Organ Defects Research Articles

Characterization of knock-in zebrafish models with a novel SLC4A3 variant identified in a short QT syndrome family

Abstract Background Short QT syndrome (SQTS) is one of the lethal inherited arrhythmia syndromes leading to ventricular fibrillation (VF) and cardiac death. It is mainly caused by pathogenic variants in ion channel related genes, especially KCNH2 which produces IKr. Recently, SLC4A3 encoding a membrane-localized anion exchanger 3 (AE3) that regulates intracellular pH (pHi), has been reported as a causative gene for SQTS. However, the molecular mechanism of SLC4A3 variants which cause SQTS remains unclear. Purpose Functional characterization of a novel SLC4A3 variant identified in a SQTS family. Methods We performed target gene and whole exome sequencing to detect pathogenic variants in a family with SQTS. Patch-clamp analyses were performed to determine the electrophysiological properties using HEK293 cells. We constructed stable cell lines expressing wild-type (WT) or the SLC4A3 variant based on HEK293 cells. To evaluate the intracellular pH (pHi) level, we measured pHi using BCECF-AM via time-lapse microscopy. To clarify the pathogenesis of the SLC4A3 variant in vivo, we injected CRISPR-Cas9 and a repair template into one-cell stage zebrafish embryos and established a SLC4A3 knock-in (KI) zebrafish model (hereafter referred to as slc4a3 zebrafish). Action potential durations (APD) were recorded in slc4a3 zebrafish at 3 days post-fertilization (dpf). Results We identified two novel variants in KCNH2 (c.280 c>t, p.H70Y) and SLC4A3 (c.1059 c>a, p.N353K) in a SQTS patient. Both variants were co-segregated in the patient’s family with short QT intervals (Figure A). By electrophysiological analysis, KCNH2-H70Y did not increase IKr. We over-expressed KCNH2 (WT and H70Y), KCNQ1, and KCNJ2 in the SLC4A3 stable cell lines (WT and N353K) though no increase of IKr, IKs, and IK1 was observed. In the analysis of pHi, cells expressing SLC4A3-N353K showed significantly slower pHi alternations than those with WT, indicating the loss-of-function effect of transport kinetics in the regulation of pHi. In the electrophysiological analysis of the slc4a3 zebrafish, which harbors the paralogous variant of SLC4A3-N353K, APD20, 50, and 70 were significantly shortened in the slc4a3 KI zebrafish (HOMO) compared to the control (WT), providing evidence for the shortened QT interval with the SLC4A3 variant in vivo (Figure B). Furthermore, slc4a3 zebrafish developed severe cardiac edema (HET and HOMO: Figure C, arrows) with no gross morphological defects in other organs, which may indicate the specific role of SLC4A3-N353K in cardiac function. Conclusion We identified a novel SLC4A3 variant, p.N353K, in a family with SQTS and revealed its contributions to the pHi control and the shortened APD. Further analysis will be necessary to clarify the mechanism by which SLC4A3-N353K causes QT shortening.

Congenital Heart Defects as One of the Causes of Perinatal Mortality

Congenital malformations are one of the most common causes of infant mortality and disability in children, and congenital heart defects (CHD) occupy a leading place in the structure of all developmental anomalies. The article presents data from a retrospective analysis of charts of children who died from complex congenital heart defects and congenital heart defects in combination with multiple developmental defects. An analysis of the pathological examination cards of 102 children from 0 to 2 years old who died in maternity hospitals and children's hospitals in Bishkek was carried out. The selection of autopsy cards of children was carried out on the basis of the Republican Pathological Bureau. As a result of pathological studies, changes in the heart and lungs were revealed. At the maternity hospital stage, out of 102 children with severe congenital heart defects, 70 newborns died, which averaged 68.6%. Among congenital heart defects, heart defects with aortopulmonary shunting with pulmonary hypertension predominated — in 45 children (44%), in particular, ventricular septal defect, atrial septal defect, then ductus-dependent heart defects were diagnosed in 25 children (24.5%), which included Tetralogy of Fallot, transposition of the great vessels. 23.5% of children had multiple congenital malformations: in all cases, congenital heart disease was recorded in combination with several malformations, such as an anomaly of the musculoskeletal system with craniofacial dimorphism, anomalies of the gastrointestinal tract and urinary system, and an anomaly of the lungs. The most common association of congenital heart disease with defects of other organs and systems was observed in cases of ventricular septal defect, atrial septal defect, patent ductus arteriosus.

Congenital laryngeal anomalies in childhood

Background. Diagnosis of congenital malformations of the larynx in children is a difficult task for otorhinolaryngologists. The development and implementation of video endoscopic techniques has made a significant contribution to the understanding of anatomical changes in the larynx during CPR. Aim. To study the clinical manifestations of congenital malformations in children over 6 years of age. Materials and methods. Eighty three (100%) children with laryngeal malformations aged 6 to 18 years (10.1±0.6) were examined, who applied to the phoniatric department of the Saint-Petersburg Research Institute of Ear, Throat, Nose and Speech from 2002 to 2023. The number of boys is 39 (47%) people, girls – 44 (53%) people. The maximum incidence of children of both sexes was observed at the age of 8–12 years. Results. It should be noted that in all patients, this pathology was detected for the first time when contacting a phoniatrist. Dysphonia is expressed from birth in 30 (36%) patients. Three children also complained of difficulty breathing from birth. In 15 (18%) children, the voice remained normal. The purpose of their visit is a preventive examination. Dysphonia in the remaining 38 (46%) children appeared during increased vocal load. The structures of the congenital malformations are presented as follows: tissue defects 36 (43%) people, organ defects 34 (41%) people, combined organ-tissue defects 10 (12%) people, neurogenic defects 3 (4%). None of the examined patients had congenital tumors. Hypoplasia or grooves of the vocal folds were diagnosed in 20 (23%) cases in the group of tissue VPR. Nine (11%) patients suffered from arytenoid cartilage dyschronia, and 7 (8%) patients suffered from dysplasia. Organ defects were represented by dystopia or “crossing” of the arytenoid cartilages in 29 (35%) and epiglottis dysgenesis in 5 (6%). Based on the clinical and endoscopic picture of the larynx, we have identified two degrees of dystopia. The first degree was diagnosed in 18 (21%), and the second in 11 (13%) children. Conclusion. Patients with both tissue and organ cysts are characterized by the formation of nodules, cysts, mucosal hyperplasia, fusiform thickened edge of the vocal cord, chronic laryngitis, hypertrophy of vestibular folds. These changes should be considered as a compensatory and adaptive mechanism in conditions of forced vocalization due to anatomical changes in the larynx.

Surface chemical polishing and passivation minimize non-radiative recombination for all-perovskite tandem solar cells

All-perovskite tandem solar cells have shown great promise in breaking the Shockley–Queisser limit of single-junction solar cells. However, the efficiency improvement of all-perovskite tandem solar cells is largely hindered by the surface defects induced non-radiative recombination loss in Sn–Pb mixed narrow bandgap perovskite films. Here, we report a surface reconstruction strategy utilizing a surface polishing agent, 1,4-butanediamine, together with a surface passivator, ethylenediammonium diiodide, to eliminate Sn-related defects and passivate organic cation and halide vacancy defects on the surface of Sn–Pb mixed perovskite films. Our strategy not only delivers high-quality Sn–Pb mixed perovskite films with a close-to-ideal stoichiometric ratio surface but also minimizes the non-radiative energy loss at the perovskite/electron transport layer interface. As a result, our Sn–Pb mixed perovskite solar cells with bandgaps of 1.32 and 1.25 eV realize power conversion efficiencies of 22.65% and 23.32%, respectively. Additionally, we further obtain a certified power conversion efficiency of 28.49% of two-junction all-perovskite tandem solar cells.

Porous Frustrated Lewis Pairs Catalyst Constructed on Defective Zirconium-Based Metal-Organic Frameworks for Hydrogenation Reactions with H2.

A porous metal-organic framework (MOF)-based frustrated Lewis pairs (FLPs) were prepared via a ligand replacement strategy to generate organic linker defects in zirconium-based MOF (MOF-808), thereby exposing Zr sites as Lewis acid. Due to the rigid features of the MOF skeleton, the unsaturated metal cluster and the adjacent lattice oxygen (Lewis bases) are in sterically hindered positions, which formed FLP sites with efficient H2 activation ability. This porous heterogeneous FLP catalyst [MOF-808-OH (15%)] exhibits high performance styrene hydrogenation to ethylbenzene with 99% yield. The high structural stability and reusability enabled the catalyst to maintain an over 98% activity after five cycles. This work provides a defect modulation strategy to prepare MOF-based solid FLP catalysts.

General Dietary Recommendations for People with Down Syndrome.

Down syndrome (DS) is caused by trisomy of chromosome 21 and is associated with characteristic features of appearance, intellectual impairment to varying degrees, organ defects, and health problems typical of this syndrome. Studies on the frequency of consumption of food products in this group show many irregularities, in particular too low consumption of vegetables and fruits, wholegrain cereal products and dairy products, and excessive consumption of meat products and sweets. It is necessary to correct eating habits. The diets of people with trisomy 21 should be consistent with the recommendations of rational nutrition for the general population and take into account specific dietary modifications related to the occurrence of diseases and health problems characteristic of this syndrome.

Flusilazole induced developmental toxicity, neurotoxicity, and cardiovascular toxicity via apoptosis and oxidative stress in zebrafish

Flusilazole is a well-known triazole fungicide applied to various crops and fruits worldwide. Flusilazole residues are frequently detected in the environment, and many researchers have reported the hazardous effects of flusilazole on non-target organisms; however, the developmental toxicity of flusilazole has not been fully elucidated. In this study, we investigated flusilazole-induced developmental defects in zebrafish, which are used in toxicology studies to assess the toxic effects of chemicals on aquatic species or vertebrates. We confirmed that flusilazole exposure affected the viability and hatching rate of zebrafish larvae, and resulted in morphological defects, reduced body length, diminished eye and head sizes, and inflated pericardial edema. Apoptosis, oxidative stress, and inflammation were also observed. These factors interrupted the normal organ formation during early developmental stages, and transgenic models were used to identify organ defects. We confirmed the effects of flusilazole on the nervous system using olig2:dsRed transgenic zebrafish, and on the cardiovascular system using cmlc2:dsRed and fli1:eGFP transgenic zebrafish. Our results demonstrate the developmental toxicity of flusilazole and its mechanisms in zebrafish as well as the detrimental effects of flusilazole.

Myosin1G promotes Nodal signaling to control zebrafish left-right asymmetry

Myosin1D (Myo1D) has recently emerged as a conserved regulator of animal Left-Right (LR) asymmetry that governs the morphogenesis of the vertebrate central LR Organizer (LRO). In addition to Myo1D, the zebrafish genome encodes the closely related Myo1G. Here we show that while Myo1G also controls LR asymmetry, it does so through an entirely different mechanism. Myo1G promotes the Nodal-mediated transfer of laterality information from the LRO to target tissues. At the cellular level, Myo1G is associated with endosomes positive for the TGFβ signaling adapter SARA. myo1g mutants have fewer SARA-positive Activin receptor endosomes and a reduced responsiveness to Nodal ligands that results in a delay of left-sided Nodal propagation and tissue-specific laterality defects in organs that are most distant from the LRO. Additionally, Myo1G promotes signaling by different Nodal ligands in specific biological contexts. Our findings therefore identify Myo1G as a context-dependent regulator of the Nodal signaling pathway.

Evaluate the Ni-ZnO/g-C3N4 Nanocomposite for Photocatalytic Degradation of Organic Defect Degradation and Antibacterial Activity

Evaluate the Ni-ZnO/g-C3N4 Nanocomposite for Photocatalytic Degradation of Organic Defect Degradation and Antibacterial Activity

Juridical Analysis of Marriage for Couples Who Change Gender Based on Law No. 1 of 1974 concerning Marriage and Islamic Law

The case of gender change in Indonesia is quite common in society. This has legal implications in various aspects, especially regarding marriage. As in the Decision of the Sumber District Court No. 60/Pdt.P/2021/PN.Sbr, the judge granted the gender change. Following this decision, legal consequences related to the validity of the marriage arise. Based on this description, the formulated issues are how Islamic law views gender change and what the legal consequences are for marriage for those who have changed their gender. In discussing this topic, the author uses a normative juridical method by examining the Marriage Law and Islamic Law, particularly related to the marriage of people who have changed their gender. According to the perspective of Islamic law, gender change in Indonesia is considered haram (forbidden) because it contradicts the Quran, Hadith, and the views of scholars, including the MUI Fatwa No. 03/UMNas-VII/MUI/2010. However, surgery aimed at perfecting sexual organs is permissible and considered halal in Islam. For instance, the case of the applicant Hamidah is an effort to cure her genital organ defect and has no legal implications, so it is allowed by law. When Hamidah, also known as Muhammad Hamdan, wants to marry a woman, it should no longer be an issue because religiously Hamidah's actions are justified by religion, and the elements contained in Article 4 of the Compilation of Islamic Law (KHI) and Article 2 Paragraph 1 of the Marriage Law have been fulfilled. Overall, the legality of gender change through the District Court's decision becomes important to determine the legal consequences of marriage, particularly regarding gender status in inheritance distribution and the ability to have offspring.

GATA6 regulates WNT and BMP programs to pattern precardiac mesoderm during the earliest stages of human cardiogenesis.

Haploinsufficiency for GATA6 is associated with congenital heart disease (CHD) with variable comorbidity of pancreatic or diaphragm defects, although the etiology of disease is not well understood. Here, we used cardiac directed differentiation from human embryonic stem cells (hESCs) as a platform to study GATA6 function during early cardiogenesis. GATA6 loss-of-function hESCs had a profound impairment in cardiac progenitor cell (CPC) specification and cardiomyocyte (CM) generation due to early defects during the mesendoderm and lateral mesoderm patterning stages. Profiling by RNA-seq and CUT&RUN identified genes of the WNT and BMP programs regulated by GATA6 during early mesoderm patterning. Furthermore, interactome analysis detected GATA6 binding with developmental transcription factors and chromatin remodelers suggesting cooperative regulation of cardiac lineage gene accessibility. We show that modulating WNT and BMP inputs during the first 48 hours of cardiac differentiation is sufficient to partially rescue CPC and CM defects in GATA6 heterozygous and homozygous mutant hESCs. This study provides evidence of the regulatory functions for GATA6 directing human precardiac mesoderm patterning during the earliest stages of cardiogenesis to further our understanding of haploinsufficiency causing CHD and the co-occurrence of cardiac and other organ defects caused by human GATA6 mutations.

Синдром Алажиля в клінічній практиці дитячого хірурга

Alagille syndrome (AGS) is one of the most problematic for the diagnosis of hereditary, multisystem, cholestatic liver diseases in combination with other congenital defects. Timely diagnosis and treatment (including liver transplantation - LT) improves the quality of life (QoL), prevents irreversible liver changes, multiple organ failure and mortality. Aim – to study the possibilities and features of the differential diagnosis of AGS, the impact of complex treatment, surgical correction (including LT) on the course of the disease, the dynamics of clinical and laboratory indicators, physical development (FD) and neuropsychological development (NPD), QoL. Materials and methods. Verification of the diagnosis of AGS included clinical, biochemical, instrumental examinations, genetic markers of AGS. Quality of life was evaluated: assessment of skin itching (on a categorical scale, according to the visual analogue scale of pruritus; the level of anxiety was determined according to the Hamilton scale (modified). FD and NPD were evaluated by pediatricians and pediatric neurologists before and after treatment. The assessment of FD according to centile tables was carried out in accordance with WHO standards. The assessment of NPD was carried out: development delay for one, two, three epicrisis terms; degree of NPD delay. Results. Against the background of treatment, biochemical and clinical indicators improved. Itching of the skin (according to the categorical scale of itching, visual analogue scale of pruritus), decreased the anxiety index. The dynamics of the FD and NPD were positive. Conclusions. Modern possibilities of diagnosis of AGS include genetic and histological methods, which makes it possible to start pathogenetic therapy early, to decide the time and ways of surgical intervention (including LT). The presence of concomitant congenital defects of other organs and systems, the characteristic appearance of children with AGS require a multidisciplinary examination with the involvement of multidisciplinary specialists. Complex and timely treatment of AGS contributes to the normalization of clinical and biochemical indicators, FD, NPD, quality of life. Radical treatment of AGS by means of LT should be considered before the period of irreversible multiorgan changes, taking into account the preservation of FD and NPD. The research was carried out in accordance with the principles of the Declaration of Helsinki. Informed consent of the child and child's parents was obtained for the research. The author declares no conflict of interest.

Common and Uncommon Mouse Models of Growth Hormone Deficiency

Abstract Mouse models of growth hormone deficiency (GHD) have provided important tools for uncovering the various actions of GH. Nearly 100 years of research using these mouse lines has greatly enhanced our knowledge of the GH/IGF-1 axis. Some of the shared phenotypes of the 5 “common” mouse models of GHD include reduced body size, delayed sexual maturation, decreased fertility, reduced muscle mass, increased adiposity, and enhanced insulin sensitivity. Since these common mouse lines outlive their normal-sized littermates—and have protection from age-associated disease—they have become important fixtures in the aging field. On the other hand, the 12 “uncommon” mouse models of GHD described herein have tremendously divergent health outcomes ranging from beneficial aging phenotypes (similar to those described for the common models) to extremely detrimental features (such as improper development of the central nervous system, numerous sensory organ defects, and embryonic lethality). Moreover, advancements in next-generation sequencing technologies have led to the identification of an expanding array of genes that are recognized as causative agents to numerous rare syndromes with concomitant GHD. Accordingly, this review provides researchers with a comprehensive up-to-date collection of the common and uncommon mouse models of GHD that have been used to study various aspects of physiology and metabolism associated with multiple forms of GHD. For each mouse line presented, the closest comparable human syndromes are discussed providing important parallels to the clinic.

Meaning and Clinical Interest of Minor Malformations and Normal Variants in Neonatology.

Congenital malformations can be found in all organ systems of a newborn. Almost two-thirds of congenital malformations have an unknown cause. There are minor (mM) and major (MM) congenital malformations. Searching for minor malformations has its vital place in everyday neonatology practice. Minor malformations are defined as physical variants that have no medical consequences and are mostly located on the face and distal parts of the extremities and are easily noticed. Minor malformations occur in approximately 15% of newborns. Minor congenital malformations are of great importance because they can be an indicator of the existence of major congenital malformations and syndromes. In a one-year retrospective study that analyzed the occurrence of 38 minor malformations through the year 2023 at the University Clinical Hospital of Mostar, there was an incidence of 10.59% of minor malformations. The most frequently recorded minor malformation was deep a sacral dimple at 44.72%, then poorly modeled ears at 15.08%, and moderate rectal diastasis at 14.58%. Three or more minor congenital malformations indicate one or more major congenital malformations. Major congenital malformations are severe structural defects of tissues and organs that endanger life, create serious functional disturbances and hinder the development of the child. In our country, there is currently a recorded incidence of 8.04%. The search for minor malformations in the newborn period is of great importance to children and the whole family, and the search must not be neglected.

Specific Birth Defects Following Antiseizure Medications Used By Pregnant Women With Epilepsy.

Previous research has been limited in the comprehensive study of associations between the use of individual antiseizure medications (ASMs) in pregnancy and specific groups of birth defects, and systematic reviews and meta-analyses on the topic are limited by pooled samples and study designs. This study investigated birth defects related to ASM use in pregnancy in children born to women with epilepsy in Sweden over 20 years. We used data from Swedish national registers to follow a cohort of 17,996 children born to women diagnosed with epilepsy any time before conception in Sweden from 1996 to 2016, following them through 2017. We examined maternal-reported use of the 4 most commonly reported ASMs: lamotrigine (n = 2,148, 11.9%), carbamazepine (n = 1,940, 10.8%), valproic acid (n = 1,043, 5.80%), and levetiracetam (n = 587, 3.26%). We identified birth defects using diagnoses recorded at the time of discharge from the hospital and inpatient and outpatient diagnoses recorded in the first year of life. Models were estimated in a stepped fashion: unadjusted, adjusted for covariates, among a subcohort born to women diagnosed 10 years before conception (n = 14,586), and restricted to monotherapy. Valproic acid use in pregnancy had the strongest and most widespread associations with birth defects in children, with carbamazepine also having links to several birth defects, including respiratory system and genital organ defects. Lamotrigine use in pregnancy was associated with cleft lip/palate and chromosomal abnormalities. Levetiracetam was most often used with other ASMs and preliminarily associated with many birth defects. Our findings support avoidance of valproic acid use in pregnancy whenever possible. Lamotrigine and carbamazepine may be safer alternatives. However, these medications were also associated with certain birth defects, including some not reported previously. We are among the first to examine the possible effects of levetiracetam use in pregnancy, though more research is needed to investigate this further.

Tracheal regeneration and mesenchymal stem cell augmenting potential of natural polyphenol-loaded gelatinmethacryloyl bioadhesive

Hydrogels incorporating natural biopolymer and adhesive substances have extensively been used to develop bioactive drugs and to design cells encapsulating sturdy structure for biomedical applications. However, the conjugation of the adhesive in most hydrogels is insufficient to maintain long-lasting biocompatibility inadequate to accelerate internal organ tissue repair in the essential native cellular microenvironment. The current work elaborates the synthesis of charged choline-catechol ionic liquid (BIL) adhesive and a hydrogel with an electronegative atom rich polyphenol (PU)-laden gelatinmethacryloyl (GelMA) to improve the structural bioactivities for in vivo tracheal repair by inducing swift crosslinking along with durable mechanical and tissue adhesive properties. It was observed that bioactive BIL and PU exhibited potent antioxidant (IC 50 % of 7.91 μg/mL and 24.55 μg/mL) and antibacterial activity against E. coli, P. aeruginosa and S. aureus. The novel integration of photocurable GelMA-BIL-PU revealed outstanding mechanical strength, biodegradability and sustained drug release. The in vitro study showed exceptional cell migration and proliferation in HBECs, while in vivo investigation of the GelMA-BIL-PU hydrogel on a rat's tracheal model revealed remarkable tracheal reconstruction, concurrently reducing tissue inflammation. Furthermore, the optimized GelMA-BIL-PU injectable adhesive bioink blend demonstrated superior MSCs migration and proliferation, which could be a strong candidate for developing stem cell-rich biomaterials to address multiple organ defects.

Management of Amenorrhoea (Ihtibas-al-Tamth) in Unani System of Medicine: A Review

Menstrual patterns can be an indicator of overall health and self-perception of well-being. Amenorrhoea is the absence of menses in women of reproductive agewhich may be primary or secondary. Primary amenorrhoea refers to the absence of menarche at the age of 16 and secondary amenorrhoea is the cessation of menses for at least 6 months in already cycling women. Secondary amenorrhoea is more common than primary amenorrhea. Ihtibas al-Tamth (amenorrhoea) is defined in the Unani system of medicine as the absence of monthly bleeding for more than 2 months or a decrease in the quantity of menstrual blood. The etiologies of amenorrhoea may be considered categorically as outflow tract abnormalities, primary ovarian insufficiency, hypothalamic or pituitary disorders, other endocrine gland disorders, sequelae of chronic disease, physiologic, or induced. The causes of Ihtibas al-Tamth are related to Quwwat Dafia al-Badan, Madda and Johar Khun-i-Hayd, or Ala Makhraj -i-Hayd. Su’-i-Mizaj Barid, Yabis, Harr or Harr wa Yabis, Su’-i-Mizaj Maddi or Sada can lead to Du’f al-Quwwat-i-Dafia. Abnormality in quality and quantity of Madda in Su’-i-Mizaj Maddi can also lead to ihtibas al-tamth. Amenorrhoea is not a diagnosis but a symptom indicating anatomical, genetic and neuroendocrine abnormalities. It can be determined by two different groups of causes: (a) anatomical defects of the genital organs; (b) endocrine dysfunctions. Both congenital and acquired anomalies in the structure of the uterus and vagina could produce amenorrhoea; nevertheless, in most patients, amenorrhoea is related to an ovarian malfunction. Symptoms usually associated with amenorrhoea are headache, nausea, back ache and lower abdominal pain, tiredness, and some respiratory problems. Main principle of treatment includes Tawleed-i-Dam, Tanqiya-i-Akhlat Ghaleeza, Talteef-i-Khilt, Tafteeh-i-Uruq Raham and Tahzeel if obesity is the cause. Surgical intervention if hymen is imperforated. Some regimenal therapies are also beneficial in amenorrhoea, such as Fasd-i-Safin, Hammam-i-Murattib and Hijama-i-Nariya on calf area. Some Unani drugs, which are beneficial in amenorrhoea, are Habb-i-Mudir, Safoof-i-Baboona, Kushta Faulad, and Safoof Muhazzil. In the present scenario, it is utmost important to educate the patients to live a healthy and hygienic life and to avoid those factors which cause amenorrhoea.

Embryotoxicity of fluconazole on developing chick embryos

Abstract Background Fluconazole is a first-generation triazole used as an antifungal treatment for skin, hair, and nail infections. The study aimed to assess the embryotoxicity and teratological effects of fluconazole on chick embryos. Fertilized eggs were divided into four groups: two experimental groups treated with different concentrations of fluconazole (0.1 ml/egg, 0.2 ml/egg) containing 12 and 11 eggs, respectively, one group treated with distilled water (10 eggs), and a control group (10 eggs) left untreated. The liquid form of fluconazole was administered on the 4th day of incubation, and observations were made on the 9th day. Results There were different anomalies observed in them like hydrocephaly, microcephaly shorting of the beak, agenesis, Amelia, micromelia, anophthalmia, microphthalmia, and kyphosis. There were also observed the morphometric measurements with a difference of significant (p < 0.001) and (p < 0.01) in CR length, body weight, head circumference, eye circumference, forelimb, and hind limb. Different vital organ defects were also observed in histological studies. Fluconazole in various combinations has been found to cause embryotoxicity and teratological consequences in chick embryos. Conclusion The current study showed that fluconazole is teratogenic in creating chick undeveloped organisms. The embryotoxic impacts were recorded on structural morphometric and graphic levels.

Programming sp3 Quantum Defects along Carbon Nanotubes with Halogenated DNA.

Atomic defect color centers in solid-state systems hold immense potential to advance various quantum technologies. However, the fabrication of high-quality, densely packed defects presents a significant challenge. Herein we introduce a DNA-programmable photochemical approach for creating organic color-center quantum defects on semiconducting single-walled carbon nanotubes (SWCNTs). Key to this precision defect chemistry is the strategic substitution of thymine with halogenated uracil in DNA strands that are orderly wrapped around the nanotube. Photochemical activation of the reactive uracil initiates the formation of sp3 defects along the nanotube as deep exciton traps, with a pronounced photoluminescence shift from the nanotube band gap emission (by 191 meV for (6,5)-SWCNTs). Furthermore, by altering the DNA spacers, we achieve systematic control over the defect placements along the nanotube. This method, bridging advanced molecular chemistry with quantum materials science, marks a crucial step in crafting quantum defects for critical applications in quantum information science, imaging, and sensing.

Hexaconazole induces developmental toxicities via apoptosis, inflammation, and alterations of Akt and MAPK signaling cascades

Hexaconazole is a highly effective triazole fungicide that is frequently applied in various countries to elevate crop productivity. Given its long half-life and high water solubility, this fungicide is frequently detected in the environment, including water sources. Moreover, hexaconazole exerts hazardous effects on nontarget organisms. However, little is known about the toxic effects of hexaconazole on animal development. Thus, this study aimed to investigate the developmental toxicity of hexaconazole to zebrafish, a valuable animal model for toxicological studies, and elucidate the underlying mechanisms. Results showed that hexaconazole affected the viability and hatching rate of zebrafish at 96 h postfertilization. Hexaconazole-treated zebrafish showed phenotypic defects, such as reduced size of head and eyes and enlarged pericardiac edema. Moreover, hexaconazole induced apoptosis, DNA fragmentation, and inflammation in developing zebrafish. Various organ defects, including neurotoxicity, cardiovascular toxicity, and hepatotoxicity, were observed in transgenic zebrafish models olig2:dsRed, fli1:eGFP, and l-fabp:dsRed. Furthermore, hexaconazole treatment altered the Akt and MAPK signaling pathways, which possibly triggered the organ defects and other toxic mechanisms. This study demonstrated the developmental toxicity of hexaconazole to zebrafish and elucidated the underlying mechanisms.