Factors associated with non-pathogenic antibodies against desmoglein-3 in pemphigus foliaceus

Abstract Background Anti-desmoglein (Dsg)1 is produced in pemphigus foliaceus (PF), affecting exclusively the skin. Pemphigus vulgaris (PV) shows the production of anti-Dsg3 in the mucosal form, and anti-Dsg1 and 3 in the mucocutaneous form. Anti-Dsg3 autoantibodies have been rarely reported in PF. Objectives To determine the factors associated with the production and pathogenicity of anti-Dsg3 in PF. Methods Comparative analytical study of three patients groups: 16 PF-anti-Dsg3+, and 42 PF-anti-Dsg3(-) and 22 PV treatment-naïve cases. Serum was used in the anti-Dsg1 and 3 ELISA, and in immunoblotting (IB) with human epidermis extract. The expression of Dsg1 and 3 in paraffin sections was analyzed by immunohistochemistry (IHC). HLA-DRB1 alleles were compiled from a database. Results In the PF-anti-Dsg3+ group: age range similar to that of the PV group (p > 0.9999); predominance of the generalized form of PF (p = 0.002); anti-Dsg3 titers lower than those of PV (p < 0.0001); IB confirmed Dsg3 identification in one (8.33%) of 12 patients; IHC showed exclusive cytoplasmic internalization of Dsg1; HLA-DRB1 alleles of susceptibility to PF, with the absence of alleles associated with PV, in the five typed patients. Study limitations Most of the patients in the PF-anti-Dsg3+ group were undergoing treatment. Conclusion The presence of anti-Dsg3 antibodies in PF was related to older age (comparable to that of PV) and the generalized form of PF. The non-pathogenicity of anti-Dsg3 antibodies in PF can be attributed to the low serum anti-Dsg3 titers, the lack of Dsg3 internalization as detected by IHC, and the absence of PV-associated HLA-DRB1 alleles.

Captopril inhibits the overproduction of proopiomelanocortin and adrenocorticotropic hormone in the pituitary gland of male diabetic mice in close relationship with an increase in glucocorticoid receptor expression.

Prior investigation shows that diabetic patients present hypothalamus-pituitary-adrenal (HPA) axis hyperactivity related to impaired negative feedback. This study investigates the effect of Captopril on the overproduction of adrenocorticotropic hormone (ACTH) and its precursor proopiomelanocortin (POMC) in the pituitary gland of male diabetic mice. Diabetes was induced by intravenous injection of alloxan into fasted Swiss-webster mice, and the animals were treated with Captopril for 14 consecutive days, starting 7 days post-diabetes induction. Plasma corticosterone levels were evaluated by ELISA, while pituitary gland expressions of angiotensin-II type 1 receptor (AT1), angiotensin-II type 2 receptor (AT2), ACTH, Bax, Bcl-2, KI-67, POMC, and glucocorticoid receptor (GR) were evaluated using immunohistochemistry or Western blot. Diabetic mice showed pituitary gland overexpression of AT1, without altering AT2 levels, which were sensitive to Captopril treatment. Furthermore, diabetic mice presented hypercortisolism, along with an increase in the number of corticotroph cells, POMC and ACTH expression, and number of proliferative cells, and a decrease of GR expression in the pituitary gland. In addition, treatment with Captopril reduced systemic corticosterone levels, corticotroph and proliferative cell numbers, and Bcl-2, POMC, and ACTH expression in the pituitary gland of diabetic mice, besides increasing the expression of Bax and GR. In conclusion, these findings show that Captopril is a promising therapy for treating complications associated with HPA axis hyperactivity in diabetic patients, in a mechanism probably related to the downregulation of POMC production in the pituitary gland and subsequent reduction of systemic corticosterone levels.

Modular and Portable System Design for 3D Imaging of Breast Tumors Using Electrical Impedance Tomography.

This paper presents a prototype of a portable and modular electrical impedance tomography (EIT) system for breast tumor detection. The proposed system uses MATLAB to generate three-dimensional representations of breast tissue. The modular architecture of the system allows for flexible customization and scalability. It consists of several interconnected modules. Each module can be easily replaced or upgraded, facilitating system maintenance and future enhancements. Testing of the prototype has shown promising results in preliminary screening based on experimental studies. Agar models were used for the experimental stage of this project. The 3D representations provide clinicians with valuable information for accurate diagnosis and treatment planning. Further research and refinement of the system is warranted to validate its performance in future clinical trials.

Decreased Nuclear Immunoexpression of ING3 is a Frequent Event in Lip Carcinogenesis.

PURPOSE: Evaluate the immunohistochemical expression of the ING3 in actinic cheilitis and squamous cell carcinoma of the lower lip. METHODS: Forty-five specimens of actinic cheilitis and 48 specimens of squamous cell carcinoma of the lower lip were submitted to immunohistochemical detection of ING3. The protein expression in different cellular sublocations was compared between the two groups, and associations with the clinicopathological variables were analyzed. A significance level of 5% was adopted for all tests. RESULTS: Deaths were significantly more frequent in tumors with a high histopathological risk score (p < 0.05). In actinic cheilitis, significant differences were found in the nucleus-cytoplasmic expression of ING3 and expression restricted to the cytoplasm with binary histopathological grading (p < 0.05). In squamous cell carcinoma of the lower lip, there was no statistically significant difference when comparing ING3 expressions with clinical and morphological parameters (p > 0.05). Nucleo-cytoplasmic ING3 expression was significantly lower in squamous cell carcinoma of the lower lip when compared to actinic cheilitis (p < 0.05) and the expression restricted to the cytoplasm was significantly higher in squamous cell carcinoma of the lower lip (p < 0.05). CONCLUSION: The results of this study suggest that there is a marked decrease in the nuclear expression of ING3 as malignant progression occurs, indicating an impaired tumor suppressor function of this protein in actinic cheilitis and squamous cell carcinoma of the lower lip.

Fetal Diagnosis of a Ductus Arteriosus Aneurysm: A Case Report.

The ductus arteriosus aneurysm (DAA) is considered a rare anatomical alteration that consists of a dilation of this vascular structure. It has been reported that the DAA can resolve in the immediate postnatal stage and do not generate any consequences for the neonate. However, have been described some cases in which the DAA is complicated due to thromboembolic events, rupture of the lesion, respiratory symptoms, and even death. We present a case report of aneurysm of the ductus arteriosus diagnosed at 24 weeks of gestation with detailed imaging study. Also, we highlight the importance of the use of fundamental tools in the diagnosis: 3D ultrasound, multiplanar reconstruction, spatio-temporal image correlation (STIC), and omniview.

Recycling of Acrylonitrile Butadiene Styrene from Electronic Waste for the Production of Eco-Friendly Filaments for 3D Printing.

In this work, acrylonitrile butadiene styrene (ABS) copolymer from electronic waste (e-waste) was used to produce filaments for application in 3D printing. Recycled ABS (rABS) from e-waste was blended with virgin ABS (vABS) in different concentrations. By differential scanning calorimetry, it was observed that the values of the glass transition temperatures for vABS/rABS blends ranged between the values of vABS and rABS. Torque rheometry analysis showed that the processability of vABS was not compromised with the addition of rABS. Rheological measurements showed that the viscosity of vABS was higher than that of rABS at low frequencies and indicated that vABS and rABS are immiscible. Impact strength (IS) tests of the 3D printed samples showed an increase in the IS with an increase in the rABS content up to 50 wt%. Blending vABS with rABS from e-waste is promising and proved to be feasible, making it possible to recycle a considerable amount of plastics from e-waste and, thus, contributing to the preservation of the environment.

Influenza outbreak during the surge of SARS-CoV-2 omicron in a metropolitan area from southern Brazil: genomic surveillance.

Influenza circulation was significantly affected in 2020-21 by the COVID-19 pandemic. During this time, few influenza cases were recorded. However, in the summer of 2021-22, an increase in atypical influenza cases was observed, leading to the resurgence of influenza in the southernmost state of Brazil, Rio Grande do Sul (RS). The present study aimed to identify the circulation of FLUAV, FLUBV and SARS-CoV-2 and characterize the influenza genomes in respiratory samples using high-throughput sequencing technology (HTS). Respiratory samples (n = 694) from patients in RS were selected between July 2021 and August 2022. The samples were typed using reverse transcriptase real-time PCR (RT-qPCR) and showed 32% (223/694) of the samples to be positive for SARS-CoV-2, 7% for FLUAV (H3) (49/694). FLUBV was not detected. RT-qPCR data also resulted in FLUAV and SARS-CoV-2 co-infections in 1.7% (4/223) of samples tested. Whole genome sequencing of FLUAV produced 15 complete genomes of the H3N2 subtype, phylogenetically classified in the 3C.2a1b.2a.2a.3 subclade and revealing the dominance of viruses in the southern region of Brazil. Mutation analysis identified 72 amino acid substitutions in all genes, highlighting ongoing genetic evolution with potential implications for vaccine effectiveness, viral fitness, and pathogenicity. This study underscores limitations in current surveillance systems, advocating for comprehensive data inclusion to enhance understanding of influenza epidemiology in southern Brazil. These findings contribute valuable insights to inform more effective public health responses and underscore the critical need for continuous genomic surveillance.

Characterization of SNPs in meat quality-related genes in Argentine Coastal Creole pigs and their potential as a porcine genetic resource.

The Coastal Creole pigs in Argentina are predominantly found in the wild and can trace their lineage directly back to the Iberian breeds introduced by Spanish colonizers. They currently stand as the sole Creole breed in the country recognized by the FAO. However, there exists a dearth of studies assessing their genetic potential within the swine industry. Therefore, this study aimed to genetically characterize the meat quality of Coastal Creole pigs based on seven single nucleotide polymorphisms (SNPs) within the Ryr1, PRKAG3, MC4R, H-FABP, and CAST genes. A total of N = 158 samples were collected from specimens distributed along the coastal region. Our findings revealed all loci to exhibit polymorphism, underscoring the population's remarkable genetic diversity. Furthermore, a higher frequency of alleles favorable for the PRKAG3191I>V/200R>Q, MC4R1426A>G, CAST76872G>A, and Ryr11843C>T genes was observed, while alleles unfavorable predominated for H-FABP1811G>C and CAST638Ser>Arg. The results obtained in this research are highly encouraging, reflecting the genetic potential of these pigs to be utilized in swine production programs.

Inhibiting SNX10 induces autophagy to suppress invasion and EMT and inhibits the PI3K/AKT pathway in cervical cancer.

PURPOSE: Cervical cancer (CC) is a prevalent malignancy among women with high morbidity and poor prognosis. Sorting nexin 10 (SNX10) is a newly recognized cancer regulatory factor, while its action on CC progression remains elusive. Hence, this study studied the effect of SNX10 on CC development and investigated the mechanism. METHODS: The SNX10 level in CC and the overall survival of CC cases with different SNX10 expressions were determined by bioinformatics analysis in GEPIA. The SNX10 expression in tumor tissues and clinical significance were studied in 64 CC cases. The overall survival was assessed using Kaplan-Meier analysis. The formation of LC3 was evaluated using immunofluorescence. Cell invasion was measured using the Transwell assay. Epithelial-to-mesenchymal transition (EMT) was determined by observing cell morphology and assessing EMT marker levels. A xenograft tumor was constructed to evaluate tumor growth. RESULTS: SNX10 was elevated in CC tissues and cells, and the CC cases with high SNX10 levels exhibited poor overall survival. Besides, SNX10 correlated with the FIGO stage, lymph node invasion, and stromal invasion of CC. SNX10 silencing induced CC cell autophagy and suppressed CC cell invasion and EMT. Meanwhile, silenced SNX10 could suppress invasion and EMT via inducing autophagy. Furthermore, SNX10 inhibition suppressed the PI3K/AKT pathway. Moreover, silenced SNX10 restrained the tumor growth, autophagy, and EMT of CC in vivo. CONCLUSION: SNX10 was enhanced in CC and correlated with poor prognosis. Silenced SNX10 induced autophagy to suppress invasion and EMT and inhibited the PI3K/AKT pathway in CC, making SNX10 a valuable molecule for CC therapy.

Stolen Identities, Suspended Lives. Embodied Active Imagination in Clinical Work with Victims of State Terrorism.

Each collective trauma holds its own particularities and forms of horror. When the violence is exerted by the government responsible for the care of the population it is termed state terrorism. The traumatic experience and its subsequent negation create a profound dissociation between two narratives: the explicit, which conceals the true facts, and the implicit, which remains unconscious and unbridgeable. In the gap between the two, life becomes suspended. From a Jungian perspective, this can be understood as the interruption of the process of translation and integration (terms that I will explore in some depth) from implicit sensory phenomena to an explicit representational narrative. This profoundly affects the development of the ego-self axis. In turn, it creates a special challenge for analytic technique that calls for new ways of listening to, and meeting the patient in, that non-verbal, unrepresented territory. Drawing upon clinical material, an embodied perspective of Jungian clinical work is offered to show how the inclusion of the body of patient and analyst enables access to the non-represented, though implicitly encoded, traumatic affective memories stored in the somatic unconscious.

Chaque traumatisme collectif a ses particularités et ses formes d'horreur. Lorsque la violence est exercée par le gouvernement responsable de la prise en charge de la population, on parle de terrorisme d'État. L'expérience traumatique et sa négation ultérieure créent une dissociation profonde entre deux récits : l'explicite, qui dissimule les faits réels, et l'implicite, qui reste inconscient et insurmontable. Dans l'écart entre les deux, la vie est suspendue. D'un point de vue jungien, cela peut être compris comme l'interruption du processus de «traduction et d'intégration¼ (termes que j'explorerai plus en profondeur) des phénomènes sensoriels implicites à un récit représentationnel explicite. Cela affecte profondément le développement de l'axe ego­soi. En conséquence, cela crée un défi particulier pour la technique analytique et invite à de nouvelles façons d'écouter et de rencontrer le patient dans ce territoire non verbal et non représenté. En s'appuyant sur le matériel clinique, une perspective incarnée du travail clinique jungien est proposée. Il s'agit de montrer qu'inclure les corps du patient et de l'analyste permet d'accéder à ce qui n'est pas représenté, par le biais de mémoires affectives traumatiques implicitement encodées et stockées dans l'inconscient somatique.

Cada trauma colectivo tiene sus propias particularidades y formas del horror. Cuando la violencia es ejercida por el gobierno responsable del cuidado de la población se denomina Terrorismo de Estado. La experiencia traumática y su posterior negación crean una profunda disociación entre dos narrativas: la explícita, que oculta los verdaderos hechos, y la implícita, que permanece inconsciente e inabordable. En la brecha entre ambas, la vida queda suspendida. Desde una perspectiva Junguiana, dicha suspensión puede entenderse como la interrupción en el proceso de "traslación e integración" (términos que exploraré con cierta profundidad) de los fenómenos sensoriales implícitos en una narrativa representacional explícita, afectando profundamente el desarrollo del eje ego­self. A su vez, crea un desafío especial para la técnica analítica que exige nuevas formas de escuchar y encontrarse con el paciente en ese territorio no­verbal y no­representado. A partir de material clínico, se ofrece una perspectiva somática del trabajo clínico Junguiano para mostrar cómo la inclusión del cuerpo de paciente y analista posibilita el acceso a estados no­representados, a través de memorias afectivas traumáticas codificadas implícitamente y almacenadas en el inconsciente somático.

Emergence of blaOXA-181-bearing tigecycline-resistant Klebsiella aerogenes in China.

We report the isolation of a blaOXA-181-positive, tigecycline-resistant Klebsiella aerogenes strain KA04 from a Chinese inpatient's fecal sample. Species identification was performed using MALDI-TOF MS. The antibiotic susceptibilities were assessed via the broth microdilution method. To elucidate the transmission and genetic structure of the blaOXA-181 gene, conjugation assays and whole-genome sequencing (WGS) were performed. KA04 displayed resistance to carbapenems, quinolones, piperacillin/tazobactam and tigecycline. Through WGS and conjugation experiments, it was possible to confirm blaOXA-181 and qnrS1 genes causing antibiotic resistance were located on a 51-kb IncX3 type mobile plasmid, blaOXA-181 gene could be successfully transferred into E. coli EC600 at a conjugation frequency of 1.1 × 10- 4. tet(A) gene was located on both the chromosome and non-transmissible IncFIB(K) plasmid. This is a tigecycline-resistant K. aerogenes harboring blaOXA-181 isolate from human fecal sample, highlighting a significant public health concern. Further comprehensive surveillance is needed.

First Brazilian Case Report of Unrelated Patients with Identical ISG15 Mutation.

BACKGROUND: ISG15 deficiency is a mixed syndrome of Mendelian susceptibility to mycobacterial infections (MSMD), a rare inherited condition characterized primarily by recurrent infections from low-virulence mycobacteria and monogenic type I interferonopathy. OBJECTIVE: To characterize the laboratory and molecular features of two patients from different families affected by the same ISG15 variant. METHODS: We began with clinical characterization and investigation, assessed IL-12/IFN-γ production, performed genetic characterization through WES and Sanger sequencing, conducted an in silico molecular analysis of the genetic ISG15 variant's protein impact, and utilized RNAseq for transcriptome analysis to understand pathway impacts on ISG15-deficient subjects from unrelated families. RESULTS: A mutation in the ISG15 gene was identified, affecting two patients treated in different hospitals and cities in Brazil (Fortaleza and Sao Paulo), who are also members of unrelated families. Both patients showed low IFN-γ production when stimulated with BCG or BCG + IL-12. ISG15 deficiency presented with two distinct clinical phenotypes: infectious and neurological. It was identified that both patients are homozygous for the variant (c.83 T > A). Furthermore, it was observed that the mutant protein p.L28Q results in an unstable protein with increased flexibility (ΔΔG: -2.400 kcal/mol). Transcriptome analysis revealed 1321 differentially expressed genes, with significant upregulation in interferon pathways, showing higher expression in patients compared to controls. CONCLUSION: This study describes the first reported cases in Brazil of two unrelated patients with the same ISG15 mutation c.83 T > A, exhibiting infectious features such as mycobacterial infections and systemic candidiasis, neurological findings, and skin lesions, without adverse reactions to the BCG vaccine. CLINICAL IMPLICATIONS: Reporting ISG15 gene mutations in Brazilian patients enhances understanding of genetic susceptibilities, guiding effective diagnostics and treatment. Identifying high-risk individuals aids clinical practices, genetic counseling, and influences public health policies. We have identified the first case in Brazil of the same ISG15 variant c.83 T > A that was identified in two unrelated patients with distinct clinical phenotypes, infectious and neurological.

Functional UV Blocking and Superhydrophobic Coatings Based on Functionalized CeO2 and Al2O3 Nanoparticles in a Polyurethane Nanocomposite.

Water repellency has significant potential in applications like self-cleaning coatings, anti-staining textiles, and electronics. This study introduces a novel nanocomposite system incorporating functionalized Al2O3 and CeO2 nanoparticles within a polyurethane matrix to achieve hydrophobic and UV-blocking properties. The nanoparticles were functionalized using an octadecyl phosphonic acid solution and characterized by FTIR and XPS, confirming non-covalent functionalization. Spin-coated polyurethane coatings with functionalized and non-functionalized Al2O3, CeO2, and binary Al2O3-CeO2 nanoparticles were analyzed. The three-layered Al2O3-CeO2-ODPA binary system achieved a contact angle of 166.4° and 85% transmittance in the visible range. Incorporating this binary functionalized system into a 0.4% w/v polyurethane solution resulted in a nanocomposite with 75% visible transmittance, 60% at 365 nm UV, and a 147.7° contact angle after three layers. These findings suggest that ODPA-functionalized nanoparticles, when combined with a polymer matrix, offer a promising approach to developing advanced hydrophobic and UV-protective coatings with potential applications across various industrial sectors.

Low Levels of Complement Factor H in the First Trimester of Pregnancy Are Associated with Spontaneous Preterm Birth.

Preterm birth (PTB) remains a significant public health concern, and prediction is an important objective, particularly in the early stages of pregnancy. Many studies have relied on cervical characteristics in the mid-trimester, with limited results. It is therefore crucial to identify novel biomarkers to enhance the ability to identify women at risk. The complement pathway is implicated in the process of placentation, and recent proteomics studies have highlighted the potential roles of some complement proteins in the pathophysiology of PTB. To determine the association between the occurrence of spontaneous preterm birth (sPTB) and the concentration of complement C3, factor B, and factor H in the blood of pregnant women during the first trimester. This prospective cohort study included women with singleton pregnancies, both with and without a history of sPTB, from two health institutions in Bucaramanga, Colombia. The outcome was sPTB before 37 weeks. A blood sample was obtained between 11 + 0 to 13 + 6 weeks. ELISA immunoassay was performed to quantify the levels of C3, factor B, and factor H. A total of 355 patients were analyzed, with a rate of sPTB of 7.6% (27/355). The median plasma concentration for C3, factor B, and factor H were 488.3 µg/mL, 352.6 µg/mL, and 413.2 µg/mL, respectively. The median concentration of factor H was found to be significantly lower in patients who delivered preterm compared to patients who delivered at term (382 µg/mL vs. 415 µg/mL; p = 0.034). This study identified a significant association between low first-trimester levels of factor H and sPTB before 37 weeks. These results provide relevant information about a new possible early biomarker for sPTB. However, the results must be confirmed in different settings, and the predictive value must be examined.

3-Alkoxy-1-Benzyl-5-Nitroindazole Derivatives Are Potent Antileishmanial Compounds.

Indazoles have previously been identified as molecules with antiprotozoal activity. In this study, we evaluate the in vitro activity of thirteen 3-alkoxy-1-benzyl-5-nitroindazole derivatives (series D) against L. amazonensis, L. infantum, and L. mexicana. In vitro, cytotoxicity against mouse peritoneal macrophages and growth inhibitory activity in promastigotes were evaluated for all compounds, and those showing adequate activity and selectivity were tested against intracellular amastigotes. Transmission and scanning electron microscopy were employed to study the effects of 3-alkoxy-1-benzyl-5-nitroindazole and 2-benzyl-5-nitroindazolin-3-one derivatives on promastigotes of L. amazonensis. Compounds NV6 and NV8 were active in the two life stages of the three species, with the latter showing the best indicators of activity and selectivity. 3-alkoxy-1-benzyl-5-nitroindazole derivatives (series D) showed in vitro activity comparable to that of amphotericin B against the promastigote stage of Leishmania spp. Two compounds were also found to be active the amastigote stage. Electron microscopy studies confirmed the antileishmanial activity of the indazole derivatives studied and support future research on this family of compounds as antileishmanial agents.

1,3,4-oxadiazoles as inhibitors of the atypical member of the BET family bromodomain factor 3 from Trypanosoma cruzi (TcBDF3).

Chagas disease, caused by the protozoan parasite Trypanosoma cruzi, affects millions globally, with increasing urban cases outside of Latin America. Treatment is based on two compounds, namely, benznidazole (BZ) and nifurtimox, but chronic cases pose several challenges. Targeting lysine acetylation, particularly bromodomain-containing proteins, shows promise as a novel antiparasitic target. Our research focuses on TcBDF3, a cytoplasmic protein, which is crucial for parasite differentiation that recognizes acetylated alpha-tubulin. In our previous study, A1B4 was identified as a high-affinity binder of TcBDF3, showing significant trypanocidal activity with low host toxicity in vitro. In this report, the binding of TcBDF3 to A1B4 was validated using differential scanning fluorescence, fluorescence polarization, and molecular modeling, confirming its specific interaction. Additionally, two new 1,3,4-oxadiazoles derived from A1B4 were identified, which exhibited improved trypanocide activity and cytotoxicity profiles. Furthermore, TcBDF3 was classified for the first time as an atypical divergent member of the bromodomain extraterminal family found in protists and plants. These results make TcBDF3 a unique target due to its localization and known functions not shared with higher eukaryotes, which holds promise for Chagas disease treatment.

Autophagy and inflammasome activation are associated with poor response to FLT3 inhibitors in patients with FLT3-ITD acute myeloid leukemia.

Beyond its clinical diversity and severity, acute myeloid leukemia (AML) is known for its complex molecular background and for rewiring biological processes to aid disease onset and maintenance. FLT3 mutations are among the most recurring molecular entities that cooperatively drive AML, and their inhibition is a critical molecularly oriented therapeutic strategy. Despite being a promising avenue, it still faces challenges such as intrinsic and acquired drug resistance, which led us to investigate whether and how autophagy and inflammasome interact and whether this interaction could be leveraged to enhance FLT3 inhibition as a therapeutic strategy. We observed a strong and positive correlation between the expression of key genes associated with autophagy and the inflammasome. Gene set enrichment analysis of the FLT3-ITD samples and their ex vivo response to five different FLT3 inhibitors revealed a common molecular signature compatible with autophagy and inflammasome activation across all poor responders. Inflammasome activation was also shown to strongly increase the likelihood of a poor ex vivo response to the FLT3 inhibitors quizartinib and sorafenib. These findings reveal a distinct molecular pattern within FLT3-ITD AML samples that underscores the necessity for further exploration into how approaching these supportive parallel yet altered pathways could improve therapeutic strategies.

Design of a low-cost force insoles to estimate ground reaction forces during human gait.

This paper proposes a low-cost electronic system for estimating ground reaction forces (GRF) during human gait. The device consists of one master node and two slave nodes. The master node sends instructions to slave nodes that sample and store data from two force insoles located at the participant's feet. These insoles are equipped with 14 piezo-resistive FlexiForce A301 sensors (FSR). The slave nodes are attached to the ankles and feet of each participant. Subsequently, the start command is transmitted through the master node, which is connected to the USB port of a personal computer (PC). Once the walking session is completed, the information obtained by the slave nodes can be downloaded by accessing the access point generated by these devices through Wi-Fi communication. The GRF estimation system was validated with force platforms (BTS Bioengineering P6000, Italy), giving on average a fit measure equal to 68 . 71 % ± 4 . 80 % in dynamic situations. Future versions of this device are expected to increase this fit by using machine learning models.

MicroRNA-1307-3p contributes to breast cancer progression through PRM2.

BACKGROUND: Despite advances in screening and therapy, breast cancer (BC) remains the predominant cancer in women globally. Dysregulation of microRNAs (miRNAs) is pivotal in carcinogenesis across various cancers, including BC. Evidence indicates that miR-1307-3p is upregulated in BC tumors, yet its target genes are not fully elucidated. This study aimed to explore how miR-1307-3p regulates BC proliferation, migration, invasion, and angiogenesis and to identify potential target genes. METHODS: Basal miR-1307-3p levels were quantified in BC cell lines MDA-MB-231 and MCF-7, as well as MCF-10A using quantitative real-time reverse transcription-PCR (RT-qPCR). The impact of miR-1307-3p inhibition on BC cell proliferation, migration, invasion, and angiogenesis was assessed. Nine miRNA-target prediction databases identified potential miR-1307-3p targets. Target expression was validated using RT-qPCR, Western blot, and dual-luciferase reporter assays. MiR-1307-3p was overexpressed in MDA-MB-231 and MCF-7 compared to MCF-10A. RESULTS: Inhibiting miR-1307-3p significantly reduced BC cell proliferation, migration, invasion, and angiogenesis. Bioinformatics analysis identified 17 potential miR-1307-3p targets, with protamine 2 (PRM2) overexpression confirmed via Western blot and dual-luciferase assays. CONCLUSION: MiR-1307-3p overexpression in BC promotes proliferation, migration, invasion, and angiogenesis. PRM2 emerges as a novel miR-1307-3p target in BC.

Reaction force constant as a descriptor of the principle of non-perfect synchronization.

CONTEXT: In this study, a small set of 1,3-dipolar cycloaddition reactions that proceed at the same exothermicity is presented. Our main objective was to extend the application of the reaction force constant concept to gain an understanding of the reactivity principles. Inspired by a recent article where we show that the Bell-Evans-Polanyi principle is fulfilled under the condition of an equal degree of (a)synchronicity, here, we demonstrate that the reaction force constant is also a suitable descriptor to quantify the principle of non-perfect synchronization proposed by Bernasconi as a way to understand deviations from the Bell-Evans-Polanyi principle. METHODS: Reaction profiles V ( ξ ) , F ( ξ ) , and κ ( ξ ) were performed at the B3LYP/6-31G(d,p) level of theory. The stabilizing interactions were characterized using the energy decomposition analysis combined with the natural orbitals for chemical valence, EDA-NOCV, method. The present work was done using Gaussian 09 and Multiwfn programs.