Functional Aptamers In Vitro Evolution for Intranuclear Blockage of RNA-Protein Interaction.

Over the last 30 years, despite considerable research and endeavors aimed at harnessing aptamers as pharmaceutical molecules, the progress in developing aptamer-based drugs has been falling short of expectations. Sequential steps of affinity molecule acquisition and functional screening are typically required for discovering affinity-based macromolecule therapeutics, which can be time-consuming and limiting in candidate selection. Additionally, aptamers often necessitate tedious postselection modifications to overcome pharmacokinetic limitations, which usually impede the binding affinity. Herein, we propose a novel in vitro screening platform termed Functional Aptamers in vitro Evolution (FAIVE), which integrates affinity molecule acquisition with functional screening and introduces chemical diversity during the process. This platform aims to rapidly generate functional aptamers capable of binding to target proteins and regulating their functions. Illustrated by targeting intranuclear RNA-protein interactions involving HIV-1 Tat protein and TAR RNA, FAIVE demonstrates a selection of functional aptamers with significant intracellular blocking effects. The study also explores lipid nanoparticle delivery systems to enhance intracellular delivery efficiency, expanding aptamer targeting potential to broader intracellular and intranuclear domains. This study emphasizes the potential of FAIVE to expedite the development of aptamer-based drugs and facilitate the creation of more versatile and effective therapeutics.

Interference-induced generation of a chirp-free short isolated attosecond pulse in the water window region with multicolor laser fields.

Compensating for the intrinsic attosecond chirp (atto-chirp) of wideband high-order harmonics in the water window region is a significant challenge, in order to obtain isolated attosecond pulses (IAPs) with a width of tens of attoseconds (as). Here, we propose to realize the generation of IAP with duration as short as 20 as, central energy of 365 eV, and bandwidth exceeding 150 eV from chirp-free high harmonics generated by a four-color driving laser, without the necessity for atto-chirp compensation with natural materials. Unlike any other gating methods that an IAP arises from only one electron ionization event, we take advantage of the interference between harmonic radiation produced by multiple ionizing events. We further demonstrate that such chirp-free short IAP survives after taking account of macroscopic propagation effects. Given that the synthesized multicolor laser field can also effectively increase the harmonic flux, this work provides a practical way for experiments to generate the broad bandwidth chirp-free IAPs in the water window region.

Amino-Acid-Induced Circular Polarized Luminescence in One-Dimensional Manganese(II) Halide Hybrid.

Circular polarized luminescence (CPL)-active materials attract great attentions owing to their widely applications in 3D optical displays and encrypted transmission. Inspired by the strategies adopted in perovskite based CPL materials, herein, CPL-active hybrids (D)- and (L)-(tert-butyl prolinate)MnCl3 were successfully prepared by assembling chiral D/L tert-butyl prolinate with manganese (II) chloride. Single crystal structures show the as-formed hybrids possess one-dimensional (1D) structure containing linear chains of face-sharing MnCl6 octahedral surrounded by prolinate cations. The 1D Mn(II) hybrids display strong red emission peaked at 646 nm with PLQY of 67.1 % and 57.2 % for d-type and l-type, respectively, representing the highest PLQY for 1D MnII hybrids. Interestingly, the 1D Mn(II) hybrids exhibit prominent circular dichroism (CD) signals and remarkable CPL activity with the dissymmetry factor g of 6.1*10-3 and -6.3*10-3 from 550 to 800 nm for (D)- and (L)-(tert-butyl prolinate)MnCl3 , respectively, owing to the existence of chiral cations. It is worthy noted the obtained g represents the highest value for non-lead organic-inorganic hybrids.

Interactional, functional, and biological properties of lactone sophorolipid (LSL) and collagen oligopeptides (COP) in aqueous solution.

For the mixed aqueous solution of LSL and COP, the interaction mode and mechanism have been comprehensively studied using multispectral methods including fluorescence spectrum, ultraviolet-visible (UV-vis )adsorption spectra, and circular dichroism (CD) spectra. The surface activity, particle size, foaming, emulsifying, viscosity, and antibacterial properties were evaluated in detail using a surface tension measurement (ST), dynamic light scattering (DLS), oscillometric method, spectrophotometer, Ubbelohde viscometer, and zone of inhibition separately. Compared with the single LSL or COP aqueous solution, the mixed system shows different performance optimizations in different aspects. The surface activity and foaming properties are mainly attributed to LSL, and the viscosity is attributed to COP. Fluorescence spectroscopy results show using LSL addition that the fluorescence distribution of COP has significant changes and a static quenching mechanism was proved. The results of UV-vis and CD spectra also show the changing conformation of COP using LSL addition. Data on thermodynamic parameters demonstrated that the combination of LSL and COP gives a spontaneous exothermic process and is an enthalpy-driven process. The interaction mechanism between LSL and COP is very helpful for the application and development of the mixed mild biosurfactant-protein system used in the cosmetic and food industries.

Sonar Dome Geometry Design Using CFD to Reduce Ship Resistance at Cruise Speed.

The objective of this study is to design the hull-mounted sonar dome of a ship. The goal is to reduce the ship total resistance and improve the flow field around the sonar dome for the ship design speed. OpenFOAM 6 was applied to analyze the viscous flow around the ship bow and then optimize the sonar dome geometry. The length, width and depth of the original geometry were maintained. Only the local geometry was fine-tuned considering the back slope and front tip by using Rhinoceros 6. The verification and validation was performed for the original hull form against towing tank resistance data. The grid independence was checked for the optimal design in different design stages. To ensure less influence on the interior equipment installation and to be able to re-use the non-steel dome part, the best resistance reduction is almost 2%. With a larger allowance of shape deformation, the maximal reduction could reach slightly higher than 3%. The flow field is improved for smaller flow separation and vortex, and less fluid nose in sonar detection is expected. The main reason of the resistance reduction is the decrease of the pressure component. In conclusion, a sonar dome design procedure is proposed, and an optimal geometry is suggested.

Comprehensive analysis of fatty acids in human milk of four Asian countries.

Human milk lipids provide not only energy but also indispensable bioactive components such as essential fatty acids. To establish the recommended daily intake value and guidelines for infant formula, a reference library of fatty acid composition has been generated from 4 Asian countries (South Korea, China, Vietnam, and Pakistan). Regardless of country, palmitic acid (C16:0), linoleic acid (C18:1), and linolenic acid (C18:2) were the 3 most abundant fatty acids in human milk and account for more than 75% of total fatty acids (total FA). However, there were several considerable differences between fatty acids, particularly n-3 and n-6 (omega-3 and omega-6) groups. Chinese mothers' milk had a high concentration of linoleic acid at 24.38 ± 10.02% of total FA, which may be due to maternal diet. Among the 4 countries, Pakistani mothers' milk contained a high amount of saturated fatty acid (56.83 ± 5.96% of total FA), and consequently, polyunsaturated fatty acids, including n-3 and n-6, were significantly lower than in other countries. It is noteworthy that docosahexaenoic acid (DHA) in Pakistani mothers' milk was 44.8 ± 33.3 mg/L, which is only 25 to 30% of the levels in the other 3 countries, suggesting the need for DHA supplementation for infants in Pakistan. Moreover, the ratio of n-6 to n-3 was also remarkably high in Pakistani mothers' milk (15.21 ± 4.96), being 1.4- to 1.7-fold higher than in other countries. The average DHA:ARA ratio in Asian human milk was 1.01 ± 0.79. Korean mothers' milk showed a high DHA:ARA ratio, with a value of 1.30 ± 0.98, but Pakistani mothers' milk had a significantly lower value (0.42 ± 0.12). The fatty acid compositions and anthropometric data of mother (body mass index, age) did not show any correlation. The obtained data might provide information about human milk compositions in the Asian region that could benefit from setting up recommended nutrient intake and infant formula for Asian babies.

Growing with dinosaurs: natural products from the Cretaceous relict Metasequoia glyptostroboides Hu & Cheng-a molecular reservoir from the ancient world with potential in modern medicine.

After the sensational rediscovery of living exemplars of the Cretaceous relict Metasequoia glyptostroboides-a tree previously known exclusively from fossils from various locations in the northern hemisphere, there has been an increasing interest in discovery of novel natural products from this unique plant source. This article includes the first complete compilation of natural products reported from M. glyptostroboides during the entire period in which the tree has been investigated (1954-2014) with main focus on the compounds specific to this plant source. Studies on the biological activity of pure compounds and extracts derived from M. glyptostroboides are reviewed for the first time. The unique potential of M. glyptostroboides as a source of bioactive constituents is founded on the fact that the tree seems to have survived unchanged since the Cretaceous era. Since then, its molecular defense system has resisted the attacks of millions of generations of pathogens. In line with this, some recent landmarks in Metasequoia paleobotany are covered. Initial spectral analysis of recently discovered intact 53 million year old wood and amber of Metasequoia strongly indicate that the tree has remained unchanged for millions of years at the molecular level.

Anti-tumor activity evaluation of novel chrysin-organotin compound in MCF-7 cells.

Chrysin (5,7-dihydroxylflavone, Chry) is a natural flavonoid extracted from plants and propolis. In this work, a novel chrysin-organotin (Chry-Sn) compound with enhanced anticancer activities was synthesized by the reaction of chrysin and triphenyltin chloride, and its potential anticancer effects against cancer cells were measured using various methods. Sulforhodamine B (SRB) results showed that chrysin and Chry-Sn had significant inhibition effects on the proliferation of MCF-7, A549 and HeLa human cancer cell lines in a dose- and time- dependent manner. These results suggested that Chry-Sn possessed enhanced anticancer effects. Hoechst 33258 staining and acridine orange staining results showed apoptosis and nuclei fragments significantly increased after being treated with chrysin and Chry-Sn respectively. Moreover, chrysin and Chry-Sn significantly increased ROS levels in MCF-7 cells. Western blot results showed that chrysin and Chry-Sn activated caspase 3 and induced autophagy by increasing LC3-II level. All results showed collectively that Chry-Sn could be a more promising drug than chrysin in anticancer treatment.

Prevalence of visual impairment and eye diseases in Malaysia: A cross-sectional prospective study at the University of Malaya Medical Centre.

Introduction: The prevalence of visual impairment and ocular diseases changes over time. This measure can help general practitioners in anticipating common eye disorders that may require ophthalmological referrals to government hospitals. This study aimed to evaluate the prevalence of visual impairment and ocular diseases in an outpatient ophthalmology clinic in a public hospital and the types of investigations frequently conducted to diagnose these diseases. Methods: A cross-sectional prospective study was conducted over three weeks in the eye clinic of the University of Malaya Medical Centre. The electronic medical records of all patients who attended the outpatient clinic were assessed to collect data on sex, age, type of visit, visual acuity, ocular presentation, investigations conducted and diagnosis of eye diseases. Visual impairment and blindness were categorised as per the World Health Organization criteria. Results: Among 1002 patients, 327 had visual impairments (32.63%), and nine had blindness (0.9%). Cataracts were the most common ocular disease diagnosed (n=294, 29.74%), followed by glaucoma (n=123, 12.28%) and diabetic retinopathy (n=84, 8.38%). Optical coherence tomography was the most common investigation performed (n=272, 64.9%), followed by Humphrey visual field testing (n=53,12.6%). Conclusion: Untreated refractive error is the leading cause of visual impairment in children, while cataract, glaucoma and diabetic retinopathy are the main contributors to visual impairment and blindness in elderly individuals. Our study highlights the urgent need for general practitioners to recognise avoidable visual impairment in all age groups to help prevent blindness.

Prenatal diagnosis of non-typical Chiari malformation type I associated with de novo Nuclear Factor I A gene mutation: a case report.

BACKGROUND: Chiari malformation is one of the most common Central nervous system (CNS) abnormalities that can be detected in routine fetal scanning. Chiari malformation type I (CMI) is a congenital defect characterized by a displacement of the cerebellar tonsils through the foramen magnum. The etiology of CMI has not been well established and suggested having multifactorial contributions, especially genetic deletion. Clinical characteristics of this anomaly may express in different symptoms from neurological dysfunction and/or skeletal abnormalities in the later age, but it is rarely reported in pregnancy. CASE PRESENTATION: We present a case in which the Chiari malformation type I was diagnosed with comorbidities of facial anomalies (flatting forehead and micrognathia) and muscular-skeletal dysmorphologies (clenched hands and clubfeet) at the 24+6 weeks of gestation in a 29-year-old Vietnamese pregnant woman. The couple refused an amniocentesis, and the pregnancy was followed up every 4 weeks until a spontaneous delivery occurred at 38 weeks. The newborn had a severe asphyxia and seizures at birth required to have an emergency resuscitation at delivery. He is currently being treated in the intensive neonatal care unit. He carries the novel heterozygous NFIA gene mutation confirmed after birth. No further postnatal malformation detected. CONCLUSION: CMI may only represent with facial abnormalities and muscle-skeletal malformations at the early stage of pregnancy, which may also alert an adverse outcome. A novel heterozygous NFIA gene mutation identified after birth helps to confirm prenatal diagnosis of CMI and to provide an appropriate consultation.

Progress of nanopreparation technology applied to volatile oil drug delivery systems.

Traditional Chinese medicine volatile oil has a long history and possesses extensive pharmacological activity. However, volatile oils have characteristics such as strong volatility, poor water solubility, low bioavailability, and poor targeting, which limit their application. The use of volatile oil nano drug delivery systems can effectively improve the drawbacks of volatile oils, enhance their bioavailability and chemical stability, and reduce their volatility and toxicity. This article first introduces the limitations of the components of traditional Chinese medicine volatile oils, discusses the main classifications and latest developments of volatile oil nano formulations, and briefly describes the preparation methods of traditional Chinese medicine volatile oil nano formulations. Secondly, the limitations of nano formulation technology are discussed, along with future challenges and prospects. A deeper understanding of the role of nanotechnology in traditional Chinese medicine volatile oils will contribute to the modernization of volatile oils and broaden their application value.

Pituitary Suppression with Gonadotropin-Releasing Hormone Agonist Prior to Artificial Endometrial Preparation in Frozen-Thawed Embryo Transfer Cycles: A Systematic Review and Meta-Analysis of Different Protocols and Infertile Populations.

This study investigates the effect of GnRHa pretreatment on pregnancy outcomes in artificial endometrial preparation for frozen-thawed embryo transfer (AC-FET) cycles. A systematic review of English language studies published before 1 September 2022, was conducted, excluding conference papers and preprints. Forty-one studies involving 43,021 participants were analyzed using meta-analysis, with a sensitivity analysis ensuring result robustness. The study found that GnRHa pretreatment generally improved the clinical pregnancy rate (CPR), implantation rate (IR), and live birth rate (LBR). However, discrepancies existed between randomized controlled trials (RCTs) and observational studies; RCTs showed no significant differences in outcomes for GnRHa-treated cycles. Depot GnRHa protocols outperformed daily regimens in LBR. Extended GnRHa pretreatment (two to five cycles) significantly improved CPR and IR compared to shorter treatment. Women with polycystic ovary syndrome (PCOS) saw substantial benefits from GnRHa pretreatment, including improved CPR and LBR and reduced miscarriage rates. In contrast, no significant benefits were observed in women with regular menstruation. More rigorous research is needed to solidify these findings.

Prevalence of common autosomal recessive mutation carriers in women in the Southern Vietnam following the application of expanded carrier screening.

The common autosomal recessive (AR) mutation carrier is still unknown in Vietnam. This study aims to identify the most common AR gene mutation carriers in women of reproductive age to build a Vietnamese-specific carrier screening panel for AR and X-linked disorders in the preconception and prenatal healthcare program. A cross-sectional study was conducted at University Medical Center-Branch 2 in Ho Chi Minh City from December 1st, 2020, to June 30th, 2023. 338 women have consented to take a 5 mL blood test to identify 540 recessive genes. The carrier screening panel was designed based on the American College of Medical Genetics and Genomics (ACMG)-recommended genes and suggestions from 104 clinical experts in Vietnam. Obstetricians and genetic experts counseled all positive testing results to discuss the possibility of recessive diseases in their offspring. The most common recessive disorders were defined at a prevalence of 1 in 60 or greater, and those were added to a Vietnamese-specific carrier screening panel. 338 non-pregnant and pregnant women underwent the expanded carrier screening (ECS). The carrier frequency was 63.6%, in which 215 women carried at least one AR gene mutation. GJB2 hearing impairment was identified as the most common chronic condition (1 in 5). The second most common AR disorder was beta-thalassemia (1 in 16), followed by cystic fibrosis (1 in 23), G6PD deficiency (1 in 28), Wilson's disease (1 in 31), Usher's syndrome (1 in 31), and glycogen storage disease (1 in 56). Seven common recessive genes were added in ethnic-based carrier screening. Women in the South of Vietnam have been carried for many recessive conditions at high frequency, such as hearing impairment, genetic anemia, and cystic fibrosis. It is necessary to implement a preconception and prenatal screening program by using seven widely popular AR genes in a Vietnamese-specific carrier screening panel to reduce the burden related to AR and X-linked disorders.

The direct renin inhibitor aliskiren localizes and persists in rat kidneys.

The aims of this study were to 1) determine whether renal localization of aliskiren and its antihypertensive and renoprotective effects persist after administration of the drug is stopped and 2) define the renal localization of aliskiren by light microscopy autoradiography. Hypertensive double transgenic rats (dTGR) overexpressing genes for human renin and angiotensinogen were treated with aliskiren (3 mg·kg(-1)·day(-1) sc; osmotic minipumps) or enalapril (18 mg/l in drinking water). After a 2-wk treatment, dTGR were assigned to either continued treatment with aliskiren ("continued"), or to cessation of their respective treatment ("stopped") for a 3-wk washout. One week of treatment with aliskiren and enalapril reduced blood pressure and albuminuria vs. baseline. After cessation of either treatment, blood pressure had returned to pretreatment levels and albuminuria remained relatively low for 1 wk, but rose thereafter similarly in both groups. In contrast, renal mRNA for transforming growth factor-ß and renal collagen IV was reduced by aliskiren (continued and stopped groups), but not after cessation of enalapril. Similar patterns were found for collagen IV protein expression. Even 3 wk after stopping aliskiren treatment, renal levels of the drug exceeded its IC50, whereas enalaprilat was not detected. To localize aliskiren accumulation, Wistar rats were treated with [(3)H]-aliskiren for 7 days. Autoradiography demonstrated specific labeling in glomeruli, arterioles, and afferent arterioles as well as in the distal nephron. Labeling could still be observed even after 7 days' washout. These results suggest that the renophilic properties of aliskiren are different from enalapril and could have contributed to the renoprotective mechanism of this renin inhibitor.

Lymphangioma of the vagina.

BACKGROUND: Vaginal lymphangioma is an extremely rare lesion. Lymphangioma in other areas is usually asymptomatic, and bleeding is a common complication and presentation. CASE: We describe the identification of a vaginal lymphangioma in a 47-year-old woman and discuss the histopathology, diagnosis, and management, based on colposcopy and histology results. CONCLUSION: Vaginal lymphangioma should be identified by histopathology to exclude other malignant tumours in the vagina and to plan appropriate therapy.

Contexte : Le lymphangiome vaginal est une lésion extrêmement rare. Lorsqu'il affecte d'autres parties du corps, le lymphangiome est habituellement asymptomatique; les saignements en constituent une complication et une présentation courantes. Cas : Nous décrivons l'identification d'un lymphangiome vaginal chez une femme de 47 ans et nous discutons de son histopathologie, de son diagnostic et de sa prise en charge, en fonction des résultats de la colposcopie et de l'histologie. Conclusion : Le lymphangiome vaginal devrait être identifié par histopathologie afin d'écarter la présence possible d'autres tumeurs malignes dans le vagin et de planifier un traitement adéquat.

Overexpression of allene oxide cyclase promoted tanshinone/phenolic acid production in Salvia miltiorrhiza.

KEY MESSAGE: This study provides a desirable candidate gene resource (SmAOC) to increase the content of valuable natural products via appropriate JA pathway genetic engineering. Jasmonates (JAs) are important signal molecules in plants. They regulate transcripts of defense and secondary biosynthetic metabolite genes in response to environmental stresses. Currently, JAs are widely used as elicitors to improve the content of useful secondary metabolism in plants. Synthesis of the naturally occurring enantiomer of various jasmonates is catalyzed by allene oxide cyclase (AOC, EC 5.3.99.6). Here, we cloned and characterized the AOC gene (SmAOC) from Salvia miltiorrhiza. As expected, SmAOC expression was induced by abiotic stimuli such as methyl jasmonate (MeJA), ultraviolet radiation (UV) and low temperature (4 °C) in S. miltiorrhiza plantlets. To demonstrate whether the engineered internal JAs pool by overexpressing AOC gene could promote secondary metabolism production, the SmAOC was incorporated into S. miltiorrhiza hairy roots. The results revealed that SmAOC overexpression significant enhanced the yields of tanshinone IIA, rosmarinic acid (RA) and lithospermic acid B (LAB) in S. miltiorrhiza hairy roots. In addition, expression levels for key genes involved in the biosynthetic pathway of diterpenes and phenolic acids were also altered. These suggest that genetic manipulation of AOC would be helpful for improving the production of valuable secondary metabolites by regulating the biosynthesis of JAs.

Synthesis and biological evaluation of novel benzothiazole-2-thiol derivatives as potential anticancer agents.

A series of novel benzothiazole-2-thiol derivatives were synthesized and their structures determined by 1H-NMR, 13C-NMR and HRMS (ESI). The effects of all compounds on a panel of different types of human cancer cell lines were investigated. Among them, pyridinyl-2-amine linked benzothiazole-2-thiol compounds 7d, 7e, 7f and 7i exhibited potent and broad-spectrum inhibitory activities. Compound 7e displayed the most potent anticancer activity on SKRB-3 (IC(50) = 1.2 nM), SW620 (IC(50) = 4.3 nM), A549 (IC(50) = 44 nM) and HepG2 (IC(50) = 48 nM) and was found to induce apoptosis in HepG2 cancer cells.

Dynamic stability of cholesterol and desmosterol in human milk from four Asian countries.

Cholesterol is one of the functional nutrients in human milk, which is indispensable for infant growth. In this study, the concentration of cholesterol and desmosterol in human milk from four Asian countries (n = 578), including Korea, China, Vietnam, and Pakistan, were investigated. The average cholesterol concentrations of Korea and China were similar ranging between 90.2-91.6 mg/L, but those from Vietnam and Pakistan were higher at 113.8 and 175.7 mg/L, respectively. The relative standard deviations were 31-36%, except for Pakistan (51%), showing a broad distribution of 48 to 612 mg/L. Desmosterol concentrations were similar, ranging between 11.2 and 12.8 mg/L except for Pakistan, which was lower than other countries at 9.4 mg/L. In addition, the cholesterol and desmosterol concentrations during the lactation periods were not significantly different in all four Asian countries. Mothers' BMI did not significantly impact the cholesterol and desmosterol concentration in maternal milk within the same country. Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-022-01141-9.

Synthesis, structure-activity relationships and preliminary antitumor evaluation of benzothiazole-2-thiol derivatives as novel apoptosis inducers.

A series of novel benzothiazole-2-thiol derivatives were synthesized, and their anti-proliferative activities on HepG2 and MCF-7 cells were investigated. Most compounds had inhibitory effects on cell growth, and some of them were more effective than cisplatin. Compounds 6m and 6t displayed good inhibitory activities against a panel of different types of human cancer cell lines, with IC(50) values in the low micromolar range. Further biological evaluation indicated that 6m induced apoptosis in HepG2 cancer cells. Structure-activity relationships were also proposed.

Stillbirth following severe symmetric fetal growth restriction due to reactivation of Epstein-Barr virus infection in pregnancy.

Epstein-Barr virus (EBV) infection in pregnancy and consequent fetal outcomes are rarely reported. The majority of cases described strongly support the possibility of transmission of this virus in utero and during delivery, resulting in stillbirth and/or congenital defects. We present a case of EBV reactivation in pregnancy that caused a severe symmetrical fetal growth restriction (FGR) and ultimately spontaneous fetal death. A 36-year-old woman, whose infection status was undetermined, was diagnosed with severe FGR at 24 weeks' gestation. The fetal karyotype was normal. EBV DNA was detected in the amniotic fluid and maternal immunoglobulin G antibodies were positive. At 30 weeks' gestation, the fetus died spontaneously. Placental examination found evidence of deciduitis and villitis. Reactivation of EBV infection appears to be related to FGR and warrants further research to determine the optimal management strategy in pregnancy.