To investigate the change from baseline of inflammatory markers in tears of dry eye disease (DED) subjects owing to meibomian gland dysfunction (MGD) after intense pulsed light (IPL) treatment and ...meibomian gland expression (MGE) compared to sham treatment, and the correlations with ocular surface parameters.
Randomized, double-masked, controlled study.
Those randomized into the active treatment arm received 3 consecutive treatments (14∼16 J/cm2) approximately 4 weeks apart in the periocular region. Control eyes received 3 treatments in the same intervals of 0 J/cm2. Tear samples in all eyes were collected and analyzed at baseline, week 12, and/or week 4 for interleukin (IL)-17A, IL-6, and prostaglandin E2 (PGE2). The correlations between cytokines and ocular surface parameters were analyzed before and after IPL treatment.
All of the inflammatory markers declined in value compared to baselines. IL-17A and IL-6 showed statistically significant decreases compared to sham treatment at each measured time point. PGE2 showed statistically significant decreases compared to sham at week 12. Results showed that the expressions of IL-17A and IL-6 correlated well with ocular surface parameters of the lower eyelid before IPL. The changed values of IL-6 and PGE2 in tears correlated with the changed values of partial ocular surface parameters after IPL treatment in study eyes, respectively.
The study results suggest that IPL can significantly reduce inflammatory markers in tears of patients suffering with DED owing to MGD after IPL treatment. These findings indicate that IL-17A and IL-6 play roles in the pathogenesis of DED owing to MGD, and the reduction of the inflammatory factors is consistent with the improvement of partial clinical symptoms and signs.
A series of meta-amido bromophenol derivatives were designed and synthesized. The compounds were found to potently inhibit the growth of Mycobacterium tuberculosis H37Ra. They also exhibited moderate ...inhibitory activity against Mycobacterium tuberculosis H37Rv and multidrug-resistant strains. The compounds did not show inhibitory activity against normal Gram-positive and Gram-negative bacteria. Moderate cytotoxicities and good metabolic stability were observed for the selected compounds. The results demonstrated meta-amido bromophenols as a new class of antitubercular agents with good potentials.
Plant-derived nature products, known as herb formulas, have been commonly used in Traditional Chinese Medicine (TCM) for disease prevention and treatment. The herbs have been traditionally classified ...into different categories according to the TCM Organ systems known as Meridians. Despite the increasing knowledge on the active components of the herbs, the rationale of Meridian classification remains poorly understood. In this study, we took a machine learning approach to explore the classification of Meridian. We determined the molecule features for 646 herbs and their active components including structure-based fingerprints and ADME properties (absorption, distribution, metabolism and excretion), and found that the Meridian can be predicted by machine learning approaches with a top accuracy of 0.83. We also identified the top compound features that were important for the Meridian prediction. To the best of our knowledge, this is the first time that molecular properties of the herb compounds are associated with the TCM Meridians. Taken together, the machine learning approach may provide novel insights for the understanding of molecular evidence of Meridians in TCM.
The performances of photoelectrochemical (PEC) sensors mainly depend on the physical/chemical properties of photoactive materials. Therefore, the preparation of semiconductors with strong light ...absorption capacity, high photoelectric conversion efficiency, effective carrier separation and good light stability, has received much interest in the field of PEC sensing. As bismuth oxyhalides (BiOX, X = Cl, Br, I)-based photocatalysts present wider light absorption range, adjustable band gap and good light stability, they have been widely studied and applied in PEC sensing. This paper reviews the functionalization methods of BiOX and highlights the impact of functionalization on their morphology, composition, structure and properties. Importantly, the sensing strategies of BiOX-based functional materials in photoanodic and photocathodic sensing are systematically summarized. Finally, the challenges and opportunities for the BiOX-based PEC sensors are prospected.
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•Functionalization methods of BiOX are summarized.•Applications of BiOX-based photoanodic and photocathodic sensors are reviewed.•An opinion to the development trends of PEC sensors based on BiOX is presented.
Abstract
We analyze the 3D morphology and kinematics of 13 open clusters (OCs) located within 500 pc of the Sun, using Gaia EDR 3 and kinematic data from the literature. Members of OCs are identified ...using the unsupervised machine-learning method
StarGO,
using five parameters (
X
,
Y
,
Z
,
). The OC sample covers an age range of 25 Myr to 2.65 Gyr. We correct the asymmetric distance distribution that is due to parallax error using Bayesian inversion. The uncertainty in the corrected distance for a cluster at 500 pc is 3.0–6.3 pc, depending on the intrinsic spatial distribution of its members. We determine the 3D morphology of the OCs in our sample and fit the spatial distribution of stars within the tidal radius in each cluster with an ellipsoid model. The shapes of the OCs are well described with oblate spheroids (NGC 2547, NGC 2516, NGC 2451A, NGC 2451B, and NGC 2232), prolate spheroids (IC 2602, IC 4665, NGC 2422, Blanco 1, and Coma Berenices), or triaxial ellipsoids (IC 2391, NGC 6633, and NGC 6774). The semimajor axis of the fitted ellipsoid is parallel to the Galactic plane for most clusters. Elongated filament-like substructures are detected in three young clusters (NGC 2232, NGC 2547, and NGC 2451B), while tidal-tail-like substructures (tidal tails) are found in older clusters (NGC 2516, NGC 6633, NGC 6774, Blanco 1, and Coma Berenices). Most clusters may be supervirial and expanding.
N
-body models of rapid gas expulsion with a star formation efficiency of ≈1/3 are consistent with clusters more massive than 250
M
⊙
, while clusters less massive than 250
M
⊙
tend to agree with adiabatic gas expulsion models. Only five OCs (NGC 2422, NGC 6633, NGC 6774, Blanco 1, and Coma Berenices) show clear signs of mass segregation.
During drug development, safety is always the most important issue, including a variety of toxicities and adverse drug effects, which should be evaluated in preclinical and clinical trial phases. ...This review article at first simply introduced the computational methods used in prediction of chemical toxicity for drug design, including machine learning methods and structural alerts. Machine learning methods have been widely applied in qualitative classification and quantitative regression studies, while structural alerts can be regarded as a complementary tool for lead optimization. The emphasis of this article was put on the recent progress of predictive models built for various toxicities. Available databases and web servers were also provided. Though the methods and models are very helpful for drug design, there are still some challenges and limitations to be improved for drug safety assessment in the future.
The combination of chirality and phase transition materials has broad application prospects. Therefore, based on the quasi-spherical theory and the thought strategy of introducing chirality, we have ...successfully synthesized a pair of chiral enantiomeric ligand R/S-triethyl (2-hydroxy-propyl) ammonium iodide, which can be combined with tin hexachloride anion to obtain a pair of new organic-inorganic hybrid enantiomeric high-temperature plastic phase transition materials: R/S-CH3CH(OH)CH2N(CH2CH3)32SnCl6 (1-R/1-S), which has a high temperature phase transition of Tc=384 K, crystallized in P21 chiral space group at room temperature, and has obvious CD signal. In addition, compound 1-R and 1-S also has good low-loss dielectric switch and broadband gap. This work is conducive to the research of chiral high-temperature reversible plastic phase transition materials, and promotes the development of multi-functional phase transition materials.
Abstract
MicroRNAs (miRNAs) are small non-coding RNAs (typically consisting of 18–25 nucleotides) that negatively control expression of target genes at the post-transcriptional level. Owing to the ...biological significance of miRNAs, miRTarBase was developed to provide comprehensive information on experimentally validated miRNA–target interactions (MTIs). To date, the database has accumulated >13,404 validated MTIs from 11,021 articles from manual curations. In this update, a text-mining system was incorporated to enhance the recognition of MTI-related articles by adopting a scoring system. In addition, a variety of biological databases were integrated to provide information on the regulatory network of miRNAs and its expression in blood. Not only targets of miRNAs but also regulators of miRNAs are provided to users for investigating the up- and downstream regulations of miRNAs. Moreover, the number of MTIs with high-throughput experimental evidence increased remarkably (validated by CLIP-seq technology). In conclusion, these improvements promote the miRTarBase as one of the most comprehensively annotated and experimentally validated miRNA–target interaction databases. The updated version of miRTarBase is now available at http://miRTarBase.cuhk.edu.cn/.
Human papillomavirus (HPV) is the well‐established etiologic factor for cervical neoplasia. Cervical conization constitutes an effective treatment for high‐grade cervical intraepithelial neoplasia ...(HG‐CIN). We conducted an observational study for long‐term outcomes and HPV genotype changes after conization for HG‐CIN. Between 2008 and 2014, patients with newly diagnosed HG‐CIN before conization (surveillance new SN group) and those who had undergone conization without hysterectomy (surveillance previous SP group) were enrolled. HPV testing and Pap smear were performed periodically for the SN and SP (collectively S) groups. All other patients receiving conization for HG‐CIN during the study period were identified from our hospital database. Those eligible but not enrolled into our study were assigned to the non‐surveillance (non‐S) group. For the S group (n = 493), the median follow‐up period was 74.3 months. Eighty‐four cases had recurrent CIN Grade 2 or worse (CIN2+) (5‐year cumulative rate: 14.8%), of which six had invasive cancer. Among the 84 patients, 65 (77.4%) exhibited type‐specific persistence in the paired HPV results, whereas only 7 (8.3%) harbored new HPV types that belonged to the 9‐valent vaccine types. Among the 7397 non‐S patients, 789 demonstrated recurrent CIN2+, of which 57 had invasive cancer. The stages distribution of those progressed to invasive cancer in the non‐S group were more advanced than the S group (P = .033). Active surveillance might reduce the severity of those progressed to cancer. Because a majority of the patients with recurrent CIN2+ had persistent type‐specific HPV infections, effective therapeutic vaccines are an unmet medical need.
What's new?
High‐grade cervical intraepithelial neoplasia (HG‐CIN), a cervical carcinoma precursor, frequently is caused by high‐risk human papillomavirus (hr‐HPV) infection. HG‐CIN can be treated by cervical conization, though the procedure does not eradicate hr‐HPV, potentially enabling CIN recurrence. Here, in Taiwanese patients, investigation of HPV genotype changes in relation to HG‐CIN status after conization shows that 77.4 percent of patients with recurrent CIN 2 grade or worse (CIN2+) after conization had persistent type‐specific HPV infections. Vaccination against the remaining high‐risk HPVs prevented recurrent CIN2+ in only 8.3 percent of patients, revealing an unmet need for effective therapeutic vaccines.
Tumour lineage plasticity is an emerging hallmark of aggressive tumours. Tumour cells usually hijack developmental signalling pathways to gain cellular plasticity and evade therapeutic targeting. In ...the present study, the secreted protein growth and differentiation factor 1 (GDF1) is found to be closely associated with poor tumour differentiation. Overexpression of GDF1 suppresses cell proliferation but strongly enhances tumour dissemination and metastasis. Ectopic expression of GDF1 can induce the dedifferentiation of hepatocellular carcinoma (HCC) cells into their ancestral lineages and reactivate a broad panel of cancer testis antigens (CTAs), which further stimulate the immunogenicity of HCC cells to immune-based therapies. Mechanistic studies reveal that GDF1 functions through the Activin receptor-like kinase 7 (ALK7)-Mothers against decapentaplegic homolog 2/3 (SMAD2/3) signalling cascade and suppresses the epigenetic regulator Lysine specific demethylase 1 (LSD1) to boost CTA expression. GDF1-induced tumour lineage plasticity might be an Achilles heel for HCC immunotherapy. Inhibition of LSD1 based on GDF1 biomarker prescreening might widen the therapeutic window for immune checkpoint inhibitors in the clinic.
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