bluuebunny/crossref_metadata_2025 huggingface dataset:
Status of Analgesic Drugs and Quality of Life Results for Diabetic Peripheral Neuropathy in China
Authors: Lian Jingxuan , Wang Haijun , Cui Rongrong , Zhang Chaoxia , Fu Jianfang
Published: January 2022

Objective

The purpose of this study is to describe the current clinical situation of patients with painful diabetic peripheral neuropathy (DPN) and related anxiety, depression, and the quality of life of patients in mainland China, and to report the current status of the use of analgesics.

Methods

Between June 15, 2021, and October 15, 2021, a total of 401 participants participated in the study. Recruitment was carried out using a multi-level sampling method. Participants’ demographics, medical history, analgesic use, Michigan Symptom Score (MNSI), Numerical Rating Scale (NRS) pain score, Patient Health Questionnaire 9 (PHQ-9) score, Generalized Anxiety Disorder 7 (GAD) -7) Score, quality of life score (SF-12) and diabetes treatment status were collected.

Results

Among the participants, there were 236 male patients and female patients. Participants were 322 patients over 40 years old. Regarding the use of analgesics: 132 patients reported using analgesics, 221 patients reported not using analgesics, and 48 patients reported having used analgesics. The results of the scale showed that the scores of NRS, GAD-7, PHQ-9 and SF-12 were 5.12 ± 2.15, 6.33 ± 3.67, 8.46 ± 4.07 and 47.84 ± 19.92 for patients who used analgesics, Compared with patients who did not use analgesics (NRS: 1.99 ± 1.7, GAD-7: 1.81 ± 2.81, PHQ-9: 3.13 ± 4.10, SF-12: 78.34 ± 21.66) there are significant differences (p< 0.001). In addition, patients’ NRS scores are also closely related to GAD-7, PHQ-9 and SF-12 scores.

Conclusion

The severity of symptoms, mental status and quality of life of patients who used analgesics were more severe than those of patients who did not use analgesics. Pregabalin is still the preferred analgesic for patients with painful DPN, and the use of opioids in my country is extremely low, which is consistent with current international guidelines. Age, diabetic duration, DPN duration, PHQ-9 score, GAD-7 score and SF-12 scores are closely related to NRS pain scores. In addition, there are still a considerable number of patients who have not used analgesics due to financial burdens and other reasons, suggesting that China still has insufficient pain management in DPN patients.
Measurement of SARS-CoV-2 Antibody Titers Improves the Prediction Accuracy of COVID-19 Maximum Severity by Machine Learning in Non-Vaccinated Patients
Authors: Kurano Makoto , Ohmiya Hiroko , Kishi Yoshiro , Okada Jun , Nakano Yuki , Yokoyama Rin , Qian Chungen , Xia Fuzhen , He Fan , Zheng Liang , Yu Yi , Jubishi Daisuke , Okamoto Koh , Moriya Kyoji , Kodama Tatsuhiko , Yatomi Yutaka
Published: January 2022

Numerous studies have suggested that the titers of antibodies against SARS-CoV-2 are associated with the COVID-19 severity, however, the types of antibodies associated with the disease maximum severity and the timing at which the associations are best observed, especially within one week after symptom onset, remain controversial. We attempted to elucidate the antibody responses against SARS-CoV-2 that are associated with the maximum severity of COVID-19 in the early phase of the disease, and to investigate whether antibody testing might contribute to prediction of the disease maximum severity in COVID-19 patients. We classified the patients into four groups according to the disease maximum severity (severity group 1 (did not require oxygen supplementation), severity group 2a (required oxygen supplementation at low flow rates), severity group 2b (required oxygen supplementation at relatively high flow rates), and severity group 3 (required mechanical ventilatory support)), and serially measured the titers of IgM, IgG, and IgA against the nucleocapsid protein, spike protein, and receptor-binding domain of SARS-CoV-2 until day 12 after symptom onset. The titers of all the measured antibody responses were higher in severity group 2b and 3, especially severity group 2b, as early as at one week after symptom onset. Addition of data obtained from antibody testing improved the ability of analysis models constructed using a machine learning technique to distinguish severity group 2b and 3 from severity group 1 and 2a. These models constructed with non-vaccinated COVID-19 patients could not be applied to the cases of breakthrough infections. These results suggest that antibody testing might help physicians identify non-vaccinated COVID-19 patients who are likely to require admission to an intensive care unit.
Realism in Immune Ecology Studies: Artificial Diet Enhances a Caterpillar's Immune Defense but Does Not Mask the Effects of a Plastic Immune Strategy
Authors: Costantin Eduardo C. , Viol Daniel L. , Del Puppo Nathalia P. , Elliot Simon L.
Published: January 2022

The immune system is considered a functional trait in life-history theory and its modulation is predicted to be costly and highly dependent on the host's nutrition. Therefore, the nutritional status of an individual has a great impact on an animal's immune ecology. Herbivorous insects are commonly used as model organisms in eco-immunology studies and the use of an artificial diet is the predominant rearing procedure to test them. However, this diet differs from what herbivores experience in nature and it is unclear to what degree this distinction might impact on the relevance of these studies for the real world. Here, we compared plant-based vs. artificial diet in a set of three experiments to investigate the interaction of both diets with a plastic immune strategy known as Density-Dependent Prophylaxis (DDP). We used as a model organism the velvetbean caterpillar Anticarsia gemmatalis, which is known to adjust its immune defense in line with the DDP hypothesis. Our main results showed that larvae fed with artificial diet had 20.5% more hemocytes circulating in the hemolymph and died 20% more slowly when infected with an obligate (viral) pathogen. Crucially, however, we did not find any indication of fitness costs related to DDP. The use of artificial diet did not interact with that of DDP except in the case of host survival after infection, where the DDP effect was only observable in this diet. Our findings suggest the use of an artificial diet does not mask resource allocation conflicts between immune investment and fitness related traits, but to some extent it might lead to an overestimation of immune parameters and host survival time after infection. We believe that this is the first study to compare an artificial diet and a host plant covering all these aspects: immune parameters, life-history traits, and host survival after infection. Here we provide evidence that, besides the quantitative effects in immune parameters and host survival time, the use of artificial diet interacts only marginally with a density-dependent immune response. This provides support for the use of artificial diets in eco-immunology studies with insects.
Degradation of Diatom Protein in Seawater: A Peptide-Level View
Authors: Duffy Megan E. , Adams Cheyenne M. , Homolka Khadijah K. , Neibauer Jacquelyn A. , Mayer Lawrence M. , Keil Richard G.
Published: January 2022

Peptides and proteins were identified during a controlled laboratory degradation of the marine diatom Thalassiosira weissflogii by a surface seawater microbiome. Samples from each time point were processed both with and without the protease trypsin, allowing a partial differentiation between peptides produced naturally by microbial enzymatic degradation and peptides produced from the laboratory digestion of intact protein. Over the 12-day degradation experiment, 31% of the particulate organic carbon was depleted, and there was no preferential degradation of the overall protein pool. However, there was distinct differentiation in the cellular location, secondary structure and modifications between peptides produced by microbial vs. laboratory breakdown. During the initial period of rapid algal decay and bacterial growth, intracellular components from the cytoplasm were consumed first, resulting in the accumulation of membrane-associated proteins and peptides in the detrital pool. Accompanying the enrichment of membrane protein material was an increase in the importance of ɑ-helix motifs. Methylated arginine, a post-translational modification common in cell senescence, was found in high amounts within the microbially produced detrital peptide pool, suggesting a link between in-cell modification and resistance to immediate degradation. Another modification—asparagine deamidation—accumulated within the detrital peptides. Protein taxonomies showed the bacterial community decomposing the algal material was rich in Proteobacteria, and protein annotations showed abundant transportation of solubilized carbohydrates and small peptides across membranes. At this early stage of diagenesis, no changes in bulk amino acids (THAA) were observed, yet a proteomic approach allowed us to observe selective changes in diatom protein preservation by using amino acid sequences to infer subcellular location, secondary structures, and post-translational modifications (PTMs).
Comparative Profiling of Survival, Growth, and Intestinal Microbial Community of Pearl Oyster Pinctada maxima Juvenile in the Industrial Farming: The Feasibility of Using Spray-Dried Microalgae Powder
Authors: Yang Shouguo , Li Xi , Vasquez Hebert Ely , Wang Aimin , Shi Yaohua , Li Jiaoni , Zhang Xingzhi , Zheng Xing , Gu Zhifeng
Published: January 2022

Industrial farming is an alternative mode for Pinctada maxima juvenile cultivation to avoid mass mortality caused by natural disasters. Suitable and enough food is crucial for successful industrial bivalve farming. To investigate the feasibility of live microalga instead of spray-dried microalgal powder in P. maxima juvenile industrial farming, this study replaces a positive control live microalgal diet [Isochrysis zhanjiangensis (L-iso) and Platymonas subcordiformis (L-pla)] with spray-dried I. zhanjiangensis powder (P-iso) and P. subcordiformis powder (P-pla). Continuous feeding trials (30 days) were conducted on the P. maxima juvenile (1.2008 ± 0.0009 g initial weight and 30.12 ± 0.05 mm initial shell length), under laboratory conditions. Survival, growth performance, and intestinal microbial community were studied and compared across the groups. Results showed that survival rate (SR) did not differ significantly across the groups (ranged from 84 to 86%, P > 0.05). The growth performance in spray-dried microalgal groups, including total weight (TW), shell height (SH), absolute growth rate (AGR), and relative growth rate (RGR) for SH and TW, was slightly lower than that in live microalgal groups, while the activities of pepsin (PES), amylase (AMS), and lipase (LPS) were significantly higher (P < 0.05). The best growth performance was observed in the L-iso group, followed by the L-pla group. A 16S rRNA-based sequencing revealed that Proteobacteria was the dominant phylum in P. maxima juvenile intestinal bacterial community under controlled conditions, which accounted for 62–82% across groups. The intestinal bacteria at the genus level were more sensitive to diets, whereas Burkholderia was the dominant genus in both L-iso (66.52 ± 6.43%) and L-pla groups (54.00 ± 5.66%), while Mycoplasma, Alphaproteobacteria, and Oxyphotobacteria were in both P-iso and P-pla groups. The P-pla group got higher ACE, Chao1, and Simpson and Shannon indices (P < 0.05). The above results suggested that the spray-dried P-iso and P-pla can serve as substitutes for live microalga in P. maxima juvenile industrial farming under controlled conditions. The finding in this study provides basic data to optimize industrial farming technology and healthy management for P. maxima juvenile.
A Superior Contiguous Whole Genome Assembly for Shrimp (Penaeus indicus)
Authors: Katneni Vinaya Kumar , Shekhar Mudagandur Shashi , Jangam Ashok Kumar , Krishnan Karthic , Prabhudas Sudheesh K. , Kaikkolante Nimisha , Baghel Dushyant Singh , Koyadan Vijayan K. , Jena Joykrushna , Mohapatra Trilochan
Published: January 2022

Penaeid shrimp fishery and culture is a commercial enterprise contributing to employment, nutritional security and foreign exchange of developing countries. The genetic improvement programs being operated in shrimp benefit hugely from genomic resources. We report here a high-quality genome assembly for a penaeid shrimp, Penaeus indicus, which is the only Crustacean assembly to meet the reference standards of 1 and 10 Mb N50 lengths for contigs and scaffolds, respectively, among genomes of >1.5 Gb assembly length. The assembly is 1.93 Gb length (34.4 Mb scaffold N50) with 28,720 protein-coding genes and 49.31% repeat elements. The P. indicus assembly has 31.99% of simple sequence repeats, the highest among sequenced animal genomes. In comparison to other shrimp genomes having short contig lengths, the P. indicus assembly has 346 un-gapped contigs of over 1 Mb length and betters other shrimp genomes on sequence contiguity. This contiguous genome revealed 15,563 coding single nucleotide polymorphisms (SNPs) of which 2,572 are non-synonymous. The assembly and the SNP data resources have applications to genetic improvement programs, evolutionary studies and stock management.
Oral Chinese Herbal Medicine on Immune Responses During Coronavirus Disease 2019: A Systematic Review and Meta-Analysis
Authors: Shi Shihua , Wang Fei , Yao Huan , Kou Shuo , Li Weihao , Chen Bonan , Wu Yongcan , Wang Xiaomin , Pei Caixia , Huang Demei , Wang Yilan , Zhang Pan , He Yacong , Wang Zhenxing
Published: January 2022

Background

Cellular immune responses including lymphocyte functions and immune effector cells are critical for the control of coronavirus infection. Chinese herbal medicine (CHM) potentially has a therapeutic effect for treatment of coronavirus disease 2019 (COVID-19). Nevertheless, there are limited clinical practice suggestions on immunogenicity of the CHM against SARS-CoV-2. To assess the effect of oral CHM on immunogenicity and whether oral CHM improves the clinical parameters through the immunity profile during COVID-19, we performed the present study.

Methods

For this systematic review and meta-analysis, 11 databases were searched for relevant studies assessing oral CHM for COVID-19 on November 20, 2020 (updated March 9, 2021). Primary outcomes mainly included immunity profiles. Secondary outcomes included all-cause mortality; the remission time of fever, cough, chest tightness, and fatigue. The random effect was used to estimate the heterogeneity of the studies. Summary relative risks, weight mean difference and standardized mean difference were measured with 95% confidence intervals. Modified Jadad scale and Newcastle-Ottawa Scale were used to assess the risk of bias of randomized controlled trials (RCTs) and observational studies, respectively. The certainty of evidence was evaluated using the GRADE approach.

Results

We analyzed findings from 3,145 patients in 30 eligible studies. Compared with routine treatment, oral CHM, as an adjuvant medicine, improved lymphocyte counts, CD4+, and CD4+/CD8+ ratio with low quality of evidence; improved CD3+ with moderate quality of evidence; and reduced TNF-α with low certainty of evidence. Besides, oral CHM, as an adjuvant medicine reduced the time to clinical symptoms remission with a lower risk of all-cause mortality, compared with routine treatment alone.

Conclusion

CHM may be recommended as an adjuvant immunotherapy for disease modification and symptom relief in COVID-19 treatment. However, large RCTs objectively assessing the efficacy of CHM on immune responses in COVID-19 are needed to confirm our findings.
Different Types of ANCA Determine Different Clinical Phenotypes and Outcome in ANCA-Associated Vasculitis (AAV)
Authors: Bantis Kostas , Stangou Maria J. , Kalpakidis Savvas , Nikolaidou Christina , Lioulios George , Mitsoglou Zoi , Iatridi Fotini , Fylaktou Asimina , Papagianni Aikaterini
Published: January 2022

Aim

Accumulating evidence supports the use of antineutrophil cytoplasmic antibody (ANCA) type to classify different clinical entities. We aimed to evaluate whether the presence and type of ANCA determine different diseases, based on clinical phenotypes, renal involvement, and response to treatment.

Patients and Methods

Differences in terms of clinical manifestations, disease activity, laboratory parameters, and histology were recorded between patients with focal necrotizing glomerulonephritis (FNGN) due to myeloperoxidase (MPO-), proteinase 3-ANCA(+) [PR3-ANCA(+)], and ANCA(-) disease at time of diagnosis. Patients were treated with the same protocol and followed-up for 24 months, in a scheduled basis of every month for the first year and every 3 months for the second year. Primary end points were: (i) Combined end-stage renal disease (ESRD) and/or death and (ii) The presence of major or minor relapse during follow-up and secondary endpoint was the combination of ESRD and reduction of estimated glomerular filtration rate (eGFR) ≥ 50%.

Results

A total of 92 patients (M/F 39/53, mean age 59.1 ± 15 years) diagnosed with FNGN due to ANCA-associated vasculitis (AAV), 36 (39.1%) patients diagnosed with PR3-ANCA, 39 (42.4%) patients diagnosed with MPO-ANCA, and 17 (18.5%) patients diagnosed with ANCA(-) were included. Number of involved systems differed significantly between PR3-, MPO-ANCA, and ANCA(-), with only renal involvement in 3, 25.5, and 29% of patients, two systems involved in 33, 31, and 59% of patients, and > 3 systems involved in 64, 43.5, and 12% of patients, respectively (p = 0.002). Histology classification revealed focal, crescentic, mixed, and sclerotic type in 14, 64, 19, and 3% of PR3-ANCA(+), 8, 28, 18, and 46% of MPO-ANCA, and 41, 29, 6, and 24% of ANCA(-), respectively (p < 0.0001). Primary end point of ESRD ± Death was reached in 11 (30.6%), 16 (41%), and 6 (35.5%) patients with PR3-ANCA(+), MPO-ANCA(+), and ANCA(-), respectively (p = NS); similarly, ESRD± > 50% eGFR reduction in 8 (22.2%), 15 (38.5%), and 5 (29.4%) patients, respectively (p = NS), meaning that patients with MPO-ANCA(+) showed a propensity to decline renal function. Rate of relapse was increased in the presence of patients with PR3-ANCA(+), 14 (38.9%), 4 (11.8%), and 2 (10.3%) of patients with PR3-ANCA(+), MPO-ANCA(+), and ANCA(-), had at least one relapse during the two-year follow-up (p = 0.006).

Conclusion

Clinical phenotype and renal histology differ significantly between PR3-ANCA(+), MPO-ANCA(+), and ANCA(-) disease and FNGN; however, renal function outcome is similar, despite the increased rate of relapses in patients with PR3-ANCA(+).
Local Methotrexate Injection Followed by Dilation and Curettage for Cesarean Scar Pregnancy: A Prospective Non-randomized Study
Authors: Tan Kai-Liang , Chen Yu-Mei , Zeng Wei , Meng Ying , Jiang Li
Published: January 2022

Purpose

To evaluate the clinical effects and outcomes of local intra-gestational sac methotrexate injection followed by dilation and curettage for treatment of cesarean scar pregnancies (CSP).

Method

This prospective non-randomized study was conducted on patients diagnosed with CSP between 2018 and 2020 at the Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region. Patients were categorized into two groups according to the treatments, i.e., local intra-gestational sac methotrexate injection followed by dilation and curettage (group A), and uterine artery embolization in combination with dilation and curettage (group B). The choices of treatment reflect the patients' decision after they thoroughly understood the benefits and risks of the two therapies. Clinical data were then collected and compared between these two alternatives.

Results

Seventy-seven patients with CSP were enrolled in the study. Of this total, 41 vs. 36 were respectively categorized into group A and group B. Similar success rates were observed between these two groups (92.7 vs. 97.2%; RR = 27.362, 95% CI: 0.496–1.51E3, p = 0.106). However, the overall occurrence of complications in group A was significant lower when compared with group B (17.1 vs. 52.8%; RR = 0.236, 95% CI: 0.077–0.728, p = 0.012). Lower abdominal pain (unrelated to infection) and intrauterine adhesions were the two primary complications exhibited in group B of the present study, with rates of 38.9 and 22.2% respectively.

Conclusions

Local intra-gestational sac methotrexate injection followed by dilation and curettage is an effective and safe treatment for CSP that also drastically reduces the risks of complications. Further multiple center randomized trials with large series are warranted to confirm these findings.
Elevated Serum D-Dimer May Reflect the Presence of Gut Inflammation in Spondyloarthritis
Authors: Feng Jiaqi , Li Jia , Li Yixuan , Jin Yuyang , Du Fang , Chen Xiaoxiang
Published: January 2022

Background

To investigate the association of D-dimer with gut inflammation in spondyloarthritis (SpA).

Methods

Sixty-five patients with SpA and 70 healthy controls were included. Demographic, clinical, and laboratory parameters were collected. The differences of clinical and laboratory parameters were compared between patients with SpA and healthy controls, and between patients with SpA, with and without gut inflammation. The associations of D-dimer with laboratory data were analyzed. The predictive value of D-dimer was obtained by a receiver operator characteristic (ROC) curve analysis. The independent risk factors for gut inflammation in SpA were investigated by binary logistic regression analysis.

Results

Patients with SpA had higher D-dimer than healthy controls (P = 0.016). D-dimer was positively correlated with platelet (PLT), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP), and negatively correlated with hemoglobin (Hb). Besides, significant differences were observed in D-dimer between SpA patients with and without gut inflammation (P < 0.001). Furthermore, SpA patients with gut inflammation were more likely to have peripheral joint involvement than those without gut inflammation (P < 0.001). The AUC of D-dimer was 0.865 at cut-off value of 0.29 mg/L, with a sensitivity of 82.6%, and a specificity of 81%. Elevated D-dimer (OR = 15.451, 95% CI: 3.030–78.780, P = 0.001) was independently associated with gut inflammation in SpA.

Conclusion

D-dimer may be a potential biomarker for identifying SpA patients with gut inflammation.
The Role of Pre-therapeutic 18F-FDG PET/CT in Pediatric Hemophagocytic Lymphohistiocytosis With Epstein-Barr Virus Infection
Authors: Lu Xia , Wei Ang , Yang Xu , Liu Jun , Li Siqi , Kan Ying , Wang Wei , Wang Tianyou , Zhang Rui , Yang Jigang
Published: January 2022

Objective

To evaluate the role of pre-therapeutic 18F-FDG PET/CT in pediatric hemophagocytic lymphohistiocytosis (HLH) with Epstein-Barr virus (EBV) infection.

Methods

This retrospective study included 29 HLH children (1–16 years) with EBV infection, who underwent pre-therapeutic 18F-FDG PET/CT from July 2018 to November 2020. Pathology results were considered as the reference standard. These patients were divided into two groups: EBV-induced malignancy-associated HLH (M-HLH, N = 9) and EBV-induced non-malignancy-associated HLH (NM-HLH, N = 20). The regions of interest (ROIs) of the liver, spleen (Sp), bone marrow (BM), lymph nodes (LN), hypermetabolic lesions, liver background (LiBG), and mediastinum (M) were drawn with software 3D-Slicer. The volumetric and metabolic parameters, including maximum standard uptake value (SUVmax), metabolic tumor volume, and total lesion glycolysis of these ROIs, clinical parameters, and laboratory parameters were compared between the two groups. The efficiency of the above parameters in predicting the treatment response and overall survival (OS) was analyzed.

Results

Receiver operating characteristic curve analysis indicated that SUVmax-lesions and SUVmax-LN/M (AUC = 0.822, 0.819, cut-off = 6.04, 5.74, respectively) performed better in differentiating M-HLH from NM-HLH. It had the best diagnostic performance when age was added with the SUVmax-LN/M (AUC = 0.933, sensitivity = 100%, specificity = 85.0%). The presence of extranodal hypermetabolic lesions in multiple organs indicated the M-HLH (P = 0.022). Older age, higher SUVmax-LN and SUVmax-lesions, and the presence of serous effusion were associated with poorer treatment response at the 2nd and 4th week (not reaching partial remission). Multivariate analysis showed that SUVmax-lesions > 7.66 and SUVmax-Sp/LiBG > 2.01 were independent prognostic factors for overall survival (P = 0.025, 0.036, respectively).

Conclusions

18F-FDG PET/CT could be a valuable technique for identifying the underlying malignancy and predicting prognosis in pediatric HLH with EBV infection. M-HLH could be considered when SUVmax-lesions > 6.04, SUVmax-LN/M > 5.74, and the presence of extranodal hypermetabolic lesions in multiple organs on 18F-FDG PET/CT. SUVmax-lesions and SUVmax-Sp/LiBG might be independent prognostic factors for OS.
Dissecting the Role of SAL1 in Metabolizing the Stress Signaling Molecule 3′-Phosphoadenosine 5′-Phosphate in Different Cell Compartments
Authors: Ashykhmina Natallia , Chan Kai Xun , Frerigmann Henning , Van Breusegem Frank , Kopriva Stanislav , Flügge Ulf-Ingo , Gigolashvili Tamara
Published: January 2022

Plants possess the most highly compartmentalized eukaryotic cells. To coordinate their intracellular functions, plastids and the mitochondria are dependent on the flow of information to and from the nuclei, known as retrograde and anterograde signals. One mobile retrograde signaling molecule is the monophosphate 3′-phosphoadenosine 5′-phosphate (PAP), which is mainly produced from 3′-phosphoadenosine 5′-phosphosulfate (PAPS) in the cytosol and regulates the expression of a set of nuclear genes that modulate plant growth in response to biotic and abiotic stresses. The adenosine bisphosphate phosphatase enzyme SAL1 dephosphorylates PAP to AMP in plastids and the mitochondria, but can also rescue sal1 Arabidopsis phenotypes (PAP accumulation, leaf morphology, growth, etc.) when expressed in the cytosol and the nucleus. To understand better the roles of the SAL1 protein in chloroplasts, the mitochondria, nuclei, and the cytosol, we have attempted to complement the sal1 mutant by specifically cargoing the transgenic SAL1 protein to these four cell compartments. Overexpression of SAL1 protein targeted to the nucleus or the mitochondria alone, or co-targeted to chloroplasts and the mitochondria, complemented most aspects of the sal1 phenotypes. Notably, targeting SAL1 to chloroplasts or the cytosol did not effectively rescue the sal1 phenotypes as these transgenic lines accumulated very low levels of SAL1 protein despite overexpressing SAL1 mRNA, suggesting a possibly lower stability of the SAL1 protein in these compartments. The diverse transgenic SAL1 lines exhibited a range of PAP levels. The latter needs to reach certain thresholds in the cell for its impacts on different processes such as leaf growth, regulation of rosette morphology, sulfate homeostasis, and glucosinolate biosynthesis. Collectively, these findings provide an initial platform for further dissection of the role of the SAL1–PAP pathway in different cellular processes under stress conditions.
Toll-Like Receptors Serve as Biomarkers for Early Diagnosis and Prognosis Assessment of Kidney Renal Clear Cell Carcinoma by Influencing the Immune Microenvironment: Comprehensive Bioinformatics Analysis Combined With Experimental Validation
Authors: Zou Xiong , Guo Bingqian , Ling Qiang , Mo Zengnan
Published: January 2022

Background: Toll-like receptors (TLRs) are important initiators of innate and acquired immune responses. However, its role in kidney renal clear cell carcinoma (KIRC) remains unclear.

Methods: TLRs and their relationships with KIRC were studied in detail by ONCOMINE, UALCAN, GEPIA, cBioPortal, GeneMANIA, FunRich, LinkedOmics, TIMER and TRRUST. Moreover, we used clinical samples to verify the expressions of TLR3 and TLR4 in early stage of KIRC by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR), flow cytometry (FC) and immunohistochemistry (IHC).

Results: The expression levels of TLRs in KIRC were generally different compared with adjacent normal tissues. Moreover, the expressions of TLR3 and TLR4 elevated significantly in the early stage of KIRC. Overexpressions of TLR1, TLR3, TLR4 and TLR8 in KIRC patients were associated with longer overall survival (OS), while inhibition of TLR9 expression was related to longer OS. Additionally, overexpressions of TLR1, TLR3 and TLR4 in KIRC patients were associated with longer disease free survival (DFS). There were general genetic alterations and obvious co-expression correlation of TLRs in KIRC. The PPI network between TLRs was rather complex, and the key gene connecting the TLRs interaction was MYD88. The GO analysis and KEGG pathway analysis indicated that TLRs were closely related to adaptive immunity, innate immunity and other immune-related processes. RELA, NFKB1, IRF8, IRF3 and HIF1A were key transcription factors regulating the expressions of TLRs. What’s more, the expression levels of all TLRs in KIRC were positively correlated with the infiltration levels of dendritic cells, macrophages, neutrophils, B cells, CD4+ T cells and CD8+ T cells. Finally, the results of RT-qPCR, FC and IHC confirmed that TLR3 and TLR4 were significantly elevated in the early stage of KIRC.

Conclusion: The occurrence and development of KIRC are closely related to TLRs, and TLRs have the potential to be early diagnostic biomarkers of KIRC and biomarkers for judging the prognosis and immune status of KIRC. This study may provide new insights into the selection of KIRC immunotherapy targets.
No Evidence for a Role of Oral Contraceptive-Use in Emotion Recognition But Higher Negativity Bias in Early Follicular Women
Authors: Kimmig Ann-Christin Sophie , Bischofberger Jasper Amadeus , Birrenbach Annika Dorothea , Drotleff Bernhard , Lämmerhofer Michael , Sundström-Poromaa Inger , Derntl Birgit
Published: January 2022

Accuracy in facial emotion recognition has shown to vary with ovarian hormones, both in naturally cycling women, as well as in women taking oral contraceptives. It remains uncertain however, if specific – endogenous and exogenous – hormonal levels selectively impact recognition of certain basic emotions (or neutral faces) and if this relationship coincides with certain affective states. Therefore, we investigated 86 women under different hormonal conditions and compared their performance in an emotion recognition task as well as self-reported measures of affective states. Based on self-reported cycle days and ovulation testing, the participants have been split into groups of naturally cycling women during their early follicular phase (fNC, n = 30), naturally cycling women during their peri-ovulatory phase (oNC, n = 26), and women taking oral contraceptives (OC, n = 30). Participants were matched for age and did not differ in education or neuropsychological abilities. Self-reported anxiety and depressive affective state scores were similar across groups, but current affective state turned out to be significantly more negative in fNC women. Independent of negative affective state, fNC women showed a significantly higher negativity bias in recognizing neutral faces, resulting in a lower recognition accuracy of neutral faces compared to oNC and OC women. In the OC group only, negative affective state was associated with lower recognition accuracy and longer response times for neutral faces. Furthermore, there was a significant, positive association between disgust recognition accuracy and negative affective state in the fNC group. Low progesterone levels during the early follicular phase were linked to higher negative affective state, whereas in the peri-ovulatory phase they were linked to elevated positive affective state. Overall, previous findings regarding impaired emotion recognition during OC-use were not confirmed. Synthetic hormones did not show a correlation with emotion recognition performance and affective state. Considering the important role of emotion recognition in social communication, the elevated negativity bias in neutral face recognition found for fNC women may adversely impact social interactions in this hormonal phase.
Reactive Astrocytes Contribute to Alzheimer’s Disease-Related Neurotoxicity and Synaptotoxicity in a Neuron-Astrocyte Co-culture Assay
Authors: Wasilewski David , Villalba-Moreno Nelson David , Stange Inke , Glatzel Markus , Sepulveda-Falla Diego , Krasemann Susanne
Published: January 2022

Pathological hallmarks of Alzheimer’s disease (AD) include deposition and accumulation of amyloid- β (Aβ), neurofibrillary tangle formation, and neuronal loss. Pathogenesis of presymptomatic disease stages remains elusive, although studies suggest that the early structural and functional alterations likely occur at neuronal dendritic spines. Presymptomatic alterations may also affect different CNS cell types. However, specific contributions of these cell types as cause or consequence of pathology are difficult to study in vivo. There is a shortage of relatively simple, well-defined, and validated in vitro models that allow a straightforward interpretation of results and recapitulate aspects of pathophysiology. For instance, dissecting the AD-related processes (e.g., neurotoxicity vs. synaptotoxicity) may be difficult with the common cell-based systems such as neuronal cell lines or primary neurons. To investigate and characterize the impact of reactive astrocytes on neuronal morphology in the context of AD-related cues, we modified an in vitro co-culture assay of primary mouse neurons and primary mouse astrocytes based on the so-called Banker “sandwich” co-culture assay. Here, we provide a simple and modular assay with fully differentiated primary mouse neurons to study the paracrine interactions between the neurons and the astrocytes in the co-culture setting. Readouts were obtained from both cell types in our assay. Astrocyte feeder cells were pre-exposed to neuroinflammatory conditions by means of Aβ42, Aβ40, or lipopolysaccharide (LPS). Non-cell autonomous toxic effects of reactive astrocytes on neurons were assessed using the Sholl analysis to evaluate the dendritic complexity, whereas synaptic puncta served as a readout of synaptotoxicity. Here, we show that astrocytes actively contribute to the phenotype of the primary neurons in an AD-specific context, emphasizing the role of different cell types in AD pathology. The cytokine expression pattern was significantly altered in the treated astrocytes. Of note, the impact of reactive astrocytes on neurons was highly dependent on the defined cell ratios. Our co-culture system is modular, of low cost, and allows us to probe aspects of neurodegeneration and neuroinflammation between the two major CNS cell types, neurons, and astrocytes, under well-defined experimental conditions. Our easy-to-follow protocol, including work-flow figures, may also provide a methodological outline to study the interactions of astrocytes and neurons in the context of other diseases in the future.
Chronic Intermittent Hypoxia-Induced Aberrant Neural Activities in the Hippocampus of Male Rats Revealed by Long-Term in vivo Recording
Authors: Xu Linhao , Li Qian , Ke Ya , Yung Wing-Ho
Published: January 2022

Chronic intermittent hypoxia (CIH) occurs in obstructive sleep apnea (OSA), a common sleep-disordered breathing associated with malfunctions in multiple organs including the brain. How OSA-associated CIH impacts on brain activities and functions leading to neurocognitive impairment is virtually unknown. Here, by means of in vivo electrophysiological recordings via chronically implanted multi-electrode arrays in male rat model of OSA, we found that both putative pyramidal neurons and putative interneurons in the hippocampal CA1 subfield were hyper-excitable during the first week of CIH treatment and followed by progressive suppression of neural firing in the longer term. Partial recovery of the neuronal activities was found after normoxia treatment but only in putative pyramidal neurons. These findings correlated well to abnormalities in dendritic spine morphogenesis of these neurons. The results reveal that hippocampal neurons respond to CIH in a complex biphasic and bidirectional manner eventually leading to suppression of firing activities. Importantly, these changes are attributed to a larger extent to impaired functions of putative interneurons than putative pyramidal neurons. Our findings therefore revealed functional and structural damages in central neurons in OSA subjects.
Shared Decision Making for Radioiodine Therapy and the Actual Pattern of Care in Intermediate-Risk Differentiated Thyroid Carcinoma
Authors: Eilsberger Friederike , Luster Markus , Reiners Christoph
Published: January 2022

Radioiodine therapy (RAI) is usually a standard procedure performed after thyroidectomy in differentiated thyroid cancer (DTC). While the indication for RAI in high-risk patients has been established in various national and international guidelines, there is an ongoing discussion with regard to intermediate-risk patients. In addition to the inconsistent definition of this risk category, the absence of large multinational prospective randomized controlled trials forms the basis of the debate. In this context, the actual pattern of care and national guidelines in the country where the patient is living plays an important role with respect to regional iodine supply and goiter prevalence, preoperative diagnostics (fine needle aspiration biopsy), and corresponding surgical strategies. Participatory decision-making between physician and informed patient, which is demanded in principle today anyway, is of particular importance in this situation. This article will discuss the approach of shared decision making for radioiodine therapy in intermediate-risk DTC.
Twelve Antioxidant Peptides From Protein Hydrolysate of Skipjack Tuna (Katsuwonus pelamis) Roe Prepared by Flavourzyme: Purification, Sequence Identification, and Activity Evaluation
Authors: Wang Jiao , Wang Yu-Mei , Li Long-Yan , Chi Chang-Feng , Wang Bin
Published: January 2022

For using aquatic by-products to manufacture high-value products, Skipjack tuna (Katsuwonus pelamis) roes were degreased, pretreated with microwave, and hydrolyzed using five proteases. The protein hydrolysate (TRPH) generated using Flavourzyme displayed the strongest 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity. Twelve antioxidative peptides were prepared from TRPH by ultrafiltration and chromatography methods and determined to be SGE, VDTR, AEM, QDHKA, TVM, QEAE, YEA, VEP, AEHNH, QEP, QAEP, and YVM with molecular weights of 291.24, 489.50, 349.41, 597.59, 349.44, 475.42, 381.36, 343.37, 606.58, 372.35, 443.42, and 411.49 Da, respectively. AEM, QDHKA, YEA, AEHNH, and YVM presented the strongest scavenging activity on DPPH radical (EC50 values of 0.250±0.035, 0.279±0.017, 0.233±0.012, 0.334±0.011, and 0.288±0.015 mg/ml, respectively), hydroxyl radical (EC50 values of 0.456±0.015, 0.536±0.021, 0.476 ± 0.051, 0.369 ± 0.052, and 0.413 ± 0.019 mg/ml, respectively), and superoxide anion free radical (EC50 values of 0.348 ± 0.018, 0.281 ± 0.013, 0.305 ± 0.022, 0.198 ± 0.011, and 0.425 ± 0.021 mg/ml, respectively). Moreover, AEM, QDHKA, YEA, AEHNH, and YVM presented high lipid peroxidation inhibition ability, Ferric-reducing power, and significant protective function on H2O2-induced Chang liver cells. Therefore, AEM, QDHKA, YEA, AEHNH, and YVM could be natural antioxidant ingredients used in pharmaceutical and functional products.
Optimization of Supercritical CO2 Extraction of Moringa oleifera Seed Oil Using Response Surface Methodological Approach and Its Antioxidant Activity
Authors: Chen Xuexiang , Li Zhuobin , Smith Sarah A. , Chen Mingxiu , Liu Hanbin , Zhang Jing , Tang Lirong , Li Jie , Liu Qishan , Wu Xian
Published: January 2022

Moringa (Moringa oleifera) seed oil is an edible vegetable oil rich in unsaturated fatty acids. In this study, the supercritical CO2 fluid extraction method was employed to obtain the maximum yield of moringa seed oil. The effects of temperature, time, and pressure, three characteristics of extractions, on the extraction rate of Moringa seed oil were investigated by single factor test and response surface methodological approach. The optimal process conditions of supercritical CO2 fluid extraction of moringa seed oil were determined as extraction temperature of 45°C, extraction time of 2.5 h, extraction pressure of 50 MPa, and CO2 flow rate of 240 L/h, resulting in a maximum yield of 38.54%. Composition analysis shows that the extracted moringa seed oil is rich in unsaturated fatty acids, including oleic acid, octadecanoic acid, palmitic acid, stearic acid, eicosanoic acid, etc. Furthermore, we found that Moringa seed oil exerted potent antioxidant activities on DPPH and hydroxyl radicals, and its efficacy was comparable to commercial peanut oil and tea oil. Overall, this novel extraction method of moringa seed oil may increase its potential value and application in the food and nutraceutical industries.
Escape From Cisplatin-Induced Senescence of Hypoxic Lung Cancer Cells Can Be Overcome by Hydroxychloroquine
Authors: Olszewska Aleksandra , Borkowska Agata , Granica Monika , Karolczak Justyna , Zglinicki Bartosz , Kieda Claudine , Was Halina
Published: January 2022

Chemotherapy is the commonly used treatment for advanced lung cancer. However, it produces side effects such as the development of chemoresistance. A possible responsible mechanism may be therapy-induced senescence (TIS). TIS cells display increased senescence-associated β-galactosidase (SA-β-gal) activity and irreversible growth arrest. However, recent data suggest that TIS cells can reactivate their proliferative potential and lead to cancer recurrence. Our previous study indicated that reactivation of proliferation by TIS cells might be related with autophagy modulation. However, exact relationship between both processes required further studies. Therefore, the aim of our study was to investigate the role of autophagy in the senescence-related chemoresistance of lung cancer cells. For this purpose, human and murine lung cancer cells were treated with two commonly used chemotherapeutics: cisplatin (CIS), which forms DNA adducts or docetaxel (DOC), a microtubule poison. Hypoxia, often overlooked in experimental settings, has been implicated as a mechanism responsible for a significant change in the response to treatment. Thus, cells were cultured under normoxic (~19% O2) or hypoxic (1% O2) conditions. Herein, we show that hypoxia increases resistance to CIS. Lung cancer cells cultured under hypoxic conditions escaped from CIS-induced senescence, displayed reduced SA-β-gal activity and a decreased percentage of cells in the G2/M phase of the cell cycle. In turn, hypoxia increased the proliferation of lung cancer cells and the proportion of cells proceeding to the G0/G1 phase. Further molecular analyses demonstrated that hypoxia inhibited the prosenescent p53/p21 signaling pathway and induced epithelial to mesenchymal transition in CIS-treated cancer cells. In cells treated with DOC, such effects were not observed. Of importance, pharmacological autophagy inhibitor, hydroxychloroquine (HCQ) was capable of overcoming short-term CIS-induced resistance of lung cancer cells in hypoxic conditions. Altogether, our data demonstrated that hypoxia favors cancer cell escape from CIS-induced senescence, what could be overcome by inhibition of autophagy with HCQ. Therefore, we propose that HCQ might be used to interfere with the ability of senescent cancer cells to repopulate following exposure to DNA-damaging agents. This effect, however, needs to be tested in a long-term perspective for preclinical and clinical applications.
Nomograms Incorporating the CNLC Staging System Predict the Outcome of Hepatocellular Carcinoma After Curative Resection
Authors: Liao Rui , Wei Xu-Fu , Che Ping , Yin Kun-Li , Liu Lei
Published: January 2022

Purpose

Prediction models of postoperative outcomes of patients with hepatocellular carcinoma (HCC) after surgery based on the China liver cancer (CNLC) staging system are rare. This study aimed to compare the prognostic abilities of CNLC, Tumor-Node-Metastasis (TNM) 8th edition, and Barcelona Clinic Liver Cancer (BCLC) staging systems for HCC after curative resection. We developed two nomograms incorporating the CNLC staging system to predict the postoperative recurrence-free survival (RFS) and overall survival (OS) of HCC patients.

Patients and methods

The prognostic abilities of the CNLC, TNM and BCLC staging systems for HCC after curative resection were compared using receiver operating characteristic (ROC) curves. Two nomograms incorporating five selected risk factors were constructed based on multivariate Cox regression in the primary cohort of 312 HCC patients. It was validated with an independent validation cohort of 130 HCC patients. The predictive performance and discrimination ability of the two nomograms were further evaluated and compared with those of the TNM and BCLC staging systems.

Results

The CNLC staging system had a higher area under the receiver operating characteristic curve (AUROC) value for both OS (AUC=0.692) and RFS (AUC=0.673) than the TNM (ROC=0.667 for OS and 0.652 for RFS) and BCLC (ROC=0.671 for OS and 0.670 for RFS) staging systems. The independent predictors of OS (cirrhosis, gamma-glutamyl transpeptidase (GGT), tumor differentiation and CNLC staging system) and RFS (α-fetoprotein (AFP) and CNLC staging system) were incorporated into the two nomograms. The OS and RFS nomograms consistently outperformed the TNM and BCLC staging systems in the primary cohort. These results were verified in the validation cohort. In the 442 patients with HCC, the RFS nomogram could predict early recurrence very well.

Conclusion

The two proposed nomograms incorporating the CNLC staging system can predict the outcomes of patients with HCC after curative hepatectomy in clinical practice.
Personalized Medicine for Prostate Cancer: Is Targeting Metabolism a Reality?
Authors: Fidelito Gio , Watt Matthew J. , Taylor Renea A.
Published: January 2022

Prostate cancer invokes major shifts in gene transcription and metabolic signaling to mediate alterations in nutrient acquisition and metabolic substrate selection when compared to normal tissues. Exploiting such metabolic reprogramming is proposed to enable the development of targeted therapies for prostate cancer, yet there are several challenges to overcome before this becomes a reality. Herein, we outline the role of several nutrients known to contribute to prostate tumorigenesis, including fatty acids, glucose, lactate and glutamine, and discuss the major factors contributing to variability in prostate cancer metabolism, including cellular heterogeneity, genetic drivers and mutations, as well as complexity in the tumor microenvironment. The review draws from original studies employing immortalized prostate cancer cells, as well as more complex experimental models, including animals and humans, that more accurately reflect the complexity of the in vivo tumor microenvironment. In synthesizing this information, we consider the feasibility and potential limitations of implementing metabolic therapies for prostate cancer management.