Upper gastrointestinal cancers (including oesophageal cancer and gastric cancer) are the most common cancers worldwide. Artificial intelligence platforms using deep learning algorithms have made ...remarkable progress in medical imaging but their application in upper gastrointestinal cancers has been limited. We aimed to develop and validate the Gastrointestinal Artificial Intelligence Diagnostic System (GRAIDS) for the diagnosis of upper gastrointestinal cancers through analysis of imaging data from clinical endoscopies.
This multicentre, case-control, diagnostic study was done in six hospitals of different tiers (ie, municipal, provincial, and national) in China. The images of consecutive participants, aged 18 years or older, who had not had a previous endoscopy were retrieved from all participating hospitals. All patients with upper gastrointestinal cancer lesions (including oesophageal cancer and gastric cancer) that were histologically proven malignancies were eligible for this study. Only images with standard white light were deemed eligible. The images from Sun Yat-sen University Cancer Center were randomly assigned (8:1:1) to the training and intrinsic verification datasets for developing GRAIDS, and the internal validation dataset for evaluating the performance of GRAIDS. Its diagnostic performance was evaluated using an internal and prospective validation set from Sun Yat-sen University Cancer Center (a national hospital) and additional external validation sets from five primary care hospitals. The performance of GRAIDS was also compared with endoscopists with three degrees of expertise: expert, competent, and trainee. The diagnostic accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of GRAIDS and endoscopists for the identification of cancerous lesions were evaluated by calculating the 95% CIs using the Clopper-Pearson method.
1 036 496 endoscopy images from 84 424 individuals were used to develop and test GRAIDS. The diagnostic accuracy in identifying upper gastrointestinal cancers was 0·955 (95% CI 0·952–0·957) in the internal validation set, 0·927 (0·925–0·929) in the prospective set, and ranged from 0·915 (0·913–0·917) to 0·977 (0·977–0·978) in the five external validation sets. GRAIDS achieved diagnostic sensitivity similar to that of the expert endoscopist (0·942 95% CI 0·924–0·957 vs 0·945 0·927–0·959; p=0·692) and superior sensitivity compared with competent (0·858 0·832–0·880, p<0·0001) and trainee (0·722 0·691–0·752, p<0·0001) endoscopists. The positive predictive value was 0·814 (95% CI 0·788–0·838) for GRAIDS, 0·932 (0·913–0·948) for the expert endoscopist, 0·974 (0·960–0·984) for the competent endoscopist, and 0·824 (0·795–0·850) for the trainee endoscopist. The negative predictive value was 0·978 (95% CI 0·971–0·984) for GRAIDS, 0·980 (0·974–0·985) for the expert endoscopist, 0·951 (0·942–0·959) for the competent endoscopist, and 0·904 (0·893–0·916) for the trainee endoscopist.
GRAIDS achieved high diagnostic accuracy in detecting upper gastrointestinal cancers, with sensitivity similar to that of expert endoscopists and was superior to that of non-expert endoscopists. This system could assist community-based hospitals in improving their effectiveness in upper gastrointestinal cancer diagnoses.
The National Key R&D Program of China, the Natural Science Foundation of Guangdong Province, the Science and Technology Program of Guangdong, the Science and Technology Program of Guangzhou, and the Fundamental Research Funds for the Central Universities.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
High‐nickel (Ni ≥ 90%) cathodes with high specific capacity hold great potential for next‐generation lithium‐ion batteries (LIBs). However, their practical application is restricted by the high ...interfacial reactivity under continuous air erosion and electrolyte assault. Herein, a stable high‐nickel cathode is rationally designed via in situ induction of a dense amorphous Li2CO3 on the particle surface by a preemptive atmosphere control. Among the residual lithium compounds, Li2CO3 is the most thermodynamically stable one, so a dense Li2CO3 coating layer can serve as a physical protection layer to isolate the cathode from contact with moist air. Furthermore, amorphous Li2CO3 can be transformed into a robust F‐rich cathode electrolyte interphase (CEI) during cycling, which reinforces the cathode's interfacial stability and improves the electrochemical performance. The assembled coin cell with this modified cathode delivers a high discharge capacity of 232.4 mAh g–1 with a superior initial Coulombic efficiency (CE) of 95.1%, and considerable capacity retention of 90.4% after 100 cycles. Furthermore, no slurry gelation occurs during the large‐scale electrode fabrication process. This work opens a valuable perspective on the evolution of amorphous Li2CO3 in LIBs and provides guidance on protecting unstable high‐capacity cathodes for energy‐storage devices.
A high‐nickel cathode (Ni ≥ 90%) is developed through controlling the surface residual lithium composition with a formed amorphous Li2CO3 protective layer. This cathode can resist corrosion by air, and will be converted into a stable cathode electrolyte interphase during the electrochemical process, resulting in enhanced storage performance and extended cycle life for high‐nickel cathodes.
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Tuberous sclerosis complex (TSC) integrates upstream stimuli and regulates cell growth by controlling the activity of mTORC1. TSC complex functions as a GTPase-activating protein (GAP) towards small ...GTPase Rheb and inhibits Rheb-mediated activation of mTORC1. Mutations in TSC genes cause tuberous sclerosis. In this study, the near-atomic resolution structure of human TSC complex reveals an arch-shaped architecture, with a 2:2:1 stoichiometry of TSC1, TSC2, and TBC1D7. This asymmetric complex consists of two interweaved TSC1 coiled-coil and one TBC1D7 that spans over the tail-to-tail TSC2 dimer. The two TSC2 GAP domains are symmetrically cradled within the core module formed by TSC2 dimerization domain and central coiled-coil of TSC1. Structural and biochemical analyses reveal TSC2 GAP-Rheb complimentary interactions and suggest a catalytic mechanism, by which an asparagine thumb (N1643) stabilizes γ-phosphate of GTP and accelerate GTP hydrolysis of Rheb. Our study reveals mechanisms of TSC complex assembly and GAP activity.
Multidrug‐resistant bacteria present a major threat to public health that urgently requires new drugs or treatment approaches. Here, we conduct integrated proteomic and metabolomics analyses to ...screen for molecular candidates improving survival of mice infected with Vibrio parahaemolyticus, which indicate that L‐Alanine metabolism and phagocytosis are strongly correlated with mouse survival. We also assess the role of L‐Alanine in improving mouse survival by in vivo bacterial challenge experiments using various bacteria species, including V. parahaemolyticus, Escherichia coli, Pseudomonas aeruginosa, and Klebsiella pneumoniae. Functional studies demonstrate that exogenous L‐Alanine promotes phagocytosis of these multidrug‐resistant pathogen species. We reveal that the underlying mechanism involves two events boosted by L‐Alanine: TLR4 expression and L‐Alanine‐enhanced TLR4 signaling via increased biosynthesis and secretion of fatty acids, including palmitate. Palmitate enhances binding of lipopolysaccharide to TLR4, thereby promoting TLR4 dimer formation and endocytosis for subsequent activation of the PI3K/Akt and NF‐κB pathways and bacteria phagocytosis. Our data suggest that modulation of the metabolic environment is a plausible approach for combating multidrug‐resistant bacteria infection.
Synopsis
L‐Alanine administration prophylactically and therapeutically protects hosts from infection by multidrug‐resistant bacteria. L‐Alanine enhances the phagocytosis of macrophages by boosting TLR4‐PI3K/AKT‐NFκB signaling and toll‐like receptor 4 expression.
L‐Alanine can be used as prophylactic and therapeutic reagents against infection by multidrug‐resistant bacteria.
L‐Alanine promotes macrophage phagocytosis of multidrug‐resistant bacteria by increasing the production of fatty acids.
Fatty acids enhance LPS‐induced TLR4 dimerization and endocytosis to activate PI3K/AKT and NF‐κB signaling.
L‐Alanine upregulates TLR4 expression in macrophages.
L‐Alanine administration prophylactically and therapeutically protects hosts from infection by multidrug‐resistant bacteria. L‐Alanine enhances the phagocytosis of macrophages by boosting TLR4‐PI3K/AKT‐NFκB signaling and toll‐like receptor 4 expression.
Full text
Available for:
FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
There is little evidence that adjuvant therapy after radical surgical resection of hepatocellular carcinoma (HCC) improves recurrence-free survival (RFS) or overall survival (OS). We conducted a ...multicentre, randomised, controlled, phase IV trial evaluating the benefit of an aqueous extract of
Murr (Huaier granule) to address this unmet need.
A total of 1044 patients were randomised in 2:1 ratio to receive either Huaier or no further treatment (controls) for a maximum of 96 weeks. The primary endpoint was RFS. Secondary endpoints included OS and tumour extrahepatic recurrence rate (ERR). The Huaier (n=686) and control groups (n=316) had a mean RFS of 75.5 weeks and 68.5 weeks, respectively (HR 0.67; 95% CI 0.55 to 0.81). The difference in the RFS rate between Huaier and control groups was 62.39% and 49.05% (95% CI 6.74 to 19.94; p=0.0001); this led to an OS rate in the Huaier and control groups of 95.19% and 91.46%, respectively (95% CI 0.26 to 7.21; p=0.0207). The tumour ERR between Huaier and control groups was 8.60% and 13.61% (95% CI -12.59 to -2.50; p=0.0018), respectively.
This is the first nationwide multicentre study, involving 39 centres and 1044 patients, to prove the effectiveness of Huaier granule as adjuvant therapy for HCC after curative liver resection. It demonstrated a significant prolongation of RFS and reduced extrahepatic recurrence in Huaier group.
NCT01770431; Post-results.
Due to their low toxicity, excellent biocompatibility and attractive optical properties, graphene quantum dots (GQDs) have attracted significant attention in the analytical and biological fields. The ...controllable intrinsic nature of graphene nano-sheets,
e.g.
, size, layer, edge state or shape, offer the chance to fabricate GQDs with tunable photoluminescence behaviors. Carboxylic moieties on the surface and edges of GQDs can provide efficient reactive sites for interaction with various polymeric, organic, inorganic and biological species. This not only provides the chance to tune the optical properties of GQDs
via
facile chemical approaches such as surface modulation and doping, but also makes GQDs eco-friendly alternatives to replace the traditional fluorescent probes in biological assays. This review highlights new insights into the various strategies for tuning the optical features of GQDs, and their employment as attractive and powerful probes for bio-sensing/imaging. The challenges and future perspectives in the related fields are discussed.
This review highlights new insights into the various strategies used to tune the optical features of graphene quantum dots, and their use as attractive and powerful probes for bio-sensing/imaging.
We report a facile green approach for in situ growth of silver nanoparticles (AgNPs) on the surface of graphene quantum dots (GQDs). GQDs serve as both reducing agent and stabilizer, and no ...additional reducing agent and stabilizer is necessary. The GQDs/AgNPs hybrid exhibits a superior absorbance fading response toward the reduction of H2O2. A simple colorimetric procedure is thus proposed for ultrasensitive detection of H2O2 without additional chromogenic agent. It provides a record detection limit of 33 nM for the detection of H2O2 by the AgNPs-based sensing system. This colorimetric sensing system is further extended to the detection of glucose in combination with the specific catalytic effect of glucose oxidase for the oxidation of glucose and formation of H2O2, giving rise to a detection limit of 170 nM. The favorable performances of the GQDs/AgNPs hybrid are due to the peroxidase-like activity of GQDs.
Full text
Available for:
IJS, KILJ, NUK, PNG, UL, UM
The spontaneous α-to-δ phase transition of the formamidinium-based (FA) lead halide perovskite hinders its large scale application in solar cells. Though this phase transition can be inhibited by ...alloying with methylammonium-based (MA) perovskite, the underlying mechanism is largely unexplored. In this Communication, we grow high-quality mixed cations and halides perovskite single crystals (FAPbI3)1–x (MAPbBr3) x to understand the principles for maintaining pure perovskite phase, which is essential to device optimization. We demonstrate that the best composition for a perfect α-phase perovskite without segregation is x = 0.1–0.15, and such a mixed perovskite exhibits carrier lifetime as long as 11.0 μs, which is over 20 times of that of FAPbI3 single crystal. Powder XRD, single crystal XRD and FT-IR results reveal that the incorporation of MA+ is critical for tuning the effective Goldschmidt tolerance factor toward the ideal value of 1 and lowering the Gibbs free energy via unit cell contraction and cation disorder. Moreover, we find that Br incorporation can effectively control the perovskite crystallization kinetics and reduce defect density to acquire high-quality single crystals with significant inhibition of δ-phase. These findings benefit the understanding of α-phase stabilization behavior, and have led to fabrication of perovskite solar cells with highest efficiency of 19.9% via solvent management.
Full text
Available for:
IJS, KILJ, NUK, PNG, UL, UM
Endophytic fungi or endophytes exist widely inside the healthy tissues of living plants, and are important components of plant micro-ecosystems. Over the long period of evolution, some co-existing ...endophytes and their host plants have established a special relationship with one and another, which can significantly influence the formation of metabolic products in plants, then affect quality and quantity of crude drugs derived from medicinal plants. This paper will focus on the increasing knowledge of relationships between endophytic fungi and medicinal plants through reviewing of published research data obtained from the last 30 years. The analytical results indicate that the distribution and population structure of endophytes can be considerably affected by factors, such as the genetic background, age, and environmental conditions of their hosts. On the other hand, the endophytic fungi can also confer profound impacts on their host plants by enhancing their growth, increasing their fitness, strengthening their tolerances to abiotic and biotic stresses, and promoting their accumulation of secondary metabolites. All the changes are very important for the production of bioactive components in their hosts. Hence, it is essential to understand such relationships between endophytic fungi and their host medicinal plants. Such knowledge can be well exploited and applied for the production of better and more drugs from medicinal plants.
A series of novel disulfides containing 1,3,4-thiadiazole moiety were designed, synthesized, and the structures of all products were identified by spectral data (IR, NMR, and high resolution ...(HR)-MS). Their in vitro antiproliferative activities were evaluated using 2-(2-methoxy-4-nitro-phenyl)-3-(4-nitro-phenyl)-5-(2,4-disulfopheyl)-2H-tetrazolium monosodium salt (CCK-8) assay against human cancer cell lines, A549 (human lung cancer cell), HeLa (human cervical cancer cell), SMMC-7721 (human liver cancer cell) and normal cell lines L929. The bioassay results indicated that most of the tested compounds 6a–k, 7a–k and 8a–k exhibited antiproliferation with different degrees, and some compounds showed better effects than positive control 5-fluorouracil (5-FU) against various cancer cell lines. Among these compounds, compound 6e exhibited the most potent inhibitory activity against A549 cells with IC50 value of 3.62 µM. Compounds 6i, 7a, 7g, 8a and 8b showed significantly antiproliferative activities against HeLa cells with IC50 values of 3.88, 3.76, 3.59, 3.38 and 3.12 µM, respectively. Compounds 6a, 7a and 8a owned high antiproliferative activities against SMMC-7721 cells with IC50 values of 2.54, 2.69 and 2.31 µM, respectively. Furthermore, all of the tested compounds showed weak cytotoxic effect against the normal cell lines L929. Based on the preliminary results, the substituent groups are vital for improving the potency and selectivity of this class of compounds.
PDF
