bluuebunny/crossref_metadata_2025 huggingface dataset:
On Threshold Resummation S-Factor for a System of Two Relativistic Spinor Particles with Arbitrary Masses
Authors: Chernichenko Yu. D. , Kaptari L. P. , Solovtsova O. P.
Published: January 2021

We present a new threshold resummation S-factor obtained for a composite system of two relativistic spin 1/2 particles of arbitrary masses interacting via a Coulomb-like chromodynamical potential. The analysis is performed in the framework of a relativistic quasipotential approach in the Hamiltonian formulation of the quantum field theory in the relativistic configuration representation. The pseudoscalar, vector, and pseudovector systems are considered. The difference in the behavior of the S-factor for these cases is discussed. A connection between the new and the previously obtained S-factors for spinless particles of arbitrary masses and relativistic spinor particles of equal masses is established.
The Effect of MMP-2 Inhibitor 1 on Osteogenesis and Angiogenesis During Bone Regeneration
Authors: Jiang Liangjun , Sheng Kunkun , Wang Cong , Xue Deting , Pan Zhijun
Published: January 2021

Bone regeneration is a popular research focus around the world. Recent studies have suggested that the formation of a vascular network as well as intrinsic osteogenic ability is important for bone regeneration. Here, we show for the first time that matrix metalloproteinase (MMP) 2 inhibitor 1 (MMP2-I1) has a positive role in the osteogenesis of human bone marrow mesenchymal stem cells (hBMSCs) and angiogenesis of human vascular endothelial cells (HUVECs). MMP2-I1 activated the p38/mitogen-activated protein kinase signaling pathway to promote the osteogenesis of hBMSCs, and promoted the angiogenesis of HUVECs via the hypoxia-inducible factor-1α signaling pathway. We also found that MMP2-I1 enhanced bone formation using a rat tibial defect model and prevented bone loss using an ovariectomy-induced mouse model of osteoporosis. Data from the mouse model demonstrated that MMP2-I1 generated more type H vessels (CD31hiEmcnhi) when preventing bone loss. These results provide important insights into the regulatory effects of MMP2-I1 on bone regeneration.
SHP2 Nuclear/Cytoplasmic Trafficking in Granulosa Cells Is Essential for Oocyte Meiotic Resumption and Maturation
Authors: Idrees Muhammad , Kumar Vikas , Joo Myeong-Don , Ali Niaz , Lee Keun-Woo , Kong Il-Keun
Published: January 2021

Src-homology-2-containing phosphotyrosine phosphatase (SHP2), a classic cytoplasmic protein and a major regulator of receptor tyrosine kinases and G protein-coupled receptors, plays a significant role in preimplantation embryo development. In this study, we deciphered the role of SHP2 in the somatic compartment of oocytes during meiotic maturation. SHP2 showed nuclear/cytoplasmic localization in bovine cumulus and human granulosa (COV434) cells. Follicle-stimulating hormone (FSH) treatment significantly enhanced cytoplasmic SHP2 localization, in contrast to the E2 treatment, which augmented nuclear localization. Enhanced cytoplasmic SHP2 was found to negatively regulate the expression of the ERα-transcribed NPPC and NPR2 mRNAs, which are vital for oocyte meiotic arrest. The co-immunoprecipitation results revealed the presence of the SHP2/ERα complex in the germinal vesicle-stage cumulus–oocyte complexes, and this complex significantly decreased with the progression of meiotic maturation. The complex formation between ERα and SHP2 was also confirmed by using a series of computational modeling methods. To verify the correlation between SHP2 and NPPC/NPR2, SHP2 was knocked down via RNA interference, and NPPC and NPR2 mRNAs were analyzed in the control, E2, and FSH-stimulated COV434 cells. Furthermore, phenyl hydrazonopyrazolone sulfonate 1, a site-directed inhibitor of active SHP2, showed no significant effect on the ERα-transcribed NPPC and NPR2 mRNAs. Taken together, these findings support a novel nuclear/cytoplasmic role of SHP2 in oocyte meiotic resumption and maturation.
Mitochondrial tRNA Mutation and Regulation of the Adiponectin Pathway in Maternally Inherited Hypertension in Chinese Han
Authors: Bai Jing , Ma Qiang , Lan Yunfeng , Chen Yating , Ma Shanshan , Li Jiaxin , Liu Chuanbin , Fu Zihao , Lu Xu , Huang Yun , Li Yang
Published: January 2021

Some essential hypertension (EH) patients show maternal inheritance, which is the mode of mitochondrial DNA inheritance. This study examines the mechanisms by which mitochondrial mutations cause EH characterized by maternal inheritance. The study enrolled 115 volunteers, who were divided into maternally inherited EH (group A, n = 17), non-maternally inherited EH (group B, n = 65), and normal control (group C, n = 33) groups. A mitochondrial tRNA (15910 C>T) gene mutation was significantly correlated with EH and may play an important role in the pathogenesis of maternally inherited EH. Examining two families carrying the mitochondrial tRNA 15910 C>T mutation, which disrupted base pairing and may affect the stability and function of mitochondrial tRNAThr, we find that the overall incidence of EH was 59.3% in the maternal family members and 90% in males, significantly higher than in the general population in China (23.2%), and that the EH began at a younger age in those carrying mitochondrial tRNA 15910 C>T. To reveal the mechanism through which mitochondrial tRNA 15910 C>T causes maternally inherited EH, we cultured human peripheral blood mononuclear cells from family A2 in vitro. We find that cells carrying mitochondrial tRNA 15910 C>T were more viable and proliferative, and the increased ATP production resulted in raised intracellular reactive oxygen species (ROS). Moreover, the mitochondrial dysfunction resulted in reduced APN levels, causing hypoadiponectinemia, which promoted cell proliferation, and produced more ROS. This vicious cycle promoted the occurrence of EH with maternally inherited mitochondrial tRNA 15910 C>T. The mitochondrial tRNA 15910 C>T mutation may induce hypertension by changing the APN, AdipoR1, PGC-1α, and ERRα signaling pathways to elevate blood pressure. We discover a new mitochondrial mutation (tRNA 15910 C>T) related to EH, reveal part of the mechanism by which mitochondrial mutations lead to the occurrence and development of maternally inherited EH, and discuss the role of APN in it.
RNF180 Inhibits Proliferation and Promotes Apoptosis of Colorectal Cancer Through Ubiquitination of WISP1
Authors: Wei Feng , Ba Sang , Jin Mei , Ci Ren , Wang Xuelian , E Fusheng , Long Ziwen
Published: January 2021

Colorectal cancer (CRC) is the third leading cause of cancer-related deaths globally and is biologically and clinically heterogeneous. Due to lack of gene expression signatures for risk and prognosis stratification of CRC, identifying novel molecular biomarkers and therapeutic targets may potentially improve CRC prognosis and treatment. RNF180 has been shown to play key contributions to the development of several types of cancers. In the current study, we investigate its role in CRC. In this study, we show that RNF180 expression was significantly downregulated in human CRC tumors and cell lines. Overexpression of RNF180 in CRC cells markedly inhibited cell viability and induced cell apoptosis, while depletion of RNF180 dramatically enhanced cell survival. Moreover, WISP1 was found to be the critical downstream molecule that mediated the tumor suppressive effects of RNF180. Mechanistically, RNF180 ubiquitinated WISP1, resulting in WISP1 downregulation and ultimately leading to suppression of CRC tumor growth in patient-derived xenograft (PDX) mouse models. Last, 5-FU and RNF180 had synergetic effect on the apoptosis induction and tumor growth inhibition. Our findings revealed a crucial role of RNF180 in suppressing tumor growth by ubiquitinating WISP1 in CRC.
HIF-1α Protects Granulosa Cells From Hypoxia-Induced Apoptosis During Follicular Development by Inducing Autophagy
Authors: Tang Zonghao , Xu Renfeng , Zhang Zhenghong , Shi Congjian , Zhang Yan , Yang Hongqin , Lin Qingqiang , Liu Yiping , Lin Fengping , Geng Baorong , Wang Zhengchao
Published: January 2021

Owing to the avascular structure of the ovarian follicle, proliferation of granulosa cells (GCs) and development of follicles occur under hypoxia, which is obviously different from the cell survival requirements of most mammalian cells. We hypothesized that autophagy may exert an inhibitory effect on GC apoptosis. To decipher the underlying mechanism, we constructed a rat follicular development model using pregnant mare serum gonadotropin and a cell culture experiment in hypoxic conditions (3% O2). The present results showed that the autophagy level was obviously increased and was accompanied by the concomitant elevation of hypoxia inducible factor (HIF)-1α and BNIP3 (Bcl-2/adenovirus E1B 19kDa-interacting protein 3) in GCs during follicular development. The levels of Bax (Bcl2-associated X) and Bcl-2 (B-cell lymphoma-2) were increased, while the activation of caspase-3 exhibited no obvious changes during follicular development. However, inhibition of HIF-1α attenuated the increase in Bcl-2 and promoted the increase in Bax and cleaved caspase-3. Furthermore, we observed the downregulation of BNIP3 and the decrease in autophagy after treatment with a specific HIF-1α activity inhibitor (echinomycin), indicating that HIF-1α/BNIP3 was involved in autophagy regulation in GCs in vivo. In an in vitro study, we also found that hypoxia did not obviously promote GC apoptosis, while it significantly enhanced the activation of HIF-1α/BNIP3 and the induction of autophagy. Expectedly, this effect could be reversed by 3-methyladenine (3-MA) treatment. Taken together, these findings demonstrated that hypoxia drives the activation of HIF-1α/BNIP3 signaling, which induces an increase in autophagy, protecting GC from apoptosis during follicular development.
Characteristics of Slow Slip Event in March 2020 Revealed From Borehole and DONET Observatories
Authors: Ariyoshi Keisuke , Iinuma Takeshi , Nakano Masaru , Kimura Toshinori , Araki Eiichiro , Machida Yuya , Sueki Kentaro , Yada Shuichiro , Nishiyama Takehiro , Suzuki Kensuke , Hori Takane , Takahashi Narumi , Kodaira Shuichi
Published: January 2021

We have detected an event of pore pressure change (hereafter, we refer it to “pore pressure event”) from borehole stations in real time in March 2020, owing to the network developed by connecting three borehole stations to the Dense Oceanfloor Network System for Earthquakes and Tsunamis (DONET) observatories near the Nankai Trough. During the pore pressure event, shallow very low-frequency events (sVLFEs) were also detected from the broadband seismometers of DONET, which suggests that the sVLFE migrated toward updip region along the subduction plate boundary. Since one of the pore pressure sensors have been suffered from unrecognized noise after the replacement of sensors due to the connecting operation, we assume four cases for crustal deformation component of the pore pressure change. Comparing the four possible cases for crustal deformation component of the volumetric strain change at C0010 with the observed sVLFE migration and the characteristic of previous SSEs, we conclude that the pore pressure event can be explained from SSE migration toward the updip region which triggered sVLFE in the passage. This feature is similar to the previous SSE in 2015 and could be distinguished from the unrecognized noise on the basis oft-test. Our new finding is that the SSE in 2020 did not reach very shallow part of the plate interface because the pore pressure changes at a borehole station installed in 2018 close to the trough axis was not significant. In the present study, we estimated the amount, onset and termination time of the pore pressure change for the SSE in 2020 by fitting regression lines for the time history. Since the change amount and duration time were smaller and shorter than the SSE in 2015, respectively, we also conclude that the SSE in 2020 had smaller magnitude that the SSE in 2015. These results would give us a clue to monitor crustal deformation along the Nankai Trough directly from other seafloor observations.
Attribution of the Principal Components of the Summertime Ozone Valley in the Upper Troposphere and Lower Stratosphere
Authors: Chang Shujie , Shi Chunhua , Guo Dong , Xu Jianjun
Published: January 2021

The key factors affecting the variation of the ‘ozone valley’, which appears during the boreal summer in the upper troposphere and lower stratosphere (UTLS) over the South Asian High (SAH) and its adjacent areas, have not been determined. This study has performed statistical analysis to improve the understanding of the roles of the sea surface temperature (SST), tropopause height, and the West Pacific Subtropical High (WPSH) on the ozone valley. Based on the European Center for Medium-Range Weather Forecasts Interim Re-Analysis (ERA5), Modern Era Retrospective Analysis for Research and Applications dataset version 2 (MERRA2), and the Stratospheric Water and Ozone Satellite Homogenized (SWOOSH) observation dataset, we examined the principal components of the zonal deviation of the total column ozone (TCO*) in the UTLS by applying the empirical orthogonal function (EOF), Liang-Kleeman information flow method, regression analysis, and composite analysis. The variations of the TCO* anomalies show three dominant modes, namely the east-west dipole mode in the low latitude region, the east-west tripole mode in the middle latitude region, and the south-north mode. According to the regression analysis and information flow, the three leading principal components of TCO* variations are related to the SST near Indonesia and the western Pacific Ocean in low latitudes, the tropopause height over the Iranian Plateau (IP), and the strength of the SAH over the eastern part of the Tibetan Plateau (TP), which is linked to the synchronousness between the SAH and the WPSH. For the east-west dipole mode in the low latitude region, composite analysis shows the interaction between the atmosphere and ocean causes the strengthening of the southern trough at 850 hPa and the divergence at 200 hPa, resulting in a decrease of the TCO* in the UTLS near the low latitude region around the TP. For the east-west tripole mode in the middle latitude region, the composite analysis shows obvious negative anomalies over the IP, where the TCO* reduces and the extent of the ozone valley over the IP increases with the rise of the tropopause. Comparatively, the south-north mode shows obvious positive anomalies over the TP, where the TCO* increases and the extent of the ozone valley over the TP decreases with a weak SAH. This mode is closely related to the location of the WPSH. In summary, the leading factors affecting the three dominant modes for the variations of the TCO* anomalies are SST, tropopause height, and the WPSH.
Toward a Medical Gastric Bypass: Chronic Feeding Studies With Liraglutide + PYY3-36 Combination Therapy in Diet-Induced Obese Rats
Authors: Dischinger Ulrich , Hasinger Julia , Königsrainer Malina , Corteville Carolin , Otto Christoph , Fassnacht Martin , Hankir Mohamed , Seyfried Florian Johannes David
Published: January 2021

Background

Combination therapies of anorectic gut hormones partially mimic the beneficial effects of bariatric surgery. Thus far, the effects of a combined chronic systemic administration of Glucagon-like peptide-1 (GLP-1) and peptide tyrosine tyrosine 3-36 (PYY3-36) have not been directly compared to Roux-en-Y gastric bypass (RYGB) in a standardized experimental setting.

Methods

High-fat diet (HFD)-induced obese male Wistar rats were randomized into six treatment groups: (1) RYGB, (2) sham-operation (shams), (3) liraglutide, (4) PYY3-36, (5) PYY3-36+liraglutide (6), saline. Animals were kept on a free choice high- and low-fat diet. Food intake, preference, and body weight were measured daily for 4 weeks. Open field (OP) and elevated plus maze (EPM) tests were performed.

Results

RYGB reduced food intake and achieved sustained weight loss. Combined PYY3-36+liraglutide treatment led to similar and plateaued weight loss compared to RYGB. Combined PYY3-36+liraglutide treatment was superior to PYY3-36 (p ≤ 0.0001) and liraglutide (p ≤ 0.05 or p ≤ 0.01) mono-therapy. PYY3-36+liraglutide treatment and RYGB also reduced overall food intake and (less pronounced) high-fat preference compared to controls. The animals showed no signs of abnormal behavior in OF or EPM.

Conclusions

Liraglutide and PYY3-36 combination therapy vastly mimics reduced food intake, food choice and weight reducing benefits of RYGB.
A Zero-Inflated Latent Dirichlet Allocation Model for Microbiome Studies
Authors: Deek Rebecca A. , Li Hongzhe
Published: January 2021

The human microbiome consists of a community of microbes in varying abundances and is shown to be associated with many diseases. An important first step in many microbiome studies is to identify possible distinct microbial communities in a given data set and to identify the important bacterial taxa that characterize these communities. The data from typical microbiome studies are high dimensional count data with excessive zeros due to both absence of species (structural zeros) and low sequencing depth or dropout. Although methods have been developed for identifying the microbial communities based on mixture models of counts, these methods do not account for excessive zeros observed in the data and do not differentiate structural from sampling zeros. In this paper, we introduce a zero-inflated Latent Dirichlet Allocation model (zinLDA) for sparse count data observed in microbiome studies. zinLDA builds on the flexible Latent Dirichlet Allocation model and allows for zero inflation in observed counts. We develop an efficient Markov chain Monte Carlo (MCMC) sampling procedure to fit the model. Results from our simulations show zinLDA provides better fits to the data and is able to separate structural zeros from sampling zeros. We apply zinLDA to the data set from the American Gut Project and identify microbial communities characterized by different bacterial genera.
Predicting Genome Architecture: Challenges and Solutions
Authors: Belokopytova Polina , Fishman Veniamin
Published: January 2021

Genome architecture plays a pivotal role in gene regulation. The use of high-throughput methods for chromatin profiling and 3-D interaction mapping provide rich experimental data sets describing genome organization and dynamics. These data challenge development of new models and algorithms connecting genome architecture with epigenetic marks. In this review, we describe how chromatin architecture could be reconstructed from epigenetic data using biophysical or statistical approaches. We discuss the applicability and limitations of these methods for understanding the mechanisms of chromatin organization. We also highlight the emergence of new predictive approaches for scoring effects of structural variations in human cells.
Irradiated Tumor Fibroblasts Avoid Immune Recognition and Retain Immunosuppressive Functions Over Natural Killer Cells
Authors: Yang Nannan , Lode Kristin , Berzaghi Rodrigo , Islam Ashraful , Martinez-Zubiaurre Inigo , Hellevik Turid
Published: January 2021

Recent studies have demonstrated that radiotherapy is able to induce anti-tumor immune responses in addition to mediating direct cytotoxic effects. Cancer-associated fibroblasts (CAFs) are central constituents of the tumor stroma and participate actively in tumor immunoregulation. However, the capacity of CAFs to influence immune responses in the context of radiotherapy is still poorly understood. This study was undertaken to determine whether ionizing radiation alters the CAF-mediated immunoregulatory effects on natural killer (NK) cells. CAFs were isolated from freshly resected non-small cell lung cancer tissues, while NK cells were prepared from peripheral blood of healthy donors. Functional assays to study NK cell immune activation included proliferation rates, expression of cell surface markers, secretion of immunomodulators, cytotoxic assays, as well as production of intracellular activation markers such as perforin and granzyme B. Our data show that CAFs inhibit NK cell activation by reducing their proliferation rates, the cytotoxic capacity, the extent of degranulation, and the surface expression of stimulatory receptors, while concomitantly enhancing surface expression of inhibitory receptors. Radiation delivered as single high-dose or in fractioned regimens did not reverse the immunosuppressive features exerted by CAFs over NK cells in vitro, despite triggering enhanced surface expression of several checkpoint ligands on irradiated CAFs. In summary, CAFs mediate noticeable immune inhibitory effects on cytokine-activated NK cells during co-culture in a donor-independent manner. However, ionizing radiation does not interfere with the CAF-mediated immunosuppressive effects.
Delving Into the Origin of Destructive Inflammation in COVID-19: A Betrayal of Natural Host Defense Peptides?
Authors: Garcia-Fandino Rebeca , Piñeiro Ángel
Published: January 2021

In contrast to other pathogenic agents that directly destroy host cells and tissues, the lethal power of SARS-CoV-2 resides in the over-reactive immune response triggered by this virus. Based on numerous evidences indicating that the lipid composition of host membranes is dramatically affected by COVID-19, and in the fact that our endogenous antimicrobial peptides (AMPs) are sensitive to the membrane composition of pathogenic agents, we propose that such destructive immune response is due to the direct action of AMPs. In a scenario where most host cell membranes are dressed by a pathogenic lipid composition, AMPs can indiscriminately attack them. This is why we use the “AMP betrayal” term to describe this mechanism. Previously proposed cytokine/bradykinin storm mechanisms are not incompatible with this new proposal. Interestingly, the harmful action of AMPs could be prevented by new therapies aimed to reestablish the lipid composition or to inhibit the action of specific peptides.
The New Frontier of Host-Directed Therapies for Mycobacterium avium Complex
Authors: Crilly Nathan P. , Ayeh Samuel K. , Karakousis Petros C.
Published: January 2021

Mycobacterium avium complex (MAC) is an increasingly important cause of morbidity and mortality, and is responsible for pulmonary infection in patients with underlying lung disease and disseminated disease in patients with AIDS. MAC has evolved various virulence strategies to subvert immune responses and persist in the infected host. Current treatment for MAC is challenging, requiring a combination of multiple antibiotics given over a long time period (for at least 12 months after negative sputum culture conversion). Moreover, even after eradication of infection, many patients are left with residual lung dysfunction. In order to address similar challenges facing the management of patients with tuberculosis, recent attention has focused on the development of novel adjunctive, host-directed therapies (HDTs), with the goal of accelerating the clearance of mycobacteria by immune defenses and reducing or reversing mycobacterial-induced lung damage. In this review, we will summarize the evidence supporting specific adjunctive, HDTs for MAC, with a focus on the repurposing of existing immune-modulatory agents targeting a variety of different cellular pathways. We also highlight areas meriting further investigation.
A Review of Holography in the Aquatic Sciences: In situ Characterization of Particles, Plankton, and Small Scale Biophysical Interactions
Authors: Nayak Aditya R. , Malkiel Ed , McFarland Malcolm N. , Twardowski Michael S. , Sullivan James M.
Published: January 2021

The characterization of particle and plankton populations, as well as microscale biophysical interactions, is critical to several important research areas in oceanography and limnology. A growing number of aquatic researchers are turning to holography as a tool of choice to quantify particle fields in diverse environments, including but not limited to, studies on particle orientation, thin layers, phytoplankton blooms, and zooplankton distributions and behavior. Holography provides a non-intrusive, free-stream approach to imaging and characterizing aquatic particles, organisms, and behaviorin situat high resolution through a 3-D sampling volume. Compared to other imaging techniques, e.g., flow cytometry, much larger volumes of water can be processed over the same duration, resolving particle sizes ranging from a few microns to a few centimeters. Modern holographic imaging systems are compact enough to be deployed through various modes, including profiling/towed platforms, buoys, gliders, long-term observatories, or benthic landers. Limitations of the technique include the data-intensive hologram acquisition process, computationally expensive image reconstruction, and coherent noise associated with the holograms that can make post-processing challenging. However, continued processing refinements, rapid advancements in computing power, and development of powerful machine learning algorithms for particle/organism classification are paving the way for holography to be used ubiquitously across different disciplines in the aquatic sciences. This review aims to provide a comprehensive overview of holography in the context of aquatic studies, including historical developments, prior research applications, as well as advantages and limitations of the technique. Ongoing technological developments that can facilitate larger employment of this technique towardin situmeasurements in the future, as well as potential applications in emerging research areas in the aquatic sciences are also discussed.
Seasonal and Spatial Changes of Primary Production in the Baltic Sea (Europe) Based on in situ Measurements in the Period of 1993–2018
Authors: Zdun Agnieszka , Stoń-Egiert Joanna , Ficek Dariusz , Ostrowska Mirosława
Published: January 2021

The seasonal and spatial variability of primary production (PP) measured using 14C method in two regions: open waters of the Baltic Sea and the Gulf of Gdansk were discussed. The statistical analyses of 26-years dataset (from 1993 to 2018) allow to confirm some regularities of productivity and find some features resulting mainly from changing environmental conditions like solar insolation, temperature, and chlorophyll a concentration. In the dataset, production values varied from 0.005 to 7.8 g C m–2 day–1 in open waters and from 0.07 to 12.9 g C m–2 day–1 in the Gulf of Gdansk. Analysis showed that PP in open waters were 6–17% lower than in Gulf of Gdansk in most of the cases. In both regions, the periods of intense productivity in spring and autumn were observed, but vegetation begins a month earlier in the Gulf of Gdansk than in open waters. Probably the accumulation of nutrients after the winter causes the spring bloom (April–May) in both regions to be more intense (even two times higher) than the autumn bloom (September–October) associated with favorable hydrological conditions resulting from summer insolation. The presented results showed slight downward trends in productivity in both regions, the most visible in the spring in the Bay of Gdansk. This confirms the recent reports on a possible improvement in the eutrophication state of the Baltic Sea.
Meteorological Factors and the Transmissibility of Hand, Foot, and Mouth Disease in Xiamen City, China
Authors: Xu Jingwen , Yang Meng , Zhao Zeyu , Wang Mingzhai , Guo Zhinan , Zhu Yuanzhao , Rui Jia , Wang Yao , Liu Xingchun , Lin Shengnan , Luo Li , Su Yanhua , Zhao Benhua , Zhou Yulin , Frutos Roger , Chen Tianmu
Published: January 2021

Background: As an emerging infectious disease, the prevention and control of hand, foot, and mouth disease (HFMD) poses a significant challenge to the development of public health in China. In this study, we aimed to explore the mechanism of the seasonal transmission characteristics of HFMD and to reveal the correlation and potential path between key meteorological factors and the transmissibility of HFMD.

Methods: Combined with daily meteorological data such as average temperature, average relative humidity, average wind velocity, amount of precipitation, average air pressure, evaporation capacity, and sunshine duration, a database of HFMD incidence and meteorological factors was established. Spearman rank correlation was used to calculate the correlation between the various meteorological factors and the incidence of HFMD. The effective reproduction number (Reff) of HFMD was used as an intermediate variable to further quantify the dynamic relationship between the average temperature and Reff.

Results: A total of 43,659 cases of HFMD were reported in Xiamen from 2014 to 2018. There was a significantly positive correlation between the average temperature and the incidence of HFMD (r = 0.596, p < 0.001), and a significantly negative correlation between the average air pressure and the incidence of HFMD (r = −0.511, p < 0.001). There was no correlation between the average wind velocity (r = 0.045, p > 0.05) or amount of precipitation (r = 0.043, p > 0.05) and incidence. There was a temperature threshold for HFMD's transmissibility. Owing to the seasonal transmission characteristics of HFMD in Xiamen, the temperature threshold of HFMD's transmissibility was 13.4–18.4°C and 14.5–29.3°C in spring and summer and in autumn and winter, respectively.

Conclusions: HFMD's transmissibility may be affected by the average temperature; the temperature threshold range of transmissibility in autumn and winter is slightly wider than that in spring and summer. Based on our findings, we suggest that the relevant epidemic prevention departments should pay close attention to temperature changes in Xiamen to formulate timely prevention strategies before the arrival of the high-risk period.
Lung Recruitment, Individualized PEEP, and Prone Position Ventilation for COVID-19-Associated Severe ARDS: A Single Center Observational Study
Authors: Sang Ling , Zheng Xia , Zhao Zhanqi , Zhong Min , Jiang Li , Huang Yongbo , Liu Xiaoqing , Li Yimin , Zhang Dingyu
Published: January 2021

Background: Patients with coronavirus disease 2019 (COVID-19) may develop severe acute respiratory distress syndrome (ARDS). The aim of the study was to explore the lung recruitability, individualized positive end-expiratory pressure (PEEP), and prone position in COVID-19-associated severe ARDS.

Methods: Twenty patients who met the inclusion criteria were studied retrospectively (PaO2/FiO2 68.0 ± 10.3 mmHg). The patients were ventilated under volume-controlled mode with tidal volume of 6 mL/kg predicted body weight. The lung recruitability was assessed via the improvement of PaO2, PaCO2, and static respiratory system compliance (Cstat) from low to high PEEP (5–15 cmH2O). Patients were considered recruitable if two out of three parameters improved. Subsequently, PEEP was titrated according to the best Cstat. The patients were turned to prone position for further 18–20 h.

Results: For recruitability assessment, average value of PaO2 was slightly improved at PEEP 15 cmH2O (68.0 ± 10.3 vs. 69.7 ± 7.9 mmHg, baseline vs. PEEP 15 cmH2O; p = 0.31). However, both PaCO2 and Cstat worsened (PaCO2: 72.5 ± 7.1 vs. 75.1 ± 9.0 mmHg; p < 0.01. Cstat: 17.5 ± 3.5 vs. 16.6 ± 3.9 ml/cmH2O; p = 0.05). Only four patients (20%) were considered lung recruitable. Individually titrated PEEP was higher than the baseline PEEP (8.0 ± 2.1 cmH2O vs. 5 cmH2O, p < 0.001). After 18–20 h of prone positioning, investigated parameters were significantly improved compared to the baseline (PaO2: 82.4 ± 15.5 mmHg. PaCO2: 67.2 ± 6.4 mmHg. Cstat: 20.6 ± 4.4 ml/cmH2O. All p < 0.001 vs. baseline).

Conclusions: Lung recruitability was very low in COVID-19-associated severe ARDS. Individually titrated PEEP and prone positioning might improve lung mechanics and blood gasses.
Anti-Foc RT4 Activity of a Newly Isolated Streptomyces sp. 5–10 From a Medicinal Plant (Curculigo capitulata)
Authors: Yun Tianyan , Zhang Miaoyi , Zhou Dengbo , Jing Tao , Zang Xiaoping , Qi Dengfeng , Chen Yufeng , Li Kai , Zhao Yankun , Tang Wen , Huang Jiaquan , Wang Wei , Xie Jianghui
Published: January 2021

Fusarium wilt of banana caused by Fusarium oxysporum f. sp. cubense (Foc) is a disastrous soil-borne fungal disease. Foc tropical race 4 (Foc TR4) can infect almost all banana cultivars. Until now, there is a shortage of safety and effective control methods and commercial banana cultivars with a resistance against Foc TR4. Biocontrol using environmentally friendly microbes is a promising strategy for the management of Foc TR4. Here, a strain 5–10, newly isolated from a medicinal plant (Curculigo capitulata), exhibited a high antifungal activity against Foc TR4. Combing the morphological characteristics and molecular identification, strain 5–10 was classified as a Streptomyces genus. The sequenced genome revealed that more than 39 gene clusters were involved in the biosynthesis of secondary metabolites. Some multidrug resistance gene clusters were also identified such as mdtD, vatB, and vgaE. To improve the anti-Foc TR4 activity of the strain 5–10 extracts, an optimization method of fermentation broth was established. Antifungal activity increased by 72.13% under the fermentation system containing 2.86 g/L of NaCl and 11.57% of inoculation amount. After being treated with the strain 5–10 extracts, the Foc TR4 hyphae shrinked, deformed, and ruptured. The membrane integrity and cell ultrastructure incurred irreversible damage. Streptomyces sp. 5–10 extracts play a fungicidal role in Foc TR4. Hence, Streptomyces sp. 5–10 will be a potential biocontrol agent to manage fungal diseases by exploring the microbial fertilizer.
Mild Cognitive Impairment Patients Have Higher Regulatory T-Cell Proportions Compared With Alzheimer's Disease-Related Dementia Patients
Authors: Fu Jiping , Duan Jinhai , Mo Jianwei , Xiao Hao , Huang Yuedong , Chen Weiping , Xiang Shaotong , Yang Fan , Chen Yongjun , Xu Shuwen
Published: January 2021

Objectives: The role of neuroinflammation in the pathogenesis of Alzheimer's disease (AD) has attracted much attention recently. Regulatory T-cells (Tregs) play an important role in modulating inflammation. We aimed to explore the Treg-related immunosuppression status at different stages of AD.

Methods: Thirty healthy control (HC) subjects, 26 patients with mild cognitive impairment (MCI), 30 patients with mild probable AD-related dementia, and 28 patients with moderate-to-severe probable AD-related dementia underwent detailed clinical history taking, structural MRI scanning, and neuropsychological assessment. Peripheral blood samples were taken to measure the percentage of CD4+CD25+CD127low/− Tregs by flow cytometry and the levels of interleukin (IL-10), interleukin (IL-35), and transforming growth factor β (TGF-β) by ELISA.

Results: The percentage of Tregs in the blood of MCI patients was the highest (9.24%); there was a significant difference between patients with MCI and patients with probable AD-related dementia. The level of TGF-β in patients with MCI (47.02 ng/ml) was significantly increased compared with patients with AD-related dementia. There were positive correlations between Treg percentage, IL-35, and Mini-mental state evaluation scores in patients with MCI and probable AD-related dementia.

Conclusions: Patients with MCI have stronger Treg-related immunosuppression status compared with patients with probable AD-related dementia.
Vestibular Function After the 2016 Kumamoto Earthquakes: A Retrospective Chart Review
Authors: Miwa Toru
Published: January 2021

This retrospective chart review aimed to examine both the vestibular function and causes of dizziness experienced by individuals following a series of major earthquakes and repetitive aftershocks. All patients with balance disorders who experienced the 2016 Kumamoto earthquakes and their aftershocks completed questionnaires relevant to balance disorders and were enrolled in this study after providing informed consent. There were 2.8 times more patients with balance disorders post the earthquake. Anxiety (P = 0.02), orthostatic dysregulation (P = 0.005), and motion sickness scores (P = 0.03) were all significantly higher after the earthquakes. A subset of participants underwent clinical equilibrium testing, showing significant deteriorations in the equilibrium test results (stabilometry: P = 0.01), cervical vestibular-evoked myogenic potentials (P = 0.04), and head-up tilt (P = 0.03) after the earthquake. The findings of this study also suggest that earthquake-induced disequilibrium may be further influenced by physical stressors, including sensory disruptions induced by earthquake vibrations, changes in the living conditions, and autonomic stress. This study increases our understanding of human equilibrium in response to natural disasters. Moreover, these findings will facilitate the management of dizziness experienced during or after such disasters. Future studies should identify strategies for mitigating autonomic dysfunction to prevent post-earthquake dizziness.
Association Study of Alcohol Dehydrogenase and Aldehyde Dehydrogenase Polymorphism With Alzheimer Disease in the Taiwanese Population
Authors: Wu Yah-Yuan , Lee Yun-Shien , Liu Yu-Li , Hsu Wen-Chuin , Ho Wei-Min , Huang Yu-Hua , Tsai Shih-Jen , Kuo Po-Hsiu , Chen Yi-Chun
Published: January 2021

Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) are two major alcohol-metabolizing enzymes. Moderate alcohol intake is a protective modified factor in Alzheimer’s disease (AD) while heavy alcohol intake and abstinence increased dementia risk. The associations between Alzheimer’s disease and alcohol-metabolizing genes are uncertain. This study examined the association of AD with sevenADH/ALDHsingle-nucleotide polymorphisms (SNPs),ADH1Crs2241894,ADH1Brs1229984,ALDH1B1rs2073478,ALDH2rs886205, rs4767944, rs4648328, and rs671. We enrolled 157 AD and 168 age- and sex-matched control subjects in pilot study to examine the association of AD withADH/ALDHSNPs. ReconstructedALDH2haplotypes were performed. We measured plasma level of ADH1C and checked the interaction effect of AD–rs2241894 genotype on plasma ADH1C level. In extension study, we further examined 339 AD and 2,504 healthy control from the Taiwan Biobank. In pilot study, we observed thatADH1Crs2241894 TT genotype was negatively associated with AD in a recessive genetic model (OR = 0.25, 95% CI 0.09–0.75,p< 0.0001) in women. A strong linkage disequilibrium was observed among the four examined SNPs ofALDH2. No haplotype was related to AD. The plasma ADH1C level in AD was higher than that in control. After adjusted by age, sex, hypertension, diabetes mellitus, and alcohol, we found a significant interaction effect of AD–rs2241894 genotype on plasma ADH1C level (p= 0.04). This interaction effect was attributable to the association between AD and plasma ADH1C level (β estimate = 366, 95% CI 92.7∼639.4,p= 0.009). The genetic distribution ofADH1Crs2241894 showed strong ethnic heterogeneity, in which the T allele was the minor allele accounting for 28.5% in our study and 23.6% in East Asians, while it was a major allele in Americans, Europeans, and the global populations. No association was discovered between AD and the five SNPs: rs2241894, rs1229984, rs2073478, rs886205, and rs671 in the extension study. In summary, this study revealed a suggestive association between ADH1C rs2241894 and female AD in the pilot study, but failed to confirm this finding in a population database. Further age-matched and large sample size case-control studies are needed before rs2241894 can be interpreted as a protective genetic factor of AD.
Respiratory Tract Infections in Inflammatory Bowel Disease Patients Taking Vedolizumab: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Authors: Marafini Irene , Troncone Edoardo , Rocchetti Irene , Monteleone Giovanni
Published: January 2021

The ongoing COVID-19 pandemic has raised concerns about the risk of SARS-CoV-2 infection in patients with Crohn’s disease (CD) and patients with ulcerative colitis (UC) taking immunosuppressants or biologics. We conducted a systematic review and meta-analysis to assess the risk of respiratory infections in patients with inflammatory bowel disease (IBD) treated with vedolizumab. We searched PubMed, EMBASE and Scopus to identify randomized controlled trials (RCT) comparing vedolizumab to placebo in patients with IBD. Outcomes were the rate of respiratory tract infections (RTI), upper respiratory tract infections (URTI) and lower respiratory tract infections (LRTI) among patients receiving vedolizumab as compared with placebo. Pooled rates were reported as Odds Ratios (OR) with 95% Confidence Interval (CI). Eight RCT involving 3,287 patients (1873 CD and 1415 UC) were analyzed; 2,493 patients received vedolizumab and 794 received placebo. The rates of RTI and URTI were statistically higher in vedolizumab-treated patients compared to placebo [OR = 1.63; 95% CI (1.07–2.49); OR = 1.64 95% CI (1.07–2.53) respectively]. UC patients, but not CD patients, receiving vedolizumab had a higher risk to develop RTI and URTI [OR = 1.98; 95% CI (1.41–2.77); OR = 2.02; 95% CI (1.42–2.87)] compared to placebo-treated patients. The number of LRTI was small in both treatment groups. Data confirm the good safety profile of vedolizumab even though RTI were more frequent in patients receiving vedolizumab and the risk of URTIs was significantly higher in patients with UC.
Role of Active Components of Medicinal Food in the Regulation of Angiogenesis
Authors: Pan Dezhi , Gong Xue , Wang Xiaoqin , Li Minhui
Published: January 2021

Angiogenesis refers to the formation of new blood vessels from the endothelial cells of existing arteries, veins, and capillaries. Angiogenesis is involved in a variety of physiological and pathological processes, such as the formation of malignant and development of atherosclerosis and other diseases. In recent years, many studies have shown that the active components of food have a certain regulatory effect on angiogenesis and negligible clinical limitations. With the increasing attention being paid to medicine and food homology, exploring the effect of active food components on angiogenesis is of great significance. In this review, we discuss the source, composition, pharmacological activity, and mechanism of action of certain active components of medicinal foods in detail. These could help prevent angiogenesis-related complications or provide a basis for healthier dietary habits. This review can provide a theoretical basis for the research and development of highly efficient anti-angiogenic drugs with low toxicity.
The Associations Between Physical Performance and Anthropometric Characteristics in Obese and Non-obese Schoolchild Handball Players
Authors: Hermassi Souhail , van den Tillaar Roland , Bragazzi Nicola Luigi , Schwesig René
Published: January 2021

This study investigated the relationship of body fat and fitness measures in schoolchild handball players. Twenty-eight young male handball players from handball first youth league volunteered for the present investigation (age: 10.9 ± 0.72 years; body mass: 54.8 ± 22.9 kg; height: 1.48 ± 0.10 m; body fat: 27.6 ± 9.23%). Measures included the Yo-Yo Intermittent Recovery Test level 1 (Yo-Yo IR1), jumping ability [squat and counter-movement jumps (SJ, CMJ)], and sprint tests (10 m, 15 m). Anthropometry was assessed by body mass, body mass index (BMI), and fat percentage (%BF). The power of the upper limb was measured as the total distance thrown overhead using a 2 kg medicine ball. Intrarater reliability for all parameters showed a coefficient of variation (CV) below 10% and an intraclass correlation coefficient (ICC) above 0.75. All ICC were excellent (ICC ≥ 0.96). Reliability as shown by the CV differed between 1.0 (sprint 15 m) and 5.6 (sprint 10 m). With the exception of medicine ball throw, we found significant differences between non-obese and obese in all performance parameters. The differences ranged from ηp2 = 0.47 (sprint 10 m) to ηp2 = 0.09 (medicine ball throw). The two-step-linear regression analysis using the predictors body height and body weight (step 1) and body fat (step 2) showed a marked increase of explained variance by adding body fat. The largest r2 changes were calculated for sprint 10 m (0.54), CMJ (0.49), and sprint 15 m (0.42). The lowest influence of the predictors was observed for medicine ball throw (step 1: r2 = 0.03, step 2: r2 = 0.07). With the exception of sprint parameters (β-coefficient sprint 10 m: -0.74; β-coefficient sprint 20: -0.66), a decrease of %BF leads to a higher performance in all parameters. %BF in youth handball players should be an important concern for practitioners working in this team sport in contrast to the frequently used BMI. It seems sensible and appropriate to engage very young children in physical activities such as team handball in order to improve their physical fitness. Decrease in% body fat could be considered both as a training and nutritional target to enhance and optimize sport performance-related outcomes.
Effects of Complex Training on Sprint, Jump, and Change of Direction Ability of Soccer Players: A Systematic Review and Meta-Analysis
Authors: Thapa Rohit K. , Lum Danny , Moran Jason , Ramirez-Campillo Rodrigo
Published: January 2021

The aim of this meta-analysis was to evaluate the effects of complex training (CT) on sprint, jump, and change of direction (COD) ability among soccer players. After an electronic search, 10 peer-reviewed articles were considered in the meta-analysis. The athletes included in this meta-analysis were amateur to professional level male soccer players (age range, 14–23 years). These studies incorporated CT in soccer players who were compared to a control group. Significant moderate to large improvements were observed in the CT group [sprint: standard mean difference (SMD) = 0.92–1.91; jump: SMD = 0.96–1.58; COD: SMD = 0.97–1.49] when compared to control groups. Subgroup analysis were also conducted based on age, duration, and competitive level. The beneficial effects of CT were greater in players <18 vs. ≥18 years (linear sprinting; SMD = 2.01 vs. −0.13), after ≥8 vs. <8 weeks (jumping and COD; SMD = 1.55–2.01 vs. 0.31–0.64, respectively) and among professional vs. amateur players (linear sprinting and with COD; SMD = 1.53–1.58 vs. 0.08–0.63, respectively). In conclusion, regular soccer training programs may be supplemented with CT to improve sprint, jump, and COD performance. A longer duration of CT (≥8 weeks) seems to be optimal in improving the physical abilities of soccer players. Professional players and <18 years players may benefit more from CT program.