Search

Kaposi's sarcoma-associated herpesvirus (KSHV) can cause a variety of malignancies. Ganciclovir (GCV) is one of the most efficient drugs against KSHV, but its non-specificity can cause other side effects in patients. Nucleic acid miR-34a-5p can inhibit the transcription of KSHV RNA and has great potential in anti-KSHV therapy, but there are still problems such as easy degradation and low delivery efficiency. Here, we constructed a co-loaded dual-drug nanocomplex (GCV@ZIF-8/PEI-FA+miR-34a-5p) that contains GCV internally and adsorbs miR-34a-5p externally. The folic acid (FA)-coupled polyethyleneimine (PEI) coating layer (PEI-FA) was shown to increase the cellular uptake of the nanocomplex, which is conducive to the enrichment of drugs at the KSHV infection site. GCV and miR-34a-5p are released at the site of the KSHV infection through the acid hydrolysis characteristics of ZIF-8 and the "proton sponge effect" of PEI. The co-loaded dual-drug nanocomplex not only inhibits the proliferation and migration of KSHV-positive cells but also decreases the mRNA expression level of KSHV lytic and latent genes. In conclusion, this co-loaded dual-drug nanocomplex may provide an attractive strategy for antiviral drug delivery and anti-KSHV therapy. [ABSTRACT FROM AUTHOR]

Background: Optical coherence tomography (OCT) or OCT angiography (OCTA) has been investigated in few research studies of psychiatric disorders. No research has been done using OCT or OCTA in patients with borderline personality disorder (BPD). Methods: OCTA measured foveal avascular zone (FAZ), macular vessel density (MVD), and peripapillary vessel density (PVD). OCT measured the peripapillary retinal fiber layer (RNFL) and central retinal thickness (CRT). The study utilized the Ottawa Self‐Injury Inventory, Hamilton Anxiety Rating Scale (HAMA), and Global Assessment of Functioning (GAF) to assess the symptom characteristics of individuals with BPD. Results: Fifty‐nine eyes of BPD patients and 58 eyes of normal subjects were analyzed, MVD of the superficial retinal capillary plexus declined noticeably in most subfields (p < 0.05). Significant differences were observed in the whole inner ring and outer ring index between BPD and HC groups (p < 0.05). The patients with BPD exhibited lower RNFL and CRT, the difference was significant (p < 0.05). CRT indicated a significant negative correlation with the Ottawa Self‐Injury Inventory (p < 0.05). In addition, we observed that there was a negative correlation identified between the MVD of the inner ring and HAMA (p < 0.05). Meanwhile, the MVD of the outer ring was positively correlated with GAF (p < 0.05). The areas under the receiver operating characteristic curves (AUROCs) for distinguishing BPD and HC eyes in OCTA were the highest for fovea MVD (0.679), followed by outer ring MVD (0.669), inner ring MVD (0.641), FAZ (0.579). In OCT, CRT was highest for BPD (0.711), followed by RNFL (0.625). Conclusion: The OCT and OCTA can non‐invasively detect microvascular and morphology changes of the retina in BPD patients compared to healthy control subjects. [ABSTRACT FROM AUTHOR]

Research has shown the diagnostic potential of optical coherence tomography (OCT) and OCT angiography (OCTA) in various psychiatric disorders. However, there is few research focusing on changes specific to Major Depressive Disorder (MDD), and the diagnostic value of OCT combined with OCTA parameters for MDD remains unclear. In this study, we investigated microvascular and morphology changes in the retina of MDD patients using a combination of OCTA and OCT parameters, and to examine their correlation with MDD mood and cognitive function in order to assess their diagnostic capability. Our findings revealed a significant decline in macular vessel density (MVD) in the superficial retinal capillary plexus (SRCP) across all subfields, except the NO area. We also observed a significant positive correlation between fovea and Stroop-1, as well as between temporal inner (TI) and Stroop-3 in MDD patients. Furthermore, we identified a negative correlation between fovea and Self-Rating Depression Scale, as well as between Superior outer (SO) and Difficulties in Emotion Regulation Scale-C in MDD patients. The sample size was small. Anatomical variables in blood flow may contribute to variability between subjects and outcomes. The diagnostic value of OCTA suggests their potential as valuable tools for monitoring and diagnosing MDD. • A significant decrease in macular vessel density in the superficial retinal capillary plexus in MDD compared to healthy controls. • Positive correlation between fovea/ temporal inner and Stroop Color-Word Test in MDD. • Negative correlation between fovea and depressive symptom in MDD • The combined diagnostic potential of OCT and OCTA suggests their utility as valuable tools for diagnosing MDD. [ABSTRACT FROM AUTHOR]

A cyst with mural nodule(s) (CMN) is a rare imaging finding of cerebellar metastasis (CMET). It is a great challenge to differentiate it from cerebellar hemangioblastoma (CHB). In the present study, we explore the differences in the magnetic resonance imaging (MRI) characteristics of the 2 tumors. Patients with pathologically confirmed CMET or CHB at our hospital from July 2009 to September 2021 were enrolled in the present study. All the patients underwent conventional head MRI (before and after contrast administration) before surgery and had ≥1 lesion in the cerebellum that presented as CMN on MRI. The clinical and MRI features were compared between the 2 groups. A total of 33 patients (10 with CMET and 23 with CHB) met the study criteria. The CMET patients were significantly older than were the CHB patients (median age, 59.5 years vs. 37 years; P = 0.002). Compared with the CHB group, the CMET group showed significantly higher occurrence rates of multiple mural nodules (72.7% vs. 8.7%), lack of vascular flow voids (100% vs. 65.2%), isointense or hypointense mural nodules on fluid-attenuated inversion recovery imaging (100.0% vs. 22.7%), restricted diffusion of mural nodules (22.2% vs. 0.0%), mildly enhanced mural nodules (90.9% vs. 4.3%), and a ring-enhanced pattern of the cyst wall (100% vs. 8.7%; P < 0.05 for all). When CMN is detected in the cerebellum on MRI, older age, multiple mural nodules, absence of vascular flow voids, isointense or hypointense mural nodule on fluid-attenuated inversion recovery sequence, restricted diffusion of the mural nodule, mildly enhanced mural nodules, and a ring-enhanced pattern of the cyst wall are the clinical and imaging features that strongly indicate the likelihood of metastasis, rather than CHB. [ABSTRACT FROM AUTHOR]

The asymmetric addition reactions between varied nonaromatic aldehydes and diethylzinc catalyzed by chiral phosphoramide L 1 and thiophosphorodiamide L 4 were thoroughly investigated. Both ligands worked very well for α-branched aliphatic and α-branched α,β-unsaturated aldehydes. For α-nonbranched aliphatic aldehydes, L 4 behaved much better than L 1 . For α-nonbranched α,β-unsaturated aldehydes, L 4 showed high enantioselectivities and L 1 only gave racemic alcohol products. [ABSTRACT FROM AUTHOR]

Background: In diabetic retinopathy (DR), hypoxia-inducible factor (HIF-1α) induces oxidative stress by upregulating glycolysis. This process leads to neurodegeneration, particularly photoreceptor cell damage, which further contributes to retinal microvascular deterioration. Further, the regulation of Wnt-inhibitory factor 1 (WIF1), a secreted Wnt signaling antagonist, has not been fully characterized in neurodegenerative eye diseases. We aimed to explore the impact of WIF1 on photoreceptor function within the context of DR. Method: Twelve-week-old C57BL/KsJ-db/db mice were intravitreally injected with WIF1 overexpression lentivirus. After 4 weeks, optical coherence tomography (OCT), transmission electron microscopy (TEM), H&E staining, and electroretinography (ERG) were used to assess the retinal tissue and function. The potential mechanism of action of WIF1 in photoreceptor cells was explored using single-cell RNA sequencing. Under high-glucose conditions, 661 W cells were used as an in vitro DR model. WIF1-mediated signaling pathway components were assessed using quantitative real-time PCR, immunostaining, and western blotting. Result: Typical diabetic manifestations were observed in db/db mice. Notably, the expression of WIF1 was decreased at the mRNA and protein levels. These pathological manifestations and visual function improved after WIF1 overexpression in db/db mice. TEM demonstrated that WIF1 restored damaged mitochondria, the Golgi apparatus, and photoreceptor outer segments. Moreover, ERG indicated the recovery of a-wave potential amplitude. Single-cell RNA sequencing and in vitro experiments suggested that WIF1 overexpression prevented the expression of glycolytic enzymes and lactate production by inhibiting the canonical Wnt signaling pathway, HIF-1α, and Glut1, thereby reducing retinal and cellular reactive oxygen species levels and maintaining 661 W cell viability. Conclusions: WIF1 exerts an inhibitory effect on the Wnt/β-catenin-HIF-1α-Glut1 glycolytic pathway, thereby alleviating oxidative stress levels and mitigating pathological structural characteristics in retinal photoreceptor cells. This mechanism helps preserve the function of photoreceptor cells in DR and indicates that WIF1 holds promise as a potential therapeutic candidate for DR and other neurodegenerative ocular disorders. Highlights: WIF1 inhibits HIF-1α-Glut1 glycolytic pathway in photoreceptor cells Improves oxidative stress and ameliorates pathological structural characteristics. Helps preserve the function of photoreceptor cells in diabetic retinopathy WIF1 is an excellent candidate for targeted therapy against diabetic retinopathy. [ABSTRACT FROM AUTHOR]

Purpose: To describe and evaluate the application of a new 3‐D printing‐assisted personalized macular buckle for patients with myopic foveoschisis (MFS). Methods: Twelve eyes of 12 patients with MFS were included in this study. Preoperative MRI images were subsequently measured after marker implantation and imported into the MIMICS software for the 3‐D reconstruction of a virtual model of an eyeball and a marker. The virtual eyeball model was designed according to the degree of retinoschisis, which was measured using optical coherence tomography preoperatively. A macular buckle was designed using a titanium stent, assisted by 3‐D printing; furthermore, it was surgically placed in combination with pars plana vitrectomy. Visual acuity, axial length and anatomic outcomes were analysed pre‐ and postoperatively. Results: Macular schisis in all patients was completely resolved after the surgery without any postoperative complications. The mean postoperative best corrected visual acuity (LogMAR) improved significantly from 1.21 to 0.92 during the 6‐month follow‐up period (p < 0.001) and reached 0.9 (p < 0.001) after 2 years. The axial length was significantly shortened during the 2 years postoperatively follow‐up period (p < 0.01). The average axial lengths in all patients decreased from 30.62 mm preoperatively to 29.81 mm 1 month postoperatively and remained around 30.16 mm from 1 year after the surgery. Conclusion: The 3‐D printing technique is useful to predict the indentation height and position of the macular buckle. The 3D‐printing‐assisted macular buckle, in combination with vitrectomy, is an effective, safe and accurate treatment modality for MFS. [ABSTRACT FROM AUTHOR]

Both ligands QUI and TPA show high efficiency in the title reaction. [ABSTRACT FROM AUTHOR]

Aims: Alterations in neuronal activity and cerebral hemodynamics have been reported in idiopathic generalized epilepsy (IGE) patients, possibly resulting in neurovascular decoupling; however, no neuroimaging evidence confirmed this disruption. This study aimed to investigate the possible presence of neurovascular decoupling and its clinical implications in childhood IGE using resting‐state fMRI and arterial spin labeling imaging. Methods: IGE patients and healthy participants underwent resting‐state fMRI and arterial spin labeling imaging to calculate degree centrality (DC) and cerebral blood flow (CBF), respectively. Across‐voxel CBF‐DC correlations were analyzed to evaluate the neurovascular coupling within the whole gray matter, and the regional coupling of brain region was assessed with the CBF/DC ratio. Results: The study included 26 children with IGE and 35 sex‐ and age‐matched healthy controls (HCs). Compared with the HCs, the IGE group presented lower across‐voxel CBF‐DC correlations, higher CBF/DC ratio in the right posterior cingulate cortex/precuneus, middle frontal gyrus, and medial frontal gyrus (MFG), and lower ratio in the left inferior frontal gyrus. The increased CBF/DC ratio in the right MFG was correlated with lower performance intelligence quotient scores in the IGE group. Conclusion: Children with IGE present altered neurovascular coupling, associated with lower performance intelligence quotient scores. The study shed a new insight into the pathophysiology of epilepsy and provided potential imaging biomarkers of cognitive performances in children with IGE. [ABSTRACT FROM AUTHOR]

In this study, a strategy of anti-freezing organic hydrogel system is proposed, which can be used as a medical gel dressing for the prevention and treatment of frostbite in extra cold regions. The supramolecular polymer organic hydrogel is a double network gel dressing. β-Cyclodextrin and azobenzene groups form the first supramolecular network through supramolecular host-guest interaction, and acrylamide copolymerization with crosslinker forms the second layer of covalent network. Compared with acrylamide hydrogels, the stress required to reach the same strain at –25°C is 12 times higher than that at 25°C, while the stress required by organic hydrogels at the same conditions slightly changes, indicating that organic hydrogels also show good flexibility at low temperatures. At the same time, double-network organic hydrogel could recover to 70% of original tensile capacity after self-healing. [ABSTRACT FROM AUTHOR]

[Display omitted] In this study, an alcohol dehydrogenase derived from Lactobacillus kefir (LkADH) was engineered and a simple and practical bioreduction system was developed for the preparation of (R)-2-chloro-1-(2, 4-dichlorophenyl) ethanol ((R)-CDPO), a key intermediate for the synthesis of antifungal drugs. Through active pocket iterative saturation mutagenesis, mutant LkADH-D18 (Y190C/V196L/M206H/D150H) was obtained with high stereoselectivity (99% ee, R vs 87% ee , S) and increased activity (0.44 µmol·min−1·mg−1). LkADH-D18 demonstrated NAD(P)H regeneration capability using a high concentration of isopropanol (IPA) as a co-substrate. Using 40% IPA (v/v), 400 mM of (R)-CDPO (90.1 g·L-1) was obtained via complete substrate conversion using 40 mg·mL−1 LkADH-D18 wet cells. The biocatalytic process catalyzed at constant pH with the cheap co-solvent IPA contributed to improved isolated yield of (R)-CDPO (97%), lower reaction cost, and simpler downstream purification, indicating the potential utility of LkADH-D18 in future industrial applications. [ABSTRACT FROM AUTHOR]

(S)-4-Chlorophenylpyridylmethanol and (R)-4-chlorobenzhydrol are key pharmaceutical intermediates for the synthesis of bepotastine and cloperastine, respectively. However, the biocatalytic approach to prepare these bulky diaryl ketones remains challenging because of the low activity of naturally occurring alcohol dehydrogenases (ADH). In the present study, ADH seq5, which has an adequate binding pocket volume and accepts bulky diaryl ketones, was further engineered with a binding pocket of increased hydrophobicity. Based on molecular simulation and binding free energy analyses, a small mutation library was constructed, and mutant seq5-D150I with a threefold increase in kcat and a low Km was obtained successfully. The comparison of kinetic parameters, binding free energy, docking conformation, and critical catalytic distances calculated by molecular dynamic simulations revealed the source of increased activity. To develop a practical approach with seq5-D150I, reaction conditions including pH, temperature, buffer, and metal ions were optimised and applied to synthesise (S)-4-chlorophenylpyridylmethanol and (R)-4-chlorobenzhydrol with high enantiomeric excess. The space-time yields for (S)-4-chlorophenylpyridylmethanol and (R)-4-chlorobenzhydrol increased dramatically to as high as 263.4 g∙L−1 day−1 and 150 g∙L−1 day−1, respectively, which, to our knowledge, is the highest reported yield to date. These results show that the biocatalytic approach with seq5-D150I may be practical for future industrial applications. Key points An alcohol dehydrogenase was engineered based on binding free energy analysis. The mutant seq5-D150I obtained a threefold increase in kcatand a low Km. Two important pharmaceutical intermediates were obtained with high space-time yield. [ABSTRACT FROM AUTHOR]

The white-rot fungi Phanerochaete chrysosporium have been widely applied in heavy metal bioremediation, which commonly results in a stress exposure. Exposure studies showed that Cd bioaccumulation triggered H 2 O 2 generation. Thereafter, the H 2 O 2 , as signal molecules, activated the enzymatic antioxidant response in the case of the conjunction of SOD and CAT. High levels of R (SOD/CAT) were found initially under Cd exposure, and then a significant decline occurred in time-course Cd exposure. Antioxidant activities also provided an alternative as an indication of the existence of antioxidant response upon Cd exposure, via coupling H 2 O 2 level with the variation in antioxidant activities. This finding potentially has implications for the understanding of tolerance behavior and detoxification mechanisms, which is beneficial to expand the application of P. chrysosporium in bioremediation biotechnology. [ABSTRACT FROM AUTHOR]

This study examines the role of oxalic acid in the uptake of Cd and participation in detoxification process in Phanerochaete chrysosporium. Cd-induced oxalic acid secretion was observed with growth inhibition and enzyme inactivation (LiP and MnP) of P. chrysosporium. The peak value of oxalic acid concentration was 16.6 mM at initial Cd concentration of 100 mg L. During the short-term uptake experiments, the uptake of Cd was enhanced and accelerated in the presence of oxalic acid and resulted in alleviated growth and enzyme inhibition ratios. The formation of a metal-oxalate complex therefore may provide a detoxification mechanism via effect on metal bioavailability, whereby many fungi can survive and grow in environments containing high concentrations of toxic metals. The present findings will advance the understanding of fungal resistance to metal stress, which could show promise for a more useful application of microbial technology in the treatment of metal-polluted waste. [ABSTRACT FROM AUTHOR]

Highlights: [•] Low concentration of Pb2+ could enhance the production of OH. [•] OH production declined when the initial Pb2+ concentration reached 400mgkg−1. [•] A remarkable correlation was found between OH content and oxalate concentration. [•] No obvious relationship was found between OH content and lignin degradation rate. [ABSTRACT FROM AUTHOR]

Abstract: We have developed a series of new chiral thiophosphorodiamide ligands derived from (1R,2R)-(+)-1,2-diphenylethylenediamine, which are the structural relatives of thioureas. An investigation into their catalytic properties in asymmetric additions of diethylzinc to aldehydes has shown that N,N,N′,N′-tetra-substituted chiral thiophosphorodiamides can give (R)-secondary alcohols with up to 98% yield and 98% ee, while N,N′-di-substituted chiral thiophosphorodiamides give (S)-secondary alcohols with up to 99% yield and 97% ee values. The enantioselectivity switch is highly efficient with a broad substrate scope. We have also proposed hypothetical reaction pathways, which result in an enantioselectivity switch. [Copyright &y& Elsevier]

This study analyzed the optical coherence tomography angiography (OCTA) macular parameters in primary angle-closure glaucoma (PACG) patients after acute primary angle closure (APAC) episodes. Thirty-three patients with 33 APAC eyes and 33 primary angle closure suspect (PACS) eyes and 33 age-matched normal subjects (controls) were enrolled. Macular vessel density (VD) in central, inner, outer and full regions and foveal avascular zone (FAZ) parameters (area, perimeter and circularity index) were compared between APAC, PACS, and control eyes. For resolved APAC eyes, the VD in each macular region was significantly lower than that in control eyes, with less central and inner macular VD than PACS eyes. The central macular VD was significantly lower in PACS eyes than in controls. There was no difference in FAZ area and perimeter between APAC, PACS, and control eyes. FAZ circularity was highest in control eyes, followed by PACS eyes, and lowest in APAC eyes. The AUC, sensitivity and specificity of FAZ circularity were 0.944, 93.9% and 84.8%, respectively, in APAC eyes and 0.881, 84.8% and 81.8%, respectively, in PACS eyes. Therefore, FAZ circularity had the best discrimination capability for detecting both APAC and PACS eyes. Macular assessment with OCTA could provide an accurate early-stage diagnostic tool for PACG. [ABSTRACT FROM AUTHOR]

An abstract of the article "Enantioselectivity Switch Controlled by N,N′-Di- or N,N,N′,N′-Tetra-Substituted Chiral Thiophosphorodiamide Ligands, Structural Relatives of Thioureas, in Catalytic Additions of Diethylzinc to Aldehydes" by Huifeng Yue is presented.