bluuebunny/crossref_metadata_2025 huggingface dataset:
Antimicrobial Peptide Mimics for Clinical Use: Does Size Matter?
Authors: Svenson Johan , Molchanova Natalia , Schroeder Christina I.
Published: June 2022

The search for efficient antimicrobial therapies that can alleviate suffering caused by infections from resistant bacteria is more urgent than ever before. Infections caused by multi-resistant pathogens represent a significant and increasing burden to healthcare and society and researcher are investigating new classes of bioactive compounds to slow down this development. Antimicrobial peptides from the innate immune system represent one promising class that offers a potential solution to the antibiotic resistance problem due to their mode of action on the microbial membranes. However, challenges associated with pharmacokinetics, bioavailability and off-target toxicity are slowing down the advancement and use of innate defensive peptides. Improving the therapeutic properties of these peptides is a strategy for reducing the clinical limitations and synthetic mimics of antimicrobial peptides are emerging as a promising class of molecules for a variety of antimicrobial applications. These compounds can be made significantly shorter while maintaining, or even improving antimicrobial properties, and several downsized synthetic mimics are now in clinical development for a range of infectious diseases. A variety of strategies can be employed to prepare these small compounds and this review describes the different compounds developed to date by adhering to a minimum pharmacophore based on an amphiphilic balance between cationic charge and hydrophobicity. These compounds can be made as small as dipeptides, circumventing the need for large compounds with elaborate three-dimensional structures to generate simplified and potent antimicrobial mimics for a range of medical applications. This review highlight key and recent development in the field of small antimicrobial peptide mimics as a promising class of antimicrobials, illustrating just how small you can go.
Cleaner Fish Labroides dimidiatus Presence Does Not Indirectly Affect Demersal Zooplankton
Authors: Grutter Alexandra S. , Nishikawa Natsumi , Uribe-Palomino Julian , Richardson Anthony J.
Published: June 2022

Coral reef mutualisms involve complex trophic ecological relationships that produce indirect effects. Excluding mutualistic cleaner fish Labroides dimidiatus from reefs indirectly increases the abundance of many fishes and reduces demersal stages of their ectoparasitic prey (gnathiid isopods). Whether cleaners affect populations of planktivorous fishes that consume demersal zooplankton, and consequently indirectly affect the rest of the demersal zooplankton community — via presumed changes in planktivory — is unknown. Therefore, using a long-term cleaner fish manipulation on patch reefs (July 2000 to December 2012, Great Barrier Reef), we tested whether cleaner treatment (removal or control) affects planktivorous fish abundance and diversity, and demersal zooplankton biomass, abundance, and diversity. Fish surveys, 9 and 12 years after removing cleaners revealed fewer fish on removal compared to control reefs for one of the three most abundant planktivores, but not total abundance (Pomacentridae, 26 species), diversity, and composition. Emerging zooplankton were sampled during the day and night over nine sampling trips across 12 years. There was no effect of cleaner treatment on post-removal values, compared with pre-removal values in July 2000, for zooplankton biomass, abundance, diversity, and composition (34 taxa). Zooplankton abundance showed no diel differences, but diversity, and occasionally biomass, were higher at night. Zooplankton composition also showed diel differences, with three taxa contributing the most to this dissimilarity [Cirripeda nauplii, Facetotecta (Arthopoda), Oikopleuridae (Chordata)]. Zooplankton diversity did not differ among times, abundance was higher in January 2002 relative to July 2000, and composition differed among all times. The lack of detectable indirect effects of cleaner fish presence on zooplankton (non-gnathiid) may partly be due to cleaners’ variable effect on planktivorous fish abundance, but also the result of invertebrate planktivory and other processes that affect zooplankton populations not investigated here. Nevertheless, the pronounced diel and temporal changes in zooplankton observed likely influence coral reef trophic interactions.
Zooplankton Dominance Shift in Response to Climate-Driven Salinity Change: A Mesocosm Study
Authors: Hall Clio A. M. , Lewandowska Aleksandra M.
Published: June 2022

Climate change predictions indicate global changes in salinity with negative implications for plankton food webs; an important baseline for functioning of marine ecosystems. Current understanding of how salinity change will impact plankton communities is mostly limited to the salinization of freshwater environments, with little known about the effects of changing salinity in marine systems. In this study, we investigate the effect of salinity change on zooplankton communities under different salinity change scenarios of the Baltic Sea. Projections for future salinity change derived from regional physical-biogeochemical models were used to set-up an outdoor mesocosm experiment in the coastal area of the Gulf of Finland. Each mesocosm was inoculated with natural plankton using a mixture of both marine and freshwater communities, mimicking the natural influx of freshwater species from rivers into the Baltic Sea. Zooplankton diversity and composition changed possibly due to different salinity tolerances among the species. Among zooplankton, rotifers dominated in low salinities (74%) and cladocerans and copepods (69%) in high salinities. Our results suggest that the zooplankton community will shift to a rotifer dominated community in areas with declining salinity due to the intolerance of other zooplankton groups to freshening.
Coupling Imaging and Omics in Plankton Surveys: State-of-the-Art, Challenges, and Future Directions
Authors: Pierella Karlusich Juan José , Lombard Fabien , Irisson Jean-Olivier , Bowler Chris , Foster Rachel A.
Published: June 2022

A major challenge in characterizing plankton communities is the collection, identification and quantification of samples in a time-efficient way. The classical manual microscopy counts are gradually being replaced by high throughput imaging and nucleic acid sequencing. DNA sequencing allows deep taxonomic resolution (including cryptic species) as well as high detection power (detecting rare species), while RNA provides insights on function and potential activity. However, these methods are affected by database limitations, PCR bias, and copy number variability across taxa. Recent developments in high-throughput imaging applied in situ or on collected samples (high-throughput microscopy, Underwater Vision Profiler, FlowCam, ZooScan, etc) has enabled a rapid enumeration of morphologically-distinguished plankton populations, estimates of biovolume/biomass, and provides additional valuable phenotypic information. Although machine learning classifiers generate encouraging results to classify marine plankton images in a time efficient way, there is still a need for large training datasets of manually annotated images. Here we provide workflow examples that couple nucleic acid sequencing with high-throughput imaging for a more complete and robust analysis of microbial communities. We also describe the publicly available and collaborative web application EcoTaxa, which offers tools for the rapid validation of plankton by specialists with the help of automatic recognition algorithms. Finally, we describe how the field is moving with citizen science programs, unmanned autonomous platforms with in situ sensors, and sequencing and digitalization of historical plankton samples.
Otolith Marking With Strontium for Stock Assessment in Coilia nasus
Authors: Liu Ming-Zhi , Jiang Ri-jin , Zhang Hui , Yang Fan , Li Xia-Fang , Feng Guang-Peng , Yin Rui , Chen Feng
Published: June 2022

Mass stock enhancement and release are excellent ways to recover Coilia nasus resources. However, it is challenging to evaluate stock enhancement effectively, and it is important to establish a method suitable for estimating C. nasus populations. We explored the effectiveness of marking otoliths in these fish with strontium by immersing C. nasus in hexahydrate strontium chloride solutions. We used laser ablation inductively coupled plasma mass spectrometry to measure the strontium content of otoliths and fish bodies. The larvae (40 d post hatch) were reared in five different concentrations of strontium (0, 12, 24, 48, and 60 mg/L) for 7 d, followed by treatment in non-additive water for 3 wk. The results showed that the cumulative mortality rate was not significantly different between treatment and control groups (P>0.05), except in the group treated with 24 mg/L strontium. The swimming and feeding behaviors did not change significantly, indicating that strontium did not negatively affect survival in this species. The strontium/calcium ratios of otoliths in the control group were stable (1.78–2.32 mmol/mol), whereas those of the experimental (marked) groups ranged widely (4.47–61.02 mmol/mol). The strontium/calcium ratios increased with increasing strontium concentration, but gradually returned to baseline values, resulting in a 100% success rate of marking with strontium. Following immersion in 12 mg/L strontium, strontium levels in the body returned to normal after 24 d. In summary, a treatment of 12 mg/L strontium for 4 d was identified as viable for marking. We confirmed the feasibility of strontium marking for the mass marking and release of C. nasus. This marking method does not affect the physiology of the fish and may provide a new approach for reasonable and scientific stock assessment of C. nasus post hatch.
Sources and Leakages of Microplastics in Cruise Ship Wastewater
Authors: Folbert Maartje E. F. , Corbin Christopher , Löhr Ansje J.
Published: June 2022

To date, the contribution of sea-based sources to the global marine litter and plastic pollution problem remains poorly understood. Cruise ships produce large amounts of wastewater and concentrate their activities in fragile and ecologically valuable areas. This paper explores for the first time the sources of microplastics in cruise ship wastewater, as well as their pathways from source to sea. It thereto uses a novel approach for the identification of sources and pathways, based on scientific literature on microplastic sources and pathways, literature on cruise operations and wastewater management as well as a questionnaire among cruise lines. The study highlights personal care and cosmetic products, cleaning and maintenance products and synthetic microfibers released from textiles in laundry as relevant source categories. Untreated grey water and the overboard discharge of biosludge, resulting from the treatment of sewage and grey water, were identified as key pathways. Cruise lines can reduce microplastic emissions by adapting their purchasing policies for personal care, cosmetic, cleaning and maintenance products and professional textiles. In addition, the holistic management of all wastewater streams and resulting waste products is essential to prevent leakages of microplastics from cruise ships to vulnerable coastal and marine ecosystems. Furthermore, the approach can be used to guide company-level assessments and can be modified to address microplastic leakages in other maritime sectors.
Combined Application of Er:YAG and Nd:YAG Lasers Enhances Osseointegration at Dental Bone-Implant Interface
Authors: Zhao Tianyuan , Li Meihua
Published: June 2022

The combination of a bone and an implant surface is a dynamic biological process. By improving the osseointegration efficiency of the bone tissue around the implant surface, the implant can obtain long-term stability. In this study, we have investigated the potential applications of dual-wavelength lasers (Er:YAG laser and Nd:YAG laser) in implantations and observed their possible efficacy in promoting tissue repair around the implant. The animal experimental model of a rabbit femoral defect implant was used to simulate the process of tissue reconstruction around the implant in humans. The results indicated that by micro-CT observation, it was obvious that the bone mineral density (BMD) values of the dual-wavelength laser group were significantly higher than those of other groups. Furthermore, VG staining clearly showed that there was no obvious physiological gap detected between the implant and the surrounding bone tissues in the dual-wavelength laser group. HE staining further revealed that no significant influx of inflammatory cells was observed around the implants. Immunohistochemical staining of OCN and VEGF showed that the positive area percentages of the dual-wavelength laser group were significantly higher than other groups at the same time point. Therefore, the application of a dual-wavelength laser in implantations can exhibit a positive effect on promoting the reconstruction of bone tissues.
Sacubitril-Valsartan Increases Ultrafiltration in Patients Undergoing Peritoneal Dialysis: A Short-Term Retrospective Self-Controlled Study
Authors: Zhang Fen , Zhang Tingting , Yang Sisi , Wang Di , Zhuo Qianqian , Qin Xianhui , Gong Nirong , Ai Jun
Published: June 2022

Aim

There are few data about the effectiveness and safety of angiotensin receptor-neprilysin inhibitor (ARNI) sacubitril-valsartan in end-stage renal disease (ESRD) patients undergoing peritoneal dialysis (PD). The present study was conducted to evaluate the association between sacubitril-valsartan treatment and peritoneal ultrafiltration (PUF) in PD patients.

Methods and Results

Forty-seven ESRD patients undergoing PD for at least 3 months without severe congestive heart failure (CHF) were included in this study. Sacubitril-valsartan (generally 100 mg b.i.d) was administered after consultation with the nephrologist. Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) were required to be discontinued 36 h before prescribing sacubitril-valsartan. Other treatments and dialysis modality did not change. Baseline demographic and clinical parameters were collected before ARNI administration, and daily PUF, urine volume, total output, blood pressure (BP), and body weight were collected within 7 days before and after ARNI treatment. After treated with sacubitril-valsartan, 30 patients (63.8%) had a significant increase of PUF [up to 150.4 (110.7, 232.1) ml per day], while the remaining 17 (36.2%) had a slight decrease. The overall increase of PUF was 66.4 (21.4, 123.2) ml/24 h within the 7 days after sacubitril-valsartan administration, which was significantly higher than those before (P = 0.004). Total output, BP, and body weight also significantly improved. No adverse drug reactions were observed.

Conclusions

Our study indicated that sacubitril-valsartan was associated with the increase of short-term PUF and total output in PD patients.
The Influence of HbA1c and Gestational Weight Gain on Pregnancy Outcomes in Pregnant Women With Gestational Diabetes Mellitus
Authors: Zhang Qiuhong , Lee Chee Shin , Zhang Lixia , Wu Qi , Chen Yunyan , Chen Danqing , Qi Lu , Liang Zhaoxia
Published: June 2022

Background

To investigate the influence of HbA1c level and GWG on pregnancy outcomes in pregnant women with GDM.

Methods

A total of 2,171 pregnant women with GDM were retrospectively included and categorized as follows: (1) normal (HbA1c <6%) and elevated (HbA1c ≥6%) HbA1c groups according to the HbA1c level in the second trimester, and (2) inadequate, appropriate, and excessive GWG groups according to the IOM guidelines.

Results

In pregnant women with GDM, advanced age and high pre-pregnancy BMI were high-risk factors for elevated HbA1c. Pregnant women with elevated HbA1c had higher OGTT levels than those with normal HbA1c, and the risks of adverse pregnancy outcomes were higher (P < 0.05). The risks of primary cesarean section, hypertensive disorders during pregnancy, and macrosomia in pregnant women with excessive GWG were significantly higher than those with inadequate and appropriate GWG (P < 0.05). When GWG was appropriate, the risk of hypertensive disorders during pregnancy in the elevated HbA1c group was higher than that in the normal HbA1c group. When GWG was excessive, the risks of postpartum hemorrhage, macrosomia, and neonatal asphyxia in the elevated HbA1c group were significantly higher than in the normal HbA1c group (P < 0.05).

Conclusion

Monitoring and controlling blood glucose levels have shown effectiveness in reducing the adverse pregnancy outcomes in women with GDM, particularly for those who had excessive GWG.
A Dynamic Nomogram Predicting Portal Vein Thrombosis in Cirrhotic Patients During Primary Prophylaxis for Variceal Hemorrhage
Authors: Zhang Shuo , Ji Bing , Zhong Xuan , Zhong Lan , Yang Li , Yang Changqing
Published: June 2022

Background

Portal vein thrombosis (PVT) would exert a further increase in resistance to portal blood flow, resulting in worsening portal hypertension and poor outcome. This study aimed to identify risk factors and develop an clinically applicable dynamic nomogram predicting the occurrence of PVT in cirrhotic patients during primary prophylaxis for variveal hemorrhage (VH).

Methods

The multi-center retrospective study enrolled cirrhotic patients with high-risk varices, which were further divided into training and validation cohorts for 3 years follow-up. A dynamic nomogram based on the Cox proportional hazard regression model was developed with the cutoff value calculated by X-title analysis. The performance of the nomogram was evaluated with Harrell’s concordance index (C-index), calibration curve and decision curve analysis.

Results

91 (34.0%) of the whole cohort were diagnosed with PVT during 3-year follow-up. Variables including carvedilol (P < 0.001), low portal vein velocity (P < 0.001), increased size of esophageal varices (P = 0.005), and high HbA1c (P < 0.001) and procalcitonin (P = 0.015) were identified to be independently associated with PVT, which were further incorporated into the dynamic nomogram with optimal cutoff (8.8 and 14.6) for risk-stratification. The C-indexes (0.894 of internal validation and 0.892 of external validation) and calibration curves demonstrated ideal discrimination and calibration. The thresholds for more reasonable application of the nomogram were 0–0.27, 0–0.66, and 0.04–1.00 at 1, 2, and 3-year, respectively.

Conclusion

The dynamic nomogram could be accurately and reliably used for clinical risk-stratification of PVT in cirrhotic patients during primary prophylaxis for VH.
Multi-Omics Integrative Analysis of Lung Adenocarcinoma: An in silico Profiling for Precise Medicine
Authors: Ruan Xinjia , Ye Yuqing , Cheng Wenxuan , Xu Li , Huang Mengjia , Chen Yi , Zhu Junkai , Lu Xiaofan , Yan Fangrong
Published: June 2022

Lung adenocarcinoma (LUAD) is one of the most common histological subtypes of lung cancer. The aim of this study was to construct consensus clusters based on multi-omics data and multiple algorithms. In order to identify specific molecular characteristics and facilitate the use of precision medicine on patients we used gene expression, DNA methylation, gene mutations, copy number variation data, and clinical data of LUAD patients for clustering. Consensus clusters were obtained using a consensus ensemble of five multi-omics integrative algorithms. Four molecular subtypes were identified. The CS1 and CS2 subtypes had better prognosis. Based on the immune and drug sensitivity predictions, we inferred that CS1 may be less responsive to immunotherapy and less sensitive to chemotherapeutic drugs. The high immune infiltration of CS2 cells may respond well to immunotherapy. Additionally, the CS2 subtype may also respond to EGFR molecular targeted therapy. The CS3 and CS4 subtypes were associated with poor prognosis. These two subtypes had more mutations, especially TP53 ones, as well as higher sensitivity to chemotherapeutics for lung cancer. However, CS3 was enriched in immune-related pathways and may respond to anti-PD1 immunotherapy. In addition, CS1 and CS4 were less sensitive to ferroptosis inhibitors. We performed a comprehensive analysis of the five types of omics data using five clustering algorithms to reveal the molecular characteristics of LUAD patients. These findings provide new insights into LUAD subtypes and potential clinical treatment strategies to guide personalized management and treatment.
The Influence of Social Media in Promoting Knowledge Acquisition and Pathology Excellence in Nigeria
Authors: Folaranmi Olaleke Oluwasegun , Ibiyeye Kehinde Muibat , Odetunde Olabode Ali , Kerr Darcy A.
Published: June 2022

The use of social media has evolved from platforms designed primarily for social connection and news sharing to include vibrant virtual academic environments. These platforms allow pathologists from across the globe to interact, exchange knowledge, and collaborate. Pathology in Nigeria, as in much of Africa, faces severe knowledge and practice gaps, with a lack of supporting modern laboratory infrastructure. Social media represents a potentially highly valuable avenue to help address some of these deficiencies. In this Perspective piece, we highlight our experience with the increasing role of social media in providing quality medical education in pathology globally, with an emphasis on how it bridges many of these gaps in Nigeria. Social media sites serve as sources of readily accessible, free, high-quality information to pathologists and trainees through academic discussions, quizzes, journal clubs, and informal consultations. They also provide opportunities for professional networking and research collaborations. Despite the availability and wide reach of these platforms, social media as a tool for advancement of knowledge in pathology is still undersubscribed in this part of the world. Improving awareness of and support for these tools will ideally help mitigate some of the challenges of practicing pathology in low and middle-income settings.
Mutation in phcA Enhanced the Adaptation of Ralstonia solanacearum to Long-Term Acid Stress
Authors: Liu Ying , Tan Xi , Pan Yanxin , Yu Jiamin , Du Yiran , Liu Xiaojiao , Ding Wei
Published: June 2022

Bacterial wilt, caused by the plant pathogen Ralstonia solanacearum, occurs more severely in acidified soil according to previous reports. However, R. solanacearum cannot grow well in acidic environments under barren nutrient culture conditions, especially when the pH is lower than 5. With the worsening acidification of farmland, further determination of how R. solanacearum adapts to the long-term acidic environment is worthwhile. In this study, experimental evolution was applied to evaluate the adaptability and mechanism of the R. solanacearum experimental population responding to long-term acid stress. We chose the CQPS-1 strain as the ancestor, and minimal medium (MM medium) with different pH values as the culture environment to simulate poor soil. After 1500 generations of serial passage experiments in pH 4.9 MM, acid-adapted experimental strains (denoted as C49 strains) were obtained, showing significantly higher growth rates than the growth rates of control experimental strains (serial passage experiment in pH 6.5 MM, denoted as C65 strains). Competition experiments showed that the competitive indices (CIs) of all selected clones from C49 strains were superior to the ancestor in acidic environment competitiveness. Based on the genome variation analysis and functional verification, we confirmed that loss of function in the phcA gene was associated with the acid fitness gain of R. solanacearum, which meant that the inactivation of the PhcA regulator caused by gene mutation mediated the population expansion of R. solanacearum when growing in an acidic stress environment. Moreover, the swimming motility of acid evolution strains and the phcA deletion mutant was significantly enhanced compared to CQPS-1. This work provided evidence for understanding the adaptive strategy of R. solanacearum to the long-term acidic environment.
Features and Functions of the Conserved Herpesvirus Tegument Protein UL11 and Its Binding Partners
Authors: Yang Linjiang , Wang Mingshu , Cheng Anchun , Yang Qiao , Wu Ying , Huang Juan , Tian Bin , Jia Renyong , Liu Mafeng , Zhu Dekang , Chen Shun , Zhao Xinxin , Zhang Shaqiu , Ou Xumin , Mao Sai , Gao Qun , Sun Di
Published: June 2022

The herpesvirus UL11 protein is encoded by the UL11 gene and is a membrane-anchored protein with multiple functions. In the last stage of viral replication, UL11 participates in the secondary envelopment process. It also plays a key role in primary envelopment, the transportation of newly assembled viral particles through cytoplasmic vesicles, and virion egress from the cell. UL11 is an important accessory protein and sometimes cooperates with other proteins that participate in virus-induced cell fusion. Cell fusion is necessary for cell-to-cell transmissions. This review summarizes the latest literature and discusses the roles of UL11 in viral assembly, primary and secondary envelopment, and cell-to-cell transmission to obtain a better understanding of the UL11 protein in the life cycle of herpesviruses and to serve as a reference for studying other viruses. Additionally, some recently discovered characteristics of UL11 are summarized.
Insight Into the Molecular Mechanisms Underpinning the Mycoremediation of Multiple Metals by Proteomic Technique
Authors: Dey Priyadarshini , Malik Anushree , Singh Dileep Kumar , Haange Sven-Bastiaan , von Bergen Martin , Jehmlich Nico
Published: June 2022

We investigated the fungus Aspergillus fumigatus PD-18 responses when subjected to the multimetal combination (Total Cr, Cd2+, Cu2+, Ni2+, Pb2+, and Zn2+) in synthetic composite media. To understand how multimetal stress impacts fungal cells at the molecular level, the cellular response of A. fumigatus PD-18 to 30 mg/L multimetal stress (5 mg/L of each heavy metal) was determined by proteomics. The comparative fungal proteomics displayed the remarkable inherent intracellular and extracellular mechanism of metal resistance and tolerance potential of A. fumigatus PD-18. This study reported 2,238 proteins of which 434 proteins were exclusively expressed in multimetal extracts. The most predominant functional class expressed was for cellular processing and signaling. The type of proteins and the number of proteins that were upregulated due to various stress tolerance mechanisms were post-translational modification, protein turnover, and chaperones (42); translation, ribosomal structure, and biogenesis (60); and intracellular trafficking, secretion, and vesicular transport (18). In addition, free radical scavenging antioxidant proteins, such as superoxide dismutase, were upregulated upto 3.45-fold and transporter systems, such as protein transport (SEC31), upto 3.31-fold to combat the oxidative stress caused by the multiple metals. Also, protein–protein interaction network analysis revealed that cytochrome c oxidase and 60S ribosomal protein played key roles to detoxify the multimetal. To the best of our knowledge, this study of A. fumigatus PD-18 provides valuable insights toward the growing research in comprehending the metal microbe interactions in the presence of multimetal. This will facilitate in development of novel molecular markers for contaminant bioremediation.
Scientists’ Assessments of Research on Lactic Acid Bacterial Bacteriocins 1990–2010
Authors: Martinenghi Laura D. , Leisner Jørgen J.
Published: June 2022

The antimicrobial activity of bacteriocins from lactic acid bacteria has constituted a very active research field within the last 35 years. Here, we report the results of a questionnaire survey with assessments of progress within this field during the two decades of the 1990s and the 2000s by 48 scientists active at that time. The scientists had research positions at the time ranging from the levels of Master’s and Ph.D. students to principal investigators in 19 Asian, European, Oceanian and North American countries. This time period was evaluated by the respondents to have resulted in valuable progress regarding the basic science of bacteriocins, whereas this was not achieved to the same degree with regard to their applications. For the most important area of application, food biopreservation, there were some success stories, but overall the objectives had not been entirely met due to a number of issues, such as limited target spectrum, target resistance, poor yield as well as economic and regulatory challenges. Other applications of bacteriocins such as enhancers of the effects of probiotics or serving as antimicrobials in human clinical or veterinary microbiology, were not evaluated as having been implemented successfully to any large extent at the time. However, developments in genomic and chemical methodologies illustrate, together with an interest in combining bacteriocins with other antimicrobials, the current progress of the field regarding potential applications in human clinical microbiology and food biopreservation. In conclusion, this study illuminates parameters of importance not only for R&D of bacteriocins, but also for the broader field of antimicrobial research.
RAB42 is a Potential Biomarker that Correlates With Immune Infiltration in Hepatocellular Carcinoma
Authors: Peng Hao , Du Xuanlong , Zhang Yewei
Published: June 2022

Backgrounds: Hepatocellular carcinoma (HCC) is a malignant cancer with high mortality. Previous studies have reported that RAB42 is associated with prognosis and progression in glioma. However, the role of RAB42 in HCC is still unknown. Therefore, we aimed to elucidate the value of RAB42 in the predicting prognosis of HCC, and its relationship with immune cells infiltration.

Methods: UALCAN, HCCDB, and MethSurv databases were used to examine the expression and methylation levels of RAB42 in HCC and normal samples. cBioPortal and MethSurv were used to identify genetic alterations and DNA methylation of RAB42, and their effect on prognosis. The correlations between RAB42 and the immune cells and cancer-associated fibroblasts infiltration were analyzed by TIMER, TISIDB, and GEPIA database. The LinkedOmics database was used to analyze the enriched pathways associated with genes co-expressed with RAB42. EdU assay was used to evaluate the proliferation ability of liver cancer cells, and transwell assay was used to detect the invasion and migration ability of liver cancer cells.

Results: The expression levels of RAB42 were increased in HCC tissues than that in normal tissues. Highly expressed RAB42 was significantly correlated with several clinical parameters of HCC patients. Moreover, increased RAB42 expression clearly predicted poor prognosis in HCC. Furthermore, multivariate Cox regression analysis showed that RAB42 was an independent prognostic factor in HCC. The RAB42 genetic alteration rate was 5%. RAB42 DNA methylation in HCC tissues was lower than that in normal tissues. Among the 7 DNA methylation CpG sites, two were related to the prognosis of HCC. The results of gene set enrichment analysis (GSEA) showed that RAB42 was associated with various immune cells and cancer-associated fibroblasts infiltration in HCC. Meanwhile, we found RAB42 methylation was strongly correlated with immune infiltration levels, immunomodulators, and chemokines. Experiments in vitro indicated that knockdown of RAB42 inhibited the proliferation, invasion, and migration of liver cancer cells.

Conclusions: Our study highlights the clinical importance of RAB42 in HCC and explores the effect of RAB42 on immune infiltration in the tumor microenvironment, and RAB42 may act as a pro-oncogene that promotes HCC progression.
Comprehensive Analyses of Ferroptosis-Related Alterations and Their Prognostic Significance in Glioblastoma
Authors: Tian Yuan , Liu Hongtao , Zhang Caiqing , Liu Wei , Wu Tong , Yang Xiaowei , Zhao Junyan , Sun Yuping
Published: June 2022

Background: This study was designed to explore the implications of ferroptosis-related alterations in glioblastoma patients.

Method: After obtaining the data sets CGGA325, CGGA623, TCGA-GBM, and GSE83300 online, extensive analysis and mutual verification were performed using R language-based analytic technology, followed by further immunohistochemistry staining verification utilizing clinical pathological tissues.

Results: The analysis revealed a substantial difference in the expression of ferroptosis-related genes between malignant and paracancerous samples, which was compatible with immunohistochemistry staining results from clinicopathological samples. Three distinct clustering studies were run sequentially on these data. All of the findings were consistent and had a high prediction value for glioblastoma. Then, the risk score predicting model containing 23 genes (CP, EMP1, AKR1C1, FMOD, MYBPH, IFI30, SRPX2, PDLIM1, MMP19, SPOCD1, FCGBP, NAMPT, SLC11A1, S100A10, TNC, CSMD3, ATP1A2, CUX2, GALNT9, TNFAIP6, C15orf48, WSCD2, and CBLN1) on the basis of “Ferroptosis.gene.cluster” was constructed. In the subsequent correlation analysis of clinical characteristics, tumor mutation burden, HRD, neoantigen burden and chromosomal instability, mRNAsi, TIDE, and GDSC, all the results indicated that the risk score model might have a better predictive efficiency.

Conclusion: In glioblastoma, there were a large number of abnormal ferroptosis-related alterations, which were significant for the prognosis of patients. The risk score-predicting model integrating 23 genes would have a higher predictive value.
Ferroptosis in Chronic Liver Diseases: Opportunities and Challenges
Authors: Zhou Xiaoxi , Fu Yadong , Liu Wei , Mu Yongping , Zhang Hua , Chen Jiamei , Liu Ping
Published: June 2022

Ferroptosis, an iron-dependent non-apoptotic cell death characterized by lipid peroxidation, is a cell death pathway discovered in recent years. Ferroptosis plays an important role in tumors, ischemia-reperfusion injury, neurological diseases, blood diseases, etc. Recent studies have shown the importance of ferroptosis in chronic liver disease. This article summarizes the pathological mechanisms of ferroptosis involved in System Xc−, iron metabolism, lipid metabolism, and some GPX4-independent pathways, and the latest research on ferroptosis in chronic liver diseases such as alcoholic liver disease, non-alcoholic fatty liver disease, liver fibrosis, hepatocellular carcinoma. In addition, the current bottleneck issues that restrict the research on ferroptosis are proposed to provide ideas and strategies for exploring new therapeutic targets for chronic liver diseases.
Exploring the Association of Leukocyte Telomere Length and Hearing Threshold Shifts of Adults in the United States
Authors: Long Lili , Meng Zhaoli , Jia Zhenchao , Tang Xinghua
Published: June 2022

Background

Although telomere length has a significant relationship with various age-related diseases, studies on its relationship with hearing status in adults are limited and equivocal. This study investigated the associations between mean telomere length (MTL) and low-, speech-, and high-frequency hearing threshold shifts of adults in the United States.

Methods

A total of 2,027 adults, aged 20-69 years, from the National Health and Nutrition Examination Surveys (NHANES, 1999–2002) were included in the analytic sample. The quantitative polymerase chain reaction method was used for the MTL assay, and MTL was expressed using the telomere-to-single copy gene (T/S) ratio. Hearing loss was defined as a pure-tone average (PTA) for the better ear at ≥ 20 dB HL at frequencies 500, 1,000, 2,000, and 4,000 Hz. Univariate and multivariate linear regression analyses and smooth curve fittings were conducted to evaluate the correlation between MTL and low-, speech-, and high-frequency hearing levels.

Results

The mean age of the participants was 40.60 ± 12.76 years, including 952 men (weighted, 48.67%) and 303 (weighted, 12.88%) participants with hearing loss. After adjusting for potential confounders in the multivariate linear regression model, the relationship between MTL and hearing thresholds was not statistically significant. Smooth curve fittings indicated a non-linear relationship between MTL and high-frequency PTA hearing threshold shifts. MTL was inversely related to high-frequency PTA to the turning point (T/S ratio = 0.82) (adjusted β−21.45, 95% CI −37.28, −5.62; P = 0.008). When the T/S ratio exceeded0.82, MTL was not associated with high-frequency PTA (adjusted β0.18, 95% CI −2.21, 2.57; P = 0.8809).

Conclusion

Our findings revealed that MTL was associated with high-frequency PTA hearing threshold shifts of adults in the United States in a non-linear manner.
Decreased Cerebral Amyloid-β Depositions in Patients With a Lifetime History of Major Depression With Suspected Non-Alzheimer Pathophysiology
Authors: Wu Kuan-Yi , Lin Kun-Ju , Chen Chia-Hsiang , Liu Chia-Yih , Wu Yi-Ming , Chen Cheng-Sheng , Yen Tzu-Chen , Hsiao Ing-Tsung
Published: June 2022

Cerebral amyloid-β (Aβ) depositions in depression in old age are controversial. A substantial proportion of individuals with late-life major depressive disorder (MDD) could be classified as having suspected non-Alzheimer’s disease pathophysiology (SNAP) by a negative test for the biomarker amyloid-β (Aβ−) but positive neurodegeneration (ND+). This study aimed to evaluate subthreshold Aβ loads in amyloid-negative MDD, particularly in SNAP MDD patients. This study included 46 amyloid-negative MDD patients: 23 SNAP (Aβ−/ND+) MDD and 23 Aβ−/ND− MDD, and 22 Aβ−/ND− control subjects. All subjects underwent 18F-florbetapir PET, FDG-PET, and MRI. Regions of interest (ROIs) and voxel-wise group comparisons were performed with adjustment for age, gender, and level of education. The SNAP MDD patients exhibited significantly deceased 18F-florbetapir uptakes in most cortical regions but not the parietal and precuneus cortex, as compared with the Aβ−/ND− MDD and control subjects (FDR correction, p < 0.05). No correlations of neuropsychological tests or depression characteristics with global cortical uptakes, but significant positive correlations between cognitive functions and adjusted hippocampal volumes among different groups were observed. The reduced Aβ depositions in the amyloid-negative MDD patients might be attributed mainly to the SNAP MDD patients. Our results indicated that meaningfully low amounts of subclinical Aβ might contain critical information on the non-amyloid-mediated pathogenesis.
The Mechanism and Function of Glia in Parkinson's Disease
Authors: Zhang Xinguo , Zhang Ruiqi , Nisa Awan Maher Un , Bai Jie
Published: June 2022

Parkinson's disease (PD) is a neurodegenerative disease that primarily affects elderly people. The mechanism on onset and progression of PD is unknown. Currently, there are no effective treatment strategies for PD. PD is thought to be the loss of midbrain dopaminergic neurons, but it has recently been discovered that glia also affects brain tissue homeostasis, defense, and repair in PD. The neurodegenerative process is linked to both losses of glial supportive-defensive functions and toxic gain of glial functions. In this article, we reviewed the roles of microglia, astrocytes, and oligodendrocytes in the development of PD, as well as the potential use of glia-related medications in PD treatment.
Advancements in the Quest to Map, Monitor, and Manipulate Neural Circuitry
Authors: Swanson Jessica L. , Chin Pey-Shyuan , Romero Juan M. , Srivastava Snigdha , Ortiz-Guzman Joshua , Hunt Patrick J. , Arenkiel Benjamin R.
Published: June 2022

Neural circuits and the cells that comprise them represent the functional units of the brain. Circuits relay and process sensory information, maintain homeostasis, drive behaviors, and facilitate cognitive functions such as learning and memory. Creating a functionally-precise map of the mammalian brain requires anatomically tracing neural circuits, monitoring their activity patterns, and manipulating their activity to infer function. Advancements in cell-type-specific genetic tools allow interrogation of neural circuits with increased precision. This review provides a broad overview of recombination-based and activity-driven genetic targeting approaches, contemporary viral tracing strategies, electrophysiological recording methods, newly developed calcium, and voltage indicators, and neurotransmitter/neuropeptide biosensors currently being used to investigate circuit architecture and function. Finally, it discusses methods for acute or chronic manipulation of neural activity, including genetically-targeted cellular ablation, optogenetics, chemogenetics, and over-expression of ion channels. With this ever-evolving genetic toolbox, scientists are continuing to probe neural circuits with increasing resolution, elucidating the structure and function of the incredibly complex mammalian brain.
Treatment Enhances Betweenness Centrality of Fronto-Parietal Network in Parkinson’s Patients
Authors: Liu Qing , Shi ZhongYan , Wang Kexin , Liu Tiantian , Funahashi Shintaro , Wu Jinglong , Zhang Jian
Published: June 2022

Previous studies have demonstrated a close relationship between early Parkinson’s disease and functional network abnormalities. However, the pattern of brain changes in the early stages of Parkinson’s disease has not been confirmed, which has important implications for the study of clinical indicators of Parkinson’s disease. Therefore, we investigated the functional connectivity before and after treatment in patients with early Parkinson’s disease, and further investigated the relationship between some topological properties and clinicopathological indicators. We included resting state-fMRI (rs-fMRI) data from 27 patients with early Parkinson’s disease aged 50–75 years from the Parkinson’s Disease Progression Markers Initiative (PPMI). The results showed that the functional connectivity of 6 networks, cerebellum network (CBN), cingulo_opercular network (CON), default network (DMN), fronto-parietal network (FPN), occipital network (OCC), and sensorimotor network (SMN), was significantly changed. Compared to before treatment, the main functional connections were concentrated in the CBN after treatment. In addition, the coefficients of these nodes have also changed. For betweenness centrality (BC), the FPN showed a significant improvement in treatment (p < 0.001). In conclusion, the alteration of functional networks in early Parkinson’s patients is critical for clarifying the mechanisms of early diagnosis of the disease.
Therapeutic Advances in Multiple Sclerosis
Authors: Yang Jennifer H. , Rempe Torge , Whitmire Natalie , Dunn-Pirio Anastasie , Graves Jennifer S.
Published: June 2022

Multiple sclerosis (MS) is an autoimmune disease affecting the central nervous system that causes significant disability and healthcare burden. The treatment of MS has evolved over the past three decades with development of new, high efficacy disease modifying therapies targeting various mechanisms including immune modulation, immune cell suppression or depletion and enhanced immune cell sequestration. Emerging therapies include CNS-penetrant Bruton's tyrosine kinase inhibitors and autologous hematopoietic stem cell transplantation as well as therapies aimed at remyelination or neuroprotection. Therapy development for progressive MS has been more challenging with limited efficacy of current approved agents for inactive disease and older patients with MS. The aim of this review is to provide a broad overview of the current therapeutic landscape for MS.
Circular RNA FUNDC1 for Prediction of Acute Phase Outcome and Long-Term Survival of Acute Ischemic Stroke
Authors: Zu Juan , Zuo Lei , Zhang Lin , Wang Zan , Shi Yachen , Gu Lihua , Zhang Zhijun
Published: June 2022

Circular RNAs (CircRNAs) have shown promising potential in the diagnosis and the prediction of outcomes of stroke. This study aimed to explore the potential value of circRNAs for identifying acute neurological deterioration and estimating long-term survival for acute ischemic stroke (AIS). One hundred healthy controls and 200 patients with AIS within 72 h were recruited, 140 of whom were admitted within 24 h after onset. CircRNA levels in peripheral blood were measured by quantitative polymerase chain reaction (qPCR). Compared to the controls, the levels of three circRNAs were significantly increased in three subgroups of patients, including large artery atherosclerosis (LAA) stroke, small artery occlusion (SAO) stroke, and cardioembolism (CE) stroke (all P < 0.001). Among, LAA stroke patients had higher levels of circular RNA FUNDC1 (circFUNDC1) compared to SAO stroke patients (P = 0.015). CircFUNDC1 levels were positively correlated with National Institutes of Health Stroke Scale (NIHSS) scores on the 7th day only in LAA patients (P = 0.048, r = 0.226). It should be noted that the levels of circFUNDC1 in patients with early neurological deterioration (END), admitted within 24 h after onset, were significantly higher than those without END (P = 0.013). In addition, circFUNDC1 levels positively correlated with baseline NIHSS scores (P = 0.016, r = 0.203) or the 7th day NIHSS scores (P = 0.001, r = 0.289) in patients within 24 h after onset. Importantly, after 18 months of follow-up, a significant difference was observed on survival Kaplan-Meier curves (P = 0.042) between AIS patients with low (below cut-off) or high circFUNDC1 levels (above cut-off). Circulating circFUNDC1 could be a potential biomarker for predicting acute-phase outcome and long-term survival in AIS.