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Although plastid genome (plastome) structure is highly conserved across most seed plants, investigations during the past two decades have revealed several disparately related lineages that experienced substantial rearrangements. Most plastomes contain a large inverted repeat and two single-copy regions, and a few dispersed repeats; however, the plastomes of some taxa harbour long repeat sequences (>300 bp). These long repeats make it challenging to assemble complete plastomes using short-read data, leading to misassemblies and consensus sequences with spurious rearrangements. Single-molecule, long-read sequencing has the potential to overcome these challenges, yet there is no consensus on the most effective method for accurately assembling plastomes using long-read data. We generated a pipeline, plastid Genome Assembly Using Long-read data (ptGAUL), to address the problem of plastome assembly using long-read data from Oxford Nanopore Technologies (ONT) or Pacific Biosciences platforms. We demonstrated the efficacy of the ptGAUL pipeline using 16 published long-read data sets. We showed that ptGAUL quickly produces accurate and unbiased assemblies using only ~50× coverage of plastome data. Additionally, we deployed ptGAUL to assemble four new Juncus (Juncaceae) plastomes using ONT long reads. Our results revealed many long repeats and rearrangements in Juncus plastomes compared with basal lineages of Poales. The ptGAUL pipeline is available on GitHub: https://github.com/Bean061/ptgaul.

Estimating the counterfactual outcome of treatment is essential for decision-making in public health and clinical science, among others. Often, treatments are administered in a sequential, time-varying manner, leading to an exponentially increased number of possible counterfactual outcomes. Furthermore, in modern applications, the outcomes are high-dimensional and conventional average treatment effect estimation fails to capture disparities in individuals. To tackle these challenges, we propose a novel conditional generative framework capable of producing counterfactual samples under time-varying treatment, without the need for explicit density estimation. Our method carefully addresses the distribution mismatch between the observed and counterfactual distributions via a loss function based on inverse probability re-weighting, and supports integration with state-of-the-art conditional generative models such as the guided diffusion and conditional variational autoencoder. We present a thorough evaluation of our method using both synthetic and real-world data. Our results demonstrate that our method is capable of generating high-quality counterfactual samples and outperforms the state-of-the-art baselines.

The impact of water stress and nitrogen (N) nutrition on leaf respiration (R), carbon balance and water use efficiency (WUE) remains largely elusive. Therefore, the objective of the present study was to investigate the effect of soil water and N stresses on growth, physiological responses, leaf structure, carbon gain and WUE of maize. The plants were subjected to different soil water and N regimes to maturity. The results showed that the photosynthesis (An) and stomatal conductance (Gs) decreased significantly under the water stressed treatments across the N treatments mainly ascribed to the decreased plant water status. The moderate water stress reduced the photosynthetic capacity and activity and also caused damage to the structure of leaves, resulting in the significant reduction of An, and thus decreased WUEi. The dark respiration (Rd) was significantly decreased due to the damage of mitochondria, however, the Rd/An increased significantly and the carbon gain was seriously compromised, eventually inhibiting biomass growth under the moderately water stressed treatment. Increasing N dose further aggravated the severity of water deficit, decreased An, Gs and WUEi, damaged the structure and reduced the number of mitochondria of leaves, while increased Rd/An considerably under moderate water stress. Consequently, the biomass accumulation, carbon gain and plant level WUEp in the moderately water stressed treatment decreased markedly under the high N supply. Therefore, excessive N application should be avoided when plants suffer soil water stress in maize production.

Phosphotyrosine (pTyr)-regulated protein complexes play critical roles in cancer signaling. The systematic characterization of these protein complexes in tumor samples remains a challenge due to their limited access and the transient nature of pTyr-mediated interactions. We developed a hybrid chemical proteomics approach, termed Photo-pTyr-scaffold, by engineering Src homology 2 (SH2) domains, which specifically bind pTyr proteins, with both trifunctional chemical probes and genetic mutations to overcome these challenges. Dynamic SH2 domain-scaffolding protein complexes were efficiently cross-linked under mild UV light, captured by biotin tag, and identified by mass spectrometry. This approach was successfully used to profile native pTyr protein complexes from breast cancer tissue samples on a proteome scale with high selectivity, achieving about 100 times higher sensitivity for detecting pTyr signaling proteins than that afforded by traditional immunohistochemical methods. Among more than 1,000 identified pTyr proteins, receptor tyrosine kinase PDGFRB expressed on cancer-associated fibroblasts was validated as an important intercellular signaling regulator with poor expression correlation to ERBB2, and blockade of PDGFRB signaling could efficiently suppress tumor growth. The Photo-pTyr-scaffold approach may become a generic tool for readily profiling dynamic pTyr signaling complexes in clinically relevant samples.

Phosphotyrosine (pTyr)-regulated protein complexes play critical roles in cancer signaling. The systematic characterization of these protein complexes in tumor samples remains a challenge due to their limited access and the transient nature of pTyr-mediated interactions. We developed a hybrid chemical proteomics approach, termed Photo-pTyr-scaffold, by engineering Src homology 2 (SH2) domains, which specifically bind pTyr proteins, with both trifunctional chemical probes and genetic mutations to overcome these challenges. Dynamic SH2 domain-scaffolding protein complexes were efficiently cross-linked under mild UV light, captured by biotin tag, and identified by mass spectrometry. This approach was successfully used to profile native pTyr protein complexes from breast cancer tissue samples on a proteome scale with high selectivity, achieving about 100 times higher sensitivity for detecting pTyr signaling proteins than that afforded by traditional immunohistochemical methods. Among more than 1,000 identified pTyr proteins, receptor tyrosine kinase PDGFRB expressed on cancer-associated fibroblasts was validated as an important intercellular signaling regulator with poor expression correlation to ERBB2, and blockade of PDGFRB signaling could efficiently suppress tumor growth. The Photo-pTyr-scaffold approach may become a generic tool for readily profiling dynamic pTyr signaling complexes in clinically relevant samples.

Yi Qian,1,* Jing Tao,1,2,* Xiuqing Li,3 Hua Chen,1 Qi Lu,1 Junzhe Yang,1 Hong Pan,1 Cong Wang,4 Wenbin Zhou,1 Xiaoan Liu1 1Department of Breast Surgery, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China; 2Department of General Surgery, Nanjing Pukou Hospital, Nanjing, China; 3Department of Pathology, Jiangsu Province Hospital of Traditional Chinese Medicine, Nanjing, China; 4Department of Pathology, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China *These authors contributed equally to this work Introduction: Neoadjuvant chemotherapy (NAC) has become a standard treatment for locally advanced breast cancer. The present study was designed to investigate the predictive value of different peripheral inflammation/immune biomarker responses to NAC and prognosis in breast cancer patients. Materials and methods: A total of 180 breast cancer patients treated with NAC in the First Affiliated Hospital with Nanjing Medical University between January 2008 and March 2015 were enrolled in the study. The associations between inflammation/immune indicators and pathological complete response (pCR) were determined, and the prognostic value of inflammation/immune indicators was also evaluated. Results: In the univariate analysis, patients with a high pretreatment peripheral lymphocyte count (>2.06×109/L) showed a higher pCR rate than those with a low lymphocyte count (23.9% vs 10.4%, P=0.023). The pCR rate of patients with a neutrophil: lymphocyte ratio ≤2.15 was significantly higher than that of patients with a high neutrophil: lymphocyte ratio (20% vs 7.8%; P=0.03). However, multivariate analysis revealed that only the high lymphocyte count was predictive for pCR (odds ratio: 4.375, 95% CI: 1.429–13.392, P=0.010). In the survival analysis, patients with a higher neutrophil count (>2.65×109/L) were confirmed to have a shorter disease-free survival (hazard ratio: 4.322, 95% CI: 1.

Jiayan Chen,1,* Chi Zhang,1,* Fei Li,1,* Liping Xu,1 Hongcheng Zhu,1 Shui Wang,2 Xiaoan Liu,2 Xiaoming Zha,2 Qiang Ding,2 Lijun Ling,2 Wenbin Zhou,2 Xinchen Sun1 1Department of Radiation Oncology, 2Department of Breast Surgery, The First Affiliated Hospital, Nanjing Medical University, Nanjing, People’s Republic of China *These authors contributed equally to this work Background: Radiofrequency ablation (RFA) is a minimally invasive thermal ablation technique. We conducted a meta-analysis based on eligible studies to assess the efficacy and safety of RFA for treating patients with breast cancer.Methods: A literature search was conducted in PubMed, Embase, and Web of Science databases. Eligible studies were clinical trials that assessed RFA in patients with breast cancer. The outcomes included complete ablation rate, recurrence rate, excellent or good cosmetic rates, and complication rate. A random-effects or fixed-effects model was used to pool the estimate, according to the heterogeneity among the included studies.Results: Fifteen studies, with a total of 404 patients, were included in this meta-analysis. Pooled results showed that 89% (95% confidence interval: 85%–93%) of patients achieved a complete ablation after RFA treatment and 96% of patients reported a good-to-excellent cosmetic result. Although the pooled result for recurrence rate was 0, several cases of relapse were observed at different follow-up times. No RFA-related complications were recorded, except for skin burn with an incidence of 4% (95% confidence interval: 1%–6%).Conclusion: This meta-analysis showed that RFA can be a promising alternative option for treating breast cancer since it produces a higher complete ablation rate with a low complication rate. Further w

The deposit occurs in a Mesozoic volcanic basin in southeastern China and contains soda metasomatic-type and fluorite-hydromica-type uranium mineralisation. Fluid inclusion studies show that the hydrothermal solution for the metasomatic-type mineralisation changed from alkaline to near-neutral while from the pre-ore stage to the mineralisation stage, the fluid for the hydromica-type deposits changed from weakly acidic to near-neutral. The difference between the Eh value for water and the critical redox potential of uranium reduction precipitation is termed relative redox potential between water and uranium and is a geochemical parameter controlling the reduction and precipitation of uranium. Uranium deposits could be formed not only in the transitional zones with distinctly increased reducing agents, but also in the neutralising zones without increase in the amount of reducing agents or decrease in Eh of the solution., The deposit occurs in a Mesozoic volcanic basin in southeastern China and contains soda metasomatic-type and fluorite-hydromica-type uranium mineralisation. Fluid inclusion studies show that the hydrothermal solution for the metasomatic-type mineralisation changed from alkaline to near-neutral while from the pre-ore stage to the mineralisation stage, the fluid for the hydromica-type deposits changed from weakly acidic to near-neutral. The difference between the Eh value for water and the critical redox potential of uranium reduction precipitation is termed relative redox potential between water and uranium and is a geochemical parameter controlling the reduction and precipitation of uranium. Uranium deposits could be formed not only in the transitional zones with distinctly increased reducing agents, but also in the neutralising zones without increase in the amount of reducing agents or decrease in Eh of the solution.

The orefield consists of typical volcanogenic hydrothermal deposits with two main types of uranium mineralisation, soda metasomatic and fluorite-hydromica type. The whole rock is 140 Ma or Late Jurassic in age. Sr and Nd isotope ratios suggest that the volcanic rocks were formed mainly through remelting of lower crustal materials. U-Pb dating of pitchblende and Rb-Sr dating of the altered rock give ages of about 120 Ma for the soda metasomatic mineralisation and 100 Ma for the fluorite-hydromica mineralisation. H and O isotope analysis of minerals and fluid inclusions show that delta values for O vary remarkably (7.2 to -9.14 per mil) whereas H isotope composition is relatively stable. Studies of the protolith and altered rocks reveal a marked decrease of O delta values from 10 to 4 per mil during the process of alteration, suggesting that the mineralising fluids contained mainly meteoric water. Pb isotope characteristics show that the ore-forming minerals may have been extracted from the volcanic rocks by leaching., The orefield consists of typical volcanogenic hydrothermal deposits with two main types of uranium mineralisation, soda metasomatic and fluorite-hydromica type. The whole rock is 140 Ma or Late Jurassic in age. Sr and Nd isotope ratios suggest that the volcanic rocks were formed mainly through remelting of lower crustal materials. U-Pb dating of pitchblende and Rb-Sr dating of the altered rock give ages of about 120 Ma for the soda metasomatic mineralisation and 100 Ma for the fluorite-hydromica mineralisation. H and O isotope analysis of minerals and fluid inclusions show that delta values for O vary remarkably (7.2 to -9.14 per mil) whereas H isotope composition is relatively stable. Studies of the protolith and altered rocks reveal a marked decrease of O delta values from 10 to 4 per mil during the process of alteration, suggesting that the mineralising fluids contained mainly meteoric water. Pb isotope characteristics show that the ore-forming minerals may have been extracted from the volcanic rocks by leaching.