Switch Volmer-Heyrovsky to Volmer-Tafel Pathway for Efficient Acidic Electrocatalytic Hydrogen Evolution by Correlating Pt Single Atoms with Clusters.

As cost-effective catalysts, platinum (Pt) single-atom catalysts (SACs) have attracted substantial attention. However, most studies indicate that Pt SACs in acidic hydrogen evolution reaction (HER) follow the slow Volmer-Heyrovsky (VH) mechanism instead of the fast kinetic Volmer-Tafel (VT) pathway. Here, this work propose that the VH mechanism in Pt SACs can be switched to the faster VT pathway for efficient HER by correlating Pt single atoms (SAs) with Pt clusters (Cs). Our calculations reveal that the correlation between Pt SAs and Cs significantly impacts the electronic structure of exposed Pt atoms, lowering the adsorption barrier for atomic hydrogen and enabling a faster VT mechanism. To validate these findings, this work purposely synthesize three catalysts: l-Pt@MoS2, m-Pt@MoS2 and h-Pt@MoS2 with low, moderate, and high Pt-loading, having different distributions of Pt SAs and Cs. The m-Pt@MoS2 catalyst with properly correlating Pt SAs and Cs exhibits outstanding performance with an overpotential of 47 mV and Tafel slope of 32 mV dec-1. Further analysis of the Tafel values confirms that the m-Pt@MoS2 sample indeed follows the VT reaction mechanism, aligning with the theoretical findings. This study offers a deep understanding of the synergistic mechanism, paving a way for designing novel-advanced catalysts.

Interfacial Synergy in Mo2C/MoC Heterostructure Promoting Sequential Polysulfide Conversion in High-Performance Lithium-Sulfur Battery.

A rational design of sulfur host is the key to conquering the"polysulfide shuttle effects" by accelerating the polysulfide conversion. Since the process involves solid-liquid-solid multistep phase transitions, purposely-engineered heterostructure catalysts with various active regions for catalyzing conversion steps correspondingly are beneficial to promote the overall conversion process. However, the functionalities of the materials surface and interface in heterostructure catalysts remain unclear. In this work, an Mo2C/MoC catalyst with abundant Mo2C surface-interface-MoC surface tri-active-region is developed by in situ converting the MoZn-metal organic framework. The experimental and simulation studies demonstrate the interface can catch long-chain polysulfides and promote their conversion. Instead, the Mo2C and MoC tend to accommodate the short-chain polysulfide and accelerate their conversion and the Li2S dissociation. Benefitting from the high catalytic ability, the Li-S battery assembled with the Mo2C/MoC-S cathode shows more discrete redox reactions and delivers a high initial capacity of 1603.6 mAh g-1 at 1 C charging-discharging rate, which is over twofolds of the one assembled using individual hosts, and 80.4% capacity can be maintained after 1000 cycles at 3 C rate. This work has demonstrated a novel synergy between the interface and material surface, which will help the future design of high-performance Li-S batteries.

The significance and prognostic value of multifocal papillary thyroid carcinoma in children and adolescents.

INTRODUCTION: The prognostic value of multifocality in paediatric papillary thyroid carcinoma (PTC) patients remains a subject of debate. This study aimed to explore the clinical significance and prognostic value of multifocality in children and adolescents with PTC. METHODS: This study retrospectively analysed the clinicopathological characteristics and postoperative follow-up data of 338 PTC patients aged ≤ 20 years from May 2012 to July 2022. The clinical and pathological characteristics of 205 patients with unifocal lesions and 133 patients with multifocal lesions were compared. A logistic regression model evaluated the relationship between multifocal lesions and disease recurrence/persistence in children and adolescents with PTC. Based on the median follow-up time of children with multifocal PTC, 114 patients with multifocal PTC older than 20 years were added, and the clinicopathological characteristics were compared between the 133. paediatric/adolescent patients and 114 adult patients with multifocal PTC. RESULTS: Among the paediatric and adolescent patients, over a median follow-up time of 49 months, 133 had multifocal disease and 205 had unifocal disease. Multifocal PTC patients exhibited stronger invasiveness in the form of extrathyroidal extension, tumour diameter, lymph node metastasis, and distant metastasis. Multifocality (OR 2.68; p = 0.017), lateral lymph node metastasis (OR 2.85; p = 0.036), and distant metastasis (OR 4.28; p = 0.010) were identified as independent predictive factors for the recurrence/persistence of disease. Comparing the paediatric/adolescent vs. adult multifocal patients, the former demonstrated greater tumour invasiveness. Lateral lymph node metastasis (OR 6.36; P = 0.012) and distant metastasis (OR 3.70; P = 0.027) were independent predictive factors for recurrence/persistence of disease in multifocal patients, while age was not (OR 0.95; P = 0.455). CONCLUSION: Tumour multifocality independently predicts persistent/recurrent disease in paediatric and adolescent PTC patients.

Jacalin-related lectin 45 (OsJRL45) isolated from 'sea rice 86' enhances rice salt tolerance at the seedling and reproductive stages.

BACKGROUND: Rice (Oryza sativa L.) is one of the most widely cultivated grain crops in the world that meets the caloric needs of more than half the world's population. Salt stress seriously affects rice production and threatens food security. Therefore, mining salt tolerance genes in salt-tolerant germplasm and elucidating their molecular mechanisms in rice are necessary for the breeding of salt tolerant cultivars. RESULTS: In this study, a salt stress-responsive jacalin-related lectin (JRL) family gene, OsJRL45, was identified in the salt-tolerant rice variety 'sea rice 86' (SR86). OsJRL45 showed high expression level in leaves, and the corresponding protein mainly localized to the endoplasmic reticulum. The knockout mutant and overexpression lines of OsJRL45 revealed that OsJRL45 positively regulates the salt tolerance of rice plants at all growth stages. Compared with the wild type (WT), the OsJRL45 overexpression lines showed greater salt tolerance at the reproductive stage, and significantly higher seed setting rate and 1,000-grain weight. Moreover, OsJRL45 expression significantly improved the salt-resistant ability and yield of a salt-sensitive indica cultivar, L6-23. Furthermore, OsJRL45 enhanced the antioxidant capacity of rice plants and facilitated the maintenance of Na+-K+ homeostasis under salt stress conditions. Five proteins associated with OsJRL45 were screened by transcriptome and interaction network analysis, of which one, the transmembrane transporter Os10g0210500 affects the salt tolerance of rice by regulating ion transport-, salt stress-, and hormone-responsive proteins. CONCLUSIONS: The OsJRL45 gene isolated from SR86 positively regulated the salt tolerance of rice plants at all growth stages, and significantly increased the yield of salt-sensitive rice cultivar under NaCl treatment. OsJRL45 increased the activity of antioxidant enzyme of rice and regulated Na+/K+ dynamic equilibrium under salinity conditions. Our data suggest that OsJRL45 may improve the salt tolerance of rice by mediating the expression of ion transport-, salt stress response-, and hormone response-related genes.

3D flexible compositing resonant cavity system for high-performance SERS sensing.

Arrayed resonant cavity with outstanding optical trapping ability have received increasing attention in surface-enhanced Raman spectroscopy (SERS). Here, a three-dimensional (3D) composite AgNPs-Al2O3/Au/inverted patterned sapphire substrate PMMA (IPSSPMMA) flexible resonant cavity system is theoretically and experimentally investigated as a flexible SERS sensor. With the help of an effective plasma coupling (localized surface plasmons (LSPs) and surface plasmon polaritons (SPPs)), as shown by the Finite Element Method, a resonant cavity between IPSSPMMA and a particle-film nanostructure is created. Moreover, the proposed fabrication scheme can be easily used for large-scale fabrication. To measure the performance of IPSSPMMA, Rhodamine 6 G (R6G) and Crystalline violet (CV) were used as probe molecules with limit of detection (LOD) of 6.01 × 10-12 M and 5.36 × 10-10 M, respectively, and enhancement factors (EF) of R6G up to 8.6 × 109. Besides, in-situ detection of CV on the surface of aquatic products with a LOD of 3.96 × 10-5 M, enables highly sensitive in-situ detection of surface analytes. The Raman performance and in-situ detection results demonstrate that the proposed flexible compositing resonant cavity system has the advantages of ultra-sensitivity, stability, uniformity, and reproducibility, and has great potential for applications in the food safety field.

Cascade bunch focusing on chip using terahertz pulses to drive prism arrays.

The dielectric laser accelerator (DLA) is a promising candidate for next-generation table-top and even on-chip particle accelerators. Long-range focusing of a tiny-size electron bunch on chip is crucial for the practical applications of DLA, which has been a challenge. Here we propose a bunch focusing scheme, which uses a pair of readily available few-cycle terahertz (THz) pulses to drive an array of millimeter-scale prisms via the inverse Cherenkov effect. The THz pulses are reflected and refracted multiple times through the prism arrays, synchronizing with and periodically focusing the electron bunch along the bunch channel. Cascade bunch-focusing is realized by making the electromagnetic field phase experienced by electrons in each stage of the array, that is, the synchronous phase, in the focusing phase region. The focusing strength can be adjusted via changing the synchronous phase and THz field intensity, optimization of which will sustain the stable bunch transportation in a tiny-size bunch channel on chip. This bunch-focusing scheme sets a base for developing a long-acceleration-range and high-gain DLA.

Effective Treatment of SSTR2-Positive Small Cell Lung Cancer Using 211At-Containing Targeted α-Particle Therapy Agent Which Promotes Endogenous Antitumor Immune Response.

Small cell lung cancer (SCLC) is a neuroendocrine tumor with a high degree of malignancy. Due to limited treatment options, patients with SCLC have a poor prognosis. We have found, however, that intravenously administered octreotide (Oct) armed with astatine-211 ([211At]SAB-Oct) is effective against a somatostatin receptor 2 (SSTR2)-positive SCLC tumor in SCLC tumor-bearing BALB/c nude mice. In biodistribution analysis, [211At]SAB-Oct achieved the highest concentration in the SCLC tumors up to 3 h after injection as time proceeded. A single intravenous injection of [211At]SAB-Oct (370 kBq) was sufficient to suppress SSTR2-positive SCLC tumor growth in treated mice by inducing DNA double-strand breaks. Additionally, a multitreatment course (370 kBq followed by twice doses of 370 kBq for a total of 1110 kBq) inhibited the growth of the tumor compared to the untreated control group without significant off-target toxicity. Surprisingly, we found that [211At]SAB-Oct could up-regulate the expressions of calreticulin and major histocompatibility complex I (MHC-I) on the tumor cell membrane surface, suggesting that α-particle internal irradiation may activate an endogenous antitumor immune response through the regulation of immune cells in the tumor microenvironment, which could synergically enhance the efficacy of immunotherapy. We conclude that [211At]SAB-Oct is a potential new therapeutic option for SSTR2-positive SCLC.

An automated surgical decision-making framework for partial or radical nephrectomy based on 3D-CT multi-level anatomical features in renal cell carcinoma.

OBJECTIVES: To determine whether 3D-CT multi-level anatomical features can provide a more accurate prediction of surgical decision-making for partial or radical nephrectomy in renal cell carcinoma. METHODS: This is a retrospective study based on multi-center cohorts. A total of 473 participants with pathologically proved renal cell carcinoma were split into the internal training and the external testing set. The training set contains 412 cases from five open-source cohorts and two local hospitals. The external testing set includes 61 participants from another local hospital. The proposed automatic analytic framework contains the following modules: a 3D kidney and tumor segmentation model constructed by 3D-UNet, a multi-level feature extractor based on the region of interest, and a partial or radical nephrectomy prediction classifier by XGBoost. The fivefold cross-validation strategy was used to get a robust model. A quantitative model interpretation method called the Shapley Additive Explanations was conducted to explore the contribution of each feature. RESULTS: In the prediction of partial versus radical nephrectomy, the combination of multi-level features achieved better performance than any single-level feature. For the internal validation, the AUROC was 0.93 ± 0.1, 0.94 ± 0.1, 0.93 ± 0.1, 0.93 ± 0.1, and 0.93 ± 0.1, respectively, as determined by the fivefold cross-validation. The AUROC from the optimal model was 0.82 ± 0.1 in the external testing set. The tumor shape Maximum 3D Diameter plays the most vital role in the model decision. CONCLUSIONS: The automated surgical decision framework for partial or radical nephrectomy based on 3D-CT multi-level anatomical features exhibits robust performance in renal cell carcinoma. The framework points the way towards guiding surgery through medical images and machine learning. CLINICAL RELEVANCE STATEMENT: We proposed an automated analytic framework that can assist surgeons in partial or radical nephrectomy decision-making. The framework points the way towards guiding surgery through medical images and machine learning. KEY POINTS: • The 3D-CT multi-level anatomical features provide a more accurate prediction of surgical decision-making for partial or radical nephrectomy in renal cell carcinoma. • The data from multicenter study and a strict fivefold cross-validation strategy, both internal validation set and external testing set, can be easily transferred to different tasks of new datasets. • The quantitative decomposition of the prediction model was conducted to explore the contribution of each extracted feature.

Biocompatible conjugated polymer nanoparticles labeled with 225Ac for tumor endoradiotherapy.

Recently, endoradiotherapy based on actinium-225 (225Ac) has attracted increasing attention, which is due to its α particles can generate maximal damage to cancer cells while minimizing unnecessary radiation effects on healthy tissues. Herein, 111In/225Ac-radiolabeled conjugated polymer nanoparticles (CPNs) coated with amphiphilic polymer DSPE-PEG-DOTA have been developed as a new injectable nano-radiopharmaceuticals for cancer endoradiotherapy under the guidance of nuclear imaging. Single photon emission computed tomography/computed tomography (SPECT/CT) using 111In-DOTA-PEG-CPNs as nano probe indicates a prolonged retention of radiolabeled nanocarriers, which was consistent with the in vivo biodistribution examined by direct radiometry analysis. Significant inhibition of tumor growth has been observed in murine 4T1 models treated with 225Ac-DOTA-PEG-CPNs when compared to mice treated with PBS or DOTA-PEG-CPNs. The 225Ac-DOTA-PEG-CPNs group experienced no single death within 24 days with the median survival considerably extended to 35 days, while all the mice treated with PBS or DOTA-PEG-CPNs died at 20 days post injection. Additionally, the histopathology studies demonstrated no obvious side effects on healthy tissues after treatment with 225Ac-DOTA-PEG-CPNs. All these results reveal that the new 225Ac-labeled DOTA-PEG-CPNs is promising as paradigm for endoradiotherapy.

Clinical management and prognosis of spinal myxopapillary ependymoma: a single-institution cohort of 72 patients.

PURPOSE: Myxopapillary ependymoma (MPE) was classified as grade 2 tumor in the 2021 World Health Organization central nervous system classification because of its high recurrence probability. This study aimed to investigate predictive factors and management of tumor recurrence. METHODS: Seventy-two patients with spinal MPE underwent initial surgical treatment at our hospital between 2011 and 2021. Kaplan-Meier curves and Cox regression were used to analyze the correlation between clinical variables and progression-free survival (PFS). RESULTS: The median age at diagnosis was 33.5 years (range 8-60 years). Twenty-one patients (29.2%) had preoperative spinal drop metastases. Gross total resection (GTR) was performed in 37 patients (51.4%). The median follow-up was 7.2 years, and the follow-up rate was 88.9% (64 of 72 cases). Twelve of the 64 patients (18.9%) relapsed, and preoperative drop metastasis occurred in 7 patients (58.3%). The estimated 5-year and 10-year PFS rates were 82% and 77%, respectively. Univariate analysis showed that GTR was associated with improved PFS (hazard ratio [HR] 0.149, p = 0.014), while preoperative drop metastasis (HR 3.648, p = 0.027) and tumor involvement sacrococcygeal region (HR 7.563, p = 0.003) were associated with tumor recurrence. Adjuvant radiotherapy (RT) was significantly associated with improved PFS in patients with preoperative drop metastasis (p = 0.039). CONCLUSION: Complete surgical resection under the premise of protecting neurological function is an important factor in reducing spinal MPE recurrence. Adjuvant RT is recommended when the tumor invades the capsule with preoperative drop metastasis or adhesion to the nerve and cannot reach GTR.

Long-term outcomes of foramen magnum decompression with duraplasty for Chiari malformation type I in adults: a series of 297 patients.

OBJECTIVE: Foramen magnum decompression with duraplasty (FMDD) is one of the most frequently utilized surgical treatments for Chiari malformation type I (CMI) in adults. However, its long-term outcomes remain controversial. The object of this study was to evaluate the long-term outcomes of FMDD in adults with CMI. METHODS: In total, 297 adults with CMI who had undergone FMDD at the authors' institution between 2011 and 2020 were included in this retrospective study. Long-term (> 1 year) outcomes were evaluated using the Chicago Chiari Outcome Scale (CCOS), visual analog scale (VAS), and Japanese Orthopaedic Association (JOA) scale. RESULTS: The median patient age was 44 years (range 18-65 years). The mean clinical follow-up period was 67 months (range 14-123 months). Compared with preoperative conditions, the postoperative syringomyelia regression rate was 91.3% (242/265), and the cerebellar tonsil ascended in 18.2% of patients (54/297), was stable in 64.3% (191/297), and continuously descended in 17.5% (52/297). Long-term clinical follow-up data were acquired from 267 patients. According to the CCOS score, the patient's condition improved in 62.5% of cases (167/267), was stable in 31.8% (85/267), and worsened in 5.6% (15/267). According to the VAS score, the patient's condition improved in 59.5% of cases (110/185), remained unchanged in 27.6% (51/185), and worsened in 13.0% (24/185) among the follow-up patients with relevant data. According to the JOA score, the patient's condition improved in 40.1% of cases (107/267), remained unchanged in 50.2% (134/267), and worsened in 9.7% (26/267). Notably, there was no association between clinical outcomes and syringomyelia regression (p = 0.227) or changes in the cerebellar tonsillar position (p = 0.323). CONCLUSIONS: FMDD is a simple, safe, and effective surgical procedure for adult CMI that yields significant and sustained improvement in clinical and radiological outcomes. However, clinical improvement does not always correlate with syringomyelia regression and cerebellar tonsillar shift.

OsJRL40, a Jacalin-Related Lectin Gene, Promotes Salt Stress Tolerance in Rice.

High salinity is a major stress factor affecting the quality and productivity of rice (Oryza sativa L.). Although numerous salt tolerance-related genes have been identified in rice, their molecular mechanisms remain unknown. Here, we report that OsJRL40, a jacalin-related lectin gene, confers remarkable salt tolerance in rice. The loss of function of OsJRL40 increased sensitivity to salt stress in rice, whereas its overexpression enhanced salt tolerance at the seedling stage and during reproductive growth. ß-glucuronidase (GUS) reporter assays indicated that OsJRL40 is expressed to higher levels in roots and internodes than in other tissues, and subcellular localization analysis revealed that the OsJRL40 protein localizes to the cytoplasm. Further molecular analyses showed that OsJRL40 enhances antioxidant enzyme activities and regulates Na+-K+ homeostasis under salt stress. RNA-seq analysis revealed that OsJRL40 regulates salt tolerance in rice by controlling the expression of genes encoding Na+/K+ transporters, salt-responsive transcription factors, and other salt response-related proteins. Overall, this study provides a scientific basis for an in-depth investigation of the salt tolerance mechanism in rice and could guide the breeding of salt-tolerant rice cultivars.

In Vitro Anticancer Ability of Nano Fluorescent 111 In-MIL-68/PEG-FA on Hela Cells.

In past decades, nanoscale metal-organic frameworks (NMOFs) have drawn more and more attention in multimodal imaging and targeting therapy of various malignant cancers. Here, we proposed to dope 111 In into fluorescent In-based NMOFs (In-MIL-68-NH2 ), with an attempt to prepare a new nanomedicine with great anticancer potential. As a proof of concept, the obtained NMOF (In-MIL-68/PEG-FA) with targeting motifs is able to act as a fluorescent probe to achieve Hela cell imaging. Moreover, the Auger electron emitter 111 In built in corresponding radioactive NMOF (111 In-MIL-68/PEG-FA) can bring clear damage to cancer cells, leading to a high cell killing rate of 59.3 % within 48 h. In addition, the cell cycle presented a significant dose-dependent G2/M inhibiting mode, which indicates that 111 In-MIL-68/PEG-FA has the ability to facilitate the cancer cells to enter apoptotic program. This work demonstrated the potential of 111 In-labelled NMOFs in specific killings of cancer cells, providing a new approach to develop nanomedicines with theranostic function.

Targeted Alpha Therapy of Glioma Using 211At-Labeled Heterodimeric Peptide Targeting Both VEGFR and Integrins.

Targeted radionuclide therapy based on α-emitters plays an increasingly important role in cancer treatment. In this study, we proposed to apply a heterodimeric peptide (iRGD-C6-lys-C6-DA7R) targeting both VEGFR and integrins as a new vector for 211At radiolabeling to obtain high-performance radiopharmaceuticals with potential in targeted alpha therapy (TAT). An astatinated peptide, iRGD-C6-lys(211At-ATE)-C6-DA7R, was prepared with a radiochemical yield of ∼45% and high radiochemical purity of >95% via an electrophilic radioastatodestannylation reaction. iRGD-C6-lys(211At-ATE)-C6-DA7R showed good stability in vitro and high binding ability to U87MG (glioma) cells. Systematic in vitro antitumor investigations involving cytotoxicity, apoptosis, distribution of the cell cycle, and reactive oxygen species (ROS) clearly demonstrated that 211At-labeled heterodimeric peptides could significantly inhibit cell viability, induce cell apoptosis, arrest the cell cycle in G2/M phase, and increase intracellular ROS levels in a dose-dependent manner. Biodistribution revealed that iRGD-C6-lys(211At-ATE)-C6-DA7R had rapid tumor accumulation and fast normal tissue/organ clearance, which was mainly excreted through the kidneys. Moreover, in vivo therapeutic evaluation indicated that iRGD-C6-lys(211At-ATE)-C6-DA7R was able to obviously inhibit tumor growth and prolong the survival of mice bearing glioma xenografts without notable toxicity to normal organs. All these results suggest that TAT mediated by iRGD-C6-lys(211At-ATE)-C6-DA7R can provide an effective and promising strategy for the treatment of glioma and some other tumors.

PET imaging of VEGFR and integrins in glioma tumor xenografts using 89Zr labelled heterodimeric peptide.

Vascular endothelial growth factor receptor (VEGFR) and integrin αv are over-expressed in angiogenesis of variety malignant tumors with key roles in angiogenesis, and have been proven as valuable targets for cancer imaging and treatment. In this study, a heterodimeric peptide targeting VEGFR and integrin was designed, and radiolabeled with zirconium-89 (89Zr) for PET imaging of glioma. 89Zr-DFO-heterodimeric peptide, a the newly developed probe, was prepared with radiochemical yield of 88.7 ± 2.4%. Targeted binding capability of 89Zr-DFO-heterodimeric peptide towards U87MG cells was investigated in murine glioma xenograft models, which shows that the designed probe has good binding ability to both targeting sites. Biodistribution indicated that kidney metabolism is the main pathway and tumor uptake of 89Zr-DFO-heterodimeric peptide reached the peak of 0.62 ± 0.10% ID/g . U87MG xenograft could be clearly visualized by microPET/CT imaging through 1 to 3 h post-injection of 89Zr-DFO-heterodimeric peptide. Importantly, the tumor radiouptake was significantly reduced after blocking, and the imaging effect of this radioactive compound was more obvious than that of monomeric peptide probes. 89Zr-DFO-heterodimeric peptide has been demonstrated to show potential as a new radiopharmaceutical probe towards glioma, and multi-target probes do have advantages in tumor imaging.

In vitro and in vivo evaluation of 211At-labeled fibroblast activation protein inhibitor for glioma treatment.

Glioma is the most common primary intracranial tumor without effective treatment. Positron emission tomography tracers labeled with 68Ga targeting fibroblast activation protein (FAP) have shown favorable characteristics in the diagnosis of glioma. However, to the best of our knowledge, FAP-targeted endoradiotherapy has never been explored in glioma. Hence, in this study, we investigated the therapeutic effect of 211At-labeled fibroblast activation protein inhibitor (FAPI) for glioma in vitro and in vivo. By astatodestannylation reaction, we prepared 211At-FAPI-04 with a radiochemical yield of 45 ± 6.7% and radiochemical purity of 98%. With good stability in vitro, 211At-FAPI-04 showed fast and specific binding to FAP-positive U87MG cells, and could significantly reduce the cell viability, arrested cell cycle at G2/M phase and suppressed cell proliferative efficacy. Biodistribution studies revealed that 6-fold higher accumulation in tumor sites was achieved by intratumoral injection in comparison with intravenous injection. In U87MG xenografts, 211At-FAPI-04 obviously suppressed the tumor growth and prolonged the median survival in a dose-dependent manner without obvious toxicity to normal organs. In addition, reduced proliferation and increased apoptosis were also observed after 211At-FAPI-04 treatment. All these results suggest that targeted alpha-particle therapy (TAT) mediated by 211At-FAPI-04 can provide an effective and promising strategy for the treatment of glioma.

THz-driven dielectric particle accelerator on chip.

Recently, terahertz (THz)-driven particle accelerators have drawn increasing attention. The development of high-energy-gain THz accelerators on chip has been a challenge. Here we propose a concept of an on-chip THz-driven particle accelerator that uses few-cycle THz pulses to drive dielectric prisms. It avoids the serious waveguide dispersion of previous THz linacs based on dielectric lined waveguides and enhances the electron-energy gain. In addition, we propose to use prism stacks to overcome the asynchronization effect when accelerating low-energy particles, by which a longer acceleration length with even higher energy gain can be realized. Compared with the available on-chip dielectric laser accelerators, the proposed scheme avoids serious dielectric dispersion and enhances accelerated bunch charge. Hence, it promises an attractive particle accelerator on chip.

Synthesis and Preliminary Evaluation of 131I-Labeled FAPI Tracers for Cancer Theranostics.

As an excellent target for cancer theranostics, fibroblast activation protein (FAP) has become an attractive focus in cancer research. A class of FAP inhibitors (FAPIs) with a N-(4-quinolinoyl)-Gly-(2-cyanopyrrolidine) scaffold were developed, which displayed nanomolar affinity and high selectivity. Compared with 90Y, 177Lu, 225Ac, and 188Re, 211At seems to be more favored as a therapeutic candidate for FAPI tracers which have fast washout and short retention in tumor sites. Thus, the current study reported the synthesis of two FAPI precursors for 211At and 131I labeling and the preliminary evaluation of 131I-labeled FAPI analogues for cancer theranostics. FAPI variants with stannyl precursors were successfully synthesized and labeled with 131I using a radioiododestannylation reaction. Two radioactive tracers were obtained with high radiochemical purity over 99% and good radiochemical yields of 58.2 ± 1.78 and 59.5 ± 4.44% for 131I-FAPI-02 and 131I-FAPI-04, respectively. Both tracers showed high specific binding to U87MG cells in comparison with little binding to MCF-7 cells. Compared to 131I-FAPI-02, 131I-FAPI-04 exhibited higher affinity, more intracellular uptake, and longer retention time in vitro. Biodistribution studies revealed that both tracers were mainly excreted through the kidneys as well as the hepatobiliary pathway due to their high lipophilicity. In addition, higher accumulation, longer dwell time, and increased tumor-to-organ ratios were achieved by 131I-FAPI-04, which was clearly demonstrated by SPECT/CT imaging. Furthermore, intratumor injection of 131I-FAPI-04 significantly suppressed the tumor growth in U87MG xenograft mice without significant toxicity observed. The above results implied that FAP-targeted alpha endoradiotherapy (specific to 211At) should be used to treat tumors in the near future, considering the chemical similarity between iodine and astatine can ensure the labeling of the latter onto the designed FAPIs.

A comprehensive model including preoperative peripheral blood inflammatory markers for prediction of the prognosis of diffuse spinal cord astrocytoma following surgery.

PURPOSE: Due to the rarity of diffuse spinal cord astrocytoma, an effective model is still lacking to stratify their prognosis. Here, we aimed to establish a prognostic model through comprehensively evaluating clinicopathological features and preoperative peripheral blood inflammatory markers in 89 cases. METHODS: We performed univariate and multivariate Cox regression to identify prognosis factors. The Kaplan-Meier curves and ROC curves were employed to compare the prognostic value of selected factors. RESULTS: In addition to clinicopathological factors, we revealed the preoperative peripheral blood leukocyte count, neutrophils-to-lymphocytes ratio (NLR), and platelet-to-lymphocyte ratio (PLR) were also significantly correlated with overall survival of spinal cord astrocytoma in univariate Cox regression, and NLR was still significant in multivariate Cox analysis. Further, we demonstrated that NLR ≤ 3.65 and preoperative McCormick score (MMS) ≤ 3 were independently correlated with better survival of WHO grade IV tumors. Meanwhile, Ki-67 < 10% and resection extent ≥ 90% were independent prognostic factors in WHO grade II/III tumors. Finally, we developed a prognostic model that had better predictive efficiencies than WHO grade and histological grade for 1-year (AUC = 76.6), 2- year (AUC = 80.9), and 3-year (AUC = 80.3) survival. This model could classify tumors into 4 classifications with increasingly poor prognosis: 1, WHO grade II/III, with Ki-67 < 10% and resection extent ≥ 90%; 2, WHO grade II/III, Ki-67 ≥ 10% or resection < 90%; 3, WHO grade IV, NLR ≤ 3.65 and MMS ≤ 3; 4, WHO grade IV, with NRL > 3.65 or MMS = 4. CONCLUSION: We successfully constructed a comprehensive prognostic model including preoperative peripheral blood inflammatory markers, which can stratify diffuse spinal cord astrocytoma into 4 subgroups.

Transforming terahertz plasmonics within subwavelength hole arrays into enhanced terahertz mission via Smith-Purcell effect.

We illustrate the transformation of terahertz plasmonics within an array of rectangular sub-wavelength holes (RSHs) into coherent and enhanced terahertz emission via Smith-Purcell effect. The radiative plasmonic modes within each RSH of the array are successively excited by an free-electron beam, which then generate coherent radiation by constructive interference. Compared with the case without taking plasmonics into consideration, the radiation field intensity is enhanced by more than an order of magnitude, affording a promising way of developing high-power terahertz radiation. We perform detailed analysis of the plasmonic modes within the RSH by using the dielectric waveguide theory, and the results are verified by numerical simulations. The influences of the RSH parameters on the radiation properties are revealed and discussed.