bluuebunny/crossref_metadata_2025 huggingface dataset:
Characteristics of Mycobacterium tuberculosis PtpA interaction and activity on the alpha subunit of human mitochondrial trifunctional protein, a key enzyme of lipid metabolism
Authors: Margenat Mariana , Betancour Gabriela , Irving Vivian , Costábile Alicia , García-Cedrés Tania , Portela María Magdalena , Carrión Federico , Herrera Fernando E. , Villarino Andrea
Published: June 2023

During Mycobacterium tuberculosis (Mtb) infection, the virulence factor PtpA belonging to the protein tyrosine phosphatase family is delivered into the cytosol of the macrophage. PtpA interacts with numerous eukaryotic proteins modulating phagosome maturation, innate immune response, apoptosis, and potentially host-lipid metabolism, as previously reported by our group. In vitro, the human trifunctional protein enzyme (hTFP) is a bona fide PtpA substrate, a key enzyme of mitochondrial β-oxidation of long-chain fatty acids, containing two alpha and two beta subunits arranged in a tetramer structure. Interestingly, it has been described that the alpha subunit of hTFP (ECHA, hTFPα) is no longer detected in mitochondria during macrophage infection with the virulent Mtb H37Rv. To better understand if PtpA could be the bacterial factor responsible for this effect, in the present work, we studied in-depth the PtpA activity and interaction with hTFPα. With this aim, we performed docking and in vitro dephosphorylation assays defining the P-Tyr-271 as the potential target of mycobacterial PtpA, a residue located in the helix-10 of hTFPα, previously described as relevant for its mitochondrial membrane localization and activity. Phylogenetic analysis showed that Tyr-271 is absent in TFPα of bacteria and is present in more complex eukaryotic organisms. These results suggest that this residue is a specific PtpA target, and its phosphorylation state is a way of regulating its subcellular localization. We also showed that phosphorylation of Tyr-271 can be catalyzed by Jak kinase. In addition, we found by molecular dynamics that PtpA and hTFPα form a stable protein complex through the PtpA active site, and we determined the dissociation equilibrium constant. Finally, a detailed study of PtpA interaction with ubiquitin, a reported PtpA activator, showed that additional factors are required to explain a ubiquitin-mediated activation of PtpA. Altogether, our results provide further evidence supporting that PtpA could be the bacterial factor that dephosphorylates hTFPα during infection, potentially affecting its mitochondrial localization or β-oxidation activity.
Stability analysis of tunnel in sandy cobble strata under different pre-reinforcement techniques
Authors: Li Xiaobin , Zhao Ying , Xue Haifang , Zhang Lei , Gong Xiaoqin
Published: June 2023

Excavating tunnels in sandy cobble strata carries a high risk of ground collapse caused by instability of the tunnel face. In order to prevent instability at the tunnel face during excavation, this paper focuses on studying the effects of various pre-reinforcement method on the stability of tunnel in the sand-cobble strata. Firstly, pre-reinforcement projects suitable for these tunnels are proposed. Then, using FLAC3D to established numerical models, then simulate the excavation process under six different working conditions: non-reinforced, pre-reinforcement with advance small pipes, pre-reinforcement with pipe-roof, pre-reinforcement with GFRP bolts, pre-reinforcement with advance small pipes and GFRP bolts, and pre-reinforcement with pipe-roof and GFRP blots. The displacement and stress fields of the soil behind and in front of the tunnel face under each condition are obtained. The results show that the use of GFRP bolts for pre-reinforcement can effectively control the deformation of the surrounding rock in front and behind the tunnel face, and pre-reinforcement with advance small pipes or pipe-roof can reduce the settlement of the tunnel crown. Pre-reinforcement by the combination of GFRP bolts with advance small pipes or pipe-roof can better ensure the stability of the tunnel during the excavation process.
Association between remnant cholesterol and chronic kidney disease in Chinese hypertensive patients
Authors: Yuan Ting , Ding Congcong , Xie Yanyou , Zhou Xinlei , Xie Chong , Wang Tao , Yu Chao , Zhou Wei , Zhu Lingjuan , Bao Huihui , Cheng Xiaoshu
Published: June 2023

Background

Remnant cholesterol (RC) and chronic kidney disease (CKD) have not been definitively linked in individuals with different characteristics. This study aims to investigate the relationship between serum RC level and CKD and examine possible effect modifiers in Chinese patients with hypertension.

Methods

Our study is based on the Chinese H-type Hypertension Project, which is an observational registry study conducted in real-world settings. The outcome was CKD, defined as an estimated glomerular filtration rate of less than 60 ml/min·1.73 m2. Multivariate logistic regression and smooth curve fitting were used to analyze the association between RC and CKD. Subgroup analyses were subsequently conducted to examine the effects of other variables.

Results

The mean age of the 13,024 patients with hypertension at baseline was 63.8 ± 9.4 years, and 46.8% were male. A conspicuous linear positive association was observed between RC level and CKD (per SD increment; odds ratio [OR], 1.15; 95% confidence interval [CI], 1.08–1.23). Compared with the lowest quartile group of RC, the risk of CKD was 53% higher (OR, 1.53; 95% CI, 1.26–1.86) in the highest quartile group. Furthermore, a stronger positive association between RC level and CKD was found among participants with a higher body mass index (BMI <24 vs. ≥24 kg/m2; P-interaction = 0.034) or current non-smokers (smoker vs. non-smoker; P-interaction = 0.024).

Conclusions

Among Chinese adults with hypertension, RC level was positively associated with CKD, particularly in those with a BMI of ≥24 kg/m2 and current non-smokers. These findings may help improve lipid management regimens in patients with hypertension.
Correlation between hearing impairment and the Triglyceride Glucose Index: based on a national cross-sectional study
Authors: Liu Long , Qin Maolin , Ji Jiabiao , Wang Weiqing
Published: June 2023

Objective

Data from the National Health and Nutrition Examination Survey (NHANES) were used to assess the association between the triglyceride-glucose (TyG) index and hearing impairment (HI).

Methods

We used eight survey cycles from NHANES 2001–2012 and 2015–2018 to conduct this cross-sectional study. HI was designed as an dependent variable, and the TyG index was selected as an exposure factor (independent variable). The correlation between the two variables was assessed using multiple logistic regression. In order to assess whether there was a non-linear relationship between the TyG index and HI, the TyG index was distributed and a test for trend was conducted (P for trend), followed by smooth curve fitting (penalized spline) and generalized additive model (GAM) regression. We also performed a subgroup analysis to identify sensitive groups whose responses were clearly associated with independent variables.

Results

10,906 participants were finally included in the study, and those with a higher TyG index had a higher frequency of hearing impairment. There was a linear positive correlation between the TyG index and HI. For the low-frequency HI, however, this positive correlation was not statistically significant (OR = 1.05, 95% CI: 0.98, 1.14); however, it was more stable for the high-frequency HI (OR = 1.12, 95% CI: 1.03, 1.22). Additionally, as the TyG index increased, this positive association increased as well (P for trend = 0.05). The HPTA test showed a positive association with more severe HI (simultaneous) as the independent variable increased (OR = 1.14, 95% CI: 1.05–1.24), and this association was even more significant with increasing severity (P for trend 0.05). According to the subgroup analysis, the positive association between TyG index and high-frequency HI was more significant in females, 40–69 years old, without hypertension or diabetes, and when strict high-frequency HI was significant in males, females, 40–69 years old, with hypertension and diabetes.

Conclusion

Participants with a higher TyG index may have a higher risk of HI. TyG index and HI risk showed a linear relationship, which became even more significant when HPTA was included.
Lean nonalcoholic fatty liver disease and sarcopenia
Authors: Chen Milian , Cao Ying , Ji Guang , Zhang Li
Published: June 2023

Nonalcoholic fatty liver disease (NAFLD) has become one of the most common chronic liver diseases in the world. The risk factor for NAFLD is often considered to be obesity, but it can also occur in people with lean type, which is defined as lean NAFLD. Lean NAFLD is commonly associated with sarcopenia, a progressive loss of muscle quantity and quality. The pathological features of lean NAFLD such as visceral obesity, insulin resistance, and metabolic inflammation are inducers of sarcopenia, whereas loss of muscle mass and function further exacerbates ectopic fat accumulation and lean NAFLD. Therefore, we discussed the association of sarcopenia and lean NAFLD, summarized the underlying pathological mechanisms, and proposed potential strategies to reduce the risks of lean NAFLD and sarcopenia in this review.
Assessing the viability of a grid-connected PV power plant in Mubi, Adamawa State, Nigeria
Authors: Luqman Raji , Kehinde Issa Abdul-Jeleel , Owolabi Abdulhameed Babatunde , Yakub Abdulfatai Olatunji , Same Noel Ngando , Yahaya Abdullahi , Yasin Naveed , Kavgic Miroslava , Suh Dongjun , Huh Jeung-Soo
Published: June 2023

This paper is based on a techno-economic analysis and the environmental impact of a proposed 1 MW solar photovoltaic (PV) power plant at the main campus of the Federal Polytechnic Mubi (FPM) in north-eastern Nigeria. A photovoltaic power plant converts solar radiation into electricity that can be used as a source of electrical power to meet the daily energy requirements of homes, equipment, and all tertiary institutions. RETScreen Expert software was used to evaluate the techno-economic and environmental sustainability of installing a grid-connected PV power plant. The research results revealed that with an annual solar radiation of 5.74 kWh/m2/day, the maximum annual energy production was estimated to be 1,550.98 MWh. It was discovered that the maximum energy production in March was 146.89 MWh. The project’s profitability and economic sustainability were determined with a good internal rate of return (IRR) of 11.9% and a positive net present value (NPV) of $681,164. The proposed PV power plant has a simple payback period of 11.4 years. The maximum greenhouse gas (GHG) emission reduction is 670.9 tCO2, equivalent to 61.7 ha of forest-absorbing carbon emissions.
A comparison among bio-derived acids as selective eco-friendly leaching agents for cobalt: the case study of hard-metal waste enhancement
Authors: Oumarou Amadou Amadou , Cera Martina , Trudu Stefano , Piredda Martina , Cara Stefano , De Gaudenzi Gian Pietro , Matharu Avtar Singh , Marchiò Luciano , Tegoni Matteo , Muntoni Aldo , De Gioannis Giorgia , Serpe Angela
Published: June 2023

Peculiar chemical, mechanical, and magnetic properties make cobalt a key metal for a variety of “hot” applications like the cathode production of Li-ion batteries. Cobalt is also the preferred metallic binder for tungsten carbide tool manufacturing. The recent increasing criticality of cobalt and tungsten is driving the interest of manufacturers and researchers toward high-rate recycling of hard-metal (HM) waste for limiting the demand for raw materials. A simple and environmentally friendly hydrometallurgical route for Co-selective dissolution from HM wastes was developed by using weak, bio-derived, and biodegradable organic acids (OAs). In this study, OAs, namely, acetic (HAc), citric (H3Cit), maleic (H2Mal), lactic (HLac), succinic (H2Suc), lactobionic (HLB), and itaconic (H2It) acids, were selected for their pKa1 values spanning from 1.8 to 4.7 and systematically tested as selective cobalt leaching agents from WC-Co-based wastes in water, isolating the formed complexes in the solid state. Thereby, all of them seemed to be efficient in selective Co leaching, achieving almost quantitative Co dissolution from HM by-products still at low concentration levels and room conditions in a short time, leaving the residual WC unreacted and ready to be re-employed for industrial purposes. Nevertheless, two main categories of organic acids were distinguished depending on their oxidizing/complexing behavior: class 1 OAs, where the metal oxidation is carried out by H+, and class 2 OAs, where oxidation is carried out by an external oxidant like O2. A combined experimental/theoretical investigation is described here to show the reasons behind this peculiar behavior and lay the foundation for a wider discussion on the leaching capabilities of OAs toward elemental metals. Due to the demonstrated effectiveness, low cost, eco-friendliness, and large availability through biotechnological fermentative processes, particular attention is devoted here to the use of HLac in hydrometallurgy as an example of class 2 OA. WC-Co materials recovered by HLac mild hydrometallurgy demonstrated a metallurgical quality suitable for re-employment in the HM manufacturing process.
Key driver of textile and apparel industry management: fashion brand ESG and brand reputation
Authors: Yu Heeseung , Ahn Minhwan , Han Eunkyoung
Published: June 2023

The aim of this study was to develop and validate multidimensional criteria that can be used to evaluate fashion brand ESG management. This research used both qualitative and quantitative research methods to derive multi-dimensional and wide-ranging questions that could help explain fashion brand ESG with a high level of detail. A Delphi study was conducted with a group of 30 professionals to derive the initial items for fashion brand ESG management, and these items were used to design a questionnaire that was then administered to 800 consumers. Based on the results of exploratory and confirmatory factor analysis, 13 items were used to construct the scale. Convergent and discriminant validity were also verified between the factors. Finally, it was confirmed that the items on the ESG practices scale significantly affected a fashion brand’s reputation and consumer intention to purchase that brand as mediated by reputation. The results of this research are expected to provide a theoretical framework for future ESG research that can help fashion brands achieve more effective ESG management and increase their reputation and sales.
Soil texture analysis by laser diffraction and sedimentation and sieving–method and instrument comparison with a focus on Nordic and Baltic forest soils
Authors: Callesen Ingeborg , Palviainen Marjo , Armolaitis Kęstutis , Rasmussen Charlotte , Kjønaas O. Janne
Published: June 2023

Purpose

Laser diffraction (LD) for determination of particle size distribution (PSD) of the fine earth fraction appeared in the 1990s, partly substituting the Sieving and Sedimentation Method (SSM). Whereas previous comparison between the two methods predominantly encompasses agricultural soils, less attention has been given to forest soils, including pre-treatment requirements related to their highly variable contents of carbon and Alox+ Feox. In this small collaborative learning study we compared (1) national SSM results with one type/protocol of LD analysis (Coulter), (2) LD measurements performed on three different LD instruments / laboratories, and (3) the replication error for LD Coulter analysis of predominantly sandy and loamy forest soils.

Methods

We used forest soil samples from Denmark, Norway and Lithuania and their respective national SSM protocols / results. LD analyses were performed on Malvern Mastersizer 2000, Sympatec HELOS version 1999, and Coulter LS230, located at University of Copenhagen, Aarhus University and Helsinki University, respectively. The protocols differed between laboratories, including the use of external ultrasonication prior to LD analysis.

Results

The clay and silt fractions content (<20 μm) from the LD analysis were not comparable with SSM results, with differences ranging from −0.5 to 22.3 percentage points (pp) for clay. Preliminary results from loamy samples with spodic material suggested inconsistent effects of external ultrasonication to disperse aggregates. The comparison between the three LD instruments showed a range in the clay and silt fractions content of 1.9–5.3 and 6.2–8.1 pp, respectively. Differences may be related to the instruments, protocols, and content of a given particle size fraction. The replication error of the Coulter LD protocol was found to be <3 pp in sandy soils, but up to 10 pp in loamy soils.

Conclusion

Differences in the clay fraction results partly affected the classification of soil types. The fast replication of the LD analysis enables more quality control of results. The pedological evaluation of non-silicate constituents and optional pre-treatment steps (e.g., soil organic matter or sesquioxides) remains the same for LD and SSM. For comparison of results, detailed descriptions of the analytical protocol including pre-treatments are needed irrespective of instrument and theoretical approach.
Case report: Extending the spectrum of clinical and molecular findings in FOXC1 haploinsufficiency syndrome
Authors: Garza Flores Alexandra , Nordgren Ida , Pettersson Maria , Dias-Santagata Dora , Nilsson Daniel , Hammarsjö Anna , Lindstrand Anna , Batkovskyte Dominyka , Wiggs Janey , Walton David S. , Goldenberg Paula , Eisfeldt Jesper , Lin Angela E. , Lachman Ralph S. , Nishimura Gen , Grigelioniene Giedre
Published: June 2023

FOXC1 is a ubiquitously expressed forkhead transcription factor that plays a critical role during early development. Germline pathogenic variants in FOXC1 are associated with anterior segment dysgenesis and Axenfeld-Rieger syndrome (ARS, #602482), an autosomal dominant condition with ophthalmologic anterior segment abnormalities, high risk for glaucoma and extraocular findings including distinctive facial features, as well as dental, skeletal, audiologic, and cardiac anomalies. De Hauwere syndrome is an ultrarare condition previously associated with 6p microdeletions and characterized by anterior segment dysgenesis, joint instability, short stature, hydrocephalus, and skeletal abnormalities. Here, we report clinical findings of two unrelated adult females with FOXC1 haploinsufficiency who have ARS and skeletal abnormalities. Final molecular diagnoses of both patients were achieved using genome sequencing. Patient 1 had a complex rearrangement involving a 4.9 kB deletion including FOXC1 coding region (Hg19; chr6:1,609,721-1,614,709), as well as a 7 MB inversion (Hg19; chr6:1,614,710-8,676,899) and a second deletion of 7.1 kb (Hg19; chr6:8,676,900-8,684,071). Patient 2 had a heterozygous single nucleotide deletion, resulting in a frameshift and a premature stop codon in FOXC1 (NM_001453.3): c.467del, p.(Pro156Argfs*25). Both individuals had moderate short stature, skeletal abnormalities, anterior segment dysgenesis, glaucoma, joint laxity, pes planovalgus, dental anomalies, hydrocephalus, distinctive facial features, and normal intelligence. Skeletal surveys revealed dolichospondyly, epiphyseal hypoplasia of femoral and humeral heads, dolichocephaly with frontal bossin gand gracile long bones. We conclude that haploinsufficiency of FOXC1 causes ARS and a broad spectrum of symptoms with variable expressivity that at its most severe end also includes a phenotype overlapping with De Hauwere syndrome.
Variational inference for detecting differential translation in ribosome profiling studies
Authors: Walker David C. , Lozier Zachary R. , Bi Ran , Kanodia Pulkit , Miller W. Allen , Liu Peng
Published: June 2023

Translational efficiency change is an important mechanism for regulating protein synthesis. Experiments with paired ribosome profiling (Ribo-seq) and mRNA-sequencing (RNA-seq) allow the study of translational efficiency by simultaneously quantifying the abundances of total transcripts and those that are being actively translated. Existing methods for Ribo-seq data analysis either ignore the pairing structure in the experimental design or treat the paired samples as fixed effects instead of random effects. To address these issues, we propose a hierarchical Bayesian generalized linear mixed effects model which incorporates a random effect for the paired samples according to the experimental design. We provide an analytical software tool, “riboVI,” that uses a novel variational Bayesian algorithm to fit our model in an efficient way. Simulation studies demonstrate that “riboVI” outperforms existing methods in terms of both ranking differentially translated genes and controlling false discovery rate. We also analyzed data from a real ribosome profiling experiment, which provided new biological insight into virus-host interactions by revealing changes in hormone signaling and regulation of signal transduction not detected by other Ribo-seq data analysis tools.
New techniques: a roadmap for the development of HCC immunotherapy
Authors: Jiang Dizhi , Ma Xinyue , Zhang Xun , Cheng Bo , Wang Ruiqing , Liu Yuan , Zhang Xinyu
Published: June 2023

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. The absence of effective early diagnostic methods and the limitations of conventional therapies have led to a growing interest in immunotherapy as a novel treatment approach for HCC. The liver serves as an immune organ and a recipient of antigens from the digestive tract, creating a distinctive immune microenvironment. Key immune cells, including Kupffer cells and cytotoxic T lymphocytes, play a crucial role in HCC development, thus offering ample research opportunities for HCC immunotherapy. The emergence of advanced technologies such as clustered regularly interspaced short palindromic repeats (CRISPR) and single-cell ribonucleic acid sequencing has introduced new biomarkers and therapeutic targets, facilitating early diagnosis and treatment of HCC. These advancements have not only propelled the progress of HCC immunotherapy based on existing studies but have also generated new ideas for clinical research on HCC therapy. Furthermore, this review analysed and summarised the combination of current therapies for HCC and the improvement of CRISPR technology for chimeric antigen receptor T cell therapy, instilling renewed hope for HCC treatment. This review comprehensively explores the advancements in immunotherapy for HCC, focusing on the use of new techniques.
Toxoplasma gondii gra5 deletion mutant protects hosts against Toxoplasma gondii infection and breast tumors
Authors: Chen Min , Yang Pei , Xin Zixuan , Chen Jiating , Zou Weihao , Zhou Lijuan , Yang Lili , Peng Jiao , Peng Hongjuan
Published: June 2023

Toxoplasma gondii is the causative agent of toxoplasmosis, a zoonotic disease that poses a threat to human health and a considerable loss to livestock farming. At present, clinical therapeutic drugs mainly target T. gondii tachyzoites and fail to eradicate bradyzoites. Developing a safe and effective vaccine against toxoplasmosis is urgent and important. Breast cancer has become a major public health problem and the therapeutic method needs to be further explored. Many similarities exist between the immune responses caused by T. gondii infection and the immunotherapy for cancers. T. gondii dense granule organelles secrete immunogenic dense granule proteins (GRAs). GRA5 is localized to the parasitophorous vacuole membrane in the tachyzoite stage and the cyst wall in the bradyzoite stage. We found that T. gondii ME49 gra5 knockout strain (ME49Δgra5) was avirulent and failed to form cysts but stimulated antibodies, inflammatory cytokines, and leukocytes infiltration in mice. We next investigated the protective efficacy of ME49Δgra5 vaccination against T. gondii infection and tumor development. All the immunized mice survived the challenge infection of either wild-type RH, ME49, VEG tachyzoites, or ME49 cysts. Moreover, ME49Δgra5 tachyzoite inoculation in situ attenuated the growth of murine breast tumor (4T1) in mice and prevented 4T1’s lung metastasis. ME49Δgra5 inoculation upregulated the levels of Th1 cytokines and tumor-infiltrating T cells in the tumor microenvironment and triggered anti-tumor responses by increasing the number of natural killer, B, and T cells, macrophages, and dendritic cells in the spleen. Collectively, these results suggested that ME49Δgra5 was a potent live attenuated vaccine against T. gondii infection and breast cancer.
Infliximab trough levels are associated with endoscopic healing but not with transmural healing at one year treatment with infliximab in pediatric patients with Crohn’s disease
Authors: Choi So Yoon , Kwon Yiyoung , Choi Sujin , Lee So Mi , Choe Byung-Ho , Kang Ben
Published: June 2023

Introduction

It is well known that infliximab (IFX) trough levels (TLs) are associated with endoscopic healing (EH) in Crohn’s disease (CD). We investigated whether IFX TLs are associated with transmural healing (TH) in pediatric patients with CD following 1-year treatment.

Methods

Pediatric patients with CD treated with IFX were included in this single-center prospective study. IFX TL tests, magnetic resonance enterography (MRE), and colonoscopies were simultaneously conducted after 1-year IFX treatment. TH was defined as a wall thickness of ≤3 mm without inflammatory signs evaluated using MRE. EH was defined as a Simple Endoscopic Score for Crohn’s disease of <3 points on colonoscopy.

Results

Fifty-six patients were included. EH and TH were observed in 60.7% (34/56) and 23.2% (13/56) of patients, respectively. IFX TLs were higher in patients with EH (median, 5.6 vs. 3.4 µg/mL, P = 0.002), whereas IFX TLs showed no significant difference in patients with and without TH (median, 5.4 vs. 4.7 µg/mL, P = 0.574). No significant difference was observed in EH and TH between patients whose intervals were shortened or not. Multivariate logistic regression analysis showed that IFX TLs and disease duration to IFX initiation were associated with EH (odds ratio [OR] = 1.82, P = 0.001, and OR = 0.43, P = 0.02, respectively).

Discussion

In pediatric patients with CD, IFX TLs were associated with EH but not with TH. Further studies investigating long-term TH and proactive dosing based on therapeutic drug monitoring may clarify whether an association between IFX TLs and TH exists.
Case report: Successful treatment with daratumumab for pure red cell aplasia in a patient with mixed lymphoid chimerism after ABO-mismatched stem cell transplant for sickle cell disease
Authors: Dovern E. , Biemond B. J. , Nur E.
Published: June 2023

Pure red cell aplasia (PRCA) is a serious complication after ABO-mismatched allogeneic hematopoietic stem cell transplantation (HSCT). Following HSCT, persistent anti-donor isohemagglutinins against donor ABO antigens are considered the immunological cause of PRCA. Patients with post-transplant PRCA are at risk for graft rejection and prolonged red blood cell transfusion dependency. No standard treatment exists. Recently however, the anti-CD38 monoclonal antibody daratumumab has been reported to be an effective treatment for post-transplant PRCA in patients with complete donor chimerism. Here, we describe the first case of PRCA in a patient with mixed lymphoid patient/donor chimerism that was successfully treated with daratumumab. This is also the first report of a transplant recipient with sickle cell disease who was treated with this relatively new approach. Fourteen months post-transplantation and twelve months after treatment with daratumumab, our patient has a normal complete blood count and the anti-donor isohemagglutinins remain undetectable despite mixed lymphoid chimerism. Mixed chimerism is a common manifestation in adult patients with sickle cell disease transplanted with non-myeloablative conditioning and a matched sibling donor. The application of non-myeloablative HSCT for patients with sickle cell disease is steadily increasing. Therefore, the incidence of PRCA in this setting might also increase. As the risk of graft rejection due to PRCA can be especially high in patients with mixed chimerism, clinicians should be aware that daratumumab can be an effective treatment in the setting of mixed chimerism.
Marine mammal morphometrics: 3D modeling and estimation validation
Authors: Zhang Changqun , Zhou Haojie , Christiansen Fredrik , Hao Yujiang , Wang Kexiong , Kou Zhangbing , Chen Ruipeng , Min Jie , Davis Randall , Wang Ding
Published: June 2023

Techniques of 3D modeling have earned increasing popularity in scientific studies as they offered unprecedented traits in representing objects. As with all mathematical models, the 3D model will be useful once its accuracy has been validated with direct measurements and the robustness of its predictive capability tested. Although measures of body mass and volume are essential to comprehend the life history of animals, such morphometrics, especially total volume, are challenging to obtain from marine mammals due to their elusive nature, aquatic lifestyle, and large size. In this study, accurate measurements of body volume were directly detected from fresh carcasses of eleven finless porpoises (Neophocaena asiaeorientalis sunameri) and used to validate 3D models recreated from the same animals using Blender 3D graphics. Published models using truncated cones or elliptical shapes, based on 3, 5, 8, or 19 measurements of girths or heights & widths along the body, were also applied to porpoises to verify their accuracy. The Blender-generated 3D model produced the most accurate estimates of body volume compared to conventional truncated models, with a mean error of only 2.5% to the direct volume measurements. When photogrammetric images are available, the model can predict the body volumes based on total length alone. Similar accuracy was possible with the elliptical model using 19 height & width measurements (5% increments in total length). However, significant (p < 0.001) inaccuracy resulted from truncated models with 3, 5, or 8 girth measurements and elliptical models with 3 or 5 height & width measurements, and the accuracy of these models also decreased significantly as the number of measurement sites was reduced. Moreover, Blender 3D models can be extrapolated to animals with images absent, and such predicted volumes were tested to be trustworthy (overall skill = 0.998, r = 0.998, p < 0.01). Therefore, we recommend that researchers use either digital 3D models or elliptical models with 5% increments sectioning the torso to obtain accurate estimates of the body volumes of free-ranging marine mammals.
Comparative transcriptome analysis reveals the growth and development in larval stages of the swimming crab Portunus trituberculatus
Authors: Chen Jiameng , Chen Xiayue , Mu Changkao , Wang Chunlin , Ye Yangfang , Li Ronghua , Song Weiwei , Shi Ce , Liu Lei , Wang Huan
Published: June 2023

Portunus trituberculatus, an economically important marine crab that was widely distributed along the coast of China, has been in short supply of high-quality crab seedlings in recent years. The larval development of P. trituberculatus is regulated by numerous biological processes at different biological levels, particularly regarding gene expression during the larval development process. Understanding the changes in these critical genes can help further regulate these biological processes to increase crab seedlings’ survival and improve crab quality. In this study, the molecular mechanisms of morphological and physiological changes in larval stages of P. trituberculatus were investigated using DNA microarrays. A total of 109,533 unigenes were obtained, of which 16 genes were differentially expressed during the whole development stages with evident timeliness. The enrichment analysis and comparison of differentially expressed genes (DEGs) showed three types of physiological activities, chitin development, energy metabolism, and neuroendocrine development. The physiological activities were evident in the early development of P. trituberculatus, especially at the Z4-M stage, which is crucial for the growth and development of crab larvae. These DEGs, cuticle proteins, retinol dehydrogenase (RDHs), Juvenile Hormone Epoxide Hydrolase (JHEH), and other vital genes were differentially expressed at the Z4-M stage. Moreover, the insulin-like androgenic gland (IAG), which was reported to be associated with sex differentiation, was highly expressed in the megalopa stage, indicating that the gender differentiation divide may occur at the beginning of this stage. Overall, this research provides a theoretical basis for the development of the swimming crab larvae, which could contribute to the artificial growing seedlings technology of P. trituberculatus.
Large and in charge: cortisol levels vary with sex, diet, and body mass in an Antarctic predator, the leopard seal
Authors: Sperou Emily S. , Crocker Daniel E. , Borras-Chavez Renato , Costa Daniel P. , Goebel Michael E. , Kanatous Shane B. , Krause Douglas J. , Trumble Stephen J. , Kienle Sarah S.
Published: June 2023

Evaluating physiological responses in the context of a species’ life history, demographics, and ecology is essential to understanding the health of individuals and populations. Here, we measured the main mammalian glucocorticoid, cortisol, in an elusive Antarctic apex predator, the leopard seal (Hydrurga leptonyx). We also examined intraspecific variation in cortisol based on life history (sex), morphometrics (body mass, body condition), and ecological traits (δ15N, δ13C). To do this, blood samples, life history traits, and morphometric data were collected from 19 individual leopard seals off the Western Antarctic Peninsula. We found that adult leopard seals have remarkably high cortisol concentrations (100.35 ± 16.72 μg/dL), showing the highest circulating cortisol concentration ever reported for a pinniped: 147 μg/dL in an adult male. Leopard seal cortisol concentrations varied with sex, body mass, and diet. Large adult females had significantly lower cortisol (94.49 ± 10.12 μg/dL) than adult males (120.85 ± 6.20 μg/dL). Similarly, leopard seals with higher isotope values (i.e., adult females, δ15N: 11.35 ± 0.69‰) had lower cortisol concentrations than seals with lower isotope values (i.e., adult males, δ15N: 10.14 ± 1.65‰). Furthermore, we compared cortisol concentrations across 26 closely related Arctoid taxa (i.e., mustelids, bears, and pinnipeds) with comparable data. Leopard seals had the highest mean cortisol concentrations that were 1.25 to 50 times higher than other Arctoids. More broadly, Antarctic ice seals (Lobodontini: leopard seal, Ross seal, Weddell seal, crabeater seal) had higher cortisol concentrations compared to other pinnipeds and Arctoid species. Therefore, high cortisol is a characteristic of all lobodontines and may be a specialized adaptation within this Antarctic-dwelling clade. Together, our results highlight exceptionally high cortisol concentrations in leopard seals (and across lobodontines) and reveal high variability in cortisol concentrations among individuals from a single location. This information provides the context for understanding how leopard seal physiology changes with life history, ecology, and morphology and sets the foundation for assessing their physiology in the context of a rapidly changing Antarctic environment.
Biomechanical study of two-level oblique lumbar interbody fusion with different types of lateral instrumentation: a finite element analysis
Authors: Zhong Yuan , Wang Yujie , Zhou Hong , Wang Yudong , Gan Ziying , Qu Yimeng , Hua Runjia , Chen Zhaowei , Chu Genglei , Liu Yijie , Jiang Weimin
Published: June 2023

Objective

The aim of this study was to verify the biomechanical properties of a newly designed angulated lateral plate (mini-LP) suited for two-level oblique lumbar interbody fusion (OLIF). The mini-LP is placed through the lateral ante-psoas surgical corridor, which reduces the operative time and complications associated with prolonged anesthesia and placement in the prone position.

Methods

A three-dimensional nonlinear finite element (FE) model of an intact L1–L5 lumbar spine was constructed and validated. The intact model was modified to generate a two-level OLIF surgery model augmented with three types of lateral fixation (stand-alone, SA; lateral rod screw, LRS; miniature lateral plate, mini-LP); the operative segments were L2–L3 and L3–L4. By applying a 500 N follower load and 7.5 Nm directional moment (flexion-extension, lateral bending, and axial rotation), all models were used to simulate human spine movement. Then, we extracted the range of motion (ROM), peak contact force of the bony endplate (PCFBE), peak equivalent stress of the cage (PESC), peak equivalent stress of fixation (PESF), and stress contour plots.

Results

When compared with the intact model, the SA model achieved the least reduction in ROM to surgical segments in all motions. The ROM of the mini-LP model was slightly smaller than that of the LRS model. There were no significant differences in surgical segments (L1–L2, L4–L5) between all surgical models and the intact model. The PCFBE and PESC of the LRS and the mini-LP fixation models were lower than those of the SA model. However, the differences in PCFBE or PESC between the LRS- and mini-LP-based models were not significant. The fixation stress of the LRS- and mini-LP-based models was significantly lower than the yield strength under all loading conditions. In addition, the variances in the PESF in the LRS- and mini-LP-based models were not obvious.

Conclusion

Our biomechanical FE analysis indicated that LRS or mini-LP fixation can both provide adequate biomechanical stability for two-level OLIF through a single incision. The newly designed mini-LP model seemed to be superior in installation convenience, and equally good outcomes were achieved with both LRS and mini-LP for two-level OLIF.
Synthetic artificial intelligence using generative adversarial network for retinal imaging in detection of age-related macular degeneration
Authors: Wang Zhaoran , Lim Gilbert , Ng Wei Yan , Tan Tien-En , Lim Jane , Lim Sing Hui , Foo Valencia , Lim Joshua , Sinisterra Laura Gutierrez , Zheng Feihui , Liu Nan , Tan Gavin Siew Wei , Cheng Ching-Yu , Cheung Gemmy Chui Ming , Wong Tien Yin , Ting Daniel Shu Wei
Published: June 2023

Introduction

Age-related macular degeneration (AMD) is one of the leading causes of vision impairment globally and early detection is crucial to prevent vision loss. However, the screening of AMD is resource dependent and demands experienced healthcare providers. Recently, deep learning (DL) systems have shown the potential for effective detection of various eye diseases from retinal fundus images, but the development of such robust systems requires a large amount of datasets, which could be limited by prevalence of the disease and privacy of patient. As in the case of AMD, the advanced phenotype is often scarce for conducting DL analysis, which may be tackled via generating synthetic images using Generative Adversarial Networks (GANs). This study aims to develop GAN-synthesized fundus photos with AMD lesions, and to assess the realness of these images with an objective scale.

Methods

To build our GAN models, a total of 125,012 fundus photos were used from a real-world non-AMD phenotypical dataset. StyleGAN2 and human-in-the-loop (HITL) method were then applied to synthesize fundus images with AMD features. To objectively assess the quality of the synthesized images, we proposed a novel realness scale based on the frequency of the broken vessels observed in the fundus photos. Four residents conducted two rounds of gradings on 300 images to distinguish real from synthetic images, based on their subjective impression and the objective scale respectively.

Results and discussion

The introduction of HITL training increased the percentage of synthetic images with AMD lesions, despite the limited number of AMD images in the initial training dataset. Qualitatively, the synthesized images have been proven to be robust in that our residents had limited ability to distinguish real from synthetic ones, as evidenced by an overall accuracy of 0.66 (95% CI: 0.61–0.66) and Cohen’s kappa of 0.320. For the non-referable AMD classes (no or early AMD), the accuracy was only 0.51. With the objective scale, the overall accuracy improved to 0.72. In conclusion, GAN models built with HITL training are capable of producing realistic-looking fundus images that could fool human experts, while our objective realness scale based on broken vessels can help identifying the synthetic fundus photos.
Preventive role of cinnamaldehyde against tenuazonic acid- and Freund’s adjuvant-induced histopathological and biochemical alterations in the mouse model
Authors: Kumari Ankita , Singh Karuna
Published: June 2023

Introduction

This study was designed to assess the protective role of cinnamaldehyde (Cin) against the synergistic effect of tenuazonic acid (TeA) and Freund’s adjuvant on different organs of Swiss albino mice.

Methods

TeA was administered singly and in combination with Freund’s adjuvant intra-peritoneally. The mice were divided into control (vehicle treated), mycotoxicosis-induced (MI) groups, and treatment groups. The route of administration of TeA was intra-peritoneal. The treatment group (FAICT) received Cin orally as a protective agent against TeA-induced mycotoxicosis. The effects on performance, differential leukocyte counts (DLC), and pathological measurements in eight organs (liver, lungs, kidney, spleen, stomach, heart, brain, and testis) were taken into consideration.

Results

The body weight and feed consumption decreased significantly in the MI groups, which were reversed in the FAICT group. The necropsy observations revealed an increase in the relative organ-to-body weight percentage in the MI groups, which was restored to normal in the FAICT group. Freund’s adjuvant enhanced the effects of TeA on DLC. The antioxidant enzymes SOD and CAT decreased, while MDA increased in the MI groups. Caspase-3 activity was reduced in all organs and remained stable in the treatment group. TeA elevated the ALT concentration in the liver and kidneys and the AST in the liver, kidney, heart, and brain tissues. The oxidative stress induced by TeA in the MI groups was ameliorated in the treatment group. Histopathological observations consisted of NASH, pulmonary oedema and fibrosis, renal crystals and inflammation, splenic hyperplasia, gastric ulceration and cyst, cerebral axonopathy, testicular hyperplasia, and vacuolation in the MI groups. However, no such pathology was recorded in the treatment group.

Discussions

Thus, it can be concluded that the toxicity of TeA was found to be enhanced when combined with Freund’s adjuvant. However, Cin exhibited promising protective effects against TeA + Freund’s adjuvant toxicity and reverted the pathological alterations caused by them. Additionally, this study emphasizes Freund’s adjuvant’s ability to increase mycotoxicity rather than just acting as an immunopotentiator.
Comparative pathogenicity of BA.2.12, BA.5.2 and XBB.1 with the Delta variant in Syrian hamsters
Authors: Mohandas Sreelekshmy , Shete Anita , Kumar Abhimanyu , Wakchaure Kundan , Rai Vishal , Mote Chandrasekhar , Dighe Hitesh , Sarkale Prasad , Gawande Pranita , Yemul Jyoti , Suryawanshi Annasaheb , Joshi Yash , Yadav Pragya D.
Published: June 2023

Omicron variant is evolving into numerous sub variants with time and the information on the characteristics of these newly evolving variants are scant. Here we performed a pathogenicity evaluation of Omicron sub variants BA.2.12, BA.5.2 and XBB.1 against the Delta variant in 6–8-week-old Syrian hamster model. Body weight change, viral load in respiratory organs by real time RT-PCR/titration, cytokine mRNA quantification and histopathological evaluation of the lungs were performed. The intranasal infection of the BA.2.12, BA.5.2 and XBB.1 variants in hamster model resulted in body weight loss/reduced weight gain, inflammatory cytokine response and interstitial pneumonia with lesser severity compared to the Delta variant infection. Among the variants studied, BA.2.12 and XBB.1 showed lesser viral shedding through the upper respiratory tract, whereas the BA.5.2 showed comparable viral RNA shedding as that of the Delta variant. The study shows that the Omicron BA.2 sub variants may show difference in disease severity and transmissibility amongst each other whereas the overall disease severity of the Omicron sub variants studied were less compared to the Delta variant. The evolving Omicron sub variants and recombinants should be monitored for their properties.
A limited overlap of interactions between the bacterial community of water and sediment in wetland ecosystem of the Yellow River floodplain
Authors: Han Zhiguang , Wang Cong , Lei Binghai , Hui Nan , Yu Yanyan , Shi Yu , Zheng Junqiang
Published: June 2023

Introduction

Aquatic ecosystems in floodplains provide homes for a variety of active bacterial populations. However, the coexistence pattern of bacterial communities of water and sediment in these ecosystems is unclear.

Methods

In the present study, Illumina Mi-Seq sequencing were to assess bacteria's co-occurrence patterns in the water and sediment of different time dynamics and plant communities of the Yellow River floodplain ecosystem.

Results and discussion

The results showed that compared to water, the α-diversity of the bacterial community was way greater in sediment. The bacterial community structure significantly differed between water and sediment, and there was a limited overlap of interactions between the bacterial community of water and sediment. In addition, bacteria in water and sediment coexisting show different temporal shifts and community assembly patterns. The water was selected for specific groups of microorganisms that assemble over time in a non-reproducible and non-random way, whereas the sediment environment was relatively stable, and the bacterial communities were gathered randomly. The depth and plant cover significantly influenced the structure of a bacterial community in the sediment. The bacterial community in sediment formed a more robust network than those in water to cope with external changes. These findings improved our comprehension of the ecological trends of water and sediment bacterium colonies coexisting enhanced the biological barrier function, and the capacity of floodplain ecosystems to provide services and offered support for doing so.