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Abstract This work presents a novel methodology for elucidating the characteristics of aggregation‐induced emission (AIE) systems through the application of data science techniques. A new set of chemical fingerprints specifically tailored to the photophysics of AIE systems is developed. The fingerprints are readily interpretable and have demonstrated promising efficacy in addressing influences related to the photophysics of organic light‐emitting materials, achieving high accuracy and precision in the regression of emission transition energy (mean absolute error (MAE) ∼ 0.13eV) and the classification of optical features and excited state dynamics mechanisms (F1score ∼ 0.94). Furthermore, a conditional variational autoencoder and integrated gradient analysis are employed to examine the trained neural network model, thereby gaining insights into the relationship between the structural features encapsulated in the fingerprints and the macroscopic photophysical properties. This methodology promotes a more profound and thorough comprehension of the characteristics of AIE and guides the development strategies for AIE systems. It offers a solid and overarching framework for the theoretical analysis involved in the design of AIE‐generating compounds and elucidates the optical phenomena associated with these compounds.

Abstract Objectives Pro-protein convertase subtilisin/kexin 9 (PCSK9) decreases the clearance of the pathogenic lipids, supporting the potential role of PCSK9 in the prognosis of sepsis. Methods In this prospective cohort study, patients with sepsis were consecutively recruited from 1 to 2020 to 30 September 2021 at the First People’s Hospital of Huaihua, China. All the eligible patients were categorized into low-PCSK9 and high-PCSK9 groups, based on their PCSK9 levels at admission. Time-dependent receiver operating characteristic curves and Cox proportional hazards regression were used to evaluate the association between PCSK9 level and 28-day mortality of sepsis. Results Of the 203 enrolled patients, 56 (27.59%) died during the 28-day follow-up. The PCSK9 level was positively related to the C-reactive protein level. The cut-off point of PCSK9 levels for 28-day mortality risk was 370 ng/ml. Through comparison between high-PCSK9 (> 370 ng/ml) with low-PCSK9 (≤ 370 ng/ml) groups, the adjusted HR for mortality was 2.56 (95% CI: 1.25–5.23, p = 0.01). Conclusions The 28-day mortality of sepsis increased significantly as the baseline circulating PCSK9 level exceeded 370 ng/ml, indicating circulating PCSK9 levels may be a potential biomarker to predict the prognosis of sepsis.

Abstract Excessive and prolonged ultraviolet radiation (UVR) exposure causes photodamage, photoaging, and photocarcinogenesis in human skin. Therefore, safe and effective sun protection is one of the most fundamental requirements. Living organisms tend to evolve various natural photoprotective mechanisms to avoid photodamage. Among them, melanin is the main functional component of the photoprotective system of human skin. Polydopamine (PDA) is synthesized as a mimic of natural melanin, however, its photoprotective efficiency and mechanism in protecting against skin damage and photoaging remain unclear. In this study, the novel sunscreen products based on melanin-inspired PDA nanoparticles (NPs) are rationally designed and prepared. We validate that PDA NPs sunscreen exhibits superior effects on photoprotection, which is achieved by the obstruction of epidermal hyperplasia, protection of the skin barrier, and resolution of inflammation. In addition, we find that PDA NPs are efficiently intake by keratinocytes, exhibiting robust ROS scavenging and DNA protection ability with minimal cytotoxicity. Intriguingly, PDA sunscreen has an influence on maintaining homeostasis of the dermis, displaying an anti-photoaging property. Taken together, the biocompatibility and full photoprotective properties of PDA sunscreen display superior performance to those of commercial sunscreen. This work provides new insights into the development of a melanin-mimicking material for sunscreens.

BackgroundResearch on non-target organ damage of biological pesticides has attracted much attention. Rotenone exposure may be far beyond the occupational environment, and the exposureduring pregnancy may be increased through bioaccumulation, fruit or vegetable residues, and other forms of oral intake. At present, the effects of rotenone on placental development and its mechanism are still unknown. ObjectiveTo investigate the developmental damage of rat placenta and evaluate the expression levels of glycogen synthase kinase (GSK-3β) and beta catenin (β-catenin) followed by rotenone exposure through the placental barrier during pregnancy, as well as to propose possible associated mechanisms. MethodsEighteen sexually mature SD female infertile rats without specific pathogens were selected and divided into three groups: blank control group (0.9% saline), corn oil group, and rotenone group (corn oil + 2 mg·kg−1 rotenone) by random number method, six female animals in each group. Another six male rats were selected and mated to the female rats at night with a female to male ratio of 3:1 per cage. Pregnant rats were given 0.9% saline, corn oil, and 2 mg·kg−1 rotenone preparation by isovolumetric gavage once daily for the entire gestation period (19 d), and their conditions were observed after the last dose. The pregnant rats were anesthetized, and the size of the placenta and blood perfusion were detected by ultrasound the next day of the last dose of rotenone. Then, 3 pregnant rats in each group were sacrificed immediately and the placenta and umbilical cord tissues were dissected. The remaining 9 pregnant rats gave birth naturally, and the fetuses were observed for developmental evaluation and weighed. The histopathological changes of umbilical cord and placenta were observed by hematoxylin-eosin staining. The reactive oxygen species levels of placenta tissues were detected by flow cytometry. The Ca2+-ATPase activity of placenta tissues was detected by colorimetric method. The localization and levels of GSK-3β and β-catenin expression of placenta were detected by immunohistochemistry. The p-GSK-3β/GSK-3β and p-β-catenin/β-catenin protein expression in placental tissues were measured by Western blotting. ResultsNo injury or death was recorded during the pregnant rats receiving rotennon administration. Adverse pregnancy outcomes such as fetal absorption and postpartum stillbirth were found in the rotenone group, and the weight of the fetal mice decreased (P

A Fe-Co dual-metal co-doped N containing the carbon composite (FeCo-HNC) was prepared by adjusting the ratio of iron to cobalt as well as the pyrolysis temperature with the assistance of functionalized silica template. Fe1Co-HNC, which was formed with 1D carbon nanotubes and 2D carbon nanosheets including a rich mesoporous structure, exhibited outstanding oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) catalytic activities. The ORR half-wave potential is 0.86 V (vs. reversible hydrogen electrode, RHE), and the OER overpotential is 0.76 V at 10 mA cm−2 with the Fe1Co-HNC catalyst. It also displayed superior performance in zinc–air batteries. This method provides a promising strategy for the fabrication of efficient transition metal-based carbon catalysts.

Abstract Background Although the treatments of skin wounds have greatly improved with the increase in therapeutic methods and agents, available interventions still cannot meet the current clinical needs. Therefore, the development of new pro-regenerative therapies remains urgent. Owing to their unique characteristics, both nanomaterials and peptides have provided novel clues for the development of pro-regenerative agents, however, more efforts were still be awaited and anticipated. Results In the current research, Hollow polydopamine (HPDA) nanoparticles were synthesized and HPDA nanoparticles loading with RL-QN15 (HPDAlR) that was an amphibian-derived peptide with obvious prohealing activities were prepared successfully. The characterization, biodistribution and clearance of both HPDA nanoparticles and HPDAlR were evaluated, the loading efficiency of HPDA against RL-QN15 and the slow-releasing rate of RL-QN15 from HPDAlR were also determined. Our results showed that both HPDA nanoparticles and HPDAlR exerted no obvious toxicity against keratinocyte, macrophage and mice, and HPDA nanoparticles showed no prohealing potency in vivo and in vitro. Interestingly, HPDAlR significantly enhanced the ability of RL-QN15 to accelerate the healing of scratch of keratinocytes and selectively modulate the release of healing-involved cytokines from macrophages. More importantly, in comparison with RL-QN15, by evaluating on animal models of full-thickness injured skin wounds in mice and oral ulcers in rats, HPDAlR showed significant increasing in the pro-regenerative potency of 50 and 10 times, respectively. Moreover, HPDAlR also enhanced the prohealing efficiency of peptide RL-QN15 against skin scald in mice and full-thickness injured wounds in swine. Conclusions HPDA obviously enhanced the pro-regenerative potency of RL-QN15 in vitro and in vivo, hence HPDAlR exhibited great potential in the development of therapeutics for skin wound healing. Graphic Abstract

Abstract Background Skin wound healing remains a considerable clinical challenge, thus stressing the urgent need for the development of new interventions to promote repair. Recent researches indicate that both peptides and nanoparticles may be potential therapies for the treatment of skin wounds. Methods In the current study, the mesoporous polydopamine (MPDA) nanoparticles were prepared and the peptide RL-QN15 that was previously identified from amphibian skin secretions and exhibited significant potential as a novel prohealing agent was successfully loaded onto the MPDA nanoparticles, which was confirmed by results of analysis of scanning electron microscopy and fourier transform infrared spectroscopy. The encapsulation efficiency and sustained release rate of RL-QN15 from the nanocomposites were determined. The prohealing potency of nanocomposites were evaluated by full-thickness injured wounds in both mice and swine and burn wounds in mice. Results Our results indicated that, compared with RL-QN15 alone, the prohealing potency of nanocomposites of MPDA and RL-QN15 in the full-thickness injured wounds and burn wounds in mice was increased by up to 50 times through the slow release of RL-QN15. Moreover, the load on the MPDA obviously increased the prohealing activities of RL-QN15 in full-thickness injured wounds in swine. In addition, the obvious increase in the prohealing potency of nanocomposites of MPDA and RL-QN15 was also proved by the results from histological analysis. Conclusions Based on our knowledge, this is the first research to report that the load of MPDA nanoparticles could significantly increase the prohealing potency of peptide and hence highlighted the promising potential of MPDA nanoparticles-carrying peptide RL-QN15 for skin wound therapy. Graphic abstract

Chronic wound healing remains a considerable clinical challenge worldwide. We previously identified a pro-regenerative agent, i.e., hollow dopamine nanoparticles (HPDA) loaded with potent pro-healing peptide RL-QN15 (HPDAlR), with significant skin wound healing activity. In the current study, in consideration of clinical application, we successfully prepared a new zinc alginate hydrogel embedded with HPDAlR (HPDAlR&ZA) to treat diabetic wounds. HPDAlR&ZA exhibited no obvious toxicity against keratinocytes, human umbilical vein endothelial cells (HUVECs), human skin fibroblasts (HSFs), and mice. HPDAlR&ZA significantly promoted keratinocyte, HUVEC, and HSF proliferation, as well as HUVEC migration and angiogenesis. HPDAlR&ZA also modulated the expression of cytokines from macrophages. Diabetic mouse full-thickness skin wound and diabetic patient in vitro skin wound models showed that HPDAlR&ZA resisted the inflammatory response by rapidly polarizing M1 macrophages to M2 macrophages, thereby reconstructing blood supply, increasing collagen deposition, and accelerating diabetic wound repair and skin regeneration. In summary, HPDAlR&ZA is a biodegradable hydrogel wound dressing and an efficient treatment strategy for diabetic wound repair, with strong anti-oxidant, anti-inflammatory, and pro-angiogenic features.

Abstract Background Integrase inhibitors (INIs)-based antiretroviral therapies (ART) are more recommended than efavirenz (EFV)-based ART for people living with HIV/AIDS (PLWHA). Yet, the advantage of integrase inhibitors in treating TB/HIV coinfection is uncertain. Therefore, the objective of this systematic review is to evaluate the effects and safety of INIs- versus EFV-based ART in TB/HIV coinfection, and demonstrate the feasibility of the regimens. Methods Four electronic databases were systematically searched through September 2020. Fixed-effects models were used to calculate pooled effect size for all outcomes. The primary outcomes were virologic suppression and bacteriology suppression for INIs- versus EFV-based ART. Secondary outcomes included CD4+ cell counts change from baseline, adherence and safety. Results Three trials (including 672 TB/HIV patients) were eligible. ART combining INIs and EFV had similar effects for all outcomes, with none of the point estimates argued against the INIs-based ART on TB/HIV patients. Compared to EFV-based ART as the reference group, the RR was 0.94 (95% CI 0.85 to 1.05) for virologic suppression, 1.00 (95% CI 0.95 to 1.05) for bacteriology suppression, 0.98 (95% CI 0.95 to 1.01) for adherence. The mean difference in CD4+ cell counts increase between the two groups was 14.23 cells/μl (95% CI 0− 6.40 to 34.86). With regard to safety (adverse events, drug-related adverse events, discontinuation for drugs, grade 3–4 adverse events, IRIS (grade 3–4), and death), INIs-based regimen was broadly similar to EFV-based regimens. The analytical results in all sub-analyses of raltegravir- (RAL) and dolutegravir (DTG) -based ART were valid. Conclusion This meta-analysis demonstrates similar efficacy and safety of INIs-based ART compared with EFV-based ART. This finding supports INIs-based ART as a first-line treatment in TB/HIV patients. The conclusions presented here still await further validation owing to insufficient data.

Inflammatory response and cell death play key roles in the mechanism of myocardial cell injury induced by heat stroke (HS) in rats. Ferroptosis is a newly discovered regulatory type of cell death, which is involved in the occurrence and development of various cardiovascular diseases. However, the role of ferroptosis in the mechanism of cardiomyocyte injury caused by HS remains to be clarified. The purpose of this study was to investigate the role and potential mechanism of Toll-like receptor 4 (TLR4) in cardiomyocyte inflammation and ferroptosis under HS conditions at the cellular level. The HS cell model was established by exposing H9C2 cells at 43 °C for 2 h and then recovering at 37 °C for 3 h. The association between HS and ferroptosis was investigated by adding the ferroptosis inhibitor, liproxstatin-1, and the ferroptosis inducer, erastin. The results show that the expressions of ferroptosis-related proteins recombinant solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4) were decreased, the contents of glutathione (GSH) were decreased, and the contents of malondialdehyde (MDA), reactive oxygen species (ROS), and Fe2+ were increased in H9C2 cells in the HS group. Moreover, the mitochondria of the HS group became smaller and the membrane density increased. These changes were consistent with the effects of erastin on H9C2 cells and were reversed with liproxstatin-1. The addition of TLR4 inhibitor TAK-242 or NF-κB inhibitor PDTC reduced the expressions of NF-κB and p53, increased the expressions of SLC7A11 and GPX4, reduced the contents of TNF-α, IL-6 and IL-1β, increased the content of GSH and reduced MDA, ROS, and Fe2+ levels in H9C2 cells under the HS condition. TAK-242 may improve the mitochondrial shrinkage and membrane density of H9C2 cells induced by HS. In conclusion, this study illustrated that inhibition of the TLR4/NF-κB signaling pathway can regulate the inflammatory response and ferroptosis induced by HS, which provides new information and a theoretical basis for the basic research and clinical treatment of cardiovascular injuries caused by HS.

Abstract Background Baricitinib, an oral-administrated selective inhibitor of the JAK1 and JAK2, is recently approved for rheumatoid arthritis (RA) treatment. With the aim to provide some insights on the clinical safety, the current study mainly focused on the effect of baricitinib on low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) levels and cardiovascular risk. Methods The net change scores [least squares mean (LSM) and mean change] of LDL-C and HDL-C levels from baseline with the comparison of baricitinib versus placebo were pooled, respectively. Risk rations (RR) of major cardiovascular events (MACEs) and differences of cardiovascular risk scores at the end of treatment across groups were compared. Results Six trials with randomized 3552 patients were finally included in summary analysis. Results showed that baricitinib significantly increased LDL-C levels, the net mean change was 13.15 mg/dl with 95% CI 8.89~17.42 (I2 = 0) and the net LSM was 11.94 mg/dl with 95% CI 7.52~16.37 (I2 = 84%). HDL-C also increased obviously with the net LSM change was 7.19 mg/dl (95% CI, 6.05~8.33, I2 = 47%) and net mean change was 5.40 mg/dl (95% CI, 3.07~7.74, I2 = 10%). Subgroup and meta-regression analysis demonstrated baricitinib induced LDL-C and HDL-C increases in a dose-response manner. However, both the pooled RRs of MACEs and differences of cardiovascular risk scores were not statistically significant across groups. Conclusion This study confirmed that baricitinib induced a stable dose-response increase in LDL-C and HDL-C levels. Since the causality association between altered lipids and cardiovascular risk was not identified yet, this issue cannot be completely dismissed. Future research is needed to fully dissect the implications of these lipid changes.