Hyperbranched Polymer Dots with Strong Absorption and High Fluorescence Quantum Yield for In Vivo NIR-II Imaging.

In order to improve the fluorescence quantum yield (QY) of NIR-II-emitting nanoparticles, D-A-D fluorophores are typically linked to intramolecular rotatable units to reduce aggregation-induced quenching. However, incorporating such units often leads to a twisted molecular backbone, which affects the coupling within the D-A-D unit and, as a result, lowers the absorption. Here, we overcome this limitation by cross-linking the NIR-II fluorophores to form a 2D polymer network, which simultaneously achieves a high QY by well-controlled fluorophore separation and strong absorption by restricting intramolecular distortion. Using the strategy, we developed polymer dots with the highest NIR-II single-particle brightness among reported D-A-D-based nanoparticles and applied them for imaging of hindlimb vasculatures and tumors as well as fluorescence-guided tumor resection. The high brightness of the polymer dots offered exceptional image quality and excellent surgical results, showing a promising performance for these applications.

Identification of variants in 94 Chinese patients with hereditary spherocytosis by next-generation sequencing.

Hereditary spherocytosis (HS) is the most common type of hereditary erythrocyte membrane disease and has varied phenotypic features and genetic patterns. We herein performed a retrospective study of 94 patients with HS and aimed to investigate the genetic variations and genotype-phenotype correlations using targeted next-generation sequencing. In 79/94 (84%) patients, 83 HS variants including 67 novel variants were identified. Pathogenic variants of SPTB, ANK1, SLC4A1, SPTA1, and EPB42 were found in 32/79(41%), 22/79(28%), 15/79 (19%), 8/79 (9%), and 3/79 (4%) of the patients respectively, revealing that SPTB is the most frequently mutated HS gene in Eastern China. Most SPTB and ANK1 gene variations were nonsense and frameshift variations. Missense variants were the main variant type of SLC4A1, SPTA1, and EPB42 genes. Interestingly, one SPTA1 variant (p. Arg1757Cys) showed an autosomal dominant inheritance pattern and one EPB42 variant (p. Gln377His) was apparent as a hotspot variation. Furthermore, genotype-phenotype analysis was performed among the five mutated gene groups. Besides the finding that patients with the SLC4A1 variant had the highest mean corpuscular hemoglobin levels, no clear correlations between genotype and phenotype were observed.

Magnifying image-enhanced endoscopy-only mode boosted early cancer diagnostic efficiency: a multicenter randomized controlled trial.

BACKGROUND AND AIMS: Magnifying image-enhanced endoscopy (MIEE) is an advanced endoscopy with image enhancement and magnification used in preoperative examination. However, its impact on the detection rate is unknown. METHODS: We conducted an open-label, randomized, parallel (1:1:1), controlled trial in 6 hospitals in China. Patients were recruited between February 14, 2022 and July 30, 2022. Eligible patients were aged ≥18 years and undergoing gastroscopy in outpatient departments. Participants were randomly assigned to the MIEE-only mode (o-MIEE) group, white-light endoscopy-only mode (o-WLE) group, and MIEE when necessary mode (n-MIEE) group (initial WLE followed by switching to another endoscope with MIEE if necessary). Biopsy sampling of suspicious lesions of the lesser curvature of the gastric antrum was performed. Primary and secondary aims were to compare detection rates and positive predictive value (PPV) of early cancer and precancerous lesions in these 3 modes, respectively. RESULTS: A total of 5100 recruited patients were randomly assigned to the o-MIEE (n = 1700), o-WLE (n = 1700), and n-MIEE (n = 1700) groups. In the o-MIEE, o-WLE, and n-MIEE groups, 29 (1.51%; 95% confidence interval [CI], 1.05-2.16), 4 (.21%; 95% CI, .08-.54), and 8 (.43%; 95% CI, .22-.85) early cancers were found, respectively (P < .001). The PPV for early cancer was higher in the o-MIEE group compared with the o-WLE and n-MIEE groups (63.04%, 33.33%, and 38.1%, respectively; P = .062). The same trend was seen for precancerous lesions (36.67%, 10.00%, and 21.74%, respectively). CONCLUSIONS: The o-MIEE mode resulted in a significant improvement in diagnosing early upper GI cancer and precancerous lesions; thus, it could be used for opportunistic screening. (Clinical trial registration number: ChiCTR2200064174.).

Synergistic Recognition-Triggered Charge Transfer Enables Rapid Visual Colorimetric Detection of Fentanyl.

As a new psychoactive substance, abuse of fentanyl (FTN) is currently spreading around the world, resulting in an urgent need of on-site and rapid analytical methods for detection of FTN. Here, we present a synergistic recognition strategy for rapid, cost-effective, selective, sensitive, and visual colorimetric detection of FTN by taking advantage of Rose Bengal (RB) as the specific probe. This assay is based on the halogen- and hydrogen-bonding interactions between them, generating a charge transfer and accompanying a red shift in the RB absorption band as well as color change from red to purple. The utility of the present visual colorimetric assay is demonstrated in aqueous solution, diluted urine, and domestic sewage samples. A detection limit of 0.7 mg·L-1 in aqueous solution is achieved, and the naked-eye detection of FTN is also realized in different real matrices within 6 min. Moreover, this method is insusceptible to interference from various substances (other opioids, cutting agents of street drugs, FTN precursors, amino acids, and small-molecular amines). Additionally, we successfully fabricate a smartphone-based portable device to determine FTN, which is appropriate for field tests. The present work not only provides the first visual assay for FTN but also reveals the molecular structure-property relationship, which will guide the design and development of various probes for recognizing FTN.

Cell dehydration enables massive production of engineered membrane vesicles with therapeutic functions.

Extracellular vesicles (EVs) have emerged as promising biomaterials for the treatment of different disease. However, only handful types of EVs with clinical transformation potential have been reported to date, and their preparation on a large scale under biosafety-controlled conditions is limited. In this study, we characterize a novel type of EV with promising clinical application potential: dehydration-induced extracellular vesicles (DIMVs). DIMV is a type of micron-diameter cell vesicle that contains more bioactive molecules, such as proteins and RNA, but not DNA, than previously reported cell vesicles. The preparation of DIMV is extraordinarily straightforward, which possesses a high level of biosafety, and the protein utilization ratio is roughly 600 times greater than that of naturally secreted EVs. Additional experiments demonstrate the viability of pre- or post-isolation DIMV modification, including gene editing, nucleic acid encapsulation or surface anchoring, size adjustment. Finally, on animal models, we directly show the biosafety and immunogenicity of DIMV, and investigate its potential application as tumour vaccine or drug carrier in cancer treatment.

Research Progress on Multifunctional Modified Separator for Lithium-Sulfur Batteries.

Lithium-sulfur batteries (LSBs) are recognized as one of the second-generation electrochemical energy storage systems with the most potential due to their high theoretical specific capacity of the sulfur cathode (1675 mAhg-1), abundant elemental sulfur energy storage, low price, and green friendliness. However, the shuttle effect of polysulfides results in the passivation of the lithium metal anode, resulting in a decrease in battery capacity, Coulombic efficiency, and cycle stability, which seriously restricts the commercialization of LSBs. Starting from the separator layer before the positive sulfur cathode and lithium metal anode, introducing a barrier layer for the shuttle of polysulfides is considered an extremely effective research strategy. These research strategies are effective in alleviating the shuttle of polysulfide ions, improving the utilization of active materials, enhancing the battery cycle stability, and prolonging the cycle life. This paper reviews the research progress of the separator functionalization in LSBs in recent years and the research trend of separator functionalization in the future is predicted.

[Application of Bionano-DNA Full-Length Optical Mapping Technology in Genetic Diagnosis of Hemophilia A Carriers].

OBJECTIVE: To apply Bionano Saphyr visual full-length DNA optical mapping technology to the precise genetic diagnosis of hemophilia A carriers. METHODS: For 2 suspected F8 gene deficiency female carriers who could not be diagnosed by conventional next-generation sequencing technology, the full-length DNA optical mapping technology was used to detect and scan the sample X chromosome full-length visual haplotype characteristic map, which was compared with the normal haplotype. The gene structure variation information of the samples was obtained by compare with DNA atlas library. RESULTS: The average fluorescent marker length of the X chromosome DNA molecular where the F8 gene was located in the two samples was greater than 2.5 Mbp, and the average copy number was greater than 20×. After comparative analysis, one of the samples was a proximal inversion of intron 22 of the F8 gene, and another was an inversion of intron 22 accompanied by multiple deletions of large fragments. CONCLUSIONS: Bionano technology has a good detection rate for gene defects with large length and complex variation. In the absence of a proband or accurate genetic diagnosis results of the proband, the application of this technology to detect the heterozygous complex variant of the F8 gene is of great significance for the prenatal diagnosis and pre-pregnancy diagnosis of hemophilia carriers.

Myrislignan attenuates lipopolysaccharide-induced inflammation reaction in murine macrophage cells through inhibition of NF-κB signalling pathway activation.

Myrislignan is a new kind of lignan isolated from Myristica fragrans Houtt. Its antiinflammatory effects have not yet been reported. In the present study, the antiinflammatory effects and the underlying mechanisms of myrislignan in lipopolysaccharide (LPS)-induced inflammation in murine RAW 264.7 macrophage cells were investigated. Myrislignan significantly inhibited LPS-induced production of nitric oxide (NO) in a dose-dependent manner. It inhibited mRNA expression and release of interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α). This compound significantly inhibited mRNA and protein expressions of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) dose-dependently in LPS-stimulated macrophage cells. Further study showed that myrislignan decreased the cytoplasmic loss of inhibitor κB-α (IκB-α) protein and the translocation of NF-κB from cytoplasm to the nucleus. Our results suggest that myrislignan may exert its antiinflammatory effects in LPS-stimulated macrophages cells by inhibiting the NF-κB signalling pathway activation.

Exposure of Larvae to Sublethal Thiacloprid Delays Bee Development and Affects Transcriptional Responses of Newly Emerged Honey Bees.

Understanding the cause of honey bee (Apis mellifera) population decline has attracted immense attention worldwide in recent years. Exposure to neonicotinoid pesticides is considered one of the most probable factors due to the physiological and behavioral damage they cause to honey bees. However, the influence of thiacloprid, a relatively less toxic cyanogen-substituted form of neonicotinoid, on honey bee (Apis mellifera L.) development is not well studied. The toxicity of sublethal thiacloprid to larvae, pupae, and emerging honey bees was assessed under laboratory conditions. We found that thiacloprid reduced the survival rate of larvae and pupae, and delayed the development of bees which led to lower bodyweight and size. Furthermore, we identified differentially expressed genes involved in metabolism and immunity though RNA-sequencing of newly-emerged adult bees. GO enrichment analysis identified genes involved in metabolism, catalytic activity, and transporter activity. KEGG pathway analysis indicated that thiacloprid induced up-regulation of genes related to glutathione metabolism and Toll-like receptor signaling pathway. Overall, our results suggest that chronic sublethal thiacloprid can affect honey bee colonies by reducing survival and delaying bee development.

[A new natural polyphenol BJA32531 inhibited the proliferation and regulated miRNA expression in human HepG2 hepatocarcinoma cells].

OBJECTIVE: To study the effect of 1,2,6-Tri-O-galloyl-beta-D-glucopyranose (BJA32531) on the miRNA expression during BJA32531-induced cytotoxicity in human HepG2 hepatocarcinoma cells. METHODS: Cell proliferation was assessed using a colorimetric assay (cell counting kit-8). Apoptosis was assessed by annexin V and propidium iodide staining. The miRNA expression profile of the cancer cells was analyzed by a miRNA array and quantitative real-time PCR. RESULTS: BJA32531 inhibited the cell proliferation and increased apoptosis in HepG2 cancer cells. Cellular exposure to BJA32531 influenced the miRNA expression pattern in the cells, including 19 upregulated and 85 down-regulated miRNAs in the cells. The up-regulations of let-7a and miR-10b as well as the down-regulations of miR-132 and miR-125b were verified to be consistent with the the results of the miRNA array. CONCLUSION: Our study suggests that the mechanisms by which BJA32531 exerted the antiproliferative effects on HepG2 cancer cells may be related to its regulation of miRNA.

Pt3Ni@C Composite Material Designed and Prepared Based on Volcanic Catalytic Curve and Its High-Performance Static Lithium Polysulfide Semiliquid Battery.

There are many challenges for the Static lithium polysulfide semiliquid battery in its commercial application, such as poor stability of the cathode material and further amplification of the lithium polysulfide shuttle effect. Therefore, this manuscript introduced a new type of Pt3Ni@C composite material as cathode working electrode based on the principle of volcanic catalytic curve. Through symmetric battery test, CV, polarization curves and impedance test, it was found that Pt3Ni@C composite material had good catalytic activity of lithium polysulfide to improve electrochemical kinetics. When the catholyte was Li2S8 and the charge-discharge voltage range was 1.8~2.6 V, the capacity maintained at approximately 550 mAh g-1, and the coulombic efficiency maintained at approximately 95% after 100 cycles at a current rate of 0.5 mA cm-2. The Pt3Ni@C composite material is a potential cathode material with the specific capacity and long cycling stability of the static lithium polysulfide semiliquid battery.

Triterpenoids from Ganoderma lucidum and Their Potential Anti-inflammatory Effects.

Ganoderma lucidum, as food, tea, dietary supplement, and medicine, is widely used in China and Eastern Asian countries. In order to discover its anti-inflammatory constituents and provide some references for the usage of G. lucidum and G. sinense, two official species in China, the fruiting bodies of G. lucidum were studied, leading to the isolation of six new triterpenoids (1-6) and 27 known analogues (7-33). Compound 4 exhibited the most potent inhibition on nitric oxide (NO) production induced by lipopolysaccharide (LPS) in RAW264.7 macrophage cells. The production of IL-6 and IL-1ß, as well as the expression of iNOS, COX-2, and NF-κB were dose-dependently reduced by 4. The phosphorylations of IκBα and IKKß in LPS-induced macrophage cells were blocked by 4. Therefore, 4 could be used as a potential anti-inflammatory candidate and the total triterpenoids might be developed as value-added functional food for the prevention of inflammation. In combination of previous studies, it should be cautious for the interchangeable usage of G. lucidum and G. sinense.

Excitation-wavelength-dependent photoluminescence of silicon nanoparticles enabled by adjustment of surface ligands.

We herein present pioneering studies to reveal that excitation-wavelength-dependent photoluminescence properties of fluorescent silicon nanoparticles (SiNPs) can be realized by rationally designing surface ligands, i.e., several kinds of oxidized indole derivatives. The resultant ligand-decorated SiNPs exhibit strong fluorescence, with significant excitation-wavelength-dependent emissive shifting from ∼420 nm to ∼550 nm. Taking advantage of their unique optical merits, we further exploit the resultant ligand-decorated SiNPs as novel fluorescent labels for anti-counterfeiting and cell imaging.

1,3,4-tri-O-galloyl-6-O-caffeoyl-ß-D-glucopyranose, a new anti-proliferative ellagitannin, regulates the expression of microRNAs in HepG(2) cancer cells.

OBJECTIVE: MicroRNAs (miRNAs) play important roles in cell proliferation, differentiation and apoptosis. 1, 3, 4-tri-O-galloyl-6-O-caffeoyl-ß-D-glucopyranose (BJA32515) is a new natural ellagitannin compound extracted from Balanophora Japonica MAKINO. The effect of BJA32515 on the expression of miRNAs in cancer cells has not yet been explored. Objective The present study was carried out to examine the changes in miRNA expression profiles in human HepG(2) hepatocarcinoma cells following BJA32515 exposure. METHODS: The proliferation of BJA32515-exposed HepG(2) cells was assessed using a colorimetric assay (cell counting kit-8). The miRNA expression profile of the cancer cells was analyzed using a miRNA array and quantitative real-time PCR. Apoptosis was assessed by annexin V and propidium iodide staining. RESULTS: BJA32515 inhibited the cell proliferation and increased apoptosis in HepG(2) cancer cells. The exposure to BJA32515 also caused alterations in the miRNA expression profile in the cells, with 33 miRNAs upregulated and 59 down-regulated. The up-regulation of let-7a and miR-29a and the down-regulation of miR-373 and miR-197 were verified by quantitative real-time PCR. CONCLSION: BJA32515-modifed miRNA expression may mediate the antiproliferative effect of this compound in HepG(2) cancer cells.

TGFBI gene mutation analysis in a Chinese pedigree of Avellino corneal dystrophy.

AIM: To analyze phenotype and genotype of a Chinese pedigree with Avellino corneal dystrophy (ACD). METHODS: Complete ophthalmic examinations were performed on all the family members. Exons of TGFBI were amplified by polymerase chain reaction, sequenced, and compared with a reference database. RESULTS: A single heterozygous G>A (R124H) point mutation was identified in exon 4 of TGFBI in three affected members and two unaffected children who were offsprings of the affected members, but not in the other family members. CONCLUSION: Mutation R124H in TGFBI was identified in this pedigree and appeared to be the disease causing mutation. Atypical phenotype and low penetrance was observed in this pedigree.