Mussel-Inspired Polymer-Based Composites for Efficient Thermal Management in Dry and Underwater Environments.

To address the escalating power consumption of processors in data centers and the growing emphasis on environmental sustainability, the prospective shift from traditional air-cooling to immersion liquid cooling necessitates multiple functional integrations in polymer-based thermal conductive materials. Here, drawing inspiration from mussels, we showed a copolymer, poly(dimethylsiloxane-co-dopamine methacrylate) (PDMS-DMA), with a variety of reversible molecular interactions and simply combined with liquid metal (EGaIn) can yield a flexible, waterproof, and electrically insulating thermal conductive composite. The obtained PDMS-DMA/EGaIn composites demonstrate a harmonious blend of attributes, including a low modulus (75.8 kPa), high thermal conductivity of 6.9 W m-1 K-1, and rapid room-temperature self-healing capabilities, capable of complete repair within 20 min, even under water. Based on its electrically insulating and water resistance properties, PDMS-DMA/EGaIn emerges as a promising candidate for efficient and stable heat transfer in both air and underwater thermal management. Consequently, this water-resistant polymer-based composite holds significance for application in thermal protective layers for future immersion liquid cooling systems.

Temporal vascular arcade angle in fundus image was associated with the rate of spherical equivalent refractive error and axial length changes in myopia children with young school age.

PURPOSE: To evaluate temporal vascular arcade angle and its influencing factors in myopic children. METHODS: It was a retrospective study, we reviewed the records of 119 patients aged 6-10 years with myopia (spherical equivalent refractive error (SER) ≤ -0.05D) in the third year of follow-up in Beijing Hyperopia Reserve Research. We measured temporal vascular arcade angles on the fundus photographs and measured 3-year rate of spherical equivalent(D/year) and axial length (AXL) changes(mm/year). RESULTS: Mean age at initial visit was 7.71±1.20 years and mean SER was -1.32±1.09D. Children were divided into two groups according to the refractive status of children at baseline: Myopia onset group (SER>-0.50D at baseline) (n = 107) and Myopia progression group (SER≤-0.50D at baseline) (n = 12). The mean SER in Myopia progression group was much smaller than Myopia onset group (P < 0.001) and mean AXL in Myopia progression group was much longer than Myopia onset group (P = 0.042). AXL (r=-0.320, P < 0.001), SER change rate (r=-0.209, P = 0.022) and AXL change rate (r=-0.232, P = 0.011) were associated with temporal vascular arcade angle in all participants. In Myopia onset group, AXL (r=-0.317, P < 0.001) and AXL change rate (r=-0.190, P = 0.05) were associated with temporal vascular arcade angle. There were no parameters were associated with temporal vascular arcade angle (all P > 0.05) in Myopia progression group. Only AXL (r=-0.306, P = 0.018) was associated with temporal vascular arcade angle in girls while AXL (r=-0.370, P = 0.004), SER change rate (r=-0.317, P = 0.013) and AXL change rate (r=-0.365, P = 0.004) were all associated with the Angle in boys. CONCLUSION: Temporal vascular arcade angle was associated with the rate of SER and AXL changes in myopia onset children, and showed gender differences. These may suggest that lamina cribrosa location has different influencing factors in different genders and different stages of myopia development. Due to the small number of people in Myopia progression group, large sample size studies are still needed in the future.

Relationship between the length of macular Bruch's membrane on fundus photograph and myopia occurrence in pre-myopia children aged 3-6 years: a 3-year longitudinal study.

PURPOSE: To evaluate the occurrence and influencing factors of myopia occurrence in pre-myopia children aged 3-6 years. METHODS: This study included 204 pre-myopia (-0.50D-0.50D). The length of macular BM was shorter in Myopia group than that in Non-myopia group (P<0.001). Baseline SE and the length of macular BM were independent influencing factors which associated with myopia occurrence (OR, 0.031; 95% CI, 0.008-0.117, P<0.001 and OR, 0.204; 95% CI, 0.055-0.763, P=0.018, respectively) by multivariate binary logistic regression analysis. SE changes process represents the changes of SE, Myopia group had the bigger SE changes (P<0.001). And in the multivariate liner regression analysis, age was the common influencing factor of SE changes process in total participants, Non-myopia group and Myopia group (B=0.244, P<0.001; B=0.078, P=0.010; B=0.161, P=0.046, respectively) CONCLUSIONS: Initial SE and the length of macular BM in pre-myopia children aged 3-6 years were the independent factors of the occurrence of myopia. And initial age was the common factor that associated with SE changes process.

Chinese Medicine Prolongs Overall Survival of Chinese Patients with Advanced Gastric Cancer: Treatment Pattern and Survival Analysis of a 20-Year Real-World Study.

OBJECTIVE: To describe the treatment patterns and survival status of advanced gastric cancer (AGC) in China in the past two decades, and objectively evaluate the impact of standardized Chinese medicine (CM) treatment on the survival of AGC patients. METHODS: This multicenter registry designed and propensity score analysis study described the diagnosis characteristics, treatment-pattern development and survival status of AGC from 10 hospitals in China between January 1, 2000 and July 31, 2021. Overall survival (OS) was evaluated between non-CM cohort (standard medical treatment) and CM cohort (integrated standard CM treatment ≥3 months). Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were performed to adjust any difference in average outcomes for bias. RESULTS: A total of 2,001 patients histologically confirmed locally advanced and/or metastasis stomach and gastroesophageal junction adenocarcinoma were enrolled. Among them, 1,607 received systemic chemotherapy, 215 (10.74%) accepted molecular targeted therapy, 44 (2.2%) received checkpoint inhibitor therapy, and 769 (38.43%) received CM. Two-drug regimen was the main choice for first-line treatment, with fluoropyrimidine plus platinum as the most common regimen (530 cases, 60.09%). While 45.71% (16 cases) of patients with HER2 amplification received trastuzumab in first-line. The application of apatinib increased (33.33%) in third-line. The application of checkpoint inhibitors has increased since 2020. COX analysis showed that Lauren mixed type (P=0.017), cycles of first-line treatment >6 (P=0.000), CM (P=0.000), palliative gastrectomy (P=0.000), trastuzumab (P=0.011), and apatinib (P=0.008) were independent prognostic factors for the OS of AGC. After PSM and IPTW, the median OS of CM cohort and non-CM cohort was 18.17 and 12.45 months, respectively (P<0.001). CONCLUSIONS: In real-world practice for AGC in China, therapy choices consisted with guidelines. Two-drug regimen was the main first-line choice. Standardized CM treatment was an independent prognostic factor and could prolong the OS of Chinese patients with AGC. (Registration No. NCT02781285).

Regulatable Orthotropic 3D Hybrid Continuous Carbon Networks for Efficient Bi-Directional Thermal Conduction.

Vertically oriented carbon structures constructed from low-dimensional carbon materials are ideal frameworks for high-performance thermal interface materials (TIMs). However, improving the interfacial heat-transfer efficiency of vertically oriented carbon structures is a challenging task. Herein, an orthotropic three-dimensional (3D) hybrid carbon network (VSCG) is fabricated by depositing vertically aligned carbon nanotubes (VACNTs) on the surface of a horizontally oriented graphene film (HOGF). The interfacial interaction between the VACNTs and HOGF is then optimized through an annealing strategy. After regulating the orientation structure of the VACNTs and filling the VSCG with polydimethylsiloxane (PDMS), VSCG/PDMS composites with excellent 3D thermal conductive properties are obtained. The highest in-plane and through-plane thermal conductivities of the composites are 113.61 and 24.37 W m-1 K-1, respectively. The high contact area of HOGF and good compressibility of VACNTs imbue the VSCG/PDMS composite with low thermal resistance. In addition, the interfacial heat-transfer efficiency of VSCG/PDMS composite in the TIM performance was improved by 71.3% compared to that of a state-of-the-art thermal pad. This new structural design can potentially realize high-performance TIMs that meet the need for high thermal conductivity and low contact thermal resistance in interfacial heat-transfer processes.

Tessellated fundus occurs earlier than myopia in children aged 3-6 years.

BACKGROUND/OBJECTIVES: Tessellated fundus can exist in normal healthy eyes. This study aims to evaluate the occurrence and influencing factors of tessellated fundus in preschool children aged 3-6 years. SUBJECTS/METHODS: This kindergarten-based cross-sectional study included 1716 children with an age range of 3-6 years. All participants underwent a comprehensive eye examination and a questionnaire. According to the number of quadrants occupied by tessellated fundus around the optic disc in fundus photographs, it was divided into four grades. RESULTS: 600 (35.0%) children had peripapillary tessellation. According to the spherical equivalent (SE), the subjects were divided into three groups: Hyperopia group (SE > + 0.75D, n = 1194)；Pre-myopia group (-0.50D < SE ≤ + 0.75D, n = 455); Myopia group (SE ≤ -0.50D, n = 67). The proportion of peripapillary tessellated fundus was 33.0%, 38.0%, 50.7% respectively. According to the regression analysis, in the non-myopia group (Pre-myopia group and Hyperopia group), the occurrence of peripapillary tessellated fundus was associated with longer axial length (OR, 1.566; 95% CI: 1.229-1.996, p < 0.001) and larger corneal radius of curvature (OR, 1.837; 95% CI: 1.006-3.354, p = 0.048). However, in Pre-myopia group, the corneal radius of curvature was not associated with the occurrence of peripapillary tessellated fundus (p = 0.830). In Hyperopia group, the corneal radius of curvature was associated with the occurrence of peripapillary tessellated fundus (OR, 2.438; 95% CI: 1.160-5.122, p = 0.019). CONCLUSIONS: The occurrence of peripapillary tessellated fundus is more than 30% in 3-6 year old preschool children. Tessellated fundus can also occur in non-myopic children, and is related to the length of axial length and large radius of corneal curvature.

Boosting synergism of chemo- and immuno-therapies via switching paclitaxel-induced apoptosis to mevalonate metabolism-triggered ferroptosis by bisphosphonate coordination lipid nanogranules.

Conventional chemotherapy based on cytotoxic drugs is facing tough challenges recently following the advances of monoclonal antibodies and molecularly targeted drugs. It is critical to inspire new potential to remodel the value of this classical therapeutic strategy. Here, we fabricate bisphosphonate coordination lipid nanogranules (BC-LNPs) and load paclitaxel (PTX) to boost the chemo- and immuno-therapeutic synergism of cytotoxic drugs. Alendronate in BC-LNPs@PTX, a bisphosphonate to block mevalonate metabolism, works as both the structure and drug constituent in nanogranules, where alendronate coordinated with calcium ions to form the particle core. The synergy of alendronate enhances the efficacy of paclitaxel, suppresses tumor metastasis, and alters the cytotoxic mechanism. Differing from the paclitaxel-induced apoptosis, the involvement of alendronate inhibits the mevalonate metabolism, changes the mitochondrial morphology, disturbs the redox homeostasis, and causes the accumulation of mitochondrial ROS and lethal lipid peroxides (LPO). These factors finally trigger the ferroptosis of tumor cells, an immunogenic cell death mode, which remodels the suppressive tumor immune microenvironment and synergizes with immunotherapy. Therefore, by switching paclitaxel-induced apoptosis to mevalonate metabolism-triggered ferroptosis, BC-LNPs@PTX provides new insight into the development of cytotoxic drugs and highlights the potential of metabolism regulation in cancer therapy.

Efficacy and safety of pralsetinib in Chinese advanced RET-mutant medullary thyroid cancer patients.

Pralsetinib has demonstrated efficacious activity in various solid tumors, including medullary thyroid cancer (MTC), as observed in the phase 1/2 global ARROW study (BLU-667-1101; NCT03037385). We evaluated the safety and efficacy of pralsetinib in Chinese patients with advanced RET-mutant MTC. In the extension cohort of ARROW, adult patients with advanced MTC, who had not received systemic therapy (except for cytotoxic chemotherapy), were treated with pralsetinib (400 mg once daily, orally). The primary endpoints were blinded independent central-reviewed (BICR) objective response rate (ORR) and safety. Between October 9, 2019, and April 29, 2020, 34 patients were enrolled at 12 centers across China. Among them, 28 patients tested positive for RET mutations in the central laboratory, and 26 of these, with measurable disease at baseline per BICR, were included in the analysis set for tumor response. As of April 12, 2021 (data cutoff), the ORR was 73.1% (95% CI: 52.2-88.4), and the median duration of response was not reached. The most common (≥15%) grade ≥3 treatment-related adverse events (TRAEs) in the 28 patients with RET-mutant MTC were neutrophil count decreased (8/28, 28.6%), blood creatine phosphokinase increased (6/28, 21.4%), and lymphocyte count decreased (5/28, 17.9%). Serious TRAEs were reported by six patients (21.4%), with the most common event being pneumonia (3/28, 10.7%). No patient discontinued treatment or died from pralsetinib-related adverse events. Pralsetinib demonstrated broad, deep, and durable efficacy, as well as a manageable and acceptable safety profile in Chinese patients with advanced RET-mutant MTC.

Selective internal radiation therapy with yttrium-90 resin microspheres followed by anatomical hepatectomy: A potential curative strategy in advanced hepatocellular carcinoma.

About 80% of hepatocellular carcinoma (HCC) patients are in advanced stages and ineligible for curative surgery. Palliative treatments just maintained limited survival, thus an effective downstaging therapy is badly needed. Here we report an initially unresectable patient who underwent radical hepatectomy after successful downstaging with selective internal radiation therapy (SIRT). A 34-year-old man was diagnosed with China Liver Cancer Staging (CNLC) IIIa HCC. Due to insufficient future liver remnant and vascular involvement, the patient was suggested to be unresectable. SIRT with yttrium-90 resin microspheres was given. At three months post-SIRT, a complete response was achieved. The tumor was downstaged to CNLC Ia stage. The patient underwent anatomical hepatectomy 5 months after SIRT. Histopathological examination of the resected specimen showed 4% viable tumor cells inside a necrotic mass. To our knowledge, this is the first case who underwent SIRT with yttrium-90 resin microspheres in China mainland. The success of the downstaging in this case renders a possible cure to be achieved in an initially unresectable patient. In addition, the nearly complete tumor necrosis in the resected specimen indicates a good prognosis post-surgery. This is the first case who underwent SIRT with yttrium-90 resin microspheres in China mainland. SIRT followed by anatomical hepatectomy is a potentially curative strategy for unresectable HCC, which deserves a confirmative trial in the future.

Patterned liquid metal embedded in brush-shaped polymers for dynamic thermal management.

Interface thermal resistance has become a crucial barrier to effective thermal management in high-performance electronics and sensors. The growing complexity of operational conditions, such as irregular and dynamic surfaces, demands thermal interface materials (TIMs) to possess high thermal conductivity and soft elasticity. However, developing materials that simultaneously combine soft elasticity and high thermal conductivity remains a challenging task. Herein, we utilize a vertically oriented graphene aerogel (VGA) and rationally design liquid metal (LM) networks to achieve directional and adjustable pathways within the composite. Subsequently, we leverage the advantages of the low elastic modulus and high deformation capabilities of brush-shaped polydimethylsiloxane (BPDMS), together with the bicontinuous thermal conduction path constructed by VGA and LM networks. Ultimately, the designed composite of patterned liquid metal/vertically oriented graphene aerogel/brush-shaped PDMS (LM-VGA/BPDMS) shows a high thermal conductivity (7.11 W m-1 K-1), an ultra-low elastic modulus (10.13 kPa), excellent resilience, and a low interface thermal resistance (14.1 K mm2 W-1). This LM-VGA/BPDMS soft composite showcases a stable heat dissipation capability at dynamically changing interfaces, as well as excellent adaptability to different irregular surfaces. This strategy holds important application prospects in the fields of interface thermal management and thermal sensing in extremely complex environments.

Prognostic Implications of LRP1B and Its Relationship with the Tumor-Infiltrating Immune Cells in Gastric Cancer.

BACKGROUND: Recent studies have shown that low-density lipoprotein receptor-related protein 1b (LRP1B), as a potential tumor suppressor, is implicated in the response to immunotherapy. The frequency of LRP1B mutation gene is high in many cancers, but its role in gastric cancer (GC) has not been determined. METHODS: The prognostic value of LRP1B mutation in a cohort containing 100 patients having received radical gastrectomy for stage II-III GC was explored. By analyzing the data of LRP1B mRNA, the risk score of differentially expressed genes (DEGs) between LRP1B mutation-type and wild-type was constructed based on the TCGA-STAD cohort. The infiltration of tumor immune cells was evaluated by the CYBERSORT algorithm and verified by immunohistochemistry. RESULTS: LRP1B gene mutation was an independent risk factor for disease-free survival (DFS) in GC patients (HR = 2.57, 95% CI: 1.28-5.14, p = 0.008). The Kaplan-Meier curve demonstrated a shorter survival time in high-risk patients stratified according to risk score (p < 0.0001). CYBERSORT analysis showed that the DEGs were mainly concentrated in CD4+ T cells and macrophages. TIMER analysis suggested that LRP1B expression was associated with the infiltration of CD4+ T cells and macrophages. Immunohistochemistry demonstrated that LRP1B was expressed in the tumor cells (TCs) and immune cells in 16/89 and 26/89 of the cohort, respectively. LRP1B-positive TCs were associated with higher levels of CD4+ T cells, CD8+ T cells, and CD86/CD163 (p < 0.05). Multivariate analysis showed that LRP1B-positive TCs represented an independent protective factor of DFS in GC patients (HR = 0.43, 95% CI: 0.10-0.93, p = 0.042). CONCLUSIONS: LRP1B has a high prognostic value in GC. LRP1B may stimulate tumor immune cell infiltration to provide GC patients with survival benefits.

The spatiotemporal journey of nanomedicines in solid tumors on their therapeutic efficacy.

The rapid development of nanomedicines is revolutionizing the landscape of cancer treatment, while effectively delivering them into solid tumors remains a formidable challenge. Currently, there is a huge disconnect on therapeutic response between regulatory approved nanomedicines and laboratory reported nanoparticles. The discrepancy is mainly resulted from the failure of using the classic overall pharmacokinetics behaviors of nanomedicines in tumors to predict the antitumor efficacy. Increasing evidence has revealed that the therapeutic efficacy predominantly relies on the intratumoral spatiotemporal distribution of nanomedicines. This review focuses on the spatiotemporal distribution of systemically administered chemotherapeutic nanomedicines in solid tumor. Firstly, the intratumoral biological barriers that regulate the spatiotemporal distribution of nanomedicines are described in detail. Next, the influences on antitumor efficacy caused by the spatial distribution and temporal drug release of nanomedicines are emphatically analyzed. Then, current methodologies for evaluating the spatiotemporal distribution of nanomedicines are summarized. Finally, the advanced strategies to positively modulate the spatiotemporal distribution of nanomedicines for an optimal tumor therapy are comprehensively reviewed.

Efficacy and safety of pralsetinib in patients with advanced RET fusion-positive non-small cell lung cancer.

BACKGROUND: Pralsetinib is a potent, selective RET inhibitor targeting oncogenic RET alterations. As part of the global, phase 1/2 ARROW trial (NCT03037385), the efficacy and safety of pralsetinib in Chinese patients with advanced RET fusion-positive non-small cell lung cancer (NSCLC) were evaluated. METHODS: Adult patients with advanced, RET fusion-positive NSCLC with or without prior platinum-based chemotherapy were enrolled into two cohorts receiving 400-mg once-daily oral pralsetinib. Primary end points were objective response rates assessed by blinded independent central review and safety. RESULTS: Of 68 patients enrolled, 37 had received prior platinum-based chemotherapy (48.6% with ≥3 prior systemic regimens) and 31 were treatment-naïve. As of March 4, 2022 (data cutoff), of the patients with measurable lesions at baseline, a confirmed objective response was observed in 22 (66.7%; 95% confidence interval [CI], 48.2-82.0) of 33 pretreated patients, including 1 (3.0%) complete response and 21 (63.6%) partial responses; and in 25 (83.3%; 95% CI, 65.3-94.4) of 30 treatment-naïve patients, including two (6.7%) complete responses and 23 (76.7%) partial responses. Median progression-free survival was 11.7 months (95% CI, 8.7-not estimable) in pretreated patients and 12.7 months (95% CI, 8.9-not estimable) in treatment-naïve patients. The most common grade 3/4 treatment-related adverse events in 68 patients were anemia (35.3%) and decreased neutrophil count (33.8%). Eight (11.8%) patients discontinued pralsetinib because of treatment-related adverse events. CONCLUSION: Pralsetinib showed robust and durable clinical activity with a well-tolerated safety profile in Chinese patients with RET fusion-positive NSCLC. CLINICAL TRIAL REGISTRATION: NCT03037385.

Interim survival analysis of the randomized phase III GEMSTONE-302 trial: sugemalimab or placebo plus chemotherapy as first-line treatment for metastatic NSCLC.

The randomized, double-blinded, multi-center, phase III GEMSTONE-302 ( NCT03789604 ) study evaluated the efficacy and safety of sugemalimab versus placebo in combination with chemotherapy as first-line treatment for metastatic non-small-cell lung cancer (NSCLC). In this study, 479 treatment-naive patients with stage IV squamous or non-squamous NSCLC without known EGFR sensitizing mutations, ALK, ROS1 or RET fusions were randomized (2:1) to receive 1,200 mg of sugemalimab (n = 320) or placebo (n = 159) every 3 weeks in combination with platinum-based chemotherapy for up to four cycles, followed by maintenance therapy with sugemalimab or placebo for squamous NSCLC and sugemalimab or placebo plus pemetrexed for non-squamous NSCLC. Placebo-treated patients could cross over to receive sugemalimab monotherapy on disease progression. The primary endpoint was investigator-assessed progression-free survival (PFS) and the secondary endpoints included overall survival (OS) and objective response rate. Sugemalimab plus chemotherapy has demonstrated significant PFS prolongation in the primary analysis as reported previously. As of 22 November 2021, the prespecified interim OS analysis showed significant improvement with the addition of sugemalimab to chemotherapy (median OS = 25.4 versus 16.9 months; hazard ratio = 0.65; 95% confidence interval = 0.50-0.84; P = 0.0008). Sugemalimab plus chemotherapy provided superior PFS and OS compared to placebo plus chemotherapy, supporting the use of sugemalimab as a first-line treatment option for metastatic NSCLC.

Tailoring Dense, Orientation-Tunable, and Interleavedly Structured Carbon-Based Heat Dissipation Plates.

The controllability of the microstructure of a compressed hierarchical building block is essential for optimizing a variety of performance parameters, such as thermal management. However, owing to the strong orientation effect during compression molding, optimizing the alignment of materials perpendicular to the direction of pressure is challenging. Herein, to illustrate the effect of the ordered microstructure on heat dissipation, thermally conductive carbon-based materials are fabricated by tailoring dense, orientation-tunable, and interleaved structures. Vertically aligned carbon nanotube arrays (VACNTs) interconnected with graphene films (GF) are prepared as a 3D core-ordered material to fabricate compressed building blocks of O-VA-GF and S-VA-GF. Leveraging the densified interleaved structure offered by VACNTs, the hierarchical O-VA-GF achieves excellent through-plane (41.7 W m-1 K-1 ) and in-plane (397.9 W m-1 K-1 ) thermal conductivities, outperforming similar composites of S-VA-GF (through-plane: 10.3 W m-1 K-1 and in-plane: 240.9 W m-1 K-1 ) with horizontally collapsed carbon nanotubes. As heat dissipation plates, these orderly assembled composites yield a 144% and 44% enhancement in the cooling coefficient compared with conventional Si3 N4 for cooling high-power light-emitting diode chips.

Highly Thermally Conductive Adhesion Elastomer Enhanced by Vertically Aligned Folded Graphene.

Heat and stress transfer at an interface are crucial for the contact-based tactile sensing to measure the temperature, morphology, and modulus. However, fabricating a smart sensing material that combines high thermal conductivity, elasticity, and good adhesion is challenging. In this study, a composite is fabricated using a directional template of vertically aligned folded graphene (VAFG) and a copolymer matrix of poly-2-[[(butylamino)carbonyl]oxy]ethyl ester and polydimethylsiloxane, vinyl-end-terminated polydimethylsiloxane (poly(PBAx-ran-PDMS)). With optimized chemical cross-linking and supermolecular interactions, the poly(PBA-ran-PDMS)/VAFG exhibits high thermal conductivity (15.49 W m-1 K-1 ), an high elastic deformation, and an interfacial adhesion of up to 6500 N m-1 . Poly(PBA-ran-PDMS)/VAFG is highly sensitive to temperature and pressure and demonstrates a self-learning capacity for manipulator applications. The smart manipulator can distinguish and selectively capture unknown materials in the dark. Thermally conductive, elastic, and adhesive poly(PBA-ran-PDMS)/VAFG can be developed into core materials in intelligent soft robots.

A porcine reproductive and respiratory syndrome virus (PRRSV)-specific IgM as a novel adjuvant for an inactivated PRRSV vaccine improves protection efficiency and enhances cell-mediated immunity against heterologous PRRSV challenge.

Current strategies for porcine reproductive and respiratory syndrome (PRRS) control are inadequate and mainly restricted to immunization using different PRRS virus (PPRSV) vaccines. Although there are no safety concerns, the poor performance of inactivated PRRSV vaccines has restricted their practical application. In this research, we employed the novel PRRSV-specific IgM monoclonal antibody (Mab)-PR5nf1 as a vaccine adjuvant for the formulation of a cocktail composed of inactivated PRRSV (KIV) and Mab-PR5nf1 along with a normal adjuvant to enhance PRRSV-KIV vaccine-mediated protection and further compared it with a normal KIV vaccine and modified live virus vaccine (MLV). After challenge with highly pathogenic (HP)-PRRSV, our results suggested that the overall survival rate (OSR) and cell-mediated immunity (CMI), as determined by serum IFN-γ quantification and IFN-γ ELISpot assay, were significantly improved by adding PRRSV-specific IgM to the PRRSV-KIV vaccine. It was also notable that both the OSR and CMI in the Mab-PR5nf1-adjuvanted KIV group were even higher than those in the MLV group, whereas the CMI response is normally poorly evoked by KIV vaccines or subunit vaccines. Compared with those in piglets immunized with the normal KIV vaccine, viral shedding and serum neutralizing antibody levels were also improved, and reduced viral shedding appeared to be a result of enhanced CMI caused by the inclusion of IgM as an adjuvant. In conclusion, our data provide not only a new formula for the development of an effective PRRSV-KIV vaccine for practical use but also a novel method for improving antigen-specific CMI induction by inactivated vaccines and subunit vaccines.

Highly Thermally Conductive Polymer/Graphene Composites with Rapid Room-Temperature Self-Healing Capacity.

Composites that can rapidly self-healing their structure and function at room temperature have broad application prospects. However, in view of the complexity of composite structure and composition, its self-heal is facing challenges. In this article, supramolecular effect is proposed to repair the multistage structure, mechanical and thermal properties of composite materials. A stiff and tough supramolecular frameworks of 2-[[(butylamino)carbonyl]oxy]ethyl ester (PBA)-polydimethylsiloxane (PDMS) were established using a chain extender with double amide bonds in a side chain to extend prepolymers through copolymerization. Then, by introducing the copolymer into a folded graphene film (FGf), a highly thermally conductive composite of PBA-PDMS/FGf with self-healing capacity was fabricated. The ratio of crosslinking and hydrogen bonding was optimized to ensure that PBA-PDMS could completely self-heal at room temperature in 10 min. Additionally, PBA-PDMS/FGf exhibits a high tensile strength of 2.23 ± 0.15 MPa at break and high thermal conductivity of 13 ± 0.2 W m-1 K-1; of which the self-healing efficiencies were 100% and 98.65% at room temperature for tensile strength and thermal conductivity, respectively. The excellent self-healing performance comes from the efficient supramolecular interaction between polymer molecules, as well as polymer molecule and graphene. This kind of thermal conductive self-healing composite has important application prospects in the heat dissipation field of next generation electronic devices in the future.

A pH-/Enzyme-Responsive Nanoparticle Selectively Targets Endosomal Toll-like Receptors to Potentiate Robust Cancer Vaccination.

Toll-like receptor (TLR) agonists are potent immune-stimulators that hold great potential in vaccine adjuvants as well as cancer immunotherapy. However, TLR agonists in free form are prone to be eliminated quickly by the circulatory system and cause systemic inflammation side effects. It remains a challenge to achieve precise release of TLR7/8 agonist in the native form at the receptor site in the endosomal compartments while keeping stable encapsulation and inactive in nontarget environment. Here, we report a pH-/enzyme-responsive TLR7/8 agonist-conjugated nanovaccine (TNV), which responds intelligently to the acidic environment and cathepsin B in the endosome, precisely releases TLR7/8 agonist to activate its receptor signaling at the endosomal membrane, stimulates DCs maturation, and provokes specific cellular immunity. In vivo experiments demonstrate outstanding prophylactic and therapeutic efficacy of TNV in mouse melanoma and colon cancer. The endosome-targeted responsive nanoparticle strategy provides a potential delivery toolbox of adjuvants to advance the development of tumor nanovaccines.