bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of dam construction on the reproduction of the Yellow River carp (Cyprinus carpio) in lower reaches of the Yellow River, China
Authors: Ruan Qiongyao , Li Wenda , Zhang Shanghong , Tang Caihong , Hou Jun
Published: January 2023

The construction of dams changes the natural flow of rivers, affects the integrity of river ecosystems, and causes a series of ecological and environmental problems, such as habitat fragmentation and reduction in fish resources. This study took a section of the Yellow River in China from the Xiaolangdi Dam to Gaocun as the research area. The Yellow River carp (Cyprinus carpio) was selected as an indicator species for its economic value. A habitat suitability model for the Yellow River carp coupled with a one-dimensional hydrodynamic model was built. It was used to simulate dynamic changes in the reproductive habitat suitability of the Yellow River carp before and after the construction of the Xiaolangdi Dam. We demonstrated the spatial distribution of the carp’s spawning reaches before and after the Xiaolangdi Dam construction and investigated its influence on the spawning activity and larval development of the species accordingly. The results apparently showed that the construction and operation of the Xiaolangdi Dam delayed the breeding time of the Yellow River carp and decreased its quality by 5.28%. In particular, the larval fish development was greatly affected by the dam, with the quality being reduced by 8.95%. Furthermore, the habitat suitability of the spawning reaches slightly decreased as the extent of spawning reaches decreased by 16.23%, and several spawning reaches were lost entirely. This study shed light on the response of the Yellow River carp to hydrological and physical changes in the period 1980–1990 before the construction of the Xiaolangdi Dam and 2006–2018 after the construction. Thus, it is a valuable reference for the ecological scheduling of discharges of the Xiaolangdi Dam.
Systematic errors in annotations of truncations, loss-of-function and synonymous variants
Authors: Vihinen Mauno
Published: January 2023

Description of genetic phenomena and variations requires exact language and concepts. Vast amounts of variation data are produced with next-generation sequencing pipelines. The obtained variations are automatically annotated, e.g., for their functional consequences. These tools and pipelines, along with systematic nomenclature, mainly work well, but there are still some problems in nomenclature, organization of some databases, misuse of concepts and certain practices. Therefore, systematic errors prevent correct annotation and often preclude further analysis of certain variation types. Problems and solutions are described for presumed protein truncations, variants that are claimed to be of loss-of-function based on the type of variation, and synonymous variants that are not synonymous and lead to sequence changes or to missing protein.
Inflammation and histone modification in chronic pain
Authors: Jiang Wei , Zhang Li-Xi , Tan Xuan-Yu , Yu Peng , Dong Ming
Published: January 2023

Increasing evidence suggests that epigenetic mechanisms have great potential in the field of pain. The changes and roles of epigenetics of the spinal cord and dorsal root ganglia in the chronic pain process may provide broad insights for future pain management. Pro-inflammatory cytokines and chemokines released by microglia and astrocytes, as well as blood-derived macrophages, play critical roles in inducing and maintaining chronic pain, while histone modifications may play an important role in inflammatory metabolism. This review provides an overview of neuroinflammation and chronic pain, and we systematically discuss the regulation of neuroinflammation and histone modifications in the context of chronic pain. Specifically, we analyzed the role of epigenetics in alleviating or exacerbating chronic pain by modulating microglia, astrocytes, and the proinflammatory mediators they release. This review aimed to contribute to the discovery of new therapeutic targets for chronic pain.
A novel assay that characterizes properdin function shows neutrophil-derived properdin has a distinct oligomeric distribution
Authors: Moore Sara R. , Menon Smrithi S. , Galwankar Neeti S. , Khuder Sadik A. , Pangburn Michael K. , Ferreira Viviana P.
Published: January 2023

Properdin acts as an essential positive regulator of the alternative pathway of complement by stabilizing enzymatic convertases. Identical properdin monomers form head-to-tail associations of oligomers in a reported 20:54:26 ratio (most often described as an approximate 1:2:1 ratio) of tetramers (P4), trimers (P3), and dimers (P2), in blood, under normal physiological conditions. Oligomeric size is proportional to properdin function with tetramers being more active, followed by trimers and dimers. Neutrophils are the most abundant granulocyte, are recruited to inflammatory microenvironments, and are a significant source of properdin, yet the ratio of properdin oligomers released from neutrophils is unknown. The oligomer ratio of neutrophil-derived properdin could have functional consequences in local microenvironments where neutrophils are abundant and complement drives inflammation. We investigated the oligomer properties of neutrophil-derived properdin, as compared to that of normal human sera, using a novel ELISA-based method that detects function of properdin in a way that was proportional to the oligomeric size of properdin (i.e., the larger the oligomer, the higher the detected function). Unexpectedly, neutrophil-derived properdin had 5-fold lower function than donor-matched serum-derived properdin. The lower function was due to a lower percentage of tetramers/trimers and more dimers, indicating a significantly different P4:P3:P2 ratio in neutrophil-derived properdin (18:34:48) as compared to donor-matched serum (29:43:29). Release of lower-order oligomers by neutrophils may constitute a novel regulatory mechanism to control the rate of complement activation in cellular microenvironments. Further studies to determine the factors that affect properdin oligomerization and whether, or how, the predominant dimers in neutrophil-derived properdin, assimilate to the ~1:2:1 ratio found in serum are warranted.
Revisiting the biogenic silica burial flux determinations: A case study for the East China seas
Authors: Zhu Dongdong , Sutton Jill N. , Leynaert Aude , Tréguer Paul J. , Schoelynck Jonas , Gallinari Morgane , Ma Yuwei , Liu Su Mei
Published: January 2023

The Coastal and Continental Margin Zones (CCMZs) contribute to 40% of the total burial flux of biogenic silica (bSi) of the world ocean. However, the accurate determination of the bSi content (bSiO2%) in marine sediments remains a challenge. The alkaline methods commonly used to quantitatively determine bSiO2% can completely digest the amorphous silica of diatoms but are less effective at digesting radiolarians and sponge spicules. In addition, the lithogenic silica (lSi) found in sediments is partly digested during these alkaline extractions, which can bias the accuracy of the determined bSiO2%. This is of importance in CCMZs where the lSi:bSi ratio is high. In this study, we examined sediments collected in the CCMZs of East China seas, an environment of peculiar interest given the large amount of lSi deposited by the Yellow River and the Yangtze River. The results show that alkaline digestions using stronger solutions and pretreatment steps resulted in an overestimate of the bSiO2% due to increased leaching of silica mainly from authigenic silicates and clays, whereas weak digestions underestimated the bSiO2% owing to incomplete digestion of sponge spicules. We found that the use of the Si/Al method accurately corrects for the lSi fraction in marine sediments, and thereby improves the determinations of bSiO2% in the sediments of East China seas CCMZs. Ensuring full digestion of all bSi remains challenging, in particular for sponge spicules, motivating both verifications via microscopy and longer extraction times. To emphasize the influence of these methodological differences, we revised the bSi burial flux in the East China seas and provide a new estimate of 253 (± 286) Gmol-SiO2 yr-1, which is one third of the previous estimates. We discuss the potential contribution from radiolarian and sponges and we propose a new general protocol for the determination of bSi in sediments that minimizes the methodological bias in bSi determination.
Fisheries impact on the Sea of Marmara ecosystem structure and functioning during the last three decades
Authors: Saygu İsmet , Akoglu Ekin , Gül Güzin , Bedikoğlu Dalida , Demirel Nazli
Published: January 2023

The Sea of Marmara (SoM), without doubt, is one of the most disturbed marine ecosystems of the Mediterranean basin. As a semi-enclosed and a recognized eutrophic basin, it has a unique natural characteristic by permanent stratification at ~25 m depth. The SoM ecosystem is under threat by multiple stressors from excessive nutrient enrichment, overfishing, invasive species, habitat loss to the climate change. Within this study, an assessment on the SoM ecosystem structure and functioning and its changes over time have been achieved. Hence, we firstly evaluate the SoM ecosystem over a period of three decades from the 1990s to the 2010s by using three mass-balance Ecopath models, secondly, we delineate the prevailing ecosystem structure and functioning in each period, thirdly we determine how the fishing impact contributed to the changes in the SoM since the 1990s and finally establish a baseline for the management and future studies of the ecosystem. The comparison of the models’ results for three consecutive time periods of the SoM showed that the energetic capacity of the ecosystem decreased significantly over the three decades while the decrease in cycling indices indicated that the SoM ecosystem became fragile to anthropogenic disturbances. According to ecosystem theory indices, the SoM is an immature ecosystem at a stage of autotrophic succession, with a very high total primary production, much more above unity that greatly exceeds total respiration. Our results highlighted that the SoM ecosystem was under bottom-up control exerted by mesozooplankton; however, anchovy was a bottleneck in energy transfers to higher trophic levels creating also a wasp-waist control in the food-web. The bycatch of demersal species with long life span, sharks and rays, brought them to the brink of going commercial extinction. Overall, the changes in the SoM ecosystem were due to the trophic cascades exerted by fisheries exploitation in addition to the changes in the productivity of the system. We conclude that the concomitant impacts of stressors on the SoM have been so diverse that an immediate action plan is required. Therefore, we propose a tentative outlook that will help in ecosystem monitoring and better management of the SoM.
Investigation of the physical-mechanical properties and durability of high-strength concrete with recycled PET as a partial replacement for fine aggregates
Authors: Qaidi Shaker , Al-Kamaki Yaman , Hakeem Ibrahim , Dulaimi Anmar F. , Özkılıç Yasin , Sabri Mohanad , Sergeev Vitaly
Published: January 2023

In this study, PET plastic waste, which is a type of polymer commonly used in the manufacture of plastic bottles, has been incorporated into concrete by partially replacing the natural fine aggregate. An experimental study was conducted by casting and testing 90 concrete cylinders and 54 concrete cubes. A concrete mixture was designed in which the natural fine aggregate was substituted partially with PET plastic waste (PW) at a ratio of 0%, 25%, and 50%, with various w/c ratios of .40, .45, and .55. Physical, mechanical, and durability properties were assessed. The downside of the test results show degradation in each of the following characteristics: slump, compressive strength, splitting tensile strength, ultrasonic pulse velocity, water absorption, and porosity. The degradation of these characteristics increased with the increase in the volume of plastic aggregate (PA) and the w/c ratio. While the positive side of the results showed that with the increase of the PA volume and the w/c ratio, the fresh and dry densities decreased further, and by using 50% PET, the dry density became below 2000 kg/m3. Therefore, it is classified as lightweight concrete. Moreover, the fracture of concrete changed from brittle to more ductile compared to control concrete. Also, the thermal conductivity decreased significantly (11%–47%), and by using 50% of PET, the thermal conductivity became less than .71 W/mK, and accordingly, classified as a bearing insulator.
Study on the mechanical characteristics of a fibre reinforced flexible pipe under radial compression loads
Authors: Sun Zhenwen , Huang Weiping , Lu Hailong , Yan Jun , Yin Yuanchao , Bu Yufeng
Published: January 2023

Fibre reinforced flexible pipes are subjected to radial compression loads caused by the tensioner during pipe laying, which may lead to excessive deformation or even damage of the pipe. In this study, the mechanical characteristics of a glass fibre reinforced unbonded flexible pipe are investigated under radial compression loading. In the theoretical analysis, the hoop reinforcement layer of the pipe is considered equivalent to an orthotropic circular tube. An analytical equation for calculating the radial stiffness of the circular tube per unit length is then derived based on the classical elastic theory of the ring. Radial compression tests are carried out with a universal testing machine and displacement loading within the elastic deformation range is applied to two 500 mm long samples. A 3D numerical model is established to simulate the compression process of the flexible pipe, through which the distribution characteristics of the displacement, strain and stress of the hoop reinforcement layer are also obtained. The load-displacement curves obtained from the tests and numerical model are linearly fitted to calculate the radial stiffness of the pipe. The radial stiffness obtained by the numerical model is very close to that obtained by the analytical method. However, owing to factors such as material defects and initial ovality, the radial stiffness measured experimentally is lower than the analytical result.
Stromal cells support the survival of human primary chronic lymphocytic leukemia (CLL) cells through Lyn-driven extracellular vesicles
Authors: de Oliveira Thaís Dolzany , vom Stein Alexander , Rebollido-Rios Rocio , Lobastova Liudmila , Lettau Marcus , Janssen Ottmar , Wagle Prerana , Nguyen Phuong-Hien , Hallek Michael , Hansen Hinrich P.
Published: January 2023

Introduction

In chronic lymphocytic leukemia (CLL), the tumor cells receive survival support from stromal cells through direct cell contact, soluble factors and extracellular vesicles (EVs). The protein tyrosine kinase Lyn is aberrantly expressed in the malignant and stromal cells in CLL tissue. We studied the role of Lyn in the EV-based communication and tumor support.

Methods

We compared the Lyn-dependent EV release, uptake and functionality using Lyn-proficient (wild-type) and -deficient stromal cells and primary CLL cells.

Results

Lyn-proficient cells caused a significantly higher EV release and EV uptake as compared to Lyn-deficient cells and also conferred stronger support of primary CLL cells. Proteomic comparison of the EVs from Lyn-proficient and -deficient stromal cells revealed 70 significantly differentially expressed proteins. Gene ontology studies categorized many of which to organization of the extracellular matrix, such as collagen, fibronectin, fibrillin, Lysyl oxidase like 2, integrins and endosialin (CD248). In terms of function, a knockdown of CD248 in Lyn+ HS-5 cells resulted in a diminished B-CLL cell feeding capacity compared to wildtype or scrambled control cells. CD248 is a marker of certain tumors and cancer-associated fibroblast (CAF) and crosslinks fibronectin and collagen in a membrane-associated context.

Conclusion

Our data provide preclinical evidence that the tyrosine kinase Lyn crucially influences the EV-based communication between stromal and primary B-CLL cells by raising EV release and altering the concentration of functional molecules of the extracellular matrix.
Synergistic effect of Bacillus subtilis and Paecilomyces lilacinus in alleviating soil degradation and improving watermelon yield
Authors: Chen Peng , Zhang Jinglei , Li Mei , Fang Feng , Hu Jindong , Sun Zuowen , Zhang Ansheng , Gao Xingxiang , Li Jian
Published: January 2023

Continuous cropping of watermelon (Citrullus lanatus) may lead to soil degradation. As a soil conditioner, microbial agent has great potential in improving soil function and enhancing plant growth. In this study, we aimed to explore how microbial agent relieves the soil sickness of watermelon by analyzing watermelon performance, soil physicochemical properties and microbial community structures. Results suggested that microbial agent treatments significantly changed the photosynthetic efficiency of upper and lower leaves, which helped improve the growth of watermelon. The single fruit weight, fruit sugar degree and total phosphorus of soil following treatment with a mixture of Paecilomyces lilacinus DZ910 and Bacillus subtilis KC1723 (treatment D_K) were higher than those in single biofertilizer treatments and control. The soil microbial community under microbial agent treatments also changed significantly, indicating the feasibility of using microbial agents as soil remediations. The proportions of Pseudomonas and Flavobacterium, changed significantly after using microbial agents. Pseudomonas increased significantly after B. subtilis KC1723 and D_K treatments, while Flavobacterium increased significantly after using all three kinds of microbial agents compared to control. Increases in these bacteria were positively correlated with agronomic variables of watermelon. The fungi Aspergillus and Neocosmospora in the soil, which create an soil sickness of watermelon, decreased after KC1723 and D_K treatments. Meanwhile, Aspergillus and Neocosmospora were positively related to Myceliophthora incidence and negatively correlated with watermelon growth (single fruit weight and photosynthetic efficiency of upper leaves). Our microbial agent, especially D_K, represents a useful technique for alleviating soil sickness in watermelon.
Recent advances in ferroptosis and therapeutic strategies for glioblastoma
Authors: Lu Qixiong , Lu Xiaoyang , Zhang Yuansheng , Huang Wei , Zhou Hu , Li Tao
Published: January 2023

Ferroptosis is an emerging form of cell death characterized by the over-accumulation of iron-dependent lipid peroxidation. Ferroptosis directly or indirectly disturbs glutathione peroxidases cycle through diverse pathways, impacting the cellular antioxidant capacities, aggravating accumulation of reactive oxygen species in lipid, and it finally causes oxidative overload and cell death. Ferroptosis plays a significant role in the pathophysiological processes of many diseases. Glioblastoma is one of the most common primary malignant brain tumors in the central nervous system in adults. Although there are many treatment plans for it, such as surgical resection, radiotherapy, and chemotherapy, they are currently ineffective and the recurrent rate is almost up to 100%. The therapies abovementioned have a strong relationship with ferroptosis at the cellular and molecular level according to the results reported by numerous researchers. The regulation of ferroptosis can significantly determine the outcome of the cells of glioblastoma. Thus ferroptosis, as a regulated form of programed cell death, has the possibility for treating glioblastoma.
Activity-regulated growth of motoneurons at the neuromuscular junction is mediated by NADPH oxidases
Authors: Sobrido-Cameán Daniel , Oswald Matthew C. W. , Bailey David M. D. , Mukherjee Amrita , Landgraf Matthias
Published: January 2023

Neurons respond to changes in the levels of activity they experience in a variety of ways, including structural changes at pre- and postsynaptic terminals. An essential plasticity signal required for such activity-regulated structural adjustments are reactive oxygen species (ROS). To identify sources of activity-regulated ROS required for structural plasticity in vivo we used the Drosophila larval neuromuscular junction as a highly tractable experimental model system. For adjustments of presynaptic motor terminals, we found a requirement for both NADPH oxidases, Nox and dual oxidase (Duox), that are encoded in the Drosophila genome. This contrasts with the postsynaptic dendrites from which Nox is excluded. NADPH oxidases generate ROS to the extracellular space. Here, we show that two aquaporins, Bib and Drip, are necessary ROS conduits in the presynaptic motoneuron for activity regulated, NADPH oxidase dependent changes in presynaptic motoneuron terminal growth. Our data further suggest that different aspects of neuronal activity-regulated structural changes might be regulated by different ROS sources: changes in bouton number require both NADPH oxidases, while activity-regulated changes in the number of active zones might be modulated by other sources of ROS. Overall, our results show NADPH oxidases as important enzymes for mediating activity-regulated plasticity adjustments in neurons.
Presenting symptoms as prognostic measures of mental health recovery among service members with concussion
Authors: Remigio-Baker Rosemay A. , Hungerford Lars D. , Ettenhofer Mark L. , Barnard Lori L. , Babakhanyan Ida , Ivins Brian , Stuessi Keith , Monasterio Carlos Diego J. , Bailie Jason M.
Published: January 2023

Background

Comorbid mental illness may negatively impact recovery from concussion. This study evaluated whether the level of symptom clusters at clinic intake contribute to poor mental health recovery in concussed patients during treatment, which may in turn serve as a target intervention.

Objective

The objective of this study is to examine the association between the level of initial symptoms and mental health symptoms among service members with concussion.

Methods

Data were obtained from 483 active duty service members treated in interdisciplinary treatment programs for traumatic brain injury, all of which were concussions. Pre-treatment symptom clusters included self-reported hyperarousal, dissociation/depression, cognitive dysfunction/headache and neurological symptoms. The outcomes, clinically-relevant decreases in depressive symptoms (assessed by the 8-item Patient Health Questionnaire, PHQ-8) and PTSD symptoms (assessed by the PTSD Checklist for DSM-5, PCL-5), were defined as a decrease in PHQ-8 > 5 and PCL-5 > 7, respectively. Poisson regression with robust error variance was used to evaluate the relationship between the level of each symptom cluster and clinically-relevant decrease in outcomes.

Results

Participants with higher (vs. lower) levels of pre-treatment hyperarousal and dissociation/depression symptom cluster were less likely to improve in depressive and PTSD symptoms during treatment. The level of cognitive/headache and neurological symptom clusters were not significantly associated with any symptom changes.

Conclusion

These findings support the need for individualized treatment for symptoms identified and treated after determining concussion history, with particular attention to high levels of hyperarousal and dissociation/depression prior to treatment.
Microvascular impairments detected by optical coherence tomography angiography in multiple sclerosis patients: A systematic review and meta-analysis
Authors: Liu Jing , Song Shuang , Gu Xiaoya , Li Hui , Yu Xiaobing
Published: January 2023

Purpose

A systematic review and meta-analysis was conducted to investigate changes in retinal and choroidal microvasculature in patients with multiple sclerosis (MS) using optical coherence tomography angiography (OCTA).

Methods

PubMed and Google Scholar were searched for studies that compared retinal and choroidal microvasculature between MS and healthy controls (HC) with OCTA. MS patients were divided into 2 groups: MS with (MSON) or without optic neuritis (MSNON).

Results

Totally, 13 studies including 996 MS eyes and 847 HC eyes were included. Compared with the HC, the vessel density of the whole superficial vascular complex (SVC) was reduced by 2.27% and 4.30% in the MSNON and MSON groups, respectively. The peripapillary vessel density was 2.28% lower and 4.96% lower in the MSNON and MSON groups, respectively, than in the HC. Furthermore, the MSON group had significant lower vessel density of the SVC (mean difference [MD] = −2.17%, P < 0.01) and lower peripapillary vessel density (MD = −2.02%, P = 0.02) than the MSNON group. No significant difference was found in the deep vascular complex or choriocapillaris densities among MSNON, MSON or HC groups (P > 0.05). Meta-regression analyses suggested that illness duration and the Expanded Disability Status Scale scores of MS patients were possible sources of heterogeneity (P < 0.05).

Conclusion

The retinal SVC and peripapillary vessel density decreased significantly in MS eyes, especially in eyes with optic neuritis. Retinal microvasculature is a potential biomarker of disease progression in MS.
Pepperberg plot: Modeling flash response saturation in retinal rods of mouse
Authors: Caruso Giovanni , Klaus Colin , Hamm Heidi E. , Gurevich Vsevolod V. , Bisegna Paolo , Andreucci Daniele , DiBenedetto Emmanuele , Makino Clint L.
Published: January 2023

Retinal rods evolved to be able to detect single photons. Despite their exquisite sensitivity, rods operate over many log units of light intensity. Several processes inside photoreceptor cells make this incredible light adaptation possible. Here, we added to our previously developed, fully space resolved biophysical model of rod phototransduction, some of the mechanisms that play significant roles in shaping the rod response under high illumination levels: the function of RGS9 in shutting off G protein transducin, and calcium dependences of the phosphorylation rates of activated rhodopsin, of the binding of cGMP to the light-regulated ion channel, and of two membrane guanylate cyclase activities. A well stirred version of this model captured the responses to bright, saturating flashes in WT and mutant mouse rods and was used to explain “Pepperberg plots,” that graph the time during which the response is saturated against the natural logarithm of flash strength for bright flashes. At the lower end of the range, saturation time increases linearly with the natural logarithm of flash strength. The slope of the relation (τD) is dictated by the time constant of the rate-limiting (slowest) step in the shutoff of the phototransduction cascade, which is the hydrolysis of GTP by transducin. We characterized mathematically the X-intercept (Φo) which is the number of photoisomerizations that just saturates the rod response. It has been observed that for flash strengths exceeding a few thousand photoisomerizations, the curves depart from linearity. Modeling showed that the “upward bend” for very bright flash intensities could be explained by the dynamics of RGS9 complex and further predicted that there would be a plateau at flash strengths giving rise to more than ~107 photoisomerizations due to activation of all available PDE. The model accurately described alterations in saturation behavior of mutant murine rods resulting from transgenic perturbations of the cascade targeting membrane guanylate cyclase activity, and expression levels of GRK, RGS9, and PDE. Experimental results from rods expressing a mutant light-regulated channel purported to lack calmodulin regulation deviated from model predictions, suggesting that there were other factors at play.
Exercise reduces the anxiogenic effects of meta-chlorophenylpiperazine: The role of 5-HT2C receptors in the bed nucleus of the stria terminalis
Authors: Fox James H. , Boucher Melissa N. , Abedrabbo Khalil S. , Hare Brendan D. , Grimmig Bethany A. , Falls William A. , Hammack Sayamwong E.
Published: January 2023

Introduction

Two weeks of voluntary exercise in group-housed mice produces a reduction in anxiety-like behaviors across a number of different measures, including a reduction in the anxiety levels typically produced by the anxiogenic serotonergic drug m-chlorophenylpiperazine (mCPP), an agonist at 5-HT2C/2b receptors. We have previously demonstrated that 2-weeks of voluntary exercise blunted the anxiogenic effects of systemic mCPP, and we have also shown that mCPP infused into the bed nucleus of the stria terminalis (BNST) is anxiogenic. Here we follow up on these reports.

Methods

In Experiment 1 we infused several doses of mCPP into the BNST with or without the 5-HT2C antagonist SB242084. In Experiment 2, we administered mCPP into amygdala subregions and the dorsal hippocampus to investigate site specificity. In Experiment 4 we lesioned the BNST and subsequently infused mCPP systemically, and in Experiment 4 we used RNAscope® to assess BNST 5-HT2C transcripts following wheel running.

Results

BNST mCPP infusion increased acoustic startle responding, which was by 5-HT2C antagonism, while neither mCPP infused into the amygdala nor hippocampus was anxiogenic. Lesions of the BNST prevented the anxiogenic effect of systemically administered mCPP. Lastly, exercise reduced 5-HT2C transcripts in the BNST.

Discussion

These results suggest that the BNST is a critical site of action for the effects of exercise on mCPP. Together these data suggest that exercise may reduce 5-HT2C receptor function in the BNST, which may, in part, explain some of the anxiolytic effects associated with wheel running.
Association of vitamin and/or nutritional supplements with fall among patients with diabetes: A prospective study based on ACCORD and UK Biobank
Authors: He Lingfang , Ma Tianqi , Zhang Guogang , Cheng Xunjie , Bai Yongping
Published: January 2023

Aims

To assess the associations of vitamin and/or nutritional supplements (VNS) with falls among patients with diabetes.

Methods

9,141 and 21,489 middle-aged participants with diabetes from Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial and UK Biobank were included. Use of VNS was collected at baseline, and fall events were recorded using annual questionnaires in ACCORD and electric records in UK Biobank during follow-up. The associations of VNS use with fall risk were analyzed using logistic regression models in ACCORD and Fine-Gray sub-distribution hazard models in UK Biobank. The role of specific supplements was also estimated in UK Biobank, adjusting for confounding factors and multiple comparisons.

Results

45.9% (4,193/9,141, 5.5 median follow-up years) patients in ACCORD and 10.5% (2,251/21,489, 11.9 median follow-up years) in UK Biobank experienced fall and in-patient events during follow-up, respectively. In ACCORD, VNS using was associated with an increased risk of fall (full-adjusted odds ratio [OR]: 1.26, P < 0.05). In UK Biobank, despite no significant association between VNS overall and in-patient fall, vitamin B, calcium, and iron using increased the risk of falls significantly (full-adjusted hazard ratio range: 1.31–1.37, P < 0.05).

Conclusions

Use of specific VNS increased the risk of fall among patients with diabetes. The non-indicative use of nutritional supplements for patients with diabetes might be inadvisable.
Recovery of a hypolipidemic polysaccharide from artificially cultivated Sanghuangporus vaninii with an effective method
Authors: Zhang Zuo-fa , Song Ting-ting , Chen Jian-fei , Lv Guo-ying
Published: January 2023

In this study, an effective method was developed to extract the polysaccharide from Sanghuangporus vaninii (PFSV) by destroying the cell wall. Box-Behnken design was employed to determine the optimal processing conditions as follows: processing temperature (80°C), processing time (0.81 h) and amount of HCl (1.5 ml). Under these conditions, the yield of PFSV reached 5.94 ± 0.16%. The purified polysaccharide (PFSV-2) was found to be a hetero-polysaccharide with an average molecular weight of 20.377 kDa. The backbone of PFSV-2 was composed of an →6)-α-Galp-(1→ and →2,6)-β-Manp-(1→ and →2)-α-Fucp-(1→ and was branched of t-α-Manp-(1→ at position 2 of residue B. PFSV-2 showed hypolipidemic activity by decreasing lipid accumulation and the levels of total cholesterol and triglycerides in zebrafish larvae. Furthermore, PFSV-2 downregulated the pparg, fasn, and HMGCRb genes and upregulated the pparab and acaca genes. These findings suggested PFSV-2 may be a promising candidate in lipid regulation therapy.
A four oxidative stress gene prognostic model and integrated immunity-analysis in pancreatic adenocarcinoma
Authors: Wang Hao , Tian Ruo-Fei , Liang Xue , Fan Jing , Duan Zi-Chuan , Fan Xin-Yu , Zhang Jia-Jia , Yao Dong-Sheng , Chen Zhi-Nan , Li Ling
Published: January 2023

Background and aims

Pancreatic adenocarcinoma (PAAD) is highly aggressive and characterized by a poor prognosis. Oxidative stress has great impacts on the occurrence and development of tumors. However, the predictive role of oxidative stress related genes on PAAD patients’ prognosis remains unclear. In this study, we aimed to construct a prognostic model for PAAD based on oxidative stress genes and to evaluate its predictive value.

Methods

The Cancer Genome Atlas (TCGA) and three Gene Expression Omnibus (GEO) datasets were used to identify differentially expressed oxidative stress genes. Univariate Cox regression, Kaplan-Meier and multivariate Cox regression analysis were used to select genes and to construct a prognosis model. According to the median value of the model’s risk score, patients were divided into high and low risk groups, and gene set enrichment analysis (GSEA), immune infiltration and immunotherapy effect, drug resistance and the expression of immune checkpoint related genes and synthetic driver genes of T cell proliferation were analyzed. Finally, the mRNA and protein levels of four genes in PAAD were verified by the clinical proteomic tumor analysis consortium (CPTAC) database and the immunostaining of patients’ tissue.

Results

55 differentially expressed oxidative stress genes were identified, and four genes including MET, FYN, CTTN and CDK1 were selected to construct a prognosis model. GESA indicated that immune related pathways, metabolic pathways and DNA repair pathways were significantly enriched in the high risk group as compared to the low risk group. The frequency of genetic mutations was also significantly higher in high risk groups than that in low risk groups. Moreover, the infiltration level of 23 immune cells as well as the expression of immune checkpoint related and synthetic driver genes of T cell proliferation were significantly altered, with the better immunotherapy effect occurring in low risk group. In patient PAAD tissues, the mRNA and protein levels of these four genes were up-regulated.

Conclusion

We have successfully constructed a four oxidative stress gene prognostic model that has important predictive value for PAAD patients, and this model might be a promising guidance for prognostic prediction and efficacy monitoring in clinical individualized therapy.
Perfluorocarbon emulsion enhances MR-ARFI displacement and temperature in vitro: Evaluating the response with MRI, NMR, and hydrophone
Authors: Holman Ryan , Lorton Orane , Guillemin Pauline C. , Desgranges Stéphane , Santini Francesco , Preso Davide Bernardo , Farhat Mohamed , Contino-Pépin Christiane , Salomir Rares
Published: January 2023

Sonosensitive perfluorocarbon F8TAC18-PFOB emulsion is under development to enhance heating, increase thermal contrast, and reduce treatment times during focused ultrasound tumor ablation of highly perfused tissue. The emulsion previously showed enhanced heating during ex vivo and in vitro studies. Experiments were designed to observe the response in additional scenarios by varying focused ultrasound conditions, emulsion concentrations, and surfactants. Most notably, changes in acoustic absorption were assessed with MR-ARFI. Phantoms were developed to have thermal, elastic, and relaxometry properties similar to those of ex vivo pig tissue. The phantoms were embedded with varying amounts of F8TAC18-PFOB emulsion or lecithin-PFOB emulsion, between about 0.0-0.3% v:w, in 0.05% v:w increments. MR-ARFI measurements were performed using a FLASH-ARFI-MRT sequence to obtain simultaneous displacement and temperature measurements. A Fabry-Perot hydrophone was utilized to observe the acoustic emissions. Susceptibility-weighted imaging and relaxometry mapping were performed to observe concentration-dependent effects. 19F diffusion-ordered spectroscopy NMR was used to measure the diffusion coefficient of perfluorocarbon droplets in a water emulsion. Increased displacement and temperature were observed with higher emulsion concentration. In semi-rigid MR-ARFI phantoms, a linear response was observed with low-duty cycle MR-ARFI sonications and a mono-exponential saturating response was observed with sustained sonications. The emulsifiers did not have a significant effect on acoustic absorption in semi-rigid gels. Stable cavitation might also contribute to enhanced heating.
Hybrid peptide NTP-217 triggers ROS-mediated rapid necrosis in liver cancer cells by induction of mitochondrial leakage
Authors: Yin Hao , Fu Xingyan , Gao Hanyu , Gao Han , Ma Yannan , Chen Xitong , Zhang Xueqi , Du Shan-Shan , Qi Yun-Kun
Published: January 2023

Liver cancer is the third leading cause of cancer-associated mortality globally, and >830,000 patients with liver cancer undergoing treatment succumbed to the disease in 2020, which indicates the urgent need to develop a more effective anti-liver cancer drug. In our previous study, nucleus-targeting hybrid peptides obtained from the fusion of LTX-315 and the rhodamine B group possessed potent anti-adherent cancer cell activity. Hybrid peptides accumulated in the cell nucleus and damaged the nuclear membrane, resulting in the transfer of reactive oxygen species (ROS) from the cytoplasm to the nucleus and the induction of apoptosis. However, the source of the high concentration of ROS within the cytoplasm is unclear. Moreover, although our previous study demonstrated that hybrid peptides possessed potent anticancer activity against adherent cancer cells, their efficacy on liver cancer remained unexplored. The current study found that the hybrid peptide NTP-217 killed liver cancer cells after 4-h treatment with a half-maximal inhibitory concentration of 14.6-45.7 μM. NTP-217 could stably accumulate in the liver tumor tissue and markedly inhibited liver tumor growth in mice. Furthermore, NTP-217 destroyed mitochondria and induced the leakage of mitochondrial contents, resulting in the generation of a substantial quantity of ROS. Unlike the apoptosis induced by 24 h of treatment by NTP-217, 4 h of treatment caused ROS-mediated necrotic cell death. These findings suggested that short-time treatment with hybrid peptides could trigger ROS-mediated rapid necrosis in liver cancer cells, and provided a basis for the future development of hybrid peptides as anti-liver cancer agents.
Case report: Ewing sarcoma with EWSR–ERG fusion elevates procalcitonin extremely in the long term without infection
Authors: Chen Ying , Qin Tao , Chen Yan , Gao Ming
Published: January 2023

Background

Ewing sarcoma (ES) represents a rare, aggressive bone and soft-tissue cancer. Unlike breast, liver, pancreatic, and prostate cancers, Ewing sarcoma has had no representative tumor marker until now. The use of procalcitonin (PCT) as a tumor marker is also rarely reported. PCT is a clinically recognized and widely used inflammatory marker in recent years. In rare cases, PCT may also be falsely positive due to non-infectious factors. In the few previously reported papers regarding the correlation between tumors and PCT, we learned that abnormalities of PCT level can also be impacted by individual cancers.

Case presentation

Here, we first reported a case of Ewing sarcoma with markedly elevated PCT without infection and carried out some literature review. The patient was a middle-aged man with extraskeletal Ewing sarcoma whose lesion was located in the distal abdominal ileum. He had a sudden and unprovoked onset of high fever during chemotherapy before surgery. After multiple examinations, the patient’s blood routine, C-reactive protein, blood culture, and CT examination showed no signs of infection, and even the culture from the end of the central venous catheter showed no pathogen growth. Only PCT increased dramatically to more than 200 ng/ml. PCT remained at this level for several months until a single abdominal lumpectomy was performed before it dropped to near-normal levels.

Conclusion

In our report, PCT is significantly elevated in Ewing sarcoma in the absence of infection. Not only that, but we particularly highlighted the precipitous drop in PCT following tumor resection.
Magnetic resonance imaging radiomics to differentiate ovarian sex cord-stromal tumors and primary epithelial ovarian cancers
Authors: Cheng Meiying , Tan Shifang , Ren Tian , Zhu Zitao , Wang Kaiyu , Zhang Lingjie , Meng Lingsong , Yang Xuhong , Pan Teng , Yang Zhexuan , Zhao Xin
Published: January 2023

Objective

To evaluate the diagnostic ability of magnetic resonance imaging (MRI) based radiomics and traditional characteristics to differentiate between Ovarian sex cord-stromal tumors (SCSTs) and epithelial ovarian cancers (EOCs).

Methods

We consecutively included a total of 148 patients with 173 tumors (81 SCSTs in 73 patients and 92 EOCs in 75 patients), who were randomly divided into development and testing cohorts at a ratio of 8:2. Radiomics features were extracted from each tumor, 5-fold cross-validation was conducted for the selection of stable features based on development cohort, and we built radiomics model based on these selected features. Univariate and multivariate analyses were used to identify the independent predictors in clinical features and conventional MR parameters for differentiating SCSTs and EOCs. And nomogram was used to visualized the ultimately predictive models. All models were constructed based on the logistic regression (LR) classifier. The performance of each model was evaluated by the receiver operating characteristic (ROC) curve. Calibration and decision curves analysis (DCA) were used to evaluate the performance of models.

Results

The final radiomics model was constructed by nine radiomics features, which exhibited superior predictive ability with AUCs of 0.915 (95%CI: 0.869-0.962) and 0.867 (95%CI: 0.732-1.000) in the development and testing cohorts, respectively. The mixed model which combining the radiomics signatures and traditional parameters achieved the best performance, with AUCs of 0.934 (95%CI: 0.892-0.976) and 0.875 (95%CI: 0.743-1.000) in the development and testing cohorts, respectively.

Conclusion

We believe that the radiomics approach could be a more objective and accurate way to distinguish between SCSTs and EOCs, and the mixed model developed in our study could provide a comprehensive, effective method for clinicians to develop an appropriate management strategy.
Systematic analysis and case series of the diagnosis and management of trichilemmal carcinoma
Authors: Sun Jiachen , Zhang Lihua , Xiao Minglu , Li Shiyi , Chen Runkai , Li Ying , Yang Yuguang
Published: January 2023

Background

Trichilemmal carcinoma (TLC) is a rare malignant cutaneous adnexal neoplasm, with no relatively comprehensive research.

Objective

The aim of this study is to perform an updated statistical analysis so as to better understand TLC’s epidemiology, clinical features, diagnosis, and treatment.

Methods

The diagnosis and treatment of three TLC cases in our department were summarized. Then, all TLC cases published in the literature were retrieved for a comprehensive analysis, followed by the analysis of global trends and regional distribution, demographic characteristics, clinical features, pathogenesis, histopathological features, and treatment and prognosis of TLC.

Results

Of the 231 cases, the incidence of TLC has shown an upward trend recently, especially in China, in Asia. The susceptible population is men aged 60–80 and women over 80, and the most prone location is head and neck. The phenotype of TLC is not always typical and may be misdiagnosed because of the coexistence of other diseases. There is a linear relationship between the diameter and its duration or thickness. UV, locally present skin lesions, trauma, scarring, organ transplantation, and genetic disorders may trigger the occurrence of TLC. Periodic acid–Schiff staining and CD34, but not Epithelial Membrane Antigen (EMA), were helpful in the diagnosis of TLC. Although effective, surgical excision and Mohs micrographic surgery need further improvement to reduce recurrence of TLC. Carcinoma history is an independent risk factor for TLC recurrence.

Limitations

The limitation of this study is the lack of randomized controlled trial on TLC treatment and recurrence.

Conclusion

TLC has the possibility of invasive growth and recurrence, especially in patients with longer duration and carcinoma history.
Novel, alternative splicing signature to detect lymph node metastasis in prostate adenocarcinoma with machine learning
Authors: Xie Ping , Batur Jesur , An Xin , Yasen Musha , Fu Xuefeng , Jia Lin , Luo Yun
Published: January 2023

Background

The presence of lymph node metastasis leads to a poor prognosis for prostate cancer (Pca). Recently, many studies have indicated that gene signatures may be able to predict the status of lymph nodes. The purpose of this study is to probe and validate a new tool to predict lymph node metastasis (LNM) based on alternative splicing (AS).

Methods

Gene expression profiles and clinical information of prostate adenocarcinoma cohort were retrieved from The Cancer Genome Atlas (TCGA) database, and the corresponding RNA-seq splicing events profiles were obtained from the TCGA SpliceSeq. Limma package was used to identify the differentially expressed alternative splicing (DEAS) events between LNM and non-LNM groups. Eight machine learning classifiers were built to train with stratified five-fold cross-validation. SHAP values was used to explain the model.

Results

333 differentially expressed alternative splicing (DEAS) events were identified. Using correlation filter and the least absolute shrinkage and selection operator (LASSO) method, a 96 AS signature was identified that had favorable discrimination in the training set and validated in the validation set. The linear discriminant analysis (LDA) was the best classifier after 100 iterations of training. The LDA classifier was able to distinguish between LNM and non-LNM with an area under the receiver operating curve of 0.962 ± 0.026 in the training set (D1 = 351) and 0.953 in the validation set (D2 = 62). The decision curve analysis plot proved the clinical application of the AS-based model.

Conclusion

Machine learning combined with AS data could robustly distinguish between LNM and non-LNM in Pca.