Electroacupuncture ameliorates chronic unpredictable mild stress-induced depression-like behavior and cognitive impairment through suppressing oxidative stress and neuroinflammation in rats.

BACKGROUND: Depression is associated with lowered mood, anxiety, anhedonia, cognitive impairments, and even suicidal tendencies in severe cases. Yet few studies have directed acupuncture's mechanism toward enhancing axonal repair correlated with synaptic plasticity and anti-inflammatory effects related to oxidative stress in the hippocampus. METHODS: Male Sprague-Dawley (SD) rats were randomly divided into control group (CON), chronic unpredictable mild stress (CUMS) group, CUMS + electroacupuncture group (EA), and CUMS + fluoxetine group (FLX) (n = 10/group). Rats were given a 28-day treatment at the Shangxing (GV23) and Fengfu (GV16) acupoints with electroacupuncture or fluoxetine (2.1 mg/kg). RESULTS: Rats exposed to CUMS induced depression-like behaviors and spatial learning-memory impairment, changed the ionized calcium binding adaptor molecule 1 (IBA-1), Vglut1, myelin basic protein (MBP), and postsynaptic density protein 95 (PSD95) level of hippocampal, increased the Nod-like receptor protein 3 (NLRP3), atypical squamous cell (ASC), Caspase level and hippocampal reactive oxygen species (ROS), and prompted the activation of Epha4-mediated signaling and an inflammatory response. Conversely, electroacupuncture administration reduced these changes and prevented depression-like behaviors and cognitive impairment. Electroacupuncture also promoted hippocampal expression of Sirtuin1(SIRT1), Nuclear factor erythroid 2-like (Nrf2), Heme oxygenase-1 (HO-1); reduced the expression of interleukin-1ß (IL-1ß), interleukin-18 (IL-18), and tumor necrosis factor-alpha (TNF-α); and prevented neural damage, particularly the synaptic myelin sheath, and neuroinflammation by regulating Eph receptor A4 (EphA4) in the hippocampal. CONCLUSION: These results indicate that electroacupuncture prevents depression-like behaviors with cognitive impairment and synaptic and neuronal damage, probably by reducing EphA4, which mediates ROS hyperfunction and the inflammatory response.

Acupuncture alleviates CUMS-induced depression-like behaviors of rats by regulating oxidative stress, neuroinflammation and ferroptosis.

BACKGROUND: The treatment of depression with acupuncture has been documented. The mechanism behind acupuncture's curative and preventative effects is still unknown. METHODS: The current study examined the effects of acupuncture on depression-like behaviors in a rat model of chronic unpredictable mild stress (CUMS), while also exploring its potential mechanisms. A total of six groups of rats were randomly assigned: control, CUMS, acupuncture, fluoxetine, acupoint catgut embedding and sham acupoint catgut embedding. Fluoxetine (2.1 mg/kg) and acupoint catgut embedding were used for comparative research to acupuncture. The modelling evaluation is measured by body weight and behavior tests. Western blotting and reverse transcription-polymerase chain reaction were used to detect the proteins and mRNA expression of Silent information regulator 1 (Sirt1)/ nuclear factor-erythroid 2-related factor 2 (Nrf2)/ heme oxygenase-1 (HO-1)/ Glutathione peroxidase 4 (GPX4) pathway in the hippocampus. The expression of oxidative stress (OS)-related proteins and inflammatory cytokines in the serum was detected with ELISA. Immunofluorescence showed microglia and astrocytes activity in the hippocampus. RESULTS: Acupuncture and fluoxetine could alleviate CUMS-induced depression-like behaviors. Acupuncture was also found to effectively reverse the levels of MDA, SOD, GSH, GSH-PX and T-AOC, IL-1ß, IL-6 and TNF-α in the serum of CUMS-induced rats. Rats with CUMS showed decreased levels of Sirt1, Nrf2, HO-1 and GPX4 in the hippocampus, while acupuncture treatment could partly reverse the diminished effects. In addition, acupuncture treatment significantly reduced the activation of hippocampal microglia and astrocytes in CUMS-induced rats. CONCLUSION: The study's findings indicate that acupuncture has the potential to mitigate depression-like behaviors in rats induced with CUMS by mitigating OS and reducing neuroinflammation.

The effect of acupuncture on lateral habenular nucleus and intestinal microflora in depression model rats.

BACKGROUND: Depression is a severe emotional condition that significantly affects the quality of life. Acupuncture exerts preventive effects on depression in rats with post-chronic unpredictable mild stress (CUMS). Methods The study involved chronic unpredictable mild stress (CUMS) depression model mice to administer acupuncture as a preventative measure to investigate the mechanism of acupuncture's antidepressant and observe the effect of acupuncture on impact via the Lateral Habenula (LHb) and Gut-Liver-Brain Axis. The researcher investigated molecules correlating with a nitric oxide/cyclic guanosine monophosphate (NO/cGMP) pathway and assessed inflammation in the LHb and liver. In addition, 16 S rDNA bioinformatics study revealed the quantity and variety of gut microbiota. Rats were randomly divided into five groups: control (CON), CUMS, CUMS + acupuncture (AP), CUMS + fluoxetine (FX) and CUMS + N(G) -nitro -L- arginine methyl ester (LNAME) group. Except for the CON group, other rats were exposed to CUMS condition for 28 days. Simultaneously, manual acupuncture (at Fengfu and Shangxing acupoints, once every other day) and fluoxetine gavage (2.1 mg/kg, 0.21 mg/mL, daily) were conducted to the groups of AP and FX, respectively, after stressors. Rats in LNAME group were treated with LNAME normal saline (10 mg/kg, 1 mg/mL, i.p.) solution. Behavioural tests and biological detection methods were conducted sequentially to evaluate depressionlike phenotype in rats. RESULTS: The results showed CUMS induced depression-like behaviours, hyper-activation of NO/cGMP signaling pathway, inflammation in serum, LHb and liver, and dysbiosis of the gut microbiota. These changes could be prevented and ameliorated by acupuncture to varying extents. CONCLUSION: Acupuncture prevented and attenuated depression-like phenotype induced by CUMS, possibly via regulating the NO/cGMP signaling pathway and thus improving inflammation in serum, LHb and liver, and gut microbiota dysbiosis. In addition, these can be evidence of the existence of the gut-liver-brain axis.

Uranium uptake is mediated markedly by clathrin-mediated endocytosis and induce dose-dependent toxicity in HK-2 cells.

The objective of this study was to explore the endocytosis mechanisms of uranium uptake in HK-2 cells and its toxic effects. Our results demonstrated that uranium exposure impairs redox homeostasis and increases the permeability of the cell membrane and mitochondrial membrane, which may induce cell apoptosis by cytochrome-c leakage. Alkaline phosphatase activity increased after uranium exposure, which may be involved in the process of intracellular mineralisation of uranium, leading to severe cell necrosis. Furthermore, our findings demonstrated that the clathrin-mediated endocytosis process contributed substantially to uranium uptake in HK-2 cells and the total uranium uptake was highly correlated with cell viability, reaching a high correlation coefficient (r = -0.853) according to Pearson correlation analysis. In conclusion, the uptake of uranium into mammalian cells was mainly facilitated by the clathrin-mediated endocytosis pathway and induced dose-dependent cellular toxicity, including redox homeostasis imbalance, membrane injury, cell apoptosis and necrosis.

The effects of acupuncture on depression by regulating BDNF-related balance via lateral habenular nucleus BDNF/TrkB/CREB signaling pathway in rats.

Depression is a major mental disease worldwide, causing dysfunction of Lateral Habenular (LHb). As a non-invasive alternative, acupuncture (AP) has been widely used to treat depression in clinic, yet few basic studies have been focused on the effects and mechanism of acupuncture on synaptic plasticity in LHb. Therefore, this study aimed to explore the potential mechanism of the antidepressant effect of acupuncture. Male Sprague-Dawley (SD) rats were randomly divided into control, chronic unpredictable mild stress (CUMS), AP, fluoxetine (FLX), acupoint catgut embedding (ACE), sham-ACE groups (n = 9/group). Rats were given a 28-day treatment at the Shangxing (GV23) and Fengfu (GV16) acupoints with acupuncture, ACE, sham-ACE or fluoxetine (2.1 mg/kg). The results showed that AP, FLX and ACE suppressed the behavioral deficits, increased the level of the 5-hydroxytryptamine and FNDC5/IRISIN in serum, also reduced the expression of pro-BDNF impacted by CUMS. Both AP and FLX ameliorated the %area of IBA-1, GFAP, BrdU and DCX in the LHb and increased the expression of BDNF/TrkB/CREB, with non-significant difference between the two groups These findings suggest that AP therapy relieves depression-related manifestations in depressed rats, suggesting a potential mechanism via the BDNF/TrkB/CREB pathway in LHb.

Rumen-Protected Lysine and Methionine Supplementation Reduced Protein Requirement of Holstein Bulls by Altering Nitrogen Metabolism in Liver.

The aim of this study was to investigate the effect of low-protein diets supplemented with rumen-protected lysine (RPLys) and methionine (RPMet) on growth performance, rumen fermentation, blood biochemical parameters, nitrogen metabolism, and gene expression related to N metabolism in the liver of Holstein bulls. Thirty-six healthy and disease-free Holstein bulls with a similar body weight (BW) (424 ± 15 kg, 13 months old) were selected. According to their BW, they were randomly divided into three groups with 12 bulls in each group in a completely randomized design. The control group (D1) was fed with a high-protein basal diet (CP13%), while bulls in two low-protein groups were supplied a diet with 11% crude protein and RPLys 34 g/d·head + RPMet 2 g/d·head (low protein with low RPAA, T2) or RPLys 55 g/d·head + RPMet 9 g/d·head (low protein with high RPAA, T3). At the end of the experiment, the feces and urine of dairy bulls were collected for three consecutive days. Blood and rumen fluid were collected before morning feeding, and liver samples were collected after slaughtering. The results showed that the average daily gain (ADG) of bulls in the T3 group was higher than those in D1 (p < 0.05). Compared with D1, a significantly higher nitrogen utilization rate (p < 0.05) and serum IGF-1 content (p < 0.05) were observed in both T2 and T3 groups; however, blood urea nitrogen (BUN) content was significantly lower in the T2 and T3 groups (p < 0.05). The content of acetic acid in the rumen of the T3 group was significantly higher than that of the D1 group. No significant differences were observed among the different groups (p > 0.05) in relation to the alpha diversity. Compared with D1, the relative abundance of Christensenellaceae_R-7_group in T3 was higher (p < 0.05), while that of Prevotellaceae _YAB2003_group and Succinivibrio were lower (p < 0.05). Compared with D1 and T2 group, the T3 group showed an expression of messenger ribonucleic acid (mRNA) that is associated with (CPS-1, ASS1, OTC, ARG) and (N-AGS, S6K1, eIF4B, mTORC1) in liver; moreover, the T3 group was significantly enhanced (p < 0.05). Overall, our results indicated that low dietary protein (11%) levels added with RPAA (RPLys 55 g/d +RPMet 9 g/d) can benefit the growth performance of Holstein bulls by reducing nitrogen excretion and enhancing nitrogen efficiency in the liver.

Cellular transport of uranium and its cytotoxicity effects on CHO-k1 cells.

Uranium is a radioactive heavy metal and a significant public health concern; however, its associated underlying toxicological mechanisms remain largely unknown. In this work, the uptake and efflux processes of uranium in CHO-k1 cells were studied and the cytotoxicity effects were explored. It was found that both the uptake and efflux processes took place rapidly and half of the internalized uranium was expelled within 8 h. The uranium exposure caused a decrease of cell viability and adhesion ability in a dose-dependent manner and blocked the cell cycle at the G1 stage. In addition, gene expression analysis revealed relative changes in the transcription of metabolism related genes. Further studies revealed that the cytotoxicity of uranium could be alleviated by exposing cells to a lower temperature or by the addition of amantadine-HCl, an endocytosis inhibitor. Interestingly, after uranium exposure, needle-like precipitates were observed in both intracellular and extracellular regions. These findings collectively suggest that the cellular transport of uranium is a rapid process that disturbs cell metabolism and induces cytotoxicity, and this impact could be reduced by slowing down endocytic processes.

[Clinical observation of chiropractic manipulation in the treatment of degenerative scoliosis].

OBJECTIVE: To observe clinical efficacy of chiropractic manipulation in the treatment of degenerative scoliosis (DS). METHODS: From June 2017 to September 2019, 120 patients with degenerative scoliosis were randomly divided into treatment group (60 cases) and control group(60 cases). The patients in treatment group were treated with chiropractic manipulation once every other day for 4 weeks. The patients in control group were treated with eperisone hydrochloride tablets combined with thoracolumbar orthopedic(TSLO)brace, oral eperisone hydrochloride tablets 50 mg three times a day, wearing TSLO brace for not less than 8 hours a day. The course of treatment was 4 weeks. After the patients were selected into the group, visual analogue scale (VAS) and Oswestry Disability Index (ODI) were recorded before treatment, 1, 2, 3, 4 weeks after treatment and 1 month after treatment. The full length X-ray of the spine was taken before and 4 weeks after treatment, and the scoliosis Cobb angle, sagittal vertical axis (SVA) and lumbar lordosis (LL) were measured and compared. The adverse reactions during the treatment were recorded. RESULTS: There were significant differences in VAS and ODI between two groups at each time point after treatment (P<0.001), VAS and ODI at 2 weeks after treatment (PVAS=0.025, PODI=0.032) and 3 weeks after treatment(PVAS=0.040, PODI=0.044) in treatment group were significantly different from those in control group, but there was no significant difference in VAS and ODI at other time points between treatment group and control group (P>0.05). There was significant difference in Cobb angle between treatment group(P=0.010) and control group(P=0.017) after treatment, but there was no significant difference in LL and SVA between treatment group and control group. There was no significant difference in Cobb angle, LL and SVA between two groups before and after treatment. During the treatment, there were 4 mild adverse reactions in the control group and no adverse reactions in the treatment group. CONCLUSION: Chiropractic manipulation can effectively relieve pain and improve lumbar function in patients with degenerative scoliosis. The onset of action is faster than that oral eperisone hydrochloride tablets combined with TSLO brace, and it has better safety and can improve Cobb angle of patients with degenerative scoliosis.

Vitamin E and selenium supplementation synergistically alleviate the injury induced by hydrogen peroxide in bovine granulosa cells.

Dairy cows are susceptible to reproductive disorders, which are thought to be associated with oxidative stress. In the study, we investigated the effects of vitamin E (VE) and selenium (Se) on the proliferation, apoptosis, and steroidogenesis in bovine ovarian granulosa cells under hydrogen peroxide (H2O2) - induced oxidative stress and elaborated the underlying mechanisms. Our results showed that VE or Se could stimulate the granulosa cell proliferation, possibly due to up-regulating the expression of CCND1 and decreasing the P21 levels under oxidative stress. VE or Se treatment also increased the secretion of estradiol (E2) and progesterone (P4), which could be owing to improving the expression of genes associated with steroidogenesis (StAR, HSD3ß1, and CYP19A1) expression. VE or Se treatment down-regulated the apoptosis-related genes (BAX, CASP3) expression and decreased cell apoptosis. Furthermore, VE or Se treatment inhibited reactive oxidative species (ROS) and malondialdehyde (MDA) generation, increased total antioxidant capacity (T-AOC), and the activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px). Additionally, VE or Se treatment also alleviated the endoplasmic reticulum stress, activated the nuclear factor erythroid 2-related factor 2 (NRF2), and up-regulated the expression of its downstream genes, including NQO1, HO-1, GCLM, GCLC. More importantly, compared with either VE or Se treatment alone, their combined treatment showed a better protective effect against oxidative damage. Overall, our results indicated that VE and Se synergistically stimulated the granulosa cell proliferation and steroidogenesis, decreased cell apoptosis, mitigated the endoplasmic reticulum stress by activating the NRF2 signal pathway.

Effect of traditional Chinese manipulation on ankle sprains: A systematic review and meta-analysis.

BACKGROUND: This systematic review and meta-analysis was performed to evaluate the clinical efficacy and safety of traditional Chinese manipulation in treating ankle sprains. METHODS: Seven databases were searched from inception to July 2020. A meta-analysis of randomized controlled trials comparing traditional Chinese manipulation and other conservative therapy for ankle sprains was conducted. The Cochrane Handbook tool was applied to access the quality and risk of bias of each study. The meta-analysis was performed with Review Manager 5.3 software (Nordic Cochrane Centre, Copenhagen, Denmark). RESULTS: In total, 14 articles and 1112 patients were included. The total effective rate of ankle manipulation was much higher than that of other conservative therapy (risk ratio [RR], 1.23; 95% confidence interval [CI], 1.17-1.30; P < .00001). The Baird-Jackson score (RR, 10.14; 95% CI, 5.57-14.70; P < .0001), visual analog scale score (RR, -1.78; 95% CI, -3.14 to -0.43; P = .01), and American Orthopaedic Foot and Ankle Society ankle-hindfoot score (RR, 15.70; 95% CI, 12.72-18.68; P < .00001) were significantly lower in the manipulation group than in the control group. Further subgroup analysis showed that the visual analog scale score of the rotating-traction-poking manipulation was significantly lower than that of the control group (RRRTPM, -2.56; 95% CI, -4.54 to -0.58; P = .01), while there were no significant differences between the effects of other manipulations and the control group (RRother manipulation, -0.62; 95% CI, -1.52 to 0.28; P = .18). CONCLUSION: Traditional Chinese manipulation might have a better effect on ankle sprains than other types of conservative treatment. The rotating-traction-poking manipulation might achieve better effects than other manipulation techniques in terms of alleviating pain intensity. However, considering the overall high or unclear risk of bias, the evidence identified does not allow for a robust conclusion concerning the efficacy and safety of traditional Chinese manipulation for treating ankle sprains. High-quality randomized controlled trials are needed to confirm these findings.

Effects of prepartum zinc-methionine supplementation on feed digestibility, rumen fermentation patterns, immunity status, and passive transfer of immunity in dairy cows.

The aim of this study was to determine the effects of prepartum supplementation of zinc-methionine (Zn-Met) on feed digestibility, rumen fermentation patterns, and immunity status in dams and passive immunity transfer in their calves. A randomized complete design was used in this study. Forty multiparous Holstein dairy cows in late pregnancy (60 d before the expected calving date) were blocked by parity (2.1 ± 0.3), body weight (651 ± 52 kg), and expected calving date, and randomly assigned to 1 of 4 treatments. Cows were supplemented with Zn as Zn-Met at 0, 20, 40, or 60 mg/kg of dry matter (DM) from 60 d before expected calving date to the calving day. Though the nutrient digestibility was not affected by Zn supplementation, DM intake, Zn digestibility, and Zn deposition increased linearly with increasing Zn-Met supplementation. Ruminal pH and molar proportion of individual volatile fatty acids were similar, whereas a linear decrease and increase were observed in ruminal ammonia and microbial crude protein concentration, respectively, with increasing Zn-Met supplementation. Maternal serum concentration of alkaline phosphatase, carboxypeptidase, Cu and Zn superoxide dismutase, and total antioxidant capacity were greater in cows supplemented with >40 mg of Zn/kg of DM compared with the control group. With increasing Zn-Met supplementation, maternal blood concentration of IL-1 decreased linearly, whereas IL-2 and IL-6 increased linearly, and no differences were observed in IL-4. Concentration of nonesterified fatty acids and ß-hydroxybutyric acids in maternal blood was similar between treatments. No difference was observed in colostrum composition with increasing Zn-Met supplementation. Concentration of Zn and immunoglobulins (including IgA, IgG, and IgM) in maternal blood did not differ among treatments. However, Zn concentration in colostrum and blood of calves increased linearly. The concentration of IgA and IgM in colostrum increased linearly with increasing Zn-Met supplementation, whereas no differences in immunoglobulins were observed in calf blood. In conclusion, Zn supplementation as Zn-Met at 40 of mg/kg of DM may improve antioxidant activity of dam and potentially increase passive immunity transfer in calves.

A randomized controlled study for Yuanhu Zhitong dropping pills in the treatment of knee osteoarthritis.

BACKGROUND: Knee osteoarthritis (KOA) is a common chronic disorder of knee and the leading cause of pain in the elderly with an overall prevalence of 50% in people over 60 years of age. This disease is an important factor affecting the quality of life of middle-aged and elderly people, and its main symptom is knee joint pain. Due to the pain, the knee joint activity function is limited, bringing great pain to patients, affecting their quality of life, effective prevention, and treatment of KOA is a modern medical problem. METHODS: The 60 patients who met the inclusion criteria were randomly divided into the treatment group and the control group. In this study, single center, randomized control and equivalent clinical trial were used for treatment. The treatment group received Yuanhu Zhitong dropping pills within 4 weeks, and the control group received diclofenac sodium sustained-release capsule treatment within 4 weeks. The main measures were visual analogue scale (VAS), WOMAC osteoarthritis index score and gastrointestinal symptoms rating scale (GSRS).Secondary measures included biochemical markers and adverse reactions during treatment. RESULT: The results of this trial will be published on the website of China Clinical Trial Registration Center (http://www.chictr.org.cn/searchprojen.aspx) and in peer-reviewed journals or academic conferences. CONCLUSIONS: This study is to assess the efficacy and safety of Yuanhu Zhitong dropping pills for knee osteoarthritis (KOA). REGISTRATION: PROSPERO (registration number ChiCTR1900024712).

Considerations in the Selection of Renal Dosage Adjustments for Patients with Serious Infections and Lessons Learned from the Development of Ceftazidime-Avibactam.

An extensive clinical development program (comprising two phase 2 and five phase 3 trials) has demonstrated the efficacy and safety of ceftazidime-avibactam in the treatment of adults with complicated intra-abdominal infection (cIAI), complicated urinary tract infection (cUTI), and hospital-acquired pneumonia (HAP), including ventilator-associated pneumonia (VAP). During the phase 3 clinical program, updated population pharmacokinetic (PK) modeling and Monte Carlo simulations using clinical PK data supported modified ceftazidime-avibactam dosage adjustments for patients with moderate or severe renal impairment (comprising a 50% increase in total daily dose compared with the original dosage adjustments) to reduce the risk of subtherapeutic drug exposures in the event of rapidly improving renal function. The modified dosage adjustments were included in the ceftazidime-avibactam labeling information at the time of initial approval and were subsequently evaluated in the final phase 3 trial (in patients with HAP, including VAP), providing supportive data for the approved U.S. and European ceftazidime-avibactam dosage regimens across renal function categories. This review describes the analyses supporting the ceftazidime-avibactam dosage adjustments for renal impairment and discusses the wider implications and benefits of using modeling and simulation to support dosage regimen optimization based on emerging clinical evidence.

Determining the carrying capacity and environmental risks of livestock and poultry breeding in coastal areas of eastern China: an empirical model.

The scale of regional livestock and poultry breeding (LPB) is generally not determined by the supporting capacity (fodder supply), but by the environmental carrying capacity of wastes from the LPB. The soil's own nutrient-supplying capacity used to be overlooked, which consequently produced an inaccurate result of carrying capacity estimation of the LPB. An empirical method was, therefore, employed to evaluate the soil's own nutrient-supplying capacity and further determine the carrying capacity and environmental risks of the LPB accurately. Thirteen counties along the coast of Jiangsu were selected to conduct this study, according to the framework of planting-breeding balance. Our results indicate that, including the soil's own nutrient-supplying capacity in the estimation of the carrying capacity of the LPB, it can reduce the original carrying capacity by 50%. This suggests that our empirical method can significantly increase the accuracy of estimating the carrying capacity of the LPB. The carrying capacity of the LPB in the study area varies from 1.5 to 48.08 pigs/hm2, with a mean of 14 pigs/hm2 based on phosphorus (P) balance. Furthermore, four sub-regions (Ganyu, Dongtai, Dafeng, and Guannan) that have a high P pollution risk should focus on controlling the scale of the LPB. The nitrogen (N) pollution risk in the study area is generally low. Results suggest that the soil's own nutrient-supplying capacity plays an important role in estimating the carrying capacity of the LPB accurately. This study can provide insights on reducing environmental risks of the LPB, which may be beneficial for decision makers.

Pollination of Cretaceous flowers.

Insect pollination of flowering plants (angiosperms) is responsible for the majority of the world's flowering plant diversity and is key to the Cretaceous radiation of angiosperms. Although both insects and angiosperms were common by the mid-Cretaceous, direct fossil evidence of insect pollination is lacking. Direct evidence of Cretaceous insect pollination is associated with insect-gymnosperm pollination. Here, we report a specialized beetle-angiosperm pollination mode from mid-Cretaceous Burmese amber (99 mega-annum [Ma]) in which a tumbling flower beetle (Mordellidae), Angimordella burmitina gen. et sp. nov., has many tricolpate pollen grains attached. A. burmitina exhibits several specialized body structures for flower-visiting behavior including its body shape and pollen-feeding mouthparts revealed by X-ray microcomputed tomography (micro-CT). The tricolpate pollen in the amber belongs to the eudicots that comprise the majority of extant angiosperm species. These pollen grains exhibit zoophilous pollination attributes including their ornamentation, size, and clumping characteristics. Tricolpate pollen grains attached to the beetle's hairs are revealed by confocal laser scanning microscopy, which is a powerful tool for investigating pollen in amber. Our findings provide direct evidence of insect pollination of Cretaceous angiosperms, extending the range insect-angiosperm pollination association by at least 50 million years. Our results support the hypothesis that specialized insect pollination modes were present in eudicots 99 million years ago.

Simple Preparation of LaPO4:Ce, Tb Phosphors by an Ionic-Liquid-Driven Supported Liquid Membrane System.

In this work, LaPO4:Ce, Tb phosphors were prepared by firing a LaPO4:Ce, Tb precipitate using an ionic-liquid-driven supported liquid membrane system. The entire system consisted of three parts: a mixed rare earth ion supply phase, a phosphate supply phase, and an ionic-liquid-driven supporting liquid membrane phase. This method showed the advantages of a high flux, high efficiency, and more controllable reaction process. The release rate of PO43- from the liquid film under different types of ionic liquid, the ratio of the rare earth ions in the precursor mixture, and the structure, morphology, and photoluminescence properties of LaPO4:Ce, Tb were investigated by inductively coupled plasma-atomic emission spectroscopy, X-ray diffraction, Raman spectra, scanning electron microscopy, and photoluminescence emission spectra methods. The results showed that a pure phase of lanthanum orthophosphate with a monoclinic structure can be formed. Due to differences in the anions in the rare earth supply phase, the prepared phosphors showed micro-spherical (when using rare earth sulfate as the raw material) and nanoscale stone-shape (when using rare earth nitrate as the raw material) morphologies. Moreover, the phosphors prepared by this method had good luminescent properties, reaching a maximum emission intensity under 277 nm excitation with a predominant green emission at 543 nm which corresponded to the 5D4-7F5 transition of Tb3+.

Habitual Tea Consumption and Risk of Fracture in 0.5 Million Chinese Adults: A Prospective Cohort Study.

BACKGROUND: Tea consumption may have favorable effects on risk of fracture. However, little is known about such association in Chinese adults. The aim of this study was to examine the association between tea consumption and risk of hospitalized fracture in Chinese adults. METHODS: The present study included 453,625 participants from the China Kadoorie Biobank (CKB). Tea consumption was self-reported at baseline. Hospitalized fractures were ascertained through linkage with local health insurance claim databases. THE RESULTS: During a median of 10.1 years of follow-up, we documented 12,130 cases of first-time any fracture hospitalizations, including 1376 cases of hip fracture. Compared with never tea consumers, daily tea consumption was associated with lower risk of any fracture (hazard ratio (HR): 0.88; 95% confidence interval (CI): 0.83, 0.93). Statistically significant reduced risk of hip fracture was shown among daily consumers who most commonly drank green tea (HR: 0.80; 95% CI: 0.65, 0.97) and those who had drunk tea for more than 30 years (HR: 0.68; 95% CI: 0.52, 0.87). Our conclusions: Habitual tea consumption was associated with moderately decreased risk of any fracture hospitalizations. Participants with decades of tea consumption and those who preferred green tea were also associated with lower risk of hip fracture.

BCL6 mediates the effects of Gastrodin on promoting M2-like macrophage polarization and protecting against oxidative stress-induced apoptosis and cell death in macrophages.

Cerebral palsy (CP) is the most common childhood disability worldwide, yet biomarkers for predicting CP are lacking. By subjecting peripheral blood samples from 62 CP patients and 30 healthy controls to Affymetrix GeneChip® PrimeView™ HumanGene Expression Microarray analysis, we identified the novel biomarker B-cell lymphoma 6 (BCL6) as the most upregulated gene in the CP samples. Gastrodin is a traditional Chinese medicine and bioactive compound that promotes adductor angle release, as well as gross and fine motor performance by increasing Gross Motor Function Measure-66 and Fine Motor Function Measure-45 scores. Gastrodin upregulates the mRNA expression of Mgl2 and Mrc1, M2 macrophage markers, and arginase activity, an M2 polarization indicator, in murine RAW264.7 macrophages. Moreover, these effects were blocked by BCL6 siRNA, which also abrogated the protective effects of Gastrodin against hydrogen peroxide-induced apoptosis and death in RAW264.7 cells. Our work identified BCL6 as a novel biomarker for early prediction of CP. Moreover, we demonstrated that Gastrodin not only stimulated polarization toward M2-like macrophages, which promote tissue repair, but also rescued macrophages from oxidative stress, apoptosis and death by inducing BCL6 expression. BCL6-targeted therapeutic strategies have promise for improving motor performance in CP patients.

Symmetrically Substituted Xanthone Amphiphiles Combat Gram-Positive Bacterial Resistance with Enhanced Membrane Selectivity.

This is the first report of the design of a new series of symmetric xanthone derivatives that mimic antimicrobial peptides using a total synthesis approach. This novel design is advantageous because of its low cost, synthetic simplicity and versatility, and easy tuning of amphiphilicity by controlling the incorporated cationic and hydrophobic moieties. Two water-soluble optimized compounds, 6 and 18, showed potent activities against Gram-positive bacteria, including MRSA and VRE (MICs = 0.78-6.25 µg/mL) with a rapid bactericidal effect, low toxicity, and no emergence of drug resistance. Both compounds demonstrated enhanced membrane selectivity that was higher than those of most membrane-active antimicrobials in clinical trials or previous reports. The compounds appear to kill bacteria by disrupting their membranes. Significantly, 6 was effective in vivo using a mouse model of corneal infection. These results provide compelling evidence that these compounds have therapeutic potential as novel antimicrobials for multidrug-resistant Gram-positive infections.