Thermo-sensitive PLGA-PEG-PLGA hydrogel for sustained release of EGF to inhibit cervical cancer recurrence.

Overexpression of epidermal growth factor receptor (EGFR) in cancer is a key cause of recurrence of cervical cancer (CC). Although the EGF-EGFR pathway has been studied for decades, preventing tumor growth and recurrence caused by peripheral EGF remains a great challenge. In this work, a strategy is proposed to reduce the stimulation of high concentration EGF on tumor growth by using a thermo-sensitive hydrogel. The hydrogel is a triblock copolymer composed of polyethylene glycol (PEG) and poly (lactide glycolide) (PLGA). Based on the excellent temperature sensitivity, carrier capacity, swelling property and biocompatibility, the hydrogel can absorb the liquid around the tumor by injection and release EGF continuously at low concentration. The inhibitory effect of hydrogel on tumor growth is fully confirmed by an implanted tumor mouse model with human cervical cancer cell lines (HeLa) using triple-immunodeficient NCG mice. Compared with free EGF, the EGF-loaded hydrogel can hardly induce surface plasmon resonance (SPR) response, which proves that hydrogel can effectively weaken cytoskeleton rearrangement and inhibit cell migration by continuously releasing low concentration EGF. In addition, the EGF-loaded hydrogel can reduce cell proliferation by delaying the progress of cell cycle progression. Taken together, the hydrogel can effectively protect tumor microenvironment from the stimulation of high concentration EGF, delay cancer cellular processes and tumor growth, and thus providing an approach for inhibiting tumor recurrence of CC.

In-depth proteomic analysis identifies key gene signatures predicting therapeutic efficacy of anti-PD-1/PD-L1 monotherapy in non-small cell lung cancer.

Background: Immunotherapy has opened up a new era of individualized treatment for non-small cell lung cancer (NSCLC) with negative driver gene mutations. Anti-programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) antibodies have been the main options for immunotherapy over the past decade. Screening for predictive markers of anti-PD-1/PD-L1-responsive patients remains a focus in the field of immunotherapy, especially on the protein level in which relevant proteomic biomarkers are still lacking. Methods: We collected samples from 23 patients with NSCLC who received anti-PD-1/PD-L1 monotherapy and were followed up for three years. The proteomic profile of the tumor was obtained by mass spectrometry (MS). Meanwhile, we combined the RNA sequencing (RNA-seq) data of 27 patients treated with anti-PD-1/PD-L1 therapy in a previous study to establish an integrated gene network. Weighted correlation network analysis (WGCNA) and elastic network were implemented to screen the top gene modules for predicting treatment-responsive patients. Gene expression related mutational patterns were also retrieved for validation in the Memorial Sloan-Kettering Cancer Center (MSKCC) cohort. Results: Our results showed the gene expression profile of MOXD1, PHAF1, KRT7, ANKRD30A, TMEM184A, KIR3DL1, and KCNK4 could better predict the durable response to anti-PD-1/PD-L1 therapy, with the specificity and sensitivity of 0.76 and 0.6, respectively. Besides, the mutational gene profile associated with these genes also suggested an association with favorable response in the MSKCC cohort. Patient-specific protein-protein interaction (PPI) network also indicated strong correlation among KRT7, TMEM184A and ANKRD30A. Conclusions: Our study indicated that key gene signatures identified by machine learning model could be utilized for clinical screening of patients who might benefit from anti-PD-1 therapy. Further mechanistic investigations around these genes are warranted.

Efficacy and safety of local ablative therapy for patients with NSCLC and coexisting interstitial lung disease.

BACKGROUND: The effective therapeutic approach is still an unmet need for patients diagnosed with both lung cancer and interstitial lung disease (ILD). This is primarily due to the possible risk of ILD exacerbation caused by surgery or radiotherapy. The current study aimed to investigate the efficacy and safety of local ablative therapy (LAT) for this specific population. METHODS: Consecutive patients with non-small cell lung cancer (NSCLC) and ILD who received LAT between January 2018 and August 2022 were enrolled, and propensity score matching (PSM) was utilized to match the non-ILD group. The primary endpoint was recurrence-free survival (RFS), and secondary endpoints included overall survival (OS), adverse events (AEs) and hospital length of stay (HLOS). RESULTS: The PSM algorithm yielded matched pairs in the ILD group (n = 25) and non-ILD group (n = 72) at a ratio of 1:3. There were no statistically significant differences in RFS (median 16.4 vs. 18 months; HR = 1.452, p = 0.259) and OS (median: not reached vs. 47.9 months; HR = 1.096, p = 0.884) between the two groups. Meanwhile, no acute exacerbation of ILD was observed in the ILD group. However, the incidence of pneumothorax, especially pneumothorax requiring chest tube drainage, was significantly higher (36.0% vs. 11.2%, p = 0.005) among patients with NSCLC and co-existing ILD, which resulted in longer HLOS (p = 0.045). CONCLUSION: Although ILD was associated with a higher incidence of pneumothorax, the efficacy of LAT for NSCLC patients with ILD was comparable to those without ILD, suggesting that LAT might be a reliable and effective treatment option for this population, particularly in the early stage.

Solvent-Resistant Adhesive Gel with Thermal Post-Tunability.

Adhesives have received extensive attention in flexible bioelectronics, wearable electronic medical devices, and biofuel cells. However, it is a challenge to achieve late regulation of performance once polymer-based gels are formed. Here, a double-network organogel composed of a hydrophilic and hydrophobic polymer network and a polyamide acid network was successfully prepared. In diverse liquid environments (including isopropyl alcohol, glycerol, epichlorohydrin, n-propanol, dichloromethane, triethanolamine, ethanol absolute, hydrogen peroxide, and ethyl acetate), the organogel adhesive demonstrated remarkable properties. It exhibits a strong tensile strength of 200 kPa, a high fracture strain reaching 560%, and an impressive adhesion strength of 38 kPa. In addition, the organogel demonstrates exceptional adhesive properties toward polytetrafluoroethylene, plastics, metals, rubber, and glass. Note that the organogel could also regulate adhesive and tough performance by thermally triggering a cyclization reaction even after the organogel has been formed. The strategy provides a new idea for designing soft materials with post-tunability.

Hierarchical Porous Aerogels With Multiple Adsorptive Interactions for Dye Wastewater Purification.

Aerogels present a huge potential for removing organic dyes from printing and dyeing wastewater (PDW). However, the preparation of aerogels with multiple dye adsorption capabilities remains a challenge, as many existing aerogels are limited to adsorbing only a single type of dye. Herein, a composite aerogel (CG/T-rGO) with the addition of carboxymethyl chitosan, gelatin and tannic acid reduced graphene oxide (T-rGO) was synthesized by freeze-drying technology. The electrostatic interactions between dye molecular and GEL/CMCS (CG) networks, as well as the supramolecular interactions (H-bonds, electrostatic interactions and π-π stacks) between T-rGO, have endowed the aerogel with the ability to adsorb multiple types of dye, such as methylene blue (MB) and methyl orange (MO). Results exhibited that the prepared CG/T-rGO aerogel possessed strong mechanical strength and a porous 3D network structure with a porosity of 96.33 %. Using MB and MO as adsorbates, the adsorption capacity (88.2 mg/g and 66.6 mg/g, respectively) and the mechanism of the CG/T-rGO aerogel were investigated. The adsorption processes of aerogel for MB and MO were shown to follow the pseudo-second-order kinetic model and Langmuir isotherm model, indicating the chemical adsorption of a monolayer. The proposed aerogel in this work has promising prospects for dye removal from PDW.

Thermochromic Hydrogels with Opaque-Transparent Gradient Transition for Switchable Window and Temperature Monitor.

In recent years, the thermochromic hydrogel was acted as suitable sandwiching material to adjust light transmission. However, to accurately control the thermochromic temperature in a wide range still was a significant challenge. Here, a simple method was explored to prepare hydrogels with gradient opaque-transparent transition thermochromic temperature from 5 °C to 53 °C, which was regulated by the aggregation state of sodium dodecyl sulfate micelles by adding potassium tartrate hemihydrate and cations. Using Li+ , Na+ , and K+ as cations, the accuracy was controlled at 1 °C. Moreover, the transmittance of the hydrogel was not changed when the thermochromic temperature was adjusted. As a result, an intelligent window was fabricated by utilizing thermochromic hydrogel as a sandwiching layer into the outer glass layers, which could effectively and stably regulate the visible and infrared light. The temperature monitors/detectors were also designed, which showed excellent temperature monitoring/detecting ability. Therefore, this low-cost, high-efficient, large-scale prepared thermochromic hydrogel provided more potential for intelligent temperature devices.

Gum Arabic-based three-dimensional printed hydrogel for customizable sensors.

Most three-dimensional (3D) printed hydrogel exhibit non-idealized rheological properties in the process of direct ink writing and complicated curing. Therefore, accurate writability and convenient curing for 3D printed hydrogel remain a challenge. In this paper, we developed a typical 3D printed hydrogel which realized direct ink writing (DIW) at temperatures similar to human body. Silicon dioxide (SiO2) and Gum Arabic (GA) formed the Bingham fluid to ensure shape stability. The rapid initiation system of potassium persulfat (KPS) and N,N,N',N' -tetramethylethylenediamine (TMEDA) allowed the 3D printed hydrogel precursor solution to transiently form a hydrophobic conjoined cross-linking network structure of acrylamide (AAM) and lauryl methacrylate (LMA) after printing, resulting in preferable mechanical properties. Hydrogel precursor solution showed better rheological properties with the nature of Bingham fluids, and achieved transient cross-linking at 30 °C for 10 s in the rheological test. A variety of 3D printed hydrogel with individual strain sensing properties are prepared as customizable sensor that could monitor significant strain signals within 0-20 % strain with high sensitivity. Moreover, they were discovered excellent temperature sensitivity over a wide operating range (0-80 °C). The 3D printing hydrogel sensors were expected to have broad application prospects in flexible wearable devices and medical monitoring.

Cellulose nanofiber hydrogel with high conductivity electrolytes for high voltage flexible supercapacitors.

Although flexible double layer capacitors based on hydrogels overcome the drawbacks of commercial double layer capacitors such as low safety and non-deformability, it is still considered as attractive challenges to achieve high conductivity for hydrogel electrolytes as well as high operating voltages for hydrogel flexible supercapacitors. In this paper, ion migration channels were engineered by immobilizing positive and negative charges on polymer skeleton and dispersing cellulose nanofibers in the polymerized polyelectrolyte network, providing ultra-high ionic conductivity (103 mS cm-1). In addition, K3[Fe(CN)6] was introduced through a soaking method, leading to redox reactions on the surface of carbon electrode during charging and discharging, supporting a relatively wide voltage window (1.8 V). Moreover, the specific capacitance at high current remained 55 % of the specific capacitance at low current, indicating excellent rate performance. In addition, the device displayed high cycling stability (80.05 % after 10,000 cycles). Notably, we successfully light up the red LED with only one device. Accordingly, this work provides a feasible design concept for the development of cellulose nanofibers (CNF) hydrogel-based solid-state electrolyte with high conductivity for flexible supercapacitors with wide potential window and high energy density.

A Novel Self-Pumping Janus Dressing for Promoting Wound Immunomodulation and Diabetic Wound Healing.

Self-pumping dressings become one of the optimal solutions for the controlled management of chronic diabetic wound exudate and wound healing. However, present self-pumping dressings are not only prone to breakage of the loose hydrophobic layer but also have cumbersome and complicated preparation steps, which hinder the application of self-pumping dressings in diabetic wound treatment. Herein, a novel self-pumping structure of superabsorbent Janus dressing is designed to improve the strength of the hydrophobic layer and promote diabetic wound healing. The Janus dressing consists of a hydrophobic layer with a drainage agent (drainage layer) and a fluffy 3D nanofiber cotton (absorbent layer). Regardless of the thickness of the drainage layer, the drainage agent in the drainage layer provides the fluid to penetrate the drainage layer to the absorbent layer for unidirectional fluid draining. In design proof, the superabsorbent Janus dressing provides unidirectional drainage of inflammatory exudate and regulation of macrophage polarization, resulting in faster diabetic wound healing than single-layer dressings. Thus, the Janus dressing demonstrates important clinical implications to offer a novel design and preparation strategy for accelerating diabetic wound healing.

Stable zinc anode interface and environmentally adaptable hydrogel electrolytes for stable operation of zinc-ion hybrid supercapacitors.

Hydrogel-based zinc ion hybrid supercapacitors (ZIHS) have stood out from many energy storage device candidates due to their battery-level energy density, inherent flexibility, and safety. Nevertheless, the inevitable dendrite growth of Zn anodes and sharp capacity degradation at low-temperature seriously hinder their practical application. Herein, a dense ZnF2 solid electrolyte interface protective layer was constructed in situ on the Zn electrode surface by a simple chemical deposition method, effectively isolating the water molecules and alleviating the water-induced dendrite growth and parasitic reaction. To achieve the flexible ZIHS with environmental adaptability, a self-adhesion and anti-freezing zwitterionic hydrogel electrolyte was fabricated to afford superior ionic conductivity (97.1 mS cm-1), excellent anti-drying ability, and robust interfacial adhesion. Benefitting from the integrated merits of the as-designed electrolyte and electrode, the ZIHS delivered excellent mechanical adaptability, favorable energy density (103.9 Wh kg-1 at 270.1 W kg-1), broad operating temperature range (-40 to 40 °C), along with long-term cycling stability (12,000 cycles) with 90.3 % capacity retention at -25 °C. Notably, the unencapsulated ZIHS achieved exceptional electrochemical stability in an open environment. This finding provides valuable insights for constructing durable, flexible, and environmentally adaptable zinc-based energy storage systems.

Tough, recyclable and biocompatible carrageenan-modified polyvinyl alcohol ionic hydrogel with physical cross-linked for multimodal sensing.

Biocompatibility hydrogel conductors are considered as sustainable bio-electronic materials for the application of wearable sensors and implantable devices. However, they mostly face the limitations of mismatched mechanical properties with skin tissue and the difficulty of recycling. In this regard, here, a biocompatible, tough, reusable sensor based on physical crosslinked polyvinyl alcohol (PVA) ionic hydrogel modified with ι-carrageenan (ι-CG) helical network was reported. Through simulating the ion transport and network structure of biological systems, the ionic hydrogels with skin-like mechanical features exhibit large tensile strain of 640 %, robust fracture strength of 800 kPa, soft modulus and high fatigue resistance. Meanwhile, the ionic hydrogel-based sensors possess a high response to strain/pressure over a wide range and could be utilized for multimodal sensing of human activity signals. Benefit from biosafety and temperature reversibility of ι-CG and PVA endow hydrogels with not only biocompatibility, but also meaningfully recyclability. The as-prepared hydrogels could be freely reconstructed into new flexible electronics and safely integrated with the human skin. It could be anticipated that the physically cross-linked ionic hydrogel conductor could expand the options for next-generation bio-based sensors.

Fibronectin promotes tumor angiogenesis and progression of non-small-cell lung cancer by elevating WISP3 expression via FAK/MAPK/ HIF-1α axis and activating wnt signaling pathway.

BACKGROUND: Fibronectin, an extracellular matrix protein, has been reported to be associated with heterogeneous cancer stemness, angiogenesis and progression in multiple cancer types. However, the roles and the underlying mechanism of fibronectin on the progression NSCLC need to be further elucidated. METHODS: Public dataset such as Kaplan-Meier Plotter was used to determine the prognostic significance of genes. The correlation of different protein expression in clinical and xenograft tissues was tested by immunohistochemistry experiment. Both in vitro and in vivo experiments were performed to determine the role of fibronectin on the tumor growth, metastasis, and angiogenesis in NSCLC. The activation of key signaling pathway under fibronectin was examined by WB assay. RNA-seq was applicated to screening the target gene of fibronectin. Rescue experiment was performed to confirm the role of target gene in fibronectin-mediated function in NSCLC. Finally, luciferase and CHIP assays were used to elucidate the mechanism by which fibronectin regulated the target gene. RESULTS: Our results revealed that fibronectin was up-regulated in cancer tissues compared with the normal ones in NSCLC patients. Dish- coated fibronectin enhanced the tumor growth, metastasis, and angiogenesis of NSCLC in vitro and in vivo by promoting EMT and maintaining stemness of NSCLC cells. As expected, fibronectin activated FAK and its downstream MAPK/ERK signaling pathway. WISP3 was screened as a potential target gene of fibronectin. Interestingly, WISP3 effectively activated Wnt signaling pathway, and knockdown of WISP3 effectively blocked the influence of fibronectin on the migration, invasion and vascular structure formation potential of NSCLC cells. Our data also manifested that fibronectin elevated the transcription of WISP3 gene by promoting the binding of HIF-1α to the promoter region of WISP3 in NSCLC cells. CONCLUSIONS: Our findings sketched the outline of the route for fibronectin exert its role in NSCLC, in which fibronectin activated downstream FAK and MAPK/ERK signaling pathways, and mediated the accumulation of HIF-1α. Then, HIF-1α enabled the transcription of WISP3, and subsequently promoted the activation of Wnt signaling pathway, and finally enhanced the tumor growth, metastasis, and angiogenesis in NSCLC.

Stretchable Organohydrogel with Adhesion, Self-Healing, and Environment-Tolerance for Wearable Strain Sensors.

Stretchable hydrogels as landmark soft materials have been efficiently utilized in the field of wearable sensing devices. However, these soft hydrogels mostly cannot integrate transparency, stretchability, adhesiveness, self-healing, and environmental adaptability into one system. Herein, a fully physically cross-linked poly(hydroxyethyl acrylamide)-gelatin dual-network organohydrogel is prepared in a phytic acid-glycerol binary solvent via a rapid ultraviolet light initiation. The introduction of gelatin as the second network endows the organohydrogel with desirable mechanical performance (high stretchability up to 1240%). The presence of phytic acid not only synergizes with glycerol to impart environment-tolerance to the organohydrogel (from -20 to 60 °C) but also increases the conductivity. Moreover, the organohydrogel demonstrates a durable adhesive performance toward diverse substrates, a high self-healing efficiency through heat treatment, and favorable optical transparency (transmittance of 90%). Furthermore, the organohydrogel achieves high sensitivity (gauge factor of 2.18 at 100% strain) and rapid response time (80 ms) and could detect both tiny (a low detection limit of 0.25% strain) and large deformations. Therefore, the assembled organohydrogel-based wearable sensors are capable of monitoring human joint motions, facial expression, and voice signals. This work proposes a facile route for multifunctional organohydrogel transducers and promises the practical application of flexible wearable electronics in complex scenarios.

Molecular correlation of response to pyrotinib in advanced NSCLC with HER2 mutation: biomarker analysis from two phase II trials.

BACKGROUND: Non-small cell lung cancer (NSCLC) with HER2 mutation has entered into the era of targeted therapy. However, both anti-HER2 antibody-drug conjugates (ADCs) and tyrosine kinase inhibitors (TKIs) showed moderate objective response rate (ORR) and median progression-free survival (PFS). The aim of this study was to investigate the molecular features of responders to pyrotinib in advanced NSCLC with HER2 mutation. METHODS: Patients from our two previous phase II trials were pooled analyzed. Their circulating tumor DNA (ctDNA) were detected by next-generation sequencing (NGS) panels, and the correlation with the efficacy of pyrotinib was investigated. RESULTS: This pooled analysis included 75 patients, and 50 of them with baseline plasma samples were finally enrolled with a median age of 57 years old. The overall ORR and median PFS were 28% and 7.0 months respectively. Biomarker analysis showed that 5 patients were ctDNA nonshedding. Patients with TP53 wild type were significantly associated with higher disease control rate (97.1%vs. 68.8%, p = 0.010), PFS (median 8.4 vs. 2.8 months, p = 0.001) and overall survival (OS, median 26.7 vs. 10.4 months, p < 0.001) than those with mutations. ctDNA of nonshedding and clearance exhibited significantly longer PFS (median: 10.2 vs. 9.8 vs. 5.6 months, p = 0.036) and a trend of longer OS (median: 35.3 vs. 18.1 vs. 14.6 months, p = 0.357) than those not. CONCLUSION: Patients with TP53 wild type, ctDNA nonshedding, or clearance showed superior efficacy of pyrotinib in patients with HER2-mutated advanced NSCLC, which might be helpful to guide the utility of pyrotinib in clinical setting. TRIAL REGISTRATION: The patients were from two registered clinical trials (ClinicalTrials.gov: NCT02535507, NCT02834936).

Personalized circulating tumor DNA detection to monitor immunotherapy efficacy and predict outcome in locally advanced or metastatic non-small cell lung cancer.

OBJECTIVE: Immune checkpoint inhibitors (ICIs) or combined with chemotherapy exhibit substantial efficacy for the treatment of advanced non-small cell lung cancer (NSCLC). However, reliable biomarkers that can monitor response to first-line ICIs ± chemotherapy remain unclear. METHODS: A total of 16 tumor tissues and 46 matched peripheral blood samples at baseline and during treatment were retrospectively collected from 19 locally advanced or metastatic NSCLC patients. The circulating tumor DNA (ctDNA) burden by tumor-informed assay was detected to monitor and predict the therapeutic response and survival of NSCLC patients treated with first-line ICIs or plus chemotherapy. RESULTS: We found that ctDNA was only positively detected in one patient by tumor-agnostic assay with a mean variant allele fraction (VAF) of 6.40%, whereas it was positively detected in three patients by tumor-informed assay with a mean VAF of 8.83%, 0.154%, and 0.176%, respectively. Tumor-informed assays could sensitively detect ctDNA in 93.75% (15/16) of patients. Trends in the level of ctDNA from baseline to first evaluation was consistent with the radiographic changes. There was a greater decrease in ctDNA after treatment compared with baseline in patients with partial response compared to patients with stable disease/progressive disease. Patients with over a 50% reduction in ctDNA had a significant progression-free survival and overall survival benefit. CONCLUSION: The tumor-informed assay was favorable for ctDNA detection, and early dynamic changes in plasma ctDNA may be a valuable biomarker for monitoring the efficacy and predicting the outcome in advanced NSCLC patients treated with first-line ICIs ± chemotherapy.

Association of PD-L1 expression with efficacy of alectinib in advanced NSCLC patients with ALK fusion.

BACKGROUND: Programmed cell death-ligand 1 (PD-L1) expression was found to be a biomarker of inferior efficacy of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in EGFR-mutated non-small cell lung cancer (NSCLC). However, whether PD-L1 expression could also serve as a similar biomarker in anaplastic lymphoma kinase (ALK)-positive patients, especially for those treated with front-line alectinib, remains unclear. The aim of the study is to investigate the association of PD-L1 expression and efficacy of alectinib in this setting. METHODS: From January 2018 to March 2020, 225 patients with ALK-rearranged lung cancer were consecutively collected at Shanghai Pulmonary Hospital, Tongji University. Baseline PD-L1 expression was detected using immunohistochemistry (IHC) in 56 patients of advanced ALK-rearranged lung cancer who received front-line alectinib. RESULTS: Among the 56 eligible patients, 30 (53.6%) were PD-L1 expression negative, 19 (33.9%) patients had TPS 1%-49% and 7 (12.5%) had TPS ≥ 50%.We found no statistically significant associations between PD-L1 positivity and objective response rate (ORR, 90.0% vs. 80.8%, p = 0.274) or progression-free survival (PFS, not reached vs. not reached, HR: 0.98, 95 %CI: 0.37-2.61, p = 0.97) in patients treated with alectinib. Meanwhile, patients with PD-L1 high expression (TPS ≥ 50%) had a trend of longer PFS (not reached vs. not reached, p = 0.61). CONCLUSIONS: PD-L1 expression might not serve as a predict biomarker for the efficacy of front-line alectinib in ALK-positive NSCLC patients.

Special issue "The advance of solid tumor research in China": FGFR4 alterations predict efficacy of immune checkpoint inhibitors in nonsmall cell lung cancer.

Immune checkpoint inhibitors (ICIs), which represent the new standard of care for advanced nonsmall cell lung cancer (NCSLC), are not effective in many patients. Biomarkers are needed to guide treatment. Sequencing data of an ICI-treated cohort were analyzed to identify genomic signatures predicting ICI efficacy, followed by validation using multiple independent cohorts. Their predictive mechanism was explored by evaluating the tumor immune microenvironment and tumor mutational burden (TMB). In the discovery cohort, patients carrying FGFR4 alterations (FGFR4altered ) had a better objective response rate (ORR) (50.0% vs 19.4%; P = .057) and improved median progression-free survival (mPFS) (13.17 vs 3.17 months; HR 0.37; 95% CI 0.14-1; P = .04) than wild-type patients (FGFR4wt ). In the publicly available validation cohorts, FGFR4 alterations correlated with higher ORR (100% vs 31%; P = .028), longer median overall survival (mOS) (not reached [NR] vs 11 months; HR 0.28, 95% CI 0.09-0.89, P = .02), and mPFS (NR vs 6.07 months; HR 0.05, 95% CI 0-3.94, P = .039). FGFR4 alterations were confirmed as an independent predictor of superior PFS (P = .014) and OS (P = .005). FGFR4altered patients also exhibited a significantly improved disease control rate (100% vs 60%, P = .045) and prolonged mPFS (9.70 vs 3.16 months; P = .095) compared to FGFR4wt patients in our Shanghai Pulmonary Hospital cohort. FGFR4 alterations associated with a higher TMB levels, more CD8+ T cells in the tumor stroma, and a higher M1/M2 ratio for tumor-associated macrophages in the tumor center and stroma. Thus, FGFR4 alterations may serve as a potential independent predictor of ICI efficacy in NSCLC.

Alginate foam gel modified by graphene oxide for wound dressing.

Recently, hydrogel dressings have been rapidly developed for wound healing. However, it is still a huge challenge to endow hydrogel wound dressings with excellent hemostatic performance. Here, a new wound treatment material, foam gel wound dressing, is reported, which possesses rapid hemostasis and antibacterial properties. The foam gel dressing is composed of chitooligosaccharide modified graphene oxide (CG) nanocomposites and calcium alginate foam substrate. In this system, CG has a strong interaction with platelets, which is helpful for rapid hemostasis. So the wound dressing could stop bleeding quickly within 10 s. Meanwhile, CG also provides excellent antibacterial properties to dressings, which is conducive to wound healing. Full-thickness wound healing experiments showed that compared with blank control and CG-free foam gel dressings, CG-loaded foam gel dressings shows better healing properties, and the wounds covered with them are almost completely healed within 12 days. In addition, histological morphology analysis displays CG-loaded wound dressing could significantly accelerate wound healing by reducing the inflammatory response and promoting vascular remodeling. This unique strategy provides a simple and practical method for the clinical application of the next generation of wound dressings.

Immune checkpoint inhibitors plus chemotherapy in patients with locally advanced or metastatic pulmonary sarcomatoid carcinoma: a multicentric real-world study.

Introduction: Immune checkpoint inhibitors (ICIs) have demonstrated promising efficacy as monotherapy in patients with pulmonary sarcomatoid carcinoma (PSC). We performed the current multi-institutional, real-world study to assess the efficacy of ICIs plus chemotherapy in patients with PSC. Methods: All consecutive patients with locally advanced or metastatic PSC from three centers treated with ICIs between January 2018 and July 2021 were enrolled. Programmed death ligand 1 (PD-L1) expression was stained and evaluated using immunohistochemical with 22C3. Single-cell RNA sequencing (scRNA-seq) was performed in two patients with PSC and two patients with adenocarcinoma to understand the cell-type-specific transcriptome landscape of cancer cells and tumor microenvironment (TME) of PSC. Results: A cohort of 42 PSC patients was identified. In the overall population, the objective response rate (ORR) was 73.8%, median progression-free survival (mPFS) was 10.3 months and median overall survival was not reached and 2-year survival rate was 51.2%. For 34 treatment-naïve patients who received first-line ICIs plus chemotherapy, the ORR was 70.6%, mPFS was 10.3 months and 2-year survival rate was 57.8%. In patients with PD-L1 tumor proportion score (TPS) < 1%, 1-49%, and ⩾50%, the ORR was 33.3%, 72.7%, and 85.7% and mPFS was 6.0, 6.7, and 10.3 months, respectively. Notably, two patients with transformed PSC from lung adenocarcinoma after epidermal growth factor receptor-tyrosine kinase inhibitor treatment also responded well to ICIs plus chemotherapy. scRNA-seq revealed immune-cell-inflamed TME, lower intratumoral heterogeneity, and activated immune response pathway in PSC. Conclusions: Our study demonstrated remarkable efficacy of ICIs plus chemotherapy as first-line therapy for patient with locally advanced or metastatic PSC.