Establishment and verification of novel TNM staging system for lung mucinous adenocarcinoma.

BACKGROUND: Lung adenocarcinoma is a high-mortality rate cancer. Within this category, Lung mucinous adenocarcinoma (LMAC) is a rare and distinct subtype of lung adenocarcinoma necessitating further investigation. The study was launched to compare the difference of survival features between LMAC and lung non-mucinous adenocarcinoma (LNMAC) and to investigate the significance and demand for developing a new staging system tailored to LMAC. METHODS: This retrospective study assessed the suitableness of the current staging system for LMAC. It compared the overall survival (OS) between LMAC and LNMAC from 2004 to 2020 (LNMAC: 160,387; LMAC: 6,341) and instituted a novel classification framework for LMAC based on US population. Verification group consisting of patients from two Chinese medical centers from 2010 to 2018 (n = 392) was set to ascertain the applicability of this novel system. The primary endpoint was OS. To minimize the bias, propensity score match (PSM) was employed. Survival analysis and Log-rank test were executed to explore the survival features of LMAC. RESULTS: The results indicated that the existed staging system was not suitable for LMAC. Patients diagnosed with LMAC exhibited a superior OS compared to those with LNMAC in stage IA2 (P < 0.0001), IA3 (P < 0.0001), IB (P = 0.0062), IIA (P = 0.0090), IIB (P = 0.0005). In contrast, a worse OS in stage IVA (P = 0.0103) was found in LMAC patients. The novel classification system proposed for LMAC proved to be highly applicable and demonstrated substantial efficacy, as confirmed by the verification group. CONCLUSION: The newly established classification system was more effective for LMAC, but it necessitates large-scale verification to confirm its applicability and reliability.

Plasmonic trimers designed as SERS-active chemical traps for subtyping of lung tumors.

Plasmonic materials can generate strong electromagnetic fields to boost the Raman scattering of surrounding molecules, known as surface-enhanced Raman scattering. However, these electromagnetic fields are heterogeneous, with only molecules located at the 'hotspots', which account for ≈ 1% of the surface area, experiencing efficient enhancement. Herein, we propose patterned plasmonic trimers, consisting of a pair of plasmonic dimers at the bilateral sides and a trap particle positioned in between, to address this challenge. The trimer configuration selectively directs probe molecules to the central traps where 'hotspots' are located through chemical affinity, ensuring a precise spatial overlap between the probes and the location of maximum field enhancement. We investigate the Raman enhancement of the Au@Al2O3-Au-Au@Al2O3 trimers, achieving a detection limit of 10-14 M of 4-methylbenzenethiol, 4-mercaptopyridine, and 4-aminothiophenol. Moreover, single-molecule SERS sensitivity is demonstrated by a bi-analyte method. Benefiting from this sensitivity, our approach is employed for the early detection of lung tumors using fresh tissues. Our findings suggest that this approach is sensitive to adenocarcinoma but not to squamous carcinoma or benign cases, offering insights into the differentiation between lung tumor subtypes.

Sialic acid-modified doxorubicin liposomes target tumor-related immune cells to relieve multiple inhibitions of CD8+ T cells.

In different types of cancer treatments, cancer-specific T cells are required for effective anticancer immunity, which has a central role in cancer immunotherapy. However, due to the multiple inhibitions of CD8+ T cells by tumor-related immune cells, CD8+ T-cell mediated antitumor immunotherapy has not achieved breakthrough progress in the treatment of solid tumors. Receptors for sialic acid (SA) are highly expressed in tumor-associated immune cells, so SA-modified nanoparticles are a drug delivery nanoplatform using tumor-associated immune cells as vehicles. To relieve the multiple inhibitions of CD8+ T cells by tumor-associated immune cells, we prepared SA-modified doxorubicin liposomes (SL-DOX, Scheme 1A). In our study, free SA decreased the toxicity of SL-DOX to tumor-associated immune cells. Compared with common liposomes, SL-DOX could inhibit tumor growth more effectively. It is worth noting that SL-DOX could not only kill tumor-related neutrophils and monocytes to relieve the multiple inhibitions of CD8+ T cells but also induce immunogenic death of tumor cells to promote the infiltration and differentiation of CD8+ T cells (Scheme 1B). Therefore, SL-DOX has potential value for the clinical therapeutic effect of CD8+ T cells mediating anti-tumor immunotherapy.

UV radiation and temperature increase alter the PSII function and defense mechanisms in a bloom-forming cyanobacterium Microcystis aeruginosa.

The aim was to determine the response of a bloom-forming Microcystis aeruginosa to climatic changes. Cultures of M. aeruginosa FACHB 905 were grown at two temperatures (25°C, 30°C) and exposed to high photosynthetically active radiation (PAR: 400-700 nm) alone or combined with UVR (PAR + UVR: 295-700 nm) for specified times. It was found that increased temperature enhanced M. aeruginosa sensitivity to both PAR and PAR + UVR as shown by reduced PSII quantum yields (Fv/Fm) in comparison with that at growth temperature (25°C), the presence of UVR significantly exacerbated the photoinhibition. M. aeruginosa cells grown at high temperature exhibited lower PSII repair rate (Krec) and sustained nonphotochemical quenching (NPQs) induction during the radiation exposure, particularly for PAR + UVR. Although high temperature alone or worked with UVR induced higher SOD and CAT activity and promoted the removal rate of PsbA, it seemed not enough to prevent the damage effect from them showing by the increased value of photoinactivation rate constant (Kpi). In addition, the energetic cost of microcystin synthesis at high temperature probably led to reduced materials and energy available for PsbA turnover, thus may partly account for the lower Krec and the declination of photosynthetic activity in cells following PAR and PAR + UVR exposure. Our findings suggest that increased temperature modulates the sensitivity of M. aeruginosa to UVR by affecting the PSII repair and defense capacity, thus influencing competitiveness and abundance in the future water environment.

Warming modulates the photosynthetic performance of Thalassiosira pseudonana in response to UV radiation.

Diatoms form a major component of phytoplankton. These eukaryotic organisms are responsible for approximately 40% of primary productivity in the oceans and contribute significantly to the food web. Here, the influences of ultraviolet radiation (UVR) and ocean warming on diatom photosynthesis were investigated in Thalassiosira pseudonana. The organism was grown at two temperatures, namely, 18°C, the present surface water temperature in summer, and 24°C, an estimate of surface temperature in the year 2,100, under conditions of high photosynthetically active radiation (P, 400-700 nm) alone or in combination with UVR (P + UVR, 295-700 nm). It was found that the maximum photochemical yield of PSII (Fv/Fm) in T. pseudonana was significantly decreased by the radiation exposure with UVR at low temperature, while the rise of temperature alleviated the inhibition induced by UVR. The analysis of PSII subunits turnover showed that high temperature alone or worked synergistically with UVR provoking fast removal of PsbA protein (KPsbA), and also could maintain high PsbD pool in T. pseudonana cells. With the facilitation of PSII repair process, less non-photochemical quenching (NPQ) occurred at high temperature when cells were exposed to P or P + UVR. In addition, irrespective of radiation treatments, high temperature stimulated the induction of SOD activity, which partly contributed to the higher PSII repair rate constant (Krec) as compared to KPsbA. Our findings suggest that the rise in temperature could benefit the photosynthetic performance of T. pseudonana via modulation of its PSII repair cycle and protective capacity, affecting its abundance in phytoplankton in the future warming ocean.

Tear Film Lipid Layer Changes Following Combined Effect of Heated Eye Mask with Intense Pulsed Light Therapy for Evaporative Dry Eye: A Randomized Control Study.

Background: Dry eye disease (DED) is a complex ocular surface inflammatory disorder with a multifactorial etiology. Therapies such as intense pulsed light (IPL) and heated eye mask (HEM) have been reported to improve the tear film lipid layer (TFLL) and signs and symptoms of DED. Methods: This randomized study aimed to compare the effects of IPL combined with HEM (IPL+HEM) group, IPL group, and control group in participants with evaporative DED. All participants were examined at baseline (D0), day 21 (D21), day 42 (D42), and day 84 (D84) for noninvasive tear breakup time (NITBUT), TFLL, corneal conjunctival staining (CS), meibomian gland quality (MGQ), meibomian gland expressibility (MGEx), and Ocular Surface Disease Index (OSDI). Results: The mean age of participants was IPL+HEM: 28.06 ± 3.88 years, IPL: 29.88 ± 4.68 years, and control: 28.52 ± 3.77 years. At D84, significant improvements in TFLL (p < 0.05), noninvasive tear breakup time (NITBUT) (p < 0.05), corneoconjunctival staining (CS) (p < 0.05), MGQ (p < 0.05), MGEx (p < 0.05), and OSDI (p < 0.05) were found in the IPL+HEM and IPL groups, whereas the control group had no significant improvements. Furthermore, ΔTFLL significantly correlated with ΔNITBUT (r = -0.678, p < 0.001), ΔCS (r = 0.321, p < 0.001), ΔMGQ (r = 0.669, p < 0.001), ΔMGEx (r = 0.598, p < 0.001), and ΔOSDI score (r = 0.649, p < 0.001). Conclusions: IPL therapy in combination with HEM and IPL therapy only can significantly improve the quality of TFLL and clinically reduce the sign and symptoms of evaporative DED. However, IPL therapy in combination with HEM was found to be more effective than IPL therapy alone.

Phaco-goniosynechialysis versus phaco-trabeculectomy in patients with refractory primary angle-closure glaucoma: a comparative study.

PURPOSE: To compare the effects of phacoemulsification with intraocular lens implantation (phaco) combined with goniosynechialysis (phaco + GSL) versus phaco with trabeculectomy (phaco + trab) for the management of primary angle-closure glaucoma (PACG) refractory to peripheral anterior synechiae (PAS) of over 180°. METHODS: This retrospective study followed 77 eyes of 77 patients for at least 6 months. Intraocular pressure (IOP), best-corrected visual acuity (BCVA), number of glaucoma drugs, and PAS were recorded at the preoperative baseline and evaluated at each postoperative follow-up visit. The National Eye Institute Visual Functioning Questionnaire-25 (NEI VFQ-25) was administered to patients enrolled in this study. Pearson's correlation analysis and multivariate linear analysis were performed to identify factors influencing changes in NEI VFQ-25 scores and to identify factors associated with increases in NEI VFQ-25 scores after the operation. RESULTS: In total, seventy-seven eyes were included (43 with phaco + GSL and 34 with phaco + trab). Comparing preoperative baseline and month 6 after surgery measurements revealed that both groups found significant improvements in IOP, PAS, BCVA and the number of glaucoma drugs (P < 0.05). Baseline NEI VFQ-25 scores were similar in the two groups, but there was a significant difference in postoperative NEI VFQ-25 scores (74.47 ± 10.39 in phaco + GSL vs. 69.57 ± 8.54 in phaco + trab, P = 0.048 < 0.05), and the phaco + GSL group had better scores at the time of the last follow-up. The change in preoperative scores and the number of glaucoma drugs was significantly correlated with postoperative scores in the phaco + GSL group. CONCLUSION: Phaco + GSL treatment is as safe and effective as phaco + trab for refractory PACG patients, and patients' subjective experience improved significantly after phaco + GSL surgery.

Monolayer Iron Oxychloride with a Resonant Band Structure for Ultrasensitive Molecular Sensing.

Two-dimensional layered materials (2DLMs) are expected to be next-generation commercial sensors for surface-enhanced Raman scattering (SERS) sensing owing to their unique structural features and physicochemical properties. The low sensitivity and poor universality of 2DLMs are the dominant barriers toward their practical applications. Herein, we report that monolayer iron oxychloride (FeOCl) with a naturally suitable band structure is a promising candidate for ultrasensitive SERS sensing. The generally boosted Raman scattering cross section of different analyte-FeOCl systems benefits from the resonant photoinduced charge transfer processes and strong ground-state interactions. In addition, the strong adsorption ability of monolayer FeOCl is crucial for rapid detection in practical applications, which is proven to be much better than those of conventional SERS sensors. Consequently, monolayer FeOCl enables diverse SERS applications, including multicomponent analysis, chemical reaction monitoring, and indirect ion sensing.

Albumin-based nanoparticle for dual-modality imaging of the lymphatic system.

The lymphatic system is a complex network of lymphatic vessels, lymph nodes, and lymphoid organs. The current understanding of the basic mechanism and framework of the lymphatic system is relatively limited and not ideal for exploring the function of the lymphatic system, diagnosing lymphatic system diseases, and controlling tumor metastasis. Imaging modalities for evaluating lymphatic system diseases mainly include lymphatic angiography, reactive dye lymphatic angiography, radionuclide lymphatic angiography, computed tomography, and ultrasonography. However, these are insufficient for clinical diagnosis. Some novel imaging methods, such as magnetic resonance imaging, positron emission computed tomography, single-photon emission computed tomography, contrast-enhanced ultrasonography, and near-infrared imaging with agents such as cyanine dyes, can reveal lymphatic system information more accurately and in detail. We fabricated an albumin-based fluorescent probe for dual-modality imaging of the lymphatic system. A near-infrared cyanine dye, IR-780, was absorbed into bovine serum albumin (BSA), which was covalently linked to a molecule of diethylenetriaminepentaacetic acid to chelate gadolinium Gd3+. The fabricated IR-780@BSA@Gd3+ nanocomposite demonstrates strong fluorescence and high near-infrared absorption and can be used as a T1 contrast agent for magnetic resonance imaging. In vivo dual-modality fluorescence and magnetic resonance imaging showed that IR-780@BSA@Gd3+ rapidly returned to the heart through the lymphatic circulation after it was injected into the toe webs of mice, facilitating good lymphatic imaging. The successful fabrication of the new IR-780@BSA@Gd3+ nanocomposite will facilitate the study of the mechanism and morphological structure of the lymphatic system.

CircDHDDS/miR-361-3p/WNT3A Axis Promotes the Development of Retinoblastoma by Regulating Proliferation, Cell Cycle, Migration, and Invasion of Retinoblastoma Cells.

Retinoblastoma (RB) is a common intraocular malignant tumor. The growing evidence has reported that circular RNAs (circRNAs) play critical roles in RB development. Therefore, the purpose of the study is to investigate the regulatory mechanism of circDHDDS in RB. The real-time quantitative polymerase chain reaction (RT-qPCR) assay was used to quantify the expression levels of circDHDDS, miR-361-3p, and WNT3A in RB tissues and cells (RPCs, Y-79, and WERI-Rb-1). The proliferation and cell cycle of RB cells were assessed by colony formation assay and flow cytometry assays, respectively. The migration and invasion of RB cells were measured by transwell assay. The protein expression levels of Nectin-3 (CD113), SOX2, Nanog, and WNT3A were measured by Western blot assay. The functional targets of circDHDDS and miR-361-3p were predicted by bioinformatics databases, and the dual-luciferase reporter assay was used to confirm the interaction relationship between miR-361-3p and circDHDDS or WNT3A. The functional role of circDHDDS silencing in vivo was evaluated by xenograft experiment. We found that circDHDDS was overexpressed in RB tissues and cells compared with normal retinas tissues and retinal pigment epithelial cells, correspondingly. Furthermore, silencing of circDHDDS impeded proliferation, migration, invasion, and induced cell cycle arrest in vitro, which were abolished by knockdown of miR-361-3p. The in vivo experiments also suggested that tumor growth was inhibited by knockdown of circDHDDS. Moreover, we also found that miR-361-3p specifically bound to WNT3A, and overexpression of miR-361-3p suppressed RB development by decreasing WNT3A expression. Summarily, circDHDDS, a molecule sponge of miR-361-3p, regulated the expression of WNT3A. Therefore, circDHDDS/miR-361-3p/WNT3A axis stimulated the development of RB by regulation of proliferation, cell cycle program, migration, and invasion of RB cells.

Salivary acquired pellicle-inspired DpSpSEEKC peptide for the restoration of demineralized tooth enamel.

Salivary acquired pellicle (SAP) is a layer of proteins and glycoproteins of salivary origin that tightly coat the tooth surface. Statherin is an important part of the SAP. The initial six-peptide sequence DpSpSEEK (where pS denotes phosphorylated serine) of the N-terminus of statherin can be immobilized on a hydroxyapatite (HAP) surface and the negatively charged domains of the DpSpSEEK side chain can catch free Ca2+ in saliva due to the charge adsorption effect. In order to prepare more functional materials based on DpSpSEEK, we designed a cysteine-labeled peptide sequence DpSpSEEKC, which could conjugate other macromolecules by forming a sulfur-based linkage. In this work, we measured the adsorption of DpSpSEEKC to HAP by various methods. We also coated DpSpSEEKC on a demineralized tooth enamel surface to evaluate its biomineralization capacity. The DpSpSEEKC-coated samples were characterized after immersion in artificial saliva for 2 weeks. The results showed that DpSpSEEKC has a strong adsorption capacity to HAP and could induce remineralization on the demineralized tooth enamel surface due to its carboxyl and phosphate groups. Compared with the control samples, the mechanical properties of the DpSpSEEKC-coated samples were obviously improved. In conclusion, DpSpSEEKC can provide a potential method for restoring demineralized tooth enamel.