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Ten undescribed diterpenoids (1-10) and three undescribed phenanthrene derivatives (11-13), together with seven known compounds, were isolated from the roots of Baliospermum solanifolium. Their structures were determined by a combination of spectroscopic data analysis, electronic circular dichroism calculations and single-crystal X-ray diffraction studies. Compounds 1-7 (baliosperoids A-G) represent the examples of 20-nor-ent-podocarpane class first discovered in nature. In particular, compound 7 possesses a unique 2,3-seco ring system incorporating γ-butanolide moiety. All isolates were assessed for their cytotoxic activities against HT-29, HCT-116, HCT-15, MCF-7, and A549 cell lines as well as their inhibitory effects on lipopolysaccharide-induced NO production in RAW264.7 cells. Compound 1, a 20-nor-ent-podocarpane-type diterpenoid possessing a Δ 1,2 double bond, not only exhibited considerable proliferation inhibition against five human cancer cell lines, with IC 50 values ranging from 4.13 to 23.45 μM, but also displayed the most potent inhibitory activity on NO production with IC 50 value at the nanomolar level (0.63 ± 0.21 μM)., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Purpose: We evaluated the feasibility and safety of using a new unibody outer double-branched stent-graft system to reconstruct the canine ascending aorta, aortic arch, and supra-aortic vessels., Materials and Methods: The outer-branched stent-graft was a unibody design. The branched stent-graft consisted of a main stent-graft and 2 branches. The introducer system included a tri-channel catheter, 2 detachable sleeves, a front fixing device, a constraining wire, and a curved outer sheath. The branched stent-graft was loaded into the introducer system. Ten adult mongrel dogs underwent general anesthesia, and the branched stent-grafts were deployed into the canine ascending aorta, aortic arch, and supra-aortic vessels by the introducer system. All animals were followed up for 3 months. At the end of the follow-up period, computed tomographic angiography (CTA) was performed to observe the patency of the branched stent-grafts., Results: The mean operation time was 142.7±13.7 minutes. The mean fluoroscopy time was 20.73±2.22 minutes. The mean dosage of contrast agent was 95.9±8.7 mL. During the operation, the tri-channel catheters successfully paralleled the wires in the aorta. All 10 branched stent-grafts were successfully implanted into the canine ascending aorta and aortic arch. There were no symptoms of cerebral embolization and no incision infection during the follow-up period. Computed tomographic angiography and specimens showed that the branched stent-grafts and native vessels were patent, the inner surfaces of the branched stent-grafts were covered by neointima, and there was no retrograde aortic dissection in the ascending aorta., Conclusions: This animal research demonstrated that the unibody outer double-branched stent-graft system could be applied to reconstruct the canine ascending aorta, aortic arch, and supra-aortic vessels., Clinical Impact: Thoracic endovascular aortic repair has been the main treatment method for aortic aneurysms or dissections involving the descending thoracic aorta. However, the aortic arch and ascending aorta remain the last segments of the aorta without a validated and routinely used endovascular option. In this research, we designed a new unibody outer branched stent-graft system to reconstruct the distal ascending aorta, aortic arch and supra-aortic vessels. The unibody outer branched stent-graft system could be applied to treat aortic pathologies which involve the middle and distal proximal ascending aorta, aortic arch and proximal descending aorta., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

A fast scanner of optical-resolution photoacoustic microscopy is inherently vulnerable to perturbation, leading to severe image distortion and significant misalignment among multiple 2D or 3D images. Restoration and registration of these images is critical for accurately quantifying dynamic information in long-term imaging. However, traditional registration algorithms face a great challenge in computational throughput. Here, we develop an unsupervised deep learning based registration network to achieve real-time image restoration and registration. This method can correct artifacts from B-scan distortion and remove misalignment among adjacent and repetitive images in real time. Compared with conventional intensity based registration algorithms, the throughput of the developed algorithm is improved by 50 times. After training, the new deep learning method performs better than conventional feature based image registration algorithms. The results show that the proposed method can accurately restore and register the images of fast-scanning photoacoustic microscopy in real time, offering a powerful tool to extract dynamic vascular structural and functional information., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier GmbH.)

Background: Increasing evidence suggests that DXS253E is critical for cancer development and progression, but the function and potential mechanism of DXS253E in colorectal cancer (CRC) remain largely unknown. In this study, we evaluated the clinical significance and explored the underlying mechanism of DXS253E in CRC., Methods: DXS253E expression in cancer tissues was investigated using the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The Kaplan-Meier plot was used to assess the prognosis of DXS253E. The cBioPortal, MethSurv, and Tumor Immune Estimation Resource (TIMER) databases were employed to analyze the mutation profile, methylation, and immune infiltration associated with DXS253E. The biological functions of DXS253E in CRC cells were determined by CCK-8 assay, plate cloning assay, Transwell assay, flow cytometry, lactate assay, western blot, and qRT-PCR., Results: DXS253E was upregulated in CRC tissues and high DXS253E expression levels were correlated with poor survival in CRC patients. Our bioinformatics analyses showed that high DXS253E gene methylation levels were associated with the favorable prognosis of CRC patients. Furthermore, DXS253E levels were linked to the expression levels of several immunomodulatory genes and an abundance of immune cells. Mechanistically, the overexpression of DXS253E enhanced proliferation, migration, invasion, and the aerobic glycolysis of CRC cells through the AKT/mTOR pathway., Conclusions: We demonstrated that DXS253E functions as a potential role in CRC progression and may serve as an indicator of outcomes and a therapeutic target for regulating the AKT/mTOR pathway in CRC., (© 2024. The Author(s).)

Hierarchical assembly of arc-like fractal nanostructures not only has its unique self-similarity feature for stability enhancement but also possesses the structural advantages of highly exposed surface-active sites for activity enhancement, remaining a great challenge for high-performance metallic nanocatalyst design. Herein, we report a facile strategy to synthesize a novel arc-like hierarchical fractal structure of PtPd bimetallic nanoparticles (h-PtPd) by using pyridinium-type ionic liquids as the structure-directing agent. Growth mechanisms of the arc-like nanostructured PtPd nanoparticles have been fully studied, and precise control of the particle sizes and pore sizes has been achieved. Due to the structural features, such as size control by self-similarity growth of subunits, structural stability by nanofusion of subunits, and increased numbers of exposed active atoms by the curved homoepitaxial growth, h-PtPd displays outstanding electrocatalytic activity toward oxygen reduction reaction and excellent stability during hydrothermal treatment and catalytic process.

Photoacoustic microscopy can image many biological molecules and nano-agents in vivo via low-scattering ultrasonic sensing. Insufficient sensitivity is a long-standing obstacle for imaging low-absorbing chromophores with less photobleaching or toxicity, reduced perturbation to delicate organs, and more choices of low-power lasers. Here, the photoacoustic probe design is collaboratively optimized and a spectral-spatial filter is implemented. A multi-spectral super-low-dose photoacoustic microscopy (SLD-PAM) is presented that improves the sensitivity by ≈33 times. SLD-PAM can visualize microvessels and quantify oxygen saturation in vivo with ≈1% of the maximum permissible exposure, dramatically reducing potential phototoxicity or perturbation to normal tissue function, especially in imaging of delicate tissues, such as the eye and the brain. Capitalizing on the high sensitivity, direct imaging of deoxyhemoglobin concentration is achieved without spectral unmixing, avoiding wavelength-dependent errors and computational noises. With reduced laser power, SLD-PAM can reduce photobleaching by ≈85%. It is also demonstrated that SLD-PAM achieves similar molecular imaging quality using 80% fewer contrast agents. Therefore, SLD-PAM enables the use of a broader range of low-absorbing nano-agents, small molecules, and genetically encoded biomarkers, as well as more types of low-power light sources in wide spectra. It is believed that SLD-PAM offers a powerful tool for anatomical, functional, and molecular imaging., (© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Estrogen plays a protective role in colorectal cancer (CRC) and primarily functions through estrogen receptor β (ERβ). However, clinical strategies for CRC therapy associated with ERβ are still under investigation. Our discoveries identified WFDC3 as a tumor suppressor that facilitates estrogen-induced inhibition of metastasis through the ERβ/TGFBR1 signaling axis. WFDC3 interacts with ERβ and increases its protein stability by inhibiting its proteasome-dependent degradation. WFDC3 represses TGFBR1 expression through ERβ-mediated transcription. Blocking TGFβ signaling with galunisertib, a drug used in clinical trials that targets TGFBR1, impaired the migration of CRC cells induced by WFDC3 depletion. Moreover, there was clinical significance to WFDC3 in CRC, as CRC patients with high WFDC3 expression in tumor cells had favorable prognoses. Therefore, this work suggests that WFDC3 could be an indicator for therapies targeting the estrogen/ERβ pathway in CRC patients., (© 2023. The Author(s).)

Purpose: To evaluate the feasibility and efficacy of a transmesenteric vein extrahepatic portosystemic shunt (TmEPS) for the treatment of cavernous transformation of the portal vein (CTPV)., Materials and Methods: The clinical data of 20 patients with CTPV who underwent TmEPS between December 2020 and January 2022 ​at Henan Provincial People's Hospital were retrospectively collected. The superior mesenteric vein (SMV) trunk was patent or partially occluded in these patients. An extrahepatic portosystemic shunt between the inferior vena cava and the SMV was established using a stent graft through an infraumbilical median longitudinal mini-laparotomy. The technical success, efficacy, and complication rates were evaluated, and the pre- and postoperative SMV pressures were compared. Patients' clinical outcomes and shunt patency were assessed., Results: TmEPS was successfully performed in 20 patients. The initial puncture success rate of the balloon-assisted puncture technique is 95%. The mean SMV pressure decreased from 29.1 ​± ​2.9 ​mmHg to 15.6 ​± ​3.3 ​mmHg (p ​< ​0.001). All symptoms of portal hypertension resolved. No fatal procedural complications occurred. During the follow-up period, hepatic encephalopathy occurred in two patients. The remaining patients remained asymptomatic. All shunts were patent., Conclusions: TmEPS is a feasible, safe, and effective treatment option for patients with CTPV., Competing Interests: Tianxiao Li is an associate editors-in-chief for Journal of Interventional Medicine and was not involved in the editorial review or the decision to publish this article. All authors declare that there are no competing interests., (© 2023 Shanghai Journal of Interventional Radiology Press. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co. Ltd.)

Simultaneous photoacoustic (PA) and ultrasound (US) imaging provides rich optical and acoustic contrasts with high sensitivity, specificity, and resolution, making it a promising tool for diagnosing and assessing various diseases. However, the resolution and penetration depth tend to be contradictory due to the increased attenuation of high-frequency ultrasound. To address this issue, we present simultaneous dual-modal PA/US microscopy with an optimized acoustic combiner that can maintain high resolution while improving the penetration of ultrasound imaging. A low-frequency ultrasound transducer is used for acoustic transmission, and a high-frequency transducer is used for PA and US detection. An acoustic beam combiner is utilized to merge the transmitting and receiving acoustic beams with a predetermined ratio. By combining the two different transducers, harmonic US imaging and high-frequency photoacoustic microscopy are implemented. In vivo experiments on the mouse brain demonstrate the simultaneous PA and US imaging ability. The harmonic US imaging of the mouse eye reveals finer iris and lens boundary structures than conventional US imaging, providing a high-resolution anatomical reference for co-registered PA imaging., Competing Interests: Lidai Wang has a financial interest in PATech Limited, which, however, did not support this work. All authors declare no competing interests., (© 2023 Optica Publishing Group under the terms of the Optica Open Access Publishing Agreement.)

Screening cancer genomes has provided an in-depth characterization of genetic variants such as copy number variations (CNVs) and gene expression changes of non-coding transcripts. Single-dimensional experiments are often designed to differentiate a patient cohort into various sets with the aim of identifying molecular changes among groups; however, this may be inadequate to decipher the causal relationship between molecular signatures in individual patients. To overcome this challenge with respect to personalized medicine, we implemented a patient-specific multi-dimensional integrative approach to uncover coherent signals from multiple independent platforms. In particular, we focused on the consistent gene dosage effects of CNVs for both mRNA and long non-coding RNA (lncRNA) expression in nine colorectal cancer patients. We identified 511 CNV-lncRNA-mRNA regulatory triplets associated with CNVs and aberrant expression of both mRNAs and lncRNAs. By filtering out inconsistent changes among CNVs, mRNAs, and lncRNAs, we further characterized 165 coherent motifs associated with 56 genes. In total, 108 motifs were linked with 31 copy number gains, 44 upregulated lncRNAs, and 45 upregulated mRNAs. Another 57 coherent downregulated motifs were also collected. We discuss how for many of these CNV-lncRNA-mRNA regulatory triplets, their clinical impact remains to be explored, including survival time, microsatellite instability, tumor stage, and primary tumor sites. By validating two example CNV-lncRNA-mRNA triplets with up- and down-regulation, we confirmed that individual variations in multiple dimensions are a robust tool to identify reliable molecular signals for personalized medicine. In summary, we utilized a patient-specific computational pipeline to explore the consistent CNV-driven motifs consisting of lncRNAs and mRNAs. We also identified LSM14B as a potential promoter in colorectal cancer progression, suggesting that it may serve as a target for colorectal cancer treatment., Competing Interests: Declaration of competing interest The authors have declared no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Angiogenesis has great potential in the treatment of acute limb ischemia (ALI). Here, we aimed to investigate the effect and mechanism of Aryl hydrocarbon receptor (AhR) on angiogenesis in ALI., Methods: The ALI mouse model was constructed by femoral artery ligation, and the cell ischemia injury was induced by Hypoxia/serum deprivation. The laser doppler perfusion imaging was executed to detect the limb blood flow velocity. The tube formation assay was performed to evaluate angiogenesis. The cell viability was measured by 3-(45)-dimethylthiahiazo(-z-y1)-35-di-phenytetrazoliumromide. The cell migration was detected by wound healing assay. Hematoxylin-eosin, immunohistochemistry, immunofluorescence, dual-luciferase reporter gene assay, and Chromatin immunoprecipitation assay were conducted., Results: In ALI models, AhR expression was increased and translocated from cytoplasm to nucleus. Besides, necrosis and inflammatory infiltration were also increased in gastrocnemius tissues of model mice. In addition, AhR loss (LV-sh-AhR) promoted cell viability, angiogenesis, and migration, and also elevated the levels of vascular endothelial growth factor (VEGF), Tie2, and Ang2 in HUVEC models with Hypoxia/serum deprivation injury. Meanwhile, the interaction between AhR and signal transducer and activator of transcription 1 (STAT1), as well as STAT1 and VEGF, has also been confirmed. Co-transfection of LV-sh-AhR and LV-STAT1 suppressed cell viability, angiogenesis, and migration of injured HUVECs. Furthermore, injection of AAV2/9-shAhR in vivo also promoted angiogenesis, which was consistent with the in vitro experimental results., Conclusions: In ALI models, activated AhR was translocated to the nucleus and down-regulated VEGF expression by promoting the transcriptional activity of STAT1, thereby inhibiting endothelial angiogenesis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Acoustic-resolution photoacoustic micro- scopy (AR-PAM) system can provide 3-D images of facial tissues. The lateral resolution of AR-PAM depends on the numerical aperture (NA) of the acoustic lens and the central frequency of the ultrasonic transducer. There is a trade-off between resolution enhancement and imaging depth. The acoustic beam is tight in the acoustic focal plane but expands in the out-of-focus regions, deteriorating the resolution. High-NA AR-PAM has depth-variant resolution. Synthetic aperture focusing technique (SAFT) based on a virtual detector (VD) concept can compensate for the beam shape and improve the lateral resolution via beamforming. Although, beamforming can enhance the resolution but the lateral resolution in the focal plane is still limited by acoustic diffraction. Structured-illumination can shift the spatial spectrum of an image to low frequencies hence high-frequency contents can be reserved to overcome the diffraction limit. Conventional structured-illumination via using a three-phase-shifting method can improve the resolution by two folds. Here, a modified phase-shifting method is used to generate the second harmonic of the fringes and double the spectral shift. In this idea, higher frequency information compared to the three-phase shifting method can fall into the band-limited system response. The modified phase-shifting method expands the spatial bandwidth and increases the lateral resolution by five folds. The mathematical relations and the theory are discussed in the context. Tungsten filament result shows resolution improvement from 44.6 [Formula: see text] to 11.3 [Formula: see text] by the modified structured illumination. In vivo and ex vivo experimental results validate the system performance.

The East Friesian sheep is one of the important high-yielding dairy sheep breeds, but still little is known about their genetic and genomic variation during domestication. Therefore, we analyzed the genomic data of 46 sheep with the aim of identifying candidate genes that are closely related to milk production traits. Our genomic data consisted of 20 East Friesian sheep and 26 Asian Mouflon wild sheep. Finally, a total of 32590241 SNPs were identified, of which 0.61% (198277) SNPs were located in exonic regions. After further screening, 122 shared genomic regions in the top 1% of F ST and top 1% of Nucleotide diversity ratio were obtained. After genome annotation, these 122 candidate genomic regions were found to contain a total of 184 candidate genes. Finally, the results of KEGG enrichment analysis showed four significantly enriched pathways ( P < 0.05): beta-Alanine metabolism ( SMOX, HIBCH ), Pathways in cancer ( GLI2, AR, TXNRD3, TRAF3, FGF16 ), Non-homologous end-joining ( MRE11 ), Epstein-Barr virus infection ( TRAF3, PSMD13, SIN3A ). Finally, we identified four important KEGG enrichment pathways and 10 candidate genes that are closely related to milk production in East Friesian sheep. These results provide valuable candidate genes for the study of milk production traits in East Friesian sheep and lay an important foundation for the study of milk production traits., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Li, Yuan, Wang, Zhang, Zhao, Chen, Xu, Zhao, Li and Zhang.)

Optical-resolution photoacoustic microscopy offers high-resolution, label-free hemodynamic and functional imaging to many biomedical applications. However, long-standing technical barriers, such as limited field of view, bulky scanning probes, and slow imaging speed, have limited the application of optical-resolution photoacoustic microscopy. Here, we present freehand scanning photoacoustic microscopy (FS-PAM) that can flexibly image various anatomical sites. We develop a compact handheld photoacoustic probe to acquire 3D images with high speed, and great flexibility. The high scanning speed not only enables video camera mode imaging but also allows for the first implementation of simultaneous localization and mapping (SLAM) in photoacoustic microscopy. We demonstrate fast in vivo imaging of some mouse organs, and human oral mucosa. The high imaging speed greatly reduces motion artifacts and distortions from tissue moving, breathing, and unintended handshaking. We demonstrate small-lesion localization in a large region of the brain. FS-PAM offers a flexible high-speed imaging tool with an extendable field of view, enabling more biomedical imaging applications., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Lidai Wang reports financial support was provided by City University of Hong Kong. Lidai Wang has patent pending to United States Patents and Trademark Office., (© 2022 Published by Elsevier GmbH.)

Background: Effective theranostic of hepatocellular carcinoma (HCC) in an early-stage is imminently demanded to improve its poor prognosis. Combination of the near-infrared (NIR) photoacoustic imaging (PAI) and fluorescence imaging (FLI) can provide high temporospatial resolution, outstanding optical contrast, and deep penetration and thus is promising for accurate and sensitive HCC diagnosis., Methods: A versatile CXCR4-targeted Indocyanine green (ICG)/Platinum (Pt)-doped polydopamine melanin-mimic nanoparticle (designated ICG/Pt@PDA-CXCR4, referred to as IPP-c) is synthesized as an HCC-specific contrast agent for high-resolution precise diagnostic PAI/FLI and optical imaging-guided targeted photothermal therapy (PTT)/photodynamic therapy (PDT) of orthotopic small hepatocellular carcinoma (SHCC)., Results: The multifunctional targeted nanoparticle yields superior HCC specificity, high imaging contrast in both PAI and FLI, good stability, reliable biocompatibility, effective singlet oxygen generation and superior photothermal conversion efficiency (PCE, 58.7%) upon 808-nm laser irradiation. The targeting ability of IPP-c was validated in in vitro experiments on selectively killing the CXCR4-overexpressing HCC cells. Moreover, we test the efficient dual-modal optical precision diagnosis properties of IPP-c via in vivo experiments on targeted particle accumulation in an early-stage SHCC mouse model (tumor diameter about 1.2 mm). Then, under the guidance of real-time optical imaging, effective and mini-invasive PTT/PDT of orthotopic SHCCs were demonstrated without damaging adjacent liver tissues or other major organs., Conclusion: This study presented a multifunctional CXCR4-targeted nanoparticle to conduct effective and mini-invasive phototherapeutics of orthotopic SHCCs via the real-time quantitative guidance by optical imaging, which provided a new perception for building a versatile targeted nanoplatform for phototheranostics of early-stage HCC., Competing Interests: The authors declare that they have no conflict of interest., (© 2022 Qi et al.)

Accurate identification and quantification of microvascular patterns are important for clinical diagnosis and therapeutic monitoring using optical-resolution photoacoustic microscopy (OR-PAM). Due to its limited depth of field, conventional OR-PAM may not fully reveal microvascular patterns with enough details in depth range, which affects the segmentation and quantification. Here, we propose a robust vascular quantification approach via combining multi-focus image fusion with enhancement filtering (MIFEF). The multi-focus image fusion is constructed based on multi-scale gradients and image matting to improve image fusion quality by considerably achieving accurate focus measurement for initial segmentation as well as decision map refinement. The enhancement filtering identifies the vessels and handles noise without deforming microvasculature. The performance of the MIFEF were evaluated employing a leaf phantom, mouse livers and brains. The proposed method for OR-PAM can significantly facilitate the clinical provision of optical biopsy of vascular-related diseases.

Background: To establish a canine model of aortic arch aneurysm that is suitable for research on new devices and techniques applied to the aortic arch., Materials and Methods: Fifteen mongrel dogs underwent surgery. The autologous pericardial patch was sewn on the aortotomy site in the anterior wall of the aortic arch. The animals were followed up for 3 months postoperatively. Computed tomography angiography was used to visualize and measure the aneurysm model. Hematoxylin and eosin staining was used to observe the histological characteristics of the aneurysm model. Changes in aneurysm diameter over time were analyzed using analysis of variance., Results: One dog died of hemorrhage during surgery. Fourteen dogs survived the surgical procedure. Two of them died on the first postoperative day because of ruptures at the suturing margin. The diameter of the aneurysm model was twice as large as that of the aortic arch. There was no significant change in the maximum diameter of the aneurysm model during the follow-up period., Conclusions: We established a controllable and stable aortic arch aneurysm model created with an autologous pericardium patch. The aneurysm model can be used to research endoleaks after thoracic endovascular aortic repair and new endovascular techniques can be applied to the aortic arch., Competing Interests: We declare that we do not have any commercial or associative interest that represents a conflict of interest in connection with the work submitted., (© 2022 Shanghai Journal of Interventional Radiology Press. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co. Ltd.)

Autophagy plays a crucial role in colorectal cancer (CRC) development. Our previous study suggested that serine/threonine protein kinase 25 (STK25) regulates aerobic glycolysis in CRC cells. Glycolysis modulates cellular autophagy during tumor growth; however, the role of STK25 in autophagy remains unclear. In this study, we found that STK25 expression was decreased in CRC tissues and CRC patients with high STK25 expression had a favorable prognosis. Functional assays suggested that STK25 inhibition promoted autophagy in CRC cells. Overexpression of STK25 exhibited the opposite effects. Moreover, the results of western blot demonstrated that silencing STK25 induced autophagy by activating the JAK2/STAT3 pathway. Therefore, STK25 could be a potential indicator for therapies targeting the JAK2/STAT3 pathway in CRC., (© 2022 Wiley Periodicals LLC.)

Genomic instability plays a key role in the initiation and progression of colorectal cancer (CRC). Although cancer driver genes in CRC have been well characterized, identifying novel genes associated with carcinogenesis and treatment remains challenging because of tumor heterogeneity. Here, we analyzed the genomic alterations of 45 samples from CRC patients in northern China by whole-exome sequencing. In addition to the identification of six well-known CRC driver genes (APC, TP53, KRAS, FBXW7, PIK3CA, and PABPC), two tumor-related genes (MTCH2 and HSPA6) were detected, along with RRP7A and GXYLT1, which have not been previously linked to cancer. GXYLT1 was mutated in 40% (18/45) of the samples in our cohort. Functionally, GXYLT1 promoted migration and invasion in vitro and metastasis in vivo, while the GXYLT1 S212* mutant induced significantly greater effect. Furthermore, both GXYLT1 and GXYLT1 S212* interacted with ERK2. GXYLT1 induced metastasis via a mechanism involving the Notch and MAPK pathways, whereas the GXYLT1 S212* mutant mainly promoted metastasis by activating the MAPK pathway. We propose that GXYLT1 acts as a novel metastasis-associated driver gene and GXYLT1 S212* might serve as a potential indicator for therapies targeting the MAPK pathway in CRC., (© 2022. The Author(s).)

Circular RNA (circRNA) is a non-coding RNA molecule that lacks polyadenylated tails and is highly stable, abundant, and conserved in human cells. CircRNAs can serve as a competing endogenous RNA (ceRNA) to sponge microRNAs (miRNA) and block their effects on target mRNA expression. CircRNAs also have possible relevance to cancer and therefore may be considered as ideal biomarkers for monitoring cancer progression. Of the about 300,000 predicted human circRNAs, only a few have validated biological functions related to cancer. To better understand the ceRNA role of circRNAs in colorectal cancer (CRC), we performed genome-wide circRNA-based RNA-sequencing (RNA-Seq) on nine CRC tumor samples and their paired histologically normal adjacent tissue samples. By profiling the mRNA expression in the same patients, we further explored the expression correlation between circRNAs and mRNAs generated from the same parental gene. Focusing on the concordant differential expression between circRNAs and mRNAs, we substantially reduced the regulatory noise. In total, we identified 694 circRNA-mRNA pairs that were consistently up or downregulated between tumor and normal tissues. These 694 circRNA-mRNA pairs are from 182 protein-coding genes associated with hormone responses and chemotaxis. Of these 182 genes, 43 are downstream targets of three highly conserved miRNAs (miR-410-3p, miR-135a, and miR-30a). Interestingly, these 43 genes are highly mutated in another cohort from eight independent CRC studies, which have significant effects on patient survival time. Focusing on miR-410-3p and its target oncogene MET, we experimentally validated the ceRNA regulatory motif of circMET. Notably, circMET is substantially upregulated in CRC cell lines and could promote cell proliferation and growth. By confirming the regulatory relationship between miR-410-3p and circMET, we propose a new mechanism for the observed sustained activation of MET in CRC. In conclusion, our work identifies a novel regulatory role of circMET and provides a potential diagnostic biomarker for CRC., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Rational composition design of trimetallic phosphide catalysts is of significant importance for enhanced surface reaction and efficient catalytic performance. Herein, hierarchical Co x Ni y Fe z P with precise control of stoichiometric metallic elements ( x:y:z = (1-10):(1-10):1) has been synthesized, and Co 1.3 Ni 0.5 Fe 0.2 P, as the most optimal composition, exhibits remarkable catalytic activity ( η = 320 mV at 10 mA cm -2 ) and long-term stability (ignorable decrease after 10 h continuous test at the current density of 10 mA cm -2 ) toward oxygen evolution reaction (OER). It is found that the surface P in Co 1.3 Ni 0.5 Fe 0.2 P was replaced by O under the OER process. The density function theory calculations before and after long-term stability tests suggest the clear increasing of the density of states near the Fermi level of Co 1.3 Ni 0.5 Fe 0.2 P/Co 1.3 Ni 0.5 Fe 0.2 O, which could enhance the OH - adsorption of our electrocatalysts and the corresponding OER performance., Electronic Supplementary Material: Supplementary material is available in the online version of this article at 10.1007/s40843-022-2061-x., (© Science China Press and Springer-Verlag GmbH Germany, part of Springer Nature 2022.)

Optical-resolution photoacoustic microscopy (OR-PAM) can image blood oxygen saturation (sO 2 ) in vivo with high resolution and excellent sensitivity and offers a great tool for neurovascular study and early cancer diagnosis. OR-PAM ignores the wavelength-dependent optical attenuation in superficial tissue, which cause errors in sO 2 imaging. Monte Carlo simulation shows that variations in imaging depth, vessel diameter, and focal position can cause up to  ∼ 60 % decrease in sO 2 imaging. Here, we develop a self-fluence-compensated OR-PAM to compensate for the wavelength-dependent fluence attenuation. We propose a linearized model to estimate the fluence attenuations and use three optical wavelengths to compensate for them in sO 2 calculation. We validate the model in both numerical and physical phantoms and show that the compensation method can effectively reduce the sO 2 errors. In functional brain imaging, we demonstrate that the compensation method can effectively improve sO 2 accuracy, especially in small vessels. Compared with uncompensated ones, the sO 2 values are improved by 10~30% in the brain. We monitor ischemic-stroke-induced brain injury which demonstrates great potential for the pre-clinical study of vascular diseases.

Optical-resolution photoacoustic microscopy (OR-PAM) enjoys superior spatial resolution and has received intense attention in recent years. The application, however, has been limited to shallow depths because of strong scattering of light in biological tissues. In this work, we propose to achieve deep-penetrating OR-PAM performance by using deep learning enabled image transformation on blurry living mouse vascular images that were acquired with an acoustic-resolution photoacoustic microscopy (AR-PAM) setup. A generative adversarial network (GAN) was trained in this study and improved the imaging lateral resolution of AR-PAM from 54.0 µm to 5.1 µm, comparable to that of a typical OR-PAM (4.7 µm). The feasibility of the network was evaluated with living mouse ear data, producing superior microvasculature images that outperforms blind deconvolution. The generalization of the network was validated with in vivo mouse brain data. Moreover, it was shown experimentally that the deep-learning method can retain high resolution at tissue depths beyond one optical transport mean free path. Whilst it can be further improved, the proposed method provides new horizons to expand the scope of OR-PAM towards deep-tissue imaging and wide applications in biomedicine., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Authors.)

Early diagnosis and effective treatment of hepatocellular carcinoma (HCC) is quite critical for improving patients' prognosis. The combination of second near-infrared window photoacoustic imaging (NIR-II PAI) and T 2 -magnetic resonance imaging ( T 2 -MRI) is promising for achieving omnibearing information on HCC diagnosis due to the complementary advantages of outstanding optical contrast, high temporospatial resolution and soft-tissue resolution. Thus, the rational design of a multifunctional targeted nanoplatform with outstanding performance in dual-modal NIR-II PAI/ T 2 -MRI is particularly valuable for precise diagnosis and imaging-guided non-invasive photothermal therapy (PTT) of early-stage HCC. Herein, a versatile targeted organic-inorganic hybrid nanoprobe was synthesized as a HCC-specific contrast agent for sensitive and efficient theranostics. The developed multifunctional targeted nanoprobe yielded superior HCC specificity, reliable stability and biocompatibility, high imaging contrast in both NIR-II PAI and T 2 -MRI, and an excellent photothermal conversion efficiency (74.6%). Furthermore, the theranostic efficiency of the targeted nanoprobe was systematically investigated using the orthotopic early HCC-bearing mice model. The NIR-II PAI exhibited sensitive detection of ultra-small HCCs (diameter less than 1.8 mm) and long-term real-time monitoring of the tumor and nanoprobe targeting process in deep tissues. The T 2 -MRI demonstrated clear imaging contrast and a spatial relationship between micro-HCC and adjacent structures for a comprehensive description of the tumor. Moreover, when using the targeted nanoprobe, the non-invasively targeted PTT of orthotopic early HCC was carried out under reliable dual-modal imaging guidance with remarkable anti-tumor efficiency and biosafety. This study provides an insight for constructing a multifunctional targeted nanoplatform for precise and comprehensive theranostics of early-stage HCC, which would greatly benefit the patients in the era of precision medicine.

A novel super-resolution volumetric photoacoustic microscopy, based on the theory of structured-illumination, is proposed in this paper. The structured-illumination will be introduced in order to surpass the diffraction limit in a photoacoustic microscopy (PAM) structure. Through optical excitation of the targeted object with a sinusoidal spatial fringe pattern, the object's frequency spectrum is forced to shift in the spatial frequency domain. The shifting in the desired direction leads to the passage of the high-frequency contents of the object through the passband of the acoustic diffraction frequency response. Finally, combining the low-frequency image with the high-frequency parts in four regular orientations in the spatial frequency domain is equivalent to imaging the targeted object with an imaging system of two-fold bandwidth and thus half lateral resolution. In order to obtain the image of out-of-focus regions and improve the lateral resolution outside the focal region of a PAM imaging system, Fourier-domain reconstruction algorithm based on the synthetic aperture focusing technique (SAFT) using the virtual detector concept is utilized for reduction in the required computational load and time. The performance of the proposed imaging system is validated with in vivo and ex vivo targets. The experimental results obtained from several tungsten filaments in the depth range of 1.2 mm, show an improvement of -6 dB lateral resolution from 55- [Formula: see text] to 25- [Formula: see text] and also an improvement of signal-to-noise ratio (SNR) from 16-22 dB to 27-33 dB in the proposed system.

We report fiber-based dual-foci fast-scanning OR-PAM that can double the scanning rate without compromising the imaging resolution, the field of view, and the detection sensitivity. To achieve fast scanning speed, the OR-PAM system uses a single-axis water-immersible resonant scanning mirror that can confocally scan the optical and acoustic beams at 1018 Hz with a 3-mm range. Pulse energies of 45∼100-nJ are sufficient for acquiring vascular and oxygen-saturation images. The dual-foci method can double the B-scan rate to 2036 Hz. Using two lasers and stimulated Raman scattering, we achieve dual-wavelength excitation on both foci, and the total A-line rate is 3.2-MHz. In in vivo experiments, we inject epinephrine and monitor the hemodynamic and oxygen saturation response in the peripheral vessels at 1.7 Hz over 2.5 × 6.7 mm 2 . Dual-foci OR-PAM offers a new imaging tool for the study of fast physiological and pathological changes., Competing Interests: The authors report no declarations of interest, (© 2021 The Authors.)

Effective and noninvasive diagnosis and prompt treatment of early-stage hepatocellular carcinoma (HCC) are urgently needed to reduce its mortality rate. Herein, the integration of high-resolution diagnostic second near-infrared (NIR-II) photoacoustic computed tomography (PACT) and imaging-guided targeted photothermal ablation of orthotopic small HCC (SHCC) is presented for the first time, which was enabled by a plasmonic platinum (Pt)-doped polydopamine melanin-mimic nanoagent. As designed, an antibody-modified nanoagent (designated Pt@PDA-c) with a plasmonic blackbody-like NIR absorption and superior photothermal conversion efficiency (71.3%) selectively targeted and killed CXCR4-overexpressing HCC (HepG2) cells, which was validated in in vitro experiments. The targeted accumulation properties of Pt@PDA-c in vivo were previously recognized by demonstrating effective NIR-II PA imaging and photothermal ablation in a subcutaneous HCC mouse model. Subsequently, with real-time quantitative guidance by PACT for the accurate diagnosis of intraabdominal SHCC (approximately 4 mm depth), the effective and noninvasive photothermal ablation of SHCCs was successfully demonstrated in an orthotopic tumor-bearing mouse model without damaging adjacent liver tissues. These results show a great potential of NIR-II PACT-guided noninvasive photothermal therapy as an innovative phototheranostic approach and expand the biomedical applications of melanin-mimic materials. STATEMENT OF SIGNIFICANCE: In this paper, we report the first diagnostic NIR-II photoacoustic computed tomography (PACT)-guided noninvasive photothermal ablation of small hepatocellular carcinoma (SHCC) located in deep tissues in orthotopic tumor-bearing mice; this process is empowered by a polydopamine-based melanin-mimic tumor-targeting nanoagent doped with plasmonic platinum that provides superior NIR-II (1064 nm) absorption and photothermal conversion efficiency of 71.3%. Following surface modification with anti-CXCR4 antibodies, the nanoagent (namely Pt@PDA-c) can selectively target CXCR4-overexpressed HepG2 carcinoma cells and tumor lesions, and serve as the theranostic agent for both NIR-II PACT-based diagnosis of orthotopic SHCC (diameter less than 5 mm) and efficient NIR-II PTT in vivo. This study may also extend the potential of melanin-derived blackbody materials for optical-biomedical and water distillation applications., Competing Interests: Declaration of Competing Interest All authors have no competing financial interest to declare., (Copyright © 2021. Published by Elsevier Ltd.)

We report wide-field polygon-scanning functional OR-PAM that for the first time achieves 1-MHz A-line rate of oxygen saturation in vivo. We address two technical challenges. The first is a 1-MHz dual-wavelength pulsed laser that has sufficient pulse energy and ultrafast wavelength switching. The second is a polygon-scanning imaging probe that has a fast scanning speed, a large field of view, and great sensitivity. The OR-PAM system offers a B-scan rate of 477.5 Hz in a 12-mm range and a volumetric imaging rate of ∼1 Hz over a 12 × 5 mm 2 scanning area. We image microvasculature and blood oxygen saturation in a 12 × 12 mm 2 scanning area in 5 s. Dynamic imaging of oxygen saturation in the mouse ear is demonstrated to monitor fast response to epinephrine injection. The new wide-field fast functional imaging ability broadens the biomedical application of OR-PAM., Competing Interests: The authors declare no conflicts of interest., (© 2020 The Authors.)

Limited by the numerical aperture of ultrasonic detection, optical resolution photoacoustic microscopy (OR-PAM) has not achieved optimal sensitivity. To address this problem, we have developed a high acoustic numerical aperture ($ {\sim} 0.74 $∼0.74) OR-PAM (HNA-OR-PAM). Via engineering the acoustic lens, we implement the highest acoustic numerical aperture that a spherical concave lens can achieve. The sensitivity of HNA-OR-PAM is improved to around 160%-the state-of-the-art OR-PAM. Without averaging, the new system can image oxygen saturation in vivo with only 10-nJ pulse energy. The improved sensitivity allows us to image weaker absorbers, penetrate deeper, and reduce nonlinear effects induced by high pulse energy. Moreover, the photoacoustic view angle is augmented to 51.8 deg and makes tilted features more visible. We validate the improved view angle in both a phantom study and brain imaging.

Dichroism is a material property that causes anisotropic light-matter interactions for different optical polarizations. Dichroism relates to molecular types and material morphology and thus can be used to distinguish different dichroic tissues. In this paper, we present single-shot dichroism photoacoustic microscopy that can image tissue structure, linear dichroism, and polarization angle with a single raster scanning. We develop a fiber-based laser system to split one laser pulse into three with different polarization angles, sub-microseconds time delay, and identical pulse energy. A dual-fiber optical-resolution photoacoustic microscopy system is developed to acquire three A-lines per scanning step. In such a way, dichroism imaging can achieve the same speed as single-wavelength photoacoustic microscopy. Moreover, the three polarized pulses originate from one laser pulse, which decreases pulse energy fluctuations and reduces dichroism measurement noise by ∼35 %. The new dichroism photoacoustic imaging technique can be used to image endogenous or exogenous polarization-dependent absorption contrasts, such as dichroic tumor or molecule-labeled tissue., Competing Interests: C.L. and L.W. have a financial interest in PATech Limited, which, however, did not support this work., (© 2019 The Authors.)

By using the commercially available ruthenium pincer complex (Ru-MACHO-BH) as a catalyst, the challenging direct hydrogenation of lactams and analogues has been successfully accomplished to deliver corresponding value-added amino alcohols in good-to-excellent yields under mild reaction conditions. Remarkably, in addition to N-protected lactams, unprotected ones could also be readily reduced in the presence of a catalytic amount of weak base or even under neutral reaction conditions, which further highlights the broad substrate scope and the protocol efficiency., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A series of bulky pyridine-bridged NHC-Ru complexes have been rationally designed and synthesized; these exhibited very high catalytic activity in the hydrogenation of cyclic and linear carbonates under mild reaction conditions. In the presence of catalytic amounts of a weak base, a broad range of substrates with different ring size and steric bulk were well tolerated, providing methanol and the corresponding diols in excellent yields with a catalyst loading as low as 0.5 mol %., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background and Purpose: Antiplatelet therapy is widely used for the primary or secondary prevention of stroke. Drugs like clopidogrel have emerged as alternatives for traditional antiplatelet therapy, and dual therapy with clopidogrel and aspirin is of particular interest. We conducted this meta-analysis to systematically review studies about dual therapy comparing monotherapy with aspirin alone., Methods: Randomized controlled trials were searched in PubMed (1966-May, 2015), EMBASE (1947-May, 2015), the Cochrane Central Register of Controlled Trials (CENTRAL) (1948-May, 2015), WHO International Clinical Trial (ICTRP) (2004-May, 2015), China Biology Medicine disc (CBM disc) (1978-May, 2015) and were included into the final analysis according to the definite inclusion criteria mentioned in the study selection section. Risk ratio (RR) was pooled with 95% confidence interval (CI) for dichotomous data. The heterogeneity was considered significant if the χ2 test was significant (P value < 0.10) or the I2 > 50.00%. Subgroup analyses were carried out on the long and short time periods, the race and region., Results: We included 5 studies involving 24,084 patients. A pooled analysis showed that dual therapy with clopidogrel and aspirin had a lower stroke incidence than monotherapy in both the short term and long term (RR = 0.69, 95% CI: 0.59-0.82, P <0.05; RR = 0.84, 95% CI: 0.72-0.98, P = 0.03, respectively). With regard to safety, dual therapy had a higher risk of bleeding than monotherapy for both periods (RR = 1.51, 95% CI: 1.03-2.23, P = 0.04; RR = 1.54, 95% CI: 1.32-1.79, P<0.05, respectively)., Conclusions: Dual therapy with clopidogrel and aspirin could be a preferable choice to prevent stroke in patients who have had a previous stroke or transient ischemic attack, as well as those who are at high risk for stroke. And the effect of dual therapy seems to be more obvious for short-term. However, it is associated with a higher risk of bleeding.

Due to its special coordination ability to Cu(II)-terpyridine complexes, a simple and straightforward visual recognition of p-DMAP out of its analogues has been realized via selective metallogel collapse. In combination with the selective gel collapse and the self-healing properties of metallohydrogel , its potential application towards chemo-switch is also demonstrated.

A conchal non-pneumatized sphenoid sinus was previously considered to be a contraindication to the endoscopic transsphenoidal route to the sella due to its small sellar floor and poor anatomical landmarks, such as the optic nerve canal, opticocarotid recess and internal carotid arteries canal. The present study aimed to investigate the methodology and characteristics of the endoscopic transsphenoidal resection of sellar tumors with a conchal sphenoid sinus. Two patients with sellar tumor patients and non-pneumatized sphenoid sinuses received endoscopic transsphenoidal surgery. The two conchal sphenoid sinuses were accessed safely, total resection was achieved and no serious complications occurred. Therefore, the presence of a conchal non-pneumatized sphenoid is not an absolute contraindication for employing the endoscopic transsphenoidal route in the resection of sellar tumors; a positive outcome may be achieved, in particular when the surgery is performed by an experienced otolaryngologist.

Background: Tea and coffee are the most commonly consumed beverages in the worldwide. The relationship between tea and coffee consumption on the risk of laryngeal cancer was still unclear., Methods: Relevant studies were identified by searching electronic database (Medline and EMBASE) and reviewing the reference lists of relevant articles until Oct. 2013. Observational studies that reported RRs and 95% CIs for the link of tea and coffee consumption on the risk of laryngeal cancer were eligible. A meta-analysis was obtained to combine study-specific RRs with a random-effects model., Results: A total of 2,803 cases and 503,234 controls in 10 independent studies were identified. The overall analysis of all 10 studies, including the case-control and cohort studies, found that tea drinking was not associated with laryngeal carcinoma (RR = 1.03; 95% CI: 0.66-1.61). However, coffee consumption was significantly associated with the laryngeal carcinoma (RR = 1.47; 95% CI: 1.03-2.11). A dose-response relationship between coffee intake and laryngeal carcinoma was detected; however, no evidence of dose-response link between tea consumption and laryngeal carcinoma risk was detected., Conclusions: The results from this meta-analysis of observational studies demonstrate that coffee consumption would increase the laryngeal cancer risk, while tea intake was not associated with risk of laryngeal carcinoma.

Objective: To study the expression of phosphorylated extracellular regulator kinase (ERK1/2) on nasal polyps., Method: The immunohistochemistry and Western-blot were used to study the phosphorylation of ERK1/2 on the normal nasal mucosa and nasal polyps., Result: The phosphorylated ERK1/2 was mainly expressed on the hyperplastic epithelium, inflammatory cells, glandular epithelium and endothelium of nasal polyps by immunohistochemistry, which was much stronger on nasal polyps than that of normal mucosa. The expression of phosphorylated ERK1/2 was 4.2 times than that of normal mucosa., Conclusion: The study indicated that the phosphorylation of ERK1/2 might play an important role on the occurrence and progression of nasal polyps.

The InGaZnO thin films are fabricated on the quartz glass using pulsed laser deposition (PLD), where the target is prepared by mixing the Ga(2)O(3), In(2)O(3), and ZnO powders at a mol ratio of 1:1:8 before the solid-state reactions in a tube furnace at the atmospheric pressure. The product thin films were characterized comprehensively by X-ray diffraction, atomic force microscopy, Hall-effect investigation, and X-ray photoelectron spectroscopy. Thus, we demonstrate semiconductor thin-film materials with high smoothness, high transmittance in visible region, and excellent electrical properties.

Objective: To study the expression of MMP-9 and eosinophils in nasal polyps and its influence on the prognosis., Method: Study the expression of MMP-9 and EOS on the tissue of nasal polyps of patients who were cured or recurrent and normal nasal mucosa (NM) by immunohistochemistry and HE staining., Result: In the patients of recurrent group (Group B), the expression of MMP-9 was much stronger than that of good prognosis group (Group A) and NM. The MMP-9 was stronger in the eosinophil nasal polyps than that of non-eosinophil groups. The percentage of EOS in Group A was 16.67%, while 62.50% in the Group B., Conclusion: The stronger expression of MMP-9 on Group B and eosinophil group indicated that MMP-9 might affect the prognosis of nasal polyps through inducing the number of EOS in the mucosa. MMP-9 may be one of the risk factors for the relapse of nasal polyps.

Objective: Genomic instability reflecting the susceptibility of the genome to acquire multiple genetic alterations plays a major role in tumorigenesis and tumor progression. We evaluated the prognostic significance of the extent of genomic instability in nasopharyngeal carcinoma., Study Design and Setting: Genomic instability was assessed by inter-simple sequence repeats polymerase chain reaction (inter-SSR PCR) in 38 patients with nasopharyngeal carcinoma. Characterization and verification of band alterations shared in different tumors were carried out by sequencing and nest PCR., Results: 31 (81.6%) of 38 patients showed genomic alterations, and genomic instability index ranged from 0 to 16.2%. A gain-based genomic damage shared in 6 tumors was identified on chromosome 6q27, a new mutator phenotype in nasopharyngeal carcinoma. Significantly more genomic alteration was found in patients without 5-year survival than that with 5-year survival (P<0.05), suggesting that higher genomic instability predicts a poor prognosis in nasopharyngeal carcinoma., Conclusions and Significance: Our data suggests that genomic instability can be an early event marker in carcinogenesis of nasopharyngeal carcinoma. Also, aggravation of genomic alterations is a poor prognosis for cancer recovery.