Discovery of ß-sitosterol's effects on molecular changes in rat diabetic wounds and its impact on angiogenesis and macrophages.

Diabetes care, particularly for diabetic foot ulcers (DFUs)-related complications, increases treatment costs substantially. Failure to provide timely and appropriate treatment for severe DFUs significantly increases amputation risk. Neovascularization and macrophage polarization play an important role in diabetic wound healing during different stages of the wound repair process. Therefore, a new treatment method that promotes neovascularization and macrophage polarization may accelerate diabetic wound healing. ß-sitosterol possesses anti-inflammatory, lipid-lowering, and antidiabetic properties. However, its therapeutic potential in diabetic wound healing remains underexplored. This study evaluated the healing effects of ß-sitosterol on diabetic ulcer wounds in rats. We found that ß-sitosterol can promote angiogenesis, alternatively activated macrophages (M2 macrophage) proliferation, and collagen synthesis in diabetic wounds. Transcriptomics analysis and proteomics analysis revealed that MAPK, mTOR and VEGF signaling pathways were enriched in ß-sitosterol-treated wounds. Molecular docking revealed Ndufb5 maybe the target of ß-sitosterol-treated wounds. Our findings confirm the significant diabetic wound healing effects of ß-sitosterol in a rat model. ß-sitosterol treatment to diabetic wounds accelerates wound healing through promoting M2 macrophage proliferation and angiogenesis. Interestingly, we also found that the process of M2 macrophage proliferation accompanies angiogenesis. Thus, ß-sitosterol may be a promising therapeutic approach to enhance diabetic wound healing and reduce amputation in diabetes.

Proteomics and transcriptomics explore the effect of mixture of herbal extract on diabetic wound healing process.

BACKGROUND: The annual incidence of diabetic foot ulcers (DFUs) has been reported to vary from 0.2% to 11% in diabetes-specific clinical settings and less than 0.1% to 8% in community- and population-based cohorts. According to the International Diabetes Foundation, approximately 40 million to 60 million people worldwide are affected by DFUs, and a recent meta-analysis indicates a global prevalence of 6.3% among adults with diabetes, or about 33 million individuals. The cost of diabetes care is significant, amounting to $273 billion in direct and $90 billion in indirect expenses annually, in America. Foot complications in diabetes care excess annual expenditures ranging from 50% to 200% above the baseline cost of diabetes-related care. The cost of advanced-stage ulcers can be more than $50,000 per wound episode, and the direct expenses of major amputation are even higher. DFUs can be treated using various methods, including wound dressings, antibiotics, pressure-off loading, skin substitutes, stem cells, debridement, topical oxygen therapy, gene therapy and growth factors. For severe DFUs patients are at risk of amputation if treatment is not timely or appropriate. Amputating limbs not only causes physical pain to patients, but also brings economic burden due to lost productivity, and decreased employment linked to DFUs. Currently, long-term use of local antibiotics in clinical practice is prone to induce drug resistance, while growth factors do not effectively inhibit bacterial growth and control inflammation in wounds. Stem cell and gene therapies are still in the experimental stage. The method of local debridement combined with negative pressure therapy is expensive. Therefore, we urgently need an affordable, non-surgical method to treat diabetic ulcers. Extracts of bark of Bauhinia purpurea, Paeoniae rubrae, Angelica dahurica (Hoffm.) Benth. & Hook.f. ex Franch. & Sav. (Hoffm.) Benth. & Hook.f. ex Franch. & Sav., Acorus calamus L, and Radix Angelicae biseratae have been used as traditional remedies to treat inflammation-related diseases and cutaneous wounds due to their anti-inflammatory properties and their ability to promote vascular renewal. However, there have been few studies on the mixture of these five herbal extracts on diabetic wound healing. PURPOSE: This study was designed to assess the healing effect of a mixture of five aforementioned herbal extracts on diabetic ulcer wounds in rats, and to reveal the potential mechanisms behind any potential wound healing using transcriptomics and proteomics. STUDY DESIGN: We designed the experiment to explore the effects of five herbal extracts on diabetic wound healing process through in vivo experiments and to investigate the underlying mechanisms through proteomics and transcriptomics. METHODS: We used a mixture of five aforementioned herbal extract to treat rat model of diabetic established by intraperitoneal injection of streptozotocin, and a 2 × 2 cm round full-thickness skin defect was created on the back of the rat. Staphylococcus aureus (1 ml of 1.5 × 109 cfu/ml) was evenly applied to the wound. The wound was then observed for 72 h. The infected ulcer model of diabetic rats was considered to be successfully established if the wound was found to be infected with S. aureus. According to different medications, the rats were divided into three groups, namely mixture of herbal extract (MHE), Kangfuxin solution (KFS) and control (Ctrl). The effects of the medicine on wound healing were observed. HE staining and Masson staining were performed to evaluate the histopathological changes and collagen synthesis. IHC staining was used to assess the neovascularization, and M2 macrophage proliferation was determined by immunofluorescence staining. Proteomic and transcriptomic studies were performed to explore potential mechanism of five herbal extracts to promote wound healing. UHPLC-QE-MS was performed to identify the chemical composition of mixture of herbal extract. RESULTS: The study show that the mixed herbal extract promotes angiogenesis, proliferation of M2 macrophages, and collagen synthesis. Transcriptomics showed that rno-miR-1298, rno-miR-144-5p, and rno-miR-92a-1-5p are vital miRNAs which also play a significant role in role in regulating wound healing. Proteomics results showed that the following proteins were important in wounds treated with MHE: Rack1, LOC100362366, Cops2, Cops6, Eif4e, Eif3c, Rpl12, Srp54, Rpl13 and Lsm7. Autophagy, PI3-Akt and mTOR signaling pathways were enriched after treatment with MHE compared to other groups. CONCLUSION: Herein, we have shown that MHE containing extracts of bark of Bauhinia purpurea, P. rubrae, A. dahurica (Hoffm.) Benth. & Hook.f. ex Franch. & Sav., A. calamus L, and R. A. biseratae has significant wound healing effects in the diabetic ulcer wound rat model. These results suggest that local application of MHE in diabetic wounds can accelerate the wound healing process. Moreover, in vivo experiments revealed that the diabetic wound healing process was primarily mediated by angiogenesis and M2 macrophage transition. Therefore, this study may provide a promising and non-surgical therapeutic strategy to accelerate diabetic wound healing, thereby decreasing the number of limb amputations in diabetic patients.

Tuning Photophysical Properties via Positional Isomerization of the Pyridine Ring in Donor-Acceptor-Structured Aggregation-Induced Emission Luminogens Based on Phenylmethylene Pyridineacetonitrile Derivatives.

A series of aggregation-induced emission (AIE)-featured phenylmethylene pyridineacetonitrile derivatives named o-DBCNPy ((Z)-3-(4-(di-p-tolylamino)phenyl)-2-(pyridin-2-yl)acrylonitrile), m-DBCNPy ((Z)-3-(4-(di-p-tolylamino)phenyl)-2-(pyridin-3-yl)acrylonitrile), and p-DBCNPy ((Z)-3-(4-(di-p-tolylamino)phenyl)-2-(pyridin-4-yl)acrylonitrile) have been synthesized by tuning the substitution position of the pyridine ring. The linkage manner of the pyridine ring had influences on the molecular configuration and conjugation, thus leading to different photophysical properties. The absorption and fluorescence emission peak showed a bathochromic shift when the linking position of the pyridine ring changed from the meta to the ortho and para position. Meanwhile, o-DBCNPy exhibited the highest fluorescence quantum yield of 0.81 and the longest fluorescence lifetime of 7.96 ns as a neat film among all three isomers. Moreover, non-doped organic light-emitting diodes (OLEDs) were assembled in which the molecules acted as the light-emitting layer. Due to the relatively prominent emission properties, the electroluminescence (EL) performance of the o-DBCNPy-based OLED was superior to those of the devices based on the other two isomers with an external quantum efficiency (EQE) of 4.31%. The results indicate that delicate molecular modulation of AIE molecules could endow them with improved photophysical properties, making them potential candidates for organic photoelectronic devices.

Adolescent Hypertension Induced by Obesity and the Efficacy of Comprehensive Intervention.

Context: With the development of the Chinese economy, people's quality of life has improved, obesity caused by excessive nutrition has increased among teenagers, and the age of patients with obesity-induced hypertension has become younger and younger. Objective: The study intended to analyze the factors affecting hypertension in adolescents to find methods to effectively prevent and treat hypertension in that age group. Design: The research team designed a prospective controlled study. Setting: The study took place at the First People's Hospital of Nantong in Nantong, Jiangsu, China from 2020 to 2022 years. Participants: Participants were 1000 students in Grades 7 to 9 at the Si'an middle school in Nantong, China. Intervention: From the 1000 participants, among of them 500 cases of hypertension. The research team (n = 500) participants who were obese and hypertensive and assigned them to the hypertension group, the control group (n = 500) participants with normal weights and no hypertension assigned them to a control group. Participants with obesity-induced hypertension received a comprehensive intervention. Outcome Measures: The research team used a questionnaire and a physical examination to collect data about participants' ages, heights, weights, demographic characteristics, waist circumferences, hip circumferences, and knowledge of hypertension and blood pressure and analyzed the relationships between those factors. The team measured blood pressure, blood lipids, blood glucose, and body mass index at baseline and postintervention. Results: Significant differences existed between the hypertension and control groups at general data: (1) weight-63.49 ± 13.22 kg and 52.59 ± 10.21 kg, respectively (P = .000); (2) waist circumference-75.44 ± 10.92 cm and 68.73 ± 8.15 cm, respectively (P = .001); (3) hip circumference-92.10 ± 7.98 cm and 85.95 ± 7.91 cm, respectively (P = .000); (4) body mass index (BMI)-22.12 ± 4.02 kg/m2 and 19.58 ± 3.34 kg/m2, respectively (P = .002); (5) waist-hip ratio-0.83 ± 0.08 and 0.81 ± 0.07, respectively (P = .003); and (6) waist-to-height ratio-0.46 ± 0.07 and 0.44 ± 0.06, respectively (P = .000). Only age (p=0.006), hip circumference(p=0.000), and BMI (P = .000) were significantly and positively correlated with hypertension. The regression coefficients for age, hip circumference, and BMI were 0.182, 0.062 and 0.096, respectively. The changes in the hypertension group's mean systolic blood pressure (SBP), diastolic blood pressure (DBP), BMI, body fat, trunk fat, abdominal fat, upper-limb fat, and lower-limb fat between baseline and postintervention were statistically significant. Significant decreases in the hypertension group's triglycerides, total cholesterol, and glycated albumin had occurred between baseline and postintervention (all P < .01), and that group's glucagon (P = .011) had significantly increased. No significant changes had occurred in that group's blood glucose, glycated hemoglobin, insulin, and insulin resistance index between baseline and postintervention (P < .05). Conclusions: Obesity increases the risk of hypertension, and comprehensive interventions can effectively prevent and treat adolescent hypertension.

Achieving Ultralong-Cycle Zinc-Ion Battery via Synergistically Electronic and Structural Regulation of a MnO2 Nanocrystal-Carbon Hybrid Framework.

Aqueous rechargeable zinc-ion batteries (ZIBs) have attracted burgeoning interests owing to the prospect in large-scale and safe energy storage application. Although manganese oxides are one of the typical cathodes of ZIBs, their practical usage is still hindered by poor service life and rate performance. Here, a MnO2 -carbon hybrid framework is reported, which is obtained in a reaction between the dimethylimidazole ligand from a rational designed MOF array and potassium permanganate, achieving ultralong-cycle-life ZIBs. The unique structural feature of uniform MnO2 nanocrystals which are well-distributed in the carbon matrix leads to a 90.4% capacity retention after 50 000 cycles. In situ characterization and theoretical calculations verify the co-ions intercalation with boosted reaction kinetics. The hybridization between MnO2 and carbon endows the hybrid with enhanced electrons/ions transport kinetics and robust structural stability. This work provides a facile strategy to enhance the battery performance of manganese oxide-based ZIBs.

Native and engineered extracellular vesicles for wound healing.

Extracellular vesicles (EVs) that act as messengers mediate communication between parent and recipient cells through their contents, including nucleic acids, proteins, and lipids. These endogenous vesicles have emerged as a novel cell-free strategy for the treatment of diseases. EVs can be released by various types of cells with unique biological properties. Recent studies have shown that native EVs are used as therapeutic agents to promote tissue repair by delivering various growth factors and trophic factors including VEGF, EGF, TFN-α, IL-1ß, and TGF-ß to participate in all physiological processes of wound healing. Furthermore, to improve their specificity, safety, and efficiency for wound healing, the content and surface of EVs can be designed, modified, and engineered. The engineering strategies of EVs are divided into parent cell modification and indirect modification of EVs. The therapeutic potential of current EVs and engineered EVs for wound healing still requires the exploration of their large-scale clinical applications through innovative approaches. Herein, we provide an overview of the current biological knowledge about wound healing and EVs, as well as the application of native EVs in promoting wound healing. We also outline recent advances in engineering EV methodologies to achieve ideal therapeutic potential. Finally, the therapeutic applications of engineered EVs in wound healing are reviewed, and the challenges and prospects for the translation of engineered EVs to clinical applications are discussed.

The complete mitochondrial genome of drywood termite, Incisitermes minor (Isoptera: Kalotermitidae).

The complete mitochondrial genome of drywood termite, Incisitermes minor, is reported in this study. The circular mitogenome has a length of 15,970 bp and encodes 37 genes including 13 protein-coding genes (PCGs), 22 transfer RNA (tRNA), two ribosomal RNA (rRNA), and a non-coding control region (D-loop). The percentage of A and T (65.44%) within this mitogenome is much higher than that of G and C (34.56%). The phylogenetic tree revealed that mitogenomes of Kalotermitidae formed one clade. The tree also revealed that I. minor was closest to Cryptotermes secundus, and was a sister group to Neotermes. I. minor is a only species in which mitogenome has been completed so far among the Incisitermes termite. The data provide resource for ecological and evolution analysis within termites especially Kalotermitidae.

The complete mitochondrial genome of Pericapritermes nitobei (Isoptera: Termitidae).

The complete circular mitochondrial genome of a higher termite Pericapritermes nitobei has a length of 15,224bp and encodes 37 genes including 13 protein-coding genes (PCGs), 22 transfer RNA (tRNA), 2 ribosomal RNA (rRNA) and a non-coding control region (D-loop). Protein coding genes (PCGs) in this circular mitogenome start with standard ATN initiation codons and end with complete termination codons TAN except for cox2 and nad5 genes with an incomplete stop codon T. The percentage of A and T (67.49%) is higher than that of G and C (32.51%). The phylogenetic tree revealed that mitogenomes of Pericapritermes formed one clade. The tree also revealed that Pericapritermes dolichocephalus and Pericapritermes latignathus constituted a sister group to P. nitobei. The date here provide a resource for genetics and evolution analysis within termites especially Pericapritermes genus.

[Investigation of psychological state and its influencing factors in children with epilepsy].

OBJECTIVE: To evaluate the psychological state of children with epilepsy and analyze its influencing factors. METHODS: The Mental Health Scale for Child and Adolescent was used to survey 113 children with epilepsy and 114 normal children to evaluate and compare their psychological state. Questionnaires were used to investigate the general status of all subjects and the disease condition and treatment of children with epilepsy. The possible influencing factors for the psychological state of children with epilepsy were analyzed. RESULTS: The mental health status of children with epilepsy was poorer than that of normal children in cognition, thinking, emotion, will-behavior, and personality traits (P<0.05). Multivariate logistic regression analysis showed that family education, family relations, seizure frequency, seizure duration, EEG epileptiform discharges in the last six months, and number of types of antiepileptic drugs were correlated with the psychological state of children with epilepsy. CONCLUSIONS: There is a wider range of psychological health problems in children with epilepsy than in normal children. Poor family living environment, poor seizure control, and use of many antiepileptic drugs are the risk factors affecting the psychological state of children with epilepsy. Improving family living environment, controlling seizures, and monotherapy help to improve the psychological state of children with epilepsy.

Cis elements for transporter associated with antigen-processing-2 transcription: two new promoters and an essential role of the IFN response factor binding element in IFN-gamma-mediated activation of the transcription initiator.

Expression of cell surface MHC class I:peptide complex requires coordinated expression of multiple genes such as MHC class I heavy chain, beta(2)-microglobulin (beta(2)m), transporters associated with antigen-processing (TAP)-1 and TAP-2, and proteosomal components low-molecular weight polypeptide (LMP)-2 and LMP-7. All of these genes are expressed at defined and distinct levels in normal tissues, and are inducible by IFN-gamma. While the cis elements involved in transcription of the MHC class I heavy chain, beta(2)m, TAP-1 and LMP-2 have been analyzed extensively, those for TAP-2 and LMP-7 have not been well studied. Here we systematically analyzed the cis elements for TAP-2 transcription. We found at least two independent elements that are sufficient to activate transcription of a reporter gene. One (hereby called TAP-2 P1) is located 5' to the TAP-2 exon 1, while the other (hereby called TAP-2 P2) is a transcription initiator residing in intron 1. Analysis of the 5' sequence of TAP-2 mRNA indicates that both promoters are active. Moreover, while the TAP-2 promoter region contains cis elements that can mediate TAP-2 induction by IFN-gamma, such as gamma-activation site and IFN response factor binding element (IRFE), only the IRFE is required for IFN-gamma induction of TAP-2 promoter in vitro. The IRFE appears to work as an enhancer for the initiator (P2). Together with another promoter recently identified by others, TAP-2 therefore has three independent promoters that can be differentially regulated.