Genetic Analysis of Two Novel GPI Variants Disrupting H Bonds and Localization Characteristics of 55 Gene Variants Associated with Glucose-6-phosphate Isomerase Deficiency.

OBJECTIVE: Glucose-6-phosphate isomerase (GPI) deficiency is a rare hereditary nonspherocytic hemolytic anemia caused by GPI gene variants. This disorder exhibits wide heterogeneity in its clinical manifestations and molecular characteristics, often posing challenges for precise diagnoses using conventional methods. To this end, this study aimed to identify the novel variants responsible for GPI deficiency in a Chinese family. METHODS: The clinical manifestations of the patient were summarized and analyzed for GPI deficiency phenotype diagnosis. Novel compound heterozygous variants of the GPI gene, c.174C>A (p.Asn58Lys) and c.1538G>T (p.Trp513Leu), were identified using whole-exome and Sanger sequencing. The AlphaFold program and Chimera software were used to analyze the effects of compound heterozygous variants on GPI structure. RESULTS: By characterizing 53 GPI missense/nonsense variants from previous literature and two novel missense variants identified in this study, we found that most variants were located in exons 3, 4, 12, and 18, with a few localized in exons 8, 9, and 14. This study identified novel compound heterozygous variants associated with GPI deficiency. These pathogenic variants disrupt hydrogen bonds formed by highly conserved GPI amino acids. CONCLUSION: Early family-based sequencing analyses, especially for patients with congenital anemia, can help increase diagnostic accuracy for GPI deficiency, improve child healthcare, and enable genetic counseling.

Joint-tissue integrative analysis identifies high-risk genes for Parkinson's disease.

The loss of dopaminergic neurons in the substantia nigra and the abnormal accumulation of synuclein proteins and neurotransmitters in Lewy bodies constitute the primary symptoms of Parkinson's disease (PD). Besides environmental factors, scholars are in the early stages of comprehending the genetic factors involved in the pathogenic mechanism of PD. Although genome-wide association studies (GWAS) have unveiled numerous genetic variants associated with PD, precisely pinpointing the causal variants remains challenging due to strong linkage disequilibrium (LD) among them. Addressing this issue, expression quantitative trait locus (eQTL) cohorts were employed in a transcriptome-wide association study (TWAS) to infer the genetic correlation between gene expression and a particular trait. Utilizing the TWAS theory alongside the enhanced Joint-Tissue Imputation (JTI) technique and Mendelian Randomization (MR) framework (MR-JTI), we identified a total of 159 PD-associated genes by amalgamating LD score, GTEx eQTL data, and GWAS summary statistic data from a substantial cohort. Subsequently, Fisher's exact test was conducted on these PD-associated genes using 5,152 differentially expressed genes sourced from 12 PD-related datasets. Ultimately, 29 highly credible PD-associated genes, including CTX1B, SCNA, and ARSA, were uncovered. Furthermore, GO and KEGG enrichment analyses indicated that these genes primarily function in tissue synthesis, regulation of neuron projection development, vesicle organization and transportation, and lysosomal impact. The potential PD-associated genes identified in this study not only offer fresh insights into the disease's pathophysiology but also suggest potential biomarkers for early disease detection.

Generation of mitochondrial replacement monkeys by female pronucleus transfer.

Mutations in mitochondrial DNA (mtDNA) are maternally inherited and have the potential to cause severe disorders. Mitochondrial replacement therapies, including spindle, polar body, and pronuclear transfers, are promising strategies for preventing the hereditary transmission of mtDNA diseases. While pronuclear transfer has been used to generate mitochondrial replacement mouse models and human embryos, its application in non-human primates has not been previously reported. In this study, we successfully generated four healthy cynomolgus monkeys ( Macaca fascicularis) via female pronuclear transfer. These individuals all survived for more than two years and exhibited minimal mtDNA carryover (3.8%-6.7%), as well as relatively stable mtDNA heteroplasmy dynamics during development. The successful establishment of this non-human primate model highlights the considerable potential of pronuclear transfer in reducing the risk of inherited mtDNA diseases and provides a valuable preclinical research model for advancing mitochondrial replacement therapies in humans.

Preferred Orientation Deposition via Multifunctional Gel Electrolyte with Molecular Anchor Enabling Highly Reversible Zn Anode.

The high activity of water molecules results in a series of awful parasitic reaction, which seriously impede the development of aqueous zinc batteries. Herein, a new gel electrolyte with multiple molecular anchors is designed by employing natural biomaterials from chitosan and chlorophyll derivative. The gel electrolyte firmly anchors water molecules by ternary hydrogen bonding to reduce the activity of water molecules and inhibit hydrogen evolution reaction. Meanwhile, the multipolar charged functional groups realize the gradient induction and redistribution of Zn2+ , which drives oriented Zn (002) plane deposition of Zn2+ and then achieves uniform Zn deposition and dendrite-free anode. As a result, it endows the Zn||Zn cell with over 1700 h stripping/plating processes and a high efficiency of 99.4% for the Zn||Cu cell. In addition, the Zn||V2 O5 full cells also exhibit capacity retention of 81.7% after 600 cycles at 0.5 A g-1 and excellent long-term stability over 1600 cycles at 2 A g-1 , and the flexible pouch cells can provide stable power for light-emitting diodes even after repeated bending. The gel electrolyte strategy provides a reference for reversible zinc anode and flexible wearable devices.

Remodeling Zinc Deposition via Multisite Zincophilic Chlorophyll for Powerful Aprotic Zinc Batteries.

The organic electrolyte can resolve the hurdle of hydrogen evolution in aqueous electrolytes but suffers from sluggish electrochemical reaction kinetics due to a compromised mass transfer process. Herein, we introduce a chlorophyll, zinc methyl 3-devinyl-3-hydroxymethyl-pyropheophorbide-a (Chl), as a multifunctional electrolyte additive for aprotic zinc batteries to address the related dynamic problems in organic electrolyte systems. The Chl exhibits multisite zincophilicity, which significantly reduces the nucleation potential, increases the nucleation sites, and induces uniform nucleation of Zn metal with a nucleation overpotential close to zero. Furthermore, the lower LUMO of Chl contributes to a Zn-N-bond-containing SEI layer and inhibits the decomposition of the electrolyte. Therefore, the electrolyte enables repeated zinc stripping/plating up to 2000 h (2 Ah cm-2 cumulative capacity) with an overpotential of only 32 mV and a high Coulomb efficiency of 99.4%. This work is expected to enlighten the practical application of organic electrolyte systems.

Bimetal Substitution Enabled Energetic Polyanion Cathode for Sodium-Ion Batteries.

The practical application of Na-superionic conductor structured materials is hindered by limited energy density and structure damage upon activating the third Na+. We propose a bimetal substitution strategy with cheaper Fe and Ni elements for costive vanadium in the polyanion to improve both ionic and electronic conductivities, and a single two-phase reaction during Na+ intercalation/deintercalation and much reduced Na+ diffusion barrier are uncovered by ex-situ X-ray diffraction and density functional theory calculations. Thus, the obtained cathode, Na3Fe0.8VNi0.2(PO4)3, shows excellent electrochemical performances including high specific capacity (102.2 mAh g-1 at 0.1C), excellent rate capability (79.3 mAh g-1 at 20C), cycling stability (84.6% of capacity retention over 1400 cycles at 20C), low-temperature performance (89.7 mAh g-1 at 2C and -10 °C), and structure stability in an extended voltage window for the third Na+ utilization. A competitive energy density of ≈287 Wh kg-1 for full batteries based on cathode and anode materials is also confirmed.

Combined assessment of tumour cell nest size and desmoplastic reaction as an excellent prognostic predictor in oesophageal squamous cell carcinoma.

AIMS: Tumour budding (TB) activity, cell nest size (CNS), and desmoplastic reaction (DR) have been confirmed to be significantly correlated with prognosis in oesophageal squamous cell cancer (ESCC) recently. However, there are limited data on the prognostic significance of combined assessment of cellular dissociation and tumour stroma in ESCC. METHODS: In all, 265 cases with resected ESCCs diagnosed between January 2018 and August 2019 were retrospectively reviewed. All slides were reviewed for assessing TB, CNS, and DR. The Cellular Dissociation Grading and our Combined CNS and DR (CNS/DR) Grading systems were adopted to re-grade ESCCs. RESULTS: High TB activity, small CNS, and immature DR had a strong association with shorter overall survival (OS) and progression-free survival (PFS) (P < 0.001, respectively) in ESCC. Combined assessment of CNS and DR in a 4-tiered grading system displayed a prognostic excellence for survival (P < 0.001), and outperformed the Cellular Dissociation Grading for both OS (area under the curve [AUC], 0.728 versus 0.644, P = 0.043) and PFS (AUC, 0.763 versus 0.667, P = 0.018) by receiver operator characteristic curves. Also, Combined CNS/DR Grading showed superiority in recognizing a G4 subgroup with the worst outcome in our cohort, to whom the most urgent attention needs to be called. CONCLUSIONS: This is the first study to propose a novel Combined Grading system based on CNS and DR in ESCC, which has been demonstrated to be relatively superior to Cellular Dissociation Grading in predicting prognosis. The findings shed new light on the histopathological grading of ESCC and facilitates identifying biologically aggressive ESCCs.

DNA Logic Nanodevices for the Sequential Imaging of Cancer Markers through Localized Catalytic Hairpin Assembly Reaction.

Monitoring tumor biomarkers is crucial for cancer diagnosis, progression monitoring, and treatment. However, identifying single or multiple biomarkers with the same spatial locations can cause false-positive feedback. Herein, we integrated the DNA tetrahedron (DT) structures with logic-responsive and signal amplifying capability to construct transmembrane DNA logic nanodevices (TDLNs) for the in situ sequential imaging of transmembrane glycoprotein mucin 1 (MUC1) and cytoplasmic microRNA-21 (miR-21) to cell identifications. The TDLNs were developed by encoding two metastable hairpin DNAs (namely, H1 and H2) in a DT scaffold, in which the triggering toeholds of H1 for miR-21 were sealed by the MUC1-specific aptamer (MUC1-apt). The TDLNs not only had the function of signal amplification owing to the localized catalytic hairpin assembly (CHA) reaction through spatial constraints effect of DT structures but also performed an AND logic operation to output a green Cy3 signal in MCF-7 cells, where MUC1 protein and miR-21 were simultaneously expressed. These results showed that the newly developed TDLNs have better molecular targeting and recognition ability so as to be easily identify cell types and diagnose cancer early.

A dual conducting network corbelled hydrated vanadium pentoxide cathode for high-rate aqueous zinc-ion batteries.

Aqueous zinc-ion batteries (ZIBs) are widely recognized for their excellent safety and high theoretical capacity but are hindered by the scarcity of cathode materials with high-rate performance and stability. Herein, a dual conducting network corbelled hydrated vanadium pentoxide that involves structural water as a pillar to enlarge the layer spacing of vanadium pentoxide and ensure cycling stability was reported. Along with the proton co-insertion, the hydrated vanadium pentoxide delivers nearly theoretical specific capacities of 524.6 mA h g-1 at 0.3 A g-1 and 258.7 mA h g-1 at 10 A g-1, which was largely due to non-faradaic contribution, and retains 196.8 mA h g-1 at 4.8 A g-1 after 1100 cycles. Notably, a high energy density of 409.3 W h kg-1 at 0.3 A g-1 and a power density of 6666.4 W kg-1 at 10 A g-1 have also been achieved. The design strategy offers a potential path to develop high-rate ZIBs.

Photoinduced Hydroxylation of Organic Halides under Mild Conditions.

Presented in this paper is photoinduced hydroxylation of organic halides, providing a mild access to a range of functionalized phenols and aliphatic alcohols. These reactions generally proceed under mild reaction conditions with no need for a photocatalyst or a strong base and show a wide substrate scope as well as excellent functional group tolerance. This work highlights the unique role of NaI that allows a challenging transformation to proceed under mild reaction conditions.

Experimental study on the clinical effects of Xiaoru Sanjie Jiaonang on mammary glands hyperplasia and ki-67.

OBJECTIVE: This study aims to observe the effect and mechanism of Xiaoru Sanjie Jiaonang (XRSJ) on the treatment of mammary gland hyperplasia, and provide a theoretical basis and clinical evidence for clinical expansion. METHODS: Japanese white rabbits were randomly divided into three groups: high-, middle- and low-dose groups; Xiaoyao Pill group; model control group; normal control group. The observation points were as follows: before XRSJ administration, three months after XRSJ administration, and three months after XRSJ discontinuance. Changes in breast height, morphological changes of the mammary gland under a light and electron microscope, and the expression of ki-67 were observed. At the same time, patients diagnosed with mammary gland hyperplasia at an Outpatient Clinic were selected and divided into treatment groups. These patients received XRSJ and Xiaoyao Pills, respectively, for one month, while patients in the control group did not receive any drug treatment. Clinical efficacy was observed while rechecking at the Outpatient Clinic after three months. Treatment with a therapeutic dose of XRSJ could significantly reduce breast height, decrease the number of lobules and acini in hyperplastic mammary glands and the layer number of ductal glandular epithelial cells, substantially lower the content of serum estradiol (E2), significantly downregulate the expression of ki-67 protein in mammary tissues, and inhibit mammary gland hyperplasia. CONCLUSION: XRSJ treatment can relieve mammary tissue hyperplastic lesions, reduce E2 levels and downregulate the expression of ki-67. It has a significant therapeutic effect on mammary gland hyperplasia.

[Effects of orchinol on invasion, migration and Wnt3a/ß-catenin signaling pathway of human gastric cancer SGC-7901 cells].

The purpose of this study was to investigate the inhibitory effect of the main 9,10-dihydrophenanthrene orchinol isolated from Spiranthes sinensis Radix et Herba on the invasion and migration of human gastric cancer SGC-7901 cells and its preliminary molecular mechanism. SGC-7901 cells were cultured in vitro, after the cells were treated with different final concentrations(5, 10, 20, 40, 80 µmol·L⁻¹) of orchinol for 24, 48 or 72 hours, the effect of orchinol on cell viability was measured by MTT assay. Wound healing and Transwell assays were performed to determine the effects of different final concentrations(5, 10, 20, 40 µmol·L⁻¹) of orchinol for 48 hour on invasion and migration abilities of SGC-7901 cells, respectively. The protein expression levels of ß-catenin, Wnt-3α, DvL2, cyclinD1 and GSK-3ß were detected by Western blot. The results showed that 5-80 µmol·L⁻¹ orchinol inhibited the viability of SGC-7901 cells in a dose-dependent and time-dependent manner, and the IC58 values of 24, 48 and 72 hours were 77.79, 42.96 and 7.85 µmol·L⁻¹, respectively. Compared with the control group, the ability of invasion and migration of SGC-7901 cells was significantly inhibited after treated with 5, 10 and 20 µmol·L⁻¹ orchinol for 48 hours (P<0.05, P<0.01), and the dose-effect relationship was observed. The results of Western blot showed that orchinol could significantly down-regulate the protein expression levels of ß-catenin, Wnt3a, DvL2 and cyclinD1, and up-regulate the protein expression level of GSK-3ß(P<0.05, P<0.01, P<0.001). The above results suggest that orchinol can obviously inhibit the invasion and migration of SGC-7901 cells, which may be related to its inhibition of Wnt3a/ß-catenin signaling pathway and the proteins expression of downstream genes.

Protoporphyrin IX fluorescence as potential indicator of psoriasis severity and progression.

BACKGROUND AND OBJECTIVES: In psoriatic lesions, fluorescence diagnosis with blue light can detect protoporphyrin IX accumulation, especially after topical 5-aminolaevulinic acid (ALA) application. However, variable fluorescence distributions, interpersonal variations and long incubation time limit its wide application in clinic. This study is aimed to identify a consistent and convenient method to facilitate diagnosis and evaluation of psoriatic lesions. METHODS: 104 psoriatic lesions from 30 patients were evaluated. Single lesion PSI scoring and fluorescence by macrospectrofluorometry were recorded on each lesion before and after treatment with narrow-band UVB. RESULTS: Punctate red fluorescence, emitted mainly by protoporphyrin IX, is observed in some psoriatic lesions. According to psoriasis severity index, fluorescence-positive lesions are more severe than lesions without fluorescence. We found a significant positive correlation between psoriasis severity and fluorescence intensity from protoporphyrin IX. CONCLUSIONS: Protoporphyrin IX-induced red fluorescence can be used as a novel and convenient approach for psoriasis diagnosis and progression evaluation.

Antimicrobial effects of a bioactive glass combined with fluoride or triclosan on Streptococcus mutans biofilm.

OBJECTIVE: The objective of this study was to investigate the antibacterial effects on a cariogenic biofilm of a bioactive glass (BAG) combined with either sodium fluoride (NaF) or triclosan (TCS). DESIGN: According to minimal bactericidal concentrations, 37.5mg/ml of BAG, 4.69 mg/ml of NaF, and 15.53 µg/ml of TCS solutions were prepared. When used alone, the three antimicrobial solutions were increased to double-dosage strength (2 MBC). The study contained the following experimental groups: group 1, BAG (2 MBC); group 2, NaF (2 MBC); group 3, TCS (2 MBC); group 4, BAG+NaF; group 5, BAG+TCS; group 6, control (saline). Streptococcus mutans biofilm was cultured with 0.1% sucrose anaerobically on 66 sterilized coverslips (1 × 1 cm(2)) for 24h uninterrupted. After 10 min of exposure to the experimental groups, the microbial kinetics, morphology, and viability of the S. mutans biofilms were assessed by evaluation of colony-forming units (CFUs), scanning electron microscopy (SEM), and confocal laser scanning microscopy (CLSM). RESULTS: BAG (2 MBC) used alone showed significantly stronger antibacterial effects than the other two antimicrobials used alone. The combination groups also displayed the same or greater biofilm inactivation effects as BAG (2 MBC) in the plate count test. SEM showed smaller stacks (towers) and fewer surrounding bacteria in groups BAG (2 MBC), BAG+NaF, and BAG+TCS. Confocal microscopy also determined higher live/dead ratios in groups NaF (2 MBC), TCS (2 MBC), and control than in groups BAG (2 MBC), BAG+NaF, and BAG+TCS. CONCLUSIONS: The combinations of BAG with either NaF or TCS enhanced the inactivation effects of BAG (2 MBC) on S. mutans biofilm, and these findings should be further investigated clinically for the control of dental biofilms.

[Analysis of the chemical constituents of essential oil from Ligustrum quihoui by GC-MS].

OBJECTIVE: [corrected] To study the chemical constituents of essential oil from Ligustrum quihoui. METHODS: Essential oil was extracted by steam distillation (SD). The chemical constituents of essential oil was analyzed by GC-MS. RESULTS: The chemical components in the oil were qualitatively and quantitatively analyzed by GC-MS, 76 components were seperated and 35 components were identified. The main components are n-Hexadecanoic acid (17.28%), (Z, Z, Z)-9, 12, 15-Octadecatrienoic acid, ethyl ester (12.13%), Phytol (5.80%). CONCLUSION: The method is simple, reliable and with good reprodutivity.

[Studies on chemical constituents of Dendranthema indicum var. aromaticum].

OBJECTIVE: To study chemical constituents of Dendranthema indicum var. aromaticum. METHODS: The constituents were separated and purified by column chromatography with silica gel and Semi-preparative HPLC. Their structures were identified on the basis of physical-chemical properties and spectral data. RESULTS: Seven compounds were isolated and identified as acacetin, apignein, acacetin-7-O-beta-D-glucopy ranoside, apignein-7-O-beta-D-glucopy ranosids, luteolin, beta-sitosterol and daucosterol. CONCLUSION: Apigenin, acacetin-7-O-beta-D-glucopy ranoside and apignein-7-O-beta-D-glucopy ranoside are obtained from the plant for the first time.

[Analysis of the chemical constituents of essential oil from Magnolia biondii by GC-MS].

OBJECTIVE: The chemical components of essential oil from Magnolia biondii were analyzed by GC-MS. METHODS: Essential oil was extracted by steam distillation (SD). The chemical components of essential oil were analyzed by GC-MS. RESULTS: The chemical components in the oil were qualitatively and quantitatively analyzed by GC-MS. 63 components were separated and 50 components were identified. The main components were Eucalyptol (28.92%), P-pinene (12.39%), alpha-Terpineol (8.28%). CONCLUSION: This is the first time to adopt GC-MS to analyze the chemical components of volatile oil of Magnolia biondii, and this study can provide science basis for further research development of Magnolia biondii.