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Despite progress in prevention and treatment, colorectal cancer (CRC) remains the third most common malignancy worldwide and the second most common cause of cancer death in 2020. To evaluate various characteristics of human CRC, a variety of mouse models have been established. Transplant mouse models have distinct advantages in studying the clinical behavior and therapeutic progress of CRC. Host, xenograft, and transplantation routes are the basis of transplant mouse models. As the effects of the tumor microenvironment and the systemic environment on cancer cells are gradually revealed, 3 key elements of transplanted CRC mouse models have been revolutionized. This has led to the development of humanized mice, patient-derived xenografts, and orthotopic transplants that reflect the human systemic environment, patient's tumor of origin, and tumor growth microenvironments in immunodeficient mice, respectively. These milestone events have allowed for great progress in tumor biology and the treatment of CRC. This article reviews the evolution of these events and points out their strengths and weaknesses as innovative and useful preclinical tools to study CRC progression and metastasis and to exploit novel treatment schedules by establishing a testing platform. This review article depicts the optimal transplanted CRC mouse models and emphasizes the significance of surgical models in the study of CRC behavior and treatment response.

To analyse the role played by Sappanone A, a bioactive ingredient isolated from the heartwood of Caesalpinia sappan, in the regulation of oral epithelial cell viability under radiation.Cell viability of human oral keratinocytes (HOKs) and mouse salivary gland cells under ionising radiation was analysed. Expression of Ki67 was measured by immunohistochemical staining. Fragmentation of deoxyribonucleic acid (DNA) was measured by comet assay. Cell death was analysed using trypan blue exclusion assay. Cell viability was measured using a Cell Counting Kit 8 (CCK8; Abcam, Cambridge, UK) assay.Sappanone A decreased cell viability of HOK cells and mouse salivary gland cells under ionising radiation. In addition, Sappanone A enhanced radiation-induced genomic DNA fragmentation, accompanied by impaired homologous recombination and non-homologous end joining DNA repair. Mechanistic evaluation revealed that Sappanone A counteracted radiation-induced inosine monophosphate dehydrogenase 2 (IMPDH2) activation, and that this effect could be abolished by reconstituted expression of a Sappanone A-binding defective IMPDH2 mutant.The present study highlights a novel role played by Sappanone A in the modulation of radiosensitivity of oral epithelial cells.

We studied metastasis-promoting effect of transmembrane protease TMPRSS4 on mismatch repair (MMR)-deficient colorectal cancer liver metastasis in BALB/c nude mouse model. Histomorphological and histopathological studies showed that the number of liver metastases in the study group were significantly higher than that in the control group (p

Background This study is to investigate the preventive and therapeutic effect of intraportal oridonin on colorectal cancer liver metastasis (CRCLM). Methods The inhibitory effect of oridonin on HT29 cells was determined by CCK-8 and MTT assays. The preventive and therapeutic effect of intraportal oridonin on CRCLM were investigated by establishing BALb/c nude mice hemispleen models of colon cancer liver metastasis. The microscopic characteristics of tumor tissues were observed by hematoxylin-eosin staining, immunohistochemistry and TUNEL staining. On the other hand, liver function enzymes, such as alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP), were detected to evaluate the hepatotoxicity of intraportal oridonin. The serum levels of tumor markers, including carcinoembryonic antigen (CEA) and α-fetoprotein (AFP), were used to investigate the intervention effect of intraportal oridonin on CRCLM. Results Oridonin exerted an inhibitory effect on the proliferation of HT29 cells in vitro. Intraportal oridonin was found to effectively prevent the occurrence and formation of CRCLM, whilst intraportal oridonin can also exert a therapeutic effect on CRCLM. Additionally, liver enzymes testing indicated that intraportal oridonin possesses non-hepatotoxicity, instead can effectively alleviate liver injury caused by tumor. Furthermore, intraportal oridonin was also revealed to decrease the serum levels of AFP and CEA. Conclusions Intraportal oridonin can effectively inhibit the formation of liver metastatic tumor and exert a certain degree of preventive and therapeutic effect on CRCLM. These findings indicate intraportal oridonin to be a promising anti-metastasis agent for CRCLM.

Multiparameter integrated sensors are required for the next generation of flexible wearable electronics. However, mutual interference between detected signals is a technical bottleneck for a flexible tactile sensor to realize pressure-strain monitoring simultaneously and sensitively. Herein, a flexible dual-parameter pressure-strain sensor based on the three-dimensional (3D) tubular graphene sponge (TGS) and spider web-like stretchable electrodes is designed and fabricated. As the pressure-sensitive module, the unique 3D-TGS with an uninterrupted network of tubular graphene and high graphitic degree demonstrates great robust compressibility, supporting compression to ∼20% without shape collapse. The spider web-like stretchable electrodes as the strain-sensitive module are fabricated by a spray-embedded process based on the hierarchical multiscale hybrid nanocomposite of Ag nanowires (NWs) and carbon nanotubes (CNTs) with an optimal mass ratio. By comparing the output signals of spider web-like flexible electrodes, the magnitude and direction of the applied force can be effectively monitored simultaneously. Moreover, the potential applications of the flexible dual-parameter pressure-strain device in human-machine interaction are also explored, showing great promise in artificial intelligence and wearable systems.

NBe5Hnn−3 (n = 0–5) (0A–5A) species with a novel planar pentacoordinate nitrogen (ppN) were designed by the isoelectronic substitution of the C atom in planar pentacoordinate carbon (ppC) species CBe5Hnn−4 (n = 0–5) with an N atom. The highly flexible H atoms found in ppC species CBe5H22− and CBe5H3− were fixed upon the nitrogen substitution, as mirrored by the non-flexible H atoms in their ppN analogues NBe5H2− (2A) and NBe5H3 (3A). Moreover, the N atom was found to fit the H-surrounded Be5 rings better than the C atom because the ppC species CBe5H4 and CBe5H5+ adopted non-planar structures due to size-mismatch between the C atom and the H-surrounded Be5 ring, but their ppN analogues NBe5H4+ (4A) and NBe5H52+ (5A) adopted perfect planar structures. The electronic structure analyses revealed that the N atoms in 0A–5A were involved in four doubly occupied orbitals, including three six-center two-electron (6c-2e) σ bonds and one 6c-2e π bond. Therefore, these ppN species not only obey the octet rule, but also possess the interesting σ and π double aromaticity, which contributes to the stabilization. Consequently, 2A, 4A, and 5A are charged kinetically viable global energy minima, and are suitable for the gas phase generation and spectroscopic characterization.

Background This study aimed to investigate the expression pattern and prognostic significance of HOXB13 in rectal cancer. Methods HOXB13 expression in rectal cancer and normal adjacent tissues was detected by reverse transcriptase-polymerase chain reaction and immunohistochemistry, and its clinicopathological characteristics and prognosis were statistically tested. Furthermore, we evaluated the association between tumor immune infiltrating cells and HOXB13 using the tumor immune estimation resource (TIMER) database. The potential biological mechanism associated with HOXB13 overexpression was investigated by gene set enrichment analysis (GSEA). Results The expression of HOXB13 messenger RNA and protein in human rectal cancer tissues were significantly higher than those in the normal adjacent tissues ( P Conclusion Our study showed an essential role of HOXB13 in rectal cancer immunity and prognosis. Significantly, the overexpression of HOXB13 leads to the worse prognosis for patients with rectal cancer, which will contribute to understanding molecular mechanisms associated with tumor pathogenesis and prognosis in this disease.

Wearable touch panels, a typical flexible electronic device, can recognize and feed back the information of finger touch and movement. Excellent wearable touch panels are required to accurately and quickly monitor the signals of finger movement as well as the capacity of bearing various types of deformation. High-performance thermistor materials are one of the key functional components, but to date, a long-standing bottleneck is that inorganic semiconductors are typically brittle while the electrical properties of organic semiconductors are quite low. Herein, a high-performance flexible temperature sensor is reported by using plastic Ag

Stretchable strain sensor, an important paradigm of wearable sensor which can be attached onto clothing or even human skin, is widely used in healthcare, human motion monitoring and human-machine interaction. Pattern-available and facile manufacturing process for strain sensor is pursued all the time. A carbon nanotube (CNT)/silver nanowire (AgNW)-based stretchable strain sensor fabricated by a facile process is reported here. The strain sensor exhibits a considerable Gauge factor of 6.7, long-term durability (>1000 stretching cycles), fast response and recovery (420 ms and 600 ms, respectively), hence the sensor can fulfill the measurement of finger movement. Accordingly, a smart glove comprising a sensor array and a flexible printed circuit board is assembled to detect the bending movement of five fingers simultaneously. Moreover, the glove is wireless and basically fully flexible, it can detect the finger bending of wearer and display the responses distinctly on an APP of a smart phone or a host computer. Our strain senor and smart glove will broaden the materials and applications of wearable sensors.

Background The objective of the clinical trial is to determine whether our novel multimodal approach can improve the anastomotic leakage (AL) in patients undergoing low anterior resection (LAR) for rectal cancer. Methods From September 2019 to December 2020, a total of 33 patients who underwent LAR in our hospital were divided to receive a defunctioning stoma (DS) or multi-modal approach. The multi-modal approach consists of three intraoperative preventive measures (pelvic floor peritoneum closure, transanal drainage tube and abdominal drains) combined with a standardised pathway for early detection and active management of AL. The short-term indicators observed postoperatively were as follows: (1) incidence of AL; (2) additional operation time after LAR; (3) ileostomy complications; (4) postoperative hospital stay; (5) mortality. Long-term endpoints comprise: (1) Wexner incontinence scale; (2) anorectal manometry measurements. Results No significant difference was observed in the rates of postoperative AL between both groups (P>0.05). Remarkable divergences in the ileostomy complications, Wexner score, and manometric evaluation were not noted between the groups (P>0.05). Both the maximal resting pressure and maximal squeezing pressure at 6 month were significantly decreased relative to the values noted before treatment (P Discussion In conclusion, the multi-modal approach achieves the same effect as DS in the prevention and management of AL during LRA with shorter operation time, meanwhile overcomes the adverse impact brought by DS. Therefore, our multiinterventional program may be used to replace the DS procedure during LRA.

Skin-like electronics that can provide comprehensively tactile sensing is required for applications such as soft robotics, health monitoring, medical treatment, and human-machine interfaces. In particular, the capacity to monitor the contact parameters such as the magnitude, direction, and contact location of external forces is crucial for skin-like tactile sensing devices. Herein, a flexible electronic skin which can measure and discriminate the contact parameters in real time is designed. It is fabricated by integrating the three-dimensional (3D) hollow MXene spheres/Ag NW hybrid nanocomposite-based embedded stretchable electrodes and T-ZnOw/PDMS film-based capacitive pressure sensors. To the best of our knowledge, it is the first stretchable electrode to utilize the 3D hollow MXene spheres with the essential characteristic, which can effectively avoid the drawbacks of stress concentration and shedding of the conductive layer. The strain-resistance module and the pressure-capacitance module show the excellent sensing performance in stability and response time, respectively. Moreover, a 6 × 6 sensor array is used as a demonstration to prove that it can realize the multiplex detection of random external force stimuli without mutual interference, illustrating its potential applications in biomimetic soft wearable devices, object recognition, and robotic manipulation.

Computational design has played an important role in planar hyper-coordinate carbon (phC) chemistry. However, none of numerous computationally predicted phC species were subsequently successfully synthesized in the condensed phase, perhaps due to the frustrating issue of oxidation. In the present work, we studied the influence of stepwise oxidation on the structure, stability, and properties of phC species using the milestone planar pentacoordinate carbon (ppC) species CAl5+ as an example. Our results indicated that the ppC structure of CAl5+ would be directly destroyed with one, two, or six O atom(s) per molecule present and indirectly with three or four O atoms, but maintained with five O atoms due to the ppC isomer of CAl5O5+ being a kinetically stable global energy minimum displaying σ and π double aromaticity. Moreover, the magnitudes of the first to fifth vertical oxygen affinities (VOAs) for CAl5+ were determined to be very high (-85.5 to -116.3 kcal mol-1), probably due to the existence of peripheral diffuse Al-Al bond(s). However, the sixth VOA was reduced significantly to -50.2 kcal mol-1, consistent with the absence of any diffuse Al-Al bond in the corresponding CAl5O5+ species. So CAl5O5+ may be insensitive to oxidation. Therefore, the ppC species D5h CAl5O5+ might be resistant to being degraded under a delicate control of oxidation level (producing five O atoms per CAl5+ molecule).

NBe

To determine whether sophocarpine (SC) can enhance the inhibiting effect of oxaliplatin on colorectal cancer (CRC) liver metastasis (CRCLM)-in vitro and in vivo. The inhibitory effect of SC and/or oxaliplatin on the proliferation, invasion, and migration of CRC cells was determined by CCK-8, MTT, wound healing migration, and transwell assay. Western blot and immunohistochemistry were used to evaluate the inhibitory effect of SC and/or oxaliplatin on the epithelial-mesenchymal transition (EMT) process. Nude mouse models of human CRCLM were established to test the anti-metastasis effect of SC and oxaliplatin in the single or combined form. SC exerted an inhibitory effect on the proliferation, invasion, and migration of CRC cells both in vitro and in vivo. The combination index of SC and oxaliplatin was 0.58. In addition, the inhibitory effect of SC in combination with oxaliplatin was found to be significantly stronger compared with that mediated by either SC or oxaliplatin alone, suggesting that SC can effectively enhance the inhibitory effect of oxaliplatin on CRCLM both in vitro and in vivo. SC was also revealed to reverse EMT process in cell lines and tissues, as reflected by the observed downregulation of N-cadherin and vimentin expression and the upregulation of E-cadherin expression. Taken together, data from the present study suggest that SC administration can inhibit CRC cell proliferation, invasion, migration, and EMT, while enhancing the inhibitory effects of oxaliplatin both in vitro and in vivo. These findings indicate (that) SC to be a promising anti-metastasis agent for CRCLM.

Computational design has played an important role in planar hyper-coordinate carbon (phC) chemistry. However, none of numerous computationally predicted phC species were subsequently successfully synthesized in the condensed phase, perhaps due to the frustrating issue of oxidation. In the present work, we studied the influence of stepwise oxidation on the structure, stability, and properties of phC species using the milestone planar pentacoordinate carbon (ppC) species CAl

As a member of the homeobox family, HOXC9 is overexpressed in several malignant tumors and may be regarded as a biomarker for prognostic evaluation. However, the expression pattern and prognostic significance of HOXC9 in gastric cancer have not been detailedly studied. HOXC9 mRNA expression difference in normal tissues and gastric cancer tissues were investigated using RT-PCR, and immunohistochemistry was used to analyze HOXC9 protein expression in precancerous lesions and gastric cancer at different stages, and its clinicopathological characteristics and survival were statistically tested. Compared to the normal gastric mucosa tissues, the expression levels of HOXC9 mRNA in the human gastric cancer tissues were significantly higher. HOXC9 protein levels of gastric cancer were obviously higher than that in other noncancerous tissues (P

Ultrashort metal-metal distances (USMMDs, dM-M < 1.900 A) have been realized computationally between the main group metal beryllium. However, due to their ionic charge state and the insufficient stability of their electronic structures and/or thermodynamic stabilities, the known species with ultrashort Be-Be distances are unsuitable for synthesis in the condensed phase, which deters the applications of these interesting structures from being explored. In the present study, using our previously reported global minima species [XH3-Be2H3-XH3]+ (X = N and P) with ultrashort Be-Be distances and well-defined electronic structures as their parent molecules, we designed a series of neutral polygons retaining ultrashort Be-Be distances. These polygons also possess well-defined electronic structures and good thermodynamic stabilities, which are demonstrated by their large HOMO-LUMO gaps of 6.20-7.68 eV, very high vertical detachment energies (VDEs) of 8.96-11.29 eV, rather low vertical electron affinities (VEAs) of -1.21 to +1.78 eV, and unexpectedly high formation energies relative to the building blocks of E- and Be2H3+ (-105.2 to -153.2 kcal mol-1 for the formation of an E-Be bond). The good stability with regard to their electronic structures and thermochemistry reveal their high feasibility to be synthesized in the condensed phase. Thus, we anticipate experimental studies on these interesting nano-polygons to realize structures with USMMDs between main group metals and explore their possible application.

The diagonal relationship between beryllium and aluminum and the isoelectronic relationship between BeH unit and Al atom were utilized to design nine new planar and quasi-planar pentacoordinate carbon (ppC) species CAlnBemHxq (n + m = 5, q = 0, ±1, x = q + m − 1) (1a–9a) by attaching H atoms onto the Be atoms in CAl4Be, CAl3Be2−, CAl2Be32−, and CAlBe43−. These ppC species are σ and π double aromatic. In comparison with their parents, these H-attached molecules are more stable electronically, as can be reflected by the more favourable alternative negative–positive–negative charge-arranging pattern and the less dispersed peripheral orbitals. Remarkably, seven of these nine molecules are global energy minima, in which four of them are kinetically stable, including CAl3Be2H (2a), CAl2Be3H− (4a), CAl2Be3H2 (5a), and CAlBe4H4+ (9a). They are the promising target for the experimental realization of species with a ppC.

The subject of metal-metal bonding interactions in molecular systems continues to attract research interest. Chromium heretofore has been the only element known to afford metal-metal distances shorter than 1.700 Å in the form of Cr-Cr multiple bonds. In this computational study, the effect of a triple bond on reducing interatomic distances is simulated through forming three non-classical bonding orbitals between two beryllium atoms, thereby realizing the remarkably short Be-Be distances (1.692-1.735 Å) in kinetically stable global minimum species [L → Be2H3 ← L]+ (L = NH3, PH3, and noble gases Ne-Xe). Such diberyllium complexes make promising candidates for experimental realization. In particular, the Be-Be distance of 1.692 Å in [Ne → Be2H3 ← Ne]+ represents the first example of global minimum having a main group metal-metal distance under 1.700 Å. [TEA → Be2H3 ← TEA]+, which contains the bulky triethylamine (TEA) ligands, is designed as a more promising target for synthesis and isolation in condensed states.

Monocyclic Bn rings can act as n-electron σ-donors to stabilize a non-classical planar hypercoordinate atom at ring center, forming wheel-like structures. Herein, we report that BenHn rings can also serve as n-electron σ-donors to construct star-like structures including B©Be6H6+ and TM©Be7H7q (TM is a group 10–12 metal with q = −1, 0, and 1, respectively) by complying with octet or 18-electron rules. Electronic structure analyses show that these species are stabilized by the σ-donation and π-backdonation between the central atom and the peripheral BenHn ring, the favorable Coulomb attraction due to the negative–positive–negative charge population pattern on the central atom, the middle Ben layer, and the outer Hn layer, as well as the σ–π double aromaticity. Importantly, three of the ten species, including B©Be6H6+, Cu©Be7H7, and Au©Be7H7, were confirmed to be kinetically stable global minima, thereby providing promising targets for experimental preparations.

As an indispensable and prevailing kind of flexible sensors, pressure sensors have been extensively used in the field of flexible electronics. To enhance the performance and broaden the applications of flexible pressure sensors, emerging nanomaterials with excellent electromechanical properties have been explored and developed over recent years. Herein, the latest progresses in flexible pressure sensors based on metal and carbonaceous nanomaterial are reviewed in this paper. Firstly, fundamental considerations of pressure sensors including transduction principles, evaluation parameters and nano-micro structures are presented. Furthermore, flexible pressure sensors based on carbonaceous nanomaterials, transition metal carbides and carbonitrides (Mxene), along with metal nanomaterials are reviewed and classified by different transduction principles. At last, a number of applications on electronic skin (E-skin) involving metal and carbonaceous nanomaterial-based flexible pressure sensors are introduced, including pressure distribution sensing, force direction detection, multifunctional sensing and system integration.