bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluating China’s Role in Achieving the 1.5 °C Target of the Paris Agreement
Authors: Xiong Weiwei , Tanaka Katsumasa , Ciais Philippe , Yan Liang
Published: August 2022

Now that many countries have set goals for reaching net zero emissions by the middle of the century, it is important to clarify the role of each country in achieving the 1.5 °C target of the Paris Agreement. Here, we evaluated China’s role by calculating the global temperature impacts caused by China’s emission pathways available in global emissions scenarios toward the 1.5 °C target. Our results show that China’s contribution to global warming in 2050 (since 2005) is 0.17 °C on average, with a range of 0.1 °C to 0.22 °C. The peak contributions of China vary from 0.1 °C to 0.23 °C, with the years reached distributing between 2036 and 2065. The large difference in peak temperatures arises from the differences in emission pathways of carbon dioxide (CO2), methane (CH4), and sulfur dioxide (SO2). We further analyzed the effect of the different mix of CO2 and CH4 mitigation trajectories in China’s pathways on the global mean temperature. We found that China’s near-term CH4 mitigation reduces the peak temperature in the middle of the century, whereas it plays a less important role in determining the end-of-the-century temperature. Early CH4 mitigation action in China is an effective way to shave the peak temperature, further contributing to reducing the temperature overshoot along the way toward the 1.5 °C target. This underscores the necessity for early CO2 mitigation to ultimately achieve the long-term temperature goal.
Carcass Characteristics and Beef Quality of Young Grass-Fed Angus x Salers Bovines
Authors: Liu Jingjing , Ellies-Oury Marie-Pierre , Pannier Liselotte , Gruffat Dominique , Durand Denis , Noel Faustine , Sepchat Bernard , Legrand Isabelle , Prache Sophie , Hocquette Jean-François
Published: August 2022

To characterize carcass and meat attributes, such as beef eating quality in specific farming conditions, 31 young grass-fed crossbred Angus x Salers cattle in two farming systems (a mono-cattle system versus a mixed system with beef cattle and sheep) were used in this study. Three muscle cuts (striploin—m. longissimus dorsi et thoracis; bolar blade—m. triceps brachii caput longum; internal flank plate—m. obliquus internus abdominis) were used for consumer eating quality testing and striploin was used for panelist eating quality assessment, and objective measurements [Warner–Bratzler shear force (WBSF) and fatty acid (FA) and antioxidant contents]. Results indicated that the farming system had no impact on carcass characteristics or meat quality, but it tended to affect FA content, which is likely explained by between-system differences in animal maturity (assessed by ossification score). Animal gender had significant effects on three eating quality traits evaluated by untrained consumers, with higher flavor liking, overall liking, and overall meat eating quality (MQ4) scores in females than in males. Additionally, FA contents were correlated with sensory quality traits to varying extents: consumer-scored tenderness, flavor, and overall liking were mainly positively correlated with ω-3 and ω-6 polyunsaturated fatty acid (PUFA) contents, and panelist-evaluated tenderness and abnormal flavor were more positively correlated with total lipids, saturated fatty acid (SFA), and monounsaturated fatty acid (MUFA) contents. Overall, this study showed that specific grass-fed crossbred Angus x Salers cattle can produce lean meat rich in ω-3 PUFAs with a low ω-6/ω-3 ratio and with “better than average” beef eating quality.
Si-Wu Water Extracts Protect against Colonic Mucus Barrier Damage by Regulating Muc2 Mucin Expression in Mice Fed a High-Fat Diet
Authors: Ruan Zheng , Yu Yujuan , Han Peiheng , Zhang Li , Hu Zhongyi
Published: August 2022

A high-fat diet (HFD) could cause gut barrier damage. The herbs in si-wu (SW) include dang gui (Angelica sinensis (Oliv.) Diels), shu di huang (the processed root of Rehmannia glutinosa Libosch.), chuan xiong (rhizome of Ligusticum chuanxiong Hort.), and bai shao (the root of Paeonia lactiflora f. pilosella (Nakai) Kitag.). Si-wu water extracts (SWE) have been used to treat blood deficiency. Components of one herb from SW have been reported to have anti-inflammatory and anti-obesity activities. However, there have been no reports about the effects of SWE on gut barrier damage. Therefore, the aim of the study was to explore the effect of SWE on gut barrier damage. In this study, we found that SWE effectively controlled body weight, liver weight, and feed efficiency, as well as decreased the serum TC level in HFD-fed mice. Moreover, SWE and rosiglitazone (Ros, positive control) increased the colonic alkaline phosphatase (ALP) level, down-regulated serum pro-inflammatory cytokine levels, and reduced intestinal permeability. In addition, SWE increased goblet cell numbers and mucus layer thickness to strengthen the mucus barrier. After supplementation with SWE and rosiglitazone, the protein expression of CHOP and GRP78 displayed a decrease, which improved the endoplasmic reticulum (ER) stress condition. Meanwhile, the increase in Cosmc and C1GALT1 improved the O-glycosylation process for correct protein folding. These results collectively demonstrated that SWE improved the mucus barrier, focusing on Muc2 mucin expression, in a prolonged high-fat diet, and provides evidence for the potential of SWE in the treatment of intestinal disease-associated mucus barrier damage.
Detection and Degradation Characterization of 16 Quinolones in Soybean Sprouts by Ultra-High Performance Liquid Chromatography-Tandem Mass Spectrometry
Authors: Deng Hao , Feng Yujie , Wu Guang , Zhang Ronghu , Li Bei , Yin Qingchun , Luo Lin
Published: August 2022

Recently, there have been increasing safety concerns about the illegal abuse of quinolone in soybean sprouts. This study aimed to establish an ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for the simultaneous detection of 16 quinolones (QNs) in soybean sprouts, and then reveal their degradation characteristics. The samples were extracted with acetonitrile (with 1% formic acid), purified by a C18 adsorbent, and separated by an ACQUITY UPLC BEH C18 (1.7 μm, 2.1 mm × 100 mm) column. The internal standard method was applied for quantitative determination. The results demonstrated that the quantification linear range for 16 QNs was between 2.0 ng/mL and 50.0 ng/mL. The detection limits were between 0.5 μg/kg and 4.0 μg/kg, and the quantification limits were between 2.0 μg/kg and 20.0 μg/kg. This method was used to screen for quinolones in 50 batches of market soybean sprouts; the obtained results showed good agreement with those of the standard method. It was found that QNs possessed longer degradation half-life (T1/2) in the storage stage of soybean sprouts, while they degraded to some extent during the germination stage via active enzyme action. In particular, ciprofloxacin was the most stable QNs with a T1/2 of 70.71 d during the storage stage of soybean sprouts. This work not only offers an accurate and efficient QNs residual analysis strategy but also provides a reference for the supervision and management of QNs in foods.
Prebiotic Properties of Exopolysaccharides from Lactobacillus helveticus LZ-R-5 and L. pentosus LZ-R-17 Evaluated by In Vitro Simulated Digestion and Fermentation
Authors: Xu Mengjia , Li Zhi , Zhao Xiaogan , Li Wei
Published: August 2022

The in vitro digestion and fermentation behaviors of Lactobacillus helveticus LZ-R-5- and L. pentosus LZ-R-17-sourced exopolysaccharides (LHEPS and LPEPS) were investigated by stimulated batch-culture fermentation system. The results illustrated that LHEPS was resistant to simulated saliva and gastrointestinal (GSI) digestion, whereas LPEPS generated a few monosaccharides after digestion without significant influence on its main structure. Additionally, LHEPS and LPEPS could be consumed by the human gut microbiota and presented stronger bifidogenic effect comparing to α-glucan and β-glucan, as they promote the proliferation of Lactobacillus and Bifidobacterium in cultures and exhibited high values of selectivity index (13.88 and 11.78, respectively). Furthermore, LPEPS achieved higher contents of lactic acid and acetic acid (35.74 mM and 45.91 mM, respectively) than LHEPS (35.20 mM and 44.65 mM, respectively) during fermentation for 48 h, thus also resulting in a larger amount of total SCFAs (110.86 mM). These results have clearly indicated the potential prebiotic property of EPS fractions from L. helveticus LZ-R-5 and L. pentosus LZ-R-17, which could be further developed as new functional food prebiotics to beneficially improve human gut health.
The Reliability of Sampling to Measure the Weight of Seized Powder Containing Heroin
Authors: Kadane Joseph B. , Wilkinson Emily , Yohannan Josh
Published: August 2022

Techniques used in forensic analysis have to find an appropriate balance between fairness to the defendant and efficiency and safety for forensic personnel. Safety issues are particularly acute in analyzing large seizures of bags likely containing heroin, possibly laced with fentanyl. National and local law specifies penalties that depend on the weight of seized powder containing heroin. Local custom makes available to the prosecution and the defense a preliminary report showing the presence of heroin and an indication of the powder weight seized. Such a report, even if it involves uncertainty, can be useful to both parties in understanding the likely sentencing range, with a view toward plea bargaining. An earlier methodological paper demonstrates how data from a sample of bags can be used to create a probability distribution for the weight of seized powder. The aim of this paper is to study whether sampling itself creates substantial additional uncertainty. To this end, we apply the above method to four populations with weights known for each item in the population. We draw eight random samples of size five from each population. Applying the proposed method to each sample, the results show that the variation created by drawing these samples is trivial. We conclude that the proposed method, which is convenient and safer for personnel, can be used without prejudice against the defendant.
Analysis of Common SNPs across Continents Reveals Major Genomic Differences between Human Populations
Authors: Fedorova Larisa , Khrunin Andrey , Khvorykh Gennady , Lim Jan , Thornton Nicholas , Mulyar Oleh A. , Limborska Svetlana , Fedorov Alexei
Published: August 2022

Common alleles tend to be more ancient than rare alleles. These common SNPs appeared thousands of years ago and reflect intricate human evolution including various adaptations, admixtures, and migration events. Eighty-four thousand abundant region-specific alleles (ARSAs) that are common in one continent but absent in the rest of the world have been characterized by processing 3100 genomes from 230 populations. Also computed were 17,446 polymorphic sites with regional absence of common alleles (RACAs), which are widespread globally but absent in one region. A majority of these region-specific SNPs were found in Africa. America has the second greatest number of ARSAs (3348) and is even ahead of Europe (1911). Surprisingly, East Asia has the highest number of RACAs (10,524) and the lowest number of ARSAs (362). ARSAs and RACAs have distinct compositions of ancestral versus derived alleles in different geographical regions, reflecting their unique evolution. Genes associated with ARSA and RACA SNPs were identified and their functions were analyzed. The core 100 genes shared by multiple populations and associated with region-specific natural selection were examined. The largest part of them (42%) are related to the nervous system. ARSA and RACA SNPs are important for both association and human evolution studies.
Life-Course Associations between Blood Pressure-Related Polygenic Risk Scores and Hypertension in the Bogalusa Heart Study
Authors: Sun Xiao , Pan Yang , Zhang Ruiyuan , De Anda-Duran Ileana , Huang Zhijie , Li Changwei , Shi Mengyao , Razavi Alexander C. , Bazzano Lydia A. , He Jiang , Sofer Tamar , Kelly Tanika N.
Published: August 2022

Genetic information may help to identify individuals at increased risk for hypertension in early life, prior to the manifestation of elevated blood pressure (BP) values. We examined 369 Black and 832 White Bogalusa Heart Study (BHS) participants recruited in childhood and followed for approximately 37 years. The multi-ancestry genome-wide polygenic risk scores (PRSs) for systolic BP (SBP), diastolic BP (DBP), and hypertension were tested for an association with incident hypertension and stage 2 hypertension using Cox proportional hazards models. Race-stratified analyses were adjusted for baseline age, age2, sex, body mass index, genetic principal components, and BP. In Black participants, each standard deviation increase in SBP and DBP PRS conferred a 38% (p = 0.009) and 22% (p = 0.02) increased risk of hypertension and a 74% (p < 0.001) and 50% (p < 0.001) increased risk of stage 2 hypertension, respectively, while no association was observed with the hypertension PRSs. In Whites, each standard deviation increase in SBP, DBP, and hypertension PRS conferred a 24% (p < 0.05), 29% (p = 0.01), and 25% (p < 0.001) increased risk of hypertension, and a 27% (p = 0.08), 29% (0.01), and 42% (p < 0.001) increased risk of stage 2 hypertension, respectively. The addition of BP PRSs to the covariable-only models generally improved the C-statistics (p < 0.05). Multi-ancestry BP PRSs demonstrate the utility of genomic information in the early life prediction of hypertension.
IbMYB308, a Sweet Potato R2R3-MYB Gene, Improves Salt Stress Tolerance in Transgenic Tobacco
Authors: Wang Chong , Wang Lianjun , Lei Jian , Chai Shasha , Jin Xiaojie , Zou Yuyan , Sun Xiaoqiong , Mei Yuqin , Cheng Xianliang , Yang Xinsun , Jiao Chunhai , Tian Xiaohai
Published: August 2022

The MYB (v-myb avian myeloblastosis viral oncogene homolog) transcription factor family plays an important role in plant growth, development, and response to biotic and abiotic stresses. However, the gene functions of MYB transcription factors in sweet potato (Ipomoea batatas (L.) Lam) have not been elucidated. In this study, an MYB transcription factor gene, IbMYB308, was identified and isolated from sweet potato. Multiple sequence alignment showed that IbMYB308 is a typical R2R3-MYB transcription factor. Further, quantitative real-time PCR (qRT-PCR) analysis revealed that IbMYB308 was expressed in root, stem, and, especially, leaf tissues. Moreover, it showed that IbMYB308 had a tissue-specific profile. The experiment also showed that the expression of IbMYB308 was induced by different abiotic stresses (20% PEG-6000, 200 mM NaCl, and 20% H2O2). After a 200 mM NaCl treatment, the expression of several stress-related genes (SOD, POD, APX, and P5CS) was upregulation in transgenic plants, and the CAT activity, POD activity, proline content, and protein content in transgenic tobacco had increased, while MDA content had decreased. In conclusion, this study demonstrated that IbMYB308 could improve salt stress tolerance in transgenic tobacco. These findings lay a foundation for future studies on the R2R3-MYB gene family of sweet potato and suggest that IbMYB308 could potentially be used as an important positive factor in transgenic plant breeding to improve salt stress tolerance in sweet potato plants.
Jania adhaerens Primes Tomato Seed against Soil-Borne Pathogens
Authors: Righini Hillary , Roberti Roberta , Cetrullo Silvia , Flamigni Flavio , Quintana Antera Martel , Francioso Ornella , Panichi Veronica , Cianchetta Stefano , Galletti Stefania
Published: August 2022

Managing soil-borne pathogens is complex due to the restriction of the most effective synthetic fungicides for soil treatment. In this study, we showed that seed priming with Jania adhaerens water-soluble polysaccharides (JA WSPs) was successful in protecting tomato plants from the soil-borne pathogens Rhizoctonia solani, Pythium ultimum, and Fusarium oxysporum under greenhouse conditions. WSPs were extracted from dry thallus by autoclave-assisted method, and the main functional groups were characterized by using FT-IR spectroscopy. WSPs were applied by seed treatment at 0.3, 0.6 and 1.2 mg/mL doses, and each pathogen was inoculated singly in a growing substrate before seeding/transplant. Overall, WSPs increased seedling emergence, reduced disease severity and increased plant development depending on the dose. Transcriptional expression of genes related to phenylpropanoid, chlorogenic acid, SAR and ISR pathways, and chitinase and β-1,3 glucanase activities were investigated. Among the studied genes, HQT, HCT, and PR1 were significantly upregulated depending on the dose, while all doses increased PAL and PR2 expression as well as β-1,3 glucanase activity. These results demonstrated that, besides their plant growth promotion activity, JA WSPs may play a protective role in triggering plant defense responses potentially correlated to disease control against soil-borne pathogens.
Oral Fosfomycin Formulation in Bacterial Prostatitis: New Role for an Old Molecule-Brief Literature Review and Clinical Considerations
Authors: Marino Andrea , Stracquadanio Stefano , Bellanca Carlo Maria , Augello Egle , Ceccarelli Manuela , Cantarella Giuseppina , Bernardini Renato , Nunnari Giuseppe , Cacopardo Bruno
Published: August 2022

Bacterial prostatitis infections are described as infections that are difficult-to-treat, due to prostate anatomic characteristics along with clinical difficulty in terms of diagnosis and management. Furthermore, the emergence of multidrug resistant (MDR) bacteria, such as extended-spectrum beta-lactamase (ESBL) producer Escherichia coli, also representing the main causative pathogen in prostatitis, poses major problems in terms of antibiotic management and favorable clinical outcome. Oral fosfomycin, an antibiotic commonly used for the treatment of uncomplicated urinary tract infections (UTIs), has been recently evaluated for the treatment of bacterial prostatitis due to its favorable pharmacokinetic profile, its activity against MDR gram-positive and gram-negative bacteria, safety profile, and multiple synergic effect with other antibiotics as well as the low resistance rate. This review addresses fosfomycin pharmacokinetics and pharmacodynamics and discusses the latest clinical evidence on its clinical use to treat acute and chronic bacterial prostatitis in hospitalized patients and in outpatients. As described in several reports, oral fosfomycin may represent a valid therapeutic option to treat susceptible germs commonly causing prostatitis, such as E. coli and other Enterobacterales as well as Enterococcus faecium, even as a first-line regimen in particular clinical settings (patients with previous treatment failure, with allergies or outpatients). Stronger data from further studies, including randomized controlled trials, would be helpful to establish the proper dosage and specific indications.
Pea Protein-Derived Peptides Inhibit Hepatic Glucose Production via the Gluconeogenic Signaling in the AML-12 Cells
Authors: Liao Wang , Cao Xinyi , Xia Hui , Wang Shaokang , Sun Guiju
Published: August 2022

Pea protein is considered to be a high quality dietary protein source, but also it is an ideal raw material for the production of bioactive peptides. Although the hypoglycemic effect of pea protein hydrolysate (PPH) has been previously reported, the underlying mechanisms, in particular its effect on the hepatic gluconeogenesis, remain to be elucidated. In the present study, we found that PPH suppressed glucose production in mouse liver cell-line AML-12 cells. Although both of the gluconeogenic and insulin signaling pathways in the AML-12 cells could be regulated by PPH, the suppression of glucose production was dependent on the inhibition of the cAMP response element-binding protein (CREB)-mediated signaling in the gluconeogenic pathway, but not the activation of insulin signaling. Findings from the present study have unveiled a novel role of PPH underlying its anti-diabetic activity, which could be helpful to accelerate the development of functional foods and nutraceuticals using PPH as a starting material.
Estimation Strategy Selection Is Modulated by Snapshot Emotional Priming, but Not Math Anxiety
Authors: Zhu Chuanlin , Zhao Xinyi , Han Xinhua , Wang Yun , Liu Dianzhi , Luo Wenbo
Published: August 2022

The present study explored the role of snapshot emotional priming and math anxiety in estimation strategy selection. Participants were asked to complete a two-digit multiplication estimation task (e.g., 34 × 67) under explicit (Experiment 1) and implicit (Experiment 2) snapshot emotional priming conditions by freely choosing to use DU (down-up, e.g., doing 30 × 70 = 2100 for 34 × 67) or UD (up-down, e.g., doing 40 × 60 = 2400 for 34 × 67) strategies to arrive as close as possible to the correct answer. In Experiment 1, individuals’ estimation performance was positively influenced by explicit happy priming (shorter RT (reaction time)), while not affected by explicit fear priming. In Experiment 2, individuals’ estimation ACC (accuracy) when using the UD strategy was negatively affected by both implicit happy and fear priming, but their RT when using DU and UD strategies was positively impacted by implicit happy priming. In both experiments, the correlations between math anxiety and estimation performance (ACC, RT, and strategy selection adaptivity) was not significant. The present study suggests that fear priming was not always detrimental to individuals’ estimation performance, and happy priming did not always universally improve individuals’ estimation performance. Additionally, estimation strategy selection was not influenced by math anxiety.
A Practical Risk-Based Model for Early Warning of Seafarer Errors Using Integrated Bayesian Network and SPAR-H
Authors: Zhang Wenjun , Meng Xiangkun , Yang Xue , Lyu Hongguang , Zhou Xiang-Yu , Wang Qingwu
Published: August 2022

Unsafe crew acts (UCAs) related to human errors are the main contributors to maritime accidents. The prediction of unsafe crew acts will provide an early warning for maritime accidents, which is significant to shipping companies. However, there exist gaps between the prediction models developed by researchers and those adopted by practitioners in human risk analysis (HRA) of the maritime industry. In addition, most research regarding human factors of maritime safety has concentrated on hazard identification or accident analysis, but not on early warning of UCAs. This paper proposes a Bayesian network (BN) version of the Standardized Plant Analysis Risk–Human Reliability Analysis (SPAR-H) method to predict the probability of seafarers’ unsafe acts. After the identification of performance-shaping factors (PSFs) that influence seafarers’ unsafe acts during navigation, the developed prediction model, which integrates the practicability of SPAR-H and the forward and backward inference functions of BN, is adopted to evaluate the probabilistic risk of unsafe acts and PSFs. The model can also be used when the available information is insufficient. Case studies demonstrate the practicability of the model in quantitatively predicting unsafe crew acts. The method allows evaluating whether a seafarer is capable of fulfilling their responsibility and providing an early warning for decision-makers, thereby avoiding human errors and sequentially preventing maritime accidents. The method can also be considered as a starting point for applying the efforts of HRA researchers to the real world for practitioners.
Accumulation of Co, Ni, Cu, Zn and Cd in Aboveground Organs of Chinese Winter Jujube from the Yellow River Delta, China
Authors: Zhang Zaiwang , Zhang Qiong , Liu Guoli , Zhao Jian , Xie Wenjun , Shang Shuai , Luo Jie , Liu Juanjuan , Huang Wenwen , Li Jialiang , Zhang Yanpeng , Xu Jikun , Zhang Jiqiang
Published: August 2022

In the present study, winter jujube organs including fruit, fruiting leaf and foliage leaf, and associated soils in 14 typical orchards in Binzhou City, Shandong Province, China were collected and determined for the mass fractions of Co, Ni, Cu, Zn, and Cd. The mass fractions of Co, Ni, Cu, Zn, and Cd in plant tissues generally showed an order of Cu > Zn > Ni > Co > Cd as well as those in the soils decreased as Zn > Cu > Ni > Co > Cd. The values of single factor index and Nemerow pollution index suggested the jujube fruits were not polluted by heavy metals. Values of estimated daily intake for all the elements were far below their associated acceptable reference values, indicating no health risks would be caused by a single trace element. The results of targeted hazard quotient (THQ) of the metals in the fruits decreased as Cu > Ni > Zn > Cd accompanying total THQ (TTHQ) lower than 1 showing no hazard would be caused by those metals. Correlation analysis showed soil might not be the main source of heavy metals in winter jujube organs. Bioaccumulation factors (BAFs) for Co, Ni, Zn and Cd in fruits and leaves were far below 1 suggesting their low bioavailablities. The relatively great BAFs of Cu in the leaves might be due to the application of fertilizers and pesticides containing great amounts of Cu through soil and foliar spraying. To sum up, heavy metals tended not to be a major threat to winter jujube cultivation, and winter jujube had great edible safety.
Mental Distress during the COVID-19 Pandemic: A Cross-Sectional Study of Women Receiving the Comprehensive Social Security Allowance in Hong Kong
Authors: Cui Jialiang , Cheung Vanessa Hoi Mei , Huang Wenjie , Kan Wan Sang
Published: August 2022

Welfare recipients were often considered the least deserving of COVID-related support. Despite the recent attention paid to the impact of COVID-19 pandemic on mental health, few studies have explored the mental distress experienced by welfare recipients. This cross-sectional study on female Comprehensive Social Security Allowance recipients in Hong Kong aimed to explore their level of mental distress and its association with a range of risk factors specific to welfare recipients. Hence, 316 valid cases from a local community center responded to our online survey. We found that 52.3%, 23.4%, and 78% of the participants showed moderate to extremely severe depression, anxiety, and stress symptoms, respectively. A higher level of mental distress was associated with having a psychiatric diagnosis, poorer social, and greater concerns over disciplining children, the living environment, daily expenses and being infected by COVID-19. Unexpectedly, being married, having a permanent residence, and having a job were not significant protective factors for this group. The models explained 45.5%, 44.6%, and 52.5% of the overall variance in the level of depression, anxiety, and stress (p < 0.01), respectively. Our findings have important implications for supporting female welfare recipients during a public health crisis and may help frontline staff and professionals provide prompt assistance to this group in need.
Implementation of the South African Triage Scale (SATS) in a New Ambulance System in Beira, Mozambique: A Retrospective Observational Study
Authors: Conti Andrea , Sacchetto Daniela , Putoto Giovanni , Mazzotta Marcello , De Meneghi Giovanna , De Vivo Emanuela , Lora Ronco Lorenzo , Hubloue Ives , Della Corte Francesco , Barone-Adesi Francesco , Ragazzoni Luca , Caviglia Marta
Published: August 2022

In 2019, an urban ambulance system was deployed in the city of Beira, Mozambique to refer patients from peripheral health centres (HCs) to the only hospital of the city (Beira Central Hospital—HCB). Initially, the system worked following a first-in–first-out approach, thus leading to referrals not based on severity condition. With the aim of improving the process, the South African Triage Scale (SATS) has been subsequently introduced in three HCs. In this study, we assessed the impact of SATS implementation on the selection process and the accuracy of triage performed by nurses. We assessed 552 and 1608 referral charts from before and after SATS implementation, respectively, and we retrospectively calculated codes. We compared the expected referred patients’ codes from the two phases, and nurse-assigned codes to the expected ones. The proportion of referred orange and red codes significantly increased (+12.2% and +12.9%) while the proportion of green and yellow codes decreased (−18.7% and −5.8%). The overall rates of accuracy, and under- and overtriage were 34.2%, 36.3%, and 29.5%, respectively. The implementation of SATS modified the pattern of referred patients and increased the number of severe cases receiving advanced medical care at HCB. While nurses’ accuracy improved with the routine use of the protocol, the observed rates of incorrect triage suggest that further research is needed to identify factors affecting SATS application in this setting.
Targeted Modification of Mammalian DNA by a Novel Type V Cas12a Endonuclease from Ruminococcus bromii
Authors: Vasilev Ruslan , Gunitseva Natalia , Shebanova Regina , Korzhenkov Aleksei , Vlaskina Anna , Evteeva Marta , Polushkina Irina , Nikitchina Natalia , Toshchakov Stepan , Kamenski Piotr , Patrushev Maxim , Mazunin Ilya
Published: August 2022

Type V Cas12a nucleases are DNA editors working in a wide temperature range and using expanded protospacer-adjacent motifs (PAMs). Though they are widely used, there is still a demand for discovering new ones. Here, we demonstrate a novel ortholog from Ruminococcus bromii sp. entitled RbCas12a, which is able to efficiently cleave target DNA templates, using the particularly high accessibility of PAM 5′-YYN and a relatively wide temperature range from 20 °C to 42 °C. In comparison to Acidaminococcus sp. (AsCas12a) nuclease, RbCas12a is capable of processing DNA more efficiently, and can be active upon being charged by spacer-only RNA at lower concentrations in vitro. We show that the human-optimized RbCas12a nuclease is also active in mammalian cells, and can be applied for efficient deletion incorporation into the human genome. Given the advantageous properties of RbCas12a, this enzyme shows potential for clinical and biotechnological applications within the field of genome editing.
In Vitro Bioactivity and Antibacterial Effects of a Silver-Containing Mesoporous Bioactive Glass Film on the Surface of Titanium Implants
Authors: Wang Yueh-Ching , Lin Sheng-Hui , Chien Chi-Sheng , Kung Jung-Chang , Shih Chi-Jen
Published: August 2022

Peri-implantitis is defined as a bacterial infection-induced inflammation and suppuration of soft and hard tissues surrounding a dental implant. If bacteria further invade the alveolar bone, they can easily cause bone loss and even lead to the early failure of a dental implant surgery. In the present study, an 80SiO2–15CaO–5P2O5 mesoporous bioactive glass film system containing 1, 5, and 10 mol% of silver was prepared on titanium implant discs (MBG–Ag–coated Ti) using sol-gel and spin coating methods. The wettability and adhesion strength of the films were evaluated using contact angle measurements and adhesion strength tests, respectively. The phase composition, chemical bonding, morphology, and oxidation states of the films were analyzed via X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), and X-ray photoelectron spectroscopy (XPS). In vitro bioactivity analysis of the films was performed by immersion in a simulated body fluid (SBF) for 24 h. Disk diffusion tests were performed on the early colonizing bacteria Aggregatibacter actinomycetemcomitans and Streptococcus mutans to evaluate the antibacterial ability of the films. A silver-containing mesoporous bioactive glass film with excellent biocompatibility and antibacterial properties was successfully prepared.
Transgenic Sweet Orange Expressing the Sarcotoxin IA Gene Produces High-Quality Fruit and Shows Tolerance to ‘Candidatus Liberibacter asiaticus’
Authors: Longhi Talita Vigo , de Carvalho Deived Uilian , Duin Izabela Moura , da Cruz Maria Aparecida , Leite Junior Rui Pereira
Published: August 2022

Huanglongbing (otherwise known as HLB or greening) is currently the most devastating citrus disease worldwide. HLB is primarily associated with the phloem-inhabiting bacterium ‘Candidatus Liberibacter asiaticus’ (CLas). Currently, there are no citrus species resistant to CLas. Genetic transformation is one of the most effective approaches used to induce resistance against plant diseases. Antimicrobial peptides (AMPs) have shown potential breakthroughs to improve resistance to bacterial diseases in plants. In this paper, we confirm the Agrobacterium-mediated transformation of Pera sweet orange expressing the AMP sarcotoxin IA (stx IA) gene isolated from the flesh fly Sarcophaga peregrina and its reaction to CLas, involving plant performance and fruit quality assessments. Four independent transgenic lines, STX-5, STX-11, STX-12, and STX-13, and a non-transgenic control, were graft-inoculated with CLas. Based on our findings, none of the transgenic plants were immune to CLas. However, the STX-5 and STX-11 lines showed reduced susceptibility to HLB with mild disease symptoms and low incidence of plants with the presence of CLas. Fruit and juice quality were not affected by the genetic transformation. Further, no residues of the sarcotoxin IA protein were found in the juice of the STX-11 and STX-12 fruits, though detected in the juice of the STX-5 and STX-13 lines, as revealed by the immunoblotting test. However, juices from all transgenic lines showed low traces of sarcotoxin IA peptide in its composition. The accumulation of this peptide did not cause any deleterious effects on plants or in fruit/juice. Our findings reinforce the challenges of identifying novel approaches to managing HLB.
Role of the WNT/β-catenin/ZKSCAN3 Pathway in Regulating Chromosomal Instability in Colon Cancer Cell lines and Tissues
Authors: Cho Young-Eun , Kim Jeong-Hee , Che Young-Hyun , Kim Yong-Jun , Sung Ji-Youn , Kim Yoon-Wha , Choe Bong-Geun , Lee Sun , Park Jae-Hoon
Published: August 2022

Zinc finger protein with KRAB and SCAN domains 3 (ZKSCAN3) acts as an oncogenic transcription factor in human malignant tumors, including colon and prostate cancer. However, most of the ZKSCAN3-induced carcinogenic mechanisms remain unknown. In this study, we identified ZKSCAN3 as a downstream effector of the oncogenic Wnt/β-catenin signaling pathway, using RNA sequencing and ChIP analyses. Activation of the Wnt pathway by recombinant Wnt gene family proteins or the GSK inhibitor, CHIR 99021 upregulated ZKSCAN3 expression in a β-catenin-dependent manner. Furthermore, ZKSCAN3 upregulation suppressed the expression of the mitotic spindle checkpoint protein, Mitotic Arrest Deficient 2 Like 2 (MAD2L2) by inhibiting its promoter activity and eventually inducing chromosomal instability in colon cancer cells. Conversely, deletion or knockdown of ZKSCAN3 increased MAD2L2 expression and delayed cell cycle progression. In addition, ZKSCAN3 upregulation by oncogenic WNT/β-catenin signaling is an early event of the adenoma–carcinoma sequence in colon cancer development. Specifically, immunohistochemical studies (IHC) were performed using normal (NM), hyperplastic polyps (HPP), adenomas (AD), and adenocarcinomas (AC). Their IHC scores were considerably different (61.4 in NM; 88.4 in HPP; 189.6 in AD; 246.9 in AC). In conclusion, ZKSCAN3 could be responsible for WNT/β-catenin-induced chromosomal instability in colon cancer cells through the suppression of MAD2L2 expression.
TNF-α Affects Signature Cytokines of Th1 and Th17 T Cell Subsets through Differential Actions on TNFR1 and TNFR2
Authors: Pesce Bárbara , Ribeiro Carolina H. , Larrondo Milton , Ramos Verónica , Soto Lilian , Catalán Diego , Aguillón Juan Carlos
Published: August 2022

Tumor necrosis factor (TNF)-α is a pleiotropic cytokine implicated in the etiology of several autoimmune diseases, including rheumatoid arthritis (RA). TNF-α regulates diverse effector functions through the activation of TNF-α receptor (TNFR)1 and TNFR2. Although the detrimental role of this cytokine has been addressed in distinct disease settings, the effects of TNF-α on cytokine production by isolated CD4+ T helper type 1 (Th1) and Th17 cells, two T cell subpopulations that contribute to the pathogenesis of RA, have not been completely elucidated. Here, we show that TNF-α promotes a reduction and expansion in the frequency of both T cell subsets producing IFN-γ and IL-17, respectively. Selective blockade of TNFR1 or TNFR2 on Th1 and Th17 cells revealed that TNFR2 mediates the decrease in IFN-γ production, while signaling through both receptors augments IL-17 production. We also demonstrate that Th1, but not Th17 cells from RA patients present lower levels of TNFR1 compared to healthy controls, whereas TNFR2 expression on both T cell types is similar between patients and controls. Since TNF-α receptors levels in RA patients are not significantly changed by the therapeutic blockade of TNF-α, we propose that targeting TNFR2 may represent an alternative strategy to normalize the levels of key cytokines that contribute to RA pathogenesis.
CXCL14 Attenuates Triple-Negative Breast Cancer Progression by Regulating Immune Profiles of the Tumor Microenvironment in a T Cell-Dependent Manner
Authors: Gibbs Carla , So Jae Young , Ahad Abdul , Michalowski Aleksandra M. , Son Deok-Soo , Li Yang
Published: August 2022

Triple-negative breast cancer (TNBC) is aggressive and has a poor overall survival due to a lack of therapeutic targets compared to other subtypes. Chemokine signature revealed that TNBC had low levels of CXCL14, an orphan homeostatic chemokine to regulate the immune network. Here, we investigated if CXCL14 plays a critical role in TNBC progression, focusing on survival rates, tumor growth and metastasis, and immune profiles in the tumor microenvironment. Analysis of human breast-cancer datasets showed that low CXCL14 expression levels were associated with poor survival rates in patients with breast cancer, particularly for TNBC subtypes. Overexpression of CXCL14 in TNBC 4T1 orthotopic mouse model significantly reduced tumor weights and inhibited lung metastasis. Furthermore, the CXCL14 overexpression altered immune profiles in the tumor microenvironment as follows: decreased F4/80+ macrophages and CD4+CD25+ Treg cells, and increased CD8+T cells in primary tumors; decreased Ly6C+ myeloid cells and CD4+CD25+ Treg cells and increased CD4+ and CD8+T cells in lung metastatic tumors. CXCL14-induced reduction of tumor growth and metastasis was diminished in T cell-deficient nude mice. Taken together, our data demonstrate that CXCL14 inhibits TNBC progression through altering immune profiles in the tumor microenvironment and it is mediated in a T cell-dependent manner. Thus, CXCL14 could be used as a biomarker for prognosis.
DNA and RNA Binding Proteins: From Motifs to Roles in Cancer
Authors: Bonczek Ondrej , Wang Lixiao , Gnanasundram Sivakumar Vadivel , Chen Sa , Haronikova Lucia , Zavadil-Kokas Filip , Vojtesek Borivoj
Published: August 2022

DNA and RNA binding proteins (DRBPs) are a broad class of molecules that regulate numerous cellular processes across all living organisms, creating intricate dynamic multilevel networks to control nucleotide metabolism and gene expression. These interactions are highly regulated, and dysregulation contributes to the development of a variety of diseases, including cancer. An increasing number of proteins with DNA and/or RNA binding activities have been identified in recent years, and it is important to understand how their activities are related to the molecular mechanisms of cancer. In addition, many of these proteins have overlapping functions, and it is therefore essential to analyze not only the loss of function of individual factors, but also to group abnormalities into specific types of activities in regard to particular cancer types. In this review, we summarize the classes of DNA-binding, RNA-binding, and DRBPs, drawing particular attention to the similarities and differences between these protein classes. We also perform a cross-search analysis of relevant protein databases, together with our own pipeline, to identify DRBPs involved in cancer. We discuss the most common DRBPs and how they are related to specific cancers, reviewing their biochemical, molecular biological, and cellular properties to highlight their functions and potential as targets for treatment.
Investigation into Phishing Risk Behaviour among Healthcare Staff
Authors: Yeng Prosper Kandabongee , Fauzi Muhammad Ali , Yang Bian , Nimbe Peter
Published: August 2022

A phishing attack is one of the less complicated ways to circumvent sophisticated technical security measures. It is often used to exploit psychological (as as well as other) factors of human users to succeed in social engineering attacks including ransomware. Guided by the state-of-the-arts in a phishing simulation study in healthcare and after deeply assessing the ethical dilemmas, an SMS-based phishing simulation was conducted among healthcare workers in Ghana. The study adopted an in-the-wild study approach alongside quantitative and qualitative surveys. From the state-of-the-art studies, the in-the-wild study approach was the most commonly used method as compared to laboratory-based experiments and statistical surveys because its findings are generally reliable and effective. The attack results also showed that 61% of the targeted healthcare staff were susceptible, and some of the healthcare staff were not victims of the attack because they prioritized patient care and were not susceptible to the simulated phishing attack. Through structural equation modelling, the workload was estimated to have a significant effect on self-efficacy risk (r = 0.5, p-value = 0.05) and work emergency predicted a perceived barrier in the reverse direction at a substantial level of r = −0.46, p-value = 0.00. Additionally, Pearson’s correlation showed that the perceived barrier was a predictor of self-reported security behaviour in phishing attacks among healthcare staff. As a result, various suggestions including an extra workload balancing layer of security controls in emergency departments and better security training were suggested to enhance staff’s conscious care behaviour.
Pyrethroids in an AlphaFold2 Model of the Insect Sodium Channel
Authors: Zhorov Boris S. , Dong Ke
Published: August 2022

Pyrethroid insecticides stabilize the open state of insect sodium channels. Previous mutational, electrophysiological, and computational analyses led to the development of homology models predicting two pyrethroid receptor sites, PyR1 and PyR2. Many of the naturally occurring sodium channel mutations, which confer knockdown resistance (kdr) to pyrethroids, are located within or close to these receptor sites, indicating that these mutations impair pyrethroid binding. However, the mechanism of the state-dependent action of pyrethroids and the mechanisms by which kdr mutations beyond the receptor sites confer resistance remain unclear. Recent advances in protein structure prediction using the AlphaFold2 (AF2) neural network allowed us to generate a new model of the mosquito sodium channel AaNav1-1, with the activated voltage-sensing domains (VSMs) and the presumably inactivated pore domain (PM). We further employed Monte Carlo energy minimizations to open PM and deactivate VSM-I and VSM-II to generate additional models. The docking of a Type II pyrethroid deltamethrin in the models predicted its interactions with many known pyrethroid-sensing residues in the PyR1 and PyR2 sites and revealed ligand-channel interactions that stabilized the open PM and activated VSMs. Our study confirms the predicted two pyrethroid receptor sites, explains the state-dependent action of pyrethroids, and proposes the mechanisms of the allosteric effects of various kdr mutations on pyrethroid action. The AF2-based models may assist in the structure-based design of new insecticides.
Thromboembolic Antiphospholipid Syndrome (APS): Efficacy and Safety of Different Anticoagulants-Results of the APSantiCO Registry
Authors: Schulz Annabel , Herrmann Eva , Ott Olivia , Lindhoff-Last Edelgard
Published: August 2022

Background: The particular challenge in dealing with patients with thromboembolic antiphospholipid syndrome (APS) is to establish an adequate therapy regime, as patients suffer from an increased risk of relapse despite antithrombotic treatment (ATT). Vitamin K antagonists (VKA) are the standard medication of choice. The current data on the use of direct oral anticoagulants (DOAC) in APS patients remain limited. Methods: The results of the retrospective APSantiCO registry are presented. In 80 patients with APS, the efficacy and safety of different ATT regimens were analyzed. Results: At the time of inclusion, 43.8% of patients were treated with VKA and 36.3% with DOAC. Medication regimes changed several times and 279 treatment phases were further analyzed with a total treatment length of 7529 months. The incidence of recurrent arterial thrombosis was significantly larger in the DOAC group compared with the VKA group (p < 0.001), while the incidence of recurrent venous thrombosis was comparable between both groups, as was the incidence of bleedings. Heavy menstrual bleeding was the most frequently observed bleeding complication. Conclusions: The data suggest that DOAC may be an alternative to VKA for APS patients with venous thromboembolism, while VKA should be used in APS-related arterial thrombosis.
MYRF: A New Regulator of Cardiac and Early Gonadal Development—Insights from Single Cell RNA Sequencing Analysis
Authors: Calonga-Solís Verónica , Fabbri-Scallet Helena , Ott Fabian , Al-Sharkawi Mostafa , Künstner Axel , Wünsch Lutz , Hiort Olaf , Busch Hauke , Werner Ralf
Published: August 2022

De novo variants in the myelin regulatory factor (MYRF), a transcription factor involved in the differentiation of oligodendrocytes, have been linked recently to the cardiac and urogenital syndrome, while familiar variants are associated with nanophthalmos. Here, we report for the first time on a patient with a de novo stop-gain variant in MYRF (p.Q838*) associated with Scimitar syndrome, 46,XY partial gonadal dysgenesis (GD) and severe hyperopia. Since variants in MYRF have been described in both 46,XX and 46,XY GD, we assumed a role of MYRF in the early development of the bipotential gonad. We used publicly available single cell sequencing data of human testis and ovary from different developmental stages and analysed them for MYRF expression. We identified MYRF expression in the subset of coelomic epithelial cells at stages of gonadal ridge development in 46,XX and 46,XY individuals. Differential gene expression analysis revealed significantly upregulated genes. Within these, we identified CITED2 as a gene containing a MYRF binding site. It has been shown that Cited2−/− mice have gonadal defects in both testis and ovary differentiation, as well as defects in heart development and establishment of the left–right axis. This makes MYRF a potential candidate as an early regulator of gonadal and heart development via upregulation of the transcriptional cofactor CITED2.