Tuning the plasmonic properties of silver nanopatterns fabricated by shadow nanosphere lithography

Regular silver (Ag) nanopatterns, from disconnected nanotriangles to well coupled triangular clusters of nanoparticles, were prepared by shadow nanosphere lithography at different incident angles θ from 0 degrees to 20 degrees with continuous azimuthal rotation. The resulting nanopatterns were consistent with predictions by numerical calculations and Monte Carlo simulations of adatoms with high diffusivity. The visible localized surface plasmon resonance of these nanopatterns was tuned by θ systematically due to the change in size, shape, and arrangement of Ag nanopatterns. These resonances were consistent with finite-difference time-domain simulations using realistic nanopatterns based upon scanning electron micrographs. Such a simple fabrication strategy can be used to optimize surface enhanced Raman scattering substrate fabrication, as well as other plasmonics based applications

Advances in basic research, clinical diagnosis and treatment of bladder cancer in 2022

Bladder cancer (BCa) is a common malignant tumor of the urinary tract. Significant progress has been made in both basic and clinical research on BCa, which has further elucidated the drivers of BCa development at the gene and protein levels, and explored the structure and interactions of the tumor microenvironment. The early diagnostic index nuclear matrix protein 22 (NMP22) of BCa has great clinical limitations, and new biomarkers are constantly being developed to make early diagnosis more accurate. A breakthrough has been made in the comprehensive treatment of BCa, including the combination of immune checkpoint inhibitor therapy on cisplatin-based first-line chemotherapy, the application of antibody-drug conjugate (ADC), and the combination of these drugs in different stages of BCa. In order to better describe the recently achieved research results, a review of the research progress of BCa in 2022 was presented

FGF Receptor-Mediated Gene Delivery Using Ligands Coupled to PEI-β-CyD

A novel vector with high gene delivery efficiency and special cell-targeting ability was developed using a good strategy that utilized low-molecular-weight polyethylenimine (PEI; molecular weight: 600 KDa [PEI600]) crosslinked to β-cyclodextrin (β-CyD) via a facile synthetic route. Fibroblast growth factor receptors (FGFRs) are highly expressed in a variety of human cancer cells and are potential targets for cancer therapy. In this paper, CY11 peptides, which have been proven to combine especially with FGFRs on cell membranes were coupled to PEI-β-CyD using N-succinimidyl-3-(2-pyridyldithio) propionate as a linker. The ratios of PEI600, β-CyD, and peptide were calculated based on proton integral values obtained from the 1H-NMR spectra of the resulting products. Electron microscope observations showed that CY11-PEI-β-CyD can efficiently condense plasmid DNA (pDNA) into nanoparticles of about 200 nm, and MTT assays suggested the decreased toxicity of the polymer. Experiments on gene delivery efficiency in vitro showed that CY11-PEI-β-CyD/pDNA polyplexes had significantly greater transgene activities than PEI-β-CyD/pDNA in the COS-7 and HepG2 cells, which positively expressed FGFR, whereas no such effect was observed in the PC-3 cells, which negatively expressed FGFR. Our current research indicated that the synthesized nonviral vector shows improved gene delivery efficiency and targeting specificity in FGFR-positive cells

Phosphorylation of Shox2 Is Required for Its Function to Control Sinoatrial Node Formation

Background: Inactivation of Shox2, a member of the short‐stature homeobox gene family, leads to defective development of multiple organs and embryonic lethality as a result of cardiovascular defects, including bradycardia and severe hypoplastic sinoatrial node (SAN) and sinus valves, in mice. It has been demonstrated that Shox2 regulates a genetic network through the repression of Nkx2.5 to maintain the fate of the SAN cells. However, the functional mechanism of Shox2 protein as a transcriptional repressor on Nkx2.5 expression remains completely unknown. Methods and Results: A specific interaction between the B56δ regulatory subunit of PP2A and Shox2a, the isoform that is expressed in the developing heart, was demonstrated by yeast 2‐hybrid screen and coimmunoprecipitation. Western blotting and immunohistochemical assays further confirmed the presence of phosphorylated Shox2a (p‐Shox2a) in cell culture as well as in the developing mouse and human SAN. Site‐directed mutagenesis and in vitro kinase assays identified Ser92 and Ser110 as true phosphorylation sites and substrates of extracellular signal‐regulated kinase 1 and 2. Despite that Shox2a and its phosphorylation mutants possessed similar transcriptional repressive activities in cell cultures when fused with Gal4 protein, the mutant forms exhibited a compromised repressive effect on the activity of the mouse Nkx2.5 promoter in cell cultures, indicating that phosphorylation is required for Shox2a to repress Nkx2.5 expression specifically. Transgenic expression of Shox2a, but not Shox2a‐S92AS110A, mutant in the developing heart resulted in down‐regulation of Nkx2.5 in wild‐type mice and rescued the SAN defects in the Shox2 mutant background. Last, we demonstrated that elimination of both phosphorylation sites on Shox2a did not alter its nuclear location and dimerization, but depleted its capability to bind to the consensus sequences within the Nkx2.5 promoter region. Conclusions: Our studies reveal that phosphorylation is essential for Shox2a to repress Nkx2.5 expression during SAN development and differentiation

A high-resolution haplotype-resolved Reference panel constructed from the China Kadoorie Biobank Study

Precision medicine depends on high-accuracy individual-level genotype data. However, the whole-genome sequencing (WGS) is still not suitable for gigantic studies due to budget constraints. It is particularly important to construct highly accurate haplotype reference panel for genotype imputation. In this study, we used 10 000 samples with medium-depth WGS to construct a reference panel that we named the CKB reference panel. By imputing microarray datasets, it showed that the CKB panel outperformed compared panels in terms of both the number of well-imputed variants and imputation accuracy. In addition, we have completed the imputation of 100 706 microarrays with the CKB panel, and the after-imputed data is the hitherto largest whole genome data of the Chinese population. Furthermore, in the GWAS analysis of real phenotype height, the number of tested SNPs tripled and the number of significant SNPs doubled after imputation. Finally, we developed an online server for offering free genotype imputation service based on the CKB reference panel (https://db.cngb.org/imputation/). We believe that the CKB panel is of great value for imputing microarray or low-coverage genotype data of Chinese population, and potentially mixed populations. The imputation-completed 100 706 microarray data are enormous and precious resources of population genetic studies for complex traits and diseases

BMPRIA mediated signaling is essential for temporomandibular joint development in mice

The central importance of BMP signaling in the development and homeostasis of synovial joint of appendicular skeleton has been well documented, but its role in the development of temporomandibular joint (TMJ), also classified as a synovial joint, remains completely unknown. In this study, we investigated the function of BMPRIA mediated signaling in TMJ development in mice by transgenic loss-of- and gain-of-function approaches. We found that BMPRIA is expressed in the cranial neural crest (CNC)-derived developing condyle and glenoid fossa, major components of TMJ, as well as the interzone mesenchymal cells. Wnt1-Cre mediated tissue specific inactivation of BmprIa in CNC lineage led to defective TMJ development, including failure of articular disc separation from a hypoplastic condyle, persistence of interzone cells, and failed formation of a functional fibrocartilage layer on the articular surface of the glenoid fossa and condyle, which could be at least partially attributed to the down-regulation of Ihh in the developing condyle and inhibition of apoptosis in the interzone. On the other hand, augmented BMPRIA signaling by Wnt1-Cre driven expression of a constitutively active form of BmprIa (caBmprIa) inhibited osteogenesis of the glenoid fossa and converted the condylar primordium from secondary cartilage to primary cartilage associated with ectopic activation of Smad-dependent pathway but inhibition of JNK pathway, leading to TMJ agenesis. Our results present unambiguous evidence for an essential role of finely tuned BMPRIA mediated signaling in TMJ development

Antioxidant Capacity and Proanthocyanidin Composition of the Bark of Metasequoia glyptostroboides

Metasequoia glyptostroboides Hu et Cheng is the only living species in the genus Metasequoia Miki ex Hu et Cheng (Taxodiaceae), which is well known as a “living fossil” species. In the Chinese folk medicine, the leaves and bark of M. glyptostroboides are used as antimicrobic, analgesic, and anti-inflammatory drug for dermatic diseases. This study is the first to report the free radical scavenging capacity, antioxidant activity, and proanthocyanidin composition of the bark of M. glyptostroboides. We observed total of six extracts and fractions, which were easily obtained by water-ethanol extraction and followed by a further separation with D101 resin column chromatography, had significant DPPH radical, superoxide anion radical, and hydroxyl radical scavenging capacity, total antioxidative capacity (T-AOC), lipid peroxidation inhibitory activity, and metal ions chelating capacity. The fraction MGEB, which was obtained by 60% ethanol extraction and followed by a further separation with D101 resin column chromatograph, possessed the highest proanthocyanidin content and the highest free radical scavenging and antioxidant activities. Furthermore, MGEB could significantly protect against CCl4 induced acute liver injury through inhibition of oxidative stress in mice. In addition, ten proanthocyanidins were isolated from MGEB, and six of them were firstly reported from this plant

Variations in olfactory function among bipolar disorder patients with different episodes and subtypes

PurposeMost studies on olfactory function in individuals with bipolar disorder (BD) have not distinguished between the different subtypes or between the acute phase (mania or depression) and euthymic state. In this study, we compared olfactory function among BD patients with different subtypes and episodes to explore the potential use of olfactory function as a biomarker for the early identification of BD.Patients and methodsThe study sample consisted of 117 BD patients who were hospitalized between April 2019 and June 2019, and 47 healthy volunteers as controls. The BD patients were divided into a bipolar I disorder (BD I) (n = 86) and bipolar II disorder (BD II) group (n = 31) according to the different subtypes, and divided into depressive BD (n = 36), manic BD (n = 44), or euthymic BD (n = 37) groups according to the types of episodes they experienced. We assessed olfactory sensitivity (OS) and olfactory identification (OI) via the Sniffin’ Sticks test and used the Hamilton Depression Rating Scale (HAMD) and Young Manic Rating Scale (YMRS) to evaluate BD characteristics among all subjects.ResultsCompared with controls, the participants with BD showed decreased OS and OI. We found statistically significant differences in OS and OI between the BD I group and controls, as well as differences in OS between the BD I and BD II group. Least-significant difference multiple comparisons revealed statistically significant differences in OS between the depressive BD group, manic BD group and controls and also between the manic BD and euthymic BD group. OI was positively correlated with the YMRS score in the BD I group and OS was negatively correlated with the HAMD score in the BD II group.ConclusionThis may be the first study to compare olfactory function in patients with BD I vs. BD II via pairwise comparisons. Our findings suggest that OS may have potential as a biomarker for distinguishing the different subtypes of BD and as a state-related biomarker for differentiating the acute phase from the euthymic state of BD. However, further prospective research is warranted