Miracle-dz/UniFAR-FTUs huggingface dataset:
Phage-delivered sensitisation with subsequent antibiotic treatment reveals sustained effect against antimicrobial resistant bacteria

Temperate phages integrated with clustered regularly interspaced short palindromic repeat (CRISPR)/Cas systems have been gaining attention as potential strategies for combating bacteria resistant to antimicrobials. To further advance this technology, phage recombination procedure should be improved, and the bactericidal effect should be examined in detail and compared with conventional lytic phage strategy. The possibility of the emergence of mutational resistance, a phenomenon commonly observed with lytic phage therapy, should be illustrated. Methods: Here, we developed a novel one-step cloning method to fulfil the recombination of CRISPR/Cas9 system within the genome of a new isolated lysogenic Escherichia coli phage. Then, we proposed and developed a phage-delivered resistance eradication with subsequent antibiotic treatment (PRESA) strategy. The removal efficiency and antimicrobial effect of the plasmids were analysed. Long-term antimicrobial effect was evaluated by continued OD600 monitoring for 240 hours to illustrate the potential mutational resistance, compared with the lytic phage strategy. The treatment effect of PRESA was evaluated in vivo by determining bacterial loads in the skin and intestine of infected mice, in contrast with lytic phage therapy. Genome sequencing was performed to identify mutations in bacterial cells treated with phage strategies. Results: Phage-delivered CRISPR targeting efficiently eradicated and blocked the transfer of the antibiotic resistance plasmid. PRESA decreased the bacterial load by over 6- and 5-logs in vitro and in vivo, respectively. Importantly, while lytic phages induced mutational phage resistance at 24 h in vitro and 48 hours in vivo, PRESA demonstrated a constant effect and revealed no resistant mutants. Genes involved in DNA mismatch repair were upregulated in cells undergoing Cas9-based plasmid cleavage, which may reduce the development of mutations. Conclusion: The PRESA strategy for eradicating resistant bacteria showed high bactericidal efficacy and a sustained inhibition effect against resistant bacteria. By restoring the efficacy of low-cost antibiotics, PRESA could be developed as an efficient and economical therapy for infections of antibiotic resistant bacteria.
Cane toads reduce the abundance and site occupancy of Merten’s water monitor (Varanus mertensi)

Introduced into Australia in 1935, the cane toad (Chaunus [Bufo] marinus) threatens native vertebrate predators. However, there have been few rigorous quantitative studies on species threatened by this toxic invasive species. This study examines the changes in abundance and proportion of sites occupied by Merten’s water monitor (Varanus mertensi) at a site in the Northern Territory following invasion by cane toads. The study was located at Manton Dam Recreation Area, 70 km south of Darwin, and ran for 18 months. Cane toads were first detected at the study site in February 2005, three months after the first survey, and their abundance remained low until February 2006, when an increase was observed. The abundance of V. mertensi declined substantially 8 months after the arrival of cane toads and remained low. The probability of detection of V. mertensi varied considerably within and among surveys, and was higher in the wet season surveys. The proportion of sites occupied by V. mertensi at the start of the study was 0.95 ± 0.03. Site occupancy remained high for 6 months after the arrival of cane toads, but declined gradually to a low of 0.15 ± 0.16 within 12 months. There has been demonstrable change in the abundance and proportion of sites occupied by V. mertensi following the colonisation of cane toads, but the population has been able to persist. Monitoring of populations impacted by cane toads may provide unique opportunities to understand processes underlying local extinction and colonisation of native predators following the impact of invasive species.
Altitudinal differentiation in the diapause response of two species of dung flies

1. Seasonality is a prime selective factor promoting genetic differentiation of populations. Local adaptation in diapause response was investigated in the two geographically and altitudinally widespread dung flies Scathophaga stercoraria (Diptera: Scathophagidae) and Sepsis cynipsea (Diptera: Sepsidae).
Government Consumption, Government Debt and Economic Growth

This paper compares the effects of government consumption and government debt on economic growth by using data from 83 countries, including both developed and developing markets, over the period between 1960 and 2014. Linear regressions reveal that the negative effects of government consumption are relatively higher than the negative effects of government debt. A nonlinear investigation further suggests that the restrictions on government expenditure to prevent negative growth are shown to be more important for countries with lower trade openness, lower inflation, or higher financial depth, whereas the restrictions on government debt are shown to be more important for countries with higher trade openness, lower inflation or higher financial depth.
The Visual Responses of Flying Mosquitoes.

Summary. 1. Observations were made on females of the yellow-fever mosquito, Aedes (Stegomyia) wgypti, which had not had a blood meal. 2. When suspended by a silk fibre they orientated inaccurately but consistently away from the source of an horizontal beam of artificial light. 3. They orientated accurately towards a vertical black stripe on a white background, and would rotate maintaining this position when the stripe was rotated around them up to 25 revolutions per minute. 4. Presented with two black stripes the mosquitoes faced one or other stripe, and not between the two. Light stimulation of the front part of the eye evoked a more powerful turning-away response than stimulation of the sides. 5. The mosquitoes were attracted by and followed stripes which were moving, abandoning stationary similarly striped or darker walls to do so. 6. Unsuspended, freely flying mosquitoes in a wind tunnel orientated consistently up wind, keeping position or making headway as long as the background was visible, but not in darkness. Without a wind, but with transverse stripes moving along the floor, they flew with or ahead of the stripe movement, the visual equivalent of flying up wind. 7. The above evidence that up wind orientation involves a visual “compensation” mechanism is discussed, and a theory of the mechanism put forward. 8. The lateral ommatidia initiate the responses to light and to moving objects, working in a different way from the dorsal and ventral ommatidia, which are concerned in up wind orientation. Interplay between the two classes of response may take place. The work was carried out in the Department of Entomology of the London School of Hygiene and Tropical Medicine, during my tenure of the Avebury Studentship. I wish to thank Professor P. A. Buxton and all the members of his department, especially Dr. V. B. Wigglesworth, for their hospitality and fruitful suggestions.
Root damage by conspecific larvae induces preference for oviposition in cabbage root flies

In nature, herbivorous insects probably rarely encounter host plants that are free of other herbivores. These herbivores may have altered the suitability of a plant for the development of further herbivores, e.g. by induction of chemical, physical, or phenological responses of the plant (Karban & Myers, 1989). Sensory and behavioural mechanisms to detect and avoid intra- or interspecific competitors on a potential host plant are known for several insects. For instance, Pieris brassicae, P. rapae and Danaus plexippus all prefer plants for oviposition which are free of conspecific eggs or larvae (Rothschild & Schoonhoven, 1977). Similarly, oviposition by Trichoplusia ni on cabbage leaves is deterred by the presence of feeding conspecific larvae or their frass (Renwick & Radke, 1980). For Delia radicum (Dipt., Anthomyiidae), oviposition is deterred by the presence of frass from the caterpillars of Evergestis forficalis on host leaves (Jones & Finch, 1987).
Yield potential progress in short bread wheats in Northwest Mexico

Germplasm from the spring wheat (Trificum oesfivum L.) breeding program at the International Center for Improvement of Maize and Wheat (CIMMYT has had a major impact on the yield of irrigated spring wheats in most developing countries in the past 30 yr. The rate and nature of yield potential progress in this germplasm was measured cornparing eight outstanding short cultivars released in northwest Mexico between 1962 and 1988. They were grown under irrigation and optimal management, including disease and lodging protection, in each of six winter growing seasons (1989-1990 to 1994-1995) at the CIANO (Centro de Investigaciones Agricolas del Noroeste) experiment station in Sonora, Mexico. There were highly significant effects of cultivar on grain yield, and, although cultivar x year interaction was significant, there were few significant crossover interactions between pairs of genotypes and years in the grain yield data set. Yield averaged across the 6 yr increased linearly from 6680 kg ha -l for the earliest cultivar, Pitic 62, to 8475 kg ha -l for Bacanora 88, the latest. The rate of progress against year of release was 67 kg ha -1 yr -1 (r = 0.99, P< 0.001), or 0.88% per year. Grain yield progress was correlated with kernel number per square meter (r = 0.84, P < 0.01) and harvest index (r = 0.81, P < 0.02), but not with total biomass production, kernel weight, days to anthesis, spikes per square meter, or kernels per spike. Thus linear progress in yield within short germplasm has continued at least until the late 1980s, and the yield components studied did not indicate any clear direction for future progress, apart from that suggested by the strong relationships between grain yield and harvest index and grain yield and kernels per square meter, as has been seen in most studies of yield progress in cereals.
Testing Port-Orford-cedar for resistance to Phytophthora.

Root rot mortality of Port-Orford-cedar (Chamaecyparis lawsoniana) in western Oregon and Washington and northwestern California is caused almost exclusively by Phytophthora lateralis. Progression of P. lateralis lesions was slower on four cedar trees selected for phenotypic resistance than on randomly selected trees. Inoculations of seedlings and rooted cuttings with zoospores or infested soil and of excised branches with inserted mycelium gave similar results on the selected trees
Association of clinical and radiographic findings with the outcomes of 93 patients with COVID-19 in Wuhan, China

Rationale: To retrospectively analyze serial chest CT and clinical features in patients with coronavirus disease 2019 (COVID-19) for the assessment of temporal changes and to investigate how the changes differ in survivors and nonsurvivors. Methods: The consecutive records of 93 patients with confirmed COVID-19 who were admitted to Wuhan Union Hospital from January 10, 2020, to February 22, 2020, were retrospectively reviewed. A series of chest CT findings and clinical data were collected and analyzed. The serial chest CT scans were scored on a semiquantitative basis according to the extent of pulmonary abnormalities. Chest CT scores in different periods (0 - 5 days, 6 - 10 days, 11 - 15 days, 16 - 20 days, and > 20 days) since symptom onset were compared between survivors and nonsurvivors, and the temporal trend of the radiographic-clinical features was analyzed. Results: The final cohort consisted of 93 patients: 68 survivors and 25 nonsurvivors. Nonsurvivors were significantly older than survivors. For both survivors and nonsurvivors, the chest CT scores were not different in the first period (0 - 5 days) but diverged afterwards. The mortality rate of COVID-19 monotonously increased with chest CT scores, which positively correlated with the neutrophil-to-lymphocyte ratio, neutrophil percentage, D-dimer level, lactate dehydrogenase level and erythrocyte sedimentation rate, while negatively correlated with the lymphocyte percentage and lymphocyte count. Conclusions: Chest CT scores correlate well with risk factors for mortality over periods, thus they may be used as a prognostic indicator in COVID-19. While higher chest CT scores are associated with a higher mortality rate, CT images taken at least 6 days since symptom onset may contain more prognostic information than images taken at an earlier period.
Hepatoma cell-intrinsic TLR9 activation induces immune escape through PD-L1 upregulation in hepatocellular carcinoma

A TLR9 agonist in combination with a PD-1 inhibitor produced powerful antitumor responses in a clinical trial despite TLR9 agonists as monotherapies failing to generate systemic antitumor immune responses due to immunosuppressive effects. However, the mechanism involved in the improved response induced by their combination remains unknown. Methods: Subcutaneous and orthotopic Hepa1-6 tumor model was used for single-drug and combined-drug treatment. We used TLR9 agonist stimulation or lentiviral vectors to overexpress TLR9 and activate TLR9 signaling. We next investigated the crosstalk between PARP1 autoPARylation and ubiquitination and between STAT3 PARylation and phosphorylation mediated by TLR9. Tissue chips were used to analyze the relationships among TLR9, PARP1, p-STAT3 and PD-L1 expression. Results: In this study, we found that the TLR9 agonist in combination with anti-PD-1 therapy or anti-PD-L1 therapy yielded an additive effect that inhibited HCC growth in mice. Mechanistically, we found that TLR9 promoted PD-L1 transcription by enhancing STAT3 Tyr705 phosphorylation. Then, we observed that TLR9 negatively regulated PARP1 expression, which mediated a decrease in STAT3 PARylation and an increase in STAT3 Tyr705 phosphorylation. Moreover, we found that TLR9 enhanced PARP1 autoPARylation by inhibiting PARG expression, which then promoted the RNF146-mediated ubiquitination and subsequent degradation of PARP1. Finally, we observed positive associations between TLR9 and p-STAT3 (Tyr705) or PD-L1 expression and negative associations between TLR9 and PARP1 in HCC patient samples. Conclusions: We showed that hepatoma cell-intrinsic TLR9 activation regulated the crosstalk between PARP1 autoPARylation and ubiquitination and between STAT3 PARylation and phosphorylation, which together upregulated PD-L1 expression and finally induces immune escape. Therefore, combination therapy with a TLR9 agonist and an anti-PD-1 antibody or anti-PD-L1 had much better antitumor efficacy than either monotherapy in HCC.
Depletion of the diabetic gut microbiota resistance enhances stem cells therapy in type 1 diabetes mellitus

Microbiome, considered as the “second genome” of the host, is altered in type 1 diabetes mellitus (T1DM) patients to a state of dysbiosis. Mesenchymal stem cell (MSC) transplantation is a promising treatment for T1DM but is limited by several factors in the diabetic host. In this study, we tested the hypothesis that dysbiotic gut microbiota may limit MSC therapy, and modulating gut microbiota may help to improve the effects of MSC transplantation. Methods: NOD/Ltj mice, treated with adipose-derived stem cells (ADSCs), were fed with an antibiotics cocktails (Abx) for 1 week. The blood glucose levels, insulitis, intestinal permeability and gut bacteria translocation to the pancreas were evaluated. 16s rRNA and colon tissue transcription sequencing were performed to analyze beneficial bacteria and reactive host biomolecules in the ADSCs+Abx group. Based on the sequencing results, specific bacteria were gavaged orally to diabetic mice to confirm their effect on ADSCs transplantation in T1DM was determined. Results: We found that the recolonized the diabetic gut microbiota abolished the therapeutic effect of ADSCs. On the contrary, depletion of the diabetic gut microbiota by antibiotics treatment in diabetic mice significantly enhanced the therapeutic effects of ADSCs as measured by reversal of hyperglycemia, insulitis, and increased insulin output. Mechanistically, treatment with antibiotics increased the abundance of Bifidobacterium in the gut and reduced bacterial translocation to the pancreas by promoting Mucin2 expression and thickening the mucus layer through TRPM7. The mechanism was confirmed the re-colonization of the gut by B.breve through oral gavage that produced similar results. Conclusions: These results provide the rationale for a new approach to improve MSC therapy for T1DM by altering the gut microbiota.
Exercise protects proliferative muscle satellite cells against exhaustion via the Igfbp7-Akt-mTOR axis

Background and Purpose: The exhaustion of muscle satellite cells (SCs) is correlated with muscle diseases, including sarcopenia and Duchenne muscular dystrophy. Exercise benefits skeletal muscle homeostasis and promotes proliferation of SCs. Elucidating the molecular mechanism underlying the muscle function-improving effect of exercise has important implications in regenerative medicine. Methods: Herein, we investigated the effect of 4-week treadmill training on skeletal muscle and SCs in mice. Hematoxylin and eosin (HE) staining was utilized to detect the morphometry of skeletal muscles. Flow cytometry and immunofluorescence were conducted to analyze the abundance and cell cycle of SCs. RNA sequencing was performed to elucidate the transcriptional regulatory network of SCs. The ChIP-PCR assay was used to detect enrichment of H3K27ac at the promoters of Akt. Results: We observed that exercise resulted in muscle hypertrophy and improved muscle regeneration in mice. Unexpectedly, exercise promoted cell cycling but suppressed the Akt-mTOR pathway in SCs. Proliferative SCs in “exercised mice” required suppressed mTOR activity to limit mitochondrial metabolism, maintaining the “limited activation status” of SCs against exhaustion. Mechanistically, exercise upregulated the expression of Igfbp7, thereby impeding the phosphorylation of Akt and resulting in inhibited mTOR activity and limited mitochondrial metabolism. The limited mitochondrial metabolism resulted in hypoacetylation of histone 3 and reduced enrichment of H3K27ac at promoters of Akt, decreasing the transcription of Akt. Moreover, repeatedly injured mice showed a preserved SC pool and improved muscle regeneration by the suppression of Akt-mTOR signaling. Conclusions: The findings of our study show that exercise protects proliferative SCs against exhaustion via the Igfbp7-Akt-mTOR axis. These findings establish a link between mechanical signaling, mitochondrial metabolism, epigenetic modification, and stem cell fate decisions; thus, present potential therapeutic targets for muscle diseases correlated with SC exhaustion.
STIM1 is a metabolic checkpoint regulating the invasion and metastasis of hepatocellular carcinoma

Background: Cancer cells undergoing invasion and metastasis possess a phenotype with attenuated glycolysis, but enhanced fatty acid oxidation (FAO). Calcium (Ca2+)-mediated signaling pathways are implicated in tumor metastasis and metabolism regulation. Stromal-interaction molecule 1 (STIM1) triggered store-operated Ca2+ entry (SOCE) is the major route of Ca2+ influx for non-excitable cells including hepatocellular carcinoma (HCC) cells. However, whether and how STIM1 regulates the invasion and metastasis of HCC via metabolic reprogramming is unclear. Methods: The expressions of STIM1 and Snail1 in the HCC tissues and cells were measured by immunohistochemistry, Western-blotting and quantitative PCR. STIM1 knockout-HCC cells were generated by CRISPR-Cas9, and gene-overexpression was mediated via lentivirus transfection. Besides, the invasive and metastatic activities of HCC cells were assessed by transwell assay, anoikis rate in vitro and lung metastasis in vivo. Seahorse energy analysis and micro-array were used to evaluate the glucose and lipid metabolism. Results: STIM1 was down-regulated in metastatic HCC cells rather than in proliferating HCC cells, and low STIM1 levels were associated with poor outcome of HCC patients. During tumor growth, STIM1 stabilized Snail1 protein by activating the CaMKII/AKT/GSK-3β pathway. Subsequently, the upregulated Snail1 suppressed STIM1/SOCE during metastasis. STIM1 restoration significantly diminished anoikis-resistance and metastasis induced by Snail1. Mechanistically, the downregulated STIM1 shifted the anabolic/catabolic balance, i.e., from aerobic glycolysis towards AMPK-activated fatty acid oxidation (FAO), which contributed to Snail1-driven metastasis and anoikis-resistance. Conclusions: Our data provide the molecular basis that STIM1 orchestrates invasion and metastasis via reprogramming HCC metabolism.
Human amniotic mesenchymal stromal cells promote bone regeneration via activating endogenous regeneration

Rationale: The effectiveness of stem cell based-therapy for bone regeneration has been demonstrated; yet, clinical application of autologous stem cells is still limited by invasive acquisition, long culture processes, and high cost. Besides, it remains controversial whether autologous stem cells could directly participate in tissue repair after differentiation. Thus, increasing allogeneic stem cells have been developed into drugs to indirectly activate endogenous regeneration and induce tissue regeneration. Human amniotic mesenchymal stromal cells (HAMSCs) have been extensively studied, showing multiple regulatory functions, but mechanisms of HAMSCs in promoting bone regeneration are remain unclear. Methods: Proteome profile of HAMSCs and their functions on vascularized bone regeneration were investigated in vitro, while rabbit cranial defect model was used to further detect the effects of bone formation in vivo. Results: HAMSCs secrete many osteogenic, angiogenic, and immunomodulatory cytokines. In vitro, HAMSCs can promote human bone-marrow mesenchymal stromal cells (HBMSCs) migration and osteogenic differentiation; promote the capillary-tube formation of human umbilical vascular endothelial cells (HUVECs), induce HUVECs migration and pro-angiogenic genes expression, and promote M2 macrophage polarization. Further, in vivo studies suggested that transplanted HAMSCs could survive and induce M2 macrophages to secrete bone morphogenetic protein-2 (BMP-2) and vascular endothelial growth factor (VEGF) in rabbits' skull defects at an early stage, and, in turn, promote more new bone formation. Conclusion: HAMSCs have good biocompatibility and paracrine function to promote bone repair by stimulating endogenous regeneration.
Numerical Study on Time Dependent Maxwell Nanofluid Slip Flow over Porous Stretching Surface with Chemical Reaction

The recent study deals with the numerical analysis of an unsteady Maxwell nanofluid flow passing through a porous stretch surface with slip boundary condition with chemical reaction effect using Buongiorno's mathematical model. The water based fluid and the gold nanoparticles (Au) are preferred for this study. The similarity transformations are applied to renovate the governing model equations into a set of ordinary non-linear differential equations. The solutions of the coupled non-linear dimensionless equations are numerically decoded using the Nachtsheim-Swigert shooting method together with the Runge-Kutta iterative technique for various values of the flow control parameters. In addition, the built-in function bvp4c of MATLAB is used to enhance the consistency of numerical results. The numerical results are graphically demonstrated and narrated from the physical point of view for the non-dimensional velocity, temperature and concentration profiles, as well as the local coefficient of skin friction, Nusselt number and Sherwood number for different parameters of materials, such as the volume fraction parameter, Deborah number, unsteadiness, slip, stretching, suction and chemical reaction parameters. It is witnessed that the heat transfer rate is widely controlled by the Deborah number for Au-water nanofluid. The outcomes of this analysis clearly indicate the considerable influence of the suction imposed in the model.