Ultrasound imaging guided targeted sonodynamic therapy enhanced by magnetophoretically controlled magnetic microbubbles.

Sonodynamic therapy (SDT) utilizes ultrasonic excitation of a sensitizer to generate reactive oxygen species (ROS) to destroy tumor. Two dimensional (2D) black phosphorus (BP) is an emerging sonosensitizer that can promote ROS production to be used in SDT but it alone lacks active targeting effect and showed low therapy efficiency. In this study, a stable dispersion of integrated micro-nanoplatform consisting of BP nanosheets loaded and Fe3O4 nanoparticles (NPs) connected microbubbles was introduced for ultrasound imaging guided and magnetic field directed precision SDT of breast cancer. The targeted ultrasound imaging at 18 MHz and efficient SDT effects at 1 MHz were demonstrated both in-vitro and in-vivo on the breast cancer. The magnetic microbubbles targeted deliver BP nanosheets to the tumor site under magnetic navigation and increased the uptake of BP nanosheets by inducing cavitation effect for increased cell membrane permeability via ultrasound targeted microbubble destruction (UTMD). The mechanism of SDT by magnetic black phosphorus microbubbles was proposed to be originated from the ROS triggered mitochondria mediated apoptosis by up-regulating the pro-apoptotic proteins while down-regulating the anti-apoptotic proteins. In conclusion, the ultrasound theranostic was realized via the magnetic black phosphorus microbubbles, which could realize targeting and catalytic sonodynamic therapy.

Ultrasound image-guided cancer gene therapy using iRGD dual-targeted magnetic cationic microbubbles.

The gene therapy attracted more and more attention for the tumor therapy. To obtain a safe gene therapy system, the new gene vectors beyond the virus were developed for a high gene therapy efficiency. The ultrasound mediated gene therapy was safer and the plasmid DNA could be delivered by the microbubbles and combined with the ultrasound to increase the gene transfection efficiency. In this work, the cationic microbubbles decorated with Cyclo(Cys-Arg-Gly-Asp-Lys-Gly-Pro-AspCys) (iRGD peptides) and magnetic Fe3O4 nanoparticles (MBiM) was designed for targeted ultrasound contrast imaging guided gene therapy of tumors. The ultrasound image intensity was dramatically enhanced at the tumor site that received MBiM with the magnet applied, compared to those administrated the non-targeted microbubbles (MBb) or the microbubbles with only one target material on the surface (MBM and MBbi). The pGPU6/GFP/Neo-shAKT2 was used as a sample gene, which down regulate the AKT2 protein expression for the cancer therapy. It illustrated that MBiM/AKT2 had the highest gene transfection efficiency in the studied microbubbles mediated by the ultrasound, leading to the AKT2 protein expression downregulation and the strongest tumor killing effect in vitro and in vivo. In summary, a novel and biocompatible gene delivery platform via MBiM with both the endogenous and external targeting effects for breast cancer theranostics was developed.

Thermally Crosslinked F-rich Polymer to Inhibit Lead Leakage for Sustainable Perovskite Solar Cells and Modules.

High-performance perovskite solar cells have demonstrated commercial viability, but still face the risk of contamination from lead leakage and long-term stability problems caused by defects. Here, an organic small molecule (octafluoro-1,6-hexanediol diacrylate) is introduced into the perovskite film to form a polymer through in situ thermal crosslinking, of which the carbonyl group anchors the uncoordinated Pb2+ of perovskite and reduces the leakage of lead, along with the -CF2 - hydrophobic group protecting the Pb2+ from water invasion. Additionally, the polymer passivates varieties of Pb-related and I-related defects through coordination and hydrogen bonding interactions, regulating the crystallization of perovskite film with reduced trap density, releasing lattice strain, and promoting carrier transport and extraction. The optimal efficiencies of polymer-incorporated devices are 24.76 % (0.09 cm2 ) and 20.66 % (14 cm2 ). More importantly, the storage stability, thermal stability, and operational stability have been significantly improved.

Sleep quality status, anxiety, and depression status of nurses in infectious disease department.

Objective: To investigate the current status of sleep quality and influencing factors of clinical nurses in infectious disease hospitals, and to provide basis and reference for improving their sleep status and providing psychological support. Methods: Using convenience sampling method, clinical nurses from a tertiary hospital for infectious diseases were selected as the survey subjects in September 2021. General information questionnaire, Pittsburgh Sleep Quality Questionnaire (PSQI), Generalized Anxiety Disorder Scale (GAD-7), Depression Screening Scale (PHQ-9) were used for questionnaire surveys, and multiple linear regression was used to analyze the impact of decreased sleep quality in clinical nurses factor. Results: A total of 460 questionnaires were returned, of which 442 were valid, effective rate is 96.09%. The Pittsburgh sleep quality index (PSQI) score of 442 clinical nurses was 7.07 ± 2.14, of which 60 (13.57%) had sleep disorders; the Generalized Anxiety Disorder Scale (GAD-7) score was 4.77 ± 3.50, of which 182 (41.18%) had varying degrees of anxiety; The score of PHQ-9 was 5.95 ± 3.79, of which 187 (42.31%) had different degrees of depressive symptoms. The stepwise multiple linear regression analysis which involved PHQ-9 and GAD-7 scores showed that: both the PHQ-9 score and the GAD-7 score were positively correlated with the sleep quality score, and the PHQ-9 score increased every time 1 point, sleep quality score increased by 0.239 points; GAD-7 score increased by 1 point, sleep quality score increased by 0.150 points. The overall model test (F = 109.760, P < 0.001) regression model is meaningful. Conclusion: Decreased sleep quality is common among clinical nurses in infectious disease hospitals, and the sleep status of nurses is positively correlated with anxiety and depression. Nursing managers pay attention to sleep quality of clinical nurses in infectious disease hospitals and carry out effective interventions to improve the sleep quality of nurses.

Contrast-enhanced ultrasound imaging using long-circulating cationic magnetic microbubbles in vitro and in vivo validations.

Traditional encapsulated microbubbles are recently used as delivery carriers for drugs and genes, but they have low efficiency. If the local microbubble concentration could be increased, this might be able to improve the therapeutic efficacy of diseases. In this study, we developed novel cationic magnetic microbubbles (MBM), which could simultaneously realize targeted aggregation under a magnetic field as well as ultrasonographic real-time visualization. Their physicochemical properties, biocompatibility, ultrasonography, magnetic response characteristics, and biodistribution were systematically evaluated. Here, the MBM were 2.55 ± 0.14 µm in size with a positive zeta potential, and had a good biocompatibility. They were able to enhance ultrasonographic contrast both in vitro and in vivo. MBM could be attracted by an external magnet for directional movement and aggregation in vitro. We confirmed that MBM also had a great magnetic response in vivo, by means of fluorescence imaging and contrast-enhanced ultrasound imaging. Following intravenous injection into tumor-bearing mice, MBM showed excellent stability in the internal circulation, and could accumulate in the tumor vasculature through magnetic targeting. With the excellent combination of magnetic response and acoustic properties, cationic magnetic microbubbles (MBM) have promising potential for use as a new kind of drug/gene carrier for theranostics in the future.

[Study on sesquiterpenes from agarwood originating from Gyrinops salicifolia].

Two sesquiterpenes were isolated from the agarwood originating from Gyrinops salicifolia with various chromatographic techniques, and their structures were determined as 12-hydroxy-dihydrocyperolone(1) and(rel)-4ß,5ß,7ß-eremophil-9-en-12,8α-olide(2), through a combined analysis of physicochemical properties and spectroscopic evidence. Compound 1 was a new compound. Compound 2 showed cytotoxicities against K562 and BEL-7401 cell lines, with IC_(50) values of(17.85±0.04) and(21.82±0.07) mg·L~(-1), respectively [taxol as positive control, with IC_(50) values of(1.97±0.11) and(6.31±0.08) mg·L~(-1)].

Three New 2-(2-Phenylethyl)chromone Derivatives of Agarwood Originated from Gyrinops salicifolia.

Two new 2-(2-phenylethyl)chromone derivatives (1⁻2), comprising 5,6,7,8-tetrahydro-2-(2-phenylethyl)chromone and benzylacetone moieties, together with one new 2-(2-phenylethenyl)chromone (3) were isolated from the ethyl acetate extraction of agarwood originated from Gyrinops salicifolia Ridl. All structures were unambiguously elucidated on the basis of 1D and 2D NMR spectra as well as by HRESIMS data. All isolated compounds were tested for acetylcholinesterase (AChE) inhibitory activity and cytotoxic activity against human myeloid leukemia cell line (K562). However, none of the compounds displayed AChE inhibitory activity at a concentration of 50 µg mL-1 or cytotoxic activity against K562 cell line.

Use of Breast Magnetic Resonance Imaging and Ultrasonography for Identifying Nonpalpable Axillae Metastases in Newly Diagnosed Breast Cancer Patients.

BACKGROUND: The metastasis of axillary lymph node (ALNs) is a critical step in the initial cancer staging of newly diagnosed breast cancer (BC) patients. Various imaging modalities can enhance the sensitivity of clinical examination in assessing the ALN status. PATIENTS AND METHODS: We enrolled 135 patients with BC, confirmed via histopathology, including 4 bilateral BC cases. A total of 139 ipsilateral ALNs adjacent to the breast lesion were examined via physical examination, ultrasonography (US), and magnetic resonance imaging (MRI); of these, 100 were nonpalpable ALNs, as determined by experienced breast surgeons and physicians. The relative size parameters on MRI and US images were recorded. Receiver operating characteristic (ROC) analyses were conducted, and the area under the ROC curve (AUC) was compared. RESULTS: Of 139 ALNs, 67 (48%) were malignant and 72 (52%) were benign on pathological examination. In all of the ALNs, the US short diameter appeared to be the most discriminative quantitative measurement for detecting positive findings (AUC, 0.854). In nonpalpable ALNs as well, the US short diameter exhibited the greatest discriminability (AUC, 0.746). However, the 2-dimensional and 3-dimensional parameters on MRI did not exhibit any significant differences between the enrolled and nonpalpable ALNs (P > .05). CONCLUSION: The shortest diameter on US exhibited better discriminative ability than MRI for predicting positive ALNs in nonpalpable axillae. Moreover, the 2-dimensional and 3-dimensional parameters on MRI did not differ in terms of discriminability.

Construction of different calibration models by FTIR/ATR spectra and their application in screening of phenylketonuria.

OBJECTIVE: To construct different calibration models by using FTIR/ATR spectra and apply them for the screening of phenylketonuria for the newborns. METHOD: 69 dried blood spots samples were collected, of which the concentrations of phenylalanine (Phe) and tyrosine (Tyr) were determined by tandem mass spectrometry method. The FTIR/ATR method was used to collect the spectra of the samples. After various pretreatments with the original spectra, such as smoothing, derivative, vector normalization, Concave rubberband correction, the new spectra were fed into different methods to construct calibration models for the Phe concentrations of the samples. The kernel function, consensus strategy and their combination were integrated into the popular partial least squares method. The obtained models were then assessed by calculating coefficient of determination, root mean square error, mean relative error, etc. RESULT: After a careful comparison, the cKPLS model performed the best, and the result yielded were much more accurate and stable. CONCLUSION: The present cKPLS model, due to the combination of the kernel function and the consensus strategy, can be successfully applied to the prediction of Phe concentration for the phenylketonuria newborns. Also, we believe that the cKPLS method will be of help for FTIR/ATR spectra calibration problems in other complex systems.

Electrotransformation of Haemophilus parasuis with in vitro modified DNA based on a novel shuttle vector.

The objective of the present study was to establish a valid transformation method of Haemophilus parasuis, the causative agent of Glässer's disease in pigs, using a novel H. parasuis-Escherichia coli shuttle vector. A 4.2kb endogenous plasmid pYC93 was extracted from an H. parasuis field isolate and completely sequenced. Analysis of pYC93 revealed a region approximately 800bp showing high homology with the defined replication origin oriV of pLS88, a native plasmid identified in Haemophilus ducreyi. Based on the origin region of pYC93, E. coli cloning vector pBluescript SK(+) and the Tn903 derived kanamycin cassette, a shuttle vector pSHK4 was constructed by overlapping PCR strategy. When electroporation of the 15 H. parasuis serovar reference strains and one clinical isolate SH0165 with pSHK4 was performed, only one of these strains yielded transformants with an efficiency of 8.5×10(2)CFU/µg of DNA. Transformation efficiency was notably increased (1.3×10(5)CFU/µg of DNA) with vector DNA reisolated from the homologous transformants. This demonstrated that restriction-modification systems were involved in the barrier to transformation of H. parasuis. By utilizing an in vitro DNA modification method with cell-free extracts of the host H. parasuis strains, 15 out of 16 strains were transformable. The novel shuttle vector pSHK4 and the established electrotransformation method constitute useful tools for the genetic manipulation of H. parasuis to gain a better understanding of the pathogen.

Identification and analysis of potential virulence-associated genes in Haemophilus parasuis based on genomic subtraction.

Haemophilus parasuis is a commensal bacterium in the swine upper respiratory tract, but virulent strains can invade host and cause Glässer's disease under certain conditions. In order to explore the virulence difference in H. parasuis strains, a virulent isolate, SH0165 (serotype 5), and an avirulent isolate, 7140 (serotype 4), were selected to investigate genetic differences by genomic subtraction. A total of 560 clones were screened by dot-blot and PCR, and 33 fragments present in SH0165 but absent from 7140 were identified. They encode eight gene categories, the sclB family, restriction modification system, phage products, transport system, outer membrane proteins, metabolism, and DNA synthesis and insertion sequences. We investigated the distribution of 21 fragments in 15 reference strains. Six fragments were more prevalent in virulent strains than avirulent strains based on statistical analysis; three fragments were SH0165-specific, and the remaining 12 were diversely distributed. Having analyzed these significantly differential fragments, including the sclB family, ABC-type transporter, fhuA and nhaC, we presume that these genes are associated with virulence in H. parasuis.