High-latitude invasion and environmental adaptability of the freshwater mussel Limnoperna fortunei in Beijing, China.

The invasive freshwater mussel Limnoperna fortunei (Dunker, 1857) has spread widely throughout Asia and South America, especially via interbasin water diversion and navigation. The middle route of the South-to-North Water Transfer Project (SNWTP), whose terminal is Beijing, has diverted more than 60 billion m3 of water from the Yangtze River Basin to Northern China since December 2014. L. fortunei has spread north to Beijing along the SNWTP, biofouling its channels and tunnels. To determine the status of L. fortunei's invasion in Beijing, we systematically inspected the water bodies receiving southern water, including all branches of the SNWTP, water treatment plants, lakes, reservoirs, and rivers. We measured the densities of adults and veligers of L. fortunei and conducted eDNA analyses of water samples. A generalized linear model and canonical correspondence analysis were adopted to investigate the correlations between environmental (e.g., water temperature, conductivity, pH, total nitrogen, and phosphorus) and biological (e.g., chlorophyll a, plankton density, and community composition) variables and the densities of adults and veligers of L. fortunei. Water temperature is the most important factor in determining the densities of D-shaped and pediveliger veligers, with explanatory variable contributions of 56.2% and 43.9%, respectively. The pH affects the densities of D-shaped, umbonated, and pediveliger veligers. The density of plantigrade veligers is negatively correlated with the conductivity and positively correlated with the concentration of chlorophyll a. Canonical correspondence analysis shows a weak correlation between the dominant phytoplankton taxa and the density of veligers. The densities of D-shaped, umbonated, and pediveliger veligers are positively correlated with the density of small phytoplankton (12.54 ± 4.33 µm), and the density of plantigrade veligers is positively correlated with the density of large (16.12 ± 5.96 µm) phytoplankton. The density of planktonic veligers is well correlated with local abiotic variables, and that of plantigrade veligers is less correlated with local abiotic variables. This finding implies that controlling early-stage veligers by altering water temperature, pH, and food size might effectively control the establishment of further L. fortunei colonies.

Trigeminal Ganglion Electrical Stimulation for Trigeminal Nerve Postherpetic Neuralgia: A Retrospective Study.

Purpose: To investigate the clinical outcome of trigeminal ganglion electrical stimulation for the treatment of trigeminal postherpetic neuralgia (TPHN). Patients and Methods: A retrospective analysis of clinical data was performed on six patients who suffered from severe postherpetic neuralgia involving the trigeminal nerve maxillary and mandibular branch. They were admitted under the Pain Management Department of the First Hospital of Shanxi Medical University from July 2022 to February 2023 and underwent trigeminal ganglion electrical stimulation therapy. Visual analogue scale (VAS) scores, pregabalin dosage, pittsburgh sleep quality index (PSQI), self-rating anxiety scale (SAS), and self-rating depression scale (SDS) were recorded before treatment, as well as after treatment at 1, 4, 8, 12, and 24-week. Adverse reactions related to the treatment were also documented. Results: After trigeminal ganglion electrical stimulation therapy, the VAS scores, PSQI scores, anxiety scores, depression scores, and pregabalin dosage of six patients showed significant reductions at 1, 4, 8, 12, and 24 weeks. (P < 0.05). No serious adverse reactions occurred in any of the patients. Conclusion: Trigeminal ganglion electrical stimulation effectively relieved postherpetic neuralgia in the distribution areas of the trigeminal nerve 2 and 3 branches, reduced the dosage of analgesics, improved the quality of sleep, and alleviated anxiety and depression symptoms in patients. Our data suggested that It was a safe and effective clinical.

Shikonin suppresses small cell lung cancer growth via inducing ATF3-mediated ferroptosis to promote ROS accumulation.

Small cell lung cancer (SCLC) is a subtype of lung cancer with a very poor overall survival rate due to its extremely high proliferation and metastasis predilection. Shikonin is an active ingredient extracted from the roots of Lithospermum erythrorhizon, and exerts multiple anti-tumor functions in many cancers. In the present study, the role and underlying mechanism of shikonin in SCLC were investigated for the first time. We found that shikonin effectively suppressed cell proliferation, apoptosis, migration, invasion, and colony formation and slightly induced apoptosis in SCLC cells. Further experiment indicated the shikonin could also induced ferroptosis in SCLC cells. Shikonin treatment effectively suppressed the activation of ERK, the expression of ferroptosis inhibitor GPX4, and elevated the level of 4-HNE, a biomarker of ferroptosis. Both total ROS and lipid ROS were increased, while the GSH levels were decreased in SCLC cells after shikonin treatment. More importantly, our data identified that the function of shikonin was dependent on the up-regulation of ATF3 by performing rescue experiments using shRNA to silence the expression of ATF3, especially in the total and lipid ROS accumulaiton. Xenograft model was established using SBC-2 cells, and the results revealed that shikonin also significantly inhibited tumor growth by inducing ferroptosis. Finally, our data further confirmed that shikonin activated ATF3 transcription by impairing the recruitment of HDAC1 mediated by c-myc on the ATF3 promoter, and subsequently elevating of histone acetylation. Our data documented that shikonin suppressed SCLC by inducing ferroptosis in a ATF3-dependent manner. Shikonin upregulated the expression of ATF3 expression via promoting the histone acetylation by inhibiting c-myc-mediated HDAC1 binding on ATF3 promoter.

Management strategy of the naked carp (Gymnocypris przewalskii) in the Qinghai lake using matrix population modeling.

Naked carp (Gymnocypris przewalskii) is the only fish species commercially harvested in Qinghai Lake, which is the largest inland saltwater lake in China. Multiple ecological stresses such as long-term overfishing, drying-up of riverine inflows, and decreases in spawning habitat caused the naked carp population to decrease from 320,000 tons before the 1950s to only 3000 tons by the early 2000s. We used matrix projection population modeling to quantitatively simulate the dynamics of the naked carp population from the 1950s to the 2020s. Five versions of the matrix model were developed from the field and laboratory information that represented different population states (high but declining, low abundance, very low abundance, initial recovery, pristine). Equilibrium analysis was applied to density-independent versions of the matrices and population growth rate, age composition, and elasticities were compared among versions. Stochastic, density-dependent version of the most recent decade (recovering) version was used to simulate the time-dependent responses to a range of levels of artificial reproduction (addition of age-1 from hatchery) and of the pristine version to simulate combinations of fishing rate and minimum age of harvest. Results showed the major role of overfishing in the population decline and that the population growth rate was most sensitive to the survival of juveniles and the spawning success of early-age adults. Dynamic simulations showed a rapid population response to artificial reproduction when population abundance was low and that if artificial reproduction continues at its current level, then population biomass would reach 75% of its pristine biomass after 50 years. Simulations with the pristine version identified sustainable fishing levels and the importance of protecting the first few ages of maturity. Overall, modeling results showed that artificial reproduction under conditions of no fishing is an effective approach to restoring the naked carp population. Further effectiveness should consider maximizing survival in the months just after release and maintaining genetic and phenotypic diversity. More information on density-dependent growth, survival, and reproduction, as well as on the genetic diversity and growth and migratory behavior (phenotypic variation) of released and native-spawned fish, would help inform management and conservation strategies and practices going forward.

Channel abandonment alters trophic characteristics of highland rivers.

The Qinghai-Tibet Plateau (QTP) serves as a collection of unique ecosystems featured as oligotrophic and hypometabolic conditions, and is particularly vulnerable to threats posed by anthropogenic and natural disturbances. Active fluvial processes on the QTP, especially the lateral migration of rivers and channel abandonment accompanied by variations in the hydrological connectivity, and changes in river geomorphology, intensively modify this highland river-floodplain system. However, little is known about how these processes alter the trophic characteristics of highland river system on earth. In this study, we conducted field investigations on a typical meandering river, the Quanji River (QR), located in the northeastern QTP by sampling macroinvertebrates, surveying trophic sources, and measuring a range of environmental conditions. Based on the collected data, we identified four biotopes for the QR through hierarchical clustering, established the representative food web for each biotope through the allometric diet breadth model, and estimated the biomass storage and flux within food web for each biotope through the biomass balance model. Our results show that the identified biotopes differed markedly in hydrological connectivity. Biotopes 1 and 2, which were in the main river channel represented the condition of high connectivity, Biotope 3 in the open channel represented the median connectivity, while Biotope 4 in the semi-open/closed channel represented the low connectivity. In contrast to the unimodal pattern commonly observed in lowland rivers, indices for the highland QR, including the taxa richness, trophic group richness, biomass flux, biomass transfer efficiency, and trophic stability demonstrated a single-valley response pattern to the hydrological connectivity. We argue that the intermediate disturbance hypothesis still works on highland river ecosystems, whereas the optimal disturbance occurs in the low connectivity rather than median connectivity. We attribute this skewness to the low resistance and resilience of highland macroinvertebrate community in the face of hydrodynamic disturbances brought by flood events, and the biological disturbances from the predation by endemic migratory fish (Gymnocypris przewalskii) in QR. This study reveals that lateral migration and channel abandonment play important roles in highland river systems in the QTP in the context of biological and energetic perspectives and suggests that management strategies for highland rivers should be made different from those of lowland rivers.

High-content screening of active components of Traditional Chinese Medicine inhibiting TGF-ß-induced cell EMT.

The epithelial mesenchymal transition (EMT) has roles in metastasis and invasion during fibrotic diseases and cancer progression. Some Traditional Chinese Medicines (TCMs) have shown inhibitory effects with respect to the EMT. The current study attempted to establish a multiparametric high-content method to screen for active monomeric compounds in TCM with the ability to target cellular EMT by assessing phenotypic changes. A total of 306 monomeric compounds from the MedChemExpress (MCE) compound library were screened by the high-content screening (HCS) system and 5 compounds with anti-EMT activity, including camptothecin (CPT), dimethyl curcumin (DMC), artesunate (ART), sinapine (SNP) and berberine (BER) were identified. To confirm anti-EMT activity, expression of EMT markers was assessed by qRT-PCR and Western blotting, and cell adhesion and migration measured by cell function assays. The results revealed that CPT, DMC, ART, SNP and BER inhibited transforming growth factor-ß1 (TGF-ß1)-induced expression of vimentin and α-SMA, upregulated expression of E-cadherin, increased cell adhesion and reduced cell migration. In summary, by quantifying the cell morphological changes during TGF-ß1-induced EMT through multi-parametric analysis, TCM compounds with anti-EMT activity were successfully screened using the HCS system, a faster and more economical approach than conventional methods.

Swimming behavior and hydrodynamics of the Chinese cavefish Sinocyclocheilus rhinocerous and a possible role of its head horn structure.

The blind troglobite cavefish Sinocyclocheilus rhinocerous lives in oligotrophic, phreatic subterranean waters and possesses a unique cranial morphology including a pronounced supra-occipital horn. We used a combined approach of laboratory observations and Computational Fluid Dynamics modeling to characterize the swimming behavior and other hydrodynamic aspects, i.e., drag coefficients and lateral line sensing distance of S. rhinocerous. Motion capture and tracking based on an Artificial Neural Network, complemented by a Particle Image Velocimetry system to map out water velocity fields, were utilized to analyze the motion of a live specimen in a laboratory aquarium. Computational Fluid Dynamics simulations on flow fields and pressure fields, based on digital models of S. rhinocerous, were also performed. These simulations were compared to analogous simulations employing models of the sympatric, large-eyed troglophile cavefish S. angustiporus. Features of the cavefish swimming behavior deduced from the both live-specimen experiments and simulations included average swimming velocities and three dimensional trajectories, estimates for drag coefficients and potential lateral line sensing distances, and mapping of the flow field around the fish. As expected, typical S. rhinocerous swimming speeds were relatively slow. The lateral line sensing distance was approximately 0.25 body lengths, which may explain the observation that specimen introduced to a new environment tend to swim parallel and near to the walls. Three-dimensional simulations demonstrate that just upstream from the region under the supra-occipital horn the equipotential of the water pressure and velocity fields are nearly vertical. Results support the hypothesis that the conspicuous cranial horn of S. rhinocerous may lead to greater stimulus of the lateral line compared to fish that do not possess such morphology.

Iron Phosphate Nanozyme-Hydrogel with Multienzyme-like Activity for Efficient Bacterial Sterilization.

Pathogenic bacteria infections have posed a threat to human health worldwide. Nanomaterials with natural enzymatic activity provide an opportunity for the development of new antibacterial pathways. We successfully constructed iron phosphate nanozyme-hydrogel (FePO4-HG) with the traits of positive charge and macropores. Interestingly, FePO4-HG displayed not only peroxidase-like activity under acidic bacterial infectious microenvironment but also superoxide dismutase-catalase-like synergistic effects in neutral or weak alkaline conditions, thus protecting normal tissues from the peroxidase-like protocol with exogenous H2O2 damage. Furthermore, the positive charge and macropore structure of FePO4-HG could capture and restrict bacteria in the range of ROS destruction. Obviously, FePO4-HG exhibited excellent antibacterial ability against MRSA and AREC with the assistance of H2O2. Significantly, the FePO4-HG + H2O2 system could efficiently disrupt the bacterial biofilm formation and facilitate the glutathione oxidation process to rapid bacterial death with low cytotoxicity. Moreover, FePO4-HG was unsusceptible to bacterial resistance development in MRSA. Animal experiments showed that the FePO4-HG + H2O2 group could efficiently eliminate the MRSA infection and present excellent wound healing without inflammation and tissue adhesions. With further development and optimization, FePO4-HG has great potential as a new class of antibacterial agents to fight antibiotic-resistant pathogens.

Reprogramming the spleen into a functioning 'liver' in vivo.

OBJECTIVE: Liver regeneration remains one of the biggest clinical challenges. Here, we aim to transform the spleen into a liver-like organ via directly reprogramming the splenic fibroblasts into hepatocytes in vivo. DESIGN: In the mouse spleen, the number of fibroblasts was through silica particles (SiO2) stimulation, the expanded fibroblasts were converted to hepatocytes (iHeps) by lentiviral transfection of three key transcriptional factors (Foxa3, Gata4 and Hnf1a), and the iHeps were further expanded with tumour necrosis factor-α (TNF-α) and lentivirus-mediated expression of epidermal growth factor (EGF) and hepatocyte growth factor (HGF). RESULTS: SiO2 stimulation tripled the number of activated fibroblasts. Foxa3, Gata4 and Hnf1a converted SiO2-remodelled spleen fibroblasts into 2×106 functional iHeps in one spleen. TNF-α protein and lentivirus-mediated expression of EGF and HGF further enabled the total hepatocytes to expand to 8×106 per spleen. iHeps possessed hepatic functions-such as glycogen storage, lipid accumulation and drug metabolism-and performed fundamental liver functions to improve the survival rate of mice with 90% hepatectomy. CONCLUSION: Direct conversion of the spleen into a liver-like organ, without cell or tissue transplantation, establishes fundamental hepatic functions in mice, suggesting its potential value for the treatment of end-stage liver diseases.

Perspectives on emerging pressures and their integrated impact on large river systems: An insight from the Yellow River basin.

The Yellow River, with a developmental and historical significance to China, is now facing several emerging pressures, which are degrading the river status and creating challenges for high-quality development in the basin. Numerous studies on such emerging pressures, present scattered outcomes, and trigger uncertainties and deficient assumptions on the river's problems. This review integrated such scattered information and investigated the emerging pressures, their drivers and integrated impacts at the basin level. The study intended to prioritize those pressures needing expeditious consideration, and carried a discussion on the alternative pathways to the solution. To determine the critical emerging pressures, a literature review was conducted and experts' opinion was sought. The outcome further led to a comprehensive review, data collection, and analysis of three groups of emerging pressures. The review recognized 'Water Stress' in the lower reach, primarily caused by an abated flow, as the most distressing emerging pressure inflicting social, ecological, and economic consequences. Such decline in flow was mostly induced by a recent increase in 'Anthropogenic activities', such as intensive water withdrawal for irrigation (≥27 BCM), and construction of check dams in the Loess Plateau region (trapping~5 BCM water). The increasing 'Pollution' in the river, besides threatening public health and ecology, also contributed to the water stress by rendering certain stretches of the river biologically dead and unsuitable for any use. The 'Climate Change', with its key negative effect on precipitation in the middle sub-basin, overall contributed small (8-11 %) to the observed reduction in river flow. With increasing challenges for the adopted engineering solutions tackling the water stress, the study suggested the use of a demand management approach, employing adaptive policy measures, as an alternative or supplementary solution to the current approach. In addition, the study highlights that regular reviewing and reforming the key decisions based on evidence and updated information, and taking a participatory approach, may offer a sustainable pathway to the environment as well as socio-economic goals.

Antifibrotic effect of Gancao Ganjiang decoction is mediated by PD-1 / TGF-ß1 / IL-17A pathway in bleomycin-induced idiopathic pulmonary fibrosis.

ETHNOPHARMACOLOGICAL RELEVANCE: Firstly prescribed in the ancient Chinese book Jingui Yaolue, Gancao Ganjiang decoction (GGD) is a traditional Chinese herbal formula that has been widely used to treat "atrophic lung disease". GGD is a popular and widely used traditional Chinese medicine. The decoction is extracted from the dried rhizomes and roots of Glycyrrhiza uralensis Fisch. and Zingiber officinale Roscoe (2:1). AIM OF STUDY: To investigate the therapeutic effect of idiopathic pulmonary fibrosis (IPF) of GGD, a bleomycin-induced IPF murine model was used in this study. MATERIALS AND METHODS: Mice were induced by bleomycin instillation and GGD was orally administered. Changes on mice weight were recorded during the experiment. Lung weight was recorded on days 14 and 28, and pulmonary index was calculated accordingly. Pathological evaluation, including fibrosis analysis of lung tissue, was assessed by H&E and Masson staining. The expression of PD-1, p-STAT3 and IL-17A were detected by immunohistochemistry (IHC). The expression of p-STAT3 in lung tissues of mice were detected by Western blot. The level of IL-17A in lung tissue were detected by ELISA. The expression of PD-1 in CD4+ T cells in peripheral blood of mice was detected by flow cytometry. The levels of hydroxyproline and TGF-ß1 in lung tissue were detected by ELISA. The expression of E-cadherin, vimentin and α-SMA in lung tissues of mice were detected by qRT-PCR and Western blot. RESULTS: GGD can increase body weight and reduce pulmonary index in mice with pulmonary fibrosis. As such, GGD can significantly improve the inflammatory and alleviate IPF in the lung tissue of mice. GGD treatment was capable of reducing the content of PD-1 in lung tissue as well as the expression of PD-1 in CD4+ T cells in peripheral blood. Likewise, GGD was able to reduce the content of p-STAT3, IL-17A and TGF-ß1. In addition, GGD stimulation could inhibit epithelial-mesenchymal transformation (EMT) by increasing the expression of E-cadherin and reducing vimentin and α-SMA, thus reducing extracellular matrix (ECM) deposition. CONCLUSION: Our results indicate that GGD positively affects IPF by regulating PD-1/TGF-ß1/IL-17A pathway.

Honeysuckle-derived microRNA2911 inhibits tumor growth by targeting TGF-ß1.

BACKGROUND: Honeysuckle is a time-honored herb with anticancer activity in traditional Chinese medicine. Recently, accumulating reports are suggesting that the microRNAs in this medicinal plant not only play a physiological role in their original system, but also can be transmitted to another species as potential therapeutic components. In the numerous bioactive investigations, the anti-tumor effects of these microRNAs in the magical herb are rarely studied, especially the special miR2911, a honeysuckle-encoded atypical microRNA, with high stability during the boiling process and unique biological activity to target TGF-ß1 mRNA. METHODS: Luciferase assay was conducted to test the ability of miR2911 to target TGF-ß1 mRNA. ELISA was performed to determine the expression level of TGF-ß1 of mouse colorectal adenocarcinoma CT26 cells when treated with miR2911 and tumor tissue in Sidt1+/+ and Sidt1-/- mice. qRT-PCR was performed to examine the level of expression of miR2911. Tumor-bearing wild and nude mice were employed to evaluate the anti-tumor effect of honeysuckle and miR2911 in vivo. Tumor tissue necrosis was observed by H&E staining. Besides, the infiltration of T lymphocytes across solid tumors was tested by immunostaining staining. RESULTS: Our results showed that honeysuckle slowed the development of colon cancer down. Further research showed that miR2911 could bind strongly to TGF-ß1 mRNA and down-regulate the expression of TGF-ß1 and had a high stability under boiling and acid condition. Moreover, SIDT1 mediated dietary miR2911 inter-species absorption. And we found that miR2911 had a similar anticancer effect as honeysuckle. Mechanistically, miR2911 reversed the tumor-promoting effect of TGF-ß1 by an increase of T lymphocytes infiltration, resulting in slowing the colon cancer process in immunocompetent mice. Consistent with this inference, the anti-tumor effect of miR2911 was revealed to be abolished in T cell immune deficiency mice. CONCLUSION: Taken together, honeysuckle-derived miR2911 showed an anti-tumor effect in colon cancer through targeting TGF-ß1 mRNA. The down-regulation of TGF-ß1 promoted T lymphocytes infiltration, and accordingly impeded the colon tumor development.

A Lanthanide-Containing Coordination Polymer Using Tetraphenylethene-Based Linkers with Selective Fe3+ Sensing and Efficient Iodine Adsorption Activities.

As a star ligand, the construction of coordination polymers (CPs) based on tetrakis(4-carboxyphenyl)ethylene (H4TCPE) has drawn much attention, due to not only the various coordination configurations but also the intriguing chromophore feature causing aggregation-induced emission (AIE). Herein, by the solvothermal reaction of H4TCPE as connected nodes with lanthanide La(III) salts, the first example of the La(III)-TCPE-based CP (1) has been obtained. The structural analyses indicate that 1 exhibits a 3D framework connected by the sharing carboxylate groups with two kinds of 1D rhombic channels when viewed along the c direction. The photophysical properties of 1 have been explored by luminescence, photoluminescence decay, and quantum yield in the solid state. 1 shows strong luminescence in tetrahydrofuran that was attributed to a "pseudo-AIE process" and sensitive and selective sensing activity of Fe3+ toward metal ions via the obvious luminescent quenching. The sensing mechanism has been investigated and reveals a synergetic effect of the competitive absorption and weak interactions between 1 and Fe3+. Moreover, the high porosity, multiple conjugated π-electrons within the tetrakis(4-carboxyphenyl)ethylene backbone, and the uncoordinated carboxyl oxygen sites in this material also provide the capacity for iodine adsorption. The adsorption experiments indicate that 1 could efficiently remove almost complete I2 from the cyclohexane solution after 24 h contact time with an adsorption capacity of 690 mg/g toward I2.

A new species of Behningia Lestage, 1929 (Ephemerotera: Behningiidae) from China.

A new species of sand-burrowing mayfly (Ephemeroptera: Behningiidae), Behningia nujiangensis Zhou Bisset, is described based on more than 50 nymphs collected from the Nujiang River in Yunnan Province, P.R. China. This is the first species of the family Behningiidae discovered in China. It is also the second species of genus Behningia, and the third species of the family Behningiidae collected from the Oriental biogeographic region. The shapes of the labrum and the labium in B. nujiangensis are markedly different from those found in other species of Behningia. Differences in the mandibles, the galea-lacina of maxillae, and both the prothoracic and metathoracic legs differentiate B. nujiangensis from both B. baei and B. ulmeri. The biology of and conservation challenges for B. nujiangensis are also briefly discussed.

New power of self-assembling carbonic anhydrase inhibitor: Short peptide-constructed nanofibers inspire hypoxic cancer therapy.

Carbonic anhydrase (CA) IX overexpresses exclusively on cell membranes of hypoxic tumors, regulating the acidic tumor microenvironment. Small molecules of CA inhibitor modified with short peptide successfully achieve CA IX-targeted self-assembly that localizes CA inhibitors on hypoxic cancer cell surfaces and enhances their inhibition efficacy and selectivity. CA IX-related endocytosis also promotes selective intracellular uptake of these nanofibers under hypoxia, in which nanofiber structures increase in size with decreasing pH. This effect subsequently causes intracellular acid vesicle damage and blocks protective autophagy. The versatility of tunable nanostructures responding to cell milieu impressively provokes selective toxicities and provides strategic therapy for hypoxic tumors. Moreover, in vivo tests demonstrate considerable antimetastatic and antiangiogenesis effects in breast tumors, and particularly remarkable enhancement of antitumor efficacy in doxorubicin administration. With its biocompatible components and distinctive hypoxia therapies, this nanomaterial advances current chemotherapy, providing a new direction for hypoxic cancer therapy.

River health assessment of the Yellow River source region, Qinghai-Tibetan Plateau, China, based on tolerance values of macroinvertebrates.

For decades, the river health of the Yellow River source region (YRSR) on the Qinghai-Tibetan Plateau has been a focal issue owing to its unique geographic location and ecological functions. This study investigated the ecological status of the headwater streams, the main stem, and the tributaries of the Yellow River in the YRSR using the tolerance values of macroinvertebrates and those related to biotic indices. The macroinvertebrate assemblages of the headwater streams were characterized by lower biodiversity than the tributaries downstream, based on comparisons of taxonomical composition, functional feeding group composition, and the pollution-tolerant capacity of taxa. The headwater streams had a lower ratio (16%) of pollution-sensitive macroinvertebrate taxa than that of the tributaries downstream (30%). The biotic indices (family- and genus-level biotic indices) indicated that the ecological health of the headwater streams was comparably poorer than that of the downstream tributaries. The combined effect of vulnerable natural conditions and increasing human disturbance is likely the main cause of eco-environmental degradation in the Yellow River headwater streams.

Responses of macroinvertebrate assemblages to environmental variations in the river-oxbow lake system of the Zoige wetland (Bai River, Qinghai-Tibet Plateau).

The biodiversity value of river-oxbow lake systems in high plateau peatland has been little recognized, and there are many gaps in our understanding of their ecology. In this study, we investigated the river-oxbow lake system of the Bai River basin, the main tributary of the Yellow River Source in the Zoige wetland from 2015 to 2016, in attempt to show how the environmental variations, especially hydrological connectivity and macrophyte biomass in the river-oxbow lake system influenced macroinvertebrates. Habitat patches were investigated in 11 river cross-sections and 18 oxbow lakes in the Bai River basin. Through hierarchical clustering and non-metric multidimensional scaling, four main types of habitats were identified in the river-oxbow lake system in the plateau: sand-bed river, cobble-bed river, sparse-macrophyte oxbow lake, and luxuriant-macrophyte oxbow lake. The luxuriant-macrophyte oxbows were characterized by high dissolved oxygen concentrations, alkalinity, and higher macroinvertebrate richness, density, biomass, and the Improved Shannon-Wiener Index in comparison to the other habitat types. Additionally, influential patterns of environmental variables on macroinvertebrates were analyzed using redundancy analysis. Lasso regression models were established to describe how macroinvertebrate density responded to macrophyte biomass and other variables, and how macrophyte biomass responded to hydrological connectivity and oxbow size. It was revealed that reduced hydrological connectivity and reduced oxbow size played important roles in increasing the biomass of submerged macrophyte, and dense macrophyte was directly responsible for the high biodiversity of macroinvertebrates. Different from the commonly believed unimodal influential pattern that medium hydrological connectivity supports the highest biodiversity in oxbow lakes reported in previous studies, macroinvertebrates in the high plateau river-oxbow lake systems benefited from low connectivity and reduced size. Oxbow lakes, especially those covered with luxuriant macrophytes, diversified the macroinvertebrate assemblages and enhanced primary consumer biomass at the regional scale.

PEG-Detachable Polymeric Micelles Self-Assembled from Amphiphilic Copolymers for Tumor-Acidity-Triggered Drug Delivery and Controlled Release.

The development of an intelligent biomaterial system that can efficiently accumulate at the tumor site and release a drug in a controlled way is very important for cancer chemotherapy. PEG is widely selected as a hydrophilic shell to acquire prolonged circulation time and enhanced accumulation at the tumor site, but it also restrains the cellular transport and uptake and leads to insufficient therapeutic efficacy. In this work, a PEG-detachable pH-responsive polymer that forms micelles from copolymer cholesterol grafted poly(ethylene glycol) methyl ether- Dlabile-poly(ß-amino ester)- Dlabile-poly(ethylene glycol) methyl ether (MPEG- Dlabile-PAE- g-Chol) is developed to overcome the aforementioned challenges based on pH value changes among normal physiological, extracellular (pHe), and intracellular (pHi) environments. PEGylated doxorubicin (DOX)-loaded polymeric micelles (DOX-PMs) can accumulate at the tumor site via an enhanced permeability and retention effect, and the PEG shell is detachable induced by cleavage of the pHe-labile linker between the PEG segment and the main chain. Meanwhile, the pHi-sensitive poly(ß-amino ester) segment is protonated and has a high positive charge. The detachment of PEG and protonation of PAE facilitate cellular uptake of DOX-PMs by negatively charged tumor cells, along with the escape from endo-/lysosome due to the "proton-sponge" effect. The DOX molecules are controlled release from the carriers at specific pH values. The results demonstrate that DOX-PMs have the capability of showing high therapeutic efficacy and negligible cytotoxicity compared with free DOX in vitro and in vivo. Overall, we anticipate that this PEG-detachable and tumor-acidity-responsive polymeric micelle can mediate effective and biocompatible drug delivery "on demand" with clinical application potential.

Hyaluronic acid modified MPEG-b-PAE block copolymer aqueous micelles for efficient ophthalmic drug delivery of hydrophobic genistein.

The ophthalmic drug delivery is a challenge in the clinical treatment of ocular diseases. The traditional drug administration usually shows apparent limitations, such as the low bioavailability from the reason of low penetration of the cornea and the short survival time of drug in the eyes. To overcome these shortcomings, we propose an amphiphilic polymer micelle modified with hyaluronic acid (HA) for high efficient ophthalmic delivery of genistein, a widely used hydrophobic drug for treatment of ocular angiogenesis. The MPEG-b-PAE copolymer was synthesized by the Michael addition reaction, and the final drug carrier MPEG-b-PAE-g-HA was obtained by the process of esterification. Then, genistein was packaged in this drug carrier, getting the final micelles with size of about 84.5 nm. The cell viability tests showed that the micelles take no obvious cytotoxicity to the human cornea epithelium cells. The functionalities of drug slow release and cornea penetration ability were demonstrated in a series ex vivo experiments. Further, the vascular inhibition test illustrated that the micelles could significantly inhibit the angiogenesis of human umbilical vein endothelial cells. These results indicate that the constructed polymer has high feasibility to be used as drug carrier in the treatment of ocular diseases.