Organoids derived from patients provide a new opportunity for research and individualized treatment of malignant peritoneal mesothelioma.

BACKGROUND: Malignant peritoneal mesothelioma (MPM) is an extremely rare and highly invasive tumor. Due to the lack of accurate models that reflect the biological characteristics of primary tumors, studying MPM remains challenging and is associated with an exceedingly unfavorable prognosis. This study was aimed to establish a new potential preclinical model for MPM using patient-derived MPM organoids (MPMOs) and to comprehensively evaluate the practicality of this model in medical research and its feasibility in guiding individualized patient treatment. METHODS: MPMOs were constructed using tumor tissue from MPM patients. Histopathological analysis and whole genome sequencing (WGS) were employed to determine the ability of MPMOs to replicate the original tumor's genetic and histological characteristics. The subcutaneous and orthotopic xenograft models were employed to assess the feasibility of establishing an in vivo model of MPM. MPMOs were also used to conduct drug screening and compare the results with retrospective analysis of patients after treatment, in order to evaluate the potential of MPMOs in predicting the effectiveness of drugs in MPM patients. RESULTS: We successfully established a culture method for human MPM organoids using tumor tissue from MPM patients and provided a comprehensive description of the necessary medium components for MPMOs. Pathological examination and WGS revealed that MPMOs accurately represented the histological characteristics and genomic heterogeneity of the original tumors. In terms of application, the success rate of creating subcutaneous and orthotopic xenograft models using MPMOs was 88% and 100% respectively. Drug sensitivity assays demonstrated that MPMOs have different medication responses, and these differences were compatible with the real situation of the patients. CONCLUSION: This study presents a method for generating human MPM organoids, which can serve as a valuable research tool and contribute to the advancement of MPM research. Additionally, these organoids can be utilized as a means to evaluate the effectiveness of drug treatments for MPM patients, offering a model for personalized treatment approaches.

Plastic Transition to Switch Nonlinear Optical Properties Showing the Record High Contrast in a Single-Component Molecular Crystal.

To switch bulk nonlinear optical (NLO) effects represents an exciting new branch of NLO material science, whereas it remains a great challenge to achieve high contrast for "on/off" of quadratic NLO effects in crystalline materials. Here, we report the supereminent NLO-switching behaviors of a single-component plastic crystal, 2-(hydroxymethyl)-2-nitro-1,3-propanediol (1), which shows a record high contrast of at least ∼150, exceeding all the known crystalline switches. Such a breakthrough is clearly elucidated from the slowing down of highly isotropic molecular motions during plastic-to-rigid transition. The deep understanding of its intrinsic plasticity and superior NLO property allows the construction of a feasible switching mechanism. As a unique class of substances with short-range disorder embedded in long-range ordered crystalline lattice, plastic crystals enable response to external stimuli and fulfill specific photoelectric functions, which open a newly conceptual avenue for the designing of new functional materials.

ABX3-Type Organic-Inorganic Hybrid Phase Transition Material: 1-Pentyl-3-methylimidazolium Tribromoplumbate.

A new one-dimensional ABX3-type organic-inorganic hybrid phase transition compound, 1-pentyl-3-methylimidazolium tribromoplumbate (1), where the Pb(II) ion exhibits hemicoordination geometry, resulting in anionic (PbBr3)n chains of an edge-shared PbBr5 polyhedron, has been successfully synthesized. 1 undergoes a reversible second-order phase transition at about 136 K. The dielectric constants of 1 exhibit an obvious steplike anomaly tuned between a high dielectric state in the high-temperature phase and a low state in the low-temperature phase. The origin of its phase transition is ascribed to the order-disorder transformation of the cation coupled with the relative displacement of the Br atoms. These findings provide a new approach to exploring a novel ABX3-type compound with functional phase transition properties.

Deep-ultraviolet transparent phosphates RbBa2(PO3)5 and Rb2Ba3(P2O7)2 show nonlinear optical activity from condensation of [PO4](3-) units.

It is challenging to explore deep-ultraviolet (deep-UV) nonlinear optical (NLO) materials that can achieve a subtle balance between deep-UV transparency and high NLO activity. Known deep-UV NLO materials are almost exclusively limited to borates, except few newly discovered phosphates despite their small NLO activities. Here we report two asymmetric phosphates, RbBa2(PO3)5 (I) and Rb2Ba3(P2O7)2 (II), which feature [PO3]∞ chains and [P2O7](4-) dimers formed by condensation of [PO4](3-) units, respectively. Remarkably, I achieves the desired balance, with the shortest deep-UV absorption edge at 163 nm and the largest NLO activity of 1.4 × KDP (KH2PO4) in deep-UV NLO phosphates. According to first-principles calculations, the enhanced macroscopic SHG response of I can be attributed to the [PO3]∞ chains which exhibit significantly larger microscopic SHG coefficients as compared with the [P2O7](4-) dimers.

Risk and prognosis of second cutaneous melanoma after radiotherapy for breast cancer: A population-based analysis.

Radiation therapy (RT), a primary treatment for breast cancer (BC), may be associated with increased non-BC tumor risk. We aimed to examine second cutaneous melanoma (SCM) risk in BC patients who underwent RT and to assess their survival outcomes. Data from 520,977 BC patients diagnosed between 1973-2018 were collected from the Surveillance, Epidemiology, and End Results (SEER) database. Cumulative SCM incidence was estimated using the Fine-Gray competing risk model. Poisson regression analysis was conducted to calculate the standardized incidence ratio (SIR) and estimate the SCM relative risk in patients who underwent RT compared to those who did not. Overall survival (OS) and cancer-specific survival (CSS) were assessed using the Kaplan‒Meier method. Among the 520,977 BC patients, 243,676 (46.8%) underwent surgery and RT, while 277,301 (53.2%) only underwent surgery. Our results suggest that BC patients receiving RT had a higher SCM risk than those who did not (hazard ratio [HR] 1.40; 95% confidence interval [CI] 1.30-1.51; P < 0.001). SCM incidence was also higher in BC patients treated with RT than in the general US population (SIR 1.12; 95% CI 1.05-1.19; P < 0.05). However, SCM patients who received RT had a significantly higher 10-year survival rate than those who did not receive RT (14.90% vs 5.94%; P < 0.001). No significant difference was found in 10-year OS or 5-year CSS between SCM following RT and only primary cutaneous melanoma (OPCM), but SCM patients who did not receive RT had a significantly lower 10-year OS, with no significant difference in CSS. This study suggests an increased SCM likelihood in BC patients due to RT, although the overall risk is minimal.

Identification and Validation of SLC9A2 as A Potential Tumor Suppressor in Colorectal Cancer: Integrating Bioinformatics Analysis with Experimental Confirmation.

OBJECTIVE: To uncover the mechanisms underlying the development of colorectal cancer (CRC), we applied bioinformatic analyses to identify key genes and experimentally validated their possible roles in CRC onset and progression. METHODS: We performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis on differentially expressed genes (DEGs), constructed a protein-protein interaction (PPI) network to find the top 10 hub genes, and analyzed their expression in colon adenocarcinoma (COAD) and rectum adenocarcinoma (READ). We also studied the correlation between these genes and immune cell infiltration and prognosis and validated the expression of SLC9A2 in CRC tissues and cell lines using qRT-PCR and Western blotting. Functional experiments were conducted in vitro to investigate the effects of SLC9A2 on tumor growth and metastasis. RESULTS: We found 130 DEGs, with 45 up-regulated and 85 down-regulated in CRC. GO analysis indicated that these DEGs were primarily enriched in functions related to the regulation of cellular pH, zymogen granules, and transmembrane transporter activity. KEGG pathway analysis revealed that the DEGs played pivotal roles in pancreatic secretion, rheumatoid arthritis, and the IL-17 signaling pathway. We identified 10 hub genes: CXCL1, SLC26A3, CXCL2, MMP7, MMP1, SLC9A2, SLC4A4, CLCA1, CLCA4, and ZG16. GO enrichment analysis showed that these hub genes were predominantly involved in the positive regulation of transcription. Gene expression analysis revealed that CXCL1, CXCL2, MMP1, and MMP7 were highly expressed in CRC, whereas CLCA1, CLCA4, SLC4A4, SLC9A2, SLC26A3, and ZG16 were expressed at lower levels. Survival analysis revealed that 5 key genes were significantly associated with the prognosis of CRC. Both mRNA and protein expression levels of SLC9A2 were markedly reduced in CRC tissues and cell lines. Importantly, SLC9A2 overexpression in SW480 cells led to a notable inhibition of cell proliferation, migration, and invasion. Western blotting analysis revealed that the expression levels of phosphorylated ERK (p-ERK) and phosphorylated JNK (p-JNK) proteins were significantly increased, whereas there were no significant changes in the expression levels of ERK and JNK following SLC9A2 overexpression. Correlation analysis indicated a potential link between SLC9A2 expression and the MAPK signaling pathway. CONCLUSION: Our study suggests that SLC9A2 acts as a tumor suppressor through the MAPK pathway and could be a potential target for CRC diagnosis and therapy.

Study on the Effect of Bushen Zhuanggu Tablet Combined with Conventional Regimen on Bone Mineral Density Improvement, Functional Recovery and Fracture Risk Prevention in Patients with Postmenopausal Osteoporosis.

Objective: This case-control study was to explore the effect of Bushen Zhuanggu tablet combined with routine regimen on bone mineral density (BMD) improvement, functional recovery, and fracture prevention in postmenopausal osteoporosis (PMOP) patients. Methods: 180 postmenopausal osteoporosis patients were randomly selected from communities A, B, and C cohorts as research subjects from January to May 2021. The study subjects were divided into three groups. The groups were in a 1 : 1 ratio according to the principles of nonrandomised, concurrent controlled trials, and methods. There were 60 participants in each group (group A, group B, and group C). Group A was treated with Bushen Zhuanggu tablet for antiosteoporosis + basic treatment (calcium supplement and vitamin D). Group C was given Bushen Zhuanggu tablet for antiosteoporosis intervention. Group B was given basic treatment (calcium supplement and vitamin D supplementation) as a control group. The follow-up time was 6 months after treatment. Finally, we compare the differences in calcium and phosphorus metabolism indexes, BMD, bone metabolism indexes, upper and lower limb muscle strength, and quality of life scores. Results: Group A, B, and C's effective rate was 98.33%, 80.00%, and 93.33%, respectively. The group A's effective rate was significantly higher than that in group B and C, and the difference was statistically significant (P < 0.05). After 6 months intervention, the levels of serum Ca2+, serum phosphorus (P), serum creatinine (Cr), and parathyroid hormone (PTH) in 3 groups decreased. Ca, P, Scr, and PTH levels in group A were the lowest among study groups, and the difference was statistically significant (P < 0.05). The increase in the BMD of lumbar spine, the left femoral neck, and Ward's triangle area of the three groups were observed with the highest data in group A. After 6 months of treatment, the levels of serum N-terminal propeptide of type I procollagen, PINP, and serum osteocalcin (OC) increased, while the levels of ß-cross-linked C-terminal telopeptide of type I collagen (ß-CTX) and alkaline phosphatase (ALP) decreased in the three groups. The improvement of all bone metabolic indexes in group A was significantly better than that in B and C groups, and the difference was statistically significant (P < 0.05). The enhanced upper limb muscle strength and the shorter standing-walking timing test (TUGT) time were observed after 6 months of treatment. The improvement effect of upper and lower limb muscle strength in group A was significantly better than that in B and C groups, and the difference was statistically significant (P < 0.05). There were significant differences in physiological function, life function, general health status, physical pain, mental state, emotional function, vitality, and social function among the three groups after 6 months treatment, and the difference was statistically significant (P < 0.05). The score of quality of life in group A was higher than that in B and C groups, and the difference was statistically significant (P < 0.05). Conclusion: Bushen Zhuanggu tablet combined with conventional therapy is effective in the postmenopausal osteoporosis treatment, which effectively increase the BMD, regulate calcium and phosphorus metabolism, promote the recovery of limb function, prevent the recurrence of fracture, and improve the patients' quality of life. This treatment scheme is worth popularizing.

Upregulation of Apolipoprotein L6 Improves Tumor Immunotherapy by Inducing Immunogenic Cell Death.

In the past few years, immune checkpoint blockade (ICB) therapy has emerged as a breakthrough treatment for cancers and has demonstrated inspiring effects in tumor patients with Epstein-Barr virus (EBV) infection. To allow more patients to benefit from immunotherapy, exploring novel biomarkers based on EBV-related tumors and immunotherapy cohorts was pursued in the present study. The essential biomarkers that may enhance antitumor immunity across EBV-related tumors were identified using the large-scale transcriptomic profiles of EBV-associated tumors and tumor immunotherapy cohorts. The clinical significance of vital genes was evaluated in multiple tumor immunotherapy cohorts. Moreover, the potential function of essential genes in immunotherapy was explored via bioinformatic analyses and verified by qRT-PCR, Western blot analysis, CCK8 assay and flow cytometry. Apolipoprotein L6 (APOL6) was considered the essential biomarker for enhancing antitumor immunity across EBV-positive tumors. The upregulation of APOL6 was correlated with increased response rates and prolonged survival in multiple tumor immunotherapy cohorts. Bioinformatic analyses suggested that APOL6 may enhance tumor immunotherapy by inducing immunogenic cell death. Pancreatic cancer cells transfected with APOL6 overexpression plasmid underwent apoptosis, necroptosis, and pyroptosis with immunogenic features. The biomarker upregulated in EBV-related tumors could further elucidate the drivers of immunotherapy response. The upregulation of APOL6 could improve immunotherapy by triggering immunogenic cell death, thus offering a new target to optimize cancer immunotherapy.

A 3D polar nanotubular coordination polymer with dynamic structural transformation and ferroelectric and nonlinear-optical properties.

A chiral coordination nanotube, [Cd(3)(BPT)(2)(H(2)O)(9)]·2H(2)O (Cd-1; BPT = biphenyl-3,4',5-tricarboxylate), has been synthesized from achiral components and structurally characterized. It consists of homochiral channels based on right-handed helical chains and shows an interdigitated interaction to give a chiral 3D network. The chiral nanotubular framework exhibts dynamic structural transformation upon removal of the guest molecules, and the polarity of this compound induces it to display both ferroelectric and nonlinear-optical properties.

Bis(imidazolium) L-tartrate: a hydrogen-bonded displacive-type molecular ferroelectric material.

A hydrogen-bonded ionic cocrystal with imidazole as molecular rotator and L-tartaric acid as homochiral component is reported as a displacive-type ferroelectric material. It undergoes a paraelectric-ferroelectric phase transition at 252 K with exceptional dielectric responses triggered by atomic displacements.

Point cloud registration of arrester based on scale-invariant points feature histogram.

Arrester is an important lightning protection device in the electrical field. The parameters of arrester such as creepage distance, umbrella distance and diameter are important for product quality, but they are difficult to measure because the shape of arrester is irregular. However, the three-dimensional (3D) reconstruction technique is efficient in measuring arrester parameters. The uniform distributed structure of umbrella skirt on the arrester surface restrict the registration of point cloud. In this paper, a scale-invariant points features histogram (SIPFH) descriptor is proposed; the descriptor combines the characteristics of Scale-invariant Feature Transform (SIFT) and fast point feature histogram (FPFH). Moreover, the improved Levenberg-Marquardt (LM) algorithm is presented, the maximum distance of corresponding points in the iterative process is adjusted to realize the local optimization. The point cloud registration method consists of two parts: primary registration method based on SIPFH, and secondary registration method based on improved LM algorithm. Point clouds of different arresters are collected to establish datasets, some of which have interference. Experimental results indicate that the root mean square error of the method is less than 0.02 m; the average running time is 2.7 s, which is [Formula: see text] of the conventional method based on FPFH.

S100A10 Promotes Pancreatic Ductal Adenocarcinoma Cells Proliferation, Migration and Adhesion through JNK/LAMB3-LAMC2 Axis.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive tumors, characterized by diagnosis at an advanced stage and a poor prognosis. As a member of the S100 protein family, S100A10 regulates multiple biological functions related to cancer progression and metastasis. However, the role of S100A10 in PDAC is still not completely elucidated. In this study, we reported that S100A10 was significantly up-regulated in PDAC tissue and associated with a poor prognosis by integrated bioinformatic analysis and human PDAC tissue samples. In vitro, down-regulation of S100A10 reduced the proliferation, migration, and adhesion of PDAC cell lines, whereas up-regulation of S100A10 showed the opposite effect. Furthermore, LAMB3 was proved to be activated by S100A10 using RNA-sequencing and western blotting. The effect of LAMB3 on the proliferation, migration, and adhesion of PDAC cells was similar to that of S100A10. Up-regulation or down-regulation of LAMB3 could reverse the corresponding effect of S100A10. Moreover, we validated S100A10 activates LAMB3 through the JNK pathway, and LAMB3 was further proved to interact with LAMC2. Mice-bearing orthotopic pancreatic tumors showed that S100A10 knocked-down PANC-1 cells had a smaller tumor size than the control group. In conclusion, S100A10 promotes PDAC cells proliferation, migration, and adhesion through JNK/LAMB3-LAMC2 axis.

Ultrahigh pyroelectric figures of merit associated with distinct bistable dielectric phase transition in a new molecular compound: di-n-butylaminium trifluoroacetate.

Ultrahigh pyroelectric figures of merit are achieved in a new phase-transition material, di-n-butylaminium trifluoroacetate, of which the peak values are an order of magnitude larger than those of their inorganic counterparts. Such an attractive behavior of pyroelectric detectivity is strongly related to its distinct bistable dielectric behavior, which recalls excellent thermoelectric response in organic molecular phase-transition systems.

A host-guest inclusion compound for reversible switching of quadratic nonlinear optical properties.

A host-guest inclusion compound [(DPA)(18-crown-6)]ClO4 (DPA = dipropylamine) undergoes a reversible phase transition at 214 K, which enables it to switch the NLO response between SHG-ON and SHG-OFF states associated with the order-disorder transition of the guest DPA cations and a slight tilting of the host 18-crown-6 molecules.

Thermodynamic phase transition triggered by distinct distortion and ordering of dipropylammonium picrate.

Dipropylammonium picrate (compound 1) undergoes a first-order phase transition at 185.0 K. Differential scanning calorimetry (DSC) measurements show reversible anomaly peaks with a thermal hysteresis of 10.2 K. Dielectric responses with distinct anisotropy and striking anomaly further confirm the phase transition. Detailed structural analyses demonstrate that the phase transition in 1 is dominated by order-disorder transformations of the dipropylammonium (DPA) cations and the picrate anions. Moreover, the unique distortions of the terminal propyl moieties in the flexible chain-like DPA cation also play an important role in this structural phase transition. All these results indicate that 1 is a potential phase-transition material.

Phase transition originating from order-disorder transformations of carboxy oxygen atoms coupled with dynamic proton motions in [PhCH2 NH(CH3)2]2 C2O4⋠H2 C2O4.

A new molecular phase transition material, [PhCH(2) NH(CH(3))(2)](2) C(2)O(4)⋅H(2)C(2)O(4), which undergoes a reversible phase transition at 151.6 K, has been successfully synthesized. Differential scanning calorimetry (DSC), specific heat capacity, and dielectric measurements confirm its reversible phase transition with a large thermal hysteresis of 15.1 K, demonstrating that the phase transition is typical first order. Variable-temperature single-crystal X-ray diffraction analyses reveal that the order-disorder transformations of carboxy oxygen atoms induce the structural phase transition. A slight reorientation of the oxalic acid unit is discovered to accompany the ordering of carboxy oxygen atoms at low temperature. The DSC measurement result of the deuterated analog is different to that of 1, indicating that proton dynamic motions in hydrogen bonds also contribute to the phase transition.

Switchable dielectric phase transition induced by a twisting transformation in diglycine methanesulfonate.

A new glycine-based reversible phase transition compound diglycine methanesulfonate (1) has been successfully synthesized. Differential scanning calorimetry (DSC) measurements of 1 showed a pair of broad peaks around 134 K (T(c)=phase transition temperature) with a slight thermal hysteresis during the heating/cooling cycle, thereby indicating that this compound undergoes a reversible second-order phase transition. Dielectric measurements further confirmed the phase transition and revealed a switchable response to the ambient temperature change for the dielectric constants of 1, namely, the dielectric constants have a distinctive step-like anomaly switching between a high dielectric state in the room temperature phase (RTP) and a low state in the low temperature phase (LTP). Variable-temperature single-crystal X-ray diffraction analyses show that 1 undergoes an atypical transition from the space group P21/m in the RTP to P21/c in the LTP. The origin of the switchable dielectric phase transition is ascribed to the movement of the moieties in 1 from the equilibrium position, and this stems from the twisting of the molecules in the compound. We believe that these findings will be useful in exploring switchable dielectric phase transition materials.