Fully Active Delivery of Nanodrugs In Vivo via Remote Optical Manipulation.

The active delivery of nanodrugs has been a bottleneck problem in nanomedicine. While modification of nanodrugs with targeting agents can enhance their retention at the lesion location, the transportation of nanodrugs in the circulation system is still a passive process. The navigation of nanodrugs with external forces such as magnetic field has been shown to be effective for active delivery, but the existing techniques are limited to specific materials like magnetic nanoparticles. In this study, an alternative actuation method is proposed based on optical manipulation for remote navigation of nanodrugs in vivo, which is compatible with most of the common drug carriers and exhibits significantly higher manipulation precision. By the programmable scanning of the laser beam, the motion trajectory and velocity of the nanodrugs can be precisely controlled in real time, making it possible for intelligent drug delivery, such as inverse-flow transportation, selective entry into specific vascular branch, and dynamic circumvention across obstacles. In addition, the controlled mass delivery of nanodrugs can be realized through indirect actuation by the microflow field. The developed optical manipulation method provides a new solution for the active delivery of nanodrugs, with promising potential for the treatment of blood diseases such as leukemia and thrombosis.

Genome-Wide Identification and Expression Pattern of MYB Family Transcription Factors in Erianthus fulvus.

MYB family genes have many functions and are widely involved in plant abiotic-stress responses. Erianthus fulvus is an important donor material for stress-resistance genes in sugarcane breeding. However, the MYB family genes in E. fulvus have not been systematically investigated. In this study, 133 EfMYB genes, including 48 Ef1R-MYB, 84 EfR2R3-MYB and 1 Ef3R-MYB genes, were identified in the E. fulvus genome. Among them, the EfR2R3-MYB genes were classified into 20 subgroups. In addition, these EfMYB genes were unevenly distributed across 10 chromosomes. A total of 4 pairs of tandemly duplicated EfMYB genes and 21 pairs of segmentally duplicated EfMYB genes were identified in the E. fulvus genome. Protein-interaction analysis predicted that 24 EfMYB proteins had potential interactions with 14 other family proteins. The EfMYB promoter mainly contains cis-acting elements related to the hormone response, stress response, and light response. Expression analysis showed that EfMYB39, EfMYB84, and EfMYB124 could be significantly induced using low-temperature stress. EfMYB30, EfMYB70, EfMYB81, and EfMYB101 responded positively to drought stress. ABA treatment significantly induced EfMYB1, EfMYB30, EfMYB39, EfMYB84, and EfMYB130. All nine genes were induced using MeJA treatment. These results provide comprehensive information on EfMYB genes and can serve as a reference for further studies of gene function.

[Heavy Metal Pollution and Health Risk Assessment in Karst Basin Around a Lead-Zinc Mine].

Water quality is one of the most important environmental issues in the sustainable development of karst areas. To investigate heavy metal pollution and assess health risk in karst water basins around mines, 18 groups of water samples were collected from the river and groundwater in the Sidi River karst basin, and the concentrations of nine types of heavy metals(Cu, Pb, Zn, Cd, Mn, Fe, As, Cr, and Sr) were determined. Sample data were analyzed using principal component analysis, correlation analysis, water quality index, the Nemerow comprehensive pollution index, hazard quotient, and hazard index. The results showed that the Sidi River was slightly alkaline. The farther the river water samples were from the tailings reservoir, the lower were the concentrations of Cu, Pb, Zn, Cd, Mn, Fe, As, and Sr in the river water. Principal component and correlation analyses showed that heavy metals in the Sidi River karst basin mainly came from mine discharge(55.42%), carbonate weathering dissolution(21.41%), and human activities(14.72%). Eighty-two percent of the samples in the river and all the samples in the groundwater were excellent water. The Nemerow comprehensive pollution index in the river was 4.12 with strong pollution. All the hazard indices were below 1, and Pb, Zn, As, Cd, and Cr were potentially threatening metals in the Sidi River karst basin. The concentration of heavy metals changed significantly after entering the karst conduit, indicating that the unique properties of the karst aquifer affected the spatial variation of the heavy metal concentration. The results of this study can provide data reference for water resource prevention and human health protection in the Sidi River karst basin and similar karst basins.

Optically Programmable Living Microrouter in Vivo.

With high reconfigurability and swarming intelligence, programmable medical micromachines (PMMs) represent a revolution in microrobots for executing complex coordinated tasks, especially for dynamic routing of various targets along their respective routes. However, it is difficult to achieve a biocompatible implantation into the body due to their exogenous building blocks. Herein, a living microrouter based on an organic integration of endogenous red blood cells (RBCs), programmable scanning optical tweezers and flexible optofluidic strategy is reported. By harvesting energy from a designed optical force landscape, five RBCs are optically rotated in a controlled velocity and direction, under which, a specific actuation flow is achieved to exert the well-defined hydrodynamic forces on various biological targets, thus enabling a selective routing by integrating three successive functions, i.e., dynamic input, inner processing, and controlled output. Benefited from the optofluidic manipulation, various blood cells, such as the platelets and white blood cells, are transported toward the damaged vessel and cell debris for the dynamic hemostasis and targeted clearance, respectively. Moreover, the microrouter enables a precise transport of nanodrugs for active and targeted delivery in a large quantity. The proposed RBC microrouter might provide a biocompatible medical platform for cell separation, drug delivery, and immunotherapy.

Effect of Void Defects on the Indentation Behavior of Ni/Ni3Al Crystal.

Inconel 718 (IN 718) superalloys are widely used as engineering materials owing to their superior mechanical performance. And voids are unavoidable defects in IN 718 superalloy preparation, which dramatically affect the mechanical properties of IN 718 superalloys. In this work, the effects of void radius, distance from the top of the void to the substrate surface, and substrate temperature on the mechanical properties of the Ni/Ni3Al crystal are systematically investigated. It is shown that voids affect the formation of stair-rod dislocations and Shockley dislocations in the substrate, which in turn determines the mechanical properties. Thus, with the increase in void radius, Young's modulus and hardness gradually decrease. With the increase in void distance, Young's modulus and hardness increase and finally tend to be stable. In addition, the increase in substrate temperature leads to the interphase boundary becoming irregular and increases the defects in the γ and γ″ phases. As a result, Young's modulus and hardness of the substrate decrease. This work aims to provide a guideline for investigating the indentation properties of Ni-based superalloys using MD.

Genome-Wide Identification, Evolution, and Expression Analyses of AP2/ERF Family Transcription Factors in Erianthus fulvus.

The AP2/ERF transcription factor family is one of the most important gene families in plants and plays a vital role in plant abiotic stress responses. Although Erianthus fulvus is very important in the genetic improvement of sugarcane, there are few studies concerning AP2/ERF genes in E. fulvus. Here, we identified 145 AP2/ERF genes in the E. fulvus genome. Phylogenetic analysis classified them into five subfamilies. Evolutionary analysis showed that tandem and segmental duplication contributed to the expansion of the EfAP2/ERF family. Protein interaction analysis showed that twenty-eight EfAP2/ERF proteins and five other proteins had potential interaction relationships. Multiple cis-acting elements present in the EfAP2/ERF promoter were related to abiotic stress response, suggesting that EfAP2/ERF may contribute to adaptation to environmental changes. Transcriptomic and RT-qPCR analyses revealed that EfDREB10, EfDREB11, EfDREB39, EfDREB42, EfDREB44, EfERF43, and EfAP2-13 responded to cold stress, EfDREB5 and EfDREB42 responded to drought stress, and EfDREB5, EfDREB11, EfDREB39, EfERF43, and EfAP2-13 responded to ABA treatment. These results will be helpful for better understanding the molecular features and biological role of the E. fulvus AP2/ERF genes and lay a foundation for further research on the function of EfAP2/ERF genes and the regulatory mechanism of the abiotic stress response.

Association between napping and 24-hour blood pressure variability among university students: A pilot study.

Background: Blood pressure variability (BPV) has been reported to be a predictor of cardiovascular and some cognitive diseases. However, the association between napping and BPV remains unknown. This study aimed to explore the association between napping and BPV. Materials and methods: A cross-sectional study including 105 university students was conducted. Participants' 24 h ambulatory blood pressure monitoring (24 h ABPM) were measured, and napping behaviors were investigated. BPV were measured by the 24 h ABPM, included standard deviation (SD), coefficient of variation (CV), and average real variability (ARV). Results: Among the participants, 61.9% reported daytime napping. We found that nap duration was significantly associated with daytime CV of diastolic blood pressure (DBP) (r = 0.250, P = 0.010), nighttime CV of systolic blood pressure (SBP) (r = 0.217, P = 0.026), 24 h WCV of DBP (r = 0.238, P = 0.014), 24 h ARV of SBP (r = 0.246, P = 0.011) and 24 h ARV of DBP (r = 0.291, P = 0.003). Compared with the no napping group, 24 h WCV of DBP, daytime CV of DBP, and daytime SD of DBP were significantly higher in participants with napping duration >60 min. With multiple regression analysis we found that nap duration was an independent predictor for 24 h ARV of SBP (ß = 0.859, 95% CI, 0.101-1.616, P = 0.027) and 24 h ARV of DBP (ß = 0.674, 95% CI, 0.173-1.175, P = 0.009). Conclusions: Napping durations are associated with BPV among university students. Especially those with napping durations >60 min had a significantly higher BPV than those non-nappers.

Differential expression profiles analysis of DNA methylation between “disease” and “syndrome” in coronary heart disease-induced unstable angina patientswith Qi deficiency and blood stasis syndrome / 数字中医药（英文）

Objective@#To explore the differential expression profiles of DNA methylation sites/regions and potential molecular mechanisms in the peripheral blood of coronary heart disease (CHD)-induced unstable angina pectoris patients with or without Qi deficiency and blood stasis syndrome, and to provide scientific evidence for the conbination of disease and syndrome.@*Methods@#According to the pre-determined inclusion and exclusion criteria, the study subjects were enrolled and divided into two groups namely CHD-induced unstable angina group (G group) and healthy control group (J group) to conduct “disease” analysis, while G group was further divided into Qi deficiency and blood stasis syndrome group (case group) and non-Qi deficiency blood stasis syndrome group (control group) to perform “syndrome” analysis. The general data and clinical information of the study subjects were collected. The peripheral venous blood was extracted on an empty stomach, and the Illumina Infinium MethylationEPIC BeadChip (850K methylation chip) was used to detect the differential expressionprofiles of DNA methylation in each group, ChAMP software (V 2.14.0) was used for the differential methylation data analysis, with a threshold of the adjusted P value (adj.P.val) < 0.01. Gene Ontology (GO) and Kyoto Encyclopedia of Genomes (KEGG) were employed for the functional and pathway enrichment analyses of related mapped genes.@*Results@#A total of 263 differentially methylated CpG positions (DMPs) were screened out between G and J groups, including 191 hypermethylated positions such as cg05845204 and cg08906898, and 72 hypomethylated positions such as cg26919182 and cg13149459. These positions were mainly mapped to 148 genes encompassing RNA binding motif protein 39 (RBM39), acetyl-CoA acyltransferase 2 (ACAA2), protein phosphatase 1 regulatory subunit 12B (PPP1R12B), and the dual-specificity tyrosine phosphorylation-regulated kinase 2 (DYRK2). GO functional enrichment analysis revealed that the genes of the DMPs were primarily enriched in protein localization to chromosomes, regulation of cell morphogenesis, negative regulation of calcium-mediated signals, etc. KEGG pathway analysis suggested that the genes were mainly enriched in fatty acid metabolism and endocytosis pathways. In addition, a total of 23 differential methylation regions (DMRs) were identified, with overlapping genes such as transmembrane protein 232 (TMEM232), ribosomal protein large P1 (RPLP1), peroxisomal biogenesis factor 10 (PEX10), and forkhead box N3 (FOXN3) recognized. It was found that GO functions were mainly enriched in the negative regulation of Ras protein signal transduction, small GTPase-mediated signal transduction, negative regulation, etc. A total of 1 703 differential methylation sites were screened out between case and control groups, including 444 increased methylation positions such as cg05573767 and 1 259 decreased methylationpositions such as cg19938535, and cg03893872. These positions were mapped to 1 108 genes such as ribosomal protein S6 kinase A2 (RPS6KA2), leucine rich repeat containing 16A (LRRC16A), and hedgehog acyltransferase (HHAT). According to the GO functional enrichment analysis, the genes relating to the DMPs were mainly enriched in biological functions such as transmembrane receptor protein serine/threonine kinase signaling pathway and axonogenesis. The KEGG pathway enrichment analysis suggested the involvement of Rap1 signaling pathway, adenosine 5’-monophosphate-activated protein kinase (AMPK) signaling pathway, etc. A total of 21 DMRs were identified, including 22 overlapping genes such as mucin 4 (MUC4), three prime repair exonuclease 1 (TREX1), and LIM homeobox 6 (LHX6). GO analysis demonstrated that the genes primarily participated in molecular functions such as positive regulation of transmembrane transport, regulation of fatty acid metabolism, and copper ion binding.@*Conclusion@#This study reveals the methylation patterns of DMPs and DMRs in patients with Qi deficiency and blood stasis syndrome caused by CHD-induced unstable angina pectoris. Potential epigenetic regulation of fatty acid metabolism, Rap1 signaling, and other molecular functions are involved in the development of CHD between the "disease" and "syndrome".

An Optically Controlled Virtual Microsensor for Biomarker Detection In Vivo.

Current technologies for the real-time analysis of biomarkers in vivo, such as needle-type microelectrodes and molecular imaging methods based on exogenous contrast agents, are still facing great challenges in either invasive detection or lack of active control of the imaging probes. In this study, by combining the design concepts of needle-type microelectrodes and the fluorescence imaging method, a new technique is developed for detecting biomarkers in vivo, named as "optically controlled virtual microsensor" (OCViM). OCViM is established by the organic integration of a specially shaped laser beam and fluorescent nanoprobe, which serve as the virtual handle and sensor tip, respectively. The laser beam can trap and manipulate the nanoprobe in a programmable manner, and meanwhile excite it to generate fluorescence emission for biosensing. On this basis, fully active control of the nanoprobe is achieved noninvasively in vivo, and multipoint detection can be realized at sub-micrometer resolution by shifting a nanoprobe among multiple positions. By using OCViM, the overexpression and heterogenous distribution of biomarkers in the thrombus is studied in living zebrafish, which is further utilized for the evaluation of antithrombotic drugs. OCViM may provide a powerful tool for the mechanism study of thrombus progression and the evaluation of antithrombotic drugs.

Associations between PM2.5 exposure and infant growth: A mediation analysis of oral microbiota.

BACKGROUND: Previous studies have linked growth retardation with ambient fine particulate matter (PM2.5) exposure. However, few studies explored such association from the perspective of microbiota, such as oral microbiota. We aimed to identify the potential role of oral microbiota in the links between PM2.5 exposure and infant growth. METHODS: Baseline information of 335 recruited mother-child pairs was collected by structured questionnaires. Growth indicators (weight, length) of one-year-old infants were abstracted from medical records when they had physical examination and corresponding z scores were calculated. 16S rRNA gene amplicon sequencing was performed to assess oral microbiota of infants and co-abundance groups (CAGs) were further calculated. We assessed PM2.5 levels by inverse distance weighting (IDW). Generalized linear regression and mediation analysis were performed to determine associations between PM2.5 exposure, oral microbiota and growth indicators. RESULTS: Per 10 µg m-3 increment of PM2.5 in the period of 10th month-examination was associated with decreased length z score (ß = -1.97, 95%CI: -3.83, -0.11). Oral microbiota correlated with weight z score and body mass index (BMI) z score was identified by Spearman correlation analysis. CAG4 was statistically associated with increased weight z score (ß = 3.40, 95%CI: 0.29, 6.51) and BMI z score (ß = 5.44, 95%CI: 1.00, 9.87). Several bacteria in the level of genus and CAG associated with PM2.5 exposure were additionally identified (P < 0.05). Mediation analysis revealed that PM2.5 in the period of birth-3rd month impacted the z scores of weight and BMI by altering relative abundance of Megasphaera (P < 0.05). CONCLUSION: PM2.5 exposure from 10th to 12th month after birth could retard infant linear growth. PM2.5 might impact oral microbiota of one-year-old infants. Growth-related bacteria and CAGs were identified. Megasphaera might function as mediator between PM2.5 exposure during birth-3rd month and infant z scores of weight and BMI.

Exploration and preliminary clinical investigation of an adhesive approach for primary tooth restoration.

The current study aims to investigate a suitable adhesive for primary tooth enamel. Shear bond strength (SBS) of primary teeth and the length of resin protrusion were analyzed using one-way ANOVA with Bonferroni multiple comparison tests after etching with 35% H 3PO 4. SBS and marginal microleakage tests were conducted with Single Bond Universal (SBU)/Single Bond 2 (SB2) adhesives with or without pre-etching using a nonparametric Kruskal-Wallis test. Clinical investigations were performed to validate the adhesive for primary teeth restoration using Chi-square tests. Results showed that the SBS and length of resin protrusion increased significantly with the etching time. Teeth in the SBU with 35% H 3PO 4 pre-etching groups had higher bond strength and lower marginal microleakage than those in the SB2 groups. Mixed fractures were more common in the 35% H 3PO 4 etched 30 s + SB2/SBU groups. Clinical investigations showed significant differences between the two groups in cumulative retention rates at the 6-, 12- and 18-month follow-up evaluations, as well as in marginal adaptation, discoloration, and secondary caries at the 12- and 18-month follow-up assessments. Together, pre-etching primary teeth enamel for 30 s before SBU treatment improved clinical composite resin restoration, which can provide a suitable approach for restoration of primary teeth.

Chaihu Longgu Muli Decoction relieving temporal lobe epilepsy in rats by inhibiting TLR4 signaling pathway through miR-146a-3p and miR-146a-5p / 数字中医药（英文）

@#Objective To explore the effect and mechanism of Chaihu Longgu Muli Decoction (柴胡龙骨牡蛎汤, CHLGMLD) in rats with temporal lobe epilepsy (TLE). Methods A total of 80 Sprague-Dawley (SD) male rats were randomized into control (CON), model (MOD), carbamazepine (CBZ, 0.1 g/kg), CHLGMLD low dose (CHLGMLD-L, 12.5 g/kg), and high dose (CHLGMLD-H, 25 g/kg) groups, with 16 rats in each group. TLE rat models were established in the four groups with the use of lithium-pilocarpine except for the CON group. After the successful establishment of TLE models, all drugs were administered through gavage, and distilled water was given to rats in the CON and MOD groups for four weeks. The frequency and duration of seizures before and after treatment were recorded for the evaluation of the alleviation degree. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression levels of miR-146a-3p and miR-146a-5p. The expression levels of toll-like receptor 4 (TLR4), interleukin-1 receptor-associated kinase 1 (IRAK1), tumor necrosis factor (TNF) receptor-associated factor 6 (TRAF6), TAK1-binding protein (TAB), nuclear factor-kappa B (NF-κB), and interleukin-1 beta (IL-1β) in hippocampus were tested by immunofluorescence assay. Correlation analysis between the above factors and expressions of miR-146a-3p and miR-146a-5p were performed separately. Results CHLGMLD decreased the frequency (P < 0.05) and duration (P < 0.01) of seizures in rats. CHLGMLD down-regulated the expression levels of miR-146a-5p and miR-146a-3p (P < 0.05), and inhibited the expression levels of TLR4, IRAK1, TRAF6, TAB, NF-κB, and IL-1β (P < 0.01). The correlation analysis revealed that the expression levels of TLR4, IRAK1, TRAF6, TAB, NF-κB, and IL-1β were positively correlated with the expression levels of miR-146a-3p and miR-146a-5p detected by qRT-PCR, respectively (P < 0.01). Conclusion CHLGMLD can inhibite the TLR4 signaling pathway by lowering the expression levels of miR-146a-3p and miR-146a-5p to alleviate hippocampal dentate gyrus inflammation in TLE rats, thus relieving seizures.

Effect of Hepatitis B Virus Infection on Sperm Quality and Outcomes of Assisted Reproductive Techniques in Infertile Males.

Background: Hepatitis B virus (HBV) infection is one of the health problems and has adverse effects on public health. However, the consequences of male HBV carriers for assisted reproductive techniques (ART) remain unclear. Objective: To examine whether men with HBV would impact sperm quality and the intrauterine insemination (IUI)/ in vitro fertilization (IVF)/ intracytoplasmic sperm injection (ICSI) outcomes. Methods: We retrospectively analyzed data from 681 infertile couples for IUI/IVF/ICSI fresh cycle outcomes. Case group was 176 infertile couples with male HBV infection undergoing embryo transfer in our center (99 for IVF and 77 for ICSI) and 51 infertile couples for IUI. Negative control was 454 non-infected infertility couples, matched for female age, BMI and infertility duration (102 for IUI and 198 for IVF and 154 for ICSI). Results: Sperm viability among infertile men with HBV infection was significantly lower than control group (74.1 ± 13.7 vs. 77.0 ± 12.8, P < 0.01). Sperm motility was significantly decreased in HBV positive men in comparison to the control group (32.5 ± 14.6 vs. 35.5 ± 12.9, P < 0.05). In IVF/ICSI cycles, two groups had similar results in two pronuclear (2PN) fertilization rate, implantation rate, clinical pregnant rate and abortion rate (P > 0.05). There was also no difference in the clinical pregnant rate and abortion rate in IUI cycles (P > 0.05). Conclusion: Men with HBV infection will affect their sperm quality, but not affect the outcomes of ART.

Baihe Jizihuang Tang Ameliorates Chronic Unpredictable Mild Stress-Induced Depression-Like Behavior: Integrating Network Pharmacology and Brain-Gut Axis Evaluation.

Baihe Jizihuang Tang (BHT) is a traditional Chinese medicine (TCM) prescription, which can also be used as a nutritional food with medicinal value. Herein, we aimed to clarify the antidepressive effects and molecular mechanism of BHT. Network pharmacological analysis; chronic unpredictable mild stress (CUMS) rat model assessment; behavioral tests; analysis of hippocampal neurotransmitter levels, hippocampal pathological structure, and hypothalamic-pituitary-adrenal (HPA) axis; western blot analysis; 16s RNA sequencing; ultraperformance liquid chromatography (UPLC)/mass spectrometry (MS); and high-performance liquid chromatography (HPLC)/ultraviolet (UV) analysis were used. We found 8 potentially active components and 12 targets from the database. KEGG analysis suggested that BHT significantly affected BDNF/tyrosine receptor kinase B levels, glutamate binding, synaptic transmission based on neurotransmitter signal, and the response to glucocorticoid signaling pathways. Consistently, 7 chemical components were identified using UPLC/quadrupole time-of-flight/MS; among them, regalosides A, B, C, and E were unique components of lily of TCM, and their content in BHT was significantly different: regaloside A > B > E > C. BHT could nourish hippocampal neurons, affect neurotransmitter metabolism, reduce HPA axis hyperactivity, improve deficits in hippocampal tissue structure, and change depressive behavior. Moreover, BHT regulated BDNF expression in the hippocampus and improved intestinal flora deficits in CUMS rats by changing the content of Bifidobacterium, Rothia, Glutamicibacter, and Lactobacillus at the genus level. Collectively, BHT attenuated CUMS-induced depression-like behavior by regulating BDNF and intestinal flora disorder through the brain-gut axis. Therefore, including BHT in the medication list may constitute a potential strategy for preventing depression.

Design of ultrasonic standing wave levitation support for three-dimensional printed filaments.

Fused deposition modeling (FDM) three-dimensional (3D) printing is the process of forming a part by depositing molten thermoplastic materials layer by layer. Support structures need to be added below the overhangs or bridges in 3D printing. This paper proposes an idea for support-free FDM printing by studying the method of filament levitation. In this paper, an ultrasonic phased array device is designed, and different slender objects with length much longer than the sound wavelength are levitated in the air by multiple standing wave points. Experiments show that slender objects can be stably held at the sound pressure nodes in the standing wave field. After adding the ultrasonic field in FDM printing, the maximum deformation of single filament due to gravity on the bridge structure decreases from 5 to 2 mm. This proves that it is feasible for an ultrasonic phased array system to play an important role in the field of support-free FDM printing.

In silico analysis of the potential mechanism of a preventive Chinese medicine formula on coronavirus disease 2019.

ETHNOPHARMACOLOGICAL RELEVANCE: With the spread of Coronavirus Disease (2019) (COVID-19), combination with traditional Chinese medicine (TCM) has been widely used as a prevention and therapy strategy in China. Xin guan No.1 (XG-1) prescription is a preventive formula recommended by the Hunan Provincial Administration of TCM to prevent the pandemic of COVID-19. AIM OF THE STUDY: To explore the potential preventive mechanisms of XG-1 against COVID-19 in the combination of network pharmacology approach, single-cell RNA expression profiling analysis, molecular docking and retrospective study. MATERIALS AND METHODS: Encyclopedia of Traditional Chinese Medicine (ETCM) database was used to determine the meridian tropism, active components and target genes of XG-1. Gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analysis were conducted by R Cluster Profiler package (3.14.3). Single cell RNA sequencing (scRNA-seq) data of human lung (GSE122960) was downloaded from Gene Expression Omnibus (GEO) database and analyzed by R Seurat package (3.1.2). Cytoscape (3.7.2) was used to construct the interaction network. The main ingredients in XG-1 were identified by HPLC- Q-TOF- MS and used for molecular docking with COVID-19 3CL hydrolytic enzyme and angiotensin converting enzyme II (ACE2). A retrospective study of 47 close contact participants from Dongtang Community of Hunan Province was conducted to evaluated the preventive effect of XG-1. RESULTS: According to the network pharmacology analysis, XG-1 formula was closely related to lung-, spleen- and stomach-meridians and include a total of 206 active components and 853 target genes. GO and KEGG pathway enrichment revealed that XG-1 mainly regulated cellular amino acid metabolism process and neuroactive ligand-receptors interaction. The scRNA-seq profiling showed that angiotensin converting enzyme 2 (ACE2) was principally expressed in alveolar type 2 epithelial cells (AT2). 153 genes were up-regulated in AT2 cells expressing ACE2 and 12 genes were obtained by intersecting with XG-1 target genes, of which 3 were related to immunity. Five main chemical ingredients were detected in XG-1 sample by HPLC-Q-TOF-MS. The molecular docking showed that Rutin, Liquiritin and Astragaloside Ⅳ had a good affinity with COVID-19 3CL hydrolytic enzyme and ACE2. Compared with participants who didn't take XG-1, preventive treatment with XG-1gradules resulted in a significant lower rate of testing positive for SARS-CoV-2 nucleic acid (P < 0.0001). CONCLUSION: The present study showed that XG-1 exerts a preventive effect in close contacts against COVID-19. The underlying mechanism may be related to modulate immunity response through multiple components, pathways, and several target genes co-expressed with ACE2. These findings provide preliminary evidences and methodological reference for the potential preventive mechanism of XG-1 against COVID-19.

Chaihu-Longgu-Muli Decoction exerts an antiepileptic effect in rats by improving pyroptosis in hippocampal neurons.

ETHNOPHARMACOLOGICAL RELEVANCE: Chaihu-Longgu-Muli Decoction (CLMD) is a classic prescription created by Zhong-jing Zhang, a famous ancient Chinese medical scientist, to harmonize uncontrollable body activities and calm the minds. Now Traditional Chinese Medicine (TCM) physicians often apply it to treat psychiatric diseases such as epilepsy. AIM OF THE STUDY: This study investigated the mechanism of the effect of Chaihu-Longgu-Muli Decoction (CLMD) on hippocampal neurons pyroptosis in rats with Temporal Lobe Epilepsy (TLE). MATERIALS AND METHODS: The lithium chloride-pilocarpine-induced TLE rat model was established. The behavioral testing was performed and, the expression of IL-1ß and TNF-α in serum was detected by ELISA, qRT-PCR was used to detect the mRNA expression of NLRP3, Caspase-1, IL-1ß and TNF-α in hippocampus. The expression of NLRP3 and Caspase-1 in hippocampal dentate gyrus was detected by immunofluorescence assay. RESULTS: CLMD could significantly suppress the frequency and duration time of epileptic seizures, reduce the expression of NLRP3, Caspase-1 TNF-α and IL-1ß. CONCLUSIONS: CLMD exerted an obvious antiepileptic effect by improving pyroptosis in hippocampal neurons of TLE rats.

Network Pharmacology-Based Strategy Reveals the Effects of Hedysarum multijugum Maxim.-Radix Salviae Compound on Oxidative Capacity and Cardiomyocyte Apoptosis in Rats with Diabetic Cardiomyopathy.

OBJECTIVE: To explore the effects of the Hedysarum multijugum Maxim.-Radix Salviae compound (Huangqi-Danshen Compound (HDC)) on oxidative capacity and cardiomyocyte apoptosis in rats with diabetic cardiomyopathy by a network pharmacology-based strategy. METHODS: Traditional Chinese Medicine (TCM)@Taiwan, TCM Systems Pharmacology Database and Analysis Platform (TCMSP), TCM Integrated Database (TCMID), and High-Performance Liquid Chromatography (HPLC) technology were used to obtain and screen HDC's active components, and the PharmMapper database was used to predict HDC human target protein targets. The DCM genes were collected from the GeneCards and OMIM databases, and the network was constructed and analyzed by Cytoscape 3.7.1 and the Database for Annotation, Visualization, and Integrated Discovery (DAVID). Finally, HDC was used to intervene in diabetic cardiomyopathy (DCM) model rats, and important biological processes and signaling pathways were verified using techniques such as immunohistochemistry. RESULTS: A total of 176 of HDC's active components and 442 potential targets were obtained. The results of network analysis show that HDC can regulate DCM-related biological processes (such as negative regulation of the apoptotic process, response to hypoxia, the steroid hormone-mediated signaling pathway, cellular iron ion homeostasis, and positive regulation of phosphatidylinositol 3-kinase signaling) and signaling pathways (such as the HIF-1 signaling pathway, the estrogen signaling pathway, insulin resistance, the PPAR signaling pathway, the VEGF signaling pathway, and the PI3K-Akt signaling pathway). Animal experiments show that HDC can reduce fasting plasma glucose (FPG), HbA1c, and malondialdehyde (MDA) and increase superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) (P < 0.05). The results of immunohistochemistry showed that HDC can regulate the protein expression of apoptosis-related signaling pathways in DCM rats (P < 0.05). CONCLUSION: It was initially revealed that HDC improves DCM through its antiapoptotic and anti-inflammatory effects. HDC may play a therapeutic role by improving cardiomyocyte apoptosis in DCM rats.

A metabolomic study on the association of exposure to heavy metals in the first trimester with primary tooth eruption.

BACKGROUND: The influence of prenatal heavy metals exposure on primary tooth eruption in humans is rarely reported. AIM: Based on the cohort study design, we investigated the association of exposure to 12 heavy metals in the first trimester with primary tooth eruption, and the maternal metabolisms in the first trimester which might be related to the above relationship. METHODS: Maternal urine samples were collected in their first trimester, and 12 metals (Ti, V, Fe, Co, Cu, As, Se, Cd, Sn, Hg, Tl, U) were measured using the inductively coupled plasma mass spectrometry method. The maternal metabolome in the first trimester was analyzed by ultrahigh performance liquid chromatography coupled mass spectrometry based metabolomics using urine samples. The infant's first tooth eruption time and number of teeth at age one were recorded by oral examination and questionnaire. RESULTS: No significant associations were observed between heavy metals exposure in the first trimester and primary tooth eruption, except for Co. The level of Co was positively associated with time of infant's first tooth eruption, and was negatively associated with the number of teeth at age one. Based on metabolomic profiling, glycine was revealed as the key mediating metabolite, which showed negative correlation with Co and opposite effect of Co in the primary tooth eruption. CONCLUSIONS: Prenatal Co exposure in the first trimester might delay the primary tooth eruption in children through the decreased glycine-disrupted dentin formation, providing the first evidence and novel insights into the control of prenatal heavy metals exposure for ensuring normal (timely) primary tooth eruption.

Associations of maternal, perinatal and postnatal factors with the eruption timing of the first primary tooth.

We recruited 1296 mothers in their first trimester from the Affiliated Obstetrics and Gynecology Hospital of Nanjing Medical University between May 2014 and September 2015 to investigate the associations of maternal, perinatal and postnatal factors with the eruption timing of the first primary tooth (ETFPT) in a Chinese population. We collected maternal demographic information and clinical data during the perinatal and postnatal period, and oral examinations of the infants were performed by a doctor at 6, 9 and 12 months of age. Multiple regression analysis was used to identify significant explanatory variables for ETFPT. The mean age at eruption of the first primary tooth for all the infants was 6.82 ± 1.90 months. After adjustment for confounders, higher maternal childbearing age (ß = 0.57; 95%CI = 0.13-1.02), female sex (ß = 0.26; 95%CI = 0.07-0.52), and low birth weight (ß = 0.98; 95%CI = 0.20-1.76) were significantly associated with delayed eruption of the first primary tooth, while macrosomia (ß = -0.79; 95%CI = -1.30--0.28) was significantly associated with earlier eruption of the first primary tooth. Maternal childbearing age, infant sex and infant birth weight were significant determinants of ETFPT.