Feasibility of Ultrasound-Guided Percutaneous Axillary Artery Cannulation for Veno-Arterial Extracorporeal Membrane Oxygenation and its Effect on the Recovery of Spontaneous Heartbeat in Patients with ECPR.

Objective: The measurement of the right and left axillary arteries and aortic arch and their vessels by multi-row spiral CT angiography provides the basis for clinical catheter selection and depth for axillary artery placement. This study reported the clinical experience of 7 patients who successfully underwent ultrasound-guided percutaneous axillary artery cannulation for veno-arterial extracorporeal membrane oxygenation (VA-ECMO). Methods: Patients who had CT angiography of the thoracic aorta at our institution between January 2020 and March 2022 were assessed for eligibility and included. The diameters of the cephalic trunk (D1), right common carotid artery (D2), right axillary artery (D3), left common carotid artery (D4), left axillary artery opening (D5), right axillary artery cannulation length (L1), and left axillary artery cannulation length (L2) were measured. The tangential angles α, ß, and γ of the cephalic trunk, left common carotid artery and left subclavian and aorta was measured using an automatic angle-forming tool. The decision to use a 15F cannula for ultrasound-guided percutaneous axillary artery cannulation in veno-arterial extracorporeal membrane oxygenation (VA-ECMO) aims to achieve optimal vascular access. This cannula size strikes a balance, providing sufficient blood flow rates for ECMO support while minimizing the risk of complications associated with larger cannulas. Precise measurements of arterial dimensions, including the cephalic trunk, common carotid arteries, and axillary arteries, play a crucial role in guiding catheter selection and determining the depth of axillary artery placement. These measurements allow for tailored approaches based on individual patient characteristics, enhancing the safety and efficacy of the intervention. Additionally, measuring tangential angles (α, ß, and γ) provides insights into arterial alignment, optimizing the cannula trajectory for efficient blood flow. The use of an automatic angle-forming tool enhances measurement precision, contributing to procedural accuracy, minimizing complications, and ensuring the success of ultrasound-guided percutaneous axillary artery cannulation. In summary, the choice of a 15F cannula and precise measurements are essential components of the methodology, emphasizing safety, efficacy, and personalized approaches in VA-ECMO. From March to June 2022, 7 patients (6 males and 1 female) in our intensive care medicine department underwent successful ultrasound-guided percutaneous axillary artery cannulation for VA-ECMO with 15F cannula, including 3 cases with extracorporeal cardiopulmonary resuscitation (ECPR) and 4 cases with circulatory collapse. Results: 292 patients met the study criteria, 215 males and 77 females, with a mean age of 67.2±14.2 years. The measurements showed that D1 was (13.1±2.0) mm, D2 was (8.8±2.5) mm, D3 was (6.1±1.2) mm, D4 was (8.3±3.5) mm, D5 was (6.1±1.1) mm, L1 was (114.1±17.8) mm, and L2 was (128.4±20.2) mm. The tangential angles α of the cephalic trunk left common carotid artery and left subclavian artery to the aorta were (43.8°±17.1°), ß was (50.7°±14.8°), and γ was (62.4°±19.1°). Males had significantly wider D3 and D5, longer L1 and L2, and smaller gamma angles than females (P < .05). Three ECPR cases showed no recovery of the spontaneous heartbeat with femoral artery cannulation for VA-ECMO but recovered spontaneous heartbeat after axillary artery cannulation for VA-ECMO was adopted. The measurements in this study have important implications for veno-arterial extracorporeal membrane oxygenation (VA-ECMO) procedures. They provide crucial information about arterial dimensions, including the cephalic trunk, common carotid arteries, and axillary arteries. This information guides clinicians in selecting catheters and determining the ideal depth for percutaneous axillary artery cannulation during ECMO interventions. Notable gender differences in arterial dimensions highlight the need for personalized approaches in ECMO procedures. Customizing catheter choices and cannulation depth based on individual patient characteristics, informed by these measurements, improves the safety and effectiveness of the intervention. The measured tangential angles (α, ß, and γ) offer insights into arterial alignment, crucial for optimizing cannula trajectory and ensuring proper alignment for efficient blood flow. The use of an automatic angle-forming tool enhances measurement precision, contributing to procedural accuracy and minimizing the risk of complications during ECMO procedures. In summary, these measurements directly enhance the precision and safety of VA-ECMO procedures, underscoring the importance of personalized approaches based on individual anatomical variations and improving overall intervention success and outcomes. Conclusion: Ultrasound-guided percutaneous axillary artery cannulation for VA-ECMO with a 15F cannula is clinically feasible. Axillary artery cannulation for VA-ECMO contributes to the restoration of spontaneous heartbeat in ECPR patients more than femoral artery cannulation, and the possible mechanism is a better improvement of coronary blood flow. However, the study has limitations, including a modest sample size and a single-center, retrospective design, impacting its generalizability. To validate and extend these findings, further research with larger and diverse cohorts, including prospective investigations, is necessary to ensure their applicability across various clinical settings and patient demographics in VA-ECMO.

Mechanisms underlying the therapeutic effects of Xiaoyaosan in treating hyperplasia of mammary glands based on network pharmacology.

This study utilized network pharmacology to investigate the effects of Xiaoyaosan (XYS) on the intervention of hyperplasia of mammary glands (HMG) by targeting specific genes and signaling pathways. The active ingredients and targets of XYS, which consisted of 8 traditional Chinese medicines (TCM), were identified using TCMSP. The gene targets associated with HMG were obtained from the GeneCards Database, and the intersection data between the 2 was integrated. Cytoscape 3.8.1 software was used to construct a network diagram illustrating the relationship between compounds, drug active ingredients, target proteins, and the disease. The protein-protein interaction network diagram was generated using STRING, and the core targets were analyzed. A total of 133 active ingredients in XYS and 7662 active ingredient targets were identified. Among them, 6088 targets were related to HMG, and 542 were common targets between the active ingredients and the disease. The protein-protein interaction (PPI) core network contained 15 targets, with 5 key targets playing a crucial role. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analyses have indicated that XYS has the potential to treat HMG by interfering with the AGE-RAGE signaling pathway in diabetic complications, the MAPK signaling pathway, and the PI3K-Akt signaling pathway. Additionally, molecular docking studies have shown excellent binding properties between the drug components and key targets. Thus, this study provides a theoretical foundation for a better understanding of the pharmacological mechanism and clinical application of XYS in the comprehensive treatment of HMG.

Morusin inhibits breast cancer-induced osteolysis by decreasing phosphatidylinositol 3-kinase (PI3K)-mTOR signalling.

Bone metastases caused by breast cancer pose a major challenge to the successful treatment of breast cancer patients. Many researchers have suggested that herbal medicines are extremely effective at preventing and treating cancer-associated osteolysis. Previous studies have revealed that Morusin (MOR) is cytotoxic to many cancer cells ex vivo. Nevertheless, how MOR contributes to osteolysis induced by breast cancer is still unknown, and the potential mechanism of action against osteolysis is worthy of further study. The protective effect and molecular mechanism of MOR in inhibiting breast cancer cell-induced osteolysis were verified by experiments and network pharmacology. Cell function was assessed by cell proliferation, osteoclast (OC) formation, bone resorption, and phalloidin staining. Tumour growth was examined by micro-CT scanning in vivo. To identify potential MOR treatments, the active ingredient-target pathway of breast cancer was screened using network pharmacology and molecular docking approaches. This study is the first to report that MOR can prevent osteolysis induced by breast cancer cells. Specifically, our results revealed that MOR inhibits RANKL-induced osteoclastogenesis and restrains the proliferation, invasion and migration of MDA-MB-231 breast cells through restraining the PI3K/AKT/MTOR signalling pathway. Notably, MOR prevented bone loss caused by breast cancer cell-induced osteolysis in vivo, indicating that MOR inhibited the development of OCs and the resorption of bone, which are essential for cancer cell-associated bone distraction. This study showed that MOR treatment inhibited osteolysis induced by breast cancer in vivo. MOR inhibited OC differentiation and bone resorption ex vivo and in vivo and might be a potential drug candidate for treating breast cancer-induced osteolysis.

Understanding the onion aphid Neotoxoptera formosana's (Hemiptera: Aphididae) interaction with Allium (Asparagales: Amaryllidaceae) crops: a comprehensive study of feeding patterns and life history traits.

The onion aphid, Neotoxoptera formosana, poses a significant threat to Allium crops worldwide, causing considerable economic losses and quality degradation. To develop effective pest management strategies, it is crucial to understand the feeding behavior and life history of this pest on different Allium crops. In this study, the electrical penetration graph (EPG) technique was used to monitor the thorn-feeding behavior of the onion aphid on 4 Allium crops: leek, chive, garlic, and shallot. The EPG data revealed distinct feeding patterns, with garlic and shallots being more preferred hosts than chives. Additionally, the aphids primarily fed on the phloem in garlic and shallots. Analysis of life history trait showed that chives provided the most favorable conditions for aphid development and reproduction, while leek exhibited relatively unfavorable conditions. Examination of leaf histology also revealed differences among the crops, which may influence aphid feeding behavior. This study provides valuable insights into the interaction between the onion aphid and different Allium crops, aiding in the development of comprehensive pest control strategies to minimize crop damage and economic losses. The use of advanced techniques like EPG contributes to a more detailed understanding of aphid behavior and shows promise for improving pest management in other plant-pest interactions.

[Genome-wide identification and expression analysis of TCP gene family of Andrographis paniculata under abiotic stress].

Andrographis paniculata is an important medicinal plant in the Lingnan region of China, which has the functions of clearing heat, removing toxins, and resisting bacteria and inflammation. The TCP gene family is a class of transcription factors that regulate plant growth, development, and stress response. In order to analysis the role of the TCP gene family under abiotic stress in A. paniculata, this study identified the TCP gene family of A. paniculata at the genome-wide level and analyzed its expression pattern in response to abiotic stress. The results showed that the A. paniculata TCP gene family had 23 members, with length of amino acid ranging from 136 to 508, the relative molecular mass between 14 854.71 and 55 944.90 kDa, and the isoelectric point between 5.67 and 10.39. All members were located in the nucleus and unevenly distributed on 13 chromosomes. Phylogenetic analysis classified them into three subfamilies: PCF, CIN and CYC/TB1. Gene structure and conserved motif analysis showed that most members of the TCP gene family contained motif 1, motif 2, motif 3 in the same order and 1-3 CDS. The analysis of promoter cis-acting elements showed that the transcriptional expression of the TCP gene family in A. paniculata might be induced by light, hormones, and adversity stress. In light of the expression pattern analysis and qRT-PCR verification, the expression of ApTCP4, ApTCP5, ApTCP6, and ApTCP11 involved in response by various abiotic stresses such as drought, high temperature, and MeJA. This study lays the foundation for in-depth exploration of the functions of A. paniculata TCP genes in response to abiotic stress.

[Chemical constituents and mechanism of Chuanzhi Tongluo Capsules based on UPLC-Q-Exactive Orbitrap-MS and network pharmacology].

The chemical constituents of Chuanzhi Tongluo Capsules were analyzed and identified using ultra-high performance liquid chromatography-quadrupole/electrostatic field orbitrap high-resolution mass spectrometry(UPLC-Q-Exactive Orbitrap-MS) to clarify the pharmacological substance basis. In addition, network pharmacology was employed to explore the mechanism of Chuanzhi Tongluo Capsules in the treatment of cerebral infarction. Gradient elution was performed using acetonitrile and 1% acetic acid in water as the mobile phase. Mass spectrometry was performed in positive and negative ion modes. Xcalibur 4.2 software was used for compound analysis, including accurate mass-to-charge ratio and MS/MS fragment information, combined with the comparison of reference standards and literature data. A total of 152 compounds were identified, including 32 organic acids, 35 flavonoids and their glycosides, 33 diterpenes, 13 phthalides, 12 triterpenes and triterpene saponins, 23 nitrogen-containing compounds, and 4 other compounds, and their fragmentation patterns were analyzed. SwissTargetPrediction, GeneCards, DAVID, and other databases were used to predict and analyze the core targets and mechanism of Chuanzhi Tongluo Capsules. Protein-protein interaction(PPI) network topology analysis identified 10 core targets, including TNF, VEGFA, EGFR, IL1B, and CTNNB1. KEGG enrichment analysis showed that Chuanzhi Tongluo Capsules mainly exerted their effects through the regulation of lipid and atherosclerosis, glycoproteins in cancer, MicroRNAs in cancer, fluid shear stress, and atherosclerosis-related pathways. Molecular docking was performed between the key constituents and core targets, and the results demonstrated a strong binding affinity between the key constituents of Chuanzhi Tongluo Capsules and the core targets. This study comprehensively elucidated the chemical constituents of Chuanzhi Tongluo Capsules and explored the core targets and mechanism in the treatment of cerebral infarction based on network pharmacology, providing a scientific reference for the study of the pharmacological substance basis and formulation quality standards of Chuanzhi Tongluo Capsules.

Liver organoids: a promising three-dimensional model for insights and innovations in tumor progression and precision medicine of liver cancer.

Primary liver cancer (PLC) is one type of cancer with high incidence rate and high mortality rate in the worldwide. Systemic therapy is the major treatment for PLC, including surgical resection, immunotherapy and targeted therapy. However, mainly due to the heterogeneity of tumors, responses to the above drug therapy differ from person to person, indicating the urgent needs for personalized treatment for PLC. Organoids are 3D models derived from adult liver tissues or pluripotent stem cells. Based on the ability to recapitulate the genetic and functional features of in vivo tissues, organoids have assisted biomedical research to make tremendous progress in understanding disease origin, progression and treatment strategies since their invention and application. In liver cancer research, liver organoids contribute greatly to reflecting the heterogeneity of liver cancer and restoring tumor microenvironment (TME) by co-organizing tumor vasculature and stromal components in vitro. Therefore, they provide a promising platform for further investigation into the biology of liver cancer, drug screening and precision medicine for PLC. In this review, we discuss the recent advances of liver organoids in liver cancer, in terms of generation methods, application in precision medicine and TME modeling.

The Efficacy of Prenatal Yoga on Labor Pain: A Systematic Review and Meta-analysis.

Objective: This study investigated the effects of prenatal yoga on labor pain. Methods: A systematic review of articles on prenatal yoga for childbirth pain was conducted, and relevant pain score results data were collected for the meta-analysis. The intervention group was treated with yoga movement, and the control group, with routine prenatal examination. All randomized controlled trials were included, but pregnancies with internal complications were excluded. Results: A total of 47 references were obtained from PubMed, Embase, the Cochrane database, and ClinicalTrials.gov. After applying the exclusion criteria, five studies were included for the review and meta-analysis. A total of 581 women were enrolled. The SMD value summarized for the four studies was -1.05, and the 95% confidence interval was -1.45 to -0.65, which was statistically significant (z = 5.15; P < .01), suggesting that yoga can significantly reduce labor pain. Conclusions: Prenatal yoga can relieve labor pain and is recommended for pregnant women.

Epidemiological Investigation of 387 Individuals Over 65 Years Old With Osteoporotic Fractures.

Context: With the rapidly aging population globally, osteoporosis (OP) has become a major public health problem, and fracture is a common complication of OP. Older adults, especially postmenopausal women, have a higher incidence of OP. Objective: The study intended to analyze the clinical information, epidemiological characteristics, treatments, and follow-up results of patients with osteoporotic fractures (OPFs) in adults over 65 years old, to provide data support for the prevention, treatment, and use of OPF focus groups in clinical practice. Design: The research team performed a retrospective analysis using electronic medical records and related imaging data of patients. Setting: The study took place at Hebei General Hospital in Hebei, China. Participants: Participants were 387 patients over 65 years old with osteoporotic fractures who had been admitted to the hospital between July 2012 and July 2018. Outcome Measures: The research team recorded participants' ages, genders, fracture causes, and fracture sites. The team performed a follow-up analysis on refractures, treatment with anti-osteoporotic drugs, exercise, and survival status within the 3 years after surgery. Results: The study's male-to-female ratio was 1:3.1, and the rate of osteoporotic fracture for females was significantly higher than that of males. The mean age of participants with fractures was 75.6 ± 8.5 years, and most fractures occurred in participants 78 to 85 years old. Of the 387 participants, 169 participants had hip fractures (43.67%); 98 had vertebral compression fractures (25.32%); 51 had distal radius and ulna fractures (13.18%); 42 had proximal humerus fractures (10.85%); and 27 had other fractures (6.98%). The number of women with fractures at each site was greater than the number of men, but the differences weren't statistically significant (P > .05). The main causes of injury were falls (71.58%), and the main place of the occurrence of injury was at home (65.6%). Of the 387 participants, 346 had surgical treatment (89.41%), and the effective rate of surgical treatment was 99.42%. Three years after surgery, the research team followed up with 235 participants, for a follow-up rate of 60.72%. Within the 3 years of the follow-up period, 61 participants had refractures (25.63%), 29 received treatment with regular anti-osteoporotic drugs (12.34%), 36 exercised twice or more a week (15.32%), and 32 had died for various reasons (13.62%). Conclusions: The study preliminarily described the epidemiological characteristics of 387 osteoporotic fractures in adults over 65 years old. More women had fractures than men; the hip was the most common fracture site, and falls were the main cause of injury. Most of the fractures occurred in the place of residence, and the refracture rate was 25.96% at three years after surgery.

BPA and its alternatives BPF and BPAF exaggerate hepatic lipid metabolism disorders in male mice fed a high fat diet.

Alternatives to Bisphenol A (BPA), such as BPF and BPAF, have found increasing industrial applications. However, toxicological research on these BPA analogues remains limited. This study aimed to investigate the effects of BPA, BPF, and BPAF exposure on hepatotoxicity in mice fed with high-fat diets (HFD). Male mice were exposed to the bisphenols at a dose of 0.05 mg per kg body weight per day (mg/kg bw/day) for eight consecutive weeks, or 5 mg/kg bw/day for the first week followed by 0.05 mg/kg bw/day for seven weeks under HFD. The low dose (0.05 mg/kg bw/day) was corresponding to the tolerable daily intake (TDI) of BPA and the high dose (5 mg/kg bw/day) was corresponding to its no observed adverse effect level (NOAEL). Biochemical analysis revealed that exposure to these bisphenols resulted in liver damage. Metabolomics analysis showed disturbances of fatty acid and lipid metabolism in bisphenol-exposed mouse livers. BPF and BPAF exposure reduced lipid accumulation in HFD mouse liver by lowering glyceride and cholesterol levels. Transcriptomics analysis demonstrated that expression levels of genes related to fatty acid synthesis and metabolism were changed, which might be related to the activation of the PPAR signaling pathway. Besides, a feedback regulation mechanism might exist to maintain hepatic metabolic homeostasis. For the first time, this study demonstrated the effects of BPF and BPAF exposure in HFD-mouse liver. Considering the reality of the high prevalence of obesity nowadays and the ubiquitous environmental distribution of bisphenols, this study provides insight and highlights the adverse effects of BPA alternatives, further contributing to the consideration of the safe use of such compounds.

Hybrid Au-star@Prussian blue for high-performance towards bimodal imaging and photothermal treatment.

In recent years, branched or star-shaped Au nanostructures composed of core and protruding arms have attracted much attention due to their unique optical properties and morphology. As the clinically adapted nanoagent, prussian blue (PB) has recently gained widespread attention in cancer theranostics with potential applications in magnetic resonance (MR) imaging. In this article, we propose a hybrid star gold nanostructure（Au-star@PB）as a novel theranostic agent for T1-weighted magnetic resonance imaging (MRI)/ photoacoustic imaging（PAI） and photothermal therapy (PTT) of tumors. Importantly, the Au-star@PB nanoparticles function as effective MRI/PA contrast agents in vivo by increasing T1-weighted MR/PAI signal intensity and as effective PTT agents in vivo by decreasing the tumor volume in MCF-7 tumor bearing BALB / c mouse model as well as in vitro by lessening tumor cells growth rate. Interestingly, we found the main photothermal effect of Au-star@PB is derived from Au-star, but not PB. In summary, the hybrid structure of Au-star@PB NPs with good biological safety, significant photostability, dual imaging capability, and high therapeutic efficiency, might offer a novel avenue for the future diagnosis and treatment of cancer.

Kruppel-like Factors 3 Regulates Migration and Invasion of Gastric Cancer Cells Through NF-κB Pathway.

Context: The poorly understood regulatory mechanisms impede gastric cancer therapy. Kruppel-like factors (KLFs) are associated with the development of various tumors, The studies on the role of the KLF transcription factor 13 (KLF13) in gastric cancer progression haven't been studied. Objective: The current study aimed to investigate the role of KLF13 in the migration and invasion of gastric cancer and the regulatory mechanism of KLF13 in gastric cancer progression. Design: The research team performed a laboratory study. Setting: The study took place at the Zengcheng District People's Hospital of Guangzhou in Zengcheng, China. Participants: In addition to using normal gastric cells, GES1, and seven gastric cancer cell lines, the research team compared the fresh, gastric cancer tissues (T) and paired, adjacent, noncancerous gastric tissues (ANT) from eight patients undergoing surgical resection at the hospital. The research team also downloaded the data for 33 gastric cancer tissues and adjacent, normal gastric tissues from the Cancer Genome Atlas' TCGA database. Intervention: The research team used: (1) short hairpin RNAs (shRNAs) to knock down KLF13, (2) wound healing and transwell invasion analyses to determine the effects of KLF13 on the migration and invasion of gastric cancer, and (3) a Luciferase reporter assay to determine the effects of KLF13 on nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activity. Results: KLF13 was upregulated in gastric cancer cells and tissues, and the patients with a high KLF13 expression had poor outcome. Downregulation of KLF13 significantly inhibited the migration and invasion of gastric cancer cells. Mechanistically, downregulation of KLF13 significantly inhibited NF-κB activity, and its targets such as: (1) snail family transcriptional repressor 1 (SNAI1 or Snail), (2) snail family transcriptional repressor 2 (SNAI2 or Slug), (3) zinc finger e-box binding homeobox 1 (ZEB1), (4) Smad interacting protein 1 (Sip1), (5) twist family basic helix-loop-helix (BHLH) transcription factor (Twist), (6) matrix metallopeptidase 2 (MMP2), and (7) MMP9. Tumor necrosis factor alpha (TNF-α) can activate NF-κB. Treating with TNF-α can reverse the effects of KLF13 downregulation on migration and invasion, confirming that KLF13 promotes the migration and invasion of gastric cancer cells through activating the NF-κB pathway. Conclusions: KLF13 promoted the migration and invasion of gastric cancer cells through activating the NF-κB pathway, providing a new target for gastric cancer therapy.

Acupuncture for metabolic syndrome: A protocol for systematic review and meta-analysis.

BACKGROUND: Metabolic syndrome (MS) is showing an epidemic trend worldwide, and its annual incidence is increasing. Conventional treatment options have limitations and it is necessary to develop new management strategies for MS. METHODS: Eligible randomized controlled clinical trials (RCTs) were screened by searching multiple Chinese and English databases. References to the included literature, gray literature in OpenGrey, and other relevant literature, such as clinical studies registered in ClinicalTrials.gov, were also manually searched. Relevant data were extracted, and meta-analysis was performed using Reviewer Manager 5.4. RESULTS: This study provides a high-quality review of the efficacy and safety of acupuncture in the treatment of MS, and provides a basis for the clinical application of acupuncture in the treatment of MS. CONCLUSION: This study provides evidence of the effectiveness and safety of acupuncture in the treatment of MS.

Effects of autotoxicity and allelopathy on seed germination and seedling growth in Medicago truncatula.

Autotoxicity is a form of intraspecific allelopathy, in which a plant species inhibits the establishment or growth of the same species through the release of toxic chemical compounds into the environment. The phenomenon of autotoxicity in crops is best traced in alfalfa (Medicago sativa). A close relative of alfalfa, M. truncatula, has been developed into an excellent model species for leguminous plants. However, it is not known whether M. truncatula has autotoxicity. In this study, M. truncatula root exudates showed a negative impact on the growth of M. truncatula seedlings, indicating autotoxicity. Detailed analyses with plant extracts from M. truncatula and alfalfa revealed varying degrees of suppression effects in the two species. The extracts negatively affected seed germination potential, germination rate, radicle length, hypocotyl length, synthetic allelopathic effect index, plant height, root growth, fresh weight, dry weight, net photosynthetic rate, transpiration rate, and stomatal conductance in both M. truncatula and alfalfa. The results demonstrated that autotoxicity and allelopathic effects exist in M. truncatula. This opens up a new way to use M. truncatula as a model species to carry out in-depth studies of autotoxicity and allelopathy to elucidate biochemical pathways of allelochemicals and molecular networks controlling biosynthesis of the chemicals.

Assay establishment and validation of a high-throughput organoid-based drug screening platform.

BACKGROUND: Organoids are three-dimensional structures that closely recapitulate tissue architecture and cellular composition, thereby holding great promise for organoid-based drug screening. Although growing in three-dimensional provides the possibility for organoids to recapitulate main features of corresponding tissues, it makes it incommodious for imaging organoids in two-dimensional and identifying surviving organoids from surrounding dead cells after organoids being treated by irradiation or chemotherapy. Therefore, significant work remains to establish high-quality controls to standardize organoid analyses and make organoid models more reproducible. METHODS: In this study, the Z-stack imaging technique was used for the imaging of three-dimensional organoids to gather all the organoids' maximum cross sections in one imaging. The combination of live cell staining fluorescent dye Calcein-AM and ImageJ assessment was used to analyze the survival of organoids treated by irradiation or chemotherapy. RESULTS: We have established a novel quantitative high-throughput imaging assay that harnesses the scalability of organoid cultures. Using this assay, we can capture organoid growth over time, measure multiple whole-well organoid readouts, and show the different responses to drug treatments. CONCLUSIONS: In summary, combining the Z-stack imaging technique and fluorescent labeling methods, we established an assay for the imaging and analysis of three-dimensional organoids. Our data demonstrated the feasibility of using organoid-based platforms for high-throughput drug screening assays.

Approximate analytical model for transient transport and oxygen-limited biodegradation of vapor-phase petroleum hydrocarbon compound in soil.

Volatile organic compounds (VOCs) contamination may occur in subsurface soil due to various reasons and pose great threat to people. Petroleum hydrocarbon compound (PHC) is a typical kind of VOC, which can readily biodegrade in an aerobic environment. The biodegradation of vapor-phase PHC in the vadose zone consumes oxygen in the soil, which leads to the change in aerobic and anaerobic zones but has not been studied by the existing analytical models. In this study, a one-dimensional analytical model is developed to simulate the transient diffusion and oxygen-limited biodegradation of PHC vapor in homogeneous soil. Laplace transformation and Laplace inversion of the Talbot method are adopted to derive the solution. At any given time, the thickness of aerobic zone is determined by the dichotomy method. The analytical model is verified against numerical simulation and experimental results first and parametric study is then conducted. The transient migration of PHC vapor can be divided into three stages including the pure aerobic zone stage (Stage I), aerobic-anaerobic zones co-existence stage (Stage II), and steady-state stage (Stage III). The proposed analytical model should be adopted to accommodate scenarios where the transient effect is significant (Stage II), including high source concentration, deep contaminant source, high biodegradation capacity, and high water saturation. The applicability of this model to determine the breakthrough time for better vapor intrusion assessment is also evaluated. Lower first-order biodegradation rate, higher source concentration, and shallower source depth all lead to smaller breakthrough time.

A Neural Circuit from the Paraventricular Thalamus to the Bed Nucleus of the Stria Terminalis for the Regulation of States of Consciousness during Sevoflurane Anesthesia in Mice.

BACKGROUND: The neural circuitry underlying sevoflurane-induced modulation of consciousness is poorly understood. This study hypothesized that the paraventricular thalamus bed nucleus of the stria terminalis pathway plays an important role in regulating states of consciousness during sevoflurane anesthesia. METHODS: Rabies virus-based transsynaptic tracing techniques were employed to reveal the neural pathway from the paraventricular thalamus to the bed nucleus of the stria terminalis. This study investigated the role of this pathway in sevoflurane anesthesia induction, maintenance, and emergence using chemogenetic and optogenetic methods combined with cortical electroencephalogram recordings. Both male and female mice were used in this study. RESULTS: Both γ-aminobutyric acid-mediated and glutamatergic neurons in the bed nucleus of the stria terminalis receive paraventricular thalamus glutamatergic projections. Chemogenetic inhibition of paraventricular thalamus glutamatergic neurons prolonged the sevoflurane anesthesia emergence time (mean ± SD, hM4D-clozapine N-oxide vs. mCherry-clozapine N-oxide, 281 ± 88 vs. 172 ± 48 s, P < 0.001, n = 24) and decreased the induction time (101 ± 32 vs. 136 ± 34 s, P = 0.002, n = 24), as well as the EC5 0 for the loss or recovery of the righting reflex under sevoflurane anesthesia (mean [95% CI] for the concentration at which 50% of the mice lost their righting reflex, 1.16 [1.12 to 1.20] vs. 1.49 [1.46 to 1.53] vol%, P < 0.001, n = 20; and for the concentration at which 50% of the mice recovered their righting reflex, 0.95 [0.86 to 1.03] vs. 1.34 [1.29 to 1.40] vol%, P < 0.001, n = 20). Similar results were observed during suppression of the paraventricular thalamus bed nucleus-stria terminalis pathway. Optogenetic activation of this pathway produced the opposite effects. Additionally, transient stimulation of this pathway efficiently induced behavioral arousal during continuous steady-state general anesthesia with sevoflurane and reduced the depth of anesthesia during sevoflurane-induced burst suppression. CONCLUSIONS: In mice, axonal projections from the paraventricular thalamic neurons to the bed nucleus of the stria terminalis contribute to regulating states of consciousness during sevoflurane anesthesia.

Metabolomics coupled with network pharmacology study on the protective effect of Keguan-1 granules in LPS-induced acute lung injury.

CONTEXT: Keguan-1 (KG-1) plays a vital role in enhancing the curative effects, improving quality of life, and reducing the development of acute lung injury (ALI). OBJECTIVE: To unravel the protective effect and underlying mechanism of KG-1 against ALI. MATERIALS AND METHODS: C57BL/6J mice were intratracheally instilled with lipopolysaccharide to establish the ALI model. Then, mice in the KG-1 group received a dose of 5.04 g/kg for 12 h. The levels of proinflammatory cytokines, chemokines, and pathological characteristics were determined to explore the effects of KG-1. Next, untargeted metabolomics was used to identify the differential metabolites and involved pathways for KG-1 anti-ALI. Network pharmacology was carried out to predict the putative active components and drug targets of KG-1 anti-ALI. RESULTS: KG-1 significantly improved the levels of TNF-α (from 2295.92 ± 529.87 pg/mL to 1167.64 ± 318.91 pg/mL), IL-6 (from 4688.80 ± 481.68 pg/mL to 3604.43 ± 382.00 pg/mL), CXCL1 (from 4361.76 ± 505.73 pg/mL to 2981.04 ± 526.18 pg/mL), CXCL2 (from 5034.09 ± 809.28 pg/mL to 2980.30 ± 747.63 pg/mL), and impaired lung histological damage. Untargeted metabolomics revealed that KG-1 significantly regulated 12 different metabolites, which mainly related to lipid, amino acid, and vitamin metabolism. Network pharmacology showed that KG-1 exhibited anti-ALI effects through 17 potentially active components acting on seven putative drug targets to regulate four metabolites. DISCUSSION AND CONCLUSIONS: This work elucidated the therapeutic effect and underlying mechanism by which KG-1 protects against ALI from the view of the metabolome, thus providing a scientific basis for the usage of KG-1.

Tea and tea drinking: China's outstanding contributions to the mankind.

BACKGROUND: Tea trees originated in southwest China 60 million or 70 million years ago. Written records show that Chinese ancestors had begun drinking tea over 3000 years ago. Nowadays, with the aging of populations worldwide and more people suffering from non-communicable diseases or poor health, tea beverages have become an inexpensive and fine complementary and alternative medicine (CAM) therapy. At present, there are 3 billion people who like to drink tea in the world, but few of them actually understand tea, especially on its development process and the spiritual and cultural connotations. METHODS: We searched PubMed, Google Scholar, Web of Science, CNKI, and other relevant platforms with the key word "tea", and reviewed and analyzed tea-related literatures and pictures in the past 40 years about tea's history, culture, customs, experimental studies, and markets. RESULTS: China is the hometown of tea, tea trees, tea drinking, and tea culture. China has the oldest wild and planted tea trees in the world, fossil of a tea leaf from 35,400,000 years ago, and abundant tea-related literatures and art works. Moreover, tea may be the first Chinese herbal medicine (CHM) used by Chinese people in ancient times. Tea drinking has many benefits to our physical health via its antioxidant, anti-inflammatory, immuno-regulatory, anticancer, cardiovascular-protective, anti-diabetic, and anti-obesity activities. At the moment, COVID-19 is wreaking havoc across the globe and causing severe damages to people's health and lives. Tea has anti-COVID-19 functions via the enhancement of the innate immune response and inhibition of viral growth. Besides, drinking tea can allow people to acquire a peaceful, relaxed, refreshed and cheerful enjoyment, and even longevity. According to the meridian theory of traditional Chinese medicine, different kinds of tea can activate different meridian systems in the human body. At present, black tea (fermented tea) and green tea (non-fermented tea) are the most popular in the world. Black tea accounts for over 90% of all teas sold in western countries. The world's top-grade black teas include Qi Men black in China, Darjeeling and Assam black tea in India, and Uva black tea in Sri Lanka. However, all top ten famous green teas in the world are produced in China, and Xi Hu Long Jing tea is the most famous among all green teas. More than 700 different kinds of components and 27 mineral elements can be found in tea. Tea polyphenols and theaflavin/thearubigins are considered to be the major bioactive components of black tea and green tea, respectively. Overly strong or overheated tea liquid should be avoided when drinking tea. CONCLUSIONS: Today, CAM provides an array of treatment modalities for the health promotion in both developed and developing countries all over the world. Tea drinking, a simple herb-based CAM therapy, has become a popular man-made non-alcoholic beverage widely consumed worldwide, and it can improve the growth of economy as well. Tea can improve our physical and mental health and promote the harmonious development of society through its chemical and cultural elements.