Delphinieae flowers originated from the rewiring of interactions between duplicated and diversified floral organ identity and symmetry genes.

Species of the tribe Delphinieae (Ranunculaceae) have long been the focus of morphological, ecological, and evolutionary studies due to their highly specialized, nearly zygomorphic (bilaterally symmetrical) spiral flowers with nested petal and sepal spurs and reduced petals. The mechanisms underlying the development and evolution of Delphinieae flowers, however, remain unclear. Here, by conducting extensive phylogenetic, comparative transcriptomic, expression, and functional studies, we clarified the evolutionary histories, expression patterns, and functions of floral organ identity and symmetry genes in Delphinieae. We found that duplication and/or diversification of APETALA3-3 (AP3-3), AGAMOUS-LIKE6 (AGL6), CYCLOIDEA (CYC), and DIVARICATA (DIV) lineage genes was tightly associated with the origination of Delphinieae flowers. Specifically, an AGL6-lineage member (such as the Delphinium ajacis AGL6-1a) represses sepal spur formation and petal development in the lateral and ventral parts of the flower while determining petal identity redundantly with AGL6-1b. By contrast, two CYC2-like genes, CYC2b and CYC2a, define the dorsal and lateral-ventral identities of the flower, respectively, and form complex regulatory links with AP3-3, AGL6-1a, and DIV1. Therefore, duplication and diversification of floral symmetry genes, as well as co-option of the duplicated copies into the preexisting floral regulatory network, have been key for the origin of Delphinieae flowers.

Phase 1b/2 study of penpulimab (AK105), an antiprogrammed cell death-1 immunoglobulin G1 antibody, in advanced or metastatic solid tumors (AK105-204).

BACKGROUND: Penpulimab, a new-generation antiprogrammed cell death-1 immunoglobulin G1 monoclonal antibody, was engineered to optimize receptor occupancy and eliminate fragment crystallizable γ-mediated effector function. In this multicenter, phase 1b/2, multicohort study, the objective was to investigate the efficacy, safety, and immunogenicity of penpulimab in advanced solid tumors. METHODS: Patients who had unresectable, advanced solid tumors were enrolled from six centers and received 200 mg penpulimab on day 1 every 2 weeks for up to 24 months. The primary end point was the objective response rate (ORR) according to Response Evaluation Criteria in Solid Tumors, version criteria 1.1. RESULTS: Between September 2, 2019, and January 1, 2020, 65 patients were enrolled and received penpulimab. At the time of data cutoff (May 11, 2022), the median follow-up was 12.6 months (range, 1.1-28.6 months). The ORR was 12.3 (95% confidence interval [CI], 5.5%-22.8%), with three (4.6%) complete responses and five (7.7%) partial responses. Twelve patients (18.5%) achieved stable disease, resulting in a disease control rate of 30.8% (95% CI, 19.9%-43.4%). The median duration of response was not reached (95% CI, 6.70 months to not estimable). In all cohorts, the median progression-free survival was 1.74 months (95% CI, 1.41-2.69 months), and the median overall survival was 16.59 months (95% CI, 7.82-22.18 months). Grade 3 or greater treatment-related adverse events and immune-related adverse events occurred in 9.2% and 27.7% of patients, respectively. Positive antidrug antibody responses to penpulimab were observed in one patient (1.8%). CONCLUSIONS: Penpulimab showed promising antitumor activity with an acceptable safety profile, offering a potential new treatment approach for solid tumors. These findings supported the evaluation of penpulimab's durable activity and safety, as monotherapy or in combination therapy, in specific malignancies.

Apatinib Plus Toripalimab (Anti-PD1 Therapy) as Second-Line Therapy in Patients With Advanced Gastric or Esophagogastric Junction Cancer: Results From a Randomized, Open-Label Phase II Study.

BACKGROUND: This study aimed to assess the activity of apatinib plus toripalimab in the second line for patients with advanced gastric or esophagogastric junction cancer (GC/EGJC). METHODS: In this open-label, phase II, randomized trial, patients with advanced GC/EGJC who progressed after first-line chemotherapy were enrolled and received 250 mg apatinib per day plus 240 mg toripalimab on day 1 per 3 weeks (arm A) or physician's choice of chemotherapy (PC, arm B). The primary endpoint of this study was the 1-year survival rate. Progression-free survival (PFS), overall survival (OS), overall response rate (ORR), and safety were assessed as secondary endpoints. RESULTS: Twenty-five patients received apatinib plus toripalimab while 26 were enrolled in arm B. The 1-year survival rates of the 2 groups were 43.3% and 42.3%, respectively (P = .903). The PFS was 2.77 versus 2.33 months (P = .660). The OS was 8.30 versus 9.88 months (P = .539). An objective response was reported in 20.0% of patients in arm A compared to 26.9% in arm B (P = .368), respectively. A total of 6 (24.0%) patients experienced adverse events of grade ≥ 3 in arm A, while 9 (34.6%) patients suffered from adverse events of grade ≥ 3 in arm B. No drug-related deaths occurred in either group. CONCLUSION: Toripalimab plus apatinib treatment in second-line therapy of advanced GC/EGJC showed manageable toxicity but did not improve clinical outcomes relative to PC treatment (ClinicalTrials.gov Identifier: NCT04190745).

Penpulimab, an anti-PD1 IgG1 antibody in the treatment of advanced or metastatic upper gastrointestinal cancers.

BACKGROUND: The safety and anti-tumor activity of penpulimab in patients with advanced upper gastrointestinal (UGI) cancers were evaluated in this study. METHODS: Patients with advanced UGI cancers naive to immune checkpoint inhibitors were enrolled in two trials of penpulimab. In the Phase Ia/Ib trial in Australia, patients received penpulimab intravenous infusion of 1, 3 and 10 mg/kg every 2 weeks in dose-escalation phase and 200 mg every 2 weeks in dose-expansion phase. In the phase Ib/II trial conducted in China, patients received 200 mg penpulimab every 2 weeks. Primary endpoints were safety and tolerability for the phase Ia/Ib trial and the objective response rate for the phase Ib/II trial. The safety and efficacy of penpulimab in patients with UGI cancers in these two trials were evaluated. RESULTS: A total of 67 patients with UGI cancers from Australia and China were enrolled in these two trials and had received penpulimab with a median of 6 (1-64) doses. 44.8% of patients experienced at least one treatment-related adverse event (TRAE), and 7.5% of patients experienced a grade ≥3 TRAE. Among 60 patients evaluable for response, the confirmed objective response rates ranged between 11.1 and 26.3% across cohorts for pancreatic cancer, cholangiocarcinoma, gastric or Gastroesophageal junction carcinoma (Gastric/GEJ), and hepatocellular carcinoma. 11/13 (85.0%) responders had ongoing responses at data cutoff date. CONCLUSIONS: Penpulimab monotherapy demonstrated an acceptable safety and encouraged anti-tumor activity in patients with advanced UGI cancers. Further exploration in a large cohort of patients is warranted. TRIAL REGISTRATION: Phase Ia/Ib trial in Australia (NCT03352531) and phase Ib/II trial in China (NCT04172506).

Effect of aqueous extract of seed of broccoli on inflammatory cytokines and Helicobacter pylori infection: a randomized, double-blind, controlled trial in patients without atrophic gastritis.

The purpose of this study was to investigate the anti-inflammatory effect of an aqueous extract of seed of broccoli (AESB) in Helicobacter pylori (HP)-infected patients without atrophic gastritis. This was a double-centre, randomized, double-blind, controlled study. A total of 110 HP-infected subjects were randomized to receive either AESB or placebo for 2 months. Inflammatory cytokine (IL-8, IFN-γ, TNF-α, CRP, IL-17A, IL-1ß, IL-18), pepsinogen I, II (PG I, PG II), and gastrin-17 (G-17) measurements and 13C-urea breath tests were performed at baseline and at 60 days. At 60 days, there was no significant difference in any of the inflammatory cytokines, pepsinogen or gastrin between the two groups. However, IL-8, IFN-γ, PG I, PG I/PG II ratio (PGR), and G-17 were reduced by 9.02 pg/mL, 5.08 pg/mL, 24.56 ng/mL, 1.75 and 0.3 pmol/L, respectively, in the AESB group compared with baseline (all P < 0.05). The HP eradication rates in the AESB group and placebo group were 11.11 and 3.70% at 60 days, respectively (P > 0.05). No treatment-related adverse events were reported. Thus, AESB may reduce the risk of gastric mucosal lesions and decrease the risk of gastric cancer by relieving inflammatory cytokines. The safety profile of AESB was satisfactory. This study is registered with the Chinese Clinical Trials Registry (Registration No. ChiCTR2100054249).

Observation of split evanescent field distributions in tapered multicore fibers for multiline nanoparticle trapping and microsensing.

The optical attractive force in tapered single-mode fibers (SMFs) is usually uniformly distributed around the tapered section and has been found to be important for trapping and manipulating targeted atoms and nanoparticles. In contrast, a peculiar phenomenon of the evanescent field splitting along the azimuth axis can be experimentally observed by tapering a weakly-coupled MCF into a strongly-coupled MCF to generate supermode interference. Moreover, the supermode interference produces a hexagonally distributed evanescent field and its six vertices give rise to the multiline optical attractive force. For such spectral resonances, the optimum extinction ratio for the transmission dips is given by 47.4 dB, this being determined using an index liquid to cover the tapered MCF. The resonant dips move to a greater extent at longer wavelengths, with the optimum tuning efficiency of 392 nm/RIU for index sensing. The split evanescent fields respectively attract the excited upconversion nanoparticles in the liquid to be linearly aligned and running down the tapered region over the fiber surface, emitting green light with 60° symmetry. The charged nanoparticles were periodically self-organized, with a period of around 1.53 µm. The parallel lines, with 60° rotational symmetry, can be useful for (1) indicating the exact locations of the side-cores or orientations of the tapered MCF; (2) as precision alignment keys for micro-optical manipulation; and (3) enhancing the upconversion light, or for use in lasers, coupling back to the MCF. The split evanescent fields can be promising for developing new evanescent field-based active and passive fiber components with nano-structures.

3D aluminum/silver hierarchical nanostructure with large areas of dense hot spots for surface-enhanced raman scattering.

Plasmonic nanomaterials possessing large-volume, high-density hot spots with high field enhancement are highly desirable for ultrasensitive surface-enhanced Raman scattering (SERS) sensing. However, many as-prepared plasmonic nanomaterials are limited in available dense hot spots and in sample size, which greatly hinder their wide applications in SERS devices. Here, we develop a two-step physical deposition protocol and successfully fabricate 3D hierarchical nanostructures with highly dense hot spots across a large scale (6 × 6 cm2 ). The nanopatterned aluminum film was first prepared by thermal evaporation process, which can provide 3D quasi-periodic cloud-like nanostructure arrays suitable for noble metal deposition; then a large number of silver nanoparticles with controllable shape and size were decorated onto the alumina layer surfaces by laser molecular beam epitaxy, which can realize large-area accessible dense hot spots. The optimized 3D-structured SERS substrate exhibits high-quality detection performance with excellent reproducibility (13.1 and 17.1%), whose LOD of rhodamine 6G molecules was 10-9 M. Furthermore, the as-prepared 3D aluminum/silver SERS substrate was applied in detection of melamine with the concentration down to 10-7 M and direct detection of melamine in infant formula solution with the concentration as low 10 mg/L. Such method to realize large-area hierarchical nanostructures can greatly simplify the fabrication procedure for 3D SERS platforms, and should be of technological significance in mass production of SERS-based sensors.

Napabucasin Attenuates Resistance of Breast Cancer Cells to Tamoxifen by Reducing Stem Cell-Like Properties.

BACKGROUND Tamoxifen (TAM) is the first-line drug for estrogen receptor-positive (ER+) breast cancer (BC) treatment. However, its resistance is a main obstacle in clinical practice. Thus, new therapeutic agents are urgently needed to fight TAM resistance. MATERIAL AND METHODS Here, we constructed TAM-resistant ER+BC cells with TAM resistance, named MCF-7-R. Western blot, quantitative real-time PCR (qRT-PCR), ALDH1 activity analysis, and spheroid-forming detection were used to detect the stemness of cells and the effects of napabucasin (NP) on BC cell stemness. Cell counting kit-8 (CCK8) assay was used to evaluate the effects of NP on cell viability. RESULTS MCF-7-R cells exhibited higher stemness compared with the parental MCF-7 cells, which was evident by the increased spheroid formation ability at diluted concentration, aldehyde dehydrogenase (ALDH) activity, and expression of stemness critical biomarkers (Oct4, Nanog, and Sox2). Additionally, it was found that napabucasin (NP) specifically killed MCF-7-T cells, characterized by remarkably decreased IC50 value. Notably, NP reduced MCF-7-R cell stemness, which was evident as the decreased stemness marker expression, spheroid-forming capacity, and ALDH1 activity. Importantly, NP attenuated TAM resistance of MCF-7-R cells and enhanced sensitivity of MCF-7 cells to TAM. Mechanistic study showed that NP inhibited STAT3 activation, and overexpression of STAT3 rescued NP-mediated inhibition of the stemness-like characteristics of MCF-7-R cells. CONCLUSIONS NP might be used as an adjuvant therapy for ER+ BC patients with TAM resistance.

High performance blue light detector based on ZnO nanowire arrays.

Organic-inorganic hybrid heterojunctions are ever so promising for low-cost and high-efficient photoelectric devices. We report a p-n junction diode composed of inorganic ZnO nanowire arrays (ZNAs) and organic 2, 2', 7, 7'-tetrakis-(N, N-di-p-methoxyphenylamine)- 9, 9'-spirobifluorene (spiro-MeOTAD). A maximum photoresponsivity of 1.32 mA/W is observed under illumination at zero bias. We also demonstrate that the photocurrent time response is observed to be rapid, consistent, as well as repeatable. On blue light weak irradiance (410 nm, 75 µW/cm2), the rise time constant and decay time constant were found to be 0.12 and 0.06 s, respectively. These results suggest ZNAs/spiro-MeOTAD heterojunction as a candidate for an efficient self-powered blue light detector.

High-performance self-powered UV photodetectors based on TiO2 nano-branched arrays.

Nano-branched TiO2 arrays were fabricated on fluorine-doped tin oxide (FTO) glass by a facile two-step chemical synthesis process. Self-powered UV photodetectors based on photoelectrochemical cells (PECs) were assembled using these TiO2 nano-branched arrays as photoanodes. These visible-blind self-powered UV photodetectors exhibit high sensitivity and high-speed photoresponse. Compared with photodetectors based on bare TiO2 nanorod arrays, TiO2 nano-branched arrays show drastically improved photodetecting performance as photoanodes. The photosensitivity increases from 0.03 to 0.22 A W(-1) when optimized nano-branched TiO2 arrays are used, corresponding to an incident photon-to-current conversion efficiency higher than 77%. The UV photodetectors also exhibit excellent spectral selectivity and fast response (0.05 s decay time). The improved performance is attributed to a markedly enlarged TiO2/electrolyte contact area and good electron conductivity in the one-dimensional, well-aligned TiO2 nanorod trunk.

Roles of the APETALA3-3 ortholog in the petal identity specification and morphological differentiation in Delphinium anthriscifolium flowers.

The genus Delphinium (Ranunculaceae) with its unique and highly complex floral structure is an ideal system to address some key questions in terms of morphological and evolutionary studies in flowers. In D. anthriscifolium, for example, the original eight petal primordia differentiate into three types at maturity (i.e., two dorsal spurred, two lateral flat, and four ventral reduced petals). The mechanisms underlying their identity determination and morphological differentiation remain unclear. Here, through a comprehensive approach combining digital gene expression (DGE) profiles, in situ hybridization, and virus-induced gene silencing (VIGS), we explore the role of the APETALLATA3-3 (AP3-3) ortholog in D. anthriscifolium. Our findings reveal that the DeanAP3-3 not only functions as a traditionally known petal identity gene but also plays a critical role in petal morphological differentiation. The DeanAP3-3 gene is expressed in all the petal primordia before their morphological differentiation at earlier stages, but shows a gradient expression level difference along the dorsventral floral axis, with higher expression level in the dorsal spurred petals, intermediate level in the lateral flat petals and lower level in the ventral reduced petals. VIGS experiments revealed that flowers with strong phenotypic changes showed a complete transformation of all the three types of petals into non-spurred sepals. However, in the flowers with moderate phenotypic changes, the transformation of spurred petals into flat petals is associated with moderate silencing of the DeanAP3-3 gene, suggesting a significant impact of expression level on petal morphological differentiation. This research also shed some insights into the role of changes in gene expression levels on morphological differentiation in plants.

Continuation of immunotherapy beyond progression is beneficial to the survival of advanced non-small-cell lung cancer.

PURPOSE: To investigate the potential clinical importance of continuing immunotherapy beyond progression in patients with advanced non-small-cell lung cancer (aNSCLC). METHODS: The data of patients with aNSCLC who experienced progressive disease after receiving first-line immunotherapy plus chemotherapy were collected from multiple centers for the period from January 1, 2018 to May 31, 2022. According to the second-line treatment, the patients were classified into two groups: the continuation of immunotherapy beyond progression (CIBP) group and the discontinuation of immunotherapy beyond progression (DIBP) group. The efficacy and safety of the treatment were compared between the groups. RESULTS: Overall, data from 169 patients were analyzed; 93 patients were enrolled in the CIBP group and 76 patients were in the DIBP group. The median second-line progression-free survival was 5.5 months in the CIBP group, which for the DIBP group was 3.4 (p = 0.011). The median overall survival of the CIBP group was 13.3 months, whereas that of the DIBP group was 8.8 months (p = 0.031). The disease control rate of the CIBP group (79.57%) was observably higher than that of the DIBP group (64.47%; p = 0.028). Among patients who responded better (complete or partial response) to prior therapy, the median progression-free survival was 5.5 months and 3.3 months in the CIBP and DIBP groups respectively (p = 0.022), and the median overall survival was 14.8 months and 8.8 months in the CIBP and DIBP groups respectively (p = 0.046). CONCLUSIONS: Continuing immunotherapy as a second-line treatment could be beneficial to the survival of patients with aNSCLC with disease progression beyond initial chemotherapy combined with immunotherapy.

The mechanism underlying asymmetric bending of lateral petals in Delphinium (Ranunculaceae).

During the process of flower opening, most petals move downward in the direction of the pedicel (i.e., epinastic movement). In most Delphinium flowers, however, their two lateral petals display a very peculiar movement, the mirrored helical rotation, which requires the twist of the petal stalk. However, in some lineages, their lateral petals also exhibit asymmetric bending that increases the degree of mirrored helical rotation, facilitating the formation of a 3D final shape. Notably, petal asymmetric bending is a novel trait that has not been noticed yet, so its morphological nature, developmental process, and molecular mechanisms remain largely unknown. Here, by using D. anthriscifolium as a model, we determined that petal asymmetric bending was caused by the localized expansion of cell width, accompanied by the specialized array of cell wall nano-structure, on the adaxial epidermis. Digital gene analyses, gene expression, and functional studies revealed that a class I homeodomain-leucine zipper family transcription factor gene, DeanLATE MERISTEM IDENTITY1 (DeanLMI1), contributes to petal asymmetric bending; knockdown of it led to the formation of explanate 2D petals. Specifically, DeanLMI1 promotes cell expansion in width and influences the arrangement of cell wall nano-structure on the localized adaxial epidermis. These results not only provide a comprehensive portrait of petal asymmetric bending for the first time but also shed some new insights into the mechanisms of flower opening and helical movement in plants.

Effects of sintilimab plus chemotherapy as first-line treatment on health-related quality of life in patients with advanced esophageal squamous cell carcinoma: results from the randomized phase 3 ORIENT-15 study.

Background: In ORIENT-15 study, sintilimab plus chemotherapy demonstrated significant improvement on overall survival (OS) versus placebo plus chemotherapy in first-line treatment of advanced esophageal squamous cell carcinoma (ESCC). Here, we report effect of sintilimab plus chemotherapy on health-related quality of life (HRQoL) in patients with advanced ESCC. Methods: From December 14, 2018 to August 28, 2022, HRQoL was evaluated in all randomized patients using European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 items (QLQ-C30), EORTC Quality of Life Questionnaire Oesophageal Cancer Module 18 items (QLQ-OES18), and visual analogue scale (VAS) of the EuroQol five-dimensional five-level questionnaire (EQ-5D-5L). Mean scores of each scale were described by treatment group through week 60. Least-squares mean (LSM) score change from baseline through week 24 were analyzed using the mixed-model repeated-measures method. Time to the first onset of deterioration (TTD) and OS for each scale were estimated. Clinical Trials Registration: NCT03748134. Findings: As of August 28, 2022, 689 of 690 enrolled patients were assessed for HRQoL analysis (sintilimab group: 340, placebo group: 349). Median follow-up was 32.2 months. Differences in LSM favored sintilimab over placebo for QLQ-C30 social functioning (LSM difference: 3.06, 95% CI: 0.55 to 5.57; P = 0.0170), pain (-2.24, 95% CI: -4.30 to -0.17; P = 0.0337), fatigue (-2.24, 95% CI: -4.46 to -0.02; P = 0.0479), constipation (-3.27, 95% CI -5.49 to -1.05; P = 0.0039), QLQ-OES18 pain (-1.77, 95% CI -3.11 to -0.43; P = 0.0097), trouble swallowing saliva (-2.09, 95% CI: -3.77 to -0.42; P = 0.0146), and choked when swallowing (-3.23, 95% CI: -5.60 to -0.86; P = 0.0076). TTD favored sintilimab over placebo for QLQ-OES18 dysphagia (Hazard ratio [HR]: 0.76, 95% CI: 0.61-0.94, P = 0.0104), and trouble swallowing saliva (HR: 0.48, 95% CI: 0.35-0.67, P < 0.0001). Improved OS were observed in patients with better performance in several functioning and symptom scales of QLQ-C30 and QLQ-QES18. Interpretation: The statistically significant differences of several HRQoL scales and improvements in delayed deterioration observed in our study further support the use of sintilimab plus chemotherapy as first-line treatment for advanced ESCC. Funding: This study was funded by Innovent Biologics and was co-funded by Eli Lilly.

Clinical characteristics and treatment efficacy of immune checkpoint inhibitors (ICIs) in patients with ICIs-induced Adrenal insufficiency.

BACKGROUND: Adrenal insufficiency (AI) caused by immune checkpoint inhibitors (ICIs) is an extremely rare immune-related adverse event (irAE). The detailed clinical characteristics and outcomes of patients with ICI-induced AI are unavailable. This study aimed to explore the clinical characteristics and efficacy of treatment in patients with ICI-induced AI. METHODS: We retrospectively collected information on patients diagnosed with AI caused by ICIs at LiShui Municipal Central Hospital and Zhejiang Cancer Hospital, including baseline characteristics, laboratory results, symptoms, treatment outcomes of AI, and hormone use. Survival outcomes were calculated using the Kaplan-Meier method and stratified according to the different situations. RESULTS: From December 2020 to February 2023, among 1014 patients treated with ICI therapy, a total of twenty patients were diagnosed with ICI-induced AI. Most of the patients were men (80%, n = 16), with a performance status (PS) of 0 - 1 (95%, n = 19). The median (range) age was 65.9 (49-80) years and 14 patients (70%) were treated with ICIs as first-line therapy. The majority of the patients (70%, n = 14) experienced grade 3 - 4 AI. All patients received corticosteroid replacement therapy, and only 7 patients recovered. The median time to the diagnosis of AI after starting ICI therapy was 5.2 (3.0 - 7.5) months. The objective response rate was 70% and  median progression-free survival in these patients was 16.0 months (95% confidence interval: 11.7 - 20.3 months). CONCLUSIONS: ICI-induced AI is a rare irAE, and close monitoring of cortisol levels is important. Patients diagnosed with AI after receiving immunotherapy seem to have a favorable outcome.

Chinese expert consensus on the multidisciplinary management of pneumonitis associated with immune checkpoint inhibitor.

Immune checkpoint inhibitors (ICIs) have successfully treated a number of different types of cancer, which is of great significance for cancer treatment. With the widespread use of ICIs in clinical practice, the increasing checkpoint inhibitor pneumonia (CIP) will be a challenge to clinicians. To guide the diagnosis and treatment of CIP, we conducted in-depth discussions based on the latest evidence, forming a consensus among Chinese experts on the multidisciplinary management of CIP.

LncRNA PCGsEM1 Contributes to the Proliferation, Migration and Invasion of Non-small Cell Lung Cancer Cells via acting as a Sponge for miR-152-3p.

BACKGROUND: Long non-coding RNAs (lncRNAs) have been reported to play important roles in cellular biological function. Aberrant expression of lncRNAs has been found to be related to the progression of various diseases. LncRNA prostate cancer gene expression marker 1 (PCGEM1) has been demonstrated to be involved in the initiation and progression of human cancers. However, to date, the clinical and functional significance of PCGEM1 expression in NSCLC progression remains unknown. METHODS: The expression of LncRNA PCGEM1 and miR-152-3p in NSCLC tissues and cells was analyzed using quantitative real-time RT-PCR. Experiments using NSCLC cells were conducted to explore the influence of PCGEM1 on tumor cell proliferation, migration and invasion. RESULTS: Increased expression of PCGEM1 was observed in NSCLC tissues and cells compared with the corresponding controls (all P < 0.001). PCGEM1 expression was associated with NSCLC patients' lymph node metastasis and TNM stage (all P < 0.05), and the knockdown of PCGEM1 in NSCLC cells led to inhibited cell proliferation, migration and invasion. The further luciferase reporter assay and expression results showed that miR-152-3p might be a target gene of PCGEM1 and mediate the effects of PCGEM1 on cell proliferation, migration and invasion in NSCLC. CONCLUSION: Thus, the findings from the present study indicate that the NSCLC patients have significantly increased PCGEM1 and decreased miR-152-3p expression and that the knockdown of PCGEM1 may inhibit NSCLC cell proliferation, migration and invasion by sponging miR-152-3p. The PCGEM1/miR-152-3p axis may provide novel therapeutic targets for NSCLC treatment.

Bioscaffold arrays decorated with Ag nanoparticles as a SERS substrate for direct detection of melamine in infant formula.

Three-dimensional (3D) plasmonic structures have been intensively investigated as high performance surface enhanced Raman scattering (SERS) substrates. Here, we demonstrate a 3D biomimetic SERS substrate prepared by deposition of silver nanoparticles (Ag NPs) on the bioscaffold arrays of cicada wings using laser molecular beam epitaxy. This deposition method can offer a large number of nanoparticles with average diameter of ∼10 nm and nanogaps of sub-10 nm on the surface of chitin nanopillars to generate a high density of hotspots. The prepared 3D Ag/cicada SERS substrate shows a limit of detection (LOD) for Rhodamine 6G as low as 10-7 M, high enhancement factor of 1.09 × 105, and excellent signal uniformity of 6.8%. Moreover, the molecular fingerprints of melamine in infant formula can be directly extracted with an LOD as low as 10 mg L-1, without the need for functional modification. The prepared SERS-active substrate, due to its low cost, high-throughput, and good detection performance, can be widely used in applications such as food safety and environmental monitoring.

Expression of CD133 protein in osteosarcoma and its relationship with the clinicopathological features and prognosis.

OBJECTIVE: The objective of this study is to evaluate the association between expression of CD133 protein and the clinicopathological features of patients with osteosarcoma. METHODS: This study retrospectively analyzed 28 cases of osteosarcoma in our hospital from 2007 to 2016, as well as 21 cases of osteochondroma in the same period as control group. The expression of CD133 protein in paraffin specimens of two groups of patients was detected with immunohistochemistry SP assay. RESULTS: CD133-positive staining was observed in the cytoplasm or cell membrane. The positive rate of CD133 protein expression in osteosarcoma tissue was significantly higher than that of in osteochondroma (60.7% vs. 19.0%), with statistically significant difference (P < 0.01). The patients of osteosarcoma were followed up for 11-94 months, and the median survival time was 47 months. During follow-up period, there were 16 cases of lung, spine, or retroperitoneal metastasis. At the end of the follow-up, 15 cases were dead and 13 cases were still alive. Distant metastasis and Enneking staging were significantly correlated with CD133-positive expression in osteosarcoma patients (P < 0.05), and the proportion of CD133-positive expression was high in both distant metastasis and Enneking staging. The median disease-free survival time was 21 and 32 months for CD133-positive and CD133-negative expression patients with osteosarcoma, respectively, with statistically significant difference (P < 0.05). However, the median survival time of the CD133-positive and CD133-negative expression groups was 46 and 49 months, without statistically significant difference (P > 0.05). CONCLUSION: The expression of CD133 protein in patients with osteosarcoma was significantly high and related to the distant metastasis, which may be a potential prediction biomarker for poor prognosis of osteosarcoma patients.