Photosynthetic carbon allocation in native and invasive salt marshes undergoing hydrological change.

Biogeochemical processes mediated by plants and soil in coastal marshes are vulnerable to environmental changes and biological invasion. In particular, tidal inundation and salinity stress will intensify under future rising sea level scenarios. In this study, the interactive effects of flooding regimes (non-waterlogging vs. waterlogging) and salinity (0, 5, 15, and 30 parts per thousand (ppt)) on photosynthetic carbon allocation in plant, rhizodeposition, and microbial communities in native (Phragmites australis) and invasive (Spartina alterniflora) marshes were investigated using mesocosm experiments and 13CO2 pulse-labeling techniques. The results showed that waterlogging and elevated salinity treatments decreased specific root allocation (SRA) of 13C, rhizodeposition allocation (RA) 13C, soil 13C content, grouped microbial PLFAs, and the fungal 13C proportion relative to total PLFAs-13C. The lowest SRA, RA, and fungal 13C proportion occurred under the combined waterlogging and high (30 ppt) salinity treatments. Relative to S. alterniflora, P. australis displayed greater sensitivity to hydrological changes, with a greater reduction in rhizodeposition, soil 13C content, and fungal PLFAs. S. alterniflora showed an earlier peak SRA but a lower root/shoot 13C ratio than P. australis. This suggests that S. alterniflora may transfer more photosynthetic carbon to the shoot and rhizosphere to facilitate invasion under stress. Waterlogging and high salinity treatments shifted C allocation towards bacteria over fungi for both plant species, with a higher allocation shift in S. alterniflora soil, revealing the species-specific microbial response to hydrological stresses. Potential shifts towards less efficient bacterial pathways might result in accelerated carbon loss. Over the study period, salinity was the primary driver for both species, explaining 33.2-50.8 % of 13C allocation in the plant-soil-microbe system. We propose that future carbon dynamics in coastal salt marshes under sea-level rise conditions depend on species-specific adaptive strategies and carbon allocation patterns of native and invasive plant-soil systems.

Comparative analysis of primate and pig cells reveals primate-specific PINK1 expression and phosphorylation.

PTEN-induced putative kinase 1 (PINK1), a mitochondrial kinase that phosphorylates Parkin and other proteins, plays a crucial role in mitophagy and protection against neurodegeneration. Mutations in PINK1 and Parkin can lead to loss of function and early onset Parkinson's disease. However, there is a lack of strong in vivo evidence in rodent models to support the theory that loss of PINK1 affects mitophagy and induces neurodegeneration. Additionally, PINK1 knockout pigs ( Sus scrofa) do not appear to exhibit neurodegeneration. In our recent work involving non-human primates, we found that PINK1 is selectively expressed in primate brains, while absent in rodent brains. To extend this to other species, we used multiple antibodies to examine the expression of PINK1 in pig tissues. In contrast to tissues from cynomolgus monkeys ( Macaca fascicularis), our data did not convincingly demonstrate detectable PINK1 expression in pig tissues. Knockdown of PINK1 in cultured pig cells did not result in altered Parkin and BAD phosphorylation, as observed in cultured monkey cells. A comparison of monkey and pig striatum revealed more PINK1-phosphorylated substrates in the monkey brain. Consistently, PINK1 knockout in pigs did not lead to obvious changes in the phosphorylation of Parkin and BAD. These findings provide new evidence that PINK1 expression is specific to primates, underscoring the importance of non-human primates in investigating PINK1 function and pathology related to PINK1 deficiency.

Impacts of land-use change on carbon dynamics in China's coastal wetlands.

The impact of land-use and land-cover change (LULCC) on ecosystem carbon (C) dynamics has been previously documented at local and global scales, but uncertainty persists for coastal wetlands due to geographical variability and field data limitations. Field-based assessments of plant and soil C contents and stocks of various LULCC types were conducted in nine regions along the coastline of China (21°-40°N). These regions cover natural coastal wetlands (NWs, including salt marshes and mangroves) and former wetlands converted to different LULCC types, including reclaimed wetlands (RWs), dry farmlands (DFs), paddy fields (PFs) and aquaculture ponds (APs). The results showed that LULCC generally decreased the C contents and stocks of the plant-soil system by 29.6 % ± 2.5 % and 40.4 % ± 9.2 %, respectively, while it slightly increased the soil inorganic C contents and stocks. Wetlands converted to APs and RWs lost greater ecosystem organic C stocks (EOC, sum of plants and top 30 cm of soil organic C stocks) than other LULCC types. The annual potential CO2 emissions estimated from EOC loss depended on the LULCC type, with an average emission of 7.92 ± 2.94 Mg CO2-eq ha-1 yr-1. The change rate of EOC in all LULCC types showed a significantly deceasing trend with increasing latitude (p < 0.05). The loss of EOC due to LULCC was larger in mangroves than in salt marshes. The results showed that the response of plant and soil C variables to LULCC was mainly related to differences in plant biomass, median grain size, soil water content and soil NH4+-N content. This study emphasized the importance of LULCC in triggering C loss in natural coastal wetlands, which strengthens the greenhouse effect. We suggest that the current land-based climate models and climate mitigation policies must account for specific land-use types and their associated land management practices to achieve more effective emission reduction.

Transcriptome profiling in swine macrophages infected with African swine fever virus at single-cell resolution.

African swine fever virus (ASFV) is the causative agent of African swine fever, a highly contagious and usually fatal disease in pigs. The pathogenesis of ASFV infection has not been clearly elucidated. Here, we used single-cell RNA-sequencing technology to survey the transcriptomic landscape of ASFV-infected primary porcine alveolar macrophages. The temporal dynamic analysis of viral genes revealed increased expression of viral transmembrane genes. Molecular characteristics in the ASFV-exposed cells exhibited the activation of antiviral signaling pathways with increased expression levels of interferon-stimulated genes and inflammatory- and cytokine-related genes. By comparing infected cells with unexposed cells, we showed that the unfolded protein response (UPR) pathway was activated in low viral load cells, while the expression level of UPR-related genes in high viral load cells was less than that in unexposed cells. Cells infected with various viral loads showed signature transcriptomic changes at the median progression of infection. Within the infected cells, differential expression analysis and coregulated virus­host analysis both demonstrated that ASFV promoted metabolic pathways but inhibited interferon and UPR signaling, implying the regulation pathway of viral replication in host cells. Furthermore, our results revealed that the cell apoptosis pathway was activated upon ASFV infection. Mechanistically, the production of tumor necrosis factor alpha (TNF-α) induced by ASFV infection is necessary for cell apoptosis, highlighting the importance of TNF-α in ASFV pathogenesis. Collectively, the data provide insights into the comprehensive host responses and complex virus­host interactions during ASFV infection, which may instruct future research on antiviral strategies.

[Identification of important biodiversity areas by InVEST model considering opographic relief: A case study of Yunnan Province, China]. / 顾及地形起伏的InVESTæ¨¡åž‹çš„ç”Ÿç‰©å¤šæ ·æ€§é‡è¦åŒºè¯†åˆ«­­ä»¥äº‘南省为例.

Accurately identifying important areas of biodiversity is one of the key issues in ecology and biodiversity research, as well as an important basis for the delineation of the red line for ecologi-cal protection and territorial spatial planning. With China's typical plateau mountainous area (Yunnan Province) as a research case, we used the net primary productivity (NPP) quantitative index method, InVEST model and InVEST model focusing on topographic relief to identify biodiversity important areas. The results showed that NPP quantitative index method was not suitable for the plateau mountainous areas with obvious vertical zonal development. The identified area contained only 26.1% of the protected areas. The InVEST model had higher identification accuracy than the NPP quantitative index method in Yunnan Province. The identified area covered 49.4% of the protected natural areas. Fragmentation was obvious in northwest Yunnan. The InVEST model focusing on topographic relief improved the identification accuracy of important areas of biodiversity, including 71.7% of nature reserves. The deficiency of NPP quantitative index method in water area identification was made up and the fragmentation problem of InVEST model was solved. The area of biodiversity important areas was 119466.94 km2, accounting for 30.3% of the total land area of Yunnan Province. The spatial distribution showed a pattern of "three barriers, two zones and one region for multi-point development".

Reclamation-induced tidal restriction increases dissolved carbon and greenhouse gases diffusive fluxes in salt marsh creeks.

Intertidal creeks play an important role in transporting nutrients between coastal ecosystems and ocean. Reclamation is a predominant anthropogenic disturbance in coastal regions; however, the influence of reclamation on carbon and nitrogen species and greenhouse gas (GHG) fluxes in creek remains unclear. In a subtropical salt marsh of eastern China, the seasonal patterns of dissolved carbon (DOC, DIC, CO2, and CH4) and inorganic nitrogen (NH4+-N, NO2--N, and NO3--N and N2O) species, and the diffusive fluxes of CO2, CH4, and N2O, were compared between the natural tidal creeks and the reclaimed creeks. Due to notably changed hydrological and biological conditions in the reclaimed creeks, concentrations of all dissolved carbon species, NH4+-N and NO2--N increased significantly by 60.2-288.2%, while NO3--N and N2O decreased slightly, compared to the natural tidal creeks. DIC and NO3--N were the primary components of the total dissolved carbon and inorganic nitrogen in both creek types; however, their proportions decreased as a result of elevated DOC, CO2, CH4, NH4+-N, and NO2--N following reclamation. Significantly higher global warming potential (0.58 ± 0.15 g CO2-eq m-2 d-1) was found in the reclaimed creeks, making them hotspot of greenhouse effects, compared to the natural tidal creeks. Our results indicated that changes in flow velocity, salinity, Chlorophyll a, and pH were the main factors controlling the dissolved carbon and nitrogen and consequent GHG emissions, due to reclamation. This study is helpful in understanding of carbon and nitrogen sink-source shifts resulting from land use changes in coastal wetlands.

Sea-level rise will reduce net CO2 uptake in subtropical coastal marshes.

Coastal marshes have a significant capacity to sequester carbon; however, sea-level rise (SLR) is expected to result in prolonged flooding and saltwater intrusion in coastal regions. To explore the effects of SLR projections on net CO2 uptake in coastal marshes, we conducted a "double-check" investigation, including the eddy covariance (EC) measurements of the CO2 fluxes in subtropical coastal marshes along inundation and salinity gradients, in combination with a mesocosm experiment for analyzing CO2 flux components under waterlogging and increased salinity conditions. During the same measurement periods, the net ecosystem CO2 exchange (NEEEC based on the EC dataset) in an oligohaline marsh was higher than that in a low-elevation mesohaline marsh, whereas the NEEEC was lower than that in a high-elevation freshwater marsh. The declines in NEEEC between the marshes could be attributed to a greater decrease in gross primary production relative to ecosystem respiration. Waterlogging slightly increased the NEEms (NEE based on the mesocosms) because of inhibited soil respiration and slight changes in plant photosynthesis and shoot respiration. However, the NEEms measured during the drainage period decreased significantly due to the stimulated soil respiration. The NEEms decreased with increasing salinity (except under mild salinity), and waterlogging exacerbated the adverse impacts of salinity. The amplificatory effect of decreases in both leaf photosynthesis and growth under hydrological stresses contributed more to reduce the NEEms than to respiratory effluxes. Both waterlogging and increased salinity reduced the root biomass, soil microbial biomass, and activities of assayed soil enzymes (except for cellulase under waterlogging conditions), leading to limited soil respiration. The declines in plant growth, photosynthesis, and soil respiration could also be attributed to the decrease in soil nutrients under waterlogging and increased salinity conditions. We propose that the coupling of SLR-driven hydrological effects lowers the capacity of CO2 uptake in subtropical coastal marshes.

The importance of the propagule-sediment-tide "power balance" for revegetation at the coastal frontier.

Revegetation of pioneer plants is a critical phase in community establishment for mudflats in seriously degraded coastal wetlands. We tested a hypothesis of the importance of a "power balance" among propagule resilience and sedimentary and tidal disturbances for vegetation reestablishment. Our experiment used three types of propagules (seeds, seedlings, and corms) of native Scirpus species in the fringing flats with similar tidal flows and varying sedimentary intensities in the Yangtze Estuary. Regardless of the initial planting densities, the seed germination rate was extremely low in the field situation. Although the incubated seedlings were planted directly on the bare flat, the wave movement easily flushed the seedlings, even at the site with moderate sedimentary accretion. Failure of the revegetation practice using the seed and seedling materials indicated that the combined "growing and anchoring power" of young seedlings and "stabilizing power" of the sediment were insufficient to withstand the "dislodging power" of the tidal energy. In contrast, the planting approach with underground propagules (corms) proved to be feasible for vegetation establishment at the sites with moderate and low-level sedimentary intensities. The successful practice improved the tipping point of plant survival and tussock formation could be surpassed when the combined growing and anchoring power of seedlings that developed from corms with the stabilizing power of the sediment was greater than the dislodging power of the wave energy. However, at the site with high-level sedimentary intensity, the excessive sediment converted to the burying stress power as seedlings developed from the corms, revealing a burial threshold for seedling survival. The risk of seedling establishment was high when the burying stress power of the sediment far outweighed the combination of the growing power of the seedlings and the sediment removal power of the tidal current and surpassed the tipping point of vegetation die-off. Additionally, we checked the practice cost of the different approaches to ensure a highly cost-effective revegetation planning based on site suitability. This study highlights that understanding of the propagule-sediment-tide power balance offers a tool for improvement of the revegetation and management of site-specific sedimentary and hydrological environments for many degraded coastal ecosystems.

Enhancing Antitumor Efficacy by Simultaneous ATP-Responsive Chemodrug Release and Cancer Cell Sensitization Based on a Smart Nanoagent.

The exploitation of smart nanoagents based drug delivery systems (DDSs) has proven to be a promising strategy for fighting cancers. Hitherto, such nanoagents still face challenges associated with their complicated synthesis, insufficient drug release in tumors, and low cancer cell chemosensitivity. Here, the engineering of an adenosine triphosphate (ATP)-activatable nanoagent is demonstrated based on self-assembled quantum dots-phenolic nanoclusters to circumvent such challenges. The smart nanoagent constructed through a one-step assembly not only has high drug loading and low cytotoxicity to normal cells, but also enables ATP-activated disassembly and controlled drug delivery in cancer cells. Particularly, the nanoagent can induce cell ATP depletion and increase cell chemosensitivity for significantly enhanced cancer chemotherapy. Systematic in vitro and in vivo studies further reveal the capabilities of the nanoagent for intracellular ATP imaging, high tumor accumulation, and eventual body clearance. As a result, the presented multifunctional smart nanoagent shows enhanced antitumor efficacy by simultaneous ATP-responsive chemodrug release and cancer cell sensitization. These findings offer new insights toward the design of smart nanoagents for improved cancer therapeutics.

[Shallow Fire-needle Acupuncture Stimulation Plus Cupping Relieves Neuralgia and Down-regulates Serum Substance P Level in Patients with Acute Herpes Zoster].

OBJECTIVE: To observe the influence of repeated shallow fire-needle acupuncture stimulation plus cupping on local neuralgia and serum substance P(SP)content in patients with acute herpes zoster (AHZ). METHODS: A total of 60 cases of AHZ patients were randomly divided into control (medication) group and treatment (medication plus fire-needle) group (n＝30 in each). Patients of both groups were ordered to take Famciclovir (0.25 g/time, three times a day) and Mecobalamin (0.5 g/time, three times a day) orally for 7 days. In addition, patients of the treatment group were also treated by repeated shallow fire-needle stimulation and cupping, once a day for 7 days. Before and after the treatment, the patient's pain severity was assessed using visual analogue scale (VAS) and serum SP concentration was measured using ELISA. RESULTS: After the treatment, the VAS scores and serum SP concentrations in both groups were significantly decreased in comparison with those of their own pre-treatment (P<0.01), and were significantly lower in the treatment group than in the control group(P<0.01). There was a highly positive correlation between the decreased VAS score and serum SP content in the treatment group(P<0.01). CONCLUSION: Repeated shallow fire-needle stimulation plus cupping can accelerate the relief of local neuralgia in AHZ patients, which may be associated with its effect in down-regulating serum SP level.

Proteomic Analysis of Zika Virus Infected Primary Human Fetal Neural Progenitors Suggests a Role for Doublecortin in the Pathological Consequences of Infection in the Cortex.

Zika virus (ZIKV) infection is associated with severe neurological defects in fetuses and newborns, such as microcephaly. However, the underlying mechanisms remain to be elucidated. In this study, proteomic analysis on ZIKV-infected primary human fetal neural progenitor cells (NPCs) revealed that virus infection altered levels of cellular proteins involved in NPC proliferation, differentiation and migration. The transcriptional levels of some of the altered targets were also confirmed by qRT-PCR. Among the altered proteins, doublecortin (DCX) plays an important role in NPC differentiation and migration. Results showed that ZIKV infection downregulated DCX, at both mRNA and protein levels, as early as 1 day post infection (1 dpi), and lasted throughout the virus replication cycle (4 days). The downregulation of DCX was also observed in a ZIKV-infected fetal mouse brain model, which displayed decreased body weight, brain size and weight, as well as defective cortex structure. By screening the ten viral proteins of ZIKV, we found that both the expression of NS4A and NS5 were correlated with the downregulation of both mRNA and protein levels of DCX in NPCs. These data suggest that DCX is modulated following infection of the brain by ZIKV. How these observed changes of DCX expression translate in the pathological consequences of ZIKV infection and if other cellular proteins are equally involved remains to be investigated.

Ecophysiological response of native and exotic salt marsh vegetation to waterlogging and salinity: Implications for the effects of sea-level rise.

The ecophysiological characteristics of native Phragmites australis and exotic Spartina alterniflora grown under waterlogging and salinity were investigated to explore their adaptation potential to sea level rise. The seasonal course of phenotypic traits, photosynthetic activity and chlorophyll fluorescence parameters of P. australis did not change remarkably under shallow flooding, whereas these variables were sensitive to increasing salinity. Waterlogging exacerbated the negative effects of salinity on shoot growth and photosynthetic activity of P. australis, and the combined stresses led to an absence of tassel and reproductive organs. By contrast, S. alterniflora performed well under both stresses and showed an obvious adaptation of salt secretion with increasing salinity. Light salinity was the optimal condition for S. alterniflora, and the tassel growth, chlorophyll content and fluorescence characters under moderate stresses did not differ notably. The Na+ and Cl- concentrations in leaves of both species increased, and the K+ content decreased in response to salinity. Under moderate and high saline levels, the ion concentrations in S. alterniflora were maintained at relatively consistent levels with increased salt secretion. We expect the degradation of P. australis and further colonization of S. alterniflora under prolonged flooding and saltwater intrusion from sea level rise on the coastline of China.

Characterization of a candidate tetravalent vaccine based on 2'-O-methyltransferase mutants.

Dengue virus (DENV) is one of the most widespread arboviruses. The four DENV serotypes infect about 400 million people every year, causing 96 million clinical dengue cases, of which approximately 500'000 are severe and potentially life-threatening. The only licensed vaccine has a limited efficacy and is only recommended in regions with high endemicity. We previously reported that 2'-O-methyltransferase mutations in DENV-1 and DENV-2 block their capacity to inhibit type I IFNs and render the viruses attenuated in vivo, making them amenable as vaccine strains; here we apply this strategy to all four DENV serotypes to generate a tetravalent, non-chimeric live-attenuated dengue vaccine. 2'-O-methyltransferase mutants of all four serotypes are highly sensitive to type I IFN inhibition in human cells. The tetravalent formulation is attenuated and immunogenic in mice and cynomolgus macaques and elicits a response that protects from virus challenge. These results show the potential of 2'-O-methyltransferase mutant viruses as a safe, tetravalent, non-chimeric dengue vaccine.

Near-atomic structure of Japanese encephalitis virus reveals critical determinants of virulence and stability.

Although several different flaviviruses may cause encephalitis, Japanese encephalitis virus is the most significant, being responsible for thousands of deaths each year in Asia. The structural and molecular basis of this encephalitis is not fully understood. Here, we report the cryo-electron microscopy structure of mature Japanese encephalitis virus at near-atomic resolution, which reveals an unusual "hole" on the surface, surrounded by five encephalitic-specific motifs implicated in receptor binding. Glu138 of E, which is highly conserved in encephalitic flaviviruses, maps onto one of these motifs and is essential for binding to neuroblastoma cells, with the E138K mutation abrogating the neurovirulence and neuroinvasiveness of Japanese encephalitis virus in mice. We also identify structural elements modulating viral stability, notably Gln264 of E, which, when replaced by His264 strengthens a hydrogen-bonding network, leading to a more stable virus. These studies unveil determinants of neurovirulence and stability in Japanese encephalitis virus, opening up new avenues for therapeutic interventions against neurotropic flaviviruses.Japanese encephalitis virus (JEV) is a Flavivirus responsible for thousands of deaths every year for which there are no specific anti-virals. Here, Wang et al. report the cryo-EM structure of mature JEV at near-atomic resolution and identify structural elements that modulate stability and virulence.

Polyphenol-Inspired Facile Construction of Smart Assemblies for ATP- and pH-Responsive Tumor MR/Optical Imaging and Photothermal Therapy.

Smart assemblies have attracted increased interest in various areas, especially in developing novel stimuli-responsive theranostics. Herein, commercially available, natural tannic acid (TA) and iron oxide nanoparticles (Fe3 O4 NPs) are utilized as models to construct smart magnetic assemblies based on polyphenol-inspired NPs-phenolic self-assembly between NPs and TA. Interestingly, the magnetic assemblies can be specially disassembled by adenosine triphosphate, which shows a stronger affinity to Fe3 O4 NPs than that of TA and partly replaces the surface coordinated TA. The disassembly can further be facilitated by the acidic environment hence causing the remarkable change of the transverse relaxivity and potent "turn-on" of fluorescence (FL) signals. Therefore, the assemblies for specific and sensitive tumor magnetic resonance and FL dual-modal imaging and photothermal therapy after intravenous injection of the assemblies are successfully employed. This work not only provides understandings on the self-assembly between NPs and polyphenols, but also will open new insights for facilely constructing versatile assemblies and extending their biomedical applications.

Semipermeable Functional DNA-Encapsulated Nanocapsules as Protective Bioreactors for Biosensing in Living Cells.

The development of functional DNA-based nanosensors in living cells has experienced some design challenges, including, for example, poor cellular uptake, rapid nuclease degradation, and high false positives. Herein, we designed selectively permeable poly(methacrylic acid) (PMA) nanocapsules to encapsulate functional DNAs for metal ions and small-molecules sensing in living cells. Since functional DNAs are concentrated in the nanocapsules, an increasing reaction rate is obtained in vitro. During endocytosis, polymeric capsules simultaneously improve cellular uptake of functional DNAs and preserve their structural integrity inside the confined capsule space. More importantly, selective shell permeability allows for the free diffusion of small molecular targets through capsule shells but limits the diffusion of large biomolecules, such as nuclease and nonspecific protein. Compared to the free DNAzyme, PMA nanocapsules could reduce false positives and enhance detection accuracy. Furthermore, PMA nanocapsules are biocompatible and biodegradable. Through the controllability of wall thickness, permeability, and size distribution, these nanocapsules could be expanded easily to other targets, such as microRNAs, small peptides, and metabolites. These nanocapsules will pave the way for in situ monitoring of various biological processes in living cells and in vivo.

[Alternative stable states in coastal intertidal wetland ecosystems of Yangtze estuary, China]. / 长江口滨海湿地潮间带生态系统的多稳态特征.

Alternative stable states phenomenon widely exists in a variety of ecosystems and is closely related to ecosystem health and sustainable development. Although alternative stable states research has become the focus and hotspot of the ecology researches, only a few empirical evidences supported its behavior and mechanisms in coastal wetland ecosystems up to now. In our study, ta-king the intertidal wetland ecosystem in Chongming Dongtan Nature Reserve as study area, we aimed to: 1) test the existence of alternative stable states based on judgment conditions (bimodal characteristic and threshold effect) and determine the relative stable state types; 2) explore the formation mechanisms of alternative stable states by monitoring hydrological conditions, sediment accretion dynamics as well as vegetation growth parameters and analyzing the positive feedbacks between saltmarsh vegetation and sedimentary geomorphology. Our results showed that: 1) Normalized difference vegetation index (NDVI) frequentness distribution revealed obvious bimodality at saltmarsh pioneer zone. Propagule biomass threshold limited the establishment of plant patches representing the "saltmarsh" state. The presence of bimodality and biomass threshold demonstrated there are "mudflat" stable state and "saltmarsh" stable state with distinct structure and function in intertidal wetland ecosystem. 2) Current velocities, turbidities and direction perpendicular to the vegetation zone were the most important factors responsible for the sediments rapid accretion at saltmarsh pioneer zone in spring and summer. Sediments accretion significantly promoted the growth of saltmarsh plant. The positive feedbacks between plant growth and sediments accretion resulted in the formation of alternative stable states. 3) The expansion pattern of saltmarshes in the Chongming Dongtan intertidal wetland ecosystem also suggested that increases of sediments accretion could trigger the formation of "mudflat" stable state and "saltmarsh" stable state on landscape scale. The results from this study could enrich regime shift mechanisms researches and provide the scientific supports for coastal zone protection, restoration and comprehensive management, which could have important theoretical and practical meaning.

Manganese-iron layered double hydroxide: a theranostic nanoplatform with pH-responsive MRI contrast enhancement and drug release.

Stimuli-responsive theranostic platforms are highly desirable for efficient cancer treatment because of their improved specificity and sensitivity. In this work, we report a manganese-iron layered double hydroxide (MnFe-LDH) for the first time and demonstrate that it can serve as a pH-responsive nanoplatform for cancer theranostics. The MnFe-LDH can respond to the acidic microenvironment of solid tumors to release paramagnetic Mn2+ and Fe3+ ions, resulting in great enhancement of the T1 MRI contrast of the tumor area. In addition, the layered structure enables MnFe-LDH to effectively deliver chemotherapeutic drugs in a pH-controlled manner, and therefore it can simultaneously inhibit the growth of solid tumors. We believe that this novel MnFe-LDH with pH-responsive property holds great promise in cancer theranostic applications.

Subcellular Clearance and Accumulation of Huntington Disease Protein: A Mini-Review.

Huntington's disease (HD) is an autosomal dominant, progressive neurodegenerative disease caused by an expanded polyglutamine (polyQ) tract in the N-terminal region of mutant huntingtin (mHtt). As a result, mHtt forms aggregates that are abundant in the nuclei and processes of neuronal cells. Although the roles of mHtt aggregates are still debated, the formation of aggregates points to deficient clearance of mHtt in brain cells. Since the accumulation of mHtt is a prerequisite for its neurotoxicity, exploring the mechanisms for mHtt accumulation and clearance would advance our understanding of HD pathogenesis and help us develop treatments for HD. We know that the ubiquitin-proteasome system (UPS) and autophagy play important roles in clearing mHtt; however, how mHtt preferentially accumulates in neuronal nuclei and processes remains unclear. Studying the clearance of mHtt in neuronal cells is a challenge because neurons are morphologically and functionally polarized, which means the turnover of mHtt may be distinct in different cellular compartments. In this review, we discuss our current knowledge about the clearance and accumulation of mHtt and strategies examining mHtt clearance and accumulation in different subcellular regions.

Long-term lamivudine for chronic hepatitis B and cirrhosis: A real-life cohort study.

AIM: To investigate clinical outcomes of chronic hepatitis B (CHB) and liver cirrhosis (LC) patients under whole-course management with lamivudine (LAM). METHODS: This was a retrospective-prospective cohort study based on two nonrandom cohorts of Chinese patients (LAM group and history control group). Two hundred thirty-eight patients with LAM treatment for at least 12 mo under whole-course management were included in the LAM group. The management measures included regular follow-up and timely adjustment of the therapeutic regimen according to drug-resistance and relapse. Two hundred thirty-eight patients with CHB or LC without any antiviral treatment and with follow-up over 12 mo were included in the history control group. The LAM and control group patients were 1:1 matched by propensity score method to ensure both patients were similar in general datum, sex, age, E antigen, and diagnosis. The incidence rates of endpoint events [LC, hepatocellular carcinoma (HCC), and death] were compared between the LAM and control groups. RESULTS: Hepatitis B virus-DNA < 1000 copies per mL rate and rate of alanine transaminase < 1.3 of the upper normal limit in LAM and control groups were 89.1% vs 18.5% (P < 0.05) and 89.8% vs 31.1% (P < 0.05), respectively. Viral breakthrough occurred in 77 patients (32.4%); the one-, three-, and five-year cumulative rates were 6.8%, 33.1%, and 41.3%, respectively. In total, 44.5% (106/238) of patients had once stopped LAM, and 63 (59.4%) of them developed virologic relapse; the relapse rate of patients with and without reaching Asian Pacific Association for the Study of the Liver endpoint criteria were 52.4% and 69.8%, respectively. Six CHB patients in the LAM group developed LC compared to 47 patients in the control group; the three-, and five-year cumulative rates of CHB at baseline of LAM were lower than those of the control group: 0.7% vs 12.0% and 1.8% vs 23.8% (P < 0.01), respectively. The incidence of HCC in CHB at baseline of LAM was lower than that of the control group; the three-, and five-year cumulative rates were 0% vs 3.2% and 1.1% vs 3.2% (P = 0.05), respectively. The incidence of HCC in LC at baseline of LAM was lower than that of the control group: 9.8% (5/51) vs 25.0% (12/48), and the three-, and five-year cumulative rates were 4.5% vs 20.7% and 8.1% vs 37.5% (P < 0.01), respectively. The mortality rate in the LAM group was lower than the control group. CONCLUSION: Standardized long-term LAM treatment in combination with comprehensive management can reduce the incidence rates of LC and HCC as well as hepatitis B virus-related deaths.