Miracle-dz/UniFAR-FTUs huggingface dataset:
ZNF251 haploinsufficiency confers PARP inhibitors resistance in BRCA1-mutated cancer cells through modulation of RAD51 and DNA-PKcs-dependent pathways

Poly (ADP-ribose) polymerase (PARP) inhibitors represent a promising new class of agents that have demonstrated efficacy in treating various cancers, particularly those that carry BRCA1/2 mutations. The cancer associated BRCA1/2 mutations disrupt DNA double strand break (DSB) repair by homologous recombination (HR). PARP inhibitors (PARPis) have been applied to trigger synthetic lethality in BRCA1/2-mutated cancer cells by promoting the accumulation of toxic DSBs. Unfortunately, resistance to PARPis is common and can occur through multiple mechanisms, including the restoration of HR and/or the stabilization of replication forks. To gain a better understanding of the mechanisms underlying PARPi resistance, we conducted an unbiased CRISPR-pooled genome-wide library screen to identify new genes whose deficiency confers resistance to the PARPi olaparib. Our study revealed that ZNF251, a zinc finger protein, is a novel gene whose haploinsufficiency confers PARPi resistance in multiple breast and ovarian cancer lines harboring BRCA1 mutations. Mechanistically, we discovered that ZNF251 haploinsufficiency leads to constitutive stimulation of RAD51-mediated HR and DNA-PKcs - mediated non-homologous end joining (NHEJ) repair of DSBs as well as DNA-PKcs-mediated fork protection in BRCA1-mutated cancer cells. Moreover, we demonstrated that RAD51 and DNA-PKcs inhibitors reversed PARPi resistance of ZNF251 haploinsufficient cancer cells harboring BRCA1 mutations. Our findings provide important insights into the mechanisms underlying PARPi resistance and highlight the unexpected role of RAD51 and DNA-PKcs in this phenomenon.
TEAD1 trapping by the Q353R–Lamin A/C causes dilated cardiomyopathy

Mutations in the LMNA gene encoding Lamin A and C (Lamin A/C), major components of the nuclear lamina, cause laminopathies including dilated cardiomyopathy (DCM), but the underlying molecular mechanisms have not been fully elucidated. Here, by leveraging single-cell RNA sequencing (RNA-seq), assay for transposase-accessible chromatin using sequencing (ATAC-seq), protein array, and electron microscopy analysis, we show that insufficient structural maturation of cardiomyocytes owing to trapping of transcription factor TEA domain transcription factor 1 (TEAD1) by mutant Lamin A/C at the nuclear membrane underlies the pathogenesis of Q353R-LMNA–related DCM. Inhibition of the Hippo pathway rescued the dysregulation of cardiac developmental genes by TEAD1 in LMNA mutant cardiomyocytes. Single-cell RNA-seq of cardiac tissues from patients with DCM with the LMNA mutation confirmed the dysregulated expression of TEAD1 target genes. Our results propose an intervention for transcriptional dysregulation as a potential treatment of LMNA-related DCM.
Formulation and Evaluation of Herbal Hair Tonic

Nowadays, people are interested in hair preparations and conditioner materials, such as shampoos, hair tonic and conditioner formulations containing herbal extracts. Hair tonic is a product which is used to style hair. The objective of present study involves preparation of herbal hair tonic by using jojoba, tulsi, and coconut oil and its evaluation for antifungal and antibacterial activity. The final preparation of these ingredients is formulated in batches with change in concentration. Each formulation is tested for antibacterial and antifungal activity. The formulation of different concentrations were characterized for proximate analysis including moisture content, total ash, acid insoluble ash, water soluble ash, water insoluble ash, sulphated ash. The formulation gives good results for antifungal and antibacterial activity also the formulation having good consistency good spreadiability, homogeneity, appearance and pH.
Taxonomic and functional biogeographies of soil bacterial communities across the Tibet plateau are better explained by abiotic conditions than distance and plant community composition

The processes governing soil bacteria biogeography are still not fully understood. It remains unknown how the importance of environmental filtering and dispersal differs between bacterial taxonomic and functional biogeography, and whether their importance is scale‐dependent. We sampled soils across the Tibet plateau, with distances among plots ranging from 20 m to 1550 km. Taxonomic composition of bacterial community was characterized by 16S amplicon sequencing and functional community composition by qPCR targeting 9 functional groups involved in N dynamics. Factors representing climate, soil and plant community were measured to assess different facets of environmental dissimilarity. Both bacterial taxonomic and functional dissimilarities were more related to abiotic dissimilarity than biotic (vegetation) dissimilarity or distance. Taxonomic dissimilarity was mostly explained by differences in soil pH and mean annual temperature (MAT), while functional dissimilarity was linked to differences in soil N and P availabilities and N:P ratio. Soil pH and MAT remained the main determinants of taxonomic dissimilarity across spatial scales. In contrast, the explanatory variables of N‐related functional dissimilarity varied across the scales, with soil moisture and organic matter having the highest role across short distances (<~330 km), and available P, N:P ratio and distance being important over long distances (>~660 km). Our results demonstrate how biodiversity dimension (taxonomic versus functional aspects) and spatial scale influence the factors driving soil bacterial biogeography.
Bisimple Inverse Semigroups as Semigroups of Ordered Triples

In (8) and (13) it has been shown that certain bisimple inverse semigroups, called bisimple ω-semigroups and bisimple Z-semigroups, can be represented as semigroups of ordered triples. In these cases, two of the components of each triple are integers, and the third is drawn from a fixed group. This representation is analogous to that given by the theorem of Rees (1, p. 94) concerning completely simple semigroups, and shares the same advantages.
Two-Dimension Chaos-Based Signature Algorithm for Multivariate Public Cryptosystem

Cryptography plays an important role in confidentiality, privacy protection, integrity verification. The most widely used public key cryptosystem including RSA system and elliptic curve cryptography. Since quantum algorithm and quantum computer are both developed rapidly, the current public key cryptosystem and signature scheme are under threaten, including RSA and elliptic curve cryptography. In this paper, an internal perturbation based on two-dimension chaos system is proposed to improve the security of traditional multivariate public key signature system. The outputs of central map in multivariate public key cryptosystem are acted as initializers for a two dimension chao system. When two sequences are calculated in chaos system, the corresponding elements are multiplied one by one. When both of multivariate public key cryptosystem and chaos system are estimated, the outputs of the two system are added to get the final signature. Because of the nonlinearity and unpredictability of chaos system, the proposed signature system is able to resist bilinear attack and rank attack and as a consequence, the proposed signature scheme is more secure than traditional multivariate public key signature systems.
Numerical simulation of a viscoelastic fluid with a preconditioned Schwarz method

In this paper we apply a domain decomposition method to approach the solution of a non-Newtonian viscoelastic Oldroyd-B model. The numerical scheme is based on a fixed-point argument applied to the original non-linear system of partial differential equations decoupled into a Navier-Stokes system and a tensorial transport equation. Using a modified Schwarz algorithm, involving block preconditioners for the Navier-Stokes equations, the decoupled problems are solved iteratively. Numerical simulations on a 4:1 abrupt contraction flow problem are considered to validate the scheme.
Biological function analysis of ARHGAP39 as an independent prognostic biomarker in hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the most common subtype of liver cancer, with a high morbidity and low survival rate. Rho GTPase activating protein 39 (ARHGAP39) is a crucial activating protein of Rho GTPases, a novel target in cancer therapy, and it was identified as a hub gene for gastric cancer. However, the expression and role of ARHGAP39 in hepatocellular carcinoma remain unclear. Accordingly, the cancer genome atlas (TCGA) data were used to analyze the expression and clinical value of ARHGAP39 in hepatocellular carcinoma. Further, the LinkedOmics tool suggested functional enrichment pathways for ARHGAP39. To investigate in depth the possible role of ARHGAP39 on immune infiltration, we analyzed the relationship between ARHGAP39 and chemokines in HCCLM3 cells. Finally, the GSCA website was used to explore drug resistance in patients with high ARHGAP39 expression. Studies have shown that ARHGAP39 is highly expressed in hepatocellular carcinoma and relevant to clinicopathological features. In addition, the overexpression of ARHGAP39 leads to a poor prognosis. Besides, co-expressed genes and enrichment analysis showed a correlation with the cell cycle. Notably, ARHGAP39 may worsen the survival of hepatocellular carcinoma patients by increasing the level of immune infiltration through chemokines. Moreover, N6-methyladenosine (m6A) modification-related factors and drug sensitivity were also found to be associated with ARHGAP39. In brief, ARHGAP39 is a promising prognostic factor for hepatocellular carcinoma patients that is closely related to cell cycle, immune infiltration, m6A modification, and drug resistance.
Yolk-deprived Caenorhabditis elegans secure brood size at the expense of competitive fitness

Many egg-laying species lower fecundity when yolk is in short supply, but not C. elegans. They still produce abundant offspring, yet of decreased quality. Oviparous animals support reproduction via the incorporation of yolk as a nutrient source into the eggs. In Caenorhabditis elegans, however, yolk proteins seem dispensable for fecundity, despite constituting the vast majority of the embryonic protein pool and acting as carriers for nutrient-rich lipids. Here, we used yolk protein–deprived C. elegans mutants to gain insight into the traits that may yet be influenced by yolk rationing. We show that massive yolk provisioning confers a temporal advantage during embryogenesis, while also increasing early juvenile body size and promoting competitive fitness. Opposite to species that reduce egg production under yolk deprivation, our results indicate that C. elegans relies on yolk as a fail-safe to secure offspring survival, rather than to maintain offspring numbers.
Emerging drugs in the treatment of chronic cough

ABSTRACT Introduction Chronic cough is a debilitating condition that is among the most common reasons for seeking medical attention yet remains challenging to manage. Identifying an underlying respiratory, nasal, or upper gastrointestinal disease triggering cough is the first step in assessment, but once this has been ruled out or adequately treated, many patients remain troubled with chronic cough. Areas covered This narrative review discusses the role of existing treatments and describes the current research landscape for the development of new therapies for chronic cough greater than 8 weeks that is refractory (RCC) or unexplained (UCC). The literature search includes published studies found on pubmed and conference abstracts until 2023. Expert opinion RCC/UCC can occur due to neuronal dysregulation of the vagus nerve or central nervous system. Hence, novel anti-tussives have targeted ion channels involved in the neuronal signaling which triggers cough. Although some therapies targeting receptors such as TRPV1 have failed to show efficacy, P2X3 antagonists have emerged as the most promising therapy for patients impacted by chronic cough. Disease-specific therapies such as for idiopathic pulmonary fibrosis are in early development.
Seroprevalence of Leishmania infantum in outdoor workers from southern Italian endemic regions

Visceral leishmaniasis is a zoonotic vector‐borne disease caused by Leishmania infantum. The infection often remains asymptomatic, though clinical forms may occur in immunosuppressed individuals. Although data on leishmaniasis in humans are available worldwide, the exposure to L. infantum of workers conducting outdoor activities has been scantly investigated, and it is limited to military personnel operating in endemic regions. This study aimed to assess the seroprevalence of L. infantum in different groups of outdoor workers and the occupational risk factors. The cross‐sectional study was performed on 229 workers including forestry guards, farmers, veterinarians, geologists and agronomists from three regions of southern Italy (i.e., Apulia, Basilicata and Campania). All serum samples were screened for L. infantum‐specific IgG/IgM by using automated indirect chemiluminescent immunoassays. Overall, 5.7% (13/229) of workers was positive to anti‐L. infantum antibodies, with the highest seroprevalence in veterinarians (13.6%). An increased occupational health surveillance for L. infantum infection in outdoor workers is essential to better understand the risk of exposure in specific jobs. Furthermore, guidelines and education along with a One Health collaboration among veterinarians, physicians, parasitologists and occupational health care professionals are crucial for the prevention of this disease.
Modelisation et simulation de l'interaction onde de choc/couche limite turbulente en écoulement interne avec effets de coins

Afin de concevoir des systemes de propulsion innovants, l'amelioration des performances des prises d'air supersonique constitue un enjeu majeur. En particulier, les ecoulements intervenant au sein des entrees d'air et/ou de diffuseurs supersoniques mettent en jeu des phenomenes complexes associes aux diverses echelles spatiales et temporelles: dynamique de la turbulence parietale, interaction entre une onde de choc et une couche limite turbulente, decollements tridimensionnels et effets de coins. Malgre les contributions significatives et recentes des simulations numeriques de haute fidelite sur les instationnarites de l'interaction onde de choc/couche limite sans paroi laterales, peu d'etudes numeriques ont ete menees sur l'influence des coins dans la dynamique de l'ecoulement. En presence de parois laterales et a des nombres de Mach suffisamment eleves, l’interaction se modifie et un train de choc se forme dans le diffuseur. Dans le cadre de cette these, les equations de Navier-Stokes en regime compressible sont resolues a l'aide de schemas d'ordre eleve. Des simulations en regime supersonique de l'ecoulement dans des diffuseurs rectangulaires de largeurs differentes sont effectuees. L'etude permet la mise en evidence de l'influence du confinement et des effets de coins. Une deuxieme partie de l’etude est consacree a la comprehension des instationnarites generees par un train de choc dans un diffuseur rectangulaire a l'aide d'outils de post-traitement avances: decomposition modale dynamique et periodogramme. Les resultats montrent la presence d'un possible phenomene de resonance du diffuseur a des frequences proches de celles emises par l'ecoulement.
Design and Analysis of Phase II Cancer Trials: A Review of Statistical Methods and Guidelines For Medical Researchers

Dans les trois dernieres decennies, plusieurs methodes statistiques ont ete proposees en oncologie pour le plan et l'analyse des essais therapeutiques de phase II. Cet article est la presentation de l'ensemble des methodes proposees dans la litterature. De meme, nous donnons le developpement de quelques exemples et des indications pratiques pour la choix approprie d'un plan d'essai. A ce propos, on remarque que: 1) les essais non-controles produisent generalement des resultats fiables pour les essais initiaux de phase II et pour les essais comparatifs; pour les essais comparatifs, il doit exister une estimation soignee du taux de reponse avec le traitement standard; 2) l'analyse sequentielle de groupes est utile pour reduire le nombre de patients necessaires en moyenne dans l'essai therapeutique. Dans d'autres situations, les essais controles sont preferables mais ils demandent un plus grand nombre de sujets. Cependant, l'adoption d'analyses intermediaires ou l'analyse basee sur le controle historique peuvent le reduire.
The features of heterogeneous water droplet evaporation in high-temperature combustion products of typical flammable liquids

This paper presents the experimental results on heating and evaporation features of heterogeneous (with opaque solid particles - the size of 0.05-0.5 mm, relative mass concentration 0-1 %) water droplets (the initial size - radius 1-3 mm) during their motion through high-temperature (500-1800 K) gases. We observed a significant increase in the integral characteristics of evaporation by introducing opaque inclusions into droplets. We established the influence of energy accumulation on the conditions of droplet evaporation at the internal solid / liquid interfaces. For proportioned inclusions, we set the conditions of intensive vaporization (leading to the explosive disintegration of droplets) at internal inclusion / liquid interfaces. To summarize research results, experiments were conducted with the combustion products of kerosene, gasoline, industrial alcohol, acetone, and oil. We used the particles of graphite, carbon, and aluminum as solid inclusions. Also, we compared the integral characteristics of heterogeneous droplet evaporation under the conditions of nonstationary (gas temperature varied from 1800 K to 500 K over the length of channel) and nearly stationary (gas temperature was maintained at about 1100 K) heating.
Smooth time optimal trajectory planning for industrial manipulators

This work proposes and demonstrates a strategy for planning smooth path-constrained timeoptimal trajectories for manipulators. Such trajectories are obtained by limiting the actuator jerks required by the planned motion. Existing planning strategies incorporate the smoothness requirement either as smoothness of the actuator torques or as smoothness of the joint trajectories. The smoothness requirement is desirable for reducing strain on robot actuators while still requiring low cycle times. In this work, the trajectory smoothness is de ned in the phase plane and the planning observes the limits on the actuator jerks. The solution proposed for determining the optimal trajectories consists of approximating the time optimal control problem by a nonlinear parameter optimization problem which is solved using the exible tolerance method. It is shown that the approximate solution converges to the time optimal motion when the actuator jerks become very high. A number of simulations are performed to demonstrate the proposed strategy. These simulations show that actuator jerk limits have a negative impact on robot motion time, but they do not give any indication about robot trajectory feasibility. This aspect is studied through further simulations and experiments on an industrial robot. The results of this work show that the tracking accuracy is directly related to the actuator jerk limits. Therefore, it is necessary to impose such limits when planning feasible optimal trajectories. Finally, the performance of the smooth time optimal motion is compared to the performance of both the non-jerk limited optimal trajectory, as well as a smooth quintic trajectory. For similar actuator jerks and controller e ort, the smooth path-constrained time-optimal trajectory results in ii iii a signi cantly shorter motion time with nearly the same tracking accuracy as a quintic polynomial. Based on the results in this work, actuator jerk limits are shown to provide an improved method of achieving a compromise between high tracking accuracy, smooth joint behaviour, and optimal motion time.
Astrocytic Neuroligins Are Not Required for Synapse Formation or a Normal Astrocyte Cytoarchitecture

Astrocytes exert multifarious roles in the formation, regulation, and function of synapses in the brain, but the mechanisms involved remain unclear. Interestingly, astrocytes abundantly express neuroligins, postsynaptic adhesion molecules that bind to presynaptic neurexins. A pioneering recent study reported that loss-of-function of neuroligins in astrocytes impairs excitatory synapse formation and astrocyte morphogenesis. This study suggested a crucial synaptic function for astrocytic neuroligins but was puzzling given that constitutive neuroligin deletions do not decrease excitatory synapse numbers. Thus, we here examined the function of astrocytic neuroligins using a rigorous conditional genetic approach with deletion of all major neuroligins (Nlgn1-3) in astrocytes. Our results show that early postnatal deletion of neuroligins from astrocytes has no effect on cortical or hippocampal synapses and does not alter the cytoarchitecture of astrocytes. Thus, astrocytic neuroligins are unlikely to shape synapse formation or astrocyte development but may perform other important functions in astrocytes.
Continuous Nursing Intervention Based on Network Interactive in Early Diabetic Kidney Disease Patients

Objective To analyze the effect of continuous nursing intervention based on network interactive platform on improving blood glucose level and self-efficacy in patients with early diabetic kidney disease. Methods The control group received basic routine nursing, and the study group received continuous nursing based on the network interactive platform. The blood glucose level, renal function, inflammatory factors, self-efficacy, self-management behavior, nursing efficacy and adverse reactions were compared. Results There was no significant difference in baseline data between the two groups. After the application of continuous nursing based on network interactive platform, the blood glucose level and renal function of patients were significantly decreased, and those of the study group were lower than those of the control group. The inflammatory factors in the study group were significantly lower than those in the control group. Conclusion In the nursing of patients with early-onset diabetic kidney disease, the application of continuous nursing based on network interactive platform can effectively reduce the level of inflammatory factors, improve the level of blood glucose and renal function, improve the self-efficacy and self-management behavior of patients, and reduce the occurrence of adverse reactions. It is worthy of promotion and application in nursing.