bluuebunny/crossref_metadata_2025 huggingface dataset:
Sustained release of a highly specific GSK3β inhibitor SB216763 in the PCL scaffold creates an osteogenic niche for osteogenesis, anti-adipogenesis, and potential angiogenesis
Authors: Gong Weimin , Li Molin , Zhao Lizhou , Wang Pengtao , Wang Xiaofang , Wang Bo , Liu Xing , Tu Xiaolin
Published: July 2023

The safe and effective use of Wnt signaling is a hot topic in developing osteogenic drugs. SB216763 (S33) is a widely used highly specific GSK3β inhibitor. Here, we show that S33 initiates canonical Wnt signaling by inhibiting GSK3β activity in the bone marrow stromal cell line ST2 and increases osteoblast marker alkaline phosphatase activity, osteoblast marker gene expression including Alpl, Col1α1, and Runx2, promoting osteogenic differentiation and mineralization of ST2 cells. In addition, S33 suppressed the expression of adipogenic transcription factors Pparg and Cebpa in ST2 cells to suppress adipogenesis. ICRT-14, a specific transcriptional inhibitor of Wnt signaling, reversed the effects of S33 on the differentiation of ST2 cells. S33 also increased the expression of osteoclast cytokines RANKL and Opg but decreased the RANKL/Opg ratio and had the potential to inhibit osteoclast differentiation. In addition, we printed the PSCI3D (polycaprolactone, S33, cell-integrated 3D) scaffolds using a newly established integrated 3D printing system for hard materials and cells. S33 sustained release in the hydrogel of the scaffold with 25.4% release on day 1% and 81.7% release over 7 days. Cells in the scaffolds had good cell viability. The ratio of live/dead cells remained above 94% for 7 days, while the cells in the scaffolds proliferated linearly, and the proliferative activity of the PSCI3D scaffold group increased 1.4-fold and 1.7-fold on days 4 and 7, respectively. Similarly, in PSCI3D scaffolds, osteogenic differentiation of st2 cells was increased. The alkaline phosphatase activity increased 1.4- and 4.0-fold on days 7 and 14, respectively, and mineralization increased 1.7-fold at 21 days. In addition, PSCI3D conditioned medium promoted migration and tubulogenesis of HUVECs, and S33 upregulated the expression of Vegfa, a key factor in angiogenesis. In conclusion, our study suggests that S33 functions in osteogenesis, anti-adipogenesis, and potential inhibition of osteoclast differentiation. And the sustained release of S33 in PSCI3D scaffolds creates a safe osteogenic niche, which promotes cell proliferation, osteogenesis, and angiogenesis and has application prospects.
Synthesis and antibacterial activities of Ag-TiO2/ZIF-8
Authors: Bao Siqi , Sun Shuanghui , Li Lin , Xu Lei
Published: July 2023

In recent years, massive bacterial infections have led to human illness and death, reminding us of the urgent need to develop effective and long-lasting antimicrobial materials. In this paper, Ag-TiO2/ZIF-8 with good environmental friendliness and biological antibacterial activity was prepared by solvothermal method. The structure and morphology of the synthesized materials were characterized by XRD, FT-IR, SEM-EDS, TEM, XPS, and BET. To investigate the antibacterial activity of the synthesized samples, Escherichia coli and Bacillus subtilis were used as target bacteria for experimental studies of zone of inhibition, bacterial growth curves, minimum bactericidal concentration and antibacterial durability. The results demonstrated that 20 wt.%Ag-TiO2/ZIF-8 had the best bacteriostatic effect on E. coli and B. subtilis under dark and UV conditions compared to TiO2 and ZIF-8. Under the same conditions, the diameter of the inhibition circle of 20 wt% Ag-TiO2/ZIF-8 is 8.5–11.5 mm larger than that of its constituent material 4 wt% Ag-TiO2, with more obvious antibacterial effect and better antibacterial performance. It is also proposed that the excellent antibacterial activity of Ag-TiO2/ZIF-8 is due to the synergistic effect of Ag-TiO2 and ZIF-8 under UV light. In addition, the prepared material has good stability and durability with effective antimicrobial activity for more than 5 months.
Structure of gut microbiota and characteristics of fecal metabolites in patients with lung cancer
Authors: Lu Xingbing , Xiong Li , Zheng Xi , Yu Qiuju , Xiao Yuling , Xie Yi
Published: July 2023

Objective

The gut micro-biome plays a pivotal role in the progression of lung cancer. However, the specific mechanisms by which the intestinal microbiota and its metabolites are involved in the lung cancer process remain unclear.

Method

Stool samples from 52 patients with lung cancer and 29 healthy control individuals were collected and subjected to 16S rRNA gene amplification sequencing and non-targeted gas/liquid chromatography-mass spectrometry metabolomics analysis. Then microbiota, metabolites and potential signaling pathways that may play an important role in the disease were filtered.

Results

Firmicutes, Clostridia, Bacteroidacea, Bacteroides, and Lachnospira showed a greater abundance in healthy controls. In contrast, the Ruminococcus gnavus(R.gnavus) was significantly upregulated in lung cancer patients. In this respect, the micro-biome of the squamous cell carcinoma(SCC)group demonstrated a relatively higher abundance of Proteobacteria, Gammaproteobacteria, Bacteroides,and Enterobacteriaceae, as well as higher abundances of Fusicatenibacter and Roseburia in adenocarcinoma(ADC) group. Metabolomic analysis showed significant alterations in fecal metabolites including including quinic acid, 3-hydroxybenzoic acid,1-methylhydantoin,3,4-dihydroxydrocinnamic acid and 3,4-dihydroxybenzeneacetic acid were significantly altered in lung cancer patients. Additionally, the R.gnavus and Fusicatenibacter of lung cancer were associated with multiple metabolite levels.

Conclusion

Our study provides essential guidance for a fundamental systematic and multilevel assessment of the contribution of gut micro-biome and their metabolites in lung cancer,which has great potential for understanding the pathogenesis of lung cancer and for better early prevention and targeted interventions.
External validation of the REMEMBER score
Authors: Peivandi Armin Darius , Welp Henryk , Kintrup Sebastian , Wagner Nana Maria , Dell’Aquila Angelo Maria
Published: July 2023

Background

The use of venoarterial extracorporeal membrane oxygenation (VA-ECMO) after coronary artery bypass grafting (CABG) is associated with high in-hospital mortality rates. The pRedicting mortality in patients undergoing venoarterial Extracorporeal MEMBrane oxygenation after coronary artEry bypass gRafting (REMEMBER) score has been created to predict in-hospital mortality in this subgroup of patients. The aim of this study is to externally validate the REMEMBER score.

Methods

All CABG patients who received VA-ECMO during or after the operation at our center between 01/2012 and 12/2021 were included in the analysis. Discrimination was assessed using concordance statistics, visualized by ROC curve analysis. Calibration-in-the-large and Calibration slope were tested separately.

Results

A total of 107 patients (male: n = 78, 72.9%) were included in this study. The in-hospital mortality rate in our cohort was 45.8% compared with 55% in the original study. The REMEMBER score median predicted mortality rate was 52% (76.9–36%). However, the REMEMBER score showed low discriminative ability [AUC: 0.623 (p = 0.0244; 95% CI = 0.524–0.715)] and inaccurate calibration (intercept = 0.25074; p = 0.0195; slope = 0.39504; p = 0.0303), indicating poor performance.

Conclusions

The REMEMBER score did not predict in-hospital mortality and was therefore not applicable in our cohort of patients. Additional external validation studies in a multicenter setting are therefore advisable.
Using machine learning to identify patient characteristics to predict mortality of in-patients with COVID-19 in South Florida
Authors: Datta Debarshi , George Dalmida Safiya , Martinez Laurie , Newman David , Hashemi Javad , Khoshgoftaar Taghi M. , Shorten Connor , Sareli Candice , Eckardt Paula
Published: July 2023

Introduction

The SARS-CoV-2 (COVID-19) pandemic has created substantial health and economic burdens in the US and worldwide. As new variants continuously emerge, predicting critical clinical events in the context of relevant individual risks is a promising option for reducing the overall burden of COVID-19. This study aims to train an AI-driven decision support system that helps build a model to understand the most important features that predict the “mortality” of patients hospitalized with COVID-19.

Methods

We conducted a retrospective analysis of “5,371” patients hospitalized for COVID-19-related symptoms from the South Florida Memorial Health Care System between March 14th, 2020, and January 16th, 2021. A data set comprising patients’ sociodemographic characteristics, pre-existing health information, and medication was analyzed. We trained Random Forest classifier to predict “mortality” for patients hospitalized with COVID-19.

Results

Based on the interpretability of the model, age emerged as the primary predictor of “mortality”, followed by diarrhea, diabetes, hypertension, BMI, early stages of kidney disease, smoking status, sex, pneumonia, and race in descending order of importance. Notably, individuals aged over 65 years (referred to as “older adults”), males, Whites, Hispanics, and current smokers were identified as being at higher risk of death. Additionally, BMI, specifically in the overweight and obese categories, significantly predicted “mortality”. These findings indicated that the model effectively learned from various categories, such as patients' sociodemographic characteristics, pre-hospital comorbidities, and medications, with a predominant focus on characterizing pre-hospital comorbidities. Consequently, the model demonstrated the ability to predict “mortality” with transparency and reliability.

Conclusion

AI can potentially provide healthcare workers with the ability to stratify patients and streamline optimal care solutions when time is of the essence and resources are limited. This work sets the platform for future work that forecasts patient responses to treatments at various levels of disease severity and assesses health disparities and patient conditions that promote improved health care in a broader context. This study contributed to one of the first predictive analyses applying AI/ML techniques to COVID-19 data using a vast sample from South Florida.
Why the time is ripe for an education revolution
Authors: Lillard Angeline S.
Published: July 2023

Most American classrooms employ a teacher-text-centered model of instruction that is misaligned with the developmental science of how children naturally learn. This article reviews that science and the origins of the common instructional model, including three modifications intended to make it work better (grades, age-graded classrooms, and high-stakes testing) yet which time has shown are problematic. Considering scientific theory change, I show how parallel circumstances exist between the situation in education today and pre-Copernican astronomy, building the case that education is now ripe for a paradigm shift in its instructional model, away from teacher-text-centered learning and to highly structured instructional environments that support self-construction through limited free choice. One proven model that responds to our world's contemporary needs is described, and a prescription is offered for how to bring about a paradigm shift in educational practice.
Origins of sediments and fluids in submarine mud volcanoes off Tanegashima Island, northern Ryukyu Trench, Japan
Authors: Ijiri Akira , Setoguchi Ryoma , Mitsutome Yuki , Toki Tomohiro , Murayama Masafumi , Hagino Kyoko , Hamada Yohei , Yamagata Takeyasu , Matsuzaki Hiroyuki , Tanikawa Wataru , Tadai Osamu , Kitada Kazuya , Hoshino Tatsuhiko , Noguchi Takuro , Ashi Juichiro , Inagaki Fumio
Published: July 2023

Mud volcanoes are topographic features through which over-pressurized sediments are intruded upward and erupted, transporting fluids and sediments from the deep subsurface to the surface/seafloor. To understand material and biogeochemical cycling through mud volcanoes, we investigated the origins of sediments and fluids erupted by four submarine mud volcanoes off Tanegashima Island, along the northern Ryukyu Trench: MV#1–3 and MV#14. We estimated the ages of the source sequences of the mud volcano sediments to be middle to late Miocene based on nannofossils and 10Be ages. The sediments were characteristically enriched in illite. The similar mineral compositions and vitrinite reflectance values (0.42%–0.45%) of sediments erupted by the mud volcanoes strongly suggest that each is rooted in the same source sequence. Pore waters had Cl− concentrations ∼40% that of seawater and were proportionally enriched in 18O and depleted in D, indicating the addition of freshwater from the dehydration of clay minerals. However, the smectite and illite contents (<40%) in the clay size fraction ruled out in situ smectite dewatering as the cause of the pore water Cl− dilution. Thus, fluids derived from clay dewatering must have originated from deeper than the source sequence of the mud volcano sediments. Vertical Cl− profiles indicate that the upward fluid advection rate and eruption frequency decrease from MV#3 to MV#2, MV#1, and MV#14 (MV#14 being dormant). At the active mud volcanoes, the C1/C2 ratios (<100) and methane δ13C values (−56‰ to −42‰) indicate that hydrocarbon gases are mostly derived from the thermal decomposition of organic matter in deep sediments where the in situ temperature exceeds 80°C. At the dormant MV#14, high C1/C2 ratios (700–4,000) and low methane δ13C values (ca. −75‰) suggest the limited supply of thermogenic methane and the subsequent shallow methanogenesis. Because vitrinite reflectance values indicate that the source sediments are too immature to produce thermogenic hydrocarbons, the hydrocarbon gases, like the fluids derived from clay dewatering, were probably supplied from deeper than the source strata. The supply of deep fluids into the source sequence might be a universal phenomenon in subduction zones, and may play an important role in mud volcanism and associated biogeochemical cycling.
The dynamic expression of SOX17 in germ cells from human female foetus and adult ovaries after specification
Authors: Luo Ying-Yi , Jie Hui-Ying , Huang Ke-Jun , Cai Bing , Zhou Xiu , Liang Ming-Yi , Zhou Can-Quan , Mai Qing-Yun
Published: July 2023

Background

SOX17 has been identified as a critical factor in specification of human primordial germ cells, but whether SOX17 regulates development of germ cells after sex differentiation is poorly understood.

Methods

We collected specimens of gonadal ridge from an embryo (n=1), and ovaries of foetuses (n=23) and adults (n=3). Germ cells were labelled with SOX17, VASA (classic germ cells marker), phosphohistone H3 (PHH3, mitosis marker) and synaptonemal complex protein 3 (SCP3, meiosis marker).

Results

SOX17 was detected in both cytoplasm and nucleus of oogonia and oocytes of primordial and primary follicles from 15 to 28 gestational weeks (GW). However, it was exclusively expressed in cytoplasm of oogonia at 7 GW, and in nucleus of oocytes in secondary follicles. Co-expression rates of SOX17 in VASA+ germ cells ranged from 81.29% to 97.81% in foetuses. Co-staining rates of SOX17 and PHH3 or SCP3 were 0%-34% and 0%-57%, respectively. Interestingly, we distinguished a subpopulation of SOX17+VASA- germ cells in fetal ovaries. These cells clustered in the cortex and could be co-stained with the mitosis marker PHH3 but not the meiosis marker SCP3.

Conclusions

The dynamic expression of SOX17 was detected in human female germ cells. We discovered a population of SOX17+ VASA- germ cells clustering at the cortex of ovaries. We could not find a relationship between mitosis or meiosis and SOX17 or VASA staining in germ cells. Our findings provide insight into the potential role of SOX17 involving germ cells maturation after specification, although the mechanism is unclear and needs further investigation.
Profiles and diagnostic value of intestinal microbiota in schizophrenia patients with metabolic syndrome
Authors: Xing Mengjuan , Gao Hui , Yao Lili , Wang Li , Zhang Chengfang , Zhu Liping , Cui Donghong
Published: July 2023

Aims/hypothesis

It is widely thought that the intestinal microbiota plays a significant role in the pathogenesis of metabolic disorders. However, the gut microbiota composition and characteristics of schizophrenia patients with metabolic syndrome (MetS) have been largely understudied. Herein, we investigated the association between the metabolic status of mainland Chinese schizophrenia patients with MetS and the intestinal microbiome.

Methods

Fecal microbiota communities from 115 male schizophrenia patients (57 with MetS and 58 without MetS) were assessed by 16S ribosomal RNA gene sequencing. We assessed the variations of gut microbiome between both groups and explored potential associations between intestinal microbiota and parameters of MetS. In addition, the Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) based on the KEGG database was used to predict the function of intestinal microbiota. We also conducted Decision Tree Analysis to develop a diagnostic model for the MetS in patients with schizophrenia based on the composition of intestinal microbiota.

Results

The fecal microbial diversity significantly differed between groups with or without MetS (α-diversity (Shannon index and Simpson index): p=0.0155, p=0.0089; β-diversity: p=0.001). Moreover, the microbial composition was significantly different between the two groups, involving five phyla and 38 genera (p<0.05). In addition, a significant correlation was observed between the metabolic-related parameters and abundance of altered microbiota including HDL-c (r2 = 0.203, p=0.0005), GLU (r2 = 0.286, p=0.0005) and WC (r2 = 0.061, p=0.037). Furthermore, KEGG pathway analysis showed that 16 signaling pathways were significantly enriched between the two groups (p<0.05). Importantly, our diagnostic model based on five microorganisms established by decision tree analysis could effectively distinguish between patients with and without MetS (AUC = 0.94).

Conclusions/interpretation

Our study established the compositional and functional characteristics of intestinal microbiota in schizophrenia patients with MetS. These new findings provide novel insights into a better understanding of this disease and provide the theoretical basis for implementing new interventional therapies in clinical practice.
Abnormalities of pubertal development and gonadal function in Noonan syndrome
Authors: Patti Giuseppa , Scaglione Marco , Maiorano Nadia Gabriella , Rosti Giulia , Divizia Maria Teresa , Camia Tiziana , De Rose Elena Lucia , Zucconi Alice , Casalini Emilio , Napoli Flavia , Di Iorgi Natascia , Maghnie Mohamad
Published: July 2023

Background

Noonan syndrome (NS) is a genetic multisystem disorder characterised by variable clinical manifestations including dysmorphic facial features, short stature, congenital heart disease, renal anomalies, lymphatic malformations, chest deformities, cryptorchidism in males.

Methods

In this narrative review, we summarized the available data on puberty and gonadal function in NS subjects and the role of the RAS/mitogen-activated protein kinase (MAPK) signalling pathway in fertility. In addition, we have reported our personal experience on pubertal development and vertical transmission in NS.

Conclusions

According to the literature and to our experience, NS patients seem to have a delay in puberty onset compared to the physiological timing reported in healthy children. Males with NS seem to be at risk of gonadal dysfunction secondary not only to cryptorchidism but also to other underlying developmental factors including the MAP/MAPK pathway and genetics. Long-term data on a large cohort of males and females with NS are needed to better understand the impact of delayed puberty on adult height, metabolic profile and well-being. The role of genetic counselling and fertility related-issues is crucial.
Predictive role of serum C-peptide in new-onset renal dysfunction in type 2 diabetes: a longitudinal observational study
Authors: Sun Dongmei , Hu Yifei , Ma Yongjun , Wang Huabin
Published: July 2023

Background

Our previous cross-sectional study has demonstrated the independently non-linear relationship between fasting C-peptide with renal dysfunction odds in patients with type 2 diabetes (T2D) in China. This longitudinal observational study aims to explore the role of serum C-peptide in risk prediction of new-onset renal dysfunction, then construct a predictive model based on serum C-peptide and other clinical parameters.

Methods

The patients with T2D and normal renal function at baseline were recruited in this study. The LASSO algorithm was performed to filter potential predictors from the baseline variables. Logistic regression (LR) was performed to construct the predictive model for new-onset renal dysfunction risk. Power analysis was performed to assess the statistical power of the model.

Results

During a 2-year follow-up period, 21.08% (35/166) of subjects with T2D and normal renal function at baseline progressed to renal dysfunction. Six predictors were determined using LASSO regression, including baseline albumin-to-creatinine ratio, glycated hemoglobin, hypertension, retinol-binding protein-to-creatinine ratio, quartiles of fasting C-peptide, and quartiles of fasting C-peptide to 2h postprandial C-peptide ratio. These 6 predictors were incorporated to develop model for renal dysfunction risk prediction using LR. Finally, the LR model achieved a high efficiency, with an AUC of 0.83 (0.76 - 0.91), an accuracy of 75.80%, a sensitivity of 88.60%, and a specificity of 70.80%. According to the power analysis, the statistical power of the LR model was found to be 0.81, which was at a relatively high level. Finally, a nomogram was developed to make the model more available for individualized prediction in clinical practice.

Conclusion

Our results indicated that the baseline level of serum C-peptide had the potential role in the risk prediction of new-onset renal dysfunction. The LR model demonstrated high efficiency and had the potential to guide individualized risk assessments for renal dysfunction in clinical practice.
Phosphorus uptake mechanisms associated with phosphorus application levels in two cotton cultivars
Authors: Cai Fangyuan , Zhang Yingrong , Hou Tianyu , Zhang Man , Wang Juanhong , Chen Bolang
Published: July 2023

Poor phosphorus utilization is a common limitation of sustainable cotton production. Even so, the intrinsic potential for efficient phosphorus acquisition of the roots remains unclear. In this study, we aimed to explore if phosphorus acquisition in cotton is affected by interactions that could possibly be associated with root morphology and gene expression, between genotype and application rates. A pot experiment was conducted with seven phosphorus application rates: 0, 12.5, 25, 50, 75, 150, and 300 mg P kg−1. The agronomic characters, root morphology, and expression of the PHT1 gene in the roots of cotton varieties with different phosphorus acquisition efficiencies were measured. According to the results, the phosphorus acquisition efficiency in cultivar XLZ19 was higher than in XLZ13 for phosphorus uptake because of the upregulation of GhPTs gene expression that increased the total root length and proportion of fine roots. The Olsen-P levels in the soil ranged from 20 to 30 mg kg−1 at the seedling stage and from 15 to 25 mg kg−1 at the flowering stage, suggesting better root growth and phosphorus supply. The conversion of phosphorus fertilizers to soil Olsen-P decreased when the phosphorus application rate exceeded 50–75 mg kg−1. The phosphorus acquisition–efficient XLZ19 phenotype owes its efficiency to high GhPTs expression and morphological changes in the roots. Finally, with these crops that are highly efficient in phosphorus acquisition, agricultural practices in sustainable cotton production may consume less phosphorus fertilizers.
The direct and indirect spatial spillover effects of infrastructure on urban green and smart development
Authors: Wang Dandan , Xu Lingyan , Du Jianguo
Published: July 2023

Introduction: Economic development is not simply the accumulation of elements, but the improvement of efficiency, which is supported by infrastructure construction. In particular, the urban green and smart development (UGSD) in recent years has put forward higher requirements for infrastructure, and domestic trade as well as opening-up are of great significance during the process.

Methods: Based on the panel data of 221 prefecture-level cities in China from the year of 2005 to 2019, this paper adopts the undesirable SBM model and GML index to measure the level of UGSD. Then the spatial Durbin model is conducted to explore the direct spatial spillover effects and the spatial decomposition effects of energy, transportation, and information infrastructure on UGSD. Considering the context of dual cycle, the indirect effects of domestic trade and opening-up between infrastructures and UGSD are further analyzed.

Results: Results show that UGSD demonstrates strong spatial agglomeration and maintains a stable spatial positive correlation with different spatial matrices. In general, energy and transportation infrastructure show positive spatial spillover effects on UGSD. By contrast, information infrastructure presents positive spatial spillover effect on UGSD on the whole, while shows insignificant and negative spatial spillover effect with geographical distance matrix. Furthermore, the mediation effect indicates that both transportation and information infrastructure mainly promote local and adjacent cities’ UGSD through domestic trade with economic distance matrix. By contrast, energy infrastructure exerts positive spatial spillover effect on UGSD through weakening the negative impact of opening-up.

Discussion: The conclusions of the research show that it is necessary to construct infrastructure in a reasonable way, strengthen the positive spillover effect of intercity factors, and promote the two-wheel driving effect of domestic trade and opening-up on the relationship between infrastructure and UGSD.
Phosphatase activities and available nutrients in soil aggregates affected by straw returning to a calcareous soil under the maize–wheat cropping system
Authors: Lin Xiang-Jie , Zhang Guang-Na , Wang Zhen , Han Qing-Dian , Leng Peng
Published: July 2023

The objective of this study was to investigate the effects of different rates of straw returning on soil aggregate stability, phosphatase activities, and the available nitrogen (N) and phosphorus (P) within different soil aggregate sizes. The experiment included five treatments: 1) no straw returning and no chemical fertilizer, 2) chemical fertilizer only (150 kg N ha-1, 75 kg P ha-1, and 75 kg K ha-1), 3) 20% straw returning with chemical fertilizer, 4) 60% straw returning with chemical fertilizer, and 5) 100% straw returning with chemical fertilizer. Soil samples were collected 3.5 years after the start of the experiment and separated into four aggregate sizes (<0.25 mm, 0.25–1 mm, 1–2 mm, and 2–7 mm) using the dry sieving method. Soil acid phosphomonoesterase (AcP) and alkaline phosphomonoesterase (AlP); phosphodiesterase (PD); pyrophosphatase (PrA) activities; and soil NO3−−N, NH4+−N, and resin-P were determined within soil aggregates. The results showed that straw returning rates did not significantly impact soil aggregate distribution. However, straw returning increased soil AcP, AlP, and PD in <2 mm aggregates, and high rates of straw returning led to high enzyme activities. Soil phosphatase activities were also higher in 1–2 mm aggregates. All straw returning and chemical fertilization treatments increased soil NO3−−N and resin-P concentrations but had much less effect on soil NH4+−N concentrations. Additionally, the study revealed that soil pH, the concentrations of NH4+−N, NO3−−N, resin-P, and CaCO3 significantly influenced soil phosphatase activities, but their impact varied across different sizes of aggregates.
A melting-pot for Pterodroma petrels on Rapa Nui: ecological divergence and reproductive isolation in a contact zone
Authors: Plaza Paula , Cristofari Robin , Gouin Nicolas , Soto-Gamboa Mauricio , Luna-Jorquera Guillermo
Published: July 2023

Speciation is thought to depend on general ecological segregation rather than on strict allopatry in species with planetary-scale foraging ranges, such as Pterodroma petrels. Separation in both breeding islands and foraging grounds are generally considered to be the conditions for prezygotic isolation. However, it is unclear how both can be maintained in a context of ongoing distributional range shifts due to global change, with range contractions and expansions caused by changing land use in breeding territories and oceanographic conditions impacting productivity areas. In this context, we expect that wherever the fragile balance of allopatric segregation breaks down, gene flow may be re-established across the borders of what is currently considered separated species. In these “melting pot” areas, fine-scale ecological differentiation is likely the only force opposing panmixia in otherwise highly similar organisms. In this study, we focus on six Polynesian Pterodroma species currently found on Motu Nui, a protected islet offshore of Rapa Nui (Easter Island), four of which have likely extended their breeding range to that island recently. To understand the fine-scale interaction between these closely-related species in their new contact zone, we used an integrative approach combining ecological and genetic methods, including morphometric, bioacoustics, stable isotope niche reconstruction, breeding site characterisation, phenology traits, and both nuclear and mitochondrial DNA markers. We found that significant amounts of gene flow occur across what is currently considered species boundaries, sometimes questioning the relevance of the accepted species classification. Interestingly, our results indicate that multivariate ecological distance between individuals in a group of closely related species (P. alba, P. atrata, P. heraldica, and P. neglecta) is a relevant predictor of gene flow intensity, while more distant species such as P. ultima and P. nigripennis seem to maintain reproductive isolation. Thus, the case of Pterodroma petrels supports the idea that incomplete allopatric speciation processes may be halted or even reversed on a secondary contact zone. Beyond their direct taxonomical relevance, our results underline the importance of considering fine ecological structures for biodiversity mapping and conservation policies.
Spatial-temporal variation and driving forces of the synergy of “pollution reduction, carbon reduction, green expansion and economic growth”: evidence from 243 cities in China
Authors: Hu Chiqun , Ma Xiaoyu , Yang Lan , Chang Xiaona , Li Qiangyi
Published: July 2023

Introduction

Pollution reduction, carbon reduction, green expansion and economic growth—the synergistic effects of the four—have become essential in maintaining urban ecological security and promoting a green and low-carbon transition. And it is inherently consistent with the globally accepted concept of sustainable development.

Methods

Based on the evaluation index system and the coupling mechanism of the four, we adopt the entropy method and the coupling coordination model to measure the synergistic level of “pollution reduction, carbon reduction, green expansion and economic growth” in 243 cities above prefecture level in China from 2005 to 2020. Furthermore, the study examined the temporal and spatial evolution and regional differences by utilizing the center of gravity-standard deviation ellipse, Dagum Gini coefficient method, Kernel density estimation, and Markov chain. In addition, the spatial econometric model was used to analyze the driving factors affecting the synergistic development.

Results

The results show that the overall synergistic level is rising, the spatial distribution characteristics of “high in the east and low in the west.” The standard deviation ellipse shows a “northeast–southwest” pattern, and the center of gravity moves in a “southeast–northwest–southwest” migration trend. Regional differences are mainly rooted in inter-regional differences. The intra-regional differences are East > West > Central, with the most prominent East–West inter-regional differences. Without considering the spatial factor, the synergistic level shows a steady increase and has continuity. Under the spatial condition, the synergistic level has a positive spatial correlation. However, the positive spatial correlation decreases significantly as the years go by. Also, the probability of “rank locking” of synergistic development has been reduced, and there is a leapfrog shift. In terms of driving factors, the innovation level, level of external openness, population size, and industrial structure positively drive synergistic development. While government intervention negatively affects synergistic development.

Discussions

Based on the above findings,policy recommendations are proposed to strengthen the top-level design and build a policy system, play the radiation linkage, apply precise policies according to local conditions, and optimize the industrial structure fully. Which is of great significance for improving the urban ecological resilience and helping to achieve the “double carbon” target.
Legal approaches to risk of harm in genetic counseling: perspectives from Quebec and Qatar
Authors: Patrinos Dimitri , Ghaly Mohammed , Al-Shafai Mashael , Zawati Ma’n H.
Published: July 2023

Genetic counseling is a fast-growing profession worldwide, with genetic counselors taking on increasingly comprehensive and autonomous roles in the healthcare sector. However, the absence of appropriate legal frameworks could potentially create risks of harm to the public. Legal recognition serves to protect the public from risk of harm by regulating the safe and competent practice of healthcare professionals. Genetic counseling is not legally recognized in most world jurisdictions. Examination of the legal status of genetic counseling in different jurisdictions and whether existing legal mechanisms are adequate to address potential risks of harm is therefore timely. This paper examines the different roles of genetic counselors in the Canadian province of Quebec and the state of Qatar, the authors’ respective jurisdictions. It considers the types of harms that may be created where appropriate legal mechanisms are lacking, considering the socio-political and legal differences between the two jurisdictions. Moreover, it examines the legal status of genetic counseling in Quebec and Qatar to determine whether these statuses appropriately address the identified risks of harm. The authors argue that existing legal frameworks are inadequate to address these risks and recommend that additional regulatory mechanisms be implemented to properly protect the public from risks of harm.
Bioinformatic analysis reveals lysosome-related biomarkers and molecular subtypes in preeclampsia: novel insights into the pathogenesis of preeclampsia
Authors: Chen Yao , Liu Miao , Wang Yonghong
Published: July 2023

Background: The process of lysosomal biogenesis and exocytosis in preeclamptic placentae plays a role in causing maternal endothelial dysfunction. However, the specific lysosome-associated markers relevant to preeclampsia (PE) are not well-defined. Our objective is to discover new biomarkers and molecular subtypes associated with lysosomes that could improve the diagnosis and treatment of PE.

Methods: We obtained four microarray datasets related to PE from the Gene Expression Omnibus (GEO) database. The limma package was utilized to identify genes that were differentially expressed between individuals with the disease and healthy controls. The logistic regression analysis was used to identify core diagnostic biomarkers, which were subsequently validated by independent datasets and clinical samples. Additionally, a consensus clustering method was utilized to distinguish between different subtypes of PE. Following this, functional enrichment analysis, GSEA, GSVA, and immune cell infiltration were conducted to compare the two subtypes and identify any differences in their functional characteristics and immune cell composition.

Results: We identified 16 PE-specific lysosome-related genes. Through regression analysis, two genes, GNPTG and CTSC, were identified and subsequently validated in the external validation cohort GSE60438 and through qRT-PCR experiment. A nomogram model for the diagnosis of PE was developed and evaluated using these two genes. The model had a remarkably high predictive power (AUC values of the training set, validation set, and clinical samples were 0.897, 0.788, and 0.979, respectively). Additionally, two different molecular subtypes (C1 and C2) were identified, and we found notable variations in the levels of immune cells present in the two subtypes.

Conclusion: Our results not only offered a classification system but also identified novel diagnostic biomarkers for PE patients. Our findings offered an additional understanding of how to categorize PE patients and also highlighted potential avenues for creating treatments for individuals with PE.
Rituximab resistance in ITP and beyond
Authors: Xiao Zhengrui , Murakhovskaya Irina
Published: July 2023

The pathophysiology of immune thrombocytopenia (ITP) is complex and encompasses innate and adaptive immune responses, as well as megakaryocyte dysfunction. Rituximab is administered in relapsed cases and has the added benefit of inducing treatment-free remission in over 50% of patients. Nevertheless, the responses to this therapy are not long-lasting, and resistance development is frequent. B cells, T cells, and plasma cells play a role in developing resistance. To overcome this resistance, targeting these pathways through splenectomy and novel therapies that target FcγR pathway, FcRn, complement, B cells, plasma cells, and T cells can be useful. This review will summarize the pathogenetic mechanisms implicated in rituximab resistance and examine the potential therapeutic interventions to overcome it. This review will explore the efficacy of established therapies, as well as novel therapeutic approaches and agents currently in development.
The role of the CD8+ T cell compartment in ageing and neurodegenerative disorders
Authors: Terrabuio Eleonora , Zenaro Elena , Constantin Gabriela
Published: July 2023

CD8+ lymphocytes are adaptive immunity cells with the particular function to directly kill the target cell following antigen recognition in the context of MHC class I. In addition, CD8+ T cells may release pro-inflammatory cytokines, such as tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ), and a plethora of other cytokines and chemoattractants modulating immune and inflammatory responses. A role for CD8+ T cells has been suggested in aging and several diseases of the central nervous system (CNS), including Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, amyotrophic lateral sclerosis, limbic encephalitis-induced temporal lobe epilepsy and Susac syndrome. Here we discuss the phenotypic and functional alterations of CD8+ T cell compartment during these conditions, highlighting similarities and differences between CNS disorders. Particularly, we describe the pathological changes in CD8+ T cell memory phenotypes emphasizing the role of senescence and exhaustion in promoting neuroinflammation and neurodegeneration. We also discuss the relevance of trafficking molecules such as selectins, mucins and integrins controlling the extravasation of CD8+ T cells into the CNS and promoting disease development. Finally, we discuss how CD8+ T cells may induce CNS tissue damage leading to neurodegeneration and suggest that targeting detrimental CD8+ T cells functions may have therapeutic effect in CNS disorders.
Long-term hypoxia and reoxygenation induced oxidative stress lead to immunosuppression and apoptosis in golden pompano (Trachinotus blochii)
Authors: Gu Yue , Sun Jun Long , Yao Fu Cheng , Jiang Tian , Jin Chun Xiu , Shi Li Ping , Sun Shu Kui , Song Fei Biao , Luo Jian
Published: July 2023

The fluctuations of dissolved oxygen (DO) often lead to hypoxia in aquaculture, which has a huge adverse impact on fish. This study mainly investigated the effects of long-term hypoxia on oxidative stress, immune response, and cell apoptosis in the liver of golden pompano (Trachinotus blochii), which is not tolerant to hypoxia. So we conducted a 14 day low oxygen stress experiment on the golden pompano with a DO of 3.0 ± 0.2 mg/L, then restore the DO to normal levels and continue the 14 day reoxygenation experiment. Results showed that hypoxia and reoxygenation led to significant changes in liver structure. During hypoxia and reoxygenation, the expression of oxidative stress related genes (SOD1, SOD2, GSH-Px, and CAT) and levels of antioxidant enzymes (CAT and MDA) in the liver were increased. Liver lysozyme activity and the relative expression of the pro-inflammatory factors interleukin (IL)-1β were significantly increased, but the expression of IL-34 was down-regulated during hypoxia. The expression of IL-12β was significantly increased during reoxygenation. The expression of anti-inflammatory factor IL-11 was decreased duringreoxygenation. The expression of toll like receptors (TLRs) -7, -8, and -9 increases after hypoxia and decreases after reoxygenation, indicating that both hypoxia and reoxygenation affect the immune response. In addition, during hypoxia and reoxygenation, TUNEL-positive signals increased, the bcl2/bax ratio decreased, the expression levels of caspases-3 and -8 were significantly up-regulated during hypoxia, and expression levels of caspases-9 was up-regulated during reoxygenation. In summary, hypoxia and reoxygenation can cause oxidative stress, induce inflammatory reactions, inhibit immune processes, activate apoptosis, and lead to liver damage of the golden pompano, which may be irreversible.
Plasma treatment process for accelerating the disintegration of a biodegradable mulch film in soil and compost
Authors: Bhattacharya Swapnil , Kansara Harshal Jayesh , Lodge Jeffery , Diaz Carlos A. , Lewis Christopher L.
Published: July 2023

Biodegradable Mulch Films (BMFs) offer a sustainable alternative to traditional non-degradable (Polyethylene) PE mulch films. However, their slow rate of biodegradation can lead to plastics accumulation in soil. In this study, a commercially available BMF based on poly (butylene adipate co-terephthalate) (PBAT) and poly (lactic acid) (PLA) is examined. Here the effects of gliding arc plasma treatment on the bulk and surface properties, as well as its degradation behavior in soil and compost is studied. An increase in surface oxygen containing species and hydrophilicity was observed following plasma treatment. Only a small hydrophobic recovery was noted over 30 days. No changes in the bulk polymer molecular weight or thermal properties following treatment were noted. However, a decrease in mechanical strength was observed following gliding arc plasma treatment. The onset of film fragmentation in both soil and compost occurred earlier for a plasma treated film and we attribute this to an improvement in the initial adhesion of bacteria on the surface.
Omadacycline in the treatment of community-acquired bacterial pneumonia in patients with comorbidities: a post-hoc analysis of the phase 3 OPTIC trial
Authors: Rodriguez George D. , Warren Nathan , Yashayev Roman , Chitra Surya , Amodio-Groton Maria , Wright Kelly
Published: July 2023

Introduction

The 2019 American Thoracic Society/Infectious Disease Society of America guidelines recommend respiratory fluoroquinolones to treat community-acquired bacterial pneumonia (CABP) in adults with comorbidities. Fluoroquinolones are effective against both typical and atypical pathogens. However, fluoroquinolone treatment has a risk of adverse effects, and the Food and Drug Administration has issued black box safety warnings for their use. Inpatient use of fluoroquinolones has reduced as a result; however, most antibiotic courses are completed as outpatients and discharge prescriptions account for the majority of fluoroquinolone use. As such, a new treatment option is needed to replace fluoroquinolones. Omadacycline is an aminomethylcycline antibiotic with a broad spectrum of activity and is available as a once-daily intravenous or bioequivalent oral formulation.

Methods

This study assessed the safety and clinical efficacy of omadacycline compared with moxifloxacin for the treatment of adult CABP patients with Pneumonia Severity Index (PSI) risk class II/III and ≥1 comorbidity through a post-hoc analysis of the phase 3 OPTIC study (NCT02531438).

Results

In total, 239 omadacycline- and 222 moxifloxacin-treated patients were assessed. The median age was similar between groups (omadacycline: 57 years; moxifloxacin: 58 years), with 26.0% and 26.6%, respectively, ≥65 years of age. Early clinical response was 91.6% for patients with ≥1 comorbidity treated with omadacycline and 91.4% for those treated with moxifloxacin. Post-treatment evaluation results for overall response were 89.1% in the omadacycline group and 87.4% in the moxifloxacin group.

Conclusion

Safety warnings have reduced inpatient use of fluoroquinolones; however, outpatient and discharge prescriptions account for the majority of fluoroquinolone use. Outpatients with comorbidities need an efficacious alternative to fluoroquinolones. Omadacycline maintains the similar efficacy and benefits of fluoroquinolones as a once-daily, monotherapy, bioequivalent oral option with potent in vitro activity against the most common CABP pathogens, including S. pneumoniae and atypical pathogens, but offers a materially different safety profile consistent with its tetracycline heritage. In conclusion, both omadacycline and moxifloxacin exhibited similar efficacy in patients with PSI risk class II/III and comorbidities. Omadacycline fulfills an unmet need as an oral monotherapy treatment option for adult patients with CABP, which will further reduce the use of fluoroquinolones.

Clinical trial registration

https://www.clinicaltrials.gov/study/NCT02531438, identifer: NCT02531438; https://www.clinicaltrialsregister.eu/ctr-search/search?query=2013-004071-13, identifier: EudraCT #2013-004071-13.
Integration of multi-omics data to elucidate keystone unknown taxa within microbialite-forming ecosystems
Authors: Amorín de Hegedüs Rocío , Conesa Ana , Foster Jamie S.
Published: July 2023

Microbes continually shape Earth’s biochemical and physical landscapes by inhabiting diverse metabolic niches. Despite the important role microbes play in ecosystem functioning, most microbial species remain unknown highlighting a gap in our understanding of structured complex ecosystems. To elucidate the relevance of these unknown taxa, often referred to as “microbial dark matter,” the integration of multiple high throughput sequencing technologies was used to evaluate the co-occurrence and connectivity of all microbes within the community. Since there are no standard methodologies for multi-omics integration of microbiome data, we evaluated the abundance of “microbial dark matter” in microbialite-forming communities using different types meta-omic datasets: amplicon, metagenomic, and metatranscriptomic sequencing previously generated for this ecosystem. Our goal was to compare the community structure and abundances of unknown taxa within the different data types rather than to perform a functional characterization of the data. Metagenomic and metatranscriptomic data were input into SortMeRNA to extract 16S rRNA gene reads. The output, as well as amplicon sequences, were processed through QIIME2 for taxonomy analysis. The R package mdmnets was utilized to build co-occurrence networks. Most hubs presented unknown classifications, even at the phyla level. Comparisons of the highest scoring hubs of each data type using sequence similarity networks allowed the identification of the most relevant hubs within the microbialite-forming communities. This work highlights the importance of unknown taxa in community structure and proposes that ecosystem network construction can be used on several types of data to identify keystone taxa and their potential function within microbial ecosystems.