Miracle-dz/UniFAR-FTUs huggingface dataset:
The rapid evolution of flagellar ion selectivity in experimental populations of E. coli

Determining which cellular processes facilitate adaptation requires a tractable experimental model where an environmental cue can generate variants which rescue function. The Bacterial Flagellar Motor (BFM) is an excellent candidate – an ancient and highly conserved molecular complex for propulsion which navigates bacteria towards favourable environments. In most species, rotation is powered by H+ or Na+ ion transit through the torque-generating stator subunit of the motor complex. The ion that drives the rotor has changed over evolutionary timescales but the molecular basis of this selectivity remains unknown. Here we used CRISPR engineering to replace the native Escherichia coli H+-powered stator with Na+-powered stator genes and report the rapid and spontaneous reversion of our edit in a low sodium environment. We followed the evolution of the stators during their reversion to H+-powered motility and used whole genome and transcriptome sequencing to identify both flagellar- and non-flagellar-associated genes involved in the cell’s adaptation. Our transplant of an unfit protein and the cells’ rapid response to this edit demonstrates the adaptability of the stator subunit and highlights the hierarchical modularity of the flagellar motor.
Improved semidefinite programming upper bound on distillable entanglement

A new additive and semidefinite programming (SDP) computable entanglement measure is introduced to upper bound the amount of distillable entanglement in bipartite quantum states by operations completely preserving the positivity of partial transpose (PPT). This quantity is always smaller than or equal to the logarithmic negativity, the previously best known SDP bound on distillable entanglement, and the inequality is strict in general. Furthermore, a succinct SDP characterization of the one-copy PPT deterministic distillable entanglement for any given state is also obtained, which provides a simple but useful lower bound on the PPT distillable entanglement. Remarkably, there is a genuinely mixed state of which both bounds coincide with the distillable entanglement while being strictly less than the logarithmic negativity.
Extracellular cell-free RNA profile in human large follicles and small follicles

Background: Previous studies have shown that a large number of valuable and functional cell-free RNAs (cfRNAs) were found in follicular fluid. However, the species and characteristics of follicular fluid cfRNAs have not been reported. Furthermore, their implications are still barely understood in the evaluation of follicular fluid from follicles of different sizes, which warrants further studies. Objective: This study investigated the landscape and characteristics of follicular fluid cfRNAs, the source of organization, and the potential for distinguishing between follicles of different sizes. Methods: Twenty-four follicular fluid samples were collected from 20 patients who received in vitro fertilization (n = 9) or ICSI (n = 11), including 16 large follicular fluid and 8 small follicular fluid samples. Also, the cfRNA profile of follicular fluid samples was analyzed by RNA sequencing. Results: This result indicated that the concentration of follicular fluid cfRNAs ranged from 0.78 to 8.76 ng/ml, and fragment length was 20–200 nucleotides. The concentration and fragment length of large follicular fluid and small follicular fluid samples were not significantly different (p > 0.05). The technical replica correlation of follicular fluid samples ranged from 0.3 to 0.9, and the correlation of small follicular fluid samples was remarkably (p < 0.001) lower than that of large follicular fluid samples. Moreover, this study found that cfRNAs of the follicular fluid could be divided into 37 Ensembl RNA biotypes, and a large number of mRNAs, circRNAs, and lncRNAs were observed in the follicular fluid. The number of cfRNAs in large follicular fluid was remarkably (p < 0.05) higher than that of small follicular fluid. Furthermore, the follicular fluid contained a large amount of intact mRNA and splice junctions and a large number of tissue-derived RNAs, which are at a balanced state of supply and elimination in the follicular fluid. KEGG pathway analysis showed that differentially expressed cfRNAs were enriched in several pathways, including thyroid hormone synthesis, the cGMP-PKG signaling pathway, and inflammatory mediator regulation of TRP channels. In addition, we further showed that four cfRNAs (TK2, AHDC1, PHF21A, and TTYH1) serve as a potential indicator to distinguish the follicles of different sizes. The ROC curve shows great potential to predict follicular fluid from follicles of different sizes [area under the curve (AUC) > 0.88]. Conclusion: Overall, our study revealed that a large number of cfRNAs could be detected in follicular fluid and could serve as a potential non-invasive biomarker in distinguishing between follicles of different sizes. These results may inform the study of the utility and implementation of cfRNAs in clinical practice.
Daily requirement of softgel thyroxine is independent from gastric juice pH

Background Softgel levothyroxine (LT4) preparation showed a better in vitro dissolution profile at increasing pH as compared to tablet LT4 preparation. Clinical studies suggested a better performance of softgel LT4 preparation in patients with gastric disorders but whether this finding is related to gastric juice pH variation in vivo is not known. Methods Twenty-eight hypothyroid patients (24F/4M; median age=50 treated with tablet LT4 (median dose= 1.65 µg/kg/day) and with stable thyroid stimulating hormone (TSH) values on target (<0.8-2.5> mU/l) have been shifted to softgel LT4 preparation. The dose of softgel LT4 has been titrated to obtain a similar individual serum TSH value. All subjects followed a specific treatment schedule, taking LT4 in fasting condition and then abstaining from eating or drinking for at least 1 hour. Owing to the presence of long-lasting dyspepsia or of already known gastric disorders, all patients underwent endoscopy, upon informed consent. Gastric juice has been collected during endoscopy to measure gastric pH. Then we plotted the dose of LT4 with the gastric pH obtained in vivo, before and after the switch tablet/softgel preparation in all patients. Results Upon the switch tablet/softgel preparation, the therapeutic LT4 dose was very slightly reduced (-6%) in the whole sample. However, the individual variations revealed the existence of two populations, one without any dose reduction (A) and the other showing a dose reduction >20% (B). Upon matching with the actual gastric pH, patients with normal pH (A: n=17; 14F/3M, median 1.52) no showed a lower softgel LT4 requirement. Instead, among patients with reduced gastric acid production (B: n=11; 10F/1M, median pH 5.02) the vast majority (10/11; 91%, p<0.0001) benefited from a lower dose of softgel LT4 (median = -23%, p<0.0001). Interestingly, the dose of LT4 in tablet correlated with pH value (Spearman’s ρ =0.6409; p = 0.0002) while softgel dose was independent from gastric juice pH (Spearman’s ρ =1.952; p = 0.3194). Conclusions These findings provide evidence that softgel LT4 preparation is independent from the actual gastric pH in humans and may represent a significant therapeutic option in patients with increased LT4 requirement, owed to disorders impairing the gastric acidic output.
Biomarker-driven feedback control of synthetic biology systems for next-generation personalized medicine

Many current clinical therapies for chronic diseases involve administration of drugs using dosage and bioavailability parameters estimated for a generalized population. This standard approach carries the risk of under dosing, which may result in ineffective treatment, or overdosing, which may cause undesirable side effects. Consequently, maintaining a drug concentration in the therapeutic window often requires frequent monitoring, adversely affecting the patient’s quality of life. In contrast, endogenous biosystems have evolved finely tuned feedback control loops that govern the physiological functions of the body based on multiple input parameters. To provide personalized treatment for chronic diseases, therefore, we require synthetic systems that can similarly generate a calibrated therapeutic response. Such engineered autonomous closed-loop devices should incorporate a sensor that actively tracks and evaluates the disease severity based on one or more biomarkers, as well as components that utilize these molecular inputs to bio compute and deliver the appropriate level of therapeutic output. Here, we review recent advances in applications of the closed-loop design principle in biomedical implants for treating severe and chronic diseases, highlighting translational studies of cellular therapies. We describe the engineering principles and components of closed-loop therapeutic devices, and discuss their potential to become a key pillar of personalized medicine.
An empirical analysis of the supply chain flexibility using blockchain technology

Building a flexible supply chain can enable the firms to manage their supply chains to adapt effectively to dynamic market demand changes and thus guarantee their accelerated growth in the future. In this vein, this study aims to address several important issues in supply chain management by considering two characteristics of blockchain technology (i.e., information transparency and security of blockchain technology) and exploring the specific conditions under which firms are likely to develop trust in supply chain management. Furthermore, we argue that such supply chain trust is vital to the success of achieving and increasing supply chain flexibility. In addition, we propose that top management teams’ digital leadership within the firms plays a vital role in moderating the contribution of each dimension of blockchain technology to supply chain trust. Using data from a large sample of 338 firms in China, we perform structural equation modeling to examine our conceptual framework empirically. Our results highlight and support the idea that blockchain technology’s information transparency and security influence the trust-building in a supply chain and supply chain flexibility and articulate the particular importance of digital leadership in explaining the contribution of different blockchain technology characteristics to trust-building. Our study advances the theoretical, empirical, and managerial analysis of critical factors to build trust and achieve flexibility in supply chains.
Immunological characterization and function analysis of L-type lectin from spotted knifejaw, Oplegnathus punctatus

Lily-type lectin (LTL) plays significant roles in innate immune response against pathogen infection. LTL in animals and plants has received widespread attention. In the present study, an LTL (OppLTL) was identified from spotted knifejaw Oplegnathus punctatus. The OppLTL encoded a typical Ca2+-dependent carbohydrate-binding protein containing a CRD domain. The qRT-PCR showed that it was mainly expressed in the gill and was significantly upregulated after Vibrio anguillarum challenge. The agglutination analysis showed that the recombinant OppLTL could bind and agglutinate Gram-negative and Gram-positive bacteria in a Ca2+-dependent manner. However, the binding activity was different. Meanwhile, the recombinant OppLTL could hemagglutinate mammalian and teleost erythrocytes. Subcellular localization revealed that OppLTL was mainly detected in the cytoplasm of HEK293T cells. The dual-luciferase analysis revealed that OppLTL could inhibit the activity of the NF-κB signal pathway in HEK293T cells after OppLTL overexpression. These findings collectively demonstrated that OppLTL could be involved in host innate immune response and defense against bacterial infection in spotted knifejaw.
Relationship between gut microbiota and lymphocyte subsets in Chinese Han patients with spinal cord injury

This study is to investigate the changes of lymphocyte subsets and the gut microbiota in Chinese Han patients with spinal cord injury (SCI). We enrolled 23 patients with SCI and 21 healthy controls. Blood and fecal samples were collected. The proportion of lymphocyte subsets was detected by flow cytometry. 16S rDNA sequencing of the V4 region was used to analyze the gut microbiota. The changes of the gut microbiota were analyzed by bioinformatics. Correlation analysis between gut microbiota and lymphocyte subsets was performed. CD4 + cells, CD4 + /CD8 + ratio and CD4 + CD8 + cells in peripheral blood of SCI patients were significantly lower than those of the control group (P < 0.05). There was no significant difference in B cells and CIK cells between the SCI group and the control group. The gut microbiota community diversity index of SCI patients was significantly higher than that of healthy controls. In SCI patients, the relative abundance of Lachnospiraceae (related to lymphocyte subset regulation), Ruminococcaceae (closely related to central nervous system diseases), and Escherichia-Shigella (closely related to intestinal infections) increased significantly, while the butyrate producing bacteria (Fusobacterium) that were beneficial to the gut were dramatically decreased. Correlation analysis showed that the five bacterial genera of SCI patients, including Lachnospiraceae UCG-008, Lachnoclostridium 12, Tyzzerella 3, Eubacterium eligens group, and Rumencocciucg-002, were correlated with T lymphocyte subsets and NK cells. In the SCI group, the flora Prevotella 9, Lachnospiraceae NC2004 group, Veillonella, and Sutterella were positively correlated with B cells. However, Fusobacterium and Akkermansia were negatively correlated with B cells. Moreover, Roseburia and Ruminococcaceae UCG-003 were positively correlated with CIK cells. Our results suggest that the gut microbiota of patients with SCI is associated with lymphocyte subsets. Therefore, it is possible to improve immune dysregulation in SCI patients by modulating gut microbiota, which may serve as a new therapeutic method for SCI.
Isolation and characterization of phosphate solubilizing bacteria naturally colonizing legumes rhizosphere in Morocco

Low-cost and environmentally friendly agricultural practices have received increasing attention in recent years. Developing microbial inoculants containing phosphate (P) solubilizing bacteria (PSB) represents an emerging biological solution to improve rhizosphere P availability. The present study aims to explore PSB strains isolated from soils located at different bioclimatic stages in Morocco and present in various legumes rhizosphere to improve agronomic microbial fertilizer’s effectiveness. It was also aimed to test the isolated strains for their ability to solubilize P in NBRIP medium with Tricalcium P (Ca3 (PO4)2) (TCP), rock phosphate (RP), and their combination as a source of phosphorus, by (22) experiment design. Bacterial strains with a high P solubility index (PSI) were selected, characterized, and compared to commercial control. The vanadate-molybdate method was used to estimate P solubilization activity. Stress tolerance to salinity, acidity, drought, and temperature was tested. From all isolated strains (64), 12 were screened as promising biotechnological interest because of their P solubilization and their good resistance to different drastic conditions. Besides, the strain WJEF15 showed the most P solubility efficiency in NBRIP solid medium with a PSI of 4.1; while the WJEF61 strain was located as the most efficient strain in NBRIP-TCP liquid medium by releasing 147.62 mg.l–1 of soluble P. In contrast, in the NBRIP-RP medium, the strain WJEF15 presented maximum solubilization with 25.16 mg.l–1. The experiment design showed that a combination of RP and TCP with max level progressively increases P solubilization by 20.58%, while the WJEF63 strain has the most efficient concentration of 102.69 mg.l–1. Indeed, among the selected strains, four strains were able to limit tested fungi growth. Thus, results reveal a potential effect of selecting PSBs to support cropping cultures as plant growth-promoting rhizobacteria (PGPR).
3D in-vitro cultures of human bone marrow and Wharton’s jelly derived mesenchymal stromal cells show high chondrogenic potential

In this study, chondrogenic potentials of 3D high-density cultures of Bone Marrow (BM) and Wharton’s Jelly (WJ)-derived mesenchymal stromal cells (MSCs) was investigated by chondrogenesis- and cytokine-related gene expression over a 16-day culture period supplemented with human transforming growth factor (hTGF)-β1 at 10 ng/ml. In BM-MSC 3D models, a marked upregulation of chondrogenesis-related genes, such as SOX9, COL2A1, and ACAN (all p < 0.05) and formation of spherical pellets with structured type II collagen fibers were observed. Similarly, WJ-based high-density culture appeared higher in size and more regular in shape, with a significant overexpression of COL2A1 and ACAN (all p < 0.05) at day 16. Moreover, a similar upregulation trend was documented for IL-6 and IL-10 expression in both BM and WJ 3D systems. In conclusion, MSC-based high-density cultures can be considered a promising in vitro model of cartilage regeneration and tissue engineering. Moreover, our data support the use of WJ-MSCs as a valid alternative for chondrogenic commitment of stem cells in regenerative medicine. Graphical Abstract
Expression of CXCR4 on CD4+ T cells predicts body composition parameters in female adolescents with anorexia nervosa

Anorexia nervosa (AN) is a severe eating disorder characterized by excessive weight loss and lack of recognition of the seriousness of the current low body weight. Individuals with AN frequently exhibit an enhanced inflammatory state and altered blood levels of cytokines and chemokines. However, the expression of chemokine receptors in AN and the association with body composition parameters and treatment effects are still unknown. In this study, we examined the expression of CCR4, CCR6, CXCR3, and CXCR4 on peripheral blood T cells in female adolescents with AN before (T0, n = 24) and after 6 weeks of multimodal therapy (T1, n = 20). We also investigated their value to predict body mass index (BMI) and fat mass index (FMI) at baseline. Using multi-parameter flow cytometry, we found increased expression of CCR4, CXCR3, and CXCR4, but not CCR6, on CD4+ T cells in AN at T0 when compared to healthy controls (HC, n = 20). At T1, CXCR3 and CXCR4 expression decreased in AN. We found a close link between CCR4, CCR6 and CXCR4 expression and the adolescent mental health status in the study cohort as determined by the Strengths and Difficulties Questionnaire (SDQ). Specifically, CXCR4 expression correlated positively with emotional symptoms and peer relationship problems, as well as with the total sum score of the SDQ. In addition, CXCR4 expression on CD4+ T cells was a significant predictor of BMI and FMI in female adolescents. Our findings that CXCR4 expression on T cells is altered in adolescents with AN and predicts body composition parameters in adolescents suggest an impact of this chemokine receptor in the pathogenesis of AN.
A single-center comparison of our initial experiences in treating penile and urethral cancer with video-endoscopic inguinal lymphadenectomy (VEIL) and later experiences in melanoma cases

Background Video-endoscopic inguinal lymphadenectomy (VEIL) is a minimally invasive approach that is increasingly indicated in oncological settings, with mounting evidence for its long-term oncological safety. Objectives To present our single-center experience of treating penile and urethral cancer with VEIL, as well as its more recent application in melanoma patients. Methods We prospectively recorded our experiences with VEIL from September 2010 to July 2018, registering the patient primary indication, surgical details, complications, and follow-up. Results Twenty-nine patients were operated in one (24) or both (5) groins; 18 had penile cancer, 1 had urethral cancer, and 10 had melanoma. A mean 8.62 ± 4.45 lymph nodes were removed using VEIL and of these, an average of 1.00 ± 2.87 were metastatic; 16 patients developed lymphocele and 10 presented some degree of lymphedema; there were no skin or other major complications. The median follow-up was 19.35 months; there were 3 penile cancer patient recurrences in the VEIL-operated side. None of the melanoma patients presented a lymphatic inguinal recurrence. Conclusions VEIL is a minimally invasive technique which appears to be oncologically safe showing fewer complications than open surgery. However, complications such as lymphorrhea, lymphocele, or lymphedema were not diminished by using VEIL.
Association of healthy lifestyles on the risk of hypertension, type 2 diabetes mellitus, and their comorbidity among subjects with dyslipidemia

Background Adherence to a healthy lifestyle could reduce the risk of hypertension and diabetes in general populations; however, whether the associations exist in subjects with dyslipidemia remains unclear. This study aimed to investigate the integrated effect of lifestyle factors on the risk of hypertension, type 2 diabetes mellitus (T2DM), and their comorbidity among subjects with dyslipidemia. Methods In total of 9,339 subjects with dyslipidemia were recruited from the baseline survey of the Guangzhou Heart Study. A questionnaire survey and medical examination were performed. The healthy lifestyle score (HLS) was derived from five factors: smoking, alcohol drinking, diet, body mass index, and leisure-time physical activity. Odds ratios (ORs) with 95% confidence interval (95% CI) were calculated by using the logistic regression model and the multinomial logistic regression after adjusting for confounders. Results The prevalence of hypertension, T2DM, and their comorbidity was 47.65, 16.02, and 10.10%, respectively. Subjects with a higher HLS were associated with a lower risk of hypertension, T2DM, and their comorbidity. In comparison to the subjects with 0–2 HLS, the adjusted ORs for subjects with five HLS was 0.48 (95% CI: 0.40–0.57) and 0.67 (95% CI: 0.54–0.84) for hypertension and T2DM. Compared with subjects with 0-2 HLS and neither hypertension nor T2DM, those with five HLS had a lower risk of suffering from only one disease (OR: 0.48, 95% CI: 0.40–0.57) and their comorbidity (OR: 0.35, 95% CI: 0.26–0.47). Conclusions The results suggest that the more kinds of healthy lifestyle, the lower the risk of hypertension, T2DM, and their comorbidity among subjects with dyslipidemia. Preventive strategies incorporating lifestyle factors may provide a more feasible approach for the prevention of main chronic diseases.
Comparison of methods of isolating extracellular vesicle microRNA from HepG2 cells for High-throughput sequencing

Background: Extracellular vesicles (EVs) were reported to participate in various cellular processes based on the biomolecules, particularly microRNAs. Numerous commercial EVs isolation reagents are available. However, whether these reagents are suitable for separating EVs from the culture medium supernatant supernatant of model cell lines, such as HepG2, and whether the isolated products are suitable for High-throughput sequencing remains unclear. Methods: We examined three commonly used EVs isolation kits: the ExoQuick-TC exosome precipitation solution (EQ), Total Exosome Isolation from cell culture medium (EI), and exoEasy Maxi Kit (EM), to isolate EVs from HepG2 cell culture medium supernatants. EVs were identified based on marker proteins, particle size measurements, and electron microscopy analysis. The total amounts of microRNA and microRNA High-throughput sequencing data quality from EVs isolated by each kit were compared. Results: The total amount of EVs’ microRNA isolated from the EI and EM groups were higher than that obtained from the EQ group (EQ/EI: p = 0.036, EI/EM: p = 0.024). High-throughput sequencing data quality evaluation showed that the EI group possessed higher quality than those in the EM group. Conclusion: For the cell culture medium from HepG2, EVs’ microRNA isolated by EI reagents might be more suitable for High-throughput sequencing applications.