bluuebunny/crossref_metadata_2025 huggingface dataset:
Potentialities and Challenges of mRNA Vaccine in Cancer Immunotherapy
Authors: Duan Li-Juan , Wang Qian , Zhang Cuilian , Yang Dong-Xiao , Zhang Xu-Yao
Published: June 2022

Immunotherapy has become the breakthrough strategies for treatment of cancer in recent years. The application of messenger RNA in cancer immunotherapy is gaining tremendous popularity as mRNA can function as an effective vector for the delivery of therapeutic antibodies on immune targets. The high efficacy, decreased toxicity, rapid manufacturing and safe administration of mRNA vaccines have great advantages over conventional vaccines. The unprecedent success of mRNA vaccines against infection has proved its effectiveness. However, the instability and inefficient delivery of mRNA has cast a shadow on the wide application of this approach. In the past decades, modifications on mRNA structure and delivery methods have been made to solve these questions. This review summarizes recent advancements of mRNA vaccines in cancer immunotherapy and the existing challenges for its clinical application, providing insights on the future optimization of mRNA vaccines for the successful treatment of cancer.
The Effect of Grooming on Five Commercial Antifouling Coatings
Authors: Ralston Emily , Gardner Harrison , Hunsucker Kelli Zargiel , Swain Geoffrey
Published: June 2022

The majority of ships are coated with antifouling paint. These coatings can fail to completely protect from fouling due to mismatches between paint type and duty cycle, the presence of biocide tolerant fouling organisms, improperly applied, old or damaged paint, etc. Grooming antifouling coatings can provide a solution. Five commercially available antifouling coatings were applied to panels. Half of the replicates were groomed weekly, the other half were immersed and allowed to freely foul, undisturbed. Photographs were taken and panels were visually assessed monthly. Over the period of two years, all the undisturbed panels became fouled with a diverse community of macrofouling organisms including encrusting and arborescent bryozoans, barnacles, tube worms, oysters, tunicates and more. The groomed panels remained clean of macrofouling for an extended period of time, up to two years depending on the coating. Cover of biofilm was also low on groomed panels. Grooming was effective at maintaining different antifouling paints clear of macrofouling and decreasing cover of biofilms for up to two years of immersion.
New Contribution to the Diversity of the Anaerobic Genus Metopus (Ciliophora, Armophorea), With Descriptions of Three New Marine Species
Authors: Zhuang Wenbao , Li Ran , Feng Xiaochen , Al-Farraj Saleh A. , Hu Xiaozhong
Published: June 2022

Armophorean ciliates constitute an important component of microeukaryotic community in anaerobic or hypoxic environments. Yet, their diversity remains poorly known due to under-sampling or the scarcity of knowledge. In this study, three metopid ciliates, i.e., Metopus paraes sp. n., Metopus spiculatus sp. n., and Metopus parapellitus sp. n., collected from coastal sediments in Qingdao and Rizhao, China, were investigated using live observation, protargol staining, and molecular phylogenetic methods. M. paraes sp. n. can be distinguished by its long caudal cilia. M. spiculatus sp. n. resembles M. vestitus in many ways, but differs mainly in having a beak-like preoral dome end and a conspicuous tail. The most remarkable features of M. parapellitus sp. n. include an ovate body shape, caudal cilia located at the rear end and right posterior body, and an adoral zone that never extends onto the dorsal surface. Sequence divergences supported the species identification of these three species. Phylogenetic analyses confirmed that the Metopus is not monophyletic, and first revealed that all marine species of Metopus form a well-supported clade. The clustering of these marine forms with M. es (type species) is not rejected by the AU test, which infers that the marine clade represents the genus Metopus together with M. es.
Tidal Flats as a Significant Carbon Reservoir in Global Coastal Ecosystems
Authors: Chen Zhao Liang , Lee Shing Yip
Published: June 2022

Tidal flats are widely distributed and provide a variety of ecosystem services. Nevertheless, the consequences of tidal flat loss and implications for services such as carbon (C) sequestration have not been assessed. In unvegetated tidal flat ecosystems, sediment is the most important carbon reservoir, similar to that of vegetated coastal wetlands (i.e., mangroves, salt marshes, and seagrass). We examined the C stocks and C accumulation rate (CAR) reported from 123 locations of tidal flat around the world and compared these results with data from mangroves, salt marshes, and seagrass meadows. The global average CAR of tidal flats is 129.8 g C m-2 yr-1, with the top-meter sediments containing on average 86.3 Mg C ha-1. Globally, tidal flat can bury 6.8 Tg C (24.9 Tg CO2) per year and can store 0.9 Pg C (3.3 Pg CO2) in the top meter sediment. Assuming the same rate of loss tidal flats as in the past three decades and that all disturbed sediment C is remineralized, 4.8 Tg C will be lost from tidal flat sediments every year, equivalent to an emission of 17.6 Tg CO2 to the water column and atmosphere.
Clinical Evaluation of a Defined Zeolite-Clinoptilolite Supplementation Effect on the Selected Blood Parameters of Patients
Authors: Kraljević Pavelić Sandra , Saftić Martinović Lara , Simović Medica Jasmina , Žuvić Marta , Perdija Željko , Krpan Dalibor , Eisenwagen Sandra , Orct Tatjana , Pavelić Krešimir
Published: June 2022

The natural clinoptilolite material is an inorganic crystal mineral called zeolite. It has been extensively studied and used in industrial applications and veterinary and human medicine due to positive effects on health. Limited data is available in the scientific literature about its effects on the levels of physiologically relevant minerals in the human organism. Accordingly, we performed a comprehensive and controlled monitoring of the relevant mineral and contaminants levels in human subjects supplemented with a certified clinoptilolite material within three clinical trials with different supplementation regimens. Effects of a registered and certified clinoptilolite material PMA-zeolite on selected mineral and metal levels were determined by standard biochemical methods and inductively coupled plasma mass spectrometry (ICP-MS) in the blood of subjects enrolled in three clinical trials: short-term (28 days, Mineral Metabolism and selected Blood Parameters study MMBP), medium-term (12 weeks, Morbus Crohn study), and long-term (4 years, Osteoporosis TOP study) supplementation. Lower concentrations were observed for copper (Cu) in patients with osteoporosis, which normalized again in the long-term supplementation trial, whereas sodium (Na) and calcium (Ca) levels diminished below the reference values in patients with osteoporosis. In the short- and long-term supplementation trials, increased levels of lead (Pb) were observed in PMA-zeolite-supplemented subjects, which decreased in the continued long-term supplementation trial. Increased levels of aluminum (Al) or Pb attributable to eventual leakage from the material into the bloodstream were not detected 1 h after intake in the short-term supplementation trial. Nickel (Ni) and Al were statistically significantly decreased upon long-term 4-year supplementation within the long-term supplementation trial, and arsenic (As) was statistically significantly decreased upon 12-weeks supplementation in the medium-term trial. Alterations in the measured levels for Na and Ca, as well as for Pb, in the long-term trial are probably attributable to the bone remodeling process. Checking the balance of the minerals Cu, Ca, and Na after 1 year of supplementation might be prescribed for PMA-supplemented patients with osteoporosis.

Clinical Trial Registration

[https://clinicaltrials.gov], identifiers [NCT03901989, NCT05178719, NCT04370535, NCT04607018].
Dynamic Changes and Nomogram Prediction for Sinistral Portal Hypertension in Moderate and Severe Acute Pancreatitis
Authors: Yu Chen , Ding Ling , Jiang Meilan , Liao Qian , Huang Xin , Lei Yupeng , Ke Huajing , Xiong Huifang , He Wenhua , Xia Liang , Zeng Xianjun , Lu Nonghua , Zhu Yin
Published: June 2022

Objectives

To investigate the dynamic changes in gastric varices in patients with acute pancreatitis (AP) and to develop a novel nomogram for the early prediction of sinistral portal hypertension (SPH).

Methods

This was a retrospective, case-control study with an analysis of the quantitative, dynamic computed tomography imaging results of SPH in patients with moderate and severe AP with a long-term follow-up. Multivariate logistic regression analysis and nomogram were employed.

Results

The SPH group (n = 94) and non-SPH group (n = 94) were matched. The dynamic changes showed an increasing trend in the diameter of gastric fundus, short gastric, gastric coronary, and gastroepiploic veins, which did not recover during the one-year follow-up. Multivariate analysis showed that male (adjusted odds ratio (adjOR), 8.71; 95% confidence interval (CI), 2.86–26.53; P < 0.001), body mass index ≥27.5 kg/m2 (adjOR, 5.49; 95% CI, 1.85–16.29; P = 0.002), prothrombin time ≥12.6 s (adjOR, 2.82; 95% CI, 1.11–7.17; P = 0.03), and the patency of splenic vein [stenosis (adjOR, 8.48; 95% CI, 2.13–33.71; P = 0.002), and occlusion (adjOR, 34.57; 95% CI, 10.87–110.00; P < 0.001)] were independently associated with the development of SPH. The nomogram incorporating these factors demonstrated good discrimination, calibration and clinical utility. The area under the curve was as high as 0.92 (95% CI, 0.87–0.95).

Conclusion

The dynamic changes in varices in SPH are long-term and slowly progressing. Males and obese patients with abnormal splenic veins and coagulopathies are at high risk for developing SPH. A simple nomogram tool helps in the early, accurate prediction of SPH.
Acupuncture Analgesia in Patients With Traumatic Rib Fractures: A Randomized-Controlled Trial
Authors: Liu Chun-Ting , Hsieh Ting-Min , Wu Bei-Yu , Huang Yu-Chuen , Shih Chun-Han , Hu Wen-Long , Tsai Ming-Yen , Chen Yung-Hsiang
Published: June 2022

Pain management for traumatic rib fracture is important to prevent complications and reduce associated comorbidities. This trial investigated the analgesic efficacy of acupuncture on traumatic rib fracture. Patients with traumatic rib fracture were randomly assigned to traditional acupuncture (TA), laser acupuncture (LA) or sham laser acupuncture (SLA) groups in a 1:1:1 ratio. The intervention was performed on days 1 to 3 after treatment allocation. The acupoints included bilateral LI4 (Hegu), SJ6 (Zhigou), ST36 (Zusanli) and GB34 (Yanglingquan). The primary outcome was Numeric Rating Scale (NRS) scores for pain after the intervention. Secondary outcomes included sustained maximal inspiration (SMI) lung volume, stress responses, the use of analgesics, and associated complications. Data were analyzed via one-way analysis of variance (ANOVA) with Scheffé’s post hoc testing or chi-squared testing. Of the 120 study participants, 109 completed all interventions and measurements. The primary outcomes, which indicated average pain intensity levels and pain while deep breathing, were both significantly lower in the TA and LA groups than in the SLA group after 2 treatments. No between-group differences were observed in SMI lung volume, stress response, analgesics use or associated complications. These findings suggest that TA and LA are safe and effective analgesic modalities for pain management for traumatic rib fracture.

Clinical Trial Registration:

[ClinicalTrials.gov], identifier [NCT03822273].
Current Concepts on Pathogenic Mechanisms and Histopathology in Cutaneous Lupus Erythematosus
Authors: Fetter Tanja , Braegelmann Christine , de Vos Luka , Wenzel Joerg
Published: June 2022

Cutaneous lupus erythematosus (CLE) is an interferon (IFN)-driven autoimmune disease that may be limited to the skin or can be associated with systemic lupus erythematosus (SLE). CLE occurs in several morphologic subtypes ranging from isolated, disc-shaped plaques to disseminated skin lesions. The typical histopathologic pattern of skin lesions is named interface dermatitis and characterized by a lymphocytic infiltrate and necroptotic keratinocytes at the dermo-epidermal junction. Other histopathologic patterns primarily involve the dermis or subcutis, depending on the subtype. One critical mechanism in CLE is the chronic reactivation of innate and adaptive immune pathways. An important step in this process is the recognition of endogenous nucleic acids released from dying cells by various pattern recognition receptors (PRRs), including Toll-like receptors (TLRs) and other cytosolic receptors. Crucial cells in CLE pathogenesis comprise plasmacytoid dendritic cells (pDCs) as major producers of type I IFN, T cells exerting cytotoxic effects, and B cells, previously believed to contribute via secretion of autoantibodies. However, B cells are increasingly considered to have additional functions, supported by studies finding them to occur in highest numbers in chronic discoid lupus erythematosus (CDLE), a subtype in which autoantibodies are often absent. More precise knowledge of how CLE subtypes differ pathophysiologically may allow a tailored pharmacotherapy in the future, taking into account the specific molecular signature in relation to the morphologic subtype.
Effects of Plantation Type and Soil Depth on Microbial Community Structure and Nutrient Cycling Function
Authors: Wang Wenbo , Wang Jianjun , Wang Qianchun , Bermudez Ramon Santos , Yu Shihe , Bu Pengtu , Wang Zhanwei , Chen Dongshen , Feng Jian
Published: June 2022

Declining soil quality and microecological imbalances were evaluated in larch plantations in this study. One potential solution to this problem is the cultivation of mixed coniferous and broad-leaved plantations. However, it is unclear whether and how soil microbial community structure and nutrient cycling function would be affected by mixed plantations and soil depths. In this study, we used high-throughput sequencing technology to investigate bacterial 16S and fungal ITS regions for comparisons of soil microbial diversity among plantation types (aLarix gmeliniipure plantation, aFraxinus mandshuricapure plantation, aLarix–Fraxinusmixed plantation within theLarixrow, theFraxinusrow, and between theLarixandFraxinusrows) and soil depths (0–10, 10–20, and 20–40 cm). These data were used to evaluate variations in microbial communities and nutrient cycling function with the determining environmental factors. Our results indicated that bacteria had a stronger spatial dependence than did fungi, while plantation types significantly affected the fungal community. The relative abundance ofGaiellaceae, as well as bacterial ligninolysis, nitrate ammonification, and nitrite ammonification functions significantly increased with increasing soil depth. Compared with other plantations, the relative abundance ofInocybaceaewas significantly higher in theLarixplantation. Distance-based redundancy analysis (db-RDA) showed thatGaiellaceaeandInocybaceaeabundances were positively correlated with ammonium nitrogen content, available phosphorus content, and phosphatase activity. Our findings indicate that variations in soil available phosphorus are closely related to the relative abundances ofGaiellaceaeat different soil depths andInocybaceaein different plantation types. Mixed plantations might change the availability of soil phosphorus by controlling the relative abundance ofInocybaceae. We recommend that fungal community changes be considered in the sustainable management of mixed plantations.
Transcriptome Analysis to Identify Crucial Genes for Reinforcing Flavins-Mediated Extracellular Electron Transfer in Shewanella oneidensis
Authors: Fang Lixia , Li Yuanyuan , Li Yan , Cao Yingxiu , Song Hao
Published: June 2022

Flavins serve as the electron mediators in Shewanella oneidensis, determining the extracellular electron transfer (EET) rate. Currently, metabolic engineering of flavins biosynthetic pathway has been studied for improving EET. However, the cellular response triggered by flavins that contribute to EET remains to be elucidated. In this study, the riboflavin-overproducing strain C5 (expressing the flavins synthetic genes in plasmid PYYDT) and the PYYDT strain (harboring the empty plasmid PYYDT) in the microbial fuel cells are applied for comparative transcriptomic analyses to investigate beneficial gene targets that could improve EET. From the differentially expressed genes, we select the significantly upregulated and downregulated genes for inverse engineering in S. oneidensis. The results show that overexpression of ahpC and ccpA, and inactivation of pubA, putB, and tonB are able to improve the EET capability. Combinatorial modulation of these five genes results in the recombinant strain CM4, achieving the maximum power density of 651.78 ± 124.60 mW/m2, 1.97 folds of the parental strain. These genes modulation is speculated to reduce the ROS damage and to promote cytochrome synthesis and heme accumulation, which coherently enhance EET. Our findings facilitate in-depth understanding of the mechanism of flavins-mediated EET and provide new insights in promoting EET of S. oneidensis for electricity generation.
Phenotypic and Molecular Characterization of K54-ST29 Hypervirulent Klebsiella pneumoniae Causing Multi-System Infection in a Patient With Diabetes
Authors: Shao Chunhong , Xin Li , Mi Peiyan , Jiang Meijie , Wu Haiyan
Published: June 2022

Worldwide, hypervirulent Klebsiella pneumoniae (hvKp) is one of the leading causes of multisystem infection. Serotype K54 has also been considered as one of the hvKp-associated capsular types that are rarely reported. In this study, we reported a K54-ST29 hvKp isolated from a 58-year-old male patient with diabetes in a teaching hospital in China. The patient rapidly developed sepsis and brain abscess, with a lethal multiple-organ-system failure due to K54 hvKp infection. This K54 hvKp isolate showed high level of toxicity in a mouse infection model and was susceptible to all the tested antibiotics. The isolate was fully sequenced, and its genome was compared with the available K54 K. pneumoniae genome. We predicted 133 virulence and pathogen-related genes, including those involved in fimbriae synthesis, iron transport, and enterobactin synthesis. Sequence alignment revealed >90% similarity among seven K54 K. pneumoniae strains. Our data suggest that community-acquired infection caused by hypervirulent K54 K. pneumoniae in patients with diabetes is a concern in East Asia.
The Native Hymenoscyphus albidus and the Invasive Hymenoscyphus fraxineus Are Similar in Their Necrotrophic Growth Phase in Ash Leaves
Authors: Hietala Ari M. , Agan Ahto , Nagy Nina E. , Børja Isabella , Timmermann Volkmar , Drenkhan Rein , Solheim Halvor
Published: June 2022

The populations of European ash and its harmless fungal associate Hymenoscyphus albidus are in decline owing to ash dieback caused by the invasive Hymenoscyphus fraxineus, a fungus that in its native range in Asia is a harmless leaf endophyte of local ash species. To clarify the behavior of H. albidus and its spatial and temporal niche overlap with the invasive relative, we used light microscopy, fungal species-specific qPCR assays, and PacBio long-read amplicon sequencing of the ITS1-5.8S-ITS2 region to examine fungal growth and species composition in attached leaves of European ash. The plant material was collected from a healthy stand in central Norway, where ash saplings in late autumn showed leaflet vein necrosis like that commonly related to H. fraxineus. For reference, leaflet samples were analyzed from stands with epidemic level of ash dieback in southeastern Norway and Estonia. While H. albidus was predominant in the necrotic veins in the healthy stand, H. fraxineus was predominant in the diseased stands. Otherwise, endophytes with pathogenic potential in the genera Venturia (anamorph Fusicladium), Mycosphaerella (anamorph Ramularia), and Phoma, and basidiomycetous yeasts formed the core leaflet mycobiome both in the healthy and diseased stands. In necrotic leaf areas with high levels of either H. albidus or H. fraxineus DNA, one common feature was the high colonization of sclerenchyma and phloem, a region from which the ascomata of both species arise. Our data suggest that H. albidus can induce necrosis in ash leaves, but that owing to low infection pressure, this first takes place in tissues weakened by autumn senescence, 1–2 months later in the season than what is characteristic of H. fraxineus at an epidemic phase of ash dieback. The most striking difference between these fungi would appear to be the high fecundity of H. fraxineus. The adaptation to a host that is phylogenetically closely related to European ash, a tree species with high occurrence frequency in Europe, and the presence of environmental conditions favorable to H. fraxineus life cycle completion in most years may enable the build-up of high infection pressure and challenge of leaf defense prior to autumn senescence.
Termite Nest Associated Bacillus siamensis YC-9 Mediated Biocontrol of Fusarium oxysporum f. sp. cucumerinum
Authors: Zhou Lingfeng , Wang Junyong , Wu Fei , Yin Caiping , Kim Ki Hyun , Zhang Yinglao
Published: June 2022

The antagonistic potential of bacteria obtained from the nest of Odontotermes formosanus was assessed against Fusarium oxysporum f. sp. cucumerinum (FOC). Of 30, seven termite nest-associated bacteria strains had biocontrol potential. Among them, the strain YC-9 showed the strongest antifungal activity toward FOC. Phylogenetic analysis of the 16S rRNA amplified product of YC-9 revealed its identification as Bacillus siamensis. The in vivo antifungal activity experiment showed that the application of YC-9 at 108 cfu/ml significantly reduced the cucumber wilt incidence with a control efficacy of 73.2%. Furthermore, plant growth parameters such as fresh weight, dry weight, plant height, and root height were significantly improved by 42.6, 53.0, 20.8, and 19.3%, respectively. We found that inoculation with B. siamensis YC-9 significantly increased the activity of defensive enzymes such as peroxidase (POD), polyphenol oxidase (PPO), and phenylalanine ammonia-lyase (PAL) in diseased cucumber roots, thereby raising the resistance. PCR using gene-specific primers revealed that B. siamensis YC-9 contains biosynthetic genes for known antibiotics, including bacillomycin, iturin, and surfactin. Chemical analysis of the cultivation of B. siamensis YC-9 resulted in the isolation of five metabolites, including hexadecanoic acid (1), cyclo-(L-phenylalanylglycine) (2), cyclo-(L-trans-Hyp-L-Leu) (3), C15-surfactin (4), and macrolactin A (5), the structures of which were identified by the analysis of NMR spectroscopic data and MS. Among them, the compound 4 showed significant antifungal activity against conidial germination of FOC with an IC50 value of 5.1 μg/ml, which was comparable to that of the positive control, cycloheximide (IC50 value of 2.6 μg/ml). Based on these findings, this study suggests that termite-nest associated B. siamensis YC-9 could be a potential biological control agent for integrated control of soil-borne diseases like cucumber Fusarium wilt.
The Bacterial Flagellar Motor: Insights Into Torque Generation, Rotational Switching, and Mechanosensing
Authors: Guo Shuaiqi , Liu Jun
Published: June 2022

The flagellar motor is a bidirectional rotary nanomachine used by many bacteria to sense and move through environments of varying complexity. The bidirectional rotation of the motor is governed by interactions between the inner membrane-associated stator units and the C-ring in the cytoplasm. In this review, we take a structural biology perspective to discuss the distinct conformations of the stator complex and the C-ring that regulate bacterial motility by switching rotational direction between the clockwise (CW) and counterclockwise (CCW) senses. We further contextualize recent in situ structural insights into the modulation of the stator units by accessory proteins, such as FliL, to generate full torque. The dynamic structural remodeling of the C-ring and stator complexes as well as their association with signaling and accessory molecules provide a mechanistic basis for how bacteria adjust motility to sense, move through, and survive in specific niches both outside and within host cells and tissues.
A Nuclei-Based Conceptual Model of (Eco)evolutionary Dynamics in Fungal Heterokaryons
Authors: Lakovic Milica , Rillig Matthias C.
Published: June 2022

Filamentous fungi are characterised by specific features, such as multinuclearity, coexistence of genetically different nuclei and nuclear movement across the mycelial network. These attributes make them an interesting, yet rather underappreciated, system for studying (eco)evolutionary dynamics. This is especially noticeable among theoretical studies, where rather few consider nuclei and their role in (eco)evolutionary dynamics. To encourage such theoretical approaches, we here provide an overview of existing research on nuclear genotype heterogeneity (NGH) and its sources, such as mutations and vegetative non-self-fusion. We then discuss the resulting intra-mycelial nuclear dynamics and the potential consequences for fitness and adaptation. Finally, we formulate a nuclei-based conceptual framework, which considers three levels of selection: a single nucleus, a subpopulation of nuclei and the mycelium. We compare this framework to other concepts, for example those that consider only the mycelium as the level of selection, and outline the benefits of our approach for studying (eco)evolutionary dynamics. Our concept should serve as a baseline for modelling approaches, such as individual-based simulations, which will contribute greatly to our understanding of multilevel selection and (eco)evolutionary dynamics in filamentous fungi.
A Species-Specific Strategy for the Identification of Hemocoagulase Agkistrodon halys pallas Based on LC-MS/MS-MRM
Authors: Xian Ruiqing , Wang Congcong , Gong Liping , Hang Baojian , Wang Weijian , Zhang Xunjie , Du Hongmin , Wang Fengshan , Shi Feng
Published: June 2022

Hemocoagulase Agkistrodon halys pallas is a complex mixture composed of snake venom thrombin-like enzymes (svTLEs) and small amounts of thrombokinase-like enzymes. It has been widely used as a hemostatic with rapidly growing marketing due to its advantage of localized clotting fibrinogen other than systemic coagulation. However, svTLEs from different species have various structures, functions, and hemostatic mechanisms. To ensure the efficacy and safety of Hemocoagulase Agkistrodon halys pallas, an exclusive and sensitive method has been developed to identify specific marker peptides based on liquid chromatography-tandem mass spectrometry with multiple reaction monitoring (LC-MS/MS-MRM) mode. By combining transcriptomics and proteomics, a series of species-specific peptides of Agkistrodon halys pallas were predicted and examined by LC-MS/MS. After reduction, alkylation, and tryptic digestion were performed on Hemocoagulase Agkistrodon halys pallas, a target peptide TLCAGVMEGGIDTCNR was analyzed by LC-MS/MS-MRM. It offers a new and effective approach for the quality control of Hemocoagulase Agkistrodon halys pallas products. This method is superior to the current assays in terms of sensitivity, specificity, precision, accuracy, and throughput. The strategy can also be applied in studying other important protein-based medicines.
DEER Data Analysis Software: A Comparative Guide
Authors: Russell Hannah , Cura Robyn , Lovett Janet E.
Published: June 2022

Pulsed dipolar electron paramagnetic resonance (PDEPR) spectroscopy experiments measure the dipolar coupling, and therefore nanometer-scale distances and distance distributions, between paramagnetic centers. Of the family of PDEPR experiments, the most commonly used pulsed sequence is four-pulse double electron resonance (DEER, also known as PELDOR). There are several ways to analyze DEER data to extract distance distributions, and this may appear overwhelming at first. This work compares and reviews six of the packages, and a brief getting started guide for each is provided.
The Effect of Lifetime Noise Exposure and Aging on Speech-Perception-in-Noise Ability and Self-Reported Hearing Symptoms: An Online Study
Authors: Shehabi Adnan M. , Prendergast Garreth , Guest Hannah , Plack Christopher J.
Published: June 2022

Animal research shows that aging and excessive noise exposure damage cochlear outer hair cells, inner hair cells, and the synapses connecting inner hair cells with the auditory nerve. This may translate into auditory symptoms such as difficulty understanding speech in noise, tinnitus, and hyperacusis. The current study, using a novel online approach, assessed and quantified the effects of lifetime noise exposure and aging on (i) speech-perception-in-noise (SPiN) thresholds, (ii) self-reported hearing ability, and (iii) the presence of tinnitus. Secondary aims involved documenting the effects of lifetime noise exposure and aging on tinnitus handicap and the severity of hyperacusis. Two hundred and ninety-four adults with no past diagnosis of hearing or memory impairments were recruited online. Participants were assigned into two groups: 217 “young” (age range: 18–35 years, females: 151) and 77 “older” (age range: 50–70 years, females: 50). Participants completed a set of online instruments including an otologic health and demographic questionnaire, a dementia screening tool, forward and backward digit span tests, a noise exposure questionnaire, the Khalfa hyperacusis questionnaire, the short-form of the Speech, Spatial, and Qualities of Hearing scale, the Tinnitus Handicap Inventory, a digits-in-noise test, and a Coordinate Response Measure speech-perception test. Analyses controlled for sex and cognitive function as reflected by the digit span. A detailed protocol was pre-registered, to guard against “p-hacking” of this extensive dataset. Lifetime noise exposure did not predict SPiN thresholds, self-reported hearing ability, or tinnitus handicap in either age group. Exploratory analyses showed that worse hyperacusis scores, and a greater prevalence of tinnitus, were associated significantly with high lifetime noise exposure in the young, but not in the older group. Age was a significant predictor of SPiN thresholds and the presence of tinnitus, but not of self-reported hearing ability, tinnitus handicap, or severity of hyperacusis. Consistent with several lab studies, our online-derived data suggest that older adults with no diagnosis of hearing impairment have a poorer SPiN ability and a higher risk of tinnitus than their younger counterparts. Moreover, lifetime noise exposure may increase the risk of tinnitus and the severity of hyperacusis in young adults with no diagnosis of hearing impairment.
Transcranial Direct Current Stimulation of the Dorsolateral Prefrontal Cortex for Treatment of Neuropsychiatric Disorders
Authors: Li Qing , Fu Yu , Liu Chang , Meng Zhiqiang
Published: June 2022

Background

The dorsolateral prefrontal cortex (DLPFC) is a key node of the frontal cognitive circuit. It is involved in executive control and many cognitive processes. Abnormal activities of DLPFC are likely associated with many psychiatric diseases. Modulation of DLPFC may have potential beneficial effects in many neural and psychiatric diseases. One of the widely used non-invasive neuromodulation technique is called transcranial direct current stimulation (or tDCS), which is a portable and affordable brain stimulation approach that uses direct electrical currents to modulate brain functions.

Objective

This review aims to discuss the results from the past two decades which have shown that tDCS can relieve clinical symptoms in various neurological and psychiatric diseases.

Methods

Here, we performed searches on PubMed to collect clinical and preclinical studies that using tDCS as neuromodulation technique, DLPFC as the stimulation target in treating neuropsychiatric disorders. We summarized the stimulation sites, stimulation parameters, and the overall effects in these studies.

Results

Overall, tDCS stimulation of DLPFC could alleviate the clinical symptoms of schizophrenia, depression, drug addiction, attention deficit hyperactivity disorder and other mental disorders.

Conclusion

The stimulation parameters used in these studies were different from each other. The lasting effect of stimulation was also not consistent. Nevertheless, DLPFC is a promising target for non-invasive stimulation in many psychiatric disorders. TDCS is a safe and affordable neuromodulation approach that has potential clinical uses. Larger clinical studies will be needed to determine the optimal stimulation parameters in each condition.
Temporally Local Tactile Codes Can Be Stored in Working Memory
Authors: Bhattacharjee Arindam , Schwarz Cornelius
Published: June 2022

Tactile exploration often involves sequential touches interspersed with stimulus-free durations (e.g., the time during which the hand moves from one textured surface to the other). Whereas it is obvious that texture-related perceptual variables, irrespective of the encoding strategy, must be stored in memory for comparison, it is rather unclear which of those variables are held in memory. There are two established variables—“intensity” and “frequency”, which are “temporally global” variables because of the long stimulus integration interval required to average the signal or derive spectral components, respectively; on the other hand, a recently established third contender is the “temporally local” variable that codes for kinematic profiles of very short, suprathreshold events in the vibrotactile signal. Here, we present the first psychophysical evidence that temporally local variables can be stored in memory. To that end, we asked participants to detect changes in pulsatile indentation stimuli at their fingertips with and without a gap of 1 s between stimulus presentations. The stimuli either contained global variables alone (change of pulse rate), or a mix of local and global variables (change of pulse shape). We found, first, that humans are much better at detecting a change in stimuli when local variables are available rather than global ones alone—as evident by the fact that 21 compared to only 6 participants out of 25 yielded a valid psychophysical curve, respectively. Second, this observation persists even when there is a gap between the stimuli, implying local variables must be stored in memory. Third, an extensive array of relevant intensity definitions failed to explain participants’ performance in any consistent manner, which implies that perceptual decisions were less likely to be driven by intensity coding. Taken together, our results suggest that humans perform pulsatile change detection utilizing local pulse shape, and to a lesser degree global pulse rate, and that both parameters can be stored in memory.
A Dynamic Submaximal Fatigue Protocol Alters Wrist Biomechanical Properties and Proprioception
Authors: Albanese Giulia A. , Falzarano Valeria , Holmes Michael W. R. , Morasso Pietro , Zenzeri Jacopo
Published: June 2022

Fatigue is a temporary condition that arises as a result of intense and/or prolonged use of muscles and can affect skilled human performance. Therefore, the quantitative analysis of these effects is a topic of crucial interest in both ergonomics and clinical settings. This study introduced a novel protocol, based on robotic techniques, to quantitatively assess the effects of fatigue on the human wrist joint. A wrist manipulandum was used for two concurrent purposes: (1) implementing the fatigue task and (2) assessing the functional changes both before and at four time points after the end of the fatigue task. Fourteen participants completed the experimental protocol, which included the fatigue task and assessment sessions over 2 days. Specifically, the assessments performed are related to the following indicators: (1) isometric forces, (2) biomechanical properties of the wrist, (3) position sense, and (4) stretch reflexes of the muscles involved. The proposed fatigue task was a short-term, submaximal and dynamic wrist flexion/extension task designed with a torque opposing wrist flexion. A novel task termination criterion was employed and based on a percentage decrease in the mean frequency of muscles measured using surface electromyography. The muscle fatigue analysis demonstrated a change in mean frequency for both the wrist flexors and extensors, however, only the isometric flexion force decreased 4 min after the end of the task. At the same time point, wrist position sense was significantly improved and stiffness was the lowest. Viscosity presented different behaviors depending on the direction evaluated. At the end of the experiment (about 12 min after the end of the fatigue task), wrist position sense recovered to pre-fatigue values, while biomechanical properties did not return to their pre-fatigue values. Due to the wide variety of fatigue tasks proposed in the literature, it has been difficult to define a complete framework that presents the dynamic of fatigue-related changes in different components associated with wrist function. This work enables us to discuss the possible causes and the mutual relationship of the changes detected after the same task.
Abnormal Brain Oscillations in Developmental Disorders: Application of Resting State EEG and MEG in Autism Spectrum Disorder and Fragile X Syndrome
Authors: Liang Sophia , Mody Maria
Published: June 2022

Autism Spectrum Disorder (ASD) and Fragile X Syndrome (FXS) are neurodevelopmental disorders with similar clinical and behavior symptoms and partially overlapping and yet distinct neurobiological origins. It is therefore important to distinguish these disorders from each other as well as from typical development. Examining disruptions in functional connectivity often characteristic of neurodevelopment disorders may be one approach to doing so. This review focuses on EEG and MEG studies of resting state in ASD and FXS, a neuroimaging paradigm frequently used with difficult-to-test populations. It compares the brain regions and frequency bands that appear to be impacted, either in power or connectivity, in each disorder; as well as how these abnormalities may result in the observed symptoms. It argues that the findings in these studies are inconsistent and do not fit neatly into existing models of ASD and FXS, then highlights the gaps in the literature and recommends future avenues of inquiry.
Abnormal Insular Dynamic Functional Connectivity and Its Relation to Social Dysfunctioning in Children With Attention Deficit/Hyperactivity Disorder
Authors: Fateh Ahmed Ameen , Huang Wenxian , Mo Tong , Wang Xiaoyu , Luo Yi , Yang Binrang , Smahi Abla , Fang Diangang , Zhang Linlin , Meng Xianlei , Zeng Hongwu
Published: June 2022

Anomalies in large-scale cognitive control networks impacting social attention abilities are hypothesized to be the cause of attention deficit hyperactivity disorder (ADHD). The precise nature of abnormal brain functional connectivity (FC) dynamics including other regions, on the other hand, is unknown. The concept that insular dynamic FC (dFC) among distinct brain regions is dysregulated in children with ADHD was evaluated using Insular subregions, and we studied how these dysregulations lead to social dysfunctioning. Data from 30 children with ADHD and 28 healthy controls (HCs) were evaluated using dynamic resting state functional magnetic resonance imaging (rs-fMRI). We evaluated the dFC within six subdivisions, namely both left and right dorsal anterior insula (dAI), ventral anterior insula (vAI), and posterior insula (PI). Using the insular sub-regions as seeds, we performed group comparison between the two groups. To do so, two sample t-tests were used, followed by post-hoc t-tests. Compared to the HCs, patients with ADHD exhibited decreased dFC values between right dAI and the left middle frontal gyrus, left postcentral gyrus and right of cerebellum crus, respectively. Results also showed a decreased dFC between left dAI and thalamus, left vAI and left precuneus and left PI with temporal pole. From the standpoint of the dynamic functional connectivity of insular subregions, our findings add to the growing body of evidence on brain dysfunction in ADHD. This research adds to our understanding of the neurocognitive mechanisms behind social functioning deficits in ADHD. Future ADHD research could benefit from merging the dFC approach with task-related fMRI and non-invasive brain stimulation, which could aid in the diagnosis and treatment of the disorder.
The Role of Vti1a in Biological Functions and Its Possible Role in Nervous System Disorders
Authors: Tang Fajuan , Fan Jiali , Zhang Xiaoyan , Zou Zhuan , Xiao Dongqiong , Li Xihong
Published: June 2022

Vesicle transport through interaction with t-SNAREs 1A (Vti1a), a member of the N-ethylmaleimide-sensitive factor attachment protein receptor protein family, is involved in cell signaling as a vesicular protein and mediates vesicle trafficking. Vti1a appears to have specific roles in neurons, primarily by regulating upstream neurosecretory events that mediate exocytotic proteins and the availability of secretory organelles, as well as regulating spontaneous synaptic transmission and postsynaptic efficacy to control neurosecretion. Vti1a also has essential roles in neural development, autophagy, and unconventional extracellular transport of neurons. Studies have shown that Vti1a dysfunction plays critical roles in pathological mechanisms of Hepatic encephalopathy by influencing spontaneous neurotransmission. It also may have an unknown role in amyotrophic lateral sclerosis. A VTI1A variant is associated with the risk of glioma, and the fusion product of the VTI1A gene and the adjacent TCF7L2 gene is involved in glioma development. This review summarizes Vti1a functions in neurons and highlights the role of Vti1a in the several nervous system disorders.
RETRACTED: Obesity Accelerates Leukocyte Telomere Length Shortening in Apparently Healthy Adults: A Meta-Analysis
Authors: Khosravaniardakani Sheida , Bokov Dmitry Olegovich , Mahmudiono Trias , Hashemi Seyedeh Sedigheh , Nikrad Negin , Rabieemotmaen Shadi , Abbasalizad-Farhangi Mahdieh
Published: June 2022

Background

Shorter telomere length is associated with numerous comorbidities. Several studies have investigated the role of obesity in telomere shortening. In the current systematic review and meta-analysis, we summarized the results of studies that evaluated the association between obesity and telomere length.

Methods

A systematic search from Scopus, PubMed, Embase, and ProQuest electronic databases up to 19 March 2021 without language restriction was performed and after data extraction and screening, 19 manuscripts were eligible to be included in the final meta-synthesis.

Results

The highest category of telomere length was associated with an approximate 0.75 kg/m2 reduction in body mass index (BMI; WMD = −0.75 kg/m2; CI = −1.19, −0.31; p < 0.001; I2 = 99.4%). Moreover, overweight/obese individuals had 0.036 kbp shorter telomere length compared with non-overweight/obese adults (WMD = −0.036; CI = −0.05, −0.02; p = 0.030; I2 = 100%). According to the results of subgroupings, continent, age, and sample size could be possible sources of heterogeneity.

Conclusion

From the results, it was clear that obesity was associated with shorter telomere length. Because of the observational design of included studies, the causality inference of results should be done with caution; thus, further longitudinal studies are warranted for better inference of causal association.
Identification of Di/Tripeptide(s) With Osteoblasts Proliferation Stimulation Abilities of Yak Bone Collagen by in silico Screening and Molecular Docking
Authors: Chen Yongkai , Guo Yujie , Liu Yusi , Zhang Chunhui , Huang Feng , Chen Lingyun
Published: June 2022

Endothelial protein C receptor (EPCR), cannabinoid receptor 2 (CBR2), and estrogen receptor α (ERα) play vital roles in osteoblasts proliferation. Also, collagen peptides have osteoblasts proliferation stimulation abilities, and di/tri-peptides could be absorbed by the intestine more easily. This study obtained three di/tripeptides with potential osteoblasts proliferation stimulation abilities of yak bone collagen, namely, MGF, CF, and MF, by in silico screening. Results suggested that these three peptides exhibited good absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties. They also had strong affinities with EPCR, CBR2, and ERα, and the total -CDOCKER energy (-CE) values were 150.9469, 113.1835, and 115.3714 kcal/mol, respectively. However, further Cell Counting Kit-8 (CCK-8) assays indicated that only MGF could significantly (P < 0.05) stimulate osteoblasts proliferation at 0.3 mg/ml. At the same time, the proliferating index (PI) of the osteoblasts treated with MGF increased significantly (P < 0.05), and the alkaline phosphatase (ALP) activity decreased highly significantly (P < 0.01). In summary, MGF exhibited the potential to be an effective treatment for osteoporosis.
Lycopene in Combination With Sorafenib Additively Inhibits Tumor Metastasis in Mice Xenografted With Lewis Lung Carcinoma Cells
Authors: Chan Ya-Ping , Chuang Cheng-Hung , Lee Inn , Yang Nae-Cherng
Published: June 2022

Cancer metastasis is the leading cause of death in cancer patients. However, it is unclear whether lycopene can act as an adjuvant to increase the anti-metastatic activity of anticancer drugs. Here, we examined the anti-lung-metastatic effects and the mechanism of lycopene in combination with sorafenib in C57BL/6 mice xenografted with Lewis lung carcinoma (LLC) cells. The mice were divided into five groups: (1) tumor control; (2) lycopene (5 mg/kg); (3) sorafenib (30 mg/kg); (4) lycopene (2 mg/kg) + sorafenib (30 mg/kg); (5) lycopene (5 mg/kg) + sorafenib (30 mg/kg). The results showed that lycopene reduced the number of metastatic tumors in the lungs, which was further suppressed by the combined treatment with sorafenib. The activities of matrix metalloproteinase (MMP)-2 and−9 were further inhibited and TIMP-1 and−2, and NM23-H1, the MMPs negative modulators, were further activated in the combined treatment. Mechanistically, we found that lycopene and sorafenib could additively inhibit the mitogen-activated protein kinase (MAPK) pathways, as shown by the protein phosphorylation of ERK1/2, JNK1/2 and p38 were reduced additively. Overall, the present study demonstrates that lycopene in combination with sorafenib additively inhibits the lung metastasis of tumor, indicating lycopene has potential as an adjuvant for sorafenib in cancer treatment.
Recognition of Gallotannins and the Physiological Activities: From Chemical View
Authors: He Hua-Feng
Published: June 2022

Gallotannins, characterized with the glycosidic core and galloyl unit, are seemed as vital components of hydrolyzable tannins. Benefit from the more and more discoveries of their bioactivities and edibility, application of gallotannins in food industry, pharmacy industry, and other fields is increasing. Inheriting previous study achievements, chemical structure of gallotannins was illustrated and degradation as well as synthetic routes to gallotannins were summarized. On this basis, distribution in the nature also including the distinction of gallotannins was discussed. More than that, activities involving in antioxidant, anti-inflammatory, enzyme inhibitions, protein binding, and so on, as well as applications in the field of food industry, biopharmaceutical science, agricultural production, etc., were combed. Finally, improvement of bioavailability, chemical modification of the structure, and accurate determination of new gallotannins were pointed out to be the orientation in the future.