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Background: With the increasing of the global aging population, healthy aging and prevention of age-related diseases have become increasingly important. The liver, a vital organ involved in metabolism, detoxification, digestion, and immunity, holds a pivotal role in the aging process of organisms. Although extensive research on liver aging has been carried out, no bibliometric analysis has been conducted to evaluate the scientific progress in this area., Aim: To analyze basic knowledge, development trends, and current research frontiers in the field via bibliometric methods., Methods: We conducted bibliometric analyses via a range of analytical tools including Python, the bibliometrix package in R, CiteSpace, and VOSviewer. We retrieved publication data on liver aging research from the Web of Science Core Collection Database. A scientific knowledge map was constructed to display the contributions from different authors, journals, countries, institutions, as well as patterns of co-occurrence keywords and co-cited references. Additionally, gene regulation pathways associated with liver aging were analyzed via the STRING database., Results: We identified 4288 articles on liver aging, authored by 24034 contributors from 4092 institutions across 85 countries. Notably, the years 1991 and 2020 presented significant bursts in publication output. The United States led in terms of publications ( n = 1008, 25.1%), citations ( n = 55205), and international collaborations (multiple country publications = 214). Keywords such as "lipid metabolism", "fatty liver disease", "inflammation", "liver fibrosis" and "target" were prominent, highlighting the current research hotspots. Notably, the top 64 genes, each of which appeared in at least 8 articles, were involved in pathways essential for cell survival and aging, including the phosphatidylinositol 3-kinase/protein kinase B, Forkhead box O and p53 signaling pathways., Conclusion: This study highlights key areas of liver aging and offers a comprehensive overview of research trends, as well as insights into potential value for collaborative pursuits and clinical implementations., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Chitin-binding proteins (CBPs) play pivotal roles in numerous biological processes in arthropods, including growth, molting, reproduction, and immune defense. However, their function in the antibacterial immune defense of crustaceans remains relatively underexplored. In this study, twenty CBPs were identified and characterized in Penaeus vannamei. Expression profiling highlighted that the majority of CBPs were highly expressed in the intestine and hepatopancreas and responded to challenge by Vibrio parahaemolyticus. To explore the role of these CBPs in innate immunity, six CBPs (PvPrg4, PvKrtap16, PvPT-1a, PvPT-1b, PvExtensin and PvCP-AM1159) were selected for RNAi experiments. Silencing of only PvPrg4 and PvKrtap16 significantly decreased the cumulative mortality of V. parahaemolyticus-infected shrimp. Further studies demonstrated that inhibition of PvPrg4 and PvKrtap16 resulted in a marked upregulation of genes associated with the NF-κB and JAK-STAT signaling pathways, as well as antimicrobial peptides (AMPs), in both the intestine and hepatopancreas. These results collectively suggested that PvPrg4 and PvKrtap16 potentially promote V. parahaemolyticus invasion by negatively regulating the JAK-STAT and NF-κB pathways, thereby inhibiting the expression of AMPs. In addition, SNP analysis identified three SNPs in the exons of PvPrg4 that were significantly associated with tolerance to V. parahaemolyticus. Taken together, these findings are expected to assist in the molecular marker-assisted breeding of P. vannamei associated with anti-V. parahaemolyticus traits, as well as expand our understanding of CBP functions within the immune regulatory system of crustaceans., Competing Interests: Declaration of competing interest The authors declare no financial and commercial conflicts of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: GlcNAc2-epimerase (GNE) myopathy is a rare autosomal recessive disorder caused by pathogenic variants in the GNE gene, which is essential for the sialic acid biosynthesis pathway., Objective: This multi-centre study aimed to delineate the clinical phenotype and GNE variant spectrum in Chinese patients, enhancing our understanding of the genetic diversity and clinical manifestation across different populations., Methods: We retrospectively analysed GNE variants from 113 patients, integrating these data with external GNE variants from online databases for a global perspective, examining their consequences, distribution, ethnicity and severity., Results: This study revealed 97 distinct GNE variants, including 35 (36.08%) novel variants. Two more patients with deep intronic variant c.862+870C>T were identified, while whole genome sequencing (WGS) uncovered another two novel intronic variants: c.52-8924G>T and c.1505-12G>A. Nanopore long reads sequencing (LRS) and further PCR analysis verified a 639 bp insertion at chr9:36249241. Missense variants predominantly located in the epimerase/kinase domain coding region, indicating the impairment of catalytic function as a key pathogenic consequence. Comparative studies with Japanese, Korean and Jewish, our cohorts showed later onset ages by 2 years. The high allele frequency of the non-catalytic GNE variant, c.620A>T, might underlie the milder phenotype of Chinese patients., Conclusions: Comprehensive techniques such as WGS and Nanopore LRS warrants the identifying of GNE variants. Patients with the non-catalytic GNE variant, c.620A>T, had a milder disease progression and later wheelchair use., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Over the past 20 years, we have designed various types of expanded cervical flaps for large facial defects and achieved excellent tissue matching. This study was performed to propose a treatment strategy for flap selection for the reconstruction of different facial units. The authors retrospectively reviewed the application of cervical expanded flaps for facial rehabilitation in our department between January 2003 and January 2023. The study included 122 patients with unilateral (62.3%) and bilateral (37.7%) facial deformities ranging from the zygomatic arch to the chin. The median area of the tissue defect was 15.2 × 8.5 cm 2 (ranging from 6 × 4 cm 2 to 27 × 12 cm 2 ). The expansion period ranged from 61 to 175 days (mean: 86.5 days). Maximum and minimum sizes of pre-expanded cervical flaps were 30 × 13 cm 2 to 7 × 5 cm 2 . All the flaps could be summarized into type 1, an advanced expanded cervical flap; type 2, a wing-shaped expanded cervical flap with overlapping tissue expansion; and type 3, an expanded single-lobed transposition flap rotated based on the anterior neck. Cervical flaps reliably meet the reconstructive requirements for different facial units, especially for large cutaneous defects in the clinic. The selection of these flaps can be planned preoperatively according to the location and size of the defect or lesion., Competing Interests: None declared., (Thieme. All rights reserved.)

Gestational diabetes mellitus (GDM) with intrauterine hyperglycemia induces a series of changes in the placenta, which have adverse effects on both the mother and the fetus. The aim of this study was to investigate the changes in the placenta in GDM and its gender differences. In this study, we established an intrauterine hyperglycemia model using ICR mice. We collected placental specimens from mice before birth for histological observation, along with tandem mass tag (TMT)-labeled proteomic analysis, which was stratified by sex. When the analysis was not segregated by sex, the GDM group showed 208 upregulated and 225 downregulated proteins in the placenta, primarily within the extracellular matrix and mitochondria. Altered biological processes included cholesterol metabolism and oxidative stress responses. After stratification by sex, the male subgroup showed a heightened tendency for immune-related pathway alterations, whereas the female subgroup manifested changes in branched-chain amino acid metabolism. Our study suggests that the observed sex differences in placental protein expression may explain the differential impact of GDM on offspring.

Aim: To clarify the role of Eomesodermin (EOMES) to serve as a disease-relevant biomarker and the intracellular molecules underlying the immunophenotype shifting of CD4 + T subsets in amyotrophic lateral sclerosis (ALS)., Methods: The derivation and validation cohorts included a total of 148 ALS patients and 101 healthy controls (HCs). Clinical data and peripheral blood were collected. T-cell subsets and the EOMES expression were quantified using multicolor flow cytometry. Serum neurofilament light chain (NFL) was measured. In 1-year longitudinal follow-ups, the ALSFRS-R scores and primary endpoint events were further recorded in the ALS patients of the validation cohort., Results: In the derivation cohort, the CD4 + EOMES + T-cell subsets were significantly increased (p < 0.001). EOMES + subset was positively correlated with increased serum NFL levels in patients with onset longer than 12 months. In the validation cohort, the elevated CD4 + EOMES + T-cell proportions and their association with NFL levels were also identified. The longitudinal study revealed that ALS patients with higher EOMES expression were associated with higher progression rates (p = .010) and worse prognosis (p = .003)., Conclusions: We demonstrated that increased CD4 + EOMES + T-cell subsets in ALS were associated with disease progression and poor prognosis. Identifying these associations may contribute to a better understanding of the immunopathological mechanism of ALS., (© 2023 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Background: Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disorder, characterized by progressive limb weakness, dysphagia, dysphonia, and respiratory failure due to degeneration of upper and lower motor neurons. The pathogenesis of ALS is still unclear. Neuroinflammation has been found to be involved in its development and progression. Cytokines play a significant role in the inflammatory process. This study aims to identify novel biomarkers that may assist in the diagnosis of ALS., Methods: In Fujian Medical University Union Hospital and Huashan Hospital Fudan University, two independent centers, we prospectively recruited 50 ALS patients, and 41 healthy controls (25 ALS and 26 controls in the first stage and 25 ALS and 15 controls in the validation stage). An 18-plex Luminex kit was used to screen the serum cytokines levels in the first stage. Commercial ELISA kits were used to measure the levels of target cytokines in the validation stage. A single-molecule array HD-X platform was applied to assess the levels of serum neurofilament light chain (NFL)., Results: The levels of serum IL-18 were markedly increased in patients with ALS in the first stage ( p = 0.016 ). The ROC curve showed an area under the curve at 0.695 (95% CI 0.50-0.84) in distinguishing ALS patients from healthy controls. The IL-21 was decreased in elderly patients when grouped by 55 years old (the medium age). Furthermore, the IL-5, IL-13, IL-18, and NFL had a positive relationship with the disease progression of ALS. We also found that serum IL-18 was markedly increased in ALS patients in the validation stage (167.67 [148.25-175.59] vs 116.44 [102.43-122.19]pg/ml, p < 0.0015 )., Conclusion: In this study, we identified systemic cytokine profile changes in the serum of ALS patients, especially the elevated IL-18, as well as the decreased IL-21 in elder patients. These changes in serum cytokine profiles may shed new light on an in-depth understanding of the immunopathogenic characteristics of ALS., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Background: The aim of this study was to present the 15-year clinical results using a preexpanded pedicle medial arm flap for repairing massive facial and cervical defects., Methods: The process of our method is divided into 3 stages. In the first stage, the rectangle-shaped tissue expander was implanted subcutaneously in the medial arm region and serially inflated for ~3 months. In the second stage, the distal portion of the flap was to cover the defects, the proximal portion was overlapped with the residual lesion flap. The pedicle was divided 3 weeks later, and the extra tissue was reinserted back to the donor site., Results: A total of 27 patients were retained. All donor sites were closed directly. Maximum and minimum sizes of preexpanded cervical flaps were 2015 cm2 to 5.54 cm2. In 2 cases, partial necrosis occurred at the distal end of the flap, while the remaining flap survived completely. The median duration of follow-up was 7.5 years. During follow-up, 24 patients (88.9%) had satisfactory outcomes and 3 patients (11.1%) had partially satisfactory results., Conclusion: Using expanded pedicle medial arm flap for face or neck defects' reconstruction showed that it was safe and effective, and had satisfying results in the long-term follow-up. The flap based on the proximal pedicle has a more reliable blood supply., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 by Mutaz B. Habal, MD.)

The ATP-binding cassette (ABC) transporters have crucial roles in various biological processes such as growth, development and immune defense in eukaryotes. However, the roles of ABC transporters in the immune system of crustaceans remain elusive. In this study, 38 ABC genes were systematically identified and characterized in Penaeus vannamei. Bioinformation analysis revealed that PvABC genes were categorized into ABC A-H eight subfamilies with 17 full-transporters, 11 half transporters and 10 soluble proteins, and multiple immunity-related cis-elements were found in gene promoter regions. Expression analysis showed that most PvABC genes were widely and highly expressed in immune-related tissues and responded to the stimulation of Vibrio parahaemolyticus. To investigate whether PvABC genes mediated innate immunity, PvABCC5, PvABCF1 and PvABCB4 were selected for dsRNA interference experiment. Knockdown of PvABCF1 and PvABCC5 not PvABCB4 increased the cumulative mortality of P. vannamei and bacterial loads in hepatopancreas after infection with V. parahaemolyticus. Further analysis showed that the PvABCF1 and PvABCC5 knockdown decreased expression levels of NF-κB pathway genes and antimicrobial peptides (AMPs). Collectively, these findings indicated that PvABCF1 and PvABCC5 might restrict V. parahaemolyticus challenge by positively regulating NF-κB pathway and then promoting the expression of AMPs, which would contribute to overall understand the function of ABC genes in innate immunity of invertebrates., Competing Interests: Declaration of competing interest The authors declared no financial and commercial conflicts of interest., (Copyright © 2024. Published by Elsevier B.V.)

Biological soil crusts are of great significance for environment health and sustainable development in arid and semi-arid areas. Cyanobacteria, Microcoleus vaginatus , Scytonema sp., Nostoc sp., and Anabaena sp. are the dominant species in microbial community of biological soil crusts worldwide. Considering their broad application prospect, it is meaningful to cultivate them extensively. We examined the effects of temperature (10, 20, 25, 30, 35 ℃) and initial pH (4, 6, 8, 10, 12) on biomass and solution pH towards the four species of cyanobacteria with liquid culture in laboratory. The results showed that the biomass of the four cyanobacterial species grew slowly under 20 ℃, and that all species could grow in 25-35 ℃, with the highest growth rate at 25 and 30 ℃. The optimum culture temperature of different cyanobacterial species was slightly different. The optimum culture temperature was 25-30 ℃ for Scytonema sp. and Nostoc sp., and 30 ℃ for M. vaginatus and Anabaena sp. The four cyanobacterial species had a strong ability to adjust solution pH and proliferate in five different initial pH conditions. The highest maximum biomass and specific growth rate were recorded in the culture environment with initial pH of 4, while the lowest maximum biomass and specific growth rate were observed in initial pH of 12. Our results would provide scientific basis for the propagation of dominant cyanobacteria in biological soil crusts.

The clinical characteristics, auxiliary examinations, skin and neuropathological features of 7 patients who had reticular cyanosis with peripheral neuropathy from the Department of Neurology, Huashan Hospital, Fudan University from January 2019 to December 2022 were retrospectively analyzed. Among the 7 patients, 5 were female and 2 were male.The age of onset of peripheral neuropathy was (39.8±21.3) years and the disease duration of peripheral neuropathy was (2.7±2.3) years. Three patients had acute onset and 4 patients had chronic onset. All the patients had limb numbness, with limb weakness in 6 patients and pain in 5 cases. Neuroelectrophysiological examination revealed 1 case of mononeuropathy, 2 cases of polyneuropathy, 2 cases of peripheral neuropathy, and 2 cases of sensory neuron neuropathy. Skin biopsy was performed in 3 patients, which presented hyperplasia and expansion of blood vessels in the dermis with lymphocyte infiltration. Nerve biopsy was performed in 3 patients, indicating axonal damage. Reticular cyanosis with peripheral neuropathy characterizes with numbness and weakness of limbs, most of which were accompanied by pain. Electrophysiological changes are in various forms. The pathological changes are dominated by the damage of axonal.

Pre-eclampsia (PE) is a dangerous pathological status that occurs during pregnancy and is a leading reason for both maternal and fetal death. Autophagy is necessary for cellular survival in the face of environmental stress as well as cellular homeostasis and energy management. Aberrant microRNA (miRNA) expression is crucial in the pathophysiology of PE. Although studies have shown that miRNA (miR)-190a-3p function is tissue-specific, the precise involvement of miR-190a-3p in PE has yet to be determined. We discovered that miR-190a-3p was significantly lower and death-associated protein kinase 1 (DAPK1) was significantly higher in PE placental tissues compared to normal tissues, which is consistent with the results in cells. The luciferase analyses demonstrated the target-regulatory relationship between miR-190a-3p and DAPK1. The inhibitory effect of miR-190a-3p on autophagy was reversed by co-transfection of si-DAPK1 and miR-190a-3p inhibitors. Thus, our data indicate that the hypoxia-dependent miR-190a-3p/DAPK1 regulatory pathway is implicated in the development and progression of PE by promoting autophagy in trophoblast cells., (© 2024 Wiley Periodicals LLC.)

Aging is an independent risk factor for chronic diseases in the elderly, and understanding aging mechanisms is one of the keys to achieve early prevention and effective intervention for the diseases. Aging process is dynamic and systemic, making it difficult for mechanistic study. With recent advances in aging biomarkers and development of live-imaging technologies, more and more reporter mouse models have been generated, which can live monitor the aging process, and help investigate aging mechanisms at systemic level and develop intervention strategies. This review summarizes recent advances in live-imaging aging reporter mouse models based on widely used aging biomarkers (p16 Ink4a , p21 Waf1/Cip1 , p53 and Glb1), and discusses their applications in aging research.

Background: Accumulating evidence indicates that type II cystatin (CST) genes play a pivotal role in several tumor pathological processes, thereby affecting all stages of tumorigenesis and tumor development. However, the prognostic and predictive value of type II CST genes in GC has not yet been investigated., Methods: The present study evaluated the expression and prognostic value of type II CST genes in GC by using The Cancer Genome Atlas (TCGA) database and the Kaplan-Meier plotter (KM plotter) online database. The type II CST genes related to the prognosis of GC were then screened out. We then validated the expression and prognostic value of these genes by immunohistochemistry. We also used Database for Annotation, Visualization, and Integrated Discovery (DAVID), Gene Multiple Association Network Integration Algorithm (GeneMANIA), Search Tool for the Retrieval of Interacting Genes/Proteins (STRING), nomogram, genome-wide co-expression analysis, and other bioinformatics tools to analyze the value of type II CST genes in GC and the underlying mechanism., Results: The data from the TCGA database and the KM plotter online database showed that high expression of CST2 and CST4 was associated with the overall survival (OS) of patients with GC. The immunohistochemical expression analysis showed that patients with high expression of CST4 in GC tissues have a shorter OS than those with low expression of CST4 (HR = 1.85,95%CI: 1.13-3.03, P = 0.015). Multivariate Cox regression analysis confirmed that the high expression level of CST4 was an independent prognostic risk factor for OS., Conclusions: Our findings suggest that CST4 could serve as a tumor marker that affects the prognosis of GC and could be considered as a potential therapeutic target for GC., (© 2023. The Author(s).)

Follicle-stimulating hormone (FSH) is involved in mammalian reproduction via binding to FSH receptor (FSHR). However, several studies have found that FSH and FSHR play important roles in extragonadal tissue. Here, we identified the expression of FSHR in human and mouse pancreatic islet β-cells. Blocking FSH signaling by Fshr knock-out led to impaired glucose tolerance owing to decreased insulin secretion, while high FSH levels caused insufficient insulin secretion as well. In vitro, we found that FSH orchestrated glucose-stimulated insulin secretion (GSIS) in a bell curve manner. Mechanistically, FSH primarily activates Gαs via FSHR, promoting the cAMP/protein kinase A (PKA) and calcium pathways to stimulate GSIS, whereas high FSH levels could activate Gαi to inhibit the cAMP/PKA pathway and the amplified effect on GSIS. Our results reveal the role of FSH in regulating pancreatic islet insulin secretion and provide avenues for future clinical investigation and therapeutic strategies for postmenopausal diabetes., (© 2023. The Author(s).)

Objective: To investigate the association of isolated thyroid peroxidase antibody (TPOAb) positive in the first trimester with fetal growth., Methods: A total of 16 446 pregnant women were included in the birth cohort study, whose last menstrual period was between May 2016 and April 2019 and with singleton pregnancy. Maternal serum samples were collected when they firstly came for prenatal care in the first trimester. The pregnant women were consecutively seen and followed in the hospital and the information of pregnant women was extracted from the electronic medical information system. The pregnant women were divided into isolated TPOAb positive group ( n =1 654) and euthyroid group ( n =14 792). Three fetal ultrasound examinations were scheduled during the routine prenatal visits at the hospital and were performed by trained sonographers. All fetal growth indicators were quantified as gestational age- and gender- adjusted standard deviation score (Z-score) using the generalized additive models for location, scale and shape (GAMLSS). Fetal growth indicators included estimated fetal weight (EFW), abdominal circumference (AC), biparietal diameter (BPD), femur length (FL) and head circumference (HC). Fetal growth restriction (FGR) was defined as AC or EFW Z-score＜3rd centile based on clinical consensus. Generalized estimating equation (GEE) analysis was applied to assess the association of maternal isolated TPOAb positive with fetal growth. The generalized linear model was further used to analyze the association between isolated TPOAb positive and fetal growth indicator at different gestational ages when the fetal growth indicator was significantly associated with isolated TPOAb positive in the GEE mo-del., Results: The median gestational age at three ultrasound measurements was 23.6 (23.3, 24.1), 30.3 (29.7, 30.9), 37.3 (37.0, 37.7) weeks, respectively. The BPD Z-score was higher in isolated TPOAb positive women, compared with the euthyroid pregnant women after adjustment ( β =0.057, 95% CI : 0.014-0.100, P =0.009). The generalized linear model showed the BPD Z-score was higher in the isolated TPOAb positive women at the end of 21-25 weeks ( β =0.052, 95% CI : 0.001-0.103, P =0.044), 29-32 weeks ( β =0.055, 95% CI : 0.004-0.107, P =0.035) and 36-40 weeks ( β =0.068, 95% CI : 0.011-0.125, P =0.020), compared with the euthyroid pregnant women. There was no difference in other fetal growth indicators (EFW, AC, FL and HC) and FGR between the isolated TPOAb positive and euthyroid pregnant women., Conclusion: The BPD Z-score was slightly increased in the isolated TPOAb positive pregnant women in the first trimester, while other fetal growth indicators were not changed. The reproducibility and practical significance of this result need to be confirmed.

Purpose: The aim of this review was to summarize sex differences in glycolipid metabolic phenotypes of human and animal models after exposure to maternal hyperglycemia and overview the underlying mechanisms, providing a new perspective on the maternal hyperglycemia-triggered risk of glycolipidic disorders in offspring., Methods: A comprehensive literature search within PubMed was performed. Selected publications related to studies on offspring exposed to maternal hyperglycemia investigating the sex differences of glycolipid metabolism were reviewed., Results: Maternal hyperglycemia increases the risk of glycolipid metabolic disorders in offspring, such as obesity, glucose intolerance and diabetes. Whether with or without intervention, metabolic phenotypes have been shown to exhibit sex differences between male and female offspring in response to maternal hyperglycemia, which may be related to gonadal hormones, organic intrinsic differences, placenta, and epigenetic modifications., Conclusion: Sex may play a role in the different incidences and pathogenesis of abnormal glycolipid metabolism. More studies investigating both sexes are needed to understand how and why environmental conditions in early life affect long-term health between male and female individuals., (© 2023. The Author(s), under exclusive licence to Italian Society of Endocrinology (SIE).)

Objective: To summarize the best evidence on exercise for the prevention and treatment of diabetic foot. Methods: A bibliometric approach was used. Systematic searches were carried out to retrieve all the publicly published evidences till July 2022 on exercise for the prevention and treatment of diabetic foot, including guidelines, evidence summary, recommended practices, expert consensus, systematic review, and original research, from foreign language databases including BMJ Best Practice, UpToDate, Joanna Briggs Institute Evidence-Based Practice Database, Cochrane Library, Embase, PubMed, Guideline International Network, National Guideline Clearinghouse, Chinese databases including China National Knowledge Infrastructure, Wanfang Database, VIP Database, China Biology Medicine disc, China Clinical Guidelines Library, and the official websites of relevant academic organizations including National Institute for Health and Care Excellence of the United Kingdom, Registered Nurses' Association of Ontario of Canada, the International Working Group on the Diabetic Foot, International Diabetes Federation, American College of Sports Medicine, American Diabetes Association, and Chinese Diabetes Society. The literature was screened and evaluated for the quality, from which the evidences were extracted and evaluated to summarize the best evidences. Results: Nine guidelines, three expert consensuses, one evidence summary (with two systematic reviews being traced), two systematic reviews, 6 randomized controlled trials were retrieved and included, with good quality of literature. Totally 33 pieces of best evidences on exercise for the prevention and treatment of diabetic foot were summarized from the aspects of appropriate exercise prevention of diabetic foot, exercise therapy of diabetic foot, precautions for exercise, health education, and establishment of a multidisciplinary limb salvage team. Conclusions: Totally 33 pieces of best evidences on exercise for the prevention and treatment of diabetic foot were summarized from 5 aspects, providing decision-making basis for clinical guidance on exercise practice for patients with diabetic foot.

Background: Traumatic injury or tumor resection can lead to eyelid defects, nasal defects, and cheek defects. The temporal flap pedicled with orbicularis oculi muscle (OOM) can be used to repair these defects. This cadaver-based anatomic study aimed to evaluate the blood supply of this flap and investigate its clinical implications., Methods: Twenty hemifaces from 10 cadavers were used in this study. The number of arteries supplying OOM of the flap, the diameter of the artery entering OOM, and the maximum width of OOM were recorded. All data were presented as mean±SD values and analyzed using Student t -test. A P value<0.05 was considered statistically significant., Results: Of these 10 specimens, 7 were males and 3 were females. The average age was 67.7 years (range, 53-78 y). The number of arteries supplying OOM was 8.5±1.4 in the male and 7.8±1.2 in the female. The diameter of the zygomatico-orbital artery was detected as 0.53±0.06 mm in the male and 0.40±0.11 mm in the female. The maximum width of OOM was detected as 2.5±0.1 cm in the male and 2.2±0.1 cm in the female. Males had significantly larger average values than females in the diameter of zygomatico-orbital artery and maximum width of OOM ( P =0.012, P <0.001, respectively). However, the number of arteries supplying OOM did not differ significantly between sex ( P =0.322)., Conclusions: We conclude that the blood supply of the temporal flap pedicled with OOM is abundant and reliable. The findings provide surgeons with valuable anatomic knowledge for repairing facial defects with this flap., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 by Mutaz B. Habal, MD.)

Background: Extensive facial burn scars are a tragedy for patients and often pose a great challenge to surgeons because of the high esthetic and functional demands. For patients with healthy skin in the neck region, a cervical flap is highly recommended for facial resurfacing; however, the skin on the midline of the neck often needs more expansion than that on either side, especially for the treatment of large facial defects. The sufficient longitudinal soft tissue in the anterior neck ensures a normal neck shape as well as a normal range of cervical extension, rotation, and lateral flexion. To overcome this, we developed an expanded cervical flap with an overlapping tissue expansion technique to gain more length centrally., Methods: First, 2 tissue expanders were embedded in the anterior neck region overlapping each other at the midline of the neck. After adequate inflation of the expander, the expanded flap was dissected and rotated to repair defects in the middle and lower face. The anchor position of the flap was placed on the horizontal line of the thyroid cartilage to restore the cervicomental angle., Results: Sixteen patients were treated with this method in this single-center study. All defects affected the middle and lower face, with an area ranging from 135 to 185 cm 2 , and were caused by a massive facial burn. Among them, 12 patients suffered ectropion of the lower lip, 3 suffered limited mouth opening due to scar contraction, and one patient had a cervicomental adhesion. The area of the expanded flap was approximately 163 to 266 cm 2 . The average period of expansion was 89.5 days. Patients were followed up after the operation, with the follow-up period ranging from 6 to 12 months. In all cases, good defect coverage was achieved, with primary closure of the donor sites and a good postoperative cervical configuration., Conclusion: We conclude that the expanded cervical flap with the overlapping tissue expansion technique proved to be a reliable method for facial skin reconstruction with functional and aesthetic improvement., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 by Mutaz B. Habal, MD.)

In order to explore the impact of antibiotics (enrofloxacin) on microbial community in aquatic environment, an indoor aquatic ecological model was built, and different concentrations of enrofloxacin (0.05, 0.5, 5, and 50 mg/L) were added in the aquatic ecological model. In addition, the water and sediment samples were collected on the 0, 7, 30, and 60 days, and the changes in microbial community were studied through 16S rDNA high-throughput sequencing. The results showed that when the concentration of enrofloxacin was 50 mg/L, the relative abundance of Actinomycetes was increased. In the water, the bacterial richness and diversity communities first decreased and then gradually recovered with the passage of time; On the 7th day, the diversity and richness index of species in the treatment groups with enrofloxacin at 5 and 50 mg/L decreased to the lowest; On the 30th day, the diversity and richness index of species began to rise; On the 60th day, the diversity index and richness index of water species began to increase, while the diversity index and richness index of sediment species decreased. In conclusion, the addition of enrofloxacin negatively affected the microbial community structure in an indoor aquatic ecological model, 50 mg/L enrofloxacin could increase the relative abundance of Actinomycetes, and decrease the diversity and richness index of water and sediment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Dai, Peng, Zhang, Xie, Luo, Liu and Ma.)

Background: The safety of COVID-19 vaccines has been clarified in clinical trials; however, some immunocompromised patients, such as myasthenia gravis (MG) patients, are still hesitant to receive vaccines. Whether COVID-19 vaccination increases the risk of disease worsening in these patients remains unknown. This study aims to evaluate the risk of disease exacerbation in COVID-19-vaccinated MG patients., Methods: The data in this study were collected from the MG database at Tangdu Hospital, the Fourth Military Medical University, and the Tertiary Referral Diagnostic Center at Huashan Hospital, Fudan University, from 1 April 2022 to 31 October 2022. A self-controlled case series method was applied, and the incidence rate ratios were calculated in the prespecified risk period using conditional Poisson regression., Results: Inactivated COVID-19 vaccines did not increase the risk of disease exacerbation in MG patients with stable disease status. A few patients experienced transient disease worsening, but the symptoms were mild. It is noted that more attention should be paid to thymoma-related MG, especially within 1 week after COVID-19 vaccination., Conclusion: COVID-19 vaccination has no long-term impact on MG relapse., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Ruan, Huan, Su, Tang, Meng, Ren, Li, Hao, Zhao, Luo, Li and Chang.)

Myocardial infarction (MI) is one of the diseases with high fatality rate. Berberine (BBR) is a monomer compound with various biological functions. And some studies have confirmed that BBR plays an important role in alleviating cardiomyocyte injury after MI. However, the specific mechanism is unclear. In this study, we induced a model of MI by ligation of the left anterior descending coronary artery and we surprisingly found that BBR significantly improved ventricular remodeling, with a minor inflammatory and oxidative stress injury, and stronger angiogenesis. Moreover, BBR inhibited the secretion of Wnt5a/β-catenin pathway in macrophages after MI, thus promoting the differentiation of macrophages into M2 type. In summary, BBR effectively improved cardiac function of mice after MI, and the potential protective mechanism was associated with the regulation of inflammatory responses and the inhibition of macrophage Wnt5a/β-catenin pathway in the infarcted heart tissues. Importantly, these findings supported BBR as an effective cardioprotective drug after MI., (© 2022 The Authors. Phytotherapy Research published by John Wiley & Sons Ltd.)

Purpose: Although physical exercise may improve memory in older adults, whether the Chinese traditional fitness exercise Wuqinxi improves working memory and delays cognitive deterioration in older adults with mild cognitive impairment (MCI) has not been assessed in randomized controlled experiments., Methods: Fifty older adults with MCI based on their Montreal Cognitive Assessment scores were randomized to either a Wuqinxi exercise group or a non-exercise control group. The exercise group engaged in Wuqinxi once a week for 60 min each session for 40 weeks. Participants in the control group received no intervention and maintained their regular living habits. The n-back paradigm was used to measure changes in working memory before and after Wuqinxi exercise., Results: In the 0-back task, the response speed of older adults with MCI who participated in Wuqinxi was faster than that of older adults with MCI in the non-exercise control group (P = 0.031); there was no significant difference in accuracy between the two groups (P > 0.05). In the 1-back and 2-back tasks, there was no significant difference in response times or in accuracy between the two groups (P > 0.05)., Conclusions: In this randomized controlled study, participation in long-term Wuqinxi delayed the deterioration of working memory in older adults with MCI, suggesting that this exercise may be an effective intervention to delay or prevent the progression of MCI to Alzheimer's disease., (© 2022. The Author(s), under exclusive licence to European Geriatric Medicine Society.)

Previous programmable metasurfaces integrated with diodes or varactors require external instructions for field programmable gate arrays (FPGAs), which usually rely on computer-inputs or pre-loaded algorithms. But the complicated external devices make the coding regulation process of the programmable metasurfaces cumbersome and difficult to use. To simplify the process and provide a new interaction manner, a touch-programmable metasurface (TPM) based on touch sensing modules is proposed to realize various electromagnetic (EM) manipulations and encryptions. By simply touching the meta-units of the TPM, the state of the diodes can be changed. Through the touch controls, the TPM can achieve independent and direct manipulations of meta-units and efficient inputs of coding patterns without using a FPGA or other control modules. Various coding patterns are demonstrated to achieve diverse scattering-field control and flexible near-field EM information encryptions, which verifies the feasibility of the TPM design. The presented TPM will have wide application prospects in imaging displays, wireless communications, and EM information encryptions., (© 2022 Wiley-VCH GmbH.)

Objective: Reconstruction of facial soft-tissue defects may pose a dilemma for plastic surgeons, as the flaps must be reliable to obtain a natural appearance while minimizing donor site morbidities. This clinical study describes a reconstructive method for infraorbital and zygomatic defects using a pre-expanded rotation flap based on the orbicularis oculi muscle (OOM)., Methods: The surgeries were subdivided into 2 stages. In the first stage of the operation, a 100 to 200 mL expander was placed underneath the temporal area through a hairline incision. In the second stage, after adequate inflation of the expander, the pre-expanded rotation flap based on the OOM of the lower eyelid was raised from lateral to medial to cover the facial defects., Results: In this single-center study from February 2010 to February 2017, 16 patients underwent facial defect reconstruction using the pre-expanded flap based on the OOM. All of the defects were located at the infraorbital and zygomatic regions, and their sizes ranged from 3.0   4.0 to 7.0   14.0 cm. The causes of these defects included postburn scars (37.5%), melanocytic nevus (50%), and hemangiomas (12.5%). In all cases, good coverage was provided for the defects that were in the medial cheek or lower eyelids. There were no flap losses of any kind. There were no major complications, and all minor incidences were treated by minimal procedures. The patients were followed up after surgery, with the follow up ranging from 6 months to 108 months. The follow-up data included postoperative consultations, the defect size, the need for further procedures and the degree of satisfaction., Conclusion: The pre-expanded rotation flaps in the lateral facial area based on the OOM can ideally and safely be applied for facial defect reconstruction owing to their reliable blood supply and excellent texture match., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 by Mutaz B. Habal, MD.)

We report the discovery of superconductivity in non-centrosymmetric compounds HfNiAl, ZrNiAl, ZrNiGa, and HfPtAl by measuring their electrical transport and thermodynamic properties. HfNiAl, ZrNiAl, and ZrNiGa crystallize in the ZrNiAl-type crystal structure, whereas HfPtAl crystallizes in the HfRhSn-type crystal structure. Superconducting transitions for HfNiAl, ZrNiAl, ZrNiGa, and HfPtAl are observed at 1.0 K, 1.0 K, 0.42 K, and 0.58 K, respectively. Using the Werthamer-Helfand-Hohenberg model, the zero-temperature upper critical fields µ 0 Hc2(0) were estimated to be 0.58 T, 0.24 T, 0.08 T, and 0.34 T for HfNiAl, ZrNiAl, ZrNiGa, and HfPtAl, respectively. The observed jump in electronic heat capacity (ΔCe/γT) across the superconducting transition is 1.3, 1.3, and 1.2 for HfNiAl, ZrNiAl, and HfPtAl, respectively. After the inclusion of the spin-orbit coupling in the band structure calculations, a total of six bands for ZrNiAl, HfPtAl, and ZrNiGa, and eight bands for HfNiAl were found to cross the Fermi level. Spin-orbit coupling induced maximum splitting (ΔEASOC/ k B T c ) of the electronic bands near the Fermi level was found to be 1697, 517, 1138, and 4230 for HfNiAl, ZrNiAl, ZrNiGa, and HfPtAl, respectively. Large variation of the antisymmetric spin-orbit coupling (ASOC) among these compounds provides a great opportunity to study the effects of ASOC on the superconducting pairing states., (© 2022 IOP Publishing Ltd.)

Introduction: Phospholipase A2 Group VI (PLA2G6), encoding calcium-independent phospholipase A 2 , has been isolated as the gene responsible for an autosomal recessive form of early-onset Parkinson's disease (namely, PARK14). Compared to idiopathic Parkinson's disease (iPD), PARK14 has several atypical clinical features. PARK14 has an earlier age at onset and is more likely to develop levodopa-induced dyskinesia. In iPD, serum metabolomics has observed alterations in several metabolic pathways that are related to disease status and clinical manifestations. This study aims to describe the serum metabolomics features of patients with PARK14., Design: This case-control biomarker study tested nine patients diagnosed with PARK14. Eight age and sex-matched healthy subjects were recruited as controls. To evaluate the influence of single heterozygous mutation, we enrolled eight healthy one-degree family members of patients with PARK14, two patients diagnosed with early-onset Parkinson's disease (EOPD) who had only a single heterozygous PLA2G6 mutation, and one patient with EOPD without any known pathogenic mutation., Methods: The diagnosis of PARK14 was made according to the diagnostic criteria for Parkinson's disease (PD) and confirmed by genetic testing. To study the serum metabolic features, we analyzed participants' serum using UHPLC-QTOF/MS analysis, a well-established technology., Results: We quantified 50 compounds of metabolites from the serum of all the study subjects. Metabolites alterations in serum had good predictive accuracy for PARK14 diagnosis (AUC 0.903) and advanced stage in PARK14 (AUC 0.944). Of the 24 metabolites that changed significantly in patients' serum, eight related to lipid metabolism. Oleic acid and xanthine were associated with MMSE scores. Xanthine, L-histidine, and phenol correlated with UPDRS-III scores. Oleic acid and 1-oleoyl-L-alpha-lysophosphatidic acid could also predict the subclass of the more advanced stage in the PLA2G6 Group in ROC models., Conclusion: The significantly altered metabolites can be used to differentiate PLA2G6 pathogenic mutations and predict disease severity. Patients with PLA2G6 mutations had elevated lipid compounds in C18:1 and C16:0 groups. The alteration of lipid metabolism might be the key intermediate process in PLA2G6-related disease that needs further investigation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Chen, Lou, Sun, Luo, Liu, Luo, Wang and Wang.)

Contaminants such as heavy metals in rivers are partially retained in the sediments at the bottom as a result of the altered water regime within the cascade weirs. The associated heavy metals in the sediments can affect surface water quality and ecology for a long period. In May 2020, sediments were collected in a typical mountainous river (Liangtan River) with cascade weirs in the main urban area of Chongqing. The accumulation of sediments in each river section, the content of heavy metals, and other basic physicochemical indicators in the samples were monitored. The results showed that the average ω (As), ω (Cd), ω (Cu), ω (Hg), ω (Ni), and ω (Pb) in the sediments of the main stream of Liangtan River were (4.66±4.78), (0.361±0.256), (32.30±14.38), (0.069±0.039), (33.47±15.37), and (26.34±11.52) mg·kg -1 , respectively. A large coefficient of spatial variation regarding the content of heavy metals in the sediments across the sampling sites was observed owing to the uneven spatial distribution of pollution sources and the destruction of river connectivity by cascade weirs. The modified geoaccumulation index ( I m ) showed that Cd was the most polluted heavy metal element in the sediments. Of the monitored river sections, 12.50% approached or were at moderate pollution levels, and these sections were mainly found in the upstream and downstream reaches of Liangtan River with relatively concentrated construction lands. The potential ecological risk assessment index method (RI) and the sediment quality guideline method (SQGs) showed that, in addition to Cd and Hg with a high pollution level and strong toxicity, Ni in the sediments also posed a potential threat to the ecological safety of surface water due to its high background content in the watershed. The total amounts of As, Cd, Cu, Hg, Ni, and Pb retained in the sediments by cascade weirs were estimated to be 446.10, 47.28, 4997.80, 10.81, 5135.68, and 4048.16 kg, respectively, in which Cd, Ni, and Pb were identified to be the major threats to the ecological safety of surface water over a long period. The upper reaches prior to the weirs with the most retained heavy metals and the easier formation of an anaerobic environment are suggested to be the key areas for investigation of the endogenous release of heavy metals. Source apportionment of heavy metals in river sediments through the combination of principal component analysis and cluster analysis revealed that Cd, Cu, and Pb mainly originated from residential/industrial point source pollution. Hg mainly originated from agricultural non-point source pollution, whereas As and Ni mainly originated from natural soil erosion.

The aim of the study was to investigate the clinical effects of abdominal massage on patients with type 2 diabetes mellitus (T2DM) and its influence on the intestinal microflora. We conducted a randomized, controlled clinical trial. A total of 60 patients with T2DM, who met the inclusion criteria, were randomly allocated to the control group, the routine massage group, and the abdominal massage group. The control group received health education and maintained their hypoglycemic drug treatment plan. The routine massage group and the abdominal massage group received different massage interventions. In addition to glucose and lipid metabolism indicators, we quantitatively analyzed the gut microbiota to assess the effects of massage on the intestinal microflora of patients with T2DM. Compared with the control group, the abdominal massage improved levels of glycated hemoglobin, total cholesterol, Enterobacter, and Bifidobacteria with significant differences ( P = 0.02, P = 0.03, P = 0.03, and P = 0.03). The comparison within group showed that the levels of the four bacterial genera in the abdominal massage group revealed significant differences before and after treatment ( P = 0.006, P < 0.001, P < 0.001, and P = 0.002). The comparison between the routine massage group and the abdominal massage group was not significantly different in all levels of test indices. The abdominal massage group regulated levels of Enterobacter and Lactobacilli to a greater extent than the routine massage group. Additionally, abdominal massage decreased Enterococcus levels. The results of this study showed that abdominal massage has clinical advantages over routine massage. Specifically, this intervention may correct microflora disturbances to a certain extent., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Ying Xie et al.)

Cancer is caused by the abnormal proliferation of local tissue cells under the control of many oncogenic factors. MicroRNAs (miRNAs) are a class of evolutionarily conserved, approximately 22-nucleotide noncoding small RNAs that influence transcriptional regulationby binding to the 3'-untranslated region of target messenger RNA. As a member of the miRNA family, miR-141 acts as a suppressor or an oncomiR in various cancers and regulates cancer cell proliferation, apoptosis, invasion, and metastasis through a variety of signaling pathways, such as phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT) and constitutive activation of nuclear factor-κB (NF-κB). Target gene validation and pathway analysis have provided mechanistic insight into the role of this miRNA in different tissues. This review also outlines novel findings that suggest miR-141 may be useful as a noninvasive biomarker and as a therapeutic target in several cancers., (Copyright © 2022 Elsevier Inc. All rights reserved.)

A few long noncoding RNAs (long ncRNAs, lncRNAs) exhibit trophoblast cell type-specific expression patterns and functional roles in mouse placenta. However, the cell- and stage-specific expression patterns and functions of most placenta-derived lncRNAs remain unclear. In this study, we explored mouse placenta-associated lncRNAs using a combined bioinformatic and experimental approach. We used the FANTOM5 database to survey lncRNA expression in mouse placenta and found that 1600012P17Rik (MGI: 1919275, designated P17Rik), a long intergenic ncRNA, was the most highly expressed lncRNA at gestational day 17. Polymerase chain reaction analysis confirmed that P17Rik was exclusively expressed in placenta and not in any of the adult organs examined in this study. In situ hybridization analysis revealed that it was highly expressed in spongiotrophoblast cells and to a lesser extent in glycogen trophoblast cells, including migratory glycogen trophoblast cells invading the decidua. Moreover, we found that it is a polyadenylated lncRNA localized mainly to the cytoplasm of these trophoblast cells. As these trophoblast cells also expressed the neighboring protein-coding gene, pappalysin 2 (Pappa2), we investigated the effects of P17Rik on Pappa2 expression using Pappa2-expressing MC3T3-E1 cells and found that P17Rik transfection increased the messenger RNA (mRNA) and protein levels of Pappa2. These results indicate that mouse placenta-specific lncRNA P17Rik modulates the expression of the neighboring protein-coding gene Pappa2 in spongiotrophoblast and glycogen trophoblast cells of mouse placenta during late gestation., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Skeletal muscle myogenesis and injury-induced muscle regeneration contribute to muscle formation. Skeletal muscle stem cells, termed satellite cells (SCs), proliferate to repair injured muscle. To identify the molecular mechanism of regeneration after muscle injury as well as the genes related to muscle development in fish, in this study, the immunohistochemistry and the high-throughput RNA sequencing (RNA-seq) analysis were performed after Megalobrama amblycephala muscle was injured by needle stab. The results showed that paired box7-positive (Pax7 + ) SCs increased, and peaked at 96 to 144 h-post injury (hpi). The 6729 differentially expressed genes (DEGs), including 2125 up-regulated and 4604 down-regulated genes were found. GO terms significantly enriched by DEGs contained intercellular connections, signaling transduction and enzyme activity. KEGG enrichment analysis showed that most of the pathways were related to immunity, metabolism and cells related molecules, including actin skeleton regulation, Epstein Barr virus infection and plaque adhesion. The WGCNA results revealed that actin cytoskeleton and lipid metabolism related genes probably played crucial roles during repair after muscle injury. Collectively, all these results will provide new insights into the molecular mechanisms underlying muscle injury repair of fish., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Nuclear receptors (NRs) are a class of transcription factors that play a pivotal role in carcinogenesis, but their function in colorectal cancer (CRC) remains unclear. Here, we investigate the role NRs play in CRC pathogenesis. We found that hepatocyte nuclear factor 4 gamma (HNF4G; NR2A2), hepatocyte nuclear factor 4α (HNF4A; NR2A1), and retinoid-related orphan receptor γ (RORC; NR1F3) were significantly upregulated in CRC tissues analyzed by GEPIA bioinformatics tool. The expression of HNF4G was examined in CRC samples and cell lines by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry. Increased expression of HNF4G was strongly associated with high tumor-node-metastasis stage and poor prognosis. Moreover, overexpression of HNF4G significantly promoted the proliferation of CRC cells in vitro. Next, we found that HNF4G promoted CRC proliferation via the PI3K/AKT pathway through targeting of GNG12 and PTK2. In addition, HNF4G was verified as a direct target of microRNA-766-3p (miR-766-3p). miR-766-3p inhibited the proliferation of CRC cells by targeting HNF4G in vitro and in vivo. Collectively, our study indicates that miR-766-3p reduces the proliferation of CRC cells by targeting HNF4G expression and thus inhibits the PI3K/AKT pathway. Therefore, development of therapies which target the miR-766-3p/HNF4G axis may aid in the treatment of CRC., (© 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Combining digital information science with metasurface technology is critical for achieving arbitrary electromagnetic wave manipulation. However, there is a scarcity of contemporary scholarly studies on this subject. In this paper, we propose an Ultraviolet (UV) sensing metasurface for programmable electromagnetic scattering field manipulation by combining light control with a microwave field. The active sensing of UV light and the real-time reaction of the scattering are achieved by integrating four UV sensors on the metasurface. On the metasurface, a UV sensor ML8511 and a voltage driver module are coupled to control each row of the Positive-Intrinsic-Negative (PIN) diodes. Due to the light sensing capability of the UV sensor, the on or off state of the PIN diode integrated into the programmable metasurface can be switched efficiently through the change of light. When the incident wave changes, various discrete data are transmitted to the FPGA. Then the FPGA performs the corresponding voltage distribution to control the state of the PIN diode. Finally, different metasurface coding sequences are generated to realize different electromagnetic functions. As a result, the spatial distribution of sensing light by sensors can be used to determine the electromagnetic field and connect sensing optical information with the microwave field. The simulation and measured results show that this design is feasible. This work provides a dimension for electromagnetic waves modulation.

Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by the production of a diverse array of autoantibodies and the dysfunctional activation of the complement system. The specific association between the complement component C3a (C3a) protein and antibodies specific for double-stranded DNA (anti-dsDNA), however, has not been studied in detail to date. This study was thus designed to more fully explore circulating C3a levels in SLE patients. In total, 13 SLE patients were enrolled in this study after having been diagnosed in accordance with the SLICC classification criteria, with 7 and 6 patients respectively exhibiting positivity for anti-dsDNA and anti-Sm autoantibodies. Serum complement component C1q (C1q) and C3a levels in samples from these patients were detected via Western blotting, while other serological, biochemical, and clinical parkers associated with disease activity were detected using standard laboratory techniques. The levels of serum C3a in anti-dsDNA+ patients were significantly elevated as compared to those in anti-Sm+ patients (P < 0.01), and a positive correlation between serum C3a levels and SLE Disease Activity Index scores was detected (P < 0.05, r = 0.6134). C3a levels are correlated with the degree of SLE disease activity and other clinically relevant readouts in SLE patients. C3a levels may also enable the differentiation between inactive and active SLE, while also offering value as an advantageous biomarker for thrombophilia monitoring in SLE patients., (© 2022. The Author(s).)

Cardiac fibrosis (CF) is an irreversible pathological process that occurs in almost all kinds of cardiovascular diseases. Phosphorylation-dependent activation of c-Jun N-terminal kinase (JNK) induces cardiac fibrosis. However, whether S-nitrosylation of JNK mediates cardiac fibrosis remains an open question. A biotin-switch assay confirmed that S-nitrosylation of JNK (SNO-JNK) increased significantly in the heart tissues of hypertrophic patients, transverse aortic constriction (TAC) mice, spontaneously hypertensive rats (SHRs), and neonatal rat cardiac fibroblasts (NRCFs) stimulated with angiotensin II (Ang II). Site to site substitution of alanine for cysteine in JNK was applied to determine the S-nitrosylated site. S-Nitrosylation occurred at both Cys116 and Cys163 and substitution of alanine for cysteine 116 and cysteine 163 (C116/163A) inhibited Ang II-induced myofibroblast transformation. We further confirmed that the source of S-nitrosylation was inducible nitric oxide synthase (iNOS). 1400 W, an inhibitor of iNOS, abrogated the profibrotic effects of Ang II in NRCFs. Mechanistically, SNO-JNK facilitated the nuclear translocation of JNK, increased the phosphorylation of c-Jun, and induced the transcriptional activity of AP-1 as determined by chromatin immunoprecipitation and EMSA. Finally, WT and iNOS -/- mice were subjected to TAC and iNOS knockout reduced SNO-JNK and alleviated cardiac fibrosis. Our findings demonstrate an alternative mechanism by which iNOS-induced SNO-JNK increases JNK pathway activity and accelerates cardiac fibrosis. Targeting SNO-JNK might be a novel therapeutic strategy against cardiac fibrosis., (© 2021. The Author(s), under exclusive licence to CPS and SIMM.)

Nitrite stress is a major environmental factor that limits aquatic animal growth, reproduction and survival. Even so, some shrimps still can withstand somewhat high concentrations of nitrite environment. However, few studies have been conducted about the tolerance molecular mechanism of Litopenaeus vannamei in the high concentration nitrite. To identify the genes and pathways involved in the regulation of nitrite tolerance, we performed comparative transcriptomic analysis in the L. vannamei nitrite-tolerant (NT) and nitrite-sensitive (NS) families, and untreated shrimps were used as the control group. After 24 h of nitrite exposure (NaNO 2 , 112.5 mg/L), a total of 1521 and 868 differentially expressed genes (DEGs) were obtained from NT compared with NS and control group, respectively. Functional enrichment analysis revealed that most of these DEGs were involved in immune defense, energy metabolism processes and endoplasmic reticulum (ER) stress. During nitrite stress, energy metabolism in NT was significantly enhanced by activating the related genes expression of oxidative phosphorylation (OXPHOS) pathway and tricarboxylic acid (TCA) cycle. Meanwhile, some DEGs involved in innate immunity- related genes and pathways, and ER stress responses also were highly expressed in NT. Therefore, we speculate that accelerated energy metabolism, higher expression of immunity and ER related genes might be the important adaptive strategies for NT in relative to NS under nitrite stress. These results will provide new insights on the potential tolerant molecular mechanisms and the breeding of new varieties of nitrite tolerant L. vannamei., (Copyright © 2021. Published by Elsevier Inc.)

Rationale: Aphallia is an extremely rare congenital malformation of unknown cause, with few reports in the literature. It is usually associated with other urogenital and gastrointestinal anomalies and is believed to be a result of either the absence of a genital tubercle or chromosome polymorphism. Herein, we describe an extremely rare case of congenital aphallia with congenital urethrorectal fistula and describe our treatment for this patient., Patient Concerns: An 8-year-old boy was brought to our hospital by his parents because of congenital absence of the penis. The child was male per karyotype and had excess heterochromatin on chromosome 9 (46 XY with 9 qh+). No urethral orifice was identified, and urine passed rectally since birth; thus, urinary tract outlet obstruction led to urine reflux from the anus to the epididymis for a long time. The boy had to be placed on prophylactic antibiotics because he developed urinary tract infection and epididymitis almost every day., Diagnosis: Congenital aphallia (46 XY normal male karyotype) associated with congenital urethroretal fistula., Interventions: We performed urethral exteriorization via perineal urethroplasty and urethrorectal fistula repair. The parents approved for phallic reconstruction when the boy reached puberty., Outcome: A new external urethral orifice was created on the lower scrotum. The urinary reflux was corrected, and the epididymitis symptoms disappeared. The urethral fistula was then closed. At 8 months follow up, the patient was no longer on antibiotics and had no symptoms of urinary tract infection or epididymitis., Conclusions: Compatible treatment should be adopted to address urinary tract drainage and infection. Management requires a stepwise approach to address needs as they arise. Neophalloplasty should be performed by an experienced team in early adolescence., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Growing evidence suggests that adverse intrauterine environments could affect the long-term health of offspring. Recent evidence indicates that gestational diabetes mellitus (GDM) is associated with neurocognitive changes in offspring. However, the mechanism remains unclear. Using a GDM mouse model, we collected hippocampi, the structure critical to cognitive processes, for electron microscopy, methylome and transcriptome analyses. Reduced representation bisulfite sequencing (RRBS) and RNA-seq in the GDM fetal hippocampi showed altered methylated modification and differentially expressed genes enriched in common pathways involved in neural synapse organization and signal transmission. We further collected fetal mice brains for metabolome analysis and found that in GDM fetal brains, the metabolites displayed significant changes, in addition to directly inducing cognitive dysfunction, some of which are important to methylation status such as betaine, fumaric acid, L-methionine, succinic acid, 5-methyltetrahydrofolic acid, and S-adenosylmethionine (SAM). These results suggest that GDM affects metabolites in fetal mice brains and further affects hippocampal DNA methylation and gene regulation involved in cognition, which is a potential mechanism for the adverse neurocognitive effects of GDM in offspring., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Luo, Zou, Zhu, Cheng, Yan, Sheng, Huang and Ding.)

Transition metal and nitrogen co-doped carbon-based catalysts (TM-N-C) have become the most promising catalysts for Pt/C due to their wide range of sources, low cost, high catalytic activity, excellent stability and strong resistance to poisoning, especially Fe-N-C metal-organic frameworks (MOFs), which are some of the most promising precursors for the preparation of Fe-N-C catalysts due to their inherent properties, such as their highly ordered three-dimensional framework structure, controlled porosity, and tuneable chemistry. Based on these, in this paper, different iron sources were added to synthesis a sort of zeolitic imidazole frameworks (ZIF-8). Then the imidazole salt in ZIF-8 was rearranged into high N-doped carbon by high-temperature pyrolysis to prepare the Fe-N-C catalyst. We studied the physical characteristics of the catalysts by different iron sources and their effects on the catalytic properties of the oxygen reduction reaction (ORR). From the point of morphology, various iron sources have a positive influence on maintaining the morphology of ZIF-8 polyhedron. Fe-N/C-Fe(NO₃)₃ has the same anion as zinc nitrate, and can maintain a polyhedral morphology after high-temperature calcination. It had the highest ORR catalytic activity compared to the other four catalyst materials, which proved that there is a certain relationship between morphology and performance. This paper will provide a useful reference and new models for the development of high-performance ORR catalysts without precious metals.

Mounting evidence has shown that intrauterine hyperglycemia exposure during critical stages of development may be contributing to the increasing prevalence of diabetes. However, little is known about the mechanisms responsible for offspring metabolic disorder. In this present study, we explored intrauterine hyperglycemia exposure on fetal pancreatic metabolome, and its potential link to impaired glucose tolerance in adult offspring. Here, using a GDM mouse model, we found the metabolome profiling of pancreas from male and female fetus showing altered metabolites in several important pathways, including 5-methylcytosine, α-KG, branched-chain amino acids, and cystine, which are associated with epigenetic modification, insulin secretion, and intracellular redox status, respectively. This finding suggests that intrauterine exposure to hyperglycemia could cause altered metabolome in pancreas, which might be a metabolism-mediated mechanism for GDM-induced intergenerational diabetes predisposition., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Zhu, Luo, Cheng, Yan, Zou, Ding, Jin and Huang.)

Objective: We aimed to explore the prognostic value of a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) genes in gastric cancer (GC)., Methods: The RNA-sequencing (RNA-seq) expression data for 351 GC patients and other relevant clinical data were acquired from The Cancer Genome Atlas (TCGA). Survival analysis and a genome-wide gene set enrichment analysis (GSEA) were performed to define the underlying molecular value of the ADAMTS genes in GC development. Besides, qRT-PCR and immunohistochemistry were all employed to validate the relationship between the expression of these genes and GC patient prognosis., Results: The Log rank test with both Cox regression and Kaplan-Meier survival analyses showed that ADAMTS6 expression profile correlated with the GC patients clinical outcome. Patients with a high expression of ADAMTS6 were associated with poor overall survival (OS). Comprehensive survival analysis of the ADAMTS genes suggests that ADAMTS6 might be an independent predictive factor for the OS in patients with GC. Besides, GSEA demonstrated that ADAMTS6 might be involved in multiple biological processes and pathways, such as the vascular endothelial growth factor A (VEGFA), kirsten rat sarcoma viral oncogene (KRAS), tumor protein P53, c-Jun N-terminal kinase (JNK), cadherin (CDH1) or tumor necrosis factor (TNF) pathways. It was also confirmed by immunohistochemistry and qRT-PCR that ADAMTS6 is highly expressed in GC, which may be related to the prognosis of GC patients., Conclusion: In summary, our study demonstrated that ADAMTS6 gene could be used as a potential molecular marker for GC prognosis., (© 2021 The Author(s).)

Objective: To observe the clinical feature of familiar hereditary protein S deficiency, and to explore the related gene mutation. Methods: The blood samples were obtained from the proband and the family memebers(3 generations,6 persons). PROS1 gene of the proband and the family members was analyzed. The 15 exons and flanking sequence of PROS1 gene were analyzed by PCR and DNA sequencing. Results: Five out of 6 family members were diagnosed as having hereditary protein S deficiency. The proband suffered from pulmonary embolism. The others had no obvious thrombotic event. The gene sequencing revealed that the proband carried a c.-168C>T homozygous variant in the promoter of exon 1. His parents, brother and son all carried c.-168C>T heterozygosis variant at the same position. The gene of his wife was a wild type. Conclusion: A gene variant (c.-168C>T) of PROS1 was discovered in this Chinese family. Gene variant of PROS1 may result in protein S deficiency. Patients with protein S deficiency may suffer from vein thrombosis and(or) pulmonary embolism.

Recently, optically-transparent metasurface based on indium tin oxide (ITO) film has attracted wide attention due to its remarkable optical and electromagnetic characteristics. However, most previous researches on the ITO film mainly focus on the absorption because of its prominent loss-resistance property, but neglecting the further exploration on programmable functions. Here, we present a programmable metasurface based on an optically-transparent ITO glass, on which varactors are integrated to achieve flexible amplitude manipulation range of about 25 dB. More importantly, the presented programmable design can be applied for direct modulation on the carrier incident wave with the desired pre-designed analog wave-form. Within the 10 MHz modulation speed, both programmable amplitude manipulation and analog information modulation are demonstrated in the measurements, showing good agreement with theoretical analysis and simulations. Combining both optical transparency and programmable modulation capability, the presented metasurface will promote the potential applications in wireless communication, internet of things and other smart scenarios.

Background: There was a paucity of follow-up studies in the disease progression of early-onset PD patients with Parkin mutations (Parkin-EOPD). Here we conducted a longitudinal study to investigate the progression of motor and cognitive features of Parkin-EOPD patients., Methods: Genetic analysis was performed via target sequencing and multiplex ligation-dependent probe amplification. Thirty patients carrying homozygous or compound heterozygous Parkin mutations with at least 2 follow-up revisions were investigated as the Parkin-EOPD group. Fifty-two patients with at least 2 follow-up revisions, who did not have any known causative PD mutations, GBA or LRRK2 risk variants, a heterozygous Parkin mutation or 2 Parkin mutations without a segregation test, were defined as the genetically undefined EOPD (GU-EOPD) group. A linear mixed-effect model was implemented to evaluate longitudinal changes in motor symptoms and cognition., Results: At baseline, the Parkin-EOPD group had a lower Unified Parkinson's Disease Rating Scale score (UPDRS-III) (off-medication) than the GU-EOPD group, without significant differences in cognition. A longitudinal study showed the estimated progression rate per year (standard error) of the UPDRS-III score (off-medication) was lower in the Parkin-EOPD group (0.203 [0.3162] points per year) than in the GU-EOPD group (1.056 [0.3001] points per year). The difference in the UPDRS-III score rate between the 2 groups was 0.853 (0.4183) (P = 0.042). The Parkin-EOPD group showed better maintenance of spatial processing ability compared with the GU-EOPD group (P = 0.027)., Conclusion: Parkin-EOPD patients showed a slower deterioration of motor symptoms and a better spatial processing ability than GU-EOPD patients, which suggests that subtyping according to genetic features can help predict PD progression. © 2020 International Parkinson and Movement Disorder Society., (© 2020 International Parkinson and Movement Disorder Society.)

Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) is a complicated maternally inherited disorder lacking of sensitive and specific biomarkers. The objective of this study was to investigate the serum neurofilament light chain (NfL) as a novel biomarker of neurological dysfunction in MELAS. Patients with different status of MELAS were enrolled in this study. The Mini-Mental State Examination (MMSE) was given to the participants to evaluate cognition status. Multiple functional MRI was performed on the participants. Blood samples were collected and the serum NfL concentrations were determined by the single-molecule array technology (Simoa). This study enrolled 23 patients with MELAS, 15 people in the acute attack phase of MELAS and 10 people in the remission phase, including 2 patients in both acute attack and remission phase. Sixteen healthy controls (HCs) were also enrolled. Serum NfL level increased significantly in patients with MELAS. Serum NfL level in the acute attack group (146.73 [120.91-411.31] pg/ml, median [IQR]) was higher than in the remission group (40.31 [19.54-151.05] pg/ml, median [IQR]) and HCs group (7.70 [6.13-9.78] pg/ml, median [IQR]) (p < 0.05). The level of NfL in the remission phase group was higher than in HCs group (p < 0.05). A negative correlation was found between the serum NfL level and MMSE (p = 0.006, r = -0.650). The NfL concentration correlated positively with stroke-like lesion volume in the brain (r = 0.740, p < 0.001). Serum NfL may serve as a novel biomarker for the neurological dysfunction in MELAS patients.

Introduction: Mutations in the Parkin gene are the most common cause of autosomal recessive early-onset Parkinson's disease (PD). However, little is known about the quality of life (QoL) in Parkin -related PD. Here, we investigated the patterns of QoL in newly diagnosed Parkin -related PD patients. Methods: Newly diagnosed PD patients (diagnosis made within 12 months) who had an age of onset (AOO) below 40 and underwent a PD-related genetic testing, were recruited ( n = 148). Among them, 24 patients carried bi-allelic variants in Parkin (PD- Parkin ) and 24 patients did not have any known causative PD mutations, or risk variants (GU-EOPD). The clinical materials, relevant factors and determinants of QoL were analyzed. Results: PD- Parkin patients had a younger AOO ( p = 0.003) and longer disease duration ( p = 0.005). After adjustment for AOO and disease duration, more dystonia ( p = 0.034), and worse scores of non-motor symptoms including Beck depression inventory (BDI, p = 0.035), Epworth sleepiness scale (ESS, p = 0.044), and subdomains of depression/anxiety ( p = 0.015) and sleep disorders ( p = 0.005) in Non-motor symptoms questionnaire, were found in PD- Parkin comparing with GU-EOPD. PD- Parkin patients had poorer QoL (adjusted p = 0.045), especially in the mobility (adjusted p = 0.025), emotional well-being (adjusted p = 0.015) and bodily discomfort dimensions (adjusted p = 0.016). BDI scores ( p = 0.005) and ESS scores ( p = 0.047) were significant determinants of QoL in PD-Parkin . Conclusion: Newly diagnosed PD- Parkin patients showed worse QoL. More depression and excessive daytime sleepiness predicted worse QoL. For clinicians, management of depression and excessive daytime sleepiness is suggested to better improve QoL in patients with Parkin mutations., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Zhou, Liu, Chen, Luo, Zhao, Tang, Shen, Yu, Zuo, Wu, Ding, Wang and Sun.)

Idiopathic rapid eye movement sleep behaviour disorder (RBD) is now recognized as an early manifestation of α-synucleinopathies. Increasing experimental studies demonstrate that manipulative lesion or inactivation of the neurons within the sublaterodorsal tegmental nucleus (also known as the subcoeruleus nucleus in humans) can induce RBD-like behaviours in animals. As current RBD animal models are not established on the basis of α-synucleinopathy, they do not represent the pathological substrate of idiopathic RBD and thus cannot model the phenoconversion to Parkinson's disease. The purpose of this study was therefore to establish an α-synucleinopathy-based RBD animal model with the potential to convert to parkinsonian disorder. To this end, we first determined the functional neuroanatomical location of the sublaterodorsal tegmental nucleus in wild-type C57BL/6J mice and then validated its function by recapitulating RBD-like behaviours based on this determined nucleus. Next, we injected preformed α-synuclein fibrils into the sublaterodorsal tegmental nucleus and performed regular polysomnographic recordings and parkinsonian behavioural and histopathological studies in these mice. As a result, we recapitulated RBD-like behaviours in the mice and further showed that the α-synucleinopathy and neuron degeneration identified within the sublaterodorsal tegmental nucleus acted as the neuropathological substrates. Subsequent parkinsonian behavioural studies indicated that the α-synucleinopathy-based RBD mouse model were not stationary, but could further progress to display parkinsonian locomotor dysfunction, depression-like disorder, olfactory dysfunction and gastrointestinal dysmotility. Corresponding to that, we determined α-synuclein pathology in the substantia nigra pars compacta, olfactory bulb, enteral neuroplexus and dorsal motor nucleus of vagus nerve, which could underlie the parkinsonian manifestations in mice. In conclusion, we established a novel α-synucleinopathy-based RBD mouse model and further demonstrated the phenoconversion of RBD to Parkinson's disease in this animal model., (© The Author(s) (2020). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please email: journals.permissions@oup.com.)