bluuebunny/crossref_metadata_2025 huggingface dataset:
A Convex–Concave Procedure-Based Method for Optimal Power Flow of Offshore Wind Farms
Authors: Chen Yuwei , Li Hongke , Chen Qing , Xie Rui , Wang Xiaohe
Published: July 2022

In recent years, offshore wind farms have boomed all over the world. It is essential to manage the energy dispatch of the offshore wind power systems to reduce transmission losses. This article proposes an optimization method for the optimal power flow of offshore wind power systems based on the convex–concave procedure. First, the nonlinear variables in the power flow constraints of the offshore wind power system are relaxed with newly defined variables. Second, the non-convex constraints are reconstructed according to the variables’ characteristics so that the optimization method satisfies all constraints at the same time. Meanwhile, by applying the Taylor series expansion, the relaxation variables’ gaps are changed dynamically, and the convex relaxation is tightened to ensure the effectiveness of the proposed method. Finally, the feasibility of the relaxation and the optimized solution is verified by the simulation to realize the power optimization in the real offshore wind system.
Monitoring Surface Deformation Associated With Soil Erosion in Loess Plateau With an Improved Small Baseline Subset Interferometric Synthetic Aperture Radar Algorithm
Authors: Sun Qian , Zhang Heng , Huang Long , He Caihong
Published: July 2022

As a geomorphic process persistently occurring over the earth’s surface, soil erosion is one of the most serious environmental problems in the world nowadays, seriously threatening agriculture, natural resources, and ecosystem environments. Monitoring surface deformation associated with soil erosion will help to understand the dynamics of erosion process and the erosion mechanism. In this article, an improved small baseline subset interferometric synthetic aperture radar (SBAS-InSAR) technique is proposed to monitor the surface deformation over the wind-water erosion crisscross region in the Loess Plateau, China. In particular, a new deformation model considering both of the internal factors and external factors of soil erosion is introduced into the SBAS-InASR algorithm. The results show that the cumulative deformation is close to −200 mm during the investigated period. The deformation rate caused by precipitation is between −0.03 and 0.02 mm/mm. When the wind erosion factor changes by 1 unit, the deformation range is approximately −0.3–0.2 mm. Also, researchers found that the surface deformation is highly correlated to precipitation and wind. The root mean square errors (RMSEs) of the residual deformations estimated from the proposed model are smaller than those estimated from the conventional linear and period models, demonstrating that the proposed method is more suitable to model and analyze the surface deformation in wind-water erosion crisscross region.
Global patterns and drivers of coniferous leaf-litter decomposition in streams and rivers
Authors: Xiang Hongyong , Li Kun , Cao Lina , Zhang Zhenxing , Yang Haijun
Published: July 2022

Many streams and rivers are heterotrophic ecosystems that are highly dependent on cross-ecosystem subsidies such as leaf litter (LL). Terrestrial LL can be consumed by macroinvertebrates and microbes to fuel the detrital-based food webs in freshwaters. To date, our knowledge of LL decomposition in freshwaters is largely based on broadleaved LL, while the patterns and drivers of coniferous leaf-litter (CLL) decomposition in streams and rivers remain poorly understood. Here, we present a global investigation of CLL decomposition in streams and rivers by collecting data from 35 publications. We compared LL breakdown rates in this study with other global-scale studies (including conifers and broadleaved species), between evergreen and deciduous conifers, and between native and invasive conifers. We also investigated the climatic, geographic (latitude and altitude), stream physicochemical characteristics, and experimental factors (e.g., mesh size and experimental duration) in influencing CLL decomposition. We found that the following: (1) LL breakdown rates in this study were 18.5–28.8 and 4.9–16.8% slower than those in other global-scale studies when expressed as per day and per degree day, respectively. Conifer LL in coarse mesh bags, for evergreen and invasive conifers, decomposed 13.6, 10.3, and 10.8% faster than in fine mesh bags, for deciduous and native conifers, respectively; (2) CLL traits, stream physicochemical characteristics, and experimental factors explained higher variations in CLL decomposition than climatic and geographic factors; (3) CLL nutritional quality (N and P), water temperature, and experimental duration were better predictors of CLL decomposition than other predictors in categories of LL traits, stream physicochemical characteristics, and experimental factors, respectively; and (4) total and microbial-mediated CLL breakdown rates showed linear relationships with latitude, altitude, mean annual temperature, and mean annual precipitation. Our results imply that the replacement of native forests by conifer plantation would impose great impacts on adjacent freshwaters by retarding the LL processing rate. Moreover, future climate warming which is very likely to happen in mid- and high-latitude areas according to the IPCC 6th report would accelerate LL decomposition, with a potential consequence of food depletion for detritivores in freshwaters during hot summers.
Canary in the coal mine: Lessons from the Jarrah Forest suggest long-term negative effects of phosphorus fertilizer on biodiverse restoration after surface mining
Authors: Daws Matthew I. , Blackburn Cameron , Standish Rachel J. , Tibbett Mark
Published: July 2022

Despite nutrient enrichment having widely reported negative impacts on biodiversity, fertilizer is routinely applied inpostmining restoration to enhance plant growth and establishment. Focusing on surface mine restoration (predominately bauxite and mineral sands), we outline the long-term negative impacts of fertilizer, particularly phosphorus fertilizer, on plant community composition, species richness, fire fuel loads, and belowground impacts on nutrient-cycling. We draw from extensive research in south-western Australia and further afield, noting the geographical coincidence of surface mining, phosphorus impoverished soil and high plant biodiversity. We highlight the trade-offs between rapid plant-growth under fertilisation and the longer-term effects on plant communities and diversity. We note that the initial growth benefits of fertilisation may not persist in water-limited environments: growth of unfertilised forests can eventually match that of fertilised forest, throwing doubt on the premise that fertilisation is necessary at all.
Species distribution modeling allied with land-use reveal priority sites and species for palm (Arecaceae) conservation in Rio de Janeiro, Brazil
Authors: de Lima Thales Moreira , Portela Rita De Cássia Quitete , Mendes Eduardo Teles Barbosa , Oda Gabriela Akemi
Published: July 2022

Palms species (Arecaceae) are abundant in tropical forests and influence ecosystems in important ways. Moreover, they are a relevant feature in the Atlantic Forest biodiversity hotspot. In this study, we seek to better understand the distribution of palm richness in Rio de Janeiro state, Brazil, with the aim to support conservation decisions and actions. Maps for 15 palm species were generated through species distribution modeling and then stacked into a palm richness map, which was further combined with current land-use and protected area maps to generate a realistic portrayal of the current situation of Arecaceae in the state. Our results revealed an increasing inland-to-coast pattern of richness that matches the biogeographical subdivision of the Atlantic Forest. Considering the land-use information, the palm species potential distribution is drastically reduced, especially for some species which already have a restricted distribution in the state. We also identified the most relevant protected areas for the conservation of palms in the state and those which might have been overlooked in floristic inventories, thus requiring more detailed investigation. Moreover, we point out those species with few points, for which species distribution models could not be built, and argue that they are the ones more likely to be threatened by habitat loss and should be the focus of specimen collection and recording. Finally, we draw attention to a large medium-richness remnant located between two protected areas which probably functions as a connection between them and should be a priority area for conservation.
Identification of novel biomarkers in septic cardiomyopathy via integrated bioinformatics analysis and experimental validation
Authors: Lu Feng , Hu Feng , Qiu Baiquan , Zou Hongpeng , Xu Jianjun
Published: July 2022

Purpose:Septic cardiomyopathy (SCM) is an important world public health problem with high morbidity and mortality. It is necessary to identify SCM biomarkers at the genetic level to identify new therapeutic targets and strategies.

Method:DEGs in SCM were identified by comprehensive bioinformatics analysis of microarray datasets (GSE53007 and GSE79962) downloaded from the GEO database. Subsequently, bioinformatics analysis was used to conduct an in-depth exploration of DEGs, including GO and KEGG pathway enrichment analysis, PPI network construction, and key gene identification. The top ten Hub genes were identified, and then the SCM model was constructed by treating HL-1 cells and AC16 cells with LPS, and these top ten Hub genes were examined using qPCR.

Result:STAT3, SOCS3, CCL2, IL1R2, JUNB, S100A9, OSMR, ZFP36, and HAMP were significantly elevated in the established SCM cells model.

Conclusion:After bioinformatics analysis and experimental verification, it was demonstrated that STAT3, SOCS3, CCL2, IL1R2, JUNB, S100A9, OSMR, ZFP36, and HAMP might play important roles in SCM.
Application of 3D printing individualized guide plates in percutaneous needle biopsy of acetabular tumors
Authors: Wu Wen , Liu Siyu , Wang Lei , Wu Bing , Zhao Lulu , Jiang Wenbo , Dai Kerong , Hao Yongqiang , Fu Lingjie , Ai Songtao
Published: July 2022

Objective: The objective of the study was to investigate the effectiveness of applying the individualized guide plate which is based on digital image processing and 3D printing technology to percutaneous needle biopsy of periacetabular tumor.

Methods: From July 2017 to August 2019, 11 patients (5 males and 6 females, aged 13–70 years, mean 42.3 years) with acetabular tumors diagnosed by needle biopsy in our hospital were enrolled in this retrospective study. Preoperative CT and MRI enhancement examination were performed routinely, and the DICOM data were collected and imported into Medraw Print software. According to the specific anatomical morphology of acetabula, this study adopted the reverse calculation and direct design to print the individualized puncture guide plate using 3D printing technology. The puncture point and sampling approaches were determined by the guide plate morphology and the “double guide-hole and slideable groove” design. First, we evaluated the fitness of the 3D guide plate to the local anatomical structure, its assisted-puncture accuracy was estimated by imaging examinations, and postoperative complications were recorded. The accuracy of the needle biopsy pathological result was estimated with reference to that of the tumor resection.

Results: Our results showed that the 3D printing individualized guide plate matched the patients’ pelvic skin well, the puncture approach was consistent with the preoperative design, and no significant anatomical injuries including vascular and neural complications occurred after surgery. Nine patients’ (90%) biopsy results were consistent with their postoperative pathological results, and one patient gave up the tumor resection.

Conclusion: Based on digital image processing and 3D printing technology, the individualized guide plate can be used to guide the needle biopsy of acetabular tumors which makes the operation simpler and more precise.
BNT162b2 booster after heterologous prime-boost vaccination induces potent neutralizing antibodies and T cell reactivity against SARS-CoV-2 Omicron BA.1 in young adults
Authors: Seidel Alina , Zanoni Michelle , Groß Rüdiger , Krnavek Daniela , Erdemci-Evin Sümeyye , von Maltitz Pascal , Albers Dan P. J. , Conzelmann Carina , Liu Sichen , Weil Tatjana , Mayer Benjamin , Hoffmann Markus , Pöhlmann Stefan , Beil Alexandra , Kroschel Joris , Kirchhoff Frank , Münch Jan , Müller Janis A.
Published: July 2022

In light of the decreasing immune protection against symptomatic SARS-CoV-2 infection after initial vaccinations and the now dominant immune-evasive Omicron variants, ‘booster’ vaccinations are regularly performed to restore immune responses. Many individuals have received a primary heterologous prime-boost vaccination with long intervals between vaccinations, but the resulting long-term immunity and the effects of a subsequent ‘booster’, particularly against Omicron BA.1, have not been defined. We followed a cohort of 23 young adults, who received a primary heterologous ChAdOx1 nCoV-19 BNT162b2 prime-boost vaccination, over a 7-month period and analysed how they responded to a BNT162b2 ‘booster’. We show that already after the primary heterologous vaccination, neutralization titers against Omicron BA.1 are recognizable but that humoral and cellular immunity wanes over the course of half a year. Residual responsive memory T cells recognized spike epitopes of the early SARS-CoV-2 B.1 strain as well as the Delta and BA.1 variants of concern (VOCs). However, the remaining antibody titers hardly neutralized these VOCs. The ‘booster’ vaccination was well tolerated and elicited both high antibody titers and increased memory T cell responses against SARS-CoV-2 including BA.1. Strikingly, in this young heterologously vaccinated cohort the neutralizing activity after the ‘booster’ was almost as potent against BA.1 as against the early B.1 strain. Our results suggest that a ‘booster’ after heterologous vaccination results in effective immune maturation and potent protection against the Omicron BA.1 variant in young adults.
Intrinsic Folding Properties of the HLA-B27 Heavy Chain Revealed by Single Chain Trimer Versions of Peptide-Loaded Class I Major Histocompatibility Complex Molecules
Authors: Lenart Izabela , Truong Linh-Huyen , Nguyen Dinh Dung , Rasiukienė Olga , Tsao Edward , Armstrong Jonathan , Kumar Pankaj , McHugh Kirsty , Pereira Branca I. , Maan Balraj S. , Garstka Malgorzata A. , Bowness Paul , Blake Neil , Powis Simon J. , Gould Keith , Nesbeth Darren , Antoniou Antony N.
Published: July 2022

Peptide-loaded Major Histocompatibility Complex (pMHC) class I molecules can be expressed in a single chain trimeric (SCT) format, composed of a specific peptide fused to the light chain beta-2 microglobulin (β2m) and MHC class I heavy chain (HC) by flexible linker peptides. pMHC SCTs have been used as effective molecular tools to investigate cellular immunity and represent a promising vaccine platform technology, due to their intracellular folding and assembly which is apparently independent of host cell folding pathways and chaperones. However, certain MHC class I HC molecules, such as the Human Leukocyte Antigen B27 (HLA-B27) allele, present a challenge due to their tendency to form HC aggregates. We constructed a series of single chain trimeric molecules to determine the behaviour of the HLA-B27 HC in a scenario that usually allows for efficient MHC class I molecule folding. When stably expressed, a pMHC SCT incorporating HLA-B27 HC formed chaperone-bound homodimers within the endoplasmic reticulum (ER). A series of HLA-B27 SCT substitution mutations revealed that the F pocket and antigen binding groove regions of the HLA-B27 HC defined the folding and dimerisation of the single chain complex, independently of the peptide sequence. Furthermore, pMHC SCTs can demonstrate variability in their association with the intracellular antigen processing machinery.
Efficacy and Safety of Neoadjuvant Monoimmunotherapy With PD-1 Inhibitor for dMMR/MSI⁃H Locally Advanced Colorectal Cancer: A Single-Center Real-World Study
Authors: Zhang Xuan , Yang Renfang , Wu Tao , Cai Xinyi , Li Guoyu , Yu Kun , Li Yong , Ding Rong , Dong Chao , Li Jinsha , Hu Ruixi , Feng Qing , Li Yunfeng
Published: July 2022

Objective

To explore the efficacy and safety of single-agent programmed cell death protein-1 (PD-1) inhibitor in the neoadjuvant treatment of patients with mismatch repair-deficient (dMMR) or microsatellite instability-high (MSI-H) locally advanced colorectal cancer (LACRC) through single-center large⁃sample analysis based on real⁃world data in China.

Methods

This study was a retrospective, single-center, case series study. 33 colorectal cancer (CRC) patients with clinical stage of T3~4N0~2M0 treated in Yunnan Cancer Hospital from June 2019 to June 2021 were analyzed retrospectively. Among them, 32 patients were dMMR or MSI-H or both dMMR and MSI-H, and one patient was both dMMR and microsatellite stability (MSS) (excluded in the final analysis). All 32 patients received neoadjuvant immunotherapy (nIT) with single-agent PD⁃1 inhibitor.

Results

Among the 32 patients, 8 (25%) were locally advanced rectal cancer (LARC) and 24 (75%) were locally advanced colon cancer (LACC); 4 (12.55%) were stage II and 28 (87.5%) were stage III. The median number of cycles of 32 patients with dMMR/MSI-H LACRC receiving nIT with single-agent PD-1 blockade was 6 (4~10), and the median number of cycles to achieve partial response (PR) was 3 (2~4). Among them, three LARC patients achieved clinical complete response (cCR) and adopted the watch-and-wait (W&W) strategy. The objective response rate (ORR) of the other 29 patients with radical surgery was 100% (29/29), the pathological response rate was 100% (29/29), the rate of major pathological response (MPR) was 86.2% (25/29), and the rate of pathological complete response (pCR) was 75.9% (22/29). The incidence of immune-related adverse events (irAEs) in 32 patients during nIT was 37.5% (12/32), while the incidence of irAEs in 22 patients with operation during adjuvant immunotherapy was 27.3% (6/22), all of which were grade 1~2. No grade 3 or above irAEs were occured. The median time from the last nIT to surgery was 27 (16~42) days. There were no delayed radical resection due to irAEs in these patients. All 29 patients achieved R0 resection. The incidence of surgical-related adverse events (srAEs) in perioperative period was 10.3% (3/29).

Conclusions

Neoadjuvant monoimmunotherapy with PD-1 inhibitor has favorable ORR and pCR rate, and relatively low incidences of irAEs and srAEs for patients with dMMR/MSI-H LACRC, suggesting that this nIT regimen of single-agent PD-1 inhibitor is significantly effective and sufficiently safe.
Dysregulation of Subcutaneous White Adipose Tissue Inflammatory Environment Modelling in Non-Insulin Resistant Obesity and Responses to Omega-3 Fatty Acids – A Double Blind, Randomised Clinical Trial
Authors: Fisk Helena L. , Childs Caroline E. , Miles Elizabeth A. , Ayres Robert , Noakes Paul S. , Paras-Chavez Carolina , Antoun Elie , Lillycrop Karen A. , Calder Philip C.
Published: July 2022

Background

Obesity is associated with enhanced lipid accumulation and the expansion of adipose tissue accompanied by hypoxia and inflammatory signalling. Investigation in human subcutaneous white adipose tissue (scWAT) in people living with obesity in which metabolic complications such as insulin resistance are yet to manifest is limited, and the mechanisms by which these processes are dysregulated are not well elucidated. Long chain omega-3 polyunsaturated fatty acids (LC n-3 PUFAs) have been shown to modulate the expression of genes associated with lipid accumulation and collagen deposition and reduce the number of inflammatory macrophages in adipose tissue from individuals with insulin resistance. Therefore, these lipids may have positive actions on obesity associated scWAT hypertrophy and inflammation.

Methods

To evaluate obesity-associated tissue remodelling and responses to LC n-3 PUFAs, abdominal scWAT biopsies were collected from normal weight individuals and those living with obesity prior to and following 12-week intervention with marine LC n-3 PUFAs (1.1 g EPA + 0.8 g DHA daily). RNA sequencing, qRT-PCR, and histochemical staining were used to assess remodelling- and inflammatory-associated gene expression, tissue morphology and macrophage infiltration.

Results

Obesity was associated with scWAT hypertrophy (P < 0.001), hypoxia, remodelling, and inflammatory macrophage infiltration (P = 0.023). Furthermore, we highlight the novel dysregulation of Wnt signalling in scWAT in non-insulin resistant obesity. LC n-3 PUFAs beneficially modulated the scWAT environment through downregulating the expression of genes associated with inflammatory and remodelling pathways (P <0.001), but there were altered outcomes in individuals living with obesity in comparison to normal weight individuals.

Conclusion

Our data identify dysregulation of Wnt signalling, hypoxia, and hypertrophy, and enhanced macrophage infiltration in scWAT in non-insulin resistant obesity. LC n-3 PUFAs modulate some of these processes, especially in normal weight individuals which may be preventative and limit the development of restrictive and inflammatory scWAT in the development of obesity. We conclude that a higher dose or longer duration of LC n-3 PUFA intervention may be needed to reduce obesity-associated scWAT inflammation and promote tissue homeostasis.

Clinical Trial Registration

www.isrctn.com, identifier ISRCTN96712688.
Antibodies targeting Candida albicans Als3 and Hyr1 antigens protect neonatal mice from candidiasis
Authors: Singh Shakti , Nabeela Sunna , Barbarino Ashley , Ibrahim Ashraf S. , Uppuluri Priya
Published: July 2022

Pre-term infants in neonatal intensive care units are vulnerable to fungal sepsis. In this patient population, Candida albicans remains the predominant fungal pathogen causing high morbidity and mortality, despite antifungal therapy. Thus, new preventative/therapeutic strategies against neonatal candidiasis are needed. Previously, we have reported that vaccination with recombinant forms of the C. albicans N-termini of the cell wall proteins Als3 (rAls3p-N) and Hyr1 (rHyr1p-N) protected adult mice from disseminated candidiasis. Further, in a Phase 1b/2a NDV-3A (an rAls3p-N formulated with alum) protected women from recurrent vulvovaginal candidiasis, with anti-Als3p IgG2 isotype being a biomarker for efficacy. Here, we performed a proof of concept study to evaluate if anti-Als3p or anti-Hyr1p antibodies are important for prevention of disseminated candidiasis in neonates. Als3 and Hyr1 antigens when adjuvanted with complete Freund’s adjuvant (CFA)/incomplete Freund’s adjuvant (IFA) induced a robust antibody response with a ten-fold higher titer of IgG2, than attained by either antigen formulated with alum. Transplacental transfer of these antibodies significantly reduced fungal burden in the kidneys of mice pups, and adoptive transfer of vaccinated mothers’ sera into pups displayed similar levels of protection. Neutrophils were found important for this efficacy. Finally, anti-Hyr1 antisera potentiated the activity of fluconazole in protecting from C. albicans infection. Our current studies are the first in the field to emphasize the importance of anti-Als3 and anti-Hyr1 antibodies in preventing neonatal candidiasis. Considering that Candida infections in low birthweight infants is a lethal infection, active and passive vaccination strategies using these antigens could have profound clinical relevance.
Mitochondrial impairment and repair in the pathogenesis of systemic lupus erythematosus
Authors: Zhao Like , Hu Xianda , Xiao Fei , Zhang Xuan , Zhao Lidan , Wang Min
Published: July 2022

Nucleic acid autoantibodies, increase type I interferon (IFN-α) levels, and immune cell hyperactivation are hallmarks of systemic lupus erythematosus (SLE). Notably, immune cell activation requires high level of cellular energy that is predominately generated by the mitochondria. Mitochondrial reactive oxygen species (mROS), the byproduct of mitochondrial energy generation, serves as an essential mediator to control the activation and differentiation of cells and regulate the antigenicity of oxidized nucleoids within the mitochondria. Recently, clinical trials on normalization of mitochondrial redox imbalance by mROS scavengers and those investigating the recovery of defective mitophagy have provided novel insights into SLE prophylaxis and therapy. However, the precise mechanism underlying the role of oxidative stress-related mitochondrial molecules in skewing the cell fate at the molecular level remains unclear. This review outlines distinctive mitochondrial functions and pathways that are involved in immune responses and systematically delineates how mitochondrial dysfunction contributes to SLE pathogenesis. In addition, we provide a comprehensive overview of damaged mitochondrial function and impaired metabolic pathways in adaptive and innate immune cells and lupus-induced organ tissues. Furthermore, we summarize the potential of current mitochondria-targeting drugs for SLE treatment. Developing novel therapeutic approaches to regulate mitochondrial oxidative stress is a promising endeavor in the search for effective treatments for systemic autoimmune diseases, particularly SLE.
A genome-wide association analysis: m6A-SNP related to the onset of oral ulcers
Authors: Wu Zhuoxuan , Lin Weimin , Yuan Quan , Lyu Mingyue
Published: July 2022

Oral ulcers are one of the most common inflammatory diseases on oral mucosa that have obvious impacts on patients. Studies have shown that N6-methyladenosine (m6A) RNA transcription modification may be involved in the development of various inflammatory responses, and whether the pathogenesis of oral ulcers is related to m6A is unclear. This study aims to identify how m6A-related single nucleotide polymorphisms (m6A-SNPs) may affect oral ulcers. The UKBB dataset containing 10,599,054 SNPs was obtained from the GWAS database using the keyword “oral ulcer” and compared with the M6AVar database containing 13,703 m6A-SNPs.With 7,490 m6A-SNPs associated with oral ulcers identified, HaploReg and RegulomeDB were used for further functional validation and differential gene analysis was performed using the GEO database dataset GSE37265. A total of 7490 m6A-SNPs were detected in this study, 11 of which were related to oral ulcers (p<5E-08), and all of these SNPs showed eQTL signals. The SNP rs11266744 (p=2.00E-27) may regulate the expression of the local gene CCRL2, thereby participating in the pathogenesis of oral ulcers. In summary, by analyzing genome-wide association studies, this study showed that m6A modification may be involved in the pathogenesis of oral ulcers and CCRL2 may be the targeted gene.
The immunomodulatory function of adenosine in sepsis
Authors: Zhang Teng , Yu-Jing Li , Ma Tao
Published: July 2022

Sepsis is an unsolved clinical condition with a substantial mortality rate in the hospital. Despite decades of research, no effective treatments for sepsis exists. The role of adenosine in the pathogenesis of sepsis is discussed in this paper. Adenosine is an essential endogenous molecule that activates the A1, A2a, A2b, and A3 adenosine receptors to regulate tissue function. These receptors are found on a wide range of immune cells and bind adenosine, which helps to control the immune response to inflammation. The adenosine receptors have many regulatory activities that determine the onset and progression of the disease, which have been discoveredviathe use of animal models. A greater understanding of the role of adenosine in modulating the immune system has sparked hope that an adenosine receptor-targeted treatment may be used one day to treat sepsis.
Identification and validation of an immune signature associated with EMT and metabolic reprogramming for predicting prognosis and drug response in bladder cancer
Authors: Zhang Zhao , Yu Yongbo , Li Peng , Wang Meilan , Jiao Wei , Liang Ye , Niu Haitao
Published: July 2022

Background

Epithelial-mesenchymal transition (EMT), one leading reason of the dismal prognosis of bladder cancer (BLCA), is closely associated with tumor invasion and metastasis. We aimed to develop a novel immune−related gene signature based on different EMT and metabolic status to predict the prognosis of BLCA.

Methods

Gene expression and clinical data were obtained from TCGA and GEO databases. Patients were clustered based on EMT and metabolism scores calculated by ssGSEA. The immune-related differentially expressed genes (DEGs) between the two clusters with the most obvious differences were used to construct the signature by LASSO and Cox analysis. Time-dependent receiver operating characteristic (ROC) curves and Kaplan–Meier curves were utilized to evaluate the gene signature in training and validation cohorts. Finally, the function of the signature genes AHNAK and NFATC1 in BLCA cell lines were explored by cytological experiments.

Results

Based on the results of ssGSEA, TCGA patients were divided into three clusters, among which cluster 1 and cluster 3 had completely opposite EMT and metabolic status. Patients in cluster 3 had a significantly worse clinical prognosis than cluster 1. Immune-related DEGs were selected between the two clusters to construct the predictive signature based on 14 genes. High-risk patients had poorer prognosis, lower proportions of CD8+ T cells, higher EMT and carbohydrate metabolism, and less sensitivity to chemotherapy and immunotherapy. Overexpression of AHNAK or NFATC1 promoted the proliferation, migration and invasion of T24 and UMUC3 cells. Silencing ANHAK or NFATC1 could effectively inhibit EMT and metabolism in T24 and UMUC3 cells.

Conclusion

The established immune signature may act as a promising model for generating accurate prognosis for patients and predicting their EMT and metabolic status, thus guiding the treatment of BLCA patients.
Evaluation of dietary fish meal analog with or without supplementation of natural feed additives as the substitute of fish meal in juvenile Japanese eel, Anguilla japonica
Authors: Bae Jinho , Lee Seunghyung , Moniruzzaman Mohammad , Hamidoghli Ali , Choi Wonsuk , Lee Seunghan , Min Taesun , Kim Shin-Kwon , Bai Sungchul C.
Published: July 2022

We investigated the nine experimental diets containing fish meal (FM) and/or fish meal analog (FMA) as the major source of animal protein to determine the optimum FMA level as the substitute of FM protein in the diet of juvenile Japanese eel. In addition, two natural feed additives such as Song-Gang stone (SG) and Yucca meal (YM) were supplemented in the diet to evaluate their efficacy as the immunostimulants. The diets are as follows: 100% FM + 0% FMA in diet (FMA0), 90% FM + 10% FMA in diet (FMA10), 80% FM + 20% FMA in diet (FMA20), 70% FM + 30% FMA in diet (FMA30), 60% FM + 40% FMA in diet (FMA40), FMA0 + 0.4% SG (FMA0SG), FMA0 + 0.1% YM (FMA0YM), FMA20 + 0.4% SG (FMA20SG), and FMA20 + 0.1% YM (FMA20YM). Nine groups of Japanese eel each with three replicates were distributed (initial weight of 9 ± 0.2 g) in rectangular tanks receiving flow through water. Each group of the treatment consisted with 15 fish and fed one of the diets for 8 weeks. At the end of the feeding trial, fish fed with the FMA0 and FMA10 diets showed no significant differences in weight gain (WG), specific growth rate (SGR), feed efficiency (FE), and protein efficiency ratio (PER). Meanwhile, fish fed with FMA20, FMA30, and FMA40 diets showed significantly lower WG, SGR, FE, and PER than the fish fed with the FMA0 (control) diet. In addition, there were no significant differences among fish fed with the SG- and YM-supplemented diet groups. However, lysozyme activities in fish fed with the FMA10, FMA20, FMA30, and FMA40 were significantly lower than the fish fed with the FMA0SG, FMA0YM, FMA20SG, and FMA20YM diets. After 7 days of injection with V. Anguillarum, cumulative survival rates of fish fed with the FMA0SG and FMA0YM diets were significantly higher than the FMA0 diet group. The results revealed that the FMA could replace up to 10% of FM as a protein source in the diet of Japanese eel and both of the natural feed additives (SG and YM) could improve replacing rates of FMA from 10% to 20% without compromising growth and health status of fish.
Polystyrene microplastics alter bioaccumulation, and physiological and histopathological toxicities of cadmium in the polychaete Perinereis aibuhitensis
Authors: Cong Yi , Lou Yadi , Zhao Huan , Li Zhaochuan , Zhang Mingxing , Jin Fei , Wang Ying , Wang Juying
Published: July 2022

Heavy metal (HM) pollution in the marine environment has been of concern for decades. The potential impact of HMs carried by emerging marine pollutants such as microplastics (MPs) has attracted attention only in recent years. In this study, we investigated the single and combined chronic toxic effects (growth, burrowing behavior, and histopathology) of cadmium (Cd, three concentrations of low, medium, and high) and polystyrene (PS) microspheres (1 μm, 10 μg/L) on the coastal polychaete Perinereis aibuhitensis. Cd bioaccumulation under two exposure scenarios was also explored. Our results showed that Cd and PS did not affect worm growth for single or combined exposure, while 13.08 μg/L of Cd (CdL) alone significantly decreased the burrowing time of P. aibuhitensis in sediment. The presence of PS mitigated the hormetic effect of Cd on worm burrowing behavior, and this influence was Cd concentration-related. Cd body burdens in worms exposed to the medium and high Cd concentrations (CdM and CdH) were significantly greater than those of control worms with or without the presence of PS. In addition, Cd bioaccumulation was significantly higher with the coexistence of PS than those of Cd alone at the CdL and CdM groups. Histopathological analyses demonstrated a trend of epidermal and intestinal damages for single Cd/PS and their combined groups, and the contribution of PS-MPs should not be ignored. Our results indicate that the toxic effects and bioaccumulation pattern of Cd could be altered with the presence of PS-MPs for P. aibuhitensis, especially at environmentally relevant concentrations.
Seasonal soil-plant nitrogen dynamics of a cordgrass salt marsh in response to coastal embankments in Eastern China
Authors: Qin Ge , Feng Hongyu , Zhao Hui , Xia Lu , Yang Wen , Zhao Yongqiang , Jeelani Nasreen , An Shuqing
Published: July 2022

The effects of coastal embankments on nitrogen (N) cycling in the Spartina alterniflora salt marsh have been extensively reported. However, it remains unclear effects of the embankment on the sizes of diverse N subpools in the plant-soil subsystems year-round. This study examined seasonal changes in various N subpools of plant subsystems; soil subsystems [e.g., soil organic N (SON), recalcitrant organic N (RON), labile organic N (LON), dissolved organic N (DON), ammonium N(NH+4 N), and nitrate N(NO3-N)]; N mineralization [e.g., soil net ammonification (RA) and nitrification (RN) rate]; and immobilization [e.g., microbial biomass N (MBN)] in embanked and adjacent S. alterniflora natural salt marshes on the coast of Eastern China. The embankment significantly reduced the litter N storage by 62.7–71.8% over the four seasons and decreased the root N storage by 53.0% during winter. The SON, LON, RON, and N H +4 N concentrations declined significantly by 43.0–60.2%, 35.8–64.8%, 44.9–59.0%, and 20.8–42.2%, respectively, over the four seasons following the embankment construction. Furthermore, the embankment dramatically reduced the DON concentrations by 21.9% in spring, 14.6% in summer, and 10.4% in winter, while notably diminishing the NO3 N concentrations by 33.4% in autumn and 44.9% in winter, and the RA and RN in spring and summer. However, the embankment clearly increased the MBN concentrations during summer and autumn, the NO3 N concentrations in spring, and the RA and RN in winter at different levels. Due to the decreased soil N inputs from plants, the embankment decreased the organic and inorganic N subpools every season to varying degrees, except for the NO3 N concentration in spring. We suggest that the decreased soil salinity following embankment establishment might increase the uptake of ions by microbes, while stimulating the production of MBN. Ultimately, the NO3 N and DON were two vital N sources for S. alterniflora, and plants absorbed N from the soil to promote their biomass, as well as N concentration and storage. This study is conducive toward understanding the mechanisms behind the effects of coastal embankments on the N transfer among various N subpools in the plant and soil systems.
IFN-γ/Doxorubicin Complex Nanoparticles for Enhancing Therapy in the Context of Human Ovarian Carcinoma
Authors: Yi Rongyuan , Lv Wanwan , Zheng Shan , Zhang Ningyu , Zhang Yuheng , Yang Kai , Huang Tuo , Yang Yanning , Chu Hui , Chen Jian
Published: July 2022

The cytokine interferon gamma (IFN-γ) and doxorubicin mono-therapy has been approved by the Food and Drug Administration (FDA) for the treatment of tumors. The importance of IFN-γ in the immune system lies in its immunomodulatory effects, and the importance of doxorubicin in antitumor therapy lies in inhibiting RNA and DNA synthesis. In this work, the role of IFN-γ in the antitumor activity in combination with doxorubicin was investigated. Meanwhile, IFN-γ was used as a vehicle to load doxorubicin over immunotherapy and chemotherapy for synergistic therapy. IFN-γ/doxorubicin complex nanoparticles were prepared by a fusion method with a size of approximately 13 nm and a low polydispersity index. The doxorubicin release profile was analyzed with different pH ranges, and it showed an enhanced release in acidic pH. The ability of IFN-γ/doxorubicin complex nanoparticles to induce human ovarian carcinoma cell (Skov 3) apoptosis was evaluated by the cytotoxicity test. The cellular uptake of IFN-γ/doxorubicin complex nanoparticles was time-dependent, and the IFN-γ/doxorubicin complex nanoparticles showed a higher apoptosis efficiency than free doxorubicin by flow cytometry analysis and fluorescence imaging. This work bridged IFN-γ with doxorubicin to utilize their potential for antitumor activities, opening new avenues for their use in clinical settings.
Anti-citrullinated Protein Antibody Generation, Pathogenesis, Clinical Application, and Prospects
Authors: Liu Jiaxi , Gao Jinfang , Wu Zewen , Mi Liangyu , Li Na , Wang Yajing , Peng Xinyue , Xu Ke , Wu Fengping , Zhang Liyun
Published: July 2022

Anti-citrullinated protein antibodies (ACPAs) are autoantibodies commonly observed in patients with rheumatoid arthritis (RA). Currently, most of the mechanisms of ACPA formation and bone destruction are well-understood, however, some unknown mechanisms still exist. There have been many new advances in ACPA-related clinical applications and targeted therapies. However, the existence of different ACPA subtypes is a limitation of targeted therapy. Herein, we present an overview of the process of ACPA generation, the underlying pathogenesis, and relevant clinical application and prospects.
Clinical, epidemiological, and laboratory prognostic factors in patients with leprosy reactions: A 10-year retrospective cohort study
Authors: Antunes Douglas Eulálio , Santos Diogo Fernandes , Lima Mayara Ingrid Sousa , Caixeta Larissa Pereira , Correa Meydson Benjamin Carvalho , Moraes Emilly Caroline dos Santos , Conceição Natalia Carine Almeida , Goulart Luiz Ricardo , Goulart Isabela Maria Bernardes
Published: July 2022

Introduction

Leprosy reactions, the main cause of neural damage, can occur up to 7 years after starting multidrug therapy. We aimed to approach the prognostic factors that may influence the leprosy reactions over the follow-up time.

Methods

Retrospective cohort study, encompassing 10 years of data collection, composed of 390 patients, divided into 201 affected by reactions and 189 reaction-free individuals. Epidemiological, clinical, and laboratory variables were approached as prognostic factors associated with leprosy reactions. The association among variables was analyzed by a binomial test and survival curves were compared by the Kaplan-Meier and Cox proportional-hazards regression.

Results

51.5% (201/390) of patients were affected by leprosy reactions. These immunological events were associated with lepromatous leprosy (16.2%; 63/390; p < 0.0001) and multibacillary group (43%; 169/390; p < 0.0001). This study showed that survival curves for the prognostic factor anti-PGL-I, comparing positive and negative cases at diagnosis, differed in relation to the follow-up time (Log Rank: p = 0.0760; Breslow: p = 0.0090; Tarone-Ware: p = 0.0110). The median survival times (time at which 50% of patients were affected by leprosy reactions) were 5 and 9 months for those reactional cases with negative (26/51) and positive serology (75/150), respectively. The time-dependent covariates in the cox proportional-hazards regression showed anti-PGL-I as the main prognostic factor to predict leprosy reactions (hazard ratio=1.91; p = 0.0110) throughout the follow-up time.

Conclusions

Finally, these findings demonstrated that anti-PGL-I serology at diagnosis is the most important prognostic factor for leprosy reactions after starting multidrug therapy, thus enabling prediction of this immunological event.
The Potential Role of Vitamin D in the Development of Tuberculosis in Chinese Han Population: One Case-Control Study
Authors: Cai Li , Hou Shuangyi , Huang Yadong , Liu Shuang , Huang Xibao , Yin Xiaoxv , Jiang Nan , Tong Yeqing
Published: July 2022

Background and aims:

Spinal serum 25-hydroxyvitamin D [25[OH]D] status plays an important role in mediating innate immune responses by acting as a cofactor for induction of antimycobacterial activity and is thus involved in the development of Tuberculosis (TB). Results reported regarding the association of vitamin D with TB remained controversial. We aimed to identify any common association between 25[OH]D status and TB in the Chinese Han population.

Methods

280 subjects (70 TB patients and 210 matched controls) were recruited. TB cases were diagnosed based on the presence of acid-fast bacilli on smears from sputum and MTB isolation. Healthy controls were randomly selected from four local community-based populations. 25[OH]D was detected by electrochemiluminescence immunoassay (ECLIA) on Roche Elecsys before the initial treatment. Multivariable logistic regression analysis was used to examine the association of Vitamin D with TB.

Results

There was no significant difference in the serum vitamin D level between total cases and controls, but we found a strong tendency toward a higher serum vitamin D level in male population (P < 0.05) with TB but not in females. High serum vitamin D increased the risk of TB in the Chinese Han population (OR = 1.035, 95%CI: 1.001–1.070, P < 0.05). The serum vitamin D level was significantly decreased with age increasing in cases and controls (all P < 0.001).

Conclusions

High serum vitamin D may be an independent risk factor for TB in the Chinese Han population.
Ventilator integrated polygraphy for patients using non-invasive ventilation; Case report
Authors: López-Brull Helena , Mira-Padilla Estefanía , Hussein Sarah , Guerder Antoine , Wozniak Estelle , Esteban-Ronda Violeta , Gonzalez-Bermejo Jésus
Published: July 2022

The COVID-19 pandemic has meant that home respiratory services have needed to be reviewed. As a result, new solutions have been developed and implemented. The Vivo 45™ (Breas, Mölnlycke, Sweden) is a ventilator that offers clinicians the ability to attach effort belts to the device. This allows the clinician to review ventilator traces with the addition of thoracic and abdominal activity. This allows more flexibility for the monitoring of patients at home and in the hospital, with detection of patient ventilator asynchrony (PVA). Decreasing PVA may improve ventilator adherence and increased ventilator usage improves survival. We report three cases of patients undergoing overnight monitoring with the Vivo 45™, highlighting the benefit of ventilator integrated polygraphy. In our three cases we demonstrate a simple safe tool to optimize NIV treatment over one or two-night recordings using ventilator downloaded software with the addition of effort belts and pulse oximetry without involving more than one machine and without hospitalization in a sleep unit.
Mild reinfection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Delta variant: First case report from Indonesia
Authors: Isnaini Naniek , Mardian Yan , Lokida Dewi , Budiono Fajar , Butar-butar Deni P. , Arlinda Dona , Salim Gustiani , Kosasih Herman , Wulan Wahyu Nawang , Perodin Jacqueline , Neal Aaron , Lane H. Clifford , Karyana Muhammad
Published: July 2022

Background

Reinfection with SARS-CoV-2 has been well documented, yet little is known about the degree of protection a previous infection provides against reinfection, especially against Variants of Concern (VOC).

Case presentation

Here we describe a case of an unvaccinated 49-year-old man who experienced two sequential SARS-CoV-2 infections with two different variants, as evidenced by genomic sequencing. The first episode was caused by the Pango lineage B.1.466.2 and resulted in severe COVID-19 with 5 days in an intensive care unit (ICU). The second episode occurred approximately 6 months later, during the Delta surge in Indonesia. Genomic analysis showed that the second infection was caused by the Delta variant (Pango lineage B.1.617.2) and resulted in mild disease that did not require hospitalization. No SARS-CoV-2 nucleic acid was detected between the two episodes, but both binding and neutralizing antibodies to SARS-CoV-2 were detected prior to the reinfection, with the second infection leading to an increase in the levels of antibody.

Conclusion

We confirmed that the patient experienced a reinfection instead of persistent viral shedding from the first infection based on epidemiological, clinical, serological, and genomic analyses. Our case supports the hypothesis that SARS-CoV-2 reinfection may occur once antibody titers decrease or following the emergence of a new variant. The milder presentation in the patient’s second infection deserves further investigation to provide a clear picture of the role of post-infection immunity in altering the course of subsequent disease.
Immunomodulatory mechanisms of abatacept: A therapeutic strategy for COVID-19
Authors: Yang Dinglong , Li Hetong , Chen Yujing , Ren Weiping , Dong Mingjie , Li Chunjiang , Jiao Qiang
Published: July 2022

Coronavirus disease 2019 (COVID-19) caused by coronavirus-2 (SARS-CoV-2) infection has rapidly spread throughout the world and become a major threat to human beings. Cytokine storm is a major cause of death in severe patients. Abatacept can suppress cytokines used as antirheumatic drugs in clinical applications. This study analyzed the molecular mechanisms of abatacept treatment for COVID-19. Differentially expressed genes (DEGs) were identified by analyzing expression profiling of abatacept treatment for rheumatoid arthritis (RA) patients and SARS-CoV-2 infection patients. We found that 59 DEGs were upregulated in COVID-19 patients and downregulated following abatacept treatment. Gene set enrichment analysis (GSEA) and Gene Ontology (GO) analysis showed that immune and inflammatory responses were potential regulatory mechanisms. Moreover, we verified 8 targeting genes and identified 15 potential drug candidates for the treatment of COVID-19. Our study illustrated that abatacept could be a promising property for preventing severe COVID-19, and we predicted alternative potential drugs for the treatment of SARS-CoV-2 infection.