Physical activity attenuates the excess mortality risk from prolonged sitting time among adults with osteoporosis or osteopenia.

PURPOSE: Osteoporosis is a common generalized skeletal disorder characterized by compromised bone strength predisposing a person to an increased risk of fracture. This study aims to crystallize associations of physical activity (PA) and sedentary behaviour with the survival of adults with osteoporosis or osteopenia. METHODS: A total of 3103 participants aged 50 years or older from the National Health and Nutrition Examination Survey (NHANES) were included in the study. All participants were diagnosed with osteopenia or osteoporosis. Multivariable Cox proportional hazards regression models were used to assess the association of PA and sedentary behaviour with overall mortality, cancer-related mortality, and cardiovascular disease (CVD)-related mortality. RESULTS: During 21349 person-years of follow-up, 675 deaths were documented. Highly active participants had a lower risk of all-cause (hazard ratios [HR] = 0.61; 95% confidence interval [CI], 0.42-0.87; P for trend = 0.004), cancer-specific (HR = 0.64; 95%CI, 0.35-1.17; P for trend = 0.132), CVD-specific (HR = 0.75; 95%CI, 0.45-1.25; P for trend = 0.452), and other (HR, 0.51; 95%CI, 0.29-0.88; P for trend = 0.005) mortality than inactive participants. And sitting time was not associated with mortality among physically active participants; while among those who were insufficiently active or inactive, longer sitting time was associated with increased risks of all-cause (HR per 1-h increase = 1.05; 95% CI, 1.01-1.09), cancer-specific (HR per 1 h increase = 0.98; 95% CI, 0.90-1.07), CVD-specific (HR per 1-h increase = 1.11; 95% CI = 1.04-1.18), and other (HR per 1-h increase = 1.05; 95% CI, 0.98-1.13) mortality in a dose-response manner. CONCLUSIONS: PA can attenuate the excess mortality risk from prolonged sitting for individuals with osteoporosis and/or osteopenia. The combination of prolonged sedentary behaviour with inactive (participants without any PA during a week) PA was associated with an increased risk of mortality. The all-cause mortality risk of individuals who engage in less than 150 min/wk PA and sit more than 8 h/d is 2.02 (95% CI, 1.37-2.99) times higher than that of individuals who engage in more than 150 min/wk PA and sit less than 4 h/d.

PHPB ameliorates memory deficits and reduces oxidative injury in Alzheimer's disease mouse model by activating Nrf2 signaling pathway.

Alzheimer's disease (AD), a progressive neurodegenerative disorder, is the most common cause of dementia in elderly people and substantially affects patient quality of life. Oxidative stress is considered a key factor in the development of AD. Nrf2 plays a vital role in maintaining redox homeostasis and regulating neuroinflammatory responses in AD. Previous studies show that potassium 2-(1-hydroxypentyl)-benzoate (PHPB) exerts neuroprotective effects against cognitive impairment in a variety of dementia animal models such as APP/PS1 transgenic mice. In this study we investigated whether PHPB ameriorated the progression of AD by reducing oxidative stress (OS) damage. Both 5- and 13-month-old APP/PS1 mice were administered PHPB (100 mg·kg-1·d-1, i.g.) for 10 weeks. After the cognition assessment, the mice were euthanized, and the left hemisphere of the brain was harvested for analyses. We showed that 5-month-old APP/PS1 mice already exhibited impaired performance in the step-down test, and knockdown of Nrf2 gene only slightly increased the impairment, while knockdown of Nrf2 gene in 13-month-old APP/PS1 mice resulted in greatly worse performance. PHPB administration significantly ameliorated the cognition impairments and enhanced antioxidative capacity in APP/PS1 mice. In addition, PHPB administration significantly increased the p-AKT/AKT and p-GSK3ß/GSK3ß ratios and the expression levels of Nrf2, HO-1 and NQO-1 in APP/PS1 mice, but these changes were abolished by knockdown of Nrf2 gene. In SK-N-SH APPwt cells and primary mouse neurons, PHPB (10 µM) significantly increased the p-AKT/AKT and p-GSK3ß/GSK3ß ratios and the level of Nrf2, which were blocked by knockdown of Nrf2 gene. In summary, this study demonstrates that PHPB exerts a protective effect via the Akt/GSK3ß/Nrf2 pathway and it might be a promising neuroprotective agent for the treatment of AD.

Caffeic acid alleviates cerebral ischemic injury in rats by resisting ferroptosis via Nrf2 signaling pathway.

There are few effective and safe neuroprotective agents for the treatment of ischemic stroke currently. Caffeic acid is a phenolic acid that widely exists in a number of plant species. Previous studies show that caffeic acid ameliorates brain injury in rats after cerebral ischemia/reperfusion. In this study we explored the protective mechanisms of caffeic acid against oxidative stress and ferroptosis in permanent cerebral ischemia. Ischemia stroke was induced on rats by permanent middle cerebral artery occlusion (pMCAO). Caffeic acid (0.4, 2, 10 mg·kg-1·d-1, i.g.) was administered to the rats for 3 consecutive days before or after the surgery. We showed that either pre-pMCAO or post-pMCAO administration of caffeic acid (2 mg·kg-1·d-1) effectively reduced the infarct volume and improved neurological outcome. The therapeutic time window could last to 2 h after pMCAO. We found that caffeic acid administration significantly reduced oxidative damage as well as neuroinflammation, and enhanced antioxidant capacity in pMCAO rat brain. We further demonstrated that caffeic acid down-regulated TFR1 and ACSL4, and up-regulated glutathione production through Nrf2 signaling pathway to resist ferroptosis in pMCAO rat brain and in oxygen glucose deprivation/reoxygenation (OGD/R)-treated SK-N-SH cells in vitro. Application of ML385, an Nrf2 inhibitor, blocked the neuroprotective effects of caffeic acid in both in vivo and in vitro models, evidenced by excessive accumulation of iron ions and inactivation of the ferroptosis defense system. In conclusion, caffeic acid inhibits oxidative stress-mediated neuronal death in pMCAO rat brain by regulating ferroptosis via Nrf2 signaling pathway. Caffeic acid might serve as a potential treatment to relieve brain injury after cerebral ischemia. Caffeic acid significantly attenuated cerebral ischemic injury and resisted ferroptosis both in vivo and in vitro. The regulation of Nrf2 by caffeic acid initiated the transcription of downstream target genes, which were shown to be anti-inflammatory, antioxidative and antiferroptotic. The effects of caffeic acid on neuroinflammation and ferroptosis in cerebral ischemia were explored in a primary microglia-neuron coculture system. Caffeic acid played a role in reducing neuroinflammation and resisting ferroptosis through the Nrf2 signaling pathway, which further suggested that caffeic acid might be a potential therapeutic method for alleviating brain injury after cerebral ischemia.

Association between pyrethroid exposure and osteoarthritis: a national population-based cross-sectional study in the US.

BACKGROUND: With the restriction of organophosphorus and other insecticides, pyrethroids are currently the second most-used group of insecticides worldwide due to their advantages such as effectiveness and low toxicity for mammalian. Animal studies and clinical case reports have documented associations between adverse health outcomesand exposure to pyrethroids. At present, the association between chronic pyrethroid exposure and osteoarthritis (OA) remains elusive. METHODS: Cross-sectional data from the National Health and Nutrition Examination Survey 1999-2002 and 2007-2014 were used to explore the associations of pyrethroid exposure and OA. Urinary level of 3-phenoxybenzoic acid (3-PBA) in urine samples was used to evaluate the exposure of pyrethroid, and OA was determined on the basis of self-reported physician diagnoses. Multivariable logistic regression models were used to investigate the association between pyrethroid exposure and OA. RESULTS: Among the 6528 participants, 650 had OA. The weighted geometric mean of urinary volume-based 3-PBA concentration were 0.45 µg/L. With adjustments for major confounders, compared to participants in the lowest quartile of urinary volume-based 3-PBA, those in the highest quartilehad higher odds of OA (odds ratio, 1.39; 95% confidence interval: 1.01, 1.92). There was no nonlinear relationship between urinary volume-based 3-PBA and OA (P for non-linearity = 0.89). CONCLUSION: High urinary 3-PBA concentration was associated with increased OA odds in the US adults. Pyrethroid exposure in the population should be monitored regularly.

Surface-enhanced Raman scattering (SERS) by gold nanoparticle characterizes dermal thickening by collagen in bleomycin-treated skin ex vivo.

PURPOSE: Current skin imaging modalities, including optical, electron, and confocal microscopy, mostly require tissue fixations that could damage proteins and biological molecules. Live tissue or cell imaging such as ultrasonography and optical coherent microscope may not adequately measure the dynamic spectroscopical changes. Raman spectroscopy has been adopted for skin imaging in vivo, mostly for skin cancer imaging. However, whether the epidermal and dermal thickening in skin could be measured and distinguished by conventional Ramen spectroscopy or the surface-enhanced Raman scattering (SERS), a rapid and label-free method for noninvasive measurement remains unknown. METHODS: Human skin sections from patients of atopic dermatitis and keloid, which represent epidermal and dermal thickening, respectively, were measured by conventional Ramen spectroscopy. In mice, skin sections from imiquimod (IMQ)- and bleomycin (BLE)-treated mice, which reflect the epidermal and dermal thickening, respectively, were measured by SERS, that incorporates gold nanoparticles to generate surface plasma and enhance Raman signals. RESULTS: Conventional Ramen spectroscopy failed to consistently show the Raman shift in human samples among the different groups. SERS successfully revealed a prominent peak around 1300 cm-1 in the IMQ-treated skin; and two significant peaks around 1100 and 1300 cm-1 in BLE-treated group. Further quantitative analysis showed 1100 cm-1 peak was significantly accentuated in the BLE-treated skin than that in control skin. SERS identified in vitro a similar 1100 cm-1 peak in solutions of collagen, the major dermal biological molecules. CONCLUSION: SERS distinguishes the epidermal or dermal thickening in mouse skin with rapid and label-free measures. A prominent 1100 cm-1 SERS peak in the BLE-treated skin may result from collagen. SERS might help precision diagnosis in the future.

Room-Temperature High-Performance Thermoelectric Bi0.6 Sb0.4 Te: Elimination of Detrimental Band Inversion in BiTe.

Room-temperature thermoelectric materials are the key to miniaturizing refrigeration equipment and have great scientific and social implications, yet their application is hindered by their extreme scarcity. BiTe exhibiting strong spin-orbit coupling peaks ZT at 600 K. Herein, we discover the synergy effect of Sb doping in BiTe that eliminates the detrimental band inversion and leads to an overlap of conduction band (CB) and valence band that significantly increases the S from 33 to 124 µV K-1 . In addition, this effect enhances the µ from 58 to 92 cm2  V-1 s-1 owing to the sharp increase in the CB slope along the Γ-A in the first Brillouin zone. Furthermore, Sb doping increases the anharmonicity, shortens the phonon lifetime and lowers κlat . Finally, Se/Sb codoping further optimizes the ZT to 0.6 at 300 K, suggesting that Bi0.6 Sb0.4 Te1-y Sey is a potential room-temperature TE material.

Safety and influencing factors of coronavirus disease 2019 vaccines in maintenance hemodialysis patients / 中华肾脏病杂志

Objective:To explore the status of coronavirus disease 2019 (COVID-19) vaccines, safety and the influencing factors of adverse reactions in maintenance hemodialysis (MHD) patients.Methods:The study was a retrospective study. The MHD patients vaccinated with COVID-19 vaccines in Tianjin city from January 2020 to July 2022 were enrolled in the study. The data of general information, vaccination situation, adverse reactions, and laboratory tests before and after vaccination were collected. Logistic regression analysis was used to analyze the risk factors of adverse reactions after vaccination.Results:A total of 7 375 patients were registered to receive hemodialysis treatment in Tianjin city, of whom 1 036 patients (14.05%) vaccinated with COVID-19 vaccines were enrolled from 53 hemodialysis centers in the study, with age of (54.00±13.27) years old (17-88 years old), and 676 males (65.25%). There were 171 patients (16.51%) receiving the first dose of vaccines only, 464 patients (44.79%) receiving two doses of vaccines, 401 patients (38.71%) receiving three doses of vaccines, and 67 patients (6.47%) had adverse reactions. No serious adverse reaction occurred. The number of neutrophils after vaccination was lower than that before vaccination ( P < 0.05), while the number of lymphocytes, alanine aminotransferase, glutamic oxaloacetic aminotransferase, and serum albumin after vaccination were higher than those before vaccination (all P < 0.05). Logistic regression analysis showed that age ( OR=0.967, 95% CI 0.946-0.990, P=0.005), previous allergic history ( OR=0.013, 95% CI 0.001-0.151, P < 0.001), serum uric acid ( OR=1.004, 95% CI 1.001-1.008, P=0.020), numbers of vaccinations administered ( OR=0.505, 95% CI 0.330-0.774, P=0.002), leukocytes ( OR=0.766, 95% CI 0.628-0.935, P=0.009) and lymphocytes ( OR=0.082, 95% CI 0.045-0.148, P < 0.001) were independently correlated with the incidence of adverse reactions. Conclusions:The proportion of MHD patients vaccinated with COVID-19 vaccines is 14.05%. The incidence of adverse reactions is 6.47%, and there is no serious adverse reaction. Age, previous allergic history, serum uric acid, and numbers of vaccinations administered, leukocytes and lymphocytes are independently correlated with the incidence of adverse reactions in MHD patients.

Risk factors analysis and prediction nomogram establishment of acute kidney injury in hip fracture patients with severe underlying diseases / 中华骨科杂志

Objective:To analyze the risk factors of acute kidney injury (AKI) in hip fracture patients with serious underlying diseases and establish a prediction nomogram.Methods:Clinical information of hip fracture patients admitted to the intensive care unit (ICU) of Beth Israel Deaconess Medical Center (BIDMC) was analyzed using the Medical Information Mart for Intensive Care (MIMIC)-IV. Patient comorbidities, disease scores, vital signs and laboratory tests, surgical modalities, invasive procedures, and drug use were recorded. According to the diagnostic criteria of AKI in the Kidney Disease Improving Global Outcome (KDIGO) guideline, the enrolled patients were randomly divided into training set and validation set. Based on logistic regression analysis, least absolute shrinkage and selection operator (LASSO) logistic regression algorithm was used to analyze the risk factors of AKI after admission, and the corresponding prediction model was calculated.Results:A total of 474 patients were enrolled, including 331 in the training set and 143 in the validation set. According to the diagnostic criteria of AKI of KDIGO guidelines, the patients were divided into AKI group (159 cases) and non-AKI group (172 cases). Univariate analysis showed that age ( t=2.61, P=0.009), coronary heart disease (χ 2=2.08, P=0.038), heart failure (χ 2=2.60, P=0.009), hemoglobin ( t=1.89, P=0.059), platelets ( t=1.81, P=0.070), urea nitrogen ( t=2.83, P=0.005), blood creatinine ( t=3.65, P<0.001), blood sodium ( t=2.55, P=0.011), blood glucose ( t=2.52, P=0.012), anion gap ( t=3.44, P=0.001), diastolic blood pressure ( t=2.72, P=0.007), mean arterial pressure ( t=2.16, P=0.031), SOFA score ( t=3.69, P<0.001), simplified acute physiological function score II (SAPSII) score ( t=2.95, P=0.003), as well as furosemide (χ 2=2.03, P=0.042), vancomycin (χ 2=1.70, P=0.089), vasoactive medications (χ 2=3.74, P<0.001) and use of invasive mechanical ventilation (χ 2=4.81, P<0.001) were risk factors associated with the development of AKI in hip fracture patients. Multivariate logistic regression analysis showed that age ( OR=1.03, P<0.001), coronary heart disease ( OR=2.05, P=0.069), hemoglobin ( OR=0.88, P=0.050), blood creatinine ( OR=1.37, P=0.009), blood sodium ( OR=1.07, P=0.026), anion gap ( OR=1.09, P=0.028) and vasoactive medications ( OR=3.83, P=0.018) and the use of invasive mechanical ventilation ( OR=6.56, P<0.001) were independent predictors of the development of AKI in hip fracture patients with serious underlying diseases. The area under the curve of the nomogram prediction model constructed by the above 8 predictors was 0.789, and the calibration curve of the nomogram was close to the ideal diagonal. Decision curve analysis showed that the net benefit of the model was significant. Conclusion:The incidence of AKI is high in hip fracture patients with serious underlying diseases. Age, coronary heart disease, hemoglobin, serum creatinine, serum sodium, anion gap, vasoactive drugs, and invasive mechanical ventilation can predict the occurrence of AKI to a certain extent. Combined with the risk factors, the construction of the corresponding prediction model can predict and manage the diagnosis and treatment of AKI in patients with hip fracture complicated with severe underlying diseases.

Distinct roles of astroglia and neurons in synaptic plasticity and memory.

Long-term potentiation (LTP) in the hippocampus is the most studied form of synaptic plasticity. Temporal integration of synaptic inputs is essential in synaptic plasticity and is assumed to be achieved through Ca2+ signaling in neurons and astroglia. However, whether these two cell types play different roles in LTP remain unknown. Here, we found that through the integration of synaptic inputs, astrocyte inositol triphosphate (IP3) receptor type 2 (IP3R2)-dependent Ca2+ signaling was critical for late-phase LTP (L-LTP) but not early-phase LTP (E-LTP). Moreover, this process was mediated by astrocyte-derived brain-derived neurotrophic factor (BDNF). In contrast, neuron-derived BDNF was critical for both E-LTP and L-LTP. Importantly, the dynamic differences in BDNF secretion play a role in modulating distinct forms of LTP. Moreover, astrocyte- and neuron-derived BDNF exhibited different roles in memory. These observations enriched our knowledge of LTP and memory at the cellular level and implied distinct roles of astrocytes and neurons in information integration.

A comparison study between dimethyl itaconate and dimethyl fumarate in electrophilicity, Nrf2 activation, and anti-inflammation in vitro.

Dimethyl itaconate (DMI) is an analog of dimethyl fumarate (DMF), an approved NF-E2-related Factor 2 (Nrf2) activator for multiple sclerosis. This study evaluated the potential of DMI as an anti-inflammatory agent by comparing DMI with DMF in electrophilicity, Nrf2 activation, and anti-inflammation in vitro. The results showed that DMI was less electrophilic but better at inducing a durable activation of Nrf2 when compared with DMF. However, DMI demonstrated poor anti-inflammatory effects in Jurkat cells, bone marrow-derived dendritic cells, and RAW264.7 cells. Our study suggested that DMI was a potent electrophilic Nrf2 activator but was probably not a promising anti-inflammatory agent.

Investigation of Adhesive's Material in Hermetic MEMS Package for Interfacial Crack between the Silver Epoxy and the Metal Lid during the Precondition Test.

A hermetic Micro-Electro-Mechanical Systems (MEMS) package with a metal lid is investigated to prevent lid-off failure and improve its reliability during the precondition test. While the MEMS package benefits from miniaturization and low cost, a hermetic version is highly sensitive to internal pressure caused by moisture penetration and the reflow process, thus affecting its reliability. In this research, the finite element method is applied to analyze the contact stress between the metal lid and the silver epoxy by applying the cohesive zone model (CZM). Moreover, the red dye penetration test is applied, revealing a microcrack at the metal lid/silver epoxy interface. Further analyses indicate that the crack is caused by internal pressure. According to the experimental testing and simulation results, the silver epoxy material, the curing process, the metal lid geometry, and the bonding layer contact area can enhance the bonding strength between the metal lid and the substrate.

Effect of shear stress on KLF2 and eNOS expression in vein endothelial cells under normal physiology and uremia conditions / 国际生物医学工程杂志

Objective:To study the effect of shear stress on the expression of KLF2 and eNOS in venous endothelial cells under physiological and uremic conditions, and to explore the mechanism leading to dysfunction of venous endothelial cells.Methods:Under physiological conditions and uremia conditions, different shear stresses were simulated in the parallel plate flow cavity, and the shear stresses were applied to the venous endothelial cells of each group for 4, 12, and 24 hours. The expression of KLF2 and eNOS was detected by immunohistochemical fluorescent staining technique and real-time fluorescent quantitative PCR technique.Results:Under physiological conditions, KLF2 is obviously regulated by shear stresses. High-intensity shear stresses and physiological shear stresses will up-regulate the expression of KLF2, while low-intensity shear stresses and oscillating shear stresses will down-regulate the expression of KLF2. As the duration of action increases, the expression of KLF2 will also increase. In the state of uremia, the expression of KLF2 is significantly inhibited. Even if high shear stresses is applied, the level of KLF2 is not high-expressed as the physiological state. And under the action of low shear stresses and oscillating shear stresses, KLF2 expression is more significantly inhibited. KLF2 is mainly expressed in the nucleus. With the action of shear stresses, KLF2 is also expressed in the cytoplasm, while eNOS is mainly expressed in granular form in the cytoplasm and nucleus.Conclusions:After arteriovenous fistula operation, the expression of KLF2 and eNOS is inhibited under the action of multiple factors of uremia environment and oscillating shear stresses, which may be the main cause of the occurrence and development of venous endothelial cell dysfunction, intimal hyperplasia, and AVF failure.

A Meta-analysis of the predictive effect of neutrophil-lymphocyte ratio on acute kidney injury / 中华危重病急救医学

Objective:To systematically evaluate the predictive value of neutrophil-lymphocyte ratio (NLR) in acute kidney injury (AKI).Methods:All studies about the predictive effect of NLR on AKI were searched in the National Medical Library of the United States PubMed Database, the Embase database in the Netherlands, the Chinese Biology Medicine disc (CBMdisc) and the Chinese Evidence Based Medicine Cochrane Centre Database (CEBM/CCD). The data updated by October 2020, and regardless of language, region or whether blind method was used. Two authors independently extracted data and evaluated the quality of the studies. Data extracted from the studies were analyzed with RevMan 5.3 to assess the predictive value of NLR on AKI. A subgroup Meta-analysis was conducted to assess the predictive value of NLR on AKI according to different countries, different disease types (cardiovascular surgery, infectious diseases, other diseases including burns, cirrhosis, and emergency), and different sample sizes (≤ 300 cases and > 300 cases). The publication bias of included studies about the predictive effect of NLR on AKI were assessed by funnel plots.Results:A total of 11 studies were included in this Meta-analysis, including 4 997 patients, 1 308 patients in AKI group, and 3 689 patients in non-AKI group. The Meta-analysis results showed that: increased NLR had predictive value for the occurrence of AKI [mean difference ( MD) = 2.73, 95% confidence interval (95% CI) was 1.78-3.68, P < 0.000 01]. Subgroup analysis showed that increased NLR had predictive value for the occurrence of AKI in patients from Southeast Asia ( MD = 4.04, 95% CI was 1.09-6.99, P = 0.007) and Eurasia ( MD = 2.51, 95% CI was 1.12-3.90, P = 0.000 4). Increased NLR had predictive value for the occurrence of AKI in patients undergoing cardiovascular surgery ( MD = 0.77, 95% CI was 0.34-1.20, P = 0.000 4), infectious diseases ( MD = 4.74, 95% CI was 1.51-7.96, P = 0.004) and other diseases ( MD = 8.53, 95% CI was 6.26-10.80, P<0.000 01). Increased NLR had predictive value for the occurrence of AKI in studies with a sample size of ≤ 300 cases ( MD = 6.02, 95% CI was 4.90-7.14, P <0.000 01) and > 300 cases ( MD = 1.32, 95% CI was 0.61-2.03, P = 0.000 3). There was no significant publication bias in the included studies assessed by funnel plots. Conclusion:NLR is an important predictive tool for AKI.

Unravelling the effect of sulfur vacancies on the electronic structure of the MoS2 crystal.

Molybdenum disulfide (MoS2) is one of the two-dimensional layered semiconductor transition metal dichalcogenides (TMDCs) with great potential in electronics, optoelectronics, and spintronic devices. Sulfur vacancies in MoS2 are the most prevalent defects. However, the effect of sulfur vacancies on the electronic structure of MoS2 is still in dispute. Here we experimentally and theoretically investigated the effect of sulfur vacancies in MoS2. The vacancies were intentionally introduced by thermal annealing of MoS2 crystals in a vacuum environment. Angle-resolved photoemission spectroscopy (ARPES) was used directly to observe the electronic structure of the MoS2 single crystals. The experimental result distinctly revealed the appearance of an occupied defect state just above the valence band maximum (VBM) and an upward shift of the VBM after creating sulfur vacancies. In addition, density functional theory (DFT) calculations also confirmed the existence of the occupied defect state close to the VBM as well as two deep unoccupied states induced by the sulfur vacancies. Our results provide evidence to contradict that sulfur vacancies indicate the origin of n-type behaviour in MoS2. This work provides a rational strategy for tuning the electronic structures of MoS2.

Role of carrier-transfer in the optical nonlinearity of graphene/Bi2Te3 heterojunctions.

Two-dimensional (2D) topological insulators (TIs) have attracted a lot of attention owing to their striking optical nonlinearity. However, the ultra-low saturable intensity (SI) of TIs resulting from the bulk conduction band limits their applications, such as in mode-locking solid-state lasers. In this work, through fabricating a graphene/Bi2Te3 heterojunction which combines monolayer graphene and a Bi2Te3 nanoplate, the optical nonlinearities are analyzed. Moreover, the thickness-dependent characteristics are also investigated by varying the thickness of the Bi2Te3 when synthesizing the heterojunctions. Furthermore, with the aid of the estimated junction electron escape time, a model of the photo-excited carrier-transfer mechanism is proposed and used to describe the phenomena of depression of ultra-low saturable absorption (SA) from the Bi2Te3 bulk band. The increased modulation depth of the graphene/Bi2Te3 heterojunction can accordingly be realized in more detail. In addition, a Q-switched solid-state laser operating at 1064 nm with heterojunction saturable absorbers is built up and characterized for validating the proposed model. The laser performance with varied Bi2Te3 thickness, such as pulse duration and repetition rate, agrees quite well with our proposed model. Our work demonstrates the functionality of optical nonlinear engineering by tuning the thickness of the graphene/Bi2Te3 heterojunction and demonstrates its potential for applications.

[High-Frequency Dynamics of Water Quality and Phytoplankton Community in Inflowing River Mouth of Xin'anjiang Reservoir, China].

The tail of the reservoir is the unstable zone regarding water quality and phytoplankton community. Therefore, it is the crucial zone in aquatic ecosystem transitions. To understand the transition characteristics and driving mechanisms of water environment dynamics, high-frequency monitoring of the water environment and phytoplankton community in the tail of a deep and large reservoir, the Xin'anjiang Reservoir in southeast of China, was conducted using a water quality monitoring buoy and three-day interval water sampling during 18 months. Results show clear seasonal thermal and oxygen stratification in the river mouth of the reservoir. The nutrient and chlorophyll-a concentrations also show stratifying phenomena during the thermal stratification period. Heavy rain and inflow quickly consume the stratification. Nutrient concentrations were highly dynamic in the river mouth. The total phosphorus ranges from 0.011 mg·L-1 to 0.188 mg·L-1, and total nitrogen ranges from 0.75 mg·L-1 to 2.76 mg·L-1. Dissolved phosphorus comprised 56% of total phosphorus, and dissolved nitrogen occupied 88% of total nitrogen, respectively. Nutrient concentrations were influenced strongly by rainfall intensity and inflow rate. Total phosphorus and nitrogen concentrations were significantly related to the three-day accumulated rainfall. Nutrient concentrations in the flood season (March to June) were significantly higher than in the non-flood season (P<0.001). Seasonal phytoplankton proliferation also significantly influenced by total phosphorus concentration. The phytoplankton community changes significantly with seasons and flood events. Bacillariophytea was generally dominant throughout the year, with the predominant genus of Fragilaria spp., Cyclotella spp., Synedra spp., and Melosira spp. Cyanophyta biomass peaked in July, August, and September, with the dominant genus of Aphanizomenon spp., Microcystis spp., and Oscillatoria spp. Apart from the high temperature, storm inflow events also triggered Cyanophyta proliferation. The proliferation of Chlorophyta was similar to Cyanophyta, with the predominant genus of Pediastrum spp. and Closterium spp.. While the Cryptophyta biomass peaked during March to May, with the predominant genus of Cryptomonas spp.. Redundancy analysis shows that the influence factors of phytoplankton community dynamics include the inflow rate, temperature, water level, water transparency, total nitrogen, total phosphorus, and nitrogen to phosphorus ratio. The meteorological and hydrological factors were major factors for phytoplankton dynamics during later autumn and winter, while the nutrient will be the co-driving factors of phytoplankton community dynamics during summer and early autumn. The research confirmed the huge influence of the intensity rainfall event on the water environment in reservoirs and described the key environmental conditions for phytoplankton community dynamics. The research is useful for the design of the monitoring and forecasting system for water safety in drinking water source reservoirs.

Ischemic Postconditioning Alleviates Intestinal Ischemia-Reperfusion Injury by Enhancing Autophagy and Suppressing Oxidative Stress through the Akt/GSK-3ß/Nrf2 Pathway in Mice.

AIMS: Ischemic postconditioning (IPO) has a strong protective effect against intestinal ischemia-reperfusion (IIR) injury that is partly related to autophagy. However, the precise mechanisms involved are unknown. METHODS: C57BL/6J mice were subjected to unilateral IIR with or without IPO. After 45 min ischemia and 120 min reperfusion, intestinal tissues and blood were collected for examination. HE staining and Chiu's score were used to evaluate pathologic injury. We test markers of intestinal barrier function and oxidative stress. Finally, we used WB to detect the expression of key proteins of autophagy and the Akt/GSK-3ß/Nrf2 pathway. RESULTS: IPO significantly attenuated IIR injury. Expression levels of LC3 II/I, Beclin-1, and p62 were altered during IIR, indicating that IPO enhanced autophagy. IPO also activated Akt, inhibited GSK-3ß/Nrf2 pathway. CONCLUSION: Our study indicates that IPO can ameliorate IIR injury by evoking autophagy, activating Akt, inactivating GSK-3ß, and activating Nrf2. These findings may provide novel insights for the alleviation of IIR injury.ß/Nrf2 pathway.

Endoplasmic reticulum stress induces liver cells apoptosis after brain death by suppressing the phosphorylation of protein phosphatase 2A.

The present study aimed to investigate whether brain death (BD) induces the activation of endoplasmic reticulum stress (ERS) and protein phosphatase 2A (PP2A), and reveal the possible association with BD­induced liver cell apoptosis. A total of 30 healthy adult male Sprague­Dawley rats were randomized into three groups: Sham­operated group (S), BD group and 4­phenylbutyric acid group (BD + 4­PBA), with 10 rats in each group. All rats were anesthetized. The model of BD was established by inflating a balloon catheter that was placed into the extradural space after anesthesia. 4­PBA was administered via an intraperitoneal injection when the BD model was established. Anesthesia of the S group of rats was maintained for 6 h. Liver tissues were harvested after 6 h of BD. HE staining was used to evaluate the damage of liver. Terminal deoxynucleotidyl transferase­mediated 2'­deoxyuridine 5'­triphosphate nick­end labeling staining was used to observe the apoptosis of liver cells. Activation of ERS and PP2A was examined by western blotting and immunohistochemical staining. We reported that the apoptosis of liver cells after BD was significantly promoted than in the S group. Activation of ERS and PP2A was induced in the BD group when compared with S group. Phosphorylation of PP2A was suppressed in BD group. Application of 4­PBA decreased the activation of ERS and apoptosis rate compared with the BD group. In addition, activation of PP2A in the BD + 4­PBA group was decreased due to the reduction of PP2A phosphorylation compared with the BD group, but the levels were higher than in the S group. (P<0.05). In summary, our results indicated that BD induced ERS, then activated PP2A by suppressing the phosphorylation of PP2A, resulting in the apoptosis of liver cells.

Effect and mechanism of total glucosides of Paeoniae Radix Alba on combined model of chemical liver injury and liver yin deficiency syndrome in rats / 中草药

Objective: Based on the establishment of experimental model of liver yin deficiency syndrome, the effects of total glucosides of Paeoniae Radix Alba on the syndrome model of liver yin deficiency syndrome in rats with chemical liver injury were studied. Methods: SPF male Sprague-Dawley rats weighing (200 ± 20) g, after adaptive feeding, were randomly divided into control group, model group, Yi Guan Jian group, and total glycosides of Paeoniae Radix Alba group. Except the control group, the rats in the other groups were intraperitoneally injected with 20% CCl4 olive oil solution, and then ig treated with Aconiti Lateralis Radix Praeparata, Zingiberis Rhizoma and Cinnamomi Cortex to establish liver yin deficiency syndrome model. The Yi Guan Jian group and the total glucoside of Paeoniae Radix Alba group were administered at the same time, once a day for 6 weeks. After 6 weeks, the body weight and anal temperature of the rats were measured, and the general state was observed. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), cyclic adenosine monophosphate (cAMP), cyclic guanosine monophosphate (cGMP), 6-keto-prostaglandin F1α (6-keto-PGF1α), plasma thrombosis content of B2 (TXB2), laminin (LN) and hyaluronic acid (HA) were measured, and the activity of liver tissue interleukin-6 (IL-6), IL-10, and tumor necrosis factor (TNF-α) were measured. The expression levels of phosphatidylinositol kinase (PI3k) mRNA, protein kinase B (Akt) mRNA and protein were determined and livers were taken for pathological examination of HE. Results: Compared with the model group, the scores of the total glucosides of Paeoniae Radix Alba group were significantly increased (P < 0.05), the body weight was significantly increased (P < 0.05), and the serum ALT and AST levels were significantly decreased (P < 0.01, 0.001). The cAMP/cGMP ratio was increased significantly (P < 0.01). The LN and HA of the liver tissue of the total glycosides group were significantly decreased (P < 0.05, 0.001). The content of TNF-α and IL-6 was decreased significantly (P < 0.001), the expression level of Akt protein was decreased significantly (P < 0.05), the expression of PI3K and Akt mRNA was decreased significantly (P < 0.05, 0.001), and liver pathological sections were improved. Conclusion: The extract of Paeoniae Radix Alba has the effect of protecting liver injury with yin deficiency syndrome, which may be the material basis of supplement liver yin of Paeoniae Radix Alba. Its mechanism of action may be related to anti-inflammatory, alleviate microcirculatory disorders, and regulate the balance of cytokines IL-6 and IL-10 by inhibiting the PI3K-Akt pathway.

Study on efficacy and safety of Tong-luo Qu-tong plaster treatment for knee osteoarthritis: study protocol for a randomized, double-blind, parallel positive controlled, multi-center clinical trial.

BACKGROUND: Knee osteoarthritis (KOA) is a common chronic musculoskeletal disorder that seriously affects quality of life. Patients with KOA frequently develop one or more of the following typical symptoms: joint pain, stiffness, joint friction noise and impaired functionality. Traditional Chinese medicine (TCM) has been shown to have a superior effect and a particular advantage in the treatment of KOA; among TCM, the Tong-luo Qu-tong plaster is the convenient and most commonly used method in China to improve symptoms including pain, stiffness and limited mobility in patients with KOA, as it causes few adverse effects. But there is a lack of high-quality clinical evidences to support the therapeutic effect that Chinese adhesive plaster can have in relieving pain and stiffness. The purpose of this study will be to evaluate the efficacy and safety of Tong-luo Qu-tong plaster in patients with KOA. METHODS/DESIGN: This study will be a randomized, double-blind, parallel positive controlled, multi-center clinical trial, a non-inferiority trial design was adopted. A total of 2000 participants older than 40 years, with KOA, will be randomly allocated into an experimental group (n = 1500) and a control group (n = 500). All participants will receive a conventional conservative treatment lasting for 14 days as two courses, once daily. Tong-luo Qu-tong plaster will be administered externally to participants in the experimental group, while the control group will receive a Qi-zheng Xiao-tong plaster. The outcome of the total Western Ontario and McMaster Universities Arthritis Index scores, TCM syndrome quantitative score and visual analog scale scores will be measured during the assessment visits (baseline and 1-week and 2-week follow up). In addition, adverse events related to clinical symptoms and signs and results of laboratory tests will be documented during the clinical trials. DISCUSSION: This study will provide reliable evidence of the effectiveness and safety of Tong-luo Qutong plaster in patients with KOA. If the results are favorable, it is expected that the patients with KOA will benefit from this study, many patients may have a good alternative treatment for KOA. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT03309501 . Registered on 8 November 2017.