Atractylenolide-I Alleviates Hyperglycemia-Induced Heart Developmental Malformations through Direct and Indirect Modulation of the STAT3 Pathway.

BACKGROUND: Gestational diabetes could elevate the risk of congenital heart defects (CHD) in infants, and effective preventive and therapeutic medications are currently lacking. Atractylenolide-I (AT-I) is the active ingredient of Atractylodes Macrocephala Koidz (known as Baizhu in China), which is a traditional pregnancy-supporting Chinese herb. PURPOSE: In this study, we investigated the protective effect of AT-I on the development of CHD in embryos exposed to high glucose (HG). STUDY DESIGN AND METHODS: First, systematic review search results revealed associations between gestational diabetes mellitus (GDM) and cardiovascular malformations. Subsequently, a second systematic review indicated that heart malformations were consistently associated with oxidative stress and cell apoptosis. We assessed the cytotoxic impacts of Atractylenolide compounds (AT-I, AT-II, and AT-III) on H9c2 cells and chick embryos, determining an optimal concentration of AT-I for further investigation. Second, immunofluorescence, western blot, Polymerase Chain Reaction (PCR), and flow cytometry were utilized to delve into the mechanisms through which AT-I mitigates oxidative stress and apoptosis in cardiac cells. Molecular docking was employed to investigate whether AT-I exerts cardioprotective effects via the STAT3 pathway. Then, we developed a streptozotocin-induced diabetes mellitus (PGDM) mouse model to evaluate AT-I's protective efficacy in mammals. Finally, we explored how AT-I protects hyperglycemia-induced abnormal fetal heart development through microbiota analysis and untargeted metabolomics analysis. RESULTS: The study showed the protective effect of AT-I on embryonic development using a chick embryo model which rescued the increase in the reactive oxygen species (ROS) and decrease in cell survival induced by HG. We also provided evidence suggesting that AT-I might directly interact with STAT3, inhibiting its phosphorylation. Further, in the PGDM mouse model, we observed that AT-I not only partially alleviated PGDM-related blood glucose issues and complications but also mitigated hyperglycemia-induced abnormal fetal heart development in pregnant mice. This effect is hypothesized to be mediated through alterations in gut microbiota composition. We proposed that dysregulation in microbiota metabolism could influence the downstream STAT3 signaling pathway via EGFR, consequently impacting cardiac development and formation. CONCLUSIONS: This study marks the first documented instance of AT-I's effectiveness in reducing the risk of early cardiac developmental anomalies in fetuses affected by gestational diabetes. AT-I achieves this by inhibiting the STAT3 pathway activated by ROS during gestational diabetes, significantly reducing the risk of fetal cardiac abnormalities. Notably, AT-I also indirectly safeguards normal fetal cardiac development by influencing the maternal gut microbiota and suppressing the EGFR/STAT3 pathway.

Metabolomic Alterations in Methotrexate Treatment of Moderate-to-Severe Psoriasis.

BACKGROUND Aberrant lipid metabolism alterations in skin tissue, blood, or urine have been implicated in psoriasis. Here, we examined lipid metabolites related to psoriasis and their association with the age of disease onset. MATERIAL AND METHODS Differences in lipid metabolites before and after methotrexate (MTX) treatment were evaluated. The discovery cohort and validation cohort consisted of 50 and 46 patients, respectively, with moderate-to-severe psoriasis. After MTX treatment, the patients were divided into response (Psoriasis Area and Severity Index [PASI] 75 and above) and non-response (PASI below 75) groups, blood was collected for serum metabolomics, and multivariate statistical analysis was performed. RESULTS We detected 1546 lipid metabolites. The proportion of the top 3 metabolites was as follows: triglycerides (TG, 34.8%), phospholipids (PE, 14.5%), phosphatidylcholine (PC, 12.4%); diglycerides (DG) (16: 1/18: 1), and DG (18: 1/18: 1) showed strong positive correlations with onset age. There were marked changes in TG (16: 0/18: 0/20: 0), TG (18: 0/18: 0/22: 0), TG (14: 0/18: 0/22: 0), TG (14: 0/20: 0/20: 0), lysophosphatidylcholine (LPC) (16: 0/0: 0), LPC (18: 0/0: 0), LPC (14: 0/0: 0), and LPC (18: 1/0: 0) levels before and after 12 weeks of MTX treatment. The glycerophospholipid metabolic pathway was implicated in psoriasis development. Of the 96 recruited patients, 35% were MTX responders and 65% non-responders. PE (34: 4) and PE (38: 1) levels were significantly different between the groups. Obvious differences in lipid metabolism were found between early-onset (<40 years) and late-onset (≥40 years) psoriasis. Significant changes in serum lipid profile before and after MTX treatment were observed. CONCLUSIONS The specific lipid level changes in responders may serve as an index for MTX treatment efficacy evaluation.

HMGB1 prefers to interact with structural RNAs and regulates rRNA methylation modification and translation in HeLa cells.

BACKGROUND: High-mobility group B1 (HMGB1) is both a DNA binding nuclear factor modulating transcription and a crucial cytokine that mediates the response to both infectious and noninfectious inflammation such as autoimmunity, cancer, trauma, and ischemia reperfusion injury. HMGB1 has been proposed to control ribosome biogenesis, similar as the other members of a class of HMGB proteins. RESULTS: Here, we report that HMGB1 selectively promotes transcription of genes involved in the regulation of transcription, osteoclast differentiation and apoptotic process. Improved RNA immunoprecipitation by UV cross-linking and deep sequencing (iRIP-seq) experiment revealed that HMGB1 selectively bound to mRNAs functioning not only in signal transduction and gene expression, but also in axon guidance, focal adhesion, and extracellular matrix organization. Importantly, HMGB1-bound reads were strongly enriched in specific structured RNAs, including the domain II of 28S rRNA, H/ACA box snoRNAs including snoRNA63 and scaRNAs. RTL-P experiment showed that overexpression of HMGB1 led to a decreased methylation modification of 28S rRNA at position Am2388, Cm2409, and Gm2411. We further showed that HMGB1 overexpression increased ribosome RNA expression levels and enhanced protein synthesis. CONCLUSION: Taken together, our results support a model in which HMGB1 binds to multiple RNA species in human cancer cells, which could at least partially contribute to HMGB1-modulated rRNA modification, protein synthesis function of ribosomes, and differential gene expression including rRNA genes. These findings provide additional mechanistic clues to HMGB1 functions in cancers and cell differentiation.

Multiple organs injury and myocardial energy metabolism disorders induced by isoproterenol.

The study sought to assess the detrimental effects of isoproterenol (ISO) on major organs and investigate the potential reversibility of these adverse reactions in mice. Male mice were divided into normal control, 0.2 mg/kg.d and 3.0 mg/kg.d ISO groups, and were subcutaneously administered of the respective doses for 14 consecutive days. Subsequently, a recovery period experiment was conducted, replicating the aforementioned procedure, followed by an additional 2-week recovery period for the mice. Following 14 consecutive days of administration, mice treated with ISO exhibited notable cardiac damage manifested by abnormal ECG patterns, dysregulated energy metabolism, elevated cardiac hypertrophy, and increased heart pathological score. Additionally, the administration of ISO resulted in liver and kidney damage, as evidenced by increased pathological score, serum albumin level, and urea level. Lung damage was also observed, indicated by an increase in lung pathological score. Furthermore, the administration of ISO at a dosage of 3.0 mg/kg.d resulted in a decrease in liver mass index, serum iron content, and an increase in lung mass index. After a 2-week recovery period, mice treated with ISO showed abnormalities in ECG patterns and dysregulated myocardial energy metabolism, accompanied by a decrease in serum iron content. Histopathological examinations revealed continued pathological changes in the heart and lung, as well as significant hemosiderin deposition in the spleen. Furthermore, the group treated with ISO at a dosage of 3.0 mg/kg.d showed an increase in serum AST and TP levels. In summary, the study demonstrates that both 0.2 mg/kg.d and 3.0 mg/kg.d doses of ISO can induce damage to the heart, liver, lung, kidney, and spleen, with the higher dose causing more severe injuries. After a 2-week withdrawal period, the liver, kidney, and thymus injuries caused by 0.2 mg/kg ISO shows signs of recovery, while damage to the heart, lung, and spleen persists. The thymus injury mostly recovers, with minimal kidney pathology, but significant damage to the heart, liver, and lung remains even after the withdrawal period for the 3.0 mg/kg ISO dose.

Three­dimensional finite element analysis: Anatomical splint fixation for Colles fractures.

With the rapid development of digital research in clinical orthopedics, the efficacy and safety of splint fixation can be better evaluated through biomechanical analysis based on a three-dimensional (3D) finite element model. It is essential to address the current gap in understanding the biomechanical implications of anatomical splint fixation for Colles fractures. By employing advanced 3D finite element analysis, the present study aimed to provide a comprehensive evaluation, offering valuable insights that can contribute to enhancing the effectiveness of anatomical splint fixation in the clinical management of Colles fractures. The 3D finite element models of the forearm and hand were constructed using Mimics 15.0 according to data from computed tomography of a patient with a Colles fracture. After the validity of the model was verified, the corresponding material properties of the models were adjusted to simulate a Colles fracture. Subsequently, the reduction functions, such as radial inclination and ulnar deviation, of the simulated fracture were completed and the mechanical changes of the tissues surrounding the fracture were calculated. Anatomical splints were then placed on the surfaces of the 3D finite element models of Colles fractures at various positions to analyze the changes in the stress cloud diagram, such as for the soft tissue and anatomical splints. In the present study, the constructed 3D finite element models were accurate and valid. The maximum stress of the anatomical splints and soft tissues was 2.346 and 0.106 MPa in pronation, 1.780 and 0.069 MPa in median rotation and 3.045 and 0.057 MPa in supination, respectively. Splint stress reached the highest level in supination and soft tissue stress achieved the highest level in pronation. The peak of splint stress occurred during supination, which contrasts to the peak of soft tissue stress observed in pronation, suggesting splint fixation median rotation can effectively avoid compression of the local soft tissue.

Thyroid allostasis in drug-free affective disorder patients.

AIM: To assess the thyroid allostasis in drug-free patients with affective disorder. METHODS: Patients with major depressive disorder or bipolar disorder as drug-free, defined as those without psychiatric drugs exposure for at least 4 months before admission, from a tertiary hospital were recruited in this cross-sectional study. The primary outcomes were "structure parameters of thyroid homeostasis", which include "thyroid's secretory capacity" (SPINA-GT), "sum step-up activity of deiodinases" (SPINA-GD), the ratio of total to free thyroxine and "thyroid homeostasis central set point" (TSH index and "thyroid feedback quantile-based index" [TFQI]), calculated by TSH and thyroid hormones measured at admission. A healthy population and non-affective psychiatric disorder (schizophrenia) from the same catchment area were recruited as two comparison groups. RESULTS: A total of 1263 cases of major depressive disorder, 1619 cases of bipolar disorder, 1186 cases of schizophrenia, and 162 healthy controls were included in the study. Compared to healthy control, GD and ratio of total to free thyroxine were lower in affective disorders. Bipolar with mania episode had higher GT than bipolar with depressive episode and major depressive disorder (median level at 3.70 vs. 3.04 and 3.03, respectively). Compared with healthy control, schizophrenia had higher TSH index and TFQI, but no increase in these parameters in major depressive disorder and bipolar disorder. CONCLUSION: Affective disorders have a unique profile of thyroid allostasis with impaired step-up deiodinase activity and reduced serum protein binding of thyroid hormones, but no change in thyroid homeostasis central set point. Mania episode may be associated with higher thyroid secretory capacity.

PEX26 Functions as a Metastasis Suppressor in Colorectal Cancer.

BACKGROUND/AIMS: Aberrant Peroxisomal Biogenesis Factor 26 (PEX26) occurs in multiple cell process. However, the role of PEX26 in colorectal cancer (CRC) development remains unknown. We aimed to study PEX26 expression, regulation, and function in CRC cells. METHODS: Using the bioinformatic analysis, real-time quantitative PCR, and immunohistochemistry staining, we detected the expression of PEX26 in CRC and normal tissues. We performed functional experiments in vitro to elucidate the effect of PEX26 on CRC cells. We analyzed the RNA-seq data to reveal the downstream regulating network of PEX26. RESULTS: PEX26 is significantly down-regulated in CRC and its low expression correlates with the poor overall survival of CRC patients. We further demonstrated that PEX26 over-expression inhibits the ability of CRC cell migration, invasion, and epithelial-mesenchymal transition (EMT), while PEX26 knockdown promotes the malignant phenotypes of migration, invasion, and EMT via activating the Wnt pathway. CONCLUSION: Overall, our results showed that the loss of PEX26 contributes to the malignant phenotype of CRC. PEX26 may serve as a novel metastasis repressor for CRC.

Amorphization of different furosemide polymorphic forms during ball milling: Tracking solid-to-solid phase transformations.

Ball milling is used, not only to reduce the particle size of pharmaceutical powders, but also to induce changes in the physical properties of drugs. In this work we prepared three crystal forms of furosemide (forms Ⅰ, Ⅱ, and Ⅲ) and studied their solid phase transformations during ball milling. Powder X-ray diffraction and modulated differential scanning calorimetry were used to characterize the samples after each milling time on their path to amorphization. Our results show that forms Ⅰ and III directly converted into an amorphous phase, while form Ⅱ first undergoes a polymorphic transition to form Ⅰ, and then gradually loses its crystallinity, finally reaching full amorphousness. During ball milling of forms Ⅰ and Ⅱ, the glass transition temperature (Tg) of the amorphous fraction of the milled material remains almost unchanged at 75 °C and 74 °C, respectively (whilst the amorphous content increases). In contrast, the Tg values of the amorphous fraction of milled form III increase with increasing milling times, from 63 °C to 71 °C, indicating an unexpected phenomenon of amorphous-to-amorphous transformation. The amorphous fraction of milled forms I and II samples presented a longer structural relaxation (i.e., lower molecular mobility) than the amorphous fraction of milled form III samples. Moreover, the structural relaxation time remained the same for the increasing amorphous fraction during milling of forms I and II. In contrast, the structural relaxation times were always shorter for the amorphous fraction of form III, but increased with increasing amorphous content during milling, confirming amorphous-to-amorphous transformation.

Effects of Banxia Xiexin Decoction on apoptosis of interstitial cells of Cajal via regulation of MiR-451-5p: An in vivo and in vitro study.

ETHNOPHARMACOLOGICAL RELEVANCE: Banxia Xiexin Decoction (BXD) is a traditional Chinese medical formula applied to gastrointestinal (GI) motility disorders. Previous studies showed that miR-451-5p was down-regulated in rats with GI motility disorders induced by gastric electrical dysrhythmia. Interstitial cells of Cajal (ICCs) are pacemakers for GI motility, while loss of ICCs is responsible for GI motility disturbance. Thus, the underlying interaction mechanisms for BXD regulating ICCs apoptosis via miR-451-5p remain to be explored. AIM OF THE STUDY: In this work, the main objectives were to examine the efficacy of BXD on ICCs via miR-451-5p both in GI motility disorders rats model and in vitro, as well as the potential contributions of SCF/c-kit signaling. MATERIALS AND METHODS: Rats with gastric electrical dysrhythmia were established in male SD rats by using a single-day diet and a double fasting method (drinking diluted hydrochloric acid water during the period) for 4 weeks. The gastric slow wave (GSW) recording, RT-qPCR, and western blot were performed to examine the effects of BXD on ICCs apoptosis in rats with GED and miR-451-5p expression. In vitro assays included CCK-8, flow cytometry analysis, RT-qPCR, and western blot were applied to investigate the potential molecular mechanism of BXD on ICCs apoptosis via miR-451-5p. RESULTS: BXD promoted gastric motility, reduced ICCs apoptosis, and elevated miR-451-5p in GED rats. In addition, miR-451-5p was significantly up-regulated in ICCs after BXD treatment compared with that in ICCs with miR-451-5p inhibitor transfection. Meanwhile, high miR-451-5p expression with either BXD treatment or miRNA mimics enhanced ICCs proliferation and inhibit apoptosis. Moreover, overexpression of miR-451-5p can reverse G0/G1 arrest in ICCs by BXD treatment. Further, SCF and c-kit protein levels were detected to demonstrate that modulation of miR-451-5p by BXD treatment was involved in this signaling. CONCLUSIONS: Through this study, we demonstrated that BXD could promote ICCs proliferation and inhibit apoptosis via miR-451-5p and may involve the modulations of SCF/c-kit signaling, thus suggesting a new therapy basis for GI motility dysfunction from the perspective of modulation of ICCs apoptosis by targeting miR-451-5p.

Rheological and physicochemical properties of Spirulina platensis residues-based inks for extrusion 3D food printing.

Novel food matrices (such as microalgae, plants, fungi, and microbial proteins) with high protein content and biological value, good amino acid profile, and functionality have been explored. Phycocyanin and active polysaccharides extracted from Spirulina platensis are used as food additives, treatment of colitis, as well as obesity prevention. However, most of the remaining Spirulina platensis residues are mainly used as fish feed at present. 3D food printing is one of the promising development techniques used in the food industry. The aim of this study was to develop a novel 3D printing material of Spirulina platensis residues with shear thinning characteristics, high viscosity and rapid recovery. The effects of moisture content and pretreatment method on the rheological properties of Spirulina platensis residues were clarified. Scanning electron microscopy was used to observe the microstructure and texture profile analysis was used to determine the texture characteristics of Spirulina platensis residues, rheology was used to determine the key 3D printing factors such as viscosity and modulus of Spirulina platensis residues. More importantly, the printing process could be realized under ambient conditions. The development of microalgae residue ink promoted the high-value and comprehensive utilization of microalgae, and also broadened the application of microalgae in the food field.

Design strategies of Pt-based electrocatalysts and tolerance strategies in fuel cells: a review.

As highly efficient conversion devices, proton-exchange-membrane fuel cells (PEMFCs) can directly convert chemical energy to electrical energy with high efficiencies and lower or even zero emissions compared to combustion engines. However, the practical applications of PEMFCs have been seriously hindered by the intermediates (especially CO) poisoning of anodic Pt catalysts. Hence, how to improve the CO tolerance of the needed Pt catalysts and reveal their anti-CO poisoning mechanism are the key points to developing novel anti-toxic Pt-based electrocatalysts. To date, two main strategies have received increasing attention in improving the CO tolerance of Pt-based electrocatalysts, including alloying Pt with a second element and fabricating composites with geometry and interface engineering. Herein, we will first discuss the latest developments of Pt-based alloys and their anti-CO poisoning mechanism. Subsequently, a detailed description of Pt-based composites with enhanced CO tolerance by utilizing the synergistic effect between Pt and carriers is introduced. Finally, a brief perspective and new insights on the design of Pt-based electrocatalysts to inhibit CO poisoning in PEMFCs are also presented.

Association between dental fluorosis prevalence and inflammation levels in school-aged children with low-to-moderate fluoride exposure.

Inflammation mediates the neurological deficits caused by fluoride. Thus, whether inflammation is the underlying mechanism of dental fluorosis (DF) in school-aged children is worth exploring. A cross-sectional study was conducted to investigate the association between inflammation and the prevalence and severity of DF with low-to-moderate fluoride exposure. Fasting morning urine and venous blood samples were collected from 593 children aged 7-14 years. The fluoride content in the water and urine samples was measured using a fluoride ion-selective electrode assay. The levels of interleukin-1ß (IL-1ß) and C-reactive protein (CRP) were detected using an enzyme-linked immunosorbent assay. The Dean's index was used when performing dental examinations. Regression, stratified, and mediation analyses were performed to analyze the association between fluoride exposure, inflammation, and DF prevalence. In the adjusted regression models, the prevalence of mild DF was 1.723-fold (95% confidence interval [CI]:1.612, 1.841) and 1.594-fold (1.479, 1.717) greater than that of normal DF for each 1 mg/L increase in water and urinary fluoride content, respectively. The prevalence of mild DF increased by 3.3% for each 1 pg/mL increase in the IL-1ß level and by 26.0% for each 1 mg/L increase in the CRP level. Stratified analysis indicated a weaker association between fluoride concentration and DF prevalence in boys than in girls, and susceptibility in the boys was reflected by the association of IL-1ß with very mild and moderate DF prevalence. For every 1 mg/L increase in water and urinary fluoride levels, the proportion of IL-1ß-mediated effects on the prevalence of mild DF was 10.0% (6.1%, 15.8%) and 8.7% (4.8%, 15.2%), respectively, and the proportion of CRP-mediated effects was 9.2% (5.5%, 14.9%) and 6.1% (3.3%, 11.0%), respectively. This study indicates that the DF prevalence may be sex-specific. Inflammatory factors may partially mediate the increased prevalence of mild DF in school-aged children with low-to-moderate fluoride exposure.

An intronic splice-site variant in MBTPS2 underlies ichthyosis follicularis with atrichia and photophobia syndrome.

Ichthyosis follicularis with atrichia and photophobia (IFAP) syndrome is a rare genodermatosis characterized by a classic triad of follicular ichthyosis, alopecia, and photophobia. We report a Chinese patient displaying features of IFAP triad along with painful palmoplantar keratoderma, recurrent infections, periorificial keratotic plaques, nail dystrophy, and pachyonychia. Whole-exome sequencing revealed an intronic variant (NM_015884.3: exon7:c.970+5G>A) in the gene MBTPS2. Sanger sequencing confirmed that the variant segerated with phenotype in the family. Sequencing of cDNAs derived from the patient indicated the variant introduced a new splice donor site, leading to partial skipping of exon 7 (r.951_970del). An in vitro mini-gene assay also revealed abnormal splicing of exon 7. This study presents a case complicated with X-linked IFAP syndrome and Olmsted syndrome, and highlights the significance of using validation assays to identify the pathogenicity of intronic variants in MBTPS2.

Nicotine pretreatment alleviates MK-801-induced behavioral and cognitive deficits in mice by regulating Pdlim5/CRTC1 in the PFC.

Increasing evidence shows that smoking-obtained nicotine is indicated to improve cognition and mitigate certain symptoms of schizophrenia. In this study, we investigated whether chronic nicotine treatment alleviated MK-801-induced schizophrenia-like symptoms and cognitive impairment in mice. Mice were injected with MK-801 (0.2 mg/kg, i.p.), and the behavioral deficits were assessed using prepulse inhibition (PPI) and T-maze tests. We showed that MK-801 caused cognitive impairment accompanied by increased expression of PDZ and LIM domain 5 (Pdlim5), an adaptor protein that is critically associated with schizophrenia, in the prefrontal cortex (PFC). Pretreatment with nicotine (0.2 mg · kg-1 · d-1, s.c., for 2 weeks) significantly ameliorated MK-801-induced schizophrenia-like symptoms and cognitive impairment by reversing the increased Pdlim5 expression levels in the PFC. In addition, pretreatment with nicotine prevented the MK-801-induced decrease in CREB-regulated transcription coactivator 1 (CRTC1), a coactivator of CREB that plays an important role in cognition. Furthermore, MK-801 neither induced schizophrenia-like behaviors nor decreased CRTC1 levels in the PFC of Pdlim5-/- mice. Overexpression of Pdlim5 in the PFC through intra-PFC infusion of an adreno-associated virus AAV-Pdlim5 induced significant schizophrenia-like symptoms and cognitive impairment. In conclusion, chronic nicotine treatment alleviates schizophrenia-induced memory deficits in mice by regulating Pdlim5 and CRTC1 expression in the PFC.

Early hemodynamics after tibial transverse transport in patients with nonarterial stenosis and arterial stenosis diabetic foot.

BACKGROUND: The diagnosis of peripheral arteriopathy in the diabetic foot is complicated by diabetes and its advanced complications. It has been found that diabetic foot can be categorized into arterial stenosis and non-arterial stenosis, both of which have significant differences in hemodynamic characteristics. AIM: To evaluate the early hemodynamic changes in diabetic foot patients with nonarterial stenosis and arterial stenosis treated by tibial transverse transport (TTT) using high-frequency color Doppler ultrasonography (HFCDU) and a laser Doppler flowmeter. METHODS: Twenty-five patients with Wagner grades 3-5 diabetic foot ulcers were treated with TTT, and the wound healing time and rate were recorded. Patients were grouped according to the results of preoperative lower-extremity ultrasonography. Cases with ≥ 50% stenosis in any of the femoral, popliteal, posterior tibial, anterior tibial, and peroneal arteries of the affected limb were classified as the arterial stenosis group (n = 16); otherwise, they were classified as the nonarterial stenosis group (n = 9). Before and one month after surgery, HFCDU was used to evaluate the degree of lower limb artery lesions and hemodynamic changes in patients. The degree of femoral-popliteal atherosclerotic stenosis, the degree of vascular stenosis and occlusion of the lower-knee outflow tract, and the degree of medial arterial calcification were scored; the three scores were added together to obtain the total score of lower extremity arteriopathy. PeriScanPIM3, a laser Doppler flowmeter system, was used to detect alterations in plantar microcirculation before and 1 mo after surgery. Wound healing and hemodynamic indices were compared between the two groups. RESULTS: The wound healing time of the diabetic foot was significantly shorter in the nonarterial stenosis group than in the arterial stenosis group (47.8 ± 13 vs 85.8 ± 26, P < 0.05), and the wound healing rate of both groups was 100%. The preoperative total lower extremity arteriopathy scores were lower in the nonarterial stenosis group than those in the arterial stenosis group (18.89 ± 8.87 vs 24.63 ± 3.52, P < 0.05). The nonarterial stenosis group showed higher preoperative popliteal artery (POA) blood flow than the arterial stenosis group (204.89 ± 80.76 cc/min vs 76.75 ± 48.49 cc/min, P < 0.05). Compared with the baseline (before surgery), the postoperative POA blood flow of the affected limb in the nonarterial stenosis group decreased one month after surgery (134.11 ± 47.84 cc/min vs 204.89 ± 80.76 cc/min, P < 0.05), while that in the arterial stenosis group increased (98.44 ± 30.73 cc/min vs 61.69 ± 21.70 cc/min, P < 0.05). Although the POA blood flow in the arterial stenosis group was obviously improved one month after surgery, it was still lower than that in the nonarterial stenosis group (98.44 ± 30.73 cc/min vs 134.11 ± 47.84 cc/min, P < 0.05). The nonarterial stenosis group had higher preoperative plantar microcirculation than the arterial stenosis group (56.1 ± 9.2 vs 33.2 ± 7.5, P < 0.05); compared with the baseline, the plantar microcirculation in the arterial stenosis group was significantly improved one month after surgery (51.9 ± 7.2, P < 0.05), while that in the nonarterial stenosis group was reduced (35.9 ± 7.2, P < 0.05). CONCLUSION: Based on preoperative HFCDU findings, diabetic foot patients can be divided into two categories: Those with nonarterial stenosis and those with arterial stenosis, with obvious differences in hemodynamic changes in the early postoperative period between them. In the early stage after TTT, the blood flow volume and velocity and the plantar microcirculation perfusion of the affected limb of the diabetic foot with nonarterial stenosis decreased compared with the baseline, while those of the diabetic foot with arterial stenosis improved significantly compared with the baseline, although both had smoothly healed diabetic foot ulcers.

Role of STAT3 and NRF2 in Tumors: Potential Targets for Antitumor Therapy.

Signal transducer and activator of transcription 3 (STAT3) and nuclear factor erythroid-derived 2-like 2 (NRF2, also known as NFE2L2), are two of the most complicated transcription regulators, which participate in a variety of physiological processes. Numerous studies have shown that they are overactivated in multiple types of tumors. Interestingly, STAT3 and NRF2 can also interact with each other to regulate tumor progression. Hence, these two important transcription factors are considered key targets for developing a new class of antitumor drugs. This review summarizes the pivotal roles of the two transcription regulators and their interactions in the tumor microenvironment to identify potential antitumor drug targets and, ultimately, improve patients' health and survival.

Theoretical and experimental study of a highly sensitive SPR biosensor based on Au grating and Au film coupling structure.

A high-sensitivity surface plasmon resonance (SPR) sensor based on the coupling of Au grating and Au film is investigated through simulations and experiments. The SPR sensor is designed by using a hybrid method composed of genetic algorithm (GA) and rigorous coupled wave analysis (RCWA). The numerical results indicate the sensor has an angular sensitivity of 397.3°/RIU (refractive index unit), which is approximately 2.81 times higher than the conventional Au-based sensor and it is verified by experiments. Theoretical analysis, by finite-difference time-domain (FDTD) method, demonstrates the co-coupling between surface plasmon polaritons (SPPs) propagating on the surface of Au film and localized surface plasmons (LSPs) in the Au grating nanostructure, improving the sensitivity of the SPR sensor. According to the optimized structural parameters, the proposed sensor is fabricated using e-beam lithography and magnetron sputtering. In addition, the proposed sensor is very sensitive to the detection of small molecules. The limit of detection (LOD) for okadaic acid (OA) is 0.72 ng/mL based on an indirect competitive inhibition method, which is approximately 38 times lower than the conventional Au sensor. Such a high-sensitivity SPR biosensor has potential in the applications of immunoassays and clinical diagnosis.

Abnormal Properties of Cortical Functional Brain Network in Major Depressive Disorder: Graph Theory Analysis Based on Electroencephalography-Source Estimates.

Studies of scalp electroencephalography (EEG) had shown altered topological organization of functional brain networks in patients with major depressive disorder (MDD). However, most previous EEG-based network analyses were performed at sensor level, while the interpretation of obtained results was not straightforward due to volume conduction effect. To reduce the impact of this defect, the whole cortical functional brain networks of MDD patients were studied during resting state based on EEG-source estimates in this paper. First, scalp EEG signals were recorded from 19 patients with MDD and 20 normal controls under resting eyes-closed state, and cortical neural signals were estimated by using sLORETA method. Then, the correntropy coefficient of wavelet packet coefficients was performed to calculate functional connectivity (FC) matrices in four different frequency bands: δ, θ, α, ß, respectively. Afterwards, topological properties of brain networks were analyzed by graph theory approaches. The results showed that the global FC strength of MDD patients was significantly higher than that of healthy subjects in α band. Also, it was found that MDD patients have abnormally increased clustering coefficient and local efficiency in both α and ß bands compared to normal people. Furthermore, patients with MDD exhibited increased nodal clustering coefficients in the left lingual gryus and left precuneus in α band. In addition, ß band global clustering coefficient was positively correlated with the scores of depression severity. Therefore, the findings indicated the cortical functional brain networks in MDD patients were disruptions, which suggested it would be one of potential causes of depression.

Design of multilayer planar film structures for near-perfect absorption in the visible to near-infrared.

In this work, a near-perfect broadband absorber, consisting of Fe, MgF2, Fe, TiO2 and MgF2 planar film, is proposed and investigated through simulations and experiments. The Fe material is first applied in the multilayer film structure, and it is proved to be more favorable for achieving broadband absorption. MgF2 and TiO2 are chosen as anti-reflection coatings to decrease unwanted reflections. The proposed absorber is optimized by employing a hybrid numerical method combining the transfer matrix method (TMM) and the genetic algorithm (GA). Under normal incidence conditions, the average absorption of the absorber is 97.6% in the range of 400 to 1400 nm. The finite difference time domain (FDTD) method and phase analysis reveal that the anti-reflection property and the Fabry-Perot resonance result in broadband absorption performance. Furthermore, when an additional Fe-MgF2 layer is inserted on the bottom Fe layer, an average absorption of 97.9% in the range of 400 to 2000 nm can be achieved. Our approach could be of vital significance for numerous applications involving solar energy.

Different cellular mechanisms from low- and high-dose zinc oxide nanoparticles-induced heart tube malformation during embryogenesis.

With the wide application of nanometer materials in daily life, people pay more attention to the potential toxicity of nanoparticles to human fetal development once the nanoparticles are absorbed into the human body during pregnancy. However, there was no directly solid evidence for ZnO NPs-caused congenital heart defects. Hence, we investigated the effect of ZnO NPs exposure on early cardiogenesis using the chicken/mouse embryo models. First, we showed ZnO NPs reduced H9c2 cell viability in a dose- and time-dependent manner, while cell autophagy was significantly activated too on the same pattern. During early cardiogenesis, ZnO NPs exposure increased the chance of heart tube malformation, while precardiac cell apoptosis rises in the phenotype of closure defect and Bifida. The hypertrophy was also observed in late-stage chicken/mouse survival embryos exposed to ZnO NPs. Apart from cell apoptosis, high-dose ZnO NPs exposure led to massive programmed necrosis, and further experiments verified that ferroptosis remained primarily in ZnO NPs-induced programmed necrosis. We also revealed that the toxicology of low-dose ZnO NPs was mainly featured in the changes of expressions of key genes instead of causing precardiac cell death. MYL2 and CSRP3 could work as the downstream molecules of the above key genes in the context of ZnO NPs exposure to early cardiogenesis based on RNA sequencing. Taken together, this study for the first time revealed the potential risk of heart tube malformation induced by ZnO NPs exposure through different cellular mechanisms, which depended on low- or high-dose ZnO NPs.