Methodological validation of sedimentation velocity analytical ultracentrifugation method for Adeno-Associated Virus and collaborative calibration of system suitability substance.

Currently, adeno-associated virus (AAV) is one of the primary gene delivery vectors in gene therapy, facilitating long-term in vivo gene expression. Despite being imperative, it is incredibly challenging to precisely assess AAV particle distribution according to the sedimentation coefficient and identify impurities related to capsid structures. This study performed the systematic methodological validation of quantifying the AAV empty and full capsid ratio. This includes specificity, accuracy, precision, linearity, and parameter variables involving the sedimentation velocity analytical ultracentrifugation (SV-AUC) method. Specifically, SV-AUC differentiated among the empty, partial, full, and High Sedimentation Coefficient Substance (HSCS) AAV particles while evaluating their sedimentation heterogeneity. The intermediate precision analysis of HE (high percentage of empty capsid) and HF( high percentage of full capsid) samples revealed that the specific species percentage, such as empty or full, was more significant than 50%. Moreover, the RSD (relative standard deviation) could be within 5%. Even for empty or partial less than 15%, the RSD could be within 10%. The accuracy recovery rates of empty capsid were between 103.9% and 108.7% across three different mixtures. When the measured percentage of specific species was more significant than 14%, the recovery rate was between 77.9% and 106.6%. Linearity analysis revealed an excellent linear correlation between the empty, partial, and full in the HE samples. The AAV samples with as low as 7.4×1011 cp/mL AAV could be accurately quantified with SV-AUC. The parameter variable analyses revealed that variations in cell alignment significantly affected the overall results. Still, the detection wavelength of 235nm slightly influenced the empty, partial, and full percentages. Minor detection wavelength changes showed no impact on the sedimentation coefficient of these species. However, the temperature affected the measured sedimentation coefficient. These results validated the SV-AUC method to quantify AAV. This study provides solutions to AAV empty and full capsid ratio quantification challenges and the subsequent basis for calibrating the AAV empty capsid system suitability substance. Due to the AAV structure and potential variability complexity in detection, we jointly calibrated empty capsid system suitability substance with three laboratories to accurately detect the quantitative AAV empty and full capsid ratio. The empty capsid system suitability substance could be used as an external reference to measure the performance of the instrument. The results could be compared with multiple QC (quality control)laboratories based on the AAV vector and calibration accuracy. This is crucial for AUC to be used for QC release and promote gene therapy research worldwide.

Design, Synthesis, and Insecticidal Activity of Pyridino[1,2-a]pyrimidines Containing Indole Moeites at the 1-Position.

Research on mesoionic structures in pesticide design has gained significant attention in recent years. However, the 1-position of pyridino[1,2-a]pyrimidine is usually designed with 2-chlorothiazole, 2-chloropyridine, or cyano moieties commonly found in neonicotinoid insecticides. In order to enrich the available pharmacophore library, here, we disclose a series of new pyridino[1,2-a]pyrimidine mesoionics bearing indole-containing substituents at the 1-position. Most of these target compounds are confirmed to have good insecticidal activity against aphids through bioevaluation. In addition, a three-dimensional structure-activity relationship model is established to allow access to optimal compound F45 with an LC50 value of 2.97 mg/L. This value is comparable to the property achieved by the positive control triflumezopyrim (LC50 = 2.94 mg/L). Proteomics and molecular docking analysis suggest that compound F45 has the potential to modulate the functioning of the aphid nervous system through its interaction with neuronal nicotinic acetylcholine receptors. This study expands the existing pharmacophore library for the future development of new mesoionic insecticides based on 1-position modifications of the pyridino[1,2-a]pyrimidine scaffold.

Effects of biodegradable (PBAT/PLA) and conventional (LDPE) mulch film residues on bacterial communities and metabolic functions in different agricultural soils.

Soil health is a crucial aspect of sustainable agriculture and food production, necessitating attention to the ecological risks associated with substantial amounts of mulch film residues. Biodegradable mulch films (BDMs) carry the same risk of mulch film residues formation as low-density polyethylene (LDPE) mulch films during actual use. More information is needed to elucidate the specific impacts of mulch film residues on the soil environment. Integrated 16S rRNA gene sequencing and non-targeted metabolomics, this study revealed the response patterns of bacterial communities, metabolites, and metabolic functions in the soil from three different agricultural regions to the presence of mulch film residues. LDPE mulch film residues negatively impacted the bacterial communities in the soils of Heilongjiang (HLJ) and Yunnan (YN) and had a lesser impact on the metabolic spectrum in the soils of HLJ, YN, and Xinjiang (XJ). BDM residues had a greater negative impact on all three soils in terms of both the bacterial communities and metabolites. The impact of BDM treatment on the soils of HLJ, YN, and XJ increased sequentially in that order. It is recommended that, when promoting the use of biodegradable mulch films, a fuller assessment should be made, accounting for local soil properties.

Enhancement of Mn2+, Fe2+ and NH4+-N removal by biochar synergistic strains combined with activated sludge in real wastewater treatment.

Acinetobacter sp. AL-6 combining with biochar was adapted in activated sludge (AS & co-system) to decontaminate Mn2+, Fe2+ and NH4+-N, and treat activated sludge (AS) for its activity and settling performance improvement. Specifically, the co-system promoted the growth of bacteria in the activated sludge, thus increasing its ability to nitrify and adsorb Mn2+ and Fe2+, resulting in the removal of high concentrations of NH4+-N, Mn2+, Fe2+ and COD in the reactor by 100%, 100%, 100%, and 96.8%, respectively. And the pH of wastewater was increased from 4 to 8.5 by co-system also facilitated the precipitation of Mn2+ and Fe2+. The MLVSS/MLSS ratio increased from 0.64 to 0.95 and SVI30 decreased from 92.54 to 1.54 after the addition of co-system, which indicated that biochar helped to improve the activity and settling performance of activated sludge and prevented it from being damaged by the compound Mn2+ and Fe2+. In addition, biochar promoted the increase of the tyrosine-like protein substance and humic acid-like organic matter in the sludge EPS, thus enhanced the ability of sludge to adsorb Mn2+ and Fe2+. Concretely, compared with AS group, the proteins content and polysaccharides content of the AS & co-system group were increased by 13.14 times and 6.30 times respectively. Further, microbial diversity analysis showed that more resistant bacteria and dominant bacteria Acinetobacter sp. AL-6 in sludge enhanced the nitrification and adsorption of manganese and iron under the promotion of biochar. Pre-eminently, the more effective AS & co-system were applied to the removal of actual electrolytic manganese slag leachate taken from the contaminated site, and the removal of NH4+-N, Mn2+, Fe2+ and COD remained high at 100%, 100%, 71.82% and 94.72%, respectively, revealing advanced value for high engineering applications of AS & co-system.

Development and validation of an interpretable radiomic signature for preoperative estimation of tumor mutational burden in lung adenocarcinoma.

Background: Tumor mutational burden (TMB) is a promising biomarker for immunotherapy. The challenge of spatial and temporal heterogeneity and high costs weaken its power in clinical routine. The aim of this study is to estimate TMB preoperatively using a volumetric CT-based radiomic signature (rMB). Methods: Seventy-one patients with resectable lung adenocarcinoma (LUAD) who underwent whole-exome sequencing (WXS) from 2011 to 2014 were enrolled from the institutional biobank of Tianjin Medical University Cancer Institute and Hospital (TMUCIH). Forty-nine LUAD patients with WXS from the Cancer Genome Atlas Program (TCGA) served as the external validation cohort. Computed tomography (CT) volumes were resampled to 1-mm isotropic, semi-automatically segmented, and manually adjusted by two radiologists. A total of 3,108 radiomic features were extracted via PyRadiomics and then harmonized across cohorts by ComBat. Features with inter-segmentation intra-class correlation coefficient (ICC) > 0.8, low collinearity, and significant univariate power were passed to the least absolute shrinkage and selection operator (LASSO)-logistic classifier to discriminate TMB-high/TMB-low at a threshold of 10 mut/Mb. The receiver operating characteristic (ROC) curve analysis and calibration curve were used to determine its efficiency. Shapley values (SHAP) attributed individual predictions to feature contributions. Clinical variables and circulating biomarkers were collected to find potential associations with TMB and rMB. Results: The top frequently mutated genes significantly differed between the Chinese and TCGA cohorts, with a median TMB of 2.20 and 3.46 mut/Mb and 15 (21.12%) and 9 (18.37%) cases of TMB-high, respectively. After dimensionality reduction, rMB comprised 21 features, which reached an AUC of 0.895 (sensitivity = 0.867, specificity = 0.875, and accuracy = 0.873) in the discovery cohort and 0.878 (sensitivity = 1.0, specificity = 0.825, and accuracy = 0.857 in a consist cutoff) in the validation cohort. rMB of TMB-high patients was significantly higher than rMB of TMB-low patients in both cohorts (p < 0.01). rMB was well-calibrated in the discovery cohort and validation cohort (p = 0.27 and 0.74, respectively). The square-filtered gray-level concurrence matrix (GLCM) correlation was of significant importance in prediction. The proportion of circulating monocytes and the monocyte-to-lymphocyte ratio were associated with TMB, whereas the circulating neutrophils and lymphocyte percentage, original and derived neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio were associated with rMB. Conclusion: rMB, an intra-tumor radiomic signature, could predict lung adenocarcinoma patients with higher TMB. Insights from the Shapley values may enhance persuasiveness of the purposed signature for further clinical application. rMB could become a promising tool to triage patients who might benefit from a next-generation sequencing test.

Prediction of tumor origin in cancers of unknown primary origin with cytology-based deep learning.

Cancer of unknown primary (CUP) site poses diagnostic challenges due to its elusive nature. Many cases of CUP manifest as pleural and peritoneal serous effusions. Leveraging cytological images from 57,220 cases at four tertiary hospitals, we developed a deep-learning method for tumor origin differentiation using cytological histology (TORCH) that can identify malignancy and predict tumor origin in both hydrothorax and ascites. We examined its performance on three internal (n = 12,799) and two external (n = 14,538) testing sets. In both internal and external testing sets, TORCH achieved area under the receiver operating curve values ranging from 0.953 to 0.991 for cancer diagnosis and 0.953 to 0.979 for tumor origin localization. TORCH accurately predicted primary tumor origins, with a top-1 accuracy of 82.6% and top-3 accuracy of 98.9%. Compared with results derived from pathologists, TORCH showed better prediction efficacy (1.677 versus 1.265, P < 0.001), enhancing junior pathologists' diagnostic scores significantly (1.326 versus 1.101, P < 0.001). Patients with CUP whose initial treatment protocol was concordant with TORCH-predicted origins had better overall survival than those who were administrated discordant treatment (27 versus 17 months, P = 0.006). Our study underscores the potential of TORCH as a valuable ancillary tool in clinical practice, although further validation in randomized trials is warranted.

Transient receptor potential channels in sensory mechanisms of the lower urinary tract.

Urine storage and excretion require a network of interactions in the urinary tract and the central nervous system (CNS), which is mediated by a reservoir of water in the bladder and the outlet to the bladder neck, urethra and external urethral sphincter. Through communicating and coordinating each other, micturition system eventually showed a switch-like activity pattern. At cervicothoracic and lumbosacral spine, the spinal reflex pathway of the lower urinary tract (LUT) received mechanosensory input from the urothelium to regulate the bladder contraction activity, thereby controlled urination voluntarily. Impairment of above-mentioned any level could result in lower urinary tract dysfunction (LUTD), placed a huge burden on patients and society. Specific expression of purinergic receptors and transient receptor potential (TRP) channels are thought to play an important role in urinary excretion in the lower urinary tract. This article reviewed the knowledge about the voiding reflex and described the role and function of TRP channels during voiding.

Variation the in relationship between urban tree canopy and air temperature reduction under a range of daily weather conditions.

Mitigating heat is a vital ecosystem service of trees, particularly with climate change. Land surface temperature measures captured at a single time of day (in the morning) dominate the urban heat island literature. Less is known about how local tree canopy and impervious surface regulate air temperature throughout the day, and/or across many days with varied weather conditions, including cloud cover. We use bike-mounted air temperature sensors throughout the day in New Haven, Connecticut, USA, from 2019 to 2021 and generalized additive mixed models across 156 rides to estimate the daily variation in cooling benefits associated with tree canopy cover, and warming from impervious surface cover in 90 m buffers surrounding bike observations. Cooling is inferred by subtracting the bicycle-observed temperature from a reference station. The cooling benefits from tree canopy cover were strongest in the midday (11:00-14:00, -1.62 °C), afternoon (14:00-17:00, -1.19 °C), and morning (8:00-11:00, -1.15 °C) on clear days. The cooling effect was comparatively smaller on cloudy mornings -0.92 °C and afternoons -0.51 °C. Warming from impervious surfaces was most pronounced in the evening (17:00-20:00, 1.11 °C) irrespective of clouds, and during cloudy nights (20:00-23:00) and cloudy mornings 1.03 °C 95 % CI [1.03, 1.04]. Among the hottest observed days (top 25th percentile of reference station daily maxima), tree canopy was associated with lower temperatures on clear afternoons -1.78 °C [-1.78, -1.78], cloudy midday -1.17 °C [-1.19, -1.15], clear midday -1.12 °C [-1.12, -1.11]. We add a broader spectrum of weather conditions by explicitly including clouds, and greater temporal resolution by measuring throughout the day to bike-based urban heat research. Future mobile sampling campaigns may broaden the spatial extent with more environmental variation, representing an opportunity for public science and engagement.

Bright and Stable Red Perovskite LEDs under High Current Densities.

Perovskite LEDs (PeLEDs) have emerged as a next-generation light-emitting technology. Recent breakthroughs were made in achieving highly stable near-infrared and green PeLEDs. However, the operational lifetimes (T50) of visible PeLEDs under high current densities (>10 mA cm-2) remain unsatisfactory (normally <100 h), limiting the possibilities in solid-state lighting and AR/VR applications. This problem becomes more pronounced for mixed-halide (e.g., red and blue) perovskite emitters in which critical challenges such as halide segregation and spectral instability are present. Here, we demonstrate bright and stable red PeLEDs based on mixed-halide perovskites, showing measured T50 lifetimes of up to ∼357 h at currents of ≥25 mA cm-2, a record for the operational stability of visible PeLEDs under high current densities. The devices produce intense and stable emission with a maximum luminance of 28,870 cd m-2 (radiance: 1584 W sr-1 m-2), which is record-high for red PeLEDs. Key to this demonstration is the introduction of sulfonamide, a dipolar molecular stabilizer that effectively interacts with the ionic species in the perovskite emitters. It suppresses halide segregation and migration into the charge-transport layers, resulting in enhanced stability and brightness of the mixed-halide PeLEDs. These results represent a substantial step toward bright and stable PeLEDs for emerging applications.

Survival outcome and prognostic factors for early-onset and late-onset metastatic colorectal cancer: a population based study from SEER database.

Colorectal cancer is the third most common cancer worldwide and there has been a concerning increase in the incidence rate of colorectal cancer among individuals under the age of 50. This study compared the survival outcome between early-onset and late-onset metastatic colorectal cancer to find the differences and identify their prognostic factors. We obtained patient data from SEER database. Survival outcome was estimated using Kaplan-Meier survival curves and compared using the log-rank test. Univariate and multivariate analyses were conducted utilizing COX models to identify their independent prognostic factors. A total of 10,036 early-onset metastatic colorectal (EOCRC) cancer patients and 56,225 late-onset metastatic colorectal cancer (LOCRC) patients between 2010 and 2019 were included in this study. EOCRC has more survival benefits than LOCRC. Tumor primary location (p < 0.001), the location of metastasis (p < 0.001) and treatment modalities (p < 0.001) affect the survival outcomes between these two groups of patients. Female patients had better survival outcomes in EOCRC group (p < 0.001), but no difference was found in LOCRC group (p = 0.57). In conclusion, our study demonstrated that EOCRC patients have longer survival time than LOCRC patients. The sex differences in survival of metastatic colorectal cancer patients are associated with patients' age. These findings contribute to a better understanding of the differences between metastatic EOCRC and LOCRC, and can help inform the development of more precise treatment guidelines to improve prognosis.

Time-Lapse Macro Imaging with Dissolution Tests for Exploring the Interrelationship Between Disintegration and Dissolution Behaviors of Solid Dosages.

OBJECTIVE: This study aims to establish a Flow-through Visualization Dissolution System (FVDS) that combines time-lapse macro-imaging and a flow-through cell to simultaneously elucidate dissolution and disintegration profiles. METHODS: Three cefaclor extended-release tablets (CEC-1, CEC-2, CEC-3) from different manufacturers were subjected to dissolution tests using both the US Pharmacopeia basket method and the FVDS method. Two dissolution media plans were implemented in FVDS: i) Plan I involved dissolution in pH1.0 medium for 12 h; ii) Plan II initiated dissolution in pH1.0 medium for 1 h, followed by pH6.8 phosphate buffer for 11 h. The resulting dissolution data were fitted using classic mathematical models. Pixel information was further extracted from images obtained using FVDS and plotted over time. RESULTS: The basket method showed the cumulative dissolution of all three tablets in pH1.0, pH4.0 and water reached 80% within 6 h, but remained below 60% in the pH6.8 medium. The f2 values indicated CEC-2 was similar to CEC-1 in the pH4.0 medium, pH6.8 medium and water. Using FVDS with medium plan II, the cumulative dissolution of CEC-1 and CEC-2 reached about 80% showing similarity, while no similarity was observed between CEC-3 and CEC-1. The f2 factor of the percentage area change profiles also showed consistent results in the dissolution profile of medium plan II. However, FVDS with medium plan I cannot distinguish between CEC-2 and CEC-3. CONCLUSION: FVDS offers an alternative to traditional dissolution methods by integrating imaging analysis as a complementary tool to disintegration and dissolution testing methods.

Ochrobactrum chromiisoli sp. nov., Isolated from Chromium-Contaminated Soil.

A Gram-stain-negative, non-spore-forming, flagellated, motile, aerobic, rod-shaped bacteria strain, designated YY2XT, was isolated from chromium-contaminated soil. Phylogenetic analysis based on 16S rRNA gene, recA gene, and whole genome indicated that the strain represented a new member of the genus Ochrobactrum, family Brucellaceae, class Alphaproteobacteria. The phylogenetic trees based on 16 s rRNA gene, revealed that Falsochrobactrum ovis DSM26720T (96.7%), Ochrobactrum gallinifaecis DSM15295T (96.2%), and Pseudochrobactrum asaccharolyticum DSM25619T (96.2%) are the most closely related phylogenetic neighbors of strain YY2XT. The draft genome of YY2XT was approximately 4,650,646 bp in size with a G + C content of 53.0 mol%. Average nucleotide identity and digital DNA-DNA hybridization values among strain YY2XT and the selected Brucellaceae species were 71.4-83.1% and 13.5-42.7%, which are below the recommended cut-off values for species delineation. Growth of strain YY2XT occurred within pH 5-10 (optimum, pH 7-8), 4 â„ƒ-42 °C (optimum, 30 °C), and NaCl concentrations of 0.0-6.0% (optimum, 1.0%). Major quinone system was ubiquinone 10, the major fatty acids were C16:0, C18:1ω7c, and C16:1ω7c and the major polyamines were spermidine and putrescine. Major polar lipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylcholine, phosphatidylmonomethylethanolamine, phosphatidylethanolamine, and four undefined lipids. On the basis of the phenotypic, genotypic and chemotaxonomic traits, strain YY2XT was considered to represent a novel species of the genus Ochrobactrum, for which the name Ochrobactrum chromiisoli sp. nov. is proposed. The type strain is YY2XT (= CCTCC AB 2023035T = JCM 36000T).

Survival benefits of palliative gastrectomy for gastric cancer patients with liver metastasis: a population-based propensity score-matched cohort analysis.

Background and aims: Palliative primary tumor resection (pPTR) can benefit colorectal cancer patients with liver metastasis. Whether pPTR benefiting gastric cancer (GC) patients with liver metastasis is still controversial. Methods: Data on patients with metastatic GC diagnosed between 2010 to 2019 was extracted from SEER database. Propensity score analysis with 1:1 matching was performed. The univariable and multivariable Cox proportional hazards regression models were used to explore prognostic factors. Kaplan-Meier method was used to analyze survival outcomes. Results: Of 5691 GC patients with liver metastasis, 468 were included in the matched cohorts. The results showed that the median survival time was 6 months in the non-surgery groups and 14.5 months in the surgery groups (p < 0.001). Multivariable analysis showed that surgery was a protective prognostic factor for overall survival [hazard ratio (HR) = 0.416] as well as cancer-specific survival (HR = 0.417). Also, pPTR was only recommended for GC patients with isolated liver metastasis. Moreover, pPTR combined with chemotherapy brought the greatest therapeutic effect. Conclusion: pPTR benefits GC patients with isolated liver metastasis, and GC patients with liver metastasis receiving pPTR combined with chemotherapy had the best survival outcomes than any other therapeutic model.

Parishin treatment alleviates cardiac aging in naturally aged mice.

Background: Cardiac aging progressively decreases physiological function and drives chronic/degenerative aging-related heart diseases. Therefore, it is crucial to postpone the aging process of heart and create products that combat aging. Aims & methods: The objective of this study is to examine the effects of parishin, a phenolic glucoside isolated from traditional Chinese medicine Gastrodia elata, on anti-aging and its underlying mechanism. To assess the senescent biomarkers, cardiac function, cardiac weight/body weight ratio, cardiac transcriptomic changes, and cardiac histopathological features, heart tissue samples were obtained from young mice (12 weeks), aged mice (19 months) treated with parishin, and aged mice that were not treated. Results: Parishin treatment improved cardiac function, ameliorated aging-induced cardiac injury, hypertrophy, and fibrosis, decreased cardiac senescence biomarkers p16Ink4a, p21Cip1, and IL-6, and increased the "longevity factor" SIRT1 expression in heart tissue. Furthermore, the transcriptomic analysis demonstrated that parishin treatment alleviated the cardiac aging-related Gja1 downregulation and Cyp2e1, Ccna2, Cdca3, and Fgf12 upregulation in the heart tissues. The correlation analysis suggested a strong connection between the anti-aging effect of parishin and its regulation of gut microbiota and metabolism in the aged intestine. Conclusion: The present study demonstrates the protective role and underlying mechanism of parishin against cardiac aging in naturally aged mice.

Leucobacter edaphi sp. nov., a highly chromate-tolerant bacterium isolated from chromium containing chemical plant soil.

A Gram-positive, aerobic, rod-shaped non-motile, non-sporulating bacterium, designated CSA2T, was isolated from chromium-containing soils collected from a chemical plant. The 16S rRNA gene sequence of strain CSA2T showed the highest homology with Leucobacter chromiireducens subsp. solipictus (97.85%), Leucobacter chromiireducens subsp. chromiireducens (97.85%). The digital DNA-DNA hybridization (dDDH), average nucleotide identity (ANI) and the amino acid identity (AAI) values among strains CSA2T and the selected Leucobacter species were 20.6-23.4% (dDDH), 72.67-78.03% (ANI) and 66.39-76.16% (AAI), falling below the recommended thresholds for species delimitation. The principal fatty acids were anteiso-C15:0, iso-C16:0 and anteiso-C17:0. The polar lipids were phosphatidylglycerol, diphosphatidylglycerol and an unknown glycolipid. The major menaquinones detected were MK-10 and MK-11. The cell-wall amino acids included 2,4-diaminobutyric acid, threonine, glutamic acid, alanine and glycine. Based on molecular feature, phenotypic and chemotaxonomic, strain CSA2T was considered to be a novel species of the genus Leucobacter., and the name Leucobacter edaphi sp. nov. is proposed. The type strain is CSA2T (= JCM 34360T = CGMCC 1.18747T).

Transcriptome screening identifies TIPARP as an antiviral host factor against the Getah virus.

IMPORTANCE: Alphaviruses threaten public health continuously, and Getah virus (GETV) is a re-emerging alphavirus that can potentially infect humans. Approved antiviral drugs and vaccines against alphaviruses are few available, but several host antiviral factors have been reported. Here, we used GETV as a model of alphaviruses to screen for additional host factors. Tetrachlorodibenzo-p-dioxin-inducible poly(ADP ribose) polymerase was identified to inhibit GETV replication by inducing ubiquitination of the glycoprotein E2, causing its degradation by recruiting the E3 ubiquitin ligase membrane-associated RING-CH8 (MARCH8). Using GETV as a model virus, focusing on the relationship between viral structural proteins and host factors to screen antiviral host factors provides new insights for antiviral studies on alphaviruses.

Flat bands, non-trivial band topology and rotation symmetry breaking in layered kagome-lattice RbTi3Bi5.

A representative class of kagome materials, AV3Sb5 (A = K, Rb, Cs), hosts several unconventional phases such as superconductivity, [Formula: see text] non-trivial topological states, and electronic nematic states. These can often coexist with intertwined charge-density wave states. Recently, the discovery of the isostructural titanium-based single-crystals, ATi3Bi5 (A = K, Rb, Cs), which exhibit similar multiple exotic states but without the concomitant charge-density wave, has opened an opportunity to disentangle these complex states in kagome lattices. Here, we combine high-resolution angle-resolved photoemission spectroscopy and first-principles calculations to investigate the low-lying electronic structure of RbTi3Bi5. We demonstrate the coexistence of flat bands and several non-trivial states, including type-II Dirac nodal lines and [Formula: see text] non-trivial topological surface states. Our findings also provide evidence for rotational symmetry breaking in RbTi3Bi5, suggesting a directionality to the electronic structure and the possible emergence of pure electronic nematicity in this family of kagome compounds.

Clinicopathological and genetic characteristics of gastric neuroendocrine tumour (NET) G3 and comparisons with neuroendocrine carcinoma and NET G2.

AIMS: To characterise the clinicopathological and genetic characteristics of gastric neuroendocrine tumour G3 (gNET G3) and to compare them with those of gastric neuroendocrine carcinoma (gNEC) and gNET G2. METHODS AND RESULTS: A total of 115 gastric neuroendocrine neoplasms (NENs) were included, of which gNET G3 was different from gNET G1/G2 in terms of tumour location (P = 0.029), number (P = 0.003), size (P = 0.010), the Ki67 index (P < 0.001), lymph node metastasis (P < 0.001) and TNM stage (P = 0.011), and different from gNEC/gastric mixed neuroendocrine-non-neuroendocrine neoplasm (gMiNEN) in terms of tumour size (P = 0.010) and the Ki67 index (P = 0.001). High-resolution copy number (CN) profiling and validation experiments showed CN gains and high expression of DLL3 in gNET G3. Hierarchical clustering analysis based on CN characteristics showed that gNET G3 was separated from gNEC but mixed with gNET G2. In gene set enrichment analysis, eight pathways were significantly enriched in gNEC when comparing gNET G3 and gNEC (P < 0.05), while no pathways were enriched when comparing gNET G3 and gNET G2. Whole-exome sequencing and validation experiments showed nonsense mutation of TP53 in one gNET G3, with wild-type staining for p53. In gNEC, TP53 mutations were detected in four of eight cases, and abnormal expression of p53 was detected in all cases. CONCLUSION: Gastric NET G3 is a distinct entity with unique genetic characteristics, which are different from those of gNEC than gNET G2. Our results provide insight into some molecular alterations that may contribute to the development and progression of gNET G3 and serve as potential therapeutic targets.

Meta-analysis of the correlation between CT-based features and invasive properties of pure ground-glass nodules.

Several studies have revealed that computed tomography (CT) features can make a distinction in the invasive properties of pure ground-glass nodules (pGGNs). However, imaging parameters related to the invasive properties of pGGNs are unclear. This meta-analysis was designed to decipher the correlation between the invasiveness of pGGNs and CT-based features, and ultimately to be conducive to making rational clinical decisions. We searched a series of databases, including PubMed, Embase, Web of Science, Cochrane Library, Scopus, wanfang, CNKI, VIP, as well as CBM databases, until September 20, 2022, for the eligible publications only in Chinese or English. This meta-analysis was implemented with the Stata 16.0 software. Ultimately, 17 studies published between 2017 and 2022 were included. According to the meta-analysis, we observed a larger maximum size of lesions in invasive adenocarcinoma (IAC) versus that in preinvasive lesions (PIL) [SMD = 1.37, 95% CI (1.07-1.68), P < 0.05]. Meanwhile, there were also increased mean CT values of IAC [SMD = 0.71, 95% CI (0.35, 1.07), P < 0.05], the incidence of pleural traction sign [OR = 1.94, 95% CI (1.24, 3.03), P < 0.05], the incidence of IAC spiculation [OR = 1.55, 95% CI (1.05, 2.29), P < 0.05] in comparison to those of PIL. Nevertheless, IAC and PIL exhibited no significant differences in vacuole sign, air bronchogram, regular shape, lobulation and vascular convergence sign (all P > 0.05). Therefore, IAC and PIL manifested different CT features of pGGNs. The maximum diameter of lesions, mean CT value, pleural traction sign and spiculation are important indicators to distinguish IAC and PIL. Reasonable use of these features can be helpful to the treatment of pGGNs.