Miracle-dz/UniFAR-FTUs huggingface dataset:
Revisiting Old Ionophore Lasalocid as a Novel Inhibitor of Multiple Toxins

The ionophore lasalocid is widely used as a veterinary drug against coccidiosis. We found recently that lasalocid protects cells from two unrelated bacterial toxins, the cytotoxic necrotizing factor-1 (CNF1) from Escherichia. coli and diphtheria toxin. We evaluated lasalocid’s capacity to protect cells against other toxins of medical interest comprising toxin B from Clostridium difficile, Shiga-like toxin 1 from enterohemorrhagic E. coli and exotoxin A from Pseudomonas aeruginosa. We further characterized the impact of lasalocid on the endolysosomal and the retrograde pathways and organelle integrity, especially the Golgi apparatus. We found that lasalocid protects cells from all toxins tested and impairs the drop of vesicular pH along the trafficking pathways that are required for toxin sorting and translocation to the cytoplasm. Lasalocid also has an impact on the cellular distribution of GOLPH4 and GOLPH2 Golgi markers. Other intracellular trafficking compartments positive for EEA1 and Rab9A display a modified cellular pattern. In conclusion, lasalocid protects cells from multiple deadly bacterial toxins by corrupting vesicular trafficking and Golgi stack homeostasis.
Protective effect of baicalin aganist myocardial ischemia and reperfusion injury in rats

AIM:To study the protective effects of baicalin on myocardial ischemia-reperfusion injury in rats.METHODS:The models of myocardial ischemia-reperfusion injury were established by occluding left anterior descending coronary artery(LAD)for 30 min,followed by reperfusion for 120 min.The rate of rise and decline of left ventricular pressure(±dp/dt_(max))and end-diastolic pressure of left ventricle(LVEDP)were monitored continuously with polygraph.After reperfusion,the blood and myocardium samples were taken for determination of malondialdehyde(MDA)content,superoxide dismutase(SOD),Na~+-K~+-ATPase,Ca~(2+)-ATPase activities in myocardium,creatine kinase(CK)and lactate dehydrogenase(LDH)in serum with spectrophotometer.The uhrastruetural changes in ischemic myocardium were assessed by transmission electron microscope.RESULTS: Compared with control group,baicalin treatment with 50 mg·kg~(-1) and 100 mg·kg~(-1) depressed the changes in±dp/ dt_(max) and LVEDP,decreased plasma CK and LDH levels,reduced myocardial MDA content,and increased the activit- ies of SOD,Na~+-K~+-ATPase,and Ca~(2+)-ATPase in myocardium following ischemia-reperfusion.The ultrastructural injury in reperfused myocardium was relieved.CONCLUSION:Baicalin possesses a protective effect against my- ocardial isehnemia-reperfusion injury through scavenging oxide radicals and improving Na~+-K~+-ATPase and Ca~(2+)- ATPase activities.
The Overexpression of Tβ4 in the Hair Follicle Tissue of Alpas Cashmere Goats Increases Cashmere Yield and Promotes Hair Follicle Development

Simple Summary Cashmere goats have double coats consisting of non-modulated fine inner hairs or cashmere fibers produced by secondary hair follicles (SHFs) and guard hairs produced by primary hair follicles (PHFs). Cashmere is an important economic product worldwide. The world market for cashmere is increasing while the current production of cashmere is limited. Thymosin beta-4 (Tβ4), a 4.9 kDa protein, contains 43 amino acids. Here, we investigated whether Tβ4 overexpression would increase SHF numbers, and thus improve the cashmere yield. We produced Tβ4 transgenic goats using a tissue-specific overexpression strategy. The Tβ4 overexpression (Tβ4-OE) goats had increased hair follicle development and higher cashmere yields than the wild type (WT) goats. The development of this goat model is not only valuable as a framework for future studies of the mechanism of goat follicular development, but will also lead to the improvement of economically important cashmere traits. Abstract Increased cashmere yield and improved quality are some goals of cashmere goat breeding. Thymosin beta-4 (Tβ4) plays a key role in the growth and development of hair follicles. For the past ten years, we have evaluated the role of Tβ4 by establishing a flock of 15 cashmere goats that specifically overexpress the Tβ4 gene in the hair follicles. These Tβ4 overexpression (Tβ4-OE) cashmere goats had more secondary hair follicles than the WT goats and produced more cashmere. Meanwhile, combined analysis of the skin transcriptome and proteome in cashmere goats suggested that Tβ4 may affect hair growth by interacting with keratin type II cytoskeletal 4 epidermal (KRT4) to mediate the extracellular signal-regulated protein kinase (ERK) signaling pathway, thereby promoting the development of secondary hair follicles, and consequently, increasing cashmere yield. Thus, the specific overexpression of Tβ4 in the hair follicles of cashmere goats effectively increased the cashmere yield.
Hydroxylamine and Carboxymethoxylamine Can Inhibit Toxoplasma gondii Growth through an Aspartate Aminotransferase-Independent Pathway

Toxoplasma gondii is an obligate intracellular protozoan parasite and a successful parasitic pathogen in diverse organisms and host cell types. Hydroxylamine (HYD) and carboxymethoxylamine (CAR) have been reported as inhibitors of aspartate aminotransferases (AATs) and interfere with the proliferation in Plasmodium falciparum. Therefore, AATs are suggested as drug targets against Plasmodium. The T. gondii genome encodes only one predicted AAT in both T. gondii type I strain RH and type II strain PLK. ABSTRACT Toxoplasma gondii is an obligate intracellular protozoan parasite and a successful parasitic pathogen in diverse organisms and host cell types. Hydroxylamine (HYD) and carboxymethoxylamine (CAR) have been reported as inhibitors of aspartate aminotransferases (AATs) and interfere with the proliferation in Plasmodium falciparum. Therefore, AATs are suggested as drug targets against Plasmodium. The T. gondii genome encodes only one predicted AAT in both T. gondii type I strain RH and type II strain PLK. However, the effects of HYD and CAR, as well as their relationship with AAT, on T. gondii remain unclear. In this study, we found that HYD and CAR impaired the lytic cycle of T. gondii in vitro, including the inhibition of invasion or reinvasion, intracellular replication, and egress. Importantly, HYD and CAR could control acute toxoplasmosis in vivo. Further studies showed that HYD and CAR could inhibit the transamination activity of rTgAAT in vitro. However, our results confirmed that deficiency of AAT in both RH and PLK did not reduce the virulence in mice, although the growth ability of the parasites was affected in vitro. HYD and CAR could still inhibit the growth of AAT-deficient parasites. These findings indicated that HYD and CAR inhibition of T. gondii growth and control of toxoplasmosis can occur in an AAT-independent pathway. Overall, further studies focusing on the elucidation of the mechanism of inhibition are warranted. Our study hints at new substrates of HYD and CAR as potential drug targets to inhibit T. gondii growth.
Increased oxidative phosphorylation in lymphocytes does not atone for decreased cell numbers after burn injury

The acute systemic inflammatory response syndrome (SIRS) and multiorgan dysfunction (MOD) that occur in large burn injuries may be attributed, in part, to immunosuppressive responses such as decreased lymphocytes. However, the mitochondrial bioenergetics of lymphocytes after severe burn injury are poorly understood. The purpose of this study was to examine mitochondrial function of lymphocytes following severe burns in a swine model. Anesthetized Yorkshire swine (n = 17) sustained 40% total body surface area full-thickness contact burns. Blood was collected at pre-injury (Baseline; BL) and at 24 and 48 h after injury for complete blood cell analysis, flow cytometry, cytokine analysis, and ficoll separation of intact lymphocytes for high-resolution mitochondrial respirometry analysis. While neutrophil numbers increased, a concomitant decrease was found in lymphocytes (P < 0.001) after burn injury, which was not specific to CD4+ or CD8+ lymphocytes. No changes in immune cell population were observed from 24 h to 48 h post-injury. IL 12-23 decreased while a transient increase in IL 4 was found from BL to 24h (P < 0.05). CRP progressively increased from BL to 24h (P < 0.05) and 48h (P < 0.001) post-injury. Routine and maximal mitochondrial respiration progressively increased from BL to 24h (P < 0.05) and 48 h post-injury (P < 0.001). No changes were found in leak respiration or residual oxygen consumption. When considering the reduction in lymphocyte number, the total peripheral lymphocyte bioenergetics per volume of blood significantly decreased from BL to 24h and 48h (P < 0.05). For the first time, we were able to measure mitochondrial activity in intact lymphocyte mitochondria through high-resolution respirometry in a severely burned swine model. Our data showed that the non-specific reduction in peripheral T cells after injury was larger than the increased mitochondrial activity in those cells, which may be a compensatory mechanism for the total reduction in lymphocytes. Additional studies in the metabolic activation of T cell subpopulations may provide diagnostic or therapeutic targets after severe burn injury.
A Two-Stage Convolutional Neural Networks for Lung Nodule Detection

Early detection of lung cancer is an effective way to improve the survival rate of patients. It is a critical step to have accurate detection of lung nodules in computed tomography (CT) images for the diagnosis of lung cancer. However, due to the heterogeneity of the lung nodules and the complexity of the surrounding environment, it is a challenge to develop a robust nodule detection method. In this study, we propose a two-stage convolutional neural networks (TSCNN) for lung nodule detection. The first stage based on the improved U-Net segmentation network is to establish an initial detection of lung nodules. During this stage, in order to obtain a high recall rate without introducing excessive false positive nodules, we propose a new sampling strategy for training. Simultaneously, a two-phase prediction method is also proposed in this stage. The second stage in the TSCNN architecture based on the proposed dual pooling structure is built into three 3D-CNN classification networks for false positive reduction. Since the network training requires a significant amount of training data, we designed a random mask as the data augmentation method in this study. Furthermore, we have improved the generalization ability of the false positive reduction model by means of ensemble learning. We verified the proposed architecture on the LUNA dataset in our experiments, which showed that the proposed TSCNN architecture did obtain competitive detection performance.
A New Filler for Epoxy Resin: Study on the Properties of Graphite Carbon Nitride (g-C3N4) Reinforced Epoxy Resin Composites

In this study, graphitic carbon nitride (g-C3N4) as a novel filler was used for fabricating epoxy nanocomposites. The static mechanical, dynamic thermal-mechanical properties and thermostability of as-prepared g-C3N4/epoxy nanocomposites were significantly ameliorated compared with that of the pure epoxy matrix. The tensile modulus and flexural modulus of g-C3N4/epoxy nanocomposites increased by 31.81% and 28.28%, respectively. Meanwhile, the tensile and flexural strength was also improved by 16.02% and 12.67%, respectively. The g-C3N4/epoxy nanocomposites exhibited an increased storage modulus and glass transition temperature. The markedly improved mechanical and viscoelasticity properties were attributed to the stronger interfacial interaction caused by enlarged contact area and increased chemical bonding, and enhanced mechanical interlocking on the interface. The loss factor of epoxy nanocomposites also raised by 40% due to the comprehensive effect of frication caused by the relative slip between nanosheets, micro-constrained layer damping structure and the reversible cycle of breakage and re-established of the hydrogen bond. Meanwhile, the 10% weightlessness temperature (Tinitial), semi weightlessness temperature (Thalf) of g-C3N4/epoxy nanocomposites have increased by about 15 °C and 14 °C, respectively.
A Pilot Biomonitoring Study of Cumulative Phthalates Exposure among Vietnamese American Nail Salon Workers

Background: Many California nail salon workers are low-income Vietnamese women of reproductive age who use nail products daily that contain androgen-disrupting phthalates which may increase risk of male reproductive tract abnormalities during pregnancy. Yet, few studies have characterized phthalate exposures among this workforce. Objective: To characterize individual metabolites and cumulative phthalates exposure among a potentially vulnerable occupational group of nail salon workers. Study Design: We collected 17 post-shift urine samples from Vietnamese workers at six San Francisco Bay Area nail salons in 2011, which were analyzed for four primary phthalate metabolites: mono-n-butyl-, mono-isobutyl-, mono(2-ethylhexyl)-, and monoethyl phthalates (MnBP, MiBP, MEHP, and MEP, respectively) (g/L). Phthalate metabolite concentrations and a potency-weighted sum of parent compound daily intake ({Sigma}androgen-disruptor, g/kg/day) were compared to 203 Asian Americans from the 2011-12 National Health and Nutritional Examination Survey (NHANES) using Student t-test and Wilcoxin signed rank test. Results: Creatinine-corrected MnBP, MiBP, MEHP (g/g), and cumulative phthalates exposure ({Sigma}androgen-disruptor, g/kg/day) levels were 2.9 (p < 0.0001), 1.6 (p = 0.015), 2.6 (p < 0.0001), and 2.0 (p < 0.0001) times higher, respectively, in our nail salon worker population compared to NHANES Asian Americans. Levels exceeded the NHANES 95th or 75th percentiles among some workers. Conclusion: This pilot study suggests that nail salon workers are disproportionately exposed to multiple phthalates, a finding that warrants further investigation to assess their potential health significance.
Systematically Scrutinizing the Impact of Substitution Sites on Thermostability and Detergent Tolerance for Bacillus subtilis Lipase A

Improving an enzyme's (thermo )stability or tolerance against solvents and detergents is highly relevant in protein engineering and biotechnology. Recent developments have tended towards data-driven approaches, where available knowledge about the protein is used to identify substitution sites with high potential to yield protein variants with improved stability and, subsequently, substitutions are engineered by site directed or site saturation (SSM) mutagenesis. However, the development and validation of algorithms for data-driven approaches has been hampered by the lack of availability of large-scale data measured in a uniform way and being unbiased with respect to substitution types and locations. Here, we extend our knowledge on guidelines for protein engineering following a data-driven approach by scrutinizing the impact of substitution sites on thermostability or / and detergent tolerance for Bacillus subtilis lipase A (BsLipA) at very large-scale. We systematically analyze a complete experimental SSM library of BsLipA containing all 3439 possible single variants, which was evaluated as to thermostability and tolerances against four detergents under respectively uniform conditions. Our results provide systematic and unbiased reference data at unprecedented scale for a biotechnologically important protein, identify consistently defined hot spot types for evaluating the performance of data-driven protein engineering approaches, and show that the rigidity theory and ensemble-based approach Constraint Network Analysis yields (CNA) hot spot predictions with an up to 9-fold gain in precision over random classification.
Activity of Meropenem-Vaborbactam against Bacterial Isolates Causing Pneumonia in Patients in U.S. Hospitals during 2014 to 2018

Meropenem-vaborbactam is approved to treat hospital-acquired pneumonia (HAP), including ventilator-associated pneumonia (VAP), in Europe. Meropenem-vaborbactam activity was evaluated against 3,193 Pseudomonas aeruginosa and 4,790 Enterobacterales isolates causing pneumonia, including VAP, in hospitalized patients in the United States. Susceptibility testing was performed by using the broth microdilution method, and all carbapenem-resistant isolates were submitted for whole-genome sequencing. ABSTRACT Meropenem-vaborbactam is approved to treat hospital-acquired pneumonia (HAP), including ventilator-associated pneumonia (VAP), in Europe. Meropenem-vaborbactam activity was evaluated against 3,193 Pseudomonas aeruginosa and 4,790 Enterobacterales isolates causing pneumonia, including VAP, in hospitalized patients in the United States. Susceptibility testing was performed by using the broth microdilution method, and all carbapenem-resistant isolates were submitted for whole-genome sequencing. Meropenem-vaborbactam exhibited almost complete activity against Enterobacterales (>99.9% susceptible), including carbapenem-resistant Enterobacterales (CRE), and was also very active against P. aeruginosa isolates (89.5% susceptible).
Effects of Slaughter Age on Muscle Characteristics and Meat Quality Traits of Da-Heng Meat Type Birds

Simple Summary The current work evaluated the breast muscle performance, meat quality traits, and myofiber characteristics of Da-Heng meat type birds with 60, 90, 120, 150, 180 days of age. Older chickens often presented a higher pH, lower drip loss, higher shear force, darker, and redder breast meat. The correlation coefficients showed that myofiber characteristics played an important role in breast pH values, drip loss, and meat color. Abstract Due to the increasing demand for producing chickens with high meat quality, there is a need to determine its mode of action on chicken meat quality traits across a wider age spectrum. In this study, five groups of 200 male Da-Heng meat type birds were reared until slaughter age of 60, 90, 120, 150, 180 days old and breast muscle performance, meat quality traits, and myofiber characteristics were evaluated. The larger body weight and breast weight of chicken are based on larger myofiber diameter and area, less myofiber density for the older birds than younger birds. There was an age effect on all meat quality traits of chicken breast muscle (p < 0.05). Older chickens often presented a higher pH, lower drip loss, higher shear force, darker, and redder breast meat. The correlation coefficients showed that myofiber characteristics played an important role in breast pH values, drip loss, and meat color (p < 0.05). Besides, significant correlations were also found between meat quality traits (p < 0.05). Further studies are needed to explore the biochemical character and potential molecular mechanism of chicken breast muscle to determine the factors that causes these age-related differences in meat quality in the current study.
Dexamethasone enhances the antitumor efficacy of Gemcitabine by glucocorticoid receptor signaling

ABSTRACT Gemcitabine (Gem) is currently used as the first-line therapy for liver and pancreatic cancer but has limited efficacy in most cases. Dexamethasone (Dex) have been applied as a chemoprotectant and chemosensitizer in cancer chemotherapy. This study further explored the potential of combination of Gem and Dex and tested the hypothesis that glucocorticoid receptor signaling is essential for the synergistic antitumor activity. In the HepG2 and AsPC-1 xenograft models, the combination treatment showed a significantly synergistic antitumor activity. Immunohistochemistry of post-treatment tumors showed a significant decrease in proliferation and angiogenesis as compared to either of the treatments alone. Dex alone and the combination with Gem inhibited the expression of glucocorticoid receptor. The combination of Dex and Gem showed synergistic cytotoxicity in cell lines in vitro. The antiproliferative synergism is prevented by used glucocorticoid receptor (GR) small interfering RNA, demonstrating that the glucocorticoid receptor is required for the antiproliferative synergism of Gem and Dex. The inhibition of glucocorticoid receptor signaling pathway and induction of apoptosis via activation of caspases 3, 8 and 9, PARP, contributed to the synergistic effect of this combination therapy. These results demonstrate that Dex could potentiate the antitumor efficacy of Gem. The synergistic antitumor activity of the combination of Dex and Gem was through glucocorticoid receptor signaling. Taken together, a combination of Dex and Gem shows a significant synergistic antitumor activity and lesser toxicity both in vitro and in vivo and could be a combination chemotherapy for the treatment of highly expression of glucocorticoid receptor patients.
Daily blood loss transition after total knee arthroplasty with topical administration of tranexamic acid: Paradoxical blood loss after action of tranexamic acid

Purpose: The purpose of this study was to compare the daily blood loss transition between groups with and without topical administration of tranexamic acid (TXA) after cruciate retaining (CR) and posterior stabilized (PS) total knee arthroplasty (TKA). Methods: A total of 220 patients undergoing unilateral TKA were enrolled in CR and PS TKAs, which were divided into groups that received topical administration of TXA (TXA group) or without TXA (non-TXA group). Each group in both types of TKA included 55 patients. The daily transition of blood loss was compared between the TXA and the non-TXA groups in CR and PS TKAs. The blood loss was calculated through Nadler formula using the patient’s blood volume and hemoglobin reduction rate. Results: Total blood loss was significantly lower in the TXA group in both CR and PS TKAs (p < 0.001, respectively). The blood loss was lower for 0–24 h and 24–48 h after TKA. However, from 48 h to 72 h, it was greater in the TXA group (253.1 vs. 34.6 mL; p < 0.001) in CR TKAs. These tendencies were similar in PS TKAs after 48 h (186.2 vs. 134.9 mL, p = 0.223). Conclusions: Topical administration of TXA for reduction of blood loss seemed to be effective up to 48 h after both CR and PS TKAs. The blood loss after 48 h tended to be even greater in the TXA group. Future studies will be required to identify the pharmacokinetic evidence for this clinical finding. Level of evidence: Level II.