Comparative study of FLACS vs conventional phacoemulsification for cataract patients with high myopia.

PURPOSE: To compare the short-term changes in cornea, retina, and choroid of femtosecond laser-assisted cataract surgery (FLACS) with conventional phacoemulsification (CPS) in high myopia patients with cataract. SETTING: Affiliated Hospital of Nantong University, Jiangsu Province, China. DESIGN: Prospective single-center study. METHODS: Demographics, ocular clinical features, ultrasound power, absolute phacoemulsification time, and effective phacoemulsification time were recorded for each patient. Endothelial cell density (ECD), central corneal thickness (CCT), corrected distance visual acuity (CDVA), intraocular pressure (IOP), center foveal thickness (CFT), subfoveal choroidal thickness (SFCT), and choroidal vascularity index (CVI) were evaluated preoperatively and at 1 week, 1 month, and 3 months postoperatively. Intraoperative parameters and intraoperative/postoperative complications were recorded. RESULTS: 97 eyes (46 eyes and 51 eyes in the FLACS and CPS groups, respectively) were included and analyzed. Effective phacoemulsification time was lower in the FLACS group compared with the CPS group ( P < .05). The increase in CCT was significantly lower in the FLACS group compared with the CPS group at 1 week and 1 month ( P < .05). CDVA and IOP were similar in both groups at the final visit ( P > .05). The ECD decreased was lower among CPS patients compared with FLACS patients. CFT, SFCT, and CVI increase in both groups but were increased more in the CPS group with high myopia patients. No serious complications occurred in either group. CONCLUSIONS: FLACS is a more safety and effective in cataract patients with high myopia. It has advantages in effectively reducing EPT and promoting faster recovery of the cornea, macular, and choroidal thickness.

Synthesis of π-Conjugated Chiral Aza/Boracyclophanes with a meta and para Substitution.

We herein describe the synthesis of a new class of axially chiral aza/boracyclophanes (BDN1, BXN1, BDB1 and BXB1) using binaphthyls as chiral building blocks and the main-group (B/N) chemistry with tunable electronic effects. All macrocycles substituted with triarylamine donors or triarylborane acceptors are strongly luminescent. These macrocycles showed two distinct meta and para π-conjugation pathways, leading to the formation of quasi figure-of-eight and square-shaped conformations. Interestingly, comparison of such structural models revealed that the former type of macrocycles BXN1 and BXB1 gave higher racemization barriers relative to the other ones. The results reported here may provide a new approach to engineer the optical stability of π-conjugated chiral macrocycles by controlling π-substitution patterns. The ring constraints induced by macrocyclization were also demonstrated to contribute to the configurational persistence as compared with the open-chain analogues p-BTT and m-BTT.

Preparation and characterization of a laccase-like enzyme from Thermomicrobium roseum.

In this study, a laccase-like gene from Thermomicrobium roseum DSM 5159 (TrLac-like) (NCBI: WP_012642205.1) was recombinantly expressed in Bacillus subtilis WB600. The optimum temperature and pH for TrLac-like were 50 °C and 6.0, respectively. TrLac-like showed high tolerance to mixed systems of water and organic solvents, indicating its potential for large-scale application in various industries. It showed 36.81 % similarity with YlmD from Geobacillus stearothermophilus (PDB:6T1B) in sequence alignment; therefore, 6T1B was employed as the template for homology modeling. To improve catalytic efficiency, amino acid substitutions within 5 Å of the inosine ligand were simulated to reduce the binding energy and promote substrate affinity. Single and double substitutions (44 and 18, respectively) were prepared, and the catalytic efficiency of the mutant A248D was increased to approximately 110-fold that of the wild type, while the thermal stability was maintained. Bioinformatics analysis revealed that the significant improvement in catalytic efficiency could be attributed to the formation of new hydrogen bonds between the enzyme and substrate. With a further decrease in the binding energy, the catalytic efficiency of the multiple mutant H129N/A248D was approximately 14-fold higher than that of the wild type but lower than that of the single mutant A248D. This is possibly because kcat also decreased with the decrease of Km; consequently, the substrate could not be released in time owing to the enzyme with the combination mutation not being able to release the substrate at a high rate.

S1PR1 serves as a viable drug target against pulmonary fibrosis by increasing the integrity of the endothelial barrier of the lung.

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with unclear etiology and limited treatment options. The median survival time for IPF patients is approximately 2-3 years and there is no effective intervention to treat IPF other than lung transplantation. As important components of lung tissue, endothelial cells (ECs) are associated with pulmonary diseases. However, the role of endothelial dysfunction in pulmonary fibrosis (PF) is incompletely understood. Sphingosine-1-phosphate receptor 1 (S1PR1) is a G protein-coupled receptor highly expressed in lung ECs. Its expression is markedly reduced in patients with IPF. Herein, we generated an endothelial-conditional S1pr1 knockout mouse model which exhibited inflammation and fibrosis with or without bleomycin (BLM) challenge. Selective activation of S1PR1 with an S1PR1 agonist, IMMH002, exerted a potent therapeutic effect in mice with bleomycin-induced fibrosis by protecting the integrity of the endothelial barrier. These results suggest that S1PR1 might be a promising drug target for IPF therapy.

Chlorogenic Acid Relieves the Lupus Erythematosus-like Skin Lesions and Arthritis in MRL/lpr Mice.

Chlorogenic acid (CGA) is a phenylpropyl substance synthesized through the shikimic acid pathway. In addition to its anti-tumor, anti-inflammatory, and antioxidant abilities, CGA also has immunomodulatory effects. The aim of the present study is to investigate the therapeutic effects of CGA on the skin damage and arthritis caused by systemic lupus erythematosus (SLE) in an MRL/lpr mouse model. In the SLE model, female MRL/lpr mice at the age of 10 weeks old were treated with CGA daily or cyclophosphamide (CTX) weekly via intraperitoneal injection for three months. After treatment, CGA can significantly alleviate the skin and mucous membrane damage caused by SLE and has a certain improvement effect on arthritis. CGA could inhibit dsDNA expression to a certain extent but has no obvious regulation on ANA concentration. The ELISA and BioMAP results indicated that CGA might play an anti-inflammatory role by down-regulating the interleukin (IL)-17 level. In conclusion, our study demonstrates that CGA can alleviate multiorgan damage in MRL/lpr mice by reducing IL-17.

SymMap database and TMNP algorithm reveal Huanggui Tongqiao granules for Allergic rhinitis through IFN-mediated neuroimmuno-modulation.

Allergic rhinitis (AR) is a series of reactions to allergen mediated by immunoglobulin E (IgE) and is one of the most common allergic diseases that affects children. Traditional Chinese Medicine, due to its diverse regulatory functions, may offer new strategies for AR therapy. Huanggui Tongqiao Granules (HTG) is a Chinese formula consisting of twelve herbs and has long been prescribed for patients with AR. The aim of this study is to determine the possible targets and action mechanisms of HTG for the AR treatment. SymMap database and TMNP algorithm were employed to show that interferon-gamma (IFN-gamma), acting as a molecular link between immunity and neural circuits, is the involved key target. The enrichment of immune and virus-related signaling pathways indicated the neuroimmunomodulatory potential of HTG. Then, AR mouse model was established by ovalbumin (OVA) challenge and was used to verify the therapeutic effects of HTG in vivo. HTG significantly relieved AR symptoms and nasal mucosal inflammation, reduced OVA-specific IgE levels and balanced IFN-gamma/IL-4 ratio. Moreover, transcriptional profile based on clinical data presented that blood cell-specific IFN-gamma co-expressed gene module (BIM) was underexpressed in AR patients, further validating the potential of IFN-gamma as target for AR. Collectively, these findings suggest that HTG could be a promising candidate drug for AR.

Green-Solvent-Processable Low-Cost Fluorinated Hole Contacts with Optimized Buried Interface for Highly Efficient Perovskite Solar Cells.

Solution-processed hole contact materials, as an indispensable component in perovskite solar cells (PSCs), have been widely studied with consistent progress achieved. One bottleneck for the commercialization of PSCs is the lack of hole contact materials with high performance, cost-effective preparation, and green-solvent processability. Therefore, the development of versatile hole contact materials is of great significance. Herein, we report two novel donor-acceptor (D-A)-type hole contact molecules (FMPA-BT-CA and 2FMPA-BT-CA) with low cost and alcohol-based processability by utilizing a fluorination strategy. We showed that the fluorine atoms lead to the lowered highest occupied molecular orbital (HOMO) energy levels and larger dipole moments for FMPA-BT-CA and 2FMPA-BT-CA. Moreover, fluorination also improves the buried interfacial interaction between hole contacts and perovskite. As a result, a remarkable power conversion efficiency (PCE) of 22.37% along with good light stability could be achieved for green-solvent-processed FMPA-BT-CA-based inverted PSC devices, demonstrating the great potential of environmentally compatible hole contacts for highly efficient PSCs.

Design, synthesis, and biological evaluation of pyrrolopyrimidine derivatives as novel Bruton's tyrosine kinase (BTK) inhibitors.

Developing Bruton's tyrosine kinase (BTK) inhibitors has become a significant focus in recent years because BTK inhibition is an effective approach for the treatment of B-cell malignancies. For covalent BTK inhibitors, low oral bioavailability and low kinase selectivity remain unaddressed issues; thus, more diverse inhibitors with both novel structures and selective on target binding profiles are still needed. Here, four key regions where inhibitors bind to BTK were identified by analyzing the existing crystal structures of BTK complexes. Then, a scaffold-based molecular design work flow was established by integrating fragment-growing method, deep learning-based framework XGraphBoost and molecular docking, leading to four compounds that showed potency against BTK. Optimization of compounds 1 and 2 led to the discovery of the potent BTK inhibitor compound 42 by using in vitro potency and pharmacokinetic (PK) studies to prioritize the compounds. Compound 42 exhibited great BTK inhibition activity (IC50 = 0.7 nM) along with high oral absorption. Moreover, 42 demonstrated excellent kinase selectivity, especially over EGFR kinase, and low toxicity. In a TMD8 xenograft model, 42 significantly inhibited tumor growth (TGI = 104%) at a dosage of 50 mg/kg, indicating its potential as a novel therapeutic option for B-cell lymphomas.

The relationship between internet addiction and aggressive behavior among adolescents during the COVID-19 pandemic: Anxiety as a mediator.

The COVID-19 pandemic has brought unprecedented challenges for adolescents, who tended to experience more emotional instability, impulsivity, and aggressive behavior driven by the fear of infection and the uncertainty of network information. In the present study, we investigated the relationship between Internet addiction and aggressive behavior, and the mediating effects of depression and anxiety. There were differences in Internete addiction and aggressive behavior in gender, thus the moderating role of gender between them were explored. A total of 1148 middle school students were invited to complete the Buss Perry Aggression Questionnaire, the Internet Addition Scale, the Self-rating Depression Scale (SDS), and the Self-rating Anxiety Scale (SAS) separately. The results suggested that 1) there was a significant positive correlation between Internet addiction and aggressive behavior; 2) anxiety, but not depression, mediated the effect of Internet addiction on aggressive behavior; 3) gender did not moderate the effect of Internet addiction on aggressive behavior. The practical implication of the current findings on boosting adolescents' mental health was discussed and further suggestions were provided.

A π-extended triphenylamine based dopant-free hole-transporting material for perovskite solar cells via heteroatom substitution.

The triphenylamine (TPA) group is an important molecular fragment that has been widely used to design efficient hole-transporting materials (HTMs). However, the applicability of triphenylamine derived HTMs that exhibit low hole mobility and conductivity in commercial perovskite solar cells (PSCs) has been limited. To aid in the development of highly desirable TPA-based HTMs, we utilized a combination of density functional theory (DFT) and Marcus electron transfer theory to investigate the effect of heteroatoms, including boron, carbon, nitrogen, oxygen, silicon, phosphorus, sulfur, germanium, arsenic, and selenium atoms, on the energy levels, optical properties, hole mobility, and interfacial charge transfer behaviors of a series of HTMs. Our computational results revealed that compared with the commonly referenced OMeTPA-TPA molecule, most heteroatoms lead to deeper energy levels. Furthermore, these heteroatom-based HTMs exhibit improved hole mobility due to their more rigid molecular structures. More significantly, these heteroatoms also enhance the interface interaction in perovskite/HTM systems, resulting in a larger internal electric field. Our work represents a new approach that aids in the understanding and designing of more efficient and better performing HTMs, which we hope can be used as a platform to propel the developmental commercialization of these highly desirable PSCs.

Penetrance of MYOC gene mutation in primary open-angle glaucoma: A systematic review and meta-analysis.

PURPOSE: To investigate the penetrance of MYOC gene mutation in primary open-angle glaucoma (POAG) through systematic review and meta-analysis. To explore the factors affecting the penetrance of MYOC and provide evidence-based medical evidence for clinical work. METHODS: We searched all studies that reported the penetrance of MYOC mutation in PubMed, Embase, Web of Science, and Chinese databases including Wanfang, CNKI (China National Knowledge Infrastructure), and CBM (China Bio-Med). Random effects meta-analysis was conducted to estimate the penetrance of MYOC mutation in POAG. RESULTS: Fifty-two studies were included in this analysis after screening. Meta-analysis of the penetrance of MYOC mutation showed that the penetrance of MYOC mutation in POAG was 60% (95% CI: 51.0% to 68.0%) and the penetrance of MYOC mutation in POAG and suspected POAG was 68% (95% CI: 60.0% to 75.0%). The penetrance of MYOC mutation increases with age. Among Caucasians, Asians, and Africans, the penetrance of MYOC mutation in POAG was 55%, 71%, 54%, respectively, and the penetrance of MYOC mutation in POAG and suspected POAG was 64%, 83%, and 57%, respectively. Besides, the penetrance of different MYOC mutation sites was significantly discrepant. The penetrance of MYOC mutation in POAG ranged from 10.3% to 100% depending on the mutation sites. Some MYOC mutation sites have a certain population specificity, which is only pathogenic in Caucasians or Asians. CONCLUSIONS: The penetrance of MYOC mutation in POAG showed significant differences due to different mutation sites. The penetrance increased with the accrescent of age. Ethnic difference was an important factor affecting the penetrance of MYOC mutation. Knowing the rules and influencing factors of the penetrance of MYOC mutations is significant for the assessment of the risk of POAG in carriers with the MYOC mutation.

The Underlying Molecular Mechanism of Fence Engineering to Break the Activity-Stability Trade-Off in Catalysts for the Hydrogen Evolution Reaction.

Non-precious-metal (NPM) catalysts often face the formidable challenge of a trade-off between long-term stability and high activity, which has not yet been widely addressed. Herein we propose a distinct molecule-selective fence as a promising concept to solve this activity-stability trade-off. The fence encloses the catalyst and prevents species poisonous to the catalyst from reaching it, but allows catalytic reaction-related species to diffuse freely. We constructed a CoS2 fence layer on the external surface of highly active cobalt-doped MoS2 , achieving a remarkable catalytic stability towards the alkaline hydrogen evolution reaction and improved activity. In situ spectroscopy uncovered the underlying molecular mechanism of the CoS2 fence for breaking the activity-stability trade-off of the MoS2 catalyst. This work offers valuable guidance for rationally designing efficient and stable NPM catalysts.

Boron-nitrogen substituted planar cores: designing dopant-free hole-transporting materials for efficient perovskite solar cells.

Developing dopant-free hole-transporting materials (HTMs) is very important for improving the stability and increasing the power conversion efficiency of perovskite solar cells (PSCs). Herein, nine boron-nitrogen substituted tetrathienonaphthalene (BN-TTN) derivatives as hole-transporting materials (HTMs) were investigated using theoretical calculations combined with the Marcus theory and the Einstein relation. The results showed that the introduction of a boron-nitrogen group in tetrathienonaphthalene leads to a deep HOMO level, good thermal stability, and enhanced hydrophobicity. Importantly, most BN-TTN molecules possess larger hole mobility due to a broader distribution of the frontier molecular orbitals of the dimer. The BN-TTN core that matches with the size of the perovskite interface also increases the interfacial interaction and hole transfer from the perovskite layer to the HTM layer. The present findings can highlight the potential of BN-TTN core-based HTMs for efficient PSCs.

Emissive Nature and Molecular Behavior of Zero-Dimensional Organic-Inorganic Metal Halides Bmpip2MX4.

Zero-dimensional (0D) organic-inorganic metal halides, with their high stability and broadband emission features, have aroused great interest in optoelectronic applications. Metal halides of the type Bmpip2MX4 (M = Pb, Sn, or Ge; X = I or Br) have 0D disphenoidal coordinated structures that offer an excellent opportunity to investigate their emissive nature and molecular behavior. Herein, the photophysical properties and carrier transport behavior of 0D Bmpip2MX4 metal halides are studied by using density functional theory. Our results indicate that Bmpip2MX4 metal halides present broadband emission widths and significant Stokes shifts. In particular, Bmpip2SnBr4 possesses the largest Stokes shift (1.981 eV) and the shortest exciton self-trapping time, demonstrating the best photoluminescence emission ability. Bmpip2GeI4 exhibits the lowest electron-hole creation energy and the best photoresponse capacity. Moreover, Bmpip2PbI4 demonstrates superior transport capabilities with high carrier mobilities of 4.56 × 10-3 and 2.51 × 10-7 cm2 V-1 s-1 for hole and electron carriers, respectively, which makes it comparable even with typical hole transport materials (e.g., RR P3HT, ∼10-4 cm2 V-1 s-1). These findings highlight exciting opportunities for the future development and application of such kinds of 0D metal halides in optoelectronics.

Positional Effect of the Triphenylamine Group on the Optical and Charge-Transfer Properties of Thiophene-Based Hole-Transporting Materials.

Hybrid organic-inorganic perovskite solar cells (PSCs) have shown significant potential for use in the energy field. Typically, hole-transporting materials (HTMs) play an important role in affecting the power conversion efficiency (PCE) of PSCs. A deep understanding of the structure-property relationship plays a vital role in developing efficient HTMs. Herein, the relationship between the structure and properties of two small organic HTMs H2,5 and H3,4 were systematically investigated in terms of the electronic and optical properties, the hole-transporting behavior by using density functional theory (DFT) and Marcus electron transfer theory. The results demonstrated that the high power conversion efficiency of the H2,5-based PSC was caused by strong interactions with the perovskite material on the interface and an enhanced hole mobility in H2,5 compared with H3,4. The strong interaction derives from the short bond length of O atom of HTM and Pb atom of perovskite material, and the highly hole mobility derives from the quasi-planar conjugated conformation and tight packing model of neighboring molecules in H2,5. In addition, we found that the planar structure enhances the intermolecular interaction between HTM and perovskite materials compared with the 'V'-shaped molecule. Importantly, we also note that the HOMO level of the isolated molecule is not always proportional to the open-circuit voltages of PSCs since the HOMO level might move toward a higher level when the interaction between HTM and interface of perovskite was included. The work gives essential information for rational designing efficient HTMs.

Preparation and characterization of copper-Brevibacterium cholesterol oxidase hybrid nanoflowers.

Brevibacterium cholesterol oxidase (COD)-Cu hybrid nanoflowers were prepared, optimized and characterized for structural and catalytic properties. Regarding scanning electron microscopy (SEM), Fourier transform-infrared spectroscopy (FTIR) and X-ray diffraction (XRD) assays, COD molecules were successfully encapsulated with Cu3(PO4)2·3H2O based hybrid nanoflowers. After immobilization in hybrid nanoflowers, the interaction between COD and flavo-cofactor (FAD) was enhanced; and regarding to differential scanning calorimetry (DSC) assay, the Tm value of immobilized COD was increased from 60.5 °C (free enzyme) to 138.49 °C (nanoflowers). Additionally, in activity assay, Cu-COD nanoflowers revealed improved resistance to temperature and pH. After 10 times of recycling, approximately 70% of initial activity of Cu-COD nanoflowers was maintained, while the free COD was inactivated after 3 times of recycling. Furthermore, using cholesterol as substrate, in n-octane/water biphasic reaction system, the stability of Cu-COD nanoflowers was significantly promoted, and the initial conversion ration could be over two times as that of free enzyme. In brief, the hybrid nanoflowers dramatically enhanced the structural and thermo stability, the tolerance to biphasic mixture, and the catalytic efficiency of COD; and Cu-COD nanoflowers should be of great potential in the bioconversion of sterol derivatives.

Affinity adsorption of bovine hyaluronidase with ligands targeting to active site.

Four affinity ligands were designed from 6-chloromethyluracil and 2-aminobenzimidazole and simulated for the interaction with bovine hyaluronidase-1. Regarding sequence alignment, bovine hyaluronidase-1 precursor showed circa 83.6% similarity with human hyaluronidase-1. Regarding structural modeling and molecular docking, bovine hyaluronidase-1 interacted with ligands in the active site. Using epichlorohydrin, 1,3-propanediamine and cyanuric chloride as spacers, 6-chloromethyluracil and 2-aminobenzimidazole were composed to Sepharose beads. The modified Sepharose beads were then subjected to adsorption analysis with bovine hyaluronidase. After one step of affinity adsorption, the samples extracted from bovine testes were subjected to sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) analysis and activity assay. As calculated, the densities of four ligands on sorbents (entitled as L-1, L-2, L-3 and L-4) were 37.7 ±â€¯2.3, 36.4 ±â€¯3.2, 42.4 ±â€¯4.2 and 33.7 ±â€¯2.3 µmol/g wet gel; the theoretical maximum adsorption (Qmax) of bovine hyaluronidase on the four sorbents were 63.6 ±â€¯1.6, 72.0 ±â€¯0.7, 111.0 ±â€¯4.1 and 121.7 ±â€¯2.3 mg/g wet gel, respectively; the dissociation constants (Kd) of the four sorbents were 18.5 ±â€¯0.8, 48.1 ±â€¯4.3, 35.0 ±â€¯3.0, 40.6 ±â€¯2.7 µg/g wet gel, respectively. After optimization, the proteins captured by sorbents attaching 2-aminobenzimidazole based ligands (L-3 and L-4) revealed the main single band at approximately 50 kDa, and the purities were about 85.2 and 96.4%; the bioactivity recoveries were 83.5 and 89.4%. In addition, the bands on SDS-PAGE gel were also extracted and confirmed with linear trap quadropole mass spectrometry (LTQ-MS) analysis.