Repeated Low-Level Red Light Therapy for Myopia Control in High Myopia Children and Adolescents: A Randomized Clinical Trial.

PURPOSE: To assess the effectiveness and safety of repeated low-level red light (RLRL), which is a newly available treatment for myopia control in children and adolescents with high myopia. DESIGN: Multicenter, randomized, parallel-group, single-blind clinical trial (randomized controlled trial; NCT05184621). PARTICIPANTS: Between February 2021 and April 2022, 192 children aged 6 to 16 years were enrolled. Each child had at least 1 eye with myopia of cycloplegic spherical equivalent refraction (SER) at least -4.0 diopters (D), astigmatism of ≤2.0 D, anisometropia of ≤3.0 D, and best-corrected visual acuity (BCVA) of 0.2 logarithm of the minimum angle of resolution or better. Follow-up was completed by April 2023. METHODS: Participants were randomly assigned at a 1:1 ratio to intervention (RLRL treatment plus single-vision spectacles) or control (single-vision spectacles) groups. The RLRL treatment was administered for 3 minutes per session, twice daily with a minimum interval of 4 hours, 7 days per week. MEAN OUTCOME MEASURES: The primary outcome and key secondary outcome were changes in axial length (AL) and cycloplegic SER measured at baseline and the 12-month follow-up visit. Participants who had at least 1 postrandomization follow-up visit were analyzed for treatment efficacy. RESULTS: Among 192 randomized participants, 188 (97.91%) were included in the analyses (96 in the RLRL group and 92 in the control group). After 12 months, the adjusted mean change in AL was -0.06 mm (95% confidence interval [CI], -0.10 to -0.02 mm) and 0.34 mm (95% CI, 0.30 to 0.39 mm) in the intervention and control groups, respectively. A total of 48 participants (53.3%) in the intervention group were still experiencing axial shortening >0.05 mm at the 12-month follow-up. The mean SER change after 12 months was 0.11 D (95% CI, 0.02to 0.19 D) and -0.75 D (95% CI, -0.88 to -0.62 D) in the intervention and control groups, respectively. CONCLUSIONS: Repeated low-level red light demonstrates stronger treatment efficacy among those with high myopia, with 53.3% experiencing substantial axial shortening. Repeated low-level red light provides an excellent solution for the management of high myopia progression, a significant challenge in ophthalmology practice. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Semiconducting Titanate Supported Ruthenium Clusterzymes for Ultrasound-Amplified Biocatalytic Tumor Nanotherapies.

The external-stimulation-induced reactive-oxygen-species (ROS) generation has attracted increasing attention in therapeutics for malignant tumors. However, engineering a nanoplatform that integrates with efficient biocatalytic ROS generation, ultrasound-amplified ROS production, and simultaneous relief of tumor hypoxia is still a great challenge. Here, we create new semiconducting titanate-supported Ru clusterzymes (RuNC/BTO) for ultrasound-amplified biocatalytic tumor nanotherapies. The morphology and chemical/electronic structure analysis prove that the biocatalyst consists of Ru nanoclusters that are tightly stabilized by Ru-O coordination on BaTiO3 . The peroxidase (POD)- and halogenperoxidase-like biocatalysis reveals that the RuNC/BTO can produce abundant •O2 - radicals. Notably, the RuNC/BTO exhibits the highest turnover number (63.29 × 10-3 s-1 ) among the state-of-the-art POD-mimics. Moreover, the catalase-like activity of the RuNC/BTO facilitates the decomposition of H2 O2 to produce O2 for relieving the hypoxia of the tumor and amplifying the ROS level via ultrasound irradiation. Finally, the systematic cellular and animal experiments have validated that the multi-modal strategy presents superior tumor cell-killing effects and suppression abilities. We believe that this work will offer an effective clusterzyme that can adapt to the tumor microenvironment-specific catalytic therapy and also provide a new pathway for engineering high-performance ROS production materials across broad therapeutics and biomedical fields.

Ultralow Ru Single Atoms Confined in Cerium Oxide Nanoglues for Highly-Sensitive and Robust H2 O2 -Related Biocatalytic Diagnosis.

Exploring highly efficient, portable, and robust biocatalysts is a great challenge in colorimetric biosensors. To overcome the challenging states in creating single-atom biocatalysts, such as insufficient activity and stability, here, this work has engineered a unique CeO2 support as nanoglue to tightly anchor the Ru single-atom sites (CeO2 -Ru) with strong electronic coupling for achieving highly sensitive and robust H2 O2 -related biocatalytic diagnosis. The morphology and chemical/electronic structure analysis demonstrates that the Ru atoms are well-dispersed on CeO2 surface to form high-density active sites. Benefiting from the unique structure, the prepared CeO2 -Ru exhibits outstanding peroxidase (POD) like catalytic activity and selectivity to H2 O2 . Steady-state kinetic study results show that the CeO2 -Ru presents the highest Vmax and turnover number than the state-of-the-art POD-like biocatalysts. Consequently, the CeO2 -Ru discloses a high efficiency, good selectivity, and robust stability in the colorimetric detection of L-cysteine, glucose, and uric acid. Notably, the limit of detection (LOD) can reach 0.176 × 10-3 m for the L-cysteine, 0.095 × 10-3 m for the glucose, and 0.088 × 10-3 m for the uric acid via cascade reaction. This work suggests that the proposed unique CeO2 nanoglue will offer a new path to create single-atom noble metal biocatalysts and take a step closer to future biotherapeutic and biocatalytic applications.

Photobiomodulation at 660 nm promotes collagen synthesis via downregulation of HIF-1α expression without photodamage in human scleral fibroblasts in vitro in a hypoxic environment.

PURPOSE: The increasing prevalence of myopia is a global public health issue. Because of the complexity of myopia pathogenesis, current control methods for myopia have great limitations. The aim of this study was to explore the effect of photobiomodulation (PBM) on human sclera fibroblasts (HSFs) under hypoxia, in the hope of providing new ideas for myopia prevention and control. METHODS: Hypoxic cell model was established at 0, 6, 12, and 24 h time points to simulate myopia microenvironment and explore the optimal time point. Control, hypoxia, hypoxia plus light, and normal plus light cell models were set up for the experiments, and cells were incubated for 24 or 48 h after PBM (660 nm, 5 J/cm2), followed by evaluation of hypoxia-inducible factor 1α (HIF-1α) and collagen I a1 (COL1A1) proteins using Western blotting and immunofluorescence, and photo damage was detected by CCK-8, scratch test, and flow cytometry assays. We also used transfection technology to further elucidate the regulatory mechanism. RESULTS: The change of target proteins is most obvious when hypoxia lasts for 24 h (p < 0.01). PBM at 660 nm increased extracellular collagen content (p < 0.001) and downregulated expression of HIF-1α (p < 0.05). This treatment did not affect the migration and proliferation of cells (p > 0.05), and effectively inhibited apoptosis under hypoxia (p < 0.0001). After overexpression of HIF-1α, the effect of PBM was attenuated (p > 0.05). CONCLUSIONS: Photobiomodulation at 660 nm promotes collagen synthesis via downregulation of HIF-1α expression without photodamage.

Elevated expression of interleukin-27, IL-35, and decreased IL-12 in patients with thyroid-associated ophthalmopathy.

PURPOSE: Thyroid-associated ophthalmopathy (TAO) is a chronic autoimmune disease. The interleukin-12 (IL-12) family includes IL-12, IL-23, IL-27, and IL-35, all of which play important roles in autoimmunity. Thus far, the relationship between IL-12, IL-27, and IL-35 and the TAO has not been evaluated. METHODS: Seventy-five serum samples from patients with TAO were collected. Serum samples from 90 healthy controls (HC), 55 patients with Graves' disease (GD), 38 patients with uveitis (UV), 17 patients with Sjogren's syndrome (SS), and 65 patients with rheumatoid arthritis (RA) were collected as controls. The associations between IL-27, IL-35, IL-12, and other clinical parameters were analyzed. RESULTS: Elevated serum levels of IL-27/IL-35 and decreased serum IL-12 levels were observed in TAO patients compared to those in HC (p < 0.001). For HC, we observed good diagnostic ability to predict TAO (area under the curve = 0.74, 0.78, and 0.78, for IL-27, IL-35, and IL-12, respectively). For other autoimmune diseases, IL-27, IL-35, and IL-12 had the ability to discriminate between UV, RA, and SS (area under the curve = 0.80, 0.83, and 0.85 for IL-27; 0.52, 0.69, and 0.67 for IL-35). The positive detection rates of IL-12 were significantly lower in the TAO group than in the UV and RA groups (p = 0.002, 0.01). CONCLUSION: IL-12, IL-27, and IL-35 have the potential as biomarkers for TAO.

Pluripotent stem cell-derived NK cells with high-affinity noncleavable CD16a mediate improved antitumor activity.

Antibody-dependent cellular cytotoxicity (ADCC) is a key effector mechanism of natural killer (NK) cells that is mediated by therapeutic monoclonal antibodies (mAbs). This process is facilitated by the Fc receptor CD16a on human NK cells. CD16a appears to be the only activating receptor on NK cells that is cleaved by the metalloprotease a disintegrin and metalloproteinase-17 upon stimulation. We previously demonstrated that a point mutation of CD16a prevents this activation-induced surface cleavage. This noncleavable CD16a variant is now further modified to include the high-affinity noncleavable variant of CD16a (hnCD16) and was engineered into human induced pluripotent stem cells (iPSCs) to create a renewable source for human induced pluripotent stem cell-derived NK (hnCD16-iNK) cells. Compared with unmodified iNK cells and peripheral blood-derived NK (PB-NK) cells, hnCD16-iNK cells proved to be highly resistant to activation-induced cleavage of CD16a. We found that hnCD16-iNK cells were functionally mature and exhibited enhanced ADCC against multiple tumor targets. In vivo xenograft studies using a human B-cell lymphoma demonstrated that treatment with hnCD16-iNK cells and anti-CD20 mAb led to significantly improved regression of B-cell lymphoma compared with treatment utilizing anti-CD20 mAb with PB-NK cells or unmodified iNK cells. hnCD16-iNK cells, combined with anti-HER2 mAb, also mediated improved survival in an ovarian cancer xenograft model. Together, these findings show that hnCD16-iNK cells combined with mAbs are highly effective against hematologic malignancies and solid tumors that are typically resistant to NK cell-mediated killing, demonstrating the feasibility of producing a standardized off-the-shelf engineered NK cell therapy with improved ADCC properties to treat malignancies that are otherwise refractory.

π-Conjugated Copper Phthalocyanine Nanoparticles as Highly Sensitive Sensor for Colorimetric Detection of Biomarkers.

Though numerous nanomaterials with enzyme-like activities have been utilized as probes and sensors for detecting biological molecules, it is still challenging to construct highly sensitive detectors for biomarkers using polymeric materials. Benefiting from the π-d delocalization effect of electrons, excellent metal-chelating property, high electron transferability, and good chemical stability of π-conjugated phthalocyanine, the design of the copper phthalocyanine-based conjugated polymer nanoparticles (Cu-PcCP NPs) as a colorimetric sensor for a variety of biomarkers is reported. The Cu-PcCP NPs are synthesized through a simple microwave-assisted polymerization, and their chemical structures are thoroughly characterized. The colorimetric results of Cu-PcCP NPs demonstrate excellent peroxidase-like detecting activity and also great substrate selectivity than most of the reported Cu-based nanomaterials. The Cu-PcCP NPs can achieve a detection limit of 4.88 µM for the H2 O2 , 4.27 µM for the L-cysteine, and 21.10 µM for the glucose via a cascade catalytic system, which shows comparable detecting sensitivity as that of many earlier reported enzyme-like nanomaterials. Moreover, Cu-PcCP NPs present remarkable resistance to harsh conditions, including high temperature, low pH, and excessive salts. These highly specific π-conjugated copper-phthalocyanine nanoparticles not only overcome the current limitation of polymeric material-based sensors but also provide a new direction for designing next-generation enzyme-like nanomaterial-based colorimetric biosensors.

Concise Review: Human Pluripotent Stem Cells to Produce Cell-Based Cancer Immunotherapy.

Human pluripotent stem cells (PSCs) provide a promising resource to produce immune cells for adoptive cellular immunotherapy to better treat and potentially cure otherwise lethal cancers. Cytotoxic T cells and natural killer (NK) cells can now be routinely produced from human PSCs. These PSC-derived lymphocytes have phenotype and function similar to primary lymphocytes isolated from peripheral blood. PSC-derived T and NK cells have advantages compared with primary immune cells, as they can be precisely engineered to introduce improved anti-tumor activity and produced in essentially unlimited numbers. Stem Cells 2018;36:134-145.

Effects of occupational exposure to noise and dust on blood pressure in Chinese industrial workers.

Along with the rapid development of economy and urbanization, noise and air pollution are becoming major occupational health hazards in the process of industrial production. In this study, we collected data from 7293 industrial workers in China. The association between occupational exposure of noise and dust and blood pressure was investigated. Controlling for demographic variables, including sex, age, and length of service, a stepwise regression model with backward elimination was constructed. The results showed that both noise and dust decreased the level of systolic blood pressure (p < 0.001). This finding prompted the manufacturing industry to reduce noise and dust hazards and protect the occupational health of workers. Prospective studies in different populations are still required to verify the net contribution of noise and dust to the decrease in blood pressure.

Abdominal paracentesis drainage improves tolerance of enteral nutrition in acute pancreatitis: a randomized controlled trial.

OBJECTIVE: The objective of this study is to determine whether abdominal paracentesis drainage (APD) could improve the administration of enteral nutrition (EN) in acute pancreatitis. METHODS: Between January 2015 and April 2016, a total of 161 acute pancreatitis patients were enrolled and randomly assigned to either the APD group or the non-APD group. Several indexes associated with the administration of EN, including the gastroparesis cardinal symptom index (GCSI), the incidence of gastrointestinal adverse events, and the clinical outcomes, were recorded. RESULTS: The mean GCSI scores were 13.6 ± 2.1 before randomization and 7.1 ± 2.3 after a week in the APD group. These scores were 13.9 ± 2.4 and 9.7 ± 1.9 in the non-APD group. The incidences of gastrointestinal adverse events in the two groups were similar (p > .05), except for diarrhea. However, the patients in the APD group spent less time achieving the nutrition target (25 per kilogram of body weight per day) and fully tolerated the oral diet (p < .05). Additionally, the clinical outcomes of the APD group were better compared with those of the non-APD group. CONCLUSION: APD can improve the administration of EN in acute pancreatitis. Given the positive effect of EN on clinical outcomes, this phenomenon possibly explains why APD could improve the clinical outcomes of acute pancreatitis patients in some aspects.

Effects of extremely low frequency electromagnetic fields on human fetal scleral fibroblasts.

This study investigated the effects of extremely low frequency electromagnetic fields (ELF-EMFs) on human fetal scleral fibroblasts (HFSFs). HFSFs were subjected to 50 Hz artificial ELF-EMFs generated by Helmholtz coils with 0.1, 0.2, 0.5, and 1.0 mT field intensities for 6 to 48 h. The viability and factors involved in scleral structuring of HFSFs were determined. The growth rate of HFSFs significantly decreased after only 24 h of exposure to ELF-EMFs (0.2 mT). The messenger RNA (mRNA) expression of collagen type I (COL1A1) decreased and expression of matrix metalloproteinase-2 (MMP-2) increased significantly. There was a decrease in tissue inhibitor of MMP-2 mRNA levels between treated and control cells only at the 1.0 mT intensity level. Transforming growth factor beta-2 mRNA increased in exposed cells, and, simultaneously, fibroblast growth factor-2 mRNA levels decreased. The protein expressions of COL1A1 and MMP-2 were also significantly altered subsequent to exposure (p < 0.05). This study shows that ELF-EMFs had biological effects on HFSFs and could cause abnormality in scleral collagen.

Puerarin, an isoflavone compound extracted from Gegen (Radix Puerariae Lobatae), modulates sclera remodeling caused by extremely low frequency electromagnetic fields.

OBJECTIVE: To evaluate the protective effect of puerarin [an isoflavone compound extracted from Gegen (Radix Puerariae Lobatae)] in scleral remodeling induced by extremely low frequency electromagnetic fields (ELF-EMFs). METHODS: Human fetal scleral fibroblasts (HFSFs) were divided into 5 groups: (a) untreated controls; (b) cells treated with ELF-EMFs; (c) cells treated with ELF-EMFs and puerarin 0.1 µM; (d) cells treated with ELF-EMFs and puerarin 1 µM; (e) cells treated with ELF-EMFs and puerarin 10 µM. Cell proliferation activity was measured by the cell-counting kit-8 assay. Matrix metalloproteinase-2 (MMP-2) activity was measured by gelatin enzymography. MMP-2 and collagenⅠ(COL1A1) mRNA, protein expression were measured by Real-Time polymerase chain reaction , Western blot analysis, respectively. RESULTS: Puerarin reduced the inhibition in cell proliferation, MMP-2 activity, mRNA, protein expression of HFSFs exposed to ELF-EMFs and enhanced the COL1A1 mRNA and protein expression. CONCLUSION: Puerarin was found to participate in the matrix remodeling process. It might be a potential agent for the treatment of extracellular matrix degradation of sclera associated with ocular conditions.

Meroterpenoids with divers' rings systems from Phyllosticta capitalensis and their anti-inflammatory activity.

Four undescribed sesquiterpene-shikimates (1-4), eight undescribed monoterpene-shikimates (5-12), together with two known ones were isolated and identified from the 95% ethanol extract of the plant endophytic fungus Phyllosticta capitalensis cultured in rice medium. Capitalensis A (1) was identified as the first sesquiterpene-shikimate-conjugated spirocyclic meroterpenoid degradation product, while capitalensis B (2) is a sesquiterpene-shikimate-conjugated spirocyclic meroterpenoid with a unique D-ring formed by a C-2-O-C-9' connection. The structures of these previously undescribed compounds were elucidated by multiple techniques, including IR, HR-ESI-MS, and NMR analysis. Furthermore, their absolute configurations were established through the comprehensive approach that involved the calculations of ECD spectra, optical rotation values, and single-crystal X-ray analysis. Moreover, the anti-inflammatory activity of all isolated compounds was evaluated using a lipopolysaccharide (LPS)-induced inflammation model in BV2 microglial cells. Meanwhile, these compounds exhibited activity in inhibiting NO production. Four compounds, capitalensis C (3), capitalensis D (4), 15-hydroxyl tricycloalternarene 5b (13) and guignarenone A (14) showed strong inhibitory effects with IC50 values of 21.6 ± 1.33, 12.2 ± 1.08, 18.6 ± 1.27, and 15.8 ± 1.20 µM, respectively. In addition, the structure-activity relationship of the anti-inflammatory activity of the compounds was discussed.

COVID-19 InfoVaccines: A WHO-supported educational project to promote COVID-19 vaccination information among professionals and the general population.

COVID-19 vaccine uptake varied across countries, in part due to vaccine hesitancy fueled by a lack of trustworthy information. To help health workers provide evidence-based answers to common questions about COVID-19 vaccines and vaccination, and thereby, assist individuals´ decisions on vaccine acceptance, COVID-19 InfoVaccines, a joint WHO-EU project, was launched in February 2021 to support COVID-19 vaccine rollout in 6 Eastern European countries. COVID-19 InfoVaccines was made available in seven languages and shared on social media networks. A total of 262,592 users accessed COVID-19 InfoVaccines.com between February 11, 2021, and January 31st, 2023. The users were most interested in: general questions; vaccine efficacy and duration of protection; vaccine safety; vaccine co-administration, and dose-interval and interchangeability; though the interest in a specific theme varied in function of the epidemiological situation. A total of 118,510 (45.1%) and 46,644 (17.7%) users scrolled up to 35% and 75% of the COVID-19 InfoVaccines webpage, respectively. The average engagement rate was 71.61%. The users accessed COVID-19 InfoVaccines from 231 countries and territories, but the majority were in Ukraine (N = 38,404; 14.6%), Spain (N = 23,327; 8.9%), and Argentina (N = 21,167; 8.1%). Older Facebook users were more interested in COVID-19 information than younger individuals (X2 p-value < .0001). Two hundred twenty-eight videos were shared on YouTube. The average Click-Through-Rate on Facebook was 7.82%, and that on YouTube was 4.4%, with 60 videos having a Click-Through-Rate >5%, falling in the range of average YouTube video Click-Through-Rate (2% - 10%). As misinformation about vaccines and vaccination spreads easily and can negatively impact health-related decisions, initiatives like COVID-19 InfoVaccines are crucial to facilitate access to reliable information.

Wls-mediated Wnts differentially regulate distal limb patterning and tissue morphogenesis.

Wnt proteins are diffusible morphogens that play multiple roles during vertebrate limb development. However, the complexity of Wnt signaling cascades and their overlapping expression prevent us from dissecting their function in limb patterning and tissue morphogenesis. Depletion of the Wntless (Wls) gene, which is required for the secretion of various Wnts, makes it possible to genetically dissect the overall effect of Wnts in limb development. In this study, the Wls gene was conditionally depleted in limb mesenchyme and ectoderm. The loss of mesenchymal Wls prevented the differentiation of distal mesenchyme and arrested limb outgrowth, most likely by affecting Wnt5a function. Meanwhile, the deletion of ectodermal Wls resulted in agenesis of distal limb tissue and premature regression of the distal mesenchyme. These observations suggested that Wnts from the two germ layers differentially regulate the pool of undifferentiated distal limb mesenchyme cells. Cellular behavior analysis revealed that ectodermal Wnts sustain mesenchymal cell proliferation and survival in a manner distinct from Fgf. Ectodermal Wnts were also shown for the first time to be essential for distal tendon/ligament induction, myoblast migration and dermis formation in the limb. These findings provide a comprehensive view of the role of Wnts in limb patterning and tissue morphogenesis.

Ndrg2 regulates vertebral specification in differentiating somites.

It is generally thought that vertebral patterning and identity are globally determined prior to somite formation. Relatively little is known about the regulators of vertebral specification after somite segmentation. Here, we demonstrated that Ndrg2, a tumor suppressor gene, was dynamically expressed in the presomitic mesoderm (PSM) and at early stage of differentiating somites. Loss of Ndrg2 in mice resulted in vertebral homeotic transformations in thoracic/lumbar and lumbar/sacral transitional regions in a dose-dependent manner. Interestingly, the inactivation of Ndrg2 in osteoblasts or chondrocytes caused defects resembling those observed in Ndrg2(-/-) mice, with a lower penetrance. In addition, forced overexpression of Ndrg2 in osteoblasts or chondrocytes also conferred vertebral defects, which were distinct from those in Ndrg2(-/-) mice. These genetic analyses revealed that Ndrg2 modulates vertebral identity in segmented somites rather than in the PSM. At the molecular level, combinatory alterations of the amount of Hoxc8-11 gene transcripts were detected in the differentiating somites of Ndrg2(-/-) embryos, which may partially account for the vertebral defects in Ndrg2 mutants. Nevertheless, Bmp/Smad signaling activity was elevated in the differentiating somites of Ndrg2(-/-) embryos. Collectively, our findings unveiled Ndrg2 as a novel regulator of vertebral specification in differentiating somites.

Suppression of type I collagen in human scleral fibroblasts treated with extremely low-frequency electromagnetic fields.

PURPOSE: To investigate the expression differences of type I collagen (COL1A1) and its underlying mechanisms in human fetal scleral fibroblasts (HFSFs) that were treated with conditioned medium from retinal pigment epithelial (RPE) cells under extremely low-frequency electromagnetic fields (ELF-EMFs). METHODS: The ELF-EMFs used in this study were established by slidac and artificial coils. Growth of the treated HFSFs was evaluated by a cell-counting kit-8 assay. The expression of COL1A1 and matrix metalloproteinases-2 (MMP-2) in the treated HFSFs was detected by reverse transcription PCR (RT-PCR) and western blot, and the expression of transforming growth factor-ß2 (TGF-ß2) and basic fibroblast growth factor-2 (FGF-2) in RPE cells exposed to EMFs was detected by RT-PCR. The expression of COL1A1 and MMP-2 in HFSFs was further confirmed by immunofluorescence staining. Activation of extracellular signal-regulated kinase 1/2 (ERK1/2 also called p44/p42 mitogen-activated protein kinases [MAPK]) and p38 in HFSFs was measured by western blot. RESULTS: We found that exposure to ELF-EMFs resulted in a decreased proliferation rate of HFSFs and that addition of RPE supernatant medium could enhance this effect. Compared with that of the control cells, a significant decrease in collagen synthesis was detected in HFSFs under ELF-EMFs. However, the expression of MMP-2 was upregulated, which could be further enhanced via an RPE supernatant additive. The activities of ERK1/2 and p38 were significantly increased in HFSFs exposed to ELF-EMFs, and this effect could be enhanced by RPE supernatant medium additive. CONCLUSIONS: Our results suggested that ELF-EMFs can inhibit the expression of type I collagen in HFSFs and contribute to the remodeling of the sclera.

DRAR-CPI: a server for identifying drug repositioning potential and adverse drug reactions via the chemical-protein interactome.

Identifying new indications for existing drugs (drug repositioning) is an efficient way of maximizing their potential. Adverse drug reaction (ADR) is one of the leading causes of death among hospitalized patients. As both new indications and ADRs are caused by unexpected chemical-protein interactions on off-targets, it is reasonable to predict these interactions by mining the chemical-protein interactome (CPI). Making such predictions has recently been facilitated by a web server named DRAR-CPI. This server has a representative collection of drug molecules and targetable human proteins built up from our work in drug repositioning and ADR. When a user submits a molecule, the server will give the positive or negative association scores between the user's molecule and our library drugs based on their interaction profiles towards the targets. Users can thus predict the indications or ADRs of their molecule based on the association scores towards our library drugs. We have matched our predictions of drug-drug associations with those predicted via gene-expression profiles, achieving a matching rate as high as 74%. We have also successfully predicted the connections between anti-psychotics and anti-infectives, indicating the underlying relevance of anti-psychotics in the potential treatment of infections, vice versa. This server is freely available at http://cpi.bio-x.cn/drar/.

Effect of puerarin on matrix metalloproteinase-2 in human fetal scleral fibroblasts treated with low frequency electromagnetic fields.

OBJECTIVE: To study the effect of puerarin on matrix metalloproteinase-2 (MMP-2) gene and protein expression in human fetal scleral fibroblasts (HFSFs) exposed to extremely low frequency electromagnetic fields (ELF-EMF). METHODS: Cultured HFSFs were exposed to 0.2 mT ELF-EMF for 24 h. The experimental groups were divided into subgroups treated with 0, 0.1, 1 and 10 microM puerarin respectively. The expression of MMP-2 mRNA and protein were detected with real-time polymerase chain reaction and western-blot analysis respectively. RESULTS: MMP-2 mRNA and protein expression increased by 0.793 and 1.130 folds respectively under the exposure of ELF-EMFs at 0.2 mT flux density for 24 h. Puerarin at the concentration of 0.1 microM reversed this effect by 8.53% in mRNA and by 17.97% in protein expression (P < 0.05). The effect was more prominent at higher concentrations (1 and 10 microM, P < 0.01). CONCLUSION: Exposure to ELF-EMFs increased the expression of MMP-2 mRNA and protein in HFSF cells. Puerarin reversed the action to some extent in a specific concentration range. Our results implied that the puerarin might protect scleral tissue from increased expression induced by exposure to ELF-EMFs.

Electrocatalytic Porphyrin/Phthalocyanine-Based Organic Frameworks: Building Blocks, Coordination Microenvironments, Structure-Performance Relationships.

Metal-porphyrins or metal-phthalocyanines-based organic frameworks (POFs), an emerging family of metal-N-C materials, have attracted widespread interest for application in electrocatalysis due to their unique metal-N4 coordination structure, high conjugated π-electron system, tunable components, and chemical stability. The key challenges of POFs as high-performance electrocatalysts are the need for rational design for porphyrins/phthalocyanines building blocks and an in-depth understanding of structure-activity relationships. Herein, the synthesis methods, the catalytic activity modulation principles, and the electrocatalytic behaviors of 2D/3D POFs are summarized. Notably, detailed pathways are given for modulating the intrinsic activity of the M-N4 site by the microenvironments, including central metal ions, substituent groups, and heteroatom dopants. Meanwhile, the topology tuning and hybrid system, which affect the conjugation network or conductivity of POFs, are also considered. Furthermore, the representative electrocatalytic applications of structured POFs in efficient and environmental-friendly energy conversion areas, such as carbon dioxide reduction reaction, oxygen reduction reaction, and water splitting are briefly discussed. Overall, this comprehensive review focusing on the frontier will provide multidisciplinary and multi-perspective guidance for the subsequent experimental and theoretical progress of POFs and reveal their key challenges and application prospects in future electrocatalytic energy conversion systems.