IntroductionHereditary spastic paraplegias (HSPs) are uncommon but not rare neurodegenerative diseases. More than 100 pathogenic genes and loci related to spastic paraplegia symptoms have been ...reported. HSPs have the same core clinical features, including progressive spasticity in the lower limbs, though HSPs are heterogeneous (eg, clinical signs, MRI features, gene mutation). The age of onset varies greatly, from infant to adulthood. In addition, the slow and variable rates of disease progression in patients with HSP represent a substantial challenge for informative assessment of therapeutic efficacy. To address this, we are undertaking a prospective cohort study to investigate genetic–clinical characteristics, find surrogates for monitoring disease progress and identify clinical readouts for treatment.Methods and analysisIn this case-control cohort study, we will enrol 200 patients with HSP and 200 healthy individuals in parallel. Participants will be continuously assessed for 3 years at 12-month intervals. Six aspects, including clinical signs, genetic spectrum, cognitive competence, MRI features, potential biochemical indicators and nerve electrophysiological factors, will be assessed in detail. This study will observe clinical manifestations and disease severity based on different molecular mechanisms, including oxidative stress, cholesterol metabolism and microtubule dynamics, all of which have been proposed as potential treatment targets or modalities. The analysis will also assess disease progression in different types of HSPs and cellular pathways with a longitudinal study using t tests and χ2 tests.Ethics and disseminationThe study was granted ethics committee approval by the first affiliated hospital of Fujian Medical University (MRCTA, ECFAH of FMU (2019)194) in 2019. Findings will be disseminated via presentations and peer-reviewed publications. Dissemination will target different audiences, including national stakeholders, researchers from different disciplines and the general public.Trial registration numberNCT04006418.
Long noncoding RNAs (lncRNAs) play roles in the development and progression of many cancers; however, the contributions of lncRNAs to human gallbladder cancer (GBC) remain largely unknown. In this ...study, we identify a group of differentially expressed lncRNAs in human GBC tissues, including prognosis-associated gallbladder cancer lncRNA (lncRNA-PAGBC), which we find to be an independent prognostic marker in GBC. Functional analysis indicates that lncRNA-PAGBC promotes tumour growth and metastasis of GBC cells. More importantly, as a competitive endogenous RNA (ceRNA), lncRNA-PAGBC competitively binds to the tumour suppressive microRNAs miR-133b and miR-511. This competitive role of lncRNA-PAGBC is required for its ability to promote tumour growth and metastasis and to activate the AKT/mTOR pathway. Moreover, lncRNA-PAGBC interacts with polyadenylate binding protein cytoplasmic 1 (PABPC1) and is stabilized by this interaction. This work provides novel insight on the molecular pathogenesis of GBC.
Synopsis
Long noncoding RNAs play roles in the development and progression of many cancers. In this study the lncRNA PAGBC is identified as promoting tumorigenesis in human gallbladder cancer by competitive binding to the tumour suppressive microRNAs miR-133b and miR-511.
LncRNA-PAGBC is up-regulated in GBC and increased levels associate with poor prognosis.
LncRNA-PAGBC promotes tumour growth and metastasis, and activates AKT/mTOR signaling by competitively binding to mirR-133b and mirR-511.
LncRNA-PAGBC interacts with and is stabilized by the polyadenylate binding protein PABPC1.
Graphical Abstract
Long noncoding RNAs play roles in the development and progression of many cancers. In this study the lncRNA PAGBC is identified as promoting tumorigenesis in human gallbladder cancer by competitive binding to the tumour suppressive microRNAs miR-133b and miR-511.
Granite-related wolframite-quartz veins are the world's most important tungsten mineralization and production resource. Recent progress in revealing their hydrothermal processes has been greatly ...facilitated by the use of infrared microscopy and laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) analysis of both quartz- and wolframite-hosted fluid inclusions. However, owing to the paucity of detailed petrography, previous fluid inclusion studies on coexisting wolframite and quartz are associated with a certain degree of ambiguity. To better understand the fluid processes forming these two minerals, free-grown crystals of intergrown wolframite and quartz from the giant Yaogangxian W deposit in South China were studied using integrated in situ analytical methods including cathodoluminescence (CL) imaging, infrared microthermometry, Raman microspectroscopy, and fluid inclusion LA-ICP-MS analysis. Detailed crystal-scale petrography with critical help from CL imaging shows repetition of quartz, wolframite, and muscovite in the depositional sequence, which comprises a paragenesis far more complex than previous comparable studies. The reconstruction of fluid history in coexisting wolframite and quartz recognizes at least four successive fluid inclusion generations, two of which were entrapped concurrently with wolframite deposition. Fluctuations of fluid temperature and salinity during precipitation of coexisting wolframite and quartz are reflected by our microthermometry results, according to which wolframite-hosted fluid inclusions do not display higher homogenization temperature or salinity than those in quartz. However, LA-ICP-MS analysis shows that both primary fluid inclusions in wolframite and quartz-hosted fluid inclusions associated intimately with wolframite deposition are characterized by strong enrichment in Sr and depletion in B and As compared to quartz-hosted fluid inclusions that are not associated with wolframite deposition. The chemical similarity between the two fluid inclusion generations associated with wolframite deposition implies episodic tungsten mineralization derived from fluids exhibiting distinct chemical signatures. Multiple chemical criteria including incompatible elements and Br/Cl ratios of fluid inclusions in both minerals suggest a magmatic-sourced fluid with the possible addition of sedimentary and meteoric water. Combined with microthermometry and Raman results, fluid chemical evolution in terms of B, As, S, Sr, W, Mn, Fe, and carbonic volatiles collectively imply fluid phase separation and mixing with sedimentary fluid may have played important roles in wolframite deposition, whereas fluid cooling and addition of Fe and Mn do not appear to be the major driving factor. This study also shows that fluid inclusions in both wolframite and coexisting quartz may contain a substantial amount of carbonic volatiles (CO2 ± CH4) and H3BO3. Ignoring the occurrence of these components can result in significant overestimation of apparent salinity and miscalculation of LA-ICP-MS elemental concentrations. We suggest that these effects should be considered critically to avoid misinterpretation of fluid inclusion data, especially for granite-related tungsten-tin deposits.
Thiamethoxam (THIA), a second generation neonicotinoid insecticide in the thianicotinyl subclass, is used worldwide. Environmental studies revealed that microbial degradation is the major mode of ...removal of this pesticide from soil. However, microbial transformation of THIA is poorly understood. In the present study, we isolated a bacterium able to degrade THIA from rhizosphere soil. The bacterium was identified as
Ensifer adhaerens
by its morphology and 16S ribosomal DNA sequence analysis. High-performance liquid chromatography and mass spectrometry analysis suggested that the major metabolic pathway of THIA in
E. adhaerens
TMX-23 involves the transformation of its N-nitroimino group (=N–NO
2
) to N-nitrosoimino (=N–NO) and urea (=O) metabolites.
E
.
adhaerens
TMX-23 is a nitrogen-fixing bacterium harboring two types of
nifH
genes in its genome, one of which is 98 % identical to the
nifH
gene in the cyanobacterium
Calothrix
sp. MCC-3A.
E. adhaerens
TMX-23 released various plant-growth-promoting substances including indole-3-acetic acid, exopolysaccharides, ammonia, HCN, and siderophores. Inoculation of
E. adhaerens
TMX-23 onto soybean seeds (
Glycine max
L.) with NaCl at 50, 100, or 154 mmol/L increased the seed germination rate by 14, 21, and 30 %, respectively. THIA at 10 mg/L had beneficial effects on
E
.
adhaerens
TMX-23, enhancing growth of the bacterium and its production of salicylic acid, an important plant phytohormone associated with plant defense responses against abiotic stress. The nitrogen-fixing and plant-growth-promoting rhizobacterium
E. adhaerens
TMX-23, which is able to degrade THIA, has the potential for bioaugmentation as well as to promote growth of field crops in THIA-contaminated soil.
Celotno besedilo
Dostopno za:
CEKLJ, DOBA, EMUNI, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK
Benzimidazoles are a versatile class of scaffolds with important biological activities, whereas their synthesis in a lower‐cost and more efficient manner remains a challenge. Here, we demonstrate a ...conceptually new radical route for the high‐performance photoredox coupling of alcohols and diamines to synthesize benzimidazoles along with stoichiometric hydrogen (H2) over Pd‐decorated ultrathin ZnO nanosheets (Pd/ZnO NSs). The mechanistic study reveals the unique advantage of ZnO NSs over other supports and particularly that the features of Pd nanoparticles in facilitating the cleavage of the α‐C−H bond of alcohols and adsorbing subsequently‐generated C‐centered radicals hold the key to turning on the reaction. This work highlights a new insight into radical‐induced efficient benzimidazole synthesis pairing with H2 evolution by rationally designing semiconductor‐based photoredox systems.
We report a conceptually new, highly efficient radical route for the benzimidazole synthesis via radical‐induced cross‐coupling of alcohols and o‐arylenediamines concomitantly with hydrogen (H2) production over Pd modified ultrathin ZnO NSs (Pd/ZnO) under mild conditions.
Emerging evidence suggests that the clinical success of conventional chemotherapy is not solely attributed to tumor cell toxicity, but also results from the restoration of immunosurveillance, which ...has been largely neglected in the past preclinical and clinical research. Antitumor immune response can be primed by immunogenic cell death (ICD), a type of cell death characterized by cell-surface translocation of calreticulin (CRT), extracellular release of ATP and high mobility group box 1 (HMGB1), and stimulation of type I interferon (IFN) responses. Here we summarize recent studies showing conventional chemotherapeutics as ICD inducers, which are capable of modulating tumor infiltrating lymphocytes (TILs) and reactivating antitumor immunity within an immuno-suppressive microenvironment. Such immunological effects of conventional chemotherapy are likely critical for better prognosis of cancer patients. Furthermore, combination of ICD-inducing chemotherapeutics with immunotherapy is a promising approach for improving the clinical outcomes of cancer patients.
Uniform porous silicon hollow nanospheres are prepared without any sacrificial templates through a magnesiothermic reduction of mesoporous silica hollow nanospheres and surface modified by the ...following in situ chemical polymerization of polypyrrole. The porous hollow structure and polypyrrole coating contribute significantly to the excellent structure stability and high electrochemical performance of the nanocomposite.
Nasopharyngeal carcinoma (NPC) is a malignant epithelial tumor originating in the nasopharynx and has a high incidence in Southeast Asia and North Africa. To develop these comprehensive guidelines ...for the diagnosis and management of NPC, the Chinese Society of Clinical Oncology (CSCO) arranged a multi‐disciplinary team comprising of experts from all sub‐specialties of NPC to write, discuss, and revise the guidelines. Based on the findings of evidence‐based medicine in China and abroad, domestic experts have iteratively developed these guidelines to provide proper management of NPC. Overall, the guidelines describe the screening, clinical and pathological diagnosis, staging and risk assessment, therapies, and follow‐up of NPC, which aim to improve the management of NPC.
Highly-efficient oxygen evolution reaction (OER) and reduction of carbon dioxide (CO 2 RR) represent the two biggest scientific challenges in artificial photosynthesis. Many efficient and ...cost-affordable electrocatalysts have been reported in the development of electrochemical OER and CO 2 RR; however, during the electro-derived oxidation or reduction processes, a critical fact that, most catalysts tend to undergo structural reconstruction and/or surface rearrangement, has been widely observed, which greatly subverts the traditional conception of “catalysts”. In this respect, the research trends have gradually transferred from optimizing catalyst materials to elucidating the real active sites of the catalysts as well as understanding the underlying mechanisms behind these complex reactions. Most importantly, the in situ / operando characterization techniques are powerful tools to achieve this goal. Herein, recent advances in the in situ X-ray diffraction and absorption spectroscopy that have provided a unique opportunity to investigate the structural reconstruction and/or surface rearrangement of catalysts under realistic OER and CO 2 RR conditions are thoroughly reviewed. Finally, the challenges of the material design are discussed, and the future perspective for developing next-generation catalysts with imperative requirements of material nature is provided.
Hydrogen sulfide (H2S) has been recognized as an important gaseous signaling molecule in living systems, and is of great significance in many pathological and physiological processes. Misregulation ...of endogenous H2S is implicated in various diseases in the neuronal, gastrointestinal, circulatory, and endocrine systems. Fluorescent probe with large Stokes shift and near infrared emission, is ideal candidate for imaging applications to prevent excitation scattering, autofluorescence interference, matrix absorption caused signal loss, and sample destruction. In this study, a dual-side expansion approach was performed to develop spectra tunable hydroxyl functional flavylium derivative named HN8 with enlarged Stokes shift of 81 nm, lengthened emission of 671 nm, satisfied quantum yield of 0.23, and good fluorescence enhancement factor of 14.3-fold. Moreover, based on HN8, the screened probe HN8DNP displayed 225-fold fluorescence enhancement containing linear correlations to H2S from 0 to 50 μM with good limit of detection (LOD) of 0.31 μM. Therefore, HN8DNP was then applied for imaging exogenous H2S and drug induced enzymatic H2S generation in living cells with satisfied results, revealing the relationship between intracellular H2S levels and related enzyme activities. In a word, the present work provided a potential fluorescence probe for highly selective and sensitive detecting H2S in vitro and in living cells. And the promising dual-side expansion strategy for regulation optical feature of traditional fluorophore may meet the increasing requirements of sensing and imaging applications.
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•HN8 has Stokes shift of 81 nm, emission of 671 nm, and quantum yield of 0.23.•HN8 showed 14.3-fold fluorescence enhancement factor.•Probe HN8DNP displayed 225-fold enhancement and LOD of 0.31 μM to H2S.•Probe HN8DNP was applied for imaging exogenous H2S and enzymatic H2S generation.
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