ObjectiveEarly blight is a common destructive disease in the growth process of Solanaceae crops, which can lead to crop failure and serious losses. Traditional crop disease detection methods are difficult to detect disease characteristics in a timely manner during the incubation period of disease, and thus take scientific and effective prevention and control measures. This study obtained hyperspectral images of early blight of peppers at different infection stages through continuous monitoring with a hyperspectral imager. The earliest identifiable time during the incubation period of early blight in peppers (the earliest identifiable time during the incubation period in this experiment was 24 h after inoculation) was determined using the spectral angle cosine-correlation coefficient and Chebyshev distance. MethodsTaking the symptoms of the latent period of early blight in peppers as the research object, 13 characteristic wavelengths were selected using a genetic algorithm. An identification model of crop disease latent period symptoms based on spectral features was established through optimized combinations of characteristic wavelengths combined with a logistic regression model. Simultaneously, a recognition model of the latent period of early blight in peppers based on image texture features was established using local binary patterns. ResultsThe experiment was tested with 120 samples. The accuracy of the identification model of crop disease latent period symptoms based on spectral features reached over 93% in both the training set and the test set. The accuracy of the identification model of crop disease latent period symptoms based on texture features reached 98.96% and 100% in the training set and test set, respectively. ConclusionBoth spectral features and texture features can be used to detect and identify crop disease latent period symptoms. Texture features more significantly revealed the characteristics of the latent period of the disease compared to spectral features, effectively improving the detection performance of the model. The research results in this article can provide theoretical references for monitoring and identifying other crop disease latent period symptoms.

Brain organoids are three-dimensional (3D) neural cultures that self-organize from pluripotent stem cells (PSCs) cultured in vitro. Compared with traditional two-dimensional (2D) neural cell culture systems, brain organoids demonstrate a significantly enhanced capacity to faithfully replicate key aspects of the human brain, including cellular diversity, 3D tissue architecture, and functional neural network activity. Importantly, they also overcome the inherent limitations of animal models, which often differ from human biology in terms of genetic background and brain structure. Owing to these advantages, brain organoids have emerged as a powerful tool for recapitulating human-specific developmental processes, disease mechanisms, and pharmacological responses, thereby providing an indispensable model for advancing our understanding of human brain development and neurological disorders. Despite their considerable potential, conventional brain organoids face a critical limitation: the absence of a functional vascular system. This deficiency results in inadequate oxygen and nutrient delivery to the core regions of the organoid, ultimately constraining long-term viability and functional maturation. Moreover, the lack of early neurovascular interactions prevents these models from fully recapitulating the human brain microenvironment. In recent years, the introduction of vascularization strategies has significantly enhanced the physiological relevance of brain organoid models. Researchers have successfully developed various vascularized brain organoid models through multiple innovative approaches. Biological methods, for example, involve co-culturing brain organoids with endothelial cells to induce the formation of static vascular networks. Alternatively, co-differentiation strategies direct both mesodermal and ectodermal lineages to generate vascularized tissues, while fusion techniques combine pre-formed vascular organoids with brain organoids. Beyond biological approaches, tissue engineering techniques have played a pivotal role in promoting vascularization. Microfluidic systems enable the creation of dynamic, perfusable vascular networks that mimic blood flow, while 3D printing technologies allow for the precise fabrication of artificial vascular scaffolds tailored to the organoid’s architecture. Additionally, in vivo transplantation strategies facilitate the formation of functional, blood-perfused vascular networks through host-derived vascular infiltration. The incorporation of vascularization has yielded multiple benefits for brain organoid models. It alleviates hypoxia within the organoid core, thereby improving cell survival and supporting long-term culture and maturation. Furthermore, vascularized organoids recapitulate critical features of the neurovascular unit, including the early structural and functional characteristics of the blood-brain barrier. These advancements have established vascularized brain organoids as a highly relevant platform for studying neurovascular disorders, drug screening, and other applications. However, achieving sustained, long-term functional perfusion while preserving vascular structural integrity and promoting vascular maturation remains a major challenge in the field. In this review, we systematically outline the key stages of human neurovascular development and provide a comprehensive analysis of the various strategies employed to construct vascularized brain organoids. We further present a detailed comparative assessment of different vascularization techniques, highlighting their respective strengths and limitations. Additionally, we summarize the principal challenges currently faced in brain organoid vascularization and discuss the specific technical obstacles that persist. Finally, in the outlook section, we elaborate on the promising applications of vascularized brain organoids in disease modeling and drug testing, address the main controversies and unresolved questions in the field, and propose potential directions for future research.

Objective To establish a stable and reliable method for the determination of ethylene oxide residue,and to analyze ethylene oxide residue in multi components made of different materials involved in some medical devices,so as to provide references for sample selection and ethylene oxide residue detection of multi-component medical device kits.Methods A method for the determination of ethylene oxide residue of multi-component medical devices was developed using headspace-gas chromatography and DB-WAX column under the conditions of headspace extraction with equilibration at 80℃ for 20 min,and the weighing mass,linearity,limit of detection,limit of quantification,precision and recovery of the method were determined.Trials of the method were carried out on the items undergoing ethylene oxide sterilization,including disposable perineal care kit,disposable gynecological examination kit,disposable suture dressing kit,disposable debridement kit and the components contacting human body in the disposable dialysis kit,and the abilities of different materials of the components were analyzed in absorbing,retaining and releasing ethylene oxide.Results The method showed high linearity(r=0.999 8)in the range of ethylene oxide mass concentration from 0.4 to 16.0 μg/mL with a weighing mass of 1.00 g,which had the limit of detection being 0.11 μg/mL,the limit of quantification being 0.37 μg/mL and the relative standard deviations(RSDs)for the precision from 0.35％to 1.52％.The average recoveries of different spiked amounts of ethylene oxide in the three blank matrices ranged from 92.68％to 101.42％with the relative standard deviations(RSDs)from 2.46％to 7.59％,which all satisfied the detection requirements.The components made of rubber and acrylonitrile-butadiene-styrene copolymer(ABS)in multi-component medical device kits had the highest ethylene oxide residues,followed by the components made of wood,degreased cotton,polypropylene and polystyrene.Conclusion The method proposed gains advantages in easy operation and high specificity,quantification and reproducibility,which can be used for the determination of ethylene oxide residue in the multi-component medical device kit undergoing ethylene oxide sterilization.References are provided for sample selection of multi-component medical devices.[Chinese Medical Equipment Journal,2024,45(1):56-61]

Currently,human health due to corona virus disease 2019(COVID-19)pandemic has been seriously threatened.The coronavirus severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)spike(S)protein plays a crucial role in virus transmission and several S-based therapeutic approaches have been approved for the treatment of COVID-19.However,the efficacy is compromised by the SARS-CoV-2 evolvement and mutation.Here we report the SARS-CoV-2 S protein receptor-binding domain(RBD)inhibitor licorice-saponin A3(A3)could widely inhibit RBD of SARS-CoV-2 variants,including Beta,Delta,and Omicron BA.1,XBB and BQ1.1.Furthermore,A3 could potently inhibit SARS-CoV-2 Omicron virus in Vero E6 cells,with EC50 of 1.016 pM.The mechanism was related to binding with Y453 of RBD deter-mined by hydrogen-deuterium exchange mass spectrometry(HDX-MS)analysis combined with quan-tum mechanics/molecular mechanics(QM/MM)simulations.Interestingly,phosphoproteomics analysis and multi fluorescent immunohistochemistry(mIHC)respectively indicated that A3 also inhibits host inflammation by directly modulating the JNK and p38 mitogen-activated protein kinase(MAPK)path-ways and rebalancing the corresponding immune dysregulation.This work supports A3 as a promising broad-spectrum small molecule drug candidate for COVID-19.

The complex chemical composition and limited research ideas of traditional Chinese medicine （TCM） have led to the unclear material basis and mechanism of the medicinal effects， which is a common problem hindering the modernization of TCM in China. The introduction of computer virtual technology has provided a new perspective for TCM research. In this study， we established the research method of structure-activity omics to study the relationships between the structures and effects of different compounds in TCM based on the chemical structures of TCM components and to analyze and predict the material basis and multitarget synergistic mechanism of TCM. Furthermore， a structure-activity omics study was carried out with the anti-inflammatory and analgesic effects of Qizhi Weitong granules as an example. This study provides support for screening the pharmacodynamic components and analyzing the active ingredients of TCM and gives insights into the research on the material basis and mechanism of compound efficacy and the development of lead compounds of TCM， thus promoting the modern research and the innovative development of TCM.

ObjectiveTo explain the anti-inflammatory and analgesic effects of Corydalis Rhizoma by the means of structure-activity omics. MethodOn the basis of the previous in vitro screening study， we studied the in vivo efficacy of the alkaloids in Corydalis Rhizoma. With the targets as a bridge， the structures of chemical components in Corydalis Rhizoma were connected with the efficacy. The molecular docking of the alkaloids in Corydalis Rhizoma with the targets of inflammation and pain was carried out. According to the docking scores and the differences in the structural nucleus of Corydalis Rhizoma alkaloids， a study of structure-activity omics was carried out to summarize the rules of their connection. ResultThe alkaloids in Corydalis Rhizoma had good anti-inflammatory and analgesic effects in vivo， involving 53 chemical components and 73 targets. There were 3 074 targets associated with inflammation and pain， and 42 targets of direct action were shared by the chemical components and the disease. The protein-protein interaction （PPI） and molecular docking analysis predicted that the main active components of Corydalis Rhizoma were tetrahydropalmatine and palmatine， and the core targets were prostaglandin endoperoxide synthase 2 （PTGS2）， glutamate receptor metabotropic 5 （GRM5）， estrogen receptor 1 （ESR1）， solute carrier family 6 member 4 （SLC6A4）， and fusion oncoproteins （FOS）. According to the differences of mother nucleus， the 53 alkaloid components of Corydalis Rhizoma were classified into 8 categories， including protoberberine， berberine， and aporphine， which had high binding affinities with PTGS2， GRM5 and other targets. The relationship between the structures of Corydalis Rhizoma alkaloids and docking scores in each group showed the same law. In protoberberine， appropriate substituents with hydroxyl， alkoxy or methyl groups on the A and D rings of the parent ring were conducive to enhancing the binding activities with the two targets. In berberine， the structure containing a methyl group on position 13 had strong binding affinities with the two targets. It is hypothesized that the methyl fragment changes the binding mode between the component structure and amino acid residues， which greatly improves the binding affinity. ConclusionThis study employs the method of structure-activity omics to analyze the material basis for the anti-inflammatory and analgesic effects of alkaloids in Corydalis Rhizoma， and the structure-activity omics provides new ideas for revealing the pharmacodynamic substances of traditional Chinese medicine.

ObjectiveTo identify the pharmacodynamic substances for the anti-inflammatory and analgesic effects of Bupleuri Radix by structure-activity omics. MethodA mouse model of pain was established with formaldehyde to examine the anti-inflammatory and analgesic effects of saikosaponins in vivo. The core targets of the active components in Bupleurum Radix for the anti-inflammatory and analgesic effects were screened from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）， Online Mendelian Inheritance in Man （OMIM）， and Search Tool for Recurring Instances of Neighbouring Genes （STRING）. The key core targets with high binding affinity were screened based on the comprehensive score in the molecular docking between different types of saikosaponins and core targets. The structure-activity relationship was discussed and analyzed based on the binding of compounds to pharmacodynamic targets. ResultSaikosaponins alleviated the foot swelling induced by formaldehyde and reduced the content of prostaglandin E₂ （PGE₂） in the mouse model， showcasing a significant inhibitory effect on the inflammatory pain caused by PGE₂. Nine components and 39 targets of saikosaponins， as well as 3 074 targets of anti-inflammatory and analgesic effects were screened out， and 22 common targets shared by saikosaponins and the effects were obtained as the direct targets. The protein-protein interaction （PPI） analysis showed that the main active components of Bupleurum Radix were saikosaponins a， b₁， b₂， b₃， c， d， e， f， and v， and the key targets were fms-related receptor tyrosine kinase 1 （FLT1）， kinase insert domain receptor （KDR）， fibroblast growth factor 2 （FGF2）， vascular endothelial growth factor A （VEGFA）， and signal transducer and activator of transcription 3 （STAT3）. Molecular docking between saikosaponins and the top 5 targets with high degrees in PPI network analysis revealed 25 highly active docks， including 6 docks with scores of 5-6 and 18 docks with scores above 6. ConclusionThis study adopted structural-activity omics to analyze the material basis for the anti-inflammatory and analgesic effects of Bupleuri Radix in vivo， providing new ideas and methods for identifying the pharmacodynamic substances in traditional Chinese medicine.

ObjectiveTo explain the pharmacodynamic substances of Aurantii Fructus flavonoids that exert anti-inflammatory and analgesic effects using a structure-activity omics approach. MethodOn the basis of the previous in vitro pharmacological screening conducted by the research team， an in vivo pharmacological study of Aurantii Fructus flavonoids was carried out. Core targets of the anti-inflammatory and analgesic active components of flavonoids of Aurantii Fructus were identified using various network databases， including the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）， the Online Mendelian Inheritance in Man （OMIM）， and the Search Tool for the Retrieval of Interacting Genes/Proteins （STRING）. Computer-aided virtual screening technology was used to dock different types of Aurantii Fructus flavonoids with core targets. The key core targets with high binding activity were selected based on the comprehensive scores of each target and the active structures. Using these targets as bridges， the structures of one or more types of chemical components in Aurantii Fructus were closely linked to pharmacological effects. The structure-activity relationship between the clear pharmacodynamic compounds and their effects was explored through the binding patterns of various structures with pharmacodynamic targets. ResultAurantii Fructus flavonoids demonstrated significant anti-inflammatory and analgesic effects on dextran sulfate sodium （DSS）-induced colitis in mice， which could improve symptoms and significantly reduce the levels of inflammatory factors interleukin-6 （IL-6） and interleukin-1β （IL-1β）（P<0.05）. Twelve active components of Aurantii Fructus flavonoids were identified and categorized into nine dihydroflavonoids and three flavonoids based on their structures of the parent nuclei. Through Venn analysis， 167 anti-inflammatory and analgesic targets for Aurantii Fructus were identified. Based on degree value and molecular docking comprehensive scores， prostaglandin-endoperoxide synthase 2（PTGS2） and mitogen-activated protein kinase 3（MAPK3） were selected for further structural analysis. Structural analysis revealed that components containing glycoside structures exhibited higher binding activity with anti-inflammatory and analgesic targets. ConclusionThis study utilized a structure-activity omics approach based on in vivo pharmacodynamic experiments to analyze the material basis of the anti-inflammatory and analgesic effects of Aurantii Fructus flavonoids. The structure-activity omics approach provides new ideas and methods for elucidating the pharmacodynamic substances of Chinese medicine.

Cells not only contain membrane-bound organelles (MBOs), but also membraneless organelles (MLOs) formed by condensation of many biomacromolecules. Examples include RNA-protein granules such as nucleoli and PML nuclear bodies (PML-NBs) in the nucleus, as well as stress granules and P-bodies in the cytoplasm. Phase separation is the basic organizing principle of the form of the condensates or membraneless organelles (MLOs) of biomacromolecules including proteins and nucleic acids. In particular, liquid-liquid phase separation (LLPS) compartmentalises and concentrates biological macromolecules into liquid condensates. It has been found that phase separation of biomacromolecules requires some typical intrinsic characteristics, such as intrinsically disordered regions, modular domains and multivalent interactions. The phase separation of biomacromolecules plays a key role in many important cell activities. In recent years, the phase separation of biomacromolecules phase has become a focus of research in gene transcriptional regulation. Transcriptional regulatory elements such as RNA polymerases, transcription factors (TFs), and super enhancers (SEs) all play important roles through phase separation. Our group has previously reported for the first time that long-term inactivation or absence of assembly factors leads to the formation of condensates of RNA polymerase II (RNAPII) subunits in the cytoplasm, and this process is reversible, suggesting a novel regulatory model of eukaryotic transcription machinery. The phase separation of biomacromolecules provides a biophysical understanding for the rapid transmission of transcriptional signals by a large number of TFs. Moreover, phase separation during transcriptional regulation is closely related to the occurrence of cancer. For example, the activation of oncogenes is usually associated with the formation of phase separation condensates at the SEs. In this review, the intrinsic characteristics of the formation of biomacromolecules phase separation and the important role of phase separation in transcriptional regulation are reviewed, which will provide reference for understanding basic cell activities and gene regulation in cancer.

Objective:To investigate the perinatal risk factors and correlation between bronchopulmonary dysplasia (BPD) and retinopathy of prematurity (ROP).Methods:A retrospective analysis was performed on 173 preterm infants born at less than 32 weeks' gestation with BPD who were admitted to the neonatal intensive care unit (NICU) of the Women and Children's Hospital of Qingdao University from June 2017 to July 2022. According to the diagnostic criteria for ROP, these preterm infants were divided into the ROP group ( n=64) and the non-ROP group ( n=109). Chi-square test, two independent samples t-test, and Mann-Whitney U test were used to compare the general data, treatment, and the incidence of complications between the two groups. Multivariate logistic stepwise regression analysis was used to analyze the independent risk factors of ROP in preterm infants with BPD and the receiver operating characteristic (ROC) curve was drawn to analyze the predictive value of independent risk factors on ROP. The correlation between the severity of BPD and the incidence of ROP was analyzed. Results:The gestational age at birth [(28.0±1.1) vs. (28.8±1.2) weeks, t=4.01], the birth weight [(1 075.9±141.4) vs. (1 143.2±168.6) g, t=2.68], the partial pressure of carbon dioxide [42.5 mmHg (1 mmHg=0.133 kPa) (34.0-51.0 mmHg) vs. 47.0 mmHg (39.0-54.0 mmHg), Z=－2.31], and the total fluid intake on the first day of birth [80.0 ml (72.3-88.7 ml) vs. 83.6 ml (76.6-92.8 ml), Z=－2.28] in the ROP group were all lower than those in the non-ROP group (all P<0.05). While the prothrombin time [15.7 s (14.1-17.7 s) vs. 14.6 s (13.1-16.7 s), Z=－2.17], activated partial thromboplastin time [64.7 s (52.9-77.9 s) vs. 55.8 s (48.4-68.9 s), Z=－2.12], the proportion of patients treated with pulmonary surfactant [71.9% (46/64) vs. 49.5% (54/109), χ 2=8.25], the total duration of oxygen supplementation [50.5 d (40.0-64.0 d) vs. 45.0 d (37.0-52.0 d), Z=－2.77], the duration of invasive ventilation [5.0 d (1.0-11.0 d) vs. 1.0 d (0.0-5.0 d), Z=－4.03], the duration of noninvasive ventilation or high-flow oxygen therapy [(31.7±12.7) vs. (26.4±13.1) d, t=－2.59], and the incidence of neonatal respiratory distress syndrome [76.6% (49/64) vs. 57.8% (63/109), χ 2=6.22] were increased in the ROP group (all P<0.05). There was no significant difference in the proportion of BPD treated with corticosteroids between the ROP and non-ROP groups [60.3% (38/63) vs. 74.3% (81/109), χ 2=3.67, P=0.055]. Multivariate logistic stepwise regression analysis showed that smaller gestational age ( OR=1.599, 95% CI: 1.126-2.272, P=0.009), less fluid intake on the first day ( OR=1.033, 95% CI: 1.004-1.062, P=0.024), and longer duration of invasive ventilation ( OR=1.076, 95% CI:1.017-1.138, P=0.011) were independent risk factors for ROP in BPD infants, while glucocorticoid treatment was an independent protective factor ( OR=0.378, 95% CI:0.173-0.827, P=0.015). Most patients with mild or moderate BPD did not develop ROP [64.6% (73/113) and 66.7% (34/51)], while those with severe BPD were more likely to be complicated by ROP (7/9) ( χ 2=6.84, P=0.033). Conclusions:BPD infants with smaller gestational age, longer duration of invasive ventilation, and less fluid intake on the first day of birth are more likely to develop ROP, while glucocorticoid therapy can reduce the incidence of ROP in this population. Severe BPD may increase the risk of ROP in infants.