Clinical treatment patterns, molecular characteristics and survival outcomes of ROS1-rearranged non-small cell lung cancer: A large multicenter retrospective study.

BACKGROUND: Non-small cell lung cancer (NSCLC) harboring ROS1 rearrangements is a molecular subset that exhibits favorable responses to tyrosine kinase inhibitor (TKI) treatment than chemotherapy. This study investigated real-world treatment patterns and survival outcomes among patients with ROS1-rearranged advanced NSCLC. METHODS: We conducted a retrospective analysis of patients with ROS1-rearranged advanced NSCLC treated in four different hospitals in China from August 2018 to March 2022. The study analyzed gene fusion distribution, resistance patterns, and survival outcomes. RESULTS: ROS1 rearrangement occurs in 1.8 % (550/31,225) of our study cohort. CD74 was the most common ROS1 fusion partner, accounting for 45.8 %. Crizotinib was used in 73.9 % of patients in the first-line treatment, and an increased use of chemotherapy, ceritinib, and lorlatinib was seen in the second-line setting. Lung (43.2 %) and brain (27.6 %) were the most common sites of progression in first-line setting, while brain progression (39.2 %) was the most common site of progression in second-line. Median overall survival was 46 months (95 % confidence intervals: 39.6-52.4). First-line crizotinib use yielded significantly superior survival outcomes over chemotherapy in terms of progression-free (18.5 vs. 6.0; p < 0.001) and overall survival (49.8 vs. 37; p = 0.024). The choice of treatment in the latter line also had survival implications, wherein survival outcomes were better when first-line crizotinib was followed by sequential TKI therapy than first-line chemotherapy followed by TKI therapy. CONCLUSIONS: Our study provided insights into the real-world treatment, drug resistance patterns, and survival outcomes among patients with ROS1-rearranged NSCLC. This information serves as a valuable reference for guiding the treatment of this molecular subset of NSCLC.

Chitin whisker/chitosan liquid crystal hydrogel assisted scaffolds with bone-like ECM microenvironment for bone regeneration.

Natural bone exhibits a complex anisotropic and micro-nano hierarchical structure, more importantly, bone extracellular matrix (ECM) presents liquid crystal (LC) phase and viscoelastic characteristics, providing a unique microenvironment for guiding cell behavior and regulating osteogenesis. However, in bone tissue engineering scaffolds, the construction of bone-like ECM microenvironment with exquisite microstructure is still a great challenge. Here, we developed a novel polysaccharide LC hydrogel supported 3D printed poly(l-lactide) (PLLA) scaffold with bone-like ECM microenvironment and micro-nano aligned structure. First, we prepared a chitin whisker/chitosan polysaccharide LC precursor, and then infuse it into the pores of 3D printed PLLA scaffold, which was previously surface modified with a polydopamine layer. Next, the LC precursor was chemical cross-linked by genipin to form a hydrogel network with bone-like ECM viscoelasticity and LC phase in the scaffold. Subsequently, we performed directional freeze-casting on the composite scaffold to create oriented channels in the LC hydrogel. Finally, we soaked the composite scaffold in phytic acid to further physical cross-link the LC hydrogel through electrostatic interactions and impart antibacterial effects to the scaffold. The resultant biomimetic scaffold displays osteogenic activity, vascularization ability and antibacterial effect, and is expected to be a promising candidate for bone repair.

Clinical evidence for efficacy of pembrolizumab in MSI-H and TMB-H advanced solid tumor: results from three cancer centers in China.

BACKGROUND: Pembrolizumab has been indicated in the treatment of solid tumors with high frequency microsatellite instability (MSI-H) or high tumor mutational burden (TMB-H); however, real-world data on the effectiveness of pembrolizumab with or without chemotherapy in this molecular subset remain limited. Our retrospective study evaluated the clinical efficacy and safety of pembrolizumab in treating advanced solid tumors with either MSI-H or TMB-H. METHODS: This retrospective study analyzed data from 116 patients with MSI-H or TMB-H advanced solid cancers who received pembrolizumab with or without chemotherapy regardless of treatment setting. We analyzed objective response rate (ORR) and progression-free survival (PFS). RESULTS: The top three cancer types were colorectal (48.6% MSI-H, 6.5% TMB-H), lung (15.4% MSI-H, 84.4% TMB-H), and gastric (15.4% MSI-H, 5.1% TMB-H). The ORR with pembrolizumab was 52.6%, including complete response (CR) observed in 8.6% (n = 10) of cases and partial responses (PR) in 43.9% (n = 51). Of the 93 patients who received first-line pembrolizumab, 52 patients achieved objective response (10 CR, 42 PR), with a median PFS of 14.0 months (95% confidence intervals [CI] 6.6-21.4). Of the 23 who received subsequent-line pembrolizumab, the ORR was 39.1%, disease control rate was 91.3%, and median PFS was 5.7 months (95% CI 3.9-7.5). Treatment-related adverse events were observed in 32 patients (27.6%), with no reported treatment-related fatal adverse events. CONCLUSION: Our study provides real-world evidence on the clinical effectiveness of pembrolizumab with or without chemotherapy in the treatment of patients with MSI-H and TMB-H advanced solid cancers.

Mechanical properties of artificially structured soil and Binary-medium-based constitutive model under undrained conditions.

To investigate the mechanical properties and constitutive models of structured soil under undrained conditions, triaxial compression tests on initially anisotropic structured soil, isotropic structured soil, and remolded soil were conducted under consolidation undrained conditions at confining pressures of 25, 50, 100, and 200 kPa, respectively. The results demonstrate that the samples of structured soils with strong structural characteristics have an obvious yield strength when the consolidation stress is low. At this time, the pore water pressure in structured soils increases at the beginning of loading. As the axial strain increasing, it turns to reduce. When failure, the samples have obvious shear band. With the consolidation stress increases, the mechanical properties and deformation mechanism of structured soils are near to the remolded soil. Combining the Binary-medium theory with the analysis and discussion of the mechanical properties and deformation mechanisms of structured soil, the rationality of the corresponding Binary-medium model was verified, which shows that the constitutive model can reflect the characteristics of dilatancy and strain softening, volumetric contraction and strain hardening under the conditions of low and high confining pressure respectively. At the same time, the constitutive model can also reflect the differences in the stress-strain characteristics of the two structural soils caused by the structural differences. In general, the results agree with the experiment relative well.

Acacetin protects against sepsis-induced acute lung injury by facilitating M2 macrophage polarization via TRAF6/NF-κB/COX2 axis.

Acute lung injury (ALI) is the leading cause of death in patients with sepsis syndrome and without effective protective or therapeutic treatments. Acacetin, a natural dietary flavonoid, reportedly exerts several biological effects, such as anti-tumor, anti-inflammatory, and anti-oxidative effects. However, acacetin's effect and underlying mechanism on sepsis-induced ALI remain unclear. Here, the mouse model was established to explore the impact of acacetin on sepsis-induced ALI. Acacetin significantly increased ALI murine survival and attenuated lung injury in histological examinations. Additionally, acacetin down-regulated myeloperoxidase activity, protein concentration, and number of neutrophils and macrophages in bronchoalveolar lavage fluid. Subsequently, inflammatory cytokines, including TNF-α, IL-1ß, and IL-6, were examined. Results showed that acacetin dramatically suppressed the production of TNF-α, IL-1ß, and IL-6. These above results indicated that acacetin attenuated sepsis-induced ALI by inhibiting the inflammatory response. Moreover, acacetin inhibited the expression of markers for M1-type (iNOS, CD86) macrophages and promoted the expression of markers for M2-type (CD206, Arg1) macrophages by western blot. In addition, acacetin down-regulated the expression TRAF6, NF-κB, and Cyclooxygenase-2 (COX2) by western blot. The high concentration of acacetin had a better effect than the low concentration. Besides, over-expression of TRAF6 up-regulated the expression of COX2, CD86, and iNOS, and the ratio of p-NF-κB to NF-κB increased the mRNA levels of TNF-α, IL-1ß, and IL-6, down-regulated the expression of CD206 and Arg1. The effects of TRAF6 were the opposite of acacetin. And TRAF6 could offset the impact of acacetin. This study demonstrated that acacetin could prevent sepsis-induced ALI by facilitating M2 macrophage polarization via TRAF6/NF-κB/COX2 axis.

Flexible Hybrid Wearable Sensors for Pressure and Thermal Sensing Based on a Double-Network Hydrogel.

Flexible sensors have attracted great attention due to their wide applications in various fields such as motion monitoring and medical health. It is reasonable to develop a sensor with good flexibility, sensitivity, and biocompatibility for wearable device applications. In this study, a double-network hydrogel was obtained by blending poly(vinyl alcohol) (PVA) with poly(ethylene glycol) diacrylate (PEGDA), which combines the flexibility of the PVA network and the fast photocuring ability of PEGDA. Subsequently, polydopamine-coated carbon nanotubes were used as conductive fillers of the PVA-PEG hydrogel matrix to prepare a flexible sensor that exhibits an effective mechanical response and significant stability in mechanics and conductivity. More importantly, the resistance of the sensor is very sensitive to pressure and thermal changes due to the optimized conductive network in the hydrogel. A motion monitoring test showed that the flexible sensor not only responds quickly to the motion of different joints but also keeps the output signal stable after many cycles. In addition, the excellent cell affinity of the hybrid hydrogel also encourages its application in health monitoring and motion sensors.

A route to metalloligands consolidated silver nanoclusters by grafting thiacalix[4]arene onto polyoxovanadates.

Metalloligands provide a potent strategy for manipulating the surface metal arrangements of metal nanoclusters, but their synthesis and subsequent installation onto metal nanoclusters remains a significant challenge. Herein, two atomically precise silver nanoclusters {Ag14[(TC4A)6(V9O16)](CyS)3} (Ag14) and {Ag43S[(TC4A)2(V4O9)]3(CyS)9(PhCOO)3Cl3(SO4)4(DMF)3·6DMF} (Ag43) are synthesized by controlling reaction temperature (H4TC4A = p-tert-butylthiacalix[4]arene). Interestingly, the 3D scaffold-like [(TC4A)6(V9O16)]11- metalloligand in Ag14 and 1D arcuate [(TC4A)2(V4O9)]6- metalloligand in Ag43 exhibit a dual role that is the internal polyoxovanadates as anion template and the surface TC4A4- as the passivating agent. Furthermore, the thermal-induced structure transformation between Ag14 and Ag43 is achieved based on the temperature-dependent assembly process. Ag14 shows superior photothermal conversion performance than Ag43 in solid state indicating its potential for remote laser ignition. Here, we show the potential of two thiacalix[4]arene modified polyoxovanadates metalloligands in the assembly of metal nanoclusters and provide a cornerstone for the remote laser ignition applications of silver nanoclusters.

Modulating of Bouligand Structure and Chirality Constructed Bionically Based on the Self-Assembly of Chitin Whiskers.

Chitin can self-assemble into a liquid crystal phase with supramolecular chirality and Bouligand structure, which is widely found in the exoskeletons of arthropods. However, bionically replicating this structure via the self-assembly of chitin whiskers (CHWs) is still a challenge. Here, the effects of several internal and external parameters on the self-assembly of CHWs were revealed based on liquid crystal phase, chirality, Bouligand structure, and rheological properties. The formation of chiral liquid crystal phase and Bouligand structure largely depends on the concentration of CHWs and, meanwhile, is affected by the aspect ratio and zeta potential of CHWs and the self-assembly time. Impressively, introducing electrolytes and changing pH significantly affect the thickness of the electrical double layer, thereby also affecting the self-assembly of CHWs. This study offers a comprehensive understanding of CHWs' self-assembly process, which is beneficial for the bionic design of new nature-inspired functional materials with chiral characteristic and Bouligand structure.

Clinical activity of pembrolizumab with or without chemotherapy in advanced pulmonary large-cell and large-cell neuroendocrine carcinomas: a multicenter retrospective cohort study.

BACKGROUND: Immune checkpoint inhibitors (ICI)-based combination strategies have improved the survival outcomes in advanced non-small cell lung cancers; however, data regarding their efficacy remains limited for uncommon histological types, including large-cell carcinoma (LCC) and large-cell neuroendocrine carcinoma (LCNEC). METHODS: We retrospectively analyzed a total of 60 patients with advanced LCC and LCNEC - 37 treatment-naïve and 23 pre-treated - who received pembrolizumab with or without chemotherapy. Treatment and survival outcomes were analyzed. RESULTS: Of the 37 treatment-naïve patients who received first-line pembrolizumab combined with chemotherapy, the 27 patients with LCC had an overall response rate (ORR) of 44.4% (12/27) and a disease control rate (DCR) of 88.9% (24/27); whereas 10 patients with LCNEC had an ORR of 70% (7/10) and DCR of 90% (9/10). The median progression-free survival (mPFS) was 7.0 months (95% confidence intervals [CI]: 2.2-11.8) and median overall survival (mOS) was 24.0 months (95%CI: 0.0-50.1) for first-line pembrolizumab plus chemotherapy of LCC (n = 27), whereas mPFS was 5.5 months (95%CI: 2.3-8.7) and mOS was 13.0 months (95%CI: 11.0-15.0) for first-line pembrolizumab plus chemotherapy of LCNEC (n = 10). Of the 23 pre-treated patients who received subsequent-line pembrolizumab with or without chemotherapy, mPFS was 2.0 months (95% CI: 0.6-3.4) and mOS was 4.5 months (95% CI: 0.0-9.0) for LCC and mPFS was 3.8 months (95% CI: 0.0-7.6) and mOS was not reached for LCNEC. CONCLUSION: Our study provides real-world clinical evidence of the anti-tumor activity of pembrolizumab plus chemotherapy in advanced LCC and LCNEC, indicating that this regimen could serve as a treatment option, particularly as first-line therapy, for improving the survival outcomes of patients with these rare histological subtypes of lung cancer. TRIAL REGISTRATION: NCT05023837(ESPORTA, 27/08/2021).

Smart nanostructures for targeted oxygen-producing photodynamic therapy of skin photoaging and potential mechanism.

Background: Photodynamic therapy increases collagen and decreases solar fibrosis in photoaged skin; however, the efficacy of photodynamic therapy is limited in tissues with a hypoxic microenvironment. Methods: A novel autogenous oxygen-targeted nanoparticle, named MCZT, was synthesized based on the zeolitic imidazole framework material ZIF-8, methyl aminolevulinate, catalase and an anti-TRPV1 monoclonal antibody, and its effects on skin photoaging were investigated. Results: MCZT was successfully synthesized and showed uniform particle size, good dispersion, and excellent biocompatibility and safety. Moreover, MCZT effectively alleviated UV-induced inflammation, cellular senescence and apoptosis in HFF-1 cells. In in vivo models, MCZT ameliorated UV-evoked erythema and wrinkling, inflammation and oxidative stress, as well as the loss of collagen fibers and water, in the skin of mice. Conclusion: These findings suggest that MCZT holds promising potential for the treatment of skin photoaging.

CMOS Radio Frequency Energy Harvester (RFEH) with Fully On-Chip Tunable Voltage-Booster for Wideband Sensitivity Enhancement.

Radio frequency energy harvesting (RFEH) is one form of renewable energy harvesting currently seeing widespread popularity because many wireless electronic devices can coordinate their communications via RFEH, especially in CMOS technology. For RFEH, the sensitivity of detecting low-power ambient RF signals is the utmost priority. The voltage boosting mechanisms at the input of the RFEH are typically applied to enhance its sensitivity. However, the bandwidth in which its sensitivity is maintained is very poor. This work implements a tunable voltage boosting (TVB) mechanism fully on-chip in a 3-stage cross-coupled differential drive rectifier (CCDD). The TVB is designed with an interleaved transformer architecture where the primary winding is implemented to the rectifier, while the secondary winding is connected to a MOSFET switch that tunes the inductance of the network. The TVB enables the sensitivity of the rectifier to be maintained at 1V DC output voltage with a minimum deviation of -2 dBm across a wide bandwidth of 3 to 6 GHz of 5G New Radio frequency (5GNR) bands. A DC output voltage of 1 V and a peak PCE of 83% at 3 GHz for -23 dBm input power are achieved. A PCE of more than 50% can be maintained at the sensitivity point of 1 V with the aid of TVB. The proposed CCDD-TVB mechanism enables the CMOS RFEH to be operated for wideband applications with optimum sensitivity, DC output voltage, and efficiency.

Identification of KCNK1 as a potential prognostic biomarker and therapeutic target of breast cancer.

BACKGROUND: Breast cancer is the most common malignant cancer and is the second most common cause of cancer-related deaths among females worldwide. Thus, it warrants the urgent development of new therapeutic targets and strategies. Potassium channels are aberrantly expressed in various tumors and are related to tumor progression. However, studies on potassium channels in breast cancer remain limited. METHOD: First, The Cancer Genome Atlas (TCGA) and Gene Set Enrichment Analysis (GSEA) were used to screen the differentially expressed potassium channels in breast cancer. Several other databases were utilized for further data analysis and visualization, including Gene Expression Profiling Interactive Analysis 2 (GEPIA2), Human Protein Atlas (HPA), GeneMANIA, Tumor Immune Estimation Resource 2 (TIMER2), Catalog of Somatic Mutations in Cancer (COSMIC), cBioPortal, and UCSC Xena tool. Besides, cell proliferation was detected by cell counting kit-8 (CCK8) and 5-Ethynyl-20-deoxyuridine (EdU), and cell migration was detected by wound healing and Transwell assays after knocking down KCNK1. Furthermore, the effect of KCNK1 knockdown on the sensitivity of breast cancer cells to paclitaxel was also evaluated. RESULT: KCNK1 was overexpressed in breast cancer. Higher KCNK1 expression predicted an unfavorable prognosis. Moreover, the abnormal expression of KCNK1 was attributed to promoter hypomethylation of KCNK1 in breast cancer. Besides, cell proliferation and migration were significantly inhibited post-KCNK1 silencing, while KCNK1 knockdown significantly increased breast cancer cell sensitivity to paclitaxel. CONCLUSION: Taken together, our findings demonstrated that KCNK1 is a potential prognostic biomarker and therapeutic target of breast cancer. Thus, targeting KCNK1 might help synergize with paclitaxel function in breast cancer treatment.

Bone ECM-like 3D Printing Scaffold with Liquid Crystalline and Viscoelastic Microenvironment for Bone Regeneration.

Implanting a 3D printing scaffold is an effective therapeutic strategy for personalized bone repair. As the key factor for the success of bone tissue engineering, the scaffold should provide an appropriate bone regeneration microenvironment and excellent mechanical properties. In fact, the most ideal osteogenic microenvironment is undoubtedly provided by natural bone extracellular matrix (ECM), which exhibits liquid crystalline and viscoelastic characteristics. However, mimicking a bone ECM-like microenvironment in a 3D structure with outstanding mechanical properties is a huge challenge. Herein, we develop a facile approach to fabricate a bionic scaffold perfectly combining bone ECM-like microenvironment and robust mechanical properties. Creatively, 3D printing a poly(l-lactide) (PLLA) scaffold was effectively strengthened via layer-by-layer electrostatic self-assembly of chitin whiskers. More importantly, a kind of chitin whisker/chitosan composite hydrogel with bone ECM-like liquid crystalline state and viscoelasticity was infused into the robust PLLA scaffold to build the bone ECM-like microenvironment in 3D structure, thus highly promoting bone regeneration. Moreover, deferoxamine, an angiogenic factor, was encapsulated in the composite hydrogel and sustainably released, playing a long-term role in angiogenesis and thereby further promoting osteogenesis. This scaffold with bone ECM-like microenvironment and excellent mechanical properties can be considered as an effective implantation for bone repair.

RSK2 promotes melanoma cell proliferation and vemurafenib resistance via upregulating cyclin D1.

BRAF inhibitors are commonly used in targeted therapies for melanoma patients harboring BRAFV600E mutant. Despite the benefit of vemurafenib therapy, acquired resistance during or after treatment remains a major obstacle in BRAFV600E mutant melanoma. Here we found that RSK2 is overexpressed in melanoma cells and the high expression of RSK2 indicates poor overall survival (OS) in melanoma patients. Overexpression of RSK2 leads to vemurafenib resistance, and the deletion of RSK2 inhibits cell proliferation and sensitizes melanoma cells to vemurafenib. Mechanistically, RSK2 enhances the phosphorylation of FOXO1 by interacting with FOXO1 and promoting its subsequent degradation, leading to upregulation of cyclin D1 in melanoma cells. These results not only reveal the presence of a RSK2-FOXO1-cyclin D1 signaling pathway in melanoma, but also provide a potential therapeutic strategy to enhance the efficacy of vemurafenib against cancer.

Current understanding on the role of CCT3 in cancer research.

Chaperonin containing TCP1 Subunit 3 (CCT3) is an important member of the chaperone protein family, providing a favorable environment for the correct folding of proteins in cell division, proliferation, and apoptosis pathways, which is involved in a variety of biological processes as well as the development and invasion of many malignant tumors. Many malignancies have been extensively examined with CCT3. It is presently used as a possible target for the treatment of many malignancies since it is not only a novel biomarker for the screening and diagnosis of different tumors, but it is also closely associated with tumor progression, prognosis, and survival. Recent studies have shown that the expression of CCT3 is up-regulated in some tumors, such as liver cancer, breast cancer, colon cancer, acute myeloid leukemia, etc. In this paper, we review the role of CCT3 in various tumors.

Dual-Cross-linked Liquid Crystal Hydrogels with Controllable Viscoelasticity for Regulating Cell Behaviors.

The liquid crystal properties and viscoelasticity of the natural bone extracellular matrix (ECM) play a decisive role in guiding cell behavior, conducting cell signals, and regulating mineralization. Here, we develop a facile approach for preparing a novel polysaccharide hydrogel with liquid crystal properties and viscoelasticity similar to those of natural bone ECM. First, a series of chitin whisker/chitosan (CHW/CS) hydrogels were prepared by chemical cross-linking with genipin, in which CHW can self-assemble to form cholesteric liquid crystals under ultrasonic treatment and CS chains can enter into the gaps between the helical layers of the CHW cholesteric liquid crystal phase to endow morphological stability and good mechanical properties. Subsequently, the obtained chemically cross-linked liquid crystal hydrogels were immersed into the desired concentration of the NaCl solution to form physical cross-linking. Due to the Hofmeister effect, the as-prepared dual-cross-linked liquid crystal hydrogels showed an enhanced modulus, viscoelasticity similar to that of natural ECM with relatively fast stress relaxation behavior, and fold surface morphology. Compared to both CHW/CS hydrogels without liquid crystal properties and CHW/CS liquid crystal hydrogels without further physical cross-linking, the dual-cross-linked CHW/CS liquid crystal hydrogels are more favorable for the adhesion, proliferation, and osteogenic differentiation of bone marrow mesenchymal stem cells. This approach could inspire the design of hydrogels mimicking the liquid crystal properties and viscoelasticity of natural bone ECM for bone repair.

Disease progression patterns and molecular resistance mechanisms to crizotinib of lung adenocarcinoma harboring ROS1 rearrangements.

This retrospective study investigated the association between the pattern of disease progression and molecular mechanism of acquired resistance in a large cohort of 49 patients with ROS1-rearranged advanced non-small-cell lung cancer treated with first-line crizotinib. We found that treatment-emergent ROS1 point mutations were the major molecular mechanism of crizotinib resistance, particularly for patients who developed extracranial-only disease progression. Our findings highlight the importance of rebiopsy and gene testing for subsequent-line therapeutic management.

Suppression of CCT3 inhibits melanoma cell proliferation by downregulating CDK1 expression.

The eukaryotic chaperonin family is vital for cell survival. The dysregulation of chaperonin-containing TCP-1 subunit 3 (CCT3) is implicated in several types of malignant tumors' development. However, its functional role in melanoma remains unknown. Here we elucidate the functional contribution to CCT3 to melanoma progression. The results indicated that CCT3 highly expressed in melanoma tissues, and CCT3 overexpression is correlated with clinical stage in melanoma patients. Knockdown of CCT3 by shRNA in melanoma cells inhibited cell proliferation and cell cycle progression and induced cell apoptosis in vitro. In vivo, tumor growth in the nude mice was significantly inhibited after CCT3 silencing. Importantly, the gene array analysis showed that CCT3 depletions inhibited cyclins and cell cycle regulation signaling and further evaluation demonstrated that CDK1 expression was significantly decreased after CCT3 knockdown. Additionally, Functional rescues experiments also indicated that decreased cell proliferation due to CCT3 silencing was rescued by CDK1 overexpression. Overall, our findings suggest that CCT3 depletions prohibited melanoma progression by downregulating CDK1 expression and is a potential therapeutic target for melanoma.

Involvement of CXCL17 and GPR35 in Gastric Cancer Initiation and Progression.

The expression of CXC motif chemokine 17 (CXCL17) and its reported membrane receptor G-protein-coupled receptor 35 (GPR35) in different gastric pathological lesions and their clinical implications are largely unknown. In this study, a total of 860 pathological sections were immune-stained with either anti-CXCL17 or anti-GPR35 antibodies. Their expression was scored within the area of the normal gastric gland of non-atrophic gastritis (NAG-NOR), intestinal metaplasia of atrophic gastritis (AG-IM), IM adjacent to GC (GC-IM), and GC tissue. The clinical significance and potential function of CXCL17 and GPR35 were explored using multiple methods. Our results suggested that CXCL17 expression was gradually upregulated during the pathological progress of gastric diseases (NAG-NOR < AG-IM < GC-IM), but significantly downregulated when GC occurred. GPR35 had a similar expression pattern but its expression in GC remained abundant. High CXCL17 expression in GC was associated with less malignant behavior and was an independent biomarker of favorable prognosis. Overexpressing CXCL17 in HGC27 cells significantly upregulated CCL20 expression. TCGA analysis identified that CXCL17 was negatively correlated with some cancer-promoting pathways and involved in inflammatory activities. CTRP analysis revealed that gastric cell lines expressing less CXCL17 and were more sensitive to the CXCR2 inhibitor SB-225002.

Heterogeneous nucleation measurements in a sheathed planar diffusive condensation particle counter.

HYPOTHESIS: While the lack of efficient tools yielding controllable uniform saturation ratios (S) has delayed basic experimental heterogeneous nucleation studies, common diffusive condensation particle counters (DCPCs) could fill this gap if their S-variation were minimized by increasing the proportion of sheath gas (σ) surrounding a central core of purified clusters. ANALYSIS: We measure the activation probability P of Tetraheptylammonium Bromide cluster cations (THA-Br)n-1THA+ in Kanomax's fast CPC while controlling S through the saturator and condenser temperatures (Ts, Tc), varying σ, and changing the size (n) of purified salt clusters via high resolution mobility selection. FINDINGS: Experimental curves P(Ts,n) obtained in 1-butanol/air at fixed Tc (13 °C) and variable n and Ts (3 ≤ n ≤ 16; 30 ≤ Ts ≤ 40 °C) rise sharply versus both n and Ts. Their steepness increases five-fold with increasing σ to about σ = 75%, with little effect thereafter. Measurements changing S would yield size distributions of unknown aerosols at fairly high resolution. Comparing P(Ts,n) data with predictions from capillary theory suggests that basic heterogeneous nucleation measurements can be carried out, but instrument improvements are still needed.