bluuebunny/crossref_metadata_2025 huggingface dataset:
Obesity-Related Neuroinflammation: Magnetic Resonance and Microscopy Imaging of the Brain
Authors: Woo Anita , Botta Amy , Shi Sammy S. W. , Paus Tomas , Pausova Zdenka
Published: August 2022

Obesity is a major risk factor of Alzheimer’s disease and related dementias. The principal feature of dementia is a loss of neurons and brain atrophy. The mechanistic links between obesity and the neurodegenerative processes of dementias are not fully understood, but recent research suggests that obesity-related systemic inflammation and subsequent neuroinflammation may be involved. Adipose tissues release multiple proinflammatory molecules (fatty acids and cytokines) that impact blood and vessel cells, inducing low-grade systemic inflammation that can transition to tissues, including the brain. Inflammation in the brain—neuroinflammation—is one of key elements of the pathobiology of neurodegenerative disorders; it is characterized by the activation of microglia, the resident immune cells in the brain, and by the structural and functional changes of other cells forming the brain parenchyma, including neurons. Such cellular changes have been shown in animal models with direct methods, such as confocal microscopy. In humans, cellular changes are less tangible, as only indirect methods such as magnetic resonance (MR) imaging are usually used. In these studies, obesity and low-grade systemic inflammation have been associated with lower volumes of the cerebral gray matter, cortex, and hippocampus, as well as altered tissue MR properties (suggesting microstructural variations in cellular and molecular composition). How these structural variations in the human brain observed using MR imaging relate to the cellular variations in the animal brain seen with microscopy is not well understood. This review describes the current understanding of neuroinflammation in the context of obesity-induced systemic inflammation, and it highlights need for the bridge between animal microscopy and human MR imaging studies.
In Peripheral Blood Mononuclear Cells Helicobacter pylori Induces the Secretion of Soluble and Exosomal Cytokines Related to Carcinogenesis
Authors: Atrisco-Morales Josefina , Ramírez Mónica , Castañón-Sánchez Carlos Alberto , Román-Román Adolfo , Román-Fernández Ilce Valeria , Martínez-Carrillo Dinorah Nashely , García-Arellano Samuel , Muñoz-Valle José Francisco , Rodríguez-Ruiz Hugo Alberto , Fernández-Tilapa Gloria
Published: August 2022

Helicobacter pylori promotes the secretion of cytokines that regulate inflammation and carcinogenesis. Immune cells secrete cytokines into the extracellular medium or packaged in exosomes. The objective of this study was to analyze the profile of soluble and exosomal cytokines that were secreted by human peripheral blood mononuclear cells (PBMCs) that were infected with H. pylori and to build a network of interaction between cytokines and cellular proteins. PBMCs were obtained by density gradient centrifugation and infected with H. pylori for 24 h. The infection was verified by immunofluorescence and Western blot for CagA. The exosomes were obtained from culture supernatant by ultracentrifugation and characterized by transmission electron microscopy, particle size analysis, and Western blot for CD9 and CD81. Cytokines were quantified using a multiplex immunoassay in the culture supernatant, intact exosomes, and lysed exosomes. H. pylori adheres to lymphocytes and translocates CagA. In PBMCs, H. pylori induces an increase in the soluble and exosomal IL-1β, IL-6, TNF-α, IL-10, IL-17A, IL-21, and IL-22. The protein–protein interaction (PPI) network shows that soluble and exosomal cytokines interact with proteins that participate in signaling pathways such as NF-κB, MAPK, PI3K-Akt, Jak-STAT, FoxO, and mTOR, that are related to carcinogenesis; moreover, TNF-α had the highest number of interactions. Cytokine-loaded exosomes represent another means of intercellular communication that is activated by H. pylori to stimulate inflammation, carcinogenesis, or cancer progression. Cytokine-loaded exosomes are likely to be associated with extragastrointestinal diseases of inflammatory origin.
The Effects of Nutrient Signaling Regulators in Combination with Phytocannabinoids on the Senescence-Associated Phenotype in Human Dermal Fibroblasts
Authors: Gerasymchuk Marta , Robinson Gregory Ian , Kovalchuk Olga , Kovalchuk Igor
Published: August 2022

Identifying effective anti-aging compounds is a cornerstone of modern longevity, aging, and skin-health research. There is considerable evidence of the effectiveness of nutrient signaling regulators such as metformin, resveratrol, and rapamycin in longevity and anti-aging studies; however, their potential protective role in skin aging is controversial. In light of the increasing appearance of phytocannabinoids in beauty products without rigorous research on their rejuvenation efficacy, we decided to investigate the potential role of phytocannabinoids in combination with nutrient signaling regulators in skin rejuvenation. Utilizing CCD-1064Sk skin fibroblasts, the effect of metformin, triacetylresveratrol, and rapamycin combined with phytocannabinoids on cellular viability, functional activity, metabolic function, and nuclear architecture was tested. We found triacetylresveratrol combined with cannabidiol increased the viability of skin fibroblasts (p < 0.0001), restored wound-healing functional activity (p < 0.001), reduced metabolic dysfunction, and ameliorated nuclear eccentricity and circularity in senescent fibroblasts (p < 0.01). Conversely, metformin with or without phytocannabinoids did not show any beneficial effects on functional activity, while rapamycin inhibited cell viability (p < 0.01) and the speed of wound healing (p < 0.001). Therefore, triacetylresveratrol and cannabidiol can be a valuable source of biologically active substances used in aging and more studies using animals to confirm the efficacy of cannabidiol combined with triacetylresveratrol should be performed.
The Effects of Probiotics, Prebiotics and Synbiotics in Non-Alcoholic Fat Liver Disease (NAFLD) and Non-Alcoholic Steatohepatitis (NASH): A Systematic Review
Authors: Carpi Rodrigo Zamignan , Barbalho Sandra M. , Sloan Katia Portero , Laurindo Lucas Fornari , Gonzaga Heron Fernando , Grippa Paulo Cesar , Zutin Tereza L. Menegucci , Girio Raul J. S. , Repetti Cláudia Sampaio Fonseca , Detregiachi Cláudia Rucco Penteado , Bueno Patrícia C. Santos , Mazuqueli Pereira Eliana de Souza Bastos , Goulart Ricardo de Alvares , Haber Jesselina Francisco dos Santos
Published: August 2022

Modifications in the microbiota caused by environmental and genetic reasons can unbalance the intestinal homeostasis, deregulating the host’s metabolism and immune system, intensifying the risk factors for the development and aggravation of non-alcoholic fat liver disease (NAFLD). The use of probiotics, prebiotics and synbiotics have been considered a potential and promising strategy to regulate the gut microbiota and produce beneficial effects in patients with liver conditions. For this reason, this review aimed to evaluate the effectiveness of probiotics, prebiotics, and symbiotics in patients with NAFLD and NASH. Pubmed, Embase, and Cochrane databases were consulted, and PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) guidelines were followed. The clinical trials used in this study demonstrated that gut microbiota interventions could improve a wide range of markers of inflammation, glycemia, insulin resistance, dyslipidemia, obesity, liver injury (decrease of hepatic enzymes and steatosis and fibrosis). Although microbiota modulators do not play a healing role, they can work as an important adjunct therapy in pathological processes involving NAFLD and its spectrums, either by improving the intestinal barrier or by preventing the formation of toxic metabolites for the liver or by acting on the immune system.
Theoretical Design of a Janus-Nanoparticle-Based Sandwich Assay for Nucleic Acids
Authors: Sato Takumi , Esashika Keiko , Yamamoto Eiji , Saiki Toshiharu , Arai Noriyoshi
Published: August 2022

Nanoparticles exhibit diverse self-assembly attributes and are expected to be applicable under unique settings. For instance, biomolecules can be sandwiched between dimer nanoparticles and detected by surface-enhanced Raman scattering. Controlling the gap between extremely close dimers and stably capturing the target molecule in the gap are crucial aspects of this strategy. Therefore, polymer-tethered nanoparticles (PTNPs), which show promise as high-performance materials that exhibit the attractive features of both NPs and polymers, were targeted in this study to achieve stable biomolecule sensing. Using coarse-grained molecular dynamics simulations, the dependence of the PTNP interactions on the length of the grafted polymer, graft density, and coverage ratio of a hydrophobic tether were examined. The results indicated that the smaller the tether length and graft density, the smaller was the distance between the PTNP surfaces (Rsurf). In contrast, Rsurf decreased as the coverage ratio of the hydrophobic surface (ϕ) increased. The sandwiching probability of the sensing target increased in proportion to the coverage ratio. At high ϕ values, the PTNPs aggregated into three or more particles, which hindered their sensing attributes. These results provide fundamental insight into the sensing applications of NPs and demonstrate the usefulness of PTNPs in sensing biomolecules.
Novel Antibiofilm Inhibitor Ginkgetin as an Antibacterial Synergist against Escherichia coli
Authors: Bai Yubin , Wang Weiwei , Shi Mengyan , Wei Xiaojuan , Zhou Xuzheng , Li Bing , Zhang Jiyu
Published: August 2022

As an opportunistic pathogen, Escherichia coli (E. coli) forms biofilm that increases the virulence of bacteria and antibiotic resistance, posing a serious threat to human and animal health. Recently, ginkgetin (Gin) has been discovered to have antiinflammatory, antioxidant, and antitumor properties. In the present study, we evaluated the antibiofilm and antibacterial synergist of Gin against E. coli. Additionally, Alamar Blue assay combined with confocal laser scanning microscope (CLSM) and crystal violet (CV) staining was used to evaluate the effect of antibiofilm and antibacterial synergist against E. coli. Results showed that Gin reduces biofilm formation, exopolysaccharide (EPS) production, and motility against E. coli without limiting its growth and metabolic activity. Furthermore, we identified the inhibitory effect of Gin on AI-2 signaling molecule production, which showed apparent anti-quorum sensing (QS) properties. The qRT-PCR also indicated that Gin reduced the transcription of curli-related genes (csgA, csgD), flagella-formation genes (flhC, flhD, fliC, fliM), and QS-related genes (luxS, lsrB, lsrK, lsrR). Moreover, Gin showed obvious antibacterial synergism to overcome antibiotic resistance in E. coli with marketed antibiotics, including gentamicin, colistin B, and colistin E. These results suggested the potent antibiofilm and novel antibacterial synergist effect of Gin for treating E. coli infections.
Stellettin B-Induced Oral Cancer Cell Death via Endoplasmic Reticulum Stress–Mitochondrial Apoptotic and Autophagic Signaling Pathway
Authors: Kuo Tsu-Jen , Jean Yen-Hsuan , Shih Po-Chang , Cheng Shu-Yu , Kuo Hsiao-Mei , Lee Yi-Ting , Lai Yu-Cheng , Tseng Chung-Chih , Chen Wu-Fu , Wen Zhi-Hong
Published: August 2022

Oral squamous cell carcinoma (OSCC) affects tens of thousands of people worldwide. Despite advances in cancer treatment, the 5-year survival rate of patients with late-stage OSCC is low at 50–60%. Therefore, the development of anti-OSCC therapy is necessary. We evaluated the effects of marine-derived triterpene stellettin B in human OC2 and SCC4 cells. Stellettin B dose-dependently decreased the viability of both cell lines, with a significant reduction in OC2 cells at ≥0.1 µM at 24 and 48 h, and in SCC4 cells at ≥1 µM at 24 and 48 h. Terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL)-positive cells were significantly observed at 20 µM of stellettin B at 48 h, with the overexpression of cleaved caspase3 and cleaved poly(ADP-ribose) polymerase (PARP). Moreover, mitochondrial respiratory functions were ablated by stellettin B. Autophagy-related LC3-II/LC3-I ratio and Beclin-1 proteins were increased, whereas p62 was decreased. At 20 µM at 48 h, the expression levels of the endoplasmic reticulum (ER) stress biomarkers calnexin and BiP/GRP78 were significantly increased and mitogen-activated protein kinase (MAPK) signaling pathways were activated. Further investigation using the autophagy inhibitor 3-methyladenine (3-MA) demonstrated that it alleviated stellettin B-induced cell death and autophagy. Overall, our findings show that stellettin B induces the ER stress, mitochondrial stress, apoptosis, and autophagy, causing cell death of OSCC cells.
Postnatal Protein Intake as a Determinant of Skeletal Muscle Structure and Function in Mice—A Pilot Study
Authors: Giakoumaki Ifigeneia , Pollock Natalie , Aljuaid Turki , Sannicandro Anthony J. , Alameddine Moussira , Owen Euan , Myrtziou Ioanna , Ozanne Susan E. , Kanakis Ioannis , Goljanek-Whysall Katarzyna , Vasilaki Aphrodite
Published: August 2022

Sarcopenia is characterised by an age-related decrease in the number of muscle fibres and additional weakening of the remaining fibres, resulting in a reduction in muscle mass and function. Many studies associate poor maternal nutrition during gestation and/or lactation with altered skeletal muscle homeostasis in the offspring and the development of sarcopenia. The aim of this study was to determine whether the musculoskeletal physiology in offspring born to mouse dams fed a low-protein diet during pregnancy was altered and whether any physiological changes could be modulated by the nutritional protein content in early postnatal stages. Thy1-YFP female mice were fed ad libitum on either a normal (20%) or a low-protein (5%) diet. Newborn pups were cross-fostered to different lactating dams (maintained on a 20% or 5% diet) to generate three groups analysed at weaning (21 days): Normal-to-Normal (NN), Normal-to-Low (NL) and Low-to-Normal (LN). Further offspring were maintained ad libitum on the same diet as during lactation until 12 weeks of age, creating another three groups (NNN, NLL, LNN). Mice on a low protein diet postnatally (NL, NLL) exhibited a significant reduction in body and muscle weight persisting up to 12 weeks, unlike mice on a low protein diet only prenatally (LN, LNN). Muscle fibre size was reduced in mice from the NL but not LN group, showing recovery at 12 weeks of age. Muscle force was reduced in NLL mice, concomitant with changes in the NMJ site and changes in atrophy-related and myosin genes. In addition, μCT scans of mouse tibiae at 12 weeks of age revealed changes in bone mass and morphology, resulting in a higher bone mass in the NLL group than the control NNN group. Finally, changes in the expression of miR-133 in the muscle of NLL mice suggest a regulatory role for this microRNA in muscle development in response to postnatal diet changes. Overall, this data shows that a low maternal protein diet and early postnatal life low-protein intake in mice can impact skeletal muscle physiology and function in early life while postnatal low protein diet favours bone integrity in adulthood.
Hyaluronic Acid Alleviates Oxidative Stress and Apoptosis in Human Tenocytes via Caspase 3 and 7
Authors: Gallorini Marialucia , Antonetti Lamorgese Passeri Cristina , Cataldi Amelia , Berardi Anna Concetta , Osti Leonardo
Published: August 2022

Rotator cuff tendinopathy (RCT) is the primary reason for shoulder surgery and its clinical management is still challenging. Hyaluronic acid (HA) has been shown to have anti-inflammatory effects in vitro and in vivo under RCT conditions, characterized by an exaggerated oxidative stress (OS). However, molecular mechanisms underlying HA-related effects are still partially disclosed. With these aims, a cell model of RCT was established by exposing primary human tenocytes to H2O2 for up to 72 h. Four different HAs by molecular weight were administered to measure nitric oxide (NO) and OS, apoptosis, and collagen 1 expression. In parallel, the well-known antioxidant ascorbic acid was administered for comparison. The present study highlights that HAs characterized by a low molecular weight are able to counteract the H2O2-induced OS by decreasing the percentage of apoptotic cells and reversing the activation of caspase 3 and 7. Likewise, NO intracellular levels are comparable to the ones of controls. In parallel, collagen 1 expression was ameliorated by HAs characterized by higher molecular weights compared to AA. These findings confirm that HA plays an antioxidant role comparable to AA depending on the molecular weight, and highlight the molecular mechanisms underlying the HA anti-apoptotic effects.
Promiscuous Lipase-Catalyzed Knoevenagel–Phospha–Michael Reaction for the Synthesis of Antimicrobial β-Phosphono Malonates
Authors: Samsonowicz-Górski Jan , Koszelewski Dominik , Kowalczyk Paweł , Śmigielski Paweł , Hrunyk Anastasiia , Kramkowski Karol , Wypych Aleksandra , Szymczak Mateusz , Lizut Rafał , Ostaszewski Ryszard
Published: August 2022

An enzymatic route for phosphorous–carbon bond formation was developed by discovering new promiscuous activity of lipase. We reported a new metal-free biocatalytic method for the synthesis of pharmacologically relevant β-phosphonomalononitriles via a lipase-catalyzed one-pot Knoevenagel–phospha–Michael reaction. We carefully analyzed the best conditions for the given reaction: the type of enzyme, temperature, and type of solvent. A series of target compounds was synthesized, with yields ranging from 43% to 93% by enzymatic reaction with Candida cylindracea (CcL) lipase as recyclable and, a few times, reusable catalyst. The advantages of this protocol are excellent yields, mild reaction conditions, low costs, and sustainability. The applicability of the same catalyst in the synthesis of β-phosphononitriles is also described. Further, the obtained compounds were validated as new potential antimicrobial agents with characteristic E. coli bacterial strains. The pivotal role of such a group of phosphonate derivatives on inhibitory activity against selected pathogenic E. coli strains was revealed. The observed results are especially important in the case of the increasing resistance of bacteria to various drugs and antibiotics. The impact of the β-phosphono malonate chemical structure on antimicrobial activity was demonstrated. The crucial role of the substituents attached to the aromatic ring on the inhibitory action against selected pathogenic E. coli strains was revealed. Among tested compounds, four β-phosphonate derivatives showed an antimicrobial activity profile similar to that obtained with currently used antibiotics such as ciprofloxacin, bleomycin, and cloxacillin. In addition, the obtained compounds constitute a convenient platform for further chemical functionalization, allowing for a convenient change in their biological activity profile. It should also be noted that the cost of the compounds obtained is low, which may be an attractive alternative to the currently used antimicrobial agents. The observed results are especially important because of the increasing resistance of bacteria to various drugs and antibiotics.
Extracellular Vesicles in Myeloid Neoplasms
Authors: Karantanou Christina , Minciacchi Valentina René , Karantanos Theodoros
Published: August 2022

Myeloid neoplasms arise from malignant primitive cells, which exhibit growth advantage within the bone marrow microenvironment (BMM). The interaction between these malignant cells and BMM cells is critical for the progression of these diseases. Extracellular vesicles (EVs) are lipid bound vesicles secreted into the extracellular space and involved in intercellular communication. Recent studies have described RNA and protein alterations in EVs isolated from myeloid neoplasm patients compared to healthy controls. The altered expression of various micro-RNAs is the best-described feature of EVs of these patients. Some of these micro-RNAs induce growth-related pathways such as AKT/mTOR and promote the acquisition of stem cell-like features by malignant cells. Another well-described characteristic of EVs in myeloid neoplasms is their ability to suppress healthy hematopoiesis either via direct effect on healthy CD34+ cells or via alteration of the differentiation of BMM cells. These results support a role of EVs in the pathogenesis of myeloid neoplasms. mainly through mediating the interaction between malignant and BMM cells, and warrant further study to better understand their biology. In this review, we describe the reported alterations of EV composition in myeloid neoplasms and the recent discoveries supporting their involvement in the development and progression of these diseases.
The Effect of Stabilization Procedures on Sports Discipline and Performance Level in Non-Elite Athletes after Acute Syndesmotic Injury: A Prospective Randomized Trial
Authors: Colcuc Christian , Wähnert Dirk , Raimann Florian J. , Stein Thomas , Weber-Spickschen Sanjay , Hoffmann Reinhard , Fischer Sebastian
Published: August 2022

Background: Suture button devices for tibiofibular syndesmosis injuries provide semirigid dynamic stabilization. The effect of stabilization procedures on sports discipline and performance level in non-elite athletes after acute syndesmotic injury has not been clarified in sports medicine research to date. Methods: A total of 47 of 56 eligible patients were analyzed and completed the 1-year follow-up. The average age was 35.5 years (range, 18–60 years). The screw fixation and knotless suture button groups comprised 26 and 21 patients, respectively. Nine patients were lost to follow-up. Patients underwent clinical and radiological evaluations preoperatively and twice during the 1-year postoperative follow-up. Function was measured using the FADI sports scale, the FAAM sports module, and a visual analogue scale for pain and function in sports. Questionnaires were completed to assess preoperative and postoperative sports levels and to evaluate the sports discipline. Results: All scores increased during the follow-up, but no significant differences were found in the FADI score, the FAAM sports module score and or the VAS score for pain and function during sport (p ≤ 0.05). Using Spearman’s rank correlation coefficient, we found no significant correlation between the groups for age, injury mechanism, or body mass index. Differences were identified in sports discipline and performance level between the groups during the follow-up period. Conclusion: No statistically significant differences could be demonstrated between the two stabilization methods in terms of return to previous sport level and return to the original sport discipline, so both procedures can be regarded as equivalent at present.
Endoprosthetic Reconstruction in Ewing’s Sarcoma Patients: A Systematic Review of Postoperative Complications and Functional Outcomes
Authors: Abu El Afieh Jude , Gray Marena , Seah Matthew , Khan Wasim
Published: August 2022

Ewing’s sarcoma (ES) is a rare primary bone cancer managed by radiotherapy, chemotherapy and surgical resection. The existing literature on limb salvage surgery with endoprostheses combines data for ES patients with osteosarcoma. This review aimed to evaluate surgical and functional outcomes of endoprosthetic reconstruction in exclusively Ewing’s patients. We believe that this is the first comprehensive review to evaluate the outcomes of limb salvage surgery with endoprostheses exclusively in Ewing’s sarcoma patients. Clinical data and outcomes were collected from PubMed, Embase, Medline and Scopus. The inclusion criteria were studies on limb salvage surgery in ES patients, where individual patient data was available. Seventeen studies with a total of 57 Ewing’s patients were included in this review. Fifty-three of the ES patients preserved the limb after limb salvage with endoprostheses. The average five-year implant survivorship was 85.9% based on four studies in this review. Postoperative complications were categorised by Henderson’s failure modes. Soft tissue failure was the most common, occurring in 35.1% of patients, followed by deep infection in 15.7% of patients. There was a suggestion of ‘good’ functional outcomes with limb salvage surgery. The salient limitation of this review is the variability and rarity of the patient population. Homogenous data in a larger population is necessary to provide more insight into outcomes of limb reconstruction in ES.
Risk Factors for Cervical Lymph Node Metastasis in Middle Eastern Papillary Thyroid Microcarcinoma
Authors: Parvathareddy Sandeep Kumar , Siraj Abdul K. , Annaiyappanaidu Padmanaban , Siraj Nabil , Al-Sobhi Saif S. , Al-Dayel Fouad , Al-Kuraya Khawla S.
Published: August 2022

Papillary thyroid microcarcinoma (PTMC) typically has an indolent course and excellent prognosis. Nonetheless, a subset of PTMC carries a risk of lymph node metastasis (LNM) and local recurrence. PTC from the Middle Eastern population is unique with respect to demographic and clinico-pathological characteristics as compared to other ethnicities of the world. The risk factors of LNM in PTMC patients of Middle Eastern ethnicity have not been fully explored. The present study aims to investigate the influencing factors of LNM in Middle Eastern PTMC patients and its predictive impact on patient’s outcome. A total of 226 confirmed PTMC cases were selected in this retrospective study. The correlation between clinico-pathological, as well as molecular, characteristics and LNM was evaluated. Multivariate analysis was performed by logistic regression and Cox proportional hazards models. Among the 226 patients, the rate of LNM was 43.8% (99/226). Bilaterality, multifocality, gross extrathyroidal extension (ETE), and intermediate-to-high American Thyroid Association (ATA) risk tumors were significantly associated with LNM in PTMC. Multivariate logistic regression analysis showed that bilaterality and gross ETE were independent predictive factors for LNM in PTMC. The recurrence-free survival (RFS) was shorter in PTMC with LNM compared to those without LNM (p = 0.0051) and was significant on multivariate analysis. In conclusion, our study showed that bilaterality and gross ETE were independent influencing factors of LNM in Saudi patients with PTMC. LNM was also associated with shorter RFS. The identification of risk factors for LNM in patients of Middle Eastern ethnicity could help the individualization of clinical management for PTMC patients.
Physical Exercise to Improve Functional Capacity: Randomized Clinical Trial in Bariatric Surgery Population
Authors: Aguilar-Cordero María José , Rodríguez-Blanque Raquel , Levet Hernández Cristina , Inzunza-Noack Javiera , Sánchez-García Juan Carlos , Noack-Segovia Jessica
Published: August 2022

Background: Bariatric surgery is a safe and effective method to lose weight over time. However, some patients fail to achieve healthy weight losses. We aimed to determine if a moderate-intensity physical exercise intervention in patients who underwent bariatric surgery increases their functional capacity thus improving bariatric surgery results. Methods: We conducted a parallel-group non-blinded randomized controlled trial at a surgery clinic in Talca, Chile. A total of 43 participants with obesity and scheduled bariatric surgery completed the six months follow-up. A physical exercise program was conducted in exercise group participants one month after bariatric surgery. Walked distance in the six-minute walk test, BMI, Borg scale of perceptive exertion results and cardiovascular variables were evaluated. Results: Patients’ weight significantly decreased after bariatric surgery but there was no difference between the groups of study. The exercise group progressed from a base value of 550 ± 75 m walked in the six-minute walk test to a sixth-month value of 649.6 ± 68.5 m (p < 0.05), whilst the control group yielded base values of 554.4 ± 35.1 and a sixth-month walked distance of 591.1 ± 75.34 (p > 0.05). Conclusions: Physical exercise in obese patients undergoing bariatric surgery increased functional capacity independently of weight losses resulting from bariatric surgery.
Long-Term Results of Surgical Treatment and Patient-Reported Outcomes in Congenital Adrenal Hyperplasia—A Multicenter European Registry Study
Authors: Krege Susanne , Falhammar Henrik , Lax Hildegard , Roehle Robert , Claahsen-van der Grinten Hedi , Kortmann Barbara , Duranteau Lise , Nordenskjöld Agneta
Published: August 2022

Representatives for congenital adrenal hyperplasia (CAH) continue to desire early feminizing surgery in girls with 46,XX-CAH. The aim of this analysis, which included 174 46,XX- individuals with salt-wasting (SW) or simple-virilizing (SV) CAH, a female gender identity, and an age > 16 years participating in a multicenter cross-sectional clinical evaluation study (dsd-LIFE), was to evaluate the long-term results of surgery and patient-reported outcomes (PRO). The gynecological examination (n = 84) revealed some shortcomings concerning surgical feminization. A clitoris was absent in 9.5% of cases, while a clitoral hood was missing in 36.7% of cases. Though all women had large labia, they didn’t look normal in 22.6% of cases. Small labia were absent in 23.8% of cases. There was no introitus vaginae, and the urethra and vagina had no separate opening in 5.1% of cases. A mucosal lining was missing in 15.4% of cases. Furthermore, 86.2% of the women had scars at the region of their external genitalia. A vaginal stenosis was described in 16.5% of cases, and a meatal stenosis was described in 2.6% of cases. Additionally, PRO data showed a very-/high satisfaction rate of 21.3%/40.2% with cosmesis and 23.8%/38.1% with functionality, while 3.3%/10.7% showed a very-/low satisfaction with cosmesis as well as 5.6%/10.3% with functionality. The remaining women—24.6% and 23.8%—were indifferent. Satisfaction concerning sex life was very-/high in 9.6%/27.7%. In 12.0%/16.9% it was very-/low. Furthermore, 33.7% had no opinion. Furthermore, 27.0%/31.6% of the women reported that clitoriplasty, but not clitoridectomy, had a very-/positive influence on their lives, while 1.3%/8.9% felt it to be very-/negative, and 28.4% were indifferent. Vaginoplasty had a very-/positive influence in 25.7%/33.8% and a very-/negative effect in 3.6%/6.8%. 29.7% had no opinion. Additionally, 75.7% of the women preferred feminizing surgery during infancy/childhood, especially concerning clitoreduction. In conclusion, though the majority of the participants (76%) preferred early feminizing surgery and 60% described a positive effect on their lives, about 10% felt it to have been negative. About 15% of the women suffered from insufficient cosmesis and functionality after surgery. Sex life was even described as poor in nearly 30%. Therefore, the decision about early genital surgery in 46,XX-CAH girls should be considered carefully. Parents should get detailed information about possible complications of surgery and should receive support to understand that postponing surgery does not inevitably cause harm for their child. Importantly, genital surgery when performed in children should only be performed in expert centers with a specialized team including surgeons who are trained in feminizing surgery.
New Era in Systemic Sclerosis Treatment: Recently Approved Therapeutics
Authors: Ebata Satoshi , Yoshizaki-Ogawa Asako , Sato Shinichi , Yoshizaki Ayumi
Published: August 2022

Systemic sclerosis (SSc) is a chronic autoimmune disease with a poor prognosis. Among the various complications of SSc, treatment options for the fibrotic lesions, skin sclerosis, and SSc-associated interstitial lung disease (SSc-ILD) have been limited. However, since 2019, the efficacy and safety of nintedanib, tocilizumab, and rituximab for SSc or SSc-ILD have been demonstrated in double-blind, randomized, placebo-controlled trials, respectively. The antifibrotic agent nintedanib was approved for SSc-ILD in all regions of the United States, Europe, and Japan after the SENSCIS study confirmed that it suppressed the reduction in forced vital capacity (FVC), a measure of SSc-ILD. Tocilizumab, an anti-interleukin-6 receptor antibody, was approved for the treatment of SSc-ILD in the United States after the FocuSSced study showed that it inhibited the decrease in FVC. Rituximab, an anti-CD20 antibody, showed improvement in both modified Rodnan skin score, a measure of skin sclerosis, and FVC in the DESIRES study, and was approved in Japan for the treatment of SSc itself. With the development of these three drugs, SSc treatment is entering a new era. This paper outlines the latest advances in SSc therapeutics, focusing on nintedanib, tocilizumab, and rituximab.
Complex Coronary Interventions: Are We Reaching a Plateau?
Authors: Franchin Luca , Boccuzzi Giacomo , Moniaci Diego , Iannaccone Mario
Published: August 2022

The complexity of coronary artery disease is currently on the rise [...]
Analysis of Outdoor Activity Space-Use Preferences in Rural Communities: An Example from Puxiu and Yuanyi Village in Shanghai
Authors: Wen Ledi , Sima Lei
Published: August 2022

The creation of outdoor activity spaces in rural communities is an important indicator to enhance the happiness of villagers and an important means to promote rural revitalization through improving the living environment. However, the urbanization trend of spatial forms has caused problems in the construction of many new rural activity spaces, such as the homogenized design and the lack of attention to the real demands of local residents. In order to understand urban-rural differences as well as inter-rural difference of outdoor activity space preferences in today’s China, so as to optimize the planning and design of public space optimization in rural communities, this study took Puxiu and Yuanyi Village in the suburbs of Shanghai as examples, executed field questionnaire surveys to ascertain villagers’ general preferences for outdoor spaces as well as their personal diversities. The results suggested that urban-rural differences were generally reflected in the practicability, economy, rurality, and diversity of the spaces, and it was found that there are significant relationships between residents’ preferences and their personal attributes, such as gender, age, and occupation. Moreover, the essentials for optimizing community activity space design that reflect urban-rural differences as well as the characteristics of different types of villages were also discussed.
Linear Lengthening in Iwaidja: An Event-Quantifying Intonation at the Phonology to Semantics/Pragmatics Interface
Authors: Caudal Patrick , Mailhammer Robert
Published: August 2022

This paper investigates the meaning of a specific intonation contour called linear lengthening intonation (LLI), which is found in the northern Australian language Iwaidja. Using an experimental field work approach, we analysed approximately 4000 utterances. We demonstrate that the semantics of LLI is broadly event-quantificational as well as temporally scalar. LLI imposes aspectual selectional restrictions on the verbs it combines with (they must be durative, i.e., cannot describe ‘punctual’, atomic events), and requires the event description effected by said verbs to exceed a contextually determined relative scalar meaning. Iwaidja differs from other northern Australian languages with similar intonation patterns in that it does not seem to have any argument NP-related incremental or event scalar meaning. This suggests that LLI is a decidedly grammatical, language-specific device and not a purely iconic kind of expression (even though it also possibly has an iconic dimension).
Characterization of Peroxidase and Laccase Gene Families and In Silico Identification of Potential Genes Involved in Upstream Steps of Lignan Formation in Sesame
Authors: Zoclanclounon Yedomon Ange Bovys , Rostás Michael , Chung Nam-Jin , Mo Youngjun , Karlovsky Petr , Dossa Komivi
Published: August 2022

Peroxidases and laccases are oxidative enzymes involved in physiological processes in plants, covering responses to biotic and abiotic stress as well as biosynthesis of health-promoting specialized metabolites. Although they are thought to be involved in the biosynthesis of (+)-pinoresinol, a comprehensive investigation of this class of enzymes has not yet been conducted in the emerging oil crop sesame and no information is available regarding the potential (+)-pinoresinol synthase genes in this crop. In the present study, we conducted a pan-genome-wide identification of peroxidase and laccase genes coupled with transcriptome profiling of diverse sesame varieties. A total of 83 and 48 genes have been identified as coding for sesame peroxidase and laccase genes, respectively. Based on their protein domain and Arabidopsis thaliana genes used as baits, the genes were classified into nine and seven groups of peroxidase and laccase genes, respectively. The expression of the genes was evaluated using dynamic transcriptome sequencing data from six sesame varieties, including one elite cultivar, white vs black seed varieties, and high vs low oil content varieties. Two peroxidase genes (SiPOD52 and SiPOD63) and two laccase genes (SiLAC1 and SiLAC39), well conserved within the sesame pan-genome and exhibiting consistent expression patterns within sesame varieties matching the kinetic of (+)-pinoresinol accumulation in seeds, were identified as potential (+)-pinoresinol synthase genes. Cis-acting elements of the candidate genes revealed their potential involvement in development, hormonal signaling, and response to light and other abiotic triggers. Transcription factor enrichment analysis of promoter regions showed the predominance of MYB binding sequences. The findings from this study pave the way for lignans-oriented engineering of sesame with wide potential applications in food, health and medicinal domains.
Effect of Smut Infection on the Photosynthetic Physiological Characteristics and Related Defense Enzymes of Sugarcane
Authors: Song Xiupeng , Mo Fenglian , Yan Meixin , Zhang Xiaoqiu , Zhang Baoqing , Huang Xing , Huang Dongmei , Pan Yangfei , Verma Krishan K. , Li Yang-Rui
Published: August 2022

Pathogen infection seriously affects plant development and crop productivity, sometimes causing total crop failure. In this study, artificial stab inoculation was used to inoculate sugarcane smut. The changes in leaf gas exchange, chlorophyll fluorescence variables, and related defense enzyme activities were measured in sugarcane cultivar ROC22 after pathogen infection. The results showed that the net photosynthetic rate (Pn), stomatal conductance (gs), and transpiration rate (Tr) downregulated in the first three days after smut infection and upregulated on the fourth day; intercellular CO2 concentration (Ci) increased in the first three days of smut infection and reduced on the fourth day. The chlorophyll fluorescence parameters, i.e., Fo, Fm, Fv/Fm, Fs, and Fv′/Fm′ decreased at the initial stage of pathogen infection but increased rapidly up to 3 days after smut infection. It can be seen that sugarcane seedlings showed a positive response to pathogen infection. The correlation coefficient relationship between Pn, gs, and Tr reached above 0.800, showing a significant correlation; Ci was positively correlated with Fv′/Fm′ and ΦPSII, reaching above 0.800 and showing a significant correlation; Fo positively correlated with Fv/Fm, Fs, and ETR; Fv /Fm was positively correlated with Fv′/Fm′; Fs significantly correlated with Fv′/Fm′; and Fv′/Fm′ positively correlated with ΦPSII. After inoculation with smut, the related defense enzymes, i.e., POD, SOD, PPO, and PAL, were increased and upregulated; photosynthetic parameters can be associated with an increase in enzymatic activities. The results of this study will help to further study of the response mechanism to smut in the sugarcane growing period and provide a theoretical reference for sugarcane resistance to smut breeding.
Up-Date on Diabetic Nephropathy
Authors: Pelle Maria Chiara , Provenzano Michele , Busutti Marco , Porcu Clara Valentina , Zaffina Isabella , Stanga Lucia , Arturi Franco
Published: August 2022

Diabetes is one of the leading causes of kidney disease. Diabetic kidney disease (DKD) is a major cause of end-stage kidney disease (ESKD) worldwide, and it is linked to an increase in cardiovascular (CV) risk. Diabetic nephropathy (DN) increases morbidity and mortality among people living with diabetes. Risk factors for DN are chronic hyperglycemia and high blood pressure; the renin-angiotensin-aldosterone system blockade improves glomerular function and CV risk in these patients. Recently, new antidiabetic drugs, including sodium–glucose transport protein 2 inhibitors and glucagon-like peptide-1 agonists, have demonstrated additional contribution in delaying the progression of kidney disease and enhancing CV outcomes. The therapeutic goal is regression of albuminuria, but an atypical form of non-proteinuric diabetic nephropathy (NP-DN) is also described. In this review, we provide a state-of-the-art evaluation of current treatment strategies and promising emerging treatments.
Recent Progress in the Diagnosis and Management of Type 2 Diabetes Mellitus in the Era of COVID-19 and Single Cell Multi-Omics Technologies
Authors: Kupai Krisztina , Várkonyi Tamás , Török Szilvia , Gáti Viktória , Czimmerer Zsolt , Puskás László G. , Szebeni Gábor J.
Published: August 2022

Type 2 diabetes mellitus (T2DM) is one of the world’s leading causes of death and life-threatening conditions. Therefore, we review the complex vicious circle of causes responsible for T2DM and risk factors such as the western diet, obesity, genetic predisposition, environmental factors, and SARS-CoV-2 infection. The prevalence and economic burden of T2DM on societal and healthcare systems are dissected. Recent progress on the diagnosis and clinical management of T2DM, including both non-pharmacological and latest pharmacological treatment regimens, are summarized. The treatment of T2DM is becoming more complex as new medications are approved. This review is focused on the non-insulin treatments of T2DM to reach optimal therapy beyond glycemic management. We review experimental and clinical findings of SARS-CoV-2 risks that are attributable to T2DM patients. Finally, we shed light on the recent single-cell-based technologies and multi-omics approaches that have reached breakthroughs in the understanding of the pathomechanism of T2DM.
Effects of Drought Stress on Peramine and Lolitrem B in Epichloë-Endophyte-Infected Perennial Ryegrass
Authors: Lin Weihu , Gao Chengfen , Wang Jianjun , Xu Wenbo , Wang Meining , Li Miaomiao , Ma Bihua , Tian Pei
Published: August 2022

Perennial ryegrass (Lolium perenne) infected by Epichloë endophytes contains alkaloids that are responsible for toxicosis in many countries. Drought may greatly affect the alkaloids contents of symbionts. The E+ perennial ryegrass was grown in pots with different soil moisture conditions (15%, 30%, 45% and 60% relative saturation moisture content, RSMC) for four months in a greenhouse of Lanzhou University, and then, the aboveground tissues were collected. The levels of peramine and lolitrem B in all plant samples were determined. The results showed that the drought stress significantly (p < 0.05) increased the peramine concentrations of perennial ryegrass but did not affect the lolitrem B concentrations. In addition, the drought stress significantly (p < 0.05) reduced the plant height and dry matter of perennial ryegrass. In conclusion, drought stress affects the peramine concentration in the perennial ryegrass–endophyte symbiont but may not affect the lolitrem B concentration.
N,N-Bis(7-nitrobenz[c][1,2,5]oxadiazol-4-yl)cystamine
Authors: Matei Iulia , Culita Dana C. , Tecuceanu Victorita , Hanganu Anamaria , Ionita Petre
Published: August 2022

Background: New amino derivatives of NBD type are of high interest due to their strong fluorescence, while compounds containing a disulphide moiety are of high interest in nano-chemistry due to their easiness of attaching to noble nanoparticles. Therefore, in this work a new fluorescent derivative of NBD and cystamine was obtained. Methods: The reaction between cystamine and NBD-chloride occurs straightforwardly, and the isolated new compound was characterized by IR, UV-Vis, fluorescence, 1H- and 13C-NMR, MS, etc. Results: Structural analysis confirmed the proposed structure and highlighted the fluorescence behavior. Conclusions: A new fluorescent derivative of cystamine was obtained and characterized by different means.
Morphology, Microstructure, and Mechanical Properties of S32101 Duplex Stainless-Steel Joints in K-TIG Welding
Authors: Cui Shuwan , Yu Yunhe , Tian Fuyuan , Pang Shuwen
Published: August 2022

In this paper, the S32101 duplex stainless steel welded joints were produced by a K-TIG welding system. The weld geometry parameters under different welding speeds were analyzed by combining the morphological characteristics of the keyhole. The microstructure and impact toughness of the base metal and weld metal zone under different welding speeds were studied. The experiment results show that the welding speed has quite an effect on the geometry profile of the weld. In addition, the characteristic parameters of the keyhole can effectively predict the geometry profile of the weld. The test results prove that the microstructure, Σ3 coincidence site lattice grain boundary, and phase boundary of ferrite and austenite have an effect on the impact property of the weld metal zone. When the proportion of the austenite, Σ3 coincidence site lattice grain boundary and random phase boundary increased, the impact property of the weld metal zone also increased.
Effects of Wollastonite Fiber and Styrene–Butadiene Latex Polymer on the Long-Term Durability of Cement-Based Repair Materials
Authors: Choo Yeon Jae , Lee Geon Hee , Lee Su-Jin , Park Chan-Gi
Published: August 2022

Concrete structures are constructed in various geographical environments and climates, and frequently fail to fulfill their original functions over time due to issues such as aging and damage. Research on concrete structure repair materials is being conducted to solve these problems. This study evaluated the durability of a repair material composed of ultra-rapid hardening cement, styrene–butadiene (SB) latex polymer, and wollastonite mineral fiber. The performance targets were as follows: compressive strength of 20 MPa at 1 day of age and 45 MPa at 28 days of age, chloride ion charge passed of less than 1000 Coulombs, carbonation depth of 20 mm or less, and resistance to repeated freezing and thawing (relative dynamic modulus of elasticity) of 80% or more. The ultra-rapid hardening cement:silica sand ratio of 1:1.5 was the experimental variable, and the unit weight of each material in the mix proportion was determined to satisfy the flow requirement of 200 ± 5 mm. This flow ensured sufficient fluidity for spraying, which is the most widely used method for applying repair material. Wollastonite mineral fiber and SB latex polymer were added at 3% and 5% of the unit weight of the binder, respectively. The mechanical property of the repair material was evaluated through compressive strength, and durability was evaluated through chloride ion penetration, alkali resistance, resistance to carbonation, water absorption, and repeated freezing and thawing tests. The compressive strength satisfied both target values, regardless of the addition of SB latex polymer and wollastonite mineral fiber. The chloride ion penetration test, which was used as an indicator of durability, showed that mixtures without SB latex and wollastonite mineral fiber were not satisfied the target charge passed of 1000 Coulombs, while mixtures with latex and mineral fiber reached the target value. Notably, the co-addition of latex and wollastonite fiber showed the highest resistance to chloride ion penetration, alkali ion, carbonation, repeated freezing and thawing, and the least absorption. The results confirmed that the durability of the repair material based on ultra-rapid hardening cement was most effectively improved by the co-addition of SB latex polymer and wollastonite mineral fiber.