Miracle-dz/UniFAR-FTUs huggingface dataset:
In vitro anti-inflammatory activities of naucleoffieine H as a natural alkaloid from Nauclea officinalis Pierrc ex Pitard, through inhibition of the iNOS pathway in LPS-activated RAW 264.7 macrophages

Abstract Naucleoffieine H, a natural indole alkaloid, was isolated and identified from Nauclea officinalis Pierrc ex Pitard which is a traditional Chinese medicine used for the treatment of various diseases, such as cold, fever, bronchitis, pneumonia, acute tonsillitis, etc. In the present study, the effect of naucleoffieine H on the anti-inflammatory activities was investigated in LPS-induced RAW 264.7 macrophages. The results showed that naucleoffieine H significantly inhibited the release of nitric oxide (the level of nitrite as a stable biomarker of NO production) and tumor necrosis factor-α (TNF-α). Interesting, naucleoffieine H down-regulated the overexpression of inflammatory protein induced nitric oxide synthase (iNOS), but no effect on the expression cyclooxygenase-2 (COX-2) protein. In addition, this bioactive alkaloid suppressed enzymatic activity of iNOS activated by LPS. The above results indicated that naucleoffieine H suppress NO and TNF-α overproduction via block the iNOS pathway in LPS-induced RAW 264.7 macrophages. Graphical Abstract
The investiture of Nemesis-Allat in Hatra

La deesse arabe Allat occupe une place importante dans le pantheon syro-mesopotamien des premiers siecles de notre ere. Identifiee, dans un contexte de syncretisme, a Athena, elle prend des allures guerrieres| identifiee a Nemesis, comme ici, elle acquiert une dimension cosmique fondee, entre autres, sur la tradition astronomique babylonienne et l'association d'Allat avec Barmaren-Dionysos. L'iconographie complexe des reliefs du temple d'Allat a Hatra, proche de l'art palmyreen, symbolise cette accession au rang de divinite cosmique
Data‐independent acquisition‐based quantitative proteomic analysis reveals differences in host immune response of peripheral blood mononuclear cells to sepsis

This study was aimed to uncover proteins that are differentially expressed in sepsis. Data‐independent acquisition (DIA) was used for analysis to identify differentially expressed proteins in peripheral blood mononuclear cells (PBMCs) of patients. A total of 24 non‐septic intensive care unit (ICU) patients, 11 septic shock patients and 27 patients diagnosed with sepsis were recruited for the mass spectrometry (MS) discovery. PBMCs were isolated from routine blood samples and digested into peptides. A DIA workflow was developed using a quadrupole‐Orbitrap liquid chromatography LC‐MS system, and mass spectra peaks were extracted by Skyline software. Orthogonal partial least‐squares discriminant analysis (OPLS‐DA) and partial least‐squares discriminant analysis (PLS‐DA) were applied to distinguish the patient groups at the level of fragment ion and peptide. Differentially expressed proteins in the patient groups were verified by enzyme‐linked immunosorbent assay (ELISA). Receiver‐operating characteristic (ROC) curves were used to evaluate the protein expression. A total of 1062 fragment ions and 122 proteins were identified in the MS‐DIA analysis conducted by Skyline software. Using gene ontology clustering analysis, we discovered that 51 of the 122 identified proteins were associated with biological processes, including carbon metabolism, biosynthesis of antibiotics, platelet activation, bacterial invasion of epithelial cells and complement, and coagulation cascades. Among them, five proteins (high‐mobility group box1 [HMGB1], matrix metalloproteinase 8 [MMP8], neutrophil gelatinase‐associated lipocalin [NGAL], lactotransferrin [LTF] and grancalcin [GCA]) were identified by ELISA as closely related to the development of sepsis. The ROC curves displayed good sensitivity and specificity.
Insights into the autotransport process of a trimeric autotransporter, Yersinia Adhesin A (YadA)

Trimeric autotransporter adhesins (TAAs) are a subset of a larger protein family called the type V secretion systems. They are localized on the cell surface of Gram‐negative bacteria, function as mediators of attachment to inorganic surfaces and host cells, and thus include important virulence factors. Yersinia adhesin A (YadA) from Yersinia enterocolitica is a prototypical TAA that is used extensively to study the structure and function of the type Vc secretion system. A solid‐state NMR study of the membrane anchor domain of YadA previously revealed a flexible stretch of small residues, termed the ASSA region, that links the membrane anchor to the stalk domain. In this study, we present evidence that single amino acid proline substitutions produce two different conformers of the membrane anchor domain of YadA; one with the N‐termini facing the extracellular surface, and a second with the N‐termini located in the periplasm. We propose that TAAs adopt a hairpin intermediate during secretion, as has been shown before for other subtypes of the type V secretion system. As the YadA transition state intermediate can be isolated from the outer membrane, future structural studies should be possible to further unravel details of the autotransport process.
Optical coherence tomography angiography in glaucoma

Purpose of review Optical coherence tomography angiography (OCTA) studies have demonstrated reduced microcirculation in the superficial optic nerve, peripapillary retina, and the macula of glaucoma patients. The scope of this review is to outline recent studies using OCTA in glaucoma and highlight how OCTA may help improve diagnosis and follow-up in glaucoma patients. Recent findings OCTA studies have provided evidence of vascular changes in the optic nerve head, peripapillary, and macula region in glaucoma in comparison to glaucoma suspects and normal eyes. Additionally, OCTA can detect longitudinal reduction of peripapillary and macula vessel density in glaucoma patients. It remains unclear whether the reduced microcirculation in glaucoma patients induces the neuronal damage or arises through reduced circulation requirements in damaged tissue. Summary OCTA is a novel imaging modality that has great potential to enhance our understanding of glaucoma and to improve our ability to detect and treat it.
Pleuropulmonary tuberculosis with spinal lesions due to metastatic malignancy differentiated definitively on imaging

A healthy 31-year-old man presenting with back pain was found to have multiple spinal enhancing lesions on MRI. An incidental asymptomatic large pleural effusion was identified on investigations for the back pain and pleural and pulmonary tuberculosis (TB) was subsequently diagnosed. The radiographical features on MRI spine were not typical of spinal TB and a Ga68 DOTATATE Positron Emission Tomography (PET)/CT confirmed metastatic paraganglioma with multiple bone metastases. Although metastatic paraganglioma is rare, this case highlights that even in young patients dual pathology needs to be considered. Most importantly, it is a reminder to physicians managing TB of the clues that help distinguish spinal TB from important alternative causes, including metastatic malignancy.
Hypoxia‐induced developmental plasticity of larval growth, gill and labyrinth organ morphometrics in two anabantoid fish: The facultative air‐breather Siamese fighting fish (Betta splendens) and the obligate air‐breather the blue gourami (Trichopodus trichopterus)

Larval and juvenile air breathing fish may experience nocturnal and/or seasonal aquatic hypoxia. Yet, whether hypoxia induces respiratory developmental plasticity in larval air breathing fish is uncertain. This study predicted that larvae of two closely related anabantid fish—the facultative air breather the Siamese fighting fish (Betta splendens) and the obligate air breathing blue gourami (Trichopodus trichopterus)—show distinct differences in developmental changes in body, gill, and labyrinth morphology because of their differences in levels of dependency upon air breathing and habitat. Larval populations of both species were reared in normoxia or chronic nocturnal hypoxia from hatching through 35–38 days postfertilization. Gill and labyrinth variables were measured at the onset of air breathing. Betta splendens reared in normoxia possessed larger, more developed gills (~3× greater area) than T. trichopterus at comparable stages. Surface area of the emerging labyrinth, the air breathing organ, was ~ 85% larger in normoxic B. splendens compared to T. trichopterus. Rearing in mild hypoxia stimulated body growth in B. splendens, but neither mild nor severe hypoxia affected growth in T. trichopterus. Condition factor, K (~ 1.3 in B. splendens, 0.7 in T. trichopterus) was unaffected by mild hypoxia in either species, but was reduced by severe hypoxia to <0.9 only in B. splendens. Severe, but not mild, hypoxia decreased branchial surface area in B. splendens by ~40%, but neither hypoxia level affected Trichopodus branchial surface. Mild, but not severe, hypoxia increased labyrinth surface area by 30% in B. splendens. However, as for branchial surface area, labyrinth surface area was not affected in Trichopodus. These differential larval responses to hypoxic rearing suggest that different larval habitats and activity levels are greater factors influencing developmental plasticity than genetic closeness of the two species.
Laser: A revolutionary boon in dentistry

Introduction: Aphthous ulcers, commonly referred to as canker sores, are autoimmune and ulcerative lesions of the oral mucosa. Due to the indeterminate etiology of these lesions, it is often difficult to find a definitive cure and current treatment options are aimed toward ameliorating the symptoms. Aim: The aim of this study is to assess the efficacy of low-level laser therapy (LLLT) in the treatment of aphthous ulcers. Objective: To evaluate the efficacy of parameters such as reduction of pain, burning sensation, and healing time. Materials and Methods: A total of 10 patients who presented with aphthous ulcers were included in the study. A single visit application of LLLT was given to each patient followed by recall visits. The first visit consisted of three sessions of low-level laser applications, lasting about 45 s, with a gap of about 30-60 s between each session, for a total laser application time of about 3 min. The pain scores and burning sensation were evaluated using visual analog scale (VAS) before and immediately post-operative laser applications, at third visit and at fifth visit. Results: For evaluation of the reduction in pain and burning sensation, the mean of the reduction in VAS scores was evaluated for all the patients; P = 0.004 was highly significant in all the study groups. Conclusion: LLLT is an effective modality for the treatment of aphthous ulcers. It provides immediate relief from pain, burning sensation and promotes healing time also.
Localization of Deep Brain Stimulation Electrode by Image Registration Is Software Dependent: A Comparative Study between Four Widely Used Software Programs

Background: The control of the anatomic position of the active contacts is essential to understand the effects and adapt the settings of the neurostimulation. The localization is commonly assessed by a registration between the preoperative MRI and the postoperative CT scan. However, its accuracy depends on the quality of the registration algorithm and many software programs are available. Objective: To compare the localization of implanted deep brain stimulation (DBS) leads in the subthalamic nucleus (STN) between four registration devices. Methods: The preoperative stereotactic MRI was co-registered and fused with the 3-month postoperative CT scan in 27 patients implanted in the STN for Parkinson’s disease (53 leads). Localizations of the active contacts were calculated in the stereotactic frame space and compared between software programs. Results: The coordinates of the active contacts were different between software programs in the 3 axes (p < 0.001) with a mean vectorial error between the deepest contact locations of 1.17 mm (95% CI 1.09–1.25). Conclusion: We found a small but significant difference in the coordinates calculated on four different devices. These results have to be considered when performing studies comparing active contact locations or when following patients with an implanted DBS lead.
Imaging Markers of Progression in Parkinson's Disease

Parkinson's disease (PD) is the second‐most common neurodegenerative disorder after Alzheimer's disease; however, to date, there is no approved treatment that stops or slows down disease progression. Over the past decades, neuroimaging studies, including molecular imaging and MRI are trying to provide insights into the mechanisms underlying PD.
Adenylyl cyclase 6 expression is essential for cholera toxin-induced diarrhea.

Background Cholera toxin (CT)-induced diarrhea is mediated by cAMP-mediated active Cl - secretion via the cystic fibrosis transmembrane conductance regulator (CFTR). Although the constitutive activation of adenylyl cyclase (AC) in response to CT is due to ADP-ribosylation of Gsα activating CFTR with consequent secretory diarrhea, the AC isoform(s) involved remain unknown. Methods We generated intestine epithelial cell-specific adenylyl cyclase 6 (AC6) knockout mice to study its role in cholera toxin-induced diarrhea. Results AC6 mRNA levels were the highest of all 9 membrane-bound AC isoforms in mouse intestinal epithelial cells. Intestinal epithelial-specific AC6 knockout mice (AC6loxloxVillinCre) had undetectable AC6 levels in small intestinal and colonic epithelial cells. No significant differences in fluid and food intake, plasma electrolytes, intestinal/colon anatomy and morphology, as well as fecal water content were observed between genotypes. Nevertheless, CT-induced fluid accumulation in vivo was completely absent in AC6loxloxVillinCre mice, associated with a lack of forskolin- and CT-induced changes in short-circuit current (Isc) of the intestinal mucosa, impaired cAMP generation in acutely isolated small intestinal epithelial cells and significantly impaired apical CFTR levels in response to forskolin. Conclusion AC6 is a novel target for the treatment of CT-induced diarrhea.
Comparison of Mycobacterium ulcerans (Buruli ulcer) and Leptospira sp. (Leptospirosis) dynamics in urban and rural settings

Background Zoonotic pathogens respond to changes in host range and/or pathogen, vector and host ecology. Environmental changes (biodiversity, habitat changes, variability in climate), even at a local level, lead to variability in environmental pathogen dynamics and can facilitate their transmission from natural reservoirs to new susceptible hosts. Whilst the environmental dynamics of aquatic bacteria are directly linked to seasonal changes of their habitat they also rely on the ecological processes underpining their transmission. However data allowing the comparison of these ecological processes are lacking. Here we compared the environmental dynamics of generalist and vector-borne aquatic bacterial pathogens in the same unit of time and space, and across rural and urban habitats in French Guiana (South America). Principal findings Using Leptospira sp. and Mycobacterium ulcerans we performed an environmental survey that allowed the detection of both pathogens in urban vs. rural areas, and during rainy vs. dry weather conditions. All samples were subjected to qPCR amplifications of LipL32 (Leptospira sp.) and IS2404 and KR (M. ulcerans) genetic markers. We found (i) a greater presence of M. ulcerans in rural areas compared with Leptospira sp. , (ii) that modified urban environments were more favourable to the establishment of both pathogens, (iii) that Leptospira sp. presence was enhanced during the rainy season and M. ulcerans during the dry period, and (iv) differences in the spatial distribution of both bacteria across urban sites, probably due to the mode of dissemination of each pathogen in the environment. Conclusions We propose that in French Guiana simplified and modified urban ecosystems might favour leptospirosis and Buruli ulcer emergence and transmission. Moreover, disease risk was also constrained by seasonality. We suggest that the prevention of aquatic bacterial disease emergence in impoverished urban areas of developing countries would benefit from seasonal diseases targeted surveys, which would maximise limited budgets from cash-strapped health agencies.
Evolutionary design of regulatory control. I. A robust control theory analysis of tradeoffs

The evolutionary design of regulatory control balances various tradeoffs in performance. Fast reaction to environmental change tends to favor plastic responsiveness at the expense of greater sensitivity to perturbations that degrade homeostatic control. Greater homeostatic stability against unpredictable disturbances tends to reduce performance in tracking environmental change. This article applies the classic principles of engineering control theory to the evolutionary design of regulatory systems. The engineering theory clarifies the conceptual aspects of evolutionary tradeoffs and provides analytic methods for developing specific predictions. On the conceptual side, this article clarifies the meanings of integral control, feedback, and design, concepts that have been discussed in a confusing way within the biological literature. On the analytic side, this article presents extensive methods and examples to study error-correcting feedback, which is perhaps the single greatest principle of design in both human-engineered and naturally designed systems. The broad framework and associated software code provide a comprehensive how-to guide for making models that focus on functional aspects of regulatory control and for making comparative predictions about regulatory design in response to various kinds of environmental challenge. The second article in this series analyzes how alternative regulatory designs influence the relative levels of genetic variability, stochasticity of trait expression, and heritability of disease.
Simultaneous diagnosis of tuberculous and non-tuberculous mycobacterial diseases: Time for a better patient management.

Tuberculosis (TB) is the deadliest infectious disease in the world which disproportionately affects low-and-middle-income countries (LMICs) where diagnostic resources and treatment options are limited. The incidence of pulmonary non-tuberculous mycobacteria (NTM) disease is also rapidly increasing in these regions traditionally dominated by TB infections. This poses significant diagnostic and treatment challenges, since these two diseases are often indistinguishable clinically or by sputum smear microscopy (SSM), the most commonly used TB diagnostic tool in LMICs. Consequently, NTM-infected patients usually receive unnecessary TB treatment for months. TB patients with NTM co-infections may also be treated incorrectly due to inaccurate SSM and Xpert™ MTB/RIF (M. tuberculosis./rifampin) results. These issues complicate the management of patients and contribute to the worsening of the current TB and NTM epidemiological features including development of drug resistant strains. It is therefore critical to develop improved diagnostic tools to accurately distinguish these two different pathogens that have many similar clinical and epidemiological features but have different treatment regimens. In this review, we will discuss limitations with current diagnostic tools and the need to develop novel techniques that can accurately and simultaneously diagnose TB and NTM disease. _.
Parathyroid hormone‐related peptide (1–34) promotes tooth eruption and inhibits osteogenesis of dental follicle cells during tooth development

Dental follicle cells (DFCs) activate and recruit osteoclasts for tooth development and tooth eruption, whereas DFCs themselves differentiate into osteoblasts to form alveolar bone surrounding tooth roots through the interaction with Hertwig's epithelial root sheath (HERS). Also during tooth development, parathyroid hormone‐related peptide (PTHrP) is expressed surrounding the tooth germ. Thus, we aimed to investigate the effect of PTHrP (1–34) on bone resorption and osteogenesis of DFCs in vitro and in vivo. In vitro studies demonstrated that DFCs cocultured with HERS cells expressed higher levels of BSP and OPN than the DFCs control group, whereas cocultured DFCs treated with PTHrP (1–34) had lower expressions of ALP, RUNX2, BSP, and OPN than the cocultured DFCs control group. Moreover, we found PTHrP (1–34) inhibited osteogenesis of cocultured DFCs by inactivating the Wnt/β‐catenin pathway. PTHrP (1–34) also increased the expression of RANKL/OPG ratio in DFCs. Consistently, in vivo study found that PTHrP (1–34) accelerated tooth eruption and inhibited alveolar bone formation. Therefore, these results suggest that PTHrP (1–34) accelerates tooth eruption and inhibits osteogenesis of DFCs by inactivating Wnt/β‐catenin pathway.
Is Language Required to Represent Others' Mental States? Evidence From Beliefs and Other Representations

An important part of our Theory of Mind-the ability to reason about other people's unobservable mental states-is the ability to attribute false beliefs to others. We investigated whether processing these false beliefs, as well as similar but nonmental representations, is reliant on language. Participants watched videos in which a protagonist hides a gift and either takes a photo of it or writes a text about its location before a second person inadvertently moves the present to a different location, thereby rendering the belief and either the photo or text false. At the same time, participants performed either a concurrent verbal interference task (rehearsing strings of digits) or a visual interference task (remembering a visual pattern). Results showed that performance on false belief trials did not decline under verbal interference relative to visual interference. We interpret these findings as further support for the view that language does not form an essential part of the process of reasoning online ("in the moment") about false beliefs.
Searching for Machiavelli but Finding Psychopathy and Narcissism

Machiavellianism is a psychological construct reflecting individual differences in manipulative and strategic thinking, pragmatic morality, and a cynical outlook on life. A recent stream of research has shown that Machiavellianism and psychopathy seem to be redundant constructs and that measures of Machiavellianism do not correspond well with theoretical expectations. In the present study, I juxtapose multiple measures of Machiavellianism against normal (i.e., the five-factor model and HEXACO) and abnormal (e.g., narcissism, psychopathy, impulsivity, and personality dysfunction) personality traits in an online sample (N = 591). Using Goldberg’s (2006) Bass–Ackwards approach, I investigate whether typical Machiavellian traits can be found anywhere in the construct hierarchy by comparing the levels of the hierarchy with expert-rated five-factor model prototypes of Machiavellianism, narcissism, psychopathy, and external correlates. Our results indicate that measures of Machiavellianism mostly reflect psychopathy and narcissism. The implications of these results are discussed, including what the future may hold for Machiavellianism.