Tumor necrosis factor mediates the impact of PM2.5 on bone mineral density: Inflammatory proteome Mendelian randomization and colocalization analyses.

To assess the causal effect of particulate matter 2.5 (PM2.5) on human bone mineral density (BMD) and to explore the possible mechanism and proportion mediated by inflammation-related protein. The genetic correlation between PM2.5 and BMD was assessed using the Linkage Disequilibrium Score (LDSC), and the causal effect between PM2.5 and BMD was assessed by two-sample Mendelian randomization (TSMR). A 2-step Mendelian randomization (MR) approach was employed to evaluate the potential role of inflammation-associated protein as the mediator in the causal association between PM2.5 and BMD. The multivariate Mendelian randomization (MVMR) study was designed to perform mediation analyses, exclude possible confounders and calculate the proportion of mediation. Subsequently, we used Bayesian colocalization analysis to consolidate the MR results. Finally, using drug-target MR design, we evaluated the potential repurposing of tumor necrosis factor (TNF) inhibitors for the treatment of osteoporosis (OP). The results of the analyses show that BMD is negatively influenced by PM2.5 (Inverse variance weighted [IVW] beta [ß] = -0.288, 95% confidence interval [CI]: -0.534 - -0.042, P < 0.05). PM2.5 has a positive causal association with TNF (IVW ß = 1.564, 95% CI: 0.155 - 2.973, P < 0.05) and a negative causal association with protachykinin-1 (TAC-1) (IVW ß = -1.654, 95% CI: -3.063 - -0.244, P < 0.05). TNF has a negative causal association with BMD (Wald ratio ß = -0.082, 95% CI: -0.165 - 0.000, P < 0.05) and TAC-1 has a positive causal association with BMD (IVW ß = 0.042, 95% CI: 0.007 - 0.077, P < 0.05). After adjusting TNF and TAC-1, PM2.5 has no causal association with BMD (IVW ß = -0.200, 95% CI: -0.579 - 0.179, P > 0.05). After adjusting PM2.5 and TAC-1, there was still a negative causal association between TNF and BMD (IVW ß = -0.089, 95% CI: -0.166 - -0.012, P < 0.05). In the final drug-target MR study, the protective effect of TNF/TNF receptor 1 (TNFR1) inhibition on BMD was observed. For every 10% decrease of circulating C-reactive protein (CRP) achieved by TNF/TNF receptor 1 (TNFR1) blockade, ß was 0.540 (95% CI: 0.040-1.040) for BMD. We found a negative causal association between PM2.5 and BMD and that causal association was mediated by TNF. The results of drug-target MR do support TNFR1 as a promising target for OP prevention among the general population.

Mendelian-randomization study reveals causal relationships between nitrogen dioxide and gut microbiota.

Exposure to nitrogen dioxide might potentially change the makeup and operation of gut microbes. Nitrogen dioxide data was procured from the IEU Open GWAS (N = 456 380). Subsequently, a two-sample Mendelian randomization study was executed, utilizing summary statistics of gut microbiota sourced from the most expansive available genome-wide association study meta-analysis, conducted by the MiBioGen consortium (N = 13 266). The causal relationship between nitrogen dioxide and gut microbiota was determined using inverse variance weighted, maximum likelihood, MR-Egger, Weighted Median, Weighted Model, Mendelian randomization pleiotropy residual sum and outlier, and constrained maximum likelihood and model averaging and Bayesian information criterion. The level of heterogeneity of instrumental variables was quantified by utilizing Cochran's Q statistic. The colocalization analysis was used to examine whether nitrogen dioxide and the identified gut microbiota shared casual variants. Inverse variance weighted estimate suggested that nitrogen dioxide was causally associated with Akkermansia (ß = -1.088, 95% CI: -1.909 to -0.267, P = 0.009). In addition, nitrogen dioxide presented a potential association with Bacteroides (ß = -0.938, 95% CI: -1.592 to -0.284, P = 0.005), Barnesiella (ß = -0.797, 95% CI: -1.538 to -0.055, P = 0.035), Coprococcus 3 (ß = 1.108, 95% CI: 0.048-2.167, P = 0.040), Eubacterium hallii group (E. hallii) (ß = 0.776, 95% CI: 0.090-1.463, P = 0.027), Holdemania (ß = -1.354, 95% CI: -2.336 to -0.372, P = 0.007), Howardella (ß = 1.698, 95% CI: 0.257-3.139, P = 0.021), Olsenella (ß = 1.599, 95% CI: 0.151-3.048, P = 0.030) and Sellimonas (ß = -1.647, 95% CI: -3.209 to -0.086, P = 0.039). No significant heterogeneity of instrumental variables or horizontal pleiotropy was found. The associations of nitrogen dioxide with Akkermansia (PH4 = 0.836) and E. hallii (PH4 = 0.816) were supported by colocalization analysis. This two-sample Mendelian randomization study found that increased exposure to nitrogen dioxide had the potential to impact the human gut microbiota.

The genetic background determines material-induced bone formation through the macrophage-osteoclast axis.

Osteoinductive materials are characterized by their ability to induce bone formation in ectopic sites. Thus, osteoinductive materials hold promising potential for repairing bone defects. However, the mechanism of material-induced bone formation remains unknown, which limits the design of highly potent osteoinductive materials. Here, we demonstrated a genetic background link among macrophage polarization, osteoclastogenesis and material-induced bone formation. The intramuscular implantation of an osteoinductive material in FVB/NCrl (FVB) mice resulted in more M2 macrophages at week 1, more osteoclasts at week 2 and increased bone formation after week 4 compared with the results obtained in C57BL/6JOlaHsd (C57) mice. Similarly, in vitro, with a greater potential to form M2 macrophages, monocytes derived from FVB mice formed more osteoclasts than those derived from C57 mice. A transcriptomic analysis identified Csf1, Cxcr4 and Tgfbr2 as the main genes controlling macrophage-osteoclast coupling, which were further confirmed by related inhibitors. With such coupling, macrophage polarization and osteoclast formation of monocytes in vitro successfully predicted in vivo bone formation in four other mouse strains. Considering material-induced bone formation as an example of acquired heterotopic bone formation, the current findings shed a light on precision medicine for both bone regeneration and the treatment of pathological heterotopic bone formation.

Biocompatible Material-Based Flexible Biosensors: From Materials Design to Wearable/Implantable Devices and Integrated Sensing Systems.

Human beings have a greater need to pursue life and manage personal or family health in the context of the rapid growth of artificial intelligence, big data, the Internet of Things, and 5G/6G technologies. The application of micro biosensing devices is crucial in connecting technology and personalized medicine. Here, the progress and current status from biocompatible inorganic materials to organic materials and composites are reviewed and the material-to-device processing is described. Next, the operating principles of pressure, chemical, optical, and temperature sensors are dissected and the application of these flexible biosensors in wearable/implantable devices is discussed. Different biosensing systems acting in vivo and in vitro, including signal communication and energy supply are then illustrated. The potential of in-sensor computing for applications in sensing systems is also discussed. Finally, some essential needs for commercial translation are highlighted and future opportunities for flexible biosensors are considered.

The nano-windmill exerts superior anti-inflammatory effects via reducing choline uptake to inhibit macrophage activation.

Macrophages' activation plays a central role during the development and progression of inflammation, while the regulation of metabolic reprogramming of macrophages has been recently identified as a novel strategy for anti-inflammatory therapies. Our previous studies have found that tetrahedral framework nucleic acid (tFNA) plays a mild anti-inflammatory effect by inhibiting macrophage activation, but the specific mechanism remains unclear. Here, by metabolomics and RNA sequencing, choline uptake is identified to be significantly repressed by decreased slc44a1 expression in tFNA-treated activated macrophages. Inspired by this result, combined with the excellent delivery capacities of tFNA, siR-slc44a1 is loaded into the tFNA to develop a new tFNA-based small interfering RNA (siRNA) delivery system named 'nano-windmill,' which exhibits a synergetic role by targeting slc44a1, finally blowing up the anti-inflammatory effects of tFNA to inhibit macrophages activation via reducing choline uptake. By confirming its anti-inflammatory effects in chronic (periodontitis) and acute (sepsis) inflammatory disease, the tFNA-based nanomedicine developed for inflammatory diseases may provide broad prospects for tFNA upgrading and various biological applications such as anti-inflammatory.

Mitochondrial Calcium Ion Nanogluttons Alleviate Periodontitis via Controlling mPTPs.

The mitochondrial permeability transition (mPT) directly affects mitochondrial function in macrophages. Under inflammatory conditions, mitochondrial calcium ion (mitoCa2+ ) overload triggers the persistent opening of mPT pores (mPTPs), further aggravating Ca2+ overload and increasing reactive oxygen species (ROS) to form an adverse cycle. However, there are currently no effective drugs targeting mPTPs to confine or unload excess Ca2+ . It is novelly demonstrated that the initiation of periodontitis and the activation of proinflammatory macrophages depend on the persistent overopening of mPTPs, which is mainly triggered by mitoCa2+ overload and facilitates further mitochondrial ROS leakage into the cytoplasm. To solve the above problems, mitochondrial-targeted "nanogluttons" with PEG-TPP conjugated to the surface of PAMAM and BAPTA-AM encapsulated in the core are designed. These nanogluttons can efficiently "glut" Ca2+ around and inside mitochondria to effectively control the sustained opening of mPTPs. As a result, the nanogluttons significantly inhibit the inflammatory activation of macrophages. Further studies also unexpectedly reveal that the alleviation of local periodontal inflammation in mice is accompanied by diminished osteoclast activity and reduced bone loss. This provides a promising strategy for mitochondria-targeted intervention in inflammatory bone loss in periodontitis and can be extended to treat other chronic inflammatory diseases associated with mitoCa2+ overload.

Hypoxia Drives Material-Induced Heterotopic Bone Formation by Enhancing Osteoclastogenesis via M2/Lipid-Loaded Macrophage Axis.

Heterotopic ossification (HO) is a double-edged sword. Pathological HO presents as an undesired clinical complication, whereas controlled heterotopic bone formation by synthetic osteoinductive materials shows promising therapeutic potentials for bone regeneration. However, the mechanism of material-induced heterotopic bone formation remains largely unknown. Early acquired HO being usually accompanied by severe tissue hypoxia prompts the hypothesis that hypoxia caused by the implantation coordinates serial cellular events and ultimately induces heterotopic bone formation in osteoinductive materials. The data presented herein shows a link between hypoxia, macrophage polarization to M2, osteoclastogenesis, and material-induced bone formation. Hypoxia inducible factor-1α (HIF-1α), a crucial mediator of cellular responses to hypoxia, is highly expressed in an osteoinductive calcium phosphate ceramic (CaP) during the early phase of implantation, while pharmacological inhibition of HIF-1α significantly inhibits M2 macrophage, subsequent osteoclast, and material-induced bone formation. Similarly, in vitro, hypoxia enhances M2 macrophage and osteoclast formation. Osteoclast-conditioned medium enhances osteogenic differentiation of mesenchymal stem cells, such enhancement disappears with the presence of HIF-1α inhibitor. Furthermore, metabolomics analysis reveals that hypoxia enhances osteoclastogenesis via the axis of M2/lipid-loaded macrophages. The current findings shed new light on the mechanism of HO and favor the design of more potent osteoinductive materials for bone regeneration.

Development of an innovative nomogram of risk factors to predict postoperative recurrence of gastrointestinal stromal tumors.

BACKGROUND: There are many staging systems for gastrointestinal stromal tumors (GISTs), and the risk indicators selected are also different; thus, it is not possible to quantify the risk of recurrence among individual patients. AIM: To develop and internally validate a model to identify the risk factors for GIST recurrence after surgery. METHODS: The least absolute shrinkage and selection operator (LASSO) regression model was performed to identify the optimum clinical features for the GIST recurrence risk model. Multivariable logistic regression analysis was used to develop a prediction model that incorporated the possible factors selected by the LASSO regression model. The index of concordance (C-index), calibration curve, receiver operating characteristic curve (ROC), and decision curve analysis were used to assess the discrimination, calibration, and clinical usefulness of the predictive model. Internal validation of the clinical predictive capability was also evaluated by bootstrapping validation. RESULTS: The nomogram included tumor site, lesion size, mitotic rate/50 high power fields, Ki-67 index, intracranial necrosis, and age as predictors. The model presented perfect discrimination with a reliable C-index of 0.836 (95%CI: 0.712-0.960), and a high C-index value of 0.714 was also confirmed by interval validation. The area under the curve value of this prediction nomogram was 0.704, and the ROC result indicated good predictive value. Decision curve analysis showed that the predicting recurrence nomogram was clinically feasible when the recurrence rate exceeded 5% after surgery. CONCLUSION: This recurrence nomogram combines tumor site, lesion size, mitotic rate, Ki-67 index, intracranial necrosis, and age and can easily predict patient prognosis.

TCM Constitution Analysis Method Based on Parallel FP-Growth Algorithm in Hadoop Framework.

This work is devoted to establishing a comparatively accurate classification model between symptoms, constitutions, and regimens for traditional Chinese medicine (TCM) constitution analysis to provide preliminary screening and decision support for clinical diagnosis. However, for the analysis of massive distributed medical data in a cloud platform, the traditional data mining methods have the problems of low mining efficiency and large memory consumption, and long tuning time, an association rules method for TCM constitution analysis (ARA-TCM) is proposed that based on FP-growth algorithm and the open-source distributed file system in Hadoop framework (HDFS) to make full use of its powerful parallel processing capability. Firstly, the proposed method was used to explore the association rules between the 9 kinds of TCM constitutions and symptoms, as well as the regimen treatment plans, so as to discover the rules of typical clinical symptoms and treatment rules of different constitutions and to conduct an evidence-based medical evaluation of TCM effects in constitution-related chronic disease health management. Secondly, experiments were applied on a self-built TCM clinical records database with a total of 30,071 entries and it is found that the top three constitutions are mid constitution (42.3%), hot and humid constitution (31.3%), and inherited special constitution (26.2%), respectively. What is more, there are obvious promotions in the precision and recall rate compared with the Apriori algorithm, which indicates that the proposed method is suitable for the classification of TCM constitutions. This work is mainly focused on uncovering the rules of "disease symptoms constitution regimen" in TCM medical records, but tongue image and pulse signal are also very important to TCM constitution analysis. Therefore, this additional information should be considered into further studies to be more in line with the actual clinical needs.

A concise access to bridged [2,2,1] bicyclic lactones with a quaternary stereocenter via stereospecific hydroformylation.

Chiral bridged [2,2,1] bicyclic lactones are privileged structural units in pharmaceutics and bioactive nature products. However, the synthetic methods for these compounds are rare. Here we report an efficient method for enantioselective construction of bridged [2,2,1] bicyclic lactones bearing a quaternary stereocenter via Rh-catalyzed asymmetric hydroformylation/intramolecular cyclization/pyridium chlorochromate (PCC) oxidation. By employing a hybrid phosphine-phosphite chiral ligand, a series of cyclopent-3-en-1-ols are transformed into corresponding γ-hydroxyl aldehydes with specific syn-selectivity. Then, hemiacetals form in situ and oxidation with PCC in one-pot affords bridged [2,2,1] bicyclic lactones in high yields and excellent enantiomeric excess. Replacing the hydroxyl group by an ester group, cyclopentanecarbaldehydes with a chiral all-carbon quaternary stereocenter in the γ-position can be generated efficiently.

Stacked Two-Dimensional MXene Composites for an Energy-Efficient Memory and Digital Comparator.

Two-dimensional MXene has enormous potential for application in industry and academia owing to its surface hydrophilicity and excellent electrochemical properties. However, the application of MXene in optoelectronic memory and logical computing is still facing challenges. In this study, an optoelectronic resistive random access memory (RRAM) based on silver nanoparticles (Ag NPs)@MXene-TiO2 nanosheets (AMT) was prepared through a low-cost and facile hydrothermal oxidation process. The fabricated device exhibited a typical bipolar switching behavior and controllable SET voltage. Furthermore, we successfully demonstrated a 4-bit in-memory digital comparator with AMT RRAMs, which can replace five logic gates in a traditional approach. The AMT-based digital comparator may open the door for future integrated functions and applications in optoelectronic data storage and simplify the complex logic operations.

Serial cellular events in bone formation initiated by calcium phosphate ceramics.

To better understand the biological mechanisms triggered by osteoinductive materials in vivo, we evaluated the timeline of cellular responses to osteoinductive materials subcutaneously implanted in FVB mice. More F4/80-positive macrophages were present in osteoinductive tri-CaP ceramic (TCP) with submicron surface topography (TCPs) than non-osteoinductive TCP with micron surface topography (TCPb) at week 1. Moreover, TCPs (but not TCPb) significantly enhanced osteoclastogenesis, and induced macrophages to polarize from M1 to M2 in the first week. The time sequence and relevance of macrophages and osteoclasts responses involved in bone formation was then evaluated through peri-implant injection of specific chemicals in mice implanted with osteoinductive TCPs. Day-1 injection of clodronate liposomes (LipClod) depleted macrophages, inhibited macrophage polarization to M2, blocked osteoclastogenesis and bone formation, while the day-6 injection was less effective. Anti-RANKL antibody (aRANKL) did not affect macrophage colonization but inhibited osteoclastogenesis. Injection of aRANKL before week 2 aborted bone formation in TCPs, while injection at week 4 partially inhibited bone formation. The overall data show that following ectopic implantation, osteoinductive materials allow macrophage colonization in hours to days, macrophage polarization to M2 in days (within 7 days), osteoclastogenesis in weeks (e.g. in 2 weeks) and bone formation thereafter (after 4 weeks). The serial cellular events verified herein bring a new insight on material-induced bone formation and pave the way to further explore the mechanisms triggered by osteoinductive materials. STATEMENT OF SIGNIFICANCE: A series of key cellular events triggered by osteoinductive calcium phosphate ceramic was revealed: macrophages colonized within hours to days, polarization of M2 macrophages occurred within 7 days, osteoclastogenesis mainly occurred in weeks (e.g. in 2 weeks) and bone formation finally arose thereafter (after 4 weeks). Moreover, such time sequence of cellular events was confirmed with specific chemicals (clodronate liposomes and anti-RANKL antibody). The findings verified herein bring a new insight on material-induced bone formation and pave the way to further explore the mechanisms triggered by osteoinductive materials.

Inorganic Perovskite Quantum Dot-Based Strain Sensors for Data Storage and In-Sensor Computing.

Although remarkable improvement has been achieved in stretchable strain sensors, challenges still exist in aspects including intelligent sensing, simultaneous data processing, and scalable fabrication techniques. In this work, a strain-sensitive device is presented by fabricating a CsPbBr3 quantum dots (QDs) floating-gate field-effect transistor (FET) sensing array on thin polyimide (PI) films. The FET exhibits an excellent on/off ratio (>103) and a large memory window (>2 V). With the introduction of CsPbBr3 QDs as the trapping layer, an additional UV response is obtained because of the photogenerated charge carriers that significantly enhance the source-drain current (IDS) of the device. At each electrical state, the IDS varies with the strains and the sensing range is from compressive +12.5% to tensile -10.8%. Excellent data retainability and mechanical durability demonstrate the high quality and reliability of the fabricated sensors. Furthermore, synapse functions including long-term potentiation (LTP), long-term depression (LTD), etc., are emulated at the device level. Linearity factor changes of LTP/LTD in different sensing scenarios demonstrate the reliability of the device and further confirm the different sensing mechanisms with/without UV illumination. Our results exhibit the potential of transistor-based devices for multifunctional intelligent sensing.

Comparison of clinicopathologic profiles and prognosis of gastric cancer in the upper, middle and lower third of the stomach: A retrospective cohort study.

Gastric cancer (GC) is the fourth most common cancer in the world and the second most common cancer in China. The aim of this study was to investigate the clinicopathologic profiles and prognosis of GC in the upper third (UT), middle third (MT) and low third (LT) of the stomach.Five hundred and forty-two patients with GC resected between January 2010 and January 2014 were retrospectively studied and divided in 3 groups according to cancer location: upper third gastric cancer (UTGC) (n = 62); MTGC (n = 131) and LTGC (n = 349). Clinical and pathological parameters including gender, age, tumor size, macroscopic types, histological types, depth of invasion, lymph node metastasis, venous infiltration and lymph embolism were compared among groups. Overall survival (OS) was calculated based on the aforementioned parameters. Univariate and multivariate survival was analyzed and Cox regression was conducted for each location. The prognostic accuracy was determined using receiver operating characteristic curve analysis.Patients with UTGC was similar to those with MTGC and both were distinct from those with LTGC based on the tumor size, macroscopic types, depth of invasion and 5-year OS. Patients with MTGC were similar to those with LTGC and distinct from UTGC patients based on gender. 5-year OS were lower for patients with UTGC than those with LTGC (P = .001) and were comparable between MTGC and LTGC. No significant differences in 5-year OS were observed between UTGC and MTGC. Cox regression revealed that macroscopic types, depth of invasion and lymph node metastasis were the independent prognostic factors for GC patients regardless of locations. Receiver operating characteristic curve analysis revealed that macroscopic types, depth of invasion and lymph node metastasis were the significantly effective prognosis for the 5-year OS in GC patients regardless of locations.Our results showed that UTGC is distinct from LTGC whereas MTGC shares some characteristics from both UTGC and LTGC.

The synergetic effect of bioactive molecule-loaded electrospun core-shell fibres for reconstruction of critical-sized calvarial bone defect-The effect of synergetic release on bone Formation.

OBJECTIVES: Bone regeneration is a complex process modulated by multiple growth factors and hormones during long regeneration period; thus, designing biomaterials with the capacity to deliver multiple bioactive molecules and obtain sustained release has gained an increasing popularity in recent years. This study is aimed to evaluate the effect of a novel core-shell electrospun fibre loaded with dexamethasone (DEX) and bone morphogenetic protein-2 (BMP-2) on bone regeneration. MATERIALS AND METHODS: The core-shell electrospun fibres were fabricated by coaxial electrospinning technology, which were composed of poly-D, L-lactide (PLA) shell and poly (ethylene glycol) (PEG) core embedded with BMP-2 and DEX-loaded micelles. Morphology, hydrophilicity, gradation, release profile of BMP-2 and DEX, and cytological behaviour on bone marrow mesenchymal stem cells (BMSCs) were characterized. Furthermore, the effect on bone regeneration was evaluated via critical-sized calvarial defect model. RESULTS: The electrospun fibres were featured by the core-shell fibrous architecture and a suitable degradation rate. The sustained release of DEX and BMP-2 was up to 562 hours. The osteogenic gene expression and calcium deposition of BMSCs were significantly enhanced, indicating the osteoinduction capacity of electrospun fibres. This core-shell fibre could accelerate repair of calvarial defects in vivo via synergistic effect. CONCLUSIONS: This core-shell electrospun fibre loaded with DEX and BMP-2 can act synergistically to enhance bone regeneration, which stands as a strong potential candidate for repairing bone defects.

Macrophage polarization plays roles in bone formation instructed by calcium phosphate ceramics.

To investigate the roles of macrophages in material-instructed bone formation, two calcium phosphate (TCP) ceramics with the same chemistry but various scales of surface topography were employed in this study. After being implanted subcutaneously in FVB mice for 8 weeks, TCPs (TCP ceramics with submicron surface topography) gave rise to bone formation, while TCPb (TCP ceramics with micron surface topography) did not, showing the crucial role of surface topography scale in material-instructed bone formation. Depletion of macrophages with liposomal clodronate (LipClod) blocked such bone formation instructed by TCPs, confirming the role of macrophages in material-instructed bone formation. Macrophage cells (i.e. RAW 264.7 cells) cultured on TCPs in vitro polarized to tissue repair macrophages as evidenced by gene expression and cytokine production, while polarizing to pro-inflammatory macrophages on TCPb. Submicron surface topography of TCP ceramics directed macrophage polarization via PI3K/AKT pathways with the synergistic regulation of integrin ß1. Finally, the tissue repair macrophage polarization on TCPs resulted in osteogenic differentiation of mesenchymal stem cells in vitro. At early implantation in FVB mice, TCPs recruited more macrophages which polarized towards tissue repair macrophages with time. The present data demonstrate the important roles of macrophage polarization in bone formation instructed by calcium phosphate ceramics.

Regime shift in fish assemblage structure in the Yangtze River following construction of the Three Gorges Dam.

Dams have well-documented ecological impacts on downstream river segments; however, long-term impacts of river impoundment have rarely been investigated in upstream reaches. Using data from long-term standardized surveys, we analyzed temporal changes in fish assemblages in the Yangtze River upstream of the Three Gorges Dam (TGD) before, during and after its construction. Our analysis indicated fish assemblage regime shifts in the two closer reaches in 2008, in accordance with the filling to 172.5 m in 2008; and in the other reach, farthest from the TGD, in 2011, indicating timing of the effects being related to distance. These shifts were evident in relative abundance of native fish species rather than non-native species and have altered community structures and functional groups. Relative abundance of the lotic guilds declined in the two closer reaches, but increased in the farthest. Invertivores declined, but piscivores and opportunistic life-history strategists increased in all reaches. We conclude that construction of TGD had led to significant changes in species distributions influenced by species functional traits. Our findings emphasize the need for long-term monitoring of fish assemblages before and after dam construction in order to understand ecological responses to hydrological changes for effective resource management in regulated rivers.

[Research progress in the mechanism of protein factors in regulating bone remodeling].

Objective: To review the role and mechanism of protein factors in bone remodeling, and provides theoretical basis for further elucidating the pathogenesis and clinical treatment of bone-related diseases. Methods: The relevant research results at home and abroad in recent years were extensively consulted, analyzed, and summarized. Results: Bone remodeling is an important physiological process to maintain bone homeostasis. Protein, as an important stimulator in bone remodeling, regulates the balance between bone resorption and bone formation. Conclusion: At present, the research on the mechanism of protein in bone remodeling is insufficient. Therefore, it is necessary to further study the specific time, process, and interaction network of protein in bone remodeling, and to confirm its mechanism in bone remodeling, so as to reveal and treat the pathogenesis of bone-related diseases.

Effects of water temperature and discharge on natural reproduction time of the Chinese sturgeon, Acipenser sinensis, in the Yangtze River, China and impacts of the impoundment of the Three Gorges Reservoir.

Chinese sturgeon, Acipenser sinensis, is a critically endangered anadromous fish species spawning in the Yangtze River of China during October and November. In this study, we analyzed the effects of hydrological factors, such as water temperature and discharge, on the natural reproduction time of the Chinese sturgeon and evaluated the impact of the impoundment of the Three Gorges Reservoir (TGR) based on our survey data from 1998 to 2011. The results showed that the first spawning dates were significantly (P < 0.05) correlated with the date of water temperature reaching 20°C (20°C WT dates), October mean discharge (Oct. discharge), and the discharge change from October to November (Oct-Nov Δdischarge). Regression analysis suggested that one day delay of 20°C WT dates could postpone the first spawning date by 0.673 days. A discharge increase of 1000 m(3)s(-1) in October could bring forward the first spawning date by two days. Our results also indicated that the impoundment of the TGR had delayed the first spawning time due to water temperature lag and flow regulation. We suggest the following ecological regulations in order to facilitate conservation of the Chinese sturgeon: to eliminate water temperature lag by regulating water temperature downstream of the Three Gorges Dam (TGD), to enhance water discharge downstream in October, and to complete impoundment before October.