RESUMEN

Alzheimer's disease (AD) is the most common form of dementia among the elderly, accounting for 60 %-70 % of cases. At present, the pathogenesis of this condition remains unclear, but the hydrolysis of acetylcholine (ACh) is thought to play a role. Acetylcholinesterase (AChE) can break down ACh transmission from the presynaptic membrane and stop neurotransmitters' excitatory effect on the postsynaptic membrane, which plays a key role in nerve conduction. Acetylcholinesterase inhibitors (AChEIs) can delay the hydrolysis of acetylcholine (ACh), which represents a key strategy for treating AD. Due to its complex etiology, AD has proven challenging to treat. Various inhibitors and antagonists targeting key enzymes and proteins implicated in the disease's pathogenesis have been explored as potential therapeutic agents. These include Glycogen Synthase Kinase 3ß (GSK-3ß) inhibitors, ß-site APP Cleaving Enzyme (BACE-1) inhibitors, Monoamine Oxidase (MAO) inhibitors, Phosphodiesterase inhibitors (PDEs), N-methyl--aspartic Acid (NMDA) antagonists, Histamine 3 receptor antagonists (H3R), Serotonin receptor subtype 4 (5-HT4R) antagonists, Sigma1 receptor antagonists (S1R) and soluble Epoxide Hydrolase (sEH) inhibitors. The drug development strategy of multi-target-directed ligands (MTDLs) offers unique advantages in the treatment of complex diseases. On the one hand, it can synergistically enhance the therapeutic efficacy of single-target drugs. On the other hand, it can also reduce the side effects. In this review, we discuss the design strategy of dual inhibitors based on acetylcholinesterase and the structure-activity relationship of these drugs.

RESUMEN

Microglia-mediated neuroinflammation plays a crucial role in ischemic stroke; consequently, understanding its regulation could facilitate the development of therapies for ischemic stroke. Chemerin 15, a 15-amino acid peptide derived from chemerin, exerts powerful anti-inflammatory effects through ChemR23, modulates macrophage polarization, and diminishes inflammatory cytokine expression in peripheral inflammation models. However, its effects on microglia and stroke remain unclear. In this study, we used an in vitro oxygen/ glucose deprivation BV2 cell model and a mouse model of ischemia-reperfusion injury to investigate the role of chemerin 15 in stroke and the underlying mechanisms. We co-cultured BV2 microglial cells with HT-22 hippocampal neurons and observed that chemerin 15 reduced apoptosis in HT-22 cells. Furthermore, we found that chemerin 15 binds to the ChemR23 receptor on the cell surface, inducing its internalization. This process regulated the activity of adenosine 5'-monophosphate-activated protein kinase and inhibited its downstream target nuclear factor kappa B. These effects could be reversed by treatment with α-NETA, a ChemR23 inhibitor. In mice with ischemia-reperfusion injury, chemerin 15 modulated microglial polarization, reduced infarct volume and neuronal apoptosis, and facilitated cognitive and neurological function recovery. Our findings suggest that chemerin 15 suppresses the microglia-mediated inflammatory response, decreases neuronal apoptosis, and enhances long-term neurological function recovery by inducing ChemR23 internalization and regulating the adenosine 5'-monophosphate-activated protein kinase/nuclear factor kappa B signaling pathway.

RESUMEN

Photothermal therapy (PTT) shows promise in cancer treatments due to its good spatiotemporal selectivity and minimal invasiveness. However, PTT has some problems such as excessive heat damage to normal tissues, tumor thermo-resistance caused by heat shock proteins (HSPs), and limited efficacy of monotherapy. Here, we construct a patch named "partitioned microneedles" (PMN-SNAP/CuS), which separates the "catalyst" bovine serum albumin-based copper sulfide nanoparticles (CuS@BSA NPs) and the "reactant" S-nitroso-N-acetylpenicillamine (SNAP) into different regions of microneedles, for enhancing mild PTT (mPTT) of melanoma. PMN-SNAP/CuS showed an excellent photothermal effect, Fenton-like catalytic activity, and nitric oxide (NO) generation ability. The combination of NO and reactive oxygen species (ROS) produced by PMN-SNAP/CuS effectively blocked the synthesis of HSPs at the source and enhanced the efficacy of mPTT. Both in vitro and in vivo results proved that PMN-SNAP/CuS significantly enhanced the inhibition of melanoma under 808 nm laser irradiation. In conclusion, our partitioned microneedle strategy based on the combination of enhanced mPTT and gas therapy (GT) provides a promising approach to enhance the therapeutic effect on melanoma.

RESUMEN

BACKGROUND: In June 2019, a patient presented with persistent fever and multiple organ dysfunction after a tick bite at a wetland park in Inner Mongolia. Next-generation sequencing in this patient revealed an infection with a previously unknown orthonairovirus, which we designated Wetland virus (WELV). METHODS: We conducted active hospital-based surveillance to determine the prevalence of WELV infection among febrile patients with a history of tick bites. Epidemiologic investigation was performed. The virus was isolated, and its infectivity and pathogenicity were investigated in animal models. RESULTS: WELV is a member of the orthonairovirus genus in the Nairoviridae family and is most closely related to the tickborne Hazara orthonairovirus genogroup. Acute WELV infection was identified in 17 patients from Inner Mongolia, Heilongjiang, Jilin, and Liaoning, China, by means of reverse-transcriptase-polymerase-chain-reaction assay. These patients presented with nonspecific symptoms, including fever, dizziness, headache, malaise, myalgia, arthritis, and back pain and less frequently with petechiae and localized lymphadenopathy. One patient had neurologic symptoms. Common laboratory findings were leukopenia, thrombocytopenia, and elevated d-dimer and lactate dehydrogenase levels. Serologic assessment of convalescent-stage samples obtained from 8 patients showed WELV-specific antibody titers that were 4 times as high as those in acute-phase samples. WELV RNA was detected in five tick species and in sheep, horses, pigs, and Transbaikal zokors (Myospalax psilurus) sampled in northeastern China. The virus that was isolated from the index patient and ticks showed cytopathic effects in human umbilical-vein endothelial cells. Intraperitoneal injection of the virus resulted in lethal infections in BALB/c, C57BL/6, and Kunming mice. The Haemaphysalis concinna tick is a possible vector that can transovarially transmit WELV. CONCLUSIONS: A newly discovered orthonairovirus was identified and shown to be associated with human febrile illnesses in northeastern China. (Funded by the National Natural Science Foundation of China and the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences.).

Asunto(s)

Fiebre , Nairovirus , Mordeduras de Garrapatas , Adulto , Anciano , Animales , Femenino , Humanos , Masculino , Ratones , Persona de Mediana Edad , Adulto Joven , Anticuerpos Antivirales/sangre , China/epidemiología , Fiebre/diagnóstico , Fiebre/epidemiología , Fiebre/virología , Nairovirus/genética , Nairovirus/aislamiento & purificación , Nairovirus/patogenicidad , Filogenia , Mordeduras de Garrapatas/complicaciones , Mordeduras de Garrapatas/virología , Prevalencia , Modelos Animales de Enfermedad , Ovinos , Caballos , Porcinos , Lactante , Preescolar , Niño , Adolescente , Anciano de 80 o más Años

RESUMEN

BACKGROUND: Colorectal cancer (CRC) is one of the most common cancers, and its progression is regulated by several factors, including circular RNA (circRNA). OBJECTIVES: The objective of this study was to determine the role, or roles, of circ_0000673 in CRC. MATERIAL AND METHODS: We used quantitative real-time polymerase chain reaction (qPCR) to detect the expression of circ_0000673, miR-548b-3p and cleavage and polyadenylation specific factor 6 (CPSF6) in DLD-1 and RKO cells. Cell Counting Kit-8 (CCK-8) and 5-ethynyl-2'-deoxyuridine (EdU) assays were used to determine circ_0000673 roles in proliferation. Wound healing and transwell assays were used to detect cell migration and invasion abilities. Expression of CPSF6 protein and stem cell-associated proteins were examined using western blot. The putative relationship between miR-548b-3p and circ_0000673 or CPSF6 was verified with dual-luciferase reporter assay. The role of circ_0000673 in CRC was also investigated in a tumor xenograft assay in nude mice. RESULTS: Circ_0000673 expression was increased in CRC tissues and cancer cells. Silencing circ_0000673 reduced tumor cell proliferation, migration and invasion, while also decreasing cell stemness. MiR-548b-3p was found to be a target of circ_0000673, while CPSF6 was a downstream target of miR-548b-3p. The tumor-regulatory effects of si-circ_0000673, anti-miR-548b-3p and oe-CPSF6 were partially reversed by anti-miR-548b-3p, si-CPSF6 and si-circ_0000673, respectively, in rescue assays. Downregulation of circ_0000673 reduced solid tumor growth in vivo. CONCLUSIONS: Circ_0000673 inhibition reduced CPSF6 expression by targeting miR-548b-3p, thereby blocking proliferation, migration and invasion of CRC tumor cells.

RESUMEN

Phosphorus concentration on the surface of seawater varies greatly with different environments, especially in coastal. The molecular mechanism by which cyanobacteria adapt to fluctuating phosphorus bioavailability is still unclear. In this study, transcriptomes and gene knockouts were used to investigate the adaptive molecular mechanism of a model coastal cyanobacterium Synechococcus sp. PCC 7002 during periods of phosphorus starvation and phosphorus recovery (adding sufficient phosphorus after phosphorus starvation). The findings indicated that phosphorus deficiency affected the photosynthesis, ribosome synthesis, and bacterial motility pathways, which recommenced after phosphorus was resupplied. Even more, most of the metabolic pathways of cyanobacteria were enhanced after phosphorus recovery compared to the control which was kept in continuous phosphorus replete conditions. Based on transcriptome, 54 genes potentially related to phosphorus-deficiency adaptation were selected and knocked out individually or in combination. It was found that five mutants showed weak growth phenotype under phosphorus deficiency, indicating the importance of the genes (A0076, A0549-50, A1094, A1320, A1895) in the adaptation of phosphorus deficiency. Three mutants were found to grow better than the wild type under phosphorus deficiency, suggesting that the products of these genes (A0079, A0340, A2284-86) might influence the adaptation to phosphorus deficiency. Bioinformatics analysis revealed that cyanobacteria exposed to highly fluctuating phosphorus concentrations have more sophisticated phosphorus acquisition strategies. These results elucidated that Synechococcus sp. PCC 7002 have variable phosphorus response mechanisms to adapt to fluctuating phosphorus concentration, providing a novel perspective of how cyanobacteria may respond to the complex and dynamic environments. Supplementary Information: The online version contains supplementary material available at 10.1007/s42995-024-00244-y.

RESUMEN

Introduction: The trend of human migration to terrestrial high altitudes (HA) has been increasing over the years. However, no published prospective studies exist with follow-up periods exceeding 1 month to investigate the cardiac change. This prospective study aimed to investigate the changes in cardiac structure and function in healthy young male lowlanders following long-term migration to HA. Methods: A total of 122 Chinese healthy young males were divided into 2 groups: those migrating to altitudes between 3600 m and 4000 m (low HA group, n = 65) and those migrating to altitudes between 4000 m and 4700 m (high HA group, n = 57). Traditional echocardiographic parameters were measured at sea level, 1 month and 1 year after migration to HA. Results: All 4 cardiac chamber dimensions, areas, and volumes decreased after both 1 month and 1 year of HA exposure. This reduction was more pronounced in the high HA group than in the low HA group. Bi-ventricular diastolic function decreased after 1 month of HA exposure, while systolic function decreased after 1 year. Notably, these functional changes were not significantly influenced by altitude differences. Dilation of the pulmonary artery and a progressive increase in pulmonary artery systolic pressure were observed with both increasing exposure time and altitude. Additionally, a decreased diameter of the inferior vena cava and reduced bicuspid and tricuspid blood flow velocity indicated reduced blood flow following migration to the HA. Discussion: 1 year of migration to HA is associated with decreased blood volume and enhanced hypoxic pulmonary vasoconstriction. These factors contribute to reduced cardiac chamber size and slight declines in bi-ventricular function.

RESUMEN

Introduction: Citrus fruit is rich in important functional constituents such as flavonoids, phenolic acids terpenes and other functional substances that play an important role for treating clinical diseases or controlling major agricultural diseases and pests. Plant secondary metabolites have become one of the most important resources of novel lead compounds, especially young citrus fruits contain multiple functional substances. 'Orah', a type of citrus reticulata, is known for its fine appearance, productivity, delicious sweetness, late-maturing characteristics, and is widely cultivated in China. Fruit thinning and rootstock selection are commonly used agronomic measures in its production to ensure its quality and tree vigor. However, few studies have demonstrated the effects of these agronomic measures on the functional substances of 'Orah'. Methods: In this study, we used HPLC coupled with UV to detect the dynamic changes of fruit quality, 13 main flavonoids, 7 phenolic acids, 2 terpenes, synephrine and antioxidant capacity in both peel and pulp of citrus fruits grafted on four rootstocks (Red orange Citrus reticulata Blanco cv. red tangerine, Ziyang xiangcheng Citrus junos Sieb. ex Tanaka, Trifoliate orange Poncirus trifoliata L. Raf, and Carrizo citrange Citrus sinensis Osb.×P.trifoliate Raf) at six different developmental stages (from 90 DAF to 240 DAF). Results: The results indicated that rootstock can significantly affect the contents of functional constituents and antioxidant capacity in 'Orah'. Additionally, it was found that pruning at either 90 DAF (days after flowering) or 150 DAF produced the most favorable outcomes for extracting functional substances. We also identified rootstock 'Trifoliate orange' has the highest total soluble solids (TSS) and 'Ziyang xiangcheng' to be the optimal in terms of comprehensive sensory of fruit quality, while 'Red orange' and 'Ziyang xiangcheng' are optimal in terms of functional substance quality, and 'Red orange' excels in antioxidant capacity. Discussion: Overall, the findings demonstrate the important role of rootstocks and developmental stage in shaping fruit sensory quality and functional substance synthesis, providing valuable insights for guiding rootstock selection, determining thinning time, and utilizing pruned fruits in a more informed manner.

RESUMEN

This study reports a significant clinical outcome following the use of bronchoscopic interventional therapy combined with pembrolizumab for treating pulmonary large cell neuroendocrine carcinoma (LCNEC), showcasing a novel approach in managing this aggressive cancer.

Asunto(s)

Anticuerpos Monoclonales Humanizados , Broncoscopía , Carcinoma Neuroendocrino , Neoplasias Pulmonares , Humanos , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/administración & dosificación , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/terapia , Carcinoma Neuroendocrino/tratamiento farmacológico , Carcinoma Neuroendocrino/patología , Carcinoma Neuroendocrino/terapia , Broncoscopía/métodos , Masculino , Resultado del Tratamiento , Carcinoma de Células Grandes/tratamiento farmacológico , Carcinoma de Células Grandes/patología , Carcinoma de Células Grandes/terapia , Antineoplásicos Inmunológicos/uso terapéutico , Antineoplásicos Inmunológicos/administración & dosificación , Persona de Mediana Edad , Terapia Combinada/métodos , Tomografía Computarizada por Rayos X/métodos , Anciano

RESUMEN

In this work, we developed a dual-targeting probe consisted of well-defined hyaluronan (HA) oligosaccharide and glucose (Glc) labeled with Rhodamine B (HGR). The probe was designed to enhance tumor targeting both in vitro and in vivo, by simultaneously targeting CD44 and Glc transporter 1 (GLUT1). The HA oligosaccharide component was crucial for accurately assessing the impact of sugar chain structure on targeting efficacy, while its unoccupied carboxyl groups could minimize interference with HA's binding affinity to CD44. In vitro studies demonstrated that HGR possessed remarkable cytocompatibility and superior targeting abilities compared to single-targeting probes. It displayed a marked preference for CD44high/GLUT1high cells rather than CD44low/GLUT1low cells. In vivo studies using murine models further confirmed the significantly enhanced targeting efficacy and excellent biocompatibility of HGR. Therefore, this designed dual-targeting probe holds potential for clinical tumor detection.

RESUMEN

Hesperetin is a flavonoid compound naturally occurring in the peel of Citrus fruits from the Rutaceae family. Previous studies have demonstrated that hesperetin exhibits various pharmacological effects, such as anti-inflammatory, anti-tumor, antioxidative, anti-aging, and neuroprotective properties. In recent years, with the increasing prevalence of diseases and the rising awareness of traditional Chinese medicine, hesperetin has garnered growing attention for its wide-ranging pharmacological effects. To substantiate its health benefits and elucidate potential mechanisms, knowledge of pharmacokinetics is crucial. However, the limited solubility of hesperetin restricts its bioavailability, thereby diminishing its efficacy as a beneficial health agent. To enhance the bioavailability of hesperetin, various novel formulations have been developed, including nanoparticles, liposomes, and cyclodextrin inclusion complexes. This article reviews recent advances in the pharmacokinetics of hesperetin and methods to improve its bioavailability, as well as its pharmacological effects and mechanisms, aiming to provide a theoretical basis for clinical applications.

RESUMEN

Background: Research on individual differences in brain structural features of internet gaming disorder (IGD) and established addictions such as tobacco use disorder (TUD) is currently limited. This study utilized normative modeling to analyze the cortical thickness (CT) development patterns of male patients with IGD and TUD, aiming to provide further insights into whether IGD qualifies as an addiction. Methods: Surface-based brain morphometry (SBM) was used to calculate CT from T1-weighted magnetic resonance imaging data of 804 male participants (665 healthy individuals, 68 IGD and 71 TUD). Gaussian process regression was employed to generate normative models of CT development. Deviation maps were produced to depict deviations of IGD and TUD participants from the typical developmental patterns. Results: Both addiction groups exhibited widespread cortical thinning, particularly in regions such as the bilateral temporal pole and medial orbitofrontal cortex. The TUD group demonstrated a higher degree of individualization and limited spatial overlap compared to the IGD group. Opposite trends in CT changes were observed between the two groups in the bilateral pericalcarine cortex and pars triangularis. Conclusions: These findings regarding the similarities and differences between IGD and TUD provide support for the idea that IGD shares common features with substance-related addictions and contribute to a deeper understanding of the neural mechanisms underlying IGD.

RESUMEN

Chronic hepatitis B virus (HBV) infection poses a major global health challenge with massive morbidity and mortality. Despite a preventive vaccine, current treatments provide limited virus clearance, necessitating lifelong commitment. The HBV surface antigen (HBsAg) is crucial for diagnosis and prognosis, yet its high-resolution structure and assembly on the virus envelope remain elusive. Utilizing extensive datasets and advanced cryo-electron microscopy analysis, we present structural insights into HBsAg at a near-atomic resolution of 3.7 angstroms. HBsAg homodimers assemble into subviral particles with D2- and D4-like quasisymmetry, elucidating the dense-packing rules and structural adaptability of HBsAg. These findings provide insights into how HBsAg assembles into higher-order filaments and interacts with the capsid to form virions.

Asunto(s)

Cápside , Antígenos de Superficie de la Hepatitis B , Virus de la Hepatitis B , Virión , Humanos , Cápside/química , Cápside/ultraestructura , Microscopía por Crioelectrón , Antígenos de Superficie de la Hepatitis B/química , Virus de la Hepatitis B/ultraestructura , Virus de la Hepatitis B/química , Virus de la Hepatitis B/fisiología , Multimerización de Proteína , Envoltura Viral/química , Envoltura Viral/ultraestructura , Virión/ultraestructura , Virión/química , Ensamble de Virus , Hepatitis B Crónica/virología , Conjuntos de Datos como Asunto

RESUMEN

Acute kidney injury (AKI) is an important clinical syndrome characterised by a sudden decline in renal function, often accompanied by renal inflammation and tubular epithelial cell damage. It has been reported that inhibiting DNA methylation significantly suppress the progression of AKI. In the current study, we investigate the effect of the DNA methyltransferase (DNMT) inhibitor RG108 in cisplatin- and hypoxia-reoxygenation-induced AKI. The expression of kidney injury molecules and inflammatory factors was examined by immunofluorescence, Western blotting and Real-time PCR. The results demonstrated that RG108 treatment significantly reduced kidney inflammation and injury. Furthermore, RNA-seq analysis was performed to reveal the regulatory mechanism of RG108 in AKI. The expression of the FOS and JUN genes, which are downstream of the MAPK pathway, were significant increased in AKI. Meanwhile, the expression of FOS and JUN were both inhibited by RG108, which is similar to what we found treatment with a specific JNK inhibitor and a specific p38 MAPK inhibitor, and thus attenuated renal inflammation and injury. In conclusion, we suggest that RG108 inhibits P38 MAPK/FOS and JNK/JUN pathways and attenuates renal injury and inflammatory responses. In these results, RG108 may become a novel MAPK pathway inhibitor and a clinical candidate for the treatment of AKI.

RESUMEN

How the factors affecting the formation and transformation of the intermediates in Pd(II)-catalyzed aromatic C-H activation: A comprehensive study with the Pd(II)/LA platform. Using the Pd(II)/Lewis acid (LA)-catalyzed C-H activation of electron-rich acetanilides as a platform, the C-H activation intermediates, including the precomplex η2-intermediate, the agostic hydrogen intermediate, and the palladacycle compound have been well-characterized. This work presents how the catalyst source, substrate, and solvent affect the formation of the η2-intermediate and its equilibrium with the agostic hydrogen intermediate, and the transformation of the agostic hydrogen intermediate to the palladacycle compound through C-H activation. The findings disclosed above are provided as a guideline for the catalyst design of the oxidative olefination of acetanilide with dioxygen, and the catalytic efficiency matched well with the mechanistic findings.

RESUMEN

SEquence Evaluation through k-mer Representation (SEEKR) is a method of sequence comparison that utilizes sequence substrings called k-mers to quantify non-linear similarity between nucleic acid species. We describe the development of new functions within SEEKR that enable end-users to estimate p values that ascribe statistical significance to SEEKR-derived similarities as well as visualize different aspects of k-mer similarity. We apply the new functions to identify chromatin-enriched lncRNAs that contain XIST-like sequence features and demonstrate the utility of applying SEEKR on lncRNA fragments to identify potential RNA-protein interaction domains. We also highlight ways in which SEEKR can be applied to augment studies of lncRNA conservation, and outline the best practice of visualizing RNA-Seq read density to evaluate support for lncRNA annotations prior to their in-depth study in cell types of interest.

RESUMEN

INTRODUCTION: Chronic Pancreatitis Prognosis Score (COPPS) was developed to discriminate disease severity and predict risk for future hospitalizations. In this cohort study, we evaluated if COPPS predicts the likelihood of hospitalization(s) in an American cohort. METHODS: The Chronic Pancreatitis, Diabetes, and Pancreatic Cancer consortium provided data and serum from subjects with chronic pancreatitis (N = 279). COPPS was calculated with baseline data and stratified by severity (low, moderate, and high). Primary endpoints included number and duration of hospitalizations during 12-month follow-up. RESULTS: The mean ± SD COPPS was 8.4 ± 1.6. COPPS correlated with all primary outcomes: hospitalizations for any reason (number: r = 0.15, P = 0.01; duration: r = 0.16, P = 0.01) and pancreas-related hospitalizations (number: r = 0.15, P = 0.02; duration: r = 0.13, P = 0.04). The severity distribution was 13.3% low, 66.0% moderate, and 20.8% high. 37.6% of subjects had ≥1 hospitalization(s) for any reason; 32.2% had ≥1 pancreas-related hospitalizations. All primary outcomes were significantly different between severity groups: hospitalizations for any reason (number, P = 0.004; duration, P = 0.007) and pancreas-related hospitalizations (number, P = 0.02; duration, P = 0.04). The prevalence of continued drinking at follow-up ( P = 0.04) was higher in the low and moderate groups. The prevalence of anxiety at enrollment ( P = 0.02) and follow-up ( P < 0.05) was higher in the moderate and high groups. DISCUSSION: Statistically, COPPS significantly correlated with hospitalization outcomes, but the correlations were weaker than in previous studies, which may be related to the outpatient nature of the PROspective Evaluation of Chronic Pancreatitis for EpidEmiologic and Translational StuDies cohort and lower prevalence of high severity disease. Studies in other prospective cohorts are needed to understand the full utility of COPPS as a potential tool for clinical risk assessment and intervention.

RESUMEN

Acute intermittent porphyria (AIP) is caused by mutations in the gene encoding hydroxymethylbilane synthase (HMBS), a key enzyme in the heme biosynthesis pathway. AIP is an autosomal dominant disorder characterized by low penetrance and a highly heterogenous clinical presentation. The estimated prevalence of AIP is 5-10 cases per 100,000 persons, with acute attacks manifesting in less than 1% of the at-risk population. This low frequency of attacks suggests significant roles for oligogenic inheritance and environmental factors in the pathogenesis of the disease. In recent years, identification of several modifier genes has advanced our understanding of the factors influencing AIP penetrance and disease severity. This review summarizes these factors including the impact of specific HMBS mutations, oligogenic inheritance, mitochondrial DNA copy number, age, sex, the influence of sex hormones, and the role of environmental factors. Further studies into the etiology of AIP disease penetrance should inform pathogenesis, potentially allowing for the development of more precise diagnostic and therapeutic approaches.

RESUMEN

Novel optically active π-conjugated polymers having a chiral bifacial indacenodithiophene backbone were synthesized by Suzuki-Miyaura cross coupling polymerization with benzothiadiazole comonomer. The obtained C2-chiral polymers form amorphous thin films on HOPG and exhibit good chirality-induced spin selectivity with spin polarization of nearly 70%.