De novo creation of fluorescent molecules via adversarial generative modeling.

The development of AI for fluorescent materials design is technologically demanding due to the issue of accurately forecasting fluorescent properties. Besides the huge efforts made in predicting the photoluminescent properties of organic dyes in terms of machine learning techniques, this article aims to introduce an adversarial generation paradigm for the rational design of fluorescent molecules. Molecular SMILES is employed as the input of a GRU based autoencoder, where the encoding and decoding of the string information are processed. A generative adversarial network is applied on the latent space with a generator to generate samples to mimic the latent space, and a discriminator to distinguish samples from the latent space. It is found that the excited state property distributions of generated molecules fully match those of the original samples, with the molecular synthesizability being accessible as well. Further screening of the generated samples delivers a remarkable luminescence efficiency of molecules epitomized by the significant oscillator strength and charge transfer characteristics, demonstrating the great potential of the adversarial model in enriching the fluorescent library.

Efficient Adversarial Generation of Thermally Activated Delayed Fluorescence Molecules.

Adversarial generative models are becoming an essential tool in molecular design and discovery due to their efficiency in exploring the desired chemical space with the assistance of deep learning. In this article, we introduce an integrated framework by combining the modules of algorithmic synthesis, deep prediction, adversarial generation, and fine screening for the purpose of effective design of the thermally activated delayed fluorescence (TADF) molecules that can be used in the organic light-emitting diode devices. The retrosynthetic rules are employed to algorithmically synthesize the D-A complex based on the empirically defined donor and acceptor moieties, which is followed by the high-throughput labeling and prediction with the deep neural network. The new D-A molecules are subsequently generated via the adversarial autoencoder, with the excited-state property distributions perfectly matching those of the original samples. Fine screening of the generated molecules, including the spin-orbital coupling calculation and the excited-state optimization, is eventually implemented to select the qualified TADF candidates within the novel chemical space. Further investigation shows that the created structures fully mimic the original D-A samples by maintaining a significant charge transfer characteristic, a minimal adiabatic singlet-triplet gap, and a moderate spin-orbital coupling that are desirable for the delayed fluorescence.

A Multitask Approach to Learn Molecular Properties.

The endeavors to pursue a robust multitask model to resolve intertask correlations have lasted for many years. A multitask deep neural network, as the most widely used multitask framework, however, experiences several issues such as inconsistent performance improvement over the independent model benchmark. The research aims to introduce an alternative framework by using the problem transformation methods. We build our multitask models essentially based on the stacking of a base regressor and classifier, where the multitarget predictions are realized from an additional training stage on the expanded molecular feature space. The model architecture is implemented on the QM9, Alchemy, and Tox21 datasets, by using a variety of baseline machine learning techniques. The resultant multitask performance shows 1 to 10% enhancement of forecasting precision, with the task prediction accuracy being consistently improved over the independent single-target models. The proposed method demonstrates a notable superiority in tackling the intertarget dependence and, moreover, a great potential to simulate a wide range of molecular properties under the transformation framework.

Incidence and risk factors of anti-tuberculosis drug induced liver injury (DILI): Large cohort study involving 4652 Chinese adult tuberculosis patients.

BACKGROUND AND AIMS: Anti-tuberculosis drugs remain as an important cause of drug-induced liver injury (DILI) worldwide. Adverse drug reactions reduce the effectiveness of treatment. We aimed to determine the incidence and risk factors associated with anti-tuberculosis DILI (ATDILI). METHODS: Using established criteria and causality assessment methods, risk factors for ATDILI were identified in a contemporary cohort and validated in another cohort prospectively. Independent determinants of ATDILI were identified using Cox regression analysis. RESULTS: In the derivation cohort (n = 3155), 170 (5.4%) developed ATDILI of which 27 (15.9%) developed jaundice; 9(5.3%) developed acute liver failure (ALF) and 3 died. Among HBsAg positive patients, 11/27 (40.7%) of ATDILI developed after 3 months of starting treatment. In addition, of 218 (6.9%) who developed raised alanine transferase (ALT) levels ≥3 times upper limit normal, 193 (88.5%) resolved and 25 (11.4%) progressed to DILI. Age (HR = 1.014, 95% CI: 1.005-1.023), baseline ALT (HR = 1.014, 95% CI: 1.003-1.024), haemoglobin (HR = 1.011, 95% CI: 1.002-1.020) and HBsAg positivity (HR = 1.516, 95% CI: 1.004-2.290) were independent risk factors for DILI. In the second cohort (n = 1497) of which 85 (5.7%) developed ATDILI. Age (HR = 1.029, 95% CI: 1.003-1.056), baseline AST (HR = 1.036, 95% CI: 1.010-1.062), previous TB treatment (HR = 3.894, 95% CI: 1.304-11.625) and active drinking (HR = 3.624, 95% CI: 1.147-11.454) were risk factors for developing jaundice. CONCLUSION: Elevation of ALT of ≥3 × ULN during anti-TB treatment resolves in the vast majority without developing serious consequences. In two cohorts involving 4652 patients, incidence of ALF and death because of ATDILI are low. Age, baseline ALT, haemoglobin and HBsAg positivity are risk factors for the development of DILI and these inform monitoring and management of these patients.

A species-specific triplex PCR assay for authentication of Galli Gigerii Endothelium Corneum.

A triplex PCR assay was developed to identify animal species and adulteration of a natural medicine Galli Gigerii Endothelium Corneum (GGEC). Three species-specific primer sets were designed according to the difference in mitochondrial genome of Gallus gallus domesticus, Anas platyrhynchos and Anser anse. The PCR conditions were optimized and the assay was well validated for high specificity and sensitivity (1 mg/µL). Especially, when artificial adulterants made from the mixture of three species were analyzed, the assay has still exhibited strong capability of differentiation. By using this developed method, two batches out of fourteen commercial GGEC products were identified to be adulterated by Anser anse. The newly proposed assay showed sufficient merits as a regular tool for the identification of counterfeits or adulterants of GGEC product for their pulverized and processed form, and even Chinese patent medicines composed of these species.

Role of Drugs Used for Chronic Disease Management on Susceptibility and Severity of COVID-19: A Large Case-Control Study.

This study aimed to investigate whether specific medications used in the treatment chronic diseases affected either the development and/ or severity of coronavirus disease 2019 (COVID-19) in a cohort of 610 COVID-19 cases and 48,667 population-based controls from Zhejiang, China. Using a cohort of 578 COVID-19 cases and 48,667 population-based controls from Zhejiang, China, we tested the role of usage of cardiovascular, antidiabetic, and other medications on risk and severity of COVID-19. Analyses were adjusted for age, sex, and body mass index and for presence of relevant comorbidities. Individuals with hypertension taking calcium channel blockers had significantly increased risk (odds ratio (OR) = 1.73, 95% confidence interval (CI) 1.2-2.3) of manifesting symptoms of COVID-19, whereas those taking angiotensin receptor blockers and diuretics had significantly lower disease risk (OR = 0.22, 95% CI 0.15-0.30 and OR = 0.30, 95% CI 0.19-0.58, respectively). Among those with type 2 diabetes, dipeptidyl peptidase-4 inhibitors (OR = 6.02, 95% CI 2.3-15.5) and insulin (OR = 2.71, 95% CI 1.6-5.5) were more and glucosidase inhibitors were less prevalent (OR = 0.11, 95% CI 0.1-0.3) among with patients with COVID-19. Drugs used in the treatment of hypertension and diabetes influence the risk of development of COVID-19, but, not its severity.

Preparation and Characterization of Edible Dialdehyde Carboxymethyl Cellulose Crosslinked Feather Keratin Films for Food Packaging.

The development of edible films based on the natural biopolymer feather keratin (FK) from poultry feathers is of great interest to food packaging. Edible dialdehyde carboxymethyl cellulose (DCMC) crosslinked FK films plasticized with glycerol were prepared by a casting method. The effect of DCMC crosslinking on the microstructure, light transmission, aggregate structure, tensile properties, water resistance and water vapor barrier were investigated. The results indicated the formation of both covalent and hydrogen bonding between FK and DCMC to form amorphous FK/DCMC films with good UV-barrier properties and transmittance. However, with increasing DCMC content, a decrease in tensile strength of the FK films indicated that plasticization, induced by hydrophilic properties of the DCMC, partly offset the crosslinking effect. Reduction in the moisture content, solubility and water vapor permeability indicated that DCMC crosslinking slightly reduced the moisture sensitivity of the FK films. Thus, DCMC crosslinking increased the potential viability of the FK films for food packaging applications, offering a value-added product.

DC-SIGN mediates gastric cancer progression by regulating the JAK2/STAT3 signaling pathway and affecting LncRNA RP11-181G12.2 expression.

BACKGROUND: The molecular mechanisms of gastric cancer (GC) development are very complicated. Recent studies revealed that DC-specific intercellular adhesion molecule 3-grabbing nonintegrin (DC-SIGN)-related protein (DC-SIGNR) is involved in colon cancer and GC biological processes. However, the exact roles of DC-SIGN in GC remain unrevealed. METHODS: DC-SIGN overexpression and knockdown experiments were performed by using DC-SIGN shRNA or DC-SIGN plasmid to investigate the biological roles of DC-SIGN in proliferation, cell cycle progression, migration and invasion of GC cells in vitro. Furthermore, the lncRNA profiles of SGC-7901 cells with control shRNA and DC-SIGN shRNA were generated by using microarray analysis. Mechanistically, the relationship between DC-SIGN, RP11-181G12.2 and the JAK2/STAT3 signaling pathway was then investigated using qRT-PCR and western blot assays. Additionally, we analyzed DC-SIGN and RP11-181G12.2 expression levels in GC specimens based on the Cancer Genome Atlas database. RESULTS: In this study, the results showed that DC-SIGN was highly expressed in GC cells and significantly correlated with advanced clinical stage and lymphatic metastasis. Downregulation of DC-SIGN significantly inhibited the proliferation, cell cycle progression, migration and invasion of GC cells in vitro. The reverse results could partly be seen with the upregulation of DC-SIGN. Mechanistically, knockdown of DC-SIGN inactivated the JAK2/STAT3 signaling pathway, and overexpression of DC-SIGN activated the JAK2/STAT3 signaling pathway. In addition, through LncPath microarray analysis, we identified a lncRNA, RP11-181G12.2, that was significantly upregulated after knockdown of DC-SIGN; this was also confirmed by qRT-PCR. Furthermore, RP11-181G12.2 knockdown enhanced DC-SIGN expression in GC cells, further activating the JAK2/STAT3 signaling pathway. In contrast, DC-SIGN overexpression suppressed RP11-181G12.2 expression. CONCLUSIONS: Our study suggests that DC-SIGN might be involved in the progression of GC by regulating the JAK2/STAT3 signaling pathway and affecting lncRNA RP11-181G12.2 expression.

Diffusion-Weighted Magnetic Resonance Imaging for Early Detection of Chemotherapy Resistance in Non-Small Cell Lung Cancer.

BACKGROUND The aim of this study was to examine the role of magnetic resonance imaging-diffusion weighted imaging (MRI-DWI) in the early detection of chemotherapy resistance in non-small cell lung cancer (NSCLC) patients. MATERIAL AND METHODS MRI-DWI and computed tomography (CT) were carried out in 75 patients with newly diagnostic NSCLC before and after first, second, fourth, and sixth cycles of chemotherapy. Resistance to chemotherapy was assessed based on the change in the largest tumor diameter after chemotherapy. Diffusion of water molecule in each lesion was quantitatively measured by apparent diffusion coefficient (ADC). The diagnostic results of DWI after first and second cycle of chemotherapy were analyzed by the area under receiver operating characteristics curve (ROC). RESULTS Among the patients, 43 patients were chemo-resistance while 32 patients were chemo-sensitive. The ADC changing rate between second and first cycle of chemotherapy was significantly higher in chemo-sensitive patients compared with chemo-resistance patients (t=3.236, P=0.002). The ROC showed cutoff values of the ADC changing rate after first and second cycles of chemotherapy for resistance/sensitive discrimination were 23.6% and 5.56%, respectively. DWI after first and second cycles of therapy showed sensitivities of 55.8% and 55.8%, specificities of 65.6% and 87.5%, and area under ROC of 0.568 and 0.733, respectively. CONCLUSIONS ADC changing rate between first and second cycles of chemotherapy could sensitively distinguish chemo-sensitive and chemo-resistant tumors at earlier stages, which may direct treatment adjustment and improve the prognosis of patients.

[Limbal allografting from related live donors for limbal stem cell deficiency secondary to ocular chemical burn].

OBJECTIVE: To investigate the efficacy and complications of limbal allografting from related live donors (RL-LAT) for limbal stem cell deficiency secondary to ocular chemical burn. METHODS: Retrospective comparative case series. Limbal allografting from related live human leukocyte antigen (HLA)-matched (n = 10) and-unmatched donors (n = 2) was performed in 12 consecutive patients (12 eyes) with limbal stem cell deficiency secondary to ocular chemical burn, including 9 alkali burn and 3 acid burn; whereas allolimbal cadaver transplant was performed in another 15 patients in Zhongshan Ophthalmic Center between April 2006 to December 2007. Systemic cyclosporine A was administered to later eight recipients in living related donor group and all patients in cadaver donor group. Main outcome measures were restoration of corneal epithelium, reduction in corneal vascularization, improved corneal clarity, and visual improvement. Mean follow-up was (11.4 ± 3.6) months (from 12 to 27). RESULTS: In living related donor group, ten patients (83.3%) achieved initially reepithelialize, and epithelial healing time was (9.6 ± 3.4) d. Nine patients (75.0%) achieved stable ocular surface (stable corneal epithelium, decreased vascularization of corneal surface, and reduced corneal opacification). However, in seven eyes (77.8%) achieved stable ocular surface, gradual recurrence of peripheral corneal vascularization occurred after 5 to 8 months postoperatively. Whereas in cadaver donor group, twelve patients (80.0%) achieved initially reepithelialize, and epithelial healing time was (11.2 ± 4.6) d. Seven patients (46.7%) achieved stable ocular surface. However, in all seven eyes achieved stable ocular surface, gradual recurrence of peripheral corneal vascularization occurred after 4 to 10 months postoperatively. The differences of both the rate of initially reepithelialize and epithelial healing time between these two groups showed no statistical significance (χ(2) = 1.764, P = 0.117; t = 0.116, P = 0.133, respectively). However, the differences of both the successful rate of ocular surface reconstruction and the recurrent rate of corneal vascularization during the follow-up period between these two groups were statistically significant (χ(2) = 4.158, P = 0.015; χ(2) = 3.463, P = 0.022, respectively). In living related donor group, features of graft rejection developed in two patients with postoperative stable ocular surface, Both rejected recipients had one among HLA-matched and one among-unmatched respectively. Whereas in cadaver donor group, features of graft rejection developed in three patients with postoperative stable ocular surface. None of the donor eyes had any complications. CONCLUSIONS: Limbal allografting from related live donors is more effective to reconstruct the ocular surface of limbal stem cell deficiency secondary to ocular chemical burn than allolimbal cadaver transplant. HLA-matched limbal allografting could reduce postoperative graft rejection and systemic cyclosporine A is useful in ensuring long-term survival.

The mechanical behaviors of polytetrafluorethylene/Al/W energetic composites.

The tensile and impact properties of polytetrafluorethylene (PTFE)/Al/W reactive energetic composites were investigated using a universal materials testing machine and an improved pendulum impact tester at room temperature. Samples of four types, all containing W, of differing composition and particle size were prepared by cold pressing and sintering. With increasing W content in the PTFE/Al/W samples, the mass loss during sintering and the density of the materials obtained increased. The addition of microlevel W led to the tensile strength decreasing from 25.3 to 19.8 MPa, while the elongation changed little, but substituting nanolevel W for 5 wt% Al yields a maximal strength of 31.4 MPa. The failure behavior of PTFE/Al/W includes deformation, fracture, disorganization and reaction, in four steps. The addition of 30 wt% of coarse W particles improved the impact strength of the material, but the reactive activity increased and the perfectability of the reaction decreased.