bluuebunny/crossref_metadata_2025 huggingface dataset:
Circulating neuroactive C21- and C19-steroids in young men before and after ejaculation.
Authors: Stárka L , Hill M , Havlíková H , Kancheva L , Sobotka V
Published: May 2022

Twelve neuroactive and neuroprotective steroids, androgens and androgen precursors i.e. 3alpha,17beta-dihydroxy-5alpha-androstane, 3alpha-hydroxy-5alpha-androstan-17-one, 3alpha-hydroxy-5beta-androstan-17-one, androst-5-ene-3beta,17beta-diol, 3beta,17alpha-dihydroxy-pregn-5-en-20-one (17alpha-hydroxy-pregnenolone), 3beta-hydroxy-androst-5-en-17-one (dehydroepiandrosterone, DHEA), testosterone, androst-4-ene-3,17-dione (androstenedione), 3alpha-hydroxy-5alpha-pregnan-20-one (allopregnanolone), 3beta-hydroxy-pregn-5-en-20-one (pregnenolone), 7alpha-hydroxy-DHEA, and 7beta-hydroxy-DHEA were measured using the GC-MS system in young men before and after ejaculation provoked by masturbation. The circulating level of 17alpha-hydroxypregnenolone increased significantly, whereas the other circulating steroids were not changed at all. This fact speaks against the hypothesis that a drop in the level of neuroactive steroids, e.g. allopregnanolone may trigger the orgasm-related increase of oxytocin, reported by other authors.
Increased lipolysis of subcutaneous abdominal adipose tissue and altered noradrenergic activity in patients with Cushing‘s syndrome: an in vivo microdialysis study
Authors: Kršek M , Rosická M , Nedvídková J , Hána V , Marek J , Haluzík M , Lai EW , Pacák K
Published: May 2022

Cushing's syndrome is associated with typical central redistribution of adipose tissue. The aim of the study was to assess lipolysis and catecholamines and their metabolites in subcutaneous abdominal adipose tissue using an in-vivo microdialysis technique. Nine patients with Cushing's syndrome and nine age-, gender- and body mass index (BMI)-matched control subjects were included in the study. Local glycerol concentrations were significantly increased in subcutaneous adipose tissue of patients with Cushing's syndrome (p<0.001). Plasma noradrenaline, dihydroxyphenylglycol and dihydroxyphenylalanine were decreased in patients with Cushing's syndrome (p<0.02, p<0.05, and p<0.02, respectively). Adrenaline, noradrenaline, dihydroxyphenylglycol and dihydroxyphenylalanine concentrations in subcutaneous abdominal adipose were non-significantly higher in patients with Cushing's syndrome. In conclusion, we showed that lipolysis in subcutaneous adipose tissue of patients with Cushing's syndrome is significantly increased as compared to healthy subjects. This finding together with non-significantly increased local catecholamine concentrations in these patients suggests a possible link between increased lipolysis and catecholaminergic activity in subcutaneous adipose tissue.
An Overview on the Impacts of Textile Effluents on the Aquatic Ecosystem in Turag River at Bangladesh
Authors: Rahman Mustafijur
Published: May 2022

The Turag River has an extensive reputation for backing the coastal people’s income for years; nonetheless, its burden is enormous owing to numerous anthropogenic drivers. DEPZ (Dhaka Export Processing Zone) can be considered one of the crucial zones for textile industries. DEPZ is situated in Savar, and the nearest river is Turag, the upper tributary of the Buriganga. The Turag originates from the Bangshi River, the latter an essential branch of the Dhaleshwari River. Since this area is a cluster area for the industries, Turag has been identified as the most affected waterbody by the industrial effluents. Some research was conducted on the characteristics of the effluents and the impact on the nearby land, water bodies, and the health of the human and aquatic systems of the adjacent area of DEPZ. Still, there is a gap in research on species richness and abundance in the Turag River. IUCN red list 2000, IUCN red list 2015, and the MACH project are reliable sources of information found. Since 2015, IUCN red list has not been updated, and limited research has been conducted to update the severity of the current status. This write-up tries to review and summarize findings from other research and find the gaps. There was no quantitative inventory information on fish abundance and richness. Hopefully, it will be helpful to project the importance of protecting aquatic biodiversity, and law enforcement will be strengthened. More research is needed to save the endangered native aquatic species’ biodiversity. If used with more information, this article can be a stepping stone in the right direction for scholars.
Observational Study of Glycemic Impact of Anticipatory and Early-Race Athletic Competition Stress in Type 1 Diabetes
Authors: Hobbs Nicole , Brandt Rachel , Maghsoudipour Sadaf , Sevil Mert , Rashid Mudassir , Quinn Laurie , Cinar Ali
Published: May 2022

Athletic competitions and the associated psychological stress are a challenge for people with type 1 diabetes (T1D). This study aims to understand the influence of anticipatory and early race competition stress on blood glucose concentrations and to identify personality, demographic, or behavioral traits indicative in the scope of the impact. Ten recreational athletes with T1D competed in an athletic competition and an exercise-intensity matched non-competition “training” session for comparison. The two hours prior to exercise and the first 30 minutes of exercise were compared between the paired exercise sessions to assess the influence of anticipatory and early race stress. The effectiveness index, average CGM glucose, and the ingested carbohydrate to injected insulin ratio were compared between the paired sessions through regression. In 9 of 12 races studied, an elevated CGM for the race over the individual training session was observed. The rate of change of the CGM during the first 30 minutes of exercise notably differed between the race and training (p = 0.02) with a less rapid decline in CGM occurring during the race for 11 of 12 paired sessions and an increasing CGM trend during the race for 7 of the 12 sessions with the rate of change (mean ± standard deviation) as 1.36 ± 6.07 and -2.59 ± 2.68 mg/dL per 5 minutes for the race and training, respectively. Individuals with longer durations of diabetes often decreased their carbohydrate-to-insulin ratio on race day, taking more insulin, than on the training day while the reverse was noted for those newly diagnosed (r = -0.52, p = 0.05). The presence of athletic competition stress can impact glycemia. With an increasing duration of diabetes, the athletes may be expecting elevated competition glucose concentrations and take preventive measures.
CircFGGY Inhibits Cell Growth, Invasion and Epithelial-Mesenchymal Transition of Hepatocellular Carcinoma via Regulating the miR-545-3p/Smad7 Axis
Authors: Feng Kun-Liang , Diao Na , Zhou Zhai-Wen , Fang Chong-Kai , Wang Ji-Nan , Zhang Ying , Luo Rui , Zhong Chong
Published: May 2022

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death worldwide. Circular RNAs (circRNAs) play critical roles in the progression of HCC. However, the role of the newly identified circFGGY (hsa_circ_0006633) in the development and progression of HCC has not been explored. In this study, we found that circFGGY was significantly downregulated in tumor compared with that in adjacent normal liver tissues of patients with HCC. HCC patients with low circFGGY expression had poor overall survival after hepatectomy. Moreover, it was found that circFGGY could inhibit the proliferation, invasion and epithelial-mesenchymal transition of HCC both in vivo and in vitro. Mechanistically, circFGGY promoted the expression of Smad7, a well-known suppressor of the transforming growth factor-β signaling pathway. In addition, miR-545-3p, a tumor promoter targeting both circFGGY and Smad7, suppressed the upregulation of Smad7 caused by circFGGY overexpression. Collectively, our data revealed that circFGGY inhibits the proliferation and invasion of HCC cells by sponging miR-545-3p and promote the expression of Smad7, indicating that circFGGY functions as a tumor suppressor and could be a prognostic biomarker for HCC.
Enhanced Antifungal and Wound Healing Efficacy of Statistically Optimized, Physicochemically Evaluated Econazole-Triamcinolone Loaded Silica Nanoparticles
Authors: Maheen Safirah , Younis Hina , Khan Hafeez Ullah , Salman shafqat Syed , Ali Sajed , Rehman Atta Ur , Ilyas Saliha , Zafar Muhammad Nadeem , Shafqat Syed Rizwan , Kalam Abul , Al-Ghamdi Ahmed A.
Published: May 2022

Co-encapsulated econazole nitrate-triamcinolone acetonide loaded biocompatible, physically stable, and non-irritating mesoporous silica nanoparticles (EN-TA–loaded MSNs) were prepared and optimized by using a central composite rotatable design (CCRD) for providing better therapeutic efficacy against commonly prevailed resistant fungal infections. These drugs loaded MSNs can significantly overcome the deficiencies and problems like short duration of action, requirement of frequent administration, erythema, and burning sensation and irritation associated with conventional drug delivery systems. The stability of optimized drugs loaded MSNs prepared with 100 gm of oil at pH 5.6 with a stirring time of 2 h was confirmed from a zeta potential value of −25 mV. The remarkable compatibility of formulation ingredients was depicted by X-ray diffraction (XRD), differential scanning calorimetry (DSC), and Fourier transform infrared spectroscopy (FTIR) spectra while scanning electron microscopy (SEM) and size analysis represented a very fine size distribution of nanoparticles ranging from 450–600 nm. The CCRD clearly predicted that the optimized parameters of drugs loaded MSNs have better values of percentage yield (85%), EN release (68%), and TA release (70%). Compared to pure drugs, the decreased cytotoxicity of EN-TA–loaded MSNs was quite evident because they showed a cell survival rate of 90%, while in the case of pure drugs, the survival rate was 85%. During in vivo antifungal testing against Candida albicans performed on three different groups, each consisting of six rabbits, the EN-TA–loaded MSNs were relatively superior in eradicating the fungal infection as a single animal exhibited a positive culture test. Rapid recovery of fungal infection and a better therapeutic effect of EN-TA–loaded MSN were quite evident in wound healing and histopathology studies. Likewise, on the 14th day, a larger inhibitory zone was measured for optimized nanoparticles (15.90 mm) compared to the suspension of pure drugs (13.90 mm). In skin irritation studies, MSNs did not show a grade of erythema compared to pure drugs, which showed a four-fold grade of erythema. As a result, MSNs loaded with combination therapy seem to have the potential of improving patient compliance and tolerability by providing enhanced synergistic antifungal effectiveness at a reduced dose with accelerated wound healing and reduced toxicity of therapeutics.
Meroterpenoid Dimers from Ganoderma Mushrooms and Their Biological Activities Against Triple Negative Breast Cancer Cells
Authors: Qin Fu-Ying , Chen Yan-Yi , Zhang Jiao-Jiao , Cheng Yong-Xian
Published: May 2022

(±)-Dimercochlearlactones A−J (1–10), ten pairs of novel meroterpenoid dimers and one known spirocochlealactone A (11), were isolated from Ganoderma mushrooms. The structural elucidation of new compounds, including their absolute configurations, depends on spectroscopic analysis and electronic circular dichroism (ECD) calculations. Biological studies showed that (+)- and (–)-2, (–)-3, and (+)- and (–)-11 are cytotoxic toward human triple negative breast cancer (TNBC) cells (MDA-MB-231) with IC50 values of 28.18, 25.65, 11.16, 8.18, and 13.02 μM, respectively. Wound healing assay revealed that five pairs of meroterpenoids (±)-5−(±)-8 and (±)-10 could significantly inhibit cell mobility at 20 μM in MDA-MB-231 cells. The results provide a new insight into the biological role of Ganoderma meroterpenoids in TNBC.
Predictors of Rehabilitation Referral Among Cardiovascular Surgical Patients
Authors: Gómez González Laura , Supervia Marta , Medina-Inojosa José R. , Smith Joshua R. , López Blanco M. Esther , Miranda Vivas M. Teresa , López-Jiménez Francisco , Arroyo-Riaño M. Olga
Published: May 2022

Objective

Cardiovascular disease (CVD) continues to be the leading cause of mortality globally. Cardiac rehabilitation (CR) programs act by modifying the evolution of CVD and mortality; however, CR programs are under-used. The aim was to determine the profile of patients that received rehabilitation after cardiac surgery.

Patients and Methods

A retrospective observational study was conducted from January 2017 to December 2017 at a single center. The study sample was chosen among patients admitted to the Intensive Care Unit of the Hospital Gregorio Marañón/Gregorio Marañón General University Hospital. Socio-demographic and clinical variables were collected.

Results

In the present study, 336 patients underwent cardiac surgery of which 63.8% were men and 87.1% had ≥1 cardiovascular risk factors. Of the total cohort, 24.7% were operated for ischemic heart disease, 47.9% valvulopathy, 11% underwent combined surgery, 3.6% cardiac transplantation, 6.5% aneurysms, and 3.9% congenital disease. In-hospital respiratory rehabilitation was prescribed to all patients. Only 4.8% of the patients received motor rehabilitation and 13.8% were referred to CR. We found higher referral rates among patients with more cardiovascular risk factors, <65 years of age, and those undergoing coronary surgery and heart transplantation. Age, ischemic heart disease, and overweight were independent predictors of CR referral.

Conclusion

The benefit of CR programs after cardiac surgery is widely described; however, the referral rate to CR remains low. It is crucial to optimize referral protocols for these patients.
Cohort Study Examining the Association of Optimal Blood Pressure Control at Entry With Infrarenal Abdominal Aortic Aneurysm Growth
Authors: Thomas Manapurathe Diana , Moxon Joseph Vaughan , Krishna Smriti Murali , Quigley Frank , Bourke Michael , Bourke Bernard , Jones Rhondda E. , Golledge Jonathan
Published: May 2022

Background and Aim

The benefit of controlling cardiovascular risk factors in slowing the progression of small abdominal aortic aneurysm (AAA) is controversial. This study investigated the association of optimal blood pressure control at entry with the growth of small AAA.

Methods and Results

A total of 1,293 patients with initial AAA diameter <50 mm were followed by a median 5 (inter-quartile range, IQR, 3–7) ultrasound scans for a median of 3.6 years (IQR 1.8, 5.3). Optimal blood pressure control was defined as blood pressure ≤140/90 mmHg at recruitment. The association of optimal blood pressure control at entry with AAA growth was assessed using linear mixed effects models adjusted for established risk factors of AAA growth and factors which were unequally distributed among the blood pressure groups. Optimal blood pressure control at entry was not significantly associated with AAA growth. In the risk factor adjusted model the mean difference in AAA growth between blood pressure groups was 0.04 mm/year (95% CI −0.20, 0.13; p = 0.65). The results were similar in sensitivity analyses excluding outliers or focused on systolic or diastolic blood pressure alone.

Conclusions

This observational study suggests that optimal blood pressure control at entry is not associated with slower AAA growth.
Surgical Repair of a Quadricuspid Aortic Valve With Severe Regurgitation Utilizing “Tricuspidization” and Annular Banding: A Case and Technique Details Report
Authors: Yu Yang , Huang Ruixuan , Ding Zheng , Shi Enyi , Gu Tianxiang
Published: May 2022

The quadricuspid aortic valve (QAV) is a rare congenital disease with a prevalence of 0. 013–0.043% of cardiac cases. Most patients with QAV are treated with aortic valve replacement. A Type B QAV with dilated ascending aorta of 47.9 mm; combined with severe regurgitation is reported here. In this case, considering the patient‘s cusps are flexible and reservable, the aortic root was reconstructed utilizing tricuspidization and annular banding technique, and dilated ascending aorta was replaced at the same time.
Sediment Microstructure in Gas Hydrate Reservoirs and its Association With Gas Hydrate Accumulation: A Case Study From the Northern South China Sea
Authors: Bai Chenyang , Su Pibo , Su Xin , Guo Jujie , Cui Hongpeng , Han Shujun , Zhang Guangxue
Published: May 2022

Exploration and pilot production have confirmed that gas hydrates in the Shenhu area on the northern continental slope of the South China Sea have enormous resource potential. However, a meticulous depiction of gas hydrate reservoirs based on sediments is limited. The distributed low-flux gas hydrates are mainly deposited in the Shenhu area, and the gas hydrate saturation exhibits extreme vertical heterogeneity. In this study, we focused on the sediment microstructure of gas hydrate reservoirs. Based on the variation in gas hydrate saturation, the study interval was divided into non-gas hydrate (non-GH) as well as I-, II-, and III-gas hydrate reservoir layers. We analyzed the relationship between sediment microstructure and gas hydrate reservoirs based on computed tomography scans, specific surface area analysis, and scanning electron microscopy observations. The results showed that the sediment in gas hydrate reservoirs had three types of pores: 1) intergranular pores between coarse grains (CG-intergranular pores), 2) intergranular pores between fine grains (FG-intergranular pores), and 3) biologic grain pores (BG-pores). The CG- and FG-intergranular pores were mainly formed by the framework, which consisted of coarse minerals (such as quartz and feldspar) and clay minerals, respectively. The BG-pores were mainly formed by the coelomes of foraminifera. CG-intergranular pores and BG-pores can provide effective reservoir space and increase the permeability of sediment, which is conducive to gas hydrate accumulation. The FG-intergranular pores reduce permeability and are not conducive to gas hydrate accumulation. Clay minerals and calcareous ultramicrofossils with small grain sizes and complex microstructures fill the effective reservoir space and reduce the permeability of sediment; additionally, they improve the adsorption capacity of sediment to free gas or pore water, which is not conducive to gas hydrate formation and accumulation. The results of our study explicitly suggest that the microstructure of sediment is an important controlling factor for gas hydrate accumulation and reveals its underlying mechanism.
Middle Miocene-Pleistocene Magneto-Cyclostratigraphy from IODP Site U1501 in the Northern South China Sea
Authors: Shi Meinan , Wu Huaichun , Ferré Eric C. , Satolli Sara , Fang Qiang , Nie Yunfeng , Qin Yuhe , Zhang Shihong , Yang Tianshui , Li Haiyan
Published: May 2022

Site U1501 of International Ocean Discovery Program (IODP) Expedition 368 locates on a broad regional basement high in the northern margin of the South China Sea (SCS). This study refines the chronostratigraphy of the upper 160 m sedimentary succession from Hole U1501C using paleomagnetic measurements and cyclostratigraphic analysis on the Natural Gamma Radiation (NGR) data. Rock magnetic analysis displays that the magnetic signal of the sediments is mainly carried by single-domain (SD) and multi-domain (MD) magnetite. A total of 12 geomagnetic reversals are identified and correlated to the geomagnetic polarity time scale (GPTS) in Geologic Time Scale 2020 (GTS 2020), combining biostratigraphic data and planktonic foraminiferal oxygen records. The Milankovitch cycles of 405-kyr long orbital eccentricity, ∼100-kyr short orbital eccentricity, and obliquity cycles are identified in the NGR profile. A 15.54 Myr astronomical time scale is constructed by tuning the short eccentricity cycles filtered from the NGR profiles to the La2010 astronomical solution with the constraints of the magnetostratigraphic results, biostratigraphic age datum and planktonic foraminiferal oxygen records. This new high-resolution age model provides a new temporal constraint on the tectonic and paleoenvironmental evolution in the South China Sea.
An Overview of Multi-Energy Microgrid in All-Electric Ships
Authors: Huang Yuqing , Wang Liangxiu , Zhang Yuanwei , Wang Le , Zhao Zhangfei
Published: May 2022

Owing to the severe fossil energy shortage and carbon pollution, the extensive electrification of maritime transportation, represented by all-electric ships (AESs), has become an appealing solution to increase the efficiency and environmental friendliness of the industry. To improve energy utilization, not only renewable energy but also thermal energy has been introduced is used in AESs. However, various uncertainties that are associated with renewable energy and ship motions significantly inhibit and complicate the operation and navigation of multi-energy shipboard microgrids. Accordingly, a new coordination of optimal energy management and voyage scheduling is important in reducing both the costs and emissions of AESs. This overview characterizes shipboard microgrids and several emerging technical challenges related to joint power and voyage scheduling, and elucidates prospects for further research, based on a comprehensive survey of the relevant literature.
Decoupling Institutional Pressure on Green Supply Chain Management Efforts to Boost Organizational Performance: Moderating Impact of Big Data Analytics Capabilities
Authors: Shahzad Fakhar , Du Jianguo , Khan Imran , Wang Jian
Published: May 2022

This paper aims to empirically examine the impact of institutional pressure on green supply chain management (GSCM) efforts and the moderating role of big data analytics capabilities (BDAC) on organizational performance. This study greatly develops a research model by integrating institutional theory, the natural resource-based view (NRBV), and dynamic capability theory to explore this relationship. This article is based on structured questionnaire data of 347 supply chain personnel. We employed structural equation modeling to verify the research hypotheses. The findings provide empirical support for institutional pressures affecting GSCM efforts and organizational performance. The results also showed that the moderating effect of BDAC positively strengthened the impact of GSCM effort on organizational performance. The findings extend and refine the existing GSCM literature, providing new insights for scholars to explore this view further. Practitioners can turn their attention to incorporating institutional pressures and advanced technologies into organizational decision-making, even in times of crisis such as Covid-19.
The Variation of Functional Traits in Leaves and Current-Year Twigs of Quercus aquifolioides Along an Altitudinal Gradient in Southeastern Tibet
Authors: Zhang Xinsheng , Wang Chao , Zhou Chenni
Published: May 2022

Clarifying the adaptation mechanism of alpine plants to climate or habitat under the alpine environmental gradient on the Qinghai–Tibet Plateau is substantially important to understand the their geography in alpine regions and their responses to future climate change. The spatial distribution characteristics of functional traits in leaves and current-year twigs of Quercus aquifolioides on five consecutive altitudinal gradients in Southeastern Tibet were analyzed. The relationship between the functional traits and habitat factors (topographic and soil factors) was explored. Key results: the functional traits of leaves and current-year twigs of Quercus aquifolioides in Southeastern Tibet showed significant linear variations along the altitudinal gradients (p < 0.001). Quercus aquifolioides at low altitudes tended to have shorter current-year twigs and less leaves with larger LA (leaf area) and higher RWC (relative water content) than those at high altitudes. Strong trade-off and coordination relationship were found between the functional traits of leaves and those of current-year twigs, respectively. SL (slope) and TN (total nitrogen) contributed the most to leaf functional traits (p < 0.05); AL (altitude) was the main determinant of functional traits in current-year twigs of Quercus aquifolioides in southeast Tibet. In conclusion, our observation demonstrate that the ecological adaptation strategy of Quercus aquifolioides was formed through the trade-off mechanism among various functional traits, the variation of hydrothermal conditions and soil environmental factors caused by altitude in the alpine region lead to differences in functional traits of Quercus aquifolioides along an altitudinal gradient in southeast Tibet.
Genetic and Biological Effects of SLC12A3, a Sodium-Chloride Cotransporter, in Gitelman Syndrome and Diabetic Kidney Disease
Authors: Li Nan , Gu Harvest F.
Published: May 2022

The SLC12A3 (Solute carrier family 12 member 3) gene encodes a sodium-chloride cotransporter and mediates Na+ and Cl− reabsorption in the distal convoluted tubule of kidneys. An experimental study has previously showed that with knockdown of zebrafish ortholog, slc12a3 led to structural abnormality of kidney pronephric distal duct at 1-cell stage, suggesting that SLC12A3 may have genetic effects in renal disorders. Many clinical reports have demonstrated that the function-loss mutations in the SLC12A3 gene, mainly including Thr60Met, Asp486Asn, Gly741Arg, Leu859Pro, Arg861Cys, Arg913Gln, Arg928Cys and Cys994Tyr, play the pathogenic effects in Gitelman syndrome. This kidney disease is inherited as an autosomal recessive trait. In addition, several population genetic association studies have indicated that the single nucleotide variant Arg913Gln in the SLC12A3 gene is associated with diabetic kidney disease in type 2 diabetes subjects. In this review, we first summarized bioinformatics of the SLC12A3 gene and its genetic variation. We then described the different genetic and biological effects of SLC12A3 in Gitelman syndrome and diabetic kidney disease. We also discussed about further genetic and biological analyses of SLC12A3 as pharmacokinetic targets of diuretics.
Rituximab - Progress but Still Not a Final Resolution for Pemphigus Patients: Clinical Report From a Single Center Study
Authors: Miše Joško , Jukić Ines Lakoš , Marinović Branka
Published: May 2022

Pemphigus is a rare autoimmune disease characterized by the production of pathogenic autoantibodies against desmosomal adhesion proteins, desmoglein 1 and 3. The pathophysiological process leads to the development of blisters and erosions on mucosal and/or skin surfaces as the main clinical manifestation of the disease. Rituximab emerged as the first-line therapeutic option for pemphigus due to its ability to induce remission by depleting peripheral B lymphocytes. Our aim was to assess the efficacy of rituximab in the treatment of patients in Croatia. A single-center, retrospective study was conducted on 19 patients treated with rituximab following a rheumatoid arthritis dosing protocol between October 2015 and March 2021, with a mean follow-up of 24.1 months. After the first rituximab cycle, two patients achieved complete remission off therapy (10.5%), and six patients achieved complete remission on minimal therapy (31.6%). Partial remission was observed among ten patients (52.6%). Eight patients (44.4%) relapsed after the first rituximab cycle. The mean relapse time was 21 months. Seven patients received two rituximab cycles, and three patients received three cycles. Overall, 13 out of 19 patients experienced complete remission at some point during the study, while there were no non-responders after the rituximab treatment. No statistically significant associations were observed between age, sex, type of disease involvement and clinical remission, either on or off therapy. A steady decrease in anti-desmoglein 1 and anti-desmoglein 3 levels was measured among all patients following rituximab treatment. One patient experienced a treatment-related adverse event of infectious etiology (cellulitis). One patient died following the first rituximab cycle, with the cause of death likely not to be associated with the treatment. Rituximab is an effective disease-modifying agent in the treatment of pemphigus with the main benefit of reducing corticosteroid exposure and steroid-related side effects among pemphigus patients. However, a feature of rituximab therapy is high relapse rates and the need for repeated treatment cycles to achieve complete remission. Developing an optimal protocol for rituximab treatment and finding suitable markers for predicting relapse will improve the management of pemphigus patients.
Interfacial Behavior of the Steel–UHPC Composite Deck With Toughened Epoxy Bonding
Authors: Jiang Jinlong , Leng Jingchen , Zhang Jiangtao , Guo Jincen
Published: May 2022

Using traditional stud connectors to connect the ultra-high-performance concrete layer and steel deck is detrimental to the construction speed and fatigue performance of the composite structure. Connecting the steel–UHPC interface with toughened epoxy bonding is a potential alternative to avoid this issue. To explore whether the toughened epoxy bonding interface can reduce the amount of bridge deck studs or even cancel the studs, a numerical simulation was conducted in this paper. The non-toughened epoxy bonding interface, the toughened epoxy bonding interface, a few studs + toughened epoxy bonding interface, and the full stud connection interface were designed to study the interfacial behavior of the steel–UHPC composite deck. Moreover, the constitutive model of the toughened epoxy bonding interface is verified through the direct shear test and compression-shear test. The results show that the maximum interface shear stress of the toughened epoxy bonding interface is 0.61 MPa under the standard wheel load, which is 20.78% lower than that of the non-toughened epoxy bonding interface. Under the overload, the interface failure of the toughened epoxy bonding interface is more concentrated and exhibits a smaller damage area compared with the non-toughened epoxy bonding interface. When the interface defect is 5%, the toughened epoxy bonding interface only has a few interface damages, exhibiting good defect tolerance. Compared to the traditional full stud connection interface, the interface shear stress in the few studs + toughened epoxy bonding interface is more uniform, which avoids the stress concentration in the root of studs, and the studs’ average stress is significantly reduced by 63.21%. It is verified that using the toughened epoxy bonding interface can significantly reduce the amount of studs.
Discovery of Tick-Borne Karshi Virus Implies Misinterpretation of the Tick-Borne Encephalitis Virus Seroprevalence in Northwest China
Authors: Bai Yuan , Zhang Yanfang , Su Zhengyuan , Tang Shuang , Wang Jun , Wu Qiaoli , Yang Juan , Moming Abulimiti , Zhang Yujiang , Bell-Sakyi Lesley , Sun Surong , Shen Shu , Deng Fei
Published: May 2022

Despite few human cases of tick-borne encephalitis virus (TBEV), high rates of TBEV seroprevalence were reported among humans and animals in Xinjiang Uygur Autonomous Region in Northwestern China. In this study, the Karshi virus (KSIV) was identified and isolated from Hyalomma asiaticum ticks in Xinjiang. It belongs to the genus Flavivirus of the family Flaviviridae and is closely related to TBEV. KSIV infects cell lines from humans, other mammals and ticks, and causes encephalitis in suckling mice. High minimum infection rates (4.96%) with KSIV were detected among tick groups. KSIV infections have occurred in sheep and marmots, resulting in antibody-positive rates of 2.43 and 2.56%, respectively. We further found that, of the KSIV antibody-positive serum samples from animals, 13.9% had TBEV exposure showing cross-reaction to KSIV, and 11.1% had KSIV infection resulting in cross-reaction to TBEV; 8.3% were likely to have co-exposure to both viruses (or may be infected with one of them and present cross-reactivity with the other). The results revealed a substantial KSIV prevalence among ticks in Xinjiang, indicating exposure of animals to KSIV and TBEV. The findings implied misinterpretation of the high rates of TBEV seroprevalence among humans and animals in previous studies. There is a need to develop detection methods to distinguish KSIV from TBEV and to perform an in-depth investigation of KSIV and TBEV prevalence and incidence in Northwestern China, which would enhance our preparation to provide medical treatment of emerging diseases caused by tick-borne viral pathogens such as KSIV.
Alterations of Lysine Acetylation Profile in Murine Skeletal Muscles Upon Exercise
Authors: Liang Dehuan , Chen Cheng , Huang Song , Liu Sujuan , Fu Li , Niu Yanmei
Published: May 2022

Objective

Regular exercise is a powerful tool that enhances skeletal muscle mass and strength. Lysine acetylation is an important post-translational modification (PTM) involved in a broad array of cellular functions. Skeletal muscle protein contains a considerable number of lysine-acetylated (Kac) sites, so we aimed to investigate the effects of exercise-induced lysine acetylation on skeletal muscle proteins.

Methods

We randomly divided 20 male C57BL/6 mice into exercise and control groups. After 6 weeks of treadmill exercise, a lysine acetylation proteomics analysis of the gastrocnemius muscles of mice was performed.

Results

A total of 2,254 lysine acetylation sites in 693 protein groups were identified, among which 1,916 sites in 528 proteins were quantified. The enrichment analysis suggested that protein acetylation could influence both structural and functional muscle protein properties. Moreover, molecular docking revealed that mimicking protein deacetylation primarily influenced the interaction between substrates and enzymes.

Conclusion

Exercise-induced lysine acetylation appears to be a crucial contributor to the alteration of skeletal muscle protein binding free energy, suggesting that its modulation is a potential approach for improving exercise performance.
Neuroimmune Crosstalk Between the Peripheral and the Central Immune System in Amyotrophic Lateral Sclerosis
Authors: Yu Weiyi , He Ji , Cai Xiying , Yu Zhou , Zou Zhangyu , Fan Dongsheng
Published: May 2022

Amyotrophic lateral sclerosis (ALS) is a fatal disease characterized by the degeneration and death of motor neurons. Systemic neuroinflammation contributes to the pathogenesis of ALS. The proinflammatory milieu depends on the continuous crosstalk between the peripheral immune system (PIS) and central immune system (CIS). Central nervous system (CNS) resident immune cells interact with the peripheral immune cells via immune substances. Dysfunctional CNS barriers, including the blood–brain barrier, and blood–spinal cord barrier, accelerate the inflammatory process, leading to a systemic self-destructive cycle. This review focuses on the crosstalk between PIS and CIS in ALS. Firstly, we briefly introduce the cellular compartments of CIS and PIS, respectively, and update some new understanding of changes specifically occurring in ALS. Then, we will review previous studies on the alterations of the CNS barriers, and discuss their crucial role in the crosstalk in ALS. Finally, we will review the moveable compartments of the crosstalk, including cytokines, chemokines, and peripheral immune cells which were found to infiltrate the CNS, highlighting the interaction between PIS and CIS. This review aims to provide new insights into pathogenic mechanisms and innovative therapeutic approaches for ALS.
Sex-Specific Brain Transcriptional Signatures in Human MDD and Their Correlates in Mouse Models of Depression
Authors: Touchant Maureen , Labonté Benoit
Published: May 2022

Major depressive disorder (MDD) is amongst the most devastating psychiatric conditions affecting several millions of people worldwide every year. Despite the importance of this disease and its impact on modern societies, still very little is known about the etiological mechanisms. Treatment strategies have stagnated over the last decades and very little progress has been made to improve the efficiency of current therapeutic approaches. In order to better understand the disease, it is necessary for researchers to use appropriate animal models that reproduce specific aspects of the complex clinical manifestations at the behavioral and molecular levels. Here, we review the current literature describing the use of mouse models to reproduce specific aspects of MDD and anxiety in males and females. We first describe some of the most commonly used mouse models and their capacity to display unique but also shared features relevant to MDD. We then transition toward an integral description, combined with genome-wide transcriptional strategies. The use of these models reveals crucial insights into the molecular programs underlying the expression of stress susceptibility and resilience in a sex-specific fashion. These studies performed on human and mouse tissues establish correlates into the mechanisms mediating the impact of stress and the extent to which different mouse models of chronic stress recapitulate the molecular changes observed in depressed humans. The focus of this review is specifically to highlight the sex differences revealed from different stress paradigms and transcriptional analyses both in human and animal models.
Movie Events Detecting Reveals Inter-Subject Synchrony Difference of Functional Brain Activity in Autism Spectrum Disorder
Authors: Ou Wenfei , Zeng Wenxiu , Gao Wenjian , He Juan , Meng Yufei , Fang Xiaowen , Nie Jingxin
Published: May 2022

Recently, movie-watching fMRI has been recognized as a novel method to explore brain working patterns. Previous researchers correlated natural stimuli with brain responses to explore brain functional specialization by “reverse correlation” methods, which were based on within-group analysis. However, what external stimuli drove significantly different brain responses in two groups of different subjects were still unknown. To address this, sliding time windows technique combined with inter-Subject functional correlation (ISFC) was proposed to detect movie events with significant group differences between autism spectrum disorder (ASD) and typical development (TD) subjects. Then, using inter-Subject correlation (ISC) and ISFC analysis, we found that in three movie events involving character emotions, the ASD group showed significantly lower ISC in the middle temporal gyrus, temporal pole, cerebellum, caudate, precuneus, and showed decreased functional connectivity between large scale networks than that in TD. Under the movie event focusing on objects and scenes shot, the dorsal and ventral attentional networks of ASD had a strong synchronous response. Meanwhile, ASD also displayed increased functional connectivity between the frontoparietal network (FPN) and dorsal attention network (DAN), FPN, and sensorimotor network (SMN) than TD. ASD has its own unique synchronous response rather than being “unresponsive” in natural movie-watching. Our findings provide a new method and valuable insight for exploring the inconsistency of the brain “tick collectively” to same natural stimuli. This analytic approach has the potential to explore pathological mechanisms and promote training methods of ASD.
The Reconstruction of Causal Networks in Physiology
Authors: Günther Moritz , Kantelhardt Jan W. , Bartsch Ronny P.
Published: May 2022

We systematically compare strengths and weaknesses of two methods that can be used to quantify causal links between time series: Granger-causality and Bivariate Phase Rectified Signal Averaging (BPRSA). While a statistical test method for Granger-causality has already been established, we show that BPRSA causality can also be probed with existing statistical tests. Our results indicate that more data or stronger interactions are required for the BPRSA method than for the Granger-causality method to detect an existing link. Furthermore, the Granger-causality method can distinguish direct causal links from indirect links as well as links that arise from a common source, while BPRSA cannot. However, in contrast to Granger-causality, BPRSA is suited for the analysis of non-stationary data. We demonstrate the practicability of the Granger-causality method by applying it to polysomnography data from sleep laboratories. An algorithm is presented, which addresses the stationarity condition of Granger-causality by splitting non-stationary data into shorter segments until they pass a stationarity test. We reconstruct causal networks of heart rate, breathing rate, and EEG amplitude from young healthy subjects, elderly healthy subjects, and subjects with obstructive sleep apnea, a condition that leads to disruption of normal respiration during sleep. These networks exhibit differences not only between different sleep stages, but also between young and elderly healthy subjects on the one hand and subjects with sleep apnea on the other hand. Among these differences are 1) weaker interactions in all groups between heart rate, breathing rate and EEG amplitude during deep sleep, compared to light and REM sleep, 2) a stronger causal link from heart rate to breathing rate but disturbances in respiratory sinus arrhythmia (breathing to heart rate coupling) in subjects with sleep apnea, 3) a stronger causal link from EEG amplitude to breathing rate during REM sleep in subjects with sleep apnea. The Granger-causality method, although initially developed for econometric purposes, can provide a quantitative, testable measure for causality in physiological networks.
Perivascular Spaces, Glymphatic System and MR
Authors: Yu Linya , Hu Xiaofei , Li Haitao , Zhao Yilei
Published: May 2022

The importance of the perivascular space (PVS) as one of the imaging markers of cerebral small vessel disease (CSVD) has been widely appreciated by the neuroradiologists. The PVS surrounds the small blood vessels in the brain and has a signal consistent with the cerebrospinal fluid (CSF) on MR. In a variety of physio-pathological statuses, the PVS may expand. The discovery of the cerebral glymphatic system has provided a revolutionary perspective to elucidate its pathophysiological mechanisms. Research on the function and pathogenesis of this system has become a prevalent topic among neuroradiologists. It is now believed that this system carries out the similar functions as the lymphatic system in other parts of the body and plays an important role in the removal of metabolic waste and the maintenance of homeostatic fluid circulation in the brain. In this article, we will briefly describe the composition of the cerebral glymphatic system, the influencing factors, the MR manifestations of the PVS and the related imaging technological advances. The aim of this research is to provide a reference for future clinical studies of the PVS and glymphatic system.
Early Life Sleep Deprivation and Brain Development: Insights From Human and Animal Studies
Authors: Alrousan Ghalya , Hassan Arham , Pillai Aditya Anilkumar , Atrooz Fatin , Salim Samina
Published: May 2022

Adequate sleep especially during developmental stages of life, is considered essential for normal brain development and believed to play an important role in promoting healthy cognitive and psychosocial development, while persistent sleep disturbances and/or sleep deprivation during early life are believed to trigger many mental ailments such as anxiety disorders, depression, and cognitive impairment. Initially it was suggested that adverse mental health conditions adversely affect sleep, however, it is now accepted that this association is bidirectional. In fact, sleep disturbances are listed as a symptom of many mental health disorders. Of special interest is the association between early life sleep deprivation and its negative mental health outcomes. Studies have linked persistent early life sleep deprivation with later life behavioral and cognitive disturbances. Neurobiological underpinnings responsible for the negative outcomes of early life sleep deprivation are not understood. This is a significant barrier for early therapeutic and/or behavioral intervention, which can be feasible only if biological underpinnings are well-understood. Animal studies have provided useful insights in this area. This article focusses on the knowledge gained from the research conducted in the area of early life sleep deprivation, brain development, and behavioral function studies.
α-Synuclein Impacts on Intrinsic Neuronal Network Activity Through Reduced Levels of Cyclic AMP and Diminished Numbers of Active Presynaptic Terminals
Authors: Leite Kristian , Garg Pretty , Spitzner F. Paul , Guerin Darvas Sofia , Bähr Mathias , Priesemann Viola , Kügler Sebastian
Published: May 2022

α-synuclein (α-Syn) is intimately linked to synucleinopathies like Parkinson’s disease and dementia with Lewy bodies. However, the pathophysiological mechanisms that are triggered by this protein are still largely enigmatic. α-Syn overabundance may cause neurodegeneration through protein accumulation and mitochondrial deterioration but may also result in pathomechanisms independent from neuronal cell death. One such proposed pathological mechanism is the influence of α-Syn on non-stimulated, intrinsic brain activity. This activity is responsible for more than 90% of the brain’s energyconsumption, and is thus thought to play an eminent role in basic brain functionality. Here we report that α-Syn substantially disrupts intrinsic neuronal network burst activity in a long-term neuronal cell culture model. Mechanistically, the impairment of network activity originates from reduced levels of cyclic AMP and cyclic AMP-mediated signaling as well as from diminished numbers of active presynaptic terminals. The profound reduction of network activity due to α-Syn was mediated only by intracellularly expressed α-Syn, but not by α-Syn that is naturally released by neurons. Conversely, extracellular pre-formed fibrils of α-Syn mimicked the effect of intracellular α-Syn, suggesting that they trigger an off-target mechanism that is not activated by naturally released α-Syn. A simulation-based model of the network activity in our cultures demonstrated that even subtle effect sizes in reducing outbound connectivity, i.e., loss of active synapses, can cause substantial global reductions in non-stimulated network activity. These results suggest that even low-level loss of synaptic output capabilities caused by α-Syn may result in significant functional impairments in terms of intrinsic neuronal network activity. Provided that our model holds true for the human brain, then α-Syn may cause significant functional lesions independent from neurodegeneration.
The ERG1 K+ Channel and Its Role in Neuronal Health and Disease
Authors: Sanchez-Conde Francisco G. , Jimenez-Vazquez Eric N. , Auerbach David S. , Jones David K.
Published: May 2022

The ERG1 potassium channel, encoded by KCNH2, has long been associated with cardiac electrical excitability. Yet, a growing body of work suggests that ERG1 mediates physiology throughout the human body, including the brain. ERG1 is a regulator of neuronal excitability, ERG1 variants are associated with neuronal diseases (e.g., epilepsy and schizophrenia), and ERG1 serves as a potential therapeutic target for neuronal pathophysiology. This review summarizes the current state-of-the-field regarding the ERG1 channel structure and function, ERG1’s relationship to the mammalian brain and highlights key questions that have yet to be answered.