Autism spectrum disorder in children (hereinafter called "childhood autism") is a prevalent neurodevelopmental condition; however, ancient Chinese medical texts did not provide detailed accounts of it. The concept of "the sovereign fire illuminates, while the ministerial fire occupies its position" was first introduced in the Plain Questions: The Great Treatise on the Origin of Heavenly Influences chapter. Subsequent medical practitioners have elaborated on this idea, identifying the sovereign fire as the master of the spirit and governing life activities, while the ministerial fire is the assisting minister that supports the functions of the zang-fu organs. When these two are in harmony, they complement each other, collectively sustaining the body′s normal physiological functions. In the context of this theory, the pathogenesis of childhood autism is attributed to the imbalance between the sovereign and ministerial fires. The root cause lies in the mutual antagonism of these two fires, resulting in the dysfunction of the spirit. Central to childhood autism onset is the dimming of the sovereign fire and a deficiency in the spirit, while the displacement of the ministerial fire and the impaired function of the five viscera contribute significantly to the progression of the condition. Effective treatment for childhood autism involves restoring these imbalances: dispelling yin-related obstructions to illuminate the sovereign fire, nourishing the spleen and kidney to nourish the ministerial fire, and regulating the liver and lung to harmonize the sovereign and ministerial fires. The ultimate goal is to integrate body and spirit, harmonize the sovereign and ministerial fires, and restore the interconnectedness between spirit and the function of the five zang viscera. This article, based on the "the sovereign fire illuminates, while the ministerial fire occupies its position" theory, provides a novel perspective and insights for understanding and treating childhood autism through the holistic principles of traditional Chinese medicine. Emphasizing the integration of body and spirit offers new insights and approaches for the clinical management of childhood autism in traditional Chinese medicine.

A new method for simultaneous determination of 23 kinds of per-and polyfluoroalkyl substances(PFASs)(13 kinds of perfluoro carboxylic acids,4 kinds of perfluoro sulfonic acids,and 6 kinds of new substitutes)in plant leaf tissue by ultra-high performance liquid chromatography-tandem mass spectrometry(UHPLC-MS/MS)using automatic online solid phase extraction(SPE)to remove the matrix interference components in plant crude extracts was developed.The plant leaf samples were extracted twice with 1%formic acid-methanol solution,then evaporated to dry,redissolved with 70%methanol solution,and directly injected for analysis.After 23 kinds of target PFASs were purified automatically by online SPE with a WAX column,the six-way valve was switched to rinse PFASs onto an alkaline mobile phase system-compatible C18 analytical column.Then,the 23 kinds of target PFASs were separated within 16 min by gradient elution using a binary mobile phase system of methanol/water(Containing 0.4%ammonium hydroxide).Tandem mass spectrometry was performed in multiple reaction monitoring(MRM)mode for online detection of various PFASs,and quantification was carried out by internal standard method.The results of the method validation showed that satisfactory average recoveries of 23 kinds of PFASs in plant leaf samples(64.2%-125.5%),precision(relative standard deviations(RSDs)of 0.7%-12.8%),linearity(R2＞0.990),and sensitivity(the detection limits(S/N=3)were in the range of 0.02-0.50 μg/kg)were achieved.Finally,this method was used to detect PFASs in the marine green tide algae(Enteromorpha prolifera)and several tree leaves,and a total of 6 kinds of PFASs were detected,in which PFBA was the main contaminant.Compared with the reported offline SPE methods,the proposed online SPE technique significantly simplified the sample pretreatment process and provided an automatic,simple,and environment-friendly method for the routine monitoring of legacy and emerging PFASs in plant tissues.

ATG8-binding proteins play a key role in autophagy, selective autophagy or non-autophagy process by interacting between ATG8 and the ATG8-interacting motif (AIM) or the ubiquitin-interacting motif (UIM). There is great progress of ATG8-binding proteins in yeast and mammalian studies. However, the plant domain is still lagging behind. Therefore, the structure characteristics of plant ATG8 binding protein were firstly outlined. Unlike the single copy of ATG8 gene in yeast, many homologous genes have been identified in plant. The LIR/ AIM-docking site (LDS) of ATG8 protein contains W and L pockets and is responsible for binding to AIM. The ATG8 protein binds to UIM-containing proteins via UIM-docking site (UDS) instead of LDS. UDS is in the opposite position to LDS, so the ATG8 can bind both AIM and UIM proteins. Secondly, the structure and function of ATG8-binding proteins, especially the selective autophagy receptors, were systematically described. The protein NBR1 and Joka2, as proteaphagy receptors, guide ubiquitination protein aggregates to autophagosome for degradation by binding to AIM and ATG8 in Arabidopsis and tobacco, respectively. AtNBR1 also promotes plant immunity by binding the capsid protein of cauliflower mosaic virus and silencing suppressor HCpro of turnip mosaic virus, mediating pathogen autophagy. AtNBR1 still degrades chloroplast by microautophagy under photoinjure or chlorophagy during ibiotic stress. And the protein ORM mediates the degradation of plant immune receptor flagellin sensing 2 (FLS2) through AIM binding to ATG8. Interestingly, ATI1 and ATI2 participate in both chlorophagy and ERphagy. Otherwise, ER membrane protein AtSec62, soluble protein AtC53, and ubiquitin-fold modifier1-specific ligase 1 (UFL1) can be directly bound to ATG8 as ER autophagy receptors. As pexophagy receptor, AtPEX6 and AtPEX10 bind to ATG8 via AIM and participate in pexophagy. RPN10, as a 26S proteasome subunit, whose C-terminal UIM1 and UIM2 bind ubiquitin and ATG8, respectively, mediates the selective autophagy degradation of 26S proteasome inactivation when fully ubiquitinated. Plant-specific mitochondrial localization proteins FCS-like zinc finger (FLZ) and friendly (FMT) may also be mitophagy receptors. CLC2 binds to ATG8 via the AIM-LDS docking site and is recruited to autophagy degradation on the Golgi membrane. The tryptophan-rich sensory protein (TSPO) in Arabidopsis was involved in clearing free heme, porphyrin and plasma membrane intrinsic protein 2;7 (PIP2;7) through the combination of AIM and ATG8. The conformation of GSNOR1 changes during anoxia, exposing the interaction between AIM and ATG8, leading to selective degradation of GSNOR1. At last, the ATG8 binding proteins involved in autophagosome closure, transport and synthetic synthesis was summarized. For example, plant-specific FYVE domain protein required for endosomal sorting 1 (FREE1) is involved in the closure of autophagosomes during nutrient deficiency. Therefore, according to the recent research advances, the structure and function of plant ATG8-binding proteins were systematically summarized in this paper, in order to provide new ideas for the study of plant selective autophagy and autophagy.

This study proposed the use of the minimum slip force as an indicator to measure the clamping ability of microsurgical forceps.By analyzing the minimum slip forces of four typical tooth types of microsurgical forceps,the clamping capacity of each type was evaluated.Among the existing tooth forms,the staggered tooth type exhibited a relatively large minimum slip force.Consequently,a new tooth-shaped structure for microsurgical forceps-the hemispherical convex structure was proposed.Simulation and experimental studies demonstrated that this new dental structure could achieve stable and reliable clamping.

Objective To explore the efficacy and safety of recombinant human anti-severe acute respiratory syn-drome coronavirus 2(anti-SARS-CoV-2)monoclonal antibody injection(F61 injection)in the treatment of patients with coronavirus disease 2019(COVID-19)combined with renal damage.Methods Patients with COVID-19 and renal damage who visited the PLA General Hospital from January to February 2023 were selected.Subjects were randomly divided into two groups.Control group was treated with conventional anti-COVID-19 therapy,while trial group was treated with conventional anti-COVID-19 therapy combined with F61 injection.A 15-day follow-up was conducted after drug administration.Clinical symptoms,laboratory tests,electrocardiogram,and chest CT of pa-tients were performed to analyze the efficacy and safety of F61 injection.Results Twelve subjects(7 in trial group and 5 in control group)were included in study.Neither group had any clinical progression or death cases.The ave-rage time for negative conversion of nucleic acid of SARS-CoV-2 in control group and trial group were 3.2 days and 1.57 days(P=0.046),respectively.The scores of COVID-19 related target symptom in the trial group on the 3rd and 5th day after medication were both lower than those of the control group(both P＜0.05).According to the clinical staging and World Health Organization 10-point graded disease progression scale,both groups of subjects improved but didn't show statistical differences(P＞0.05).For safety,trial group didn't present any infusion-re-lated adverse event.Subjects in both groups demonstrated varying degrees of elevated blood glucose,elevated urine glucose,elevated urobilinogen,positive urine casts,and cardiac arrhythmia,but the differences were not statistica-lly significant(all P＞0.05).Conclusion F61 injection has initially demonstrated safety and clinical benefit in trea-ting patients with COVID-19 combined with renal damage.As the domestically produced drug,it has good clinical accessibility and may provide more options for clinical practice.

Objective To explore the feasibility of quantitative EEG parameters for prognostic prediction of patients with severe aneurysmal subarachnoid hemorrhage(SaSAH)90 d after the onset of the disease.Methods Patients with SaSAH admitted to the Neurosurgical Intensive Care Unit(NSICU)of Henan Provincial People's Hospital from September 2022 to September 2023 were prospectively consecutively enrolled,and baseline data were collected,including age,gender,medical history(hypertension,diabetes mellitus,coronary artery disease,and stroke),history of smoking,history of drinking,location of aneurysm(anterior circulation,posterior circulation),surgical modality(craniotomy,interventional surgery,hybrid surgery),Hunt-Hess classification,Glasgow coma scale(GCS)score,acute physiology and chronic health status scoring system Ⅱ(APACHE Ⅱ)score,subarachnoid hemorrhage early brain edema score(SEBES),first randomized blood glucose level after admission to NSICU,lactate level,and duration of NSICU stay.Quantitative EEG monitoring was performed in all patients within 48 h after admission to the NSICU,and amplitude-integrated electroencephalogram(aEEG)upper and lower boundaries,95％spectral edge frequency(SEF95),α change,(δ+θ)to(α+β)power ratio(DTABR),brain symmetry index(BSI),and spectral entropy were collected.Based on modified Rankin scale(mRS)scores 90 d after onset,patients were categorized into good prognosis(mRS score 2 points)and poor prognosis(mRS score 3-6 points)groups.Spearman rank correlation was used to analyze the correlation between quantitative EEG parameters and mRS scores in SaSAH patients.Multifactorial Logistic regression analysis was used to screen for correlates of poor prognosis,and receiver operating characteristic(ROC)curves were plotted to evaluate the efficacy of each index in predicting patients'poor prognosis.Results(1)A total of 72 patients with SaSAH were included,with 47 in the poor prognosis group and 25 in the good prognosis group,and the poor prognosis rate at 90 d after the onset was 65.3％.There was no statistically significant difference between the two groups in terms of gender,age,hypertension,diabetes mellitus,coronary artery disease,history of stroke,history of smoking,history of drinking,location of aneurysm,surgical modality,lactate level,and length of hospitalization in the NSICU(all P＞0.05);the differences between the Hunt-Hess grading,SEBES,and random blood glucose were statistically significant upon comparison(all P＜0.05).Compared with the good prognosis group,the changes of aEEG upper and lower boundary,SEF95,α change and spectral entropy were lower in the poor prognosis group,but DTABR and BSI were higher(all P＜0.05).(2)Spearman rank correlation analysis showed that the upper border of aEEG(r=-0.41,P＜0.01),lower border of aEEG(r=-0.54,P＜0.01),SEF95(r=-0.46,P＜0.01),α change(r=-0.53,P＜0.01)and spectral entropy(r=-0.39,P＜0.01)were negatively correlated with the mRS scores of SaSAH patients,and DTABR(r=0.52,P＜0.01)and BSI(r=0.33,P＜0.01)were positively correlated with poor prognosis of SaSAH patients.(3)The results of multifactorial Logistic regression analysis showed that Hunt-Hess grading(level Ⅳ vs.Ⅲ:OR,1.203,95％CI 1.005-1.441,P=0.044;level V vs.Ⅲ:OR,1.661,95％CI 1.109-2.487,P=0.014),SEBES(OR,1.647,95％CI 1.050-2.586;P=0.030),aEEG lower border(OR,0.687,95％CI 0.496-0.953l;P=0.024),SEF95(OR,0.436,95％CI0.202-0.937;P=0.034),α change(OR,0.368,95％CI0.189-0.717;P=0.003),DTABR(OR,1.324,95％CI 1.064-1.649;P=0.012),and BSI(OR,1.513,95％CI 1.026-2.231;P=0.036)were influencing factors of poor prognosis in SaSAH patients.ROC curve analysis showed that all of the above seven indicators had a certain predictive value for poor prognosis in SaSAH patients,among which the area under the curve of DTABR was the highest as 0.862(95％CI 0.761-0.932),with sensitivity 85.11％and specificity 80.00％.Conclusion Quantitative EEG parameters aEEG lower border,SEF95,α change,DTABR,and BSI may have certain predictive value for the short-term prognosis of SaSAH patients,which needs to be further confirmed in future multi-center large-sample studies.

ObjectiveAngle-closure glaucoma (ACG) is one of the major eye-blinding diseases. To diagnose ACG, it is crucial to examine the anterior chamber angle. Current diagnostic tools include slit lamp gonioscopy, water gonioscopy, ultrasound biomicroscopy (UBM), and anterior segment optical coherence tomography (AS-OCT). Slit lamp and water gonioscopy allow convenient observation of the anterior chamber angle, but pose risks of invasive operation and eye infections. UBM can accurately measure the structure of the anterior chamber angle. However, it is complex to operate and unsuitable for patients, who have undergone trauma or ocular surgery. Although AS-OCT provides detailed images, it is costly. The aim of this study is to explore a non-invasive, non-destructive optical reflection tomography (ORT) technique. This technique can achieve low-cost three-dimensional imaging and full-field anterior chamber angle measurement of the porcine eye. MethodsThe experiment involved assembling an optical reflection tomography system, which included a complementary metal oxide semiconductor (CMOS) camera, a telecentric system, a stepper motor, and a white light source, achieving a spatial resolution of approximately 8.5 μm. The process required positioning the porcine eye at the center of the field of the imaging system and rotating it around its central axis using a stepper motor. Reflection projection images were captured at each angle with an exposure time of 1.0 ms and an interval of 2°. The collected reflection-projection data were processed using a filtered reflection tomography algorithm, generating a series of two-dimensional slice data. These slices essentially represented cross-sectional views of the three-dimensional structural image, and were reconstructed into a complete three-dimensional structural image. Based on the reconstructed three-dimensional structural image of the porcine eye, the anterior chamber angles at different positions were measured, and a distribution map of these angles was drawn. Simultaneously, the ORT measurements were compared with the standard results obtained from optical coherence tomography (OCT) to assess the accuracy of ORT measurements. ResultsIn this study, we successfully obtained the reflection projection data of a porcine eye using ORT technology, reconstructed its three-dimensional structural image, and measured the anterior chamber angle, generating the corresponding distribution map. To better distinguish the different structural parts of porcine eye, the three-dimensional structural image was marked with blue, green, and yellow dashed lines from the outer to the inner layers. The area between the blue and green dashed lines corresponded to the sclera. The area between the green and yellow dashed lines corresponded to the iris. The area inside the yellow dashed line corresponded to the pupil. The three-dimensional structural image clearly revealed the key anatomical features of the porcine eye. It was able to measure the anterior chamber angle at different positions. Additionally, the anterior chamber angle measurements of the porcine eye using ORT were compared with the measurements obtained using a TEL320C1 type OCT system, showing an average deviation of 0.51° and a mean square error MSE of 0.317. ConclusionORT is a non-invasive, non-destructive, low-cost, and high-resolution imaging technique capable of achieving three-dimensional structural imaging and full-field anterior chamber angle measurement of a porcine eye. This technology offers a new perspective for the diagnosis of angle-closure glaucoma and is significant for the screening, diagnosis, and monitoring of eye diseases, potentially benefiting clinics and small hospitals in remote areas in the future.

Cordycepin (Cpn), a natural active compound derived from the traditional Chinese medicine Cordyceps sinensis, has antifibrotic, antioxidant, and anti-inflammatory effects, but the impact of Cpn on pulmonary fibrosis and the downstream molecular mechanism remain unclear. In this study, A549 cells were induced by transforming growth factor β1 (TGFβ1) in vitro, the viability of A549 cells was evaluated by CCK-8 assay; and migration of A549 cells were detected by wound healing assay, invasion of A549 cells were detected by transwell assay. Molecular docking and molecular dynamics simulations were used to predict the interaction of histone deacetylase 7 (HDAC7) with vimentin and the association of Cpn with HDAC7. The pulmonary fibrosis model of mice was established by bleomycin in vivo to investigate the effect of Cpn on pathological changes of lung tissue. The impact of Cpn and molecular mechanism on pulmonary fibrosis were studied by Western blot assay, cell transfection assay, immunoprecipitation assay, immunofluorescence assay, immunohistochemistry and real-time quantitative PCR (RT-qPCR). All animal experiments were approved by the Shanghai Children's Medical Center Experimental Animal Ethics Committee (grant No. SCMC-LAWEC-2022-017). Results showed that Cpn had no toxic effect on A549 cells even at the concentration of 100 μmol·L^-1. Cpn inhibited migration and invasion of A549 cells and reduced deposition of collagen, the degree of lung inflammation and fibrosis in mice; in vivo and in vitro models, Cpn significantly reversed mRNA and protein expressions of epithelial-mesenchymal transition (EMT) and lung fibrosis markers collagen I, α-smooth muscle actin (α-SMA), N-cadherin, vimentin and E-cadherin and HDAC7. Deficiency of HDAC7 suppressed TGFβ1-induced EMT and expression of collagen I; vimentin interacted with HDAC7; and molecular docking experiment revealed that Cpn was interrelated with HDAC7. In conclusion, Cpn can target HDAC7 to mediate EMT and exert its anti-fibrotic effect, the inhibition of EMT and the improvement of pulmonary fibrosis provide a new idea and choice for the development of anti-pulmonary fibrosis drug.

Brasilicardin A, a diterpene glycoside isolated from pathogenic actinomycete Nocardia brasiliensis IFM 0406, has become a novel immunosuppressant candidate due to its significant immunosuppressive activity, low toxicity and unique mechanism of action. However, brasilicardin A and its analogues have become a research hotspot to the development of this promising immunosuppressant because of the low-yield production in the natural pathogenic producer and the synthetically challenging skeleton. According to the reported biosynthetic pathway of brasilicardin A, the function of involved diterpene synthase was analyzed by bioinformatics. Then the genes bra1-5 that synthesize the brasilicardin A skeleton were directionally amplified from the pathogenic strain N. brasiliensis IFM 0406, and heterologous expression was achieved successfully in Streptomyces albus R1. The compounds were isolated and purified by using various column chromatographies including silica gel column chromatography and semi-preparative HPLC. Six new brasilicardins were established and named brasilicardin H-M. The activity of brasilicardins was screened using lipopolysaccharide (LPS)-activated mouse primary macrophage inflammation model. Brasilicardin H-M exhibited good inhibitory activity on nitric oxide (NO) release with IC₅₀ values of 28.24 ± 3.70, 37.44 ± 2.00, 39.85 ± 4.02, 26.77 ± 4.40, 65.25 ± 1.48 and 15.24 ± 2.72 μmol·L^-1, respectively (indomethacin as the positive control with IC₅₀ value of 34.28 ± 4.10 μmol·L^-1). The results indicated that six compounds had potential anti-inflammatory activity. This study laid a foundation for the elucidation of the brasilicardin A biosynthetic pathway and evaluation of the structure-activity relationship as well as new drug developments.

Antimony is a toxic metalloid and exhibits different geochemical properties in different valence states,leading to distinct migration,transformation,and behavioral patterns in the environment.To further study the transfer and source-sink relationship of antimony and its compounds in the earth's surface ecological environment,it is very important to accurately determine the isotopic composition of antimony with different speciations.In this study,a pretreatment method for chromatographic separation and determination of different speciation's antimony isotopes in water samples was established by using multi-collector inductively coupled plasma mass spectrometry(MC-ICP-MS)to measure the isotopic composition of different speciation's antimony.This method was successfully applied to detection of natural rainwater and groundwater samples from the Qilong mining area.During the pretreatment,5 mmol/L ethylenediaminetetraacetic acid dipotassium salt(EDTA)and 2 mmol/L potassium hydrogen phthalate(KHP)(pH 4.5)were used as mobile phase,successfully separating trivalent antimony(Sb(Ⅲ))and pentavalent antimony(Sb(Ⅴ))from water samples using a Hamilton PRP-X100 anion exchange chromatographic column.A series of single-factor experiments identified the optimal separation and determination conditions as a column temperature of 40 ℃ and a high-performance liquid pump flow rate of 1.5 mL/min.The recoveries of Sb(Ⅲ)and Sb(Ⅴ)from the standard solutions of Sb(Ⅲ)and Sb(Ⅴ),and the mixed oxidation states solutions were 99％±1％,103％±1％,106％±1％,and 101％±1％,respectively.Moreover,the isotopic compositions of different speciation's antimony remained consistent before and after the chromatographic column treatment,and the reliability of the method was verified by detecting different oxidation state antimony in the natural rainwater samples.This research might provide important technical support for further studies on the geochemical cycling of antimony and its compounds in the ecological environment of the Earth's surface.