process and color attention mechanism, avoiding the conditional information leverage. The color feature extraction module is constructed to provide color and semantic information for the diffusion model. Extensive experiments conducted on three benchmark datasets SEN1-2, QXS-SAROPT, and SEN12MS demonstrate that the proposed CM-Diffusion outperforms the state-of-the-art methods on both subjective and objective evaluation metrics.

Emerging data have revealed that damage to tubular epithelial cell is a driving force in the progression of diabetic kidney disease (DKD). However, the specific mechanisms by which lipotoxicity contributes to the injury of these cells, thereby influencing the development of DKD, are yet to be fully understood. Here, we analyzed the GSE 30529 microarray datasets of human tubulointerstitial tissue samples from the Gene Expression Omnibus database (GEO). Concurrently, we conducted RNA-sequencing on palmitic acid (PA)-treated human renal proximal tubule epithelial cells (HK2 cells). After normalization, the differentially expressed genes (DEGs) were screened by R software and gene ontology (GO) enrichment analysis was conducted, and lysosomal-associated protein transmembrane 5 (LAPTM5) was finally selected. Our findings indicate that the expression of LAPTM5 was obviously increased in DKD patients, and the correlation between LAPTM5, and other clinical parameters of DKD was analyzed using the Spearman correlation analysis. The potential of LAPTM5 as a prognostic biomarker for DKD was further consolidated through receiver operating characteristic (ROC) analysis. To further verify the function of LAPTM5, we established mouse or in vitro systems mimicking DKD. The results showed that a consistent upregulation of LAPTM5, which was also found to be linked with inflammatory mediators within the context of DKD. Additionally, LAPTM5 silencing significantly downregulated mRNA expression of inflammatory factors in PA-treated HK2 cells. These results indicate that LAPTM5 is a potential biomarker and therapeutic treatment target for DKD. This discovery paves the way for future research and development of targeted interventions aimed at mitigating the progression of this prevalent condition.

ABSTRACTThis study aimed to explore the therapeutic activity of Artemisia argyi essential oil (AAEO) nasal drops against avian infectious bronchitis and the underlying mechanism in the avian respiratory tract. Overall, 96 14-day-old broilers were randomly divided into 4 groups: control (control), A. argyi essential oil (AAEO) control, infectious bronchitis virus (IBV), and AAEO treatment (IBV + AAEO) groups (n = 24/group). Mortality was 25% (6/24) in the IBV group compared to 4.2% (1/24) in the AAEO treatment group. The clinical symptoms of the treatment group were significantly improved compared with those of the IBV group after 5 days of treatment. The broilers recovered at the end of the experiment. AAEO treatment relieves IBV-induced tracheal mucosal edema and bleeding and inhibits viral replication in the lungs. In addition, it enhanced SIgA secretion in the tracheal mucosa and increased type I interferon release by regulating IRF7 expression. Furthermore, we explored the mechanism underlying the therapeutic effect of AAEO. It maintains TLR7 at a high level in broilers and further upregulates MyD88, IRF7, and IL–10. Thereby enhancing the immune system and anti-inflammation. Our results suggest that AAEO can be used as a therapeutic agent for IBV.

The Guangdong, Hong Kong, and Macao Greater Bay Area (GHMA) has experienced economic development and rapid growth of transportation infrastructure in recent years. However, the economic advancement is also accompanied by serious atmospheric pollution, which threatens the health of the residents, thus, it is of great significance to explore the impact of atmospheric pollution on the health expenditures of residents in the GHMA. The article establishes a spatial econometric model to study the impact of atmospheric pollution on residents' health expenditure in the GHMA based on panel data from 2014 to 2021, using nine prefectures in the GHMA as research objects. The results show that: (1) Atmospheric pollution in the GHMA has an obvious spatial agglomeration phenomenon and spatial spillover effect, and the impact of atmospheric pollution on the health of the residents is still very serious; (2) PM2.5 emissions are positively and significantly related to the actual health care cost per person, and the rise in air pollution is the main reason for the rise in public health spending; (3) Other factors also have different impacts on residents' health expenditures. Based on the above research, the article puts forward corresponding policy recommendations.

The mesoscale eddies are prevalent oceanic circulation phenomena, exerting significant influence on various aspects of the marine environment including energy transfer, material transport and ecosystem dynamics in the Northwest Pacific Ocean. However, due to sparse vertical observational data, the understanding of the three-dimensional temperature structure of individual cases of mesoscale eddies remains limited. In recent years, utilizing surface remote sensing observations to estimate subsurface temperature anomaly has been crucial for comprehending the intricate multi-dimensional dynamic processes in the ocean. Consequently, this paper proposes an eddy residual multi-channel attention convolution network (ERCACN) with the adaptive threshold and designs the combination of various surface features to estimate the eddy subsurface temperature anomaly (ESTA). By integrating results with climatic temperature, thermal structures containing 46 levels at depths up to 1000 m could be obtained, achieving excellent daily temporal resolution and 0.25° spatial resolution. Validation using independent Argo profiles from 2016 to 2017 reveals that the combination of multiple surface variables outperforms univariate methods, and the ERCACN model demonstrates superior performance compared to other approaches. Overall, with an 8% error deemed acceptable, the ERCACN model achieves a precision of 88.08% in estimating ESTA. This method provides a novel perspective for other essential oceanic variables, contributing to a better perception of the global climate system.

PurposeBulky tumor remains as a challenge to surgery, chemotherapy and conventional radiation therapy. Hence, in efforts to overcome this challenge, we designed a novel therapeutic paradigm via strategy of Stereotactic Central/Core Ablative Radiation Therapy (SCART).), which is based on the principles of SBRT (stereotactic body radiation therapy and spatially fractionated radiation therapy (SFRT). We intend to safely deliver an ablative dose to the core of the tumor and with a low dose at tumor edge. The purpose of the phase 1 study was to determine dose-limiting toxicities (DLT)s and the Maximum Tolerated Dose (MTD) of SCART.Methods and materialsWe defined a SCART-plan volume inside the tumor, which is proportional to the dimension of tumor. VMAT/Cyberknife technique was adopted. In the current clinical trial; Patients with biopsy proven recurrent or metastatic bulky cancers were enrolled. The five dose levels were 15 Gy X1, 15Gy X3, 18GyX3, 21GyX3 and 24GyX3, while keeping the whole tumor GTV’s border dose at 5Gy each fraction. There was no restriction on concurrent systemic chemotherapy agents.Results21 patients were enrolled and underwent SCART. All 21 patients have eligible data for study follow-up. Radiotherapy was well tolerated with all treatment completed as scheduled. The dose was escalated for two patients to 24GyX3. No grade 3 or higher toxicity was observed in any of the enrolled patients. The average age of patients was 66 years (range: 14–85) and 13 (62%) patients were male. The median SCART dose was 18Gy (range: 15 - 24). Six out of the 18 patients with data for overall survival (OS) died, and the median time to death was 16.3 months (range: 1 - 25.6). The mean percent change for tumor shrinkage between first visit volumes and post-SCART volumes was 49.5% (SD: 40.89, p-value:0.009).ConclusionSCART was safely escalated to 24 GyX 3 fractions, which is the maximum Tolerated Dose (MTD) for SCART. This regimen will be used in future phase II trials.

Broad bean paste is a popular condiment in Asian countries. Leaves of Vitex negundo Linn. were used extensively in China during the koji-making of broad bean paste. Spreading V. negundo leaves on raw broad beans during fermentation was able to facilitate the rapid growth of fungi to form mature koji. We isolated two strains of fungi from mature koji, and four strains of bacteria from the rotten broad beans resulting from a failed attempt. According to microbial activity assays, two polymethoxylated flavones, 5-hydroxy-3,6,7,8,3′,4′-hexamethoxy flavone (HJ-1) and 5,4′-dihydroxy-3,6,7,8,3′-pentamethoxy flavone (HJ-2) were isolated from V. negundo leaves, and the fungal growth promotion and inhibition of bacterial growth of these two compounds were found to improve the production of broad bean koji. This study reveals the compounds present in V. negundo leaves with bioactivity against important microbes in koji manufacture, and provides a theoretical basis for the application of V. negundo in broad bean paste production.

BackgroundLung cancer is one of the most dangerous cancers in the world. Most lung cancer patients are diagnosed in the middle and later stages, which can lead to poor survival rates. The development of lung cancer is often accompanied by abnormal expression of exosomal non-coding RNAs, which means that they have the potential to serve as noninvasive novel molecular markers for lung cancer diagnosis.MethodsFor this study, we conducted a comprehensive literature search in PubMed, Web of science, Science direct, Embase, Cochrane, and Medline databases, and by reviewing published literature, The diagnostic capacity of exosomal microRNAs (miRNAs), long-chain non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) for lung cancer was evaluated. Functional enrichment analysis of miRNA target genes was performed.ResultsThe study included 41 papers, a total of 68 studies. More than 60 miRNAs, 9 lncRNAs and 14 circRNAs were involved. The combined sensitivity and specificity were 0.83(95%CI, 0.80~0.86) and 0.83(95% CI,0.79~0.87); 0.71(95% CI,0.68~0.74) and 0.79(95%CI, 0.75~0.82); 0.79(95%CI,0.67~0.87) and 0.81(95%CI,0.74~0.86), and constructed overall subject operating characteristic curves with the summarized area under the curve values of 0.90, 0.82, and 0.86.ConclusionOur study shows that exosomes miRNAs, lncRNAs and circRNAs are effective in the diagnosis of lung cancer, providing evidence for studies related to novel lung cancer diagnostic markers.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42023457087.

Since December 2019, the infection caused by Severe Acute Respiratory Syndrome Coronavirus Type 2 (SARS-CoV-2) has posed an enormous threat to human health security worldwide. Constant mutation of viral genome and varying therapeutic responses of patients infected with this virus prompted efforts to uncover more novel regulators in the pathogenesis. The involvement of N6-methyladenosine, a modified form of RNA, plays a crucial role in viral replication, viral pathogenicity, and intricate signaling pathways connected with immune responses. This review discusses research advances revealing the regulation of the life cycle of SARS-CoV-2 and antiviral responses of host cells by RNA m6A modification, highlights the biological functions of N6-methyladenosine components in SARS-CoV-2 infection and virus-host interactions, and outlines current challenges and future directions for exploring the potential clinical value of m6A modification in COVID-19.

Abstract In the study of the defense capacity of ancient military settlements, most existing studies have evaluated the defense capacity of citadels qualitatively from a historiographical perspective. There are fewer quantitative studies on defense efficiency in a specific regional context. This paper takes the coastal defense citadels system of Zhejiang in the Ming Dynasty of China as the research object. It adopts a combination of digital historical data mining and quantitative research to study the defense efficiency of the military defense area in Zhejiang in the Ming Dynasty. This paper first analyzes the defense pattern of Zhejiang's sea defense citadels system in the Ming Dynasty. It determines the control points of defense groups, quantifies the defense group area with a Voronoi diagram, and classifies and assigns the entropy value to the deployment data of guard forts in historical data. Finally, the assigned forces are superimposed on the defense area to obtain the quantified defense efficiency of each defense group, and the defense results are verified. This paper innovatively proposes an "area-force" perspective. It introduces spatial segmentation and quantitative research methods to study the defense efficiency of a specific regional defense group system in ancient times. It proves that this method is feasible and can be applied to the study of other ancient military defense areas. It also expands the scientific perspective of ancient military fortification systems, which can contribute to systematically preserving ancient military settlement heritage on a larger scale.

National parks are important spatial places for environmental education. To improve the perception and effectiveness of environmental education, it is critical to facilitate the public’s spatial experience. To explore influencing factors of perception and effectiveness of environmental education from a spatial perspective is of great significance for stimulating the public’s pro-environmental behavior and promoting the high-quality development of environmental education in national parks. Educational mode plays an important role in environmental education space, and spatial element is also an important part of it. In this study, Wuyi Mountain National Park was selected as a sample to explore whether educational methods and spatial elements affect the perception and effectiveness of environmental education through questionnaires and statistical methods. The results show that: (1) tourists prefer guided education mode, open space and road with interactive facilities and characteristic paving; (2) both educational modes and spatial elements have positive influence on the perception and effectiveness of environmental education; (3) educational mode and environmental education effectiveness are affected by the demographic characteristics, of which educational background is the main influencing factor. After analysis, it is suggested that when environmental education space is designed, tourists’ preference should be considered and personalized environmental education program should be customized, so as to improve the readability of environmental education space, and provide reference and support for strengthening the environmental education function of national parks.

PurposeTo develop and validate a deep learning radiomics (DLR) model that uses X-ray images to predict the classification of osteoporotic vertebral fractures (OVFs).Material and methodsThe study encompassed a cohort of 942 patients, involving examinations of 1076 vertebrae through X-ray, CT, and MRI across three distinct hospitals. The OVFs were categorized as class 0, 1, or 2 based on the Assessment System of Thoracolumbar Osteoporotic Fracture. The dataset was divided randomly into four distinct subsets: a training set comprising 712 samples, an internal validation set with 178 samples, an external validation set containing 111 samples, and a prospective validation set consisting of 75 samples. The ResNet-50 architectural model was used to implement deep transfer learning (DTL), undergoing -pre-training separately on the RadImageNet and ImageNet datasets. Features from DTL and radiomics were extracted and integrated using X-ray images. The optimal fusion feature model was identified through least absolute shrinkage and selection operator logistic regression. Evaluation of the predictive capabilities for OVFs classification involved eight machine learning models, assessed through receiver operating characteristic curves employing the “One-vs-Rest” strategy. The Delong test was applied to compare the predictive performance of the superior RadImageNet model against the ImageNet model.ResultsFollowing pre-training separately on RadImageNet and ImageNet datasets, feature selection and fusion yielded 17 and 12 fusion features, respectively. Logistic regression emerged as the optimal machine learning algorithm for both DLR models. Across the training set, internal validation set, external validation set, and prospective validation set, the macro-average Area Under the Curve (AUC) based on the RadImageNet dataset surpassed those based on the ImageNet dataset, with statistically significant differences observed (P

Livelihood status of rural households is the focus of disaster resettlement research. Influenced by various factors, rural households face multiple environmental and social pressures after relocation, and the study of livelihood resilience and vulnerability provides a new framework for research into the livelihoods of relocated households. There has been a call for more quantitative evidence about the links between livelihood resilience and livelihood vulnerability in the context of disaster resettlement. This study uses data from a sample of 657 individuals from the relocation area of Ankang prefecture in southern Shaanxi, China. The resilience of rural household livelihood systems is quantified in terms of two dimensions of general resilience and specific resilience using the spatial vector method from systems engineering. The IPCC framework was used to measure three dimensions of livelihood vulnerability: exposure, sensitivity, and adaptability, and a threshold regression model was applied to investigate the impacts of livelihood resilience on livelihood vulnerability. Results show that: (i) livelihood vulnerability of relocated households (−0.042) was significantly lower than that of local households (0.091), while relocated households in the process of livelihood reconstruction had a certain degree of vulnerability risk. (ii) there is a significant threshold effect of livelihood resilience on livelihood vulnerability of rural households. (iii) increasing livelihood resilience significantly reduced the degree of vulnerability of rural households, and the marginal effect of general resilience on livelihood vulnerability shows a decreasing trend. Specific resilience has a positive influence on livelihood vulnerability before it exceeds the threshold, but the effect disappears above the threshold of resilience. (iv) The threshold value of livelihood resilience of local households (0.5039) is generally lower than that of relocated households (0.6548), and relocation does improve the ability of rural households to resist uncertainty risks. It is necessary for local governments to formulate more targeted policies to reduce the livelihood vulnerability of rural households and thereby promote sustainable livelihood development.