bluuebunny/crossref_metadata_2025 huggingface dataset:
First clinical applications for the NIR-II imaging with ICG in microsurgery
Authors: Wu Yifan , Suo Yongkuan , Wang Zheng , Yu Yifeng , Duan Shuang , Liu Hongguang , Qi Baiwen , Jian Chao , Hu Xiang , Zhang Dong , Yu Aixi , Cheng Zhen
Published: October 2022

In microsurgery, it is always difficult to accurately identify the blood supply with ease, such as vascular anastomosis, digit replantation, skin avulsion reconstruction and flap transplantation. Near-infrared window I (NIR-I, 700—900 nm) imaging has many clinical applications, whereas near-infrared window II (NIR-II, 1,000–1700 nm) imaging has emerged as a highly promising novel optical imaging modality and used in a few clinical fields recently, especially its penetration distance and noninvasive characteristics coincide with the needs of microsurgery. Therefore, a portable NIR-II imaging instrument and the Food and Drug Administration (FDA) approved indocyanine green (ICG) were used to improve the operation efficiency in microsurgery of 39 patients in this study. The anastomotic vessels and the salvaged distal limbs were clearly visualized after intravenous injection of ICG. The technique enabled identification of perforator vessels and estimation of perforator areas prior to the flap obtention and made it easier to monitor the prognosis. Overall, this study highlights the use of the portable NIR- II imaging with ICG as an operative evaluation tool can enhance the safety and accuracy of microsurgery.
The uncommon function and mechanism of the common enzyme glyceraldehyde-3-phosphate dehydrogenase in the metamorphosis of Helicoverpa armigera
Authors: Zhao Wenli , Zhang Bo , Geng Zichen , Chang Yanpeng , Wei Jizhen , An Shiheng
Published: October 2022

Glyceraldehyde-3-phosphate dehydrogenase (GAPDH), a key enzyme in glycolysis, is commonly used as an internal reference gene in humans, mice, and insects. However, the function of GAPDH in insect development, especially in metamorphosis, has not been reported. In the present study, Helicoverpa armigera and Spodoptera frugiperda ovarian cell lines (Sf9 cells) were used as materials to study the function and molecular mechanism of GAPDH in larval metamorphosis. The results showed that HaGAPDH was more closely related to GAPDH of S. frugiperda and Spodoptera litura. The transcript peaks of HaGAPDH in sixth instar larvae were 6L-3 (epidermal and midgut) and 6L-1 (fat body) days, and 20E and methoprene significantly upregulated the transcripts of HaGAPDH of larvae in qRT-PCR. HaGAPDH–GFP–His was specifically localized in mitochondria in Sf9 cells. Knockdown of HaGAPDH by RNA interference (RNAi) in sixth instar larvae resulted in weight loss, increased mortality, and decreases in the pupation rate and emergence rates. HaGAPDH is directly bound to soluble trehalase (HaTreh1) physically and under 20E treatment in yeast two-hybrid, coimmunoprecipitation, and colocalization experiments. In addition, knockdown of HaGAPDH increased the Treh1 activity, which in turn decreased the trehalose content but increased the glucose content in larvae. Therefore, these data demonstrated that GAPDH controlled the glucose content within the normal range to ensure glucose metabolism and metamorphosis by directly binding with HaTreh1.
3D-printed mesoporous bioactive glass/GelMA biomimetic scaffolds for osteogenic/cementogenic differentiation of periodontal ligament cells
Authors: Mei Nianrou , Wu Yiwen , Chen Binglin , Zhuang Tian , Yu Xinge , Sui Baiyan , Ding Tingting , Liu Xin
Published: October 2022

Integrated regeneration of periodontal tissues remains a challenge in current clinical applications. Due to the tunable physical characteristics and the precise control of the scaffold microarchitecture, three-dimensionally (3D) printed gelatin methacryloyl (GelMA)-based scaffold has emerged as a promising strategy for periodontal tissue regeneration. However, the optimization of the printing biomaterial links the formulation and the relationship between the composition and structures of the printed scaffolds and their comprehensive properties (e.g. mechanical strength, degradation, and biological behaviors) remains unclear. Here, in this work, a novel mesoporous bioactive glass (BG)/GelMA biomimetic scaffold with a large pore size (∼300 μm) was developed by extrusion-based 3D printing. Our results showed that the incorporation of mesoporous bioactive glass nanoparticles (BG NPs) significantly improved shape fidelity, surface roughness, and bioactivity of 3D-printed macroporous GelMA scaffolds, resulting in the enhanced effects on cell attachment and promoting osteogenic/cementogenic differentiation in human periodontal ligament cells. The excellent maintenance of the macropore structure, the visibly improved cells spreading, the release of bioactive ions (Si4+, Ca2+), the upregulation of gene expressions of osteogenesis and cementogensis, and the increase in alkaline phosphatase (ALP) activity and calcium nodules suggested that BG NPs could endow GelMA-based scaffolds with excellent structural stability and the ability to promote osteogenic/cementogenic differentiation. Our findings demonstrated the great potential of the newly formulated biomaterial inks and biomimetic BG/GelMA scaffolds for being used in periodontal tissue regeneration and provide important insights into the understanding of cell–scaffold interaction in promoting the regeneration of functional periodontal tissues.
The CaT stretcher: An open-source system for delivering uniaxial strain to cells and tissues (CaT)
Authors: Wang Yushi , Singer Ryan , Liu Xinyue , Inman Seth J. , Cao Quynh , Zhou Quan , Noble Alex , Li Laura , Arizpe Tafoya Aidee Verónica , Babi Mouhanad , Ask Kjetil , Kolb Martin R. , Ramsay Scott , Geng Fei , Zhang Boyang , Shargall Yaron , Moran-Mirabal Jose Manuel , Dabaghi Mohammadhossein , Hirota Jeremy A.
Published: October 2022

Integration of mechanical cues in conventional 2D or 3D cell culture platforms is an important consideration for in vivo and ex vivo models of lung health and disease. Available commercial and published custom-made devices are frequently limited in breadth of applications, scalability, and customization. Herein we present a technical report on an open-source, cell and tissue (CaT) stretcher, with modularity for different in vitro and ex vivo systems, that includes the following features: 1) Programmability for modeling different breathing patterns, 2) scalability to support low to high-throughput experimentation, and 3) modularity for submerged cell culture, organ-on-chips, hydrogels, and live tissues. The strategy for connecting the experimental cell or tissue samples to the stretching device were designed to ensure that traditional biomedical outcome measurements including, but not limited to microscopy, soluble mediator measurement, and gene and protein expression remained possible. Lastly, to increase the uptake of the device within the community, the system was built with economically feasible and available components. To accommodate diverse in vitro and ex vivo model systems we developed a variety of chips made of compliant polydimethylsiloxane (PDMS) and optimized coating strategies to increase cell adherence and viability during stretch. The CaT stretcher was validated for studying mechanotransduction pathways in lung cells and tissues, with an increase in alpha smooth muscle actin protein following stretch for 24 h observed in independent submerged monolayer, 3D hydrogel, and live lung tissue experiments. We anticipate that the open-source CaT stretcher design will increase accessibility to studies of the dynamic lung microenvironment through direct implementation by other research groups or custom iterations on our designs.
Epigenetic variation: A major player in facilitating plant fitness under changing environmental conditions
Authors: Rajpal Vijay Rani , Rathore Priyanka , Mehta Sahil , Wadhwa Nikita , Yadav Priyanka , Berry Eapsa , Goel Shailendra , Bhat Vishnu , Raina Soom Nath
Published: October 2022

Recent research in plant epigenetics has increased our understanding of how epigenetic variability can contribute to adaptive phenotypic plasticity in natural populations. Studies show that environmental changes induce epigenetic switches either independently or in complementation with the genetic variation. Although most of the induced epigenetic variability gets reset between generations and is short-lived, some variation becomes transgenerational and results in heritable phenotypic traits. The short-term epigenetic responses provide the first tier of transient plasticity required for local adaptations while transgenerational epigenetic changes contribute to stress memory and help the plants respond better to recurring or long-term stresses. These transgenerational epigenetic variations translate into an additional tier of diversity which results in stable epialleles. In recent years, studies have been conducted on epigenetic variation in natural populations related to various biological processes, ecological factors, communities, and habitats. With the advent of advanced NGS-based technologies, epigenetic studies targeting plants in diverse environments have increased manifold to enhance our understanding of epigenetic responses to environmental stimuli in facilitating plant fitness. Taking all points together in a frame, the present review is a compilation of present-day knowledge and understanding of the role of epigenetics and its fitness benefits in diverse ecological systems in natural populations.
An old friend with a new face: YB-1 and its role in healthy pregnancy and pregnancy-associated complications
Authors: Fischer Florence , Schumacher Anne , Meyer Nicole , Fink Beate , Bauer Mario , Stojanovska Violeta , Zenclussen Ana Claudia
Published: October 2022

By promoting tissue invasion, cell growth and angiogenesis, the Y-box binding protein (YB-1) became famous as multifunctional oncoprotein. However, this designation is telling only part of the story. There is one particular time in life when actual tumorigenic-like processes become undoubtedly welcome, namely pregnancy. It seems therefore reasonable that YB-1 plays also a crucial role in reproduction, and yet this biological aspect of the cold-shock protein has been overlooked for many years. To overcome this limitation, we would like to propose a new perspective on YB-1 and emphasize its pivotal functions in healthy pregnancy and pregnancy-related complications. Moreover, we will discuss findings obtained from cancer research in the light of reproductive events to elucidate the importance of YB-1 at the feto-maternal interface.
Protective role of endorepellin in renal developmental programming
Authors: Tang Xiaoshan , Sun Manqing , Shen Qian , Rao Jia , Yang Xue , Fang Ye , Xiang Tianchao , Xue Shanshan , Sun Lei , Xu Hong
Published: October 2022

Adverse intrauterine and early postnatal environment cause reduced nephron endowment and subsequent hypertension, chronic kidney disease (CKD). Exploring modifiable approaches is particularly important to alleviate the global burden of CKD. Enhanced glomerular progenitor cell apoptosis is a major contributor to renal developmental programming. The differentially expressed protein perlecan, which we previously identified using proteomics, is an important extracellular matrix glycoprotein, and its domain V (endorepellin) can inhibit apoptosis through a paracrine form. In explanted mice embryonic metanephros, we found that endorepellin can rescue glomeruli-deficit phenotype resulting from malnutrition, and this protective effect was also verified in vivo using a renal developmental programming model which was given a low-protein diet during pregnancy. We further demonstrated that endorepellin significantly inhibited glomerular progenitor cell apoptosis which activates ERK1/2 phosphorylation. Our results show that endorepellin rescues the nephron number reduction in renal developmental programming, possibly through the inhibition of progenitor cell apoptosis via the ERK1/2 pathway.
Prevalence and distribution of ampc beta-lactamase producing escherichia coli and klebsiella pneumoniae isolates obtained from urine samples at a tertiary care hospital in the caribbean
Authors: Thoms Rodriguez Camille-Ann , Dawson Felecia , Cameron Jenene , Seah Christine , Reid Marvin , Melano Roberto G. , Gossell-Williams Maxine
Published: October 2022

Introduction

The aim of this study was to investigate the prevalence and distribution of AmpC beta-lactamases (BLs) in uropathogens (E. coli and K. pneumoniae) at the University Hospital of the West Indies Jamaica (UHWI).

Method

De-duplicated consecutive urine samples, collected from January to March 2020 at the UHWI, were analyzed. Screening and phenotypic confirmatory tests were conducted using resistance to cefoxitin and the Disc Approximation Test (DAT) respectively, for isolates of interest. Multiplex PCR was performed on cefoxitin resistant (CR) isolates for the detection of blaCIT, blaMOX, blaFOX, blaACC, and blaDHA genes. Whole genome sequencing (WGS) was used to further detect AmpC BL genes in PCR negative isolates with indeterminate phenotypic results.

Results

Sixty-four Gram negative isolates were obtained from 61 patients (55% female), aged 18 months to 88 years old. At least 35% (26) had complicated urinary tract infections. Only 7 out of 64 isolates were E. coli or K. pneumoniae, had antibiograms suggestive of possible AmpC BL production and were CR. DATs confirmed AmpC BL in two of these (1 K. pneumoniae; 1 E. coli), one tested negative (E. coli) and four had inconclusive results (K. pneumoniae). PCR detected blaDHA and blaCIT in two CR isolates. WGS further detected blaCMY-42 in one isolate. The prevalence of screened CR isolates with AmpC BL is 57.14% (4 of 7), representing 6.25% of the sample. AmpC BL producers tested had 100% susceptibility to meropenem and nitrofurantoin.

Conclusion

AmpC BL prevalence among E. coli and K. pneumoniae, common urinary pathogens, in the studied isolates is low. Although cefoxitin screening is helpful, phenotypic screening using the DAT can yield indeterminate results best clarified by molecular testing.
Selection of the cutoff value of the tuberculin skin test for diagnosing students who need preventive treatment: A school-based cross-sectional study
Authors: Lu Peng , Ding Xiaoyan , Sun Jiansheng , Wang Rong , Liu Jiasong , Liu Qiao , Zhu Limei , Lu Wei
Published: October 2022

Objective

Tuberculosis outbreaks in schools are common in China. This study aimed to introduce and evaluate a new screening process to help control outbreaks.

Methods

Screening information of students in three schools with tuberculosis outbreaks was collected. QuantiFERON-TB gold in-tube (QFT) results were used as the reference standard to determine the cutoff value of the tuberculin skin test (TST) for diagnosing students who need to have preventive medication.

Results

A total of 1,232 students and teachers from three different schools that all had more than three student patients with tuberculosis were included in this study. In total, 308 (25.0%) students had an induration diameter ≥10 mm; among students in a class different from the index case, the infection rate was 24.4% (264/1,084), which was lower than the rate among students in the same class (29.7%) (P = 0.157). Students in the same class as the index tuberculosis case had a much higher QFT positivity compared to those in a different class (58.1% vs. 7.7%, P < 0.0001). Diagnostic agreement between TST ≥10 mm and QFT was 36.6%. The diagnostic value reached the highest when the induration diameter of TST was ≥9 mm, with a sensitivity and specificity of 94.1% (95% CI: 89.4%–97.1%) and 27.6% (95% CI: 24.9%–30.4%), respectively. The area under the curve (AUC) was 0.664 (95% CI: 0.637–0.690, P < 0.0001).

Conclusion

In tuberculosis outbreaks in schools, if there are three or more cases of students with tuberculosis in a class or if the moderate or strong TST positivity rate is much higher than the normal range in the region, attention should be paid to those with moderately positive TST results. Interferon-gamma release assays (IGRAs) are recommended to be conducted following TST on the day of reading the results, especially among students sharing the same class with the index case. In resource-poor areas lacking IGRAs, the induration diameter of TST can be appropriately reduced from 15 to 9 mm to enhance the sensitivity of TST.
Are early social communication skills a harbinger for language development in infants later diagnosed autistic?—A longitudinal study using a standardized social communication assessment
Authors: Ravi Shruthi , Bradshaw Allison , Abdi Hervé , Meera Shoba Sreenath , Parish-Morris Julia , Yankowitz Lisa , Paterson Sarah , Dager Stephen R. , Burrows Catherine A. , Chappell Chad , St.John Tanya , Estes Annette M. , Piven Joseph , Swanson Meghan R. ,   The IBIS Network
Published: October 2022

The early emergence of social communication challenges and their impact on language in infants later diagnosed with autism has sparked many early intervention programs that target social communication skills. While research has consistently shown lower scores on social communication assessments in the first year of life, there is limited research at 12-months exploring associations between different dimensions of social communication and later language. Understanding associations between early social communication skills and language would enhance our ability to choose high priority intervention goals that will impact downstream language skills. The current study used a standardized assessment to profile social communication skills across 516 infants with a high (HL) or low likelihood (LL-Neg) for autism (84% White, 60% Male), based on the presence of a sibling with autism in the family. The primary aim of the study was to profile social communication skill development in the second year of life and to evaluate associations between social communication skills and later language. HL infants who met criteria for autism (HL-ASD, N = 81) demonstrated widespread reductions in social communication skills at 12-months compared to HL infants who did not meet criteria for autism (HL-Neg, N = 277) and LL-Neg (N = 158) infants. Across all infants in the study, those with better social communication skills at 12-months had better language at 24-months. However, within group analyses indicated that infants who met criteria for autism did not show this developmental coupling until 24-months-of-age at which point social communication was positively associated with downstream language skills. The cascading pattern of reduced social communication skills as well as overall significant positive associations with later language provide further evidence for the need to support developing social communication skills prior to formal autism diagnosis, a goal that could possibly be reached through pre-emptive interventions.
Prognostic value of circulating microRNA-21-5p and microRNA-126 in patients with acute myocardial infarction and infarct-related artery total occlusion
Authors: Mi Xiao-long , Gao Yu-ping , Hao Da-jie , Zhang Zhi-jun , Xu Zheng , Li Tong , Li Xue-wen
Published: October 2022

Background

Cardiovascular disease, including acute myocardial infarction (AMI), is a major global cause of mortality and morbidity. Specificity and sensitivity limit the utility of classic diagnostic biomarkers for AMI. Therefore, it is critical to identify novel biomarkers for its accurate diagnosis. Cumulative studies have demonstrated that circulating microRNAs (miRs) participate in the pathophysiological processes of AMI and are promising diagnostic biomarkers for the condition. This study aimed to ascertain the diagnostic accuracy of circulating miR-21-5p and miR-126 used as biomarkers in patients with AMI and infarct-related artery total occlusion (IR-ATO) or infarct-related blood-vessel recanalization (IR-BVR).

Methods

The expression of miR-21-5p and miR-126 was examined separately in 50 healthy subjects, 51 patients with IR-ATO AMI, and 49 patients with IR-BVR AMI using quantitative real-time polymerase chain reaction.

Results

When compared with the control group, the IR-ATO AMI group exhibited increased miR-21-5p (p < 0.0001) and miR-126 (p < 0.0001), and the IR-BVR AMI group exhibited increased miR-21-5p (p < 0.0001). However, there was no significant difference in miR-126 between the IR-BVR AMI and the control groups. A Spearman's correlation coefficient showed a strong correlation was found between miR-21-5p, miR-126, cardiac troponin-I, and creatine kinase isoenzyme in all three groups, while a receiver operating characteristic analysis revealed that miR-21-5p and miR-126 exhibited considerable diagnostic accuracy for IR-ATO AMI.

Conclusion

Circulating miR-21-5p and miR-126 may be promising prognostic biomarkers for patients with AMI and IR-ATO.
The influence of dipeptidyl peptidase-4 inhibitor on the progression of type B intramural hematoma
Authors: Chen Qu , Jiang Dandan , Shan Zhonggui
Published: October 2022

Objectives

Investigating whether dipeptidyl peptidase-4 inhibitors (DPP4i) could influence the progression of type B intramural hematoma (IMHB) in patients with diabetes mellitus (DM).

Materials and methods

Uncomplicated IMHB patients were matched by age, sex, and body mass index. Cox proportional hazard models were constructed to identify risk factors. A Kaplan–Meier survival analysis was used to estimate all-cause and aorta-related mortality.

Results

Ninety-six matched IMHB patients were divided into Group A (n= 32, IMHB patients without DM), Group B (n= 32, IMHB patients with DMreceiving oral antidiabetic drugs [without DPP4i]) and Group C (n= 32, IMHB patients with DM receiving oral antidiabetic drugs [with DPP4i]). Group C had the lowest rate of aorta-related adverse events (3.1%), aorta-related mortality (0.0%) and reintervention (3.1%). Cox proportional hazard models revealed that a lower eosinophil count (per 0.1, HR, 0.48; 95% CI, 0.29–0.79,P= 0.004) and a higher neutrophil to lymphocyte ratio (NLR) (HR, 1.13; 95% CI, 1.05–1.21,P= 0.001) were associated with higher occurrences of aorta-related adverse events. A lower eosinophil count (per 0.1, HR, 0.40; 95% CI, 0.18–0.89,P= 0.025) and a higher NLR (HR, 1.19; 95% CI, 1.08–1.32,P= 0.001) were also associated with increased aorta-related mortality.

Conclusion

DPP4i administration in DM patients with IMHB was associated with lower aorta-related mortality and more benign progression than in those who did not receive DPP4i or those without DM. Furthermore, a higher eosinophil count and a lower NLR ratio are potential protective factors that may explain the potential therapeutic benefit of DPP4i.
Maternal homework approach and adolescents’ academic skills: The mediating role of task values
Authors: Silinskas Gintautas , Viljaranta Jaana , Poikkeus Anna-Maija , Lerkkanen Marja-Kristiina
Published: October 2022

The present study investigated the mediating role of the task values between the types of maternal homework approach (perceptions of their child’s autonomy or direct involvement) and adolescents’ academic skills. Data were utilized from 995 mother–child dyads followed across Grades 6, 7, and 9. At each time-point, mothers answered questionnaires on the types of their homework approach, adolescents answered questionnaires about their task values for math and Finnish, and adolescents’ skills in math (arithmetic and multiplication) and reading (reading fluency and reading comprehension) were tested. Separate longitudinal structural equation models were estimated for math and for reading. The results showed, first, that maternal perceptions of their adolescents’ autonomy positively predicted adolescents’ task values but did not predict skills. Second, maternal direct involvement in homework completion negatively predicted adolescents’ math and reading skills but did not predict task values. Finally, concerning the effect of task values between homework approach and skills, task values in Grade 7 played a role in the associations between perceptions of autonomy (but not direct involvement) in Grade 6 and adolescents’ skills in Grade 9. Overall, the present study highlights the importance of student autonomy with regard to homework in promoting adolescents’ task values as well as the role of adolescents’ task values in the associations between maternal perceptions of autonomy and the development of adolescents’ math and reading skills.
Evaluating health outcomes in the treatment of hypothyroidism
Authors: Ettleson Matthew D. , Papaleontiou Maria
Published: October 2022

Clinical hypothyroidism is defined by the inadequate production of thyroid hormone from the thyroid gland to maintain normal organ system functions. For nearly all patients with clinical hypothyroidism, lifelong treatment with thyroid hormone replacement is required. The primary goal of treatment is to provide the appropriate daily dose of thyroid hormone to restore normal thyroid function for each individual patient. In current clinical practice, normalization of thyrotropin (TSH) level is the primary measure of effectiveness of treatment, however the use of a single biomarker to define adequate thyroid hormone replacement is being reevaluated. The assessment of clinical health outcomes and patient-reported outcomes (PROs), often within the context of intensity of treatment as defined by thyroid function tests (i.e., undertreatment, appropriate treatment, or overtreatment), may play a role in evaluating the effectiveness of treatment. The purpose of this narrative review is to summarize the prominent health outcomes literature in patients with treated hypothyroidism. To date, overall mortality, cardiovascular morbidity and mortality, bone health and cognitive function have been evaluated as endpoints in clinical outcomes studies in patients with treated hypothyroidism. More recent investigations have sought to establish the relationships between these end results and thyroid function during the treatment course. In addition to clinical event outcomes, patient-reported quality of life (QoL) has also been considered in the assessment of adequacy of hypothyroidism treatment. From a health care quality perspective, treatment of hypothyroidism should be evaluated not just on its effectiveness for the individual patients but also to the extent to which patients of different sociodemographic groups are treated equally. Ultimately, more research is needed to explore differences in health outcomes between different sociodemographic groups with hypothyroidism. Future prospective studies of treated hypothyroidism that integrate biochemical testing, PROs, and end result clinical outcomes could provide a more complete picture into the effectiveness of treatment of hypothyroidism.
Optimization of temperature distribution in the novel power-to-heat matrix-in-batch OnePot© reactor
Authors: Caravella Alessio , Francardi Marco , Romano Salvatore , Prenesti Giuseppe , Oliverio Manuela
Published: October 2022

In this work, we assess the optimal temperature distribution inside a new automated, stand-alone, matrix-in-batch patented reactor, named OnePot©. This novel reactor is equipped with seven rotating hot rotating cylinders—here referred to as spots—which make it possible a precise tuning of fluid temperature. To conduct this investigation, we consider two radial layout of spots, here indicated as uniform configuration and alternate one, respectively. The former characterised by a single uniform equilateral triangular pitch, whereas the latter by two different equilateral triangular pitches alternated to form a double-triangle star. We consider two different fluids, water and argon, as representative of the behaviour of liquids and gases, respectively. Furthermore, the effect of viscosity is also taken into account by forcefully increasing that of water by 100 and 1,000 times. The optimization of the temperature distribution is performed obtaining velocity and temperature fields using a computational fluid dynamic (CFD) approach. As a sort of objective function to maximise, we defined a thermal mixing efficiency to provide a quantitative measure of the temperature distribution uniformity. As a remarkable result, we find an optimal value of pitch approximately equal to 36% of the vessel diameter for both liquid water and argon gas. As for the alternate configuration, we found that it provides a better temperature distribution than the uniform one, especially at high viscosity values. This is because the inner spots are able to prevent the formation of large colder “islands” around the centre. Furthermore, we estimate the overall heat transfer coefficient between thermal spots and fluid bulk, whose values are perfectly in line with the literature ones. The modularity of our novel fully-electric reactor allows for applications in a number of industrial contexts, especially pharmaceutical ones.
Decision criteria and intelligent decision method for tunnel excavation scheme selection considering carbon emissions
Authors: Xia Zhenzhao , Mao Jingyin , Chen Guangyao , Wu Daguo , He Yao
Published: October 2022

The tunnel construction process is accompanied by high resource consumption and non-negligible greenhouse gas emissions. Reducing the carbon emissions from this process is an issue that should be considered in the decision-making stage. For tunnel construction using the drill-and-blast process, selecting a reasonable excavation scheme is a feasible method for reducing carbon emissions. This paper proposes an evaluation index system that takes into account the stability of the tunnel construction process and the reasonable assessment of carbon emission levels. For various scenarios with different focus on stability requirements, theoretical deductions are used to filter out the key indicators that should be used as assessment items. For the determination of carbon emission assessment indicators, this study is guided by the life cycle theory, and in the determined calculation boundary, the reference of previous projects and expert opinions are selected as the item source to fill the unfavorable situation in which the carbon emissions of different excavation schemes cannot be accurately calculated because of the lack of bills of quantities in the engineering decision stage. This paper also proposes an intelligent decision method based on a support vector machine to better complete the task of calculating and ranking the utility of excavation schemes to adapt the proposed multi-factor parallel evaluation system. Finally, the proposed decision indicator system and decision method were applied to the selection of the excavation scheme in an engineering case, and reasonable and realistic scoring results were obtained.
Emerging and legacy per-and polyfluoroalkyl substances in the rivers of a typical industrialized province of China: Spatiotemporal variations, mass discharges and ecological risks
Authors: Wang Runmei , Zhang Jian , Yang Yuanyuan , Chen Chang-Er , Zhang Daochang , Tang Jianhui
Published: October 2022

Per- and polyfluoroalkyl substances (PFAS) contamination has drawn considerable attention in the rivers of Shandong, China. However, their seasonal variations have not been well addressed due to the geographic scale. Here, surface waters were collected seasonally at estuaries of 13 major rivers in Shandong to investigate the spatiotemporal variations, mass discharges and ecological risks of PFAS. Two novel perfluoroalkyl ether carboxylic acids, hexafluoropropylene oxide-dimer acid (HFPO-DA) and hexafluoropropylene oxide-trimer acid (HFPO-TA), and 10 legacy PFAS were all detectable and their total concentrations (∑PFAS) ranged largely from 23 to 25,400 ng/L. Elevated levels of all target compounds were found in the Xiaoqing River but Majia and Jiaolai Rivers were also of concern. Perfluorooctanoic acid (PFOA) was dominant in all the rivers. Its concentration in the Xiaoqing River estuary increased 6-fold from 2011 to 2014 and reached a plateau during 2014–2020. The nonsignificant seasonality of the PFAS concentrations in rivers with seasonal flows may indicate their different emission patterns (i.e., higher emission in the wet season and lower emission in the dry season). The ratio of maximum to minimum concentration (Cmax/Cmin) was proposed to characterize the influence of local point sources, with Cmax/Cmin ranging from 10 to 14,000. Xiaoqing and Yellow Rivers discharged ∼98% of ∑PFAS flux to the sea, which was estimated to be 28.0 t in 2020. This study raises attention to the industrial emission patterns of PFAS. Further investigations with higher time resolution were needed to understand the emission patterns of PFAS in Shandong.
The prevalence and genetic disorders spectrum of thalassemia among breast cancer patients in Jiangxi province, China
Authors: Ding Jingxian , Huang Zhaohui , Jiang Xiaoliu , Li Qingge , Cao Yali , Guo Yonghong
Published: October 2022

Background: Thalassemia is a common inherited hematological disease with genetic disorders characterized by imbalanced synthesis of the globin chains. Due to the improvement of treatment methods, patients with thalassemia can survive for a long time. Therefore, it is not uncommon for patients with thalassemia suffering from malignant tumors. However, there are quite few reports on thalassemia patients complicated with breast cancer. Herein, we try to investigate the prevalence and genetic disorders spectrum of thalassemia in patients with breast cancer.

Methods: Blood routing tests and serum ferritin analysis were conducted in 1887 breast cancer patients treated in the department of radiation oncology during 1 April 2020 and 30 March 2022. The suspected thalassemia carriers with small mean corpuscular volume (MCV), mean corpuscular hemoglobin content (MCH) or mean corpuscular hemoglobin concentration (MCHC) but the concentration of serum ferritin within normal limits were further investigated by polymerase chain reaction (PCR) and flow through hybridization gene chip to detect common mutations of α-globin and β-globin genes using Thalassemia Geno Array Diagnostic Kit. The prevalence and genetic mutation spectrum of thalassemia among breast cancer patients were analyzed.

Results: Four hundred and eighty-nine suspected thalassemia carriers were detected by complete blood cell counts and serum ferritin analysis among 1887 breast cancer patients. One hundred and seven cases (5.7%) were identified as carriers of thalassemia, of which 55 cases (51.4%) were α-thalassemia, 50 cases (46.7%) were β-thalassemia, and 2 cases (1.9%) were co-inheritance of α-thalassemia and β-thalassemia simultaneously. In α-thalassemia, the most prevalent genotype is -SEA/αα; as for β-thalassemia, βIVS−II−654/β is the most common genotype. The degree of anemia is more severe in β-thalassemia than in α-thalassemia.

Conclusion: This is the first comprehensive molecular epidemiological investigation on thalassemia among breast cancer patients. Our data indicated that thalassemia was not uncommon in breast cancer patients. The physicians should have the knowledge to avoid misdiagnosis as iron deficiency anemia.
G3BP1 regulates breast cancer cell proliferation and metastasis by modulating PKCζ
Authors: Liu Shuang , Tian Shaoping , Lin Tianyu , He Xin , Eze Ideozu Justin , Wang Rui , Wang Yong , Yue Dan , Geng Hua
Published: October 2022

Breast cancer is a leading cause of death and morbidity among female cancers. Several factors, including hormone levels, lifestyle, and dysregulated RNA-binding proteins, have been associated with the development of breast cancer. Ras-GTPase-activating protein SH3 domain-binding protein 1 (G3BP1) and protein kinase C, Zeta isoform (PKCζ) are oncogenes implicated in numerous cancers, including breast cancer. However, their interaction and role in promoting breast cancer proliferation and metastasis have not been well-characterized. In the present study, we demonstrated that G3BP1 expression was elevated in breast cancer and that knockdown of G3BP1 diminished the proliferation and metastasis of breast cancer cells. Mechanistically, we identified proliferation and a series of metastasis-related properties, including chemotaxis, migration, Golgi polarity localization, and actin polymerization, that were modulated by G3BP1 knockdown. We found that G3BP1 and PKCζ were co-localized and interacted intracellularly, and they co-underwent membrane translocation under EGF stimulation. Following the knockdown of G3BP1, we observed the membrane translocation and phosphorylation of PKCζ were significantly impaired, suggesting that G3BP1 regulates the activation of PKCζ. Our findings indicate that G3BP1 plays multiple roles in breast cancer cell proliferation and metastasis. The activation of PKCζ by G3BP1 may be the specific mechanism underlying the process.
Causal association between rheumatoid arthritis and celiac disease: A bidirectional two-sample mendelian randomization study
Authors: Hua Lijiangshan , Xiang Shate , Xu Rixiang , Xu Xiao , Liu Ting , Shi Yanan , Wu Lingyun , Wang Rongyun , Sun Qiuhua
Published: October 2022

Objectives: Rheumatoid Arthritis (RA) has been associated with Celiac Disease (CD) in previous observational epidemiological studies. However, evidence for this association is limited and inconsistent, and it remains uncertain whether the association is causal or due to confounding or reverse causality. This study aimed to assess the bidirectional causal relationship between RA and CD.

Methods: In this two-sample Mendelian randomization (MR) study, instrumental variables (IVs) for RA were derived from a genome-wide association studies (GWAS) meta-analysis including 58,284 subjects. Summary statistics for CD originated from a GWAS meta-analysis with 15,283 subjects. The inverse-variance weighted (IVW) method was used as the primary analysis. Four complementary methods were applied, including the weighted-median, weighted mode, MR pleiotropy residual sum and outlier (MR-PRESSO) test and MR-Egger regression, to strengthen the effect estimates.

Results: Positive causal effects of genetically increased RA risk on CD were derived [IVW odds ratio (OR): 1.46, 95% confidence interval (CI): 1.19–1.79, p = 3.21E-04]. The results of reverse MR analysis demonstrated no significant causal effect of CD on RA (IVW OR: 1.05, 95% CI: 0.91–1.21, p = 0.499). According to the sensitivity analysis, horizontal pleiotropy was unlikely to distort the causal estimates.

Conclusion: This study reveals a causality of RA on CD but not CD on RA among patients of European descent. This outcome suggests that the features and indicators of CD should regularly be assessed for RA patients.
Case report: De novo pathogenic variant in WFS1 causes Wolfram-like syndrome debuting with congenital bilateral deafness
Authors: Alías Laura , López de Heredia Miguel , Luna Sabina , Clivillé Núria , González-Quereda Lídia , Gallano Pía , de Juan Júlia , Pujol Albert , Diez Santiago , Boronat Susana , Orús César , Lasa Adriana , Venegas María del Prado
Published: October 2022

Background: Congenital deafness could be the first manifestation of a syndrome such as in Usher, Pendred, and Wolfram syndromes. Therefore, a genetic study is crucial in this deficiency to significantly improve its diagnostic efficiency, to predict the prognosis, to select the most adequate treatment required, and to anticipate the development of other associated clinical manifestations.

Case presentation: We describe a young girl with bilateral congenital profound deafness, who initially received a single cochlear implant. The genetic study of her DNA using a custom-designed next-generation sequencing (NGS) panel detected a de novo pathogenic heterozygous variant in the WFS1 gene related to Wolfram-like syndrome, which is characterized by the presence of other symptoms such as optic atrophy. Due to this diagnosis, a second implant was placed after the optic atrophy onset. The speech audiometric results obtained with both implants indicate that this work successfully allows the patient to develop normal speech. Deterioration of the auditory nerves has not been observed.

Conclusion: The next-generation sequencing technique allows a precise molecular diagnosis of diseases with high genetic heterogeneity, such as hereditary deafness, while this was the only symptom presented by the patient at the time of analysis. The NGS panel, in which genes responsible for both syndromic and non-syndromic hereditary deafness were included, was essential to reach the diagnosis in such a young patient. Early detection of the pathogenic variant in the WFS1 gene allowed us to anticipate the natural evolution of the disease and offer the most appropriate management to the patient.
Myokine myostatin is a novel predictor of one-year radiographic progression in patients with rheumatoid arthritis: A prospective cohort study
Authors: Lin Jian-Zi , Ma Jian-Da , Yang Li-Juan , Zou Yao-Wei , Zhang Xue-Pei , Pan Jie , Li Qian-Hua , Li Hong-Gui , Yang Ze-Hong , Wu Tao , Zhang Qian , Mo Ying-Qian , Dai Lie
Published: October 2022

Background

Associations between rheumatoid arthritis (RA) and reduced skeletal muscle have been studied, and we firstly reported myopenia independently predict one-year radiographic progression in RA. Myokine myostatin can negatively regulate skeletal muscle mass and promote osteoclast differentiation. However, there is no report about their relationships in RA patients. We firstly explored the relationship of serum myostatin and disease characteristics, as well as aggravated joint destruction during one-year follow-up.

Methods

Consecutive RA patients were recruited from a real-world prospective cohort and completed at least one-year follow-up. Baseline serum level of myostatin was measured by enzyme-linked immunosorbent assay. Clinical data in RA patients as well as muscle index in both RA patients and healthy controls were collected. One-year radiographic progression as primary outcome was defined by a change in the total Sharp/van der Heijde modified score ≥0.5 units.

Results

Totally 344 RA patients (age 47.9 ± 12.5 years, 84.0% female) and 118 healthy control subjects (age 42.8 ± 11.3 years, 74.6% female) were recruited. Compared with healthy controls, RA patients showed a higher level of serum myostatin at baseline (3.241 ± 1.679 ng/ml vs. 1.717 ± 0.872 ng/ml, P<0.001), although lower appendicular skeletal muscle mass index (ASMI, 6.0 ± 0.9 kg/m2vs. 6.5 ± 1.0 kg/m2, P<0.001). In RA patients, those with high myostatin level showed a higher rate of radiographic progression than low myostatin group (45.3% vs. 18.6%, P<0.001). Furtherly, RA patients were stratified into four subgroups according to serum myostatin and myopenia. Compared with other three subgroups, RA patients with high myostatin overlapping myopenia had the highest rate of radiographic progression (67.2% vs. 10.3%-31.4%, P<0.001), as well as the lowest proportion of remission and the highest rate of physical dysfunction during one-year follow-up. After adjustment for confounding factors, high serum myostatin (AOR=3.451, 95%CI: 2.016-5.905) and myopenia (AOR=2.387, 95%CI: 1.416-4.022) at baseline were risk factors for one-year radiographic progression, especially for those with high myostatin overlapping myopenia (AOR=10.425, 95%CI: 3.959-27.450) as the highest-risk individuals among four subgroups. Significant synergistic interaction effect was observed between high myostatin and myopenia on one-year radiographic progression (AP=66.3%, 95%CI: 43.2%-89.3%).

Conclusion

Myostatin is a novel predictor of aggravated joint destruction in RA patients which has synergistic interaction with myopenia for predicting value.
STAT3 signaling modulates the immune response induced after antigen targeting to conventional type 1 dendritic cells through the DEC205 receptor
Authors: Sulczewski Fernando Bandeira , Martino Larissa Alves , Salles Davi , Yamamoto Márcio Massao , Rosa Daniela Santoro , Boscardin Silvia Beatriz
Published: October 2022

Conventional dendritic cells (cDC) are a group of antigen-presenting cells specialized in priming T cell responses. In mice, splenic cDC are divided into conventional type 1 DC (cDC1) and conventional type 2 (cDC2). cDC1 are specialized to prime the Th1 CD4+ T cell response, while cDC2 are mainly associated with the induction of follicular helper T cell responses to support germinal center formation. However, the mechanisms that control the functions of cDC1 and cDC2 are not fully understood, especially the signaling pathways that can modulate their ability to promote different CD4+ T cell responses. Here, we targeted a model antigen for cDC1 and cDC2, through DEC205 and DCIR2 receptors, respectively, to study the role of the STAT3 signaling pathway in the ability of these cells to prime CD4+ T cells. Our results show that, in the absence of the STAT3 signaling pathway, antigen targeting to cDC2 induced similar frequencies of Tfh cells between STAT3-deficient mice compared to fully competent mice. On the other hand, Th1 and Th1-like Tfh cell responses were significantly reduced in STAT3-deficient mice after antigen targeting to cDC1 via the DEC205 receptor. In summary, our results indicate that STAT3 signaling does not control the ability of cDC2 to promote Tfh cell responses after antigen targeting via the DCIR2 receptor, but modulates the function of cDC1 to promote Th1 and Th1-like Tfh T cell responses after antigen targeting via the DEC205 receptor.
Photoactivated adenylyl cyclases attenuate sepsis-induced cardiomyopathy by suppressing macrophage-mediated inflammation
Authors: Xia Guofang , Shi Hongyu , Su Yuanyuan , Han Beibei , Shen Chengxing , Gao Shiqiang , Chen Zhong , Xu Congfeng
Published: October 2022

Sepsis-induced myocardiopathy, characterized by innate immune cells infiltration and proinflammatory cytokines release, may lead to perfusion failure or even life-threatening cardiogenic shock. Macrophages-mediated inflammation has been shown to contribute to sepsis-induced myocardiopathy. In the current study, we introduced two photoactivated adenylyl cyclases (PACs), Beggiatoa sp. PAC (bPAC) and Beggiatoa sp. IS2 PAC (biPAC) into macrophages by transfection to detect the effects of light-induced regulation of macrophage pro-inflammatory response and LPS-induced sepsis-induced myocardiopathy. By this method, we uncovered that blue light-induced bPAC or biPAC activation considerably inhibited the production of pro-inflammatory cytokines IL-1 and TNF-α, both at mRNA and protein levels. Further, we assembled a GelMA-Macrophages-LED system, which consists of GelMA—a type of light crosslink hydrogel, gene modulated macrophages and wireless LED device, to allow light to regulate cardiac inflammation in situ with murine models of LPS-induced sepsis. Our results showed significant inhibition of leukocytes infiltration, especially macrophages and neutrophils, suppression of pro-inflammatory cytokines release, and alleviation of sepsis-induced cardiac dysfunction. Thus, our study may represent an emerging means to treat sepsis-induced myocardiopathy and other cardiovascular diseases by photo-activated regulating macrophage function.