bluuebunny/crossref_metadata_2025 huggingface dataset:
FUNDC1: A Promising Mitophagy Regulator at the Mitochondria-Associated Membrane for Cardiovascular Diseases
Authors: Li Guoyong , Li Junli , Shao Ruochen , Zhao Jiahao , Chen Mao
Published: December 2021

Mitochondrial autophagy (or mitophagy) regulates the mitochondrial network and function to contribute to multiple cellular processes. The protective effect of homeostatic mitophagy in cardiovascular diseases (CVDs) has attracted increasing attention. FUN14 domain containing 1 (FUNDC1), an identified mitophagy receptor, plays an essential role in CVDs. Different expression levels of FUNDC1 and its phosphorylated state at different sites alleviate or exacerbate hypoxia and ischemia/reperfusion injury, cardiac hypertrophy, or metabolic damage through promotion or inhibition of mitophagy. In addition, FUNDC1 can be enriched at contact sites between mitochondria and the endoplasmic reticulum (ER), determining the formation of mitochondria-associated membranes (MAMs) that regulate cellular calcium (Ca2+) homeostasis and mitochondrial dynamics to prevent heart dysfunction. Moreover, FUNDC1 has also been involved in inflammatory cardiac diseases such as septic cardiomyopathy. In this review, we collect and summarize the evidence on the roles of FUNDC1 exclusively in various CVDs, describing its interactions with different cellular organelles, its involvement in multiple cellular processes, and its associated signaling pathways. FUNDC1 may become a promising therapeutic target for the prevention and management of various CVDs.
Targeting Programmed Cell Death to Improve Stem Cell Therapy: Implications for Treating Diabetes and Diabetes-Related Diseases
Authors: Zhang Qi , Wan Xin-xing , Hu Xi-min , Zhao Wen-juan , Ban Xiao-xia , Huang Yan-xia , Yan Wei-tao , Xiong Kun
Published: December 2021

Stem cell therapies have shown promising therapeutic effects in restoring damaged tissue and promoting functional repair in a wide range of human diseases. Generations of insulin-producing cells and pancreatic progenitors from stem cells are potential therapeutic methods for treating diabetes and diabetes-related diseases. However, accumulated evidence has demonstrated that multiple types of programmed cell death (PCD) existed in stem cells post-transplantation and compromise their therapeutic efficiency, including apoptosis, autophagy, necroptosis, pyroptosis, and ferroptosis. Understanding the molecular mechanisms in PCD during stem cell transplantation and targeting cell death signaling pathways are vital to successful stem cell therapies. In this review, we highlight the research advances in PCD mechanisms that guide the development of multiple strategies to prevent the loss of stem cells and discuss promising implications for improving stem cell therapy in diabetes and diabetes-related diseases.
Targeting Mitochondrial Metabolism and RNA Polymerase POLRMT to Overcome Multidrug Resistance in Cancer
Authors: Yu Hui-Jing , Xiao Guan-Li , Zhao Yu-Ying , Wang Xin-Xin , Lan Rongfeng
Published: December 2021

Clinically, the prognosis of tumor therapy is fundamentally affected by multidrug resistance (MDR), which is primarily a result of enhanced drug efflux mediated by channels in the membrane that reduce drug accumulation in tumor cells. How to restore the sensitivity of tumor cells to chemotherapy is an ongoing and pressing clinical issue. There is a prevailing view that tumor cells turn to glycolysis for energy supply due to hypoxia. However, studies have shown that mitochondria also play crucial roles, such as providing intermediates for biosynthesis through the tricarboxylic acid (TCA) cycle and a plenty of ATP to fuel cells through the complete breakdown of organic matter by oxidative phosphorylation (OXPHOS). High OXPHOS have been found in some tumors, particularly in cancer stem cells (CSCs), which possess increased mitochondria mass and may be depends on OXPHOS for energy supply. Therefore, they are sensitive to inhibitors of mitochondrial metabolism. In view of this, we should consider mitochondrial metabolism when developing drugs to overcome MDR, where mitochondrial RNA polymerase (POLRMT) would be the focus, as it is responsible for mitochondrial gene expression. Inhibition of POLRMT could disrupt mitochondrial metabolism at its source, causing an energy crisis and ultimately eradicating tumor cells. In addition, it may restore the energy supply of MDR cells to glycolysis and re-sensitize them to conventional chemotherapy. Furthermore, we discuss the rationale and strategies for designing new therapeutic molecules for MDR cancers by targeting POLRMT.
Humulane-Type Macrocyclic Sesquiterpenoids From the Endophytic Fungus Penicillium sp. of Carica papaya
Authors: Wang Fu-Run , Yang Li , Kong Fan-Dong , Ma Qing-Yun , Xie Qing-Yi , Wu You-Gen , Dai Hao-Fu , Chen Ping , Xiao Na , Zhao You-Xing
Published: December 2021

Three new humulane-type sesquiterpenoids, penirolide A (1), penirolide B (2), and 10-acetyl-phomanoxide (3), together with three known compounds aurasperone A (4), pughiinin A (5), and cyclo(l-Leu-l-Phe) (6) were isolated from the endophytic fungus Penicillium sp. derived from the leaves of Carica papaya L. Their structures including their absolute configurations were determined based on the analysis of NMR and HRESIMS spectra, NMR chemical shifts, and ECD calculations. Compounds 2, 3, 5, and 6 significantly inhibited glucagon-induced hepatic glucose production, with EC50 values of 33.3, 36.1, 18.8, and 32.1 μM, respectively. Further study revealed that compounds 2, 3, 5, and 6 inhibited hepatic glucose production by suppression of glucagon-induced cAMP accumulation.
Virtual Screening of TADF Emitters for Single-Layer OLEDs
Authors: Lin Kun-Han , Wetzelaer Gert-Jan A. H. , Blom Paul W. M. , Andrienko Denis
Published: December 2021

Thermally-activated delayed fluorescence (TADF) is a concept which helps to harvest triplet excitations, boosting the efficiency of an organic light-emitting diode. TADF can be observed in molecules with spatially separated donor and acceptor groups with a reduced triplet-singlet energy level splitting. TADF materials with balanced electron and hole transport are attractive for realizing efficient single-layer organic light emitting diodes, greatly simplifying their manufacturing and improving their stability. Our goal here is to computationally screen such materials and provide a comprehensive database of compounds with a range of emission wavelengths, ionization energies, and electron affinities.
Micro-/Nano-Structures Fabricated by Laser Technologies for Optoelectronic Devices
Authors: Yi Jian , Zhou Hao , Wei Wei-Hua , Han Xing-Chen , Han Dong-Dong , Gao Bing-Rong
Published: December 2021

Due to unique optical and electrical properties, micro-/nano-structures have become an essential part of optoelectronic devices. Here, we summarize the recent developments in micro-/nano-structures fabricated by laser technologies for optoelectronic devices. The fabrication of micro-/nano-structures by various laser technologies is reviewed. Micro-/nano-structures in optoelectronic devices for performance improvement are reviewed. In addition, typical optoelectronic devices with micro-nano structures are also summarized. Finally, the challenges and prospects are discussed.
Differential Antibody Response to Inactivated COVID-19 Vaccines in Healthy Subjects
Authors: Zhang Jiaqi , Xing Shan , Liang Dan , Hu Wei , Ke Changwen , He Jinyong , Yuan Runyu , Huang Yile , Li Yizhe , Liu Dongdong , Zhang Xuedong , Li Lin , Lin Jianhua , Li Weili , Teng Xiangyun , Liu Yijun , Wen Wei , Kang Qiang , Wang Dawei , Liu Wanli , Xu Jianhua
Published: December 2021

The appearance and magnitude of the immune response and the related factors correlated with SARS-CoV-2 vaccination need to be defined. Here, we enrolled a prospective cohort of 52 participants who received two doses of inactivated vaccines (BBIBP-CorV). Their serial plasma samples (n = 260) over 2 months were collected at five timepoints. We measured antibody responses (NAb, S-IgG and S-IgM) and routine blood parameter. NAb seroconversion occurred in 90.7% of vaccinated individuals and four typical NAb kinetic curves were observed. All of the participants who seroconverted after the first dose were females and had relatively high prevaccine estradiol levels. Moreover, those without seroconversion tended to have lower lymphocyte counts and higher serum SAA levels than those who experienced seroconversion. The NAb titers in young vaccine recipients had a significantly higher peak than those in elderly recipients. S-IgG and S-IgM dynamics were accompanied by similar trends in NAb. Here, we gained insight into the dynamic changes in NAbs and preliminarily explored the prevaccine blood parameters related to the kinetic subclasses, providing a reference for vaccination strategies.
Full-Length Transcriptome Sequencing: An Insight Into the Dog Model of Heart Failure
Authors: Liang Xiaoyan , Bai Zechen , Wang Feifei , Han Yafan , Sun Huaxin , Xiaokereti Jiasuoer , Zhang Ling , Zhou Xianhui , Lu Yanmei , Tang Baopeng
Published: December 2021

Heart failure (HF) leads to a progressive increase in morbidity and mortality rates. This study aimed to explore the transcriptional landscape during HF and identify differentially expressed transcripts (DETs) and alternative splicing events associated with HF. We generated a dog model of HF (n = 3) using right ventricular pacemaker implantation. We performed full-length transcriptome sequencing (based on nanopore platform) on the myocardial tissues and analyzed the transcripts using differential expression analysis and functional annotation methods [Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses]. Additionally, we estimated the expression of the selected genes by quantitative real-time PCR (qRT-PCR) and detected the proportion of immune cells using flow cytometry. We found that increased B-type natriuretic peptide reduced ejection fraction, and apparent clinical signs were observed in the dog model of HF. We identified 67,458 transcripts using full-length transcriptome sequencing. A total of 785 DETs were obtained from the HF and control groups. These DETs were mainly enriched in the immune responses, especially Th1, Th2, and Th17 cell differentiation processes. Furthermore, flow cytometry results revealed that the proportion of Th1 and Th17 cells increased in patients with HF compared to controls, while the proportion of Th2 cells decreased. Differentially expressed genes in the HF and control groups associated with Th1, Th2, and Th17 cell differentiation were quantified using qRT-PCR. We also identified variable splicing events of sarcomere genes (e.g., MYBPC3, TNNT2, TTN, FLNC, and TTNI3). In addition, we detected 4,892 transcription factors and 406 lncRNAs associated with HF. Our analysis based on full-length transcript sequencing provided an analysis perspective in a dog model of HF, which is valuable for molecular research in an increasingly relevant large animal model of HF.
A Numerical Investigation of the Characteristics of Seismic Signals Induced by Rockfalls
Authors: Feng Zheng-Yi , Shen Zhao-Ru , Zhuang Rui-Chia
Published: December 2021

This study proposes a numerical coupling approach to simulate seismic signals of rockfalls and conducts a parametric analysis to explore the characteristics of the seismic signals generated by rockfalls. To validate the approach, three field rockfall tests were selected for comparison. The rockfall velocity, duration, seismic frequency, Husid plot, Arias intensity, and spectrogram of the seismic signals were compared. We found that friction between rocks and the ground affects rock falling behavior. In addition, the local damping and Rayleigh damping assignments in the numerical model have strong effects on the simulation results. The volume of the falling rock and the falling speed of the rock affect the Arias intensity. The coupling approach proposed could be extended and can potentially be used as a useful tool in rockfall hazard estimations.
The Contentious Role of Tourism in Disaster Response and Recovery in Vanuatu
Authors: Neef Andreas
Published: December 2021

Tourism is a key contributor to the economy of the Pacific Island country Vanuatu. Yet many Ni-Vanuatu have seen their access to natural resources lost or reduced as a consequence of foreign investment in the tourism industry and associated land leases, while few community members found secure employment in the tourism sector to compensate for those losses. The tension between externally driven tourism development and local resource access has been exacerbated in the aftermath of 2015 Tropical Cyclone Pam which caused extensive damage both to the tourism industry and local communities. Employing a tourism-disaster-conflict nexus lens and drawing on semi-structured interviews with hotel managers, research conversations with hotel staff and community members, and focus group discussions with community leaders, this study examines how the tourism sector has impacted post-disaster response and recovery, particularly in terms of land relations and rural livelihoods. Findings suggest that tourism can be a double-edged sword for disaster-prone communities. While resorts play an important role as first responders, their contributions to post-disaster recovery processes remain ambiguous and marred by tensions between expatriate investors and indigenous Ni-Vanuatu people. These findings also hold lessons for the tourism crisis triggered by the COVID-19 pandemic in the South Pacific and elsewhere.
Impact of Circadian Desynchrony on Spermatogenesis: A Mini Review
Authors: Fusco Ferdinando , Longo Nicola , De Sio Marco , Arcaniolo Davide , Celentano Giuseppe , Capece Marco , La Rocca Roberto , Mangiapia Francesco , Califano Gianluigi , Morra Simone , Turco Carmine , Spena Gianluca , Spirito Lorenzo , Fusco Giovanni Maria , Cirillo Luigi , De Luca Luigi , Napolitano Luigi , Mirone Vincenzo , Creta Massimiliano
Published: December 2021

The purpose of this mini review is to provide data about pre-clinical and clinical evidence exploring the impact of circadian desynchrony on spermatogenesis. Several lines of evidence exist demonstrating that disruption of circadian rhythms may interfere with male fertility. Experimental knock-out or knock-down of clock genes, physiologically involved in the regulation of circadian rhythms, are associated with impairments of fertility pathways in both animal and human models. Moreover, disruption of circadian rhythms, due to reduction of sleep duration and/or alteration of its architecture can negatively interfere in humans with circulating levels of male sexual hormones as well as with semen parameters. Unfortunately, current evidence remains low due to study heterogeneity.
Lower Limb Muscle Strength and Muscle Mass Are Associated With Incident Symptomatic Knee Osteoarthritis: A Longitudinal Cohort Study
Authors: Veronese Nicola , Stefanac Sinisa , Koyanagi Ai , Al-Daghri Nasser M. , Sabico Shaun , Cooper Cyrus , Rizzoli Renè , Reginster Jean-Yves , Barbagallo Mario , Dominguez Ligia J. , Smith Lee , Maggi Stefania
Published: December 2021

Recent literature suggests that sarcopenia, often represented by low lower limbs muscle mass and strength, can be considered a potential risk factor for knee osteoarthritis (OA), but the available literature is still limited. We therefore aimed to investigate whether sarcopenia is associated with a higher risk of radiographic (ROA) and symptomatic knee OA (SxOA) in a large cohort of North American people in the context of the OA initiative. Sarcopenia at baseline was diagnosed in case of low skeletal muscle mass (i.e., lower skeletal mass index) and poor performance in the chair stands test. The outcomes of interest for this study included ROA (radiographical osteoarthritis) if a knee developed a Kellgren and Lawrence (KL) grade ≥2 at follow-up, and SxOA (symptomatic osteoarthritis) defined as new onset of a combination of painful knee OA. Altogether, 2,492 older participants (mean age: 68.4 years, 61.4% females) were included. At baseline, sarcopenia was present in 6.1% of the population. No significant difference in ROA prevalence was observed between those with and without sarcopenia (p=0.76), whilst people with sarcopenia reported a significant higher prevalence of SxOA (p<0.0001). Using a logistic regression analysis, adjusting for potential confounders at baseline and the diagnosis of sarcopenia during follow-up, sarcopenia was associated with a higher incidence of knee SxOA (odds ratio, OR=2.29; 95%CI [confidence interval]: 1.42-3.71; p=0.001), but not knee ROA (OR=1.48; 95%CI: 0.53-4.10; p=0.45). In conclusion, sarcopenia could be associated with a higher risk of negative knee OA outcomes, in particular symptomatic forms.
Community-Based Monitoring Detects Sources and Risks of Mining-Related Water Pollution in Zimbabwe
Authors: Ruppen Désirée , Chituri Owen A. , Meck Maideyi L. , Pfenninger Numa , Wehrli Bernhard
Published: December 2021

Although mining and mineral processing are vital for many economies in the Global South, they are associated with enormous challenges of managing potentially devastating environmental impacts. In contexts where environmental oversight agencies often lack financial and personal capacities to fulfill their role, community-based monitoring might be a valid alternative to monitor potential environmental impacts. In this study, we present the setup and the implementation of a citizen science project to monitor water quality parameters in a river downstream of a coal mining area in Hwange, Western Zimbabwe. In a joint effort over 1.5 years, community monitors and scientists took close to 800 water samples in the Deka River and effluent channels. The data allowed identifying sources of pollution and relating these to past and present mining activities. The primary source of acid mine drainage came from abandoned underground mine sites. Illegal mine water dumping from active mine sites accentuated the problem and resulted in fish kills and food risks for the local population. Concentrations of manganese, nickel and arsenic were exceeding national fresh water guidelines and international drinking water standards. Manganese concentrations exceeded guidelines by a factor of 70 resulting in a public health risk. In this study, we showed that community-based monitoring offers a promising approach to establish a high-quality dataset for assessing mining-related risks if the implementation of sampling protocols is followed tightly. The monitoring scheme significantly improves the collection and interpretation of water quality data in challenging contexts where governmental institutions and industrial players are not enforcing environmental standards.
Critical Roles of Spätzle5 in Antimicrobial Peptide Production Against Escherichia coli in Tenebrio molitor Malpighian Tubules
Authors: Ali Mohammadie Kojour Maryam , Edosa Tariku Tesfaye , Jang Ho Am , Keshavarz Maryam , Jo Yong Hun , Han Yeon Soo
Published: December 2021

The dimeric cytokine ligand Spätzle (Spz) is responsible for Toll pathway activation and antimicrobial peptide (AMP) production upon pathogen challenge in Tenebrio molitor. Here, we indicated that TmSpz5 has a functional role in response to bacterial infections. We showed that the highest expression of TmSpz5 is induced by Candida albicans. However, TmSpz5 knockdown reduced larval survival against Escherichia coli and Staphylococcus aureus. To evaluate the molecular mechanism underlying the observed survival differences, the role of TmSpz5 in AMP production was examined by RNA interference and microbial injection. T. molitor AMPs that are active against Gram-negative and -positive bacteria, including Tmtenecins, Tmattacins, Tmcoleoptericins, Tmtaumatin-like-proteins, and Tmcecropin-2, were significantly downregulated by TmSpz-5 RNAi in the Malpighian tubules (MTs) following a challenge with E. coli and S. aureus. However, upon infection with C. albicans the mRNA levels of most AMPs in the dsTmSpz5-injected group were similar to those in the control groups. Likewise, the expression of the transcription factors NF-κB, TmDorX2, and TmRelish were noticeably suppressed in the MTs of TmSpz5-silenced larvae. Moreover, E. coli-infected TmSpz5 knockdown larvae showed decreased antimicrobial activity in the MTs and hindgut compared with the control group. These results demonstrate that TmSpz5 has a defined role in T. molitor innate immunity by regulating AMP expression in MTs in response to E. coli.
Interannual Abundance Fluctuations of Two Oceanic Squids in the Pacific Ocean Can Be Evaluated Through Their Habitat Temperature Variabilities
Authors: Chen Peng , Chen Xinjun , Yu Wei , Lin Dongming
Published: December 2021

Neon flying squid (Ommastrephes bartramii) and jumbo flying squid (Dosidicus gigas) are two commercially essential oceanic squids in the Pacific Ocean. An in-depth understanding of the mechanisms of their annual and interannual abundance fluctuations under environmental and climate variabilities can ensure ration and suitable management. Thus, the annual and interannual abundance fluctuations of the stock of the western winter-spring cohort of O. bartramii and D. gigas off Peru Exclusive Economic Zone (PEEZ) waters and their association with habitat temperature variabilities are explored in this study based on the historical Chinese Squid-jigging fishery data from 2003 to 2020. The habitat temperature variabilities were defined as the effective principal components of the SST at the squids’ two important habitats (spawning and feeding ground) through life histories according to the principal component analysis. The Hodrick—Prescott filter analysis was conducted to quantify the annual and interannual fluctuations of abundance and habitat temperature variabilities. Furthermore, the generalized additive model (GAM) was employed to investigate their associations. The results demonstrated different but not synchronous trends of abundance for O. bartramii and D. gigas. Regarding O. bartramii, the interannual abundance first decreased (2003∼2013) and then increased (after 2014). For D. gigas, the interannual abundance kept decreasing within 2003∼2020. Their annual trends have presented large fluctuations over years. The results of GAM indicated that using habitat temperature variabilities only can trace the abundance trend of O. bartramii and D. gigas at an interannual but not annual scale. Further studies verified that Pacific Decadal Oscillation (PDO) is a crucial factor affecting the interannual abundance trend of these two squids through the habitat temperature variabilities. However, this study indicates that the habitat temperature variabilities not only are related to other large-scale factors, which are not investigated currently at an interannual scale, but also, are combined with other small- or middle-scale factors at an annual scale on their impacts to the abundance fluctuations of these two squids. Therefore, in order to better explain the mechanisms of annual and interannual abundance fluctuations of O. bartramii and D. gigas under environmental and climate variabilities, the importance of combining other potential factors into consideration is highlighted.
Coastal Polynya Disrupts the Acoustic Backscatter Diurnal Signal Over the Eastern Laptev Sea Shelf
Authors: Dmitrenko Igor A. , Petrusevich Vladislav Y. , Kosobokova Ksenia , Komarov Alexander S. , Bouchard Caroline , Geoffroy Maxime , Koldunov Nikolay V. , Babb David G. , Kirillov Sergei A. , Barber David G.
Published: December 2021

The diel vertical migration (DVM) of zooplankton is one of the largest species migrations to occur globally and is a key driver of regional ecosystems and the marine carbon pump. The dramatic changes in the Arctic environment in recent years, mainly associated with sea-ice decline, may have wide significance for the Arctic shelf ecosystems including DVM. Observations have revealed the occurrence of DVM in ice-covered Arctic waters, however, there have yet to be observations of DVM from the extensive Siberian shelves in the Eurasian Arctic and no analysis of how the sea-ice decline may affect DVM. Here, 2 yearlong time series of acoustic backscatter, collected by moored acoustic Doppler current profilers in the eastern Laptev Sea from August 1998 to August 1999, were used to examine the annual cycle of acoustic scattering, and therefore the annual cycle of DVM in the area. The acoustic time series were used along with atmospheric and oceanic reanalysis and satellite data. Our observations show that DVM did not occur during polar night and polar day, but is active during the spring and fall transition periods when there is a diurnal cycle in light conditions. DVM began beneath the fast ice at the end of polar night and increased in intensity through spring. However, the formation of a large polynya along the landfast ice edge in late March 1999 caused DVM to abruptly cease near the fast ice edge, while DVM persisted through spring to the start of polar day at the onshore mooring. We associate this cessation of synchronized DVM ∼1 month ahead of polar day with a predator-avoidance behavior of zooplankton in response to higher polar cod abundance near the polynya. During polar day, the intensity of acoustic scattering was attributed to the riverine suspended particles. Overall, our results highlight the occurrence of DVM on the Siberian shelves, the cessation of synchronized DVM when a polynya opens up nearby, and the potential impact of significant trends toward a more extensive Laptev Sea polynya as part of changing ice conditions in the Eurasian Arctic and their impact on the Arctic shelf ecology.
Bilateral Spontaneous Pneumothorax in a COVID-19 and HIV-Positive Patient: A Case Report
Authors: Cho Young Min , Guevara Sara , Aronsohn Judith , Mumford James M. , Shore-Lesserson Linda , Miyara Santiago J. , Herrera Martin , Kirsch Claudia , Metz Christine N. , Zafeiropoulos Stefanos , Giannis Dimitrios , McCann-Molmenti Alexia , Hayashida Kei , Shinozaki Koichiro , Shoaib Muhammad , Choudhary Rishabh C. , Aranalde Gabriel I. , Becker Lance B. , Molmenti Ernesto P. , Kruer James , Hatoum Anthony
Published: December 2021

This case report describes a 60 year-old Black-American male with a past medical history of human immunodeficiency virus (HIV) infection and hyperthyroidism, who suffered a bilateral spontaneous pneumothorax (SP) in the setting of coronavirus disease 2019 (COVID-19) pneumonia. SP is a well-established complication in HIV-positive patients and only recently has been associated with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. While HIV and COVID-19 infections have been independently linked with increased risk of SP development, it is unknown if both infections interact in a synergistic fashion to exacerbate SP risk. According to the Centers for Disease Control and Prevention (CDC), patients living with HIV have a higher risk of developing severe COVID-19 infection and the mechanism remains to be elucidated. To the best of our knowledge, this is the first report of a HIV-positive patient, who in the setting of SARS-CoV-2 infection, developed bilateral apical spontaneous pneumothorax and was later found to have a left lower lobe tension pneumothorax. This case highlights the importance of considering SP on the differential diagnosis when HIV-positive patients suddenly develop respiratory distress in the setting of SARS-CoV-2 infection.
Reductive Effect of Acitretin on Blood Glucose Levels in Chinese Patients With Psoriasis
Authors: Qian Hua , Kuang Yehong , Su Juan , Chen Menglin , Chen Xiang , Lv Chengzhi , Chen Wangqing , Zhu Wu
Published: December 2021

Background: Psoriasis is a skin condition associated with increased risks of developing metabolic diseases, such as diabetes and hyperlipidaemia. Retinoid drugs, including acitretin, are commonly used to treat psoriasis due to its low cost and tolerable side effects.

Objective: This study aimed to explore the influence of acitretin on patients' metabolism levels, especially lipid and glucose.

Methods: In this retrospective study, a total of 685 psoriatic patients and 395 age/sex matched controls were enrolled. The demographic and biochemical indexes of each participant were recorded. Acitretin (30 mg/d) combined with the topical ointment calcipotriol was used to treat the psoriatic patients, and the glucose and lipid profiles of patients before and after acitretin treatment were analyzed.

Results: The blood glucose levels of 685 psoriasis patients were significantly higher than that of the control group (P < 0.001), while the blood lipid levels showed no difference between psoriatic patients and the matched controls. Triglyceride and low-density lipoprotein levels were significantly increased in 247 patients (P < 0.05) after 8 weeks of treatment with acitretin. Interestingly, there was a remarkable downward trend in body mass index (BMI) and blood glucose levels (P < 0.05) after acitretin treatment. Additionally, expression of both GLUT1 and GLUT4 in HaCaT and HepG2 cells were significantly increased when treated with acitretin. Compared to acitretin-free cells, the uptake of 2-NBDG was significantly higher in HaCaT and HepG2 cells after incubation with 5000 ng/mL acitretin for 36 h.

Conclusion: Acitretin plays a significant role of reducing the blood glucose level in psoriasis patients. The mechanism of lowering blood glucose may be through increasing glucose intake by cells, thereby reducing glucose levels in the peripheral blood.
Solid-State Fermentation With Aspergillus cristatus Enhances the Protopanaxadiol- and Protopanaxatriol-Associated Skin Anti-aging Activity of Panax notoginseng
Authors: Lee Sunmin , Reddy Chagam Koteswara , Ryu Jeoung Jin , Kyung Seoyeon , Lim Yonghwan , Park Myeong Sam , Kang Seunghyun , Lee Choong Hwan
Published: December 2021

A metabolomics approach was used to profile metabolites of Panax notoginseng fermented with Aspergillus cristatus in two ways, liquid-state fermentation (LF-P) and solid-state fermentation (SSF-P) and examine metabolite markers representing antioxidant activity and skin anti-aging. Protopanaxadiol (PPD) and protopanaxatriol (PPT) contents were higher in SSF-P than in LF-P and showed a multiplicative increase over the fermentation period of four days. PPD and PPT levels also correlated with antioxidant and anti-aging effects in skin, based on the mRNA expression of dermal extracellular matrix components. In the bioactivity validation assays, PPD and PPT significantly improved the expression of type-I collagen, fibrillin-1, and elastin in human dermal fibroblasts from both young and old subjects; these were comparable with the effects of the SSF-P extracts. Overall, our results suggest that changes in the metabolites of P. notoginseng fermented with A. cristatus enhance the quality and availability of bioactive compounds associated with skin anti-aging.
Reference Standards for Newborn Screening of Metabolic Disorders by Tandem Mass Spectrometry: A Nationwide Study on Millions of Chinese Neonatal Populations
Authors: He Falin , Yang Rulai , Huang Xinwen , Tian Yaping , Pei Xiaofang , Bohn Mary Kathryn , Zou Lin , Wang Yan , Li Haibo , Wang Ting , Gu Maosheng , Jiang Tao , Chen Xigui , Zou Hui , Wei Hongwei , Tian Weibing , Tang Tian , Adeli Khosrow , Wang Zhiguo
Published: December 2021

Introduction: The major clinical problem presently confronting the Chinese newborn screening (NBS) programs by tandem mass spectrometry (MS/MS) is the lack of comprehensive reference intervals (RIs) for disease biomarkers. To close this gap, the Chinese National Center for Clinical Laboratories (NCCL) launched a nationwide study to investigate the dynamic pattern of 35 MS/MS NBS biomarkers and establish accurate and robust RIs.

Methods: Blood spot samples from 4,714,089 Chinese neonates were tested in participating centers/laboratories and used for study analysis. MS/MS NBS biomarker trends were visually assessed by their concentrations over age. Specific partitions were determined arbitrarily by each day and sex or by the statistical method of Harris and Boyd. RIs, corresponding to the 2.5th and 97.5th percentiles, as well as the 1th, 25th, 75th and 99th percentiles were calculated for each reference partition using a non-parametric rank approach.

Results: Most MS/MS NBS biomarkers fluctuated during the first week of life, followed by a relatively stable concentration. Age and sex-specific RIs were established and presented an improved specificity over the RIs used in participating centers/laboratories. Females demonstrated higher 2.5th and 97.5th percentiles in all amino acids except arginine and ornithine than males, whereas males showed higher 2.5th and 97.5th percentiles in most acylcarnitines.

Conclusion: The present study determined the dynamic trends of 35 MS/MS biomarkers and established age and sex-specific RIs, valuably contributing to the current literature and timely evaluation of neonatal health and disease.
Recent Advances in the Understanding of Specific Efferent Pathways Emerging From the Cerebellum
Authors: Kang Seulgi , Jun Soyoung , Baek Soo Ji , Park Heeyoun , Yamamoto Yukio , Tanaka-Yamamoto Keiko
Published: December 2021

The cerebellum has a long history in terms of research on its network structures and motor functions, yet our understanding of them has further advanced in recent years owing to technical developments, such as viral tracers, optogenetic and chemogenetic manipulation, and single cell gene expression analyses. Specifically, it is now widely accepted that the cerebellum is also involved in non-motor functions, such as cognitive and psychological functions, mainly from studies that have clarified neuronal pathways from the cerebellum to other brain regions that are relevant to these functions. The techniques to manipulate specific neuronal pathways were effectively utilized to demonstrate the involvement of the cerebellum and its pathways in specific brain functions, without altering motor activity. In particular, the cerebellar efferent pathways that have recently gained attention are not only monosynaptic connections to other brain regions, including the periaqueductal gray and ventral tegmental area, but also polysynaptic connections to other brain regions, including the non-primary motor cortex and hippocampus. Besides these efferent pathways associated with non-motor functions, recent studies using sophisticated experimental techniques further characterized the historically studied efferent pathways that are primarily associated with motor functions. Nevertheless, to our knowledge, there are no articles that comprehensively describe various cerebellar efferent pathways, although there are many interesting review articles focusing on specific functions or pathways. Here, we summarize the recent findings on neuronal networks projecting from the cerebellum to several brain regions. We also introduce various techniques that have enabled us to advance our understanding of the cerebellar efferent pathways, and further discuss possible directions for future research regarding these efferent pathways and their functions.
Whole-Brain Reconstruction of Neurons in the Ventral Pallidum Reveals Diverse Projection Patterns
Authors: Feng Qiru , An Sile , Wang Ruiyu , Lin Rui , Li Anan , Gong Hui , Luo Minmin
Published: December 2021

The ventral pallidum (VP) integrates reward signals to regulate cognitive, emotional, and motor processes associated with motivational salience. Previous studies have revealed that the VP projects axons to many cortical and subcortical structures. However, descriptions of the neuronal morphologies and projection patterns of the VP neurons at the single neuron level are lacking, thus hindering the understanding of the wiring diagram of the VP. In this study, we used recently developed progress in robust sparse labeling and fluorescence micro-optical sectioning tomography imaging system (fMOST) to label mediodorsal thalamus-projecting neurons in the VP and obtain high-resolution whole-brain imaging data. Based on these data, we reconstructed VP neurons and classified them into three types according to their fiber projection patterns. We systematically compared the axonal density in various downstream centers and analyzed the soma distribution and dendritic morphologies of the various subtypes at the single neuron level. Our study thus provides a detailed characterization of the morphological features of VP neurons, laying a foundation for exploring the neural circuit organization underlying the important behavioral functions of VP.
Preventing Ischemic Cerebrovascular Events in High-Risk Patients With Non-disabling Ischemic Cerebrovascular Events Using Remote Ischemic Conditioning: A Single-Arm Study
Authors: Liu Shimeng , Gao Zongen , Meng Ran , Song Haiqing , Tang Tianping , Zhao Ya , Chen Rong , Sheng Yanzhen , Fan Qianqian , Jiang Fang , Zhang Qian , Ding Jianping , Huang Xiaoqin , Ma Qingfeng , Dong Kai , Xue Sufang , Yu Zhipeng , Duan Jiangang , Chu Changbiao , Chen Xiaohui , Huang Xingquan , Li Sijie , Ovbiagele Bruce , Zhao Wenle , Ji Xunming , Feng Wuwei
Published: December 2021

Background: Secondary stroke prevention after a high-risk, non-disabling ischemic cerebrovascular event needs to be enhanced. The study was conducted to investigate whether remote ischemic conditioning (RIC) is effective in preventing recurrent ischemic events within 3 months.

Methods: This was a four-center, single-arm, open-label Phase IIa futility trial (PICNIC-One Study). Adult patients (≥18 years of age) who had an acute minor ischemic stroke (AMIS) with a National Institutes of Health Stroke Scale score ≤ 3 or a transient ischemic attack (TIA) with moderate-to-high risk of stroke recurrence (ABCD score ≥ 4) within 14 days of symptom onset were recruited. Patients received RIC as adjunctive therapy to routine secondary stroke prevention regimen. RIC consisted of five cycles of 5-min inflation (200 mmHg) and 5-min deflation of cuffs (45 min) on bilateral upper limbs twice a day for 90 days.

Results: A total of 285 patients met the study criteria, of which 167 provided signed informed consent and were enrolled. Data from 162 were analyzed with five subjects excluded. Recurrent AIS/TIA occurred in 6/162 (3.7%) patients within 3 months, with no occurrence of hemorrhagic stroke. The top three adverse events were upper limb pain (44/162, 27.2%), petechia (26/162, 16.0%), and heart palpitation (5/162, 3.1%). About 68 (42.0%) subjects completed ≥ 50% of 45-min RIC sessions.

Conclusions: RIC is a safe add-on procedure and it has a potential benefit in reducing recurrent cerebrovascular events in patients with high-risk, non-disabling ischemic cerebrovascular events as the risk of stroke/TIA events is lower than expected; however, its compliance needs to be improved. Our study provides critical preliminary data to plan a large sample size, randomized controlled clinical study to systematically investigate the safety and efficacy of RIC in this population.
Symptom Locus and Symptom Origin Incongruity in Runner’s Dystonia – Case Study of an Elite Female Runner
Authors: Ogasawara Issei , Hattori Noriaki , Revankar Gajanan S. , Konda Shoji , Uno Yuki , Nakano Tomohito , Kajiyama Yuta , Mochizuki Hideki , Nakata Ken
Published: December 2021

Objectives: Runner’s dystonia is a task-specific dystonia that occurs in the lower limbs and trunk, with diverse symptomatology. We aimed to identify the origin of a dystonic movement abnormality using combined three-dimensional kinematic analysis and electromyographic (EMG) assessment during treadmill running.

Participant: A 20-year-old female runner who complained of right-foot collision with the left-leg during right-leg swing-phase, which mimicked right-ankle focal dystonia.

Results: Kinematic and EMG assessment of her running motion was performed, which showed a significant drop of the left pelvis during right-leg stance-phase, and a simultaneous increase of right hip adductor muscle activity. This resulted in a pronounced adduction of the entire right lower limb with respect to the pelvis segment. Trajectories of right foot were seen to encroach upon left-leg area.

Discussion: These findings suggested that the symptom of this runner was most likely a form of segmental dystonia originating from an impaired control of hip and pelvis, rather than a distal focal ankle dystonia.

Conclusion: We conclude that, for individualized symptom assessment, deconstructing the symptom origin from its secondary compensatory movement is crucial for characterizing dystonia. Kinematic and EMG evaluation will therefore be a prerequisite to distinguish symptom origin from secondary compensatory movement.
Aberrant Brain Spontaneous Activity and Synchronization in Type 2 Diabetes Mellitus Subjects Without Mild Cognitive Impairment
Authors: Li Yifan , Li Mingrui , Feng Yue , Ma Xiaomeng , Tan Xin , Chen Yuna , Qin Chunhong , Huang Haoming , Liang Yi , Qiu Shijun
Published: December 2021

Objective:We aimed to explore whether the percent amplitude of fluctuation (PerAF) measurement could provide supplementary information for amplitude of low-frequency fluctuation (ALFF) about spontaneous activity alteration in type 2 diabetes mellitus (T2DM) subjects without mild cognitive impairment (MCI). Then we further evaluated the synchronization through the method of functional connectivity (FC) to better demonstrate brain changes in a more comprehensive manner in T2DM.

Methods:Thirty T2DM subjects without MCI and thirty well-matched healthy subjects were recruited in this study. Subjects’ clinical data, neuropsychological test results, and resting-state functional magnetic resonance imaging (rs-fMRI) data were acquired. Voxel-based group difference comparisons between PerAF and ALFF were conducted. Then, seed-based FC between the recognized brain regions based on PerAF and ALFF and the rest of the whole brain was performed.

Results:Compared with healthy group, T2DM group had significantly decreased PerAF in the bilateral middle occipital gyrus and the right calcarine, increased ALFF in the right orbital inferior frontal gyrus and decreased ALFF in the right calcarine. Seed-based FC analysis showed that the right middle occipital gyrus of T2DM subjects exhibited significantly decreased FC with the right caudate nucleus and right putamen. According to the partial correlation analyses, hemoglobin A1c (HbA1c) and immediate memory scores on the auditory verbal learning test (AVLT) were negatively correlated in the T2DM group. However, we found that total cholesterol was positively correlated with symbol digit test (SDT) scores.

Conclusion:PerAF and ALFF may have different sensitivities in detecting the abnormal spontaneous brain activity in T2DM subjects. We suggest PerAF values may add supplementary information and indicate additional potential neuronal spontaneous activity in T2DM subjects without MCI, which may provide new insights into the neuroimaging mechanisms underlying early diabetes-associated cognitive decline.
Anti-Müllerian Hormone Regulation of Synaptic Transmission in the Hippocampus Requires MAPK Signaling and Kv4.2 Potassium Channel Activity
Authors: Wang Kang , Xu Fuhua , Maylie James , Xu Jing
Published: December 2021

Anti-Müllerian hormone (AMH) is a paracrine factor generated peripherally by the gonads to regulate gonadal function in adult mammals. We recently reported that AMH and AMH-specific receptor Anti-Müllerian hormone receptor 2 (AMHR2) are expressed in the hippocampus, and exogenous AMH protein rapidly increased synaptic transmission and long-term synaptic plasticity at the CA3-CA1 synapses. Here we examined the cell-specific expression of AMHR2 and the cellular mechanism of rapid boosting effect of AMH on synaptic transmission in mouse hippocampus. Immunofluorescence staining showed that AMHR2 was specifically expressed in the soma and dendrites of hippocampal pyramidal neurons, but not glial cells. Electrophysiological recordings on acute hippocampal slices showed that AMH did not affect AMPAR-mediated or N-Methyl-D-aspartic acid receptor (NMDAR)-mediated excitatory postsynaptic currents at the CA3-CA1 synapses. The small-conductance Ca2+-activated K+ channel (SK2) and A-type K+ channel (Kv4.2) contribute to shaping excitatory postsynaptic potentials (EPSPs) at the CA3-CA1 synapses. Bath application of apamin to block SK2 did not alter AMH effect on increasing EPSPs, whereas blocking Kv4.2 channel with 4-aminopyridine, or chelating internal Ca2+ with BAPTA occluded the action of AMH on boosting EPSPs. Kv4.2 activity is regulated by p38 mitogen-activated kinase (MAPK). Blocking p38 MAPK with SB203580 occluded the effect of AMH on increasing EPSPs. These results show that Kv4.2 channel contributes to the rapid action of AMH on boosting synaptic transmission in a Ca2+- and p38 MAPK-dependent manner. Our findings provide functional evidence that AMH enhances synaptic transmission through Kv4.2 channel in the hippocampus, suggesting a possible role of Kv4.2 channel in AMH-regulated neuronal process underlying learning and memory.
Artificial Intelligence Identified Resilient and Vulnerable Female Rats After Traumatic Stress and Ethanol Exposure: Investigation of Neuropeptide Y Pathway Regulation
Authors: Denny Ray R. , Connelly Krista L. , Ghilotti Marco G. , Meissler Joseph J. , Yu Daohai , Eisenstein Toby K. , Unterwald Ellen M.
Published: December 2021

Post-traumatic stress disorder (PTSD) is initiated by traumatic-stress exposure and manifests into a collection of symptoms including increased anxiety, sleep disturbances, enhanced response to triggers, and increased sympathetic nervous system arousal. PTSD is highly co-occurring with alcohol use disorder. Only some individuals experiencing traumatic stress develop PTSD and a subset of individuals with PTSD develop co-occurring alcohol use disorder. To investigate the basis of these individual responses to traumatic stress, single prolonged stress (SPS) a rodent model of traumatic stress was applied to young adult female rats. Individual responses to SPS were characterized by measuring anxiety-like behaviors with open field and elevated plus maze tests. Rats were then allowed to drink ethanol under an intermittent two bottle choice procedure for 8 weeks, and ethanol consumption was measured. An artificial intelligence algorithm was built to predict resilient and vulnerable individuals based on data from anxiety testing and ethanol consumption. This model was implemented in a second cohort of rats that underwent SPS without ethanol drinking to identify resilient and vulnerable individuals for further study. Analysis of neuropeptide Y (NPY) levels and expression of its receptors Y1R and Y2R mRNA in the central nucleus of the amygdala (CeA), basolateral amygdala (BLA), and bed nucleus stria terminalis (BNST) were performed. Results demonstrate that resilient rats had higher expression of Y2R mRNA in the CeA compared with vulnerable and control rats and had higher levels of NPY protein in the BNST compared to controls. The results of the study show that an artificial intelligence algorithm can identify individual differences in response to traumatic stress which can be used to predict subsequent ethanol drinking, and the NPY pathway is differentially altered following traumatic stress exposure in resilient and vulnerable populations. Understanding neurochemical alterations following traumatic-stress exposure is critical in developing prevention strategies for the vulnerable phenotype and will help further development of novel therapeutic approaches for individuals suffering from PTSD and at risk for alcohol use disorder.