bluuebunny/crossref_metadata_2025 huggingface dataset:
Key Determinants of Health-Related Quality of Life Among Advanced Lung Cancer Patients: A Qualitative Study in Belgium and Italy
Authors: Janssens Rosanne , Arnou Reinhard , Schoefs Elise , Petrocchi Serena , Cincidda Clizia , Ongaro Giulia , Oliveri Serena , Smith Meredith Y. , Louis Evelyne , Vandevelde Marie , Nackaerts Kristiaan , Pravettoni Gabriella , Huys Isabelle
Published: September 2021

Background: The lung cancer (LC) treatment landscape has drastically expanded with the arrival of immunotherapy and targeted therapy. This new variety of treatment options, each with its own characteristics, raises uncertainty regarding the key aspects affecting patients’ health-related quality of life (HRQL). The present qualitative study aimed to investigate how LC patients perceive their HRQL and the factors that they consider to be most influential in determining their HRQL.

Methods: This qualitative research incorporates four focus group discussions, with six LC patients in each group. In total, 24 stage III and IV LC patients were included in the discussions, with Italian (n = 12) and Belgian (n = 12) patients, age range: 42–78, median age = 62 (IQR = 9.3 years), SD = 8.5; 62% men. Using thematic analysis, transcripts and notes from the FGDs were analyzed using NVivo software (edition 12).

Results: Three main themes capturing determinants of HRQL were identified. First, patients agreed on the importance of physical aspects (symptoms and side-effects) in determining their HRQL. In particular, skin conditions, nausea, fatigue, risk of infections, sensory abnormalities, pain, and changes in physical appearance were highlighted. Second, patients worried about psychological aspects, negatively impacting their wellbeing such as uncertainties regarding their future health state, and a lower degree of autonomy and independence. Third, patients underlined the importance of social aspects, such as communication with healthcare providers and social interaction with friends, family and peers.

Conclusion: This study demonstrates that physical, psychological, and social aspects are key factors driving LC patients’ HRQL. Gaining a better understanding of how LC patients perceive their HRQL and how it is affected by their illness and therapy will aid patient-centric decision-making across the drug life cycle, by providing stakeholders (drug developers, regulators, reimbursement bodies, and clinicians) insights about the treatment and disease aspects of importance to LC patients as well as the unmet needs LC patients may have regarding available treatment modalities. Finally, this study underscores a need for individual treatment decision-making that is considerate of uncertainties among LC patients about their future health state, and ways for improving communication between healthcare providers and patients to do so.
USP47-Mediated Deubiquitination and Stabilization of TCEA3 Attenuates Pyroptosis and Apoptosis of Colorectal Cancer Cells Induced by Chemotherapeutic Doxorubicin
Authors: Hou Xiaodan , Xia Jun , Feng Yuan , Cui Long , Yang Yili , Yang Peng , Xu Xin
Published: September 2021

The ubiquitin–proteasome system regulates a variety of cellular processes including growth, differentiation and apoptosis. While E1, E2, and E3 are responsible for the conjugation of ubiquitin to substrates, deubiquitinating enzymes (DUBs) reverse the process to remove ubiquitin and edit ubiquitin chains, which have profound effects on substrates’ degradation, localization, and activities. In the present study, we found that the deubiquitinating enzyme USP47 was markedly decreased in primary colorectal cancers (CRC). Its reduced expression was associated with shorter disease-free survival of CRC patients. In cultured CRC cells, knockdown of USP47 increased pyroptosis and apoptosis induced by chemotherapeutic doxorubicin. We found that USP47 was able to bind with transcription elongation factor a3 (TCEA3) and regulated its deubiquitination and intracellular level. While ectopic expression of USP47 increased cellular TCEA3 and resistance to doxorubicin, the effect was markedly attenuated by TCEA3 knockdown. Further analysis showed that the level of pro-apoptotic Bax was regulated by TCEA3. These results indicated that the USP47-TCEA3 axis modulates cell pyroptosis and apoptosis and may serve as a target for therapeutic intervention in CRC.
Dapagliflozin Mediates Plin5/PPARα Signaling Axis to Attenuate Cardiac Hypertrophy
Authors: Yu Jing , Zhao Huanhuan , Qi Xin , Wei Liping , Li Zihao , Li Chunpeng , Zhang Xiaoying , Wu Hao
Published: September 2021

Objective: The purpose of this study was to investigate the effect of dapagliflozin (DAPA), a sodium-glucose cotransporter 2 inhibitor, on relieving cardiac hypertrophy and its potential molecular mechanism.

Methods: Cardiac hypertrophy induced by abdominal aortic constriction (AAC) in mice, dapagliflozin were administered in the drinking water at a dose of 25 mg/kg/d for 12 weeks was observed. Echocardiography was used to detect the changes of cardiac function, including LVEF, LVFS, LVEDd, LVEDs, HR and LV mass. Histological morphological changes were evaluated by Masson trichrome staining and wheat germ agglutinin (WGA) staining. The enrichment of differential genes and signal pathways after treatment was analyzed by gene microarray cardiomyocyte hypertrophy was induced by AngII (2 μM) and the protective effect of dapagliflozin (1 μM) was observed in vitro. The morphological changes of myocardial cells were detected by cTnI immunofluorescence staining. ELISA and qRT-PCR assays were performed to detect the expressions levels of cardiac hypertrophy related molecules.

Results: After 12 weeks of treatment, DAPA significantly ameliorated cardiac function and inhibited cardiac hypertrophy in AAC-induced mice. In vitro, DAPA significantly inhibited abnormal hypertrophy in AngII-induced cardiacmyocytes. Both in vivo and in vitro experiments have confirmed that DAPA could mediate the Plin5/PPARα signaling axis to play a protective role in inhibiting cardiac hypertrophy.

Conclusion: Dapagliflozin activated the Plin5/PPARα signaling axis and exerts a protective effect against cardiac hypertrophy.
Exosome-Derived ADAM17 Promotes Liver Metastasis in Colorectal Cancer
Authors: Sun Jinbing , Lu Zhihua , Fu Wei , Lu Kuangyi , Gu Xiuwen , Xu Feng , Dai Jiamin , Yang Yang , Jiang Jianlong
Published: September 2021

Exosomes derived from cancer cells are deemed important drivers of pre-metastatic niche formation at distant organs, but the underlying mechanisms of their effects remain largely unknow. Although the role of ADAM17 in cancer cells has been well studied, the secreted ADAM17 effects transported via exosomes are less understood. Herein, we show that the level of exosome-derived ADAM17 is elevated in the serum of patients with metastatic colorectal cancer as well as in metastatic colorectal cancer cells. Furthermore, exosomal ADAM17 was shown to promote the migratory ability of colorectal cancer cells by cleaving the E-cadherin junction. Moreover, exosomal ADAM17 overexpression as well as RNA interference results highlighted its function as a tumor metastasis-promoting factor in colorectal cancer in vitro and in vivo. Taken together, our current work suggests that exosomal ADAM17 is involved in pre-metastatic niche formation and may be utilized as a blood-based biomarker of colorectal cancer metastasis.
Qiangji Decoction Alleviates Neurodegenerative Changes and Hippocampal Neuron Apoptosis Induced by D-Galactose via Regulating AMPK/SIRT1/NF-κB Signaling Pathway
Authors: He Li-Ling , Wang Yun-Cui , Ai Ya-Ting , Wang Ling , Gu Si-Meng , Wang Ping , Long Qing-Hua , Hu Hui
Published: September 2021

Qiangji Decoction (QJD), a classic formula, has been widely used to treat brain aging–related neurodegenerative diseases. However, the mechanisms underlying QJD’s improvement in cognitive impairment of neurodegenerative diseases remain unclear. In this study, we employed D-galactose to establish the model of brain aging by long-term D-galactose subcutaneous injection. Next, we investigated QJD’s effect on cognitive function of the model of brain aging and the mechanisms that QJD suppressing neuroinflammation as well as improving neurodegenerative changes and hippocampal neuron apoptosis. The mice of brain aging were treated with three different dosages of QJD (12.48, 24.96, and 49.92 g/kg/d, respectively) for 4 weeks. Morris water maze was used to determine the learning and memory ability of the mice. HE staining and FJB staining were used to detect the neurodegenerative changes. Nissl staining and TUNEL staining were employed to detect the hippocampal neuron apoptosis. The contents of TNF-α, IL-1β, and IL-6 in the hippocampus were detected by using ELISA. Meanwhile, we employed immunofluorescence staining to examine the levels of GFAP and IBA1 in the hippocampus. Besides, the protein expression levels of Bcl-2, Bax, caspase-3, cleaved caspase-3, AMPKα, p-AMPKα-Thr172, SIRT1, IκBα, NF-κB p65, p-IκBα-Ser32, and p-NF-κB p65-Ser536 in the hippocampus of different groups were detected by Western blot (WB). Our findings showed that the QJD-treated groups, especially the M-QJD group, mitigated learning and memory impairments of the model of brain aging as well as the improvement of neurodegenerative changes and hippocampal neuron apoptosis. Moreover, the M-QJD markedly attenuated the neuroinflammation by regulating the AMPK/SIRT1/NF-κB signaling pathway. Taken together, QJD alleviated neurodegenerative changes and hippocampal neuron apoptosis in the model of brain aging via regulating the AMPK/SIRT1/NF-κB signaling pathway.
Upper-Critical-Solution-Temperature Polymer Modified Gold Nanorods for Laser Controlled Drug Release and Enhanced Anti-Tumour Therapy
Authors: Lin Que , Jia Mao , Fu Yi , Li Bei , Dong Zhigang , Niu Xiaoya , You Zhen
Published: September 2021

Photothermal therapy (PTT) has become effective method for the treatment of malignant cancer. The development of PTT system with high anti-tumour effect is still the feasible research direction. Here, a new type of gold nanorods (AuNRs)-doxorubicin (DOX)/mPEG10K-peptide/P(AAm-co-AN) (APP-DOX) nano drug delivery system was proposed. Among them, AuNRs was used as high-efficiency photothermal agent. APP-DOX had a suitable size and can be targeted to accumulate in tumour tissues through circulation in the body. The abundant matrix metalloproteinase 2 (MMP-2) in the tumour environment intercepted and cut off the short peptide chain structure grafted on APP-DOX. At the same time, the removal of the PEG segment leaded to an increase in the hydrophobic properties of the system. Nanoparticles aggregated into large particles, causing them to stay and aggregate further at the tumour site. When irradiated by 808 nm near-infrared laser, APP-DOX achieved a gradual heating process. High temperature can effectively ablate tumours and enable UCST polymer to achieve phase transition, resulting in more anti-cancer drugs loaded in the polymer layer DOX was released, effectively killing cancer cells. Animal experiments had verified the possibility of the nano drug-carrying system and good tumour treatment effect. What’s more worth mentioning is that compared with free DOX, the nano drug delivery system had lower biological toxicity and not cause obvious harmful effects on normal organs and tissues.
Carbamazepine Induces Platelet Apoptosis and Thrombocytopenia Through Protein Kinase A
Authors: Xiao Weiling , Zhou Kangxi , Yang Mengnan , Sun Chenglin , Dai Lan , Gu Jian , Yan Rong , Dai Kesheng
Published: September 2021

Carbamazepine is extensively used worldwide to treat a wide range of disorders such as epilepsy, peripheral neuralgia and bipolar disorder. Thrombocytopenia and hemorrhage have been identified in multiple carbamazepine-treated patients. However, the underlying mechanism remains poorly understood. Here, we show that platelets undergo apoptosis after carbamazepine treatment. The apoptotic platelets induced by carbamazepine are rapidly removedin vivo, which accounts for thrombocytopenia. We found that carbamazepine treatment attenuates the phosphorylation level of bcl-xl/bcl-2-associated death promoter (BAD), vasodilator-associated stimulated phosphoprotein (VASP) and GPIbβ in platelets, indicating an inhibition effect on protein kinase A (PKA). We further demonstrated that carbamazepine reduced PKA activity through PI3K/Akt/PDE3A signaling pathway. Pharmacological activation of PKA or inhibition of PI3K/Akt/PDE3A protects platelets from apoptosis induced by carbamazepine. Importantly, PDE3A inhibitors or PKA activator ameliorates carbamazepine-mediated thrombocytopeniain vivo. These findings shed light on a possible mechanism of carbamazepine-induced thrombocytopenia, designating PDE3A/PKA as a potential therapeutic target in the treatment of carbamazepine-induced thrombocytopenia.
Total Flavonoids of Litchi Seed Attenuate Prostate Cancer Progression Via Inhibiting AKT/mTOR and NF-kB Signaling Pathways
Authors: Chang Ming , Zhu Dan , Chen Yanjiang , Zhang Weiquan , Liu Xi , Li Xiao-Lan , Cheng Zhiping , Su Zhiheng , Zhang Jian , Lu Yi , Guo Hongwei
Published: September 2021

Litchi seeds have been traditionally used in Chinese herbal formula for urologic neoplasms including prostate cancer (PCa). However, the effective components of Litchi seeds and the mechanisms of their actions on PCa cell growth and metastasis remain unclear. In this study, we investigated the effects and molecular mechanisms of the Total Flavonoid of Litchi Seed (TFLS) in PCa PC3 and DU145 cell lines. We found that TFLS significantly inhibited the PCa cell proliferation, induced apoptosis, and prevented cell migration and invasion. Furthermore, we observed that TFLS upregulated the expression of epithelial biomarker E-cadherin and downregulated mesenchymal biomarker Vimentin. TFLS also increased the expression of cleaved-PRAP and Bax, and decreased the expression of Bcl-2 in both PC3 and DU145 cells. Besides, TFLS inhibited AKT signaling pathway by reducing the phosphorylation of AKT and activities of downstream signal transducers including mTOR, IκBα and NF-kB. Finally, TFLS treated mice exhibited a significant decrease in tumor size without toxicity in major organs in vivo. These results indicated that TFLS could suppress PCa cell growth in vivo and inhibit PCa cell proliferation and metastasis in vitro through induction of apoptosis and phenotypic reversal of EMT, which may be achieved by inhibiting the AKT/mTOR and NF-κB signaling pathways. Taken together, our data provide new insights into the role of TFLS as a novel potent anti-cancer agent for the treatment of PCa.
Interplay Between the N-Terminal Domains of Arabidopsis Starch Synthase 3 Determines the Interaction of the Enzyme With the Starch Granule
Authors: Gámez-Arjona Francisco M. , Mérida Ángel
Published: September 2021

The elongation of the linear chains of starch is undertaken by starch synthases. class 3 of starch synthase (SS3) has a specific feature: a long N-terminal region containing starch binding domains (SBDs). In this work, we analyze in vivo the contribution of these domains to the localization pattern of the enzyme. For this purpose, we divided the N-terminal region of Arabidopsis SS3 in three domains: D1, D2, and D3 (each of which contains an SBD and a coiled-coil site). Our analyses indicate that the N-terminal region is sufficient to determine the same localization pattern observed with the full-length protein. D2 binds tightly the polypeptide to the polymer and it is necessary the contribution of D1 and D3 to avoid the polypeptide to be trapped in the growing polymer. The localization pattern of Arabidopsis SS3 appears to be the result of the counterbalanced action of the different domains present in its N-terminal region.
Genome-Wide Identification and Comparison of Cysteine Proteases in the Pollen Coat and Other Tissues in Maize
Authors: Li Yanhua , Niu Liangjie , Wu Xiaolin , Faleri Claudia , Tai Fuju , Zhang Man , Liu Hui , Wang Wei , Cai Giampiero
Published: September 2021

Cysteine proteases, belonging to the C1-papain family, play a major role in plant growth and development, senescence, and immunity. There is evidence to suggest that pollen cysteine protease (CP) (ZmCP03) is involved in regulating the anther development and pollen formation in maize. However, there is no report on the genome-wide identification and comparison of CPs in the pollen coat and other tissues in maize. In this study, a total of 38 homologous genes of ZmCP03 in maize were identified. Subsequently, protein motifs, conserved domains, gene structures, and duplication patterns of 39 CPs are analyzed to explore their evolutionary relationship and potential functions. The cis-elements were identified in the upstream sequence of 39 CPs, especially those that are related to regulating growth and development and responding to environmental stresses and hormones. The expression patterns of these genes displayed remarked difference at a tissue or organ level in maize based on the available transcriptome data in the public database. Quantitative reverse transcription PCR (RT-qPCR) analysis showed that ZmCP03 was preferably expressed at a high level in maize pollen. Analyses by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblot, immunofluorescence and immunogold electron microscopy all validated the cellular localization of ZmCP03 in both the pollen coat and pollen cytoplasm. In addition, 142 CP genes from Arabidopsis (Arabidopsis thaliana), rice (Oryza sativa) and cotton (Gossypium hirsutum), together with 39 maize CPs, were retrieved to analyze their evolution by comparing with orthologous genes. The results suggested that ZmCP03 was relatively conservative and stable during evolution. This study may provide a referential evidence on the function of ZmCP03 in pollen development and germination in maize.
Identification and Molecular Analysis of Putative Self-Incompatibility Ribonuclease Alleles in an Extreme Polyploid Species, Prunus laurocerasus L.
Authors: Halász Júlia , Molnár Anna Borbála , Ilhan Gulce , Ercisli Sezai , Hegedűs Attila
Published: September 2021

Cherry laurel (Prunus laurocerasusL.) is an extreme polyploid (2n= 22x) species of the Rosaceae family where gametophytic self-incompatibility (GSI) prevents inbreeding. This study was carried out to identify theS-ribonuclease alleles (S-RNases) ofP. laurocerasususing PCR amplification of the first and second intron region of theS-RNasegene, cloning and sequencing. A total of 23 putativeS-RNase alleles (S1–S20,S5m,S13m, andS18m) were sequenced from the second (C2) to the fifth conserved region (C5), and they shared significant homology to otherPrunus S-RNases. The length of the sequenced amplicons ranged from 505 to 1,544 bp, and similar sizes prevented the proper discrimination of some alleles based on PCR analysis. We have found three putatively non-functional alleles (S5m,S18m, andS9) coding for truncated proteins. Although firm conclusions cannot be drawn, our data seem to support that heteroallelic pollen cannot induce self-compatibility in this polyploidPrunusspecies. The identities in the deduced amino acid sequences between theP. laurocerasusand otherPrunus S-RNases ranged between 44 and 100%, without a discontinuity gap separating the identity percentages of trans-specific and more distantly related alleles. The phylogenetic position, the identities in nucleotide sequences of the second intron and in deduced amino acid sequences found one or more trans-specific alleles for all butS10,S14,S18, andS20cherry laurel RNases. The analysis of mutational frequencies in trans-specific allele pairs indicated the region RC4–C5 accepts the most amino acid replacements and hence it may contribute to allele-specificity. Our results form the basis of future studies to confirm the existence and function of the GSI system in this extreme polyploid species and the alleles identified will be also useful for phylogenetic studies ofPrunus S-RNases as the number ofS-RNasesequences was limited in the Racemose group ofPrunus(whereP. laurocerasusbelongs to).
‘Resistance Mixtures’ Reduce Insect Herbivory in Strawberry (Fragaria vesca) Plantations
Authors: Koski Tuuli-Marjaana , de Jong Sanne , Muola Anne , Amby Daniel B. , Andreasson Erik , Stenberg Johan A.
Published: September 2021

The transition toward more sustainable plant protection with reduced pesticide use is difficult, because there is no “silver bullet” available among nonchemical tools. Integrating several plant protection approaches may thus be needed for efficient pest management. Recently, increasing the genetic diversity of plantations via cultivar mixing has been proposed as a possible method to reduce pest damage. However, previous studies have not addressed either the relative efficiency of exploiting cultivar mixing and intrinsic plant herbivore resistance or the potential utility of combining these approaches to increase cropping security. Here, using a full factorial experiment with 60 woodland strawberry plots, we tested for the relative and combined effect of cultivar mixing and intrinsic plant resistance on herbivore damage and yield. The experiment comprised two levels of diversity (“high” with 10 varieties and “low” with two varieties) and three levels of resistance (“resistant” comprising only varieties intrinsically resistant against strawberry leaf beetle Galerucella tenella; “susceptible” with susceptible varieties only; and “resistance mixtures” with 50:50 mixtures of resistant and susceptible varieties). The experiment was carried out over two growing seasons. Use of resistant varieties either alone or intermixed with susceptible varieties in “resistance mixtures” reduced insect herbivory. Interestingly, resistant varieties not only reduced the mean damage in “resistance mixtures” by themselves being less damaged, but also protected intermixed susceptible varieties via associational resistance. The effect of higher genetic diversity was less evident, reducing herbivory only at the highest level of herbivore damage. In general, herbivory was lowest in plots with high diversity that included at least some resistant varieties and highest in low diversity plots consisting only of susceptible varieties. Despite this, no significant difference in yield (fruit biomass) was found, indicating that strawberry may be relatively tolerant. Our results demonstrate that combined use of high genetic diversity and resistant varieties can help reduce pest damage and provide a useful tool for sustainable food production. “Resistance mixtures” may be particularly useful for sensitive food crops where susceptible varieties are high yielding that could not be completely replaced by resistant ones.
One Step Away From Extinction: A Population Genomic Analysis of A Narrow Endemic, Tropical Plant Species
Authors: Teixeira Thais M. , Nazareno Alison G.
Published: September 2021

Intraspecific genetic variation plays a fundamental role in maintaining the evolutionary potential of wild populations. Hence, the assessment of genetic diversity patterns becomes essential to guide biodiversity conservation policies, particularly for threatened species. To inform management strategies for conservation ofMimosa catharinensis– a narrow endemic, critically endangered plant species – we identified 1,497 unlinked SNP markers derived from a reduced representation sequencing method (i.e., double digest restriction site associated DNA sequencing, or ddRADseq). This set of molecular markers was employed to assess intrapopulation genetic parameters and the demographic history of one extremely small population ofM. catharinensis(N=33) located in the Brazilian Atlantic Forest. Contrary to what is expected for narrow endemic and threatened species with small population sizes, we observed a moderate level of genetic diversity forM. catharinensis[uHE(0%missing data)=0.205, 95% CI (0.160, 0.250);uHE(30%missing data)=0.233, 95% CI (0.174, 0.292)]. Interestingly,M. catharinensis, which is a lianescent shrub with no indication of seed production for at least two decades, presented high levels of outcrossing [t(0%missing data)=0.883, SE±0.0483;t(30%missing data)=0.909, SE±0.011] and an apparent absence of inbreeding [F(0%missing data)=−0.145, 95% CI (−0.189, −0.101);F(30%missing data)=−0.105, 95% CI (−0.199, −0.011)]. However, the reconstruction of demographic history ofM. catharinensisindicated that the population should be suffered a recent bottleneck. Our population genomic study tackles a central issue in evolution and conservation biology and we expect that it will be useful to help safeguard the remaining genetic diversity reported for this unique genetic resource.
Overexpression of Cinnamoyl-CoA Reductase 2 in Brassica napus Increases Resistance to Sclerotinia sclerotiorum by Affecting Lignin Biosynthesis
Authors: Liu Dongxiao , Wu Jian , Lin Li , Li Panpan , Li Saifen , Wang Yue , Li Jian , Sun Qinfu , Liang Jiansheng , Wang Youping
Published: September 2021

Sclerotinia sclerotiorum causes severe yield and economic losses for many crop and vegetable species, especially Brassica napus. To date, no immune B. napus germplasm has been identified, giving rise to a major challenge in the breeding of Sclerotinia resistance. In the present study, we found that, compared with a Sclerotinia-susceptible line (J902), a Sclerotinia-resistant line (J964) exhibited better xylem development and a higher lignin content in the stems, which may limit the invasion and spread of S. sclerotiorum during the early infection period. In addition, genes involved in lignin biosynthesis were induced under S. sclerotiorum infection in both lines, indicating that lignin was deposited proactively in infected tissues. We then overexpressed BnaC.CCR2.b, which encodes the first rate-limiting enzyme (cinnamoyl-CoA reductase) that catalyzes the reaction of lignin-specific pathways, and found that overexpression of BnaC.CCR2.b increased the lignin content in the stems of B. napus by 2.28–2.76% under normal growth conditions. We further evaluated the Sclerotinia resistance of BnaC.CCR2.b overexpression lines at the flower-termination stage and found that the disease lesions on the stems of plants in the T2 and T3 generations decreased by 12.2–33.7% and 32.5–37.3% compared to non-transgenic control plants, respectively, at 7days post-inoculation (dpi). The above results indicate that overexpression of BnaC.CCR2.b leads to an increase in lignin content in the stems, which subsequently leads to increased resistance to S. sclerotiorum. Our findings demonstrate that increasing the lignin content in the stems of B. napus is an important strategy for controlling Sclerotinia.
Accumulation of Abnormal Amyloplasts in Pulp Cells Induces Bitter Pit in Malus domestica
Authors: Qiu Lina , Hu Shanshan , Wang Yongzhang , Qu Haiyong
Published: September 2021

Apple bitter pit primarily occurs during fruit ripening and storage; however, its formation mechanism remains unclear. Although it is considered that Ca2+deficiency causes metabolic disorders in apples, there have been few studies on the mechanism of the bitter pit from the perspective of cell structure. At the fruit ripening stage, the fruit with a bitter pit on the tree was taken as the research material. In this study, the microscopic observation revealed numerous amyloplasts in the pulp cells of apples affected with bitter pit, but not in the healthy pulp. Furthermore, the results of fluorescence staining and transmission electron microscopy (TEM) revealed that the bitter pit pulp cells undergo programmed cell death (PCD), their nuclear chromosomes condense, and amyloplast forms autophagy. The cytoplasmic Ca2+concentration in the healthy fruits was lowest near the peduncle, followed by that in the calyx, whereas it was highest at the equator. In contrast, the cytoplasmic Ca2+concentration in apple fruits showing bitter pit disorder was lowest near the peduncle and highest in the calyx. Moreover, the cytosolic Ca2+concentration in the flesh cells of apples with the bitter pit was much lower than that in the healthy apple flesh cells; however, the concentration of Ca2+in the vacuoles of fruits with the bitter pit was higher than that in the vacuoles of healthy fruits. In summary, bitter pit pulp cells contain a large number of amyloplasts, which disrupts the distribution of Ca2+in the pulp cells and causes PCD. These two processes lead to an imbalance in cell metabolism and induce the formation of a bitter pit.
Comparative Chloroplast Genomes of Zosteraceae Species Provide Adaptive Evolution Insights Into Seagrass
Authors: Chen Jun , Zang Yu , Shang Shuai , Liang Shuo , Zhu Meiling , Wang Ying , Tang Xuexi
Published: September 2021

Seagrasses are marine flowering plants found in tropical and sub-tropical areas that live in coastal regions between the sea and land. All seagrass species evolved from terrestrial monocotyledons, providing the opportunity to study plant adaptation to sea environments. Here, we sequenced the chloroplast genomes (cpGenomes) of threeZosteraspecies, then analyzed and compared their cpGenome structures and sequence variations. We also performed a phylogenetic analysis using published seagrass chloroplasts and calculated the selection pressure of 17 species within seagrasses and nine terrestrial monocotyledons, as well as estimated the number of shared genes of eight seagrasses. The cpGenomes ofZosteraceaespecies ranged in size from 143,877 bp (Zostera marina) to 152,726 bp (Phyllospadix iwatensis), which were conserved and displayed similar structures and gene orders. Additionally, we found 17 variable hotspot regions as candidate DNA barcodes forZosteraceaespecies, which will be helpful for studying the phylogenetic relationships and interspecies differences between seagrass species. Interestingly, nine genes had positive selection sites, including two ATP subunit genes (atpAandatpF), two ribosome subunit genes (rps4andrpl20), two DNA-dependent RNA polymerase genes (rpoC1andrpoC2), as well asaccD,clpP, andycf2. These gene regions may have played key roles in the seagrass adaptation to diverse environments. The Branch model analysis showed that seagrasses had a higher rate of evolution than terrestrial monocotyledons, suggesting that seagrasses experienced greater environmental pressure. Moreover, a branch-site model identified positively selected sites (PSSs) inccsA, suggesting their involvement in the adaptation to sea environments. These findings are valuable for further investigations onZosteraceaecpGenomes and will serve as an excellent resource for future studies on seagrass adaptation to sea environments.
Plant Autophagy: An Intricate Process Controlled by Various Signaling Pathways
Authors: Wang Pingping , Wang Tongtong , Han Jingyi , Li Ming , Zhao Yanxiu , Su Tong , Ma Changle
Published: September 2021

Autophagy is a ubiquitous process used widely across plant cells to degrade cellular material and is an important regulator of plant growth and various environmental stress responses in plants. The initiation and dynamics of autophagy in plant cells are precisely controlled according to the developmental stage of the plant and changes in the environment, which are transduced into intracellular signaling pathways. These signaling pathways often regulate autophagy by mediating TOR (Target of Rapamycin) kinase activity, an important regulator of autophagy initiation; however, some also act via TOR-independent pathways. Under nutrient starvation, TOR activity is suppressed through glucose or ROS (reactive oxygen species) signaling, thereby promoting the initiation of autophagy. Under stresses, autophagy can be regulated by the regulatory networks connecting stresses, ROS and plant hormones, and in turn, autophagy regulates ROS levels and hormone signaling. This review focuses on the latest research progress in the mechanism of different external signals regulating autophagy.
How Can Hotel Employees Produce Workplace Environmentally Friendly Behavior? The Role of Leader, Corporate and Coworkers
Authors: Zheng Shanting , Jiang Lin , Cai Wenjing , Xu Binfeng , Gao Xiaopei
Published: September 2021

Although previous studies have acknowledged that leaders’ such environmental behaviors and environmental issues are becoming critical for long-term development, little research has focused on why, how and when perceived environmentally specific servant leadership contributes to employees’ workplace environmentally friendly behavior in the hotel industry. This paper aims to fill this research gap by using social identity theory to test employees’ green role identity as a mediator and their perceived corporate environmental responsibility and perceived coworkers’ work group green advocacy as moderators in the relationship between perceived environmentally-specific servant leadership and workplace environmentally friendly behavior. Using a sample of 527 leader-follower dyads from six hotels in mainland China at two points in time, we found that employees’ green role identity mediates the positive relationship between perceived environmentally specific servant leadership and employees’ workplace environmentally friendly behavior. Moreover, employees’ perceived corporate environmental responsibility and perceived coworkers’ work group green advocacy were found to positively moderate the relationship between perceived environmentally-specific servant leadership and green role identity and between green role identity and workplace environmentally friendly behavior, respectively. Theoretical and practical implications are discussed.
Latent Profile of Internet and Internet Game Usage Among South Korean Adolescents During the COVID-19 Pandemic
Authors: Kim Dongil , Lee Junwon , Nam JeeEun Karin
Published: September 2021

Introduction: Globally, more people are spending time on the Internet and gaming since the outbreak of the Coronavirus Disease 2019 (COVID-19). Consequently, concerns about developing behavioral addiction of adolescents have been raised. Such risk could be greater for adolescents in South Korea where the majority of adolescents have access to the Internet and own a smartphone. In fact, statistics indicate that Korean youths are spending significantly more time on the Internet and gaming during the COVID-19 pandemic. Previous studies on the patterns of time spent on the Internet and Internet gaming show inconsistent results. The aim of this study is to investigate the latent profiles of the Internet and Internet game usage among adolescents in South Korea.

Method: Data from a national survey on elementary and middle school students across South Korea were used. The sample consists of 3,149 respondents, and 2,984 responses were analyzed after removing missing responses. Latent profile analysis was performed to investigate the number of latent profiles for the Internet and Internet game usage time. To validate the profiles, differences in problematic gaming behavior, sex, and neuroticism were examined.

Results: Seven profiles were found: Casual User, Moderate User, Smartphone User, Internet User, PC Internet Gamer, Heavy User, and Excessive User. Validation of the profiles indicated differences in problematic gaming behavior, sex, and neuroticism among selected profiles.

Conclusion: This study presented different profiles of the Internet and Internet game usage among adolescents in South Korea. Profiles with higher game usage time scored higher in problematic game use compared to other profiles. Males were more likely to be in the profiles with high gaming time, and females were more likely to be in Internet and Smartphone User profiles. The results indicate that Internet and Internet gaming usage patterns could be classified by the type of device used and the content of the Internet.
Social Quarantine and Its Four Modes: Conceptional Exploration and the Theoretical Construction of the Policies Against COVID-19
Authors: Lin Ka , Mumtaz Ayesha , Rahaman Mohammad Anisur , Mok Ka Ho
Published: September 2021

Building on the studies of health quarantine from a social perspective, this article explores the complex contexts of social quarantine as a mode of public health, a mode of community action and a behavioural and psychological mode of social distancing. To establish a conceptual investigation of the “social quarantine” issue, this study investigates four approaches to quarantine: public health, social administration, behavioural norms, and psychological effects. The study identifies the features of these modes and discusses their relationships. In addition, this study constructs a preventive framework for quarantine that embraces social and health policies to enrich the understanding of policy measures for social distancing and lockdown measures. On this basis, the study evaluates the strategies of policy development in response to the COVID-19 pandemic. The study concludes that these modes can reconstruct social relations and provide some basis for theoretical analysis about the features of social quarantine, which is vital for policymakers when considering national and global prevention strategies for public health.
Acceptance and Commitment Therapy in a Low-Income Country in Sub-Saharan Africa: A Call for Further Research
Authors: Geda Yonas E. , Krell-Roesch Janina , Fisseha Yaphet , Tefera Aida , Beyero Teferra , Rosenbaum Deborah , Szabo Thomas G. , Araya Mesfin , Hayes Steven C.
Published: September 2021

A worsening trend of critical shortages in senior health care workers across low- and middle-income countries (LMICs) in sub-Saharan Africa has been documented for decades. This is especially the case in Ethiopia that has severe shortage of mental health professionals. Consistent with the WHO recommended approach of task sharing for mental health care in LMICs, Acceptance and Commitment Therapy (ACT), which is an empirically validated psychological intervention aimed at increasing psychological flexibility, may be delivered by trained laypersons who have a grassroots presence. In this paper, we discuss the need for and potential role of ACT to be delivered by health extension workers (HEWs) to address mental health care needs across Ethiopia. To this end, we also reviewed previous studies that have examined the effectiveness of ACT-based interventions in African countries including in Nigeria, Sierra Leone, Uganda, and South Africa. All studies revealed significant improvements of various mental health-related outcome measures such as decreased psychological distress and depressive symptoms, or increased subjective wellbeing and life satisfaction in the groups that received an ACT-based intervention. However, to date, there is no study that applied ACT in Ethiopia. Thus, more research is warranted to examine the effectiveness and, if proven successful, to scale up a task sharing approach of an ACT-based intervention being delivered by trained HEWs at a grassroots level, possibly paving the way for an innovative, sustainable mental health service in Ethiopia as well as other African LMICs.
Meningioma Segmentation in T1-Weighted MRI Leveraging Global Context and Attention Mechanisms
Authors: Bouget David , Pedersen André , Hosainey Sayied Abdol Mohieb , Solheim Ole , Reinertsen Ingerid
Published: September 2021

Purpose: Meningiomas are the most common type of primary brain tumor, accounting for ~30% of all brain tumors. A substantial number of these tumors are never surgically removed but rather monitored over time. Automatic and precise meningioma segmentation is, therefore, beneficial to enable reliable growth estimation and patient-specific treatment planning.

Methods: In this study, we propose the inclusion of attention mechanisms on top of a U-Net architecture used as backbone: (i) Attention-gated U-Net (AGUNet) and (ii) Dual Attention U-Net (DAUNet), using a three-dimensional (3D) magnetic resonance imaging (MRI) volume as input. Attention has the potential to leverage the global context and identify features' relationships across the entire volume. To limit spatial resolution degradation and loss of detail inherent to encoder–decoder architectures, we studied the impact of multi-scale input and deep supervision components. The proposed architectures are trainable end-to-end and each concept can be seamlessly disabled for ablation studies.

Results: The validation studies were performed using a five-fold cross-validation over 600 T1-weighted MRI volumes from St. Olavs Hospital, Trondheim University Hospital, Norway. Models were evaluated based on segmentation, detection, and speed performances, and results are reported patient-wise after averaging across all folds. For the best-performing architecture, an average Dice score of 81.6% was reached for an F1-score of 95.6%. With an almost perfect precision of 98%, meningiomas smaller than 3 ml were occasionally missed hence reaching an overall recall of 93%.

Conclusion: Leveraging global context from a 3D MRI volume provided the best performances, even if the native volume resolution could not be processed directly due to current GPU memory limitations. Overall, near-perfect detection was achieved for meningiomas larger than 3 ml, which is relevant for clinical use. In the future, the use of multi-scale designs and refinement networks should be further investigated. A larger number of cases with meningiomas below 3 ml might also be needed to improve the performance for the smallest tumors.
Air Pollution and Urban Green Space: Evidence of Environmental Injustice in Adama, Ethiopia
Authors: Flanagan Erin , Mattisson Kristoffer , Walles John , Abera Asmamaw , Eriksson Axel , Balidemaj Festina , Oudin Anna , Isaxon Christina , Malmqvist Ebba
Published: September 2021

While air pollution data in Ethiopia is limited, existing studies indicate high levels of both ambient and household air pollution; rapid urbanization also threatens the preservation of urban green spaces. In this study, environmental injustice, or the disproportionate burden of environmental exposures on persons of lower socioeconomic status (SES), was explored among women in Ethiopia using a mother and child cohort from the city of Adama. Land-use regression models were previously developed for modeling ambient nitrogen dioxide (NO2) and nitrogen oxides (NOx) throughout Adama, while household air pollution (cooking fuel type) and the presence of green space were assessed through questionnaires and home visits, respectively. The odds of being exposed to these environmental factors were analyzed in association with two SES indicators, education and occupation, using logistic regression. Our results indicate the presence of environmental injustice in Adama, as women with lower SES shouldered a higher burden of air pollution exposure and enjoyed less urban green space than their higher SES counterparts. These findings encourage the prioritization of air quality control and urban planning resources toward policy action within lower SES areas. From a societal perspective, our results also support more upstream interventions, including investment in educational and occupational opportunities. Still, a human rights approach is emphasized, as governments are responsible for protecting the right to a clean environment, especially for those disproportionately exposed. To the best of our knowledge, this is the first study on environmental injustice in Ethiopia, and the first in Sub-Saharan Africa to investigate the inequalities of ambient and household air pollution exposure as well as urban green space access in the same cohort.
Potential Key Factors, Policies, and Barriers for Rooftop Agriculture in EU Cities: Barcelona, Berlin, Bologna, and Paris
Authors: Zambrano-Prado Perla , Orsini Francesco , Rieradevall Joan , Josa Alejandro , Gabarrell Xavier
Published: September 2021

The main objective of this study is to contribute a framework and to provide an overview of potential key factors, policies, and barriers associated with the integration of rooftop urban agriculture (RUA), building on stakeholders' perspectives in four European cities (Barcelona, Berlin, Bologna, and Paris). The research was developed in two phases, namely, a workshop and a survey of stakeholders involved in RUA from the four cities. Education, environmental, research, technological innovation, food production, and social factors play an important role in implementing RUA. Productive spaces, cultural values, social cohesion, social rural-urban links, and the high cost of urban land are highlighted as factors that “promote” RUA. In contrast, the cost of water and pollution are major contextual factors that constrain RUA. Policies related to food trade and urban planning are those that most limit RUA development. Major architectural and technical barriers related to the limits on building heights, historical buildings, a lack of specific building codes, building design and roof accessibility were identified. The high cost of infrastructure and policies that prohibit RUA product sales emerged as economic constraints. Major differences among the cities studied included the perceived effect of urban policies on RUA diffusion as well as the perceived relevance of economic and pollution factors. This study revealed that extensive dissemination and the development of appropriate information about RUA are needed. The creation of new regulations, as well as modifications to urban and building codes to support RUA, is also envisaged. This approach will consider a more flexible land-use policy that allows agriculture to take place in cities as well as marketing frameworks for RUA products. For future studies, it would be useful to apply the framework developed in this study to a larger sample. A study is also needed to confirm hypothetical differences between cities.
Case Report: Nuchal Bursitis Associated With Borrelia burgdorferi Infection in a Horse
Authors: Guarino Cassandra , Pinn-Woodcock Toby , Levine David G. , Miller Julia , Johnson Amy L.
Published: September 2021

Cases of cranial nuchal bursitis associated withBorrelia burgdorferiinfection have not been thoroughly described. Here, we describe the case of a 17-year-old mare that was presented for low head carriage, dull demeanor, and resistance to haltering. Imaging supported a diagnosis of nuchal bursitis, and bursoscopy with surgical debridement of the nuchal bursa was performed.B. burgdorferiwas identified by molecular diagnostics in serial samples of the bursal fluid, with no other organisms identified. Serology revealed significant elevation in antibodies directed against OspA ofB. burgdorferi, but not the typical infection markers, OspC and OspF. Intravenous ceftiofur was administered for 80 days, and the nuchal bursa was directly injected with ceftiofur. The mare recovered and was able to return to work with no recrudescence of clinical signs over the following year to date. Infection withB. burgdorferishould be considered as a differential in cases of septic nuchal bursitis.
The Magnitude of Black/Hispanic Disparity in COVID-19 Mortality Across United States Counties During the First Waves of the COVID-19 Pandemic
Authors: Im Cindy , Munasinghe Lalani L. , Martínez José M. , Letsou William , Bagherzadeh-Khiabani Farideh , Marin Soudabeh , Yasui Yutaka
Published: September 2021

Objectives:To quantify the Black/Hispanic disparity in COVID-19 mortality in the United States (US).

Methods:COVID-19 deaths in all US counties nationwide were analyzed to estimate COVID-19 mortality rate ratios by county-level proportions of Black/Hispanic residents, using mixed-effects Poisson regression. Excess COVID-19 mortality counts, relative to predicted under a counterfactual scenario of no racial/ethnic disparity gradient, were estimated.

Results:County-level COVID-19 mortality rates increased monotonically with county-level proportions of Black and Hispanic residents, up to 5.4-fold (≥43% Black) and 11.6-fold (≥55% Hispanic) higher compared to counties with <5% Black and <15% Hispanic residents, respectively, controlling for county-level poverty, age, and urbanization level. Had this disparity gradient not existed, the US COVID-19 death count would have been 92.1% lower (177,672 fewer deaths), making the rate comparable to other high-income countries with substantially lower COVID-19 death counts.

Conclusion:During the first 8 months of the SARS-CoV-2 pandemic, the US experienced the highest number of COVID-19 deaths. This COVID-19 mortality burden is strongly associated with county-level racial/ethnic diversity, explaining most US COVID-19 deaths.