The long-term efficacy of eltrombopag in children with immune thrombocytopenia.

Immune thrombocytopenia (ITP) is the most common autoimmune disorder characterized by decreased platelet counts and impaired platelet production. Eltrombopag has been demonstrated to be safe and effective for children with ITP. It is reported eltrombopag can achieve a sustained response off treatment. However, data on its overall efficacy and safety profile are scarce in children. This study aimed to investigate the long-term efficacy of eltrombopag in children with ITP. Treatment overall response (OR), complete response (CR), response (R), durable response (DR), no response (NR), treatment free remission (TFR), and relapse rate, were assessed in 103 children with ITP during eltrombopag therapy. The OR rate, CR rate, R rate, DR rate, NR rate, TFR rate, and relapse rate were 67.0%, 55.3%, 11.7%, 56.3%, 33.0%, 60%, 36.2%, respectively. Importantly, we discovered that newly diagnosed ITP patients showed a higher DR rate, TFR rate and lower relapse rate compared to persistent and chronic ITP patients. Furthermore, the CR rate, DR rate, and TFR rate of 5 patients under six months were 100%. None of them suffered relapse. The most common adverse event (AEs) was hepatotoxicity (7.77%). Our study highlighted the critical role of eltrombopag as the second-line treatment in children with ITP who were intolerant to first-line therapy.

The effect of multiple types of workplace violence on burnout risk, sleep quality, and leaving intention among nurses.

OBJECTIVE: The aim of our study is to explore the associations between multiple types of workplace violence (WPV) and burnout risk, sleep problems, and leaving intention among nurses. METHODS: This cross-sectional survey recruited 1,742 nurses, and data on WPV experiences were collected through self-administered questionnaires. Work conditions, burnout risk scales, sleep quality, and leaving intentions were also evaluated. Multivariate logistic regression analyses were performed to examine the associations of WPV with burnout risk, sleep quality, and leaving intentions, adjusting for demographic characteristics and work conditions. RESULTS: The study found that 66.7% of nurses reported experience of WPV, with 26.9% experiencing both physical and nonphysical forms. Those who experienced multiple types of WPV reported worse work conditions, higher burnout risk, poorer sleep quality, and a stronger leaving intention compared to those without such experiences. Adjusting for working conditions, logistic regression analysis showed that nurses who experienced multiple types of WPV had 2.12-fold higher odds of high personal burnout risk, 2.36-fold higher odds of high client-related burnout risk, 1.95-fold higher odds of poor sleep quality, and 1.80-fold higher odds of high leaving intention, compared to those without WPV experiences. CONCLUSIONS: Strategies by hospital managers and policymakers to monitor and reduce workplace violence are vital for sustaining nurses' mental health, well-being, and preventing early attrition from the profession.

Whole-body replacement of larval myofibers generates permanent adult myofibers in zebrafish.

Drastic increases in myofiber number and size are essential to support vertebrate post-embryonic growth. However, the collective cellular behaviors that enable these increases have remained elusive. Here, we created the palmuscle myofiber tagging and tracking system for in toto monitoring of the growth and fates of ~5000 fast myofibers in developing zebrafish larvae. Through live tracking of individual myofibers within the same individuals over extended periods, we found that many larval myofibers readily dissolved during development, enabling the on-site addition of new and more myofibers. Remarkably, whole-body surveillance of multicolor-barcoded myofibers further unveiled a gradual yet extensive elimination of larval myofiber populations, resulting in near-total replacement by late juvenile stages. The subsequently emerging adult myofibers are not only long-lasting, but also morphologically and functionally distinct from the larval populations. Furthermore, we determined that the elimination-replacement process is dependent on and driven by the autophagy pathway. Altogether, we propose that the whole-body replacement of larval myofibers is an inherent yet previously unnoticed process driving organismic muscle growth during vertebrate post-embryonic development.

FusPB-ESM2: Fusion model of ProtBERT and ESM-2 for cell-penetrating peptide prediction.

Cell-penetrating peptides have attracted much attention for their ability to break through cell membrane barriers, which can improve drug bioavailability, reduce side effects, and promote the development of gene therapy. Traditional wet-lab prediction methods are time-consuming and costly, and computational methods provide a short-time and low-cost alternative. Still, the accuracy and reliability need to be further improved. To solve this problem, this study proposes a feature fusion-based prediction model, where the protein pre-trained language models ProtBERT and ESM-2 are used as feature extractors, and the extracted features from both are fused to obtain a more comprehensive and effective feature representation, which is then predicted by linear mapping. Validated by many experiments on public datasets, the method has an AUC value as high as 0.983 and shows high accuracy and reliability in cell-penetrating peptide prediction.

Specific convulsions and brain damage in children hospitalized for Omicron BA.5 infection: an observational study using two cohorts.

BACKGROUND: SARS-CoV-2 continues to mutate over time, and reports on children infected with Omicron BA.5 are limited. We aimed to analyze the specific symptoms of Omicron-infected children and to improve patient care. METHODS: We selected 315 consecutively hospitalized children with Omicron BA.5 and 16,744 non-Omicron-infected febrile children visiting the fever clinic at our hospital between December 8 and 30, 2022. Specific convulsions and body temperatures were compared between the two cohorts. We analyzed potential associations between convulsions and vaccination, and additionally evaluated the brain damage among severe Omicron-infected children. RESULTS: Convulsion rates (97.5% vs. 4.3%, P < 0.001) and frequencies (median: 2.0 vs. 1.6, P < 0.001) significantly differed between Omicron-infected and non-Omicron-infected febrile children. The body temperatures of Omicron-infected children were significantly higher during convulsions than when they were not convulsing and those of non-Omicron-infected febrile children during convulsions (median: 39.5 vs. 38.2 and 38.6 °C, both P < 0.001). In the three Omicron-subgroups, the temperature during convulsions was proportional to the percentage of patients and significantly differed ( P < 0.001), while not in the three non-Omicron-subgroups ( P = 0.244). The convulsion frequency was lower in the 55 vaccinated children compared to the 260 non-vaccinated children (average: 1.8 vs. 2.1, P < 0.001). The vaccination dose and convulsion frequency in Omicron-infected children were significantly correlated ( P < 0.001). Fifteen of the 112 severe Omicron cases had brain damage. CONCLUSIONS: Omicron-infected children experience higher body temperatures and frequencies during convulsions than those of non-Omicron-infected febrile children. We additionally found evidence of brain damage caused by infection with omicron BA.5. Vaccination and prompt fever reduction may relieve symptoms.

A case report of parotid gland epithelioid hemangioendothelioma.

Epithelioid hemangioendothelioma (EHE) is a rare low-grade malignant vascular tumor. It mainly occurs in the liver, lungs, bones, and other parts of the body. Reports of epithelioid hemangioendothelioma in the parotid gland are rare in both domestic and international literature. Here, we present a case report of a parotid gland epithelioid hemangioendothelioma, including its complete clinical course and imaging findings, to improve the diagnosis and treatment of this unusual disease. Case presentation: The patient, a 75-year-old female, presented with a swelling around the right ear for 2 months and pain for 20 days. Enhanced MRI of the parotid gland revealed a well-defined, round mass with homogeneous signal intensity. The mass showed low signal intensity on T1-weighted imaging, high signal intensity on T2-weighted imaging, nodular low signal intensity within, significant high signal intensity on DWI sequence, low signal intensity on ADC sequence, and heterogeneous enhancement in the arterial phase after intravenous injection of Gd-DTPA. Nodular non-enhancing low signal intensity was observed internally, and slight clearance was seen in the venous phase. The initial diagnosis before surgery was a benign lesion, but after histopathological and immunohistochemical examination, it was confirmed as epithelioid hemangioendothelioma. Intervention: Complete tumor resection was performed. Results: The patient experienced a favorable recovery, with meticulous follow-up conducted for up to 1 year revealing no signs of recurrence or metastasis. Continued patient surveillance is ongoing to substantiate and validate the long-term efficacy of the treatment. Conclusion: Due to the extreme rarity of parotid gland epithelioid hemangioendothelioma, it often leads to a high misdiagnosis rate. The most common misdiagnosis is salivary gland lymphoma, followed by epithelioid hemangiosarcoma. When the lesion is multifocal, fusiform, with internal necrosis, and shows punctate low signal intensity on T2-weighted imaging, significant enhancement in the arterial phase, particularly with more pronounced peripheral enhancement, and persistent enhancement in the venous and delayed phases, epithelioid hemangioendothelioma should be considered. However, the current clinical diagnosis of epithelioid hemangioendothelioma still primarily relies on immunohistochemical methods.

MoRF_ESM: Prediction of MoRFs in disordered proteins based on a deep transformer protein language model.

Molecular recognition features (MoRFs) are particular functional segments of disordered proteins, which play crucial roles in regulating the phase transition of membrane-less organelles and frequently serve as central sites in cellular interaction networks. As the association between disordered proteins and severe diseases continues to be discovered, identifying MoRFs has gained growing significance. Due to the limited number of experimentally validated MoRFs, the performance of existing MoRF's prediction algorithms is not good enough and still needs to be improved. In this research, we present a model named MoRF_ESM, which utilizes deep-learning protein representations to predict MoRFs in disordered proteins. This approach employs a pretrained ESM-2 protein language model to generate embedding representations of residues in the form of attention map matrices. These representations are combined with a self-learned TextCNN model for feature extraction and prediction. In addition, an averaging step was incorporated at the end of the MoRF_ESM model to refine the output and generate final prediction results. In comparison to other impressive methods on benchmark datasets, the MoRF_ESM approach demonstrates state-of-the-art performance, achieving [Formula: see text] higher AUC than other methods when tested on TEST1 and achieving [Formula: see text] higher AUC than other methods when tested on TEST2. These results imply that the combination of ESM-2 and TextCNN can effectively extract deep evolutionary features related to protein structure and function, along with capturing shallow pattern features located in protein sequences, and is well qualified for the prediction task of MoRFs. Given that ESM-2 is a highly versatile protein language model, the methodology proposed in this study can be readily applied to other tasks involving the classification of protein sequences.

The ordered lattice host framework induced guest Li+ disordering in high performance cobalt-free Ni-rich cathode materials.

Recently, due to high price, resource shortage and unstable supply of cobalt, the development of low-cost cobalt-free Ni-rich cathodes has attracted extensive attention with the ever-increasing lithium-ion batteries (LIBs) industry. Selecting cost-effective elements to replace cobalt in Ni-rich cathodes is urgent. However, the principle of structural design of Ni-rich cathode remains unclear, hampering the selection of alternative elements. Herein, the cobalt-free cathodes of LiNi0.95Mg0.05O2 (NiMg) and LiNi0.95Mn0.05O2 (NiMn) are designed as alternatives to LiNi0.96Co0.04O2 (NiCo). NiMg has comparable cycle stability with NiCo, while NiMn has inferior cycle performance. Reverse Monte Carlo modelling was used to generate structural model and uncover local structure by fitting pair distribution function. It reveals Mn causes more severe Jahn-Teller distortions and disordered lattice host framework (Ni0.95M0.05O2, M = Co/Mn/Mg) than Co and Mg due to the strong size effect and coulomb interactions of Mn in Ni0.95Mn0.05O2 layer. The outstanding cycle stability of NiMg and NiCo originates from the ordered lattice host frameworks, which relieve stress and inhibit particle breakage during cycle. Meanwhile, the ordered lattice host framework induced guest Li+ disordering reduces Li+ diffusion energy barrier, improving the rate capability. This study provides a new perspective for the structural design of cobalt-free Ni-rich cathodes.

Endovascular treatment of symptomatic severe intracranial atherosclerotic stenosis with a novel intracranial dedicated drug-eluting stent: a more effective treatment approach.

Background: Endovascular treatment of severe intracranial atherosclerotic stenosis (ICAS) using coronary drug-eluting stents (DESs) significantly reduces the risk of in-stent restenosis (ISR) and stroke recurrence. However, there are few reports regarding the treatment of ICAS with intracranial dedicated DES. Herein, we present our experience with the feasibility, safety, and medium-term follow-up outcomes of a novel intracranial DES, named NOVA stent, in patients with symptomatic severe ICAS (≥70%). Methods: From December 2021 to May 2022, patients with symptomatic severe ICAS who underwent implantation of the NOVA stent in our institution were retrospectively analyzed for procedural results, perioperative complications, imaging and clinical follow-up outcomes. Results: Twenty-four patients, 16 (66.7%) with anterior circulation lesions and 8 (33.3%) with posterior circulation lesions, were enrolled. All patients with intracranial ICA (n = 6), middle cerebral artery (n = 10), basilar artery (n = 3), intracranial vertebral artery (n = 3), and the vertebrobasilar junction (n = 2) stenosis were treated successfully using NOVA stents. The severity of stenosis ranged from 75 to 96% (mean 85.9%) before treatment and this was reduced to 0 to 20% (mean 8.6%) immediately after stent placement. Symptomatic distal embolism occurred in one case; however, there were no other perioperative complications. The mean follow-up duration was 12.2 ± 1.06 months. No symptomatic ischemic events occurred during follow-up. Follow-up cerebral angiography was performed in 22 of 24 patients (91.7%), and significant ISR occurred in one patient (4.2%). Conclusion: Our results demonstrate that implantation of the novel intracranial DES NOVA in severe ICAS is feasible, safe, and effective in selected cases, reducing the incidence of ISR, and showing excellent midterm clinical outcomes, providing a promising option for ICAS treatment.

Assessment of Retinal Microvasculature and Choroidal Vascularity After Intra-arterial Chemotherapy for Retinoblastoma.

PURPOSE: To evaluate changes in retinal microvascular density and choroidal vascularity in patients with retinoblastoma (RB) after intra-arterial chemotherapy (IAC). DESIGN: Retrospective clinical cohort study. METHODS: This study included 12 unilateral RB eyes treated with IAC (RB tumor), 12 contralateral normal eyes (RB fellow), and 12 healthy controls. The macular retinal thickness and retinal microvascular structure, including the foveal avascular zone (FAZ) area, macular and peripapillary superficial vessel density (SVD), and deep vessel density (DVD), were measured by optical coherence tomography angiography (OCTA). The choroidal thickness (ChT) and choroidal vascularity, including total choroidal area (TCA), luminal area (LA), stromal area (SA), and choroidal vascularity index (CVI), were measured by spectral-domain optical coherence tomography (SD-OCT). A comparison among the 3 groups was conducted, and the correlations among the parameters were analyzed. RESULTS: Among the 3 cohorts, the foveal retinal thickness, SVD, DVD, ChT, TCA, LA, SA, and CVI were significantly lower in RB tumor compared to RB fellow and the control eyes (all P < .01). There were no significant differences in the parameters between the contralateral and control eyes. The correlation analyses indicated a significant negative correlation between the total melphalan dose and foveal and parafoveal DVD, ChT, and LA. CONCLUSIONS: The retinal microvascular density and choroidal vascularity were lower in unilateral RB treated with IAC, and seemed to be related to the total melphalan dose. There were no measurable changes in the contralateral eyes.

Effectiveness of health education and counseling on stages of change, decisional balance, and smoking cessation self-efficacy: A prospective self-control study.

OBJECTIVE: To examine the effectiveness of health education and counseling on the stages of change, decisional balance, and smoking cessations elf-efficacy in smokers with no intention of quitting. METHODS: A prospective self-controlled design was conducted between December 2020 and December 2022. The research period was divided into a control stage (first to fourth weeks) and an experimental stage (fifth to eighth weeks). Patients with coronary artery disease (CAD) and habitually smoked were recruited. Pearson correlation and a one-factor repeated-measurement analysis were performed to assess the effectiveness of the intervention. RESULTS: In total, 108 male CAD patients with a mean age of 58.1 years were recruited. After 4 weeks of the intervention, 55 (51%) exhibited behavior change (X 2 = 18.03, p = .001). The decisional balance and smoking cessation self-efficacy scores significantly improved in the experimental stage. No significant differences were observed in the control stage. CONCLUSIONS: Four weeks of health education and counseling could effectively improve participants' stage of change, decisional balance, and smoking cessation self-efficacy. PRACTICE IMPLICATION: Healthcare professionals can play key roles in helping CAD patients successfully quit smoking through individual education and counseling.

Entropy-Driven Enhancement of the Conductivity and Phase Purity of Na4Fe3(PO4)2P2O7 as the Superior Cathode in Sodium-Ion Batteries.

Na4Fe3(PO4)2(P2O7) (NFPP) is regarded as a promising cathode material for sodium-ion batteries (SIBs) owing to its low cost, easy manufacture, environmental purity, high structural stability, unique three-dimensional Na-ion diffusion channels, and appropriate working voltage. However, for NFPP, the low conductivity of electrons and ions limits their capacity and power density. The generation of NaFeP2O7 and NaFePO4 inhibits the diffusion of sodium ions and reduces reversible capacity and rate performance during the manufacturing process in synthesis methods. Herein, we report an entropy-driven approach to enhance the electronic conductivity and, concurrently, phase purity of NFPP as the superior cathode in sodium-ion batteries. This approach was realized via Ti ions substituting different ratios of Fe-occupied sites in the NFPP lattice (denoted as NTFPP-X, T is the Ti in the lattice, X is the ratio of Ti-substitution) with the configurational entropic increment of the lattice structures from 0.68 R to 0.79 R. Specifically, 5% Ti-substituted lattice (NTFPP-0.05) inducing entropic augmentation not only improves the electronic conductivity from 7.1 × 10-2 S/m to 8.6 × 10-2 S/m but also generates the pure-phase of NFPP (suppressing the impure phases of the NaFeP2O7 and NaFePO4) of the lattice structure, which is validated by a series of characterizations, including powder X-ray diffraction (XRD), Fourier transform infrared spectra (FT-IR), X-ray photoelectron spectroscopy (XPS), and density functional theory (DFT). Benefiting from the Ti replacement in the lattice, the optimal NTFPP-0.05 composite shows a high first discharge capacity (118.5 mAh g-1 at 0.1 C), superior rate performance (70.5 mAh g-1 at 10 C), and excellent long cycling life (1200 cycles at 10 C with capacity retention of 86.9%). This research proposes a new entropy-driven approach to improve the electrochemical performance of NFPP and reports a low-cost, ultrastable, and high-rate cathode material of NTFPP-0.05 for SIBs.

UBE2J1 promotes ALV-A proviral DNA synthesis through the STAT3/IRF1 signaling pathway.

The ubiquitin-binding enzyme E2J1 is located on the endoplasmic reticulum membrane. It plays a role in transport throughout the process of ubiquitination. In mammals, UBE2J1 can promote RNA virus replication. However, the biological function of chicken UBE2J1 is unclear. In this study, chicken UBE2J1 was cloned for the first time, and UBE2J1 overexpression and shRNA knockdown plasmids were constructed. In chicken embryo fibroblasts, overexpression of UBE2J1 promoted the replication of subtype A avian leukosis virus, while knockdown of UBE2J1 inhibited the replication of ALV-A virus. In addition, we divided virus replication into virus adsorption and invasion into DF-1 cells, synthesis of proviral DNA, and release of viral particles. UBE2J1 promoted the replication of ALV-A virus by promoting the synthesis of proviral DNA. This result was caused by UBE2J1 inhibiting the production of interferon by inhibiting the STAT3/IRF1 pathway. We mutated ser at position 184 of UBE2J1 to Gly and found that this site plays a role as the phosphorylation site of UBE2J1. We confirmed that UBE2J1 promotes ALV-A replication in chicken embryo fibroblasts by inhibiting the STAT3/IRF1 pathway. This study provides new ideas and insights into ubiquitin-related proteins and antiviral immunity.

Two-component system LiaSR negatively regulated the acid resistance and pathogenicity of Listeria monocytogenes 10403S.

The glutamate decarboxylase (GAD) system is one of the acid-resistant systems of Listeria monocytogenes (L. monocytogenes), while the regulatory mechanism of GadT2/GadD2, which plays the major role in the GAD system for acid resistance, is not clear. The two-component system (TCS) is a signal transduction system that is also involved in regulating acid resistance in bacteria. By screening the TCSs of L. monocytogenes 10403S, we found that knocking out the TCS LisSR (encoded by lmo1021/lmo1022) led to a significant increase in the transcription and expression of the gadT2/gadD2 cluster. Subsequently, we constructed a complemental strain CΔliaSR. and a complemental strain with LiaS His157 to Ala, which was designated as CΔliaSRH157A. Survival assay, transcriptional and expression analysis and pathogenicity assay revealed that liaSR deletion significantly enhanced the acid resistance and pathogenicity of 10403S and significantly increased the gadT2/gadD2 transcription and expression. Mutating LiaS His157 to Ala significantly enhanced the acid resistance and pathogenicity of CΔliaSR and significantly increased the gadT2/gadD2 transcription and expression. The results suggest that the two-component system LiaSR mediates the acid resistance and pathogenicity in 10403S by inhibiting the gadT2/gadD2 cluster, and the key activation site of LiaS is His157. This study provides novel knowledge on the regulation of GAD system and the control of this foodborne pathogen.

Copper-Catalyzed Asymmetric Synthesis of Silicon-Stereogenic Benzoxasiloles.

A Cu-catalyzed asymmetric synthesis of silicon-stereogenic benzoxasiloles has been realized via intramolecular Si-O coupling of [2-(hydroxymethyl)phenyl]silanes. Cu(I)/difluorphos is found to be an efficient catalytic system for enantioselective Si-C bond cleavage and Si-O bond formation. In addition, kinetic resolution of racemic substituted [2-(hydroxymethyl)phenyl]silanes using Cu(I)/ PyrOx (pyridine-oxazoline ligands) as the catalytic system is developed to afford carbon- and silicon-stereogenic benzoxasiloles. Ring-opening reactions of chiral benzoxasiloles with organolithiums and Grignard reagents yield various enantioenriched functionalized tetraorganosilanes.

Age-stratified risk factors of re-intervention for uterine fibroids treated with high-intensity focused ultrasound.

OBJECTIVE: To estimate the rate and risk factors of re-intervention for patients with uterine fibroids (UFs) undergoing high-intensity focused ultrasound (HIFU) at different age distributions. METHOD: A retrospective cohort study was conducted in Nanchong Central Hospital, recruiting a total of 672 patients with UFs undergoing HIFU from June 2017 to December 2019. Using univariate and multivariate logistic regression, risk factors for re-intervention were assessed. RESULTS: Among 401 patients with UFs who completed the follow-up visits (median 47 months, range 34-61), 50 (12.46%) patients underwent re-intervention (such as high-intensity focused ultrasound, uterine artery embolization, myomectomy and hysterectomy). In the different age distributions, the re-intervention rate was 17.5% (34/194) in patients aged <45 years and 7.7% (16/207) in those aged ≥45 years. Regarding the younger patient group (aged <45 years), hypo- or iso-intensive fibroids in T2-weighted magnetic resonance imaging (T2WI) intensity may elevate the risk of re-intervention for UFs (odds ratio [OR] 2.96, 95% confidence interval [CI] 1.37-6.62; P = 0.007). Among the older patient group (aged ≥45 years), preoperative anemic patients had an increased risk of re-intervention compared with those without anemia (OR 3.30, 95% CI 1.01-10.37; P = 0.041). CONCLUSION: The re-intervention rate of HIFU decreased with increasing age. Among those aged <45 years, T2WI intensity was the independent risk factor for re-intervention, and among those aged ≥45 years, preoperative anemic status may be related to re-intervention outcome.

Gelatin-Based Hydrogel for Three-Dimensional Neuron Culture Application.

Gelatin is a biocompatible biomaterial composed of a variety of amino acids that provides a possibility to regulate the interaction between cationic amino acids and neural cells. Based on our first finding that the neuron viability was improved as the lysine on the gelatin was converted into a guanidine structure, a three-dimensional (3D) gelatin hydrogel composed of gelatin and poly(allylguanidine) (PAG) was prepared to investigate neural cell behaviors. As expected, improved neuron viability, neurite outgrowth, synaptogenesis, and inhibited glial cell growth were simultaneously observed in the gelatin cross-linked with the PAG hydrogel (G-PAG) but not in the gelatin hydrogel cross-linked with poly-d-lysine (PDL) or polyethylenimine (PEI). In addition, in vivo tests also illustrated that G-PAG could provide an environment for neural culture, with improving neuron viability and neurite outgrowth. Several hydrogel characteristics-including the swelling ratio, mechanical strength, and electric property-that theoretically can influence neural cell response showed no significant difference among them. Therefore, the guanidine structure of PAG was proposed to determine the behaviors of neural cells within the gelatin-polycation hydrogels, and we proposed that the neural cell behavior is regulated by a specific gelatin-neuron relationship. The information found in this study provides a concept to design and modify gelatin-based hydrogels for neural tissue engineering applications.

Geniposide promotes wound healing of skin ulcers in diabetic rats through PI3K/Akt pathway.

Continuously hyperglycation-induced lesion and poor blood flow contributed to the wound incurable and susceptible to infection. About fifteen percent of people with diabetes would develop ulcers during their lifetime, especially on the feet, which could lead to severe tissue destruction and eventual amputation. Various strategies were limited to accelerate wound healing in diabetic patients for high cost and unsatisfied effects. Geniposide is well-known for its anti-inflammation and anti-apoptosis in several pathological tissues. This study is to explore the protective effect of geniposide on wound healing rate, inflammatory response, nutritional function and cellular apoptosis in diabetic rats. Diabetic rats was induced by streptozotocin and defined as plasma glucose >300 mg/dl. Western blot and immunostaining technologies were performed to mark and quantify the target proteins. The oral administration of geniposide (200 mg/kg and 500 mg/kg) could significantly promote wound healing by the increment of lesion retraction in diabetic rats compared to model group. In the apoptotic study of skin wound in diabetic rats, the TUNEL-positive cells were greatly decreased in geniposide subgroups (P < 0.05). The levels of TNF-α, IL-1ß and IL-6 were significantly inhibited by geniposide with the IC50 value of 470 mg/kg, 464 mg/kg and 370 mg/kg body weight respectively, which might be related to the enhancement of the phosphorylation of PI3K and Akt proteins. Geniposide enhanced the repairment of skin wound in diabetic rats by inhibiting inflammatory response and apoptosis.

High Chaos Induced Multiple-Anion-Rich Solvation Structure Enabling Ultrahigh Voltage and Wide Temperature Lithium-Metal Batteries.

The optimal electrolyte for ultrahigh energy density (>400 Wh/kg) lithium-metal batteries with a LiNi0.8Co0.1Mn0.1O2 cathode is required to withstand high voltage (≥4.7 V) and be adaptable over a wide temperature range. However, the battery performance is degraded by aggressive electrode-electrolyte reactions at high temperature and high voltage, while excessive growth of lithium dendrites usually occurs due to poor kinetics at low temperature. Accordingly, the development of electrolytes has encountered challenges in that there is almost no electrolyte simultaneously meeting the above requirements. Herein, a high chaos electrolyte design strategy is proposed, which promotes the formation of weak solvation structures involving multiple anions. By tailoring a Li+-EMC-DMC-DFOB--PO2F2--PF6- multiple-anion-rich solvation sheath, a robust inorganic-rich interphase is obtained for the electrode-electrolyte interphase (EEI), which is resistant to the intense interfacial reactions at high voltage (4.7 V) and high temperature (45 °C). In addition, the Li+ solvation is weakened by the multiple-anion solvation structure, which is a benefit to Li+ desolventization at low temperature (-30 °C), greatly improving the charge transfer kinetics and inhibiting the lithium dendrite growth. This work provides an innovative strategy to manipulate the high chaos electrolyte to further optimize solvation chemistry for high voltage and wide temperature applications.