bluuebunny/crossref_metadata_2025 huggingface dataset:
Paternal De Novo Variant of TAOK1 in a Fetus With Structural Brain Abnormalities
Authors: Yu Lihua , Yang Chaoxiang , Shang Ning , Ding Hongke , Zhu Juan , Zhu Yuanyuan , Tan Haowen , Zhang Yan
Published: July 2022

A dilated lateral ventricle is a relatively common finding on prenatal ultrasound, and the causes are complex. We aimed to explore the etiology of a fetus with a dilated lateral ventricle. Trio whole-exome sequencing was performed to detect causative variants. A de novo variant of TAOK1 (NM_020791.2: c.227A>G) was detected in the proband and evaluated for potential functional impacts using a variety of prediction tools. Droplet digital polymerase chain reaction was used to exclude the parental mosaicism and to verify the phasing of the de novo variant. Based on peripheral blood analysis, the parents did not exhibit mosaicism at this site, and the de novo variant was paternally derived. Here, we describe a fetus with a de novo likely pathogenic variant of TAOK1 who had a dilated lateral ventricle and a series of particular phenotypes. This case expands the clinical spectrum of TAOK1-associated disorders. We propose a method for solving genetic disorders in which the responsible genes have not yet gone through ClinGen curation, particularly for prenatal cases.
Pyroptotic Patterns in Blood Leukocytes Predict Disease Severity and Outcome in COVID-19 Patients
Authors: Tang Yingkui , Zhang Peidong , Liu Qiuyu , Cao Luyang , Xu Jingsong
Published: July 2022

The global coronavirus disease 2019 (COVID-19) pandemic has lasted for over 2 years now and has already caused millions of deaths. In COVID-19, leukocyte pyroptosis has been previously associated with both beneficial and detrimental effects, so its role in the development of this disease remains controversial. Using transcriptomic data (GSE157103) of blood leukocytes from 126 acute respiratory distress syndrome patients (ARDS) with or without COVID-19, we found that COVID-19 patients present with enhanced leukocyte pyroptosis. Based on unsupervised clustering, we divided 100 COVID-19 patients into two clusters (PYRcluster1 and PYRcluster2) according to the expression of 35 pyroptosis-related genes. The results revealed distinct pyroptotic patterns associated with different leukocytes in these PYRclusters. PYRcluster1 patients were in a hyperinflammatory state and had a worse prognosis than PYRcluster2 patients. The hyperinflammation of PYRcluster1 was validated by the results of gene set enrichment analysis (GSEA) of proteomic data (MSV000085703). These differences in pyroptosis between the two PYRclusters were confirmed by the PYRscore. To improve the clinical treatment of COVID-19 patients, we used least absolute shrinkage and selection operator (LASSO) regression to construct a prognostic model based on differentially expressed genes between PYRclusters (PYRsafescore), which can be applied as an effective prognosis tool. Lastly, we explored the upstream transcription factors of different pyroptotic patterns, thereby identifying 112 compounds with potential therapeutic value in public databases.
Functional Properties of Protein Hydrolysates on Growth, Digestive Enzyme Activities, Protein Metabolism, and Intestinal Health of Larval Largemouth Bass (Micropterus salmoides)
Authors: Sheng Zhengyu , Turchini Giovanni M. , Xu Jianming , Fang Zishuo , Chen Naisong , Xie Ruitao , Zhang Haitao , Li Songlin
Published: July 2022

The present study was conducted to investigate the effects of dietary inclusion of protein hydrolysates on growth performance, digestive enzyme activities, protein metabolism, and intestinal health in larval largemouth bass (Micropterus salmoides). The experimental feeding trial presented in this study was based on five isonitrogenous and isolipidic diets formulated with graded inclusion levels of protein hydrolysates, and it showed that protein hydrolysates improved growth performance, reduced larval deformity rate, and increased the activity of digestive enzymes, including pepsin and trypsin. Gene expression results revealed that the supplementation of protein hydrolysates upregulated the expression of intestinal amino acid transporters LAT2 and peptide transporter 2 (PepT2), as well as the amino acid transporters LAT1 in muscle. Dietary provision of protein hydrolysates activated the target of rapamycin (TOR) pathway including the up-regulation of TOR and AKT1, and down-regulation of 4EBP1. Additionally, the expression of genes involved in the amino acids response (AAR) pathway, ATF4 and REDD1, were inhibited. Protein hydrolysates inhibited the transcription of some pro-inflammatory cytokines, including IL-8 and 5-LOX, but promoted the expression of anti-inflammatory cytokines TGF-β and IL-10. The 16S rRNA analysis, using V3-V4 region, indicated that dietary protein hydrolysates supplementation reduced the diversity of the intestine microbial community, increased the enrichment of Plesiomonas and reduced the enrichment of Staphylococcus at the genus level. In summary, protein hydrolysates have been shown to be an active and useful supplement to positively complement other protein sources in the diets for largemouth bass larvae, and this study provided novel insights on the beneficial roles and possible mechanisms of action of dietary protein hydrolysates in improving the overall performance of fish larvae.
Characterization of monoclonal antibodies that specifically differentiate field isolates from vaccine strains of classical swine fever virus
Authors: Mi Shijiang , Wang Lihua , Li Hongwei , Bao Fei , Madera Rachel , Shi Xiju , Zhang Liying , Mao Yingying , Yan Renhe , Xia Xianzhu , Gong Wenjie , Shi Jishu , Tu Changchun
Published: July 2022

Classical swine fever virus (CSFV) is a major animal pathogen threatening the global pork industry. To date, numerous anti-CSFV monoclonal antibodies (mAbs) and their recognizing epitopes have been reported. However, few mAbs were systematically characterized for the capacity to differentiate field CSFV isolates from CSF vaccine strains, and the molecular basis associated with antigenic differences between vaccines and field isolates is still largely unknown. In the present study, recombinant CSFV structural glycoproteins E2 of both virulent and vaccine strains and Erns of vaccine strain were expressed using eukaryotic cells and murine mAbs generated against E2 and Erns. After serial screening and cloning of the hybridomas, the viral spectra of mAbs were respectively determined by indirect fluorescent antibody assay (IFA) using 108 CSFVs, followed by Western blot analysis using expressed glycoproteins of all CSFV sub-genotypes including vaccine strains. The antigenic structures recognized by these mAbs were characterized by epitope mapping using truncated, chimeric, and site-directed mutated E2 and Erns proteins. We have identified two vaccine-specific, one field isolate-specific, and two universal CSFV-specific mAbs and five novel conformational epitopes with critical amino acid (aa) motifs that are associated with these five mAbs: 213EPD215, 271RXGP274, and 37LXLNDG42 on E2 and 38CKGVP42, W81, and D100/V107 on Erns. Particularly, E213 of E2 is field isolate-specific, while N40 of E2 and D100/V107 of Erns are vaccine strain-specific. Results from our study further indicate that N40D of E2 mutation in field strains was likely produced under positive selection associated with long-term mass vaccination, leading to CSFV evasion of host immune response. Taking together, this study provides new insights into the antigenic structure of CSFV E2 and Erns and the differentiating mAbs will contribute to the development of a diagnostic strategy to differentiate C-strain vaccination from natural infection (DIVA) of CSFV in terms of elimination of CSF in China.
Single-Cell Transcriptomics Reveals Killing Mechanisms of Antitumor Cytotoxic CD4+ TCR-T Cells
Authors: Liang Yanling , Xu Qumiao , Liu Songming , Li Jie , Wang Fei , Li Ziyi , Liao Lijuan , Lu Yuting , Li Yijian , Mu Feng , Sun Hai-Xi , Zhu Linnan
Published: July 2022

T cell receptor-engineered T cells (TCR-Ts) have emerged as potent cancer immunotherapies. While most research focused on classical cytotoxic CD8+ T cells, the application of CD4+ T cells in adoptive T cell therapy has gained much interest recently. However, the cytotoxic mechanisms of CD4+ TCR-Ts have not been fully revealed. In this study, we obtained an MHC class I-restricted MART-127-35-specific TCR sequence based on the single-cell V(D)J sequencing technology, and constructed MART-127-35-specific CD4+ TCR-Ts and CD8+ TCR-Ts. The antitumor effects of CD4+ TCR-Ts were comparable to those of CD8+ TCR-Ts in vitro and in vivo. To delineate the killing mechanisms of cytotoxic CD4+ TCR-Ts, we performed single-cell RNA sequencing and found that classical granule-dependent and independent cytolytic pathways were commonly used in CD4+ and CD8+ TCR-Ts, while high expression of LTA and various costimulatory receptors were unique features for cytotoxic CD4+ TCR-Ts. Further signaling pathway analysis revealed that transcription factors Runx3 and Blimp1/Tbx21 were crucial for the development and killing function of cytotoxic CD4+ T cells. Taken together, we report the antitumor effects and multifaceted killing mechanisms of CD4+ TCR-Ts, and also indicate that MHC class I-restricted CD4+ TCR-Ts could serve as potential adoptive T cell therapies.
New Insight Into the Reproductive Biology and Catch of Juveniles of the Lutjanus purpureus in a Portion of the Great Amazon Reef System Off the Northern Brazilian Coast
Authors: Freire Julliany L. , Sarmento Gabriela C. , Lutz Ítalo , Bentes Bianca , Isaac Victoria J.
Published: July 2022

The Southern red snapper, Lutjanus purpureus, is a valuable economic resource, especially in international market. However, no recent data are available on the reproductive biology of this species in Brazilian waters, in particular, the stock found on the Amazon reef. The present study evaluated the population structure and reproductive biology of L. purpureus, and the volume of the catch of juveniles taken by the local commercial fisheries. A total of 923 specimens were analyzed, of which, 577 were female and 346 male (sex ratio: 0.6:1; p < 0.05). The analysis of the gonadosomatic index (GSI) and the distribution of maturation stages indicated that the males and females are able to reproduce throughout the year, however the reproductive peak occurs simultaneously with the increase in the water discharge of the Amazon River. The spawning females were registered in the study area, indicating that L. purpureus does not perform long distance reproductive migrations, different from the previously proposed. The Fork length at first sexual maturation (FL50) was estimated to be 35.2 cm in the males and 32.1 cm in the females. The high frequency of juveniles (< FL50) captured by the commercial snapper fleet using longlines (33.67% of the total catch) and traps (42.1%) indicates the poor selectivity of the fishing gear used by the snapper fleet, which may contribute to the accelerated depletion of the L. purpureus stock. Although the results of this study show a catch percentage of juveniles >50%, it is still a significant percentage of juveniles that are being caught due to little or no guidance and enforcement of fishing gear to ensure compliance with current legislation. Considering the data presented in this study and the current situation of declining fish stocks of L. purpureus, an assessment is recommended for the inclusion of the species in the IUCN Red List of Threatened Species, which is currently a species categorized as “vulnerable” in the Brazilian Red List.
Comparative Effects of Microalgal Species on Growth, Feeding, and Metabolism of Pearl Oysters, Pinctada fucata martensii and Pinctada maxima
Authors: Ye Bingcong , Gu Zhifeng , Zhang Xingzhi , Yang Yi , Wang Aimin , Liu Chunsheng
Published: July 2022

Pinctada fucata martensii and P. maxima are two main traditional pearl oyster species that can produce seawater pearls. Our previous study showed a higher clearance rate (CR) and growth performance in P. f. martensii than in P. maxima fed with Isochrysis galbana. In this study, the P. f. martensii and P. maxima juveniles of two sizes (large and small) were fed with six different microalgae diets [I. galbana (I), Platymonas subcordiformis (P), Chaetoceros muelleri I, I+P, I+C, and P+C] to evaluate the differences in growth, feeding, and metabolism between two pearl oyster species. After 60 d of the rearing period, P. f. martensii and P. maxima fed with mixed microalgae showed a significantly higher relative growth rate (RGR) than those fed with single microalgae (P< 0.05). The RGRs were significantly higher in P. f. martensii than those in P. maxima fed with the same diets (P< 0.05). The RGRs showed a decreasing tendency with the growth in both pearl oyster species. The CRs of pearl oysters fed with mixed microalgae were significantly higher than those fed with single microalgae (P< 0.05), and the CRs of P. f. martensii were significantly higher than those of P. maxima fed with the same diets (P< 0.05). Significantly lower respiration rates (RRs) were observed in small-size P. f. martensii groups fed with I, P, and I+P diets and all large P. f. martensii groups compared to P. maxima fed with the same diets (P< 0.05). Higher activities of amylase, cellulase, lipase, and pepsin in P. f. martensiiwere observed compared to P. maxima fed with the same diets at two sizes. The pepsin activities in P. maxima decreased with the growth, while there were no consistent pepsin activities of P. f. martensii with the growth. The carbonic anhydrase activities in P. maxima were significantly higher than those in P. f. martensii fed with the same diets (P< 0.05). The carbonic anhydrase activities were highest in the I+C diet group, followed by C+P and I+P, I, C, and P groups. Significant differences were observed among different diet groups in the same pearl oyster species (P< 0.05). Our results suggest that the lower CR and activities of digestive enzymes and higher RRs and activities of carbonic anhydrase may cause a lower growth rate of P. maxima compared to P. f. martensii.
Characterization of Spermidine Synthase (SPDS) Gene and RNA−Seq Based Identification of Spermidine (SPD) and Spermine (SPM) Involvement in Improving High Temperature Stress Tolerance in Gracilariopsis lemaneiformis (Rhodophyta)
Authors: Liu Shixia , Zhang Jun , Sun Xue , Xu Nianjun
Published: July 2022

Gracilariopsis lemaneiformis, an important commercial red macroalga, is facing significant impacts from global warming, which limits algal growth and yield in China. Polyamines (PAs), spermidine (SPD) and spermine (SPM), are ubiquitous polycations important for growth and environmental stress responses including high temperature (HT) tolerance. Spermidine synthase (SPDS) gene is one of the important genes in higher PA biosynthesis, which plays critical roles in HT stress response. Here, we isolated an SPDS gene from G. lemaneiformis and further analyzed its phylogenetic tree, subcellular localization, and gene expression patterns under stress conditions. Meanwhile, supplemented with SPD and SPM were used to study the effects of PAs on HT tolerance in G. lemaneiformis. It showed exogenous 0.5 mM SPD and SPM, respectively, remarkably improved the algal relative growth rate (RGR) compared to those in the CK treatment groups under HT conditions. In addition, they both significantly elevated the activities of antioxidant enzymes and significantly upregulated the expression of genes encoding antioxidant enzymes, triggered transcription factors (TFs) signaling, and improved the expression of genes encoding small heat shock proteins (sHSP20s) during HT stress. Moreover, exogenous PA also enhanced the expression of genes involved in pyruvate metabolism, ascorbate and aldarate metabolism, and nucleotide excision repair in G. lemaneiformis, which helped to maintain better energy supply, redox homeostasis, and genome integrity under HT stress. Taken together, these data provided valuable information for functional characterization of specific gene in endogenous PA synthesis and uncovered the importance of exogenous PAs in promoting algae adaptation to HT stress.
Oceanic Fronts Shape Biodiversity of Gelatinous Zooplankton in the European Arctic
Authors: Mańko Maciej K. , Merchel Malgorzata , Kwasniewski Slawomir , Weydmann-Zwolicka Agata
Published: July 2022

Oceanic fronts constitute boundaries between hydrologically distinct water masses and comprise one of the most productive regions of the world’s ocean. Fronts associated with density gradients (active fronts) profoundly structure planktonic communities in adjacent waters, but less is known about the impacts of density-compensated (passive) fronts. Two such fronts are found in the European Arctic, the Arctic Front (AF) and the Polar Front (PF), that both separate warmer and saltier, Atlantic water from the colder, but fresher Arctic water. As scrutinized research on the influence of passive fronts on zooplankton at large spatial and temporal scales had been lacking, we tackled the question of their role in maintaining distinct communities, employing globally unique, 12-year-long gelatinous zooplankton (GZ) and hydrological time series from the European Arctic. The GZ, owing to their fast reproductive cycles and passive dispersal, reflect particularly well the local environment. We therefore compared GZ communities between zones separated by the two fronts, disentangled their drivers, and analyzed community shifts occurring whenever front relocation occurred. We have identified fifteen GZ taxa, distributed among three distinct communities, specific for front-maintained zones, and selected the following taxa as indicators of each zone: W—west of the AF, within the Greenland Sea Gyre, Beroe spp.; C—central, in between the AF and the PF, Aglantha digitale; and E—east of the PF, in the West Spitsbergen Shelf Mertensia ovum. Taxonomic composition of these communities, and their specific abundance, persisted throughout time. We also showed that relocation of either front between the sampling years was subsequently followed by the restructuring of the GZ community. Our results indicate that passive oceanic fronts maintain distinct GZ communities, with probable limited exchange across a front, and provide a new perspective for the Arctic ecosystem evolution under progressing Atlantification.
Clinical characteristics and risk factors of relative systemic hypertension and hypertension among sickle cell patients in Cameroon
Authors: Nguweneza Arthemon , Ngo Bitoungui Valentina Josiane , Mnika Khuthala , Mazandu Gaston , Nembaware Victoria , Kengne Andre P. , Wonkam Ambroise
Published: July 2022

Increased blood pressure (BP) has been associated with higher risk of stroke and mortality in Sickle Cell Disease (SCD). We investigated risk factors associated with Relative Systemic Hypertension (RSH) or systemic hypertension in SCD patients in Cameroon. Using R, Multivariate multinomial logistic regression modeling was used to examine the effects of the demographic, anthropometric, clinical, and laboratory factors to determine risk factors. A total of 815 individuals with SCD, including 380 (46.6%) males were analyzed. At baseline, the median age [interquartile range] was 18.0 [12.0–25.0] years, ranging from 3 to 66 years. Approximately three-quarters of the patients (n = 645; 79.1%) had normal BP, 151 (18.5%) had RSH and 19 (2.3%) had hypertension. Age (P < 0.001) and gender (P = 0.022) were significantly different across the BP categories. Weight (P < 0.001), height (P < 0.001), BMI (P < 0.001), pulse pressure (P = 0.020), history of stroke (P = 0.012), hemoglobin level (P = 0.002), red blood cell count (P = 0.031), creatinine (P < 0.001), and (estimated glomerular filtration rate) eGFR (P = 0.002) was also significantly different across the three BP categories. After adjustment, the significantly associated factors of RSH in the SCD patients were age [OR = 1.03, (95% CI = 1.01–1.06), P < 0.010], male gender [OR = 1.54, (95% CI = 1.04–2.27), P = 0.029], BMI [OR = 1.10, (95% CI = 1.04–1.17), P = 0.001]. After adjustment, the independent variables significantly associated factors of Hypertension in the SCD patients were age [OR = 1.05, (95% CI = 1.01–1.10), P = 0.034], male gender [OR = 3.31, (95% CI = 1.04–10.52), P = 0.042], BMI [OR = 1.14, (95% CI = 1.01–1.29), P = 0.027]. Creatinine was significantly associated with RSH [OR =1.31 (1.05–1.63), P = 0.016]. SCD patients with RSH or hypertension maybe at increased risk of renal dysfunction. We found relatively high prevalence of RSH and hypertension (20.8%) in SCD patients in Cameroon. Tailored Interventions that consider major risk factors (age, gender, and BMI) may lower BP pressure and prevent severe complications.
Shifts in Soil Microbial Community Composition, Function, and Co-occurrence Network of Phragmites australis in the Yellow River Delta
Authors: Zhu Pengcheng , Yang Shuren , Wu Yuxin , Ru Yuning , Yu Xiaona , Wang Lushan , Guo Weihua
Published: July 2022

Soil microorganisms play vital roles in regulating biogeochemical processes. The composition and function of soil microbial community have been well studied, but little is known about the responses of bacterial and fungal communities to different habitats of the same plant, especially the inter-kingdom co-occurrence pattern including bacteria and fungi. Herein, we used high-throughput sequencing to investigate the bacterial and fungal communities of fivePhragmites australishabitats in the Yellow River Delta and constructed their inter-kingdom interaction network by network analysis. The results showed that richness did not differ significantly among habitats for either the bacterial or fungal communities. The distribution of soil bacterial community was significantly affected by soil physicochemical properties, whereas that of the fungal community was not. The main functions of the bacterial and fungal communities were to participate in the degradation of organic matter and element cycling, both of which were significantly affected by soil physicochemical properties. Network analysis revealed that bacteria and fungi participated in the formation of networks through positive interactions; the role of intra-kingdom interactions were more important than inter-kingdom interactions. In addition, rare species acted as keystones played a critical role in maintaining the network structure, whileNO3−−Nlikely played an important role in maintaining the network topological properties. Our findings provided insights into the inter-kingdom microbial co-occurrence network and response of the soil microbial community composition and function to differentP. australishabitats in coastal wetlands, which will deepen our insights into microbial community assembly in coastal wetlands.
Role of transcription factors in porcine reproductive and respiratory syndrome virus infection: A review
Authors: You Xiangbin , Lei Ying , Zhang Ping , Xu Dequan , Ahmed Zulfiqar , Yang Youbing
Published: July 2022

Porcine reproductive and respiratory syndrome (PRRS) is an infectious disease caused by the PRRS virus that leads to reproductive disorders and severe dyspnoea in pigs, which has serious economic impacts. One of the reasons PRRSV cannot be effectively controlled is that it has developed countermeasures against the host immune response, allowing it to survive and replicate for long periods. Transcription Factors acts as a bridge in the interactions between the host and PRRSV. PRRSV can create an environment conducive to PRRSV replication through transcription factors acting on miRNAs, inflammatory factors, and immune cells. Conversely, some transcription factors also inhibit PRRSV proliferation in the host. In this review, we systematically described how PRRSV uses host transcription factors such as SP1, CEBPB, STATs, and AP-1 to escape the host immune system. Determining the role of transcription factors in immune evasion and understanding the pathogenesis of PRRSV will help to develop new treatments for PRRSV.
Phylogenetic analysis and accessory genome diversity reveal insight into the evolutionary history of Streptococcus dysgalactiae
Authors: Alves-Barroco Cinthia , Brito Patrícia H. , Santos-Sanches Ilda , Fernandes Alexandra R.
Published: July 2022

Streptococcus dysgalactiae (SD) is capable of infecting both humans and animals and causing a wide range of invasive and non-invasive infections. With two subspecies, the taxonomic status of subspecies of SD remains controversial. Subspecies equisimilis (SDSE) is an important human pathogen, while subspecies dysgalactiae (SDSD) has been considered a strictly animal pathogen; however, occasional human infections by this subspecies have been reported in the last few years. Moreover, the differences between the adaptation of SDSD within humans and other animals are still unknown. In this work, we provide a phylogenomic analysis based on the single-copy core genome of 106 isolates from both the subspecies and different infected hosts (animal and human hosts). The accessory genome of this species was also analyzed for screening of genes that could be specifically involved with adaptation to different hosts. Additionally, we searched putatively adaptive traits among prophage regions to infer the importance of transduction in the adaptation of SD to different hosts. Core genome phylogenetic relationships segregate all human SDSE in a single cluster separated from animal SD isolates. The subgroup of bovine SDSD evolved from this later clade and harbors a specialized accessory genome characterized by the presence of specific virulence determinants (e.g., cspZ) and carbohydrate metabolic functions (e.g., fructose operon). Together, our results indicate a host-specific SD and the existence of an SDSD group that causes human–animal cluster infections may be due to opportunistic infections, and that the exact incidence of SDSD human infections may be underestimated due to failures in identification based on the hemolytic patterns. However, more detailed research into the isolation of human SD is needed to assess whether it is a carrier phenomenon or whether the species can be permanently integrated into the human microbiome, making it ready to cause opportunistic infections.
The Burden of Gastrointestinal Complaints in Kidney Transplant Recipients Using Tacrolimus With and Without Mycophenolate Mofetil: A Randomized Controlled Study
Authors: Fatly Zainab Al , Betjes Michiel GH , van Gestel Judith , Verschragen Marieken , de Weerd Annelies E.
Published: July 2022

Background

Tacrolimus (TAC) combined with mycophenolate mofetil (MMF) is the immunosuppressive regimen in the majority of solid organ transplant recipients. Gastrointestinal complaints are frequent, which is considered predominantly a side effect of MMF. However, systematic research in this field is lacking. The aim of this study is to systematically investigate the burden of gastrointestinal complaints in TAC-treated kidney transplant recipients with and without MMF.

Methods

In a single-center, open-label, randomized controlled trial, low immunological risk recipients were randomized to either TAC and MMF or to TAC monotherapy from 6 months after kidney transplantation onwards [NTR4672],. They filled in the Gastrointestinal Symptom Rating Scale questionnaire, which covers five dimensions (abdominal pain, reflux, indigestion, constipation, and diarrhea), 6, 12, and 15 months after transplantation.

Results

Seventy-nine recipients were randomized and 72 completed all questionnaires (34 TACmono and 38 TAC/MMF). At baseline, the mean age was 59 years with 72% male, mean BMI 28 kg/m2, eGFR 55 ml/min/1.73m2, mean daily dose MMF 1200 mg and TAC 5.8 mg, with trough levels of 2.1 mg/L and 7.4 ug/L. Six months after transplantation, 75% of recipients reported troublesome symptoms (score ≥3). Diarrhea was the most troublesome (mean 3.3) and discontinuing MMF significantly reduced it (mean Δ score between month 6 and 15 TAC/MMF -0.9 vs. TACmono -1.8, p=0.03). In recipients with troublesome symptoms, abdominal pain (2.7 to 1.8, p=0.003), indigestion (2.8 to 2.3, p=0.012), and reflux (2.9 to 1.7, p=0.007) significantly decreased over time, independent of MMF use.

Conclusion

The majority of kidney transplant recipients with TAC and MMF experienced troublesome gastrointestinal symptoms 6 months after transplantation. While constipation remained troublesome, indigestion, abdominal pain, and reflux improved over time by month 15. Diarrhea only improved after discontinuing MMF.
Effects of long-term supplementation of probiotics on cognitive function and emotion in temporal lobe epilepsy
Authors: Wang Xue , Ma Rui , Liu Xinyi , Zhang Yongbo
Published: July 2022

Cognitive impairment and neuropsychiatric disorders are very common in patients with temporal lobe epilepsy (TLE). These comorbidities complicate the treatment of epilepsy and seriously affect the quality of life. So far, there is still no effective intervention to prevent the development of epilepsy-associated comorbidities. Gut dysbiosis has been recognized to be involved in the pathology of epilepsy development. Modulating gut microbiota by probiotics has shown an antiseizure effect on humans and animals with epilepsy. Whether this treatment strategy has a positive effect on epilepsy-associated comorbidities remains unclear. Therefore, this study aimed to objectively assess the effect of probiotics on cognitive function and neuropsychiatric performance of patients with TLE. Participants enrolled in an epilepsy clinic were randomly assigned to the probiotic and placebo groups. These two groups were treated with probiotics or placebo for 12 weeks, and then the cognitive function and psychological performance of participants were assessed. We enrolled 76 participants in this study, and 70 subjects were finally included in the study (35 in the probiotics group and 35 in the placebo group). Our results showed significant seizure reduction in patients with TLE treated with probiotics. No significant differences were observed on cognitive function (including intelligence and memory) between groups. For neuropsychiatric performances, supplementation of probiotics significantly decreased the Hamilton Anxiety Rating and Depression Scale scores and increased the 89-item Quality of Life in Epilepsy Inventory score in patients with TLE. In conclusion, probiotics have a positive impact on seizures control, and improve anxiety, depression, and quality of life in patients with TLE.
Brain Source Correlates of Speech Perception and Reading Processes in Children With and Without Reading Difficulties
Authors: Azaiez Najla , Loberg Otto , Hämäläinen Jarmo A. , Leppänen Paavo H. T.
Published: July 2022

Neural correlates in reading and speech processing have been addressed extensively in the literature. While reading skills and speech perception have been shown to be associated with each other, their relationship remains debatable. In this study, we investigated reading skills, speech perception, reading, and their correlates with brain source activity in auditory and visual modalities. We used high-density event-related potentials (ERPs), fixation-related potentials (FRPs), and the source reconstruction method. The analysis was conducted on 12–13-year-old schoolchildren who had different reading levels. Brain ERP source indices were computed from frequently repeated Finnish speech stimuli presented in an auditory oddball paradigm. Brain FRP source indices were also computed for words within sentences presented in a reading task. The results showed significant correlations between speech ERP sources and reading scores at the P100 (P1) time range in the left hemisphere and the N250 time range in both hemispheres, and a weaker correlation for visual word processing N170 FRP source(s) in the posterior occipital areas, in the vicinity of the visual word form areas (VWFA). Furthermore, significant brain-to-brain correlations were found between the two modalities, where the speech brain sources of the P1 and N250 responses correlated with the reading N170 response. The results suggest that speech processes are linked to reading fluency and that brain activations to speech are linked to visual brain processes of reading. These results indicate that a relationship between language and reading systems is present even after several years of exposure to print.
Convolutional Neural Networks for Classification of T2DM Cognitive Impairment Based on Whole Brain Structural Features
Authors: Tan Xin , Wu Jinjian , Ma Xiaomeng , Kang Shangyu , Yue Xiaomei , Rao Yawen , Li Yifan , Huang Haoming , Chen Yuna , Lyu Wenjiao , Qin Chunhong , Li Mingrui , Feng Yue , Liang Yi , Qiu Shijun
Published: July 2022

Purpose

Cognitive impairment is generally found in individuals with type 2 diabetes mellitus (T2DM). Although they may not have visible symptoms of cognitive impairment in the early stages of the disorder, they are considered to be at high risk. Therefore, the classification of these patients is important for preventing the progression of cognitive impairment.

Methods

In this study, a convolutional neural network was used to construct a model for classifying 107 T2DM patients with and without cognitive impairment based on T1-weighted structural MRI. The Montreal cognitive assessment score served as an index of the cognitive status of the patients.

Results

The classifier could identify T2DM-related cognitive decline with a classification accuracy of 84.85% and achieved an area under the curve of 92.65%.

Conclusions

The model can help clinicians analyze and predict cognitive impairment in patients and enable early treatment.
Upregulation of CCNB2 and Its Perspective Mechanisms in Cerebral Ischemic Stroke and All Subtypes of Lung Cancer: A Comprehensive Study
Authors: Li Ming-Jie , Yan Shi-Bai , Chen Gang , Li Guo-Sheng , Yang Yue , Wei Tao , He De-Shen , Yang Zhen , Cen Geng-Yu , Wang Jun , Liu Liu-Yu , Liang Zhi-Jian , Chen Li , Yin Bin-Tong , Xu Ruo-Xiang , Huang Zhi-Guang
Published: July 2022

Cyclin B2 (CCNB2) belongs to type B cell cycle family protein, which is located on chromosome 15q22, and it binds to cyclin-dependent kinases (CDKs) to regulate their activities. In this study, 103 high-throughput datasets related to all subtypes of lung cancer (LC) and cerebral ischemic stroke (CIS) with the data of CCNB2 expression were collected. The analysis of standard mean deviation (SMD) and summary receiver operating characteristic (SROC) reflecting expression status demonstrated significant up-regulation of CCNB2 in LC and CIS (Lung adenocarcinoma: SMD = 1.40, 95%CI [0.98–1.83], SROC = 0.92, 95%CI [0.89–0.94]. Lung squamous cell carcinoma: SMD = 2.56, 95%CI [1.64–3.48]. SROC = 0.97, 95%CI [0.95–0.98]. Lung small cell carcinoma: SMD = 3.01, 95%CI [2.01–4.01]. SROC = 0.98, 95%CI [0.97–0.99]. CIS: SMD = 0.29, 95%CI [0.05–0.53], SROC = 0.68, 95%CI [0.63–0.71]). Simultaneously, protein-protein interaction (PPI) analysis indicated that CCNB2 is the hub molecule of crossed high-expressed genes in CIS and LC. Through Multiscale embedded gene co-expression network analysis (MEGENA), a gene module of CIS including 76 genes was obtained and function enrichment analysis of the CCNB2 module genes implied that CCNB2 may participate in the processes in the formation of CIS and tissue damage caused by CIS, such as “cell cycle,” “protein kinase activity,” and “glycosphingolipid biosynthesis.” Afterward, via single-cell RNA-seq analysis, CCNB2 was found up-regulated on GABAergic neurons in brain organoids as well as T cells expressing proliferative molecules in LUAD. Concurrently, the expression of CCNB2 distributed similarly to TOP2A as a module marker of cell proliferation in cell cluster. These findings can help in the field of the pathogenesis of LC-related CIS and neuron repair after CIS damage.
Differential Excretory/Secretory Proteome of the Adult Female and Male Stages of the Human Blood Fluke, Schistosoma mansoni
Authors: Kenney Eric T. , Mann Victoria H. , Ittiprasert Wannaporn , Rosa Bruce A. , Mitreva Makedonka , Bracken Bethany K. , Loukas Alex , Brindley Paul J. , Sotillo Javier
Published: July 2022

Intricate molecular communication between schistosome flatworms and their mammalian host, as well as between paired male and female schistosomes has shaped the secreted proteome of these flatworms. Whereas the schistosome egg is responsible for the disease manifestations of chronic schistosomiasis, the long lived, adult female and male stages also release different mediators including glycans, lipids, proteins and small molecules, known as excretory/secretory products (ESPs), that facilitate their survival. Given their importance, deeper analysis focused on analyzing the ESPs from adult schistosomes would likely be informative, beyond current understanding of the complement of ESP proteins. Here, taking advantage of highly accurate and sensitive mass spectrometers, the excretory/secretory proteome from culturedSchistosoma mansonimale or female adult worms was identified, quantified, compared and contrasted using a label-free proteomic approach. Approximately 1,000 proteins were identified, from which almost 800 could be quantified. Considering the proteins uniquely identified and proteins with a significantly regulated expression pattern in male or female flukes, a total of 370 and 140 proteins were uniquely or more abundantly secreted by males and females, respectively. Using functional analysis networks showing the gene ontology terms and KEGG pathways with the highest significance, we observed that male schistosomes secrete proteins related to carbohydrate metabolism and cytoskeletal organization more abundantly than females, while female worms secreted more hydrolases and proteins involved in cellular homeostasis than males. This analysis doubles the number of reported excreted/secreted proteins fromS. mansoni, contributing to deeper understanding of the host-parasite interaction and parasitism. Furthermore, these findings expand potential vaccine and diagnostic candidates for this neglected tropical disease pathogen, and thereby also provide leads for novel intervention to control this disease and its transmission.
Cationic Mechanosensitive Channels Mediate Trabecular Meshwork Responses to Cyclic Mechanical Stretch
Authors: Chen Susu , Wang Wenyan , Cao Qilong , Wu Shen , Wang Ningli , Ji Lixia , Zhu Wei
Published: July 2022

The trabecular meshwork (TM) is responsible for intraocular pressure (IOP) homeostasis in the eye. The tissue senses IOP fluctuations and dynamically adapts to the mechanical changes to either increase or decrease aqueous humor outflow. Cationic mechanosensitive channels (CMCs) have been reported to play critical roles in mediating the TM responses to mechanical forces. However, how CMCs influence TM cellular function affect aqueous humor drainage is still elusive. In this study, human TM (HTM) cells were collected from a Chinese donor and subjected to cyclically equiaxial stretching with an amplitude of 20% at 1 Hz GsMTx4, a non-selective inhibitor for CMCs, was added to investigate the proteomic changes induced by CMCs in response to mechanical stretch of HTM. Gene ontology enrichment analysis demonstrated that inhibition of CMCs significantly influenced several biochemical pathways, including store-operated calcium channel activity, microtubule cytoskeleton polarity, toll-like receptor signaling pathway, and neuron cell fate specification. Through heatmap analysis, we grouped 148 differentially expressed proteins (DEPs) into 21 clusters and focused on four specific patterns associated with Ca2+ homeostasis, autophagy, cell cycle, and cell fate. Our results indicated that they might be the critical downstream signals of CMCs adapting to mechanical forces and mediating AH outflow.
A Quantitative Systems Pharmacology Model of Liver Lipid Metabolism for Investigation of Non-Alcoholic Fatty Liver Disease
Authors: Rieger Theodore R. , Allen Richard J. , Musante Cynthia J.
Published: July 2022

Non-alcoholic fatty liver disease is a metabolic and inflammatory disease that afflicts many people worldwide and presently has few treatment options. To enhance the preclinical to clinical translation and the design of early clinical trials for novel therapeutics, we developed a Quantitative Systems Pharmacology model of human hepatocyte lipid metabolism. The intended application of the model is for simulating anti-steatotic therapies for reversing fatty liver. We parameterized the model using literature data from humans with both normal and elevated liver fat. We assessed that the model construct was sufficient to generate a virtual population of NAFLD patients that matched relevant statistics of a published clinical cohort, and then validated the model response to treatment by simulating pioglitazone and diet intervention in the virtual population. Finally, a sensitivity analysis was performed to determine the best points of intervention for reducing hepatic steatosis. Analysis of the model suggests the most potent method for reducing hepatic steatosis is by limiting non-esterified fatty acid flux from the adipose to the liver.
An Update on the Potential Application of Herbal Medicine in Promoting Angiogenesis
Authors: Li Jingjing , Li Renkai , Wu Xiaoping , Zheng Chengwen , Shiu Polly Ho-Ting , Rangsinth Panthakarn , Lee Simon Ming-Yuen , Leung George Pak-Heng
Published: July 2022

Angiogenesis, the formation of new capillaries from pre-existing vascular networks, plays an important role in many physiological and pathological processes. The use of pro-angiogenic agents has been proposed as an attractive approach for promoting wound healing and treating vascular insufficiency-related problems, such as ischemic heart disease and stroke, which are the leading causes of death worldwide. Traditional herbal medicine has a long history; however, there is still a need for more in-depth studies and evidence-based confirmation from controlled and validated trials. Many in vitro and in vivo studies have reported that herbal medicines and their bioactive ingredients exert pro-angiogenic activity. The most frequently studied pro-angiogenic phytochemicals include ginsenosides from Panax notoginseng, astragalosides and calycosin from Radix Astragali, salvianolic acid B from Salvia miltiorrhiza, paeoniflorin from Radix Paeoniae, ilexsaponin A1 from Ilex pubescens, ferulic acid from Angelica sinensis, and puerarin from Radix puerariae. This review summarizes the progress in research on these phytochemicals, particularly those related to pro-angiogenic mechanisms and applications in ischemic diseases, tissue repair, and wound healing. In addition, an outline of their limitations and challenges during drug development is presented.
Tau Lepton Identification With Graph Neural Networks at Future Electron–Positron Colliders
Authors: Giagu Stefano , Torresi Luca , Di Filippo Matteo
Published: July 2022

Efficient and accurate reconstruction and identification of tau lepton decays plays a crucial role in the program of measurements and searches under the study for the future high-energy particle colliders. Leveraging recent advances in machine learning algorithms, which have dramatically improved the state of the art in visual object recognition, we have developed novel tau identification methods that are able to classify tau decays in leptons and hadrons and to discriminate them against QCD jets. We present the methodology and the results of the application at the interesting use case of the IDEA dual-readout calorimeter detector concept proposed for the future FCC-ee electron–positron collider.
Implications of Foliar Particulate Matter Deposition on the Physiology and Nutrient Allocation of Dominant Perennial Species of the Indo-Gangetic Plains
Authors: Singh Harshita , Singh Pallavi , Agrawal Shashi Bhushan , Agrawal Madhoolika
Published: July 2022

The ramifications of different concentrations of foliar particulate matter on the physiology, nutrient stoichiometry, allocation pattern, and their corresponding re-translocation rates were investigated for evergreen (Mangifera indica and Psidium guajava), semi-evergreen (Ficus religiosa and Azadirachta indica), and deciduous (Dalbergia sissoo) tree species in a simulation experiment over an exposure period of 2 years. Physiological parameters (Pn, gs, Ci, E, and WUE), nutrient stoichiometry (C: N) in different plant parts, and their allocation pattern for five macro- (C, N, K, Mg, Ca) and five (Zn, Ni, Mn, Cu, Fe) micro-elements at two different concentrations of particulate matter (ambient and elevated) with respect to control (no particulate load) were assessed. Significant differences in nutrient concentrations and their re-translocation rates were observed between the treatments in evergreen species compared to deciduous species. The photosynthetic rate significantly declined with an increase in foliar deposition of particulate matter. Higher variations in C, N, K, Mg, and Zn levels were found compared to other elements under particulate matter stress and the ratio of C/N showed a slight decline in mature leaves except in deciduous tree species. The nutrient stoichiometry revealed that the deciduous species were more tolerant whereas the re-translocation efficiency was maximum for the semi-evergreen tree species. The nutrient allocation was found greater in foliage compared to branch in evergreen and was opposite in semi-evergreen and deciduous tree species. The element re-translocation rate indicated an inconsistent behavior in nutrient recycling under the particulate matter load depending upon the tree species. The study entrenched a critical change in nutrient re-translocation and allocation pattern under the particulate stress in different parts of the tree, suggesting a novel approach for screening the tree species for sustainable plantation and planning of urban areas.
Cloning and function analysis of a Saussurea involucrata LEA4 gene
Authors: Kong Hui , Xia Wenwen , Hou Mengjuan , Ruan Nan , Li Jin , Zhu Jianbo
Published: July 2022

Late embryogenesis abundant proteins (LEA) help adapt to adverse low-temperature environments. The Saussurea involucrate SiLEA4, which encodes a membrane protein, was significantly up-regulated in response to low temperature stress. Escherichia coli expressing SiLEA4 showed enhanced low-temperature tolerance, as evident from the significantly higher survival numbers and growth rates at low temperatures. Moreover, tomato strains expressing SiLEA4 had significantly greater freezing resistance, due to a significant increase in the antioxidase activities and proline content. Furthermore, they had higher yields due to higher water utilization and photosynthetic efficiency under the same water and fertilizer conditions. Thus, expressing SiLEA4 has multiple advantages: (1) mitigating chilling injury, (2) increasing yields, and (3) water-saving, which also indicates the great potential of the SiLEA4 for breeding applications.