bluuebunny/crossref_metadata_2025 huggingface dataset:
Cuproptosis-Associated lncRNA Establishes New Prognostic Profile and Predicts Immunotherapy Response in Clear Cell Renal Cell Carcinoma
Authors: Xu Shengxian , Liu Dongze , Chang Taihao , Wen Xiaodong , Ma Shenfei , Sun Guangyu , Wang Longbin , Chen Shuaiqi , Xu Yong , Zhang Hongtuan
Published: July 2022

Background: Clear cell renal cell carcinoma (ccRCC) accounts for 80% of all kidney cancers and has a poor prognosis. Recent studies have shown that copper-dependent, regulated cell death differs from previously known death mechanisms (apoptosis, ferroptosis, and necroptosis) and is dependent on mitochondrial respiration (Tsvetkov et al., Science, 2022, 375 (6586), 1254–1261). Studies also suggested that targeting cuproptosis may be a novel therapeutic strategy for cancer therapy. In ccRCC, both cuproptosis and lncRNA were critical, but the mechanisms were not fully understood. The aim of our study was to construct a prognostic profile based on cuproptosis-associated lncRNAs to predict the prognosis of ccRCC and to study the immune profile of clear cell renal cell carcinoma (ccRCC).

Methods: We downloaded the transcriptional profile and clinical information of ccRCC from The Cancer Genome Atlas (TCGA). Co-expression network analysis, Cox regression method, and least absolute shrinkage and selection operator (LASSO) method were used to identify cuproptosis-associated lncRNAs and to construct a risk prognostic model. In addition, the predictive performance of the model was validated and recognized by an integrated approach. We then also constructed a nomogram to predict the prognosis of ccRCC patients. Differences in biological function were investigated by GO, KEGG, and immunoassay. Immunotherapy response was measured using tumor mutational burden (TMB) and tumor immune dysfunction and rejection (TIDE) scores.

Results: We constructed a panel of 10 cuproptosis-associated lncRNAs (HHLA3, H1-10-AS1, PICSAR, LINC02027, SNHG15, SNHG8, LINC00471, EIF1B-AS1, LINC02154, and MINCR) to construct a prognostic prediction model. The Kaplan–Meier and ROC curves showed that the feature had acceptable predictive validity in the TCGA training, test, and complete groups. The cuproptosis-associated lncRNA model had higher diagnostic efficiency compared to other clinical features. The analysis of Immune cell infiltration and ssGSEA further confirmed that predictive features were significantly associated with the immune status of ccRCC patients. Notably, the superimposed effect of patients in the high-risk group and high TMB resulted in shorter survival. In addition, the higher TIDE scores in the high-risk group suggested a poorer outcome for immune checkpoint blockade response in these patients.

Conclusion: The ten cuproptosis-related risk profiles for lncRNA may help assess the prognosis and molecular profile of ccRCC patients and improve treatment options, which can be further applied in the clinic.
Host KIR/HLA-C Genotypes Determine HIV-Mediated Changes of the NK Cell Repertoire and Are Associated With Vpu Sequence Variations Impacting Downmodulation of HLA-C
Authors: Vollmers Sarah , Lobermeyer Annabelle , Niehrs Annika , Fittje Pia , Indenbirken Daniela , Nakel Jacqueline , Virdi Sanamjeet , Brias Sebastien , Trenkner Timo , Sauer Gabriel , Peine Sven , Behrens Georg M.N. , Lehmann Clara , Meurer Anja , Pauli Ramona , Postel Nils , Roider Julia , Scholten Stefan , Spinner Christoph D. , Stephan Christoph , Wolf Eva , Wyen Christoph , Richert Laura , Norman Paul J. , Sauter Jürgen , Schmidt Alexander H. , Hoelzemer Angelique , Altfeld Marcus , Körner Christian
Published: July 2022

NK cells play a pivotal role in viral immunity, utilizing a large array of activating and inhibitory receptors to identify and eliminate virus-infected cells. Killer-cell immunoglobulin-like receptors (KIRs) represent a highly polymorphic receptor family, regulating NK cell activity and determining the ability to recognize target cells. Human leukocyte antigen (HLA) class I molecules serve as the primary ligand for KIRs. Herein, HLA-C stands out as being the dominant ligand for the majority of KIRs. Accumulating evidence indicated that interactions between HLA-C and its inhibitory KIR2DL receptors (KIR2DL1/L2/L3) can drive HIV-1-mediated immune evasion and thus may contribute to the intrinsic control of HIV-1 infection. Of particular interest in this context is the recent observation that HIV-1 is able to adapt to hostHLA-Cgenotypes through Vpu-mediated downmodulation of HLA-C. However, our understanding of the complex interplay betweenKIR/HLAimmunogenetics, NK cell-mediated immune pressure and HIV-1 immune escape is still limited. Therefore, we investigated the impact of specificKIR/HLA-Ccombinations on the NK cell receptor repertoire and HIV-1 Vpu protein sequence variations of 122 viremic, untreated HIV-1+individuals. Compared to 60 HIV-1-controls, HIV-1 infection was associated with significant changes within the NK cell receptor repertoire, including reduced percentages of NK cells expressing NKG2A, CD8, and KIR2DS4. In contrast, the NKG2C+and KIR3DL2+NK cell sub-populations from HIV-1+individuals was enlarged compared to HIV-1-controls. Stratification alongKIR/HLA-Cgenotypes revealed a genotype-dependent expansion of KIR2DL1+NK cells that was ultimately associated with increased binding affinities between KIR2DL1 and HLA-C allotypes. Lastly, our data hinted to a preferential selection of Vpu sequence variants that were associated with HLA-C downmodulation in individuals with high KIR2DL/HLA-C binding affinities. Altogether, our study provides evidence that HIV-1-associated changes in the KIR repertoire of NK cells are to some extent predetermined by hostKIR2DL/HLA-Cgenotypes. Furthermore, analysis of Vpu sequence polymorphisms indicates that differential KIR2DL/HLA-C binding affinities may serve as an additional mechanism how host genetics impact immune evasion by HIV-1.
Moringa oleifera Lam. Peptide Remodels Intestinal Mucosal Barrier by Inhibiting JAK-STAT Activation and Modulating Gut Microbiota in Colitis
Authors: Hong Zi-Shan , Xie Jing , Wang Xue-Feng , Dai Jing-Jing , Mao Jia-Ying , Bai Yu-Ying , Sheng Jun , Tian Yang
Published: July 2022

Ulcerative colitis is a chronic inflammatory bowel disease (IBD), but progress in exploring its pathogenesis and finding effective drugs for its prevention and treatment has stalled in recent years. The seeds of Moringa oleifera Lam. are rich in proteins known to have multiple physiological activities. In our earlier work, we had isolated and purified a peptide (MOP) having the sequence KETTTIVR, from M. oleifera seeds; however, its anti-inflammatory activity and mechanism in vivo were unclear. Here we used the dextran sulfate sodium (DSS)-induced colitis model to study the anti-inflammatory activity and mechanism of this MOP. Our results are the first to show that MOP can ameliorate the pathological phenotype, inflammation, and intestinal barrier disruption in mice with colitis. Furthermore, RNA sequencing revealed that MOP inhibits the Janus kinase/signal transducer and activator of transcription (JAK-STAT) pathway activation. Next, by using 16s rRNA gene sequencing, we found that MOP can ameliorate DSS-induced gut microbiota dysbiosis. In addition, an untargeted metabolomics analysis suggested that MOP is able to modulate the level of lipid and amino acid metabolites in IBD-stricken mice. Altogether, these results indicate that MOP ameliorates colitis by remodeling intestinal mucosal barrier by inhibiting JAK-STAT pathway’s activation and regulating gut microbiota and its metabolites, thus providing a basis for further processing and design of bioactive foods from M. oleifera seeds.
Practical Approaches for Providing Empirical Data on Seabird Behavior and Prey Assemblages in Tidal Channels
Authors: Fraser Shaun , Waggitt James J.
Published: July 2022

Persisting knowledge gaps relating to the ecological context and potential environmental impacts of marine renewable energy (MRE) devices continue to add substantial costs and uncertainty to MRE projects globally. Increasingly sophisticated technological approaches to environmental monitoring can have fundamental non-trivial shortcomings for environmental impact assessment (EIA), whilst substantial practical and financial costs of deployments can prevent their application. For the tidal stream energy (TSE) sector, there is a need for practical and cost-effective methods that can provide site-specific information on predator behavior and associated prey assemblages. Considering existing knowledge of animal communities in tidal channel environments, a proportional approach using shore-based observation and baited fish trap methods was developed. During April 2021, a trial of these methods was conducted in tidal channel environments in Shetland, UK. The practical application of the proposed approach is demonstrated here with results from three tidal channels including Bluemull Sound, the site of active TSE installations (the Shetland Tidal Array). Observation of predator behavior across the study sites are reported for great cormorant Phalacrocorax carbo and European shag Phalacrocorax aristotelis. Seabird diving data calculated from the shore-based observations provided metrics relevant to informing EIA and collision risk modelling including dive duration, dives per minute, and % time underwater. Fish trap deployments targeted the benthic and demersal prey of these predators in the three study sites and across a range of depths and hydrodynamic conditions. A variety of fish and invertebrate species known to be important components of benthic-foraging seabird diet were successfully captured by the traps, providing basic biological information on the prey assemblages observed in each site. The fish species observed in the highest abundance were saithe Pollachius virens and cod Gadus morhua. Benefits, limitations, and applications of this approach are discussed along with various factors relating to the performance of both methods. The shore-based observations rapidly identified relevant patterns in predator foraging activity which informed the targeted deployment of fish traps to provide complementary prey data. This novel combined approach has potential to reduce costs and uncertainty in EIA and for supporting the responsible development of the MRE industry.
A Risk-Based Assessment to Advise the Responsible Consumption of Invertebrates, Elasmobranch, and Fishes of Commercial Interest in Mexico
Authors: Saldaña-Ruiz Luz Erandi , Flores-Guzmán Alesa , Cisneros-Soberanis Frida , Cuevas-Gómez Gabriela Alejandra , Gastélum-Nava Ernesto , Rocha-Tejeda Lorena , Chavez Jose Francisco , Hernandez-Pimienta Raziel Elihu , Fernández-Rivera Melo Francisco Javier
Published: July 2022

The main key drivers of vulnerability for marine species are anthropogenic stressors, ranging from pollution and fishing to climate change. The widely documented impacts of fishing activities on marine species, the growing concern about the population status of many marine species, and the increase in per capita consumption of marine products worldwide have led to the development of environmentally responsible fishing standards and initiatives to inform consumers about the health status of the species. In Mexico, fishing is a vital source of jobs and food security for many coastal communities, but the population status of many species of commercial importance has not been evaluated. Management efforts and fisheries certification procedures and standards to achieve the sustainability of many Mexican fisheries are hindered by a lack of biological and fishery data for many species. In this study, a risk assessment methodology for data-limited fisheries, a Productivity, and Susceptibility Analysis was used to estimate the relative vulnerability of marine invertebrates and fishes commercially important in Mexico to fishing. Ninety-eight invertebrates, 66 elasmobranchs, and 367 bony fish were analyzed. The vulnerability among the 531 evaluated species is high for 115 (22%), moderate for 113 (21%), and low for 303 (57%). The most vulnerable species are the Mexican geoduck (Panopea globosa) and the Black Sea Cucumber (Holothuria atra) for invertebrates, the Spiny butterfly ray (Gymnura altavela) among elasmobranches, and the Black-and-yellow rockfish (Sebastes chrysomelas) for bony fishes. This study provides a first screening of the many species potentially affected by fisheries, prioritizes marine species for future research and management efforts, identifies the main data gaps, and sets the baseline for future research efforts and management. Furthermore, the results could improve market-based approaches like eco-labeling initiatives and the Responsible Seafood Consumption Guide, developed by Mexican authorities in collaboration with Comunidad and Biodiversidad (COBI, a civil society organization), to inform consumers about the origin and sustainability of fishery products.
Different Nitrogen Sources Fuel Symbiotic Mussels at Cold Seeps
Authors: Wang Fuqiang , Wu Ying , Feng Dong
Published: July 2022

Cold seeps globally host dense unique oasis-type ecosystems, mainly fuelled by chemosynthetic microorganisms via reduced gases such as methane and hydrogen sulfide. However, the origin and pathway of nitrogen chemosynthesis in this widely distributed symbiont ecosystem remain poorly understood. Here, we explore biomarker methods (bulk stable isotope, amino acid (AA), fatty acid (FA) and compound-specific isotope analyses in gill tissues of mussels) to demonstrate the relative contributions of inorganic and organic nitrogen to symbiotic mussels at cold seeps in the South China Sea and their impact on the synthesis and metabolism of amino acids. Gigantidas platifrons (G. platifrons) symbioses with type II methanotrophs via the Serine pathway, and Bathymodiolus aduloides (B. aduloides) thrives with sulfur-oxidizing bacteria via the Calvin pathway, as revealed by bulk δ13C and δ13C of FAs. Based on the δ15N values in gill tissues of mussels, organic nitrogen from sediment is estimated as the dominant nitrogen source for B. aduloides (97-98%), in contrast, NH4+ was the main nitrogen source for G. platifrons. Different dominant nitrogen sources result in the δ15N of AAs in the gills of two mussel species having opposite trends, which might be related to synthesis and metabolism of AAs in symbiotic bacteria and host, respectively. Our findings reveal that the mechanism of nitrogen acquisition in cold seep systems is plastic and related to DIN sources/uptake and changing environmental conditions. These findings uncover novel biosynthesis of nitrogen in the deep sea, typically at cold seeps, and may have important implications for nitrogen biogeochemistry and deep-sea conservation.
Factors Affecting Burrow Architecture of the Polychaete Perinereis Aibuhitensis
Authors: He Wei , Fang Jinghui , Zhang Yitao , Yan Yisu , Zhang Zhixin , Huang Junhang , Fang Jianguang , Mao Yuze , Jiang Zengjie , Wang Junwei
Published: July 2022

Bioturbation of infauna plays an important role in the biogeochemical processing of sediments. Infaunal animals build burrows and enlarge the sediment-water interface by their activities and so bioturbation is closely related with burrow structure and animal behavior in the sediment. The purpose of this study is to explore the characteristics of Perinereis aibuhitensis burrow structures with the factors of months and animal sizes (0-1g, 1-2g, 2-3g, 3-4g, and >4g), which would also provide useful knowledge of infauna behavioral ecology. The dimension and complexity of the burrows of P. aibuhitensis were measured by dissecting sediments. The results showed that there were three burrow shapes of P. aibuhitensis, i.e., I, Y and U shapes. Overall, the order of abundance of each of the three burrow shapes were I > Y > U. Larger P. aibuhitensis are inclined to build Y- and U-shaped burrows in June and August. There were significant differences in the tunnel diameter, burrow depth and burrow length separately between different polychaete size classes (P< 0.001). In February and August, the burrow depths and burrow lengths of P. aibuhitensis individuals with body weights of 1-2 g and 2-3 g were significantly greater than in other months (P< 0.001). P. aibuhitensis individuals of 1-2 g and 3-4 g body weight had significantly more burrow openings and branches in August than in February (P< 0.001). Within the same month, the burrow HEindex increased with increasing polychaete size, and when the sizes were 1-2 g, 2-3 g and 3-4 g, the complexity in August was higher than that in other months. This study suggests that I-shaped burrow dominants the burrow architecture of P. aibuhitensis. The polychaete with large size has a higher HEindex (burrow complexity) indicating a strong bioturbation ability. Y-shaped burrows are more conducive to the survival of P. aibuhitensis in hot weather. In order to adapt to environmental stresses outside, P. aibuhitensis usually builds deeper burrows.
Diversity of Deep-Sea Echinoderms From Costa Rica
Authors: Alvarado Juan José , Chacón-Monge José Leonardo , Azofeifa-Solano Juan Carlos , Cortés Jorge
Published: July 2022

Echinoderms are a highly diverse group and one of the most conspicuous in the deep sea, playing ecological key roles. We present a review about the history of expeditions and studies on deep-sea echinoderms in Costa Rica, including an updated list of species. We used literature and information gathered from the databases of the California Academy of Sciences, the Benthic Invertebrate Collection of the Scripps Institution of Oceanography, the National Museum of Natural History, the Museum of Comparative Zoology and the Museo de Zoología from the Universidad de Costa Rica. A total of 124 taxa (75 confirmed species) have been collected from the Costa Rican deep sea, 112 found in the Pacific Ocean, 13 in the Caribbean Sea, and one species shared between the two basins. We report 22 new records for the Eastern Tropical Pacific, 46 for Central American waters, and 58 for Costa Rica. The most specious group was Ophiuroidea with 37 taxa, followed by Holothuroidea (34 taxa), Asteroidea (23 taxa), Echinoidea (17 taxa), and Crinoidea (11 taxa). The highest number of species (64) was found between 800 m and 1200 m depth. Only two species were found deeper than 3200 m. Further efforts on identification will be required for a better comprehension of the diversity of deep-sea echinoderms. Limited research has been done regarding the biology and ecology of deep-sea echinoderms in Costa Rica, so additional approaches will be necessary to understand their ecological functions.
Assisted Natural Recovery: A Novel Approach to Enhance Diadema antillarum Recruitment
Authors: Hylkema Alwin , Debrot Adolphe O. , van de Pas Esther E. , Osinga Ronald , Murk Albertinka J.
Published: July 2022

The massive die-off of the sea urchin Diadema antillarum in 1983–1984 is one the main reasons for low coral recruitment and little coral recovery in the Caribbean. As the natural recovery of D. antillarum is slow to non-existent, multiple restoration studies have been attempted. There are currently three different approaches to obtain individuals for restocking: the translocation of wild-collected juveniles or adults, lab-reared juveniles cultured from wild-collected settlers, or lab-reared juveniles cultured from gametes. All three methods are costly and can only be applied on a relatively small scale. We here propose a fourth, new, approach, which we term assisted natural recovery (ANR) of D. antillarum populations. ANR, a concept already applied in terrestrial restoration to restore forests and grasslands, can accelerate succession by removing barriers to natural recovery. In this study, performed on the Dutch Caribbean island of Saba, suitable settlement substrate was provided in the form of bio ball streamers that were attached to the reef shortly before the settlement season. At the end of the experiment, reefs with streamers had significantly higher D. antillarum recruit densities than control reefs without additional settlement substrate, indicating that the lack of settlement substrate is an important factor constraining natural recovery. However, D. antillarum recruit abundance was low compared to the measured settlement rates, possibly due to low post-settlement survival. The size distribution of recruits showed that recruits almost never became larger than 20 mm, which is likely due to predation. We conclude that, next to low settlement availability, low post-settlement survival and high predation on recruits also constrain the natural recovery of D. antillarum populations on Saba. To improve the survival of settlers till adults, we propose to 1) reduce predation on settlers by using bio balls or other substrates that can provide shelter to larger individuals and 2) optimize the reef habitat by removing macroalgae, either manually or by facilitating other herbivores. To improve the survival of recruits, we suggest to 1) choose sites with a known lower predation density or 2) protect recruits with a corral around the reef underneath the streamers. The combination of these measures could improve prospects for ANR, and we expect this new approach can contribute to the recovery of D. antillarum populations in the future.
Metabolic Engineering to Improve Docosahexaenoic Acid Production in Marine Protist Aurantiochytrium sp. by Disrupting 2,4-Dienoyl-CoA Reductase
Authors: Liang Shitong , Yang Xuewei , Zhu Xingyu , Ibrar Muhammad , Liu Liangxu , Li Siting , Li Xia , Tian Tian , Li Shuangfei
Published: July 2022

Docosahexaenoic acid (DHA) has attracted attention from researchers because of its pharmacological and nutritional importance. Currently, DHA production costs are high due to fermentation inefficiency; however, improving DHA yield by metabolic engineering in thraustochytrids is one approach to reduce these costs. In this study, a high-yielding (53.97% of total fatty acids) DHA production strain was constructed by disrupting polyunsaturated fatty acid beta-oxidation via knockout of the 2,4-dienyl-CoA reductase (DECR) gene (KO strain) in Aurantiochytrium sp. Slight differences in cell growth was observed in the wild-type and transformants (OE and KO), with cell concentrations in stationary of 2.65×106, 2.36×106 and 2.56×106 cells mL-1 respectively. Impressively, the KO strain yielded 21.62% more neutral lipids and 57.34% greater DHA production; moreover, the opposite was observed when overexpressing DECR (OE strain), with significant decreases of 30.49% and 64.61%, respectively. Furthermore, the KO strain showed a prolonged DHA production period with a sustainable increase from 63 to 90 h (170.03 to 203.27 mg g−1 DCW), while that of the wildtype strain decreased significantly from 150.58 to 140.10 mg g−1 DCW. This new approach provides an advanced proxy for the construction of sustainable DHA production strains for industrial purposes and deepens our understanding of the metabolic pathways of Aurantiochytrium sp.
Rap2a Is Negatively Regulated by NF-κB and Contributes to Growth via Wnt Pathway in Shrimp
Authors: Wang Sheng , He Mingyu , Li Qinyao , Li Haoyang , Yin Bin , He Jianguo , Li Chaozheng
Published: July 2022

Rap2a, a member of Ras family small GTPases, plays a key role in growth and development. So far, no Rap2a homolog has been discovered in crustaceans. Herein, a Rap2a homolog from shrimp Litopenaeus vannamei, named LvRap2a, was cloned and identified. LvRap2a showed a high level of sequence conservation to other Rap2a homologs from different species. LvRap2a was found to be abundantly expressed in hemocytes, muscle, hepatopancreas and intestine tissues. Importantly, Rap2a knockdown effectively suppressed the length and weight of shrimp in a growth experiment. Mechanistically, we found that Rap2a could induce the expression of several Wnts, which are the positive regulators in cellular growth, differentiation, and tissue homeostasis. Moreover, LvRap2a expression was observed to be negatively regulated by LvDorsal (NF-κB), a transcription factor of innate immune signaling pathway. These results indicated that LvRap2a contributed to shrimp growth probably by activating the Wnt signaling pathway, and that LvRap2a could be the crosstalk between innate immunity and growth, as well as that LvRap2a could serve as a potential target for shrimp growth promotion.
Temperature-Dependent Properties of Graphene on SiC Substrates for Triboelectric Nanogenerators
Authors: Wang Sen , Wan Lingyu , Li Ding , Chen Xiufang , Xu Xiangang , Feng Zhe Chuan , Ferguson Ian T.
Published: July 2022

Graphene has excellent properties such as ultra-high electrical conductivity, high carrier mobility, and thermal conductivity, with a promising application in the field of triboelectric nanogenerators (TENGs). We present a systemic investigation to explore structural, optical, and temperature-dependent properties of single- and bi-layer graphene on SiC substrates, prepared by the decomposition of SiC and transferred substrate methods and their applications in TENGs. Compared to the transferred graphene onto a SiC substrate, graphene grown by the decomposition of SiC has a better crystalline quality and surface morphology, fewer impurities, and a more stress effect between graphene and the substrate. It also exhibited a longer correlation length of Raman phonons, implying better crystalline perfection. With the increase in temperature, the phonon correlation length, L, increases synchronously with TENG outputs. Among them, the TENG with a bi-layer graphene grown by the decomposition of SiC showed the best performance, especially at high temperatures. These studies provide an essential reference for further applications of graphene on SiC substrates in TENG-based devices.
Research Progress on the Corrosive Environment Large-Scale Evolution for Nuclear Waste Container
Authors: Zhang Qichao , Jiang Yishan , Zhao Xin , Chen Juna , Xia Dahai , Zhang Binbin , Duan Jizhou
Published: July 2022

After a nuclear waste container buried 500–1,000 m underground, it gradually experiences the dual effects of groundwater infiltration and the decay heat of radioactive nuclear waste. The decay and heat release of nuclear waste will also result in temperature stress. At the same time, the groundwater will gradually saturate the buffer/backfill materials which will produce expansion stress, thus forming a typical thermal–water–stress multi-coupling environment in the geological disposal, forming the environment where the corrosion could happen. In comparison, the information obtained through laboratories, field tests, and natural simulations are limited. However, numerical simulation is very important to predict the changes of a near-field environment. On one hand, the numerical simulation can verify the corresponding experimental data in the early stages; on the other hand, it can also predict the long-term corrosion environment change. This article mainly summarizes the large-scale evolution of a typical corrosion environment obtained by numerical simulation under different deep geological conditions in various countries, focusing on the effects of temperature, saturation, oxygen content, and radiation, which provide a reference for the research on the evolution of important corrosion environments on the surface of a nuclear waste container.
Combustion and Thermal Properties of Flame Retardant Polyurethane Foam With Ammonium Polyphosphate Synergized by Phosphomolybdic Acid
Authors: Xu Zhirong , Xu Zihui , Tao Ran , Mao Liangchen , Zhan Jing , Xiao Junfeng , Yu Tao
Published: July 2022

Phosphomolybdic acid (PMA) as a synergist was added into polyurethane (PU) rigid foam with ammonium polyphosphate (APP) to improve its flame retardancy and thermal stability. The combustion performance of PU was studied by limiting oxygen index (LOI), UL-94, and a cone calorimeter. The thermal degradation behavior of PU was determined by thermogravimetric analysis (TG) and thermogravimetric infrared spectroscopy (TG-IR). Experimental results showed that the introduction of PMA could further improve the flame retardant performance of PU/APP composites and significantly increase the amount of carbon residue at high temperatures. Adding 3wt% PMA to PU containing 12wt% APP could make the foam pass UL-94 V-0, increase the carbon residue at 800°C by 69.16% in the air atmosphere, and decrease the THR by 24.62% compared to those of PU/15APP. TG-IR results showed that the presence of PMA reduced the production of small-molecule gas-phase products. As for the mechanical properties of PU composites, the addition of PMA influences their density and compressive strength obviously. The results suggest that PMA and APP have good synergistic flame retardancy on PU and can reduce its fire risk.
Feature Genes in Neuroblastoma Distinguishing High-Risk and Non-high-Risk Neuroblastoma Patients: Development and Validation Combining Random Forest With Artificial Neural Network
Authors: Yang Sha , Zeng Lingfeng , Jin Xin , Lin Huapeng , Song Jianning
Published: July 2022

There is a significant difference in prognosis among different risk groups. Therefore, it is of great significance to correctly identify the risk grouping of children. Using the genomic data of neuroblastoma samples in public databases, we used GSE49710 as the training set data to calculate the feature genes of the high-risk group and non-high-risk group samples based on the random forest (RF) algorithm and artificial neural network (ANN) algorithm. The screening results of RF showed that EPS8L1, PLCD4, CHD5, NTRK1, and SLC22A4 were the feature differentially expressed genes (DEGs) of high-risk neuroblastoma. The prediction model based on gene expression data in this study showed high overall accuracy and precision in both the training set and the test set (AUC = 0.998 in GSE49710 and AUC = 0.858 in GSE73517). Kaplan–Meier plotter showed that the overall survival and progression-free survival of patients in the low-risk subgroup were significantly better than those in the high-risk subgroup [HR: 3.86 (95% CI: 2.44–6.10) and HR: 3.03 (95% CI: 2.03–4.52), respectively]. Our ANN-based model has better classification performance than the SVM-based model and XGboost-based model. Nevertheless, more convincing data sets and machine learning algorithms will be needed to build diagnostic models for individual organization types in the future.
Pelvic Lymph Node Lymphangiomyomatosis Found During Surgery for Gynecological Fallopian Tube Cancer: A Case Report and Literature Review
Authors: Xiao Shan , Chen Yijia , Tang Qianjue , Xu Lianwei , Zhao Li , Wang Zhenzhen , Yu Erkai
Published: July 2022

Background

Lymphangioleiomyomatosis (LAM) is a rare low-grade metastatic tumor with an unknown origin that spreads through lymphatic vessels. It is characterized by the proliferation of smooth muscle-like or epithelioid tumor cells in the lung and axial lymphatic system. Extrapulmonary LAM is a localized disease with a low incidence rate, and the location of the related lesions is atypical. It is difficult to diagnose. The LAM of pelvic lymph nodes is hidden. It is usually found through gynecological oncology surgery.

Case presentation

We report a 57-year-old postmenopausal woman with a pelvic mass and vaginal bleeding as the main symptoms. The patient had no history of pulmonary LAM, tuberous sclerosis complex (TSC), or renal angiomyolipoma and had not used exogenous hormones. We performed a total hysterectomy, bilateral adnexectomy, greater omentum resection, and pelvic lymphadenectomy under laparoscopy. The postoperative pathology confirmed high-grade serous carcinoma of the left fallopian tube, and four lymph nodes were found in the pelvic lymph nodes, suggesting lymphangiomyomatosis. Immunohistochemical results also showed that these cells could express markers of smooth muscle cells and melanoma cells. The patient was treated with chemotherapy after the operation. Chest CT did not suggest lung LAM during the postoperative follow-up, and there was no tumor recurrence.

Conclusion

The diagnosis of this disease is challenging. At the same time, due to insufficient clinical samples, it is still unknown whether there is a potential relationship between pelvic and peritoneal lymph node LAM found in the surgical staging of gynecological tumors and lung LAM and/or TSC. There is no evidence that pelvic and peritoneal lymph node LAM will increase the risk of pulmonary LAM. Therefore, additional clinical data are required to analyze and summarize the relationship between pelvic and peritoneal lymph node LAM, pulmonary LAM, and the source of LAM. We present a case of pelvic lymph node LAM and propose a hypothesis that the pathogenesis of endometriosis can be used for reference in the study of this disease.
Marine Sponges in a Snowstorm – Extreme Sensitivity of a Sponge Holobiont to Marine Oil Snow and Chemically Dispersed Oil Pollution
Authors: Vad Johanne , Duran Suja Laura , Summers Stephen , Henry Theodore B. , Roberts J. Murray
Published: July 2022

Holobionts formed by a host organism and associated symbionts are key biological units in marine ecosystems where they are responsible for fundamental ecosystem services. Therefore, understanding anthropogenic impacts on holobionts is essential. Sponges (Phylum Porifera) are ideal holobiont models. They host a complex microbial community and provide ecosystem services including nutrient cycling. At bathyal depths, sponges can accumulate forming dense sponge ground habitats supporting biodiverse associated communities. However, the impacts of spilled oil and dispersants on sponge grounds cannot be understood without considering exposures mediated through sponge filtration of marine snow particles. To examine this, we exposed the model sponge Halichondria panicea to oil, dispersant and “marine oil snow” contaminated seawater and elucidate the complex molecular response of the holobiont through metatranscriptomics. While the host response included detoxification and immune response pathways, the bacterial symbiotic response differed and was at least partially the result of a change in the host environment rather than a direct response to hydrocarbon exposure. As the sponge host reduced its pumping activity and internal tissue oxygen levels declined, the symbionts changed their metabolism from aerobic to anaerobic pathways possibly via quorum sensing. Furthermore, we found evidence of hydrocarbon degradation by sponge symbionts, but sponge mortality (even when exposed to low concentrations of hydrocarbons) implied this may not provide the holobiont with sufficient resilience against contaminants. Given the continued proposed expansion of hydrocarbon production into deep continental shelf and slope settings where sponge grounds form significant habitats it is important that dispersant use is minimised and that environmental impact assessments carefully consider the vulnerability of sponge holobionts.
Comparative Transcriptomics and Gene Knockout Reveal Virulence Factors of Neofusicoccum parvum in Walnut
Authors: Chen Jie , Han Shan , Li Shujiang , Wang Ming , Zhu Hanmingyue , Qiao Tianmin , Lin Tiantian , Zhu Tianhui
Published: July 2022

Neofusicoccum parvum can cause stem and branch blight of walnut (Juglans spp.), resulting in great economic losses and ecological damage. A total of two strains of N. parvum were subjected to RNA-sequencing after being fed on different substrates, sterile water (K1/K2), and walnut (T1/T2), and the function of ABC1 was verified by gene knockout. There were 1,834, 338, and 878 differentially expressed genes (DEGs) between the K1 vs. K2, T1 vs. K1, and T2 vs. K2 comparison groups, respectively. The expression changes in thirty DEGs were verified by fluorescent quantitative PCR. These thirty DEGs showed the same expression patterns under both RNA-seq and PCR. In addition, ΔNpABC1 showed weaker virulence due to gene knockout, and the complementary strain NpABC1c showed the same virulence as the wild-type strain. Compared to the wild-type and complemented strains, the relative growth of ΔNpABC1 was significantly decreased when grown with H2O2, NaCl, Congo red, chloramphenicol, MnSO4, and CuSO4. The disease index of walnuts infected by the mutants was significantly lower than those infected by the wild-type and complementary strains. This result indicates that ABC1 gene is required for the stress response and virulence of N. parvum and may be involved in heavy metal resistance.
The Effectiveness of Wogonin on Treating Cough Mice With Mycoplasma Pneumoniae Infection
Authors: Liang Mingchuan , Meng Yanli , Wang Xiaoxi , Wang Lei , Tang Guixin , Wang Weiming
Published: July 2022

Background: Cough is the main symptom of mycoplasma pneumoniae (MP) infection. Cough potential protein transient receptor potential A1 (TRPA1) plays an important role in cough reflex. The purpose of this study was to clarify the mechanism of wogonin, the effective component of Qinbai Qingfei concentrated pellet (Qinbai), in the treatment of cough after MP infection.

Methods: The Biacore™ system was used to detect whether there was specific binding between Qinbai and cough potential protein TRPA1. Biacore™ fishing technology and UPLC-Q-TOF-MS technology were used during fishing combined active components and identification and analysis of recovered samples. The expression levels of TRPA1, substance P (SP), calcitonin gene-related peptide (CGRP), cough-related proteins, and mRNA in the lung tissues from each group were detected by immunohistochemistry, Western blot, and real-time PCR.

Results: Biacore™ results showed that Qinbai had strong specific binding to TRPA1 protein with a binding value of 99.0 resonance unit (RU). The samples obtained from angling were identified and analyzed by UPLC-Q-TOF-MS as wogonin. The results of immunohistochemistry, Western blot, and real-time PCR showed that compared with the model group, the wogonin group had lower expressions of mRNA, TRPA1, SP, and CGRP in the lung tissue of cough mice with MP infection (p < 0.01 or p < 0.05), and the effects were superior to those of azithromycin and pentoxyverine control groups.

Conclusion: Wogonin can treat cough after MP infection by affecting the expressions of cough-related proteins, such as TRPA1, SP, and CGRP. This study provided a theoretical foundation for the clinical research of Qinbai.
Regulation of Bacterial Manganese Homeostasis and Usage During Stress Responses and Pathogenesis
Authors: Martin Julia E. , Waters Lauren S.
Published: July 2022

Manganese (Mn) plays a multifaceted role in the survival of pathogenic and symbiotic bacteria in eukaryotic hosts, and it is also important for free-living bacteria to grow in stressful environments. Previous research has uncovered components of the bacterial Mn homeostasis systems that control intracellular Mn levels, many of which are important for virulence. Multiple studies have also identified proteins that use Mn once it is inside the cell, including Mn-specific enzymes and enzymes transiently loaded with Mn for protection during oxidative stress. Emerging evidence continues to reveal proteins involved in maintaining Mn homeostasis, as well as enzymes that can bind Mn. For some of these enzymes, Mn serves as an essential cofactor. For other enzymes, mismetallation with Mn can lead to inactivation or poor activity. Some enzymes may even potentially be regulated by differential metallation with Mn or zinc (Zn). This review focuses on new developments in regulatory mechanisms that affect Mn homeostasis and usage, additional players in Mn import that increase bacterial survival during pathogenesis, and the interplay between Mn and other metals during Mn-responsive physiological processes. Lastly, we highlight lessons learned from fundamental research that are now being applied to bacterial interactions within larger microbial communities or eukaryotic hosts.
STeP-CiM: Strain-Enabled Ternary Precision Computation-In-Memory Based on Non-Volatile 2D Piezoelectric Transistors
Authors: Thakuria Niharika , Elangovan Reena , Thirumala Sandeep K. , Raghunathan Anand , Gupta Sumeet K.
Published: July 2022

We proposed 2D piezoelectric FET (PeFET)–based compute-enabled non-volatile memory for ternary deep neural networks (DNNs). PeFETs hinge on ferroelectricity for bit storage and piezoelectricity for bit sensing, exhibiting inherently amenable features for computation-in-memory of dot products of weights and inputs in the signed ternary regime. PeFETs consist of a material with ferroelectric and piezoelectric properties coupled with a transition metal dichalcogenide channel. We utilized (a) ferroelectricity to store binary bits (0/1) in the form of polarization (−P/+P) and (b) polarization-dependent piezoelectricity to read the stored state by means of strain-induced bandgap change in the transition metal dichalcogenide channel. The unique read mechanism of PeFETs enables us to expand the traditional association of +P (−P) with low (high) resistance states to their dual high (low) resistance depending on read voltage. Specifically, we demonstrated that +P (−P) stored in PeFETs can be dynamically configured in (a) a low (high) resistance state for positive read voltages and (b) their dual high (low) resistance states for negative read voltages, without afflicting a read disturb. Such a feature, which we named as polarization-preserved piezoelectric effect reversal with dual voltage polarity (PiER), is unique to PeFETs and has not been shown in hitherto explored memories. We leveraged PiER to propose a Strain-enabled Ternary Precision Computation-in-Memory (STeP-CiM) cell with capabilities of computing the scalar product of the stored weight and input, both of which are represented with signed ternary precision. Furthermore, using multi-word line assertion of STeP-CiM cells, we achieved massively parallel computation of dot products of signed ternary inputs and weights. Our array-level analysis showed 91% lower delay and improvements of 15% and 91% in energy for in-memory multiply-and-accumulate operations compared to near-memory design approaches based on 2D FET–based SRAM and PeFET, respectively. We also analyzed the system-level implications of STeP-CiM by deploying it in a ternary DNN accelerator. STeP-CiM exhibits 6.11× to 8.91× average improvement in performance and 3.2× average improvement in energy over SRAM-based near-memory design. We also compared STeP-CiM to near-memory design based on PeFETs showing 5.67× to 6.13× average performance improvement and 6.07× average energy savings.
Nano-Neurogenesis for CNS Diseases and Disorders
Authors: Tiwari Sneham , Kaushik Ajeet
Published: July 2022

Neurogenesis encompasses the formation and development of neurons in the mammalian brain, mainly occurring in hippocampus and the olfactory system. This process is rapid, accurate, and very sensitive to the external stressors including environment, diet, age, anxiety, stress, depression, diet, and hormones. The range of stressors is big and directly impacts the generation, maturation and migration, efficacy, and myelination of the neuronal cells. The field of regenerative medicine focuses on combating the direct or indirect effects of these stressors on the process of neurogenesis, and ensures increased general and neuronal communications and functioning. Understanding the deep secrets of brain signaling and devising ways to increase drug availability is tough, considering the complexity and intricate details of the neuronal networks and signaling in the CNS. It is imperative to understand this complexity and introduce potent and efficacious ways to combat diseases. This perspective offers an insight into how neurogenesis could be aided by nanotechnology and what plausible nanomaterials are available to culminate neurogenesis-related neurological disorders. The nanomaterials are promising as they are minute, robust, and effective and help in diagnostics and therapeutics such as drug delivery, maturation and neuroprotection, neurogenesis, imaging, and neurosurgery.
Microglial Engulfment of Spines in the Ventral Zona Incerta Regulates Anxiety-Like Behaviors in a Mouse Model of Acute Pain
Authors: Farzinpour Zahra , Liu An , Cao Peng , Mao Yu , Zhang Zhi , Jin Yan
Published: July 2022

Although activation of microglial cells is critical in developing brain disorders, their role in anxiety-like behaviors in pain is still vague. This study indicates that alteration of microglia’s neuronal spine engulfment capacity in ventral zona incerta (ZIV) leads to significant pain and anxiety-like behaviors in mice 1-day post-injection of Complete Freud’s Adjuvant (CFA1D). Performing whole-cell patch-clamp recordings in GABAergic neurons in the ZIV (ZIVGABA) in brain slices, we observed decreased activity in ZIvGABA and reduced frequency of the miniature excitatory postsynaptic currents (mEPSCs) in ZIVGABA of CFA1D mice compared with the saline1D mice. Besides, chemogenetic activation of ZIVGABA significantly relieved pain and anxiety-like behaviors in CFA1D mice. Conversely, in naïve mice, chemogenetic inhibition of ZIVGABA induced pain and anxiety-like behaviors. Interestingly, we found changes in the density and morphology of ZIVMicroglia and increased microglial engulfment of spines in ZIV of CFA1D mice. Furthermore, pain sensitization and anxiety-like behaviors were reversed when the ZIVMicroglia of CFA1D-treated mice were chemically inhibited by intra-ZIV minocycline injection, accompanied by the recovery of decreased ZIVGABA excitability. Conclusively, our results provide novel insights that dysregulation of microglial engulfment capacity encodes maladaptation of ZIVGABA, thus promoting the development of anxiety-like behaviors in acute pain.
Neck Pain: Do We Know Enough About the Sensorimotor Control System?
Authors: Qu Ning , Tian HaoChun , De Martino Enrico , Zhang Bin
Published: July 2022

Neck pain is a worldwide health problem. Clarifying the etiology and providing effective interventions are challenging for the multifactorial nature of neck pain. As an essential component of cervical spine function, the sensorimotor control system has been extensively studied in both healthy and pathological conditions. Proprioceptive signals generated from cervical structures are crucial to normal cervical functions, and abnormal proprioception caused by neck pain leads to alterations in neural plasticity, cervical muscle recruitment and cervical kinematics. The long-term sensorimotor disturbance and maladaptive neural plasticity are supposed to contribute to the recurrence and chronicity of neck pain. Therefore, multiple clinical evaluations and treatments aiming at restoring the sensorimotor control system and neural plasticity have been proposed. This paper provides a short review on neck pain from perspectives of proprioception, sensorimotor control system, neural plasticity and potential interventions. Future research may need to clarify the molecular mechanism underlying proprioception and pain. The existing assessment methods of cervical proprioceptive impairment and corresponding treatments may need to be systematically reevaluated and standardized. Additionally, new precise motor parameters reflecting sensorimotor deficit and more effective interventions targeting the sensorimotor control system or neural plasticity are encouraged to be proposed.