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Abstract The need for tumor postoperative treatments aimed at recurrence prevention and tissue regeneration have raised wide considerations in the context of the design and functionalization of implants. Herein, an injectable hydrogel system encapsulated with anti-tumor, anti-oxidant dual functional nanoparticles has been developed in order to prevent tumor relapse after surgery and promote wound repair. The utilization of biocompatible gelatin methacryloyl (GelMA) was geared towards localized therapeutic intervention. Zeolitic imidazolate framework-8@ceric oxide (ZIF-8@CeO2, ZC) nanoparticles (NPs) were purposefully devised for their proficiency as reactive oxygen species (ROS) scavengers. Furthermore, injectable GelMA hydrogels loaded with ZC NPs carrying doxorubicin (ZC-DOX@GEL) were tailored as multifunctional postoperative implants, ensuring the efficacious eradication of residual tumor cells and alleviation of oxidative stress. In vitro and in vivo experiments were conducted to substantiate the efficacy in cancer cell elimination and the prevention of tumor recurrence through the synergistic chemotherapy approach employed with ZC-DOX@GEL. The acceleration of tissue regeneration and in vitro ROS scavenging attributes of ZC@GEL were corroborated using rat models of wound healing. The results underscore the potential of the multifaceted hydrogels presented herein for their promising application in tumor postoperative treatments.

Abstract Fluoropyrimidine-based combination chemotherapy plus targeted therapy is the standard initial treatment for unresectable metastatic colorectal cancer (mCRC), but the prognosis remains poor. This phase 3 trial (ClinicalTrials.gov: NCT03950154) assessed the efficacy and adverse events (AEs) of the combination of PD-1 blockade-activated DC-CIK (PD1-T) cells with XELOX plus bevacizumab as a first-line therapy in patients with mCRC. A total of 202 participants were enrolled and randomly assigned in a 1:1 ratio to receive either first-line XELOX plus bevacizumab (the control group, n = 102) or the same regimen plus autologous PD1-T cell immunotherapy (the immunotherapy group, n = 100) every 21 days for up to 6 cycles, followed by maintenance treatment with capecitabine and bevacizumab. The main endpoint of the trial was progression-free survival (PFS). The median follow-up was 19.5 months. Median PFS was 14.8 months (95% CI, 11.6–18.0) for the immunotherapy group compared with 9.9 months (8.0–11.8) for the control group (hazard ratio [HR], 0.60 [95% CI, 0.40–0.88]; p = 0.009). Median overall survival (OS) was not reached for the immunotherapy group and 25.6 months (95% CI, 18.3–32.8) for the control group (HR, 0.57 [95% CI, 0.33–0.98]; p = 0.043). Grade 3 or higher AEs occurred in 20.0% of patients in the immunotherapy group and 23.5% in the control groups, with no toxicity-associated deaths reported. The addition of PD1-T cells to first-line XELOX plus bevacizumab demonstrates significant clinical improvement of PFS and OS with well tolerability in patients with previously untreated mCRC.

Abstract The Orthopoxvirus genus, especially variola virus (VARV), monkeypox virus (MPXV), remains a significant public health threat worldwide. The development of therapeutic antibodies against orthopoxviruses is largely hampered by the high cost of antibody engineering and manufacturing processes. mRNA-encoded antibodies have emerged as a powerful and universal platform for rapid antibody production. Herein, by using the established lipid nanoparticle (LNP)-encapsulated mRNA platform, we constructed four mRNA combinations that encode monoclonal antibodies with broad neutralization activities against orthopoxviruses. In vivo characterization demonstrated that a single intravenous injection of each LNP-encapsulated mRNA antibody in mice resulted in the rapid production of neutralizing antibodies. More importantly, mRNA antibody treatments showed significant protection from weight loss and mortality in the vaccinia virus (VACV) lethal challenge mouse model, and a unique mRNA antibody cocktail, Mix2a, exhibited superior in vivo protection by targeting both intracellular mature virus (IMV)-form and extracellular enveloped virus (EEV)-form viruses. In summary, our results demonstrate the proof-of-concept production of orthopoxvirus antibodies via the LNP-mRNA platform, highlighting the great potential of tailored mRNA antibody combinations as a universal strategy to combat orthopoxvirus as well as other emerging viruses.

Abstract Background Generating elite rice varieties with high yield and superior quality is the main goal of rice breeding programs. Key agronomic traits, including grain size and seed germination characteristics, affect the final yield and quality of rice. The RGA1 gene, which encodes the α-subunit of rice G-protein, plays an important role in regulating rice architecture, seed size and abiotic stress responses. However, whether RGA1 is involved in the regulation of rice quality and seed germination traits is still unclear. Results In this study, a rice mutant small and round grain 5 (srg5), was identified in an EMS-induced rice mutant library. Systematic analysis of its major agronomic traits revealed that the srg5 mutant exhibited a semi-dwarf plant height with small and round grain and reduced panicle length. Analysis of the physicochemical properties of rice showed that the difference in rice eating and cooking quality (ECQ) between the srg5 mutant and its wild-type control was small, but the appearance quality was significantly improved. Interestingly, a significant suppression of rice seed germination and shoot growth was observed in the srg5 mutant, which was mainly related to the regulation of ABA metabolism. RGA1 was identified as the candidate gene for the srg5 mutant by BSA analysis. A SNP at the splice site of the first intron disrupted the normal splicing of the RGA1 transcript precursor, resulting in a premature stop codon. Additional linkage analysis confirmed that the target gene causing the srg5 mutant phenotype was RGA1. Finally, the introduction of the RGA1 mutant allele into two indica rice varieties also resulted in small and round rice grains with less chalkiness. Conclusions These results indicate that RGA1 is not only involved in the control of rice architecture and grain size, but also in the regulation of rice quality and seed germination. This study sheds new light on the biological functions of RGA1, thereby providing valuable information for future systematic analysis of the G-protein pathway and its potential application in rice breeding programs.

Abstract Background Management guidelines and corresponding survival data for patients with recurrent retinoblastoma (RB) are lacking. This study aimed to summarize the clinical characteristics of patients with recurrent RB and analyze their survival outcomes. Methods We retrospectively analyzed 68 patients with recurrent RB who underwent treatment in our institution from January 2016 to December 2020. Patients were grouped according to location of recurrence: intraocular, orbital, and distant metastasis. Results The male:female ratio was 1.3:1 and the median age at recurrence was 37.5 months (range, 30.3–62.8). The number of patients in the intraocular recurrence, orbital recurrence, and metastasis groups was 13 (19.1%), 23 (33.8%), and 32 (47.1%), respectively. Thirty patients died, 36 were alive at last follow-up, and two were lost to follow-up. Eye enucleation was performed in 94.1% of patients. Five-year overall survival in patients with intraocular recurrence, orbital recurrence, and metastasis was 84.6%, 69.6%, and 31.3%, respectively (P = 0.001). Most deaths occurred within 2 years of recurrence. Presence of high-risk pathological factors, central nervous system invasion, and absence of combination therapy were independent predictors of worse 5-year overall survival. Conclusion The rate of eye preservation in survivors of recurrent RB was very low. Although 5-year overall survival in patients who underwent treatment for intraocular and orbital recurrence was high, it was low in those with metastasis. RB patients may need lifelong follow-up for recurrence and secondary malignancy.

Fluorescence sensing converts chemical events into measurable readings by utilizing fluorescence signals for the qualitative or quantitative detection of specific analytes. Supramolecular chemistry, reliant upon non-covalent interactions, has emerged as a potent paradigm for sensing applications, garnering significant scholarly attention. The adoption of supramolecular chemistry within the realm of sensing offers several significant advantages, including easy construction, rapid response, dynamic reversibility, and compatibility with pattern recognition. Notably, molecular recognition stands as a pivotal facet of supramolecular sensing. Among the integral constituents of supramolecular chemistry, an array of macrocyclic compounds boasts remarkable molecular recognition properties, apt for diverse guest molecules, and finds extensive utility in fluorescence sensing. This review highlights the pivotal contributions of fluorescent sensors rooted in crown ethers, cyclodextrins, calixarenes, cucurbiturils, and other macrocycles in single sensing, differential sensing and bioimaging. The versatility of these sensors extends to diverse media, encompassing aqueous environments, buffer solutions, and biofluid matrices. Additionally, this review provides insights into the future endeavors and forthcoming research directions in the field of supramolecular sensing and imaging.

In order to clarify the pathways closely linked to denervated muscle contracture, this work uses IoMT-enabled healthcare stratergies to examine changes in gene expression patterns inside atrophic muscles following brachial plexus damage. The gene expression Omnibus (GEO) database searching was used to locate the dataset GSE137606, which is connected to brachial plexus injuries. Strict criteria (|logFC|≥2 & adj.p < 0.05) were used to extract differentially expressed genes (DEGs). To identify dysregulated activities and pathways in denervated muscles, gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, and Gene Set Enrichment Analysis (GSEA) were used. Hub genes were found using Cytoscape software's algorithms, which took into account parameters like as proximity, degree, and MNC. Their expression, enriched pathways, and correlations were then examined. The results showed that 316 DEGs were predominantly concentrated in muscle-related processes such as tissue formation and contraction pathways. Of these, 297 DEGs were highly expressed in denervated muscles, whereas 19 DEGs were weakly expressed. GSEA showed improvements in the contraction of striated and skeletal muscles. In addition, it was shown that in denervated muscles, Myod1, Myog, Myh7, Myl2, Tnnt2, and Tnni1 were elevated hub genes with enriched pathways such adrenergic signaling and tight junction. These results point to possible therapeutic targets for denervated muscular contracture, including Myod1, Myog, Myh7, Myl2, Tnnt2, and Tnni1. This highlights treatment options for this ailment which enhances the mental state of patient.

The dynamic temperature data of a transformer can be utilized to accurately assess its load capability and operational longevity. This paper presents a study on the temperature rise characteristics of hot-spots in dry-type transformer windings and develops a extrapolative computational model based on various load rates, utilizing the results of transformer temperature rise tests. Firstly, the dynamic temperature rise characteristics of B-phase low-voltage (LV) winding and high-voltage (HV) winding hot-spot, along with its correlation calculation model with varying load rates, were determined based on the results of temperature rise tests. Subsequently, an extrapolative computational model for the temperature rise of the winding hot-spot, utilizing a three-section continuous load application approach, was proposed employing the lumped parameter method. The validity of this model was confirmed through verification. Lastly, a temperature rise test was conducted on another dry-type transformer to validate the universality of the model. Finally, a different dry-type transformer is chosen, and a temperature rise test is conducted to confirm the general applicability of the model. The results indicate that the calculation model for the hot-spot temperature rise of the winding under three consecutive loads is associated with the dynamic temperature rise pattern of the hot-spot of the winding between the temperature rise test with a small load rate and the temperature rise test with a large load rate. The maximum deviation between the hot-spot temperature rise test of the winding of SCB14-800/10-NX2 transformer and the results of the steady-state temperature rise value calculation is only 1.3 K, with a maximum error of the time constant value of the temperature rise being only 0.05 h. Similarly, the maximum deviation of the steady-state temperature rise value obtained from the hot-spot temperature rise test and the extrapolative computation of SCB-1250kVA/10 kV transformer winding is only 2.03 K, with a maximum error of the temperature rise time constant value being only 0.09 h. The extrapolative computational model proposed in this study conducts the temperature rise test under a small load rate instead of a large load rate, addressing the industry challenge of the challenging implementation of transformer on-site temperature rise tests and high power loss. This approach enhances inspection efficiency.

Abstract The photocatalytic reduction of CO2 represents an environmentally friendly and sustainable approach for generating valuable chemicals. In this study, a thiophene‐modified highly conjugated asymmetric covalent triazine framework (As‐CTF‐S) is developed for this purpose. Significantly, single‐component intramolecular energy transfer can enhance the photogenerated charge separation, leading to the efficient conversion of CO2 to CO during photocatalysis. As a result, without the need for additional photosensitizers or organic sacrificial agents, As‐CTF‐S demonstrates the highest photocatalytic ability of 353.2 µmol g−1 and achieves a selectivity of ≈99.95% within a 4 h period under visible light irradiation. This study provides molecular insights into the rational control of charge transfer pathways for high‐efficiency CO2 photoreduction using single‐component organic semiconductor catalysts.

To investigate the fatigue behaviour of stainless steel (SS) reinforcement, monotonic tensile and cyclic fatigue loading tests on 1.4362 duplex SS bars with diameters of 12 mm, 16 mm, and 20 mm are conducted. To keep the characteristics of reinforcement used in engineering construction, the specimens remain unprocessed. Two loading schemes for cyclic tests are considered in this work: (i) constant strain-amplitude, and (ii) variable strain-amplitude. The Ramberg-Osgood model was used to fit the experimental results. The strain-based and energy-based fatigue life equations are obtained. The strain-based fatigue life equation is compared with the present fatigue life estimation equations. Moreover, the ReinforcingSteel material model in OpenSees is calibrated with the experimental data. The results show that SS bars under cyclic experience hardening followed by softening. The bar diameter does not significantly affect the fatigue life prediction. The modified fatigue life equation suggests that SS bars have better fatigue resistance than conventional steel (CS) bars. The numerical analysis indicates that the calibrated steel material model (i.e. ReinforcingSteel) can produce a good simulation of SS bars under cyclic loading. It can improve the accuracy of numerical models of concrete components reinforced by SS bars.

Abstract Intravenous thrombolysis with recombinant tissue plasminogen activator (rtPA) is the primary treatment for ischemic stroke. However, rtPA treatment can substantially increase blood‐brain barrier (BBB) permeability and susceptibility to hemorrhagic transformation. Herein, the mechanism underlying the side effects of rtPA treatment is investigated and demonstrated that ferroptosis plays an important role. The ferroptosis inhibitor, liproxstatin‐1 (Lip) is proposed to alleviate the side effects. A well‐designed macrocyclic carrier, glucose‐modified azocalix[4]arene (GluAC4A), is prepared to deliver Lip to the ischemic site. GluAC4A bound tightly to Lip and markedly improved its solubility. Glucose, modified at the upper rim of GluAC4A, imparts BBB targeting to the drug delivery system owing to the presence of glucose transporter 1 on the BBB surface. The responsiveness of GluAC4A to hypoxia due to the presence of azo groups enabled the targeted release of Lip at the ischemic site. GluAC4A successfully improved drug accumulation in the brain, and Lip@GluAC4A significantly reduced ferroptosis, BBB leakage, and neurological deficits induced by rtPA in vivo. These findings deepen the understanding of the side effects of rtPA treatment and provide a novel strategy for their effective mitigation, which is of great significance for the treatment and prognosis of patients with ischemic stroke.

Detecting microwave signals over a wide frequency range is endowed with numerous advantages as it enables simultaneous transmission of a large amount of information and access to more spectrum resources. This capability is crucial for applications such as microwave communication, remote sensing and radar. However, conventional microwave receiving systems are limited by amplifiers and band-pass filters that can only operate efficiently in a specific frequency range. Typically, these systems can only process signals within a three-fold frequency range, which limits the data transfer bandwidth of the microwave communication systems. Developing novel atom-integrated microwave sensors, for example, radio-frequency (RF) chip–coupled Rydberg atomic receiver, provides opportunities for a large working bandwidth of microwave sensing at the atomic level. In the current work, an ultra-wide dual-band RF sensing scheme was demonstrated by space-division multiplexing two RF-chip-integrated atomic receiver modules. The system can simultaneously receive dual-band microwave signals that span a frequency range exceeding 6 octaves (300 MHz and 24 GHz). This work paves the way for multi-band microwave reception applications within an ultra-wide range by RF-chip-integrated Rydberg atomic sensor.

This study aimed to evaluate the distribution of plasma troponin I concentration and establish the 99th percentile reference for hs-cTnI in a hospitalized population without a cardiovascular discharge diagnosis from the Shandong area.

The proliferation of Internet of Things (IoT) devices has resulted in a massive increase in data generation, necessitating robust solutions for real-time data processing and analysis. The integration of Unmanned Aerial Vehicles (UAVs) with MEC systems presents a promising enhancement, providing dynamic, mobile edge computing capabilities that can adapt to changing conditions and demands. However, efficiently managing the task offloading and trajectory planning of UAVs in such scenarios poses significant challenges, particularly in maximizing coverage while minimizing time and energy consumption. In this context, this paper proposes a novel UAV-based MEC model utilizing the Multi-Agent Deep Deterministic Policy Gradient (MADDPG) reinforcement learning algorithm to optimize task scheduling and UAV trajectory in real-time. Our model enables UAVs to function as mobile edge servers, dynamically processing and routing tasks between terminal devices and edge servers based on real-time device demands. By incorporating a sophisticated reward function that prioritizes the minimization of system costs-including energy, time, and throughput maximization-our approach not only enhances the operational efficiency of UAV-assisted MEC systems but also improves the quality and responsiveness of edge computing services. After training the MADDPG model in the simulated environment, the experiments show that our approach significantly improved the performance of UAV-assisted MEC systems in real-time scenarios, converging after 50 learning episodes and achieving 90% task completion rate.

Abstract Objective Iron accumulation is associated with osteoporosis. This study aims to explore the effect of chronic iron accumulation induced by hepcidin1 deficiency on aging osteoporosis. Methods Iron accumulation in hepcidin1 knockout aging mice was assessed by atomic absorption spectroscopy and Perl’s staining. Bone microarchitecture was observed using Micro-CT. Hepcidin, ferritin, oxidative stress, and markers of bone turnover in serum were detected by enzyme-linked immunosorbent assay. Bone formation and resorption markers were measured by real-time quantitative PCR. Cell aging was induced by D-galactose treatment. CCK-8, flow cytometry, EdU assays, and Alizarin red staining were performed to reveal the role of hepcidin1 knockout in cell model. Iron Colorimetric Assay Kit and western blot were applied to detect iron and ferritin levels in cells, respectively. Results In hepcidin1-knockout mice, the ferritin and iron contents in liver and tibia were significantly increased. Iron accumulation induced by hepcidin1 knockout caused a phenotype of low bone mass and deteriorated bone microarchitecture. Osteogenic marker was decreased and osteoclast marker was increased in mice, accompanied by increased oxidative stress level. The mRNA expression levels of osteoclast differentiation markers (RANKL, Mmp9, OPG, Trap, and CTSK) were up-regulated, while bone formation markers (OCN, ALP, Runx2, SP7, and Col-1) were down-regulated in model group, compared to wild type mice. In vitro, hepcidin1 knockdown inhibited proliferation and osteogenic differentiation, while promoted apoptosis, with increased levels of iron and ferritin. Conclusion Iron accumulation induced by hepcidin1 deficiency aggravates the progression of aging osteoporosis via inhibiting osteogenesis and promoting osteoclast genesis.

Abstract The importance of uncommon/rare oncogenic drivers in non‐small cell lung cancer (NSCLC) was underscored during the 20th China Lung Cancer Summit. These drivers, while present in a significant proportion of NSCLC patients, remain a challenge for diagnosis and therapeutic targeting. In the never‐smokers/low smokers category with mutations such as EGFR and HER2, the efficacy of immune checkpoint inhibitors (ICIs) remains suboptimal, attributed to lower PD‐L1 expression and tumor mutation burden (TMB). However, heavy smokers, often with mutations like KRAS, may derive benefits from ICIs, as supported by trials like CheckMate‐057. With the complex landscape of these drivers and their clinical implications, the summit culminated in six pivotal consensus points, aiming to guide future research and clinical decisions. Despite the advancements, the detection, interpretation, and therapeutic strategies involving these drivers necessitate further exploration and standardization.