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Retinal neovascularization is a common feature of several ocular neovascular diseases, which are the leading cause of blindness in the world. Current treatments are administered through invasive intravitreal injections, leading to poor patient compliance, serious ocular complications and heavy economic burdens. Thus, an alternative less or non-invasive therapeutic strategy is in demand. Here, a non-invasive oral tyrosine kinase inhibitor, CM082, was evaluated in a retinal neovascularization model induced by hypoxia in zebrafish larvae. We found that CM082 effectively suppressed retinal neovascularization, rescued cell loss in the retinal ganglion cell layer, and rescued the visual function deficiency. Our results elucidated that CM082 mediated its therapeutic efficacy primarily through the inhibition of Vegfr2 phosphorylation. The findings demonstrated that CM082 possessed strong antiangiogenic effects and may serve as a potential treatment for angiogenesis in ocular neovascular diseases.

The goal of this study was to investigate the clinical application of free/total prostate-specific antigen (F/T PSA) ratio, considering the new broad serum total PSA (T-PSA) \"gray zone\" of 2.0-25.0 ng ml−1 in differential diagnosis of prostate cancer (PCa) and benign prostate diseases (BPD) in men over 50 years in Western China. A total of 1655 patients were included, 528 with PCa and 1127 with BPD. Serum T-PSA, free PSA (F-PSA), and F/T PSA ratio were analyzed. Receiver operating characteristic curves were used to assess the efficiency of PSA and F/T PSA ratio. There were 47.4% of cancer patients with T-PSA of 2.0-25.0 ng ml−1. When T-PSA was 2.0-4.0 ng ml−1, 4.0-10.0 ng ml−1, and 10.0-25.0 ng ml−1, the area under the curve (AUC) of F/T PSA ratio was 0.749, 0.769, and 0.761, respectively. The best AUC of F/T PSA ratio was 0.811 when T-PSA was 2.0-25.0 ng ml−1, with a specificity of 0.732, a sensitivity of 0.788, and an optimal cutoff value of 15.5%. The AUC of F/T PSA ratio in different age groups (50-59 years, 60-69 years, 70-79 years, and ≥80 years) was 0.767, 0.806, 0.815, and 0.833, respectively, and the best sensitivity (0.857) and specificity (0.802) were observed in patients over 80 years. The T-PSA trend was in accordance with the Gleason score, tumor node metastasis (TNM) stage, and American Joint Committee on Cancer prognosis group. Therefore, the F/T PSA ratio can facilitate the differential diagnosis of PCa and BPD in the broad T-PSA \"gray zone\". Serum T-PSA can be a Gleason score and prognostic indicator.

A series of novel zinc-salophen (salophen = N, N′-phenylenebis(salicylimine)) complexes (Zn-1–4) with electron donor–acceptor (D–A) structure were synthesized and characterized using a triphenylamine structure as the electron donor. Zn-salophen complexes with the same substituent sites have been reported to exhibit significant CT properties. The design of the D–A structure and the increase in the number of benzene rings to increase the length of bridging groups have led to a reduction in the energy difference between charge separation singlet and triplet states, resulting in the production of reactive oxygen species (ROS) under light irradiation. The ability has been enhanced (in terms of the production of singlet oxygen (1O2), compared with Zn-salophen, Zn-4 is 1.58 times higher). This method has been reported to enhance the intersystem crossing process of compounds, thereby enabling them to reach a triple excited state, but the generation of ROS has not been studied. Although the enhancement is not very significant, it has expanded the medical application prospects of these types of complexes and has provided a new strategy to enhance the production of ROS.

With rapid development of global wastewater treatment plants (WWTPs), acidification and enhanced CO 2 release in receiving waters caused by high-CO 2 treated wastewater input have raised concerns. Insights into the variations in dissolved inorganic carbon (DIC) species in treated wastewater contribute to understanding the mechanisms of the acidification process. Here, we investigated three large-scale municipal WWTPs that discharged into the coast of Qingdao, China, for variations in effluent DIC species and their control mechanisms. The results showed that the effluent DIC concentrations, with a range of 2554–5718 μmol/L, significantly exceeded the concentration in seawater and mainly increased from winter to spring and decreased from summer to autumn. The effluent DIC and its δ 13 C DIC showed a good negative correlation. The ratios of effluent DIC to total alkalinity (DIC/TAlk) ranged from 1.00 to 1.24, and the proportions of CO 2 in DIC ranged from 0.9 to 19.7%; both sets of values significantly exceeded those in seawater. The proportions of CO 3 2− in DIC were only ~ 0.4%. These features determined that the CO 2 concentrations in effluents fluctuated from 3 to 80 times the concentration in seawater, whereas the CO 3 2− concentrations were less than 1/15 of those in seawater. Organic matter degradation and nitrogen removal processes made important contributions to the high effluent CO 2 concentrations. The increase in solubility induced by decreased temperature may be the main cause for the higher effluent CO 2 concentrations during winter as well as spring months with low effluent temperatures. Correspondingly, the effluent pH values were significantly lower than the seawater pH values and showed a good negative logarithmic correlation with the DIC/TAlk values, reflecting the control of DIC species on the pH values in treated wastewater. Variations in DIC species in treated wastewater can cause changes in the affected region and the degree of the induced acidification in receiving waters.

The emergence of porpholactone chemistry, discovered over 30 years ago, has significantly stimulated the development of biomimetic tetrapyrrole chemistry. It offers an opportunity, through modifications of non‐pyrrolic building blocks, to clarify the relationship between chemical structure and excited‐state properties, deciphering the structural code for the biological functions of life pigments. With intriguing photophysical properties in the red to near‐infrared (NIR) regions, facile modulation of their electronic nature by fine‐tuning chemical structures, and coordination ability with diverse metal ions, these novel porphyrinoids have favorable prospects in the fields of optical materials, bioimaging and therapy, and catalysis. In this Minireview, we summarize the brief history of porpholactone chemistry, and focus on the studies carried out in our group, particularly on the regioisomeric effect, NIR lanthanide luminescence, and metal catalysis. We outline the perspectives of these compounds in the construction of porpholactone‐related biomedical applications and optical and energy materials, in order to inspire more interest and further advance bioinspired inorganic chemistry and lanthanide chemical biology. Porpholactone and its derivatives have gained significant momentum recently owing to their unique role in molecular imaging and therapy (or theranostics), chemo‐, electro‐ and photocatalysis, as well as energy and optical materials. These molecules, which have tunable properties and coordinate with many metal ions, have great potential for further research and practical applications.

Invited for this month's cover is the group of Jun‐Long Zhang, Peking University, Beijing. The cover picture shows the porpholactone cofactor, which play unique roles in molecular imaging and therapy (or theranostics), catalysis, as well as energy and optical materials. This class of molecules is ideal for more intriguing scientific research and future practical applications. Read the full text of the Minireview at 10.1002/cplu.202000494. “We recently demonstrated unprecedented applications of porpholactones such as synthetic models for the understanding of regioisomerism of porphyrins, reactivity of tunichlorin, and near‐infrared lanthanide sensitization. The main challenge that is currently pursued by our group is how to rationally harness the electronic structures or functions of such cofactors through fine‐tuning of β‐peripheral units.” Read more about the story behind the cover in the Cover Profile and about the research itself at 10.1002/cplu.2012000494.

PurposeTo evaluate the value of dynamic monitoring of procalcitonin (PCT) as a biomarker for the early diagnosis of postoperative infections in patients undergoing cardiac surgery.MethodsIn total, 252 patients who underwent cardiac surgery were retrospectively included. The postoperative patients’ PCT level, change value (△PCT), and clearance rate (△PCTc) were compared between the infected and noninfected groups in adult and pediatric patients on postoperative days (PODs) 1, 3, and 5. The area under the receiver operating characteristic (ROC) curve (AUC) was used to evaluate the diagnostic value.ResultsProcalcitonin concentration decreased progressively in the noninfected group in adult and pediatric patients; PCT concentration continued to rise until it peaked on POD 3 in the infected group. In adult patients, the AUC of PCT for diagnosis of infection on PODs 1, 3, and 5 were 0.626, 0.817, and 0.806, with the optimal cut-off values of 7.35, 3.63, and 1.73 ng/ml, respectively. The diagnostic efficiency of △PCT3 and △PCT C3 was significantly better than △PCT5 and △PCT C5 , respectively. In pediatric patients, the AUC of PCT for diagnosis of infection on PODs 1, 3, and 5 were 0.677, 0.747, and 0.756, respectively, and the optimal cut-off values were 27.62, 26.15, and 10.20 ng/ml.ConclusionThis study showed that dynamic monitoring of PCT levels could be an effective clinical means to help to discover postoperative infection earlier. The PCT level and its change indicators on POD 3 in adult patients and the PCT level on POD 5 in children can indicate infection.

Addressing both inflammation and epithelialization during the treatment of diabetic foot ulcers is an important step, but current treatment options are limited. MiRNA has important prospects in the treatment of diabetic foot refractory wound ulcers. Previous studies have reported that miR-185-5p reduces hepatic glycogen production and fasting blood glucose levels. We herein hypothesized that miR-185-5p might play an important role in the field of diabetic foot wounds. MiR-185-5p in skin tissue samples from patients with diabetic ulcers and diabetic rats were measured using quantitative real-time PCR (qRT-PCR). The streptozotocin-induced diabetes rat model (male Sprague-Dawley rats) for diabetic wound healing was conducted. The therapeutic potential was observed by subcutaneous injection of miR-185-5p mimic into diabetic rat wounds. The anti-inflammation roles of miR-185-5p on human dermal fibroblast cells were analyzed. We found that miR-185-5p is significantly downregulated in diabetic skin (people with DFU and diabetic rats) compared to controls. Further, in vitro upregulation of miR-185-5p decreased the inflammatory factors (IL-6, TNF-α) and intercellular adhesion molecule 1 (ICAM-1) of human skin fibroblasts under advanced glycation end products (AGEs). Meanwhile, the increase of miR-185-5p promoted cell migration. Our results also confirmed that the topical increase of miR-185-5p decreases diabetic wound p-nuclear factor-κB (p-NF-κB), ICAM-1, IL-6, TNF-α, and CD68 expression in diabetic wounds. MiR-185-5p overexpression boosted re-epithelization and expedited wound closure of diabetic rats. MiR-185-5p accelerated wound healing of diabetic rats, reepithelization, and inhibited the inflammation of diabetic wounds in the healing process, a potentially new and valid treatment for refractory diabetic foot ulcers.

Hypoxia in newborns tends to result in developmental deficiencies in the white matter of the brain. As previous studies of the effects of hypoxia on neuronal development in rodents and human infants have been unable to use imaging, insight into the dynamic development of oligodendrocytes (OLs) in the central nervous system under hypoxia is limited. Here, we developed a visual model to study OL development using sublethal postnatal hypoxia in zebrafish larvae. We observed that hypoxia significantly suppressed OL progenitor cell migration toward the dorsum using imaging. Further, we found that hypoxia affected myelination, as indicated by thinner myelin sheaths and by a downregulation of myelin basic protein expression. Bmp2b protein expression was also significantly downregulated following hypoxia onset. Using gain of function and loss of function experiments, we demonstrated that the Bmp2b protein was associated with the regulation of OL development. Thus, our work provides a visual hypoxia model within which to observe OL development , and reveals the underlying mechanisms involved in these processes.

There has been increasing interest in the psycho-socio-relational and sexual disorders of infertility, as the risk of psychological burden among infertile men with sexual dysfunctions is significant. The purpose of this study was to develop and to validate a predictive model to estimate individual psychological burden among infertile men with sexual dysfunction and study the association between them. Comprehensive data were collected for infertile men (n = 480) who sought treatment for infertility in a reproductive medicine center between June 2012 and December 2013. Using independent predictors of psychological burden from the least absolute shrinkage and selection operator, univariable and multivariable analyses were developed into two models. Predictive accuracy was compared between the models. We explored the association between sexual dysfunction and psychological burden. A total of 480 patients were analyzed using 10-fold cross-validation. Independent predictors of psychological burden were incorporated into a model to measure anxiety (corrected-area under curve (AUC): 77.3%) and a model to measure depression (corrected-AUC: 70.2%). Anxiety and depression were both associated with erectile dysfunction (P < 0.05), with anxiety demonstrating the strongest association. Only anxiety was associated with premature ejaculation (P < 0.05). Premature ejaculation was not found to be associated with depression (P > 0.05). Predictive models for psychological burden among infertile men with sexual dysfunction are presented, and we found that there is an association between psychological burden and sexual dysfunction. According to the models, proper counseling and treatment of sexual dysfunction in infertile men may reduce the psychological burden, help attain natural pregnancy, and improve the quality of life.