bluuebunny/crossref_metadata_2025 huggingface dataset:
Can Environmental Information Disclosure Improve Urban Green Economic Efficiency? New Evidence From the Mediating Effects Model
Authors: Lin Shihai
Published: July 2022

Environmental information disclosure is one of the important ways to realize urban sustainable development. This study explores the transmission mechanism between environmental information disclosure and urban green economic efficiency (UGEE) and solves the “black box” system between them. In this method, first, the urban green economic efficiency is calculated using the data envelopment analysis model with undesirable output. Second, the panel data model and the mediating effects model are employed to test the impact of environmental information disclosure on urban green economic efficiency and the possible mediating variables. The main conclusions of this study are as follows: 1) Environmental information disclosure significantly improves urban green economic efficiency, and reducing industrial pollutant emission and improving technological innovation are the significant transmission mechanisms. (2) There is a U-shaped curve relationship between environmental information disclosure and urban green economic efficiency and environmental information disclosure and technological innovation. On the contrary, there is an inverted U-shaped curve relationship between environmental information disclosure and industrial pollutant emission. 3) Environmental information disclosure has a greater sustainability effect in industrial cities. The conclusion shows that environmental information disclosure can improve the efficiency of urban green economy by improving the ability of urban technological innovation and reducing the emission of industrial pollutants. Environmental information disclosure plays a role of “restraining first and then promoting” to sustainable development. This research provides a reference for how to lessen information asymmetry and reduce negative externalities in the formulation of environmental regulatory policies.
Upscaling Methane Flux From Plot Level to Eddy Covariance Tower Domains in Five Alaskan Tundra Ecosystems
Authors: Wang Yihui , Yuan Fengming , Arndt Kyle A. , Liu Jianzhao , He Liyuan , Zuo Yunjiang , Zona Donatella , Lipson David A. , Oechel Walter C. , Ricciuto Daniel M. , Wullschleger Stan D. , Thornton Peter E. , Xu Xiaofeng
Published: July 2022

Spatial heterogeneity in methane (CH4) flux requires a reliable upscaling approach to reach accurate regional CH4 budgets in the Arctic tundra. In this study, we combined the CLM-Microbe model with three footprint algorithms to scale up CH4 flux from a plot level to eddy covariance (EC) tower domains (200 m × 200 m) in the Alaska North Slope, for three sites in Utqiaġvik (US-Beo, US-Bes, and US-Brw), one in Atqasuk (US-Atq) and one in Ivotuk (US-Ivo), for a period of 2013–2015. Three footprint algorithms were the homogenous footprint (HF) that assumes even contribution of all grid cells, the gradient footprint (GF) that assumes gradually declining contribution from center grid cells to edges, and the dynamic footprint (DF) that considers the impacts of wind and heterogeneity of land surface. Simulated annual CH4 flux was highly consistent with the EC measurements at US-Beo and US-Bes. In contrast, flux was overestimated at US-Brw, US-Atq, and US-Ivo due to the higher simulated CH4 flux in early growing seasons. The simulated monthly CH4 flux was consistent with EC measurements but with different accuracies among footprint algorithms. At US-Bes in September 2013, RMSE and NNSE were 0.002 μmol m−2 s−1 and 0.782 using the DF algorithm, but 0.007 μmol m−2 s−1 and 0.758 using HF and 0.007 μmol m−2 s−1 and 0.765 using GF, respectively. DF algorithm performed better than the HF and GF algorithms in capturing the temporal variation in daily CH4 flux each month, while the model accuracy was similar among the three algorithms due to flat landscapes. Temporal variations in CH4 flux during 2013–2015 were predominately explained by air temperature (67–74%), followed by precipitation (22–36%). Spatial heterogeneities in vegetation fraction and elevation dominated the spatial variations in CH4 flux for all five tower domains despite relatively weak differences in simulated CH4 flux among three footprint algorithms. The CLM-Microbe model can simulate CH4 flux at both plot and landscape scales at a high temporal resolution, which should be applied to other landscapes. Integrating land surface models with an appropriate algorithm provides a powerful tool for upscaling CH4 flux in terrestrial ecosystems.
Identification of Ferroptosis-Associated Genes in Prostate Cancer by Bioinformatics Analysis
Authors: Wo Qijun , Liu Zhenghong , Hu Linyi
Published: July 2022

Background: In order to reveal the functions of ferroptosis in prostate cancer (PCa), a ferroptosis potential index (FPI) was built. This study researched the influence of ferroptosis on gene mutations, various cellular signaling pathways, biochemical recurrence (BCR), and drug resistance in both FPI-high and FPI-low groups.

Methods: RNA-seq, somatic mutation data, and clinical data were obtained from The Cancer Genome Atlas (TCGA). FPI values were calculated. All samples were divided into FPI-high and FPI-low groups. The BCR-free survival rate, tumor mutation burden (TMB) value, cellular signaling pathway, differentially expressed genes (DEGs), and drug resistance in the two FPI groups were identified. Human PCa cells, LNCaP, were treated with ferroptosis inducer erastin or inhibitor ferrostatin-1. The expression of hub genes was detected by qRT-PCR and Western blot.

Results: A high FPI level was significantly related to poor BCR-free survival. Also, higher TMB value was found in the FPI-high group, and FPI was shown to be associated with gene mutations. Then, genes in both groups were revealed to be enriched in different pathways. A total of 310 DEGs were identified to be involved in muscle system processes and neuroactive ligand–receptor interactions. A total of 101 genes were found to be related to BCR-free survival, and a protein–protein interaction (PPI) network was constructed. Two sub-modules were identified by MCODE, and eight hub genes were screened out, among which SYT4 had higher expression levels and poorer BCR-free survival in the FPI-high group, while the remaining hub genes had lower expression levels and poorer BCR-free survival. Drug sensitivity was revealed to be different in the two groups by study on the IC50 data of different molecules and ferroptosis regulator gene (FRG) expressions. Finally, erastin increased the expression of SYT4 in LNCaP and decreased the expression of the other four genes (ACTC1, ACTA1, ACTN2, and MYH6), while ferrostatin-1 led to the opposite results. The molecular experimental results were consistent with those of bioinformatics analysis, except TNNI1, TNNC2, and NRAP.

Conclusion: The current research depicted the ferroptosis level and FRGs in PCa. Ferroptosis was related to TMB value, BCR-free survival, and drug resistance. This study will be beneficial to further research studies on ferroptosis-related molecular mechanisms.
An Immune-Related Gene Signature Can Predict Clinical Outcomes and Immunotherapeutic Response in Oral Squamous Cell Carcinoma
Authors: Zhang Liyuan , Wang Xiaopeng
Published: July 2022

Objective: Immune landscape is a key feature that affects cancer progression, survival, and treatment response. Herein, this study sought to comprehensively characterize the immune-related genes (IRGs) in oral squamous cell carcinoma (OSCC) and conduct an immune-related risk score (IRS) model for prognosis and therapeutic response prediction.

Methods: Transcriptome profiles and follow-up data of OSCC cohorts were curated from TCGA, GSE41613, and IMvigor210 datasets. An IRS model was established through univariate Cox, Random Survival Forest, and multivariate Cox analyses. Prognostic significance was evaluated with Kaplan–Meier curves, ROC, uni- and multivariate Cox, and subgroup analyses. A nomogram was conducted and assessed with C-index, ROC, calibration curves, and decision curve analyses. Immune cell infiltration and immune response were estimated with ESTIMATE and ssGSEA methods.

Results: An IRS model was constructed for predicting the overall survival and disease-free survival of OSCC, containing MASP1, HBEGF, CCL22, CTSG, LBP, and PLAU. High-risk patients displayed undesirable prognosis, and the predictive efficacy of this model was more accurate than conventional clinicopathological indicators. Multivariate Cox analyses demonstrated that this model was an independent risk factor. The nomogram combining IRS, stage, and age possessed high clinical application values. The IRS was positively associated with a nonflamed tumor microenvironment. Moreover, this signature enabled to predict immunotherapeutic response and sensitivity to chemotherapeutic agents (methotrexate and paclitaxel).

Conclusion: Collectively, our study developed a robust IRS model with machine learning method to stratify OSCC patients into subgroups with distinct prognosis and benefits from immunotherapy, which might assist identify biomarkers and targets for immunotherapeutic schemes.
Comparative Genomic and Phylogenetic Analysis of Chloroplast Genomes of Hawthorn (Crataegus spp.) in Southwest China
Authors: Wu Xien , Luo Dengli , Zhang Yingmin , Yang Congwei , Crabbe M. James C. , Zhang Ticao , Li Guodong
Published: July 2022

The hawthorns (Crataegus spp.) are widely distributed and famous for their edible and medicinal values. There are ∼18 species and seven varieties of hawthorn in China distributed throughout the country. We now report the chloroplast genome sequences from C. scabrifolia, C. chungtienensis and C. oresbia, from the southwest of China and compare them with the previously released six species in Crataegus and four species in Rosaceae. The chloroplast genome structure of Crataegus is typical and can be divided into four parts. The genome sizes are between 159,654 and 159,898bp. The three newly sequenced chloroplast genomes encode 132 genes, including 85 protein-coding genes, 37 tRNA genes, and eight rRNA genes. Comparative analysis of the chloroplast genomes revealed six divergent hotspot regions, including ndhA, rps16-trnQ-UUG, ndhF-rpl32, rps16-psbK, trnR-UCU-atpA and rpl32-trnL-UAG. According to the correlation and co-occurrence analysis of repeats with indels and SNPs, the relationship between them cannot be ignored. The phylogenetic tree constructed based on the complete chloroplast genome and intergenic region sequences indicated that C. scabrifolia has a different origin from C. chungtienensis and C. oresbia. We support the placement of C. hupehensis, C. cuneata, C. scabrifolia in C. subg. Crataegus and C. kansuensis, C. oresbia, C. kansuensis in C. subg. Sanguineae. In addition, based on the morphology, geographic distribution and phylogenetic relationships of C. chungtienensis and C. oresbia, we speculate that these two species may be the same species. In conclusion, this study has enriched the chloroplast genome resources of Crataegus and provided valuable information for the phylogeny and species identification of this genus.
Study on the Retreatment, Outcome, and Potential Predictors of Recurrence in Patients With Recurrence of Hepatitis B After Functional Cure
Authors: Lin Xiao , Song Aixin , Lu Junfeng , Zheng Sujun , Hu Zhongjie , Ma Lina , Cao Zhenhuan , Li Hong , Zheng Yanhong , Ren Shan , Chen Xinyue
Published: July 2022

Background

Studies about the retreatment and predictors for patients with hepatitis B recurrence after functional cure are rare. This study aimed to evaluate the effect of retreatment, outcome, and potential predictors of recurrence in patients with recurrence after functional cure.

Methods

A long-term follow-up was conducted with 32 cumulatively obtained patients who relapsed after cessation of pegylated interferon (Peg-IFN)-based antiviral treatment. The decision of whether to treatment or which therapeutic method to use [Peg-IFN or nucleos(t)ide analogs (NAs)] was based on the patient’s preferences and wishes. The rate of achieving functional cure and the clinical outcomes of different therapeutic methods were analyzed. Hepatitis B surface antibody (anti-HBs) and hepatitis B core antibody (anti-HBc) levels were detected in patients with blood samples during follow-up to evaluate the predictive ability of recurrence.

Results

The follow-up time of 32 recurrence cases was 42–532 weeks after recurrence (median 226 weeks). In the 20 patients who received retreatment (15 received Peg-IFN and 5 received NAs only), the rate of functional cure was 65.0% (13/20); it was 86.7% (13/15) in the patients retreated with Peg-IFN. Three cases experienced recurrence again. Five patients received NA treatment, and no functional cure was achieved. No drug intervention was administered for 12 patients, 2 of them with hepatitis B virus (HBV) DNA spontaneous clearance, and one patient achieved spontaneous hepatitis B surface antigen (HBsAg) clearance during follow-up. Patients who relapsed after functional cure with Peg-IFN treatment did not have liver cirrhosis or hepatocellular carcinoma during the follow-up, regardless of whether they received retreatment. Anti-HBs and anti-HBc levels at the end of therapy were predictors of recurrence (p < 0.001, p = 0.023). The value of combining the above two indicators in predicting recurrence was further improved, the areas under the receiver operating characteristic curves were 0.833, at combining predictors >-0.386, the predictive sensitivity and specificity for recurrence were 86.67% and 90.62%.

Conclusion

The functional cure rate was above 80% for patients with recurrence treated by Peg-IFN. During the follow-up, liver cirrhosis and hepatocellular carcinoma were not observed in all recurrence cases. High levels of anti-HBs and anti-HBc at the time of drug discontinuation are less likely to relapse.
4-Ethylguaiacol Modulates Neuroinflammation and Promotes Heme Oxygenase-1 Expression to Ameliorate Brain Injury in Ischemic Stroke
Authors: Weng Wen-Tsan , Kuo Ping-Chang , Scofield Barbara A. , Paraiso Hallel C. , Brown Dennis A. , Yu I-Chen , Yen Jui-Hung
Published: July 2022

Ischemic stroke is caused by a sudden reduction in cerebral blood flow that subsequently induces a complex cascade of pathophysiological responses, leading to brain inflammation and irreversible infarction. 4-ethylguaiacol (4-EG) is reported to suppress inflammatory immune responses. However, whether 4-EG exerts anti-inflammatory effects in ischemic stroke remains unexplored. We evaluated the therapeutic potential of 4-EG and examined the cellular and molecular mechanisms underlying the protective effects of 4-EG in ischemic stroke. The effect of 4-EG in ischemic stroke was determined by using a transient middle cerebral artery occlusion (MCAO) animal model followed by exploring the infarct size, neurological deficits, microglia activation, inflammatory cytokine production, blood–brain barrier (BBB) disruption, brain endothelial cell adhesion molecule expression, and microglial heme oxygenase-1 (HO-1) expression. Nrf2-/- and HO-1 inhibitor ZnPP-treated mice were also subjected to MCAO to evaluate the role of the Nrf2/HO-1 pathway in 4-EG-mediated protection in ischemic stroke. We found that 4-EG attenuated infarct size and neurological deficits, and lessened BBB disruption in ischemic stroke. Further investigation revealed that 4-EG suppressed microglial activation, peripheral inflammatory immune cell infiltration, and brain endothelial cell adhesion molecule upregulation in the ischemic brain. Finally, we identified that the protective effect of 4-EG in ischemic stroke was abolished in Nrf2-/– and ZnPP-treated MCAO mice. Our results identified that 4-EG confers protection against ischemic stroke and reveal that the protective effect of 4-EG in ischemic stroke is mediated through the induction of the Nrf2/HO1 pathway. Thus, our findings suggest that 4-EG could be developed as a novel therapeutic agent for the treatment of ischemic stroke.
Predicting Prognosis and Distinguishing Cold and Hot Tumors in Bladder Urothelial Carcinoma Based on Necroptosis-Associated lncRNAs
Authors: Liu Dongze , Xu Shengxian , Chang Taihao , Ma Shenfei , Wang Kaibin , Sun Guangyu , Chen Shuaiqi , Xu Yong , Zhang Hongtuan
Published: July 2022

Background

In reference to previous studies, necroptosis played an important role in cancer development. Our team decided to explore the potential prognostic values of long non-coding RNAs (lncRNAs) associated with necroptosis in bladder urothelial carcinoma (BLCA) and their relationship with the tumor microenvironment (TME) and the immunotherapeutic response for accurate dose.

Methods

To obtain the required data, bladder urothelial carcinoma transcriptome data were searched from Cancer Genome Atlas (TCGA) (https://portal.gdc.cancer.gov/). We used co-expression analysis, differential expression analysis, and univariate Cox regression to screen out prognostic lncRNAs associated with necroptosis in BLCA. Then the least absolute shrinkage and selection operator (LASSO) was conducted to construct the necroptosis-associated lncRNAs model. Based on this model, we also performed the Kaplan–Meier analysis and time-dependent receiver operating characteristics (ROC) to estimate the prognostic power of risk score. Multivariate and univariate Cox regression analysis were performed to build up a nomogram. Calibration curves, and time-dependent ROC were also conducted to evaluate nomogram. Principal component analysis (PCA) revealed a difference between high- and low-risk groups. In addition, we explored immune analysis, gene set enrichment analyses (GSEA), and evaluation of the half-maximal inhibitory concentration (IC50) in constructed model. Finally, the entire samples were divided into three clusters based on model of necroptosis-associated lncRNAs to further compare immunotherapy in cold and hot tumors.

Results

A model was built up based on necroptosis-associated lncRNAs. The model revealed good consistence between calibration plots and prognostic prediction. The area of 1-, 3-, and 5-year OS under the ROC curve (AUC) were 0.707, 0.679, and 0.675. Risk groups could be helpful for systemic therapy due to the markedly diverse IC50 between risk groups. To our delight, clusters could effectively identify cold and hot tumors, which would be beneficial to accurate mediation. Clusters 2 and 3 were considered the hot tumor, which was more sensitive to immunotherapeutic drugs.

Conclusions

The outcomes of our study suggested that necroptosis-associated lncRNAs could effectively predict patients with BLCA prognosis, which may be helpful for distinguishing the cold and hot tumors and improving individual treatment of BLCA.
Association of IL-4 and IL-10 Polymorphisms With Preterm Birth Susceptibility: A Systematic Review and Meta-Analysis
Authors: Cao Xian-Ling , Zhou Xuan-You , Xu Nai-Xin , Chen Song-Chang , Xu Chen-Ming
Published: July 2022

Objective

Preterm birth (PTB) is a typical inflammatory disease with unclear pathogenesis. The studies investigating the relationship between anti-inflammatory factors IL-4 and IL-10 gene polymorphisms and PTB produced conflicting results. This systematic review and meta-analysis aimed to summarize the effects of IL-4 and IL-10 gene polymorphisms and clarify their possible association with PTB.

Methods

A systematic literature review was conducted using PubMed, Web of Science, and Cochrane library (up to 02 April 2022). The MeSH terms, related entry terms, and other names in “Gene” database were used to find relevant articles. A fixed- or random-effects model was used to calculate the significance of IL-4 and IL-10 gene polymorphisms, depending on study heterogeneity. The odds ratios (OR) and 95% confidence intervals (CIs) were calculated in the allele, recessive, dominant, co-dominant, and over-dominant models. The Eggers publication bias plot was used to graphically represent the publication bias.

Results

Polymorphisms in two interleukins (IL-4-590C/T (rs2243250) = 5 and IL-10-592A/C (rs1800872), -819T/C (rs1800871) and -1082A/G (rs1800896) = 16) were found in 21 articles. Overall, only the over-dominant gene model AA + GG vs. AG revealed significant association between IL-10-1082A/G (rs1800896) and PTB (OR [95% CI] = 0.87 [0.76, 0.99], p = 0.04). However, in the allele model, recessive model, dominant model, co-dominant model, and over-dominant model, the polymorphisms for IL-4-590C/T (rs2243250), IL-10-592A/C (rs1800872), and IL-10-819T/C (rs1800871) were not found to be associated with the risk of PTB. In gene models, no statistically significant association was found between IL-4-590C/T (rs2243250), IL-10-592A/C (rs1800872), IL-10-819T/C (rs1800871), and IL-10-1082A/G (rs1800896) polymorphisms and PTB in subgroup analyses by racial or control group Hardy-Weinberg Equilibrium (HWE) p-value. Eggers’s publication bias plot and heterogeneity test (I2<50%, p = 0.05) of IL-10-1082A/G (rs1800896) suggested that the funnel asymmetry could be due to publication bias rather than heterogeneity.

Conclusion

The current study suggests that the over-dominant gene model AA + GG vs. AG of IL-10-1082A/G (rs1800896) polymorphism may be associated with genetic susceptibility to PTB and may have a protective function against PTB risk. There was unclear association found between IL-4-590C/T (rs2243250), IL-10-592A/C (rs1800872) and IL-10-819T/C (rs1800871) polymorphisms and PTB. Due to the limitations of included studies and the risk of publication bias, additional research is required to confirm our findings.

Systematic Review Registration

https://inplasy.com/inplasy-2022-4-0044, identifier INPLASY202240044.
Neutrophils: New Critical Regulators of Glioma
Authors: Wang Guanyu , Wang Jinpeng , Niu Chaoshi , Zhao Yan , Wu Pengfei
Published: July 2022

In cancer, neutrophils are an important part of the tumour microenvironment (TME). Previous studies have shown that circulating and infiltrating neutrophils are associated with malignant progression and immunosuppression in gliomas. However, recent studies have shown that neutrophils have an antitumour effect. In this review, we focus on the functional roles of neutrophils in the circulation and tumour sites in patients with glioma. The mechanisms of neutrophil recruitment, immunosuppression and the differentiation of neutrophils are discussed. Finally, the potential of neutrophils as clinical biomarkers and therapeutic targets is highlighted. This review can help us gain a deeper and systematic understanding of the role of neutrophils, and provide new insights for treatment in gliomas.
TLR22-Induced Pro-Apoptotic mtROS Abets UPRmt-Mediated Mitochondrial Fission in Aeromonas hydrophila-Infected Headkidney Macrophages of Clarias gariepinus
Authors: Kumar Manmohan , Sharma Shagun , Haque Munira , Kumar Jai , Hathi Umesh Prasad Sah , Mazumder Shibnath
Published: July 2022

Toll-like receptors (TLRs) are epitomized as the first line of defense against pathogens. Amongst TLRs, TLR22 is expressed in non-mammalian aquatic vertebrates, including fish. Using headkidney macrophages (HKM) of Clarias gariepinus, we reported the pro-apoptotic and microbicidal role of TLR22 in Aeromonas hydrophila infection. Mitochondria act as a central scaffold in the innate immune system. However, the precise molecular mechanisms underlying TLR22 signaling and mitochondrial involvement in A. hydrophila-pathogenesis remain unexplored in fish. The aim of the present study was to investigate the nexus between TLR22 and mitochondria in pro-apoptotic immune signaling circuitry in A. hydrophila-infected HKM. We report that TLR22-induced mitochondrial-Ca2+ [Ca2+]mt surge is imperative for mtROS production in A. hydrophila-infected HKM. Mitigating mtROS production enhanced intracellular bacterial replication implicating its anti-microbial role in A. hydrophila-pathogenesis. Enhanced mtROS triggers hif1a expression leading to prolonged chop expression. CHOP prompts mitochondrial unfolded protein response (UPRmt) leading to the enhanced expression of mitochondrial fission marker dnml1, implicating mitochondrial fission in A. hydrophila pathogenesis. Inhibition of mitochondrial fission reduced HKM apoptosis and increased the bacterial burden. Additionally, TLR22-mediated alterations in mitochondrial architecture impair mitochondrial function (ΔΨm loss and cytosolic accumulation of cyt c), which in turn activates caspase-9/caspase-3 axis in A. hydrophila-infected HKM. Based on these findings we conclude that TLR22 prompts mtROS generation, which activates the HIF-1α/CHOP signalosome triggering UPRmt-induced mitochondrial fragmentation culminating in caspase-9/-3-mediated HKM apoptosis and bacterial clearance.
Autoimmunity to Sphingosine-1-Phosphate-Receptors in Systemic Sclerosis and Pulmonary Arterial Hypertension
Authors: Gluschke Hans , Siegert Elise , Minich Waldemar B. , Hackler Julian , Riemekasten Gabriela , Kuebler Wolfgang M. , Simmons Szandor , Schomburg Lutz
Published: July 2022

Context

Pulmonary arterial hypertension (PAH) is a frequent extracutaneous manifestation of systemic sclerosis (SSc). PAH is characterized by increased vasomotor tone, progressive remodeling of pulmonary arteries and arterioles, consequentially increased pulmonary vascular resistance, right heart hypertrophy, and eventually right ventricular failure. Autoimmunity against G-protein coupled receptors (GPCRs) has been implicated in the development of SSc-associated PAH. Sphingosine-1-phosphate (S1P) receptors (S1PR) present a potential, yet so far untested antigen for PAH autoimmunity, given the documented role of S1P/S1PR signaling in PAH pathogenesis.

Objective

We hypothesized that S1P receptors (S1PR) may constitute autoantigens in human patients, and that the prevalence of autoantibodies (aAb) to S1PR1, S1PR2 and S1PR3 is elevated in SSc patients and associated with PAH.

Methods

For this exploratory study, serum samples from 158 SSc patients, 58 of whom with PAH, along with 333 healthy control subjects were screened for S1PR-aAb. S1PR1-3 were expressed as fusion proteins with luciferase in human embryonic kidney cells and used to establish novel in-vitro assays for detecting and quantifying S1PR-aAb. The fusion proteins were incubated with serum samples, the aAb-S1PR complexes formed were precipitated by protein-A, washed and tested for luciferase activity. Commercial anti-S1PR-antibodies were used to verify specificity of the assays.

Results

All three assays showed dose-dependent signal intensities when tested with S1PR-subtype specific commercial antibodies. Natural aAb to each S1PR were detected in healthy controls with a prevalence of <10% each, i.e., 2.7% for S1PR1-aAb, 3.6% for S1PR2-aAb, and 8.3% for S1PR3. The respective prevalence was higher in the cohort of SSc patients without PAH, with 17.1% for S1PR1-aAb, 19.0% for S1PR2-aAb, and 21.5% for S1PR3. In the subgroup of SSc patients with PAH, prevalence of aAb to S1PR2 and S1PR3 was further elevated to 25.9% for S1PR2-aAb, and 27.6% for S1PR3. Notably, the majority of patients with positive S1PR2-aAb (60.7%) or S1PR3-aAb (71.9%) displayed interstitial lung disease.

Conclusion

S1PR1–3 can constitute autoantigens in humans, particularly in SSC patients with PAH. The potential pathophysiological significance for the etiology of the disease is currently unknown, but the elevated prevalence of S1PR2-aAb and S1PR3-aAb in SSC patients with PAH merits further mechanistic investigations.
Identification and Expression Analysis of an Interacting Protein (LvFABP) that Mediates Vibrio parahaemolyticus AHPND Toxin Action
Authors: Gu Xiaoqian , Liu Mei , Wang Baojie , Jiang Keyong , Wang Lei
Published: July 2022

Acute hepatopancreatic necrosis disease (AHPND) caused by Vibrio parahaemolyticus causing AHPND (VPAHPND) is the most serious disease affecting shrimp farming. The PirAvp and PirBvp toxins of VPAHPND are known virulence factors. However, the corresponding target protein in shrimp that mediates their action has not been identified. By screening yeast two-hybrid cDNA libraries from intestine, stomach, and hepatopancreas of Litopenaeus vannamei, the protein with the largest increase in gene expression in shrimp hepatopancreas in response to VPAHPND challenge was identified and designated LvFABP. Analysis revealed high sequence homology of the LvFABP gene and a lipocalin/cytosolic fatty acid binding gene. Yeast two-hybrid pairwise analysis, GST-pull down assay, and far-western blot assay were performed to determine the interaction between LvFABP and PirBvp. LvFABP was able to directly bind to PirBvp. The expression of LvFABP in the hepatopancreas was significantly higher at P23 and P27 developmental stages of L. vannamei. RNA interference (RNAi) of LvFABP reduced the mortality, histopathological signs of AHPND in the hepatopancreas, and the number of virulent VPAHPND bacteria in the intestine, stomach, and hepatopancreas after VPAHPND challenge. We concluded that the LvFABP was involved in AHPND pathogenesis and acted as a VPAHPND toxin interacting protein. This is the first identification of VPAHPND toxin interacting protein from the shrimp digestive system by yeast two-hybrid library screening and were confirmed by in vitro protein interaction verification and in vivo challenge experiments. This study provides novel insight into the contributions of LvFABP towards AHPND pathogenesis in shrimp. The findings could inform AHPND preventative measures in shrimp farming.
Applications of Hydrogels in Premature Ovarian Failure and Intrauterine Adhesion
Authors: Zhang Donghai , Ding Chuanfeng , Duan Tao , Zhou Qian
Published: July 2022

Premature ovarian failure (POF) and intrauterine adhesion (IUA) that easily lead to reduced fertility in premenopausal women are two difficult diseases to treat in obstetrics and gynecology. Hormone therapy, in vitro fertilization and surgical treatments do not completely restore fertility. The advent of hydrogels offers new hope for the treatment of POF and IUA. Hydrogels are noncytotoxic and biodegradable, and do not cause immune rejection or inflammatory reactions. Drug delivery and stem cell delivery are the main application forms. Hydrogels are a local drug delivery reservoir, and the control of drug release is achieved by changing the physicochemical properties. The porous properties and stable three-dimensional structure of hydrogels support stem cell growth and functions. In addition, hydrogels are promising biomaterials for increasing the success rate of ovarian tissue transplantation. Hydrogel-based in vitro three-dimensional culture of follicles drives the development of artificial ovaries. Hydrogels form a barrier at the site of injury and have antibacterial, antiadhesive and antistenosis properties for IUA treatment. In this review, we evaluate the physicochemical properties of hydrogels, and focus on the latest applications of hydrogels in POF and IUA. We also found the limitations on clinical application of hydrogel and provide future prospects. Artificial ovary as the future of hydrogel in POF is worth studying, and 3D bioprinting may help the mass production of hydrogels.
The Prognostic Prediction Value of Positive Lymph Nodes Numbers for the Hypopharyngeal Squamous Cell Carcinoma
Authors: Pang Wendu , Luo Yaxin , Li Junhong , Cheng Danni , Rao Yufang , Mao Minzi , Qiu Ke , Dong Yijun , Liu Jun , Zou Jian , Wang Haiyang , Chen Fei
Published: July 2022

Background

The current American Joint Committee on Cancer (AJCC) system only considered the importance of the size and laterality of lymph nodes while not the positive lymph node number (PLNN) for hypopharyngeal squamous cell carcinoma (HPSCC).

Methods

A total of 973 patients with HPSCC from the Surveillance, Epidemiology, and End Results database (2004–2015) were identified. Univariate and multivariate Cox regression analyses were used to evaluate the prognostic effects. We applied six Cox regression models to compare the survival prognostic values of PLNN and AJCC systems.

Results

Positive lymph node number showed a significant association with overall survival (OS) and cancer-specific survival (CSS) (P < 0.001) in univariate and multivariable analyses. The increased PLNN of HPSCC gave rise to poor OS and CSS. The survival model incorporating a composite of PLNN and TNM classification (C-index for OS:0.682, C-index for CSS:0.702) performed better than other models.

Conclusions

A positive lymph node number could serve as a survival predictor for patients with HPSCC and a complement to enhance the prognostic assessment effects of TNM cancer staging systems.
Epidemiology and Genetic Diversity of Bartonella in Rodents in Urban Areas of Guangzhou, Southern China
Authors: Yao Xin-Yan , Liu Hong , Sun Jing , Zhang Yu-Qian , Lv Zhi-Hang , Zhang Xue-Lian , Shao Jian-Wei
Published: July 2022

Bartonella spp. are gram-negative bacteria that can infect a wide spectrum of mammals. Rodents are considered to be the natural reservoir of many Bartonella species that are transmitted by various blood-sucking arthropods. The close contact between rodents and humans in urban areas increased the chance of transmitting rodent-borne Bartonella to humans. Investigation of the epidemiological characteristics of Bartonella infection in rodents is of great significance for the prevention and control of human Bartonellosis. In this study, rodents were captured to monitor the prevalence of Bartonella in urban areas of Guangzhou city. Six official or candidate species of Bartonella, including two confirmed zoonotic species, were detected with an overall prevalence of 6.4% in rodents captured herein. In addition, Rattus norvegicus was the predominant host species for Bartonella infection, and B. queenslandensis was the dominant species circulating in rodents in these areas. These results provide insights into the prevalence and genetic diversity of Bartonella species circulating in rodents in the urban areas of Guangzhou, and also urged the surveillance of rodent-associated Bartonella species in these areas.
RETRACTED: Identification of a Novel Ferroptosis Inducer for Gastric Cancer Treatment Using Drug Repurposing Strategy
Authors: Zhang Jinping , Gao Meimei , Niu Ying , Sun Jiangang
Published: July 2022

Gastric cancer remains one of the major contributors to global cancer mortality, although there is no promising target drug in clinics. Hence, the identification of novel targeted drugs for gastric cancer is urgent. As a promising strategy for inducing ferroptosis for gastric cancer treatment, the ferroptosis inducer is a potential drug. Nevertheless, no ferroptosis inducer has entered clinics. So, our purpose was to identify a novel ferroptosis inducer for gastric cancer treatment using a drug repurposing strategy. Firstly, using a drug repurposing strategy with the aid of a commercialized compound library, HC-056456, a small molecule bioactive CatSper channel blocker, was characterized to inhibit the growth of gastric cancer line MGC-803. At the same time, this anti-proliferation effect can be blocked by ferrostatin-1, a ferroptosis inhibitor, indicating that HC-056456 is a ferroptosis inducer. Then, HC-056456 was identified to decrease GSH content via p53/SLC7A11 signaling pathway. Then Fe2+ and lipid peroxide were accumulated when cells were exposed to HC-056456. Finally, HC-056456 was found to suppress the growth of gastric cancer cells by increasing p53 and repressing SLC7A11 in vivo but not in the presence of ferrostatin-1. In sum, we systematically elucidate that HC-056456 exerts anti-gastric cancer effect by provoking ferroptosis in vitro and in vivo, suggesting its potential role in gastric cancer treatment.
Efficacy and Safety of Mirror Therapy for Post-stroke Dysphagia: A Systematic Review and Meta-Analysis
Authors: He Kelin , Wu Lei , Ni Fengjia , Li Xinyun , Liang Kang , Ma Ruijie
Published: July 2022

Background

Post-stroke dysphagia is a common symptom after stroke and one of the most frequent and severe complications of stroke. Over the recent years, mirror therapy has generated significant research interest as a non-invasive therapeutic and rehabilitative intervention for post-stroke dysphagia and has been investigated in several randomized controlled trials in single center.

Objective

In this study, we aimed to evaluate the efficacy and safety of mirror therapy for post-stroke dysphagia.

Methods

A total of seven databases were searched comprehensively from inception to the 31 December 2021, including PubMed, the Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), Chinese Biomedical Literature Service System (SinoMed), Wan-fang database, and the Chinese Scientific Journals Database (VIP) from inception to 31 December 2021. The primary outcome measure was efficacy, as measured by clinical effectiveness rate. Secondary outcomes included the water swallowing test and the incidence of pneumonia. In addition, we applied the Cochrane Risk of Bias Tool to investigate the risk of bias. Potential publication bias was evaluated by applying Egger's bias indicator test and by assessing the symmetry of data when visualized as funnel plots.

Results

A total of five randomized controlled trials (135 subjects in the experimental group and control group) were found to report the application of mirror therapy for post-stroke dysphagia and were included in this study. No publication bias was detected. Meta-analysis revealed that mirror therapy had a positive effect on the rate of clinical efficacy [odds ratio (OR) = 4.22; 95% confidence interval (CI): 2.3–7.73] and the water swallowing test [mean difference (MD) = −0.76; 95% CI = −1.29 to −0.22]. Moreover, mirror therapy reduced the incidence of pneumonia (OR = 0.13; 95% CI = 0.03–0.49). Subgroup analyses indicated that mirror therapy during the acute phase was robust but was unstable during the convalescent phase. Sensitivity analysis revealed that the results generated by our meta-analysis were robust and stable.

Conclusions

Available evidence appears to suggest that mirror therapy may have a role in the management of post-stroke dysphagia but has yet to be fully confirmed. Existing evidence from clinical trials suggests that evidence relating to the safety of mirror therapy for patients with post-stroke dysphagia is not yet sufficient.

Systematic Review Registration

Identifier: CRD42022302733.
Evaluation of Cardiovascular Concerns of Intravenous Lacosamide Therapy in Epilepsy Patients
Authors: Lu Yan-Ting , Lin Chih-Hsiang , Ho Chen-Jui , Hsu Che-Wei , Tsai Meng-Han
Published: July 2022

Objective

Voltage-gated sodium channels (VGSCs) play an important role in neuronal excitability and epilepsies. In addition to the brain, VGSCs are also abundant enriched in cardiac tissues and are responsible for normal cardiac rhythm. Theoretically, sodium channel blocking antiseizure medications (SCB-ASMs) may have unwanted cardiac side effects. Lacosamide (LCM) is increasingly used in patients with status epilepticus (SE) due to the availability of intravenous formula. The concerns about the proarrhythmic effect are even higher due to the need for rapid administration of LCM. There were limited data on the cardiac safety of intravenous LCM. Hereby, we performed a study to observe the effect of intravenous loading of LCM in patients with seizures in our Neurological Intensive Care Unit (NICU).

Methods

We retrospectively reviewed the patients using parenteral LCM for seizures in NICU. A routine infusion time of 30 min was performed. The electrocardiogram (ECG) and blood pressure were recorded before and after LCM injection.

Results

We retrospectively reviewed the clinical data of 38 patients using LCM for treating seizures. Two patients had cardiac side effects after LCM loading, one (3.0%) with new-onset first-degree AV block and the other (3.0%) with atrial premature complex. For the quantitative changes of ECG parameter analysis, there was no change in QRS complex, corrected QT intervals, and heart rate except that the PR interval was mildly increased. A mild decrease in the diastolic blood pressure and mean arterial pressure were also observed. None of the above-mentioned parameter alterations required clinical intervention.

Conclusion

We evaluated the cardiac safety concern in real-world epilepsy patients requiring intravenous LCM. Near half of this cohort responded to LCM therapy and there was no life-threatening cardiac adverse effect. Intravenous LCM does have some effects on the ECG parameters and blood pressure but without clinical relevance. Despite the theoretical concern of cardiac adverse effects of LCM, the benefit of seizure control outweighed the risk in patients with status epilepticus or seizure clusters, such as hyperthermia, pulmonary edema, cardiac arrhythmias, or cardiovascular collapse.
Relationship Between Pneumonia and Dysphagia in Patients With Multiple System Atrophy
Authors: Wada Ayako , Kawakami Michiyuki , Yamada Yuka , Kaji Kentaro , Hijikata Nanako , Liu Fumio , Otsuka Tomoyoshi , Tsuji Tetsuya
Published: July 2022

Introduction

Dysphagia is one of the most clinically significant disabilities in patients with multiple system atrophy (MSA), because it can cause aspiration pneumonia, which is potentially fatal. In this study, the Neuromuscular disease Swallowing Status Scale (NdSSS), which was developed to evaluate dysphagia in patients with neuromuscular diseases, was used to evaluate patients with MSA. In addition, correlation between a history of pneumonia and swallowing function was evaluated.

Methods

Study 1: Reliability, concurrent validity, and responsiveness of the NdSSS in patients with MSA. In 81 patients for whom evaluation items could be collected, the NdSSS was tested for its interrater and intrarater reliability using weighted kappa statistics. Concurrent validity was assessed by correlating the NdSSS with existing scales (Functional Oral Intake Scale (FOIS), Functional Intake LEVEL Scale (FILS), and the unified MSA rating scale (UMSARS)) using Spearman's rank correlation coefficients. Sixty-three patients were evaluated by videofluorographic (VF) swallowing examination. To evaluate concurrent validity, Spearman's rank correlation coefficients were calculated between the NdSSS and VF swallowing assessments. Additionally, scale responsiveness was determined using the standardized response mean (SRM) in 23 patients who could be followed up to assess their long-term course. Study 2: Cross-sectional survey of swallowing function and history of pneumonia. Data regarding history of pneumonia, UMSARS, NdSSS, age, sex, MSA subtype, and disease duration were retrospectively obtained from the medical records of 113 patients with MSA. Differences in these parameters and NdSSS stage between those with and without a history of pneumonia were examined using the Mann-Whitney test or chi-squared test. Furthermore, clinical factors related to a history of pneumonia were examined by binomial logistic regression analysis.

Results

The NdSSS showed satisfactory reliability, concurrent validity, and responsiveness. A history of pneumonia was related to the severity of MSA, age, MSA subtype, and NdSSS stage. Binomial logistic regression analysis showed that NdSSS stage (odds ratio (OR), 0.490; 95% confidence interval (CI), 0.301–0.797, p = 0.001) and MSA subtype (OR, 4.031; 95% CI, 1.225–13.269, p = 0.021) were significantly associated with a history of pneumonia.

Conclusions

In patients with MSA, the NdSSS has sufficient reliability, concurrent validity, and responsiveness for assessing dysphagia. Patients with a history of pneumonia have more severe dysphagia. We found that the pneumonia risk was related to NdSSS stage and MSA-p (predominantly parkinsonism). Meticulous care to prevent aspiration is needed from early stages of the disease.
Efficacy of Cerebrolysin Treatment as an Add-On Therapy to Mechanical Thrombectomy in Patients With Acute Ischemic Stroke Due to Large Vessel Occlusion: Study Protocol for a Prospective, Open Label, Single-Center Study With 12 Months of Follow-Up
Authors: Staszewski Jacek , Stȩpień Adam , Piusińska-Macoch Renata , Dȩbiec Aleksander , Gniadek-Olejniczak Katarzyna , Frankowska Emilia , Maliborski Artur , Chadaide Zoltan , Balo David , Król Beata , Namias Rafael , Harston George , Mróz Józef , Piasecki Piotr
Published: July 2022

This study is designed to determine the efficacy of Cerebrolysin treatment as an add-on therapy to mechanical thrombectomy (MT) in reducing global disability in subjects with acute ischemic stroke (AIS). We have planned a single center, prospective, open-label, single-arm study with a 12-month follow-up of 50 patients with moderate to severe AIS, with a small established infarct core and with good collateral circulation who achieve significant reperfusion following MT and who receive additional Cerebrolysin within 8 h of stroke onset compared to 50 historical controls treated with MT alone, matched for age, clinical severity, occlusion location, baseline perfusion lesion volume, onset to reperfusion time, and use of iv thrombolytic therapy. The primary outcome measure will be the overall proportion of subjects receiving Cerebrolysin compared to the control group experiencing a favorable functional outcome (by modified Rankin Scale 0–2) at 90 days, following stroke onset. The secondary objectives are to determine the efficacy of Cerebrolysin as compared to the control group in reducing the risk of symptomatic secondary hemorrhagic transformation, improving neurological outcomes (NIHSS 0–2 at day 7, day 30, and 90), reducing mortality rates (over the 90-day and 12 months study period), and improving: activities of daily living (by Barthel Index), health-related quality of life (EQ-5D-5L) assessed at day 30, 90, and at 12 months. The other measures of efficacy in the Cerebrolysin group will include: assessment of final stroke volume and penumbral salvage (measured by CT/CTP at 30 days) and its change compared to baseline volume, changes over time in language function (by the 15-item Boston Naming Test), hemispatial neglect (by line bisection test), global cognitive function (by The Montreal Cognitive Assessment), and depression (by Hamilton Depression Rating Scale) between day 30 and day 90 assessments). The patients will receive 30 ml of Cerebrolysin within 8 h of AIS stroke onset and continue treatment once daily until day 21 (first cycle) and they will receive a second cycle of treatment (30 ml/d for 21 days given in the Outpatient Department or Neurorehabilitation Clinic) from day 69 to 90.