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• CVA6 has become one of the main pathogens of HFMD in the Xi'an area during 2013–2019. • The rashes were more frequently on the trunk and elbows/knees in the CVA6 group than in the EV-A71/CVA16 group, with two or more rash morphologies and with a higher incidence of bullous rash and onychomadesis. • The incidence of fever and the average white blood cell (WBC) count in the CVA6 group was higher than in the EV-A71/CVA16 group. To investigate the clinical features of hand, foot, and mouth disease (HFMD) caused by coxsackievirus A6 (CVA6) and this work may help early diagnose of atypical HFMD. From January 2013 to December 2019, a total of 7,208 patients with a clinical diagnosis of HFMD in Xi'an Children's Hospital, Xi'an Central Hospital, and Xi'an Jiaotong University Second Affiliated Hospital, were included in this observational study. The clinical data, specimens and follow-up results were collected. Real-time RT‒PCR was performed for the detection and typing of enterovirus nucleic acids. Of the 7,208 clinically diagnosed HFMD patients, 5,622 were positive for enterovirus nucleic acids, and the positive proportions of CVA6, enterovirus 71 (EV-A71), coxsackievirus A16 (CVA16), and other enteroviruses were 31.0% (1,742/5,622), 27.0% (1,518/5,622), 35.0% (1,968/5,622), and 7.0% (394/5,622), respectively. Based on the etiology, patients were divided into CVA6 group, EV-A71group, and CVA16 group. The mean age at onset was significantly higher in the CVA6 group (4.62±2.13 years) than in the EV-A71 group and CVA16 group (3.45±2.25 years and 3.35±2.13 years, respectively; both P < 0.05). The male/female ratio was 1.45 (1,031/711) in the CVA6 group and was not significantly different from the other two groups. The incidence of fever was significantly higher in the CVA6 group [82.5% (1,437/1,742)] than in the EV-A71 group [51.3% (779/1,518)] and the CVA16 group [45.9% (903/1,968)] (P < 0.05). In the CVA6 group, the rashes were more frequently on the trunk and elbows/knees and were significantly different from the other two groups (P < 0.05). The number of patients with two or more rash morphologies was significantly higher in the CVA6 group than in the other two groups (P < 0.05). The incidence of bullous rash in the CVA6 group [20.2%; n = 352] was higher than in the EV-A71 group [0.33%; n = 5] and CVA16 group [0.66%; n = 13] (P < 0.05). The incidence of neurological complications was significantly higher in the EV-A71 group [52.1% (791/1,518)] than in the CVA16 group [5.1% (100/1,968)] and the CVA6 group [0.8% (14/1,742)] (P < 0.05). In the follow-up period, 160 patients (9.2%) with CVA6 HFMD experienced onychomadesis, but no onychomadesis was observed in the EV-A71 and CVA16 groups. The average WBC count was significantly higher in the CVA6 group than in the CVA16 group (P < 0.05). The number of patients with increased CRP was significantly larger in the CVA6 group than in the CVA16 group but was significantly smaller than that in the EV-A71 group (P < 0.05). CVA6 has become one of the main pathogens of HFMD in the Xi'an area during 2013–2019. The main clinical manifestations were slightly different from those of HFMD caused by EV-A71 or CVA16, with a higher frequency of fever, diverse morphologies and diffuse distribution of rashes, fewer neurological complications and some onychomadesis. [Display omitted] [ABSTRACT FROM AUTHOR]

Rates of lung cancer in China are rising rapidly, creating an urgent need for prevention. Effective prevention measures require understanding local beliefs and perceptions about the risk for developing lung cancer. This article explores the explanations that Chinese lung cancer patients and their families give about the aetiology of their disease. Fifty-three interviews were conducted among lung cancer patients and their family members at a large tumour hospital in southern China. Participants presented a complex multifactorial explanation of lung cancer associating their disease with risks like tobacco use, occupational exposures, environmental pollution, lifestyle changes, and personal characters. While these are all standard risk factors commonly associated with lung cancer, participants presented them within a larger contextual frame of structural issues that impede their ability to change their behaviours. Using a social ecological model, we demonstrate how China's socio-cultural environment shapes assumptions about the risk of lung cancer with particular reference to work, home, social situations, and the natural environment. [ABSTRACT FROM AUTHOR]

• The heterocyclic phenolic hydrazone L1 - L4 were synthesized and characterized by NMR, HRMS, IR and UV–vis. • Compound L3 demonstrated higher activity against three cancer cell lines (BGC-823, MCF-7 and A549) than the anticancer 5-FU using MTT assay. • Compound L3 is more effective in scavenging free radicals than the antioxidant BHT by DPPH and ABTS assays. • DFT, molecular docking and drug-likeness studies were also investigated for compounds L1 - L4. In this research, the anticancer and antioxidant activities of a novel class of heterocyclic phenolic hydrazone derivatives were investigated. The structure determination of the synthesized compounds was carried out through nuclear magnetic resonance spectroscopy, high-resolution mass spectrometry and infrared spectroscopy. The antiproliferative activities of the synthesized compounds were examined against three cancer cell lines (BGC-823, MCF-7 and A549). Specifically, L3 showed better antiproliferative activity against these three cancer cell lines than standard 5-FU, but had no toxic effect on normal human liver cell line (HL-7702). In addition, DPPH and ABTS methods were used to evaluate the antioxidant activity of the synthesized compounds. Compound L3 was more effective in scavenging free radicals than the antioxidant BHT. The results of the structure-activity relationship study revealed that the rules governing anticancer and antioxidant activities of these compounds were similar. Specifically, the introduction of hydroxyl groups, quinoline and benzothiazole ring usually had a positive effect on activities, while the electron-withdrawing group (F) at the C5-position of the pyrimidine ring linked to imine bond were not favorable. The DFT computations were carried out using the B3LYP functional with def2-SVP basis set and calculation was executed via Gaussian 16 software. Frontier molecular orbital (FMO) analysis showed that high chemical potential highlighted the stronger binding affinity of compounds L3 and L4 , indicating stronger potential interactions with amino acids. The electrophilic and nucleophilic reaction sites of these molecules were identified using molecular electrostatic potential (MEP). In addition, molecular docking studies were conducted to gain a deeper understanding of the interactions between 2CDU and 4AGM proteins and these compounds. Compared with the reference drugs, the studied compound showed higher binding affinity. Furthermore, the bioavailabilities of the synthesized compound have been established by the study of drug-likeness. The high human intestinal absorption (HIA) value indicated that compound L3 exhibited excellent oral efficacy. The above results indicated that the synthesized heterocyclic phenolic hydrazone derivatives may be effective pharmaceutical compounds and could be used as anticancer and antioxidant agents. [Display omitted] [ABSTRACT FROM AUTHOR]

C44H45N5O2, triclinic P 1 ‾ $P\bar{1}$ (no. 2), a = 11.2140(4) Å, b = 11.9932(5) Å, c = 14.2703(5) Å, α = 98.879(3)°, β = 102.025(3)°, γ = 91.122(3)°, Z = 2, V = 1851.98(12) Å3, R gt (F) = 0.0549, wR ref(F 2) = 0.1616, T = 293(2) K. [ABSTRACT FROM AUTHOR]

A new hemicyanine-based near-infrared "off-on" recognition Cu2+ fluorescent probe NRh-NP was designed and successfully synthesized. The structure of NRh-NP was characterized by NMR, ESI-HRMS and single crystal X-ray diffraction analysis. NRh-NP has high sensitivity, selectivity and a low limit of detection (33 nM as fluorescence sensor and 35 nM as UV sensor) to Cu2+. According to Job's plot and ESI-HRMS, the coordination ratio of NRh-NP to Cu2+ was 1:1. DFT theoretical calculations proved that the sensor mechanism was photo-induced electron transfer (PET). More importantly, NRh-NP has excellent membrane permeability and low cytotoxicity, which could be used not only for the detection of Cu2+ in human breast cancer cells (MCF-7), but also for imaging Cu2+ in living mice. [Display omitted] • The structure of NRh-NP was characterized by NMR, ESI-HRMS and single crystal X-ray diffraction analysis. • The responses of NRh-NP toward Cu2+ were fully proved by Job's plot, ESI-HRMS and DFT theoretical calculations. • NRh-NP has high sensitivity and selectivity with detection limit as low as 33 nM. • NRh-NP can be used for Cu2+ imaging in living cells and in vivo. [ABSTRACT FROM AUTHOR]

Abstract For providing new insights into the effect of the leading waves on the velocity distribution of the generated bore, a case study of the undular bore (or weak bore) with the water depth ratio 1.70 is tested in a flume, using flow visualization technique (FVT) and high-speed particle image velocimetry (HSPIV). The undular bore, generated right downstream of a suddenly lifted gate, propagates first over a horizontal bottom and then travels over a 1:20 sloping bottom. The wave gauges were used to measure the free surface elevations of the generated bore at different positions. A complete evolution of the free surface elevations of the generated bore accompanied by the dispersive leading waves, measured at different shoreward positions, is elucidated first. Illustrations of variations in wave period and height of each leading wave in the onshore direction are also made. Based on visualized images and velocity fields measured, the following flow features at different stages of the generated bores are explored: (1) The temporal and spatial variations in the flow field of the generated bore with respect to passing of the leading waves; (2) The influence of the leading waves on shifting of the velocity distribution of the generated bore, along with illustrations of flow acceleration or deceleration in the onshore direction; (3) Flow reversal zone and shear layer formation near the sloping bottom; (4) Development of a vortex train (or street) in the shear layer between two opposite currents consisting of the onshore run-up flow and the offshore flow reversal right over the sloping bottom. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the potential cytotoxicity and the underlying mechanism of amphipathic silica nanoparticles (SiO 2 NPs) exposure to human normal liver HL-7702 cells and rat normal liver BRL-3A cells. Prior to the cellular studies, transmission electron microscopy (TEM), dynamic light scattering (DLS), and X ray diffraction (XRD) were used to characterize SiO 2 NPs, which proved the amorphous nature of SiO 2 NPs with TEM diameter of 19.8 ± 2.7 nm. Further studies proved that exposure to SiO 2 NPs dose-dependently induced cytotoxicity as revealed by cell counting kit (CCK-8) and lactate dehydrogenase (LDH) assays, with more severe cytotoxicity in HL-7702 cells than BRL-3A cells. Reactive oxygen species (ROS) and glutathione (GSH) assays showed elevated oxidative stress in both cells. Morphological studies by microscopic observation, Hochest 33258 and AO/EB staining indicated significant apoptotic changes after the cells being exposed to SiO 2 NPs. Further studies by western blot indicated that SiO 2 NPs exposure to both cells up-regulated p53, Bax and cleaved caspase-3 expression and down-regulated Bcl-2 and caspase-3 levels. Activated caspase-3 activity detected by colorimetric assay kit and caspase-3/7 activity detected by fluorescent real-time detection kit were significantly increased by SiO 2 NPs exposure. In addition, antioxidant vitamin C significantly attenuated SiO 2 NPs-induced caspase-3 activation, which indicated that SiO 2 NPs-induced oxidative stress was involved in the process of HL-7702 and BRL-3A cell apoptosis. Taken together, these results suggested that SiO 2 NPs-induced cytotoxicity in HL-7702 and BRL-3A cells was through oxidative stress mediated and p53, caspase-3 and Bax/Bcl-2 dependent pathway and HL-7702 cells were more sensitive to SiO 2 NPs-induced cytotoxicity than BRL-3A cells. [ABSTRACT FROM AUTHOR]

• Nanomaterial was used as the novel adjuvant to enhance the efficacy of CSBV vaccines. • An high-efficient immunization program for production of high-titer EYA was established. • Different adjuvants, immunization protocols and CSBV vaccine types were compared. • EYA offer a significant protection rate (98.9 to 100%) against the CSBV infection. • EYA have been applied more than two years against CSBV in Chinese actual bee breeding. Chinese sacbrood virus (CSBV) poses a serious threat to the apiculture of China. Although several approaches have been attempted to control CSBV infection, their applications have been greatly limited in practical breeding of honeybees due to poor effectiveness. Egg yolk antibodies (EYA) have shown a promising protection for bees against CSBV infection. This study was conducted to produce high titer EYA and then further improve their antiviral effect. Among three vaccination groups, the EYA titer in graphene oxide-chitosan group was highest (1.591 ± 0.145), in Freund's group was modest (1.195 ± 0.040), and in white oil group was lowest (1.058 ± 0.056). After three injections of each vaccine in hens, EYA were produced at the highest level with a 14-day period. After application of EYA for more than two years in actual bee breeding, prevention and treatment assays showed that EYA confered 98.9 to 100% protection from CSBV infection. The mortality of the control group reached to a range of 91.2 to 100%. This study demonstrated that the high titer EYA have been successfully prepared with significant anti-CSBV activity and that these antibodies may feasibly be used for CSBV treatment to meet the practical needs of apiculture. [ABSTRACT FROM AUTHOR]

In this work, hydrothermal synthesis and ceramic sintering process were applied to fabricate (1− x )Pb(Zr 0.52 Ti 0.48 )O 3 −( x )CoFe 2 O 4 (PZT–CFO) ( x =0.20, 0.35, and 0.50) magnetoelectric (ME) composites. The X-ray diffraction (XRD) studies revealed that no chemical reaction occurred between individual PZT and CFO phases and confirmed the manifestation of PZT and CFO phases within the ME composite. Scanning electron microscopy (SEM) was used to investigate the microstructure and connectivity scheme in the ME composites. The dielectric constant ( ε ) and loss tangent (tan δ ) were determined as functions of frequency and temperature for all the composites prepared. The polarization–electric field ( P – E ) and magnetization–magnetic field ( M – H ) hysteresis loops obtained indicate that both ferroelectric and ferromagnetic properties coexist in the ME composites prepared. The direct (DME) and converse magnetoelectric effects (CME) were measured only for the PZT–CFO20 (20 mol% CoFe 2 O 4 ) composite sintered at 1100 °C for 4 h. The maximum values of ME voltage coefficient α M E ( dE / dH ) and ME susceptibility coefficient α m e ( dH / dE ) were 226 mV cm −1 Oe −1 at frequency of 75.1 kHz and 1.15×10 −8 s/m at frequency of 66.8 kHz, respectively. [ABSTRACT FROM AUTHOR]

Effective treatment of dye wastewater is currently a great concern and a research hotspot. Electrocatalysis has unique advantages in treating toxic and harmful refractory dye wastewater; however, it requires an external power supply, which increases energy consumption and cost. As a new energy collection technology, triboelectric nanogenerators (TENGs) have gained considerable attention. In this study, an origami multilayer spherical friction nanogenerator (Q-TENG) was developed for the removal of methylene blue (MB) from dye wastewater. The current and voltage output performances of Q-TENG were explored, and the removal and degradation mechanisms of MB were discussed. Results indicated that when the water wave acceleration a = 3 m/s 2 , the open-circuit voltage and short-circuit current reached the maximum values of 179 V and 9.4 μA, respectively. The self-powered catalytic degradation of MB using Q-TENG can produce more • OH and SO 4 -• , and the free radicals increase with increasing action time of Q-TENG, thus increasing the degradation efficiency of MB. This study provides a new strategy for solving the problem of high energy consumption during electrochemical reactions in wastewater treatment.

Self-powered wearable electronic products have rapidly advanced in the fields of sensing and health monitoring, presenting greater challenges for triboelectric materials. The limited surface polarity and structural defects in wood fibers restrict their potential as substitutes for petroleum-based materials. This study used bagasse fiber as the raw material and explored various methods, including functionalizing cellulose nanofibrils (CNFs) with polydopamine (PDA), in situ embedding of silver particles, filtration, and freeze-drying. These methods aimed to enhance the triboelectric output, antibacterial properties, and filtration properties of lignocellulosic materials. The Ag/PDA/CNF-based triboelectric nanogenerator (TENG) demonstrated an open-circuit voltage of 211 V and a short-circuit current of 18.1 μA. An aerogel prepared by freeze-drying the Ag/PDA/CNF material, combined with a polyvinylidene fluoride nanofiber structure fabricated by electrospinning, constitutes the TENG unit. A self-powered respiratory detection mask was created using this combination, achieving a filtration efficiency of 94.23% for 0.3 μm particles and an antibacterial rate exceeding 99%. In addition, it effectively responded to respiratory frequency signals of slow breathing, normal breathing, and shortness of breath, with the output electrical signal correlating with the respiratory frequency. This study considerably contributes to advancing wood fiber-based triboelectric materials as alternatives to petroleum-derived materials in self-powered wearable electronic products for medical applications., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

C-3 amidated imidazoheterocycles were synthesized via a visible light-promoted reaction of imidazoheterocycles with N -amidopyridinium salts catalyzed by 4CzIPN under mild conditions. For imidazoheterocycles and N -amidopyridinium salts with various substituents, the reaction proceeded smoothly to give the corresponding products in moderate to good yields. The reaction provides a new strategy for the synthesis of secondary amides with the imidazo[1,2- a ]pyridine core.

Purpose: The reference range for the preoperative anterior chamber angle width for ICL surgery is unclear. Our objective was to assess the clinical effect and the range of anterior chamber angle width of posterior-chamber implantable collamer lens V4c (ICL V4c) implantation in patients with anterior chamber depth (ACD) < 2.8 mm., Methods: Patients who underwent ICL V4c implantation with shallow ACD were included in this retrospective study. The patients' uncorrected and corrected distance visual acuity, angle of trabecular-iris (TIA), angle-opening distance (AOD500), trabecular-iris space area (TISA500), corneal endothelial cell density, vault, retinal nerve fiber layer thickness, intraocular pressure, visual field, and complications were analyzed., Results: Forty-one patients (68 eyes) completed at least 12 months of follow-up (median follow-up, 30 months). The effectiveness and safety indices were 1.09 ± 0.13 and 1.04 ± 0.21, respectively. The preoperative TIA values on the nasal and temporal sides were 39.78 ± 7.68 degree (range, 25.8-65.1 degree) and 41.54 ± 8.03 degree (range, 28.5-63.00 degree). Forty-seven eyes had uncorrected distance visual acuity ≥1.0, and 55 had corrected distance visual acuity ≥1.0 at the last follow-up visit. The TIA, AOD500, and TISA500 on the nasal and temporal sides were significantly reduced compared to those before surgery (all P < 0.01); no eye had an angle closure or elevated intraocular pressure. The ICL V4c vault was 290.88 ± 153.36  μ m (range, 60.0-880.0  μ m). No severe complications occurred in any patient., Conclusions: In patients with myopia with shallow ACD (2.55-2.79 mm), a preoperative TIA >25.8° is safe and effective for a relatively long time after surgery; however, an extended long-term close follow-up is needed., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2024 Juan Yuan et al.)

Background: Diabetic cardiomyopathy (DCM) is a serious complication in patients with type 1 diabetes mellitus (T1DM), which still lacks adequate therapy. Irisin, a cleavage peptide off fibronectin type III domain-containing 5, has been shown to preserve cardiac function in cardiac ischemia-reperfusion injury. Whether or not irisin plays a cardioprotective role in DCM is not known., Methods and Results: T1DM was induced by multiple low-dose intraperitoneal injections of streptozotocin (STZ). Our current study showed that irisin expression/level was lower in the heart and serum of mice with STZ-induced TIDM. Irisin supplementation by intraperitoneal injection improved the impaired cardiac function in mice with DCM, which was ascribed to the inhibition of ferroptosis, because the increased ferroptosis, associated with increased cardiac malondialdehyde (MDA), decreased reduced glutathione (GSH) and protein expressions of solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4), was ameliorated by irisin. In the presence of erastin, a ferroptosis inducer, the irisin-mediated protective effects were blocked. Mechanistically, irisin treatment increased Sirtuin 1 (SIRT1) and decreased p53 K382 acetylation, which decreased p53 protein expression by increasing its degradation, consequently upregulated SLC7A11 and GPX4 expressions. Thus, irisin-mediated reduction in p53 decreases ferroptosis and protects cardiomyocytes against injury due to high glucose., Conclusion: This study demonstrated that irisin could improve cardiac function by suppressing ferroptosis in T1DM via the SIRT1-p53-SLC7A11/GPX4 pathway. Irisin may be a therapeutic approach in the management of T1DM-induced cardiomyopathy., (© 2024. The Author(s).)

Triple motif protein 21 (TRIM21) has an antiviral function that inhibits various viral infections. However, its role in the progress of influenza A virus (IAV) infection is unclear. In this study, we investigated the role and molecular mechanism of TRIM21 in IAV infection. RT-qPCR was used to determine the level of TRIM21 mRNA, and ELISA was used to measure the levels of IFN-α, IFN-β, IL-6, and TNF-α. The levels of the TRIM21, NP, TBK1, IRF3, p-TBK1, and p-IRF3 proteins were estimated by Western blot. The results showed that, after IAV infection, TRIM21 was upregulated in clinical patient serum and A549 cells, and this was correlated with the IFN response. Overexpression of TRIM21 reduced IAV replication and transcription in in vitro cell experiments. TRIM21 also increased IFN-α and IFN-β levels and decreased IL-6 and TNF-α levels in A549 cells. In addition, overexpression of TRIM21 inhibited IAV-induced apoptosis. Further experiments demonstrated that TBK1-IRF3 signaling was activated by TRIM21 and was involved in the inhibitory effect of TRIM21 on virus replication. In summary, our study suggests that TRIM21 inhibits viral replication by activating the TBK1-IRF3 signaling pathway, further inhibiting the infection process of IAV., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Background: Esophageal cancer patients suffer from multiple and severe symptoms during the postoperative recovery period. Family caregivers play a vital role in assisting patients to cope with their symptoms., Objective: To examine the concordance of esophageal cancer patients and their caregivers on assessing patients' symptoms after surgery and identify predictors associated with the symptom concordance., Methods: In this cross-sectional study, 213 patient-caregiver dyads completed general information questionnaires, the Memorial Symptom Assessment Scale, the Depression Subscale of Hospital Anxiety and Depression Scale, the Mutuality Scale, and the Zarit Burden Interview (for caregivers). Data were analyzed using intraclass correlation coefficients, paired t tests, and binary logistic regression., Results: At the dyad level, agreement of patients' and caregivers' reported symptoms ranged from poor to fair. At the group level, patients reported significantly higher scores than caregivers in most symptoms. Of the 213 dyads, 119 (55.9%) were identified as concordant on symptom assessment. Patients' nasogastric tube, perceived mutuality, caregivers' educational background, and dyad's communication frequency with each other could predict their concordance of symptom assessment., Conclusions: There were relatively low agreements between esophageal cancer patients and caregivers on assessing patients' symptoms, and caregivers tended to underestimate patients' symptoms. The dyad's symptom concordance was influenced by patient-, caregiver-, and dyad-related factors., Implications for Practice: Having an awareness of the incongruence on assessing symptoms between esophageal cancer patients and caregivers may help healthcare professionals to comprehensively interpret patients' symptoms and develop targeted dyadic interventions to improve their concordance, contributing to optimal symptom management and health outcomes., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Due to the antitumor properties, Zn(II) complexes have attracted more and more attention. Herein, three novel tetranuclear Zn(II) complexes 1-3 based on dihydrazone pyrimidine derivatives H 2 L 1 -H 2 L 3 were synthesized and characterized using IR spectroscopy, 1 H NMR spectroscopy, single crystal X-ray diffraction analysis, XRD, TG and elemental analysis. Single crystal X-ray diffraction analysis revealed that 1-3 all displayed a [2 × 2] grid-like topology. The stability in solution, lipophilicity, confocal imaging and antitumor activities were investigated. Complexes 1-3 displayed high structural stability, membrane permeability and different lipophilicities. They can target mitochondria due to the cation charge. The MTT assay indicated that all of them exhibited stronger antiproliferative activity than the corresponding derivatives H 2 L 1 -H 2 L 3 and the well-known cisplatin against all the selected tumor cells (BGC-823, BEL-7402, MCF-7 and A549), with IC 50 values ranging from 2.83 μM to 7.97 μM. AO/EB double staining, flow cytometry and ROS detection suggested that complexes 1 and 2 could induce BGC-823 apoptosis in a dose-dependent manner. UV-Vis spectra, CD spectra, viscosity analysis and molecular docking revealed that complexes 1 and 2 interact with DNA mainly via partial intercalation and groove binding. Tetranuclear [2 × 2] grid-like Zn(II) complexes have the potential to be promising antitumor agents in the future.

Psoriasis is a common immune-mediated inflammatory skin disease, caused by disturbed interactions between keratinocytes and immune cells. Chinese medicine shows potential clinical application for its treatment. Liquiritin is a flavone compound extracted from licorice and shows potential antitussive, antioxidant and antiinflammatory effects, and therefore may have potential as a psoriasis therapeutic. The aim of this work was to examine the possible roles that liquiritin may have in treating psoriasis. HaCaT cells were stimulated by TNF-α with or without liquiritin, harvested for analysis by western blots and RT-qPCR, and the cellular supernatants were collected and analyzed by ELISA for cytokines. In addition, 4 groups of mice were examined: Normal, Vehicle, LQ-L and LQ-H. The mice were sacrificed after 6 days and analyzed using IHC, ELISA, RT-qPCR and flow cytometry. The results showed that liquiritin could significantly inhibit the progression of psoriasis both in vitro and in vivo. Liquiritin strongly suppressed the proliferation of HaCaT keratinocytes but did not affect cell viability. Moreover, liquiritin alleviated imiquimod-induced psoriasis-like skin inflammation and accumulation of Th17 cells and DCs in vivo. In TNF-α-induced HaCaT keratinocytes, both protein and mRNA expression levels of inflammatory cytokines were sharply decreased. In imiquimod-induced mice, the activation of NF-κB and AP-1 was reduced after treatment with liquiritin. Collectively, our results show that liquiritin might act as a pivotal regulator of psoriasis via modulating NF-κB and AP-1 signal pathways., (© 2023 John Wiley & Sons Ltd.)

Background: This study explored the association of marital transitions and frailty among Chinese middle-aged and older people and whether this association differs by social support., Methods: We used a sample of 12,388 adults aged ≥45 years who participated in the China Health and Retirement Longitudinal Study (CHARLS) between 2015 and 2018. Between-wave changes in marital status ("married at both times", "unmarried to married", "married to unmarried", "unmarried at both times") were used to explore the changes in frailty measured by the frailty index (FI), which was constructed from 55 health variables. Social support was evaluated based on social engagement and intergenerational support. The associations among marital transitions, social support and frailty were analyzed using generalized estimating equations (GEEs)., Results: The mean FI of 12,388 participants was 0.23 (SD = 0.13). Participants who were married to unmarried (β = 0.014, B = 0.005, P = 0.012) and unmarried at both times (β = 0.022, B = 0.003, P < 0.001) had significant a positive impact on FI compared with participants who were married at both times. Social engagement, financial support by children and providing care to grandchildren had an interactive effect with marital transitions in influencing FI., Conclusions: Being unmarried may increase frailty among Chinese middle-aged and older adults. Financial support by children may mitigate the adverse effects of being unmarried on frailty., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors. Published by Elsevier Ltd.)

Climate oscillation and its synergistic impacts on habitat fragmentation have been identified as threatening the survival of some extant species. However, the mechanisms by which semi-aquatic insects impacted by such events remain poorly understood. Herein, we studied the largest water strider in the world, Gigantometra gigas, to explore the effect of these two factors on its evolutionary history. The sequences of mitogenomic and nrDNA cluster were utilized to reconstruct phylogenetic relationship among G. gigas populations and its demographic history. Mitochondrial genes were separately reconstructed topologies of that populations and detected remarkable differences. We found that G. gigas populations conform to the isolation-by-distance model, and decline occurred at about 120 ka, which was probably influenced by the climate change during the late Pleistocene and eventually maintained a small effective population size (Ne) around 85,717. The populations in Guangdong Province of China are worthy of note in that they exhibit low genetic diversity, a small Ne around 18,899 individuals, and occupy an area with little suitable future habitat for G. gigas. This work recommends that conservation efforts are implemented to ensure the long-term survival of small G. gigas populations, and notes that further evaluation of their extinction risk under the impacts of human activities is required., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Introduction: Influenza A virus (IAV) infection causes severe lung inflammation and injury, particularly in children. Sirtuin3 (Sirt3) was confirmed to be effective in protecting the lung against injury. This study aims to explore the function and mechanism of Sirt3 on influenza development in children., Methods: The Sirt3 level in serum samples from IAV-infected children and lung epithelial cells were detected using RT-qPCR, ELISA, and Western blot assays. Cell viability and apoptosis were determined by MTT and flow cytometry assays. Virus titration was conducted by determining TCID50. Cell inflammatory response was detected by a battery of inflammatory cytokines. The contents of ROS and ATP, mitochondrial membrane potential level, and oxygen-consumption rate were examined to reflect on oxidative stress and mitochondrial dysfunction. The activity of poly (ADP-ribose) polymerase 1 (PARP-1) was measured by colorimetry., Results: Sirt3 was downregulated in IAV-infected children's serum samples and BEAS-2B cells. Overexpression of Sirt3 alleviated IAV replication and IAV-induced inflammatory injury, oxidative stress, and mitochondrial dysfunction in lung epithelial cells. Moreover, upregulation of Sirt3 deacetylated SOD2 and PARP-1 and inhibited the PARP-1 activity. Notably, the Sirt3 inhibitor (3-TYP) and PARP-1 activity agonist (nicotinamide) reversed the effects of Sirt3 overexpression on IAV replication and IAV-induced injury., Conclusion: Overexpression of Sirt3 attenuated IAV-evoked inflammatory injury and mitochondrial oxidative stress through the inhibition of PARP-1 activity in lung epithelial cells., (© 2023 S. Karger AG, Basel.)

In the present paper, on the basis of molecular hybridization, a series of 4,6-dihydrazone pyrimidine derivatives containing the pyridine moiety were synthesized, structurally characterized, and evaluated in vitro for their antitumor activity. According to the results, all the tested compounds demonstrated broad-spectrum antitumor activity against selected tumor cell lines (MCF-7, BGC-823, A549, and BEL-7402) and no obvious toxicity toward normal cells HL-7702. In particular, compounds 10a and 10f were found to be the most promising antitumor agents among the tested compounds against BGC-823 cells (IC 50 = 9.00 μM and 7.89 μM) and BEL-7402 cells (IC 50 = 6.70 μM and 7.66 μM), respectively. Compounds 10a and 10f exhibited higher potency against BGC-823 and BEL-7402 than the positive control 5-FU (IC 50 = 15.18 μM and 15.81 μM). Further mechanism investigations demonstrated that compounds 10a and 10f could significantly increase the level of cellular ROS and induce early apoptosis of BGC-823 cells in a dose-dependent manner. Moreover, the DNA binding results from UV/Vis, CD spectroscopy, and molecular docking studies indicated that 10a and 10f bind with DNA via groove binding and partial intercalation. These results demonstrated that 10a and 10f may serve as novel lead compounds for the discovery of more dihydrazone pyrimidine derivatives with improved antitumor potency and selectivity.

The hypoxia-inducible factors (HIFs) regulate the main transcriptional pathway of response to hypoxia in T cells and are negatively regulated by von Hippel-Lindau factor (VHL). But the role of HIFs in the regulation of CD4 T cell responses during infection with M. tuberculosis isn't well understood. Here we show that mice lacking VHL in T cells (Vhl cKO) are highly susceptible to infection with M. tuberculosis, which is associated with a low accumulation of mycobacteria-specific T cells in the lungs that display reduced proliferation, altered differentiation and enhanced expression of inhibitory receptors. In contrast, HIF-1 deficiency in T cells is redundant for M. tuberculosis control. Vhl cKO mice also show reduced responses to vaccination. Further, VHL promotes proper MYC-activation, cell-growth responses, DNA synthesis, proliferation and survival of CD4 T cells after TCR activation. The VHL-deficient T cell responses are rescued by the loss of HIF-1α, indicating that the increased susceptibility to M. tuberculosis infection and the impaired responses of Vhl-deficient T cells are HIF-1-dependent., (© 2022. The Author(s).)

Thyroid dysfunction and diabetes are reported to be associated with depression. However, their role in the suicide risk in patients with major depressive disorder (MDD) is unclear. The purpose of this study was to investigate and compare thyroid dysfunction and diabetes between suicide attempters and non-suicide attempters in a large sample of first-episode drug-naïve (FEND) MDD patients. A descriptive study was conducted on 1279 Chinese outpatients with a diagnosis of first-episode MDD. Their sociodemographic information, blood levels of thyroid hormones, glucose, lipids and body mass index (BMI) parameters were collected. The positive subscales of the positive and negative syndrome scale (PANSS), Hamilton Anxiety Rating Scale (HAMA), Hamilton Depression Rating Scale (HAMD) were measured for psychotic, anxiety and depressive symptoms. Our results showed that compared with non-suicide attempters (P<0.01), suicide attempters had statistically higher scores on HAMD, HAMA and PANSS psychotic symptoms, as well as higher thyroid stimulating hormone (TSH) serum levels, glucose, anti-thyroglobulin (A-TG), anti-thyroid peroxidase (A-TPO), total cholesterol (TC), triglycerides (TG), low density lipoprotein cholesterol (LDL-C), systolic blood pressure and diastolic blood pressure (all with P<0.001). These results revealed that TSH, A-TG, A-TPO, TC, TG and LDL-C may be promising biomarkers of suicide risk in MDD, implying the importance of regular assessment of blood glucose level and thyroid function parameters for suicide prevention, along with possible treatment for impaired thyroid function and diabetes for the suicide intervention in MDD patients. Such patients with abnormal blood sugar and TSH must undergo thorough screening for suicidal ideation.

Objectives: This study aimed to provide an assessment of chlorothalonil's possible carcinogenic risk posed to the public. In combination and comparison with the non-carcinogenic risk, the results hopefully could provide useful insights, early warning, and references for policy formulation., Methods: This study firstly investigated the occurrence of chlorothalonil on selected key vegetables for different scenarios, and then conducted an exposure assessment with officially published data. Lastly, both the non-carcinogenic and carcinogenic risk of chlorothalonil were calculated by using Monte-Carlo simulation., Results: Even though mean non-carcinogenic risks of chlorothalonil for all scenarios were below threshold value, the mean carcinogenic risks for maximum-risk scenario and most-likely risk scenario were mostly above threshold value. High probabilities of exceedance of threshold value existed for carcinogenic risk under all scenarios., Conclusion: Potential threat to public health existed for conventionally 'safe' pesticide if considering the possible carcinogenicity. Extra caution should be taken and the potential carcinogenic effects should be included into consideration for better protection of public health during the policy formulation process., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Sun, Liu, Wang, Yuan and Wu.)

Background: Cancer impacts both patients and their family caregivers. This study aimed to explore the interdependence between depression and intimacy in lung cancer patients and their family caregivers, providing the basis for developing a patient-caregiver centered dyadic intervention., Methods: This cross-sectional study recruited 182 dyads of lung cancer patients and their family caregivers using a convenient sampling. The depression subscale of the Hospital Anxiety and Depression Scale (HADS) and the Mutuality Scale (MS) were used to measure participants' depression and intimacy respectively; and the correlation between depression and intimacy in patients and caregivers was analyzed by establishing the actor-partner interdependence model., Results: Thirty four percent of the patients and 19.2% of the caregivers were at risk of depression, with an intimacy score of 2.67 ± 0.74 points and 2.6 ± 0.86 points, respectively; Pearson correlation analysis showed that there was a positive correlation between the depression score (r = 0.226, P < 0.01) and intimacy score (r = 0.344, P < 0.01) in patients and caregivers; and the results of actor-partner interdependence model showed that caregivers' depression had an actor effect on their own intimacy (b = -0.054, P = 0.004) as well as a partner effect on patients' intimacy (b = -0.041, P = 0.011). However, patients' depression has no influence on the intimacy of patients or caregivers., Conclusions: There is an interdependent relationship between depression and intimacy in lung cancer patients and family caregivers. Therefore, dyadic interventions can help them to cope with cancer together., (© 2022. The Author(s).)

Mitochondria are the main consumers of oxygen within the cell. How mitochondria sense oxygen levels remains unknown. Here we show an oxygen-sensitive regulation of TFAM, an activator of mitochondrial transcription and replication, whose alteration is linked to tumours arising in the von Hippel-Lindau syndrome. TFAM is hydroxylated by EGLN3 and subsequently bound by the von Hippel-Lindau tumour-suppressor protein, which stabilizes TFAM by preventing mitochondrial proteolysis. Cells lacking wild-type VHL or in which EGLN3 is inactivated have reduced mitochondrial mass. Tumorigenic VHL variants leading to different clinical manifestations fail to bind hydroxylated TFAM. In contrast, cells harbouring the Chuvash polycythaemia VHL R200W mutation, involved in hypoxia-sensing disorders without tumour development, are capable of binding hydroxylated TFAM. Accordingly, VHL-related tumours, such as pheochromocytoma and renal cell carcinoma cells, display low mitochondrial content, suggesting that impaired mitochondrial biogenesis is linked to VHL tumorigenesis. Finally, inhibiting proteolysis by targeting LONP1 increases mitochondrial content in VHL-deficient cells and sensitizes therapy-resistant tumours to sorafenib treatment. Our results offer pharmacological avenues to sensitize therapy-resistant VHL tumours by focusing on the mitochondria., (© 2022. The Author(s).)

Background: Parkinson's disease (PD) represents the second most common neurodegenerative disease., Objective: To evaluate the effects of dance therapy (DT) aimed at improving non-motor symptoms in PD., Methods: Studies were performed through PubMed, Web of Science, The Cochrane Library, Embase, and Science Direct from inception to October 27, 2021. The data were screened independently by two reviewers, and the quality of the papers was assessed using the Cochrane manual. The included studies were randomized controlled trials and quasi-randomized controlled trials, reporting random-effects standardized mean differences, and 95% confidence intervals as the effect size. I 2 statistics were used to assess heterogeneity. The main outcomes included the Montreal Cognitive Assessment Scale (MOCA), Baker Depression Scale (BDI), Parkinson's Fatigue Scale (FPS-16), and Apathy Scale (AS). RevMan 5.3 software was integrated for meta-analysis., Results: Nine literatures were analyzed for the meta-analysis with a total of 307 patients. Random effects showed that DT significantly improved cognitive of PD (MD = 1.50, 95% CI [0.52, 2.48], P = 0.0003; I 2  = 51%). However, this meta-analysis demonstrated that dance therapy had no significance for improving depression (MD = - 1.33, 95% CI [- 4.11, 1.45], P = 0.35; I 2  = 79%), fatigue (MD = 0.26, 95% CI [- 0.31, 0.83], P = 0.37; I 2  = 0%), and apathy (MD = 0.07, 95% CI [- 2.55, 2.69], P = 0.96; I 2  = 50%)., Conclusion: The meta-analysis suggests that dance can improve cognitive function in PD., (© 2021. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: Globally, nonpharmaceutical interventions for COVID-19, including stay-at-home policies, limitations on gatherings and closure of public spaces, are being lifted. We explored the effect of lifting a stay-at-home policy on virus resurgence under different conditions., Methods: Using confirmed case data from Toronto, Canada, between Feb. 24 and June 24, 2020, we ran a compartmental model with household structure to simulate the impact of the stay-at-home policy considering different levels of compliance. We estimated threshold values for the maximum number of contacts, probability of transmission and testing rates required for the safe reopening of the community., Results: After the implementation of the stay-at-home policy, the contact rate outside the household fell by 39% (from 11.58 daily contacts to 7.11). The effective reproductive number decreased from 3.56 (95% confidence interval [CI] 3.02-4.14) on Mar. 12 to 0.84 (95% CI 0.79-0.89) on May 6. Strong adherence to stay-at-home policies appeared to prevent SARS-CoV-2 resurgence, but extending the duration of stay-at-home policies beyond 2 months had little added effect on cumulative cases (25 958 for 65 days of a stay-at-home policy and 23 461 for 95 days, by July 2, 2020) and deaths (1404 for 65 days and 1353 for 95 days). To avoid a resurgence, the average number of contacts per person per day should be kept below 9, with strict nonpharmaceutical interventions in place., Interpretation: Our study demonstrates that the stay-at-home policy implemented in Toronto in March 2020 had a substantial impact on mitigating the spread of SARS-CoV-2. In the context of the early pandemic, before the emergence of variants of concern, reopening schools and workplaces was possible only with other nonpharmaceutical interventions in place., Competing Interests: Competing interests: None declared., (© 2022 CMA Impact Inc. or its licensors.)

To understand the function of cortical circuits, it is necessary to catalog their cellular diversity. Past attempts to do so using anatomical, physiological or molecular features of cortical cells have not resulted in a unified taxonomy of neuronal or glial cell types, partly due to limited data. Single-cell transcriptomics is enabling, for the first time, systematic high-throughput measurements of cortical cells and generation of datasets that hold the promise of being complete, accurate and permanent. Statistical analyses of these data reveal clusters that often correspond to cell types previously defined by morphological or physiological criteria and that appear conserved across cortical areas and species. To capitalize on these new methods, we propose the adoption of a transcriptome-based taxonomy of cell types for mammalian neocortex. This classification should be hierarchical and use a standardized nomenclature. It should be based on a probabilistic definition of a cell type and incorporate data from different approaches, developmental stages and species. A community-based classification and data aggregation model, such as a knowledge graph, could provide a common foundation for the study of cortical circuits. This community-based classification, nomenclature and data aggregation could serve as an example for cell type atlases in other parts of the body.

We investigated the antifungal susceptibility profiles of 207 independent Candida albicans strains isolated from patients with vulvovaginal candidiasis (VVC) in Xinjiang Province of China. Using CLSI M27-A3 and M27-S4 guidelines, anidulafungin and micafungin were the most active drugs against C. albicans showing an MIC 50 /MIC 90 corresponding to 0.016/0.0313 µg/mL, followed by caspofungin (0.25/0.25 µg/mL), posaconazole (0.125/0.5 µg/mL), ravuconazole (0.063/1 µg/mL), itraconazole (0.125/1 µg/mL), amphotericine B (0.5/1 µg/mL), isavuconazole (0.063/2 µg/mL), 5-flucytosine (1/2 µg/mL), voriconazole (0.125/4 µg/mL), and fluconazole (0.5/4 µg/mL). 96.1% (199)-100.0% (207) isolates were sensitive to the three echinocandins tested, amphotericine B and 5-flucytosine. The in vitro activity of triazoles against all isolates tested was variable; itraconazole and voriconazole had reduced the activity to almost half of the isolates (55.1% (114) and 51.2% (106) susceptible, respectively). Fluconazole was active against 76.3% (158) isolates tested. The new triazoles ravuconazole, isavuconazole and posaconazole showed good in vitro potency against 89.9% (186)-95.2% (197) of isolates with the geometric mean MIC (µg/mL) of 0.10, 0.12 and 0.14 µg/mL, respectively. In conclusion, our study indicates that for effective management of systemic candidiasis in Xinjiang Province of China, it is important to determine the susceptibility profiles of isolated C. albicans from patients with VVC.

Objective: To examine the effects of presentation formats on consumers' performance and perceptions in the use of personal health records (PHRs) and to compare the effects between older and young adults., Methods: A two-factor, mixed design experiment was conducted, where 36 older and 36 young participants were presented with hypothetical PHRs. The PHRs were randomly presented by six presentation formats: three tables and three line graphs, varying by visual cues. Participants' performance and perceptions in the use of PHRs were measured., Results: Presentation formats affected participants' performance and perceptions. Visual cue-enhanced line graphs and tables yielded less time and fewer errors, were considered easier and more useful in information comprehension, and resulted in higher confidence in correct comprehension of PHRs (all p's < 0.01), compared with their basic counterparts. There were age-related differences in task performance (all p's < 0.05), while young and older adults had similar perceptions for the six formats. Line graph with colored background was most preferred by both groups., Conclusion: Visual cue-enhanced presentation formats appear effective in facilitating comprehension and eliciting favorable perceptions of PHRs for both young and older adults., Practice Implications: Consumer-facing displays of PHRs could use visual cue-enhanced presentation formats to facilitate comprehension., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objective: To observe the effect of moxibustion on Toll-like receptor 4/nuclear factor-κB (TLR 4/NF-κB) signaling in the synovial tissue of the ankle joint in rats with rheumatoid arthritis (RA), so as to analyze its biological mechanism underlying improvement of RA., Methods: Fifty male SD rats were randomly divided into normal control, model, moxibustion, moxibustion ＋ TLR 4 agonist, and moxibustion ＋ TLR 4 antagonist groups ( n ＝10 rats in each). The RA model was established by subcutaneous injection of Freund's complete adjuvant (FCA, 0.1 mL/rat) at the right hind-paw and by being raised in a wind (air fan blowing), cold (about 10 ℃) and wet (purling) environment for 20 days. After 3 days of modeling, mild moxibustion was applied to bilateral "Shenshu" (BL 23) and "Zusanli" (ST 36) for 20 minutes, once daily for successive 10 days. The TLR 4 agonist (lipopolysaccharide) or TLR 4 antagonist (TAK-242) (1 mg/mL) was separately administered via the tail vein 30 min before performing moxibustion every time in the agonist group and the antagonist group. The expression of NF-κB inhibitory factor ɑ (IκBɑ), IκB kinase complex β(IκKβ), myeloid differentiation factor 88 (MyD 88), TLR 4, and NF-κB p 65 proteins in the synovial tissue of the ankle joint was detected by using Western blot., Results: Following modeling, the girth of the swollen ankle joint was obviously bigger ( P <0.01), and the expression levels of IκBɑ， IκKβ， TLR 4, MyD 88, and NF-κB p 65 proteins in the synovial tissue were considerably increased in the model group relevant to the normal control group ( P <0.01). After moxibustion intervention, the girth of the swollen ankle joint and the expression levels of IκBɑ， IκKβ， TLR 4, MyD 88, and NF-κB p 65 proteins were significantly down-regulated in the moxibustion, moxibustion ＋TLR 4 agonist, moxibustion＋TLR 4 antagonist groups compared with the model group ( P <0.01, P <0.05). Comparison among the 3 moxibustion groups showed that the lowered levels of ankle-joint girth, and IκBɑ， IκKβ， TLR 4, MyD 88, and NF-κB p 65 expression were significantly smaller in the moxibustion＋TLR 4 agonist group than in the simple moxibustion and moxibustion＋TLR 4 antagonist groups ( P <0.05， P <0.01). No significant differences were found between the moxibustion and moxibustion＋TLR 4 antagonist groups in the decreased ankle joint girth and IκBɑ， IκKβ， TLR 4, MyD 88, and NF-κB p 65 expression levels ( P >0.05), suggesting that activation of TLR 4 reduced the anti-inflammatory effect of moxibustion intervention., Conclusion: Moxibustion can reduce the ankle joint swelling in RA rats, which may be closely associated with its effect in down-regulating the expression of IκBɑ， IκKβ， TLR 4, MyD 88, and NF-κB p 65 proteins and in inhibiting TLR 4/NF-κB signaling in the synovial tissue of the ankle joint.

Despite the proliferation of health and nursing informatics applications in the past decade, factors influencing consumer acceptance of the applications are not well understood. This study was conducted to investigate factors affecting acceptance of a consumer-used nursing informatics application (ie, online health information portal) within the framework of the Technology Acceptance Model. A cross-sectional study was conducted in which 201 Chinese young adults were invited to participate in usability testing with a typical health information portal and to complete a self-report questionnaire measuring the model's constructs and five hypothesized variables drawn from consumer and portal characteristics. Hierarchical regression analyses were used to test research hypotheses. Fifteen of the 22 research hypotheses were supported. Perceived ease of use and perceived usefulness predicted satisfaction and behavioral intention, respectively, over and above the portal and consumer characteristics examined in the study. All portal and consumer characteristics had significant, although varied, impacts on the original model constructs. This study demonstrated that an adapted Technology Acceptance Model, extended with portal and consumer characteristics, provides an effective means to understand consumer acceptance of health portals. The findings hold important implications for design and implementation strategies to increase the likelihood of acceptance of consumer-used nursing informatics applications.

The human tumor suppressor SMARCB1/INI1/SNF5/BAF47 (SNF5) is a core subunit of the multi-subunit ATP-dependent chromatin remodeling complex SWI/SNF, also known as Brahma/Brahma-related gene 1 (BRM/BRG1)-associated factor (BAF). Experimental studies of SWI/SNF are currently considerably limited by the low cellular abundance of this complex; thus, recombinant protein production represents a key to obtain the SWI/SNF proteins for molecular and structural studies. While the expression of mammalian proteins in bacteria is often difficult, the baculovirus/insect cell expression system can overcome limitations of prokaryotic expression systems and facilitate the co-expression of multiple proteins. Here, we demonstrate that human full-length SNF5 tagged with a C-terminal 3 × FLAG can be expressed and purified from insect cell extracts in monomeric and dimeric forms. To this end, we constructed a set of donor and acceptor vectors for the expression of individual proteins and protein complexes in the baculovirus/insect cell expression system under the control of a polyhedrin (polh), p10, or a minimal Drosophila melanogaster Hsp70 promoter. We show that the SNF5 expression level could be modulated by the selection of the promoter used to control expression. The vector set also comprises vectors that encode a 3 × FLAG tag, Twin-Strep tag, or CBP-3 × FLAG-TEV-ProteinA triple tag to facilitate affinity selection and detection. By gel filtration and split-ubiquitin assays, we show that human full-length SNF5 has the ability to self-interact. Overall, the toolbox developed herein offers the possibility to flexibly select the promoter strength as well as the affinity tag and is suggested to advance the recombinant expression of chromatin remodeling factors and other challenging proteins.

Background: The genus Wikstroemia has about 70 species, but only a limited number of species have been studied chemically. Wikstroemia indica has long been used as a traditional crude drug in China. However, there is no report about the bioactivity of Wikstroemia scytophylla ., Objective: This paper reports the chemical investigation and biological evaluation of the W. scytophylla ., Materials and Methods: The EtOAc extraction of W. scytophylla was isolated using chromatographic methods, and the compounds were analyzed by spectroscopic methods. The in vitro antitumor activities against five human cancer cell lines were performed according to the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method., Results: The chemical investigation of the stems of W. scytophylla resulted in the isolation of 12 compounds mainly including one biflavone (1), five flavones (2-6) compounds, and six lignans (7-12), in which compound 8 was a new natural product. Compounds 1 and 7-12 were evaluated for their antitumor activities while these compounds showed weak cytotoxicity with the half maximal inhibitory (IC 50 ) values more than 40 μM., Conclusion: All of these compounds were isolated from this plant for the first time, and compounds 2-12 were first reported from genus Wikstroemia , in which compound 8 was a new natural product. Compounds 1 and 7-12 exhibited weak antitumor activities (IC 50 >40 μM). The chemotaxonomic significance of all the isolations was summarized., Summary: The chemical investigation of the stems of W. scytophylla resulted in the isolation of 12 compoundsThe 12 compounds including six lignans (7-12), in which compound 8 was a new natural productThe isolated compounds 1 and 7-12 were evaluated for their antitumor activitiesThe chemotaxonomic significance of all the isolations was summarized. Abbreviations used: MTT: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; IC50: Half maximal inhibitory; HL-60: Human leukemia cell line; SMMC-7721: Human hepatocellular carcinoma cell line; A549: Human lung tumor cell line; MCF-7: Human breast cancer cell line; SW480: Human colon cancer cell line; MS: Mass spectrometry; NMR: Nuclear Magnetic Resonance., Competing Interests: There are no conflicts of interest.

Purpose: Medulloblastomas are aggressive brain malignancies. While considerable progress has been made in the treatment of medulloblastoma patients with respect to overall survival, these patients are still at risk of developing neurologic and cognitive deficits as a result of anti-cancer therapies. It is hypothesized that targeted molecular therapies represent a better treatment option for medulloblastoma patients. Therefore, the aim of the present study was to test a panel of epigenetic drugs for their effect on medulloblastoma cells under mild hypoxic conditions that reflect the physiological concentrations of oxygen in the brain., Methods: Protein levels of histone deacetylase 1 (HDAC1) and DNA methyltransferase 1 (DNMT1) in medulloblastoma-derived cells (Daoy and D283 Med), as well as in developing and differentiated brain cells, were determined and compared. Class I and II histone deacetylase inhibitors (HDACi) and a DNMT inhibitor, 5-aza-2'-deoxycytidine (5-aza-dC), were applied to Daoy and D283 Med cells, and their effects were studied using viability, apoptosis and cancer sphere assays., Results: We found that in HDAC1 and DNMT1 overexpressing medulloblastoma-derived cells, cell death was induced under various epigenetic drug conditions tested. At low HDACi concentrations, however, a pro-proliferative effect was observed. Parthenolide, a drug that affects cancer stem cells, was found to be efficient in inducing cell death in both cell lines tested. In contrast, we found that Daoy cells were more resistant to 5-aza-dC than D283 Med cells. When suberoylanilide hydroxamic acid (SAHA) and parthenolide were individually applied to both cell lines in combination with 5-aza-dC, a synergistic effect on cell survival was observed., Conclusions: Our current results suggest that the application of HDACi in combination with drugs that target DNMT may represent a promising option for the treatment of medulloblastoma.

Objective: To investigate the pathogenic and clinical presentation and laboratory tests of bullous rash in hand, foot and mouth disease (HFMD) in Xi'an from January 2013 to December 2014 by retrospective analysis., Method: A total of 224 specimens were collected from clinically diagnosed HFMD cases who were characterized by widespread mucocutaneous bullous reactions in Xi'an Children's Hospital from January 2013 to December 2014, the identification and subtyping of the isolates were conducted with real-time fluorescent quantitative RT-PCR. A retrospective analysis was performed to analyze the clinical presentation, laboratory tests and late follow-up problems of the HFMD., Result: In the clinically diagnosed HFMD cases who were characterized by widespread mucocutaneous bullous reactions, 207 were caused by coxsackievirus A6 (CA6), accounting for 92. 4% of all cases with bullous, 4 were caused by enterovirus 71 (EV71), accounting for 1.8%, 10 were caused by coxsackievirus A16 (CA16), accounting for 4. 5%; 4 cases were negative for these viruses. In the cases positive for intestinal virus-nucleic acid, 130 were male, 90 were female; male to female ratio was 1. 44: 1, 203 were <5 years old, accounting for 92. 3%. Leukocytosis was found in 75 cases (34. 1%); high-sensitivity C-reactive protein (hsCRP) increased in 200 cases (90. 9%); elevated myocardial enzyme CK-MB was found in 35 cases (15. 9%), alanine aminotransferase increased in 15 cases (6. 8%); 187 cases had fever (85. 0%). None of the cases had serious complications such as encephalitis or myocarditis. In the course of the critical phase bullous rash or large vesicle-like changes, obvious itching, and facial rash appeared. After the fluid in the bullae was absorbed or the bullae ruptured or became ulcerated, scar formation and large areas of exfoliation occurred, with no effusion on the newly formed epithelium in the base, without significant pigmentation on later follow-up. In the late follow up process, 52 cases in CA6-positive patients (25. 1%) developed onychomadesis within 2-4 weeks after onset, 1 to 8 nails, an average of 4. 3 fell off, new nails grew, the nail bed showed no structural abnormalities and hyperplasia after falling off, the surface was smooth, had no hypertrophy, left no sequelae., Conclusion: The pathogen in HFMD characterized by widespread bullous reactions was mainly the CA6, this kind of HFMD was mainly mild type, with significant itching, later the bullae may have scar formation and skin exfoliation, in some cases onychomadesis may occur.

Objective: To observe the effect of moxibustion intervention on the expression of toll-like receptor-4 (TLR 4), myeloid differentiation factor 88(MyD 88), and nuclear factor kappa B p 65 (NF-κB p 65) genes of knee-joint synovial cells in rheumatoid arthritis (RA) rats, so as to explore its molecular mechanism underlying improving RA., Methods: Forty SD rats were randomly divided into normal control, RA model, moxibustion and medication groups (n = 10). The RA model was duplicated by raising the rats in a windy, cold and wet environment, followed by injecting Freund's complete adjuvant (0. 15 mL) into the rat's foot. Moxibustion was applied to "Shenshu" (BL 23) and "Zusanli" (ST 36) for 20 min, once daily for 15 days. Rats of the medication group were treated by intragastric administration of tripterygium wilfordii (8. 75 mL/kg), once daily for 15 days. Pathological changes of the synovial tissues were detected by H. E. stain, the contents of serum TNF-α and IL-1 detected by radioimmunoassay, and the expression levels of TLR 4 mRNA, MyD 88 mRNA and TRAF-6 mRNA of synovial tissue were analyzed by real time-PCR, and the NF-κB p 65 immunoactivity was assayed by immunohistochemistry., Results: In comparison with the normal control group, the synovial tissue of the knee-joint was impaired remarkably and infiltrated by numerous inflammatory cells, and the synovial surface got thickening because of hyperplasia in the model group. Following moxibustion and medication, these situations such as synovial infiltration of inflammatory, synovial cell proliferation were alleviated. The serum TNF-α and IL-1 contents and synovial TLR 4 mRNA, MyD 88 mRNA, TRAF-6 mRNA and NF-κB p 65 expression levels were remarkably higher in the model group than in the control group(P<0. 01). After moxibustion and medication, the contents of serum TNF-α and IL-1, the expression levels of TLR 4 mRNA, MyD 88 mRNA, TRAF-6 mRNA and NF-κB p 65 were significantly down-regulated(P<0. 01, P<0. 05)., Conclusion: Moxibustion intervention can improve pathological changes of the knee-joint synovial membrane tissue in RA rats, which may be related with its effect in inhibiting abnormal activation of TLR 4-MyD 88-NF-κB pathway in synovial tissue.

Objective: To observe the effect of moxibustion on mRNA expression of signal transducers and activators of transcription 1 (STAT 1), suppressors of cytokine signaling (SOCS) in synovium of rheumatoid arthritis (RA) rats, and to investigate its mechanism for relieving RA., Methods: 40 Wistar rats were equally and randomly divided into control, model, moxibustion, acupuncture and infrared groups (n = 8 in each group). RA model was developed by putting rats in windy, cold and damp room and injection of Freund's complete adjuvant. Bilateral "Shenshu" (BL 23) were stimulated by the respective means for 20 min in duration, once every other day, ten times in total. The swelling degree of voix pedis (perimeter) of rats was measured. The contents of serum interleukin-1 (IL-1) and interleukin-2(IL-2) were detected by radioimmunoassay, and expression of STAT 1, SOCS mRNA in synovium were assessed by RT-PCR., Results: Rats in model group had acute and severe swelling of voix pedis, together with the increase of serum IL-1 content and decrease of IL-2 content, and down-regulation of mRNA expression of both STAT 1 and SOCS in synovium(all P<0. 01). All three modalities of treatment alleviated the swelling and reversed the relevant changes(P<0. 05, P<0. 01) , however, moxibustion produced greater effects than acupuncture or infrared in elevating IL-2 content and up-regulating mRNA expression of both STAT 1 and SOCS., Conclusion: Moxibustion achieves the effects of anti-inflammation and joint swelling reduction of RA via decrease of IL-1, increase of IL-2 in serum and up-regulation of STAT 1, SOCS mRNA expression in synovium.

The binding mechanisms of the interaction of three dihydromyricetin (DMY)-metal complexes (DMY-Cu (II) complex, DMY-Mn (II) complex, DMY-Zn (II) complex) and DMY with bovine serum albumin (BSA) were investigated using fluorescence and ultraviolet spectroscopy at different temperatures. The results indicated some differences in the binding process between different DMY-metal complexes and BSA compared with that of free DMY. All of the complexes and DMY quenched the fluorescence of BSA based on static mode combined with radiationless energy transfer, yet having different binding distance based on the Förster theory. Different DMY-metal complexes can change the binding constants. The binding constants increase for DMY-Cu (II) and DMY-Mn (II) complexes, whereas the opposite is true for the DMY-Zn (II) complex compared to the one with free DMY. The DMY-metal complexes can also affect the types of the interaction. The van der Waals forces and hydrogen bonding may play a major role in the interaction of free DMY with BSA, while for the three complexes, the nature of the binding forces lies in hydrophobic forces and hydrogen bonding based on the thermodynamic parameters.

Objective: To investigate the electrophysiological and morphological changes of retinae after intravitreal injection of cyclosporin A (CsA) in experimental diabetic rats., Methods: Experimental study. SD diabetic mellitus (DM) rat models were induced with intraperitoneal injection of streptozotocin. The rats were divided into four groups, with 9 rats in each group:the normal control (group CON), the diabetic rats with or without CsA intravitreal injection respectively (group DM + CsA and group DM), and the diabetic rats with dimethyl sulfoxide (DMSO) intravitreal injection (group DM + DMSO). The intravitreal injection of CsA or contrast solution was performed 4 weeks after the modeling. The retinal function of rats was examined by electroretinogram (ERG) 48 hours after the intravitreal injection. All rats were sacrificed and the structural changes of retina were observed by optical and transmission electron microscope. The datas of ERG including amplitudes and latencies of a-wave and b-wave were analyzed by One-way ANOVA and Bonferroni post hoc test., Results: There was difference in ERG b-wave among the 4 groups under different stimuli light intensity (F = 14.760 - 28.890, all P value < 0.01). And there was difference in ERG a-wave among the 4 groups when the stimuli light intensity ≥ -0.35 log cd×s×m(-2) (F = 12.510, 15.500, both P value < 0.01). Comparing to the group CON (ERG a-wave: 82.43 ± 26.68, ERG b-wave: 208.40 ± 51.20), the ERG a-wave and b-wave amplitudes of group DM (ERG a-wave: 39.71 ± 7.61, ERG b-wave: 92.20 ± 24.42) and group DM + DMSO (ERG a-wave: 37.63 ± 17.25, ERG b-wave: 93.11 ± 22.50)(t = 5.448 - 7.872, all P value < 0.05), and the ERG b-wave of group DM + CsA (160.10 ± 43.39) (t = 3.299, P < 0.05) were declined in dark adaptation, while the ERG a-wave (63.91 ± 20.32) of group DM ± CsA had no difference (P > 0.05). The a-wave and b-wave amplitudes of group DM + CsA were significantly increased compared to the other two groups in dark adaptation (t = 3.203 - 4.759, both P < 0.05). Under optical microscope, group DM, DM + DMSO and DM + CsA had outer nuclear layer (ONL) disorder. Under transmission electron microscope, there were ultrastructure changes of the three groups. Furthermore, the ONL disorder and ultrastructure changes of group DM + CsA were less severe than the other two groups., Conclusions: Functional and morphological changes are evident in the early stages in DM rats. Intravitreal injection with CsA shows protective effects on the nerve function in DM retina.

In the title complex, [CdCl(2)(C(11)H(10)N(4))(2)(H(2)O)(2)]·6H(2)O, the Cd(II) atom is located on a twofold rotation axis and is coordinated by two N atoms from two 1-[(1H-benzimidazol-2-yl)meth-yl]-1H-imidazole ligands and two water O atoms in equatorial positions and by two Cl atoms in axial positions, leading to an elongated octa-hedral environment. The two coordinating and two of the lattice water mol-ecules are also located on twofold rotation axes. In the crystal, complex mol-ecules and solvent water mol-ecules are linked through a complex inter-molecular N-H⋯O, O-H⋯N, O-H⋯O and O-H⋯Cl hydrogen-bonding scheme into a three-dimensional network.

In the title compound, C(9)H(11)NO(2), the dihedral angle between the amide group and the benzene ring is 10.6 (1)°. In the crystal, mol-ecules are connected via N-H⋯O hydrogen bonds, supported by a C-H⋯O contact, forming chains along b. These chains are linked by C-H⋯π inter-actions to give a three-dimensional network.

In the title complex, [Co(C(6)H(14)NO(3))(N(3))] or [Co(teaH(2))N(3)], the Co(II) atom resides in a trigonal-bipymidal O(3)N(2) environment formed by three O atoms and one N atom from a simply deprotonated tetra-dentate triethano-lamine ligand, and one N atom from an azide ligand. The O atoms define the equatorial plane whereas both N atoms are in axial positions. The mononuclear units are linked through O-H⋯O hydrogen-bonding inter-actions between the ethanol OH groups and the ethano-late O atom of a neighbouring complex into chains running parallel to [010].