Pd-Catalyzed Three-Component Coupling of Cyclopropenones via Sequential C-C Bond Activation and Allylation.

A novel Pd-catalyzed three-component domino reaction for the stereoselective synthesis of highly functionalized allyl cinnamates has been developed. In this protocol, a sequential process of C-C bond activation and intermolecular allylic substitution was well-organized. The key for this transformation is the in situ generated hydrolysis product of cyclopropenone, which triggered a new reaction with vinylethylene carbonates. The reaction mechanism was investigated, demonstrating the high stereoselectivity and excellent atomic economy in this process.

Perioperative Outcomes and Survival of Modified Subxiphoid VATS Thymectomy for T2-3 Thymic Malignancies: A Retrospective Comparison Study.

OBJECTIVE: Our previous study demonstrated that modified subxiphoid VATS thymectomy (mSVT) with an auxiliary sternal retractor is feasible for locally invasive thymic malignancies. This study aimed to compare perioperative and oncological outcomes of mSVT versus median sternotomy thymectomy (MST) for locally advanced thymic malignancies. METHODS: In total, 221 patients of T2-3 thymic malignancies who underwent mSVT or MST between 2015 and 2020 were enrolled in our prospectively maintained database. A 1:1 propensity score-matching analysis was performed to balance the bias. Surgical difficulty was evaluated by a modified resection index. Perioperative and oncological results were compared between mSVT and MST groups. RESULTS: There were 72 patients in each group in the final analysis. Our results showed that the mSVT group had a shorter operative duration (98 vs. 129 min, P<0.001), less blood loss (40 vs.100 mL, P<0.001), shorter drainage duration (3 vs. 5 days, P<0.001), shorter length of hospital stay (5 vs. 6 days, P<0.001) and fewer postoperative complications (5.6% vs. 23.6%; P=0.005). No significant difference was detected in complete resection (98.6% vs. 98.6%, P =0.001) between the two groups. Conversion occurred in 5/106 (4.7%). Survival analyses indicated similar recurrence-free survival (HR=0.94; 95% CI: 0.40-2.20; p=0.883) and overall survival (HR=0.52; 95% CI: 0.05-5.02; p=0.590) between the two groups. CONCLUSION: The mSVT was safe and effective for T2-3 thymic malignancies and could be an alternative for selected patients with locally advanced thymic diseases. Further prospective studies are needed to evaluate the long-term survival of modified subxiphoid approach thoracoscopic thymectomy.

Association between pretreatment emotional distress and immune checkpoint inhibitor response in non-small-cell lung cancer.

Emotional distress (ED), commonly characterized by symptoms of depression and/or anxiety, is prevalent in patients with cancer. Preclinical studies suggest that ED can impair antitumor immune responses, but few clinical studies have explored its relationship with response to immune checkpoint inhibitors (ICIs). Here we report results from cohort 1 of the prospective observational STRESS-LUNG study, which investigated the association between ED and clinical efficacy of first-line treatment of ICIs in patients with advanced non-small-cell lung cancer. ED was assessed by Patient Health Questionnaire-9 and Generalized Anxiety Disorder 7-item scale. The study included 227 patients with 111 (48.9%) exhibiting ED who presented depression (Patient Health Questionnaire-9 score ≥5) and/or anxiety (Generalized Anxiety Disorder 7-item score ≥5) symptoms at baseline. On the primary endpoint analysis, patients with baseline ED exhibited a significantly shorter median progression-free survival compared with those without ED (7.9 months versus 15.5 months, hazard ratio 1.73, 95% confidence interval 1.23 to 2.43, P = 0.002). On the secondary endpoint analysis, ED was associated with lower objective response rate (46.8% versus 62.1%, odds ratio 0.54, P = 0.022), reduced 2-year overall survival rate of 46.5% versus 64.9% (hazard ratio for death 1.82, 95% confidence interval 1.12 to 2.97, P = 0.016) and detriments in quality of life. The exploratory analysis indicated that the ED group showed elevated blood cortisol levels, which was associated with adverse survival outcomes. This study suggests that there is an association between ED and worse clinical outcomes in patients with advanced non-small-cell lung cancer treated with ICIs, highlighting the potential significance of addressing ED in cancer management. ClinicalTrials.gov registration: NCT05477979 .

Multi-omics analysis reveals that linoleic acid metabolism is associated with variations of trained immunity induced by distinct BCG strains.

Trained immunity is one of the mechanisms by which BCG vaccination confers persistent nonspecific protection against diverse diseases. Genomic differences between the different BCG vaccine strains that are in global use could result in variable protection against tuberculosis and therapeutic effects on bladder cancer. In this study, we found that four representative BCG strains (BCG-Russia, BCG-Sweden, BCG-China, and BCG-Pasteur) covering all four genetic clusters differed in their ability to induce trained immunity and nonspecific protection. The trained immunity induced by BCG was associated with the Akt-mTOR-HIF1α axis, glycolysis, and NOD-like receptor signaling pathway. Multi-omics analysis (epigenomics, transcriptomics, and metabolomics) showed that linoleic acid metabolism was correlated with the trained immunity-inducing capacity of different BCG strains. Linoleic acid participated in the induction of trained immunity and could act as adjuvants to enhance BCG-induced trained immunity, revealing a trained immunity-inducing signaling pathway that could be used in the adjuvant development.

Predicting postinterventional rupture of intracranial aneurysms using arteriography-derived radiomic features after pipeline embolization.

Background and purpose: Postinterventional rupture of intracranial aneurysms (IAs) remains a severe complication after flow diverter treatment. However, potential hemodynamic mechanisms underlying independent predictors for postinterventional rupture of IAs remain unclear. In this study, we employed arteriography-derived radiomic features to predict this complication. Methods: We included 64 patients who underwent pipeline flow diversion for intracranial aneurysms, distinguishing between 16 patients who experienced postinterventional rupture and 48 who did not. We performed propensity score matching based on clinical and morphological factors to match these patients with 48 patients with postinterventional unruptured IAs at a 1:3 ratio. Postinterventional digital subtraction angiography were used to create five arteriography-derived perfusion parameter maps and then radiomics features were obtained from each map. Informative features were selected through the least absolute shrinkage and selection operator method with five-fold cross-validation. Subsequently, radiomics scores were formulated to predict the occurrence of postinterventional IA ruptures. Prediction performance was evaluated with the training and test datasets using area under the curve (AUC) and confusion matrix-derived metrics. Results: Overall, 1,459 radiomics features were obtained, and six were selected. The resulting radiomics scores had high efficacy in distinguishing the postinterventional rupture group. The AUC and Youden index were 0.912 (95% confidence interval: 0.767-1.000) and 0.847 for the training dataset, respectively, and 0.938 (95% confidence interval, 0.806-1.000) and 0.800 for the testing dataset, respectively. Conclusion: Radiomics scores generated using arteriography-derived radiomic features effectively predicted postinterventional IA ruptures and may aid in differentiating IAs at high risk of postinterventional rupture.

Rupture-Related Features of Cerebral Arteriovenous Malformations and Their Utility in Predicting Hemorrhage.

BACKGROUND: Evaluating rupture risk in cerebral arteriovenous malformations currently lacks quantitative hemodynamic and angioarchitectural features necessary for predicting subsequent hemorrhage. We aimed to derive rupture-related hemodynamic and angioarchitectural features of arteriovenous malformations and construct an ensemble model for predicting subsequent hemorrhage. METHODS: This retrospective study included 3 data sets, as follows: training and test data sets comprising consecutive patients with untreated cerebral arteriovenous malformations who were admitted from January 2015 to June 2022 and a validation data set comprising patients with unruptured arteriovenous malformations who received conservative treatment between January 2009 and December 2014. We extracted rupture-related features and developed logistic regression (clinical features), decision tree (hemodynamic features), and support vector machine (angioarchitectural features) models. These 3 models were combined into an ensemble model using a weighted soft-voting strategy. The performance of the models in discriminating ruptured arteriovenous malformations and predicting subsequent hemorrhage was evaluated with confusion matrix-related metrics in the test and validation data sets. RESULTS: A total of 896 patients (mean±SD age, 28±14 years; 404 women) were evaluated, with 632, 158, and 106 patients in the training, test, and validation data sets, respectively. From the training set, 9 clinical, 10 hemodynamic, and 2912 pixel-based angioarchitectural features were extracted. A logistic regression model was built using 4 selected clinical features (age, nidus size, location, and venous aneurysm), whereas a decision-tree model was constructed from 4 hemodynamic features (outflow time, stasis index, cerebral blood flow, and outflow volume ratio). A support vector machine model was designed using 5 pixel-based angioarchitectural features. In the validation data set, the accuracy, sensitivity, specificity, and area under the curve of the ensemble model for predicting subsequent hemorrhages were 0.840, 0.889, 0.823, and 0.911, respectively. CONCLUSIONS: The ensemble model incorporating clinical, hemodynamic, and angioarchitectural features showed favorable performance in predicting subsequent hemorrhage of cerebral arteriovenous malformations.

DIEANet: an attention model for histopathological image grading of lung adenocarcinoma based on dimensional information embedding.

Efficient and rapid auxiliary diagnosis of different grades of lung adenocarcinoma is conducive to helping doctors accelerate individualized diagnosis and treatment processes, thus improving patient prognosis. Currently, there is often a problem of large intra-class differences and small inter-class differences between pathological images of lung adenocarcinoma tissues under different grades. If attention mechanisms such as Coordinate Attention (CA) are directly used for lung adenocarcinoma grading tasks, it is prone to excessive compression of feature information and overlooking the issue of information dependency within the same dimension. Therefore, we propose a Dimension Information Embedding Attention Network (DIEANet) for the task of lung adenocarcinoma grading. Specifically, we combine different pooling methods to automatically select local regions of key growth patterns such as lung adenocarcinoma cells, enhancing the model's focus on local information. Additionally, we employ an interactive fusion approach to concentrate feature information within the same dimension and across dimensions, thereby improving model performance. Extensive experiments have shown that under the condition of maintaining equal computational expenses, the accuracy of DIEANet with ResNet34 as the backbone reaches 88.19%, with an AUC of 96.61%, MCC of 81.71%, and Kappa of 81.16%. Compared to seven other attention mechanisms, it achieves state-of-the-art objective metrics. Additionally, it aligns more closely with the visual attention of pathology experts under subjective visual assessment.

Ultralow Thermal Conductivity of a Chalcogenide System Pt3Bi4Q9 (Q = S, Se) Driven by the Hierarchy of Rigid [Pt6Q12]12- Clusters Embedded in Soft Bi-Q Sublattice.

Knowledge of structure-property relationships in solids with intrinsic low thermal conductivity is crucial for fields such as thermoelectrics, thermal barrier coatings, and refractories. Herein, we propose a new "rigidness in softness" structural scheme for intrinsic low lattice thermal conductivity (κL), which embeds rigid clusters into the soft matrix to induce large lattice anharmonicity, and accordingly discover a new series of chalcogenides Pt3Bi4Q9 (Q = S, Se). Pt3Bi4S9-xSex (x = 3, 6) achieved an intrinsic ultralow κL down to 0.39 W/(m K) at 773 K, which is considerably low among the Bi chalcogenide thermoelectric materials. Pt3Bi4Q9 contains the rigid cubic [Pt6Q12]12- clusters embedded in the soft Bi-Q sublattice, involving multiple bonding interactions and vibration hierarchy. The hierarchical structure yields a large lattice anharmonicity with high Grüneisen parameters (γ) 1.97 of Pt3Bi4Q9, as verified by the effective scatter of low-lying optical phonons toward heat-carrying acoustic phonons. Consequently, the rigid-soft coupling significantly inhibits heat propagation, exhibiting low acoustic phonon frequencies (∼25 cm-1) and Debye temperatures (ΘD = 170.4 K) in Pt3Bi4Se9. Owing to the suppressed κL and considerable power factor (PF), the ZT value of Pt3Bi4S6Se3 can reach 0.56 at 773 K without heavy carrier doping, which is competitive among the pristine Bi chalcogenides. Theoretical calculations predicted a large potential for performance improvement via proper doping, indicating the great potential of this structure type for promising thermoelectric materials.

Association between haemoglobin-to-red blood cell distribution width ratio at admission and all-cause mortality in adult patients with sepsis in an intensive care unit: a secondary analysis of the MIMIC-IV database.

OBJECTIVE: The association between haemoglobin-to-red blood cell distribution width ratio (HRR) and all-cause mortality remains poorly understood. This study aimed to examine the influence of HRR at the time of admission mortality over 1 year and 30 days in patients with sepsis. DESIGN: This was a secondary analysis. SETTING: This study was conducted in intensive care units (ICUs). PARTICIPANTS: Adult patients with sepsis were identified and included from an intensive care database based on eligibility criteria. PRIMARY OUTCOME AND MEASURE: The primary outcome was the rate of death within 1 year. The secondary outcome was the death rate within 30 days. RESULTS: A total of 4233 patients with sepsis who met the inclusion criteria were analysed, excluding those ineligible. These participants were divided into quartiles based on their HRR at admission. The overall mortality rates at 1 year and 30 days were 42.9% and 25.5%, respectively. A significant inverse association was observed between HRR quartiles and all-cause mortality (p<0.001). Pairwise comparisons using Kaplan-Meier analysis showed significant differences in 1-year mortality rates across the quartiles. However, no significant difference was detected in 30-day mortality between the Q3 and Q4 groups (p=0.222). Multivariate Cox regression analysis demonstrated that a higher HRR at ICU admission was independently associated with reduced mortality at 1 year (HR, 0.935; 95% CI 0.913 to 0.958; p<0.001) and 30 days (HR, 0.969; 95% CI 0.939 to 0.999; p=0.043). Furthermore, restricted cubic spline models indicated a non-linear relationship between HRR and mortality at both 1 year and 30 days (p<0.001 for both). CONCLUSIONS: This retrospective analysis demonstrated that the HRR at the time of admission was a significant prognostic marker for long-term mortality in patients with sepsis.

Duration-specific association between plasma IGFBP7 levels and diabetic complications in patients with type 2 diabetes mellitus.

OBJECTIVE: Insulin-like growth factor binding protein 7 (IGFBP7) has a strong affinity to insulin. This study aimed to evaluate the relationship between IGFBP7 and complications among type 2 diabetes mellitus (T2DM) patients. DESIGN: A total of 1449 T2DM patients were selected from a cross-sectional study for disease management registered in the National Basic Public Health Service in Changshu, China, and further tested for their plasma IGFBP7 levels. Logistic regressions and Spearman's rank correlation analyses were used to explore the associations of IGFBP7 with diabetic complications and clinical characteristics, respectively. RESULTS: Among the 1449 included T2DM patients, 403 (27.81%) had complications. In patients with shorter duration (less than five years), the base 10 logarithms of IGFBP7 concentration were associated with T2DM complications, with an adjusted odds ratio (OR) of 2.41 [95% confidence interval (95%CI) = 1.06-5.48]; while in patients with longer duration (more than five years), plasma IGFBP7 levels were not associated with T2DM complications. Furthermore, in T2DM patients with shorter duration, those with two or more types of complications were more likely to have higher levels of IGFBP7. CONCLUSION: IGFBP7 is positively associated with the risk of complication in T2DM patients with shorter duration.

A covalent organic framework as a dual-active-center cathode for a high-performance aqueous zinc-ion battery.

Organic electrode materials have shown significant potential for aqueous Zn ion batteries (AZIBs) due to their flexible structure designability and cost advantage. However, sluggish ionic diffusion, high solubility, and low capacities limit their practical application. Here, we designed a covalent organic framework (TA-PTO-COF) generated by covalently bonding tris(4-formylbiphenyl)amine (TA) and 2,7-diaminopyrene-4,5,9,10-tetraone (PTO-NH2). The highly conjugated skeleton inside enhances its electron delocalization and intermolecular interaction, leading to high electronic conductivity and limited solubility. The open channel within the TA-PTO-COF provides ionic diffusion pathways for fast reaction kinetics. In addition, the abundant active sites (C[double bond, length as m-dash]N and C[double bond, length as m-dash]O) endow the TA-PTO-COF with a large reversible capacity. As a result, the well-designed TA-PTO-COF cathode delivers exceptional capacity (255 mA h g-1 at 0.1 A g-1), excellent cycling stability, and a superior rate capacity of 186 mA h g-1 at 10 A g-1. Additionally, the co-insertion mechanism of Zn2+/H+ within the TA-PTO-COF cathode is revealed in depth by ex situ spectroscopy. This study presents an effective strategy for developing high-performance organic cathodes for advanced AZIBs.

Network pharmacological analysis on the mechanism of Linggui Zhugan decoction for nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD), represents a chronic progressive disease that imposes a significant burden on patients and the healthcare system. Linggui Zhugan decoction (LGZGD) plays a substantial role in treating NAFLD, but its exact molecular mechanism is unknown. Using network pharmacology, this study aimed to investigate the mechanism of action of LGZGD in treating NAFLD. Active ingredients and targets were identified through the integration of data from the TCMSP, GEO, GeneCards, and OMIM databases. Cytoscape 3.9.1 software, in conjunction with the STRING platform, was employed to construct network diagrams and screen core targets. The enrichment analysis of gene ontology and the Kyoto Encyclopedia of Genes and Genomes pathways were conducted by using the R. Molecular docking of the active ingredients and core targets was performed with AutoDock Vina software. We obtained 93 and 112 active ingredients and potential targets using the bioinformatic analysis of LGZGD in treating NAFLD. The primary ingredients of LGZGD included quercetin, kaempferol, and naringenin. The core targets were identified AKT1, MYC, HSP90AA1, HIF1A, ESR1, TP53, and STAT3. Gene ontology function enrichment analysis revealed associations with responses to nutrient and oxygen levels, nuclear receptor activity, and ligand-activated transcription factor activity. Kyoto Encyclopedia of Genes and Genomes signaling pathway analysis implicated the involvement of the PI3K-Akt, IL-17, TNF, Th17 cell differentiation, HIF-1, and TLR signaling pathways. Molecular docking studies indicated strong binding affinities between active ingredients and targets. LGZGD intervenes in NAFLD through a multi-ingredient, multi-target, and multi-pathway approach. Treatment with LGZGD can improve insulin resistance, oxidative stress, inflammation, and lipid metabolism associated with NAFLD.

An innovative lab-scale production for a novel therapeutic DNA vaccine candidate against rheumatoid arthritis.

BACKGROUND: Recent therapeutic-plasmid DNA vaccine strategies for rheumatoid arthritis (RA) have significantly improved. Our pcDNA-CCOL2A1 vaccine is the most prominent and the first antigen-specific tolerising DNA vaccine with potent therapeutic and prophylactic effects compared with methotrexate (MTX), the current "gold standard" treatment for collagen-induced arthritis (CIA). This study developed a highly efficient, cost-effective, and easy-to-operate system for the lab-scale production of endotoxin-free supercoiled plasmids with high quality and high yield. Based on optimised fermentation culture, we obtained a high yield of pcDNA-CCOL2A1 vaccine by PEG/MgCl2 precipitation and TRION-114. We then established a method for quality control of the pcDNA-CCOL2A1 vaccine. Collagen-induced arthritis (CIA) model rats were subjected to intramuscular injection of the pcDNA-CCOL2A1 vaccine (300 µg/kg) to test its biological activity. RESULTS: An average yield of 11.81 ± 1.03 mg purified supercoiled plasmid was obtained from 1 L of fermentation broth at 670.6 ± 57.42 mg/L, which was significantly higher than that obtained using anion exchange column chromatography and a commercial purification kit. Our supercoiled plasmid had high purity, biological activity, and yield, conforming to the international guidelines for DNA vaccines. CONCLUSION: The proposed innovative downstream process for the pcDNA-CCOL2A1 vaccine can not only provide a large-scale high-quality supercoiled plasmid DNA for preclinical research but also facilitate further pilot-scale and even industrial-scale production of pcDNA-CCOL2A1 vaccine.

Tumor volume instead of recurrent T category predicts clinical outcome of patients with locally recurrent nasopharyngeal carcinoma salvaged by carbon ion radiation therapy.

BACKGROUND: Although carbon ion radiation therapy (CIRT) substantially improves the overall survival (OS) of patients with LR-NPC, approximately 40% of the patients may develop local recurrence. The purpose of study is to assess the value of tumor volume (TV) as a predictive tool to guide individualized CIRT. METHODS: Consecutive patients with LR-NPC treated using CIRT at Shanghai Proton and Heavy Ion Center between April 2015 and May 2019 were included. TV before CIRT was delineated and calculated. The generalized additive Cox model was used to examine the relationship between TV and OS and local progression-free survival (LPFS). A cutoff value of tumor volume was identified to best discriminate patients with different 2-year OS rates, using receiver operating characteristic (ROC) analysis. RESULTS: A total of 157 patients were enrolled. The median tumor volume was 22.49 (2.52-90.13) ml. In the univariable analyses, tumor volume was significantly associated with OS (p < 0.001) and LPFS (p = 0.01). The relationships with OS (p = 0.009) and LPFS (p = 0.020) remained significant in multivariable analyses. Using ROC analysis, a TV of 26.69 ml was identified to predict the 2-year OS rate. To facilitate potential clinical use, 25 ml was designated as the final cutoff value. The 2-year OS and LPFS rates were 88.6 % vs 62.3 %, and 54.7 % vs 35.5 %, for patients with a TV ≤ 25 ml and > 25 ml, respectively. CONCLUSION: Tumor volume could predict the OS and LPFS of patients. We propose that tumor volume should be considered in the risk stratification and CIRT-based treatment for patients with LR-NPC.

Potential synergistic effects of cranial radiotherapy and atezolizumab in non-small cell lung cancer: an analysis of individual patient data from seven prospective trials.

Background: The impact of cranial radiotherapy (RT) on overall survival (OS) of patients with brain metastasis (BM) from non-small cell lung cancer (NSCLC) receiving programmed death 1/programmed death-ligand 1 (PD-1/PD-L1) inhibitors remains unclear. We aimed to examine the effect of previous cranial RT on the efficacy and neurological toxicity of PD-1/PD-L1 inhibitors in the treatment of patients with NSCLC. Methods: Patient-level data from seven prospective trials involving atezolizumab for the treatment of NSCLC [BIRCH (NCT02031458), FIR (NCT01846416), IMpower130 (NCT02367781), IMpower131 (NCT02367794), IMpower150 (NCT02366143), OAK (NCT02008227), and POPLAR (NCT01903993)] were pooled. Patients with baseline BM were divided into two subgroups based on previous cranial RT before initiation of treatment: patients with previously irradiated BM (iBM) and patients with non-irradiated BMs (niBM). Results: The per-protocol population consisted of 4,714 patients, including 3,176 in the atezolizumab group and 1,538 in the comparator chemotherapy group. In the atezolizumab group, OS was better in patients with BM (n=308) compared to patients without BM (n=2,868) [hazard ratio (HR): 0.83; 95% confidence interval (CI): 0.70-0.98; P=0.028]. Among patients with BM, patients with iBM (n=280) had a numerically longer OS (HR: 0.66; 95% CI: 0.41-1.07; P=0.090) than those with niBM (n=28). Intriguingly, OS was longer in patients with iBM than those without BM before (HR: 0.83; 95% CI: 0.70-0.99; P=0.043) and after (HR: 0.40; 95% CI: 0.32-0.49; P<0.0001) propensity score matching, while OS was similar between patients with niBM and those without BM. The survival advantage of patients with iBM over those without BM was not observed in the chemotherapy group. Atezolizumab-related serious neurological adverse events occurred in 16 (0.6%) patients without BM, none in those with niBM, and 2 (0.7%) patients with iBM. Conclusions: These data suggest potential synergistic effects of cranial RT and anti-PD-(L)1 therapy in NSCLC patients, which warrants further validation.

Cumulative incidence and risk factors of brain metastases in metastatic non-small cell lung cancer without baseline brain metastasis: Pooled analysis of individualized patient data from IMpower130, IMpower131, and IMpower150.

BACKGROUND: The objective of this study was to explore the abilities of atezolizumab plus chemotherapy in preventing brain metastases (BMs) among metastatic non-small cell lung cancer (NSCLC) without initial BMs, as well as the risk factors of BMs. METHODS: Individual patient data from three trials involving first-line atezolizumab for metastatic NSCLC (IMpower130, IMpower131, and IMpower150) were pooled. Among patients without baseline BMs and without epidermal growth factor receptor (EGFR) and/or anaplastic lymphoma kinase (ALK) mutations, those receiving atezolizumab + chemotherapy ± bevacizumab were classified as the atezolizumab plus chemotherapy group and those receiving placebo + chemotherapy ± bevacizumab were classified as the chemotherapy group. The cumulative incidences of BM (CI-BMs) between the two groups were compared. Other factors associated with the CI-BM were analyzed by Cox regression analyses. RESULTS: With a median follow-up of 17.6 months (range, 0.03-33.64 months), 74 (3.1%) of the 2380 enrolled patients developed BMs, including 50 (3.1%) and 24 (3.0%) in the atezolizumab plus chemotherapy group (n = 1589) and the chemotherapy group (n = 791), respectively. The CI-BMs at 6, 12, and 24 months were 1.7%, 2.8%, and 3.3%, respectively. After taking competing risk events into account, there was no significant difference in the CI-BMs between the two groups (p = .888). Nevertheless, the use of bevacizumab and the histology of nonsquamous NSCLC were found to be independently associated with the risk of BMs. CONCLUSIONS: In patients with metastatic EGFR/ALK wild-type NSCLC without baseline BMs, adding atezolizumab in the first-line treatment might not reduce the CI-BM. However, the administration of bevacizumab may reduce the risk of BMs.

Intracavity frequency-doubled yellow laser in an electron-phonon-coupled Nd:YVO4 crystal.

An approach to obtain a yellow laser is demonstrated for the first time to our knowledge by the employment of an Nd3+-doped YVO4 crystal and a LBO frequency-doubling crystal. Differing from the previous stimulated self-Raman radiation of Nd:YVO4, a direct 1176 nm lasing, without a high-intensity intracavity 1064 nm laser, was realized by utilizing an electron-phonon coupling effect and amplifying the thermally activated vibronic transitions. Combining with intracavity frequency-doubling, a yellow laser at 588 nm was obtained. At the pump power of 14.3 W, the output power of the yellow laser was 1.17 W, corresponding to a diode-to-visible efficiency of 8.2%. Moreover, for the first time, the yellow laser at 584 nm with output power of 164 mW was realized by tuning the filter, indicating the great potential of such an electron-phonon coupling laser for a wavelength extension in the yellow regime.

Transformed Salmonella typhimurium SL7207/pcDNA-CCOL2A1 as an orally administered DNA vaccine.

The use of attenuated bacteria for oral delivery of DNA vaccines is a recent innovation. We designed and constructed the naked plasmid DNA vaccine pcDNA-CCOL2A1, which effectively prevented and treated a rheumatoid arthritis model by inducing immunotolerance. We aimed to ensure a reliable, controllable dosage of this oral DNA vaccine preparation and establish its stability. We transformed pcDNA-CCOL2A1 via electroporation into attenuated Salmonella typhimurium SL7207. A resistant plate assay confirmed the successful construction of the transformed strain of the SL7207/pcDNA-CCOL2A1 oral DNA vaccine. We verified its identification and stability in vitro and in vivo. Significant differences were observed in the characteristics of the transformed and blank SL7207 strains. No electrophoretic restriction patterns or direct sequencing signals were observed in the original extract of the transformed strain. However, target gene bands and sequence signals were successfully detected after PCR amplification. CCOL2A1 expression was detected in the ilea of BALB/c mice that were orally administered SL7207/pcDNA-CCOL2A1. The pcDNA-CCOL2A1 plasmid of the transformed strain was retained under the resistant condition, and the transformed strain remained stable at 4 °C for 100 days. The concentration of the strain harboring the pcDNA-CCOL2A1 plasmid was stable at 109 CFU/mL after 6-8 h of incubation. The results demonstrated that the transformed strain SL7207/pcDNA-CCOL2A1 can be expressed in vivo, has good stability, and may be used to prepare the oral DNA vaccine pcDNA-CCOL2A1 with a stable, controllable dosage and the capacity to provide oral immunization. This vehicle can effectively combine both oral immunotolerance and DNA vaccination.

Angular Engineering Strategy for Enhanced Surface Nonlinear Frequency Conversion in Centrosymmetric Topological Semimetal HfGe0.92Te.

Surface nonlinear optics are essential for developments in integrated photonics and micro/nano optoelectronics. However, the nonlinear optical conversion efficiency on a surface is restricted by the finite nonlinear susceptibility of matter and the intrinsic atomic-layered interaction length between light and matter. In this work, based on an angular engineering strategy, it is demonstrated that the centrosymmetric topological semimetal HfGe0.92Te crystal has a giant and anisotropic surface second-order nonlinear susceptibility up to 5535 ± 308 pm V-1 and exhibits efficient and unprecedented second-harmonic generation (SHG). The maximum optical conversion efficiency is found to be up to 3.75‰, which is 104 times higher than that obtained from a silicon surface. Because of the linear dispersion over a wide range of energies around the Dirac points, this high conversion efficiency can be maintained with SHG wavelengths ranging from the visible region (779 nm) to the deep-UV region (257.5 nm). This study can facilitate the development of topological photonics and integrated nonlinear photonics based on topological semimetals.