bluuebunny/crossref_metadata_2025 huggingface dataset:
Relative adrenal insufficiency is a risk factor and endotype of sepsis - A proof-of-concept study to support a precision medicine approach to guide glucocorticoid therapy for sepsis
Authors: Wu Chia-Hua , Guo Ling , Hao Dan , Wang Qian , Ye Xiang , Ito Misa , Huang Bin , Mineo Chieko , Shaul Philip W. , Li Xiang-An
Published: January 2023

Introduction

25-60% of septic patients experience relative adrenal insufficiency (RAI) and glucocorticoid (GC) is frequently used in septic patients. However, the efficacy of GC therapy and whether GC therapy should be based on the status of RAI are highly controversial. Our poor understanding about the pathogenesis of RAI and a lack of RAI animal model present significant barriers to address these critical issues.

Methods

Scavenger receptor BI (SR-BI) regulates stress-induced GC (iGC) production in response to stress. We generated SF1CreSR-BIfl/fl mice and utilized the mice as a RAI model to elucidate the pathogenesis of RAI and GC therapy in sepsis. SF1CreSR-BIfl/fl mice did not express SR-BI in adrenal gland and lacked iGC production upon ACTH stimulation, thus, they are RAI.

Results and Discussion

RAI mice were susceptible to cecal ligation and puncture (CLP)-induced sepsis (6.7% survival in SF1CreSR-BIfl/fl mice versus 86.4% in SR-BIfl/fl mice; p = 0.0001). Compared to a well-controlled systemic inflammatory response in SR-BIfl/fl mice, SF1CreSR-BIfl/fl mice featured a persistent hyperinflammatory response. Supplementation of a low stress dose of GC to SF1CreSR-BIfl/fl mice kept the inflammatory response under control and rescued the mice. However, SR-BIfl/fl mice receiving GC treatment exhibited significantly less survival compared to SR-BIfl/fl mice without GC treatment. In conclusions, we demonstrated that RAI is a risk factor for death in this mouse model of sepsis. We further demonstrated that RAI is an endotype of sepsis, which features persistent hyperinflammatory response. We found that GC treatment benefits mice with RAI but harms mice without RAI. Our study provides a proof of concept to support a precision medicine approach for sepsis therapy – selectively applying GC therapy for a subgroup of patients with RAI.
Hydrothermal vent chimney-base sediments as unique habitat for meiobenthos and nanobenthos: Observations on millimeter-scale distributions
Authors: Bernhard Joan M. , Nomaki Hidetaka , Shiratori Takashi , Elmendorf Anastasia , Yabuki Akinori , Kimoto Katsunori , Tsuchiya Masashi , Shimanaga Motohiro
Published: January 2023

Hydrothermal vents are critical to marine geochemical cycling and ecosystem functioning. Although hydrothermal vent-associated megafauna and chemoautotrophic prokaryotes have received extensive dedicated study, smaller hydrothermal vent-associated eukaryotes such as meiofauna and nanobiota have received much less attention. These communities comprise critical links in trophic flow and carbon cycling of other marine habitats, so study of their occurrence and role in hydrothermal vent ecosystems is warranted. Further, an understudied vent habitat is the thin sediment cover at the base of hydrothermal vent chimneys. An initial study revealed that sediments at the base of vent chimneys of the Izu-Ogawasara Arc system (western North Pacific) support metazoan meiofauna, but very little is known about the taxonomic composition and abundance of the meiobenthic protists and nanobiota, or their millimeter-scale distributions. Using the Fluorescently Labeled Embedded Coring method (FLEC), we describe results on meiofaunal and nanobiota higher-level identifications, life positions and relative abundances within sediments from three habitats (base of vent chimneys, inside caldera but away from chimneys, and outside caldera) of the Myojin-Knoll caldera and vicinity. Results suggest that the chimney-base community is unique and more abundant compared to non-chimney associated eukaryotic communities. Supporting evidence (molecular phylogeny, scanning and transmission electron microscopy imaging) documents first known hydrothermal-vent-associated occurrences for two protist taxa. Collectively, results provide valuable insights into a cryptic component of the hydrothermal vent ecosystem.
Laboratory study of the combined wave and surge overtopping-induced normal stress on dike
Authors: Zhou Zijun , Sun Zhongbing , Zhou Yiren , Zuo Qihua , Wang Hongchuan , Chen Yongping , Huang Feiyang
Published: January 2023

Normal stress on dikes is one of the most critical parameters for a sound dike design. With more rapidly rising sea levels due to global warming, dikes are seriously threatened by overtopping induced by the combination of wave and storm surge. Compared with wave overtopping on positive freeboard, the curling breaking wave on dikes induced by the combined wave and surge overtopping may destroy the weakly protected dike crest and landward slope. Thus, in order to prevent severe damage to dikes, it is necessary to fully understand the normal stress induced by the combined wave and surge overtopping. In this paper, physical model tests were carried out to study the normal stress on dike induced by the combined wave and surge overtopping. Two characteristics of normal stress on dike were observed. The spatial distribution of normal stress on dike was also analyzed. It was found that the Weibull distribution can be used to effectively describe the statistical distribution of peak normal stresses. Furthermore, by curve fitting of the laboratory measured data, the Weibull factors on the part of the crest and the upper part of the landward slope were obtained.
Relationship between the hadley circulation and tropical SST meridional structures under different thermal conditions in the indo-pacific warm pool
Authors: Ji Xuanliang , Feng Juan , Li Jianping , Chen Xingrong
Published: January 2023

The Hadley circulation (HC), as a thermally driven large-scale meridional circulation, acts a significant role in the changes of global climate. The modulation of Indo-Pacific warm pool (IPWP) thermal conditions on the relationship between the HC and different tropical sea surface temperature (SST) meridional structures was investigated. Based on the two components of HC and SST, one equatorially asymmetric component (HEA for HC, SEA for SST) and one equatorially symmetric component (HES for HC, SES for SST), the connections of HC to different SST variations in the warm and cold IPWP are explored. The result demonstrates that the relationship of the HC to tropical SST is suppressed in the cold IPWP conditions, whereas it is equivalent to the climatology in the warm IPWP conditions. The plausible mechanism is that the cold (warm) IPWP events are in concordance with the La Niña (El Niño) decay phase. The La Niña decay phase are associated with significant equatorially asymmetric SST anomalies within the IPWP, generating an anomalous meridional circulation and favoring a strengthened equatorially asymmetric anomalous meridional circulation. By contrast, the SST anomalies associated with El Niño decay phase are insignificant. The role of La Niña decay conditions in determining the suppressed connection between SST and HC is further verified by exploring the result after 1979. A similar suppressed response contrast has been detected. Therefore, the results demonstrate that warm and cold ENSO events have impacts on the interannual thermal conditions of IPWP, whereby it plays considerable role in impacting the relationship between the HC and tropical SST. Particularly, with the rapid warming, the interconnection between ENSO events and thermal conditions of IPWP under different timescales could be altered, the influence of which on the responses of the HC to tropical SST remains uncertain and is worthy further researching.
Spatial and seasonal distributions of ten species of benthic macrofauna and twelve water environmental factors in a subtidal zone near the Daya Bay nuclear power plant
Authors: Cai Lizhe , Rao Yiyong , Zhao Xiaoyu , Yang Deyuan , Zhou Xiping , Wang Deli , Yue Xinli
Published: January 2023

In this study, we analyzed the spatial and seasonal distributions of ten species of benthic macrofauna and 12 water environmental parameters at thirty-six sampling stations in the subtidal zone near the Daya Bay Nuclear Power Plant. The results showed that there were four types of distribution characteristics for 10 species of macrobenthic animals and 12 water environmental factors near the Daya Bay nuclear power plant: (1) three species of benthic macrofauna, namely Apionsoma (Apionsoma) trichocephalus, Amphioplus (Lymanella) laevis, and P. bidentata, and six water environmental parameters, including water depth, salinity, dissolved oxygen, suspended solids, chromium, and lead increased from inside the bay to outside the bay. (2) Three species of benthic macrofauna, P. cristata, T. lata, and T. scabra, and four water environmental parameters, including oils, arsenic, total phosphorus, and silicate, decreased from inside to outside the bay. (3) Two species of benthic macrofauna, A. dibranchis, and P. undulatus and one water environmental parameter, pH, were higher in the central bay than inside and outside the bay. (4) One species of benthic macrofauna, Sigambra hanaokai, and one water environmental parameter, total nitrogen, were lower in the central bay than inside and outside the bay. Correlation and BIO-ENV analyses confirmed that water depth was the main environmental factor affecting the ten species of benthic macrofauna. Understanding the distributions of the dominant benthic macrofauna could help protect nuclear cold source systems from benthic macrofaunal blockage and explore marine ecosystem connectivity.
Marine sediment nitrogen isotopes and their implications for the nitrogen cycle in the sulfate-methane transition zone
Authors: Yang Xin , Zhang Yihao , Sun Xiaoming , Xu Li , Chen TingTing
Published: January 2023

Introduction

Recent work has proposed that the nitrogen isotopes in marine sediments can be impacted by anaerobic oxidation of methane (AOM), since nitrogen uptake by anaerobic methanotrophic archaea (ANME) modifies the nitrogen isotope compositions of bulk sediment. Thus, unraveling the AOM-driven nitrogen cycle in the sulfate-methane transition zone (SMTZ) becomes significant. Additional study of the nitrogen cycle between sediment and interstitial water in SMTZ is needed.

Methods

To better understand the nitrogen cycle in the SMTZ, we analyzed NH4+ concentrations of interstitial water and nitrogen isotopes of sediment in the core GC10 from the southwestern Taiwan Basin in the South China Sea.

Results

The defined SMTZ is located at 560–830 cmbsf, based on methane and sulfate concentrations, as well as TS/TOC ratios, δ13CTIC and δ34S values. In the SMTZ, the NH4+ concentration decreases, the δ15NTN shows a negative excursion, δ15Ndecarb displays a positive excursion.

Discussions

NH4+ concentration decrease is interpreted by sulfate-reducing ammonium oxidation (SRAO). The δ15NTN shows negative excursion, which is most likely interpreted to N2 (δ15N=0‰) released from SRAO that was fixed into marine sediment via ANME nitrogen fixation. The δ15Ndecarb shows a negative correlation with NH4+ concentrations, indicating that it was controlled by organic matter decomposition. In the SMTZ, the methane competes with organic matter for becoming the substrate of sulfate reduction bacteria, which possibly decreases the organic matter degradation rate and causes δ15Ndecarb relative positive excursion. Although δ15Ndecarb is controlled by organic matter degradation, δ15NTN still reveals a negative excursion in the SMTZ. This likely indicates that nitrogen uptake by ANME/AOM microbial consortiums mainly modifies the nitrogen isotope of soluble nitrogen in the SMTZ.

Conclusions

This study indicates unique geochemistry processes in SMTZ will modify nitrogen characteristics in sediment/interstitial water, and the latter can serve as a proxy for AOM.
Effect of wind on summer chlorophyll-a variability in the Yellow Sea
Authors: Lin Lei , Liu Dongyan , Wang Yueqi , Lv Ting , Zhao Yue , Tan Wei
Published: January 2023

Winds potentially affect primary production in shelf seas during the stratified season by enhancing upwelling and mixing. However, the exact extent and modalities of this effect in the Yellow Sea remain unclear. Here, based on the satellite and in situ observation data, statistical method, and wind-driven upwelling theory, we examined the wind effect on the chlorophyll-a (Chl-a) variability in the summer of 2002-2020 and the effect mechanism. The satellite data revealed a significantly positive correlation between anomalies of the monthly mean of the summer sea surface Chl-a and wind speed at the continental slope region (water depth of 20-60 m) in the southwestern Yellow Sea where strong wind-driven upwelling has been indicated by previous studies. The wind-driven upwelling along the continental slope was further verified using two summer in-situ observations. After a fortnight of southeasterly wind, the upwelling patterns of high salinity and rich nutrients from the Yellow Sea cold water mass were observed, and consequently, high Chl-a concentrations occurred in the upper layer of the slope region. The wind-driven upwelling occurred in the region at water depth of ~20-60 m, which is consistent with the result of the wind-driven coastal upwelling theory (0.5D < water depth < 1.25D, where D is the thickness of the Ekman layer). The dissolved inorganic nitrogen, phosphorus, and silicate fluxes contributed by wind-driven upwelling were estimated as 1345 ± 674 μmol/m2/d, 81 ± 45 μmol/m2/d and 1460 ± 899 μmol/m2/d, respectively, accounting for 30%-40% of total nutrient supply, and were several times larger than that contributed by the turbulent mixing, which can explain why the strong wind-Chl-a correlation only occurred at the upwelling region rather than the entire sea. In addition, in this region, the interannual variability of the summer mean Chl-a was negatively correlated to both the Pacific Decadal Oscillation (PDO) and El Niño-Southern Oscillation (ENSO) indexes, due to the opposite phase of the summer wind anomaly and the PDO/ENSO. This study revealed the wind effect on the shelf phytoplankton is regional and highlighted that wind could be a pivotal factor driving the climate variability of shelf primary production in the stratified season.
Shape memory polymer-based prefabricated components: Design ideas and prospects
Authors: Zhang Wencai , Li Duanling
Published: January 2023

Shape memory polymers (SMP) are the smart materials that have received the most attention and are the most commonly employed. SMP can be 4D printed to create prefabricated components with transform shapes, properties, or functions under different external excitations. Although smart equipment assembled from these prefabricated components is extensively used in various fields, a systematic overview summary of their design ideas still needs to be provided. This paper briefly analyzes current trends in the design ideas and application of SMP-based prefabricated components. By summarizing two different design ideas: structural combination and material modification, it demonstrates the application of smart equipment assembled from SMP-based prefabricated components in medical, industrial, and aerospace fields. Furthermore, current challenges with both design ideas are discussed.
Suppression characteristics of multi-layer metal wire mesh on premixed methane-air flame propagation
Authors: Feng Xiangrui , Zhang Hongming , Si Fangyuan , Dou Jiawei , Li Mingxuan , Wu Long , Wang Shengkang , Zhao Lanming
Published: January 2023

Metal wire mesh is widely used in the energy industry for its excellent protective properties as a fire stopping and explosion isolating material. In this study, the suppression characteristics of different layers of metal mesh on the dynamic behavior of premixed methane-air flame propagation were studied experimentally. A high-speed photographic schlieren system was used to photograph the explosion process to capture the changes in the microstructure of the flame, and high-frequency pressure sensors and micro-thermocouple measurements were used to capture the flame explosion pressure and temperature. The experimental results show that the suppression effectiveness of wire mesh is a reflection of the coupling of explosive flame propagation behavior and combustion state in the pipe. Increasing the number of mesh layers and mesh density can destroy the microstructure of the premixed methane-air flame front and hinder the progress of flame propagation. Increasing the number of wire mesh layers will delay the peak time of premixed flame propagation speed and reduce the peak speed values of flame propagation. Wire mesh has a pronounced attenuation effect on premixed flame temperature and explosion overpressure. The maximum flame temperature attenuation rate is 34.99%–60.95%, and the maximum explosion overpressure attenuation rate is 33.70%–74.02%. And the suppression effect is greatly enhanced as the increase of mesh layers.
Peripapillary and macular microvasculature features of non-arteritic anterior ischemic optic neuropathy
Authors: Pugazhendhi Sangeethabalasri , Yu Miaomiao , Zhou Gabriella , Chen Yuxuan , Wang Ruikang , Liao Yaping Joyce
Published: January 2023

Purpose

The hallmark of non-arteritic anterior ischemic optic neuropathy (NAION) is vascular compromise to the anterior optic nerve and thinning of the retinal nerve fiber layer (RNFL) and secondary degeneration of the retinal ganglion cell body or thinning of the ganglion cell complex (GCC). This study investigates optical coherence tomography (OCT) and OCT Angiography (OCTA) changes in chronic NAION and identifies imaging biomarkers that best predict disease.

Methods

We performed a retrospective case-control study of 24 chronic NAION eyes (18 patients) and 70 control eyes (45 patients) to compare both whole-eye and regional OCT, OCTA, static perimetry measurements. OCT measurements were quantified automatically using commercial software, and OCTA was analyzed using custom MATLAB script with large vessel removal to measure 154 total parameters per eye.

Results

We confirmed that static perimetry mean deviation (MD) was significantly worse in chronic NAION (–13.53 ± 2.36) than control (–0.47 ± 0.72; P < 0.001) eyes, and NAION eyes had 31 μm thinner RNFL (control: 95.9 ± 25.8 μm; NAION: 64.5 ± 18.0, P < 0.001), and 21.8 μm thinner GCC compared with controls (control: 81.5 ± 4.4 μm; NAION: 59.7 ± 10.5, P < 0.001). Spearman correlation analysis of OCTA parameters reveal that vessel area density (VAD) and flux are highly correlated with visual field MD and OCT measurements. Hierarchical clustering two distinct groups (NAION and control), where standardized measurements of NAION eyes were generally lower than controls. Two-way mixed ANOVAs showed significant interaction between patient status (control and chronic NAION) and structure (optic disk and macula) for annulus VAD and flux values and mean RNFL and GCC thickness. Post-hoc tests showed this effect stems from lower peripapillary values in NAION compared to controls. Separate logistic regression models with LASSO regularization identified VAD and flux are one of the best OCTA parameters for predicting NAION.

Conclusion

Ischemic insult to the optic disk is more severe likely from primary degeneration of the affected peripapillary region while macula is affected by secondary retrograde degeneration and loss of retinal ganglion cells. In addition to OCT measurements, peripapillary and macular vascular parameters such as VAD and flux are good predictors of optic nerve and retinal changes in NAION.
Five-year outcomes of selective laser trabeculoplasty: A retrospective study
Authors: Swain David L. , Eliassi-Rad Babak
Published: January 2023

Introduction

Studies have shown the efficacy of selective laser trabeculoplasty (SLT) to lower intraocular pressure (IOP) as adjuvant therapy during short-term follow-up. However, few studies have assessed the long-term efficacy of SLT on preventing worsening Humphrey visual field (HVF) parameters and thinning of the retinal nerve fiber layer (RNFL) with continued medical therapy.

Methods

A retrospective chart review was conducted of 51 eyes of 39 patients with glaucoma treated with SLT at Boston Medical Center between 2012 and 2016 with 3- and 5-year follow-up. Outcome measures included IOP, visual acuity, number of glaucoma medications, number of months to subsequent surgical intervention. HVF outcome measures included mean deviation (MD) and pattern standard deviation (PSD). Optical coherence tomography (OCT) outcome measures included RNFL mean thickness, and superior and inferior thicknesses.

Results

Twenty-five eyes received subsequent surgical intervention (mean time to intervention = 33.6 ± 20.0 months). In the eyes that did not receive another intervention, mean IOP was significantly decreased by 3.2 and 3.5 mmHg at 3- and 5-year after SLT, respectively. Mean number of glaucoma medications was significantly increased at 5-year (2.7 ± 1.6; P = 0.04), compared to pre-SLT (2.0 ± 1.1). Mean HVF MD was significantly higher at 5-year (−7.64 ± 6.57 dB) compared to pre-SLT (−5.61 ± 3.90 dB). Mean PSD significantly increased at 3-year (5.30 ± 2.91 dB) and 5-year (6.84 ± 2.62 dB), compared to pre-SLT (4.63 ± 2.70 dB; P = 0.04 and ≤0.01, respectively). On OCT, inferior quadrant RNFL thickness decreased significantly at 5-year (88.5 ± 19.3 μm), compared to pre-SLT (94.0 ± 23.2 μm).

Discussion

Although 51% of eyes had IOP controlled at 5-year post-SLT, mean number of glaucoma medications was significantly higher. Also, there was progression of MD and PSD on HVF and inferior quadrant thinning on OCT at 5-year. We found a significant association between age at SLT and risk of subsequent surgical intervention over 5-year follow-up. Our study adds to our understanding of long-term outcomes of adjuvant SLT for glaucoma patients receiving medical therapy.
Mass cytometry and single-cell RNA sequencing reveal immune cell characteristics of active and inactive phases of Crohn’s disease
Authors: Lin Wenjia , Liu Shiying , Huang Zhuojian , Li Haiwen , Lu Tianyu , Luo Yongxin , Zhong Jiamin , Xu Zewen , Liu Yu , Li Yanwu , Li Peiwu , Xu Qian , Cai Jiazhong , Li Huibiao , Chen Xin-lin
Published: January 2023

Objectives

For Crohn’s disease (CD), the alternation of the active phase and inactive phase may be related to humoral immunity and cellular immunity. This study aims to understand the characteristics of immune cells in patients with active CD (CDa) and inactive CD (CDin).

Methods

Mass cytometry (CyTOF) and single-cell RNA sequencing (scRNA-seq) data about CDa, CDin, and healthy control (HC) were included. CyTOF analysis was performed to capture gated subsets, including T cells, T regulatory (Treg) cells, B cells, innate immune cells, and natural killer (NK) cells. Differential analysis was used to identify different immune cell subsets among CDa, CDin, and HC. ScRNA-seq analysis was used to verify the results of CyTOF. CD-related signaling pathways were obtained using KEGG pathway enrichment analysis. CellChat analysis was used to infer the cell communication network among immune cell subsets.

Results

Compared to patients with CDin, patients with CDa had higher abundances of CD16+CD38+CD4+CXCR3+CCR6+ naive T cells, HLA-DR+CD38+IFNγ+TNF+ effector memory (EM) T cells, HLA-DR+IFNγ+ naive B cells, and CD14++CD11C+IFNγ+IL1B+ monocytes. KEGG analysis showed the similarity of pathway enrichment for the earlier four subsets, such as thermogenesis, oxidative phosphorylation, and metabolic pathways. The patients with CDin were characterized by an increased number of CD16+CD56dimCD44+HLA-DR+IL22+ NK cells. Compared to HC, patients with CDa demonstrated a low abundance of HLA-DR+CCR6+ NK cells and a high abundance of FOXP3+CD44+ EM Tregs. CellChat analysis revealed the interaction network of cell subsets amplifying in CDa compared with CDin.

Conclusion

Some immune subsets cells were identified for CDa and CDin. These cells may be related to the occurrence and development of CD and may provide assistance in disease diagnosis and treatment.
Congenital perineal hamartomas with rectal duplication: A case report
Authors: Zhang Yixin , Zhang Mo , Ma Wei , Yuan Zhengwei , Wang Dajia , Chen Lizhu
Published: January 2023

Background

Congenital perineal hamartomas are rare, and reports of prenatal ultrasound diagnosis are limited. Perineal hamartomas are usually associated with other structural malformations, which complicate the therapeutic regime.

Case presentation

We report a case of perineal hamartomas associated with rectal duplication in a female fetus. A review of the literature on similar cases was also presented. A fetus was first diagnosed with a perineal mass at 33 weeks of gestation using ultrasound examination in our hospital. Two-dimensional ultrasonography showed a hyperechoic mass resembling a scrotum in the perineum of the fetus. The pedicle connected the mass to the fetal anus. The masses were excised after birth, and perineal hamartomas were confirmed by pathological diagnosis. Rectal duplication, an associated malformation, was found during the surgery. The rectal duplication cyst was removed at the same time.

Conclusion

Congenital perineal masses are rare and are usually associated with urogenital and anorectal malformations. Prenatal ultrasound should be used to assess the position and relationship between the mass and perineal organs, and to exclude other combined deformities.
Deep anterior lamellar keratoplasty following thermokeratoplasty assisted epikeratophkia: A novel two-stage one-graft method to treat acute corneal hydrops
Authors: Liu Chunyu , Huang Xinyu , Shen Jiaqi , Zhang Yushan , Zhang Li , Bi Yanlong
Published: January 2023

Purpose

To evaluate the clinical effects of deep anterior lamellar keratoplasty (DALK) using a single graft after thermokeratoplasty assisted epikeratophakia for the treatment of acute corneal hydrops.

Methods

This novel surgical procedure was performed on seven eyes of seven patients between 2019 and 2020. The procedure combines a first-stage surgery of thermokeratoplasty assisted epikeratophkia with intracameral sterile air injection and a second-stage surgery of DALK using the same corneal graft for both procedures. Main outcome measures included pre- and postoperative corrected distance visual acuity (CDVA) and anterior segment optical coherence tomography (AS-OCT) parameters. Corneal transparency, epithelization, and the presence of neovascularization, were evaluated at the 1-year follow-up visit.

Results

Corneal edema resolved rapidly in six of the seven cases. The mean central corneal thickness was significantly reduced from baseline to 1 day, 1 week, 1 month, and 2 months after the first-stage surgery (P < 0.0001). At a mean of 2.1 ± 0.7 months after the first-stage surgery, DALK was successfully performed in all cases. Six months later, the mean central corneal thickness was 611 ± 31 μm and the mean thickness of the recipient’s residual stroma bed was 20 ± 6 μm at the central corneal area. Mean LogMAR CDVA improved from 1.74 ± 0.34 at baseline to 0.20 ± 0.11 after DALK (P < 0.0001). No postoperative complications appeared in our case series during the 1-year observation period.

Conclusion

Very good visual results were obtained with a novel technique (thermokeratoplasty assisted epikeratophakia followed by DALK using the same corneal graft) in the treatment of acute corneal hydrops.
Development of rapid and precise approach for quantification of bacterial taxa correlated with soil health
Authors: Abdelmoneim Taghreed Khaled , Mohamed Mahmoud S. M. , Abdelhamid Ismail Abdelshafy , Wahdan Sara Fareed Mohamed , Atia Mohamed A. M.
Published: January 2023

The structure and dynamic of soil bacterial community play a crucial role in soil health and plant productivity. However, there is a gap in studying the un−/or reclaimed soil bacteriome and its impact on future plant performance. The 16S metagenomic analysis is expensive and utilize sophisticated pipelines, making it unfavorable for researchers. Here, we aim to perform (1) in silico and in vitro validation of taxon-specific qPCR primer-panel in the detection of the beneficial soil bacterial community, to ensure its specificity and precision, and (2) multidimensional analysis of three soils/locations in Egypt (‘Q’, ‘B’, and ‘G’ soils) in terms of their physicochemical properties, bacteriome composition, and wheat productivity as a model crop. The in silico results disclosed that almost all tested primers showed high specificity and precision toward the target taxa. Among 17 measured soil properties, the electrical conductivity (EC) value (up to 5 dS/m) of ‘Q’ soil provided an efficient indicator for soil health among the tested soils. The 16S NGS analysis showed that the soil bacteriome significantly drives future plant performance, especially the abundance of Proteobacteria and Actinobacteria as key indicators. The functional prediction analysis results disclosed a high percentage of N-fixing bacterial taxa in ‘Q’ soil compared to other soils, which reflects their positive impact on wheat productivity. The taxon-specific qPCR primer-panel results revealed a precise quantification of the targeted taxa compared to the 16S NGS analysis. Moreover, 12 agro-morphological parameters were determined for grown wheat plants, and their results showed a high yield in the ‘Q’ soil compared to other soils; this could be attributed to the increased abundance of Proteobacteria and Actinobacteria, high enrichment in nutrients (N and K), or increased EC/nutrient availability. Ultimately, the potential use of a taxon-specific qPCR primer-panel as an alternative approach to NGS provides a cheaper, user-friendly setup with high accuracy.
Microbiome analysis of raw honey reveals important factors influencing the bacterial and fungal communities
Authors: Xiong Zirui Ray , Sogin Jonathan H. , Worobo Randy W.
Published: January 2023

Raw honeys contain diverse microbial communities. Previous studies have focused on isolating bacteria and fungi that are culturable, while missing a large proportion of the microbial community due to culture-based constraints. This study utilized next-generation sequencing (NGS) to analyze the composition of microorganisms in raw honey; these data can reveal environmental and physicochemical variables that are associated with different microbial communities. To examine the microbial composition (bacteria and fungi) of raw honey and analyze its association with physicochemical properties, four types of honey (monofloral, wildflower, manuka, and feral; ntotal = 36) were analyzed via amplicon metagenomics. The analyzed honey samples had relatively similar bacterial communities but more distinct and diverse fungal communities. Honey type was determined as a significant factor influencing alpha and beta diversity metrics of bacterial and fungal communities. For the bacterial communities, titratable acidity (TA) was associated with community richness and diversity. For the fungal communities, Brix, TA, and color were associated with community richness, while water activity and color were associated with community diversity. Additionally, important bacterial and fungal amplicon sequence variants (ASVs) that influenced the overall community were identified. Results from this study provide important insights into the microbial communities associated with different types of raw honey, which could improve our understanding of microbial dynamics in beehives, improve honey production, and prevent honeybee disease.
Butyrate producers, “The Sentinel of Gut”: Their intestinal significance with and beyond butyrate, and prospective use as microbial therapeutics
Authors: Singh Vineet , Lee GyuDae , Son HyunWoo , Koh Hong , Kim Eun Soo , Unno Tatsuya , Shin Jae-Ho
Published: January 2023

Gut-microbial butyrate is a short-chain fatty acid (SCFA) of significant physiological importance than the other major SCFAs (acetate and propionate). Most butyrate producers belong to the Clostridium cluster of the phylum Firmicutes, such as Faecalibacterium, Roseburia, Eubacterium, Anaerostipes, Coprococcus, Subdoligranulum, and Anaerobutyricum. They metabolize carbohydrates via the butyryl-CoA: acetate CoA-transferase pathway and butyrate kinase terminal enzymes to produce most of butyrate. Although, in minor fractions, amino acids can also be utilized to generate butyrate via glutamate and lysine pathways. Butyrogenic microbes play a vital role in various gut-associated metabolisms. Butyrate is used by colonocytes to generate energy, stabilizes hypoxia-inducible factor to maintain the anaerobic environment in the gut, maintains gut barrier integrity by regulating Claudin-1 and synaptopodin expression, limits pro-inflammatory cytokines (IL-6, IL-12), and inhibits oncogenic pathways (Akt/ERK, Wnt, and TGF-β signaling). Colonic butyrate producers shape the gut microbial community by secreting various anti-microbial substances, such as cathelicidins, reuterin, and β-defensin-1, and maintain gut homeostasis by releasing anti-inflammatory molecules, such as IgA, vitamin B, and microbial anti-inflammatory molecules. Additionally, butyrate producers, such as Roseburia, produce anti-carcinogenic metabolites, such as shikimic acid and a precursor of conjugated linoleic acid. In this review, we summarized the significance of butyrate, critically examined the role and relevance of butyrate producers, and contextualized their importance as microbial therapeutics.
Molecular mechanism of LIP05 derived from Monascus purpureus YJX-8 for synthesizing fatty acid ethyl esters under aqueous phase
Authors: Zhao Jingrong , Xu Youqiang , Lu Hongyun , Zhao Dong , Zheng Jia , Lin Mengwei , Liang Xin , Ding Ze , Dong Wenqi , Yang Maochen , Li Weiwei , Zhang Chengnan , Sun Baoguo , Li Xiuting
Published: January 2023

Fatty acid ethyl esters are important flavor chemicals in strong-flavor Baijiu. Monascus purpureus YJX-8 is recognized as an important microorganism for ester synthesis in the fermentation process. Enzyme LIP05 from YJX-8 can efficiently catalyze the synthesis of fatty acid ethyl esters under aqueous phase, but the key catalytic sites affecting esterification were unclear. The present work combined homology modeling, molecular dynamics simulation, molecular docking and site-directed mutation to analyze the catalytic mechanism of LIP05. Protein structure modeling indicated LIP05 belonged to α/β fold hydrolase, contained a lid domain and a core catalytic pocket with conserved catalytic triad Ser150-His215-Asp202, and the oxyanion hole composed of Gly73 and Thr74. Ile30 and Leu37 of the lid domain were found to affect substrate specificity. The π-bond stacking between Tyr116 and Tyr149 played an important role in stabilizing the catalytic active center of LIP05. Tyr116 and Ile204 determined the substrate spectrum by composing the substrate-entrance channel. Residues Leu83, Ile204, Ile211 and Leu216 were involved in forming the hydrophobic substrate-binding pocket through steric hindrance and hydrophobic interaction. The catalytic mechanism for esterification in aqueous phase of LIP05 was proposed and provided a reference for clarifying the synthesis of fatty acid ethyl esters during the fermentation process of strong-flavor Baijiu.
Recent applications of computational methods to allosteric drug discovery
Authors: Govindaraj Rajiv Gandhi , Thangapandian Sundar , Schauperl Michael , Denny Rajiah Aldrin , Diller David J.
Published: January 2023

Interest in exploiting allosteric sites for the development of new therapeutics has grown considerably over the last two decades. The chief driving force behind the interest in allostery for drug discovery stems from the fact that in comparison to orthosteric sites, allosteric sites are less conserved across a protein family, thereby offering greater opportunity for selectivity and ultimately tolerability. While there is significant overlap between structure-based drug design for orthosteric and allosteric sites, allosteric sites offer additional challenges mostly involving the need to better understand protein flexibility and its relationship to protein function. Here we examine the extent to which structure-based drug design is impacting allosteric drug design by highlighting several targets across a variety of target classes.
RNA polymerase III transcription and cancer: A tale of two RPC7 subunits
Authors: Cheng Ruiying , Van Bortle Kevin
Published: January 2023

RNA polymerase III composition is shaped by the mutually exclusive incorporation of two paralogous subunits, RPC7α and RPC7β, encoded by genes POLR3G and POLR3GL in vertebrates. The expression of POLR3G and POLR3GL is spatiotemporally regulated during development, and multiple reports point to RPC7α-enhanced Pol III activity patterns, indicating that Pol III identity may underly dynamic Pol III transcription patterns observed in higher eukaryotes. In cancer, upregulation of POLR3G, but not POLR3GL, is associated with poor survival outcomes among patients, suggesting differences between RPC7α and RPC7β further influence disease progression and may translate into future biomarkers and therapeutic strategies. Here, we outline our current understanding of Pol III identity and transcription and reexamine the distinct protein characteristics of Pol III subunits RPC7α and RPC7β. Drawing on both structural and genomic studies, we discuss differences between RPC7α and RPC7β and the potential mechanisms by which Pol III identity may establish differential activities during development and disease.
Transcription factor Ap2b regulates the mouse autosomal recessive polycystic kidney disease genes, Pkhd1 and Cys1
Authors: Wu Maoqing , Harafuji Naoe , O’Connor Amber K. , Caldovic Ljubica , Guay-Woodford Lisa M.
Published: January 2023

Transcription factor Ap2b (TFAP2B), an AP-2 family transcription factor, binds to the palindromic consensus DNA sequence, 5′-GCCN3-5GGC-3’. Mice lacking functional Tfap2b gene die in the perinatal or neonatal period with cystic dilatation of the kidney distal tubules and collecting ducts, a phenotype resembling autosomal recessive polycystic kidney disease (ARPKD). Human ARPKD is caused by mutations in PKHD1, DZIP1L, and CYS1, which are conserved in mammals. In this study, we examined the potential role of TFAP2B as a common regulator of Pkhd1 and Cys1. We determined the transcription start site (TSS) of Cys1 using 5′ Rapid Amplification of cDNA Ends (5′RACE); the TSS of Pkhd1 has been previously established. Bioinformatic approaches identified cis-regulatory elements, including two TFAP2B consensus binding sites, in the upstream regulatory regions of both Pkhd1 and Cys1. Based on reporter gene assays performed in mouse renal collecting duct cells (mIMCD-3), TFAP2B activated the Pkhd1 and Cys1 promoters and electromobility shift assay (EMSA) confirmed TFAP2B binding to the in silico identified sites. These results suggest that Tfap2b participates in a renal epithelial cell gene regulatory network that includes Pkhd1 and Cys1. Disruption of this network impairs renal tubular differentiation, causing ductal dilatation that is the hallmark of recessive PKD.
Smith-Lemli-Opitz syndrome: A pathophysiological manifestation of the Bloch hypothesis
Authors: Chattopadhyay Amitabha , Sharma Ashwani
Published: January 2023

The biosynthesis of cholesterol, an essential component of higher eukaryotic membranes, was worked out by Konrad Bloch (and Feodor Lynen) in the 1960s and they received the Nobel Prize around that time in recognition of their pioneering contributions. An elegant consequence of this was a hypothesis proposed by Konrad Bloch (the Bloch hypothesis) which suggests that each subsequent intermediate in the cholesterol biosynthesis pathway is superior in supporting membrane function in higher eukaryotes relative to its precursor. In this review, we discuss an autosomal recessive metabolic disorder, known as Smith-Lemli-Opitz syndrome (SLOS), associated with a defect in the Kandutsch-Russell pathway of cholesterol biosynthesis that results in accumulation of the immediate precursor of cholesterol in its biosynthetic pathway (7-dehydrocholesterol) and an altered cholesterol to total sterol ratio. Patients suffering from SLOS have several developmental, behavioral and cognitive abnormalities for which no drug is available yet. We characterize SLOS as a manifestation of the Bloch hypothesis and review its molecular etiology and current treatment. We further discuss defective Hedgehog signaling in SLOS and focus on the role of the serotonin1A receptor, a representative neurotransmitter receptor belonging to the GPCR family, in SLOS. Notably, ligand binding activity and cellular signaling of serotonin1A receptors are impaired in SLOS-like condition. Importantly, cellular localization and intracellular trafficking of the serotonin1A receptor (which constitute an important determinant of a GPCR cellular function) are compromised in SLOS. We highlight some of the recent developments and emerging concepts in SLOS pathobiology and suggest that novel therapies based on trafficking defects of target receptors could provide new insight into treatment of SLOS.
Standardization and normative data of the 48-item Yoni short version for the assessment of theory of mind in typical and atypical conditions
Authors: Isernia Sara , Rossetto Federica , Shamay-Tsoory Simone , Marchetti Antonella , Baglio Francesca
Published: January 2023

Introduction

The Yoni task is a computerized tool assessing first-and second-order affective and cognitive Theory of Mind (ToM), accounting for the multidimensional and multi-level mentalizing features. The Italian Yoni task has been validated and standardized in its 98-item version, and a 48-item short version has been proposed for a quick digital evaluation of ToM in clinical contexts.

Methods

The present study aimed to test the Yoni-48’s convergent validity, correlating the tool score with the Reading the Mind in the Eyes test (ET) and Gender Test (GT), its items discrimination ability through the Classical Test Theory, and Rash model, its reliability by evaluating the internal consistency (McDonald’s ω, Cronbach’s α, Guttman’s λ2, and Guttman’s λ6) and Spearman-Brown ϱSP split-half analysis, and to provide standardization and normative data in the Italian population.

Results

Results suggested a good convergent validity with a statistically significant association with ET (p < 0.001), while a null correlation was observed with GT (p = 0.947). The Classical Test Theory and Rash model confirmed a good discrimination ability of the Yoni-48’s second-order affective and cognitive ToM items, while weaker discrimination capacity was registered for the first-order ToM items. The inter-item reliability was optimal for clinical purposes (ω, α, λ2, λ6 ≥ 0.90). Also, the split-half reliability was high (Spearman-Brown ϱSP = 0.90). For standardization, age and education were revealed as significant predictors of Yoni accuracy scores, except for the first-order ToM score. Instead, age was the only predictor of Yoni’s response speed score. The Italian normative data showed a high Yoni accuracy in healthy adults (mean accuracy = 0.85) and speed (mean response time = 0.92). Finally, both accuracy and response time level was balanced between the affective and cognitive components of ToM.

Discussion

This study supports the psychometric properties of the Yoni-48 and provides normative data for the Italian population. Further studies are needed to test the suitability of this short version for profiling the social cognition neurocognitive phenotype.
Hippocampal functional connectivity across age in an App knock-in mouse model of Alzheimer's disease
Authors: Morrissey Zachery D. , Gao Jin , Zhan Liang , Li Weiguo , Fortel Igor , Saido Takaomi , Saito Takashi , Bakker Arnold , Mackin Scott , Ajilore Olusola , Lazarov Orly , Leow Alex D.
Published: January 2023

Introduction

Alzheimer's disease (AD) is a progressive neurodegenerative disease. The early processes of AD, however, are not fully understood and likely begin years before symptoms manifest. Importantly, disruption of the default mode network, including the hippocampus, has been implicated in AD.

Methods

To examine the role of functional network connectivity changes in the early stages of AD, we performed resting-state functional magnetic resonance imaging (rs-fMRI) using a mouse model harboring three familial AD mutations (AppNL-G-F/NL-G-F knock-in, APPKI) in female mice in early, middle, and late age groups. The interhemispheric and intrahemispheric functional connectivity (FC) of the hippocampus was modeled across age.

Results

We observed higher interhemispheric functional connectivity (FC) in the hippocampus across age. This was reduced, however, in APPKI mice in later age. Further, we observed loss of hemispheric asymmetry in FC in APPKI mice.

Discussion

Together, this suggests that there are early changes in hippocampal FC prior to heavy onset of amyloid β plaques, and which may be clinically relevant as an early biomarker of AD.
Machine Learning Reveals a Multipredictor Nomogram for Diagnosing the Alzheimer’s Disease Based on Chemiluminescence Immunoassay for Total Tau in Plasma
Authors: Zhang Lingyu , Wang Danhua , Dai Yibei , Wang Xuchu , Cao Ying , Liu Weiwei , Tao Zhihua
Published: January 2023

Background

Predicting amnestic mild cognitive impairment (aMCI) in conversion and Alzheimer’s disease (AD) remains a daunting task. Standard diagnostic procedures for AD population are reliant on neuroimaging features (positron emission tomography, PET), cerebrospinal fluid (CSF) biomarkers (Aβ1-42, T-tau, P-tau), which are expensive or require invasive sampling. The blood-based biomarkers offer the opportunity to provide an alternative approach for easy diagnosis of AD, which would be a less invasive and cost-effective screening tool than currently approved CSF or amyloid β positron emission tomography (PET) biomarkers.

Methods

We developed and validated a sensitive and selective immunoassay for total Tau in plasma. Robust signatures were obtained based on several clinical features selected by multiple machine learning algorithms between the three participant groups. Subsequently, a well-fitted nomogram was constructed and validated, integrating clinical factors and total Tau concentration. The predictive performance was evaluated according to the receiver operating characteristic (ROC) curves and area under the curve (AUC) statistics. Decision curve analysis and calibration curves are used to evaluate the net benefit of nomograms in clinical decision-making.

Results

Under optimum conditions, chemiluminescence analysis (CLIA) displays a desirable dynamic range within Tau concentration from 7.80 to 250 pg/mL with readily achieved higher performances (LOD: 5.16 pg/mL). In the discovery cohort, the discrimination between the three well-defined participant groups according to Tau concentration was in consistent agreement with clinical diagnosis (AD vs. non-MCI: AUC = 0.799; aMCI vs. non-MCI: AUC = 0.691; AD vs. aMCI: AUC = 0.670). Multiple machine learning algorithms identified Age, Gender, EMPG, Tau, ALB, HCY, VB12, and/or Glu as robust signatures. A nomogram integrated total Tau concentration and clinical factors provided better predictive performance (AD vs. non-MCI: AUC = 0.960, AD vs. aMCI: AUC = 0.813 in discovery cohort; AD vs. non-MCI: AUC = 0.938, AD vs. aMCI: AUC = 0.754 in validation cohort).

Conclusion

The developed assay and a satisfactory nomogram model hold promising clinical potential for early diagnosis of aMCI and AD participants.