bluuebunny/crossref_metadata_2025 huggingface dataset:
Mapping the Hot Spots and Evolution Main Path of Whole-Body Vibration Training Since the 21st Century: A Bibliometric Analysis
Authors: Dong Dan , Sun Mingli , Xu Dan , Han Shuang , Cui Liyuan , Cao Shu , Yang Ying , Xu Shuang
Published: July 2022

To evaluate the global scientific output of the research on whole-body vibration training (WBVT) and explore the current status and trends in this field over the past decades using bibliometric methods, we retrieved the literature related to WBVT from 2000 to the present in the Web of Science Core Collection (WoSCC). We analyzed annual publications, citations, countries, organizations, productive authors, and source 14 journals by the Web of Science online bibliometric analysis. We visualized the WBVT research trends and explored influential organizations and authors through VOSviewer. Then, we constructed a citation chronology map by HistCite to obtain the knowledge base of this field and made a primary citation path analysis by Pajek. Finally, we mined the hot spots of WBVT by BICOMB and gCLUTO. Overall, there were 1,629 publications included in this study between 2000 and 2022. The United States contributed the most publications in this field, and the country with the most active partnership was Spain. The University of Cologne ranked highest among top productive organizations. Bernardo-Filho, Mario, from Universidade do Estado do Rio de Janeiro, ranked first among the top productive authors. The Journal of Strength and Conditioning Research topped the list of journals with the most publications on WBVT by a wide margin. The WBVT research field started from Rittweger’s study on the acute physiological effects of WBVT in 2000, which was divided into two stages. The first stage focused on improving athletic ability, and the second stage gradually turned to the application in medicine. A keyword analysis showed the exercise rehabilitation of several aging chronic diseases was the research trend and hot spot of WBVT. The current study provided a time-based development and a global network hub for WBVT research, contributing to identifying core target diseases of WBVT and providing various insights for researchers in the future.
A Shuffled Replay of Events on Uniswap
Authors: Palit Imon
Published: July 2022

In this paper we introduce a new zero-intelligence framework to analyse price formation in a cryptocurrency decentralised exchange (DEX) combining agent-based modelling and real trading history. We shuffle real Uniswap order event data and replay back into the automatic market maker (AMM) matching mechanism. We study how decomposing real markets down from bounded rationality to zero-intelligence markets in a controlled experiment affects liquidity provider’s impermanent loss, trade slippage and price efficiency.
ADAR1-Mediated RNA Editing and Its Role in Cancer
Authors: Liu Jizhe , Wang Fei , Zhang Yindan , Liu Jingfeng , Zhao Bixing
Published: July 2022

It is well known that the stability of RNA, the interaction between RNA and protein, and the correct translation of protein are significant forces that drive the transition from normal cell to malignant tumor. Adenosine deaminase acting on RNA 1 (ADAR1) is an RNA editing enzyme that catalyzes the deamination of adenosine to inosine (A-to-I), which is one dynamic modification that in a combinatorial manner can give rise to a very diverse transcriptome. ADAR1-mediated RNA editing is essential for survival in mammals and its dysregulation results in aberrant editing of its substrates that may affect the phenotypic changes in cancer. This overediting phenomenon occurs in many cancers, such as liver, lung, breast, and esophageal cancers, and promotes tumor progression in most cases. In addition to its editing role, ADAR1 can also play an editing-independent role, although current research on this mechanism is relatively shallowly explored in tumors. In this review, we summarize the nature of ADAR1, mechanisms of ADAR1 editing-dependent and editing-independent and implications for tumorigenesis and prognosis, and pay special attention to effects of ADAR1 on cancers by regulating non-coding RNA formation and function.
Differential Gut Microbiota Compositions Related With the Severity of Major Depressive Disorder
Authors: Zhong Qi , Chen Jian-jun , Wang Ying , Shao Wei-hua , Zhou Chan-juan , Xie Peng
Published: July 2022

Objective

Increasing evidence shows a close relationship between gut microbiota and major depressive disorder (MDD), but the specific mechanisms remain unknown. This study was conducted to explore differential gut microbiota compositions related to the severity of MDD.

Methods

Healthy controls (HC) (n = 131) and MDD patients (n = 130) were included. MDD patients with Hamilton Depression Rating Scale (HDRS) score <25 and ≥25 were assigned into moderate (n = 72) and severe (n = 58) MDD groups, respectively. Univariate and multivariate analyses were used to analyze the gut microbiota compositions at the genus level.

Results

Thirty-six and 27 differential genera were identified in moderate and severe MDD patients, respectively. The differential genera in moderate and severe MDD patients mainly belonged to three (Firmicutes, Actinobacteriota, and Bacteroidota) and two phyla (Firmicutes and Bacteroidota), respectively. One specific covarying network from phylum Actinobacteriota was identified in moderate MDD patients. In addition, five genera (Collinsella, Eggerthella, Alistipes, Faecalibacterium, and Flavonifractor) from the shared differential genera by two MDD groups had a fair efficacy in diagnosing MDD from HC (AUC = 0.786).

Conclusions

Our results were helpful for further exploring the role of gut microbiota in the pathogenesis of depression and developing objective diagnostic methods for MDD.
Combined Transcriptomics and Metabolomics Analyses in Grass Carp Under Anesthetic Stress
Authors: Wang Tianwei , Wang Yali , Liu Xueting , Gao Xiaoning , Hu Kun
Published: July 2022

Ctenopharyngodon Idella, as a common freshwater bony fish, is more susceptible to various diseases than other carp species, so it has been proposed as a test organism for toxicological analysis In this study, C. idella were anesthetized with MS-222 and 2-PE, and the related anesthetic mechanism and toxic effects were revealed by transcriptomics and metabolomics analyses. When the concentration of MS-222 was 80 mg/L and 200 mg/L, 179 and 887 differentially expressed genes (DEGs), respectively, were identified in the brain tissue of C. idella. When the concentration of 2-PE was 0.6 mL/L and 1.2 mL/L, 498 and 514 DEGs were identified. The DEGs associated with MS-222 treatment were enriched in immune pathways, lipid metabolism, amino acid metabolism, and various signaling pathways; DEGs associated with 2-PE treatment were enriched in immunity and amino acid metabolism. In total, 304 metabolites were identified using a combination of positive and negative ion modes in mass spectrometry. The common differential metabolites identified in the MS-222 high and low concentration groups were 20-HETE and 12(R)-HETE; the common significant differential metabolite identified in the 2-PE high and low concentration groups was salidroside. In combination with the transcriptomics analysis and metabolomics analysis, the results showed that with the MS-222 and 2-PE concentrations used in this experiment, the metabolism of arachidonic acid in C. idella was inhibited by MS-222, and 2-PE affected the upstream and downstream metabolic pathways of arachidonic acid metabolism, thereby affecting the metabolism of arachidonic acid. Both anesthetics induce sedation by affecting related metabolites that affect stress response and autoimmunity. Metabolomics results showed that neither anesthetic had a significant effect on cortisol expression.
Phenotypicand Genotypic Characterization of Clinical Isolates of Intracellular Adherent–Invasive Escherichia coli Among Different Stages, Family History, and Treated Colorectal Cancer Patients in Iran
Authors: Kamali Dolatabadi Razie , Fazeli Hossein , Emami Mohammad Hassan , Karbasizade Vajihe , Maghool Fatemeh , Fahim Alireza , Rahimi Hojatollah
Published: July 2022

There is increasing evidence showing that microbial dysbiosis impacts the health and cancer risk of the host. An association between adherent–invasive Escherichia coli (AIEC) and colorectal cancer (CRC) has been revealed. Cyclomodulins (CMs) have been receiving increasing attention for carcinogenic changes. In this study, the incidence and features of intracellular AIEC and cyclomodulin-encoding genes were investigated and the phylogenetic grouping and genetic relatedness were evaluated. E. coli strains were isolated from the colorectal biopsies. Adhesion and invasion assays and intramacrophage cell survival test were performed to separate the AIEC isolates. Virulence genotyping for the genes htrA, dsbA, chuA, and lpfA and the cyclomodulin toxins was also conducted. In addition, phylogenetic grouping of the isolates was determined. Subsequently, repetitive element sequence-based PCR (rep-PCR) fingerprinting was performed. A total of 24 AIEC pathovars were isolated from 150 patients. The prevalence rates of htr, dsbA, and lpfA were 70.83% and that of chuA was 91.66%. The frequencies of the cyclomodulin toxins were as follows: cnf1, 29.2%; cnf2, 25%; colibactin, 29.2%; and cdt, 4.2%; cif was not found. Among the AIEC isolates, 4.2%, 4.2%, 54.2%, 29.2%, and 8.3% with phylotypes A or C, B1, B2, D, and E were identified, respectively. Left-sided colon carcinoma and adenocarcinoma T≥1 stage (CRC2) were colonized by B2 phylogroup AIEC-producing CMs more often than the samples from the other groups. Close genetic relatedness was observed in AIEC isolates with rep-PCR.
Future Trends for a First Course in Control Engineering
Authors: Rossiter John Anthony
Published: July 2022

This review summarises recent thinking in the academic control community on the future of control as a topic and thus on the design and focus of control courses at university. It is notable that the current thinking is quite controversial and significantly at odds with traditional practice, and thus implementing such changes will require substantial effort and will from the community.
Short-Chain Fatty Acids in the Metabolism of Heart Failure – Rethinking the Fat Stigma
Authors: Palm Constantin L. , Nijholt Kirsten T. , Bakker Barbara M. , Westenbrink B. Daan
Published: July 2022

Heart failure (HF) remains a disease with immense global health burden. During the development of HF, the myocardium and therefore cardiac metabolism undergoes specific changes, with decreased long-chain fatty acid oxidation and increased anaerobic glycolysis, diminishing the overall energy yield. Based on the dogma that the failing heart is oxygen-deprived and on the fact that carbohydrates are more oxygen-efficient than FA, metabolic HF drugs have so far aimed to stimulate glucose oxidation or inhibit FA oxidation. Unfortunately, these treatments have failed to provide meaningful clinical benefits. We believe it is time to rethink the concept that fat is harmful to the failing heart. In this review we discuss accumulating evidence that short-chain fatty acids (SCFAs) may be an effective fuel for the failing heart. In contrast to long-chain fatty acids, SCFAs are readily taken up and oxidized by the heart and could serve as a nutraceutical treatment strategy. In addition, we discuss how SCFAs activate pathways that increase long chain fatty acid oxidation, which could help increase the overall energy availability. Another potential beneficial effect we discuss lies within the anti-inflammatory effect of SCFAs, which has shown to inhibit cardiac fibrosis – a key pathological process in the development of HF.
Clinical and Echocardiographic Outcomes of Transcatheter Tricuspid Valve Interventions: A Systematic Review and Meta-Analysis
Authors: Sannino Anna , Ilardi Federica , Hahn Rebecca T. , Lancellotti Patrizio , Lurz Philipp , Smith Robert L. , Esposito Giovanni , Grayburn Paul A.
Published: July 2022

Background

Medically managed tricuspid regurgitation (TR) has detrimental outcomes. Transcatheter tricuspid valve interventions (TTVIs) represent an alternative to surgery in high-risk patients; however, only early experiences exist.

Aim

The aim of this study was to analyze the clinical and echocardiographic outcomes of TTVI.

Methods

MEDLINE, ISI Web of Science, and SCOPUS databases were searched for studies published up to June 2021. Studies reporting data on outcome post-TTVIs were included. This study was designed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) requirements. The primary endpoint was all-cause mortality at 30-day and 1-year post-TTVI.

Results

Out of 2,718 studies, 27 were included. Notably, 30-day and 1-year all-cause mortalities were 5% (95% confidence interval [CI]: 4–8%, p < 0.001) and 25% (95% CI: 12–45%, p = 0.016). Procedural success was associated with a 58% risk reduction in 1-year mortality vs. lack thereof (odds ratio 0.42, 95% CI: 0.27–0.66, p < 0.001). TTVI is associated with a significant reduction in TR severity (TR EROA, mean difference [MD] 0.31 cm2; 95% CI: 0.23–0.39 cm2, p < 0.001; regurgitant volume, MD 23.54 ml; 95% CI: 17.4–29.68 ml, p = 0.03) and increase in forward stroke volume (FSV, MD 3.98 ml; 95% CI: 0.11–7.86 ml, p = 0.04).

Conclusion

TTVI significantly reduces TR severity and increases FSV and is associated with improved survival at 1 year compared with patients without procedural success. Long-term outcomes compared with medical therapy await the results of ongoing pivotal trials; nonetheless, TTVIs appear to be a promising alternative to surgery for TR.
Aerobic Exercise Training Improves Renal Injury in Spontaneously Hypertensive Rats by Increasing Renalase Expression in Medulla
Authors: Luo Minghao , Cao Shuyuan , Lv Dingyi , He Longlin , He Zhou , Li Lingang , Li Yongjian , Luo Suxin , Chang Qing
Published: July 2022

We aimed to examine the effects of aerobic exercise training on renal function in spontaneously hypertensive rats (SHR) and elucidate their possible mechanisms. Adult male SHR and age-matched Wistar-Kyoto rats (WKY) were divided into four groups: WKY sedentary group, SHR sedentary group, low-intensity training group, and medium-intensity training group. Using molecular and biochemical approaches, we investigated the effects of 14-week training on renalase (RNLS) protein levels, renal function, and apoptosis and oxidative stress modulators in kidney tissues. In vitro, angiotensin II (Ang II)-induced human kidney proximal epithelial cells (HK-2) were treated with RNLS, and changes in apoptosis and oxidative stress levels were observed. Our results show that moderate training improved renal function decline in SHR. In addition, aerobic exercise therapy significantly increased levels of RNLS in the renal medulla of SHR. We observed in vitro that RNLS significantly inhibited the increase of Ang II-inducedapoptosis and oxidative stress levels in HK-2. In conclusion, aerobic exercise training effectively improved renal function in SHR by promoting RNLS expression in the renal medulla. These results explain the possible mechanism in which exercise improves renal injury in hypertensive patients and suggest RNLS as a novel therapy for kidney injury patients.
Inhalable Composite Microparticles Containing siRNA-Loaded Lipid-Polymer Hybrid Nanoparticles: Saccharides and Leucine Preserve Aerosol Performance and Long-Term Physical Stability
Authors: Xu You , Turan Enise Tugba , Shi Zhenning , Franzyk Henrik , Thakur Aneesh , Foged Camilla
Published: July 2022

Thermostable dry powder formulations with high aerosol performance are attractive inhalable solid dosage forms for local treatment of lung diseases. However, preserved long-term physical stability of dry powder inhaler (DPI) formulations is critical to ensure efficient and reproducible delivery to the airways during the shelf life of the drug product. Here, we show that ternary excipient mixtures of the disaccharide trehalose (Tre), the polysaccharide dextran (Dex), and the shell-forming dispersion enhancer leucine (Leu) stabilize siRNA-loaded lipid-polymer hybrid nanoparticles (LPNs) during spray drying into nanocomposite microparticles, and result in inhalable solid dosage forms with high aerosol performance and long-term stability. The stabilizing roles of Tre and Dex were also studied separately by investigating DPI formulations containing binary mixtures of Leu/Tre and Leu/Dex, respectively. DPI formulations containing binary Leu/Dex mixtures were amorphous and displayed preserved long-term physical stability of LPNs and chemical stability of siRNA in accelerated stability studies under exaggerated storage conditions (ambient temperature and relative humidity). In contrast, powders containing binary Leu/Tre mixtures were amorphous, and hence metastable, and were recrystallized after six months of storage. Ternary mixtures of Tre, Leu, and Dex provided the most efficient protection of the LPNs during the spray drying process and prevented recrystallization of amorphous Tre. Hence, in ternary mixtures, Leu, Tre, and Dex have the following functions: the shell-forming Leu functions as a dispersion enhancer and is essential for high aerosol performance, the disaccharide Tre provides LPN protection during manufacturing and storage due to efficient coverage of the LPN surface, and the polysaccharide Dex promotes the formation of porous particles and prevents recrystallization of Tre during long-term storage. Therefore, the use of ternary excipient mixtures composed of Leu, Tre, and Dex, may prevent instability problems of DPI formulations and preserve the aerosol performance during long-term storage, which is essential for effective pulmonary drug delivery.
Alluvial Sedimentary Records in Indian Precambrian Basins: Implications Toward Unique Precambrian Sedimentary Environment?
Authors: Chakraborty Partha Pratim , Bailwal Rahul , Paul Pritam P. , Sharma Aditi
Published: July 2022

“Present is the key to the past”—in this all-inclusive uniformitarians’ geological panacea, the Precambrian continental sedimentation system stands out as an odd candidate. The distinctive nature of Precambrian alluvial sedimentation, not analogous to their Phanerozoic counterparts, is highlighted in literature in the absence of rooted vegetation, soil, and an overall greenhouse atmospheric condition. Documentation from Precambrian alluvial deposits around the globe suggests a sedimentation pattern dominated by scree cones, alluvial fans, and braid-plains under the combined effects of aggressive weathering and absence of vegetation; ephemeral braid-plains convincingly outweigh the other alluvial systems in the rock record. It is also surmised that Precambrian fluvial systems, unlike their Phanerozoic-modern analogs, maintained unequivocal ephemeral character across different climatic zones with very less chance of assuming meandering channel planform in absence of buffering effects of rooted plant and adequate mud. Local ponding of muddy sediments, though visualized in some rare cases, was mostly connected with the generation of local paleoslope and unusual riverine hydrology. Recent studies, however, raised a question about the actual paucity of mud, documented meander channel planforms from Precambrian fluvial records, and drew a parallel between the character of the Pre-Silurian alluvial plain on the surface of Earth and meander channel planforms on the Martian surface, interpreted from satellite imagery data. From the collation of data on alluvial deposits from a number of Indian Precambrian basins, augmented by new data from the Bayana basin, a Paleoproterozoic basin in the North Delhi fold belt, the present study attempts to document nuances and intricacies in Precambrian alluvial sedimentation motif that include facies architecture and paleohydrology. From an extensive, though not exhaustive, database, the study intends to claim the establishment of a meander channel-form in Precambrian river systems at a local scale in areas of low discharge and availability of higher silt and mud.
Bathymetric Highs Control the Along-Strike Variations of the Manila Trench: 2D Numerical Modeling
Authors: Ma Letian , Chen Lin , Cheng Zihua , Gerya Taras , Li Jiabiao
Published: July 2022

The Manila Trench is located at the eastern boundary of the South China Sea (SCS). It develops through the subduction of the SCS beneath the Philippine Sea Plate (PSP) since the early Neogene, driven by the northwestern plate motion of the PSP. The northern segment of the Manila trench at around 18° N—21.5°N is characterized by an obvious eastward convex in the trench shape and abrupt changes of slab dip angle, whereas the southern segment of the Manila trench at around 15°N—18°N is featured by an almost straight NS-trending trench line and smooth subducting slab morphology. However, the cause for the along-strike variations along the Manila trench remains poorly understood. In this study, we use 2-D thermo-mechanical modeling to investigate how bathymetric highs embedded in the subducting slab affect the topography of overriding plate and the morphology of subducting plate. Three major factors of bathymetric highs are systematically examined: 1) the crustal properties, 2) the width, and 3) the thickness. Geodynamic results suggest that the most important factor controlling abrupt changes in dipping angle is the crustal properties of bathymetric highs. Also, reduction of crustal thickness and increasing the width of continental bathymetric highs favor the abrupt change of dipping angle, whereas thicker (≥25 km) bathymetric highs are more likely to be blocked in the subduction zone before slab break-off. According to our numerical modeling results, we suggest that dramatic changes in the dip angle in the northern Manila trench and the convex shape were caused by subduction of a large thin continental terrane, whereas the smooth morphology of subducting slab in the southern segment and straight trench were associated with normal oceanic subduction with small seamounts.
Fabrication of Ag-Doped ZnO Photocatalysts Derived From MIL-125(Zn) With Enhanced Photocatalytic Activity
Authors: Yang Xiaobing , Yang Xiangrui , Wu Shichao
Published: July 2022

Metal–organic frameworks (MOFs) have been widely used in various fields, including gas storage, separation, sensors, and catalysis, owing to their excellent performance. In this study, a zinc-based MOF [MIL-125(Zn)] was successfully synthesized using the solvothermal method, and Ag-doped ZnO (Ag/ZnO) was prepared by pyrolyzing Ag/MIL-125(Zn). The fabricated Ag/ZnO was used as a photocatalyst for rhodamine (RhB) degradation. Results showed that the MIL-125(Zn) derived from Ag/ZnO exhibits superior photocatalytic activity. It can degrade 99.4% of RhB under 20-min ultraviolet (UV) light irradiation, higher than those achieved using ZnO (73.2%) and MIL-125(ZnO) (19.6%). Furthermore, Ag/ZnO shows excellent stability. After four photocatalytic degradation cycles, the photocatalytic activity of Ag/ZnO reduces by only 3.6%. The excellent photocatalytic performance of Ag/ZnO may be attributed to the synergistic effect of Ag nanoparticles and ZnO. The possible photocatalytic mechanism of RhB degradation on the Ag/ZnO photocatalyst under UV light irradiation was proposed.
Integrative Analysis of the DICER-like (DCL) Genes From Peach (Prunus persica): A Critical Role in Response to Drought Stress
Authors: Belal Mohammad A. , Ezzat Mohamed , Zhang Yuanqiang , Xu Ziang , Cao Yunpeng , Han Yuepeng
Published: July 2022

DICER-likes (DCLs) proteins are the core component for non-coding RNA (ncRNA) biogenesis, playing essential roles in some biological processes. The DCL family has been characterized in model plants, such as Arabidopsis, rice, and poplar. However, the evolutionary aspect and the expression mechanism under drought stress were scarce and have never been reported and characterized in one of the most important worldwide cultivated fruit trees, peach (Prunus persica). Eight DCLs genes in the Prunus persica genome were detected, in addition to 51 DCLs in the other seven Rosaceae genomes. The phylogenetic analysis with Arabidopsis thaliana and RTL1 gene as outgroups suggested that DCL members are divided into four clades: DCL1, DCL2, DCL3, and DCL4 with several gene gain/loss events of DCL gene copies through the evolutionary tract of the Rosacea family. The number of homologous DCL copies within each clade, along with the chromosomal location indicated gene duplication event of the DCL2 gene occurred once for the subfamily Amygdaloideae and twice for Pyrus communis and Prunus dulics and trice for the P. persica on Chromosome number 7 genes. Another duplication event was found for the DCL3 gene that occurred once for all the eight Rosaceae species with no match in A. thaliana. The DCL genetic similarity and activity was evaluated using BLASTp and previously published RNA-seq data among different tissues and over different time points of peach trees exposed to drought conditions. Finally, the expression pattern of PrupeDCLs in response to drought stress was identified, and two of these members, Prupe.7G047900 and Prupe.6G363600, were found as main candidate genes for response to drought stress. Our data presented here provide useful information for a better understanding of the molecular evolution of DCL genes in Rosaceae genomes, and the function of DCLs in P. persica.
OsSPL88 Encodes a Cullin Protein that Regulates Rice Growth and Development
Authors: Chen Zhengai , Yin Wenjing , Li Xuan , Lu Tao , Ye Hanfei , Dai Gaoxing , Mao Yijian , Li Sanfeng , Duan Penggen , Lu Mei , Rao Yuchun , Wang Yuexing
Published: July 2022

Plant lesion mimics refer to necrotic spots spontaneously produced by the plant without mechanical damage, pathogen invasion, and adversity stress. Here, we isolated and characterized two rice (Oryza sativa L) mutants, namely, spl88-1 (spotted leaf88-1) and spl88-2 (spotted leaf88-2), which were identified from an ethyl methanesulfonate-mutagenized japonica cultivar Xiushui 11 population. Physiological and biochemical experiments indicated that more ROS accumulated in spl88-1 and spl88-2 than in wild type. spl88-1 and spl88-2 displayed spontaneous cell death and enhanced their resistance to bacterial blight by affecting the expression of defense-related genes. We isolated SPL88 by map-based cloning, which encoded a highly conserved Cullin protein. A single base deletion was detected in spl88-1 and spl88-2, in which the 132nd base C of SPL88-1 and the 381th base T of SPL88-2 were deleted, causing premature termination of protein translation. SPL88 was expressed in root, stem, leaf, leaf sheath, and panicle. The Cullin protein was localized in the cytoplasm and nucleus. The aforementioned results indicate that SPL88 regulates the growth and development of rice by affecting the expression of defense-related genes.
Case Report: First-Line Immunotherapy for Esophageal Squamous Carcinoma Combined With Hypopharyngeal Squamous Carcinoma Yields Sustained Survival Benefit
Authors: Yang Yi , Liu Xiangliang , Song Wei , Lu Jin , Yin Na , Ye Xiaojun , Chen Xiao
Published: July 2022

Esophageal cancer, as one of the most common malignant tumors in the upper gastrointestinal tract, is highly invasive, with poor prognosis and low 5-year survival rate. Hypopharyngeal cancer has a low incidence among head and neck malignant tumors, but its prognosis is poor and it is prone to recurrence, and because the upper respiratory tract has similar tissue types as the upper gastrointestinal tract, it is prone to the second primary tumor of the upper gastrointestinal tract, however, such patients with double primary carcinoma are uncommon in the clinic, and most of them are already advanced at the time of diagnosis, losing the chance of surgical resection, with poor results and poor prognosis after radiotherapy treatment, therefore, the choice of treatment strategy for such inoperable resectable patients is still a great challenge for clinicians.In this case, we report a patient with a double primary esophageal squamous carcinoma combined with hypopharyngeal squamous carcinoma without family history of tumor, who achieved complete remission after first-line chemotherapy combined with immunotherapy, with both lesions shrinking and the hypopharyngeal tumor disappearing. The survival benefit was ensured at the same time.
A Four-Cell-Senescence-Regulator-Gene Prognostic Index Verified by Genome-Wide CRISPR Can Depict the Tumor Microenvironment and Guide Clinical Treatment of Bladder Cancer
Authors: Sun Jian-Xuan , Liu Chen-Qian , Xu Jin-Zhou , An Ye , Xu Meng-Yao , Zhong Xing-Yu , Zeng Na , Ma Si-Yang , He Hao-Dong , Zhang Zong-Biao , Wang Shao-Gang , Xia Qi-Dong
Published: July 2022

Bladder cancer (BCa) is the 10th most commonly diagnosed cancer worldwide, and cellular senescence is defined as a state of permanent cell cycle arrest and considered to play important roles in the development and progression of tumor. However, the comprehensive effect of senescence in BCa has not ever been systematically evaluated. Using the genome-wide CRISPR screening data acquired from DepMap (Cancer Dependency Map), senescence genes from the CellAge database, and gene expression data from The Cancer Genome Atlas (TCGA), we screened out 12 senescence genes which might play critical roles in BCa. A four-cell-senescence-regulator-gene prognostic index was constructed using the least absolute shrinkage and selection operator (LASSO) and multivariate COX regression model. The transcriptomic data and clinical information of BCa patients were downloaded from TCGA and Gene Expression Omnibus (GEO). We randomly divided the patients in TCGA cohort into training and testing cohorts and calculated the risk score according to the expression of the four senescence genes. The validity of this risk score was validated in the testing cohort (TCGA) and validation cohort (GSE13507). The Kaplan–Meier curves revealed a significant difference in the survival outcome between the high- and low-risk score groups. A nomogram including the risk score and other clinical factors (age, gender, stage, and grade) was established with better predictive capacity of OS in 1, 3, and 5 years. Besides, we found that patients in the high-risk group had higher tumor mutation burden (TMB); lower immune, stroma, and ESTIMATE scores; higher tumor purity; aberrant immune functions; and lower expression of immune checkpoints. We also performed gene set variation analysis (GSVA) and gene set enrichment analysis (GSEA) to investigate the interaction between risk score and hallmark pathways and found that a high risk score was connected with activation of senescence-related pathways. Furthermore, we found that a high risk score was related to better response to immunotherapy and chemotherapy. In conclusion, we identified a four-cell-senescence-regulator-gene prognostic index in BCa and investigated its relationship with TMB, the immune landscape of tumor microenvironment (TME), and response to immunotherapy and chemotherapy, and we also established a nomogram to predict the prognosis of patients with BCa.
Gastric Th17 Cells Specific for H+/K+-ATPase and Serum IL-17 Signature in Gastric Autoimmunity
Authors: Della Bella Chiara , Antico Antonio , Panozzo Maria Piera , Capitani Nagaja , Petrone Luisa , Benagiano Marisa , D’Elios Sofia , Sparano Clotilde , Azzurri Annalisa , Pratesi Sara , Cianchi Fabio , Ortiz-Princz Diana , Bergman Mathijs , Bizzaro Nicola , D’Elios Mario Milco
Published: July 2022

Human gastric autoimmunity [autoimmune gastritis (AIG)] is characterized by inflammation of the gastric mucosa and parietal cell loss. The gastric parietal cell proton pump H+/K+-adenosine triphosphatase (H+/K+-ATPase) is the major autoantigen in AIG. Our work aimed to investigate the gastric H+/K+-ATPase-specific T helper 17 (Th17) responses in AIG and serum interleukin (IL)-17 cytokine subfamily in AIG patients, in healthy subjects [healthy controls (HCs)], and in patients with iron deficiency anemia (IDA) without AIG. We analyzed the activation of gastric lamina propria mononuclear cells (LPMCs) by H+/K+-ATPase and the IL-17A and IL-17F cytokine production in eight patients with AIG and four HCs. Furthermore, we compared serum levels of IL-17A, IL-17F, IL-21, IL-17E, IL-22, and IL-23 in 43 AIG patients, in 47 HCs, and in 20 IDA patients without AIG. Gastric LPMCs from all AIG patients, but not those from HCs, were activated by H+/K+-ATPase and were able to proliferate and produce high levels of IL-17A and IL-17F. AIG patients have significantly higher serum IL-17A, IL-17F, IL-21, and IL-17E (393.3 ± 410.02 pg/ml, 394.0 ± 378.03 pg/ml, 300.46 ± 303.45 pg/ml, 34.92 ± 32.56 pg/ml, respectively) than those in HCs (222.99 ± 361.24 pg/ml, 217.49 ± 312.1 pg/ml, 147.43 ± 259.17 pg/ml, 8.69 ± 8.98 pg/ml, respectively) and those in IDA patients without AIG (58.06 ± 107.49 pg/ml, 74.26 ± 178.50 pg/ml, 96.86 ± 177.46 pg/ml, 10.64 ± 17.70 pg/ml, respectively). Altogether, our results indicate that IL-17A and IL-17F are produced in vivo in the stomach of AIG patients following activation with H+/K+-ATPase and that serum IL-17A, IL-17F, IL-21, and IL-17E levels are significantly elevated in AIG patients but not in patients without AIG. These data suggest a Th17 signature in AIG and that IL-17A, IL-17F, IL-21, and IL-17E may represent a relevant tool for AIG management.
Overfishing Increases the Carbon Footprint of Seafood Production From Small-Scale Fisheries
Authors: Ferrer Erica M. , Giron-Nava Alfredo , Aburto-Oropeza Octavio
Published: July 2022

Small-scale fisheries (SSFs) and the foods they produce are extremely important, contributing 25–50% of global seafood landed for direct consumption. In some cases, SSFs provide seafoods with an exceptionally low carbon footprint, but like all food, it is important to understand the factors that regulate that footprint in the face of increasing demand and a worsening climate-ecological crisis. We utilize long-term fisheries monitoring data from Northwest Mexico to generate novel stock assessments and, subsequently, test the relationship between underlying fishery biomass and fuel intensity observed among several motorized SSFs. Using fuel data from over 4,000 individual fishing trips, in combination with estimated biomass data for 19 regional stocks, we show that the fuel footprint per kilogram of seafood increases sharply as the stock’s underlying annual biomass (B) falls below its estimated biomass at Maximum Sustainable Yield (BMSY). We find an inverse relationship betweenB/BMSYand fuel intensity using a test for simple correlation between the two (r= -0.44), a linear regression analysis (R2adj.= 0.17), and a mixed-effects model with gear type, year, and genus modelled as random effects. These results indicate that efforts to end overfishing, rebuild fishery stocks, and/or minimize intensive fishing practices will help to decrease the carbon emissions generated by motorized wild-catch fishing. We anticipate that this study will contribute an important “missing link” to discussions on how best to secure climate-resilient fisheries and, ideally, help SSF stakeholders garner recognition and support for SSFs in this context.
Predictive Value of Glycosylated Hemoglobin for Post-operative Acute Kidney Injury in Non-cardiac Surgery Patients
Authors: Wu Lan-Ping , Pang Ke , Li Bo , Le Yuan , Tang Yong-Zhong
Published: July 2022

Objective

Recent studies have indicated that patients (both with and without diabetes) with elevated hemoglobin A1c (HbA1c) have a higher rate of acute kidney injury (AKI) following cardiac surgery. However, whether HbA1c could help to predict post-operative AKI in patients after non-cardiac surgery is less clear. This study aims to explore the predictive value of pre-operative HbA1c for post-operative AKI in non-cardiac surgery.

Methods

We reviewed the medical records of patients (≥ 18 years old) who underwent non-cardiac surgery between 2011 and 2020. Patient-related variables, including demographic and laboratory and procedure-related information, were collected, and univariable and multivariable logistic regression analyses were performed to determine the association of HbA1c with AKI. The area under the receiver operating curve (AUC), net reclassification improvement index (NRI), and integrated discriminant improvement index (IDI) were used to evaluate the predictive ability of the model, and decision curve analysis was used to evaluate the clinical utility of the HbA1c-added predictive model.

Results

A total of 3.3% of patients (94 of 2,785) developed AKI within 1 week after surgery. Pre-operative HbA1c was an independent predictor of AKI after adjustment for some clinical variables (OR comparing top to bottom quintiles 5.02, 95% CI, 1.90 to 13.24, P < 0.001 for trend; OR per percentage point increment in HbA1c 1.20, 95% CI, 1.07 to 1.33). Compared to the model with only clinical variables, the incorporation of HbA1c increased the model fit, modestly improved the discrimination (change in area under the curve from 0.7387 to 0.7543) and reclassification (continuous net reclassification improvement 0.2767, 95% CI, 0.0715 to 0.4818, improved integrated discrimination 0.0048, 95% CI, -5e-04 to 0.0101) of AKI and non-AKI cases, NRI for non-AKI improvement 0.3222, 95% CI, 0.2864 to 0.3580 and achieved a higher net benefit in decision curve analysis.

Conclusion

Elevated pre-operative HbA1c was independently associated with post-operative AKI risk and provided predictive value in patients after non-cardiac surgery. HbA1c improved the predictive power of a logistic regression model based on traditional clinical risk factors for AKI. Further prospective studies are needed to demonstrate the results and clinical application.
Immunoinformatic Approach to Contrive a Next Generation Multi-Epitope Vaccine Against Achromobacter xylosoxidans Infections
Authors: Khalid Kashaf , Saeed Umar , Aljuaid Mohammad , Ali Mohammad Ishtiaq , Anjum Awais , Waheed Yasir
Published: July 2022

Achromobacter xylosoxidans, previously identified as Alcaligenes xylosoxidans, is a rod-shaped, flagellated, non-fermenting Gram-negative bacterium that has the ability to cause diverse infections in humans. As a part of its intrinsic resistance to different antibiotics, Achromobacter spp. is also increasingly becoming resistant to Carbapenems. Lack of knowledge regarding the pathogen’s clinical features has led to limited efforts to develop countermeasures against infection. The current study utilized an immunoinformatic method to map antigenic epitopes (Helper T cells, B-cell and Cytotoxic-T cells) to design a vaccine construct. We found that 20 different epitopes contribute significantly to immune response instigation that was further supported by physicochemical analysis and experimental viability. The safety profile of our vaccine was tested for antigenicity, allergenicity, and toxicity against all the identified epitopes before they were used as vaccine candidates. The disulfide engineering was carried out in an area of high mobility to increase the stability of vaccine proteins. In order to determine if the constructed vaccine is compatible with toll-like receptor, the binding affinity of vaccine was investigated via molecular docking approach. With the in silico expression in host cells and subsequent immune simulations, we were able to detect the induction of both arms of the immune response, i.e., humoral response and cytokine induced response. To demonstrate its safety and efficacy, further experimental research is necessary.
SARS-CoV-2 Whole-Genome Sequencing Using Oxford Nanopore Technology for Variant Monitoring in Wastewaters
Authors: Barbé Laure , Schaeffer Julien , Besnard Alban , Jousse Sarah , Wurtzer Sébastien , Moulin Laurent ,   OBEPINE Consortium, Le Guyader Françoise S. , Desdouits Marion
Published: July 2022

Since the beginning of the Coronavirus Disease-19 (COVID-19) pandemic, multiple Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) mutations have been reported and led to the emergence of variants of concern (VOC) with increased transmissibility, virulence or immune escape. In parallel, the observation of viral fecal shedding led to the quantification of SARS-CoV-2 genomes in wastewater, providing information about the dynamics of SARS-CoV-2 infections within a population including symptomatic and asymptomatic individuals. Here, we aimed to adapt a sequencing technique initially designed for clinical samples to apply it to the challenging and mixed wastewater matrix, and hence identify the circulation of VOC at the community level. Composite raw sewage sampled over 24 h in two wastewater-treatment plants (WWTPs) from a city in western France were collected weekly and SARS-CoV-2 quantified by RT-PCR. Samples collected between October 2020 and May 2021 were submitted to whole-genome sequencing (WGS) using the primers and protocol published by the ARTIC Network and a MinION Mk1C sequencer (Oxford Nanopore Technologies, Oxford, United Kingdom). The protocol was adapted to allow near-full genome coverage from sewage samples, starting from ∼5% to reach ∼90% at depth 30. This enabled us to detect multiple single-nucleotide variant (SNV) and assess the circulation of the SARS-CoV-2 VOC Alpha, Beta, Gamma, and Delta. Retrospective analysis of sewage samples shed light on the emergence of the Alpha VOC with detection of first co-occurring signature mutations in mid-November 2020 to reach predominance of this variant in early February 2021. In parallel, a mutation-specific qRT-PCR assay confirmed the spread of the Alpha VOC but detected it later than WGS. Altogether, these data show that SARS-CoV-2 sequencing in sewage can be used for early detection of an emerging VOC in a population and confirm its ability to track shifts in variant predominance.
Vibriosis Outbreaks in Aquaculture: Addressing Environmental and Public Health Concerns and Preventive Therapies Using Gilthead Seabream Farming as a Model System
Authors: Sanches-Fernandes Gracinda M. M. , Sá-Correia Isabel , Costa Rodrigo
Published: July 2022

Bacterial and viral diseases in aquaculture result in severe production and economic losses. Among pathogenic bacteria, species belonging to theVibriogenus are one of the most common and widespread disease-causing agents.Vibrioinfections play a leading role in constraining the sustainable growth of the aquaculture sector worldwide and, consequently, are the target of manifold disease prevention strategies. During the early, larval stages of development,Vibriospecies are a common cause of high mortality rates in reared fish and shellfish, circumstances under which the host organisms might be highly susceptible to disease preventive or treatment strategies such as vaccines and antibiotics use, respectively. Regardless of host developmental stage,Vibrioinfections may occur suddenly and can lead to the loss of the entire population reared in a given aquaculture system. Furthermore, the frequency ofVibrio–associated diseases in humans is increasing globally and has been linked to anthropic activities, in particular human-driven climate change and intensive livestock production. In this context, here we cover the current knowledge ofVibrioinfections in fish aquaculture, with a focus on the model species gilthead seabream (Sparus aurata), a highly valuable reared fish in the Mediterranean climatic zone. Molecular methods currently used for fast detection and identification ofVibriopathogens and their antibiotic resistance profiles are addressed. Targeted therapeutic approaches are critically examined. They include vaccination, phage therapy and probiotics supplementation, which bear promise in supressing vibriosis in land-based fish rearing and in mitigating possible threats to human health and the environment. This literature review suggests that antibiotic resistance is increasing amongVibriospecies, with the use of probiotics constituting a promising, sustainable approach to preventVibrioinfections in aquaculture.
Biosynthetic Mechanisms of Secondary Metabolites Promoted by the Interaction Between Endophytes and Plant Hosts
Authors: Li Zhaogao , Wen Weie , Qin Ming , He Yuqi , Xu Delin , Li Lin
Published: July 2022

Endophytes is a kind of microorganism resource with great potential medicinal value. The interactions between endophytes and host not only promote the growth and development of each other but also drive the biosynthesis of many new medicinal active substances. In this review, we summarized recent reports related to the interactions between endophytes and hosts, mainly regarding the research progress of endophytes affecting the growth and development of host plants, physiological stress and the synthesis of new compounds. Then, we also discussed the positive effects of multiomics analysis on the interactions between endophytes and their hosts, as well as the application and development prospects of metabolites synthesized by symbiotic interactions. This review may provide a reference for the further development and utilization of endophytes and the study of their interactions with their hosts.
DNA Methylation of Patatin-Like Phospholipase Domain-Containing Protein 6 Gene Contributes to the Risk of Intracranial Aneurysm in Males
Authors: Zhou Shengjun , Zhang Junjun , Zhou Chenhui , Gong Fanyong , Zhu Xueli , Pan Xingqiang , Sun Jie , Gao Xiang , Huang Yi
Published: July 2022

Objective: This study is aimed to investigate the contribution of patatin-like phospholipase domain-containing protein 6 (PNPLA6) DNA methylation to the risk of intracranial aneurysm (IA) in the Han Chinese population.

Methods: A total of 96 age- and sex-matched participants were recruited to evaluate PNPLA6 methylation via bisulfite pyrosequencing. The PNPLA6 mRNA expression in the plasma was determined using real-time quantitative reverse transcription-polymerase chain reaction. Human primary artery smooth muscle cells (HPCASMC) were used for the in vitro function study.

Results: PNPLA6 methylation was significantly higher in patients with IA than in healthy controls (p < 0.01). Sex group analysis showed that this correlation appeared in the male group (p < 0.01) but not in the female group (p > 0.05). PNPLA6 methylation was significantly associated with age in all participants (r = 0.306, p = 0.003) and in the control group (r = 0.377, p = 0.008) but not in the IA group (r = 0.127, p = 0.402). Furthermore, the PNPLA6 mRNA expression significantly decreased in patients with IA than that in the controls (p = 0.016). PNPLA6 expression was significantly inversely correlated with elevated DNA methylation in participants (r = −0.825, p < 0.0001). In addition, PNPLA6 transcription was significantly enhanced following treatment with 5-aza-2’-deoxycytidine methylation inhibitor in HPCASMC.The receiver operating characteristic analyses of curves showed that the PNPLA6 mean methylation [area under the curve (AUC) = 0.74, p < 0.001] and mRNA expression (AUC = 0.86, p < 0.001) could have a diagnostic value for patients with IA.

Conclusion: Although future functional experiments are required to test our hypothesis, our study demonstrated that PNPLA6 methylation and mRNA expression were significantly associated with the risk of IA; thus, they show potential for use in the early diagnosis of IA.