Factors Associated With the Spatial Distribution of Severe Fever With Thrombocytopenia Syndrome in Zhejiang Province, China: Risk Analysis Based on Maximum Entropy.

Background: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease that was first identified in mainland China in 2009 and has been reported in Zhejiang Province, China, since 2011. However, few studies have focused on the association between ticks, host animals, and SFTS. Objective: In this study, we analyzed the influence of meteorological and environmental factors as well as the influence of ticks and host animals on SFTS. This can serve as a foundational basis for the development of strategic policies aimed at the prevention and control of SFTS. Methods: Data on SFTS incidence, tick density, cattle density, and meteorological and environmental factors were collected and analyzed using a maximum entropy-based model. Results: As of December 2019, 463 laboratory-confirmed SFTS cases were reported in Zhejiang Province. We found that the density of ticks, precipitation in the wettest month, average temperature, elevation, and the normalized difference vegetation index were significantly associated with SFTS spatial distribution. The niche model fitted accurately with good performance in predicting the potential risk areas of SFTS (the average test area under the receiver operating characteristic curve for the replicate runs was 0.803 and the SD was 0.013). The risk of SFTS occurrence increased with an increase in tick density, and the response curve indicated that the risk was greater than 0.5 when tick density exceeded 1.4. The risk of SFTS occurrence decreased with increased precipitation in the wettest month, and the risk was less than 0.5 when precipitation exceeded 224.4 mm. The relationship between elevation and SFTS occurrence showed a reverse V shape, and the risk peaked at approximately 400 m. Conclusions: Tick density, precipitation, and elevation were dominant influencing factors for SFTS, and comprehensive intervention measures should be adjusted according to these factors to reduce SFTS incidence in Zhejiang Province.

Torsion affects the calculation of DNA twisting number.

The topological properties of DNA have long been a focal point in biophysics. In the 1970s, White proposed that the topology of closed DNA double helix follows White's formula: Lk=Wr+Tw. However, there has been controversy in the calculation of DNA twisting number, partly due to discrepancies in the definition of torsion in differential geometry. In this paper, we delved into a detailed study of torsion, revealing that the calculation of DNA twisting number should use the curve's geodesic torsion. Furthermore, we found that the discrepancy in DNA twisting numbers calculated using different torsion is N. This study elucidated the impact of torsion on the calculation of DNA twisting numbers, aiming to resolve controversies in the calculation of DNA topology and provided accurate computational methods and theoretical foundations for related research.

The Free Energy of Nucleosomal DNA Based on the Landau Model and Topology.

The free energy of nucleosomal DNA plays a key role in the formation of nucleosomes in eukaryotes. Some work on the free energy of nucleosomal DNA have been carried out in experiments. However, the relationships between the free energy of nucleosomal DNA and its conformation, especially its topology, remain unclear in theory. By combining the Landau theory, the Hopfion model and experimental data, we find that the free energy of nucleosomal DNA is at the lower level. With the help of the energy minimum principle, we conclude that nucleosomal DNA stays in a stable state. Moreover, we discover that small perturbations on nucleosomal DNA have little effect on its free energy. This implies that nucleosomal DNA has a certain redundancy in order to stay stable. This explains why nucleosomal DNA will not change significantly due to small perturbations.

The epidemiology of Aedes-borne arboviral diseases in Zhejiang, Southeast China: a 20 years population-based surveillance study.

Objective: Aedes-borne arboviral diseases were important public health problems in Zhejiang before the coronavirus disease 2019 (COVID-19) pandemic. This study was conducted to investigate the characteristics and change of the epidemiology of Aedes-borne arboviral diseases in the province. Methods: Descriptive analyses were conducted to summarize the epidemiology of Aedes-borne arboviral diseases during 2003-2022. Results: A total of 3,125 cases, including 1,968 indigenous cases, were reported during 2003-2022. Approximately three-quarters of imported cases were infected from Southeast Asia. The number of annual imported cases increased during 2013-2019 (R2 = 0.801, p = 0.004) and peaked in 2019. When compared with 2003-2012, all prefecture-level cities witnessed an increase in the annual mean incidence of imported cases in 2013-2019 (0.11-0.42 per 100,000 population vs. 0-0.05 per 100,000 population) but a drastic decrease during 2020-2022 (0-0.03 per 100,000 population). The change in geographical distribution was similar, with 33/91 counties during 2003-2012, 86/91 during 2013-2019, and 14/91 during 2020-2022. The annual mean incidence of indigenous cases in 2013-2019 was 7.79 times that in 2003-2012 (0.44 vs. 0.06 per 100,000 population). No indigenous cases were reported between 2020-2022. Geographical extension of indigenous cases was also noted before 2020-from two counties during 2003-2012 to 44 during 2013-2019. Conclusion: Dengue, chikungunya fever, zika disease, and yellow fever are not endemic in Zhejiang but will be important public health problems for the province in the post-COVID-19 era.

Energy spectrum of the ideal DNA knot on a torus.

In this study, we consider DNA as a torus knot that is formed by an elastic string. In order to determine what kinds of knot could be formed, we present its energy spectrum by combining Euler rotation, DNA's mechanical properties, and the modified Faddeev-Skyrme model. Our results theoretically demonstrated that the flexural rigidity of DNA plays an important role. If it is smaller than a critical value, DNA is likely to form a coiled structure. Conversely, above the critical value, DNA forms a twisting structure. The energy spectrum provides a way to identify the types of knots that are most likely to be created by DNA, according to the principle of energy minimisation, and with implications for its functional and packaging states in the cell nucleus.

Asperuloside alleviates lipid accumulation and inflammation in HFD-induced NAFLD via AMPK signaling pathway and NLRP3 inflammasome.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a clinical pathological syndrome of hepatic parenchymal cell steatosis caused by excessive lipid deposition, which is the chronic liver disease with the highest incidence in China. Asperuloside (ASP), a kind of iridoid compound, possesses natural pharmacological effects of anti-tumor, anti-inflammatory, antioxidant and anti-obesity. However, whether ASP can improve NAFLD remains unclear. PURPOSE: We aimed to investigate the effect of ASP on NAFLD mice induced by high-fat diet (HFD), and explore its mechanism in vivo and in vitro. METHODS: Pharmacodynamics of ASP was studied by HFD induction in NAFLD mice. HepG2 cells were induced by palmitic acid (PA) as cell model to investigate the effect of ASP on lipid deposition and inflammatory infiltration. Expression of Adenosine monophosphate - activated protein kinase (AMPK) signaling pathway and NOD-like receptor pyrin containing 3 (NLRP3) inflammasome were detected by Western blot and RT-PCR. Cytokines IL-1ß and TNF-α were detected by ELISA. RESULTS: ASP alleviated liver injury and inflammatory damage in mice with NAFLD. In addition, ASP improved lipid deposition as well as inflammatory response in HFD-induced NAFLD mice and PA-stimulated HepG2 cells. ASP ameliorated lipid deposition and inflammatory response by regulating the p-AMPK/SREBP-1c signaling pathway and NLRP3 inflammasome. CONCLUSION: Our results suggest that ASP improve lipid deposition and inflammatory infiltration in NAFLD mice via regulating the AMPK/SREBP-1c signaling pathway and NLRP3 inflammasome, which may be an effective candidate for the treatment of NAFLD.

Exploration of the Character Representation of DNA Chiral Conformations and Deformations via a Curved Surface Discrete Frenet Frame.

While undergoing structural deformation, DNA experiences changes in the interactions between its internal base pairs, presenting challenges to conventional elastic methods. To address this, we propose the Discrete Critical State (DCS) model in this paper. This model combines surface discrete frame theory with gauge theory and Landau phase transition theory to investigate DNA's structural deformation, phase transitions, and chirality. Notably, the DCS model considers both the internal interactions within DNA and formulates an overall equation using unified physical and geometric parameters. By employing the discrete frame, we derive the evolution of physical quantities along the helical axis of DNA, including geodesic curvature, geodesic torsion, and others. Our findings indicate that B-DNA has a significantly lower free energy density compared to Z-DNA, which is in agreement with experimental observations. This research reveals that the direction of base pairs is primarily governed by the geodesic curve within the helical plane, aligning closely with the orientation of the base pairs. Moreover, the geodesic curve has a profound influence on the arrangement of base pairs at the microscopic level and effectively regulates the configuration and geometry of DNA through macroscopic-level free energy considerations.

Combination of paeoniflorin and calycosin-7-glucoside alleviates ischaemic stroke injury via the PI3K/AKT signalling pathway.

CONTEXT: Paeoniflorin (PF) and calycosin-7-glucoside (CG, Paeonia lactiflora Pall. extract) have demonstrated protective effects in ischaemic stroke. OBJECTIVE: To investigate the synergistic effects of PF + CG on ischaemia/reperfusion injury in vivo and in vitro. MATERIALS AND METHODS: Male Sprague-Dawley rats were subjected to the middle cerebral artery occlusion/reperfusion (MCAO/R). After MCAO/R for 24 h, rats were randomly subdivided into 5 groups: sham, model (MCAO/R), study treatment (PF + CG, 40 + 20 mg/kg), LY294002 (20 mg/kg), and study treatment + LY294002. Males were given via intragastric administration; the duration of the in vivo experiment was 8 days. Neurologic deficits, cerebral infarction, brain edoema, and protein levels were assessed in vivo. Hippocampal neurons (HT22) were refreshed with glucose-free DMEM and placed in an anaerobic chamber for 8 h. Subsequently, HT22 cells were reoxygenated in a 37 °C incubator with 5% CO2 for 6 h. SOD, MDA, ROS, LDH and protein levels were measured in vitro. RESULTS: PF + CG significantly reduced neurobehavioral outcomes (21%), cerebral infarct volume (44%), brain edoema (1.6%) compared with the MCAO/R group. Moreover, PF + CG increased p-PI3K/PI3K (4.69%, 7.4%), p-AKT/AKT (6.25%, 60.6%) and Bcl-2/BAX (33%, 49%) expression in vivo and in vitro, and reduced GSK-3ß (10.5%, 9.6%) expression. In vitro, PF + CG suppressed apoptosis in HT22 cells and decreased ROS and MDA levels (20%, 50%, respectively). CONCLUSIONS: PF + CG showed a synergistic protective effect against ischaemic brain injury, potentially being a future treatment for ischaemic stroke.

Epidemiology of Indigenous Dengue Cases in Zhejiang Province, Southeast China.

Objective: Autochthonous transmission of the dengue virus (DENV) occurred each year from 2014 to 2018 in Zhejiang province, and became an emerging public health problem. We characterized the autochthonous transmission of the DENV and traced the source of infection for further control and prevention of dengue. Methods: Descriptive and spatiotemporal cluster analyses were conducted to characterize the epidemiology of autochthonous transmission of the DENV. Molecular epidemiology was used to identify the infection source. Results: In total, 1,654 indigenous cases and 12 outbreaks, with no deaths, were reported during 2004-2018. Before 2017, all outbreaks occurred in suburban areas. During 2017-2018, five out of eight outbreaks occurred in urban areas. The median duration of outbreaks (28 days) in 2017-2018 was shortened significantly (P = 0.028) in comparison with that in 2004-2016 (71 days). The median onset-visiting time, visiting-confirmation time, and onset-confirmation time was 1, 3, and 4 days, respectively. The DENV serotypes responsible for autochthonous transmission in Zhejiang Province were DENV 1, DENV 2, and DENV 3, with DENV 1 being the most frequently reported. Southeast Asia was the predominant source of indigenous infection. Conclusions: Zhejiang Province witnessed an increase in the frequency, incidence, and geographic expansion of indigenous Dengue cases in recent years. The more developed coastal and central region of Zhejiang Province was impacted the most.

The changing epidemiology of hemorrhagic fever with renal syndrome in Southeastern China during 1963-2020: A retrospective analysis of surveillance data.

BACKGROUND: Hemorrhagic fever with renal syndrome (HFRS) is a rodent-borne disease caused by hantavirus which was endemic Zhejiang Province, China. In this study, we aim to explore the changing epidemiology of HFRS in Zhejiang, identify high-risk areas and populations, and evaluate relevant policies and interventions to better improve HFRS control and prevention. METHODS: Surveillance data on HFRS during 1963-2020 in Zhejiang Province were extracted from Zhejiang Provincial Center for Disease Control and Prevention archives and the Chinese Notifiable Disease Reporting System. The changing epidemiological characteristics of HFRS including seasonal distribution, geographical distribution, and demographic features, were analyzed using joinpoint regression, autoregressive integrated moving average model, descriptive statistical methods, and Spatio-temporal cluster analysis. RESULTS: From 1963 to 2020, 114 071 HFRS cases and 1269 deaths were reported in Zhejiang Province. The incidence increased sharply from 1973 and peaked in 1986, then decreased steadily and maintained a stable incidence from 2004. HFRS cases were reported in all 11 prefecture-level cities of Zhejiang Province from 1963 to 2020. The joint region (Shengzhou, Xinchang, Tiantai, and surrounding areas), and Kaihua County are the most seriously affected regions throughout time. After 1990, the first HFRS incidence peak was in May-June, with another one from November to January. Most HFRS cases occurred in 21- (26.48%) and 30- years group (24.25%) from 1991 to 2004, but 41- (25.75%) and 51-years (23.30%) had the highest proportion from 2005 to 2020. Farmers accounted for most cases (78.10%), and cases are predominantly males with a male-to-female ratio of 2.6:1. It was found that the median time from onset to diagnosis was 6.5 days (IQR 3.75-10.42), and the time from diagnosis to disease report was significantly shortened after 2011. CONCLUSIONS: We observed dynamic changes in the seasonal distribution, geographical distribution, and demographic features of HFRS, which should be well considered in the development of control and prevention strategies in future. Additional researches are warranted to elucidate the environmental, meteorological, and social factors associated with HFRS incidence in different decades.

Characteristics of Three Person-to-Person Transmission Clusters of Severe Fever with Thrombocytopenia Syndrome in Southeastern China.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease worldwide. It can be transmitted from person to person, and the fatality rate is very high. During this study, three SFTS clusters including 12 associated cases were identified in three counties in Zhejiang Province from 2018 to 2020. The median age of the three index patients was 70 years, and that of secondary case patients was 59 years. Of note, the mortality rate of the index patients was 100%. The mortality rate of secondary case patients was 11%. The total secondary attack rate (SAR) was 30% (9/30). The SARs of cluster A, cluster B, and cluster C were 38% (3/8), 21% (3/14), and 38% (3/8), respectively. Additionally, the interval from onset to diagnosis was 4 days. The intervals from disease onset to confirmation of the index cases and secondary cases were 7 days and 4 days, respectively. All secondary case patients had a history of close contact with blood or body fluids of the index patients. These results indicate that SFTS patients should not be discharged until recovery. When SFTS patients die, the corpses should be transferred directly from the hospital to the crematorium for cremation by persons wearing proper protective equipment to prevent virus transmission.

Severe Fever With Thrombocytopenia Syndrome in Southeastern China, 2011-2019.

INTRODUCTION: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease, and the number of cases has increased in recent years in Zhejiang Province, China. However, whether the seasonal distribution, geographic distribution, and demographic characteristics of SFTS have changed with the increase of incidence was unclear. MATERIALS AND METHODS: Data on SFTS cases in Zhejiang Province and tick density in Daishan County from 2011 to 2019 were collected. The changing epidemiological characteristics of SFTS including seasonal distribution, geographical distribution, and demographic features were analyzed using descriptive statistical methods, Global Moran's I, local Getis-Ord G i* statistic, and spatial scan statistic. RESULTS: A total of 463 SFTS cases including 53 (11.45%) deaths were reported from 2011 to 2019 in Zhejiang Province, and the annual number of cases showed increasing tendency. SFTS cases were reported in almost half of the counties (40/89) of Zhejiang Province. Elderly farmers accounted for most cases and the proportion of farmers has increased. Most cases (81.21%) occurred during April and August. The interval from illness onset to confirmation was significantly shortened (Z = 5.194, p < 0.001). The majority of cases were reported in Zhoushan City from 2011 to 2016, but most cases were reported in Taizhou City since 2017. DISCUSSION: We observed dynamic changes in the seasonal distribution, geographical distribution, and demographic features of SFTS, and comprehensive intervention measures, such as clearance of breeding sites, killing of tick adults, and health education should be strengthened in farmers of the key areas according to the changed epidemiological characteristics.

Polymeric Nanoparticles-Based Brain Delivery with Improved Therapeutic Efficacy of Ginkgolide B in Parkinson's Disease.

PURPOSE: Ginkgolide B (GB) is a terpene lactone derivative of Ginkgo biloba that is believed to function in a neuroprotective manner ideal for treating Parkinson's disease (PD). Despite its promising therapeutic properties, GB has poor bioavailability following oral administration and cannot readily achieve sufficient exposure in treated patients, limiting its clinical application for the treatment of PD. In an effort to improve its efficacy, we utilized poly(ethylene glycol)-co-poly(ε-caprolactone) (PEG-PCL) nanoparticles as a means of encapsulating GB (GB-NPs). These NPs facilitated the sustained release of GB into the blood, thereby improving its ability to accumulate in the brain and to treat PD. METHODS AND RESULTS: Using Madin-Darby canine kidney (MDCK) cells, we were able to confirm that these NPs could be taken into cells via multiple nonspecific mechanisms including micropinocytosis, clathrin-dependent endocytosis, and lipid raft/caveolae-mediated endocytosis. Once internalized, these NPs tended to accumulate in the endoplasmic reticulum and lysosomes. In zebrafish, we determined that these NPs were readily able to undergo transport across the chorion, gastrointestinal, blood-brain, and blood-retinal barriers. In a 1-methyl-4-phenylpyridinium ion (MPP+)-induced neuronal damage model system, we confirmed the neuroprotective potential of these NPs. Following oral administration to rats, GB-NPs exhibited more desirable pharmacokinetics than did free GB, achieving higher GB concentrations in both the brain and the blood. Using a murine PD model, we demonstrated that these GB-NPs achieved superior therapeutic efficacy and reduced toxicity relative to free GB. CONCLUSION: In conclusion, these results indicate that NPs encapsulation of GB can significantly improve its oral bioavailability, cerebral accumulation, and bioactivity via mediating its sustained release in vivo.

Potential transmission of SARS-CoV-2 on a flight from Singapore to Hangzhou, China: An epidemiological investigation.

BACKGROUND: Between January 24, 2020 and February 15, 2020, an outbreak of COVID-19 occurred among 335 passengers on a flight from Singapore to Hangzhou in China. This study aimed to investigate the source of the outbreak and assess the risk of transmission of COVID-19 during the flight. METHOD: Using a standardized questionnaire, we collected information on the travelers' demographic characteristics and illness before, during, and after the flight. We also collected data on factors potentially associated with COVID-19 transmission during the flight. RESULTS: A total of 16 COVID-19 patients were diagnosed among all passengers; the overall attack rate was 4.8%. The attack rate among passengers who had departed from Wuhan was significantly higher than that among those who had departed from other places. One passenger without an epidemiological history of exposure before boarding developed COVID-19. During the flight, he was seated near four infected passengers from Wuhan for approximately an hour and did not wear his facemask correctly during the flight. CONCLUSIONS: COVID-19 transmission may have occurred during the flight. However, the majority of the cases in the flight-associated outbreak could not be attributed to transmission on the flight but were associated with exposure to the virus in Wuhan or to infected members in a single tour group.

Asiatic Acid Inhibits OVX-Induced Osteoporosis and Osteoclastogenesis Via Regulating RANKL-Mediated NF-κb and Nfatc1 Signaling Pathways.

Asiatic acid is a triterpenoid compound extracted from a medicinal plant Centella asiatica. It has been used as a highly efficient compound for the treatment of cancer and hyperlipidemia, as well as possessing potential antiinflammatory properties. However, its effects on bone metabolism and osteoporosis haven't been reported. The purpose of our research were to reveal the biomolecular effects of asiatic acid on osteoclasts, and its underlying molecular mechanisms regulating its effects on receptor activator of NF-κB ligand (RANKL)-induced signaling pathways. We found that asiatic acid inhibited multinucleated tartrate-resistant acid phosphatase (TRAcP)-positive osteoclast differentiation and osteoclast induced bone loss. Real time PCR showed that asiatic acid reduced the expression of down-cascade target genes including Ctsk, Nfatc1, Calcr, and Atp6v0d2. Western blot and luciferase reporter gene assays revealed that asiatic acid inhibits RANKL mediated NF-κB and NFATc1 signalings. Further, in vivo study demonstrated asiatic acid attenuates estrogen deficiency-induced bone loss in ovariectomized mice. MicroCT and histology analyses revealed that osteoclast numbers were significantly suppressed in asiatic acid treated groups. Furthermore, serum levels of TRAcP and CTX-1 were downregulated in treated groups. Taken together, our data show that asiatic acid can inhibit osteoclastic formation and reduce OVX-induced bone resorption through RANKL-activated NF-κB or NFATc1 signaling, suggesting that asiatic acid may be a potential and effective natural compound for the therapy of excessive RANKL-related osteolytic diseases.

Re-emergence of scrub typhus in Zhejiang Province, southern China: A 45-year population-based surveillance study.

BACKGROUND: Scrub typhus is the leading cause of treatable unidentified febrile illnesses in Southeast Asia. This study was conducted to document the epidemiological characteristics of scrub typhus and its change in Zhejiang, one of traditional epidemic provinces in China. METHODS: Scrub typhus surveillance data in Zhejiang province during 1957-1989 and 2006-2012 were obtained. Descriptive analysis was conducted to characterize the epidemiology of scrub typhus. The spatial distributions over the periods were explored using spatial autocorrelation analysis and spatiotemporal cluster analysis. RESULTS: A total of 4104 cases and 7 deaths were reported from 1957 to 1989 and 2006 to 2017. The incidence declined since 1959, remained low from 1967 to 1989, and then exponentially increased after 2006. The seasonality changed from a summer pattern between 1957 and 1989 to a bimodal peak pattern in July to August and October to November from 2006 to 2017. One primary and three secondary high-risk clusters were affirmed in both periods from 1980 to 1989 and 2006 to 2017. The primary cluster expanded southwestward and the time span of the secondary clusters extended in the later period compared to the clusters in the previous time frame. CONCLUSION: Zhejiang recently underwent a seasonality change, geographic extension, and incidence increase in scrub typhus. More attention should be paid to controlling scrub typhus.

Epidemiological profile of dengue in Zhejiang Province, southeast China.

BACKGROUND: Dengue is one of the most important vector-bore infectious diseases in China because of its drastic increase in incidence, geographic extension and profound influence on China's economy. This study aims to retrospectively uncover the epidemiological profile of dengue in Zhejiang, one of the most developed provinces in China, and to find the problem existing in dengue control and prevention. METHODOLOGY: Descriptive analyses on the dengue incidence and associated factors were performed. We also identified potential space-time cluster and generated the risk map of dengue. PRINCIPAL FINDINGS: A total of 529 cases were reported in Zhejiang Province from 2005 to 2016, and 44.4% were imported. 67.7% of cases were 25~60 years old and the overall male-to-female sex ratio was 1.09:1. Dengue was reported all year round and 70.7% of cases occurred between August and October. Indigenous cases were only reported in the period between July to November and more than half occurred in September. Geographically, dengue was most distributed in Jinghua (3.62 per million), Shaoxing (1.00 per million) and Taizhou (0.81 per million) prefecture level cities. Outbreaks were confirmed in Yiwu, Keqiao and Huangyan counties in 2009, 2015, and 2016, respectively. 73.9% cases would seek medical advice within two days after onset and be confirmed within 9 days after onset. 75.6% would be recognized as dengue within 8 days after their first visit. The time intervals between onset and confirmation (median 7 vs 6 days; Wilcoxon rank sum test Z = -2.40, P = 0.016), first visit and confirmation (median 7 vs 6 days; Wilcoxon rank sum test Z = -2.59, P = 0.009) of indigenous cases were significantly longer than those of imported ones. However, the time intervals between onset and first visit for indigenous cases was shorter (median 0 vs 1 days; Wilcoxon rank sum test Z = -2.10, P = 0.036). Fever (99.1%), fatigue (81.9), rash (63.7%), headache (67.2%) and myalgia (52.60%) were the most frequently mentioned symptoms. CONCLUSIONS: Zhejiang has recently witnessed an increase in incidence and geographic extension of dengue. Timely diagnosis is important to stop local transmission and outbreak.

Knot soliton in DNA and geometric structure of its free-energy density.

In general, the geometric structure of DNA is characterized using an elastic rod model. The Landau model provides us a new theory to study the geometric structure of DNA. By using the decomposition of the arc unit in the helical axis of DNA, we find that the free-energy density of DNA is similar to the free-energy density of a two-condensate superconductor. By using the φ-mapping topological current theory, the torus knot soliton hidden in DNA is demonstrated. We show the relation between the geometric structure and free-energy density of DNA and the Frenet equations in differential geometry theory are considered. Therefore, the free-energy density of DNA can be expressed by the curvature and torsion of the helical axis.

Bajijiasu Abrogates Osteoclast Differentiation via the Suppression of RANKL Signaling Pathways through NF-κB and NFAT.

Pathological osteolysis is commonly associated with osteoporosis, bone tumors, osteonecrosis, and chronic inflammation. It involves excessive resorption of bone matrix by activated osteoclasts. Suppressing receptor activator of NF-κB ligand (RANKL) signaling pathways has been proposed to be a good target for inhibiting osteoclast differentiation and bone resorption. Bajijiasu-a natural compound derived from Morinda officinalis F. C. How-has previously been shown to have anti-oxidative stress property; however, its effect and molecular mechanism of action on osteoclastogenesis and bone resorption remains unclear. In the present study, we found that Bajijiasu dose-dependently inhibited RANKL-induced osteoclast formation and bone resorption from 0.1 mM, and reached half maximal inhibitory effects (IC50) at 0.4 mM without toxicity. Expression of RANKL-induced osteoclast specific marker genes including cathepsin K (Ctsk), nuclear factor of activated T-cells cytoplasmic 1 (NFATc1), tartrate resistant acid phosphatase (TRAcP), vacuolar-type H⁺-ATPase V0 subunit D2 (V-ATPase d2), and (matrix metalloproteinase-2 (MMP2) was inhibited by Bajijiasu treatment. Luciferase reporter gene studies showed that Bajijiasu could significantly reduce the expression and transcriptional activity of NFAT as well as RANKL-induced NF-κB activation in a dose-dependent manner. Further, Bajijiasu was found to decrease the RANKL-induced phosphorylation of extracellular signal-regulated kinases (ERK), inhibitor of κB-α (IκB-α), NFAT, and V-ATPase d2. Taken together, this study revealed Bajijiasu could attenuate osteoclast formation and bone resorption by mediating RANKL signaling pathways, indicative of a potential effect of Bajijiasu on osteolytic bone diseases.

Sodium Tanshinone IIA Sulfonate Attenuates Scopolamine-Induced Cognitive Dysfunctions via Improving Cholinergic System.

Sodium Tanshinone IIA sulfonate (STS) is a derivative of Tanshinone IIA (Tan IIA). Tan IIA has been reported to possess neuroprotective effects against Alzheimer's disease (AD). However, whether STS possesses effect on AD remains unclear. This study aims to estimate whether STS could protect against scopolamine- (SCOP-) induced learning and memory deficit in Kunming mice. Morris water maze results showed that oral administration of STS (10 mg/kg and 20 mg/kg) and Donepezil shortened escape latency, increased crossing times of the original position of the platform, and increased the time spent in the target quadrant. STS decreased the activity of acetylcholinesterase (AChE) and increased the activity of choline acetyltransferase (ChAT) in the hippocampus and cortex of SCOP-treated mice. Oxidative stress results showed that STS increased the activity of superoxide dismutase (SOD) and decreased the levels of malondialdehyde (MDA) and reactive oxygen species (ROS) in hippocampus and cortex. In addition, western blot was carried out to detect the expression of apoptosis related proteins (Bcl-2, Bax, and Caspase-3). STS upregulated the protein expression of Bcl-2 and downregulated the proteins expression of Bax and Caspase-3. These results indicated that STS might become a promising therapeutic candidate for attenuating AD-like pathological dysfunction.