MolLoG: A Molecular Level Interpretability Model Bridging Local to Global for Predicting Drug Target Interactions.

Developing new pharmaceuticals is a costly and time-consuming endeavor fraught with significant safety risks. A critical aspect of drug research and disease therapy is discerning the existence of interactions between drugs and proteins. The evolution of deep learning (DL) in computer science has been remarkably aided in this regard in recent years. Yet, two challenges remain: (i) balancing the extraction of profound, local cohesive characteristics while warding off gradient disappearance and (ii) globally representing and understanding the interactions between the drug and target local attributes, which is vital for delivering molecular level insights indispensable to drug development. In response to these challenges, we propose a DL network structure, MolLoG, primarily comprising two modules: local feature encoders (LFE) and global interactive learning (GIL). Within the LFE module, graph convolution networks and leap blocks capture the local features of drug and protein molecules, respectively. The GIL module enables the efficient amalgamation of feature information, facilitating the global learning of feature structural semantics and procuring multihead attention weights for abstract features stemming from two modalities, providing biologically pertinent explanations for black-box results. Finally, predictive outcomes are achieved by decoding the unified representation via a multilayer perceptron. Our experimental analysis reveals that MolLoG outperforms several cutting-edge baselines across four data sets, delivering superior overall performance and providing satisfactory results when elucidating various facets of drug-target interaction predictions.

Degree of paraxiality of radially polarized twisted multi-Gaussian Schell-model beams.

The degree of paraxiality (DOP) of a radially polarized twisted multi-Gaussian Schell-model (RPT MGSM) beam is discussed, and the influence of the source parameters on its DOP is studied. It is shown that the parameters of the beam source, including the boundary characteristic, the beam waist width, the coherence width of the source correlation, and the twist factor, have a significant impact on the DOP of the RPT MGSM beam. To explain the behaviors of the DOP, the far-field divergence angle of this beam is also discussed.

First report of leaf blight caused by Stemphylium lycopersici on Salvia splendens in China.

Salvia splendens is a popular ornamental plant in China with extensive potentials, including value in traditional Chinese medicine and in environmental restoration function (Li et al. 2008). In September 2019, leaf blight disease was observed on road side plants of S. splendens in Bayi park, Nanchang city, Jiangxi province, China. The typical symptoms appeared as irregular necrotic spots or leaf blight, accompanied by extensive scorch necrosis or ultimately defoliation. Small segments cut from diseased leaves were surface sterilized in a 2% sodium hypochlorite solution for 2 min and rinsed three times with sterile distilled water. Then, the samples were placed on potato dextrose agar (PDA) plates incubated at 25°C in darkness. Pure cultures were obtained by the hyphal tip method. Morphologically, all 11 colonies were identical to each other on PDA. Two strains, YZU 191468 and YZU 191481, were selected for further study and deposited in the Fungal Herbarium of Yangtze University (YZU), Jingzhou, Hubei, China. The 7-day-old colonies were circular, 53 to 56 mm in diameter, and consisted of white mycelium with a buff margin, and were cinnamon colored in the center of the reverse side. To examine conidial morphology, the mycelium was transferred onto potato carrot agar (PCA) and incubated at 23°C with a period of 8 h light/16 h dark for 7 days. Conidia were normally solitary or two in a chain, ellipsoid or long ellipsoid, beakless, 10 to 23×30 to 60 µm in size (n=50). Based on morphology, the isolates were consistent with Stemphylium lycopersici (Yamamoto 1960). To confirm the identification, genomic DNA was extracted from both isolates and used to amplify the internal transcribed spacer rDNA region (ITS), glyceraldehydes-3-phosphate dehydrogenase (GAPDH) and calmodulin (CAL) genes with primer pairs ITS5/ITS4, gpd1/gpd2, and CALDF1/CALDR2, respectively (Woudenberg et al. 2017). Sequences were deposited in GenBank with accession numbers OP564983 and OP564984 (ITS), OP892529 and OP892530 (GAPDH), OP584970 and OP584971 (CAL). A neighbor-joining tree was constructed with Mega 7.0 based on the combined dataset with 1,000 bootstrap replicates. The resulting phylogenetic tree showed that the strains from S. splendens clustered with S. lycopersici (CBS 122639 and CBS 124980) supported with 100% bootstrap values. The molecular analyses confirmed that the species causing leaf blight symptoms was S. lycopersici. To test pathogenicity, healthy leaves of S. splendens were surface sterilized and inoculated by mycelium blocks (6 mm in diameter) and spore suspension (1×106 spore/mL) of representative strains YZU 191468 and YZU 191481, respectively. Controls were inoculated with blocks of PDA and sterile water. Each strain was inoculated on three leaves of a plant. One clean plant was used as control. The test was replicated three times. After inoculation, the plants were covered with plastic bags and incubated in a greenhouse (25℃, 80 % relative humidity, 8 h light/16 h dark). After 5 days, the inoculated leaves exhibited dark brown spots with white mycelium, followed by withering of necrotic tissues. There were no symptoms observed on the controls. The fungal isolates inoculated leaves had the same morphological characteristics as the strains used for inoculation. S. lycopersici has been found on eggplant and Zinnia elegans in China (He et al. 2019; Yang et al. 2017). To the best of our knowledge, this is the first report of S. lycopersici causing leaf blight on S. splendens in China. This finding offers a new reference for the management and control of S. splendens leaf diseases in China.

Impact of delayed diagnosis and treatment on tuberculosis infection within families: A case report.

BACKGROUND: A 32-year-old male patient was diagnosed with a 30% left pneumothorax on November 5, 2020, during which chest imaging indicated abnormalities. Despite this, pulmonary tuberculosis (TB) was not diagnosed or treated at that time due to a negative result in the MGIT960 culture. The patient experienced symptoms of cough and expectoration on April 24, 2022. Upon repeating the chest imaging, the condition had worsened, confirming the presence of pulmonary TB, leading to the patient's hospitalization. On September 1, 2022, the 11-year-old daughter of the patient was diagnosed with pulmonary tuberculosis accompanied by bronchial tuberculosis and tuberculous pleurisy. METHODS: The diagnosis of pulmonary tuberculosis was confirmed through sputum smears and Gene Xpert MTB/RIF testing, for the patient and his 11-year-old daughter in 2022. The patient underwent a 6-month combination therapy (2HRZE/4HR) comprising isoniazid, rifampicin, pyrazinamide, and ethambutol. His daughter with pulmonary tuberculosis accompanied by bronchial tuberculosis and tuberculous pleurisy underwent a 12-month combination therapy. RESULTS: Late diagnosis and treatment delays contribute to tuberculosis infections within families. Fortunately, after more than 3 months of antituberculosis treatment, the patient experienced relief from cough and sputum secretion, and there was improvement observed in the chest CT scan. Six months later, the patient was successfully cured of TB. 12 months later, his daughter also was successfully cured of TB. CONCLUSION SUBSECTIONS: Early diagnosis and treatment of tuberculosis (TB) is vital to reduce transmission, morbidity, and mortality.

[Spatial Variability and Source Apportionment of PM2.5 Carbon Components in Tianjin].

The contents of eight carbonaceous subfractions were determined by simultaneously collecting PM2.5 samples from four sites in different functional areas of Tianjin in 2021. The results showed that the organic carbon (OC) concentration was 3.7 µg·m-3 to 4.4 µg·m-3, and the elemental carbon (EC) concentration was 1.6 µg·m-3 to 1.7 µg·m-3, with the highest OC concentration in the central urban area. There was no significant difference in EC concentration. The concentration of PM2.5 showed the distribution characteristics of the surrounding city>central city>peripheral area. The OC/EC minimum ratio method was used to estimate the concentrations of secondary organic carbon (SOC) in PM2.5, and the results showed that the secondary pollution was more prominent in the surrounding city, with SOC accounting for 48.8%. The correlation between carbon subcomponents in each functional area showed the characteristics of the peripheral area>central area>surrounding area, all showing the strongest correlation between EC1 and OC2 and EC1 and OC4. By including the carbon component concentration into the positive definite matrix factorization (PMF) model for source apportionment, the results showed that road dust sources(9.7%-23.5%), coal-combustion sources (10.2%-13.3%), diesel vehicle exhaust (12.6%-20.2%)and gasoline vehicle exhaust (18.9%-38.8%)were the main sources of carbon components in PM2.5 in Tianjin. The pollution sources of carbon components were different in different functional areas, with the central city and peripheral areas mainly affected by gasoline vehicle exhaust; the surrounding city was more prominently affected by the secondary pollution and diesel vehicle exhaust.

Comparative survival analysis of bladder preservation therapy versus radical cystectomy in muscle-invasive bladder cancer.

BACKGROUND: Bladder preservation therapy is an alternative to radical cystectomy in patients with muscle-invasive bladder cancer (MIBC). The purpose of this study is to compare survival outcomes between bladder preservation therapy and radical cystectomy in MIBC patients using an Asian nationwide cancer registry database. METHODS: From the Taiwan Cancer Registry database and the Taiwan National Health Insurance Research Database, we identified bladder cancer patients from 2008 to 2018. The patients with urothelial carcinoma and clinical stage T2-T4aN0-1 M0 were included. Propensity score matching by age, gender, clinical stage, cT classification, and Charlson Comorbidity Index score was used between those receiving bladder preservation therapy or radical cystectomy. Overall survival (OS), cancer-specific survival (CSS), and disease-free survival (DFS) were compared using the Kaplan-Meier method. Multivariate Cox regression models were used to determine the predictive factors of OS, CSS, and DFS. RESULTS: Following the propensity score matching, 393 MIBC patients were analyzed, 131 (33.3%) receiving bladder preservation therapy and 262 (66.7%) receiving radical cystectomy. After 5 years of the follow-up period the overall duration was with a median of 15.6 months. The treatment groups did not differ significantly in OS, CSS, and DFS (p = 0.2681, 0.7208, and 0.3616, respectively). In multivariable Cox regression models, bladder preservation therapy remained non-inferior to radical cystectomy in OS (adjusted hazard ratio [aHR] 1.08; 95% confidence interval [CI], 0.77-1.50; p = 0.6689), CSS (aHR, 1.06; 95% CI, 0.72-1.57; p = 0.7728), and DFS (aHR, 0.76; 95% CI, 0.46-1.27; p = 0.2929). Additionally, among patients ≥80 years, the use of bladder preservation therapy compared with radical cystectomy resulted in an equivalent OS, CSS and DSS. CONCLUSION: In Asian populations, bladder preservation therapy yielded similar survival outcomes as radical cystectomy in MIBC patients. Based on the results, it is evident that a multidisciplinary approach and shared decision-making are recommended for bladder cancer treatment.

Descending mechanism by which medial prefrontal cortex endocannabinoid signaling controls the development of neuropathic pain and neuronal activity of dorsal root ganglion.

ABSTRACT: Although regulation of nociceptive processes in the dorsal horn by deep brain structures has long been established, the role of cortical networks in pain regulation is minimally explored. The medial prefrontal cortex (mPFC) is a key brain area in pain processing that receives ascending nociceptive input and exerts top-down control of pain sensation. We have shown critical changes in mPFC synaptic function during neuropathic pain, controlled by endocannabinoid (eCB) signaling. This study tests whether mPFC eCB signaling modulates neuropathic pain through descending control. Intra-mPFC injection of cannabinoid receptor type 1 (CB1R) agonist WIN-55,212-2 (WIN) in the chronic phase transiently alleviates the pain-like behaviors in spared nerve injury (SNI) rats. By contrast, intra-mPFC injection of CB1R antagonist AM4113 in the early phase of neuropathic pain reduces the development of pain-like behaviors in the chronic phase. Spared nerve injury reduced the mechanical threshold to induce action potential firing of dorsal horn wide-dynamic-range neurons, but this was reversed in rats by WIN in the chronic phase of SNI and by mPFC injection of AM4113 in the early phase of SNI. Elevated dorsal root ganglion neuronal activity after injury was also diminished in rats by mPFC injection of AM4113, potentially by reducing antidromic activity and subsequent neuronal inflammation. These findings suggest that depending on the phase of the pain condition, both blocking and activating CB1 receptors in the mPFC can regulate descending control of pain and affect both dorsal horn neurons and peripheral sensory neurons, contributing to changes in pain sensitivity.

Mitochondrial Mechanisms in Temozolomide Resistance: Unraveling the Complex Interplay and Therapeutic Strategies in Glioblastoma.

Glioblastoma (GBM) is a highly aggressive and lethal brain tumor, with temozolomide (TMZ) being the standard chemotherapeutic agent for its treatment. However, TMZ resistance often develops, limiting its therapeutic efficacy and contributing to poor patient outcomes. Recent evidence highlights the crucial role of mitochondria in the development of TMZ resistance through various mechanisms, including alterations in reactive oxygen species (ROS) production, metabolic reprogramming, apoptosis regulation, biogenesis, dynamics, stress response, and mtDNA mutations. This review article aims to provide a comprehensive overview of the mitochondrial mechanisms involved in TMZ resistance and discuss potential therapeutic strategies targeting these mechanisms to overcome resistance in GBM. We explore the current state of clinical trials targeting mitochondria or related pathways in primary GBM or recurrent GBM, as well as the challenges and future perspectives in this field. Understanding the complex interplay between mitochondria and TMZ resistance will facilitate the development of more effective therapeutic strategies and ultimately improve the prognosis for GBM patients.

Correlation of Insulin-Like Growth Factor 1 With Cognitive Functions in Mild Traumatic Brain Injury Patients.

Mild traumatic brain injury (mTBI) is a prevalent health concern with variable recovery trajectories, necessitating reliable prognostic markers. Insulin-like growth factor 1 (IGF-1) emerges as a potential candidate because of its role in cellular growth, repair, and neuroprotection. However, limited studies investigate IGF-1 as a prognostic marker in mTBI patients. This study aimed to explore the correlation of IGF-1 with cognitive functions assessed using the Wisconsin Card Sorting Test (WCST) in mTBI patients. We analyzed data from 295 mTBI and 200 healthy control participants, assessing demographic characteristics, injury causes, and IGF-1 levels. Cognitive functions were evaluated using the WCST. Correlation analyses and regression models were used to investigate the associations between IGF-1 levels, demographic factors, and WCST scores. Significant differences were observed between mTBI and control groups in the proportion of females and average education years. Falls and traffic accidents were identified as the primary causes of mTBI. The mTBI group demonstrated worse cognitive outcomes on the WCST, except for the "Learning to Learn" index. Correlation analyses revealed significant relationships between IGF-1 levels, demographic factors, and specific WCST scores. Regression models demonstrated that IGF-1, age, and education years significantly influenced various WCST scores, suggesting their roles as potential prognostic markers for cognitive outcomes in mTBI patients. We provide valuable insights into the potential correlation of IGF-1 with cognitive functions in mTBI patients, particularly in tasks requiring cognitive flexibility and problem solving.

Copper price prediction using LSTM recurrent neural network integrated simulated annealing algorithm.

Copper is an important mineral and fluctuations in copper prices can affect the stable functioning of some countries' economies. Policy makers, futures traders and individual investors are very concerned about copper prices. In a recent paper, we use an artificial intelligence model long short-term memory (LSTM) to predict copper prices. To improve the efficiency of long short-term memory (LSTM) model, we introduced a simulated annealing (SA) algorithm to find the best combination of hyperparameters. The feature engineering problem of the AI model is then solved by correlation analysis. Three economic indicators, West Texas Intermediate Oil Price, Gold Price and Silver Price, which are highly correlated with copper prices, were selected as inputs to be used in the training and forecasting model. Three different copper price time periods, namely 485, 363 and 242 days, were chosen for the model forecasts. The forecast errors are 0.00195, 0.0019 and 0.00097, respectively. Compared with the existing literature, the prediction results of this paper are more accurate and less error. The research in this paper provides a reliable reference for analyzing future copper price changes.

Comprehensive chemical profiling of two Dendrobium species and identification of anti-hepatoma active constituents from Dendrobium chrysotoxum by network pharmacology.

BACKGROUND: Dendrobium nobile and Dendrobium chrysotoxum are important species of the genus Dendrobium and have great economic and medicinal value. However, the medicinal properties of these two plants remain poorly understood. This study aimed to investigate the medical properties of D. nobile and D. chrysotoxum by conducting a comprehensive chemical profiling of the two plants. Additionally, active compounds and predictive targets for anti-hepatoma activity in D. chrysotoxum extracts were identified using Network Pharmacology. RESULTS: Chemical profiling showed that altogether 65 phytochemicals were identified from D. nobile and D. chrysotoxum, with major classes as alkaloids, terpenoids, flavonoids, bibenzyls and phenanthrenes. About 18 compounds were identified as the important differential metabolites in D. nobile and D. chrysotoxum. Furtherly, CCK-8 results showed that the extracts of stems and leaves of D. nobile and D. chrysotoxum could inhibit the growth of Huh-7 cells, and the anti-hepatoma activity of extracts were dose-dependent. Among the extracts, the extract of D. chrysotoxum showed significant anti-hepatoma activity. In order to find the potential mechanism of anti-hepatoma activity of D. chrysotoxum, five key compounds and nine key targets were obtained through constructing and analyzing the compound-target-pathway network. The five key compounds were chrysotobibenzyl, chrysotoxin, moscatilin, gigantol and chrysotoxene. Nine key targets, including GAPDH, EGFR, ESR1, HRAS, SRC, CCND1, HIF1A, ERBB2 and MTOR, could be considered as the core targets of the anti-hepatoma activity of D. chrysotoxum. CONCLUSIONS: In this study, the chemical composition difference and anti-hepatoma activity of stems and leaves of D. nobile and D. chrysotoxum were compared, and the potential anti-hepatoma mechanism of D. chrysotoxum was revealed in a multi-target and multi-pathway manner.

Time-Frequency-Energy Characteristics Analysis of Vibration Signals in Digital Electronic Detonators and Nonel Detonators Exploders Based on the HHT Method.

The China Society of Explosives and Blasting required a larger than 20% annual increase in the national use of digital electronic detonators since 2018. So, this article conducted a large number of on-site tests and then used the Hilbert-Huang Transform method to analyze and compare the vibration signals of digital electronic and nonel detonators during the excavation process of minor cross-sectional rock roadways from the perspective of time, frequency, and energy. Then, through vibration energy analysis, identification of actual delay time, and formula derivation, it was proved that the delay time error of the detonator can control vibration wave random interference and reduce vibration. The analysis results showed that when using a segmented simultaneous blasting network for excavation in small-sectioned rock tunnels, nonel detonators may provide more excellent protection to structures than digital electronic detonators. In the same segment, the timing error of nonel detonators produces a vibration wave with a random superposition damping effect, resulting in an average vibration reduction of 19.4% per segment compared to digital electronic detonators. However, digital electronic detonators are superior to nonel detonators for the fragmentation effect on rock. The research conducted in this paper has the potential to facilitate a more rational and comprehensive promotion of digital electronic detonators in China.

Analysis of factors influencing patient delay by patients with pulmonary tuberculosis in Lishui City, Zhejiang Province.

OBJECTIVE: The purpose of this study was to collect data on the current state of patient delay by patients with tuberculosis (TB) in Lishui City, Zhejiang Province who were under the care of a TB-designated hospital from 2011 to 2021 and to analyze the factors that contribute to this problem in order to provide a scientific basis for the prevention and control of TB. METHODS: In this observational study, we collected data on patients with pulmonary TB that were reported to the Chinese government's disease prevention and control information system by the Traditional Chinese Medicine Hospital in Lishui City between 2011 and 2021. The data included demographics like age, gender, occupation, household registration, current address, date of symptoms, date of first visit, and etiology results. Multivariate logistic regression analysis was used to analyze the factors influencing patient delay by patients with pulmonary TB. RESULTS: There were 3,190 cases of pulmonary TB treated in a TB-designated hospital in Lishui City, Zhejiang Province, between 2011 and 2021. Of these, 2,268 involved patient delay, with the delay rate of 71.10% and the median (Q25, Q75) days of patient delay being 36 (25, 72) days. Results of multivariate logistic regression analysis indicated the presence of risk factors-age > 60 years old (OR = 1.367, 95% CI: 1.144 ~ 1.632), pathogen positive (OR = 1.211, 95% CI: 1.033 ~ 1.419), and employed as peasants (OR = 1.353, 95% CI:1.144 ~ 1.601) for patient delay in patients with pulmonary TB. Patients with diabetes mellitus made up 64.94% of the pulmonary TB population, which was lower than the 71.58% of patients without diabetes mellitus (χ2 = 4.602, P = 0.032). Additionally, the presence of diabetes mellitus may be a protective factor in patient delay in patients with pulmonary TB (OR = 0.641, 95% CI: 0.481 ~ 0.856). CONCLUSION: High rates of patient delay, age > 60 years old, a positive etiology, and being employed as peasants are all possible risk factors for pulmonary TB in Lishui City, Zhejiang Province.

Assessment of Effective Anti-TB Regimens and Adverse Outcomes Related Risk Factors in the Elderly and Senile-Aged TB Patients.

Objective: Compared to younger patients with tuberculosis (TB), elderly and senile-aged patients with TB had a higher incidence of adverse outcomes particularly in terms of lost to follow-up and deaths. Our study aimed to gain insight into the effectiveness of anti-tuberculosis (anti-TB) treatment in the elderly or senile-aged patients and identify the risk factors for adverse outcomes. Methods: The case information was obtained from the "Tuberculosis Management Information System". From January 2011 to December 2021, this retrospective analysis was conducted in Lishui City, Zhejiang Province to observe and record the outcomes of elderly patients diagnosed with TB who agreed to receive anti-TB and(or) traditional Chinese medicine(TCM) treatment. We also employed a logistic regression model to analyze the risk factors for adverse outcomes. Results: Among the 1191 elderly or senile-aged patients with TB who received the treatment, the success rate was 84.80% (1010/1191). Using logistic regression analysis, several risk factors for adverse outcomes (failure, death, loss to follow-up) were identified, including age ≥ 80 years (OR 2.186, 95% CI 1.517~3.152, P<0.001), lesion area ≥ 3 lung fields (OR 0.410, 95% CI 0.260~0.648, P<0.001), radiographic lesions failing to improve after 2 months of treatment (OR 2.048, 95% CI 1.302~3.223, P=0.002), sputum bacteriology failing to turn negative after 2 months of treatment (OR 2.213, 95% CI 1.227~3.990, P=0.008), lack of a standardized treatment plan (OR 2.095, 95% CI 1.398~3.139, P<0.001), and non-involvement of traditional Chinese medicine (OR 2.589, 95% CI 1.589~4.216, P<0.001). Conclusion: The anti-TB treatment success rate in the elderly and senile-aged patients is suboptimal. Contributing factors include advanced age, extensive lesions, and low sputum negative conversion rate during the intensive treatment phase. The results will informative and could be useful for policy maker for to control of reemergence of TB in big cities.

[Health Impacts of Air Pollution in Tianjin].

Ambient air pollution is a dominant determinant of health. The health effects and economic losses due to air pollution are very important for decision-making. Since the implementation of the "Air Pollution Prevention and Control Action Plan" and "blue sky defense war" policies, the air quality of Tianjin has changed significantly. Here, the health effects and economic losses attributable to ambient air pollution in Tianjin from 2013 to 2020 wereestimated. For the particulate matter which has complex components, we assessed the inhalation health risks of heavy metals and polycyclic aromatic hydrocarbons (PAHs) in PM2.5. The variation in the concentration of the main components of PM2.5 was also analyzed. The results showed that improved air quality had positive health benefits. The health benefits from SO2 were the highest among the six air pollutants, and 3786 deaths were avoided in 2020 compared to in 2013 due to lower SO2 concentration. The economic losses caused by air pollutants ranged from several billion to ten billion yuan. Among the six air pollutants, particulate matter and ozone had higher health losses in recent years. The health risks of heavy metals and PAHs in PM2.5 showed a decreasing trend. However, Cr(Ⅵ), As, Cd, and Ni in PM2.5in the winter of 2020 still had respiratorysystem carcinogenic risk, whereas there was no health risk of PAHs in PM2.5in 2019-2020. The concentrations of main components of PM2.5 have decreased significantly. In the future, the reduction of health loss caused by air pollution depends on synergy governance of particulate matter and ozone and further research on health effects.

[Spatial-temporal Variation and Driving Factors of Ozone in China from 2019 to 2021 Based on EOF Technique and KZ Filter].

Based on the hourly O3 concentration data of 337 prefectural-level divisions and simultaneous surface meteorological data in China, we applied empirical orthogonal function (EOF) analysis to analyze the main spatial patterns, variation trends, and main meteorological driving factors of O3 concentration in China from March to August in 2019-2021. In this study, a KZ (Kolmogorov-Zurbenko) filter was used to decompose the time series of O3 concentration and simultaneous meteorological factors into corresponding short-term, seasonal, and long-term components in 31 provincial capitals.Then, the stepwise regression was used to establish the relationship between O3 and meteorological factors. Ultimately, the long-term component of O3 concentration after "meteorological adjustment" was reconstructed. The results indicated that the first spatial patterns of O3 concentration showed a convergent change, that is, the volatility of O3 concentration was weakened in the high-value region of variability and enhanced in the low-value region.Before and after the meteorological adjustment, the variation trend of O3 concentration in different cities was different to some extent. The adjusted curve was "flatter" in most cities. Among them, Fuzhou, Haikou, Changsha, Taiyuan, Harbin, and Urumqi were greatly affected by emissions. Shijiazhuang, Jinan, and Guangzhou were greatly affected by meteorological conditions. Beijing, Tianjin, Changchun, and Kunming were greatly affected by emissions and meteorological conditions.

Heliangin acts as a covalent ligand of RPS2 that disrupts pre-rRNA metabolic processes in NPM1-mutated acute myeloid leukemia.

Although NPM1 mutations are frequently found in acute myeloid leukemia patients, therapeutic strategies are scarce and unsuitable for those who cannot tolerate intensive chemotherapy. Here we demonstrated that heliangin, a natural sesquiterpene lactone, exerts favorable therapeutic responses in NPM1 mutant acute myeloid leukemia cells, with no apparent toxicity to normal hematogenous cells, by inhibiting their proliferation, inducing apoptosis, causing cell cycle arrest, and promoting differentiation. In-depth studies on its mode of action using quantitative thiol reactivity platform screening and subsequent molecular biology validation showed that the ribosomal protein S2 (RPS2) is the main target of heliangin in treating NPM1 mutant AML. Upon covalent binding to the C222 site of RPS2, the electrophilic moieties of heliangin disrupt pre-rRNA metabolic processes, leading to nucleolar stress, which in turn regulates the ribosomal proteins-MDM2-p53 pathway and stabilizes p53. Clinical data shows that the pre-rRNA metabolic pathway is dysregulated in acute myeloid leukemia patients with the NPM1 mutation, leading to a poor prognosis. We found that RPS2 plays a critical role in regulating this pathway and may be a novel treatment target. Our findings suggest a novel treatment strategy and lead compound for acute myeloid leukemia patients, especially those with NPM1 mutations.

Low-temperature 3D-printed collagen/chitosan scaffolds loaded with exosomes derived from neural stem cells pretreated with insulin growth factor-1 enhance neural regeneration after traumatic brain injury.

There are various clinical treatments for traumatic brain injury, including surgery, drug therapy, and rehabilitation therapy; however, the therapeutic effects are limited. Scaffolds combined with exosomes represent a promising but challenging method for improving the repair of traumatic brain injury. In this study, we determined the ability of a novel 3D-printed collagen/chitosan scaffold loaded with exosomes derived from neural stem cells pretreated with insulin-like growth factor-1 (3D-CC-INExos) to improve traumatic brain injury repair and functional recovery after traumatic brain injury in rats. Composite scaffolds comprising collagen, chitosan, and exosomes derived from neural stem cells pretreated with insulin-like growth factor-1 (INExos) continuously released exosomes for 2 weeks. Transplantation of 3D-CC-INExos scaffolds significantly improved motor and cognitive functions in a rat traumatic brain injury model, as assessed by the Morris water maze test and modified neurological severity scores. In addition, immunofluorescence staining and transmission electron microscopy showed that 3D-CC-INExos implantation significantly improved the recovery of damaged nerve tissue in the injured area. In conclusion, this study suggests that transplanted 3D-CC-INExos scaffolds might provide a potential strategy for the treatment of traumatic brain injury and lay a solid foundation for clinical translation.

Effects of Steam and Water Blanching on Drying Characteristics, Water Distribution, Microstructure, and Bioactive Components of Gastrodia Elata.

In the current work, the effects of steam and boiling water blanching on the drying characteristics, water distribution, microstructure, and contents of bioactive substances of Gastrodia elata (G. elata) were explored. Results showed that the degree of steaming and blanching was related to the core temperature of G. elata. The steaming and blanching pretreatment increased the drying time of the samples by more than 50%. The low-field nuclear magnetic resonance (LF-NMR) of treated samples showed that the relaxation time corresponded to water molecule states (bound, immobilized, and free) and G. elata became shorter, which indicated a reduction in free moisture and increased resistance of water diffusion in the solid structure during drying. Hydrolysis of polysaccharides and gelatinization of starch granules was observed in the microstructure of treated samples, which was consistent with changes in water status and drying rates. Steaming and blanching increased gastrodin and crude polysaccharide contents and decreased p-hydroxybenzyl alcohol content. These findings will contribute to a better understanding of the effect of steaming and blanching on the drying behavior and quality attributes of G. elata.