Follistatin-like protein 1 attenuates doxorubicin-induced cardiomyopathy by inhibiting MsrB2-mediated mitophagy.

Doxorubicin (DOX) is a potent chemotherapeutic drug; however, its clinical use is limited due to its cardiotoxicity. Mitochondrial dysfunction plays a vital role in the pathogenesis of DOX-induced cardiomyopathy. Follistatin-like protein 1 (FSTL1) is a potent cardiokine that protects the heart from diverse cardiac diseases, such as myocardial infarction, cardiac ischemia/reperfusion injury, and heart failure. However, its role in DOX-induced cardiomyopathy is unclear. Therefore, the present study investigated whether administering recombinant FSTL1 could mitigate DOX-induced cardiomyopathy and clarified the underlying molecular mechanisms. FSTL1 treatment attenuated DOX-induced cardiac dysfunction, cardiac fibrosis, and cellular apoptosis by inhibiting excess mitochondrial matrix protein methionine sulfoxide reductase B2 (MsrB2)-mediated mitophagy. Furthermore, FSTL1 administration reduced the expression of apoptotic proteins, including MsrB2, Bax, caspase 3, mitochondrial Parkin, and LC3-II, increased myocardial ATP content, and decreased cardiac malondialdehyde levels, thus protecting mitochondrial function against DOX-induced cardiac injury. Furthermore, FSTL1 treatment protected the contractile properties of adult cardiomyocytes against DOX-induced injury in vitro. Furthermore, carbonyl cyanide m-chlorophenylhydrazone, a mitophagy inducer, impaired the protective effects of FSTL1 in DOX-treated H9c2 cardiomyocytes. In conclusion, these results show that FSTL1 is a novel therapeutic agent against DOX-induced cardiotoxicity that improves mitochondrial function and decreases mitophagy.

Highly Reversible Zn-Air Batteries Enabled by Tuned Valence Electron and Steric Hindrance on Atomic Fe-N4-C Sites.

The bifunctional oxygen electrocatalyst is the Achilles' heel of achieving robust reversible Zn-air batteries (ZABs). Herein, durable bifunctional oxygen electrocatalysis in alkaline media is realized on atomic Fe-N4-C sites reinforced by NixCo3-xO4 (NixCo3-xO4@Fe1/NC). Compared with that of pristine Fe1/NC, the stability of the oxygen evolution reaction (OER) is increased 10 times and the oxygen reduction reaction (ORR) performance is also improved. The steric hindrance alters the valence electron at the Fe-N4-C sites, resulting in a shorter Fe-N bond and enhanced stability of the Fe-N4-C sites. The corresponding solid-state ZABs exhibit an ultralong lifespan (>460 h at 5 mA cm-2) and high rate performance (from 2 to 50 mA cm-2). Furthermore, the structural evolution of NixCo3-xO4@Fe1/NC before and after the OER and ORR as well as charge-discharge cycling is explored. This work develops an efficient strategy for improving bifunctional oxygen electrocatalysis and possibly other processes.

Dermal extracellular matrix gelatin delivering Prussian blue nanoparticles to relieve skin flap ischemia.

The survival rate of flap is a crucial factor for determining the success of tissue repair and reconstruction. Flap transplantation surgery often leads to ischemic and reperfusion injury, causing apoptosis and tissue necrosis, which significantly reduces the survival rate of flap. To address this issue, we developed a porcine skin decellularized matrix gel nanocomplex loaded with alprostadil (Alp) in Prussian blue nanoparticles (PB NPs) called Alp@PB-Gel. This gel not only maintained the cell affinity of the extracellular scaffold but also exhibited a high degree of plasticity. In vitro assays demonstrated that Alp@PB-Gel possessed antioxidant activity, scavenging ROS ability, and effectively promoted the angiogenesis and migration of human vascular endothelial cells (HUVECs) by stimulating the proliferation of vascular epithelial cells and fibroblasts. In vivo assays further confirmed that Alp@PB-Gel could effectively alleviate necrosis in the early and late stages after surgery, downregulate the levels of NLRP3 and CD68 to inhibit apoptosis and attenuate inflammation, while upregulate the levels of VEGF and CD31 to promote vascular tissue regeneration. Moreover, Alp@PB-Gel exhibited excellent cell affinity and biocompatibility, highlighting its potential for clinical application.

Total Face Reconstruction with Flap Prefabrication and Soft-Tissue Expansion Techniques.

SUMMARY: Total facial deformities always lead to psychological and functional consequences, making plastic and reconstructive surgery a great challenge. The skin of the anterior chest area is matched in thickness, texture, and color to the head and face. The purpose of this article was to discuss and evaluate reconstructive surgeons' experiences with obtaining a monoblock flap from the anterior thoracic area for entire face reconstruction using flap prefabrication, soft-tissue expansion, and facial plastic surgery following skin flap transplantation. Two patients underwent prefabricated expanded anterior thoracic flap reconstructions for total facial deformities; data collection included face defect size, flap type, the shape of the expander, expansion time, and complications. All the face flaps that were transplanted survived without major complications. It is concluded that using a prefabricated expanded flap to reconstruct an entire facial soft-tissue defect can provide a high degree of matching, a wide enough covering area, and a thin enough skin thickness to cover the face. Autologous flap grafting is easy to implement and has a high application value.

Built-in Electric Field Promotes Interfacial Adsorption and Activation of CO2 for C1 Products over a Wide Potential Window.

The unsatisfactory adsorption and activation of CO2 suppress electrochemical reduction over a wide potential window. Herein, the built-in electric field (BIEF) at the CeO2/In2O3 n-n heterostructure realizes the C1 (CO and HCOO-) selectivity over 90.0% in a broad range of potentials from -0.7 to -1.1 V with a maximum value of 98.7 ± 0.3% at -0.8 V. In addition, the C1 current density (-1.1 V) of the CeO2/In2O3 heterostructure with a BIEF is about 2.0- and 3.2-fold that of In2O3 and a physically mixed sample, respectively. The experimental and theoretical calculation results indicate that the introduction of CeO2 triggered the charge redistribution and formed the BIEF at the interfaces, which enhanced the interfacial adsorption and activation of CO2 at low overpotentials. Furthermore, the promoting effect was also extended to CeO2/In2S3. This work gives a deep understanding of BIEF engineering for highly efficient CO2 electroreduction over a wide potential window.

Matte surfaces with broadband transparency enabled by highly asymmetric diffusion of white light.

The long-standing paradox between matte appearance and transparency has deprived traditional matte materials of optical transparency. Here, we present a solution to this centuries-old optical conundrum by harnessing the potential of disordered optical metasurfaces. Through the construction of a random array of meta-atoms tailored in asymmetric backgrounds, we have created transparent matte surfaces that maintain clear transparency regardless of the strength of disordered light scattering or their matte appearances. This remarkable property originates in the achievement of highly asymmetric light diffusion, exhibiting substantial diffusion in reflection and negligible diffusion in transmission across the entire visible spectrum. By fabricating macroscopic samples of such metasurfaces through industrial lithography, we have experimentally demonstrated transparent windows camouflaged as traditional matte materials, as well as transparent displays with high clarity, full color, and one-way visibility. Our work introduces an unprecedented frontier of transparent matte materials in optics, offering unprecedented opportunities and applications.

Activity and community structure of nitrifiers and denitrifiers in nitrogen-polluted rivers along a latitudinal gradient.

Nitrogen (N) cycling in rivers is particularly active and dynamic due to excess nutrient inputs worldwide. However, the multidimensional spatial patterns of the activity and community structure of N-cycling microorganisms in rivers remain unclear, limiting our understanding of river ecological functions, especially N removal capacity. Here, we measured the nitrification and denitrification rates and identified nitrifying and denitrifying microorganisms using high-throughput sequencing of archaeal amoA, bacterial amoA, nirK, and nirS genes in channel sediments, riparian rhizosphere soils, and riparian bulk soils of 30 N-polluted rivers across China. Results showed that in the lateral dimension, nitrification rates in sediments did not differ significantly from those in rhizosphere and bulk soils, but denitrification rates were higher in sediments than in bulk soils. However, the archaeal amoA gene abundance in sediments was considerably lower than that in rhizosphere and bulk soils, and bacterial amoA gene abundance in sediments was greater than that in rhizosphere soils. In the vertical dimension, both nitrification and denitrification rates in riparian bulk soils decreased with soil depth, and topsoils harbored more nitrifying and denitrifying microbes than subsoils. Denitrification but not nitrification rates increased with latitude and altitude but decreased with increasing mean annual temperature and precipitation. Overall, these results provide new insights into the multidimensional spatial patterns of river N cycling at a large scale, which is crucial to evaluating the N removal function of global rivers.

The Chimeric Chaoyang-Zika Vaccine Candidate Is Safe and Protective in Mice.

Zika virus (ZIKV) is an emerging flavivirus that causes congenital syndromes including microcephaly and fetal demise in pregnant women. No commercial vaccines against ZIKV are currently available. We previously generated a chimeric ZIKV (ChinZIKV) based on the Chaoyang virus (CYV) by replacing the prME protein of CYV with that of a contemporary ZIKV strain GZ01. Herein, we evaluated this vaccine candidate in a mouse model and showed that ChinZIKV was totally safe in both adult and suckling immunodeficient mice. No viral RNA was detected in the serum of mice inoculated with ChinZIKV. All of the mice inoculated with ChinZIKV survived, while mice inoculated with ZIKV succumbed to infection in 8 days. A single dose of ChinZIKV partially protected mice against lethal ZIKV challenge. In contrast, all the control PBS-immunized mice succumbed to infection after ZIKV challenge. Our results warrant further development of ChinZIKV as a vaccine candidate in clinical trials.

Radiographic Study of the Nasal Valve in Different CT Evaluation Method in Asian Patients with Unilateral Cleft Lip Nose.

OBJECTIVE(S): It was the first study to apply and compare two CT methods to assess the validity and clinical significance of structural alterations of the nasal valve in patients with cleft lip nose for assessing nasal ventilation disturbance. METHODS: The study collected data from the NOSE score, as well as internal nasal valve area, internal nasal valve angle, external nasal valve area, and septal deviation angle, to evaluate the differences and correlations between those factors in patients with cleft lip and nose. RESULTS: There were significant differences among INV transverse and coronal area and INV angle on different axial standardized planes between clefted side and non-clefted side. There were statistically significant negative correlations between NOSE scores and those indicators of standard plane and acoustic-axis standardized coronal plane. NOSE score and NSD angle were the indicators of significant differences in the measured data of different complications groups (p = 0.002, p = 0.017). The correlation comparison showed that two standardized CT imaging transverse planes have similar correlations in NOSE score, NSD angle, and complications. CONCLUSION: The results of the two CT evaluation methods showed that there was a significant difference in nasal valve area on the cleft and non-cleft sides, which was significantly associated with nasal ventilation disturbance. The CT evaluation method based on standard axial 3D reconstruction is more convenient to use in the clinic, can be used for pre-surgical evaluation of nasal repair in patients with secondary nasal deformities of unilateral cleft lip, and is valuable for treatment. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Irisin improves diabetic cardiomyopathy-induced cardiac remodeling by regulating GSDMD-mediated pyroptosis through MITOL/STING signaling.

Diabetic cardiomyopathy (DCM) is a common complication of diabetes mellitus (DM). However, the mechanisms underlying DCM-induced cardiac injury remain unclear. Recently, the role of cyclic GMP-AMP synthase/stimulator of interferon gene (cGAS/STING) signaling and pyroptosis in DCM has been investigated. Based on our previous results, this study was designed to examine the impact of irisin, mitochondrial ubiquitin ligase (MITOL/MARCH5), and cGAS/STING signaling in DCM-induced cardiac dysfunction and the effect of gasdermin D (GSDMD)-dependent pyroptosis. High-fat diet-induced mice and H9c2 cells were used for cardiac geometry and function or pyroptosis-related biomarker assessment at the end of the experiments. Here, we show that DCM impairs cardiac function by increasing cardiac fibrosis and GSDMD-dependent pyroptosis, including the activation of MITOL and cGAS/STING signaling. Our results confirmed that the protective role of irisin and MITOL was partially offset by the activation of cGAS/STING signaling. We also demonstrated that GSDMD-dependent pyroptosis plays a pivotal role in the pathological process of DCM pathogenesis. Our results indicate that irisin treatment protects against DCM injury, mitochondrial homeostasis, and pyroptosis through MITOL upregulation.

Psychological evaluation of Asian female patients with rhinoplasty.

BACKGROUND: Patients requiring plastic surgery exhibit more abnormal psychological trends (e.g., body dysmorphic disorder [BDD], depression, and anxiety) than those requiring other surgeries. However, there are only a few domestic studies on the psychological aspects of the population requiring plastic surgery. Therefore, we analyzed the psychological characteristics and psychological impact of rhinoplasty in female patients. METHODS: In this study, patients were classified into 2 groups: 151 males and 60 females. The self-rating scale of body image (SSBI), self-rating anxiety scale, self-rating depression scale, and postoperative satisfaction questionnaire were used to examine the patients before and after surgery. The results were analyzed using t-test, analysis of variance, chi-square test, paired rank sum test, and Pearson correlation analysis. RESULTS: The total prevalence of BDD in female patients who underwent rhinoplasty was 7.3%. The prevalence of anxiety disorders was 31.8% and that of depression was 45.0%. Female patients with BDD were more likely to exhibit depression (55.5%) and anxiety (36.4%). The SSBI score was related to marital status (p = 0.001) and history of rhinoplasty (p = 0.000). Moreover, there was a significant negative correlation between preoperative BDD score and postoperative satisfaction (r = -0.392, p = 0.002) as well as between the previous history of rhinoplasty and postoperative satisfaction (r = -0.603, p = 0.000). CONCLUSION: Pathological psychologies such as anxiety, depression, and BDD are common in patients scheduled to undergo rhinoplasty, and BDD is more likely to be associated with depression. Rhinoplasty has little psychological impact on patients, i.e., it neither causes improvement nor deterioration. Female patients who have undergone rhinoplasty should be considered to a have high risk of BDD. Although the outcomes of surgery are generally quite positive, patients diagnosed with BDD are more likely to be dissatisfied.

A New Definition for Alar Flare Based on "Alar Flare Angle".

BACKGROUND: An accurate diagnosis and an appropriate treatment are important parts of successful rhinoplasty. We proposed a new definition for alar flares to guide our clinical work. METHODS: A retrospective study was conducted on patients with alar flares from July 2017 to July 2021, and the follow-up time ranged from 12 to 27 months, mean of 16 months. We defined the alar flare angle by the formation of two lines: the line that connects the alar to the alar root point and line that connects the alar to the pronasale. The alar flare angle, interalar distance and nasal base width were measured, and alar wedge excision or alar base excision and tip elevation were performed. Scars, complications and satisfaction scales were evaluated after surgery. Through an analysis of the database, we found that the ideal alar flare angle was between 130 degrees and 140 degrees. If it was less than 130 degrees, it represented alar flares, and patients asked for alar surgery. RESULTS: A total of 33 patients were included. All patients underwent tip elevation, 12 patients underwent external alar wedge excision, and 5 patients underwent external alar wedge excision and alar base excision. External alar wedge excision can be used to completely correct alar flares, and in our study, the alar flare angles were more than 130 degrees after surgery. One patient complained of an acceptable scar, and there was no infection or alar deformity. All patients were satisfied. CONCLUSIONS: We proposed a new definition in which an alar flare angle less than 130 degrees can be diagnosed as an alar flare. This new definition is valuable for the clinical diagnosis and treatment of alar flares. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

A New Algorithm for Secondary Repair of Unilateral Cleft Lip Nasal Deformity.

OBJECTIVES: Following primary surgery for unilateral cleft lip palate (UCLP), cleft lip nasal deformities (CLNDs) (nasal asymmetry, collapsed nasal alae, and a widened alar base) are generally inevitable and often require secondary rhinoplasty. However, reconstructing a cleft nose with an alar tissue deficiency remains challenging for rhinoplasty surgeons. METHODS: The manifestations of common deformities are described herein, and a secondary rhinoplasty technique for unilateral CLNDs using a nasolabial flap (NLF) has been proposed for patients with alar tissue deficiency. Secondary rhinoplasties were performed in 12 patients with unilateral CLNDs between 2020 and 2021 using a NLF. Photogrammetric measurements were performed preoperatively and postoperatively. A total of 12 flaps were successfully transferred. Ten patients were followed up for >1 year. RESULTS: Significant postoperative decreases in nasal alar width were measured in both the base view (p < 0.050) and the frontal view (p < 0.050). Despite the additional facial scars that occurred in some cases, all patients were satisfied with the aesthetic effects. CONCLUSIONS: The NLF achieved satisfactory results in secondary rhinoplasty of unilateral CLND for patients with nasal tissue deficiencies in whom the surgeon weighed the potential benefits over postoperative scarring. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:1648-1655, 2024.

A New Classification of Pollybeak Deformity and Its Treatment in Asian Rhinoplasty.

BACKGROUND: Supratip deformity, also known as pollybeak deformity, is a common complication of primary and secondary rhinoplasty, characterized by fullness in the supratip region. The correction of pollybeak deformity is a challenging procedure, and its management requires a thorough understanding of the pathogenic mechanism of pollybeak deformity. OBJECTIVES: This study aimed to evaluate the effectiveness of surgical methods for correcting pollybeak deformity in Asian rhinoplasty. METHODS: A retrospective chart review was conducted for 53 patients who underwent pollybeak correction between 2021 and 2022. A modified classification system for pollybeak deformity, the Supratip Fullness Rating Scale (SFRS), was developed to evaluate supratip fullness. The aesthetic outcomes of the patients were assessed by surgeons using the visual analog scale (VAS), and patient was self-assessed using the Rhinoplasty Outcome Evaluation (ROE) scale. RESULTS: The study demonstrated that our surgical method resulted in satisfactory outcomes, with a mean SFRS score change from 2.34[0.65] to 0.23[0.42], a decrease in VAS score from 7.47[1.73] to 1.79[1.67] and a high satisfaction rate of 77.36%, calculated by ROE score. No complications were reported. CONCLUSION: Our surgical method for correcting pollybeak deformity in Asian rhinoplasty can result in satisfactory outcomes, particularly in terms of aesthetic appearance, without any side effects. The use of the modified classification system (SFRS) can provide an objective evaluation of supratip fullness, thereby aiding in the management of this challenging complication. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Cellulose nanofibril/titanate nanofiber modified with CdS quantum dots hydrogel with 3D porous structure: A stable photocatalytic adsorbent for Cr(VI) removal.

A novel cellulose nanofibril/titanate nanofiber modified with CdS quantum dots hydrogel (CTH) was synthesized as an effective, stable, and recyclable photocatalytic adsorbent using cellulose nanofibril (CN), titanate nanofiber (TN), and CdS quantum dots. Within the CTH structure, CN formed an essential framework, creating a three-dimensional (3D) porous structure that enhanced the specific surface area and provided abundant adsorption sites for Cr(VI). Simultaneously, TN modified with CdS quantum dots (TN-CdS) served as a nanoscale Z-type photocatalyst, facilitating the efficient separation of photoinduced electrons and holes, further increasing the photocatalytic efficiency. The morphological, chemical, and optical properties of CTH were thoroughly characterized. The CTH demonstrated the maximum theoretical adsorption capacity of 373.3 ± 14.2 mg/g, which was 3.4 times higher than that of CN hydrogel. Furthermore, the photocatalytic reduction rate constant of the CTH was 0.0586 ± 0.0038 min-1, which was 6.4 times higher than that of TN-CdS. Notably, CTH displayed outstanding stability, maintaining 84.9 % of its initial removal efficiency even after undergoing five consecutive adsorption-desorption cycles. The remarkable performance of CTH in Cr(VI) removal was attributed to its 3D porous structure, comprising CN and TN-CdS. These findings provide novel insights into developing a stable photocatalytic adsorbent for Cr(VI) removal.

Type VI secretion system drives bacterial diversity and functions in multispecies biofilms.

Type VI secretion system (T6SS) plays an essential role in interspecies interactions and provides an advantage for a strain with T6SS in multispecies biofilms. However, how T6SS drives the bacterial community structure and functions in multispecies biofilms still needs to be determined. Using gene deletion and Illumina sequencing technique, we estimated bacterial community responses in multispecies biofilms to T6SS by introducing T6SS-containing Pseudomonas putida KT2440. Results showed that the niche structure shifts of multispecies biofilms were remarkably higher in the presence of T6SS than in the absence of T6SS. The presence of T6SS significantly drove the variation in microbial composition, reduced the alpha-diversity of bacterial communities in multispecies biofilms, and separately decreased and increased the relative abundance of Proteobacteria and Bacteroidota. Co-occurrence network analysis with inferred putative bacterial interactions indicated that P. putida KT2440 mainly displayed strong negative associations with the genera of Psychrobacter, Cellvibrio, Stenotrophomonas, and Brevundimonas. Moreover, the function redundancy index of the bacterial community was strikingly higher in the presence of T6SS than in the absence of T6SS, regardless of whether relative abundances of bacterial taxa were inhibited or promoted. Remarkably, the increased metabolic network similarity with T6SS-containing P. putida KT2440 could enhance the antibacterial activity of P. putida KT2440 on other bacterial taxa. Our findings extend knowledge of microbial adaptation strategies to potential bacterial weapons and could contribute to predicting biodiversity loss and change in ecological functions caused by T6SS.

Inhibiting Multidrug Resistance with Transferrin-Targeted Polymersomes through Optimization of Ligand Density.

Transferrin-conjugated polymersomes, transferrin-biotin/avidin/biotin-Pluronic F127-poly(lactic acid) (Tf-F127-PLA), were successfully prepared through a biotin-avidin bridging technique to study their ability to inhibit multidrug resistance of cancer cells. Hydrophilic doxorubicin (DOX) was selected as the model drug to be loaded into Tf-F127-PLA polymersomes. DOX loaded in Tf-F127-PLA polymersomes was released fast initially, followed by a slow release. The effect of the transferrin ligand density of Tf-F127-PLA/DOX polymersomes on their targeting properties was studied by both cytotoxicity and cellular uptake assays against A549 lung cancer cells. It was shown that Tf-F127-PLA/DOX polymersomes had better targeting ability than nontargeted drug-loaded polymersomes. Furthermore, Tf-F127-PLA/DOX polymersomes with 2% Tf molar content have more effective antitumor activity and a higher cellular uptake than those with 4 and 5% Tf molar content. 2% Tf-F127-PLA/DOX polymersomes also exhibited better anticancer ability in multidrug resistant cancer cells A549/ADR than nontargeted PLA-F127-PLA/DOX polymersomes. It was further proved that the endocytosis of polymersomes by A549/ADR cells was an energy-dependent endocytosis process, which was related to clathrin, macrocytosis, and caveolin. Also, the endocytosis of Tf-F127-PLA/DOX polymersomes was proven to be mediated by the transferrin receptor.

The HIFIA/LINC02913/IGF1R axis promotes the cell function of adipose-derived mesenchymal stem cells under hypoxia via activating the PI3K/AKT pathway.

OBJECTIVE: Promoting angiogenesis is crucial for tissue repair. Adipose-derived mesenchymal stem cells (ADSCs) are endowed with the ability of paracrine secretion of various angiogenic cytokines and the differentiation potential into endothelium-like cells to directly participate in angiogenesis. ADSCs are key seed cells for promoting angiogenesis in regenerative medicine and tissue engineering. This study aimed to explore the role and mechanism of C9orf106 (LINC02913) in the angiogenesis of ADSCs. METHODS: The microarray dataset GSE12884 was analyzed to identify the differentially expressed lncRNAs in ADSCs under normoxia and hypoxia. The expression of the key genes was detected using qRT-PCR, western blot assay (western blot), and immunofluorescence (IF) staining. The adipogenic ability and tube formation ability of ADSCs was detected using oil red O staining and tube formation assay, respectively. The regulatory relationship between hypoxia-inducible factor-1alpha (HIF1A) and LINC02913 was verified using chromatin immunoprecipitation (ChIP) assay and dual-luciferase reporter gene assay. A skin wound healing nude mice model was established. Hematoxylin and eosin (H&E) staining was applied to detect pathological skin damage. Immunohistochemistry (IHC) staining was used to determine the level of CD31 in skin tissues. RESULTS: LINC02913 expression was decreased in ADSCs under hypoxia; LINC02913 overexpression inhibited the proliferation, adipogenic ability, endothelial differentiation ability, and tube formation ability of ADSCs. ChIP assay and dual-luciferase reporter gene assay results showed that HIF1A could directly bind to the LINC02913 promoter region to inhibit its transcription. Through RNAact prediction and analysis of the correlation with LINC02913 expression, it was found that IGF1R may directly interact with LINCO02913. The HIF1A/LINC02913/IGF1R axis could activate the PI3K/AKT pathway to promote the biological function of ADSCs. Hypoxia-ADSCs significantly promoted vascularization in the wounded skin. The regulatory effect of LINC02913/IGF1R axis on hypoxia-ADSCs treated skin wound healing were verified. CONCLUSION: The HIF1A/LINC02913/IGF1R axis promoted the proliferation, adipogenic ability, and tube formation ability of ADSCs under hypoxia via activating the PI3K/AKT pathway.

Long-cycle Zn-air batteries at high depth of discharge enabled by a robust Zn|electrolyte interface.

It is an urgent need to improve the depth of discharge (DOD) of Zn-air batteries (ZABs), considering that most reported ZABs with long cycle life are realized at low DOD (<1%). In this work, our solid-state ZABs achieved a long cycle life of more than 220 h at 3.2% DOD (the discharge capacity of 10 mA h cm-2 per cycle). Moreover, benefiting from excellent bifunctional oxygen electrocatalysts (Fe@BNC) and robust Zn|electrolyte interface, the ZABs displayed a long cycle life of 120 h even at high DOD of 23.4% and large discharge capacity of 72 mA h cm-2. Additionally, the impact of Zn|electrolyte interface on the cycle time at different DODs is analysed and discussed. The unstable interface exacerbated the dendrite growth and uneven deposition of Zn at high DOD, leading to the decay of the cycle life. The work gives insights into the mechanism of the effect of DOD on the cycle life of the batteries.

Melatonin Restores Autophagic Flux by Activating the Sirt3/TFEB Signaling Pathway to Attenuate Doxorubicin-Induced Cardiomyopathy.

Doxorubicin (DOX) chemotherapy in cancer patients increases the risk of the occurrence of cardiac dysfunction and even results in congestive heart failure. Despite the great progress of pathology in DOX-induced cardiomyopathy, the underlying molecular mechanisms remain elusive. Here, we investigate the protective effects and the underlying mechanisms of melatonin in DOX-induced cardiomyopathy. Our results clearly show that oral administration of melatonin prevented the deterioration of cardiac function caused by DOX treatment, which was evaluated by left ventricular ejection fraction and fractional shortening as well as cardiac fibrosis. The ejection fraction and fractional shortening in the DOX group were 49.48% and 25.5%, respectively, while melatonin treatment increased the ejection fraction and fractional shortening to 60.33 and 31.39 in wild-type mice. Cardiac fibrosis in the DOX group was 3.97%, while melatonin reduced cardiac fibrosis to 1.95% in wild-type mice. Sirt3 is a mitochondrial deacetylase and shows protective effects in diverse cardiovascular diseases. Therefore, to test whether Sirt3 is a key factor in protection, Sirt3 knockout mice were used, and it was found that the protective effects of melatonin in DOX-induced cardiomyopathy were partly abolished. Further analysis revealed that Sirt3 and its downstream molecule TFEB were downregulated in response to DOX treatment, while melatonin administration was able to significantly enhance the expressions of Sirt3 and TFEB. Our in vitro study demonstrated that melatonin enhanced lysosomal function by increasing the Sirt3-mediated increase at the TFEB level, and the accumulation of autolysosomes induced by DOX treatment was attenuated. Thus, autophagic flux disrupted by DOX treatment was restored by melatonin supplementation. In summary, our results demonstrate that melatonin protects the heart against DOX injury by the restoration of autophagic flux via the activation of the Sirt3/TFEB signaling pathway.