Ormosianines A-P, Structurally Diverse Quinolizidine Alkaloids with AChE Inhibitory Effects from Ormosia yunnanensis.

Sixteen new quinolizidine alkaloids (QAs), named ormosianines A-P (1-16), and 18 known congeners (17-34) were isolated from the stems and leaves of Ormosia yunnanensis. The structures were elucidated based on spectroscopic analyses and electron circular dichroism (ECD) calculations. Structurally, ormosianines A (1) and B (2) are the first examples of cytisine and Ormosia-type alkaloids with the cleavage of the piperidine ring. Results of the acetylcholinesterase (AChE) inhibitory assay revealed that the pentacycline Ormosia-type QAs, including 1, 16, 24, and 27-29, are good AChE inhibitors. Ormosianine A (1) exhibited more potent AChE inhibitory activity with an IC50 value of 1.55 µM. Molecular docking revealed that 1 might bind to the protein 1DX4, forming two hydrogen bonds with residues SER-238 and HIS-480.

Smek1 deficiency exacerbates experimental autoimmune encephalomyelitis by activating proinflammatory microglia and suppressing the IDO1-AhR pathway.

BACKGROUND: Experimental autoimmune encephalomyelitis (EAE) is an animal disease model of multiple sclerosis (MS) that involves the immune system and central nervous system (CNS). However, it is unclear how genetic predispositions promote neuroinflammation in MS and EAE. Here, we investigated how partial loss-of-function of suppressor of MEK1 (SMEK1), a regulatory subunit of protein phosphatase 4, facilitates the onset of MS and EAE. METHODS: C57BL/6 mice were immunized with myelin oligodendrocyte glycoprotein 35-55 (MOG35-55) to establish the EAE model. Clinical signs were recorded and pathogenesis was investigated after immunization. CNS tissues were analyzed by immunostaining, quantitative polymerase chain reaction (qPCR), western blot analysis, and enzyme-linked immunosorbent assay (ELISA). Single-cell analysis was carried out in the cortices and hippocampus. Splenic and lymph node cells were evaluated with flow cytometry, qPCR, and western blot analysis. RESULTS: Here, we showed that partial Smek1 deficiency caused more severe symptoms in the EAE model than in controls by activating myeloid cells and that Smek1 was required for maintaining immunosuppressive function by modulating the indoleamine 2,3-dioxygenase (IDO1)-aryl hydrocarbon receptor (AhR) pathway. Single-cell sequencing and an in vitro study showed that Smek1-deficient microglia and macrophages were preactivated at steady state. After MOG35-55 immunization, microglia and macrophages underwent hyperactivation and produced increased IL-1ß in Smek1-/+ mice at the peak stage. Moreover, dysfunction of the IDO1-AhR pathway resulted from the reduction of interferon γ (IFN-γ), enhanced antigen presentation ability, and inhibition of anti-inflammatory processes in Smek1-/+ EAE mice. CONCLUSIONS: The present study suggests a protective role of Smek1 in autoimmune demyelination pathogenesis via immune suppression and inflammation regulation in both the immune system and the central nervous system. Our findings provide an instructive basis for the roles of Smek1 in EAE and broaden the understanding of the genetic factors involved in the pathogenesis of autoimmune demyelination.

Successfully Managing Cornual Heterotopic Pregnancy:A Case Report and Literature Review.

Cornual heterotopic pregnancy is an extremely rare, life-threatening complication during pregnancy. Here, we report a 33-year-old woman who suffered cornual heterotopic pregnancy afterin vitro fertilization embryo transfer. To prevent rupture during heterotopic pregnancy, she received laparoscopic surgery to remove the ectopic gestational sac at 7+2weeks of gestation. Ultimately, she delivered a healthy boy at 38+3 weeks of gestation. Here, we also review the clinical presentations, risk factors, treatment options and outcomes of cornual heterotopic pregnancy.

Dachengqi Decoction Attenuates Intestinal Vascular Endothelial Injury in Severe Acute Pancreatitis in Vitro and in Vivo.

BACKGROUND/AIMS: Dachengqi decoction (DCQD) is a well-known traditional Chinese herbal drug with strong anti-inflammatory effects. Angiopoietin-1 (Ang-1) plays a vital role in maintaining the stability and integrity of the vascular wall and prevents vascular leakage due to inflammatory mediators. Our previous work found that DCQD protects against pancreatic injury in rats with severe acute pancreatitis (SAP). This study aims to investigate the effects of DCQD on intestinal endothelial damage in both damaged human umbilical vein endothelial cells (HUVECs) and SAP rats. METHODS: HUVECs were randomly divided into four groups: control group, TNF-α group, TNF-α plus Ang-1 group (Ang-1 group), and TNF-α plus DCQD group (DCQD group). Cells were incubated for 6 h, 12 h, and 24 h, before collection. The treatment concentration of DCQD was decided based on a Cell Counting Kit-8 (CCK-8) assay. The monolayer permeability of the HUVECs was assessed by measuring the transendothelial electrical resistance (TEER). Apoptosis was analyzed by flow cytometry. mRNA and protein expression of aquaporin 1 (AQP-1), matrix metalloproteinase 9 (MMP9), and junctional adhesion molecule-C (JAM-C) was evaluated by RT-PCR, immunocytofluorescence, and western blot. Forty male Sprague-Dawley rats were randomized into a control group, SAP group, SAP plus Ang-1 group (Ang-1 group), and SAP plus DCQD group (DCQD group). SAP was induced by intraperitoneal injection of cerulein and lipopolysaccharide (LPS), while the control group received 0.9% saline solution. Evans blue was injected through the penile vein and the rats were then sacrificed 12 h after modeling. Levels of serum amylase, TNF-α, IL-1ß, IL-2, and IL-6 were determined by using ELISA. Intestinal tissue was analysed by histology, and capillary permeability in the tissues was evaluated by Evans blue extravasation assay. Protein and mRNA expression of AQP-1, MMP9, and JAM-C were assessed by immunohistofluorescence, western blot, and RT-PCR. RESULTS: DCQD reduced the permeability of HUVEC induced by TNF-α in vitro. Furthermore, DCQD altered the mRNA and protein levels of JAM-C, MMP9, and AQP-1 in HUVECs after TNF-α induction. SAP intestinal injury induced by cerulein combined with lipopolysaccharides was concomitant with increased expression of JAM-C and MMP9, and reduced expression of AQP-1 in intestinal tissue. Pretreatment with DCQD attenuated SAP intestinal injury and lowered the levels of serum amylase, TNF-α, IL-1ß, IL-2, and IL-6 effectively. Our study demonstrated that DCQD decreased the expression of JAM-C and MMP9 and increased the expression of AQP-1 both in vitro and in vivo. CONCLUSION: DCQD can reduce capillary endothelial damage in acute pancreatitis-associated intestinal injury and the mechanism may be associated with the regulation of endothelial barrier function-associated proteins AQP-1, MMP9, and JAM-C.

Intravenous Administration of Multiwalled Carbon Nanotubes Aggravates High-Fat Diet-Induced Nonalcoholic Steatohepatitis in Sprague Dawley Rats.

Multiwalled carbon nanotubes (MWCNTs) have been explored in pharmaceutical applications such as tumor targeting and delivery of drugs, in which MWCNTs are given through intravenous injection. However, the biosafety of MWCNTs is of concern for such application. Therefore, in the current study, we used a fatty liver model to investigate the possible toxicity of MWCNTs to the liver, as MWCNTs were retained mainly in the liver of mice after intravenous injection. Male Sprague Dawley rats were used to generate the fatty liver model, and the effects of intravenous administration of MWCNTs on fatty liver were studied. Hematoxylin and eosin staining for hepatocellular anatomy and Masson trichrome staining for hepatic fibrosis were conducted. Histologically, MWCNTs aggravated steatohepatitis with higher nonalcoholic fatty liver disease scores. Analysis of liver injury markers indicated that MWCNTs administration resulted in chronic hepatitis, along with increased liver fat and altered liver oxidation, including the increase of P6 protein and the depletion of glutathione. In conclusion, our results suggest that MWCNTs can aggravate nonalcoholic steatohepatitis in Sprague Dawley rats, and oxidative injury may be involved in this process.

[Study on biosynthesis of silver nanoparticles using fagopyri dibotryis rhizoma extract and optimization of synthesis conditions].

Silver nanoparticles were synthesized from the extract of Fagopyri Dibotryis Rhizoma and the optimization of synthesis was studied. The absorbance of UV-visible spectroscopy was determined under the different influencing factors such as extracting time of Fagopyri Dibotryis Rhizoma powder, reation temperature of synthesis, volume of Fagopyri Dibotryis Rhizoma extract and concentration of AgNO3 to seek the optimization conditions. By means of FT-IR, TEM, DLS and XRD, the silver nanoparticles were characterized. The results showed that when the boiling time of Fagopyri Dibotryis Rhizoma powder was 5 min, resultant temperature was 25 degrees C, the volume ratio of 0.1 g x mL(-1) Fagopyri Dibotryis Rhizoma extract and 1 mmol x L(-1) AgNO3 was 1 to 10, and the reaction time was 3.5 h, the obtained silver nanoparticles had mean size about 27 nm and Zeta potential about -34.3 mV with good uniformity and dispersivity. Therefore, the green synthesis method of silver nanoparticles using extract of traditional Chinese medicine is stable and feasible.

Are depressive symptoms associated with cardiovascular mortality among older Chinese: a cohort study of 64,000 people in Hong Kong?

BACKGROUND: Depression was positively associated with cardiovascular disease (CVD) or mortality in previous studies. However, whether the observed association can be explained by health status is not clear. OBJECTIVES: To study the association of depressive symptoms with CVD, stroke, and coronary heart disease (CHD) mortality in older Chinese in Hong Kong, and whether the associations varied by gender or health status. DESIGN: Prospective population-based study. SETTING: Elderly Health Centers. PARTICIPANTS: A total of 62,839 people age 65 or older (21,473 men and 41,366 women) enrolled during July 1998 to December 2001 at all 18 Elderly Health Centers of the Department of Health of Hong Kong. MEASUREMENTS: Fifteen-item Geriatric Depression Scale (GDS) was used and presence of depressive symptoms was defined by GDS score 8 or more. The cohort was followed up for mortality till March 31, 2009. RESULTS: Depressive symptoms were only associated with CHD mortality in men (hazard ratio [HR] 1.41, 95% confidence interval [CI]: 1.08-1.84; p for gender interaction = 0.02) adjusted for age, education, monthly expenditure, smoking, alcohol use, physical activity, body mass index, health status, and self-rated health. GDS score was associated with stroke mortality (similarly adjusted HR 1.02 per score, 95% CI: 1.00-1.04) in all subjects (adjusted also for gender), and CHD mortality (1.04 [1.01-1.07]) in men. Health status attenuated but did not modify any associations. CONCLUSION: Depressive symptoms were independently associated with higher CHD mortality in older Chinese men, and with higher stroke mortality in both genders. However, attenuation by health status, and lack of consistency by gender indicate that these associations could be noncausal and further studies by treatment trials and Mendelian randomization are needed.

[Study on different factors affecting the bionic enzymatic hydrolysis of icariin].

This study aims to observe different factors which affected the bionic enzymatic hydrolysis of icariin into baohuoside I and to optimize the reaction conditions in order to provide research foundation for building a novel bionic enzymolysis drug delivery system. To simulate the environment in vivo, 37 degrees C was set as the temperature and artificial intestinal juice and gastric juice were selected as the buffer solutions. Taking the conversion of baohuoside I as index, the effects of the kinds of enzyme, enzyme activity, substrate concentration, reaction time, pancreatin in artificial intestinal juice and surfactant on the conversion of baohuoside I were investigated. The results showed that cellulase, beta-glucosidase and snailase were all inactive in artificial gastric juice and no baohuoside I generated. Pancreatin in artificial intestinal juice couldn't significantly influence the activity of beta-glucosidase or snailase (P > 0.05), but noticeably decrease the activity of cellulase (P < 0.05). In artificial intestinal juice, the conversion of baohuoside I was highest by using beta-glucosidase, and the optimum reaction conditions were determined as follows: enzyme activity 10 U x mL(-1), substrate concentration 1 mg x mL(-1), 3 g x L(-1) rhamnolipid and reaction time 3 h. Under this condition, the conversion of baohuoside I was 99.8%.

The ideal treatment timing for diabetic retinopathy: the molecular pathological mechanisms underlying early-stage diabetic retinopathy are a matter of concern.

Diabetic retinopathy (DR) is a prevalent complication of diabetes, significantly impacting patients' quality of life due to vision loss. No pharmacological therapies are currently approved for DR, excepted the drugs to treat diabetic macular edema such as the anti-VEGF agents or steroids administered by intraocular route. Advancements in research have highlighted the crucial role of early intervention in DR for halting or delaying disease progression. This holds immense significance in enhancing patients' quality of life and alleviating the societal burden associated with medical care costs. The non-proliferative stage represents the early phase of DR. In comparison to the proliferative stage, pathological changes primarily manifest as microangiomas and hemorrhages, while at the cellular level, there is a loss of pericytes, neuronal cell death, and disruption of components and functionality within the retinal neuronal vascular unit encompassing pericytes and neurons. Both neurodegenerative and microvascular abnormalities manifest in the early stages of DR. Therefore, our focus lies on the non-proliferative stage of DR and we have initially summarized the mechanisms involved in its development, including pathways such as polyols, that revolve around the pathological changes occurring during this early stage. We also integrate cutting-edge mechanisms, including leukocyte adhesion, neutrophil extracellular traps, multiple RNA regulation, microorganisms, cell death (ferroptosis and pyroptosis), and other related mechanisms. The current status of drug therapy for early-stage DR is also discussed to provide insights for the development of pharmaceutical interventions targeting the early treatment of DR.

Novel, chimeric, cancer-specific, and radiation-inducible gene promoters for suicide gene therapy of cancer.

BACKGROUND: Although the promoter of the human telomerase reverse transcriptase (hTERT) gene has been widely used in gene therapy for targeted cancer cells, it has some limitations for clinical use because of its low activity and potential toxicity to certain normal cells. To overcome these defects, the authors generated novel chimeric hTERT promoters that contained the radiation-inducible sequence CC(A/T)(6) GG (known as CArG elements). METHODS: Chimeric hTERT promoters were synthesized that contained different numbers of CArG elements, and the activity of chimeric promoters was assessed in different cancer cell lines and normal cells. The potential of selected promoters to successfully control horseradish peroxidase (HRP) and prodrug indole-3-acetic acid (IAA) suicide gene therapy was tested in vitro and in vivo. RESULTS: The promoter activity assays indicated that the synthetic promoter that contained 6 repeating CArG units had the best radiation inducibility than any other promoters that contained different numbers of CArG units, and the chimeric promoters retained their cancer-specific characteristics. The chimeric promoter was better at driving radiation-inducible gene therapy than the control promoters. The sensitizer enhancement ratio of the chimeric promoter system determined by clonogenic assay was higher, and the chimeric promoter system resulted in a significantly higher apoptotic level compared with other promoter systems. The combination of chimeric/promoter-mediated gene therapy and radiotherapy significantly inhibited tumor volume in a xenograft mouse model and resulted in a significant prolongation of survival in mice. CONCLUSIONS: The current results indicated that a combinational cancer-specific promoter system that is responsive to irradiation has great potential for improving the efficacy of cancer treatment.

Depressive symptoms and suicide in 56,000 older Chinese: a Hong Kong cohort study.

OBJECTIVE: To examine dose-response associations between depressive symptoms and suicide and modification effects of sex, age and health status in older Chinese. METHODS: We used the Chinese version of the 15-item Geriatric Depression Scale (GDS) to measure depressive symptoms (GDS score ≥ 8) and Cox regression to examine association with suicide mortality in a population-based cohort of 55,946 individuals, aged 65 years or above, enrolled from July 1998 to December 2000 at one of 18 Elderly Health Centres of Hong Kong Department of Health. The cohort was followed up for suicide mortality till 31 March 2009 (mean follow-up 8.7 years). RESULTS: Depressive symptoms were associated with suicide in men [hazard ratio (HR) 2.03, 95% confidence interval (CI) 0.96-4.29] and women (HR = 2.36, 95% CI 1.31-4.24) after adjusting for age, education, monthly expenditure, smoking, alcohol drinking, physical activity, body mass index, health status, and self-rated health. There was no threshold for GDS score and suicide in either sex. Age, sex and health status did not modify the association. CONCLUSIONS: Depressive symptoms predict higher suicide risk in older Chinese in a dose-response pattern. These associations were not attenuated by adjustment for health status, suggesting that depressive symptoms in older people are likely to be an independent causal factor for suicide. The GDS score showed no threshold in predicting suicide risk, suggesting that older people with low GDS scores deserve further attention and those with very high scores need urgent intervention.

Gadolinium Enhances Dual-energy Computed Tomography Scan of Pulmonary Artery.

OBJECTIVE: To evaluate the feasibility of using gadopentetate dimeglumine (Gd-DTPA) for dual-energy computed tomography pulmonary angiography (CTPA). METHODS: Sixty-six patients were randomly divided into three groups and underwent CTPA. Group A had a turbo flash scan using an iohexol injection, Group B had a turbo flash scan using Gd-DTPA, and Group C had a dual-energy scan using Gd-DTPA. The original images of Group C were linearly blended with a blending factor of 0.5 or reconstructed at 40, 50, 60, 70, 80, 90, 100, and 110 keV, respectively. The groups were compared in terms of pulmonary artery CT value, image quality, and radiation dose. RESULTS: The pulmonary artery CT values were significantly higher in Group C40keV than in Groups B and C, but lower than in Group A. There was no significant difference in the image noise of Groups C40keV, B, and C. Moreover, Group A had the largest beam hardening artifacts of the superior vena cava (SVC), followed by Groups B and C. Group C40keV showed better vascular branching than the other three groups, among which Group B was superior to Group A. The subjective score of the image quality of Groups A, B, and C showed no significant difference, but the score was significantly higher in Group C40keV than in Groups A and B. The radiation dose was significantly lower in Group B than in Groups A and C. CONCLUSION: Gd-CTPA is recommended to patients who are unsuitable for receiving an iodine-based CTPA. Furthermore, a turbo flash scan could surpass a dual-energy scan without consideration for virtual monoenergetic imaging.

Corrigendum to: Do Stay at Home Orders and Cloth Face Coverings Control COVID-19 in New York City? Results From a SIER Model Based on Real-world Data.

[This corrects the article DOI: 10.1093/ofid/ofaa442.].

[Anti-tumor effect of suicide gene therapy using chimeric promoter plus radiotherapy on cancer cell lines].

OBJECTIVE: To explore the synergistic anti-tumor effect of radiotherapy and horseradish peroxidase/prodrug indole-3-acetic acid (HRP/IAA) gene therapy system using chimeric hTERT promoter responsive to ionizing radiation. METHODS: The synthetic hTERT promoters containing four tandem-repeat copies of radio-inducible CArG elements, and the chimeric promoter containing cytomegalovirus (CMV) early promoter were both constructed. The activities of the chimeric promoters in cancer cell lines (HeLa, A549, and MHCC97) and normal cell line (MRC-5) were detected using luciferase reporter gene expression analysis after a (60)Co γ-irradiation treatment at a series of doses(a single dose of 0 to 10 Gy). The anti-tumor effect of combining irradiation with HRP/IAA gene-directed enzyme prodrug therapy system controlled by the chimeric promoter was tested by colony formation assay, cell counting and apoptosis analysis. RESULTS: The chimeric promoters were ineffective in normal human cells, even after irradiation, but the expression of luciferase gene in tumor cells was significantly higher. The activity of the chimeric promoter in MRC-5 cells was 22.3%, 12.9% and 13.6% of that in HeLa, A549 and MHCC97 cells, respectively. After irradiation, the ratios were 11.7%, 8.7% and 8.8%, respectively. Furthermore, the chimeric promoters could successfully induce the expression of luciferase gene following different doses of radiation, with maximal inducible activity seen after 6 Gy irradiation. The chimeric promoter containing four tandem-repeat copies of radio-inducible CArG elements and CMV early promoter showed the highest activity with 6 Gy irradiation. The relative luciferase activities in HeLa, A549 and MHCC97 cells were 1.7 ± 0.2, 2.3 ± 0.2 and 2.3 ± 0.1, respectively. The chimeric promoter mediated suicide gene therapy system could increase radio-sensitivity in different cancer cells. Compared with the control system, it plus irradiation showed stronger cell proliferation inhibition, 67.3% vs. 26.1% in HeLa, 69.0% vs. 28.3% in A549, 64.6% vs. 20.8% in MHCC97 cells, and also higher apoptosis-inducing effect, 39.6% vs. 14.2% in HeLa, 33.0% vs. 12.4% in A549, and 33.2% vs. 14.2% in MHCC97 cells. CONCLUSIONS: Chimeric promoter containing hTERT promoter, CArG elements and CMV promoter preserve the tumor-specificity in telomerase-positive tumor cells, and irradiation-responsive to low dose of radiation. The suicide gene therapy using this promoter plus radiotherapy show a strong anti-tumor effect in vitro. It is expected to have a good potential for future application in gene radiotherapy.

Do Stay at Home Orders and Cloth Face Coverings Control COVID-19 in New York City? Results From a SIER Model Based on Real-world Data.

BACKGROUND: Public health interventions have been implemented to contain the outbreak of coronavirus disease 2019 (COVID-19) in New York City. However, the assessment of those interventions-for example, social distancing and cloth face coverings-based on real-world data from published studies is lacking. METHODS: The Susceptible-Exposed-Infectious-Removed (SEIR) compartmental model was used to evaluate the effect of social distancing and cloth face coverings on the daily culminative laboratory confirmed cases in New York City (NYC) and COVID-19 transmissibility. The latter was measured by Rt reproduction numbers in 3 phases that were based on 2 interventions implemented during this timeline. RESULTS: Transmissibility decreased from phase 1 to phase 3. The initial R0 was 4.60 in phase 1 without any intervention. After social distancing, the Rt value was reduced by 68%, while after the mask recommendation, it was further reduced by ~60%. CONCLUSIONS: Interventions resulted in significant reduction of confirmed case numbers relative to predicted values based on the SEIR model without intervention. Our findings highlight the effectiveness of social distancing and cloth face coverings in slowing down the spread of severe acute respiratory syndrome coronavirus 2 in NYC.

New hydroperoxylated and 20,24-epoxylated dammarane triterpenes from the rot roots of Panax notoginseng.

BACKGROUND: Root rot is a serious destructive disease of Panax notoginseng, a famous cultivated araliaceous herb called Sanqi or Tianqi in Southwest China. METHODS: The chemical substances of Sanqi rot roots were explored by chromatographic techniques. MS, 1D/2D-NMR, and single crystal X-ray diffraction were applied to determine the structures. Murine macrophage RAW264.7 and five human cancer cell lines were used separately for evaluating the antiinflammatory and cytotoxic activities. RESULTS AND CONCLUSION: Thirty dammarane-type triterpenes and saponins were isolated from the rot roots of P. notoginseng. Among them, seven triterpenes, namely, 20(S)-dammar-25-ene-24(S)-hydroperoxyl-3ß,6α,12ß,20-tetrol (1), 20(S)-dammar-3-oxo-23-ene-25-hydroperoxyl-6α,12ß,20-triol (2), 20(S)-dammar-12-oxo-23-ene-25-hydroperoxyl-3ß,6α,20-triol (3), 20(S)-dammar-3-oxo-23-ene-25-hydroperoxyl-12ß,20-diol (4), 20(S),24(R)-epoxy-3,4-seco-dammar-25-hydroxy-12-one-3-oic acid (5), 20(S),24(R)-epoxy-3,4-seco-dammar-25-hydroxy-12-one-3-oic acid methyl ester (6), and 6α-hydroxy-22,23,24,25,26,27-hexanordammar-3,12,20-trione (7), are new compounds. In addition, 12 known ones (12-16 and 19-25) were reported in Sanqi for the first time. The new Compound 1 showed comparable antiinflammatory activity on inhibition of NO production to the positive control, whereas the known compounds 9, 12, 13, and 16 displayed moderate cytotoxicities against five human cancer cell lines. The results will provide scientific basis for understanding the chemical constituents of Sanqi rot roots and new candidates for searching antiinflammatory and antitumor agents.

"Kidney Tea" and Its Bioactive Secondary Metabolites for Treatment of Gout.

Clerodendranthus spicatus, popularly known as "kidney tea" in China, is consumed traditionally as a functional food for treatment of renal inflammation, dysuria, and gout. We evaluated the effects of C. spicatus on gout by assessing activities of antihyperuricemia, anti-gouty arthritis, and analgesia in vivo, and the results indicated that the ethyl acetate fraction shows potential activities. Subsequent phytochemical investigation of this fraction led to the isolation of 32 compounds, consisting of 20 diterpenoids (including the new orthosiphonones E and F), 2 triterpenoids, 6 flavonoids, 2 lignanoids, and 2 phenolic acid derivatives. Pharmacological investigation of the pure compounds in the cellular model of hyperuricemia indicated that 12 compounds could promote the excretion of uric acid at 10 µg/mL, and compounds 3, 4, 5, and 21 had better effects than that of benzbromarone, a famous uricosuric drug. Furthermore, compounds 4, 6, 7, 9, 14, 15, 23, 26, and 31 showed significant anti-gouty arthritis activity in monosodium urate (MSU)-induced joint swelling at the dose of 50 mg/kg, while compounds 4, 5, 7, 9, and 26 exhibited significant inhibition of pain induced by acetic acid. Our findings provided scientific justification to support the traditional application of "kidney tea" for treating gout and suggested its good application prospects in the future.

Protection against COVID-19 injury by qingfei paidu decoction via anti-viral, anti-inflammatory activity and metabolic programming.

Qingfei Paidu decoction (QFPD), a multi-component herbal formula, has been widely used to treat COVID-19 in China. However, its active compounds and mechanisms of action are still unknown. Firstly, we divided QFPD into five functional units (FUs) according to the compatibility theory of traditional Chinese medicine. The corresponding common targets of the five FUs were all significantly enriched in Go Ontology (oxidoreductase activity, lipid metabolic process, homeostatic process, etc.), KEGG pathways (steroid biosynthesis, PPAR signaling pathway, adipocytokine signaling pathway, etc.), TTD diseases (chronic inflammatory diseases, asthma, chronic obstructive pulmonary Disease, etc.), miRNA (MIR183), kinase (CDK7) and TF (LXR). QFPD contained 257 specific targets in addition to HCoV, pneumonia and ACE2 co-expression proteins. Then, network topology analysis of the five components-target-pathway-disease networks yielded 67 active ingredients. In addition, ADMET estimations showed that 20 compounds passed the stringent lead-like criteria and in silico drug-likeness test with high gastrointestinal absorption and the median lethal dose (LD50 > 1600 mg/kg). Moreover, 4 specific ingredients (M3, S1, X2 and O2) and 5 common ingredients (MS1, MX16, SX1, WO1 and XO1) of QFPD presented good molecular docking score for 2019-nCov structure and non-structure proteins. Finally, drug perturbation of COVID-19 network robustness showed that all five FUs may protect COVID-19 independently, and target 8 specifically expressed drug-attacked nodes which were related to the bacterial and viral responses, immune system, signaling transduction, etc. In conclusion, our new FUNP analysis showed that QFPD had a protection effect on COVID-19 by regulating a complex molecular network with safety and efficacy. Part of the mechanism was associated with the regulation of anti-viral, anti-inflammatory activity and metabolic programming.

Potential use of actigraphy to measure sleep in monkeys: comparison with behavioral analysis from videography.

Sleep is indispensable for human health, with sleep disorders initiating a cascade of negative consequences. As our closest phylogenetic relatives, non-human primates (NHPs) are invaluable for comparative sleep studies and exhibit tremendous potential for improving our understanding of human sleep and related disorders. Previous work on measuring sleep in NHPs has mostly used electroencephalography or videography. In this study, simultaneous videography and actigraphy were applied to observe sleep patterns in 10 cynomolgus monkeys ( Macaca fascicularis) over seven nights (12 h per night). The durations of wake, transitional sleep, and relaxed sleep were scored by analysis of animal behaviors from videography and actigraphy data, using the same behavioral criteria for each state, with findings then compared. Here, results indicated that actigraphy constituted a reliable approach for scoring the state of sleep in monkeys and showed a significant correlation with that scored by videography. Epoch-by-epoch analysis further indicated that actigraphy was more suitable for scoring the state of relaxed sleep, correctly identifying 97.57% of relaxed sleep in comparison with video analysis. Only 34 epochs (0.13%) and 611 epochs (2.30%) were differently interpreted as wake and transitional sleep compared with videography analysis. The present study validated the behavioral criteria and actigraphy methodology for scoring sleep, which can be considered as a useful and a complementary technique to electroencephalography and/or videography analysis for sleep studies in NHPs.