bluuebunny/crossref_metadata_2025 huggingface dataset:
Correlation between the triglyceride-to-high-density lipoprotein cholesterol ratio and other unconventional lipid parameters with the risk of prediabetes and Type 2 diabetes in patients with coronary heart disease: a RCSCD-TCM study in China
Authors: Yang Tong , Liu Yijia , Li Lin , Zheng Yanchao , Wang Yang , Su Jinyu , Yang Rongrong , Luo Mingchi , Yu Chunquan
Published: June 2022

Objective

Type 2 diabetes mellitus (T2DM) is often accompanied by undiagnosed dyslipidemia. Research on the association of unconventional lipid markers with prediabetes (pre-DM) and T2DM simultaneously is limited in coronary heart disease (CHD) patients.

Methods

This study included 28,476 patients diagnosed with CHD. Their lipid levels, including triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C), were measured, and non-traditional lipid parameters were calculated. The patients were divided into three groups based on the diabetic status including normoglycemic (NG), pre-DM, and T2DM. Multiple logistic regression was used to compare the association of TG/HDL-C and other non-traditional lipid parameters with pre-DM and T2DM. The tertiles of TG/HDL-C included T1 (TG/HDL-C < 1.10), T2 (1.10 ≤ TG/HDL-C ≤ 1.89) and T3 (TG/HDL-C > 1.89). Low and high TG/HDL-C was defined with sex-specific cutoff points.

Results

Multiple logistic regression results showed that the non-traditional lipid parameters, including non-HDL-C, LDL-C/HDL-C, TC/HDL-C, non-HDL-C/HDL-C and TG/HDL-C, were all correlated with the risk of pre-DM and T2DM. Meanwhile TG/HDL-C showed the strongest correlation (odds ratio [OR]: 1.19; 95% confidence interval [CI] 1.16–1.23), (OR: 1.36; 95% CI 1.33–1.39). When dividing TG/HDL-C into tertiles, using T1 as a reference, T3 was observed to have the highest association with both pre-DM and T2DM (OR: 1.60; 95% CI 1.48–1.74), (OR: 2.79; 95% CI 2.60–3.00). High TG/HDL-C was significantly associated with pre-DM and T2DM (OR: 1.69; 95% CI 1.52–1.88), (OR: 2.85; 95% CI 2.60–3.12). The association of TG/HDL-C with T2DM and pre-DM existed across different sex, age, smoking, and drinking statuses.

Conclusion

Elevated non-traditional lipid parameters were significantly associated with pre-DM and T2DM in CHD patients, especially TG/HDL-C. High TG/HDL-C was the risk factor with a strong correlation with the risk of pre-DM and T2DM.
Comparative analysis of gut microbiota in healthy and diarrheic yaks
Authors: Liu JunJun , Wang Xin , Zhang Wenqian , Kulyar Muhammad Fakhar-e-Alam , Ullah Kalim , Han Zhaoqing , Qin Jianhua , Bi Chongliang , Wang Yaping , Li Kun
Published: June 2022

Background

Yak (Bos grunniens) mainly inhabiting Tibet Plateau, displayed a high incidence of diarrhea due to harsh living environment and nutritional deficit. Gut microbial community has been reported to be closely related to many diseases including diabetes, obesity and inflammatory bowel disease, but information regarding diarrheic influence on gut microbiota in yaks remains scarce. Here, this study was performed to investigate the gut bacterial and fungal alternations of diarrheic yaks.

Results

Results revealed that the gut bacterial and fungal communities of diarrheic yaks showed a distinct decline in alpha diversity, accompanied by significant shifts in taxonomic compositions. Specifically, diarrhea caused a distinct increase in the relative abundance of 1 phylum and 8 genera as well as a distinct decrease in 3 phyla and 30 genera. Fungal taxonomic analysis indicated that the relative richness of 1 phylum and 2 genera dramatically increased, whereas the relative richness of 2 phylum and 43 genera significantly decreased during diarrhea. Surprisingly, 2 bacterial genera and 5 fungal genera even cannot be detected in the gut microbiota of diarrheic yaks.

Conclusions

In summary, this study indicated that the gut bacterial and fungal compositions and diversities of yaks altered significantly during diarrhea. Moreover, these findings also contribute to understanding the gut microbial composition and diversity of yaks and developing strategies to alleviate and prevent diarrhea from gut microbial perspective.
Metabolic engineering of Pichia pastoris for myo-inositol production by dynamic regulation of central metabolism
Authors: Zhang Qiquan , Wang Xiaolu , Luo Huiying , Wang Yaru , Wang Yuan , Tu Tao , Qin Xing , Su Xiaoyun , Huang Huoqing , Yao Bin , Bai Yingguo , Zhang Jie
Published: June 2022

Background

The methylotrophic budding yeast Pichia pastoris GS115 is a powerful expression system and hundreds of heterologous proteins have been successfully expressed in this strain. Recently, P. pastoris has also been exploited as an attractive cell factory for the production of high-value biochemicals due to Generally Recognized as Safe (GRAS) status and high growth rate of this yeast strain. However, appropriate regulation of metabolic flux distribution between cell growth and product biosynthesis is still a cumbersome task for achieving efficient biochemical production.

Results

In this study, P. pastoris was exploited for high inositol production using an effective dynamic regulation strategy. Through enhancing native inositol biosynthesis pathway, knocking out inositol transporters, and slowing down carbon flux of glycolysis, an inositol-producing mutant was successfully developed and low inositol production of 0.71 g/L was obtained. The inositol production was further improved by 12.7% through introduction of heterologous inositol-3-phosphate synthase (IPS) and inositol monophosphatase (IMP) which catalyzed the rate-limiting steps for inositol biosynthesis. To control metabolic flux distribution between cell growth and inositol production, the promoters of glucose-6-phosphate dehydrogenase (ZWF), glucose-6-phosphate isomerase (PGI) and 6-phosphofructokinase (PFK1) genes were replaced with a glycerol inducible promoter. Consequently, the mutant strain could be switched from growth mode to production mode by supplementing glycerol and glucose sequentially, leading to an increase of about 4.9-fold in inositol formation. Ultimately, the dissolved oxygen condition in high-cell-density fermentation was optimized, resulting in a high production of 30.71 g/L inositol (~ 40-fold higher than the baseline strain).

Conclusions

The GRAS P. pastoris was engineered as an efficient inositol producer for the first time. Dynamic regulation of cell growth and inositol production was achieved via substrate-dependent modulation of glycolysis and pentose phosphate pathways and the highest inositol titer reported to date by a yeast cell factory was obtained. Results from this study provide valuable guidance for engineering of P. pastoris for the production of other high-value bioproducts.
Evaluation of sustainable susceptibility to Plasmodium vivax infection among colonized Anopheles darlingi and Anopheles deaneorum
Authors: Santos Najara A. C. , Andrade Alice O. , Santos Thais C. , Martinez Leandro N. , Ferreira Amália S. , Bastos Alessandra S. , Martins Mirilene M. , Pontual José D. C. , Teles Carolina B. G. , Medeiros Jansen F. , Araújo Maisa S.
Published: June 2022

Background

The colonization of mosquitoes susceptible to Plasmodium vivax via direct membrane feeding assay (DMFA) has the potential to significantly advance our knowledge of P. vivax biology, vector-parasite interaction and transmission-blocking vaccine research. Anopheles darlingi and Anopheles deaneorum are important vectors of malaria in the Western Brazilian Amazon. Since 2018, well-established colonies of these species have been maintained in order to mass produce mosquitoes destined for P. vivax infection. Plasmodium susceptibility was confirmed when the colonies were established, but susceptibility needs to be maintained for these colonies to remain good models for pathogen transmission. Thus, the susceptibility was assessed of colonized mosquitoes to P. vivax isolates circulating in the Western Amazon.

Methods

Laboratory-reared mosquitoes from F10-F25 generations were fed on P. vivax blood isolates via DMFA. Susceptibility was determined by prevalence and intensity of infection as represented by oocyst load seven days after blood feeding, and sporozoite load 14 days after blood feeding. The effect of infection on mosquito survival was evaluated from initial blood feeding until sporogonic development and survival rates were compared between mosquitoes fed on infected and uninfected blood. Correlation was calculated between gametocytaemia and prevalence/intensity of infection, and between oocyst and sporozoite load.

Results

Significant differences were found in prevalence and intensity of infection between species. Anopheles darlingi showed a higher proportion of infected mosquitoes and higher oocyst and sporozoite intensity than An. deaneorum. Survival analysis showed that An. deaneorum survival decreased drastically until 14 days post infection (dpi). Plasmodium vivax infection decreased survival in both species relative to uninfected mosquitoes. No correlation was observed between gametocytaemia and prevalence/intensity of infection, but oocyst and sporozoite load had a moderate to strong correlation.

Conclusions

Colonized An. darlingi make excellent subjects for modelling pathogen transmission. On the other hand, An. deaneorum could serve as a model for immunity studies due the low susceptibility under current colonized conditions. In the application of DMFA, gametocyte density is not a reliable parameter for predicting mosquito infection by P. vivax, but oocyst intensity should be used to schedule sporozoite experiments.
Foetal lipoprotein oxidation and preeclampsia
Authors: Gil-Acevedo LA , Ceballos Guillermo , Torres-Ramos YD
Published: June 2022

Preeclampsia (PE) is a multisystemic syndrome specific to pregnancy. Although PE is the leading cause of death from complications associated with pregnancy, its aetiology is still unknown. In PE, lipid metabolism is altered. When lipids are damaged, both the mother and the foetus may be at risk. Lipoproteins contain apolipoproteins, triacylglycerols, free and esterified cholesterol, and phospholipids, all of which are susceptible to oxidative stress when high levels of oxygen and nitrogen free radicals are present. Lipoperoxidation can occur in three stages: mild, moderate, and severe. In severe lipid damage, highly toxic products such as malondialdehyde (MDA) can be generated; under these conditions, low-density lipoprotein (LDL) proteins can be oxidized (oxLDL). oxLDL is a biomolecule that can affect the production of nitric oxide (NO), the main vasodilator derived from the endothelium. oxLDL can interfere with the transduction of the signals responsible for triggering the activation of endothelial nitric oxide synthase (eNOS), causing reduced vasodilation and endothelial dysfunction, which are the main characteristics of preeclampsia. The objective of the review was to analyse the information the current information about exists about the impact generated by the oxidation of LDL and HDL lipoproteins in neonates of women with preeclampsia and how these alterations can predispose the neonate to develop diseases in adulthood.

PE can cause foetal loss, intrauterine growth restriction, or developmental complications. Neonates of mothers with PE have a high risk of cardiovascular diseases, stroke, mental retardation, sensory deficiencies and an increased risk of developing metabolic diseases. PE not only affects the foetus, generating complications during pregnancy but also predisposes them to chronic diseases in adulthood.
Nano-priming as emerging seed priming technology for sustainable agriculture—recent developments and future perspectives
Authors: Nile Shivraj Hariram , Thiruvengadam Muthu , Wang Yao , Samynathan Ramkumar , Shariati Mohammad Ali , Rebezov Maksim , Nile Arti , Sun Meihong , Venkidasamy Baskar , Xiao Jianbo , Kai Guoyin
Published: June 2022

Nano-priming is an innovative seed priming technology that helps to improve seed germination, seed growth, and yield by providing resistance to various stresses in plants. Nano-priming is a considerably more effective method compared to all other seed priming methods. The salient features of nanoparticles (NPs) in seed priming are to develop electron exchange and enhanced surface reaction capabilities associated with various components of plant cells and tissues. Nano-priming induces the formation of nanopores in shoot and helps in the uptake of water absorption, activates reactive oxygen species (ROS)/antioxidant mechanisms in seeds, and forms hydroxyl radicals to loosen the walls of the cells and acts as an inducer for rapid hydrolysis of starch. It also induces the expression of aquaporin genes that are involved in the intake of water and also mediates H2O2, or ROS, dispersed over biological membranes. Nano-priming induces starch degradation via the stimulation of amylase, which results in the stimulation of seed germination. Nano-priming induces a mild ROS that acts as a primary signaling cue for various signaling cascade events that participate in secondary metabolite production and stress tolerance. This review provides details on the possible mechanisms by which nano-priming induces breaking seed dormancy, promotion of seed germination, and their impact on primary and secondary metabolite production. In addition, the use of nano-based fertilizer and pesticides as effective materials in nano-priming and plant growth development were also discussed, considering their recent status and future perspectives.

Graphical Abstract
Correlated physical and mental health composite scores for the RAND-36 and RAND-12 health surveys: can we keep them simple?
Authors: Andersen John Roger , Breivik Kyrre , Engelund Inger Elise , Iversen Marjolein M. , Kirkeleit Jorunn , Norekvål Tone Merete , Oterhals Kjersti , Storesund Anette
Published: June 2022

Background

The RAND-36 and RAND-12 (equivalent to versions 1 of the SF-36 Health Survey and SF-12 Health Survey, respectively) are widely used measures of health-related quality of life. However, there are diverging views regarding how to create the physical health and mental health composite scores of these questionnaires. We present a simple approach using an unweighted linear combination of subscale scores for constructing composite scores for physical and mental health that assumes these scores should be free to correlate. The aim of this study was to investigate the criterion validity and convergent validity of these scores.

Methods

We investigated oblique and unweighted RAND-36/12 composite scores from a random sample of the general Norwegian population (N = 2107). Criterion validity was tested by examining the correlation between unweighted composite scores and weighted scores derived from oblique principal component analysis. Convergent validity was examined by analysing the associations between the different composite scores, age, gender, body mass index, physical activity, rheumatic disease, and depression.

Results

The correlations between the composite scores derived by the two methods were substantial (r = 0.97 to 0.99) for both the RAND-36 and RAND-12. The effect sizes of the associations between the oblique versus the unweighted composite scores and other variables had comparable magnitudes.

Conclusion

The unweighted RAND-36 and RAND-12 composite scores demonstrated satisfactory criterion validity and convergent validity. This suggests that if the physical and mental composite scores are free to be correlated, the calculation of these composite scores can be kept simple.
Platelets involved tumor cell EMT during circulation: communications and interventions
Authors: Wang Xiaoying , Zhao Songyan , Wang Zhaoxia , Gao Tao
Published: June 2022

Distant spreading of metastatic tumor cells is still the leading cause of tumor death. Metastatic spreading is a complex process, in which epithelial-mesenchymal transition (EMT) is the primary and key event to promote it. Presently, extensive reviews have given insights on the occurrence of EMT at the primary tumor site that depends on invasive properties of tumor cells and the tumor-associated microenvironment. However, essential roles of circulation environment involved in tumor cell EMT is not well summarized. As a main constituent of the blood, platelet is increasingly found to work as an important activator to induce EMT. Therefore, this review aims to emphasize the novel role of platelet in EMT through signal communications between platelets and circulation tumor cells, and illustrate potent interventions aiming at their communications. It may give a complementary view of EMT in addition to the tissue microenvironment, help for better understand the hematogenous metastasis, and also illustrate theoretical and practical basis for the targeted inhibition.
Enhanced immune activation within the tumor microenvironment and circulation of female high-risk melanoma patients and improved survival with adjuvant CTLA4 blockade compared to males
Authors: Saad Mariam , Lee Sandra J. , Tan Aik Choon , El Naqa Issam M. , Hodi F. Stephen , Butterfield Lisa H. , LaFramboise William A. , Storkus Walter , Karunamurthy Arivarasan D. , Conejo-Garcia Jose , Hwu Patrick , Streicher Howard , Sondak Vernon K. , Kirkwood John M. , Tarhini Ahmad A.
Published: June 2022

Background

We hypothesized that a gender difference in clinical response may exist to adjuvant CTLA4 blockade with ipilimumab versus high-dose IFNα (HDI). We investigated differences in candidate immune biomarkers in the circulation and tumor microenvironment (TME).

Patients and methods

This gender-based analysis was nested within the E1609 trial that tested adjuvant therapy with ipilimumab 3 mg/kg (ipi3) and 10 mg/kg (ipi10) versus HDI in high risk resected melanoma. We investigated gender differences in treatment efficacy with ipi3 and ipi10 versus HDI while adjusting for age, stage, ECOG performance (PS), ulceration, primary tumor status and lymph node number. Forest plots were created to compare overall survival (OS) and relapse free survival (RFS) between ipi and HDI. Gene expression profiling (GEP) was performed on tumors of 718 (454 male, 264 female) patients. Similarly, serum and peripheral blood mononuclear cells (PBMC) samples were tested for soluble and cellular biomarkers (N = 321 patients; 109 female and 212 male).

Results

The subgroups of female, stage IIIC, PS = 1, ulcerated primary, in-transit metastasis demonstrated significant improvement in RFS and/or OS with ipi3 versus HDI. Female gender was significant for both OS and RFS and was further explored. In the RFS comparison, a multivariate Cox regression model including significant variables indicated a significant interaction between gender and treatment (P = 0.024). In peripheral blood, percentages of CD3+ T cells (P = 0.024) and CD3+ CD4+ helper T cells (P = 0.0001) were higher in females compared to males. Trends toward higher circulating levels of IL1β (P = 0.07) and IL6 (P = 0.06) were also found in females. Males had higher percentages of monocytes (P = 0.03) with trends toward higher percentages of regulatory T cells (T-reg). Tumor GEP analysis supported enhanced infiltration with immune cells including gammadelta T cells (P = 0.005), NK cells (P = 0.01), dendritic cells (P = 0.01), CD4+ T cells (P = 0.03), CD8+ T cells (P = 0.03) and T-reg (P = 0.008) in the tumors of females compared to males and a higher T-effector and IFNγ gene signature score (P = 0.0244).

Conclusion

Female gender was associated with adjuvant CTLA4 blockade clinical benefits and female patients were more likely to have evidence of type1 immune activation within the TME and the circulation.

Trial registration ClinicalTrials.gov NCT01274338. Registered 11 January 2011, https://www.clinicaltrials.gov/ct2/show/NCT01274338
A gene prognostic index from cellular senescence predicting metastasis and radioresistance for prostate cancer
Authors: Feng Dechao , Li Dengxiong , Shi Xu , Xiong Qiao , Zhang Facai , Wei Qiang , Yang Lu
Published: June 2022

Background

Senescent cells have been identified in the aging prostate, and the senescence-associated secretory phenotype might be linked to prostate cancer (PCa). Thus, we established a cellular senescence-related gene prognostic index (CSGPI) to predict metastasis and radioresistance in PCa.

Methods

We used Lasso and Cox regression analysis to establish the CSGPI. Clinical correlation, external validation, functional enrichment analysis, drug and cell line analysis, and tumor immune environment analysis were conducted. All analyses were conducted with R version 3.6.3 and its suitable packages.

Results

We used ALCAM and ALDH2 to establish the CSGPI risk score. High-risk patients experienced a higher risk of metastasis than their counterparts (HR: 10.37, 95% CI 4.50–23.93, p < 0.001), consistent with the results in the TCGA database (HR: 1.60, 95% CI 1.03–2.47, p = 0.038). Furthermore, CSGPI had high diagnostic accuracy distinguishing radioresistance from no radioresistance (AUC: 0.938, 95% CI 0.834–1.000). GSEA showed that high-risk patients were highly associated with apoptosis, cell cycle, ribosome, base excision repair, aminoacyl-tRNA biosynthesis, and mismatch repair. For immune checkpoint analysis, we found that PDCD1LG2 and CD226 were expressed at significantly higher levels in patients with metastasis than in those without metastasis. In addition, higher expression of CD226 significantly increased the risk of metastasis (HR: 3.65, 95% CI 1.58–8.42, p = 0.006). We observed that AZD7762, PHA-793887, PI-103, and SNX-2112 might be sensitive to ALDH2 and ALCAM, and PC3 could be the potential cell line used to investigate the interaction among ALDH2, ALCAM, and the above drugs.

Conclusions

We found that CSGPI might serve as an effective biomarker predicting metastasis probability and radioresistance for PCa and proposed that immune evasion was involved in the process of PCa metastasis.
Muscle contributions to pre-swing biomechanical tasks influence swing leg mechanics in individuals post-stroke during walking
Authors: Brough Lydia G. , Kautz Steven A. , Neptune Richard R.
Published: June 2022

Background

Successful walking requires the execution of the pre-swing biomechanical tasks of body propulsion and leg swing initiation, which are often impaired post-stroke. While excess rectus femoris activity during swing is often associated with low knee flexion, previous work has suggested that deficits in propulsion and leg swing initiation may also contribute. The purpose of this study was to determine underlying causes of propulsion, leg swing initiation and knee flexion deficits in pre-swing and their link to stiff knee gait in individuals post-stroke.

Methods

Musculoskeletal models and forward dynamic simulations were developed for individuals post-stroke (n = 15) and healthy participants (n = 5). Linear regressions were used to evaluate the relationships between peak knee flexion, braking and propulsion symmetry, and individual muscle contributions to braking, propulsion, knee flexion in pre-swing, and leg swing initiation.

Results

Four out of fifteen of individuals post-stroke had higher plantarflexor contributions to propulsion and seven out of fifteen had higher vasti contributions to braking on their paretic leg relative to their nonparetic leg. Higher gastrocnemius contributions to propulsion predicted paretic propulsion symmetry (p = 0.005) while soleus contributions did not. Higher vasti contributions to braking in pre-swing predicted lower knee flexion (p = 0.022). The rectus femoris had minimal contributions to lower knee flexion acceleration in pre-swing compared to contributions from the vasti. However, for some individuals with low knee flexion, during pre-swing the rectus femoris absorbed more power and the iliopsoas contributed less power to the paretic leg. Total musculotendon work done on the paretic leg in pre-swing did not predict knee flexion during swing.

Conclusions

These results emphasize the multiple causes of propulsion asymmetry in individuals post-stroke, including low plantarflexor contributions to propulsion, increased vasti contributions to braking and reliance on compensatory mechanisms. The results also show that the rectus femoris is not a major contributor to knee flexion in pre-swing, but absorbs more power from the paretic leg in pre-swing in some individuals with stiff knee gait. These results highlight the need to identify individual causes of propulsion and knee flexion deficits to design more effective rehabilitation strategies.
Soft robotic exosuit augmented high intensity gait training on stroke survivors: a pilot study
Authors: Shin Sung Yul , Hohl Kristen , Giffhorn Matt , Awad Louis N. , Walsh Conor J. , Jayaraman Arun
Published: June 2022

Background

Stroke is a leading cause of serious gait impairments and restoring walking ability is a major goal of physical therapy interventions. Soft robotic exosuits are portable, lightweight, and unobtrusive assistive devices designed to improve the mobility of post-stroke individuals through facilitation of more natural paretic limb function during walking training. However, it is unknown whether long-term gait training using soft robotic exosuits will clinically impact gait function and quality of movement post-stroke.

Objective

The objective of this pilot study was to examine the therapeutic effects of soft robotic exosuit-augmented gait training on clinical and biomechanical gait outcomes in chronic post-stroke individuals.

Methods

Five post-stroke individuals received high intensity gait training augmented with a soft robotic exosuit, delivered in 18 sessions over 6–8 weeks. Performance based clinical outcomes and biomechanical gait quality parameters were measured at baseline, midpoint, and completion.

Results

Clinically meaningful improvements were observed in walking speed ($$p$$
p
 < 0.05) and endurance ($$p$$
p
 < 0.01) together with other traditional gait related outcomes. The gait quality measures including hip ($$p$$
p
 < 0.01) and knee ($$p$$
p
 < 0.05) flexion/extension exhibited an increase in range of motion in a symmetric manner ($$p$$
p
 < 0.05). We also observed an increase in bilateral ankle angular velocities ($$p$$
p
 < 0.05), suggesting biomechanical improvements in walking function.

Conclusions

The results in this study offer preliminary evidence that a soft robotic exosuit can be a useful tool to augment high intensity gait training in a clinical setting. This study justifies more expanded research on soft exosuit technology with a larger post-stroke population for more reliable generalization.

Trial registration This study is registered with ClinicalTrials.gov (ID: NCT04251091)
Exposure of human cerebral microvascular endothelial cells hCMEC/D3 to laminar shear stress induces vascular protective responses
Authors: Choublier Nina , Taghi Meryam , Menet Marie-Claude , Le Gall Morgane , Bruce Johanna , Chafey Philippe , Guillonneau François , Moreau Amélie , Denizot Claire , Parmentier Yannick , Nakib Samir , Borderie Didier , Bouzinba-Segard Haniaa , Couraud Pierre-Olivier , Bourdoulous Sandrine , Declèves Xavier
Published: June 2022

Endothelial cells (ECs) are constantly submitted in vivo to hemodynamical forces derived from the blood circulation, including shear stress (SS). ECs are able to detect SS and consequently adapt their phenotype, thus affecting many endothelial functions. If a plethora of shear stress-regulated molecular networks have been described in peripheral ECs, less is known about the molecular responses of microvascular brain ECs which constitute the blood–brain barrier (BBB). In this work, we investigated the response of human cerebral microvascular ECs to laminar physiological shear stress using the well characterized hCMEC/D3 cell line. Interestingly, we showed that hCMEC/D3 cells responded to shear stress by aligning perpendicularly to the flow direction, contrary to peripheral endothelial cells which aligned in the flow direction. Whole proteomic profiles were compared between hCMEC/D3 cells cultured either in static condition or under 5 or 10 dyn.cm−2 SS for 3 days. 3592 proteins were identified and expression levels were significantly affected for 3% of them upon both SS conditions. Pathway analyses were performed which revealed that most proteins overexpressed by SS refer to the antioxidant defense, probably mediated by activation of the NRF2 transcriptional factor. Regarding down-regulated proteins, most of them participate to the pro-inflammatory response, cell motility and proliferation. These findings confirm the induction of EC quiescence by laminar physiological SS and reveal a strong protective effect of SS on hCMEC/D3 cells, suggesting a similar effect on the BBB. Our results also showed that SS did not significantly increase expression levels nor did it affect the localization of junctional proteins and did not afect either the functional activity of several ABC transporters (P-glycoprotein and MRPs). This work provides new insights on the response of microvascular brain ECs to SS and on the importance of SS for optimizing in vitro BBB models.
WeCoNET: a host–pathogen interactome database for deciphering crucial molecular networks of wheat-common bunt cross-talk mechanisms
Authors: Kataria Raghav , Kaundal Rakesh
Published: June 2022

Background

Triticum aestivum is the most important staple food grain of the world. In recent years, the outbreak of a major seed-borne disease, common bunt, in wheat resulted in reduced quality and quantity of the crop. The disease is caused by two fungal pathogens, Tilletia caries and Tilletia laevis, which show high similarity to each other in terms of life cycle, germination, and disease symptoms. The host–pathogen protein–protein interactions play a crucial role in initiating the disease infection mechanism as well as in plant defense responses. Due to the availability of limited information on Tilletia species, the elucidation of infection mechanisms is hampered.

Results

We constructed a database WeCoNET (http://bioinfo.usu.edu/weconet/), providing functional annotations of the pathogen proteins and various tools to exploit host–pathogen interactions and other relevant information. The database implements a host–pathogen interactomics tool to predict protein–protein interactions, followed by network visualization, BLAST search tool, advanced ‘keywords-based’ search module, etc. Other features in the database include various functional annotations of host and pathogen proteins such as gene ontology terms, functional domains, and subcellular localization. The pathogen proteins that serve as effector and secretory proteins have also been incorporated in the database, along with their respective descriptions. Additionally, the host proteins that serve as transcription factors were predicted, and are available along with the respective transcription factor family and KEGG pathway to which they belong.

Conclusion

WeCoNET is a comprehensive, efficient resource to the molecular biologists engaged in understanding the molecular mechanisms behind the common bunt infection in wheat. The data integrated into the database can also be beneficial to the breeders for the development of common bunt-resistant cultivars.
High-dose stereotactic radiotherapy boost in the treatment of squamous cell carcinoma of the head and neck region
Authors: Polanowski Paweł , Pietruszka Agnieszka , Księżniak-Baran Dorota , Grządziel Aleksandra , Chmielik Ewa , Kentnowski Marek , Amrogowicz Natalia , Składowski Krzysztof , Polanowska Katarzyna
Published: June 2022

Background

Surgical resection with adjuvant concurrent radiochemotherapy is the standard of care for stage III–IV oral cavity cancer. In some cases, the dynamic course of the disease is out of the prepared schedule of treatment. In that event, a stereotactic radiosurgery boost might be the only chance for disease control.

Case presentation

Here, we present a case study of a patient with oral cancer who underwent surgery. During adjuvant radiotherapy, a metastatic cervical lymph node was diagnosed based on fine-needle aspiration biopsy. To increase the total dose to the metastatic tumor, a stereotactic radiosurgery boost of 1 × 18 Gy was performed two days after the last fraction of conventional radiotherapy. The early and late tolerance of this treatment were positive. During the 18-month follow-up, locoregional recurrence was not detected. The patient died due to secondary malignancy.

Conclusions

This paper shows that a stereotactic radiosurgery boost added to adjuvant conventional radiotherapy is an effective approach permitting the maintenance of good local control in well-selected patients.
Femoral periprosthetic fracture treatment using the Ortho-Bridge System: a biomechanical study
Authors: Long Yuntao , Qi Yubin , Zuo Guilai , Zhang Qingjie , Liu Zhenlin , Wang Wen
Published: June 2022

Background

We undertook a comparative biomechanical study of type B1 fractures around femoral prostheses following cemented hip arthroplasty using the Ortho-Bridge System (OBS) and a locking compression plate/locking attachment plate structure (LCP + LAP). We aimed to investigate the biomechanical characteristics and advantages of the OBS compared with LCP + LAP when treating this fracture type.

Methods

An OBS fixation model was designed based on OBS and LCP + LAP fixation characteristics. The LCP + LAP combination (Group A) and three different OBS combinations (Groups B, C, and D) were used to fix a B1 fracture model with a femoral periprosthetic fracture. Axial compression and torsion experiments were then performed using simple and comminuted fracture models. The axial compression failure experiment was carried out, and the model stiffness during axial compression, torsion angle in torsion test, and vertical load in the final failure test were collected.

Results

When simulating simple oblique fractures, no significant difference was found among the four groups in terms of stiffness in the axial compression experiment (P = 0.257). The torsion angle of the LCP + LAP system was significantly higher compared with the OBS system (P < 0.05). When simulating a comminuted fracture, the experimental data for axial compression showed that the rigidity measurements of the three combinations of the OBS system were higher compared with the LCP + LAP system (P = 0.000) and that the torsion angles of three combinations of the OBS system were smaller compared with the LCP + LAP system (P < 0.05). In the axial compression failure test, the fixed failure mode of the LCP + LAP system was the destruction of the contact cortex at the fracture site, whereas the failure modes in the three OBS combinations involved fracture around the screws above the osteotomy and destruction of the contact cortex at the fracture site.

Conclusions

The findings revealed that the OBS produced superior biomechanical outcomes compared with LCP + LAP, especially for the bridging two-rod dual cortex. According to the performance observed after model axial compression destruction, the OBS was fixed and provided greater stress dispersion, which might make it more suitable for facilitating early functional movement and avoiding the failure of internal fixation.
Varus morphology and its surgical implication in osteoarthritic knee and total knee arthroplasty
Authors: Suardi Chiara , Stimolo Davide , Zanna Luigi , Carulli Christian , Fabrizio Matassi , Civinini Roberto , Innocenti Matteo
Published: June 2022

Background

Knee varus alignment represents a notorious cause of knee osteoarthritis. It can be caused by tibial deformity, combined tibial–femoral deformity and/or ligament imbalance. Understanding malalignment is crucial in total knee arthroplasty to restore frontal plane neutral mechanical axis. The aim of this study was to determine which factor contributes the most to varus osteoarthritic knee and its related surgical implications in performing a total knee arthroplasty.

Methods

We retrospectively evaluated 140 patients operated for total knee arthroplasty due to a varus knee. Full-leg hip to ankle preoperative X-rays were taken. Radiological parameters recorded were: mechanical axis deviation, hip–knee–ankle, anatomical–mechanical angle, medial neck shaft angle, mechanical lateral distal femoral angle (mLDFA), medial proximal tibial angle (MPTA), joint line convergence angle (JLCA), lateral proximal femoral angle, lateral distal tibial angle (LDTA), femoral bowing, and length of tibia and femur. We also determined ideals tibial and femoral cuts in mm according to mechanical alignment technique. A R2 was calculated based on the linear regression between the predicted values and the observed data.

Results

The greatest contributor to arthritic varus (R = 0.444) was MPTA. Minor contributors were mLDFA (R = 0.076), JLCA (R = 0.1554), LDTA (R = 0.065), and femoral bowing (R = 0.049). We recorded an average of 7.6 mm in lateral tibial cut thickness to restore neutral alignment.

Conclusions

The radiological major contributor to osteoarthritic varus knee alignment is related to proximal tibia deformity. As a surgical consequence, during performing total knee arthroplasty, the majority of the correction should therefore be made on tibial cut.
Therapeutic effect of autologous bone grafting with adjuvant bone morphogenetic protein on long bone nonunion: a systematic review and meta-analysis
Authors: Xie Chengxin , Wang Chenglong , Huang Yu , Li Qinglong , Tian Xin , Huang Wenwen , Yin Dong
Published: June 2022

Background

The recombinant human bone morphogenetic protein (rhBMP) is a common graft substitute for treating cases of long bone nonunion. However, the feasibility of combining an autologous bone graft (ABG) with rhBMPs remains uncertain. Thus, this systematic review and meta-analysis aimed to evaluate the synergistic effect of ABG and rhBMPs on the healing of long bone nonunion.

Methods

A systematic literature search was performed on PubMed, Web of Science, Cochrane Library, and China National Knowledge Infrastructure. Two authors independently screened the studies, extracted data, and assessed the quality of the trials. Statistical analyses were performed using Stata 12.0.

Results

Of the 202 citations, five studies involving a total of 394 cases met the eligibility criteria; thus, they were included in this study. The pooled data revealed no significant differences among the groups in terms of postoperative healing rate (risk ratio [RR] = 1.01, 95% confidence interval [CI] = 0.96–1.06, P = 0.744), healing time (standardised mean difference =  − 0.20, 95% CI = − 0.95–0.56, P = 0.610), and pain (RR = 1.44, 95% CI = 0.25–8.29, P = 0.681). The combination of ABG and rhBMPs resulted in good limb function (RR = 1.31, 95% CI = 1.04–1.66, P = 0.023).

Conclusions

The combination of ABG and rhBMPs did not result in the healing of long bone nonunion and pain reduction. Nevertheless, it conferred good limb function. Thus, the findings in this study are insufficient to support the use of rhBMPs as an adjuvant to ABG.
Conservative therapy versus arthroscopic surgery of femoroacetabular impingement syndrome (FAI): a systematic review and meta-analysis
Authors: Zhu Yanlin , Su Peng , Xu Tianhao , Zhang Lei , Fu Weili
Published: June 2022

Purpose

FAI (femoroacetabular impingement syndrome) is a common cause of hip pain, resulting in a decreased life quality. This study aims to compare the postoperative clinical outcome between arthroscopic surgery (AT) and conservative treatment (CT).

Method

The six studies were selected from PubMed, Embase and OVID database. The data were extracted and analyzed by RevMan5.3. Mean differences and 95% confidence intervals were calculated. RevMan5.3 was used to assess the risk of bias.

Result

Six observational studies were assessed. The methodological quality of the trials indicated five of six studies had a low risk of bias and one article had a high risk of bias. The differences were statistically significant between AT and CT for HOS (follow-up for 6 months), iHOT-33 (follow-up for 6 months) improvement, iHOT-33 (follow-up for 12 months) improvement, iHOT-33 (follow-up for 12 months), EQ-5D-5L index score (follow-up for 12 months) and AT showed higher benefits than CT. Meanwhile no statistically significant were found in iHOT-33 (follow-up for 6 months), EQ-5D-5L index score (follow-up for 6 months), EQ5D-VAS (follow-up for 6 months) and EQ5D-VAS (follow-up for 12 months).

Conclusion

AT and CT both can have clinical effects when facing FAI. In our meta-analysis, hip arthroscopy is statistically superior to conservative treatment in both long-term and short-term effects.
A case-driven hypothesis for multi-stage crack growth mechanism in fourth-generation ceramic head fracture
Authors: Lucchini Stefano , Baleani Massimiliano , Giardina Federico , Martelli Andrea , Castagnini Francesco , Bordini Barbara , Traina Francesco
Published: June 2022

Background

Ceramic bearings are used in total hip arthroplasty due to their excellent wear behaviour and biocompatibility. The major concern related to their use is material brittleness, which significantly impacts on the risk of fracture of ceramic components. Fracture toughness improvement has contributed to the decrease in fracture rate, at least of the prosthetic head. However, the root cause behind these rare events is not fully understood. This study evaluated head fracture occurrence in a sizeable cohort of patients with fourth-generation ceramic-on-ceramic implants and described the circumstances reported by patients in the rare cases of head fracture.

Methods

The clinical survivorship of 29,495 hip prostheses, with fourth-generation ceramic bearings, was determined using data from a joint replacement registry. The average follow-up period was 5.2 years (range 0.1–15.6). Retrieval analysis was performed in one case for which the ceramic components were available.

Results

Clinical outcomes confirmed the extremely low fracture rate of fourth-generation ceramic heads: only two out of 29,495 heads fractured. The two fractures, both involving 36 mm heads, occurred without a concurrent or previous remarkable trauma. Considering the feature of the fractured head, a multi-stage crack growth mechanism has been hypothesized to occur following damage at the head–neck taper interface.

Conclusions

Surgeons must continue to pay attention to the assembly of the femoral head: achieving a proper head seating on a clean taper is a prerequisite to decrease the risk of occurrence of any damage process within head–neck junction, which may cause high stress concentration at the contact surface, promoting crack nucleation and propagation even in toughened ceramics.
Hypoxia-inducible factors: master regulators of hypoxic tumor immune escape
Authors: Wu Qinghua , You Li , Nepovimova Eugenie , Heger Zbynek , Wu Wenda , Kuca Kamil , Adam Vojtech
Published: June 2022

Hypoxia, a common feature of the tumor microenvironment in various types of cancers, weakens cytotoxic T cell function and causes recruitment of regulatory T cells, thereby reducing tumoral immunogenicity. Studies have demonstrated that hypoxia and hypoxia-inducible factors (HIFs) 1 and 2 alpha (HIF1A and HIF2A) are involved in tumor immune escape. Under hypoxia, activation of HIF1A induces a series of signaling events, including through programmed death receptor-1/programmed death ligand-1. Moreover, hypoxia triggers shedding of complex class I chain-associated molecules through nitric oxide signaling impairment to disrupt immune surveillance by natural killer cells. The HIF-1-galactose-3-O-sulfotransferase 1-sulfatide axis enhances tumor immune escape via increased tumor cell-platelet binding. HIF2A upregulates stem cell factor expression to recruit tumor-infiltrating mast cells and increase levels of cytokines interleukin-10 and transforming growth factor-β, resulting in an immunosuppressive tumor microenvironment. Additionally, HIF1A upregulates expression of tumor-associated long noncoding RNAs and suppresses immune cell function, enabling tumor immune escape. Overall, elucidating the underlying mechanisms by which HIFs promote evasion of tumor immune surveillance will allow for targeting HIF in tumor treatment. This review discusses the current knowledge of how hypoxia and HIFs facilitate tumor immune escape, with evidence to date implicating HIF1A as a molecular target in such immune escape. This review provides further insight into the mechanism of tumor immune escape, and strategies for tumor immunotherapy are suggested.
Circ_0004087 interaction with SND1 promotes docetaxel resistance in prostate cancer by boosting the mitosis error correction mechanism
Authors: Chen Liang , Song Yarong , Hou Teng , Li Xuexiang , Cheng Lulin , Li Yunxue , Xing Yifei
Published: June 2022

Background

Acquisition of the chemoresistance to docetaxel (DTX), a microtubule-targeting agent, has been a huge obstacle in treatment for metastatic castration-resistant prostate cancer (mCRPC). Recently, strategies targeting the mitosis error correction mechanism including chromosomal passenger complex (CPC) were reported to reverse the resistance to microtubule-targeting anticancer agents. Meanwhile, accumulating evidence indicated the important roles of circRNAs in DTX resistance of prostate cancer (PCa). However, whether circRNAs could regulate DTX chemosensitivity by affecting the mitosis error correction mechanism remains unclear.

Methods

Expression patterns of circ_0004087 and BUB1 were determined through mining the public circRNA datasets and performing western blot and qRT-PCR assays. Agarose gel electrophoresis, Sanger sequencing, and RNase R treatment were conducted to examine the circular characteristics of circ_0004087. CircRNA pull-down, mass spectrometry analysis, Co-IP, and dual-luciferase reporter assays were performed to uncover the interaction among circ_0004087, SND1, and MYB. The effects of circ_0004087 and BUB1 on docetaxel-based chemotherapy were explored by flow cytometry and in vivo drug studies upon xenografted tumor model.

Results

In the present study, we revealed the profound interaction between a novel circRNA, circ_0004087, and the mitosis error correction mechanism. Mechanistically, circ_0004087 binding with transcriptional coactivator SND1 could stimulate the transactivation of MYB and enhance the expression of downstream target BUB1. In turn, elevated BUB1 expression further recruited CPC to centromeres and guaranteed the error-free mitosis of PCa cells. Biologically, the overexpression of circ_0004087 conferred while the knockdown impaired DTX resistance in PCa cells.

Conclusions

Our study uncovered the crucial role of circ_0004087/SND1/MYB/BUB1 axis in modulating the error mitosis correction mechanism and DTX chemoresistance, suggesting that circ_0004087 may serve as a valuable prognostic biomarker and a potential therapeutic target in DTX-resistant PCa patients.
Evolutionary perspectives, heterogeneity and ovarian cancer: a complicated tale from past to present
Authors: Achimas-Cadariu Patriciu , Kubelac Paul , Irimie Alexandru , Berindan-Neagoe Ioana , Rühli Frank
Published: June 2022

Ovarian cancer is composed of a complex system of cells best described by features such as clonal evolution, spatial and temporal genetic heterogeneity, and development of drug resistance, thus making it the most lethal gynecologic cancer. Seminal work on cancer as an evolutionary process has a long history; however, recent cost-effective large-scale molecular profiling has started to provide novel insights coupled with the development of mathematical algorithms. In the current review, we have systematically searched for articles that focused on the clonal evolution of ovarian cancer to offer the whole landscape of research that has been done and highlight future research avenues given its characteristic features and connections to evolutionary biology.