Dominance complementation of parental heading date alleles of Hd1, Ghd7, DTH8, and PRR37 confers transgressive late maturation in hybrid rice.

Rice (Oryza sativa L.) is a short-day plant whose heading date is largely determined by photoperiod sensitivity (PS). Many parental lines used in hybrid rice breeding have weak PS, but their F1 progenies have strong PS and exhibit an undesirable transgressive late-maturing phenotype. However, the genetic basis for this phenomenon is unclear. Therefore, effective methods are needed for selecting parents to create F1 hybrid varieties with the desired PS. In this study, we used bulked segregant analysis with F1 Ningyou 1179 (strong PS) and its F2 population, and through analyzing both parental haplotypes and PS data for 918 hybrid rice varieties, to identify the genetic basis of transgressive late maturation which is dependent on dominance complementation effects of Hd1, Ghd7, DTH8, and PRR37 from both parents rather than from a single parental genotype. We designed a molecular marker-assisted selection system to identify the genotypes of Hd1, Ghd7, DTH8, and PRR37 in parental lines to predict PS in F1 plants prior to crossing. Furthermore, we used CRISPR/Cas9 technique to knock out Hd1 in Ning A (sterile line) and Ning B (maintainer line) and obtained an hd1-NY material with weak PS while retaining the elite agronomic traits of NY. Our findings clarified the genetic basis of transgressive late maturation in hybrid rice and developed effective methods for parental selection and gene editing to facilitate the breeding of hybrid varieties with the desired PS for improving their adaptability.

Gut microbiota dynamics and fecal SCFAs after colonoscopy: accelerating microbiome stabilization by Clostridium butyricum.

BACKGROUND: Colonoscopy is a classic diagnostic method with possible complications including abdominal pain and diarrhoea. In this study, gut microbiota dynamics and related metabolic products during and after colonoscopy were explored to accelerate gut microbiome balance through probiotics. METHODS: The gut microbiota and fecal short-chain fatty acids (SCFAs) were analyzed in four healthy subjects before and after colonoscopy, along with seven individuals supplemented with Clostridium butyricum. We employed 16S rRNA sequencing and GC-MS to investigate these changes. We also conducted bioinformatic analysis to explore the buk gene, encoding butyrate kinase, across C. butyricum strains from the human gut. RESULTS: The gut microbiota and fecal short-chain fatty acids (SCFAs) of four healthy subjects were recovered on the 7th day after colonoscopy. We found that Clostridium and other bacteria might have efficient butyric acid production through bioinformatic analysis of the buk and assessment of the transcriptional level of the buk. Supplementation of seven healthy subjects with Clostridium butyricum after colonoscopy resulted in a quicker recovery and stabilization of gut microbiota and fecal SCFAs on the third day. CONCLUSION: We suggest that supplementation of Clostridium butyricum after colonoscopy should be considered in future routine clinical practice.

Small extracellular vesicle microRNAs in pediatric myasthenia gravis plasma and skeletal muscle.

BACKGROUND: The diagnosis of myasthenia gravis (MG) in children remains difficult. Circulating small extracellular vesicle (sEV)-derived miRNAs (sEV-miRNAs) have been recognized as biomarkers of various diseases and can be excreted by different cell types. These biomarker candidates also play a vital role in autoimmune diseases via intercellular communication. METHODS: In the present study, we used sEV isolation and purification methods to extract the plasma-derived sEV-miRNAs from children with MG and healthy controls. A small RNA sequencing analysis confirmed the miRNA expression features in plasma-derived sEVs from MG patients. The miRNA expression analysis in vitro was determined using microarray analysis. The enrichment and network analyses of altered sEV-miRNAs were performed using miRNA databases and Database for Annotation, Visualization, and Integrated Discovery website. Quantitative real-time polymerase chain reaction was performed for validation of sEV-miRNA. The diagnostic power of altered sEV-miRNAs was evaluated using receiver operating characteristic curve analyses. RESULTS: Twenty-four sEV-miRNAs with altered expression level were identified between groups by DESeq2 method. The miRNAs were extracted from the sEVs, which were isolated from human primary skeletal muscle cell culture treated with mAb198. The target genes and enriched pathways of sEV-miRNAs partially overlapped between cell supernatant and plasma samples. The significantly downregulated miR-143-3p was validated in quantitative real-time polymerase chain reaction analysis. CONCLUSIONS: For the first time, we report that plasma-derived sEV-miRNAs may act as novel circulating biomarkers and therapeutic targets in pediatric MG.

Weizmannia coagulans BCF-01: a novel gastrogenic probiotic for Helicobacter pylori infection control.

The widespread prevalence of Helicobacter pylori infection, particularly in China, contributes to the development of gastrointestinal diseases. Antibiotics have limitations, including adverse reactions and increased antibiotic resistance. Therefore, identification of novel gastrogenic probiotics capable of surviving the acidic gastric environment and effectively combating H. pylori infection has potential in restoring gastric microbiota homeostasis. Five novel strains of human gastrogenic Weizmannia coagulans (BCF-01-05) were isolated from healthy gastric mucosa and characterized using 16S rDNA identification. Acid resistance, H. pylori inhibition, and adherence to gastric epithelial cells were evaluated in in-vitro experiments and the molecular mechanism explored in in-vivo experiments. Among the gastric-derived W. coagulans strains, BCF-01 exhibited the strongest adhesion and H. pylori inhibition, warranting further in-vivo safety evaluation. Through 16S rRNA sequencing of a mouse model, BCF-01 was determined to significantly restore H. pylori-associated gastric dysbiosis and increase the abundance of potential probiotic bacteria. Furthermore, BCF-01 enhanced mucosal tight junction protein expression and inhibited the TLR4-NFκB-pyroptosis signaling pathway in macrophages, as demonstrated by qRT-PCR and western blotting.These findings highlight the potential of BCF-01 in the prevention and control of H. pylori infection. Specifically, treatment with BCF-01 effectively restored gastric microecology and improved H. pylori-mediated mucosal barrier destruction while reducing inflammation through inhibition of the TLR4-NFκB-pyroptosis signaling pathway in macrophages. BCF-01 is a promising alternative to traditional triple therapy for H. pylori infections, offering minimal side effects with high suitability for high-risk individuals.

Identification, characterisation and expression analysis of peanut sugar invertase genes reveal their vital roles in response to abiotic stress.

KEY MESSAGE: Sucrose invertase activity is positively related to osmotic and salt stress resistance in peanut. Sucrose invertases (INVs) have important functions in plant growth and response to environmental stresses. However, their biological roles in peanut are still not fully revealed. In this research, we identified 42 AhINV genes in the peanut genome. They were highly conserved and clustered into three groups with 24 segmental duplication events occurred under purifying selection. Transcriptional expression analysis exhibited that they were all ubiquitously expressed, and most of them were up-regulated by osmotic and salt stresses, with AhINV09, AhINV23 and AhINV19 showed the most significant up-regulation. Further physiochemical analysis showed that the resistance of peanut to osmotic and salt stress was positively related to the high sugar content and sucrose invertase activity. Our results provided fundamental information on the structure and evolutionary relationship of INV gene family in peanut and gave theoretical guideline for further functional study of AhINV genes in response to abiotic stress.

Protective effects of puerarin on liver tissue in Salmonella-infected chicks: a proteomic analysis.

Salmonella enterica is a zoonotic bacterium that not only causes serious economic losses to the livestock and poultry industries but also seriously endangers human health. Long-term indiscriminate use of antibiotics has led to drug resistance in Salmonella, and thus the identification of alternatives to antibiotics is crucial. In this study, the effects of puerarin on the S. enterica-infected chickens were investigated. A total of 360 chicks were randomly assigned as the control group (CON), the S. enterica group (S), and puerarin-treatment group (P). Chicks in the P group were fed the basal diet supplemented with 50 (P50), 100 (P100), 200 (P200), and 400 (P400) mg/kg puerarin, respectively. It was found that puerarin treatment markedly altered the serum activities of aspartate aminotransferase (AST), alanine transaminase (ALT), and superoxide dismutase (SOD), together with the malondialdehyde (MDA) and total antioxidant capacity (T-AOC) contents in the serum. The mRNA expression of IL-6, IL-1ß, TNF-α, Bcl-2, and caspase-8 in the livers of S. enterica-infected chicks was increased after infection but significantly reduced after treatment with puerarin. Histologic analysis showed that puerarin effectively mitigated morphological damage in the liver caused by S. enterica. Proteomic analysis revealed that S. enterica infection led to metabolic disorders in the liver, resulting in oxidative stress, increased inflammation, and significantly elevated levels of hepatocellular carcinoma biomarkers. The findings of the filtered sequencing were verified by using quantitative PCR (qPCR). Treatment with 100 mg/mL puerarin thus effectively alleviated disordered liver metabolism, reduced inflammation and oxidative damage and significantly reduced the levels of hepatocellular carcinoma biomarkers in the liver. The results suggest that puerarin has the potential to replace antibiotics to control Salmonella infection in poultry and thus improve food safety.

Occurrence, Distribution, and Trophic Transfer of Pharmaceuticals and Personal Care Products in the Bohai Sea.

The ubiquitous presence of pharmaceuticals and personal care products (PPCPs) in environments has aroused global concerns; however, minimal information is available regarding their multimedia distribution, bioaccumulation, and trophic transfer in marine environments. Herein, we analyzed 77 representative PPCPs in samples of surface and bottom seawater, surface sediments, and benthic biota from the Bohai Sea. PPCPs were pervasively detected in seawater, sediments, and benthic biota, with antioxidants being the most abundant PPCPs. PPCP concentrations positively correlated between the surface and bottom water with a decreasing trend from the coast to the central oceans. Higher PPCP concentrations in sediment were found in the Yellow River estuary, and the variations in the physicochemical properties of PPCPs and sediment produced a different distribution pattern of PPCPs in sediment from seawater. The log Dow, but not log Kow, showed a linear and positive relationship with bioaccumulation and trophic magnification factors and a parabolic relationship with biota-sediment accumulation factors. The trophodynamics of miconazole and acetophenone are reported for the first time. This study provides novel insights into the multimedia distribution and biomagnification potential of PPCPs and suggests that log Dow is a better indicator of their bioaccumulation and trophic magnification.

Target gene mutations endowed cross-resistance to acetolactate synthase-inhibiting herbicides in wild Brassica juncea.

Wild Brassica juncea is a troublesome weed that infests wheat fields in China. Two suspected wild B. juncea populations (19-5 and 19-6) resistant to acetolactate synthase (ALS) inhibitors were collected from wheat fields in China. To clarify their resistance profiles and resistance mechanism, the resistance levels of populations 19-5 and 19-6 to ALS-inhibiting herbicides and their underlying target-site resistance mechanism were investigated. The results showed that the 19-5 population exhibited resistance to tribenuron-methyl, pyrithiobac­sodium and florasulam, while the 19-6 population was resistant to tribenuron-methyl, pyrithiobac­sodium, imazethapyr and florasulam. Using the homologous cloning method, two ALS genes were identified in wild B. juncea, with one gene (ALS1) encoding 652 amino acids and the other (ALS2) encoding 655 amino acids. Pro-197-Arg mutation on ALS2 and Trp-574-Leu mutation on ALS1, together with the combination of these two mutations in a single plant, were observed in both 19-5 and 19-6 populations. ALS2 enzymes carrying the Pro-197-Arg mutation were cross-resistant to tribenuron-methyl, pyrithiobac­sodium, imazerthapyr and florasulam, with resistance index (RI) values of 6.23, 32.81, 7.97 and 1162.50, respectively. Similarly, ALS1 enzymes with Trp-574-leu substitutions also displayed high resistance to these four herbicides (RI values ranging from 132.61 to 3375.00). In addition, the combination of Pro-197-Arg (ALS2) and Trp-574-Leu (ALS1) mutations increased the resistance level of the ALS enzyme to ALS inhibitors, with its RI values 3.83-214.19, 6.88-37.34, 1.91-31.82 and 2.03-5.90-fold higher than a single mutation for tribenuron-methyl, pyrithiobac­sodium, imazerthapyr and florasulam, respectively. Collectively, Pro-197-Arg mutation on ALS2, Trp-574-Leu mutation on ALS1 and the combination of Pro-197-Arg (ALS2) and Trp-574-Leu (ALS1) mutations in wild B. juncea could endow broad-spectrum resistance to ALS inhibitors, which might provide guides for establishing effective strategies to prevent or delay such resistance evolution in this weed.

CTRP6 protects against ferroptosis to drive lung cancer progression and metastasis by destabilizing SOCS2 and augmenting the xCT/GPX4 pathway.

Lung cancer is a highly heterogeneous malignancy, and despite the rapid development of chemotherapy and radiotherapy, acquired drug resistance and tumor progression still occur. Thus, it is urgent to identify novel therapeutic targets. Our research aims to screen novel biomarkers associated with the prognosis of lung carcinoma patients and explore the potential regulatory mechanisms. We obtained RNA sequencing (RNA-seq) data of lung cancer patients from public databases. Clinical signature analysis, weighted gene coexpression network analysis (WGCNA) and the random forest algorithm showed that C1q/tumor necrosis factor-related protein-6 (CTRP6) is a core gene related to lung cancer prognosis, and it was determined to promote tumor proliferation and metastasis both in vivo and in vitro. Mechanistically, silencing CTRP6 was determined to promote xCT/GPX4-involved ferroptosis through functional assays related to lipid peroxidation, Fe2+ concentration and mitochondrial ultrastructure. By performing interactive proteomics analyses in lung tumor cells, we identified the interaction between CTRP6 and suppressor of cytokine signaling 2 (SOCS2) leading to SOCS2 ubiquitination degradation, subsequently enhancing the downstream xCT/GPX4 signaling pathway. Moreover, significant correlations between CTRP6-mediated SOCS2 and ferroptosis were revealed in mouse models and clinical specimens of lung cancer. As inducing ferroptosis has been gradually regarded as an alternative strategy to treat tumors, targeting CTRP6-mediated ferroptosis could be a potential strategy for lung cancer therapy.

Improving yield-related traits by editing the promoter of the heading date gene Ehd1 in rice.

KEY MESSAGE: We developed an efficient promoter editing method to create different weak Ehd1 alleles in elite japonica rice variety ZJ8 with slightly delayed heading and improved yield for use in breeding. Heading date is an important agronomic trait of rice (Oryza sativa) that determines the planting areas and cultivation seasons of different varieties, thus affecting final yield. Early heading date 1 (Ehd1) is a major rice integrator gene in the regulatory network of heading date whose expression level is negatively correlated with heading date and grain yield. Some elite japonica varieties such as Zhongjia 8 (ZJ8) show very early heading with poor agronomic traits when planted in South China. This problem can be addressed by downregulating the expression of Ehd1. In this study, we analyzed the cis-regulatory elements in the Ehd1 promoter region. We then used CRISPR/Cas9-mediated editing to modify the Ehd1 promoter at multiple target sites in ZJ8. We rapidly identified homozygous allelic mutations in the T2 generation via long-read sequencing. We obtained several Ehd1 promoter mutants with different degrees of lower Ehd1 expression, delayed heading date, and improved yield-related traits. We developed an efficient promoter editing method to create different weak Ehd1 alleles for breeding selection. Using this method, a series of heading date materials from elite varieties can be created to expand the planting area of rice and improve grain yields.

Ectopic Expression of MADS-Box Transcription Factor VvAGL12 from Grape Promotes Early Flowering, Plant Growth, and Production by Regulating Cell-Wall Architecture in Arabidopsis.

The MADS-box family, a substantial group of plant transcription factors, crucially regulates plant growth and development. Although the functions of AGL12-like subgroups have been elucidated in Arabidopsis, rice, and walnut, their roles in grapes remain unexplored. In this study, we isolated VvAGL12, a member of the grape MADS-box group, and investigated its impact on plant growth and biomass production. VvAGL12 was found to localize in the nucleus and exhibit expression in both vegetative and reproductive organs. We introduced VvAGL12 into Arabidopsis thaliana ecotype Columbia-0 and an agl12 mutant. The resulting phenotypes in the agl12 mutant, complementary line, and overexpressed line underscored VvAGL12's ability to promote early flowering, augment plant growth, and enhance production. This was evident from the improved fresh weight, root length, plant height, and seed production, as well as the reduced flowering time. Subsequent transcriptome analysis revealed significant alterations in the expression of genes associated with cell-wall modification and flowering in the transgenic plants. In summary, the findings highlight VvAGL12's pivotal role in the regulation of flowering timing, overall plant growth, and development. This study offers valuable insights, serving as a reference for understanding the influence of the VvAGL12 gene in other plant species and addressing yield-related challenges.

Development and clinical validation of a microfluidic-based platform for CTC enrichment and downstream molecular analysis.

Background: Although many CTC isolation and detection methods can provide information on cancer cell counts, downstream gene and protein analysis remain incomplete. Therefore, it is crucial to develop a technology that can provide comprehensive information on both the number and profile of CTC. Methods: In this study, we developed a novel microfluidics-based CTC separation and enrichment platform that provided detailed information about CTC. Results: This platform exhibits exceptional functionality, achieving high rates of CTC recovery (87.1%) and purification (∼4 log depletion of WBCs), as well as accurate detection (95.10%), providing intact and viable CTCs for downstream analysis. This platform enables successful separation and enrichment of CTCs from a 4 mL whole-blood sample within 15 minutes. Additionally, CTC subtypes, selected protein expression levels on the CTC surface, and target mutations in selected genes can be directly analyzed for clinical utility using immunofluorescence and real-time polymerase chain reaction, and the detected PD-L1 expression in CTCs is consistent with immunohistochemical assay results. Conclusion: The microfluidic-based CTC enrichment platform and downstream molecular analysis together provide a possible alternative to tissue biopsy for precision cancer management, especially for patients whose tissue biopsies are unavailable.

Effects of the core heading date genes Hd1, Ghd7, DTH8, and PRR37 on yield-related traits in rice.

KEY MESSAGE: We clarify the influence of the genotypes of the heading date genes Hd1, Ghd7, DTH8, and PRR37 and their combinations on yield-related traits and the functional differences between different haplotypes. Heading date is a key agronomic trait in rice (Oryza sativa L.) that determines yield and adaptability to different latitudes. Heading date 1 (Hd1), Grain number, plant height, and heading date 7 (Ghd7), Days to heading on chromosome 8 (DTH8), and PSEUDO-RESPONSE REGULATOR 37 (PRR37) are core rice genes controlling photoperiod sensitivity, and these genes have many haplotypes in rice cultivars. However, the effects of different haplotypes at these genes on yield-related traits in diverse rice materials remain poorly characterized. In this study, we knocked out Hd1, Ghd7, DTH8, or PRR37, alone or together, in indica and japonica varieties and systematically investigated the agronomic traits of each knockout line. Ghd7 and PRR37 increased the number of spikelets and improved yield, and this effect was enhanced with the Ghd7 DTH8 or Ghd7 PRR37 combination, but Hd1 negatively affected yield. We also identified a new weak functional Ghd7 allele containing a mutation that interferes with splicing. Furthermore, we determined that the promotion or inhibition of heading date by different PRR37 haplotypes is related to PRR37 expression levels, day length, and the genetic background. For rice breeding, a combination of functional alleles of Ghd7 and DTH8 or Ghd7 and PRR37 in the hd1 background can be used to increase yield. Our study clarifies the effects of heading date genes on yield-related traits and the functional differences among their different haplotypes, providing valuable information to identify and exploit elite haplotypes for heading date genes to breed high-yielding rice varieties.

BvCPD promotes parenchyma cell and vascular bundle development in sugar beet (Beta vulgaris L.) taproot.

Constitutive photomorpogenic dwarf (CPD) is a pivotal enzyme gene for brassinolide (BR) synthesis and plays an important role in plant growth, including increasing plant biomass and plant height, elongating cells, and promoting xylem differentiation. However, little is known about the function of the CPD gene in sugar beet. In the current study, we isolated CPD from Beta vulgaris L. (BvCPD), which encodes protein localized in the nucleus, cell membrane, and cell wall. BvCPD was strongly expressed in parenchyma cells and vascular bundles. The transgenic sugar beet overexpressing BvCPD exhibited larger diameter than that of the wild type (WT), which mainly owing to the increased number and size of parenchyma cells, the enlarged lumen and area of vessel in the xylem. Additionally, overexpression of BvCPD increased the synthesis of endogenous BR, causing changes in the content of endogenous auxin (IAA) and gibberellin (GA) and accumulation of cellulose and lignin in cambium 1-4 rings of the taproot. These results suggest that BvCPD can promote the biosynthesis of endogenous BR, improve cell wall components, promote the development of parenchyma cells and vascular bundle, thereby playing an important role in promoting the growth and development of sugar beet taproot.

Neoadjuvant chemoimmunotherapy cycle number selection for non-small cell lung cancer and clinical outcomes: a real-world analysis.

Objectives: Neoadjuvant chemoimmunotherapy is the optimal choice in the treatment of NSCLC; however, the optimal number of therapeutic cycles remains unclear. The primary aim of this study was to determine the optimal number of neoadjuvant therapeutic cycles in NSCLC. Methods: This study was a real-world clinical analysis that included patients who received neoadjuvant chemoimmunotherapy followed by surgery from January 2020 to August 2022. Patients were divided into two groups based on the number of therapeutic cycles: 2-cycle group and 3-4-cycles group. The primary endpoint was the major pathological response (MPR) rate. Results: A total of 251 patients were included: 150 in the 2-cycle group and 101 in the 3-4-cycles group. Baseline characteristics were well-balanced between the groups. The MPR in the 2-cycle group was 57.3% and not significantly different from that of 57.4% in the 3-4-cycles group (p=0.529). Thirty-two patients (31.7%) in the 3-4-cycles group underwent surgery > 42 days after the final cycle of neoadjuvant therapy, significantly more than the 24 patients (16.0%) in the 2-cycle group (p=0.003). The incidence of adverse events related to neoadjuvant therapy was higher in the 3-4-cycles vs 2-cycle groups (72.3% versus 58.0%, respectively; p=0.021), while the 2-cycle group had a higher rate of postoperative morbidities (28.0% versus 12.9%, respectively; p=0.004). Additionally, for patients with ≤ 44.2% regression in diameter on computed tomography after two cycles of treatment, the MPR rate was higher in the 3-4-cycles vs 2-cycle group (47.3% versus 29.9%, respectively; p=0.048). For cases with programmed death-ligand 1 expression, regarding tumor proportion score ≤ 10%, 3-4 cycles of neoadjuvant treatment increased the MPR rate compared with 2 cycles (37.5% versus 9.5%, respectively; p=0.041). Conclusion: Our data support the positive role of chemoimmunotherapy in the neoadjuvant treatment of NSCLC. Extending to 3-4 cycles instead of 2 cycles of neoadjuvant chemoimmunotherapy may improve the safety of surgery and result in a lower incidence of postoperative morbidities; however, the MPR rate may not increase significantly. CT re-evaluation during treatment and PD-L1 expression at initial diagnosis are potential indicators to guide the choice of the number of therapeutic cycles.

Transcriptomic analysis of Amaranthus retroflex resistant to PPO-inhibitory herbicides.

Amaranthus retroflexus L. is one of the malignant weeds which can cause a reduction in the soybean yield. We found a population of A. retroflexus (R-Q) resistant to fomesafen through the initial screening of whole-plant dose response bioassay in the research. The resistance index of the population (R-Q) was 183 times of the sensitive population (S-N). The resistant and sensitive populations were used as experimental materials in the paper. Strand-specific RNA-Seq analyses of R‒Q and S‒N populations obtained from herbicide-treated and mock-treated leaf samples after treatment were conducted to generate a full-length transcriptome database. We analyzed differentially expressed genes (DEGs) among the R-Q and S‒N A. retroflexus populations treated with recommended dose and mock-treated on the 1st (24 h) and 3rd (72 h) days to identify genes involved in fomesafen resistance. All 82,287 unigenes were annotated by Blastx search with E-value < 0.00001 from 7 databases. A total of 94,815 DEGs among the three group comparisons were identified. Two nuclear genes encoding PPO (PPX1 and PPX2) and five unigenes belonging to the AP2-EREBP, GRAS, NAC, bHLH and bZIP families exhibited different expression patterns between individuals of S‒N and R-Q populations. The A. retroflexus transcriptome and specific transcription factor families which can respond to fomesafen in resistant and susceptible genotypes were reported in this paper. The PPX1 and PPX2 genes of the target enzyme were identified. The study establishes the foundation for future research and provides opportunities to manage resistant weeds better.

Development and validation of web-based dynamic nomograms predictive of disease-free and overall survival in patients who underwent pneumonectomy for primary lung cancer.

Background: The tumour-node-metastasis (TNM) staging system is insufficient to precisely distinguish the long-term survival of patients who underwent pneumonectomy for primary lung cancer. Therefore, this study sought to identify determinants of disease-free (DFS) and overall survival (OS) for incorporation into web-based dynamic nomograms. Methods: The clinicopathological variables, surgical methods and follow-up information of 1,261 consecutive patients who underwent pneumonectomy for primary lung cancer between January 2008 and December 2018 at Sun Yat-sen University Cancer Center were collected. Nomograms for predicting DFS and OS were built based on the significantly independent predictors identified in the training cohort (n = 1,009) and then were tested on the validation cohort (n = 252). The concordance index (C-index) and time-independent area under the receiver-operator characteristic curve (AUC) assessed the nomogram's discrimination accuracy. Decision curve analysis (DCA) was applied to evaluate the clinical utility. Results: During a median follow-up time of 40.5 months, disease recurrence and death were observed in 446 (35.4%) and 665 (52.7%) patients in the whole cohort, respectively. In the training cohort, a higher C-reactive protein to albumin ratio, intrapericardial pulmonary artery ligation, lymph node metastasis, and adjuvant therapy were significantly correlated with a higher risk for disease recurrence; similarly, the independent predictors for worse OS were intrapericardial pulmonary artery and vein ligation, higher T stage, lymph node metastasis, and no adjuvant therapy. In the validation cohort, the integrated DFS and OS nomograms showed well-fitted calibration curves and yielded good discrimination powers with C-index of 0.667 (95% confidence intervals CIs [0.610-0.724]) and 0.697 (95% CIs [0.649-0.745]), respectively. Moreover, the AUCs for 1-year, 3-year, and 5-year DFS were 0.655, 0.726, and 0.735, respectively, and those for 3-year, 5-year, and 10-year OS were 0.741, 0.765, and 0.709, respectively. DCA demonstrated that our nomograms could bring more net benefit than the TNM staging system. Conclusions: Although pneumonectomy for primary lung cancer has brought encouraging long-term outcomes, the constructed prediction models could assist in precisely identifying patients at high risk and developing personalized treatment strategies to further improve survival.

SPR Sensor Based on a Concave Photonic Crystal Fiber Structure with MoS2/Au Layers.

We propose a surface plasmon resonance (SPR) sensor based on the concave photonic crystal fiber (PCF) coated with molybdenum disulfide (MoS2) and Au layers, which can detect the refractive index (RI) of the analyte. The finite element method (FEM) was used to verify our design, and the loss spectra of the fundamental mode are calculated. Compared with the SPR sensor with only a Au layer, the wavelength sensitivity can be improved by from 3700 to 4400 nm/RIU. Our proposed sensor works in near-infrared band and has a wide RI range from 1.19 to 1.40. The influences of the geometrical parameters of PCF and the thicknesses of Au and MoS2 layers on the loss spectra are discussed in detail, and the maximum wavelength sensitivity of 5100 nm/RIU can be achieved. Meanwhile, a high resolution of 1.96 × 10-5 RIU and the largest FOM of 29.143 can be obtained. It is believed that our findings show the sensor's excellent potential in medical testing, unknown biological detection, environmental monitoring and organic chemical detection.

Profiling of the spatiotemporal distribution, risks, and prioritization of pharmaceuticals and personal care products in coastal waters of the northern Yellow Sea, China.

Pharmaceuticals and personal care products (PPCPs) have aroused global concerns due to their ubiquitous occurrence and detrimental effects. The spatiotemporal distributions of 64 PPCPs and their synergetic ecological risks were comprehensively investigated in the seawater of Yantai Bay, and 1 H-benzotriazole (BT), ethenzamide, phenazone, propyphenazone, 4-hydroxybenzophenone and N, N'-diphenylurea were first determined in the seawater of China. Fifty-six PPCPs were detected and their concentrations were 27.5-182 ng/L, with BT contributing around 58.0%. Higher PPCP concentrations were observed in winter and spring, with the concentrations of antioxidants, analgesic/anti-inflammatory drugs and human-used antibiotics significantly higher in winter, while those of aquaculture-used antibiotics and UV filters significantly higher in summer, which was closely related with their usage patterns. Positive correlations were observed for PPCP concentrations between surface and bottom water, except summer, during which time the weak vertical exchange and varied environmental behaviors among different PPCPs resulted in the distinct compositions and concentrations. Terrestrial inputs and mariculture resulted in higher PPCP concentrations in the area located adjacent to the coast and aquaculture bases. The PPCP mixtures posed medium to high risk to crustaceans, and bisphenol A was identified as a high-risk pollutant that needs special attention.

Three-dimensional template combined with MR-guided iodine-125 brachytherapy for recurrent brain metastases.

Purpose: Treatment of recurrent brain metastases is extremely challenging. Here, we evaluated the feasibility and efficacy of an individualized three-dimensional template combined with MR-guided iodine-125 (125I) brachytherapy in the treatment of recurrent brain metastases. Material and methods: Twenty-eight patients with recurrent 38 brain metastases underwent 125I brachytherapy from December, 2017 to January, 2021. A pre-treatment brachytherapy plan and three-dimensional template were generated according to isovoxel T1-weighted MR images. 125I seeds were implanted under the guidance of three-dimensional template and 1.0-T open MR imaging. Dosimetry verification was performed based on CT/MR fusion images. Pre-operative and post-operative dosimetry parameters of D90, V100, and conformity index (CI) were compared. Overall response rate (ORR), disease control rate (DCR) at 6 months, and 1-year survival rate were calculated. Median overall survival (OS) measured from the date of 125I brachytherapy was estimated using Kaplan-Meier method. Results: No significant differences were observed between pre-operative and post-operative D90, V100, and CI values (p > 0.05). The ORR and DCR at 6 months were 91.3% and 95.7%, respectively. The 1-year survival rate was 57.1%. The median OS was 14.1 months. Two cases of minor hemorrhage and 5 cases of symptomatic brain edema were observed during the study. All clinical symptoms were alleviated after corticosteroid treatment applied for 7 to 14 days. Conclusions: A three-dimensional template combined with MR-guided 125I brachytherapy in the treatment of recurrent brain metastases is feasible, safe, and effective. This novel 125I brachytherapy strategy is an attractive alternative in the treatment of brain metastases.