Miracle-dz/UniFAR-FTUs huggingface dataset:
The activity of methylene blue against asexual and sexual stages of Plasmodium vivax

Methylene blue (MB) is an alternative for combating drug-resistant malaria parasites. Its transmission-blocking potential has been demonstrated in vivo in murine models, in vitro, and in clinical trials. MB shows high efficacy against Plasmodium vivax asexual stages; however, its efficacy in sexual stages is unknown. In this study, we evaluated the potential of MB against asexual and sexual forms of P. vivax isolated from the blood of patients residing in the Brazilian Amazon. An ex vivo schizont maturation assay, zygote to ookinete transformation assay, direct membrane feed assay (DMFA), and standard membrane feed assay (SMFA) using P. vivax gametocytes with MB exposure were performed. A cytotoxicity assay was also performed on freshly collected peripheral blood mononuclear cells (PBMCs) and the hepatocyte carcinoma cell line HepG2. MB inhibited the P. vivax schizont maturation and demonstrated an IC50 lower than that of chloroquine (control drug). In the sexual forms, the MB demonstrated a high level of inhibition in the transformation of the zygotes into ookinetes. In the DMFA, MB did not considerably affect the infection rate and showed low inhibition, but it demonstrated a slight decrease in the infection intensity in all tested concentrations. In contrast, in the SMFA, MB was able to completely block the transmission at the highest concentration (20 µM). MB demonstrated low cytotoxicity to fresh PBMCs but demonstrated higher cytotoxicity to the hepatocyte carcinoma cell line HepG2. These results show that MB may be a potential drug for vivax malaria treatment.
Growth kinetics and fitness of fluoroquinolone resistant and susceptible Campylobacter jejuni strains of cattle origin

Human enterocolitis is frequently caused by the Gram-negative microaerobic bacterium Campylobacter jejuni. Macrolides (e.g., erythromycin) and fluoroquinolones (FQs) (e.g., ciprofloxacin) are the preferred antibiotics for the treatment of human campylobacteriosis. Rapid emergence of FQ-resistant (FQ-R) Campylobacter during treatment with FQ antimicrobials is well known to occur in poultry. Cattle is also an important reservoir of Campylobacter for humans, and FQ-R Campylobacter from cattle has become highly prevalent in recent years. Even though the selection pressure may have contributed to the expansion of FQ-R Campylobacter, the actual impact of this factor appears to be rather low. In this study, we examined the hypothesis that the fitness of FQ-R Campylobacter may have also played a role in the rise seen in FQ-R Campylobacter isolates by employing a series of in vitro experiments in MH broth and bovine fecal extract. First, it was shown that FQ-R and FQ-susceptible (FQ-S) C. jejuni strains of cattle origin had comparable growth rates when individually cultured in both MH broth and the fecal extract with no antibiotic present. Interestingly, FQ-R strains had small but statistically significant increases over FQ-S strains in growth in competition experiments performed in mixed cultures with no antibiotic present. Lastly, it was observed that FQ-S C. jejuni strains developed resistance to ciprofloxacin more readily at high initial bacterial cell density (107 CFU/mL) and when exposed to low levels of the antibiotic (2–4 μg/mL) compared with that at a low level of initial bacterial cell density (105 CFU/mL) and exposure to a high level of ciprofloxacin (20 μg/mL) in both MH broth and the fecal extract. Altogether, these findings indicate that even though FQ-R C. jejuni of cattle origin may have a slightly higher fitness advantage over the FQ-S population, the emergence of FQ-R mutants from susceptible strains is primarily dictated by the bacterial cell density and the antibiotic concentration exposed under in vitro condition. These observation may also provide plausible explanations for the high prevalence of FQ-R C. jejuni in cattle production due to its overall fit nature in the absence of antibiotic selection pressure and for the paucity of development of FQ-R C. jejuni in the cattle intestine in response to FQ-treatment, as observed in our recent studies.
Liquid biopsy in hematological malignancies: current and future applications

The assessment of the cancer mutational profile is crucial for patient management, stratification, and therapeutic decisions. At present, in hematological malignancies with a solid mass, such as lymphomas, tumor genomic profiling is generally performed on the tissue biopsy, but the tumor may harbor genetic lesions that are unique to other anatomical compartments. The analysis of circulating tumor DNA (ctDNA) on the liquid biopsy is an emerging approach that allows genotyping and monitoring of the disease during therapy and follow-up. This review presents the different methods for ctDNA analysis and describes the application of liquid biopsy in different hematological malignancies. In diffuse large B-cell lymphoma (DLBCL) and Hodgkin lymphoma (HL), ctDNA analysis on the liquid biopsy recapitulates the mutational profile of the tissue biopsy and can identify mutations otherwise absent on the tissue biopsy. In addition, changes in the ctDNA amount after one or two courses of chemotherapy significantly predict patient outcomes. ctDNA analysis has also been tested in myeloid neoplasms with promising results. In addition to mutational analysis, liquid biopsy also carries potential future applications of ctDNA, including the analysis of ctDNA fragmentation and epigenetic patterns. On these grounds, several clinical trials aiming at incorporating ctDNA analysis for treatment tailoring are currently ongoing in hematological malignancies.
Association of NAD+ levels with metabolic disease in a community-based study

Background Nicotinamide adenine dinucleotide (NAD+) is a coenzyme and plays a crucial role in several metabolic processes. This study explored the association of nicotinamide adenine dinucleotide (NAD+) levels with metabolic disease (MD) in adults. Methods In this cross-sectional study, all data were collected from the Jidong community. MD was defined as the presence of one or more of the following disease components: hypertension, dyslipidemia, diabetes, hyperuricemia, obesity, and non-alcoholic fatty liver disease (NAFLD). The MD components were categorized into three groups: those with one component, those with two components, and those with three to six components. The whole blood NAD+ level was measured using a cycling assay and LC-MS/MS analysis. The participants were divided into four groups based on their NAD+ level quartiles. Multivariable logistic regression was used to evaluate the association of the whole blood NAD+ levels with MD. Results Of the 1,394 eligible participants, the average age was 43.2 years, and 74.3% had MD. In the top quartile of NAD+, the prevalence of MD and each of its components (hypertension, hyperlipidemia, diabetes, hyperuricemia, obesity, and NAFLD) were 87.9% 35.2%, 62.3%, 8.7%, 36.9%, 21.0%, and 60.5%, respectively. As compared with the lowest NAD+ quartile (≤29.4 μmol/L), the adjusted odds ratios and 95% confidence interval of the highest quartile were 3.01 (1.87-4.87) for MD, 2.48 (1.44-4.29) for 1 MD component, 2.74 (1.45-5.17) for 2 MD components, and 4.30 (2.32-7.98) for 3-6 MD components. The risk of MD began to increase at NAD+ levels of 31.0 μmol/L, as revealed by the gradient associations of NAD+ levels with MD. There was no significant interaction between age, sex, drinking, smoking, and NAD+ for MD (p for interaction ≥0.10). Conclusions Increased NAD+ was significantly associated with MD, as well as its individual components. Our findings provide new evidence for the relationship between blood NAD+ levels and MD.
A new model based on gamma-glutamyl transpeptidase to lymphocyte ratio and systemic immune-inflammation index can effectively predict the recurrence of hepatocellular carcinoma after liver transplantation

Background Liver transplantation (LT) is one of the most effective treatment modalities for hepatocellular carcinoma (HCC), but patients with HCC recurrence after LT always have poor prognosis. This study aimed to evaluate the predictive value of the gamma-glutamyl transpeptidase-to-lymphocyte ratio (GLR) and systemic immune-inflammation index (SII) in terms of HCC recurrence after LT, based on which we developed a more effective predictive model. Methods The clinical data of 325 HCC patients who had undergone LT were collected and analyzed retrospectively. The patients were randomly divided into a development cohort (n = 215) and a validation cohort (n = 110). Cox regression analysis was used to screen the independent risk factors affecting postoperative recurrence in the development cohort, and a predictive model was established based on the results of the multivariate analysis. The predictive values of GLR, SII and the model were evaluated by receiver operating characteristic (ROC) curve analysis, which determined the cut-off value for indicating patients’ risk levels. The Kaplan-Meier survival analysis and the competing-risk regression analysis were used to evaluate the predictive performance of the model, and the effectiveness of the model was verified further in the validation cohort. Results The recurrence-free survival of HCC patients after LT with high GLR and SII was significantly worse than that of patients with low GLR and SII (P<0.001). Multivariate Cox regression analysis identified GLR (HR:3.405; 95%CI:1.954-5.936; P<0.001), SII (HR: 2.285; 95%CI: 1.304-4.003; P=0.004), tumor number (HR:2.368; 95%CI:1.305-4.298; P=0.005), maximum tumor diameter (HR:1.906; 95%CI:1.121-3.242; P=0.017), alpha-fetoprotein level (HR:2.492; 95%CI:1.418-4.380; P=0.002) as independent risk factors for HCC recurrence after LT. The predictive model based on these risk factors had a good predictive performance in both the development and validation cohorts (area under the ROC curve=0.800, 0.791, respectively), and the performance of the new model was significantly better than that of single GLR and SII calculations (P<0.001). Survival analysis and competing-risk regression analysis showed that the predictive model could distinguish patients with varying levels of recurrence risk in both the development and validation cohorts. Conclusions The GLR and SII are effective indicators for evaluating HCC recurrence after LT. The predictive model based on these indicators can accurately predict HCC recurrence after LT and is expected to guide preoperative patient selection and postoperative follow-up.
Self-assembly and growth of manganese phthalocyanine on an Au(111) surface

Self-assembly and growth of manganese phthalocyanine (MnPc) molecules on an Au(111) surface is investigated by means of low-temperature scanning tunneling microscopy. At the initial stage, MnPc molecules preferentially occupy the step edges and elbow sites on the Au(111) surface, then they are separately adsorbed on the face-centered cubic and hexagonal closely packed regions due to a long-range repulsive molecule—molecule interaction. After the formation of a closely packed monolayer, molecular islands with second and third layers are observed.
Determination of the effective dose of dexmedetomidine to achieve loss of consciousness during anesthesia induction

Background Dexmedetomidine (DEX) is a sedative with greater preservation of cognitive function, reduced respiratory depression, and improved patient arousability. This study was designed to investigate the performance of DEX during anesthesia induction and to establish an effective DEX induction strategy, which could be valuable for multiple clinical conditions. Methods Patients undergoing abdominal surgery were involved in this dose-finding trial. Dixon's up-and-down sequential method was employed to determine the effective dose of DEX to achieve the state of “loss of consciousness”, and an effective induction strategy was established with continuous infusion of DEX and remifentanil. The effects of DEX on hemodynamics, respiratory state, EEG, and anesthetic depth were monitored and analyzed. Results Through the strategy mentioned, the depth of surgical anesthesia was successfully achieved by DEX-led anesthesia induction. The ED50 and ED95 of the initial infusion rate of DEX were 0.115 and 0.200 μg/kg/min, respectively, and the mean induction time was 18.3 min. The ED50 and ED95 of DEX to achieve the state of “loss of consciousness” were 2.899 (95% CI: 2.703–3.115) and 5.001 (95% CI: 4.544–5.700) μg/kg, respectively. The mean PSI on the loss of consciousness was 42.8 among the patients. During anesthesia induction, the hemodynamics including BP and HR were stable, and the EEG monitor showed decreased α and β powers and increased θ and δ in the frontal and pre-frontal cortices of the brain. Conclusion This study indicated that continuous infusion of combined DEX and remifentanil could be an effective strategy for anesthesia induction. The EEG during the induction was similar to the physiological sleep process.
Liver fibrosis and MAFLD: the exploration of multi-drug combination therapy strategies

In recent years, the prevalence of metabolic-associated fatty liver disease (MAFLD) has reached pandemic proportions as a leading cause of liver fibrosis worldwide. However, the stage of liver fibrosis is associated with an increased risk of severe liver-related and cardiovascular events and is the strongest predictor of mortality in MAFLD patients. More and more people believe that MAFLD is a multifactorial disease with multiple pathways are involved in promoting the progression of liver fibrosis. Numerous drug targets and drugs have been explored for various anti-fibrosis pathways. The treatment of single medicines is brutal to obtain satisfactory results, so the strategies of multi-drug combination therapies have attracted increasing attention. In this review, we discuss the mechanism of MAFLD-related liver fibrosis and its regression, summarize the current intervention and treatment methods for this disease, and focus on the analysis of drug combination strategies for MAFLD and its subsequent liver fibrosis in recent years to explore safer and more effective multi-drug combination therapy strategies.
The mechanism of chronic intracellular infection with Brucella spp.

Globally, brucellosis is a widespread zoonotic disease. It is prevalent in more than 170 countries and regions. It mostly damages an animal’s reproductive system and causes extreme economic losses to the animal husbandry industry. Once inside cells, Brucella resides in a vacuole, designated the BCV, which interacts with components of the endocytic and secretory pathways to ensure bacterial survival. Numerous studies conducted recently have revealed that Brucella’s ability to cause a chronic infection depends on how it interacts with the host. This paper describes the immune system, apoptosis, and metabolic control of host cells as part of the mechanism of Brucella survival in host cells. Brucella contributes to both the body’s non-specific and specific immunity during chronic infection, and it can aid in its survival by causing the body’s immune system to become suppressed. In addition, Brucella regulates apoptosis to avoid being detected by the host immune system. The BvrR/BvrS, VjbR, BlxR, and BPE123 proteins enable Brucella to fine-tune its metabolism while also ensuring its survival and replication and improving its ability to adapt to the intracellular environment.
Laser interstitial thermal therapy (LITT) for pediatric patients affected by intracranial tumors

Introduction The surgical treatment of brain tumors has evolved over time, offering different strategies tailored to patients and their specific lesions. Among these strategies, Laser Interstitial Thermal Therapy (LITT) is one of the most recent advances in pediatric neurooncological surgery, and its results and evolution are still under assessment. Methods We retrospectively analyzed data from six pediatric patients with deep-seated brain tumors treated with LITT at a single center between November 2019 and June 2022. A total of four patients underwent a stereotaxic biopsy during the same operating session. The indications and preparation for LITT, technical issues, clinical and radiological follow-up, impact on quality of life, and oncological treatment are discussed. Results The mean patient age eight years (ranging from 2 to 11 years). The lesion was thalamic in four patients, thalamo-peduncular in one, and occipital posterior periventricular in one. In total, two patients had been previously diagnosed with low-grade glioma (LGG). Biopsies revealed LGG in two patients, ganglioglioma grade I in one, and diffuse high-grade glioma (HGG) in one. Postoperatively, two patients presented with transient motor deficits. The mean follow-up period was 17 months (ranging from 5 to 32 months). Radiological follow-up showed a progressive reduction of the tumor in patients with LGG. Conclusion Laser interstitial thermal therapy is a promising, minimally invasive treatment for deep-seated tumors in children. The results of lesion reduction appear to be relevant in LGGs and continue over time. It can be used as an alternative treatment for tumors located at sites that are difficult to access surgically or where other standard treatment options have failed.
BRANCH GROBNER BASES ALGORITHM OVER BOOLEAN RING

It is well known that Grbner bases have extensive applications in many fields. In the recent years,many improvements have been made for the Grbner algorithm,the most famous of which are the F4 and F5 algorithm introduced by Faugere.Although both of the two algorithms have excellent efficiency,they need enormous memories during the computation.So we will present a new branch Grbner bases algorithm based on the zdd data structure over the boolean ring.This new algorithm not only lowers the usage of memories but also constrains the matrix generated in the computation within a reasonable size.In this paper,we will detail the theory and the proof of this basic algorithm and introduce the zdd data strucure and the branch strategy as well.For many cases,its implementation in Linux is superior to the F4 algorithm implemented by Steel in Magma.
Medial and dorsal lateral septum involving social disruption stress-primed escalation in acid-induced writhes

Introduction Stress may cause prospective escalations in abdominal pain magnitude and accumbal TRPV1 expression, while central neural circuits mediating these stress effects remain unclear. Methods Using retrograde tracing methods, we first demonstrated the existence of a medial septal-dorsal lateral septal -accumbal circuit very likely involving social disruption stress-primed escalations in acid-induced writhes and accumbal TRPV1 level. An intersectional viral strategy and virus-carrying hM3Dq and hM4Di DREADDs were, then, employed to selectively modulate GABAergic and cholinergic neuronal activity in medial and dorsal lateral septum. Results Exciting medial septal GABAergic neuron was found to prevent social disruption stress-primed escalations in acid-induced writhes and accumbal TRPV1 and PKCε expressions. Likewise, inactivating dorsal lateral septal cholinergic neurons was also effective in abolishing these stress-primed escalations. Inactivating GABAergic neuron in non-stressed animals’ medial septum was found to reproduce the stress-primed effects in causing heightened acid-induced writhes and accumbal TRPV1 and PKCε levels. Discussion These results, taken together, prompt us to conclude that social disruption stress may produce plastic changes in a newly-identified medial septal-dorsal lateral septal-accumbal circuit. Moreover, medial septal GABAergic hypoactivity and dorsal lateral septal cholinergic hyperactivity are, at least, two likely causes reflecting such stress-produced escalations in abdominal pain magnitude and pain transduction-related protein over-expression in nucleus accumbens.
Interaction between the flagellum of Candidatus Liberibacter asiaticus and the vitellogenin-like protein of Diaphorina citri significantly influences CLas titer

Huanglongbing (HLB) is a global devastating citrus disease that is mainly caused by “Candidatus Liberibacter asiaticus” (CLas). It is mostly transmitted by the insect Asian citrus psyllid (ACP, Diaphorina citri) in a persistent and proliferative manner. CLas traverses multiple barriers to complete an infection cycle and is likely involved in multiple interactions with D. citri. However, the protein–protein interactions between CLas and D. citri are largely unknown. Here, we report on a vitellogenin-like protein (Vg_VWD) in D. citri that interacts with a CLas flagellum (flaA) protein. We found that Vg_VWD was upregulated in CLas-infected D. citri. Silencing of Vg_VWD in D. citri via RNAi silencing significantly increased the CLas titer, suggesting that Vg_VWD plays an important role in the CLas–D. citri interaction. Agrobacterium-mediated transient expression assays indicated that Vg_VWD inhibits BAX- and INF1-triggered necrosis and suppresses the callose deposition induced by flaA in Nicotiana benthamiana. These findings provide new insights into the molecular interaction between CLas and D. citri.
The function of BoTCP25 in the regulation of leaf development of Chinese kale

XG Chinese kale (Brassica oleracea cv. ‘XiangGu’) is a variety of Chinese kale and has metamorphic leaves attached to the true leaves. Metamorphic leaves are secondary leaves emerging from the veins of true leaves. However, it remains unknown how the formation of metamorphic leaves is regulated and whether it differs from normal leaves. BoTCP25 is differentially expressed in different parts of XG leaves and respond to auxin signals. To clarify the function of BoTCP25 in XG Chinese kale leaves, we overexpressed BoTCP25 in XG and Arabidopsis, and interestingly, its overexpression caused Chinese kale leaves to curl and changed the location of metamorphic leaves, whereas heterologous expression of BoTCP25 in Arabidopsis did not show metamorphic leaves, but only an increase in leaf number and leaf area. Further analysis of the expression of related genes in Chinese kale and Arabidopsis overexpressing BoTCP25 revealed that BoTCP25 could directly bind the promoter of BoNGA3, a transcription factor related to leaf development, and induce a significant expression of BoNGA3 in transgenic Chinese kale plants, whereas this induction of NGA3 did not occur in transgenic Arabidopsis. This suggests that the regulation of Chinese kale metamorphic leaves by BoTCP25 is dependent on a regulatory pathway or elements specific to XG and that this regulatory element may be repressed or absent from Arabidopsis. In addition, the expression of miR319’s precursor, a negative regulator of BoTCP25, also differed in transgenic Chinese kale and Arabidopsis. miR319’s transcrips were significantly up-regulated in transgenic Chinese kale mature leaves, while in transgenic Arabidopsis, the expression of miR319 in mature leaves was kept low. In conclusion, the differential expression of BoNGA3 and miR319 in the two species may be related to the exertion of BoTCP25 function, thus partially contributing to the differences in leaf phenotypes between overexpressed BoTCP25 in Arabidopsis and Chinese kale.