Increased PKN2 and M2-Polarized Macrophages Promote HCT116 Cell Invasion.

Colorectal cancer is the third most common malignant tumor, with highly invasive and metastatic potential in the later stage. This study investigated the role of PKN2 overexpression and M2-polarized macrophages in dictating the malignant phenotype of colorectal cancer cells. HCT116 colorectal cancer cell line with PKN2 overexpression was generated to investigate the functional role of PKN2. THP-1 cells were polarized into M2-like macrophages, and the co-culture system of THP-1/M2 cells and HCT116 cells was established to examine the impacts of M2-polairzed macrophages on the malignant phenotype of colorectal cancer cells. PKN2 overexpression promoted cell proliferation, migration and invasion in HCT116 colorectal cancer cells, and reduced spontaneous cell death in the cell culture. Besides, the presence of M2-polarized THP-1 cells significantly enhanced the aggressive phenotype of HCT116 cells. Both PKN2 overexpression and M2-polarized THP-1 cells increased the expression of NF-κB p65 in HCT116 cells, indicating that enhanced NF-κB signaling may contribute to the augmented aggressiveness of HCT116 cells. These findings suggest PKN2 as an oncogenic factor in colorectal cancer and that M2-polarized THP-1 cells may promote the progression of colorectal cancer by activating NF-κB signaling.

The Enhancement Mechanism of Different Single-Transition Metal Atomic Catalysts/Sulfur Cathode on High-Performance of Li-S Batteries.

Materials with various single-transition metal atoms dispersed in nitrogenated carbons (M─N─C, M = Fe, Co, and Ni) are synthesized as cathodes to investigate the electrocatalytic behaviors focusing on their enhancement mechanism for performance of Li-S batteries. Results indicate that the order of both electrocatalytic activity and rate capacity for the M─N─C catalysts is Co > Ni > Fe, and the Co─N─C delivers the highest capacity of 1100 mAh g-1 at 1 C and longtime stability at a decay rate of 0.05% per cycle for 1000 cycles, demonstrating excellent battery performance. Theoretical calculations for the first time reveal that M─N─N─C catalysts enable direct conversion of Li2 S6 to Li2 S rather than Li2 S4 to Li2 S by stronger adsorption with Li2 S6 , which also has an order of Co > Ni > Fe. And Co─N─C has the strongest adsorption energy, not only rendering the highest electrocatalytic activity, but also depressing the polysulfides' dissolution into electrolyte for the longest cycle life. This work offers an avenue to design the next generation of highly efficient sulfur cathodes for high-performance Li-S batteries, while shedding light on the fundamental insight of single metal atomic catalytic effects on Li-S batteries.

Hydrogen-bond-modulated negative linear compressibility in a V-shaped molecular crystal.

A material with the "hidden" negative linear compressibility (NLC) will expand along a specific crystal direction upon uniformly compression to a critical pressure; such materials are thought to be promising candidates for non-linear actuators, switches and sensors. Herein, we use density functional theory (DFT) calculations to uncover the hidden NLC in a V-shaped molecular crystal, bis(5-amino-1,2,4-triazol-3-yl)methane (BATZM). The calculations indicate that the crystal is normally compressed over the pressure range of 0-3 GPa while it expands along the b-axis when the external hydrostatic pressure exceeds 3 GPa. The compressive behavior of the BATZM crystal is modulated by inter-molecular hydrogen bonds, which act as highly compressible springs at low pressures but robust struts at high pressures. Hence, the crystal prefers to compress the hydrogen bonds coupled with PLC at first and flatten the molecules, coupled with later NLC to resist the increasing external pressure. The compressive behavior of BATZM provides a strategy to design more hidden NLC materials via the rational use of the hydrogen bonds.

Risk factors analysis of lateral cervical lymph node metastasis in papillary thyroid carcinoma: a retrospective study of 830 patients.

OBJECTIVE: The aim of this study is to investigate the risk factors for lateral cervical lymph node metastasis in papillary thyroid carcinoma (PTC). METHODS: Clinicopathological data (age, gender, Hashimoto's thyroiditis, preoperative circulating tumor cells (CTCs), multifocal, maximum lesion diameter, invaded capsule, T stage, and lymph node metastasis) of 830 PTC patients diagnosed and treated in Meizhou People's Hospital from June 2021 to April 2023 were collected. The related factors of lateral cervical lymph node metastasis were analyzed. RESULTS: There were 334 (40.2%), and 103 (12.4%) PTC patients with central lymph node metastasis, and lateral cervical lymph node metastasis, respectively. Compared with patients without lateral cervical lymph node metastasis, PTC patients with lateral cervical lymph node metastasis had a higher proportion of multifocal, maximum lesion diameter > 1 cm, invaded capsule, T3-T4 stage. Regression logistic analysis showed that male (odds ratio (OR): 2.196, 95% confidence interval (CI): 1.279-3.769, p = 0.004), age < 55 years old (OR: 2.057, 95% CI: 1.062-3.988, p = 0.033), multifocal (OR: 2.759, 95% CI: 1.708-4.458, p < 0.001), maximum lesion diameter > 1 cm (OR: 5.408, 95% CI: 3.233-9.046, p < 0.001), T3-T4 stage (OR: 2.396, 95% CI: 1.241-4.626, p = 0.009), and invaded capsule (OR: 2.051, 95% CI: 1.208-3.480, p = 0.008) were associated with lateral cervical lymph node metastasis. CONCLUSIONS: Male, age < 55 years old, multifocal, maximum lesion diameter > 1 cm, T3-T4 stage, and invaded capsule were independent risk factors for lateral cervical lymph node metastasis in PTC.

Development of a New Heteropolyoxotantalate Cluster for Multidimensional Polyoxotantalate Materials.

A unique heteropolyoxotantalate (hetero-POTa) cluster [P2O7Ta5O14]7- (P2Ta5) was first developed using pyrophosphate as a key to open the ultrastable skeleton of the classical Lindqvist-type [Ta6O19]8- precursor. The P2Ta5 cluster can serve as a general and flexible secondary building unit to create a family of brand-new multidimensional POTa architectures. This work not only promotes the limited structural diversity of hetero-POTa but also provides a practical strategy for new extended POTa architectures.

Abnormal Compressive Behaviors of Metal-Organic Frameworks under Hydrostatic Pressure.

Intuition indicates that materials will contract in all crystal directions under hydrostatic pressure, i.e., all of their axes exhibit positive linear compressibility (PLC) when uniformly compressed. However, some exceptions have been found to exhibit negative linear compressibility (NLC), negative area compressibility (NAC), zero linear compressibility (ZLC), or zero area compressibility (ZAC); these materials are thought to have promising applications under high-pressure conditions, such as would be needed for highly sensitive pressure detectors and deep-sea optical devices. In this Perspective, we summarize the four kinds of abnormal compressive behaviors of MOFs under hydrostatic pressure, including the mechanisms and effects of guest, PTM, and metal atomic radius, which we hope to be helpful to develop practical future application of abnormal compressive materials.

Hidden porous boron nitride as a high-efficiency membrane for hydrogen purification.

Nanoporous atom-thick two-dimensional materials with uniform pore size distribution and excellent mechanical strength have been considered as the ideal membranes for hydrogen purification. Here, our first-principles structure search has unravelled four porous boron nitride monolayers (m-BN, t-BN, h'-BN and h''-BN) that are metastable relative to h-BN. Especially, h'-BN consisting of B6N6 rings exhibits outstanding selectivity and permeability for hydrogen purification, higher than those of common membranes. Importantly, h'-BN possesses the mechanical strength to sustain a stress of 48 GPa, which is two orders of magnitude higher than that (0.38 GPa) of a recently reported graphene-nanomesh/single-walled carbon nanotube network hybrid membrane. The excellent selectivity, permeability and mechanical strength make h'-BN an ideal candidate for hydrogen purification.

TRPM7 overexpression enhances the cancer stem cell-like and metastatic phenotypes of lung cancer through modulation of the Hsp90α/uPA/MMP2 signaling pathway.

BACKGROUND: Waixenicin A, a bioactive extract of soft coral Sarcothelia edmondsoni, has been shown to be anti-neoplastic. However, its mechanisms of action remain unclear. Cancer stem cells (CSCs) and associated stemness factors are implicated in lung cancer. Here, we investigated the role of Waixenicin A on CSCs-like and metastatic lung cancer cells. METHODS: We demonstrated and compared TRPM7 expression in the non-tumor lung tissues or bronchial epithelial 16-HBE cell line. TRPM7 was aberrantly expressed in the cancer tissues and SPCA-1, NCI-H520, SK-MES-1, A549 and 95D cell lines. RESULTS: Increased TRPM7 expression was associated with enhanced SOX2, KLF4, and CD133, Hsp90α, uPA, and MMP2 expression in lung cancer cells. TRPM7-silencing inhibited epithelial-to-mesenchymal transition (EMT), suppressed stemness markers and phenotypes, concomitantly suppressed Hsp90α/uPA/MMP2 axis. Coincidently, Waixenicin A treatment downregulated TRPM7 and oncogenic markers; Waixenicin A also attenuated the ability of lung cancer cells to form tumorspheres, in vitro. In validation, our clinicopathological analyses showed that a higher TRPM7 expression was positively correlated with the larger tumor size (p = 0.007), positive lymph node metastasis (p = 0.005) and disease grade (p = 0.003). CONCLUSIONS: Through its ability to inhibit Hsp90α/uPA/MMP2 signaling and suppress TRPM7 expression, we showed that Waixenicin A is a potential anticancer therapeutic agent for treating malignant lung cancer.

Piezochromic Luminescence of Donor-Acceptor Cocrystals: Distinct Responses to Anisotropic Grinding and Isotropic Compression.

Piezochromic luminescent materials that exhibit distinct luminescence responses to different types of mechanical stresses have been emerging as new kinds of materials which are rarely investigated. Herein, we report a donor-acceptor (D-A) charge-transfer (CT) cocrystal, which shows distinct hypochromatic and bathochromatic shifts upon anisotropic grinding and isotropic compression, respectively. Detailed spectroscopic and structural analyses revealed that the hypochromatic shifted emission under grinding is attributable to a structural reorganization from a loosely segregated-stack to a mixed-stack, while the bathochromatic shifted emission originates from the formation of a tighter packing structure. We present rare evidence of a distinct luminescent response to anisotropic grinding and isotropic compression on the basis of structural rearrangement in a D-A cocrystal, and thus enriches our insight into piezochromic luminescence.

Large Negative Linear Compressibility in InH(BDC)2 from Framework Hinging.

Materials with negative linear compressibility (NLC) counterintuitively expand along one specific direction coupled to the volume reduction when compressed uniformly. NLC with a large value is desired for compression and materials science. However, NLC is generally smaller than -20 TPa-1. High-pressure X-ray diffraction experiments reveal that the ß-quartz-like InH(BDC)2 generates an extreme NLC (-62.4 TPa-1) by framework hinging. InH(BDC)2 is much safer and lower-cost than Au+/Ag+ and CN--containing materials that dominated the fields of large NLC. This work reconfirms that a negative thermal expansion flexible framework could likely exhibit large NLC. Moreover, a large NLC could be anticipated to arise from ß-quartz-like or related frameworks composed of rigid linear ligands and flexible framework angles.

Room-temperature NaI/H2O compression icing: solute-solute interactions.

In situ Raman spectroscopy revealed that transiting the concentrated NaI/H2O solutions to an ice VI phase and then into an ice VII phase at 298 K proceeds in a way different from that activated by the solute type. Unlike the solute type that raises both the critical pressures PC1 and PC2, for the liquid-VI, the VI-VII transition simultaneously occurs in the Hofmeister series order: I > Br > Cl > F ∼ 0; concentration increase raises the PC1 faster than the PC2 that remains almost constant at higher NaI/H2O molecular number ratios. Concentration increase moves the PC1 along the liquid-VI phase boundary and it finally merges with PC2 at the triple-phase junction featured at 350 K and 3.05 GPa. The highly-deformed H-O bond is less sensitive to the concentration because of the involvement of anion-anion repulsion that weakens the electric field in the hydration shells. Observations confirm that the salt solvation lengthens the O:H nonbond and softens its phonon but relaxes the H-O bond contrastingly. Compression, however, has the opposite effect from that of salt solvation. Therefore, compression recovers the polarization-deformed O:H-O bond first and then proceeds to the phase transitions. The anion-anion interaction discriminates the effect of NaI/H2O concentration from that of the solute type at an identical concentration on the phase transitions.

Compression icing of room-temperature NaX solutions (X = F, Cl, Br, I).

In situ Raman spectroscopy revealed that transiting H2O/NaX (∼64) solutions into an ice VI phase and then into an ice VII phase at a temperature of 298 K requires excessive pressures with respect to pure water. The increase of the critical pressures varies with the solute type in the Hofmeister series order: X = I > Br > Cl > F ∼ 0. The results suggest that the solute hydration creates electric fields that lengthen and soften the O:H nonbond and meanwhile shorten and stiffen the H-O bond through O-O Coulomb repulsion. Compression, however, does the opposite to solute electrification upon the O:H-O bond relaxation. Therefore, compression of the aqueous solutions recovers the electrification-deformed O:H-O bond first and then proceeds to the phase transitions, which requires excessive energy for the same sequence of phase transitions. Ice exclusion of solute disperses the frequencies of characteristic phonons and the critical pressures with unlikely new bond formation.

Diagnostic value of circulating tumor cells in patients with thyroid cancer: a retrospective study of 1478 patients.

BACKGROUND: Circulating tumor cell (CTC) detection is one form of liquid biopsy. It is a novel technique that is beginning to be applied in the field of thyroid cancer. The present study was designed to evaluate the diagnostic value of CTCs in patients with thyroid cancer. METHODS: A total of 1478 patients were retrospectively analyzed and divided into malignant group (n = 747) and benign group (n = 731). Peripheral blood was collected, and CTCs were enriched and quantified before surgery. The baseline data of the two groups were matched by Propensity Score Matching (PSM). Receiver operating characteristic (ROC) curves were used to evaluate the diagnostic efficiency of different indicators for thyroid cancer. The malignant group before PSM was further divided into subgroups according to the BRAF V600E mutation and lymphatic metastasis (N stage), and the number of CTCs in different subgroups was compared. RESULTS: After 1:1 PSM, baseline characteristics of the malignant group and benign group were matched and assigned 315 cases in each group. The number of CTCs and the TPOAb values were comparable in the two groups (p > 0.05). The TgAb values [1.890 (1.110 - 16.010) vs 1.645 (1.030 - 7.073) IU/mL, p = 0.049] were significantly higher in the malignant group than in the benign group. After PSM, ROC analyses showed that the areas under the curve (AUCs) of CTC, TgAb and ultrasound were 0.537 (sensitivity 65.6%, specificity 45.8%), 0.546 (sensitivity 40.0%, specificity 70.8%) and 0.705 (sensitivity 77.1%, specificity 63.2%), respectively. The AUCs of the combined detection of 'CTC + ultrasound' (combine 1) and the combined detection of 'CTC + TgAb + ultrasound' (combine 2) were 0.718 (sensitivity 79.3%, specificity 61.7%) and 0.724 (sensitivity 78.0%, specificity 63.3%), respectively. The AUC of ultrasound was significantly higher than CTC (p < 0.001). There was no statistically significant difference in AUC between combination 1 and ultrasound, and between combination 2 and ultrasound (p > 0.05). The number of CTCs between the N0 and N1 subgroups, and between the BRAF mutant and BRAF wild subgroups was comparable (p > 0.05). CONCLUSIONS: As an emerging and noninvasive testing tool, the efficacy of CTCs in diagnosing thyroid cancer is limited.

Active and machine learning-enhanced discovery of new FGFR3 inhibitor, Rhapontin, through virtual screening of receptor structures and anti-cancer activity assessment.

Introduction: This study bridges traditional remedies and modern pharmacology by exploring the synergy between natural compounds and Ceritinib in treating Non-Small Cell Lung Cancer (NSCLC), aiming to enhance efficacy and reduce toxicities. Methods: Using a combined approach of computational analysis, machine learning, and experimental procedures, we identified and analyzed PD173074, Isoquercitrin, and Rhapontin as potential inhibitors of fibroblast growth factor receptor 3 (FGFR3). Machine learning algorithms guided the initial selection, followed by Quantitative Structure-Activity Relationship (QSAR) modeling and molecular dynamics simulations to evaluate the interaction dynamics and stability of Rhapontin. Physicochemical assessments further verified its drug-like properties and specificity. Results: Our experiments demonstrate that Rhapontin, when combined with Ceritinib, significantly suppresses tumor activity in NSCLC while sparing healthy cells. The molecular simulations and physicochemical evaluations confirm Rhapontin's stability and favorable interaction with FGFR3, highlighting its potential as an effective adjunct in NSCLC therapy. Discussion: The integration of natural compounds with established cancer therapies offers a promising avenue for enhancing treatment outcomes in NSCLC. By combining the ancient wisdom of natural remedies with the precision of modern science, this study contributes to evolving cancer treatment paradigms, potentially mitigating the side effects associated with current therapies.

Concept design of hybrid-actuated lower limb exoskeleton to reduce the metabolic cost of walking with heavy loads.

This paper proposes the conceptual design method for a hybrid-actuated lower limb exoskeleton based on energy consumption simulation. Firstly, the human-machine coupling model is established in OpenSim based on the proposed three passive assistance schemes. On this basis, the method of simulating muscle driving is used to find out the scheme that can reduce the metabolic rate the most with 3 passive springs models. Then, an active-passive cooperative control strategy is designed based on the finite state machine to coordinate the operation of the power mechanism and the passive energy storage structure and improve the mobility of the wearer. In the end, a simulation experiment based on the human-machine coupled model with the addition of active actuation is proceeded to evaluate its assistance performance according to reducing metabolic rate. The results show that the average metabolic cost decreased by 7.2% with both spring and motor. The combination of passive energy storage structures with active actuators to help the wearer overcome the additional consumption of energy storage can further reduce the body's metabolic rate. The proposed conceptual design method can also be utilized to implement the rapid design of a hybrid-actuated lower limb exoskeleton.

Advances in efficacy prediction and monitoring of neoadjuvant immunotherapy for non-small cell lung cancer.

The use of immune checkpoint inhibitors (ICIs) has become mainstream in the treatment of non-small cell lung cancer (NSCLC). The idea of harnessing the immune system to fight cancer is fast developing. Neoadjuvant treatment in NSCLC is undergoing unprecedented change. Chemo-immunotherapy combinations not only seem to achieve population-wide treating coverage irrespective of PD-L1 expression but also enable achieving a pathological complete response (pCR). Despite these recent advancements in neoadjuvant chemo-immunotherapy, not all patients respond favorably to treatment with ICIs plus chemo and may even suffer from severe immune-related adverse effects (irAEs). Similar to selection for target therapy, identifying patients most likely to benefit from chemo-immunotherapy may be valuable. Recently, several prognostic and predictive factors associated with the efficacy of neoadjuvant immunotherapy in NSCLC, such as tumor-intrinsic biomarkers, tumor microenvironment biomarkers, liquid biopsies, microbiota, metabolic profiles, and clinical characteristics, have been described. However, a specific and sensitive biomarker remains to be identified. Recently, the construction of prediction models for ICI therapy using novel tools, such as multi-omics factors, proteomic tests, host immune classifiers, and machine learning algorithms, has gained attention. In this review, we provide a comprehensive overview of the different positive prognostic and predictive factors in treating preoperative patients with ICIs, highlight the recent advances made in the efficacy prediction of neoadjuvant immunotherapy, and provide an outlook for joint predictors.

A Novel Zn2Cys6 Transcription Factor, TopC, Positively Regulates Trichodin A and Asperpyridone A Biosynthesis in Tolypocladium ophioglossoides.

Asperpyridone A represents an unusual class of pyridone alkaloids with demonstrated potential for hypoglycemic activity, primarily by promoting glucose consumption in HepG2 cells. Trichodin A, initially isolated from the marine fungus Trichoderma sp. strain MF106, exhibits notable antibiotic activities against Staphylococcus epidermidis. Despite their pharmacological significance, the regulatory mechanisms governing their biosynthesis have remained elusive. In this investigation, we initiated the activation of a latent gene cluster, denoted as "top", through the overexpression of the Zn2Cys6 transcription factor TopC in Tolypocladium ophioglossoides. The activation of the top cluster led to the biosynthesis of asperpyridone A, pyridoxatin, and trichodin A. Our study also elucidated that the regulator TopC exerts precise control over the biosynthesis of asperpyridone A and trichodin A through the detection of protein-nucleic acid interactions. Moreover, by complementing these findings with gene deletions involving topA and topH, we proposed a comprehensive biosynthesis pathway for asperpyridone A and trichodin A in T. ophioglossoides.

Design of a SMA-based soft composite structure for wearable rehabilitation gloves.

The combination of smart soft composite structure based shape memory alloy (SMA) and exoskeleton technology has the advantages of light weight, energy saving, and great human-exoskeleton interaction. However, there are no relevant studies on the application of SMA-based soft composite structure (SSCS) in hand exoskeletons. The main difficulty is that directional mechanical properties of SSCS need to comply with fingers movement, and SSCS can deliver enough output torque and displacement to the relevant joints. This paper aims to study the application of SSCS for wearable rehabilitation gloves and explore its bionic driving mechanism. This paper proposes a soft wearable glove (Glove-SSCS) for hand rehabilitation actuated by the SSCS, based on finger force analysis under different drive modes. The Glove-SSCS can support five-finger flexion and extension, weighs only 120 g, and adopts modular design. Each drive module adopts a soft composite structure. And the structure integrates actuation, sensing and execution, including an active layer (SMA spring), a passive layer (manganese steel sheet), a sensing layer (bending sensor) and connection layers. To obtain a high-performance SMA actuators, the performance of SMA materials was tested in terms of temperature and voltage, temperature at the shortest length, pre-tensile length and load. And the human-exoskeleton coupling model of Glove-SSCS is established and analyzed from force and motion. The results show that the Glove-SSCS can realize bidirectional movements of fingers flexion and extension, with ranges of motion are 90-110° and 30-40°, and their cycles are 13-19 s and 11-13 s. During the use of Glove-SSCS, the temperature of gloves is from 25 to 67°C, and the surface temperature of hands is from 32 to 36°C. The temperature of Glove-SSCS can be kept at the lowest temperature of SMA operation without much impact on the human body.

Oxalate-assisted assembly of two polyoxotantalate supramolecular frameworks with proton conduction properties.

An oxalate-assisted strategy was first developed for creating new polyoxotantalates (POTas). With this strategy, two brand-new POTa supramolecular frameworks based on uncommon dimeric POTa secondary building units (SBUs) were constructed and characterized. Interestingly, the oxalate ligand can not only serve as a coordination ligand to form unique POTa SBUs but also act as a key hydrogen bond acceptor to construct supramolecular architectures. Besides, the architectures show outstanding proton conductivity. The strategy opens up new opportunities for developing new POTa materials.

Investigation of the mechanism of different 3D printing performance of starch and whole flour gels from tuber crops.

This study aims to reveal the variation in 3D printing performance of whole flour and starch gels as derived from different varieties of tuber crops including cassava, potato, and yam, along with its mechanism. The whole flour of the same tuber crops showed a higher branching degree, average molecular weight (R¯h), and the proportion of AM chains for 100 < X ≤ 1000 than its starch. Due to the higher degree of branching, the crystallinity of whole flour reached a higher level. In this circumstance, G2' of the dispersion system decreased, which facilitated smooth extrusion of ink from the nozzle, thus improving the precision of printing for the final product. Besides, a higher R¯h and the percentage of AM chains for 100 < X ≤ 1000 made it easier for the material to extrude, thus enhancing the printing accuracy of the product. The higher short-range ordered structure of whole flour also enhanced the printing performance of 3D printed products. This research contributes an effective solution to the selection of starch and whole flour for food 3D printing.