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To evaluate the efficacy and safety of Cidan Capsule combined with adjuvant transarterial chemoembolization (TACE) in patients with a high risk of early recurrence after curative resection of hepatocellular carcinoma (HCC).A multicenter, randomized controlled trial was conducted in patients with high-risk recurrence factors after curative resection of HCC from 9 medical centers between July 2014 and July 2018. Totally 249 patients were randomly assigned to TACE with or without Cidan Capsule administration groups by stratified block in a 1:1 ratio. Postoperative adjuvant TACE was given 4-5 weeks after hepatic resection in both groups. Additionally, 125 patients in the TACE plus Cidan group were administrated Cidan Capsule (0.27 g/capsule, 5 capsules every time, 4 times a day) for 6 months with a 24-month follow-up. Primary endpoints included disease-free survival (DFS) and tumor recurrence rate (TRR). Secondary endpoint was overall survival (OS). Any drug-related adverse events (AEs) were observed and recorded.As the data cutoff in July 9th, 2018, the median DFS was not reached in the TACE plus Cidan group and 234.0 days in the TACE group (hazard ratio, 0.420, 95% confidence interval, 0.290-0.608; P0.01). The 1- and 2-year TRR in the TACE plus Cidan and TACE groups were 31.5%, 37.1%, and 60.8%, 63.4%, respectively (P0.01). Median OS was not reached in both groups. The 1- and 2-year OS rates in TACE plus Cidan and TACE groups were 98.4%, 98.4%, and 89.5%, 87.9%, respectively (P0.05). The most common grade 3-4 AEs included fatigue, abdominal pain, lumbar pain, and nausea. One serious AE was reported in 1 patient in the TACE plus Cidan group, the death was due to retroperitoneal mass hemorrhage and hemorrhagic shock, and was not related to study drug.Cidan Capsule in combination with TACE can reduce the incidence of early recurrence in HCC patients at high-risk of recurrence after radical hepatectomy and may be an appropriate option in postoperative anti-recurrence treatment. (Registration No. NCT02253511).

High temperatures during flowering stage affects the seed setting in maize and thereby result in significant yield penalties in recent changing climate era. Based on the daily maximum temperature data of the maize growing season from 1971 to 2019 at the surface meteorological observatory in Henan Province of China and maize observation data at the agricultural meteorological observatory, an early warning grade of high temperatures during the summer maize flowering stage was constructed. The daily maximum temperature of the summer maize flowering stage was ≥ 32 °C as the critical threshold of high temperature disaster, and ≥ 35 °C as the threshold of high temperature disaster. The number of high temperature days (HD) ≥ 32 °C and ≥ 35 °C during 10 days of the summer maize flowering stage were counted. The sequence of high temperature days of summer maize flowering stage was constructed and its normal distribution characteristics were verified. The quartile value of the normal distribution sequence was selected as the threshold value of high temperature in different grades, and the high temperature heat damage in the summer maize flowering stage was divided into three early warning meteorological grades. The index verification of the early warning meteorological grade was carried out by using the observation data of kernel number per ear in the agricultural meteorological station for maize. The results showed that the three grade indexes corresponding to the number of high temperature days with daily maximum temperature ≥ 32 °C were: 3 ≤ HD HD HD ≥ 7 (Grade III) and the three grade indexes corresponding to high temperature days ≥ 35 °C were: 2 ≤ HD HD HD ≥ 5 (Grade III). The constructed indexes were verified as follows, the number of high temperature days ≥ 32 °C at about 90% stations was significantly negatively correlated with the number of maize grains per ear, and 74% stations which the number of high temperature days ≥ 35 °C was significantly negatively correlated with the number of maize grains per ear. Applying this index to evaluate the high temperature risk in the flowering period, we can indicate that the high temperature risk had trend of increasing gradually from north to south. In conclusion, the constructed high temperature warning meteorological grade index during the flowering stage could accurately reflect the damage grade of maize during the flowering stage.

Tungsten carbide is widely used as the material of replication mold to produce small aspheric optics, and the polishing process determines the precision of the mold. However, for micro-aspheric tungsten carbide mold, the existing polishing methods are difficult to realize the from error modification during the polishing because the polishing tool is always larger than small mold. Therefore, a polishing tool which using polyester fiber cloth to wrap small-size rigid ball is used in this paper. In order to predict the tool influence function (TIF) of this polishing tool, a series of theoretical analysis and experimental verification are carried out in this paper. Firstly, by analyzing the structural and viscoelastic characteristics of the fiber cloth, the pressure distribution in the polishing contact area is determined. And the polishing speed distribution is obtained by analyzing the kinematic movement of the polishing tool; Then, combined with Preston equation, the tool influence function is derived; Afterward, through a series of single point polishing experiments, it is verified that the volume error between the theoretical removal model and the experimental removal is less than 10.8%; Finally, the tool influence function is applied to the form error corrective polishing of small size symmetric aspheric tungsten carbide mold. After one form error corrective polishing, the PV value (Peak to Valley) of form error is decreased from 0.405um to 0.068um, which verifies the effectiveness of the polishing method of small size tungsten carbide mold in form error correction.

Lung adenocarcinoma (LUAD) characterized by high metastasis and mortality is the leading subtype of non-small cell lung cancer. Evidence shows that some microRNAs (miRNAs) may act as oncogenes or tumor suppressor genes, leading to malignant tumor occurrence and progression. To better understand the molecular mechanism associated with miRNA methylation in LUAD progression and clinical outcomes, we investigated the correlation between miR-148a-3p methylation and the clinical features of LUAD. In the LUAD cell lines and tumor tissues from patients, miR-148a-3p was found to be significantly downregulated, while the methylation of miR-148a-3p promoter was notably increased. Importantly, miR-148a-3p hypermethylation was closely associated with lymph node metastasis. We demonstrated that mitogen-activated protein (MAP) kinase kinase kinase 9 (MAP3K9) was the target of miR-148a-3p and that MAP3K9 levels were significantly increased in both LUAD cell lines and clinical tumor tissues. In A549 and NCI-H1299 cells, overexpression of miR-148a-3p or silencing MAP3K9 significantly inhibited cell growth, migration, invasion and cytoskeleton reorganization accompanied by suppressing the epithelial-mesenchymal transition. In a nude mouse xenograft assay we found that tumor growth was effectively inhibited by miR-148a-3p overexpression. Taken together, the promoter methylation-associated decrease in miR-148a-3p could lead to lung cancer metastasis by targeting MAP3K9. This study suggests that miR-148a-3p and MAP3K9 may act as novel therapeutic targets for the treatment of LUAD and have potential clinical applications.

Individual tree structure mapping in cities is important for urban environmental studies. Despite mapping products for tree canopy cover and biomass are reported at multiple spatial scales using various approaches, spatially explicit mapping of individual trees and their three-dimensional structure is sparse. Here we produced an individual tree dataset including tree locations, height, crown area, crown volume, and biomass over the entire New York City, USA for 6,005,690 trees. Individual trees were detected and mapped from remotely sensed datasets along with their height and crown size information. Tree biomass in 296 field plots was measured and modelled using i-Tree Eco. Wall-to-wall tree biomass was mapped using relationships between field measurements and remotely sensed datasets and downscaled to individual trees. Validation using field-plot measurements indicated that our mapping products overestimated tree number, mean tree height and maximum tree height by 11.1%, 8.6%, and 5.3%, respectively. These overestimations were mainly due to the spatial and temporal mis-match between field measurements and remote sensing observations and uncertainties in tree segmentation algorithms. This dataset enables the evaluation of urban forest ecosystem services including regulating urban heat and promoting urban health, which can provide valuable insights for urban forest management and policy making.

Geospatial models can facilitate the delineation of food access patterns, which is particularly relevant for urban planning and health policymaking. Because community food environmental studies use different analysis units or study scales, the rigor and consistency of their evaluations cannot be ensured. This issue is known as the modifiable areal unit problem (MAUP). The paper provides a systematic review of past literature on place-based community food environmental research using different analysis units or geospatial models as they pertain to the MAUP. We identify these key findings: (1) the ZIP code zone is not recommended as an appropriate analysis unit for modeling community food access, as it did not have significant correlations with health indicators; (2) using a circular buffer of less than 0.5 km around household locations is most likely to reveal health correlations, compared with network buffers or container-based measures; (3) to reveal health effects of the community food environment, it is recommended to focus in selected regions or partitions of a study area with similar socioeconomic statuses, such as the central city or low socioeconomic status areas; (4) for studies utilizing a single statistical unit or distance measure, it is suggested to discuss the existence of the MAUP, such as evaluating the sensitivity of the model to the change of the unit or the distance measure. By highlighting the MAUP, this paper has policy implications—given that geospatial modeling of food accessibility provides support for health policy intervention, using different metrics may lead to different interpretations of health disparities and could thus misinform policy decisions. Therefore, any assessment of community food environments that may potentially lead to a policy change should consider the effects of the MAUP.

Non-small cell lung cancer (NSCLC) is characterized by a high incidence of metastasis and poor survival. As epithelial–mesenchymal transition (EMT) is well recognized as a major factor initiating tumor metastasis, developing EMT inhibitor could be a feasible treatment for metastatic NSCLC. Recent studies show that triptolide isolated from Tripterygium wilfordii Hook F attenuated the migration and invasion of breast cancer, colon carcinoma, and ovarian cancer cells, and EMT played important roles in this process. In the present study we investigated the effect of triptolide on the migration and invasion of NSCLC cell lines. We showed that triptolide (0.5, 1.0, 2.0 nM) concentration-dependently inhibited the migration and invasion of NCI-H1299 cells. Triptolide treatment concentration-dependently suppressed EMT in NCI-H1299 cells, evidenced by significantly elevated E-cadherin expression and reduced expression of ZEB1, vimentin, and slug. Furthermore, triptolide treatment suppressed β-catenin expression in NCI-H1299 and NCI-H460 cells, overexpression of β-catenin antagonized triptolide-caused inhibition on EMT, whereas knockout of β-catenin enhanced the inhibitory effect of triptolide on EMT. Administration of triptolide (0.75, 1.5 mg/kg per day, ip, every 2 days) for 18 days in NCI-H1299 xenograft mice dose-dependently suppressed the tumor growth, restrained EMT, and decreased lung metastasis, as evidence by significantly decreased expression of mesenchymal markers, increased expression of epithelial markers as well as reduced number of pulmonary lung metastatic foci. These results demonstrate that triptolide suppresses NSCLC metastasis by targeting EMT via reducing β-catenin expression. Our study implies that triptolide may be developed as a potential agent for the therapy of NSCLC metastasis.

We investigated high-resistivity cadmium zinc telluride (CdZnTe):In single crystals annealed in hydrogen to reveal the passivation effect of defects. An overall reduction in the concentration of defect levels induced by annealing was obviously observed by thermally stimulated current measurements. There is a large decrease by 56.51% in the concentration of secondly ionized Cd vacancies (T3) after hydrogenation. The concentration of firstly ionized Cd vacancies (T2) was a little bit lower (17.99%) in the hydrogenated CZT crystals. The formation of neutral InH complex and lower occupation of VCd by In dopant would result in a significant decrease (68.31%) in the trap density of $${\rm In}_{\rm Cd}^ +$$ related shallow donor (T1) after hydrogenation. The bulk resistivity was calculated from I–V characteristic curves to be ~1.97 × 1010 Ωcm before annealing and ~1.78 × 1010 Ωcm after annealing. Hall measurements also reveal n-type conduction for the hydrogenated crystals. Electron mobility was fitted to be about 110 cm2/Vs before annealing and 488 cm2/Vs after annealing, demonstrating better carrier transport properties. Electron mobility-lifetime product could be fitted to be about 3.60 × 10−4 cm2/V before annealing and 5.45 × 10−4 cm2/V after annealing, demonstrating better detector performances.

Spray drying biologics into a powder can increase thermal stability and shelf-life relative to liquid formulations, potentially eliminating the need for cold chain infrastructure for distribution in developing countries. In this study, process modelling, microparticle engineering, and a supplemented phase diagram were used to design physically stable fully amorphous spray-dried powder capable of stabilizing biological material. A greater proportion of anti-Campylobacter bacteriophage CP30A remained biologically active after spray drying using excipient formulations containing trehalose and a high glass transition temperature amorphous shell former, either trileucine or pullulan, as compared to the commonly used crystalline shell former, leucine, or a low glass transition temperature amorphous shell former, pluronic F-68. Particle formation models suggest that the stabilization was achieved by protecting the bacteriophages against the main inactivating stress, desiccation, at the surface. The most promising formulation contained a combination of trileucine and trehalose for which the combined effects of feedstock preparation, spray drying, and 1-month dry room temperature storage resulted in a titer reduction of only 0.6 ± 0.1 log10(PFU mL−1). The proposed high glass transition temperature amorphous formulation platform may be advantageous for stabilizing biologics in other spray drying applications in the biomedical engineering industry.

Chinese hackberry (Celtis sinensis Pers.) is an adaptable species widely growing in southern China. The symptoms of canker on stems of seedlings were discovered mid-July 2017 in Shuyang, Jiangsu Province. The diseased portions of the stems were dark brown due to discoloured xylem. Some seedlings showed symptoms of wilting, leaf fall, twig dieback, and tissue discolouration. The outbreak period was concentrated in July and August, suggesting that the disease spread during summer months. Possible fungal causal agents were isolated from naturally infected canker tissue and discoloured xylem. The isolate from xylem tissue with a high frequency (> 50%) was named Ls7 type. Pathogenicity tests were carried out on 4-year-old seedlings. The symptoms of canker began to develop 20 days after inoculation with Ls7 isolate and by day 35, there were dark, enlarged longitudinal lesions. A phylogenetic tree of the isolate was developed using the internal transcribed spacer, elongation factor-1α (tef1-α), β-tubulin gene (TUB) and RNA polymerase II subunit primer genes (RPB2). Based on morphological features and phylogenetic information, the pathogen was identified as Lasiodiplodia pseudotheobromae. This is the first report of L. pseudotheobromae causing canker on Chinese hackberry stems in China.

A Correction to this paper has been published: https://doi.org/10.1038/s41467-021-22487-4