The BTB-ZF gene Bm-mamo regulates pigmentation in silkworm caterpillars.

The color pattern of insects is one of the most diverse adaptive evolutionary phenotypes. However, the molecular regulation of this color pattern is not fully understood. In this study, we found that the transcription factor Bm-mamo is responsible for black dilute (bd) allele mutations in the silkworm. Bm-mamo belongs to the BTB zinc finger family and is orthologous to mamo in Drosophila melanogaster. This gene has a conserved function in gamete production in Drosophila and silkworms and has evolved a pleiotropic function in the regulation of color patterns in caterpillars. Using RNAi and clustered regularly interspaced short palindromic repeats (CRISPR) technology, we showed that Bm-mamo is a repressor of dark melanin patterns in the larval epidermis. Using in vitro binding assays and gene expression profiling in wild-type and mutant larvae, we also showed that Bm-mamo likely regulates the expression of related pigment synthesis and cuticular protein genes in a coordinated manner to mediate its role in color pattern formation. This mechanism is consistent with the dual role of this transcription factor in regulating both the structure and shape of the cuticle and the pigments that are embedded within it. This study provides new insight into the regulation of color patterns as well as into the construction of more complex epidermal features in some insects.

[Effect of Baicalin on Pyroptosis of Diffuse Large B-Cell Lymphoma Cell Lines DB and Its Mechanism].

OBJECTIVE: To investigate the effect of Baicalin on the proliferation and pyroptosis of diffuse large B-cell lymphoma cell line DB and its mechanism. METHODS: DB cells were treated with baicalin at different concentrations (0, 5, 10, 20, 40 µmol/L). Cell proliferation was detected by CCK-8 assay and half maximal inhibitory concentration (IC50) was calculated. The morphology of pyroptosis was observed under an inverted microscope, the integrity of the cell membrane was verified by LDH content release assay, and the expressions of pyroptosis-related mRNA and protein (NLRP3, GSDMD, GSDME, N-GSDMD, N-GSDME) were detected by real-time fluorescence quantitative PCR and Western blot. In order to further clarify the relationship between baicalin-induced pyroptosis and ROS production in DB cells, DB cells were divided into control group, baicalin group, NAC group and NAC combined with baicalin group. DB cells in the NAC group were pretreated with ROS inhibitor N-acetylcysteine (NAC) 2 mmol/L for 2 h. Baicalin was added to the combined treatment group after pretreatment, and the content of reactive oxygen species (ROS) in the cells was detected by DCFH-DA method after 48 hours of culture. RESULTS: Baicalin inhibited the proliferation of DB cells in a dose-dependent manner (r=-0.99), and the IC50 was 20.56 µmol/L at 48 h. The morphological changes of pyroptosis in DB cells were observed under inverted microscope. Compared with the control group, the release of LDH in the baicalin group was significantly increased (P<0.01), indicating the loss of cell membrane integrity. Baicalin dose-dependently increased the expression levels of NLRP3, N-GSDMD, and N-GSDME mRNA and protein in the pyroptosis pathway (P<0.05). Compared with the control group, the level of ROS in the baicalin group was significantly increased (P<0.05), and the content of ROS in the NAC group was significantly decreased (P<0.05). Compared with the NAC group, the content of ROS in the NAC + baicalin group was increased. Baicalin significantly attenuated the inhibitory effect of NAC on ROS production (P<0.05). Similarly, Western blot results showed that compared with the control group, the expression levels of pyroptosis-related proteins was increased in the baicalin group (P<0.05). NAC inhibited the expression of NLRP3 and reduced the cleavage of N-GSDMD and N-GSDME (P<0.05). Compared with the NAC group, the NAC + baicalin group had significantly increased expression of pyroptosis-related proteins. These results indicate that baicalin can effectively induce pyroptosis in DB cells and reverse the inhibitory effect of NAC on ROS production. CONCLUSION: Baicalin can inhibit the proliferation of DLBCL cell line DB, and its mechanism may be through regulating ROS production to affect the pyroptosis pathway.

Radio- and Photosensitizing Os(II)-Based Nanocage for Combined Radio-/Chemo-/X-ray-Induced Photodynamic Therapies, NIR Imaging, and Drug Delivery.

Integration of clinical imaging and collaborative multimodal therapies into a single nanomaterial for multipurpose diagnosis and treatment is of great interest to theranostic nanomedicine. Here, we report a rational design of a discrete Os-based metal-organic nanocage Pd6(OsL3)828+ (MOC-43) as a versatile theranostic nanoplatform to meet the following demands simultaneously: (1) synergistic treatments of radio-, chemo-, and X-ray-induced photodynamic therapies (X-PDT) for breast cancer, (2) NIR imaging for cancer cell tracking and tumor-targeting, and (3) anticancer drug transport through a host-guest strategy. The nanoscale MOC-43 incorporates high-Z Os-element to interact with X-ray irradiation for dual radiosensitization and photosensitization, showing efficient energy transfer to endogenous oxygen in cancer cells to enhance X-PDT efficacy. It also features intrinsic NIR emission originating from metal-to-ligand charge transfer (MLCT) as an excellent imaging probe. Meanwhile, its 12 pockets can capture and concentrate low-water-soluble molecules for anticancer drug delivery. These multifunctions are implemented and demonstrated by micellization of coumarin-loaded cages with DSPE-PEG2000 into coumarin ⊂ MOC-43 nanoparticles (CMNPs) for efficient subcellular endocytosis and uptake. The cancer treatments in vitro/in vivo show promising antitumor performance, providing a conceptual protocol to combine cage-cargo drug transport with diagnosis and treatment for collaborative cancer theranostics by virtue of multifunction synergism on a single-nanomaterial platform.

Evaluation of Quantitative Dual-Energy Computed Tomography Parameters for Differentiation of Parotid Gland Tumors.

RATIONALE AND OBJECTIVES: To assess the diagnostic performance of quantitative parameters from dual-energy CT (DECT) in differentiating parotid gland tumors (PGTs). MATERIALS AND METHODS: 101 patients with 108 pathologically proved PGTs were enrolled and classified into four groups: pleomorphic adenomas (PAs), warthin tumors (WTs), other benign tumors (OBTs), and malignant tumors (MTs). Conventional CT attenuation and DECT quantitative parameters, including iodine concentration (IC), normalized iodine concentration (NIC), effective atomic number (Zeff), electron density (Rho), double energy index (DEI), and the slope of the spectral Hounsfield unit curve (λHU), were obtained and compared between benign tumors (BTs) and MTs, and further compared among the four subgroups. Logistic regression analysis was used to assess the independent parameters and the receiver operating characteristic (ROC) curves were used to analyze the diagnostic performance. RESULTS: Attenuation, Zeff, DEI, IC, NIC, and λHU in the arterial phase (AP) and venous phase (VP) were higher in MTs than in BTs (p < 0.001-0.047). λHU in VP and Zeff in AP were independent predictors with an area under the curve (AUC) of 0.84 after the combination. Furthermore, attenuation, Zeff, DEI, IC, NIC, and λHU in the AP and VP of MTs were higher than those of PAs (p < 0.001-0.047). Zeff and NIC in AP and λHU in VP were independent predictors with an AUC of 0.93 after the combination. Attenuation and Rho in the precontrast phase; attenuation, Rho, Zeff, DEI, IC, NIC, and λHU in AP; and the Rho in the VP of PAs were lower than those of WTs (p < 0.001-0.03). Rho in the precontrast phase and attenuation in AP were independent predictors with an AUC of 0.89 after the combination. MTs demonstrated higher Zeff, DEI, IC, NIC, and λHU in VP and lower Rho in the precontrast phase compared with WTs (p < 0.001-0.04); but no independent predictors were found. CONCLUSION: DECT quantitative parameters can help to differentiate PGTs.

Clinical and mutational spectrum of paediatric Charcot-Marie-Tooth disease in a large cohort of Chinese patients.

Background: Charcot-Marie-Tooth disease (CMT) is the most common inherited neurological disorder suffered in childhood. To date, the disease features have not been extensively characterized in the Chinese paediatric population. In this study, we aimed to analyse the clinical profiles and genetic distributions of a paediatric CMT cohort in China. Methods: A total of 181 paediatric CMT patients were enrolled. After preexcluding PMP22 duplication/deletion by multiplex ligation-dependent probe amplification (MLPA), Sanger sequencing, targeted next-generation sequencing (NGS) or whole-exome sequencing (WES) was performed to obtain a genetic diagnosis. Detailed information was collected to explore the spectrum of subtypes and genotype-phenotype correlations. Results: Pathogenic mutations were identified in 68% of patients in this study; with PMP22 duplication, MFN2 and GJB1 were the most frequent disease-causing genes. Of note, respect to the higher prevalence worldwide, CMT1A (18.2%) was relatively lower in our cohort. Besides, the mean age at onset (8.3 ± 5.7 years) was significantly older in our series. In genotype-phenotype analyse, PMP22 point mutations were considered the most severe genotypes and were mostly de novo. In addition, the de novo mutations were identified in up to 12.7% of all patients, which was higher than that in other studies. Conclusion: We identified a relatively lower detection rate of PMP22 duplication and a higher frequency of de novo variants among paediatric patients in China. We also identified the genetic and phenotypic heterogeneity of this cohort, which may provide clues for clinicians in directing genetic testing strategies for Chinese patients with early-onset CMT.

Screening for PRX mutations in a large Chinese Charcot-Marie-Tooth disease cohort and literature review.

Background: Periaxins (encoded by PRX) play an important role in the stabilization of peripheral nerve myelin. Mutations in PRX can lead to Charcot-Marie-Tooth disease type 4F (CMT4F). Methods: In this study, we screened for PRX mutations using next-generation sequencing and whole-exome sequencing in a large Chinese CMT cohort consisting of 465 unrelated index patients and 650 healthy controls. Sanger sequencing was used for the validation of all identified variants. We also reviewed all previously reported PRX-related CMT cases and summarized the clinical manifestations and genetic features of PRX-related CMTs. Results: The hit rate for biallelic PRX variants in our cohort of Chinese CMT patients was 0.43% (2/465). One patient carried a previously unreported splice-site mutation (c.25_27 + 9del) compound heterozygous with a known nonsense variant. Compiling data on CMT4F cases and PRX variants from the medical literature confirmed that early-onset (95.2%), distal amyotrophy or weakness (94.0%), feet deformity (75.0%), sensory impairment or sensory ataxia (65.5%), delayed motor milestones (60.7%), and spinal deformity (59.5%) are typical features for CMT4F. Less frequent features were auditory impairments, respiratory symptoms, late onset, dysarthria or hoarseness, ophthalmic problems, and central nervous system involvement. The two cases with biallelic missense mutations have later onset age than those with nonsense or frameshift mutations. We did not note clear correlations between the type and site of mutations and clinical severity or distinct constellations of symptoms. Conclusion: Consistent with observations in other countries and ethnic groups, PRX-related CMT is rare in China. The clinical spectrum is wider than previously anticipated.

[Regulation of Baicalin on Growth of Extranodal NK/T Cell Lymphoma Cells through FOXO3/CCL22 Signaling Pathway].

OBJECTIVE: To investigate the effect of baicalin on the growth of extranodal NK/T cell lymphoma (ENKTCL) cells and its related mechanism. METHODS: Normal NK cells and human ENKTCL cells lines SNK-6 and YTS were cultured, then SNK-6 and YTS cells were treated with 5, 10, 20 µmol/L baicalin and set control. Cell proliferation and apoptosis was detected by Edu method and FCM method, respectively, and expressions of BCL-2, Bax, FOXO3 and CCL22 proteins were detected by Western blot. Interference plasmids were designed and synthesized. FOXO3 siRNA interference plasmids and CCL22 pcDNA overexpression plasmids were transfected with PEI transfection reagent. Furthermore, animal models were established for validation. RESULTS: In control group and 5, 10, 20 µmol/L baicalin group, the proliferation rate of SNK-6 cells was (56.17±2.96)%, (51.92±4.63)%, (36.42±1.58)%, and (14.60±2.81)%, respectively, while that of YTS cells was (58.85±2.98)%, (51.38±1.32)%, (34.75±1.09)%, and (15.45±1.10)%, respectively. In control group and 5, 10, 20 µmol/L baicalin group, the apoptosis rate of SNK-6 cells was (5.93±0.74)%, (11.78±0.34)%, (28.46±0.44)%, and (32.40±0.37)%, respectively, while that of YTS cells was (7.93±0.69)%, (16.29±1.35)%, (33.91±1.56)%, and (36.27±1.06)%, respectively. Compared with control group, the expression of BCL-2 protein both in SNK-6 and YTS cells decreased significantly (P<0.001), and the expression of Bax protein increased in SNK-6 cells only when the concentration of baicalin was 20 µmol/L (P<0.001), while that in YTS cells increased in all three concentrations(5, 10, 20 µmol/L) of baicalin (P<0.001). The expression of FOXO3 protein decreased while CCL22 protein increased in ENKTCL cell lines compared with human NK cells (P<0.001), but the expression of FOXO3 protein increased (P<0.01) and CCL22 protein decreased after baicalin treatment (P<0.001). Animal experiments showed that baicalin treatment could inhibit tumor growth. The expression of CCL22 protein in ENKTCL tissue of nude mice treated with baicalin decreased compared with control group (P<0.01), while the FOXO3 protein increased (P<0.05). In addition, FOXO3 silencing resulted in the decrease of FOXO3 protein expression and increase of CCL22 protein expression (P<0.01, P<0.001). CONCLUSION: Baicalin can inhibit proliferation and promote apoptosis of ENKTCL cell lines SNK-6 and YTS, up-regulate the expression of Bax protein, down-regulate the expression of BCL-2 protein, and down-regulate the expression of CCL22 protein mediated by FOXO3. Animal experiment shown that the baicalin can inhibit tumor growth. Baicalin can inhibit the growth and induce apoptosis of ENKTCL cells through FOXO3/CCL22 signaling pathway.

Nitroglycerin improves the visibility of fibula-free flap perforators on computed tomography angiography in patients with oral or maxillofacial lesion.

PURPOSE: To investigate the improvement of image quality and visualization of fibula-free flap (FFF) perforators on computed tomography angiography (CTA) after administration of sublingual nitroglycerin (NTG) tablets. METHODS: A total of 60 patients with oral or maxillofacial lesions before CTA of the lower extremity were randomly divided into two groups (NTG group and non-NTG group). The signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR), overall image quality and grading of vessels were evaluated and compared. The lumen diameters of the major arteries and the proximal and distal peroneal perforators were measured. The number of visible perforators in muscular clearance and muscular layer was also counted and compared between the two groups. RESULTS: The CNR of posterior tibial artery and overall image quality of CTA images in the NTG group was significantly higher than that in the non-NTG group (p < 0.05), although the SNR and CNR of other arteries did not show significant differences (p > 0.05). The lumen diameters of the peroneal artery and its perforators, anterior tibial artery, and posterior tibial artery were significantly larger in the NTG group (p < 0.001), while no significant difference prevailed in the diameter of the popliteal artery between the two groups (p = 0.298). Compared with the non-NTG group, a significant increase in the number of visible perforators was noted in the NTG group (p < 0.001). CONCLUSIONS: The administration of sublingual NTG in CTA of the lower extremity can improve the image quality and visualization of perforators, which aids to surgeons select the optimum FFF.

Improving visualization of free fibula flap perforators and reducing radiation dose in dual-energy CT angiography.

Background: The precise assessment of the perforators of the fibula free flap (FFF) is crucial for minimizing procedure-related complications when harvesting the FFF in patients with maxillofacial lesions. This study aims to investigate the utility of virtual noncontrast (VNC) images for radiation dose saving and to determine the optimal energy level of virtual monoenergetic imaging (VMI) reconstructions in dual-energy computed tomography (DECT) for visualization of the perforators of the fibula free flap (FFF). Methods: Data from 40 patients with maxillofacial lesions who received lower extremity DECT examinations in the noncontrast and arterial phase were collected in this retrospective, cross-sectional study. To compare VNC images from the arterial phase with true non-contrast images in a DECT protocol (M_0.5-TNC) and to compare VMI images with 0.5 linear images blending from the arterial phase (M_0.5-C), the attenuation, noise, signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and subjective image quality were assessed in different arteries, muscles, and fat tissues. Two readers evaluated the image quality and visualization of the perforators. The dose-length product (DLP) and CT volume dose index (CTDIvol) were used to determine the radiation dose. Results: Objective and subjective analyses showed no significant difference between the M_0.5-TNC and VNC images in the arteries and muscles (P>0.09 to P>0.99), and VNC imaging could reduce 50% of the radiation dose (P<0.001). Compared with those of the M_0.5-C images, the attenuation and CNR of VMI reconstructions at 40 kiloelectron volt (keV) and 60 keV were higher (P<0.001 to P=0.04). Noise was similar at 60 keV (all P>0.99) and increased at 40 keV (all P<0.001), and the SNR in arteries was increased at 60 keV (P<0.001 to P=0.02) in VMI reconstructions compared with those in the M_0.5-C images. The subjective scores in VMI reconstructions at 40 and 60 keV was higher than those in M_0.5-C images (all P<0.001). The image quality at 60 keV was superior to that at 40 keV (P<0.001), and there was no difference in the visualization of the perforators between 40 and 60 keV (P=0.31). Conclusions: VNC imaging is a reliable technique for replacing M_0.5-TNC and provides radiation dose saving. The image quality of the 40-keV and 60-keV VMI reconstructions was higher than that of the M_0.5-C images, and 60 keV provided the best assessment of perforators in the tibia.

Isothermal structural evolution of CL-20/HMX cocrystals under slow roasting at 190 °C.

As a new type of energetic material, cocrystal explosives demonstrate many excellent properties, such as high energy density and low sensitivity, due to the interaction between the molecules of the two components. The known decomposition temperature is 235 °C for CL-20/HMX cocrystals at a faster heating rate. CL-20 molecules could separate from the cocrystal matrix and decompose at a higher temperature, much lower than the decomposition temperature. The current work provided deep insight into the isothermal structural evolution of CL-20/HMX cocrystals with slow roasting at 190 °C. We found that the initial decomposition originates from separating CL-20 molecules from the surface along the (010) plane of the cocrystals. The gas products, such as NO2 and NO, escape from the largest exposed surface of the (010) plane and generates microbubbles and microholes. At the same time, the residual HMX molecules form δ-phase HMX crystals and shrink the volume by 72%. By increasing the time held at 190 °C, the decomposition of CL-20 molecules and recrystallization of the residual HMX molecules form a gully-like structure on the (010) plane of the CL-20/HMX cocrystal. After a long time at 190 °C, the CL-20 component completely decomposes, and all HMX molecules recrystallize in the δ-HMX form. The interaction between HMX and CL-20 molecules makes the decomposition rate of the CL-20/HMX cocrystal much slower than that of the CL-20 pure crystal with a similar decomposition activation energy during isothermal heating. This work can help to deeply understand the safety of CL-20/HMX cocrystal explosives at a temperature lower than the recognized decomposition temperature.

Radiomic and clinical data integration using machine learning predict the efficacy of anti-PD-1 antibodies-based combinational treatment in advanced breast cancer: a multicentered study.

BACKGROUND: Immune checkpoint inhibitors (ICIs)-based therapy, is regarded as one of the major breakthroughs in cancer treatment. However, it is challenging to accurately identify patients who may benefit from ICIs. Current biomarkers for predicting the efficacy of ICIs require pathological slides, and their accuracy is limited. Here we aim to develop a radiomics model that could accurately predict response of ICIs for patients with advanced breast cancer (ABC). METHODS: Pretreatment contrast-enhanced CT (CECT) image and clinicopathological features of 240 patients with ABC who underwent ICIs-based treatment in three academic hospitals from February 2018 to January 2022 were assigned into a training cohort and an independent validation cohort. For radiomic features extraction, CECT images of patients 1 month prior to ICIs-based therapies were first delineated with regions of interest. Data dimension reduction, feature selection and radiomics model construction were carried out with multilayer perceptron. Combined the radiomics signatures with independent clinicopathological characteristics, the model was integrated by multivariable logistic regression analysis. RESULTS: Among the 240 patients, 171 from Sun Yat-sen Memorial Hospital and Sun Yat-sen University Cancer Center were evaluated as a training cohort, while other 69 from Sun Yat-sen University Cancer Center and the First Affiliated Hospital of Sun Yat-sen University were the validation cohort. The area under the curve (AUC) of radiomics model was 0.994 (95% CI: 0.988 to 1.000) in the training and 0.920 (95% CI: 0.824 to 1.000) in the validation set, respectively, which were significantly better than the performance of clinical model (0.672 for training and 0.634 for validation set). The integrated clinical-radiomics model showed increased but not statistical different predictive ability in both the training (AUC=0.997, 95% CI: 0.993 to 1.000) and validation set (AUC=0.961, 95% CI: 0.885 to 1.000) compared with the radiomics model. Furthermore, the radiomics model could divide patients under ICIs-therapies into high-risk and low-risk group with significantly different progression-free survival both in training (HR=2.705, 95% CI: 1.888 to 3.876, p<0.001) and validation set (HR=2.625, 95% CI: 1.506 to 4.574, p=0.001), respectively. Subgroup analyses showed that the radiomics model was not influenced by programmed death-ligand 1 status, tumor metastatic burden or molecular subtype. CONCLUSIONS: This radiomics model provided an innovative and accurate way that could stratify patients with ABC who may benefit more from ICIs-based therapies.

Towards practical and massively parallel quantum computing emulation for quantum chemistry.

Quantum computing is moving beyond its early stage and seeking for commercial applications in chemical and biomedical sciences. In the current noisy intermediate-scale quantum computing era, the quantum resource is too scarce to support these explorations. Therefore, it is valuable to emulate quantum computing on classical computers for developing quantum algorithms and validating quantum hardware. However, existing simulators mostly suffer from the memory bottleneck so developing the approaches for large-scale quantum chemistry calculations remains challenging. Here we demonstrate a high-performance and massively parallel variational quantum eigensolver (VQE) simulator based on matrix product states, combined with embedding theory for solving large-scale quantum computing emulation for quantum chemistry on HPC platforms. We apply this method to study the torsional barrier of ethane and the quantification of the protein-ligand interactions. Our largest simulation reaches 1000 qubits, and a performance of 216.9 PFLOP/s is achieved on a new Sunway supercomputer, which sets the state-of-the-art for quantum computing emulation for quantum chemistry.

Effectiveness and safety of monoclonal antibodies against amyloid-beta vis-à-vis placebo in mild or moderate Alzheimer's disease.

Backgrounds and objectives: Currently, no consensus has been reached on the therapeutic implications of monoclonal antibodies against amyloid-beta (Aß) in Alzheimer's disease (AD). This study aimed to examine the effectiveness and safety of monoclonal antibodies against Aß as a whole and also to determine the superiority of individual antibodies vis-à-vis placebo in mild or moderate AD. Methods: Literature retrieval, article selection, and data abstraction were performed independently and in duplicate. Cognition and function were appraised by the Mini-Mental State Examination (MMSE), Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog), Disability Assessment for Dementia (DAD), and Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB). Effect sizes are expressed as standardized mean difference (SMD) with a 95% confidence interval (CI). Results: Twenty-nine articles involving 108 drug-specific trials and 21,383 participants were eligible for synthesis. Of the four assessment scales, only CDR-SB was significantly reduced after using monoclonal antibodies against Aß relative to placebo (SMD: -0.12; 95% CI: -0.2 to -0.03; p = 0.008). Egger's tests indicated a low likelihood of publication bias. At individual levels, bapineuzumab was associated with a significant increase in MMSE (SMD: 0.588; 95% CI: 0.226-0.95) and DAD (SMD: 0.919; 95% CI: 0.105-1.943), and a significant decrease in CDR-SB (SMD: -0.15; 95% CI: -0.282-0.018). Bapineuzumab can increase the significant risk of serious adverse events (OR: 1.281; 95% CI: 1.075-1.525). Conclusion: Our findings indicate that monoclonal antibodies against Aß can effectively improve instrumental activities of daily life in mild or moderate AD. In particular, bapineuzumab can improve cognition and function, as well as activities of daily life, and meanwhile, it triggers serious adverse events.

A novel inflammation-related prognostic model for predicting the overall survival of primary central nervous system lymphoma: A real-world data analysis.

Background: Primary central nervous system lymphoma (PCNSL) is a type of extranodal non-Hodgkin lymphoma. Although there are widely used prognostic scores, their accuracy and practicality are insufficient. Thus, a novel prognostic prediction model was developed for risk stratification of PCNSL patients in our research. Methods: We retrospectively collected 122 patients with PCNSL from two medical centers in China from January 2010 to June 2022. Among them, 72 patients were used as the development cohort to construct a new model, and 50 patients were used for the validation. Then, by using univariate and multivariate Cox regression analsis and Lasso analysis, the Xijing model was developed and composed of four variables, including lesion number, ß2-microglobulin (ß2-MG), systemic inflammation response index (SIRI) and Karnofsky performance status (KPS). Finally, we evaluated the Xijing model through internal and external validation. Results: Compared with the original prognostic scores, the Xijing model has an overall improvement in predicting the prognosis of PCNSL according to the time-dependent area under the curve (AUC), Harrell's concordance index (C-index), decision curve analysis (DCA), integrated discrimination improvement (IDI) and continuous net reclassification index (NRI). For overall survival (OS) and progression-free survival (PFS), the Xijing model can divide PCNSL patients into three groups, and shows more accurate stratification ability. In addition, the Xijing model can still stratify and predict prognosis similarly better in the elderly with PCNSL and subgroups received high-dose methotrexate (HD-MTX) or Bruton's tyrosine kinase inhibitors (BTKi). Finally, external validation confirmed the above results. Conclusions: Integrating four prognostic factors, including imaging findings, tumor burden, systemic inflammation response index, and comprehensive physical condition, we provided a novel prognostic model for PCNSL based on real-world data and evaluated its predictive capacity.

Densification of Two Forms of Nanostructured TATB under Uniaxial Die Pressures: A USAXS-SAXS Study.

Sequential ultra-small-angle and small-angle and X-ray scattering (USAXS and SAXS) measurements of hierarchical microstructure of a common energetic material, the high explosive 2,4,6-Triamino-1,3,5-trinitrobenzene (TATB), were performed to follow the microstructure evolution upon applied pressure. The pellets were prepared by two different routes-die pressed from a nanoparticle form and a nano-network form of TATB powder. The derived structural parameters, such as void size, porosity, and the interface area, reflected the response of TATB under compaction. Three populations of voids were observed in the probed q range from 0.007 to 7 nm-1. The inter-granular voids with size larger than 50 nm were sensitive to low pressures and had a smooth interface with the TATB matrix. The inter-granular voids with size of ~10 nm exhibited a less volume-filling ratio at high pressures (>15 kN) as indicated by a decrease of the volume fractal exponent. The response of these structural parameters to external pressures implied that the main densification mechanisms under die compaction were the flow, fracture, and plastic deformation of the TATB granules. Compared to the nanoparticle TATB, the applied pressure strongly influenced the nano-network TATB due to its more uniform structure. The findings and research methods of this work provide insights into the structural evolution of TATB during densification.

Comparison of image quality and quantitative parameters in intravoxel incoherent motion imaging at 3-T based on turbo spin-echo and echo-planar imaging in patients with oral cancer.

PURPOSE: To compare the image quality, apparent diffusion coefficient (ADC), and intravoxel incoherent motion- (IVIM) derived parameters of IVIM imaging based on turbo spin-echo (TSE) and echo-planar imaging (EPI) of patients with oral cancer and to assess the equivalence of the ADC and IVIM-derived parameters. METHODS: Thirty patients with oral cancer underwent TSE-IVIM and EPI-IVIM imaging using a 3.0-T system. The distortion ratio (DR), signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), qualitative evaluations of image quality, ADC, pure diffusion coefficient (D), pseudo-diffusion coefficient (D*), and perfusion fraction (f) were compared between the two sequences. The consistency of the quantitative parameters in oral cancer between the TSE and EPI sequences was evaluated using a Bland-Altman analysis. RESULTS: TSE-IVIM had a significantly smaller DR than EPI-IVIM (P < 0.001). The CNR of EPI-IVIM on most of the anatomical sites was significantly higher than that of TSE-IVIM (P < 0.05), while the SNR was not significantly different (P > 0.05). TSE-IVIM had significantly higher image quality, less distortion and artifacts, and lower image contrast compared with EPI-IVIM (P < 0.05). The lesion-edge sharpness and diagnostic confidence of EPI-IVIM were lower than that of TSE-IVIM, although no significant differences existed (P > 0.05). The ADC and D of TSE-IVIM had better reproducibility (intraclass correlation coefficient > 0.9). Although no significant difference existed for the ADC and IVIM-derived parameters of lesions between the two sequences (P > 0.05), wide limits of agreement were found in the Bland-Altman plots. CONCLUSION: TSE-IVIM could be used as an alternative technique to EPI-IVIM for patients with oral cancer because of its better image quality. Furthermore, TSE-IVIM can provide more accurate quantitative parameters. However, the quantitative parameters derived from the two IVIM techniques cannot be used as equivalent parameters for patients with oral cancer.

Improving the Visualization of the Adrenal Veins Using Virtual Monoenergetic Images from Dual-Energy Computed Tomography before Adrenal Venous Sampling.

(1) Background: This study explored the optimal energy level in advanced virtual monoenergetic images (VMI+) from dual-energy computed tomography angiography (DE-CTA) for adrenal veins visualization before adrenal venous sampling (AVS). (2) Methods: Thirty-nine patients were included in this prospective single-center study. The CT value, noise, signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were measured in both adrenal veins and abdominal solid organs and were then compared between VMI+ within the range of 40-80 kiloelectron volt (keV). The visualization rate of the adrenal veins and the overall image quality of solid organs were subjectively compared among different keV VMI+. The AVS success rate was recorded for 20 patients. (3) Results: For the adrenal veins, 40 keV VMI+ had the peak CT value, noise and CNR (p < 0.05). Subjectively, the visualization rate was the highest at 40 keV (100% for the right adrenal vein, and 97.4% for the left adrenal vein) (p < 0.05). For solid organs, the CT value, noise and CNR at 50 keV were lower than those at 40 keV (p < 0.05), but the SNR was similar between 40 keV and 50 keV. The overall subjective image quality of solid organs at 50 keV was the best (p < 0.05). The AVS success rate was 95%. (4) Conclusions: For VMI+, 40 keV was the preferential energy level to obtain a high visualization rate of the adrenal veins and a high success rate of AVS, while 50 keV was the favorable energy level for the depiction of abdominal organs.

Effectiveness of lenvatinib plus immune checkpoint inhibitors in primary advanced hepatocellular carcinoma beyond oligometastasis.

BACKGROUND: Targeted therapy combined with immune checkpoint inhibitors is considered a promising treatment for primary advanced hepatocellular carcinoma (HCC). Nevertheless, the difference between synchronous and asynchronous treatment of lenvatinib with programmed death receptor-1 (PD-1) inhibitor in advanced HCC is still unclear. The aim of this investigation is to evaluate the effectiveness of synchronous and asynchronous of lenvatinib and PD-1 inhibitor on the advanced HCC beyond oligometastasis. METHODS: In this study, 213 patients from four institutions in China were involved. Patients were split into two collections: (1) lenvatinib plus PD-1 inhibitor were used synchronously (synchronous treatment group); (2) patients in asynchronous treatment group received PD-1 inhibitor after 3 months of lenvatinib treatment prior to tumour progression. To analyse progression-free survival (PFS), overall survival (OS), efficacy and safety of patients in both groups, we employed propensity score matching (PSM). RESULTS: The 6-, 12- and 24-month OS rates were 100%, 93.4% and 58.1% in the synchronous treatment group and 100%, 71.5% and 25.3% in the asynchronous treatment group, respectively. In contrast to the asynchronous treatment group, the group treated synchronously exhibited a substantially enhanced OS (hazard ratio [HR], 0.45; 95% confidence interval [CI], 0.30-0.66; p < .001). The 6-, 12- and 18-month PFS rates were 82.6%, 42.6% and 10.8% in the synchronous treatment group and 63.3%, 14.2% and 0% in the asynchronous treatment group, respectively. A significant difference was observed in the PFS rate (HR, 0.46; 95% CI, 0.33-0.63; p < .001) between the two collections. CONCLUSIONS: Patients with advanced HCC beyond oligometastasis, simultaneous administration of lenvatinib and PD-1 inhibitor led to significant improvements in survival.

Structural evolution of CL-20/DNB cocrystals at high temperature: Phase transition and kinetics of thermal decomposition.

As a typical new energetic material, CL-20/DNB cocrystals have been recognized as a promising explosive owing to their excellent comprehensive performance. The thermal decomposition behavior, structural evolution and dynamic process of CL-20/DNB cocrystals under high temperature were studied by means of thermogravimetric differential heating, X-ray diffraction, Raman spectroscopy to gain insight into the cocrystal materials. The study found that the decomposition of CL-20/DNB cocrystal is a heterogeneous process accompanied by the sublimation of DNB and structural change of CL-20. The phase transition of ߠ→ Î³-CL-20 was observed at 120 °C. The kinetics of decomposition and the mechanism of micro structural evolution on CL-20/DNB cocrystals with heating were revealed. The primary NO⋯H hydrogen bonds of the cocrystal are broken, accompanied by the melting of DNB in the temperature range of 100-120 °C. Subsequently, the DNB single component decomposes completely, leading to lattice collapse of cocrystal; simultaneously, CL-20 undergoes a transition process from ß phase to γ phase. Ultimately, γ-CL-20 gradually decomposes with increasing temperature. The activation energy of cocrystal is also obtained as 129 ± 10 kJ/mol. The understanding of cocrystal explosive was deepened and the further application was promoted.

MRI-visible mesoporous polydopamine nanoparticles with enhanced antioxidant capacity for osteoarthritis therapy.

Since the progression of osteoarthritis (OA) is closely associated with synovitis and cartilage destruction, the inhibition of inflammatory responses in synovial macrophages and reactive oxygen species (ROS) induced apoptosis in chondrocytes is crucial for OA amelioration. However, most of the current anti-inflammatory and antioxidant drugs are small molecules apt to be eliminated in vivo. Herein, mesoporous polydopamine nanoparticles (DAMM NPs) doped with arginine and manganese (Mn) ions were prepared to load dexamethasone (DEX) for OA intervention. A series of in vitro studies showed that the sustained release of DEX from DAMM NPs suppressed synovial inflammation and simultaneously inhibited toll-like receptor 3 (TLR-3) production in chondrocytes, contributing to prevention of chondrocyte apoptosis through the inflammatory factor-dependent TLR-3/NF-κB signaling pathway via modulation of macrophage-chondrocyte crosstalk. In addition, DAMM NPs exerted a predominant role in removal of ROS generated in chondrocytes. Therefore, the DEX-loaded DAMM NPs significantly attenuated OA development in mice model. Importantly, the T1-T2 magnetic contrast capabilities of DAMM NPs allowed an MRI-trackable delivery, manifesting a distinct feature widely regarded to boost the potential of nanomedicines for clinical applications. Together, our developed antioxidant-enhanced DAMM NPs with MRI-visible signals may serve as a novel multifunctional nanocarriers for prevention of OA progression.