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Serous cystadenoma of the pancreas is a type of pancreatic cystic neoplasm frequently found in clinical practice. Serous cystadenoma of the pancreas can have a varied morphological presentation on imaging examinations. Therefore, it is sometimes very challenging to differentiate serous cystadenoma of the pancreas from pancreatic malignancy. In this study, we present a case of serous cystadenoma of the pancreas showing focally elevated radiotracer uptake on 68 Ga-FAPI PET/CT. Considering potential future clinical use of 68 Ga-FAPI PET/CT in malignancy, awareness of the false-positive findings is important for the differential diagnosis and management of these lesions.

In the context of relatively sufficient research that annotated WNT1 inducible signaling pathway protein 1 (WISP1) as a promoting factor in tumor progression of breast cancer, and identified the effects of ultrasound microbubble technology on enhancing the transfection efficiency and achieving better gene interference, this study managed to investigate the effects of ultrasound microbubble-mediated siWISP1 transfection on proliferation and metastasis of breast cancer cells. To achieve our research objectives, the expression of WISP1 in breast cancer tissues was retrieved from GEPIA website, and the viability of breast cancer cells (SK-BR-3 and MCF7) was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay for ultrasound intensity screening. After the transfection of siWISP1 by ultrasound microbubble or lipofectamine 6000, the content of WISP1 secreted by cells was detected through Enzyme-linked immunosorbent assay (ELISA), and WISP1 expression in cells was determined by quantitative reverse transcription polymerase-chain reaction (qRT-PCR). Besides, the cell invasion, migration, and proliferation were evaluated by wound healing, transwell, and EdU assays, respectively. In accordance with experimental results, WISP1 was highly expressed in breast cancer tissues, and the 1 W/cm

Reactive oxygen species (ROS) are constantly produced in cells, an excess of which causes oxidative stress. ROS has been linked to regulation of the Hippo pathway; however, the underlying detailed mechanisms remain unclear. Here, we report that MOB1, a substrate of MST1/2 and co-activator of LATS1/2 in the canonical Hippo pathway, interacts with and is acetylated at lysine 11 by acetyltransferase CBP and deacetylated by HDAC6. MOB1-K11 acetylation stabilizes itself by reducing its binding capacity with E3 ligase Praja2 and subsequent ubiquitination. MOB1-K11 acetylation increases its phosphorylation and activates LATS1. Importantly, upstream oxidative stress signals promote MOB1 acetylation by suppressing CBP degradation, independent of MST1/2 kinase activity and HDAC6 deacetylation effect, thereby linking oxidative stress to activation of the Hippo pathway. Functionally, the acetylation-deficient mutant MOB1-K11R promotes lung cancer cell proliferation, migration and invasion in vitro and accelerates tumor growth in vivo, compared to the wild-type MOB1. Clinically, acetylated MOB1 corresponds to better prediction of overall survival in patients with non-small cell lung cancer. Therefore, as demonstrated, an oxidative stress-CBP regulatory axis controls MOB1-K11 acetylation and activates LATS1, thereby activating the Hippo pathway and suppressing YAP/TAZ nuclear translocation and tumor progression.

This research aims to explore what challenges the management leaders face when dealing with flexible working employees in a remote working environment, based on the case of one of China's biggest publishing houses—People's Literature Publishing House. Through primary research that targets the managers and employees of the Publishing House, 63 valid questionnaires were collected. The survey was conducted to testify six pairs of variables, specifically the relationship between leaders' communication (independent variable) and employee performance (response variable), between leaders' mental support and employee performance & psychological health, between the use of technology and leadership effectiveness, and between leaders' promotion of flexible organizational culture and employee performance (e.g. engagement, productivity, creativity). The research findings show that leaders' effective communication, mental support, and promotion of flexible organizational culture are great challenges for leaders to manage the employees who work in the virtual environment and improve overall employee performance. The survey results are of great value to the virtual workplace as leaders should emphasize their skills and abilities to deal with flexible working employees, e.g. empowering, effective online communication, and motivating employees in the remote working environment, etc.

Purpose To evaluate the diagnostic accuracy and clinical impact of gallium-68-labelled fibroblast activation protein inhibitor ([68Ga]Ga-FAPI) PET/CT in primary and metastatic breast cancer and compare the results with those of standard-of-care imaging (SCI) and [18F]Fluorodeoxyglucose (FDG) PET/CT. Methods Patients with diagnosed or suspected breast cancer who underwent concomitant [68Ga] Ga-FAPI (FAPI-46) and [18F]FDG PET/CT scans from October 2019 to March 2022 were retrospectively analysed. Breast ultrasound (US) imaging was performed in all treatment-naïve patients as SCI. The maximum standard uptake value (SUVmax), tumour-to-background ratio (TBR), lesion detection rate, and tumour-node-metastasis (TNM) classifications between [68Ga]Ga-FAPI and [18F]FDG PET/CT were evaluated, and compared. Results Twenty-eight women (median age, 52.5 y; range, 28–80 y) were included. Among them, 5 patients underwent evaluation for a definitive diagnosis of suspected breast lesions, 9 underwent initial staging, and 14 were evaluated for the detection of recurrence. The sensitivities of breast US, [18F]FDG, and [68Ga]Ga-FAPI PET/CT for detecting primary breast tumours were 80%, 70%, and 100%, respectively. Regarding the diagnosis of recurrent/metastatic lesions, the per-lesion detection rate of [68Ga]Ga- FAPI PET/CT was significantly higher than that of [18F]FDG, which including local and regional recurrence (128 vs. 88), neck lymph node (LN) metastases (33 vs. 15), abdomen LN metastases (28 vs. 3), bone metastases (146 vs. 59), and liver metastases (28 vs. 11). Compared with [18F]FDG, [68Ga]Ga-FAPI PET/CT upstaged five patients’ TNM staging/re-staging (7/27, 26%) and changed five patients’ clinical management (5/27, 19%). Compared to SCI, [68Ga]Ga-FAPI upstaged ten patients' TNM staging/re-staging (9/27, 33%) and changed the therapeutic regimen of seven patients (7/27, 26%). There was no significant association between FAPI-derived SUVmax and receptor status/histologic type in both primary and metastatic lesions. Conclusion [68Ga]Ga-FAPI PET/CT was superior to [18F]FDG in diagnosing primary and metastatic breast cancer, with higher radiotracer uptake and TBR, especially in the detection of primary/recurrent tumour, abdominal LN metastases, liver, and bone metastases. [68Ga]Ga-FAPI PET/CT is superior to [18F]FDG and SCI in TNM staging and may improve tumour staging, recurrence detection, and implementation of necessary treatment modifications.

Metastases to gastrointestinal tract from breast cancer are very rare and can be diagnostically challenging. In this case, we reported 18 F-FDG and 68 Ga-FAPI PET/CT findings in a 54-year-old women with such uncommon metastases from breast cancer. Although the primary tumor of breast cancer remained radiologically occult, 68 Ga-FAPI PET/CT showed a far better tumor-to-background ratio than 18 F-FDG PET/CT for detecting the metastatic lesions, especially for detecting the retroperitoneal lymph node and rectal metastases.

Gold nanorods (GNRs) are widely used in various biomedical applications such as disease imaging and therapy due to their unique plasmonic properties. To improve their bioavailability, GNRs often need to be coated with hydrophilic polymers so as to impart stealth properties. Poly(ethylene glycol) (PEG) has been long used as such a coating material for GNRs. However, there is increasing acknowledgement that the amphiphilic nature of PEG facilitates its interaction with protein molecules, leading to immune recognition and consequent side effects. This has motivated the search for new classes of low-fouling polymers with high hydrophilicity as alternative low-fouling surface coating materials for GNRs. Herein, we report the synthesis, characterization, and application of GNRs coated with highly hydrophilic sulfoxide-containing polymers. We investigated the effect of the sulfoxide polymer coating on the cellular uptake and

68 Ga-labeled PET tracer targeting PSMA is a promising diagnostic approach for staging and restating of prostate cancer (PCa), but cases with clinically relevant PCa and false-negative PSMA PET/CT have been reported. In this case, we reported 68 Ga-PSMA, 18 F-FDG, and 68 Ga-FAPI PET/CT findings in a 65-year-old man with de novo metastatic PCa. 68 Ga-FAPI PET/CT detected non-PSMA/FDG-avid primary PCa, consisting with multiparametric MRI findings. The subsequent histopathologic examination confirmed a Gleason 4 + 5 PCa. This case highlighted that 68 Ga-FAPI PET/CT may be a useful imaging modality for primary PCa detection and localization.

Large tumor suppressor 1 (LATS1) is the key kinase controlling activation of Hippo signalling pathway. Post-translational modifications of LATS1 modulate its kinase activity. However, detailed mechanism underlying LATS1 stability and activation remains elusive. Here we report that LATS1 is acetylated by acetyltransferase CBP at K751 and is deacetylated by deacetylases SIRT3 and SIRT4. Acetylation at K751 stabilized LATS1 by decreasing LATS1 ubiquitination and inhibited LATS1 activation by reducing its phosphorylation. Mechanistically, LATS1 acetylation resulted in inhibition of YAP phosphorylation and degradation, leading to increased YAP nucleus translocation and promoted target gene expression. Functionally, LATS1-K751Q, the acetylation mimic mutant potentiated lung cancer cell migration, invasion and tumor growth, whereas LATS1-K751R, the acetylation deficient mutant inhibited these functions. Taken together, we demonstrated a previously unidentified post-translational modification of LATS1 that converts LATS1 from a tumor suppressor to a tumor promoter by suppression of Hippo signalling through acetylation of LATS1.

Ketamine in sub-anaesthetic doses has analgesic properties and an opioid-sparing effect. Intrathecal (i.t.) delivery of analgesics bypasses systemic metabolism and delivers the analgesic agent adjacent to the target receptors in the spinal cord and so small doses are required to achieve effective pain relief. In order to relieve intractable cancer-related pain, sustained-release ketamine formulations are required in combination with a strong opioid because frequent i.t. injection is not practical. In this study, ketamine or ketamine-loaded porous silicon (pSi) were encapsulated into poly(lactic-co-glycolic acid) (PLGA) microparticles by a novel supercritical carbon dioxide (scCO2) method, thereby avoiding the use of organic solvent. Multiple parameters including theoretical drug loading (DL), presence of pSi, size of scCO2 vessel, PLGA type, and use of co-solvent were investigated with a view to obtaining high DL and a sustained-release for an extended period. The most important finding was that the use of a large scCO2 vessel (60 mL) resulted in a much higher encapsulation efficiency (EE) compared with a small vessel (12 mL). In addition, pre-loading ketamine into pSi slightly improved the level of drug incorporation (i.e. EE and DL). Although the in vitro release was mainly affected by the drug payload, the use of the large scCO2 vessel reduced the burst release and extended the release period for PLGA microparticles with 10% or 20% ketamine loading. Together, our findings provide valuable information for optimization of drug delivery systems prepared with the aid of scCO2.

PET imaging targeting fibroblast activation protein (FAP) on the surface of cancer-associated fibroblasts has yielded promising tumor diagnostic results. FAP-2286 contains cyclic peptides as FAP-binding motifs to optimize tumor retention compared with the small molecule FAP inhibitor (FAPI) series (FAPI-04/46). The aim of this study was to evaluate the diagnostic accuracy of the

Polymorphous adenocarcinoma (PAC) is generally an indolent tumor that mostly commonly affects the minor salivary gland. Polymorphous adenocarcinoma with distant metastases is extremely rare. In this case, we reported 18 F-FDG and 68 Ga-FAPI PET/CT imaging findings in a rare case of epiglottic PAC with multiple bone metastases. 68 Ga-FAPI PET/CT showed superiority over 18 F-FDG PET/CT for detecting the primary and metastatic PAC. This case highlighted that 68 Ga-FAPI may be a promising radiopharmaceutical in the diagnosis of PAC, especially for detecting the PACs arising in uncommon sites.

This paper provides a practical design method for hybrid unbonded post-tensioned precast concrete joints. Such joints featured with self-centering capacities have been widely favored in recent years. However, the absence of design methods hinders their further promotion. To solve the issue, two methods for calculating mechanical behavior of the joints were first studied: characteristic points method and iterative method. The effectiveness of the methods was verified by the existing test results. On this basis, a joint design method considering both yield bearing capacity and energy dissipation capacity was proposed. Moreover, to facilitate design, some factors affecting the bearing capacity were discussed. A five-story frame structure was designed by the proposed design method, and the influence of two design factors on structural response was analyzed by utilizing nonlinear time-history method. The analysis results show that: with the increase of energy dissipation factor αs, the post-earthquake residual deformation of the structure tends to increase linearly, while the accumulated damage of the structure will decrease continuously; both overdesign and underdesign of bearing capacity of the joint are unfavorable; and near-field earthquake may cause irreparable damage to structural columns, making the residual deformation of structures contrary to the self-centering capacity of joints, which shall be considered during engineering design.

This paper investigates one kind of interpolation for scattered data by bi-cubic polynomial natural spline, in which the integral of square of partial derivative of two orders to x and to y for the interpolating function is minimal (with natural boundary conditions). Firstly, bi-cubic polynomial natural spline interpolations with four kinds of boundary conditions are studied. By the spline function methods of Hilbert space, their solutions are constructed as the sum of bi-linear polynomials and piecewise bi-cubic polynomials. Some properties of the solutions are also studied. In fact, bi-cubic natural spline interpolation on a rectangular domain is a generalization of the cubic natural spline interpolation on an interval. Secondly, based on bi-cubic polynomial natural spline interpolations of four kinds of boundary conditions, and using partition of unity technique, a Partition of Unity Interpolation Element Method (PUIEM) for fitting scattered data is proposed. Numerical experiments show that the PUIEM is adaptive and outperforms state-of-the-art competitions, such as the thin plate spline interpolation and the bi-cubic polynomial natural spline interpolations for scattered data.

The additional damping ratio (ADR) is an important indicator for evaluating the damping effect of structures with energy-dissipation devices. Most existing methods for determining the ADR require an analysis of the structural dynamic response and complex iterative calculations. An innovative simplified calculation method for determining the ADR of a structure supplemented by nonlinear viscous dampers is proposed. This method does not require the dynamic response of the structure to be calculated and only requires the structural characteristics, excitation frequency, and damper parameters. In this study, several typical calculation methods for the ADR were analysed. Then, a calculation formula for the ADR was derived with consideration of harmonic excitation under the condition where the excitation frequency is equal to the structural natural frequency, without calculation of the structural dynamic response or an iterative process. The effect of the excitation frequency on the calculated value of the ADR with different damping exponents was studied. Accordingly, the response spectrum average period (RSAP) was considered as the excitation period of ground motion to evaluate the excitation frequency, and a simplified calculation method for the ADR considering the effect of the excitation frequency characterised by the RSAP of the ground motion was established. Finally, the accuracy and effectiveness of the proposed method were verified by comparison with ADRs calculated using other methods.

Slug, a member of the Snail family of transcriptional repressors, plays a key role in cancer progression, cellular plasticity, and epithelial to mesenchymal transition (EMT). Slug is a fast-turnover protein and its stability is controlled by post-translational modifications. Here, we identified that Slug is acetylated by acetyltransferase CREB-binding protein (CBP) in breast cancer cells. CBP directly interacts with the C-terminal domain of Slug through its catalytic histone acetyltransferase (HAT) domain, leading to acetylation of Slug at lysines 166 and 211. Analysis with acetylation-specific antibodies revealed that Slug is highly acetylated in metastatic breast cancer cells. Notably, Slug acetylation, mediated by CBP at lysines 166 and 211, doubles its half-life and increases its stability. Further, acetylated Slug downregulates the expression of E-cadherin, the epithelial marker, and upregulates the expression of N-cadherin and vimentin, thereby promoting breast cancer cell migration. In conclusion, the present study demonstrates that CBP-mediated Slug acetylation increases its stability, promoting EMT and migration of breast cancer cells.

The conjugation of hydrophilic polymers to proteins is an effective approach to prolonging their circulation time in the bloodstream and, hence, improving their delivery to the target region of interest. In this work, we report the synthesis of protein-polymer conjugates using a highly water-soluble sulfoxide-containing polymer, poly(2-(methylsulfinyl)ethyl acrylate) (PMSEA), through a combination of "grafting-to" and "grafting-from" methods. Oligomeric MSEA was synthesized by conventional reversible addition-fragmentation chain transfer (RAFT) polymerization and subsequently conjugated to lysozyme to produce a macromolecular chain transfer agent. This was followed by a visible light-mediated chain extension polymerization of MSEA to obtain a lysozyme-PMSEA conjugate (Lyz-PMSEA). It was found that the Lyz-PMSEA conjugate exhibited much reduced macrophage cellular uptake compared with unmodified and PEGylated lysozyme. Moreover, the Lyz-PMSEA conjugate was able to circulate longer in the bloodstream, demonstrating significantly improved pharmacokinetics demanded for pharmaceutical applications.

The conjugation of hydrophilic low-fouling polymers to therapeutic molecules and particles is an effective approach to improving their aqueous stability and solubility, and extending their pharmacokinetics. Recent concerns over the immunogenicity of poly(ethylene glycol) has highlighted the importance of identifying alternative low fouling polymers. Herein, we report a new class of synthetic water-soluble homo-fluoropolymers with a sulfoxide side-chain structure. The incorporation of fluorine enables direct imaging of the homopolymer by 19 F MRI, negating the need for additional synthetic steps to attach an imaging moiety. These self-reporting fluoropolymers show outstanding imaging sensitivity and as such represent a new class of low-fouling polymer for bioconjugation and in vivo tracking.

In this study, we investigated the role of [This retrospective multicenter analysis included 34 patients with histologically confirmed GSRCCs from four medical centers. The maximum standard uptake value (SUVData were analyzed from 27 paired PET/CT and 7 paired PET/MRI scans for 34 GSRCC patients (16 men and 18 women) who had a median age of 51 years (range: 25-85 years). [The results from this multicenter retrospective analysis justify the clinical use of [• [

Oxidative DNA damage contributes to aging and the pathogenesis of numerous human diseases including cancer. 8-hydroxyguanine (8-oxoG) is the major product of oxidative DNA lesions. Although OGG1-mediated base excision repair is the primary mechanism for 8-oxoG removal, DNA mismatch repair has also been implicated in processing oxidative DNA damage. However, the mechanism of the latter is not fully understood. Here, we treated human cells defective in various 8-oxoG repair factors with H