Research Progress in Traditional Applications, Phytochemistry, Pharmacology, and Safety Evaluation of Cynomorium songaricum.

Cynomorium songaricum Rupr. (CSR) belongs to the family Cynomoriaceae. It is a perennial succulent parasitic herb with a reddish-brown coloration, predominantly submerged in sand and lacking chlorophyll. Traditionally, it has been used in ethnic medicine to treat various diseases, such as gastric ulcers, indigestion, bowel movements, and improving sexual function. To comprehensively collect CSR data, extensive literature searches were conducted using medical, ecological, and scientific databases such as Google Scholar, PubMed, Science Direct, Web of Science, and China National Knowledge Infrastructure (CNKI). This article summarizes and categorizes research on the uses, phytochemical characteristics, pharmacological activities, and toxicity of ethnic medicine, with the aim of establishing a solid foundation and proposing new avenues for exploring and developing potential applications of CSR. So far, a total of 98 compounds have been isolated and identified from CSR, including flavonoids, terpenes, steroids, and other compounds. It is worth noting that flavonoids and polysaccharides have significant antioxidant and anti-inflammatory properties. In addition, these compounds also show good application prospects in anti-tumor, antioxidant, anti-aging, anti-fatigue, anti-diabetes, and other aspects. Although extensive progress has been made in the basic research of CSR, further research is still needed to enhance the understanding of its mechanism of action and explore more unknown compounds. Our review indicates that CSR has broad prospects and deserves further research.

Cross-sectional association between red blood cell distribution width and regional cerebral tissue oxygen saturation in preterm infants in the first 14 days after birth.

Background: Hypoxia can threaten the metabolic functions of different systems in immature neonates, particularly the central nervous system. The red blood cell distribution width (RDW) has recently been reported as a prognostic factor in neurologic diseases. Herein, we examined the correlation between RDW and regional cerebral tissue oxygen saturation (rcSO2). Methods: This cross-sectional study included 110 preterm infants born at a gestational age (GA) of <32 weeks, or with a birth weight (BW) of <1,500 g at our institution between January and June 2,022. The rcSO2 was monitored using near-infrared spectroscopy, and RDW was extracted from the complete blood count during the first 14 days after birth. RDW and rcSO2 measurements were analyzed using a cross-sectional research method. Results: We divided the study population into two groups, with a mean rcSO2 value over the first 14 days. Fifty-three preterm had rcSO2 ≥ 55% and 57% < 55%. The 14-days-mean in the study population showing an association of lower rcSO2 values with higher RDW values. Significantly higher RDW values were observed in the low rcSO2 group compared with those in the high rcSO2 group. Threshold effect analysis showed that rcSO2 decreased with RDW values ≥18% (ß, -0.03; 95% CI, -0.04 and -0.02; p ≥ 0.0001). After adjusting for potential confounders, an RDW of ≥18% was determined as the predictive cutoff value for preterm infants with low rcSO2 (Model I: OR, 3.31; 95% CI, 1.36-8.06; p = 0.009; and Model II: OR, 3.31; 95% CI, 1.28-8.53; p = 0.013). Conclusions: An RDW of ≥18% in the first 14 days is associated with rcSO2 of <55% in preterm infants.

A 3-Year Clinical Evaluation of Endodontically Treated Posterior Teeth Restored with Resin Nanoceramic Computer-Aided Design/Computer-Aided Manufacture (CAD/CAM)-Fabricated Partial Crowns.

BACKGROUND We aimed to investigate the clinical effects of resin nanoceramic (RNC) computer-aided design/computer-aided manufacture (CAD/CAM) partial crowns on posterior teeth after root canal treatment over a 3-year period. MATERIAL AND METHODS A total of 132 posterior teeth restored with CAD/CAM partial crowns were placed in 128 patients. The observation group (n=66) was restored with RNC restorations, while the control group received lithium disilicate-based glass ceramic (LDGC) CAD restorations. Using Federation dentaire internationale (FDI) World Dental Federation clinical criteria, 2 calibrated evaluators examined the performance of the restorations at baseline, 6, 12, 18, 24, and 36 months. The Kaplan-Meier method and the log-rank test were adopted to analyze the survival rate. The influence of potential risk factors on the main pattern of failure was studied by univariate Cox regression analysis (alpha=0.05). RESULTS At the 3-year followup, the survival rate of the partial crowns was 83.1% in the RNC group, and 93.5% in the LDGC group (P=0.061). Failures were caused by debonding (66.7%), restoration fracture (26.6%), and tooth fracture (6.7%). No significant differences were found between the 2 materials at 36 months, except for the parameters of "surface luster" (P=0.002) and "occlusal contour and wear" (P=0.009). The RNC group was significantly more likely to debond than the LDGC group (hazard ratio=9.22 [1.17,72.74], P=0.01). CONCLUSIONS RNC CAD/CAM-fabricated partial crowns are a potential clinical alternative for endodontically treated posterior teeth, with a survival rate of 83.1% at the 3-year followup. The main pattern of failure was debonding, which might be influenced by surface pretreatment of the RNC material.

Comprehensive analysis of lncRNA-miRNA-mRNA networks during osteogenic differentiation of bone marrow mesenchymal stem cells.

BACKGROUND: Long non-coding RNA (lncRNA) plays crucial role in osteogenic differentiation of bone marrow mesenchymal stem cells (BMMSCs), involving in regulation of competing endogenous RNA (ceRNA) mechanisms and conduction of signaling pathways. However, its mechanisms are poorly understood. This study aimed to investigate lncRNAs, miRNAs and mRNAs expression profiles in rat BMMSCs (rBMMSCs) osteogenic differentiation, screen the potential key lncRNA-miRNA-mRNA networks, explore the putative functions and identify the key molecules, as the basis of studying potential mechanism of rBMMSCs osteogenic differentiation driven by lncRNA, providing molecular targets for the management of bone defect. METHODS: High-throughput RNA sequencing (RNA-seq) was used to determine lncRNAs, miRNAs, and mRNAs expression profiles at 14-day rBMMSCs osteogenesis. The pivotal lncRNA-miRNA and miRNA-mRNA networks were predicted from sequencing data and bioinformatic analysis, and the results were exported by Cytoscape 3.9.0 software. Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were used for functional exploration. Real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was performed to validate lncRNAs, miRNAs and mRNAs. RESULTS: rBMMSCs were identified, and the osteogenic and adipogenic differentiation ability were detected. A total of 8634 lncRNAs were detected by RNA-seq, and 1524 differential expressed lncRNAs, of which 812 up-regulated and 712 down-regulated in osteo-inductive groups compared with control groups. 30 up-regulated and 61 down-regulated miRNAs, 91 miRNAs were differentially expressed in total. 2453 differentially expressed mRNAs including 1272 up-expressed and 1181 down-expressed were detected. 10 up-regulated lncRNAs were chosen to predict 21 down-regulated miRNAs and 650 up-regulated mRNAs. 49 lncRNA-miRNA and 1515 miRNA-mRNA interactive networks were constructed. GO analysis showed the most important enrichment in cell component and molecular function were "cytoplasm" and "protein binding", respectively. Biological process related to osteogenic differentiation such as "cell proliferation", "wound healing", "cell migration", "osteoblast differentiation", "extracellular matrix organization" and "response to hypoxia" were enriched. KEGG analysis showed differentially expressed genes were mainly enriched in "PI3K-Akt signaling pathway", "Signaling pathway regulating pluripotency of stem cells", "cGMP-PKG signaling pathway", "Axon guidance" and "Calcium signaling pathway". qRT-PCR verified that lncRNA Tug1, lncRNA AABR07011996.1, rno-miR-93-5p, rno-miR-322-5p, Sgk1 and Fzd4 were consistent with the sequencing results, and 4 lncRNA-miRNA-mRNA networks based on validations were constructed, and enrichment pathways were closely related to "PI3K-Akt signaling pathway", "Signaling pathway regulating pluripotency of stem cells" and "Wnt signaling pathway". CONCLUSIONS: lncRNAs, miRNAs and mRNAs expression profiles provide clues for future studies on their roles for BMMSCs osteogenic differentiation. Furthermore, lncRNA-miRNA-mRNA networks give more information on potential new mechanisms and targets for management on bone defect.

Case report: A 10-year prognosis of neonatal diabetes caused by a novel INS gene mutation.

Background: Neonatal diabetes mellitus (NDM) is a rare form of diabetes. We analyzed a novel insulin gene (INS) mutation of a Chinese permanent neonatal diabetes mellitus (PNDM) patient to explore the clinical and genetic characteristics and put forward some opinions on treatment and its long-term management. Case description: A proband was recruited who was diagnosed with permanent neonatal diabetes on his first day after birth. His clinical and follow-up data were collected for 10 years. All of the family members were given an oral glucose tolerance test. Whole exome sequencing was performed on the proband, and the genomic DNA of family members was used for verification by first-generation Sanger sequencing technology. The pathogenic variant was screened according to the American College of Medical Genetics and Genomics classification guidelines and the clinical phenotype of the patient. Diagnostic assessment: The proband was diagnosed on the first day after birth, presenting with low birth weight, progressive hyperglycemia, and insulin deficiency. His parents and grandfathers were confirmed to have normal blood sugar levels. A novel homozygous mutation of c.1T>C in the INS gene was detected in the proband, located in the initiation codon. The heterozygous mutations were found in four family members, including his mother, father, and grandfathers. With regular insulin injections, long-term regular follow-up, close monitoring of blood glucose, balanced exercise and diet, and psychological and mutual family support, the blood glucose level was well controlled; there were no acute or chronic complications during this decade. The patient's growth and nervous system development are now no different to those of the same age. Conclusion: A favorable prognosis is presented for a permanent neonatal diabetes mellitus (PNDM) patient with a novel mutation in the INS gene in China. The present findings indicate that the genetic diagnosis, early use of insulin, close monitoring of blood glucose, and psychological and mutual family support for patients with INS mutation are necessary for their favorable long-term prognosis.

Nanopatterned Polymer Surface Modulates Twist Polymorphism in a Single Amyloid Fibril.

The periodic twist behaviors of amyloid fibrils initiated and formed on block copolymer films with nanoscale features are studied. The discovery of twist variations even in a single amyloid fibril is reported: the fibril can vary its twist extents in response to the underlying nanopatterned surfaces by keeping its neighboring crossover sections right above the periodic nanodomains and tuning the distance between neighboring crossover sections based on either the periodic nanodomain distance or the fibril contour direction. This nanopattern-induced twist polymorphism arises from the fibril's two edges, exhibiting different hydrophobic interactions with the periodic nanodomains, as demonstrated by simulation studies. This work contributes to the understanding of surface effects on twist polymorphism in amyloid fibril structures that may be important to fibril polymorphism in amyloid pathologies and bioapplications of amyloid fibrils.

Surface effects on the degree of twist in amyloid fibril structures.

Amyloid fibrils, implicated in health and diseases, commonly exhibit a periodic twist trait relevant to the structures and dynamics of the fibrils. However, the origins and modulations of fibril twist in complex in vivo environments are not yet fully understood. Here we highlight an important factor that causes twist variations in amyloid fibril structures-the presence of surrounding surfaces. Using cholesterol-containing lipid bilayers with varying cholesterol contents, we have demonstrated via atomic force microscopy that amyloid-ß peptide fibrils initiated on membranes increase their average pitch size of twisting periodicity as the cholesterol content increases. These surface-induced twist variations arise from the enhanced hydrophobic interactions between the fibril and the surface distorting the torsional elastic energy of the fibril twisting as supported by a theory of an elastic model. These findings not only provide an important insight into fibril polymorphism phenomena resulting from the surface effects but also suggest a novel solution to modulate filament twisting on the nanoscale for biomaterials applications involving nanoscale features.

Correction: Diffusion dynamics of a single collapsed homopolymer globule at the solid-liquid interface.

Correction for 'Diffusion dynamics of a single collapsed homopolymer globule at the solid-liquid interface' by Shali Cai et al., Soft Matter, 2020, DOI: 10.1039/c9sm02335f.

Diffusion dynamics of a single collapsed homopolymer globule at the solid-liquid interface.

Contradictive to the conventional wisdom that a collapsed polymer globule in poor solvents adsorb on surfaces in a way analogous to the spreading of a liquid droplet, here we have shown via single molecule measurements that a single poly(N-isoporpylacrylamide) (PNIPAM) globule can jump from one spot to another as an elastic nonadhesive ball even on a hydrophobic polystyrene surface. The molecular weight dependence of the effective surface diffusion coefficient measured for the adsorbed globule suggested that it exhibited mostly a similar globular conformation to that in the bulk solution. Both the displacement and waiting time distributions of the adsorbed globules were found to follow a power-law decay rather than an exponential process, suggesting a broad distribution of binding energies due to the difference in degree of globule deformation. These effects together reflect a character of the viscoelasticity even in a single-chain globule in dilute solutions. Our findings also demonstrate that it is not the single-chain globule but the inter-globule aggregates at high concentration that lead to irreversible adsorption on the surface, which provides novel dynamics and mechanisms of how a thermosensitive polymer adsorbs on the hydrophobic surface above its lower critical solution temperature.

Self-Coiling of Single-Stranded Protofibrils into Rings: A Pathway of Alzheimer's ß-Peptide Amyloidosis on Lipid Membranes.

An amyloidosis pathway of Alzheimer's ß-peptide Aß40 on lipid membranes, the self-coiling of single-stranded protofibrils into thermodynamically stable ring structures, is uncovered. Distinct from Aß amyloid structures reported previously, the coiled rings observed here exhibit a narrow distribution of diameters centered at ∼170 nm and their circumference thicknesses increase as a longer single-stranded protofibril wraps around the ring, indicating the coaxial loop-by-loop winding of individual protofibrils. Such self-coiling is dominated by elastic properties of the flexible protofibrils subject to thermal fluctuations and surface interactions, as supported by an entropic elasticity model from polymer physics concepts. This work not only provides insights into the fundamental physics of Alzheimer's ß-peptide amyloidosis but also is useful for designing amyloid filament materials.

Hierarchical Self-Assembly Mechanism of Ladder-Like Orientated Aß40 Single-Stranded Protofibrils into Multistranded Mature Fibrils.

The complex self-assembly processes in three dimensions of Alzheimer's ß-peptide (Aß) amyloid protofibrils into polymorphic mature fibrils, particularly the relative protofibril orientation and packing mechanism, are poorly understood. We report here the identification and quantification of the hierarchical self-assembly details among distinct Aß40 fibrils, particularly the winding pictures of two, three, and four individual single-stranded protofibrils into two-, three-, and four-stranded mature fibrils, respectively, via cross-sectional analysis of atomic force microscopy (AFM) images. The statistical polymer physics analysis of fibril flexibilities from AFM characterizations as well as molecular dynamics (MD) simulations reveal a ladder-like packing mechanism rather than a closed-packing manner for the interprotofibril association into Aß40 mature fibrils. Moreover, our MD results show atomic packing polymorphism at the well-packing interfaces even within the same multistranded fibril. This work provides mechanistic insights into the polymorphic transition of single-stranded Aß40 protofibrils into multistranded mature fibrils at the mesoscopic level, which is useful for a more comprehensive understanding of Alzheimer's ß-peptide amyloidosis.

Unravelling the mechanism of amyloid-ß peptide oligomerization and fibrillation at chiral interfaces.

In this communication, the mechanism of how surface chirality affects amyloid-ß (Aß) fibrillation was firstly unravelled at the molecular level: a chiral surface serves to control the 2D-diffusion and surface residence time of Aß molecules via the chiral recognition with Aß to allow precursor Aß to laterally diffuse and collide with each other for oligomerization and fibrillation. Surface chirality that shortens the surface residence time of Aß, for example, R-cysteine modification with carboxylic, secondary amine and thiol groups surrounding the chiral center, can retard Aß oligomerization and fibrillation. This work is essential to a deeper fundamental understanding of the effects of surface chirality on amyloidosis processes as well as the development of chiral materials to inhibit Aß fibrillation.