Quantification of silica nanoparticle uptake at environmentally relevant concentrations by gold-core embedding.

The increasing use of silica nanoparticles (SiO2 NPs) has raised concerns about potential human exposure. Assessing the health risks associated with SiO2 NPs necessitates understanding their cellular uptake, yet measuring this uptake at low, environmentally relevant concentrations presents a significant challenge. In this study, we synthesized core-shell structured Au@SiO2 NPs with diameters ranging from 50 to 200 nm and quantified their cellular uptake by analyzing the concentrations of Si and Au in A549 human lung carcinoma cells. No significant differences in cytotoxicity or cellular uptake were observed between Au@SiO2 NPs and their core-less counterparts. Additionally, the comparable cellular uptake of Au@SiO2 NPs, as evidenced by both Si and Au content, supports the use of the Au core as a tracer for SiO2 NP uptake. The inclusion of the Au core facilitated the examination of SiO2 NP uptake at concentrations an order of magnitude lower than previously possible, aligning more closely with environmental exposure levels. This is important because uptake at low concentrations cannot be accurately predicted from high-concentration data due to concentration-dependent changes in particle aggregation. Overall, Au@SiO2 NPs provide a precise method for evaluating SiO2 NP uptake at low concentrations, offering a more realistic assessment of their potential health risks compared to studies conducted at higher concentrations.

Prevalence of lumbar disc herniation in populations with different symptoms based on magnetic resonance imaging study.

BACKGROUND: Lumbar disc herniation (LDH) is common in aged human beings. This study is to investigate the prevalence of lumbar disc herniation (LDH) in different symptomatic populations attending outpatient clinics based on magnetic resonance imaging (MRI) studies, and to analyze the characteristics, distribution, and treatment strategies thereof. METHODS: Patients who visited our outpatient clinics between January 1, 2022, and December 31, 2022, with complaints of low back pain, either accompanied or unaccompanied by lower limb symptoms (radiating pain, numbness or muscle weakness), were included. All patients underwent comprehensive lumbar spine MRI examinations. The prevalence of LDH in different symptomatic populations, as well as the characteristics, distribution, and treatment strategies of disc herniation were analyzed. RESULTS: Among 8,161 individuals (3,411 males and 4,750 females), 4,496 were diagnosed with LDH, resulting in a prevalence of 55.1 %. Of these, 683 (15.2 %) individuals underwent surgical treatment. Among all patients, 3,529 exhibited only low back pain symptoms, 1,820 (51.6 %) were diagnosed with LDH, and 201 (11.0 %) received surgical treatment. Additionally, 2,673 patients with low back pain accompanied by lower limb symptoms were identified, with 1,608 individuals (82.1 %) diagnosed with LDH; 319 (19.8 %) underwent surgical treatment. Furthermore, 1,959 patients presented with lower limb symptoms only, 1,068 (54.5 %) were diagnosed with LDH, and 163 received surgical treatment (P < 0.001). The prevalence rate for males was 58.8 %, compared to females with 52.4 % (P < 0.01). The prevalence of LDH exhibited an initially increasing trend, later decreasing with advancing age. L4/5 and L5/S1 were the most commonly affected segments. CONCLUSION: LDH prevalence varies among patients with different symptoms, with a higher rate in those presenting with low back pain accompanied by lower limb symptoms. These symptomatic patients also exhibit a higher rate of surgical intervention.

Hydrogen sulfide alleviates cadmium stress in germinating carrot seeds by promoting the accumulation of proline.

Carrot (Daucus carota L.), a widely cultivated economically vegetable from the Apiaceae family, is grown globally. However, carrots can be adversely impacted by cadmium (Cd) pollution in the soil due to its propensity to accumulate in the fleshy root, thus impeding carrot growth and posing health hazards to consumers. Given the potential of hydrogen sulfide (H2S) to improve plant resistance against Cd stress, we treated germinating carrot seeds with varying concentrations of sodium hydrosulfide (NaHS), aiming to alleviate the toxic impacts of Cd stress on carrot seed germination. The results revealed that carrot seeds treated with a concentration of 0.25 mM NaHS displayed better seed germination-associated characteristics compared to seeds treated with NaHS concentrations of 0.1 mM and 0.5 mM. Further investigation revealed a rise in the expression levels of L-cysteine desulfhydrase and D-cysteine desulfhydrase, along with enhanced activity of L-cysteine desulfhydrase and D-cysteine desulfhydrase among the NaHS treatment group, thereby leading to H2S accumulation. Moreover, NaHS treatment triggered the expression of pyrroline-5-carboxylate synthase and pyrroline-5-carboxylate reductase and promoted the accumulation of endogenous proline, while the contents of soluble sugar and soluble protein increased correspondingly. Interestingly, since the application of exogenous proline did not influence the accumulation of endogenous H2S, suggesting that H2S served as the upstream regulator of proline. Histochemical staining and biochemical indices revealed that NaHS treatment led to elevated antioxidant enzyme activity, alongside a suppression of superoxide anion and hydrogen peroxide generation. Furthermore, high performance liquid chromatography analysis revealed that NaHS treatment reduced Cd2+ uptake, thereby promoting germination rate, seed vitality, and hypocotyl length of carrot seeds under Cd stress. Overall, our findings shed light on the application of NaHS to enhance carrot resistance against Cd stress and lay a foundation for exploring the regulatory role of H2S in plants responding to Cd stress.

EDC-3 and EDC-4 regulate embryonic mRNA clearance and biomolecular condensate specialization.

Animal development is dictated by the selective and timely decay of mRNAs in developmental transitions, but the impact of mRNA decapping scaffold proteins in development is unclear. This study unveils the roles and interactions of the DCAP-2 decapping scaffolds EDC-3 and EDC-4 in the embryonic development of C. elegans. EDC-3 facilitates the timely removal of specific embryonic mRNAs, including cgh-1, car-1, and ifet-1 by reducing their expression and preventing excessive accumulation of DCAP-2 condensates in somatic cells. We further uncover a role for EDC-3 in defining the boundaries between P bodies, germ granules, and stress granules. Finally, we show that EDC-4 counteracts EDC-3 and engenders the assembly of DCAP-2 with the GID (CTLH) complex, a ubiquitin ligase involved in maternal-to-zygotic transition (MZT). Our findings support a model where multiple RNA decay mechanisms temporally clear maternal and zygotic mRNAs throughout embryonic development.

A nonadjuvanted HLA-restricted peptide vaccine induced both T and B cell immunity against SARS-CoV-2 spike protein.

During COVID-19 pandemic, cases of postvaccination infections and restored SARS-CoV-2 virus have increased after full vaccination, which might be contributed to by immune surveillance escape or virus rebound. Here, artificial linear 9-mer human leucocyte antigen (HLA)-restricted UC peptides were designed based on the well-conserved S2 region of the SARS-CoV-2 spike protein regardless of rapid mutation and glycosylation hindrance. The UC peptides were characterized for its effect on immune molecules and cells by HLA-tetramer refolding assay for HLA-binding ability, by HLA-tetramer specific T cell assay for engaged cytotoxic T lymphocytes (CTLs) involvement, by HLA-dextramer T cell assay for B cell activation, by intracellular cytokine release assay for polarization of immune response, Th1 or Th2. The specific lysis activity assay of T cells was performed for direct activation of cytotoxic T lymphocytes by UC peptides. Mice were immunized for immunogenicity of UC peptides in vivo and immunized sera was assay for complement cytotoxicity assay. Results appeared that through the engagement of UC peptides and immune molecules, HLA-I and II, that CTLs elicited cytotoxic activity by recognizing SARS-CoV-2 spike-bearing cells and preferably secreting Th1 cytokines. The UC peptides also showed immunogenicity and generated a specific antibody in mice by both intramuscular injection and oral delivery without adjuvant formulation. In conclusion, a T-cell vaccine could provide long-lasting protection against SARS-CoV-2 either during reinfection or during SARS-CoV-2 rebound. Due to its ability to eradicate SARS-CoV-2 virus-infected cells, a COVID-19 T-cell vaccine might provide a solution to lower COVID-19 severity and long COVID-19.

DcMYB62, a transcription factor from carrot, enhanced cadmium tolerance of Arabidopsis by inducing the accumulation of carotenoids and hydrogen sulfide.

Cadmium (Cd) is a significant heavy metal contaminant within the environment, carrying a notable level of toxicity that presents a substantial hazard to both plant and human. Carrot (Daucus carota), a significant root vegetable crop globally, have evolved multiple transcriptional regulatory mechanisms to cope with Cd stress, with a crucial involvement of the myeloblastosis (MYB) transcription factor. In this study, the DcMYB62 gene encoding 288 amino acids, localized in the nucleus and demonstrated transcription activation property, was isolated from carrot (cv. 'Kuroda'). There was a positive relationship observed between the levels of DcMYB62 expression and the accumulation patterns of carotenoids in two distinct carrot cultivars. Further investigation revealed that the expression of DcMYB62 improved Cd tolerance of Arabidopsis by increasing seed germination rate, root length, and overall survival rate. The levels of carotenoids in DcMYB62 transgenic Arabidopsis surpassed those in wild type, accompanied by elevated expression levels of 15-cis-phytoene desaturase, zeta-carotene desaturase, and carotenoid isomerase. Meanwhile, the heterologous expression of DcMYB62 promoted the biosynthesis of abscisic acid (ABA) and hydrogen sulfide (H2S), which in turn suppressed the formation of hydrogen peroxide and superoxide anion, while also stimulating stomatal closure. Furthermore, the heterologous expression of DcMYB62 increased the transcription of genes associated with heavy metal resistance in Arabidopsis, notably nicotianamine synthase. Overall, this study contributes to understanding how DcMYB62 promote Cd stress resistance of plants by regulating the biosynthesis pathways of carotenoids, ABA, and H2S, which offers valuable insights into the regulatory mechanism connecting DcMYBs with Cd stress response of carrot.

The Effectiveness of Artificial Intelligence-based Pedicle Screw Trajectory Planning in Patients With Different Levels of Bone Mineral Density.

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: To evaluate the effectiveness of pedicle screw trajectory planning based on artificial intelligence (AI) software in patients with different levels of bone mineral density (BMD). SUMMARY OF BACKGROUND DATA: AI-based pedicle screw trajectory planning has potential to improve pullout force (POF) of screws. However, there is currently no literature investigating the efficacy of AI-based pedicle screw trajectory planning in patients with different levels of BMD. METHODS: The patients were divided into 5 groups (group A-E) according to their BMD. The AI software utilizes lumbar spine CT data to perform screw trajectory planning and simulate AO screw trajectories for bilateral L3-5 vertebral bodies. Both screw trajectories were subdivided into unicortical and bicortical modes. The AI software automatically calculating the POF and pullout risk of every screw trajectory. The POF and risk of screw pullout for AI-planned screw trajectories and AO standard trajectories were compared and analyzed. RESULTS: Forty-three patients were included. For the screw sizes, AI-planned screws were greater in diameter and length than those of AO screws (P<0.05). In groups B-E, the AI unicortical trajectories had a POF of over 200N higher than that of AO unicortical trajectories. POF was higher in all groups for the AI bicortical screw trajectories compared with the AO bicortical screw trajectories (P<0.05). AI unicortical trajectories in groups B-E had a lower risk of screw pullout compared with that of AO unicortical trajectories (P<0.05). CONCLUSIONS: AI unicortical screw trajectory planning for lumbar surgery in patients with BMD of 40-120 mg/cm3 can significantly improve screw POF and reduce the risk of screw pullout.

Combining vasoactive-inotropic score with lactate to predict mortality in post-cardiotomy patients supported with venoarterial extracorporeal membrane oxygenation.

OBJECTIVES: To determine the predictive role of combined assessment of vasoactive-inotropic score and lactate for the prognosis of patients with postcardiotomy cardiogenic shock requiring venoarterial extracorporeal membrane oxygenation. METHODS: The data of adult patients with postcardiotomy cardiogenic shock requiring venoarterial extracorporeal membrane oxygenation between January 2015 and December 2018 at a tertiary hospital was retrospectively analyzed. The incidence of in-hospital mortality and other clinical outcomes were analyzed. The associations of vasoactive-inotropic score and lactate and in-hospital mortality were assessed using logistic regression analysis. RESULTS: 222 patients were included and divided into four groups according to the cut-off points of vasoactive-inotropic score (24.3) and lactate level (6.85 mmol/L). The in-hospital mortality rates were 37.7%, 50.7%, 54.8% and 76.5% for the four groups (P < 0.001), while the rates of successful weaning off extracorporeal membrane oxygenation were 73.9%, 69%, 61.3% and 39.2% respectively (P = 0.001). The group 1 and group 2 exhibited significant differences compared to group 4 in both in-hospital mortality and weaning rates (P < 0.05). There was a statistically significant difference in the incidence of multiple organ dysfunction between group 1 and group 4 (P < 0.05). Groups 1, 2 and 3 demonstrated significantly improved cumulative 30-day survival compared with group 4 (log-rank test, P < 0.05). Logistic regression analysis revealed that age, vasoactive-inotropic score > 24.3 and lactate > 6.85 mmol/L were independently predictive of in-hospital mortality. CONCLUSIONS: Among patients with postcardiotomy cardiogenic shock requiring venoarterial extracorporeal membrane oxygenation, the initiation before reaching vasoactive-inotropic score > 24.3 and lactate > 6.85 mmol/L was associated with improved in-hospital outcomes, suggesting that combined assessment of VIS and lactate may be instructive for determining the initiation of venoarterial extracorporeal membrane oxygenation.

Vangl2 regulates intercellular junctions by remodeling actin-based cytoskeleton through the Rock signaling pathway during spermatogenesis in Eriocheir sinensis.

As a key planar cell polarity protein, Van Gogh-like 2 (Vangl2) is essential for mammalian spermatogenesis. As a decapod crustacean, Eriocheir sinensis exhibits distinct spermatogenic processes due to its unique seminiferous tubule morphology and hemolymph-testis barrier (HTB). To determine whether Vangl2 performs analogous functions in E. sinensis, we identified the Es-Vangl2. Es-Vangl2 exhibited high expression and wide distribution in the testes, indicating its crucial involvement in spermatogenesis. Following targeted knockdown of Es-Vangl2in vivo, the structure of seminiferous tubules was disrupted, characterized by vacuolization of the germinal zone and obstruction of spermatozoon release. Concurrently, the integrity of the HTB was compromised, accompanied by reduced expression and aberrant localization of junction proteins. More importantly, the regulatory influence of Es-Vangl2 was manifested through modulating the organization of microfilaments, a process mediated by epidermal growth factor receptor pathway substrate 8 (Eps8). Further studies demonstrated that these phenotypes resulting from Es-Vangl2 knockdown were attributed to the inhibition of Rock signaling pathway activity, which was verified by the Es-Rock interference and Y27632 inhibition assays. In summary, the findings highlight the pivotal role of Es-Vangl2 in stabilizing HTB integrity by regulating Eps8-mediated actin remodeling through the Rock signaling pathway in the spermatogenesis of E. sinensis.

Effects of transcranial direct current stimulation on pain and physical function in patients with knee osteoarthritis: a systematic review and meta-analysis.

BACKGROUND: Keen Osteoarthritis (KOA) is a common chronic disabling disease characterized by joint pain and dysfunction, which seriously affects patients' quality of life. Recent studies have shown that transcranial direct current stimulation (tDCS) was a promising treatment for KOA. PURPOSE: Investigate the effects of tDCS on pain and physical function in patients with KOA. METHODS: Randomized controlled trials related to tDCS and KOA were systematically searched in the PubMed, Embase, Medline, Cochrane Library, CINHL, and Web of Science databases from inception to July 23, 2024. The pain intensity was evaluated using the visual analog scale or the numeric rating scale, and the pain sensitivity was assessed using conditioned pain modulation, pressure pain threshold, heat pain threshold, or heat pain tolerance. The physical function outcome was evaluated using the Western Ontario and McMaster Universities Osteoarthritis Index or the Knee injury and Osteoarthritis Outcome Score. Statistical analysis was performed using Review Manager 5.4. RESULTS: Seven studies with a total of 503 participants were included. Compared to sham tDCS, tDCS was effective in reducing the short-term pain intensity (SMD: -0.58; 95% CI: -1.02, -0.14; p = 0.01) and pain sensitivity (SMD: -0.43; 95% CI: -0.70, -0.16; p = 0.002) but failed to significantly improve the long-term pain intensity (SMD: -0.26; 95% CI: -0.59, 0.08; p = 0.13) in KOA patients. In addition, tDCS did not significantly improve the short-term (SMD: -0.13; 95% CI: -0.35, 0.08; p = 0.22) and long-term (SMD: 0.02; 95% CI: -0.22, 0.25; p = 0.90) physical function in patients with KOA. CONCLUSIONS: The tDCS can reduce short-term pain intensity and sensitivity but fails to significantly relieve long-term pain intensity and improve the physical function in patients with KOA. Thus, tDCS may be a potential therapeutic tool to reduce short-term pain intensity and pain sensitivity in patients with KOA.

Progress of Nanomaterials Based on Manganese Dioxide in the Field of Tumor Diagnosis and Therapy.

As a pivotal transition metal oxide, manganese dioxide (MnO2) has garnered significant attention owing to its abundant reserves, diverse crystal structures and exceptional performance. Nanosizing MnO2 results in smaller particle sizes, larger specific surface areas, optimized material characteristics, and expanded application possibilities. With the burgeoning research efforts in this field, MnO2 has emerged as a promising nanomaterial for tumor diagnosis and therapy. The distinctive properties of MnO2 in regulating the tumor microenvironment (TME) have attracted considerable interest, leading to a rapid growth in research on MnO2-based nanomaterials for tumor diagnosis and treatment. Additionally, MnO2 nanomaterials are also gradually showing up in the regulation of chronic inflammatory diseases. In this review, we mainly summarized the recent advancements in various MnO2 nanomaterials for tumor diagnosis and therapy. Furthermore, we discuss the current challenges and future directions in the development of MnO2 nanomaterials, while also envisaging their potential for clinical translation.

Bidirectional wavelength-division-multiplexing fibre-free-space optical communications using polarisation multiplexing technique and tunable optical vestigial sideband filter.

To address the growing demand from emerging applications, high transmission capacity is essential for both fibre backbones and last-mile communications. This can be achieved by integrating optical fibre with optical wireless technologies, facilitating the development of fibre-free-space optical communications. Here we report a bidirectional wavelength-division-multiplexing fibre-free-space optical communication employing polarisation multiplexing technique and tunable optical vestigial sideband filter. The transmission capacity is considerably increased by integrating the polarisation multiplexing technique with the wavelength-division-multiplexing scheme. The transmission performance is extensively enhanced by using a tunable optical vestigial sideband filter and vestigial sideband-four-level pulse amplitude modulation. Moreover, the optical wireless link is substantially extended through the operation of triplet lenses. Low bit error rates and clear vestigial sideband-four-level pulse amplitude modulation eye diagrams are attained with a high aggregate transmission capacity of 480 Gb/s for downstream/upstream transmission. This capability of bidirectional fibre-free-space optical communications holds substantial potential for enhancing advanced wired-wireless communications.

Screening of herbal extracts binding with vascular endothelial growth factor by applying HerboChip platform.

BACKGROUND: Traditional Chinese medicine (TCM) has been hailed as a rich source of medicine, but many types of herbs and their functions still need to be rapidly discovered and elucidated. HerboChip, a target-based drug screening platform, is an array of different fractions deriving from herbal extracts. This study was designed to identify effective components from TCM that interact with vascular endothelial growth factor (VEGF) as a target using HerboChip. METHODS: Selected TCMs that are traditionally used as remedies for cancer prevention and wound healing were determined and extracted with 50% ethanol. Biotinylated-VEGF was hybridized with over 500 chips coated with different HPLC-separated fractions from TCM extracts and straptavidin-Cy5 was applied to identify plant extracts containing VEGF-binding fractions. Cytotoxicity of selected herbal extracts and their activities on VEGF-mediated angiogenic functions were evaluated. RESULTS: Over 500 chips were screened within a week, and ten positive hits were identified. The interaction of the identified herbal extracts with VEGF was confirmed in cultured endothelial cells. The identified herbs promoted or inhibited VEGF-mediated cell proliferation, migration and tube formation. Results from western blotting analysis demonstrated the identified herbal extracts significantly affected VEGF-triggered phosphorylations of eNOS, Akt and Erk. Five TCMs demonstrated potentiating activities on the VEGF response and five TCMs revealed suppressive activities. CONCLUSIONS: The current results demonstrated the applicability of the HerboChip platform and systematically elucidated the activity of selected TCMs on angiogenesis and its related signal transduction mechanisms.

2-Arylbenzofurans from the stems and leaves of Artocarpus tonkinensis and their potential antiproliferative activities.

Phytochemical study on the stems and leaves of Artocarpus tonkinensis led to the isolation of a new 2-arylbenzofuran, artocartone (1), as well as seven known 2-arylbenzofurans (2-8). The chemical structure of 1 was established by means of comprehensive spectroscopic analyses and the known compounds were determined by comparing their MS and NMR data with those reported data in literature. The antiproliferative activities of all isolates 1-8 against five human cancer cell lines: HL-60, SMMC-7721, A-375, MCF-7 and SW480 in vitro were evaluated. As a result, compounds 1- 8 displayed notable antiproliferative activities against various human cancer cell lines with IC50 values in the range of 0.28 ± 0.05-26.89 ± 0.18 µM.

MXene Based Flame Retardant and Electrically Conductive Polymer Coatings.

Modern polymer coatings possess tremendous multifunctionalities and have attracted immense research interest in recent decades. However, with the expeditious development of technologies and industries, there is a vast demand for the flame retardancy and electrical conductivity of engineered polymer coatings. Traditional functional materials that render the polymer coatings with these properties require a sophisticated fabrication process, and their high mass gains can be a critical issue for weight-sensitive applications. In recent years, massive research has been conducted on a newly emerged two-dimensional (2D) nanosize material family, MXene. Due to the excellent electrical conductivity, flame retardancy, and lightweightness, investigations have been launched to synthesise MXene-based polymer coatings. Consequently, we performed a step-by-step review of MXene-involved polymer coatings, from solely attaching MXene to the substrate surface to the multilayered coating of modified MXene with other components. This review examines the performances of the fire safety enhancement and electrical conductivity as well as the feasibility of the manufacturing procedures of the as-prepared polymer composites. Additionally, the fabricated polymer coatings' dual property mechanisms are well-demonstrated. Finally, the prospect of MXene participating in polymer coatings to render flame retardancy and electrical conductivity is forecasted.

Rodent model of metabolic dysfunction-associated fatty liver disease: a systematic review.

Although significant progress has been made in developing preclinical models for metabolic dysfunction-associated steatotic liver disease (MASLD), few have encapsulated the essential biological and clinical outcome elements reflective of the human condition. We conducted a comprehensive literature review of English-language original research articles published from 1990 to 2023, sourced from PubMed, Embase, and Web of Science, aiming to collate studies that provided a comparative analysis of physiological, metabolic, and hepatic histological characteristics between MASLD models and control groups. The establishment of a robust metabolic dysfunction-associated steatotic liver rodent model hinges on various factors, including animal species and strains, sex, induction agents and methodologies, and the duration of induction. Through this review, we aim to guide researchers in selecting suitable induction methods and animal species for constructing preclinical models aligned with their specific research objectives and laboratory conditions. Future studies should strive to develop simple, reliable, and reproducible models, considering the model's sensitivity to factors such as light-dark cycles, housing conditions, and environmental temperature. Additionally, the potential of diverse in vitro models, including 3D models and liver organ technology, warrants further exploration as valuable tools for unraveling the cellular mechanisms underlying fatty liver disease.

Personalized neoantigen cancer vaccines: current progression, challenges and a bright future.

Tumor neoantigens possess specific immunogenicity and personalized therapeutic vaccines based on neoantigens which have shown promising results in some clinical trials, with broad application prospects. However, the field is developing rapidly and there are currently few relevant review articles. Summarizing and analyzing the status of global personalized neoantigen vaccine clinical trials will provide important data for all stakeholders in drug development. Based on the Trialtrove database, a retrospective analysis was conducted using trial quantity as a key indicator for neo-adjuvant and adjuvant therapy anti-PD-1/PD-L1 clinical trials initiated before the end of 2022. The time trend of newly initiated trials was investigated. The sponsor type, host country, treatment mode, combination strategy, tested drugs, and targeted cancer types of these trials were summarized. As of December 2022, a total of 199 trials were included in the analysis. Among these studies, Phase I studies were the most numerous (119, 59.8%), and Phase I studies have been the predominant study type since 2015. Peptide vaccines were the largest neoantigen vaccines type, accounting for 64.8% of all clinical trials. Based on peptide delivery platforms, the proportion of trials was highest for the DC system (32, 16.1%), followed by LNP (11, 5.5%), LPX (11, 5.5%), and viruses (7, 3.5%). Most vaccines were applied in trials as a monotherapy (133/199, 66.8%), meanwhile combining immunotherapeutic drugs was the most common form for combination therapy. In terms of indications, the largest number of trials involved three or more unspecified solid tumors (50/199, 25.1%), followed by non-small cell lung cancer (24/199, 12.1%) and pancreatic cancer (15/199, 7.5%). The clinical development of personalized neoantigen cancer vaccines is still in the early stage. A clear shift in delivery systems from peptides to DC and liposomal platforms, with the largest number of studies in Asia, collectively marks a new era in the field. The adjuvant or maintenance therapy, and the combination treatment with ICIs are becoming the important clinical development orientation. As research on tumor-immune interactions intensifies, the design, development, and application of neoantigen vaccines are bound to develop rapidly, which will bring a new revolution in the future cancer treatment.

Advancing Lung Cancer Treatment with Combined c-Met Promoter-Driven Oncolytic Adenovirus and Rapamycin.

Lung cancer remains a formidable health challenge due to its high mortality and morbidity rates. Non-small cell lung cancer (NSCLC) constitutes approximately 85% of all lung cancer cases, with small cell lung cancer (SCLC) accounting for the remainder. Both NSCLC and SCLC cells express receptor tyrosine kinases, which may be overexpressed or mutated in lung cancer, leading to increased activation. The c-Met receptor tyrosine kinase, crucial for cell transformation and tumor growth, invasion, and metastasis, became the focus of our study. We used an E1B55KD-deleted, replication-selective oncolytic adenovirus (Ad.What), driven by the c-Met promoter, targeting lung cancer cells with c-Met overexpression, thus sparing normal cells. Previous studies have shown the enhanced antitumor efficacy of oncolytic adenoviruses when combined with chemotherapeutic agents. We explored combining rapamycin, a selective mTOR inhibitor with promising clinical trial outcomes for various cancers, with Ad.What. This combination increased infectivity by augmenting the expression of coxsackievirus and adenovirus receptors and αV integrin on cancer cells and induced autophagy. Our findings suggest that combining a c-Met promoter-driven oncolytic adenovirus with rapamycin could be an effective lung cancer treatment strategy, offering a targeted approach to exploit lung cancer cells' vulnerabilities, potentially marking a significant advancement in managing this deadly disease.

The high electron mobility for spin-down channel of two-dimensional spin-polarized half-metallic ferromagnetic EuSi2N4 monolayer.

The two-dimensional (2D) monolayer material MoSi2N4 was successfully synthesized in 2020[Hong et al., Science 369, 670, (2020)], exhibiting a plethora of new phenomena and unusual properties, with good stability at room temperature. However, MA2Z4 family monolayer materials involve primarily transition metal substitutions for M atoms. In order to address the research gap on lanthanide and actinide MA2Z4 materials, this work conducts electronic structure calculations on novel 2D MSi2N4 (M = La, Eu) monolayer materials by employing first-principles methods and CASTEP. High carrier mobility is discovered in the indirect bandgap semiconductor 2D LaSi2N4 monolayer (~5400 cm2 V-1 s-1) and in the spin (spin-down channel) carrier mobility of the half-metallic ferromagnetic EuSi2N4 monolayer (~2800 cm2 V-1 s-1). EuSi2N4 monolayer supplements research on spin carrier mobility in half-metallic ferromagnetic monolayer materials at room temperature and possesses a magnetic moment of 5 µB, which should not be underestimated. Furthermore, due to the unique electronic band structure of EuSi2N4 monolayer (with the spin-up channel exhibiting metallic properties and the spin-down channel exhibiting semiconductor properties), it demonstrates a 100% spin polarization rate, presenting significant potential applications in fields such as magnetic storage, magnetic sensing, and spintronics.

Intelligent medicine in focus: the 5 stages of evolution in robot-assisted surgery for prostate cancer in the past 20 years and future implications.

Robot-assisted surgery has evolved into a crucial treatment for prostate cancer (PCa). However, from its appearance to today, brain-computer interface, virtual reality, and metaverse have revolutionized the field of robot-assisted surgery for PCa, presenting both opportunities and challenges. Especially in the context of contemporary big data and precision medicine, facing the heterogeneity of PCa and the complexity of clinical problems, it still needs to be continuously upgraded and improved. Keeping this in mind, this article summarized the 5 stages of the historical development of robot-assisted surgery for PCa, encompassing the stages of emergence, promotion, development, maturity, and intelligence. Initially, safety concerns were paramount, but subsequent research and engineering advancements have focused on enhancing device efficacy, surgical technology, and achieving precise multi modal treatment. The dominance of da Vinci robot-assisted surgical system has seen this evolution intimately tied to its successive versions. In the future, robot-assisted surgery for PCa will move towards intelligence, promising improved patient outcomes and personalized therapy, alongside formidable challenges. To guide future development, we propose 10 significant prospects spanning clinical, research, engineering, materials, social, and economic domains, envisioning a future era of artificial intelligence in the surgical treatment of PCa.