Genomic heterogeneity of multiple synchronous lung cancers in Chinese population.

INTRODUCTION: It is clinically challenging to infer the phylogenetic relationship between different tumor lesions of patients with multiple synchronous lung cancers (MSLC), whether these lesions are the result of independently evolved tumor or intrapulmonary metastases. METHODS: We used the Illumina X10 platform to sequence 128 stage I lung cancer samples collected from 64 patients with MSLC. All samples were analyzed for mutation spectra and phylogenetic inference. RESULTS: We detected genetic aberrations within genes previously reported to be recurrently altered in lung adenocarcinoma including, EGFR, ERBB2, TP53, BRAF, and KRAS. Other putative driver mutations identified were enriched in RTK-RAS signaling, TP53 signaling, and cell cycle. Also, we found some interesting cases, two cases that carried EGFR L858R and T790M co-mutation in one tumor and another tumor with only EGFR 19del, and 1 case with two KRAS hotspots in the same tumor. Due to the short follow-up time and early stage, further investigation is needed to determine whether this unique mutation profile will affect their progression-free survival (PFS) and overall survival (OS). Regarding genetic evolution analysis among 64 tumor samples, 50 of them display distinct mutational profiles, suggesting these are independently evolved tumors, which is consistent with histopathological assessment. On the other hand, six patients were identified to be intrapulmonary metastasis as the mutations harbored in different lesions are clonally related. CONCLUSION: In summary, unlike intrapulmonary metastases, patients with MSLC harbor distinct genomic profiles in different tumor lesions, and we could distinguish MSLC from intrapulmonary metastases via clonality estimation.

CEGA: a method for inferring natural selection by comparative population genomic analysis across species.

We developed maximum likelihood method for detecting positive selection or balancing selection using multilocus or genomic polymorphism and divergence data from two species. The method is especially useful for investigating natural selection in noncoding regions. Simulations demonstrate that the method outperforms existing methods in detecting both positive and balancing selection. We apply the method to population genomic data from human and chimpanzee. The list of genes identified under selection in the noncoding regions is prominently enriched in pathways related to the brain and nervous system. Therefore, our method will serve as a useful tool for comparative population genomic analysis.

Recent positive selection signatures reveal phenotypic evolution in the Han Chinese population.

Characterizing natural selection signatures and relationships with phenotype spectra is important for understanding human evolution and both biological and pathological mechanisms. Here, we identified 24 genetic loci under recent selection by analyzing rare singletons in 3946 high-depth whole-genome sequencing data of Han Chinese. The loci include immune-related gene regions (MHC cluster, IGH cluster, STING1, and PSG), alcohol metabolism-related gene regions (ADH1B, ALDH2, and ALDH3B2), and the olfactory perception gene OR4C16, in which the MHC cluster, ADH1B, and ALDH2 were also identified by TOPMed and WestLake Biobank. Among the signals, the IGH cluster is particularly interesting, in which the favored allele of variant 14_105737776_C_T (rs117518546, IgG1-G396R) promotes immune response, but also increases the risk of an autoimmune disease systemic lupus erythematosus (SLE). It is also surprising that our newly discovered ALDH3B2 evolved in the opposite direction to ALDH2 for alcohol metabolism. Besides monogenic traits, we found that multiple complex traits experienced polygenic adaptation. Particularly, multi-methods consistently revealed that lower blood pressure was favored in natural selection. Finally, we built a database named RePoS (recent positive selection, http://bigdata.ibp.ac.cn/RePoS/) to integrate and display multi-population selection signals. Our study extended our understanding of natural evolution and phenotype adaptation in Han Chinese as well as other populations.

Decorating Channel Walls in Metal-Organic Frameworks with Crown Ethers for Efficient and Selective Separation of Radioactive Strontium(II).

Nuclear accidents and the improper disposal of nuclear wastes have led to serious environmental radioactive pollutions. The rational design of adsorbents for the highly efficient separation of strontium(II) is essential in treating nuclear waste and recovering radioactive strontium resources. Metal-organic frameworks (MOFs) are potential materials for the separation of aqueous metal ions owing to their designable structure and tunable functionality. Herein, a novel 3D MOF material MOF-18Cr6, in which 1D channels are formed using 18-crown-6-ether-containing ligands as channel walls, is fabricated for strontium(II) separation. In contrast to traditional MOFs designed by grafting functional groups in the framework pores, MOF-18Cr6 possesses regular 18-crown-6-ether cavities on the channel walls, which not only can transport and intake strontium(II) via the channels, but also prevent blockage of the channels after the binding of strontium(II). Consequently, the functional sites are fully utilized to achieve a high strontium(II) removal rate of 99.73 % in simulated nuclear wastewater. This study fabricates a highly promising adsorbent for the separation of aqueous radioactive strontium(II), and more importantly, can provide a new strategy for the rational design of high-performance MOF adsorbents for separating target substances from complex aqueous environments.

Aspartyl tRNA-synthetase (AspRS) gene family enhances drought tolerance in poplar through BABA-PtrIBIs-PtrVOZ signaling module.

BACKGROUND: Drought stress is a prevalent abiotic stress that significantly hinders the growth and development of plants. According to studies, ß-aminobutyric acid (BABA) can influence the ABA pathway through the AtIBI1 receptor gene to enhance cold resistance in Arabidopsis. However, the Aspartate tRNA-synthetase (AspRS) gene family, which acts as the receptor for BABA, has not yet been investigated in poplar. Particularly, it is uncertain how the AspRS gene family (PtrIBIs)r can resist drought stress after administering various concentrations of BABA to poplar. RESULTS: In this study, we have identified 12 AspRS family genes and noted that poplar acquired four PtrIBI pairs through whole genome duplication (WGD). We conducted cis-action element analysis and found a significant number of stress-related action elements on different PtrIBI genes promoters. The expression of most PtrIBI genes was up-regulated under beetle and mechanical damage stresses, indicating their potential role in responding to leaf damage stress. Our results suggest that a 50 mM BABA treatment can alleviate the damage caused by drought stress in plants. Additionally, via transcriptome sequencing, we observed that the partial up-regulation of BABA receptor genes, PtrIBI2/4/6/8/11, in poplars after drought treatment. We hypothesize that poplar responds to drought stress through the BABA-PtrIBIs-PtrVOZ coordinated ABA signaling pathway. Our research provides molecular evidence for understanding how plants respond to drought stress through external application of BABA. CONCLUSIONS: In summary, our study conducted genome-wide analysis of the AspRS family of P. trichocarpa and identified 12 PtrIBI genes. We utilized genomics and bioinformatics to determine various characteristics of PtrIBIs such as chromosomal localization, evolutionary tree, gene structure, gene doubling, promoter cis-elements, and expression profiles. Our study found that certain PtrIBI genes are regulated by drought, beetle, and mechanical damage implying their crucial role in enhancing poplar stress tolerance. Additionally, we observed that external application of low concentrations of BABA increased plant drought resistance under drought stress. Through the BABA-PtrIBIs-PtrVOZ signaling module, poplar plants were able to transduce ABA signaling and regulate their response to drought stress. These results suggest that the PtrIBI genes in poplar have the potential to improve drought tolerance in plants through the topical application of low concentrations of BABA.

Genomic and epidemiological perspectives on the first local sporadic cases of Mpox in China.

From June 7th to 11th, 2023, eight cases of Mpox were identified in Guangzhou, China. This is the first report of multiple local sporadic cases after the imported case in Chongqing, China. Epidemiological investigation revealed that these cases had no history of international travel and no connections with each other. Haplotype network and phylogenetic analyses indicated that the possible origin is likely from Japan, although the direct origin may remain uncertain due to limited genomic sequences and sampling bias in GISAID. The three Guangzhou sequences have accumulated several novel mutations, suggesting the local transmission of Mpox may have been ongoing for some time. Based on the daily cases during the early stage of Mpox outbreak in four other countries, the number of possible infected cases in Guangzhou is inferred to be more than 300, suggesting that swift and efficient control measures must be implemented to mitigate the risk of a potential epidemic.

Feasibility of an improved knotless method of chest drain wound closure:a prospective cohort clinical trial.

OBJECTIVE: Chest tube management plays a key role in minimising erioperative period. We have improved the knotless method to chest tube wounds. In this article, we demonstrate the clinical bility and safety of this method. METHOD: From 13 October 2018-3 January 2019, patients were ecutively included in our study at the First Affiliated Hospital of n Medical University, Dalian, China. They were separated into approximately equally sized groups-the knotless group and the entional group. Our improved knotless method was performed ose the chest tube wounds of patients in the knotless group, and onventional method using the pre-existing U-shaped string to the chest tube wounds of patients in the conventional group. Patient clinical information, tube-related complications, retreatment s and cosmetic scores were compared between the groups. RESULTS: The cohort comprised 102 patients; 47 in the knotless group and 55 in the conventional group. There were no statistically significant differences in patient clinical information or tube-related complications between the two groups (p>0.05; both comparisons). In the knotless group, retreatment times were shorter (p<0.001) and cosmetic scores were higher (p<0.001). CONCLUSION: This study showed that our new knotless method is safe and has wide clinical feasibility. The new method also improved patient cosmetic scores. Furthermore, it decreased the patients' economic burdens.

Attitudes and influencing factors associated with smoking cessation: An online cross-sectional survey in China.

INTRODUCTION: Quitting smoking, the critical path to reach the global targets of reducing tobacco use, can bring major and immediate health benefits to smokers. Exploring factors that help individuals to quit smoking is of great importance. The present study explored influencing factors on smoking cessation, in order to provide comprehensive reference for tobacco control policies. METHODS: Ex-smokers and current smokers were recruited online in this cross-sectional survey, from 1 October to 31 November 2022, in China. The observational data were collected using a questionnaire to collect information with respect to sociodemographic characteristics of smokers, attitudes towards smoking cessation, details of smoking cessation, and different potential factors related to smoking cessation through open-ended questions. RESULTS: A total of 638 smokers from 30 provinces were recruited as eligible respondents, with a mean age of 37.3 ± 11.7 years and a mean smoking history of 15.9 ± 13.7 years. The percentage of males was 92.3%. Of the 638 respondents, only 3.9% had no intention to stop smoking. Among 155 subjects who had quitted smoking successfully, willpower (55.5%) was considered as the most important contributing factor. Among 365 subjects who tried to quit but failed, lack of willpower (28.2%), tobacco dependence (16.2%), influence of surrounding smokers or smoking environments (15.9%), bad moods (9.9%), stress from work or life (7.9%), habits (7.1%), socialization (4.1%), and easy availability of tobacco (2.7%) were considered as the adverse factors leading to failure in quitting smoking. CONCLUSIONS: Willpower and support from family members were the vital factors that lead to successful smoking cessation. Future tobacco control policies should also focus on addressing withdrawal symptoms and creating smoke-free environments as well as other factors.

Prognostic Value of Pretreatment Serum Carcinoembryonic Antigen Level in 1130 Patients With Non-small Cell Lung Cancer: A Propensity Score Matching Cohort Study and Cumulative Meta-analysis.

OBJECTIVES: Carcinoembryonic antigen (CEA) is the most frequently used tumor marker for non-small cell lung cancer (NSCLC). The current study aimed to provide the highest-level evidence of the prognostic value of pretreatment serum CEA level for NSCLC through the appropriate statistical methodology and large-sample cohorts. METHODS: The current retrospective cohort study with 1130 patients with NSCLC treated by thoracic surgery with pretreatment serum CEA concentrations above/below 5 ng/mL. Propensity score matching, Kaplan-Miere survival analysis, and Cox proportional hazard regression models were used to study the intergroup variance. The overall/disease-free hazard ratios (HRs) of the current study were combined with the previously published studies using cumulative meta-analysis to provide the highest-level evidence. RESULTS: Intergroup confounding variables were well controlled by propensity score matching, and the survival differences were statistically significant. The Cox univariate analysis showed that the overall and disease-free HRs of the high CEA towards patients with low CEA were 1.595 (95% CI: 1.329-1.863, P = 0.004) and 1.498 (95% CI: 1.271-1.881, P = 0.004). The HRs of multivariate analysis were adjusted to 1.586 (95% CI: 1.398-1.812, P = 0.016) and 1.413 (95% CI: 1.22-1.734, P = 0.022) respectively. The cumulative meta-analysis showed that the cumulative overall HR was in accord with previous studies, and the cumulative disease-free HR turn to be statistically significant. CONCLUSIONS: Pretreatment serum CEA level was an independent influence factor of overall/disease-free survival of patients with NSCLC, and even for patients with the same pTNM stages or pathologic stages, it is used for prognosis.

High-efficiency uranium extraction from seawater by low-cost natural protein hydrogel.

Utilization of uranium resource in seawater are highly possible to meet the growth demands for the sustainable development of nuclear energy industry. Bio-adsorbents exhibit high performance in terms of adsorption selectivity, equilibrium speed, and environmental friendliness, while the high fabrication cost hinders their practical application. In this study, a low-cost soy protein isolate (SPI) is used to fabricate adsorbent named SPI hydrogel for uranium extraction. This is the first report on applying bio-adsorbents derived from low-cost natural proteins for uranium extraction. The SPI hydrogel showed high uranium adsorption capacity of 53.94 mg g-1 in simulated nuclear wastewater and 5.29 mg g-1 is achieved in natural seawater, which is higher than all currently available adsorbents based on non-modified natural biomolecules. The amino and oxygen-containing groups are identified as the functional groups for uranyl binding by providing four oxygen and two nitrogen atoms to form equatorial coordination with uranyl, which guarantees the high binding selectivity and affinity to uranyl ions. The low cost for accessing the raw material together with the environmental friendliness, high salt tolerance, high uranium adsorption ability, and high selectivity to uranium, make SPI hydrogel a promising adsorbent for uranium extraction from seawater and nuclear wastewater.

Protocol for optical detection of iodide ions in aqueous environments using a zirconium(IV)-enhanced strategy.

Detection of radioactive iodide ions (I-) is important for protecting human beings from the hazards of radioactive pollution. Herein, we present a protocol for detecting I- using a zirconium(IV)-enhanced strategy. We describe steps for optimizing the I- detection approach, establishing standard curves, and finally applying the approach. The use of zirconium(IV) greatly improves the detection performance and endows this approach with an ultralow detection limit of 0.176 nM together with wide applicability in various aqueous environments. For complete details on the use and execution of this protocol, please refer to Feng et al. (2022).1.

Ultrafast extraction of uranium from seawater using photosensitized biohybrid system with bioinspired cascaded strategy.

The highly effective utilization of uranium resources in global seawater is a viable method to satisfy the rising demands for fueling nuclear energy industry. Herein, inspired by the multi-mechanisms of the marine bacteria for uranium immobilization, CdS nanoparticles are deposited on the cell of marine bacterial strain Bacillus velezensis UUS-1 to create a photosensitized biohybrid system UUS-1/CdS. This system achieves high uranium extraction efficiency using a cascaded strategy, where the bacterial cells guarantee high extraction selectivity and the photosensitive CdS nanoparticles realize cascading photoreduction of high soluble U(VI) to low soluble U(IV) to enhance extraction capacity. As one of the fastest-acting adsorbents in natural seawater, a high extraction capacity for uranium of 7.03 mg g-1 is achieved with an ultrafast extraction speed of 4.69 mg g-1 d-1. The cascaded strategy promisingly improves uranium extraction performance and pioneers a new direction for the design of adsorbents to extract uranium from seawater.

Circulating monocyte-platelet aggregates with different monocyte subsets and their association with disease severity in chronic kidney disease.

BACKGROUND: Chronic kidney disease (CKD) is usually considered an immune inflammatory disease. Interaction between platelets and monocytes is associated with immune inflammation. Cross-talk between platelets and monocytes is reflected by formation monocyte-platelet aggregates (MPAs). This study aims to test MPAs and MPAs with the different monocyte subsets to evaluate their association with disease severity in CKD. METHODS: Forty-four hospitalized patients with CKD and twenty healthy volunteers were enrolled. The proportion of MPAs and MPAs with the different monocyte subsets were tested by flow cytometry. RESULTS: The proportion of circulating MPAs in all patients with CKD were significantly higher than those of healthy controls (p<0.001). A higher proportion of MPAs with classical monocytes (CM) was found in CKD4-5 patients (p=0.007), while another higher proportion of MPAs with non-classical monocytes (NCM) was found CKD2-3 patients (p<0.001). The proportion of MPAs with intermediate monocytes (IM) in CKD 4-5 group was significantly higher in comparison to CKD2-3 group and healthy controls (p<0.001). Circulating MPAs were found to be correlated with serum creatinine (r=0.538, p<0.001) and eGFR (r=-0.864, p<0.001). The AUC for MPAs with IM was 0.942 (95% CI 0.890-0.994, p<0.001). CONCLUSIONS: Study results highlight the interplay between platelets and inflammatory monocytes in CKD. There are alterations in circulating MPAs and MPAs with the different monocyte subsets in CKD patients compared to controls which change with CKD severity. The MPAs may have an important role in the development of CKD or as a predictive marker for monitoring disease severity.

Comparison between functional lung volume measurement and segment counting for predicting postoperative pulmonary function after pulmonary resection in lung cancer patients.

BACKGROUND: Functional lung volume (FLV) obtained from computed tomography images was a breakthrough for lung imaging and functional assessment. We compared the accuracy of the FLV measurement method and the segment-counting (SC) method in predicting postoperative pulmonary function. METHODS: A total of 113 patients who underwent two thoracoscopic surgeries were enrolled in our study. We predicted postoperative pulmonary function by the FLV measurement method and the SC method. Novel formulas based on the FLV measurement method were established using linear regression equations between the factors affecting pulmonary function and the measured values. RESULTS: The predicted postoperative forced vital capacity (ppoFVC) and forced expiratory volume in 1 s (ppoFEV1) measured by the 2 methods showed high concordance between the actual postoperative forced vital capacity (postFVC) and the forced expiratory volume in 1 s (postFEV1) [r = 0.762, P < 0.001 (FLV method) and r = 0.759, P < 0.001 (SC method) for FVC; r = 0.790, P < 0.001 (FLV method) and r = 0.795, P < 0.001 (SC method) for FEV1]. Regression analysis showed that the measured preoperative pulmonary function parameters (FVC, FEV1) and the ratio of reduced FLV to preoperative FLV were significantly associated with the actual postoperative values and could predict these parameters (all P < 0.001). The feasibility of using these equations [postFVC = 0.8 × FVC - 0.784 × ΔFLV/FLV + 0.283 (R2 = 0.677, RSD = 0.338), postFEV1 = 0.766 × FEV1 - 0.694 × ΔFLV/FLV + 0.22 (R2 = 0.743, RSD = 0.265)] to predict the pulmonary function parameters after wedge resection was also verified. CONCLUSIONS: The new FLV measurement method is valuable for predicting postoperative pulmonary function in patients undergoing lung resection surgery, with accuracy and consistency similar to those of the conventional SC method.

Functional divergence of GhAP1.1 and GhFUL2 associated with flowering regulation in upland cotton (Gossypium hirsutum L.).

The AP1/FUL transcription factors are important for floral development, but the underlying molecular mechanisms remain unclear. In this study, we cloned and identified two AP1/FUL-like genes, GhAP1.1 and GhFUL2, in upland cotton, which is a commonly cultivated economically valuable crop. Sequence alignment and phylogenetic analysis indicated that GhAP1.1 and GhFUL2, which are encoded by genes in the AP1/FUL clade, have conserved N-terminal regions but diverse C-terminal domains. Quantitative real-time PCR analysis revealed that GhAP1.1 and GhFUL2 were expressed in the flower and root, and showed opposite expression patterns during shoot apical meristem development. The upregulated expression of GhAP1.1 in Arabidopsis did not result in significant changes to the flowering time or floral organ development, and the transcript levels of the florigen FT increased and those of LFY decreased. Overexpression of GhFUL2 in Arabidopsis delayed flowering and promoted bolting by decreasing FT and LFY transcript levels. Silencing GhFUL2 in cotton dramatically increased the expression of GhFT and GhAP1.3 and promoted flowering. Yeast two-hybrid and bimolecular fluorescence complementation assays indicated that GhAP1.1 could interact with the SVP homolog GhSVP2.2, whereas GhFUL2 formed heterodimers with GhSEP3/GhSEP4 homologs and GhSVP2.2. The present results demonstrated that the functional divergence of GhAP1.1 and GhFUL2, which involved changes in sequences and expression patterns, influenced the regulation of cotton flower development.

Ongoing Positive Selection Drives the Evolution of SARS-CoV-2 Genomes.

SARS-CoV-2 is a new RNA virus affecting humans and spreads extensively throughout the world since its first outbreak in December, 2019. Whether the transmissibility and pathogenicity of SARS-CoV-2 in humans after zoonotic transfer are actively evolving, and driven by adaptation to the new host and environments is still under debate. Understanding the evolutionary mechanism underlying epidemiological and pathological characteristics of COVID-19 is essential for predicting the epidemic trend, and providing guidance for disease control and treatments. Interrogating novel strategies for identifying natural selection using within-species polymorphisms and 3,674,076 SARS-CoV-2 genome sequences of 169 countries as of December 30, 2021, we demonstrate with population genetic evidence that during the course of SARS-CoV-2 pandemic in humans, 1) SARS-CoV-2 genomes are overall conserved under purifying selection, especially for the 14 genes related to viral RNA replication, transcription, and assembly; 2) ongoing positive selection is actively driving the evolution of 6 genes (e.g., S, ORF3a, and N) that play critical roles in molecular processes involving pathogen-host interactions, including viral invasion into and egress from host cells, and viral inhibition and evasion of host immune response, possibly leading to high transmissibility and mild symptom in SARS-CoV-2 evolution. According to an established haplotype phylogenetic relationship of 138 viral clusters, a spatial and temporal landscape of 556 critical mutations is constructed based on their divergence among viral haplotype clusters or repeatedly increase in frequency within at least 2 clusters, of which multiple mutations potentially conferring alterations in viral transmissibility, pathogenicity, and virulence of SARS-CoV-2 are highlighted, warranting attention.

The distinct morphological phenotypes of Southeast Asian aborigines are shaped by novel mechanisms for adaptation to tropical rainforests.

Southeast Asian aborigines, the hunter-gatherer populations living in tropical rainforests, exhibit distinct morphological phenotypes, including short stature, dark skin, curly hair and a wide and snub nose. The underlying genetic architecture and evolutionary mechanism of these phenotypes remain a long-term mystery. We conducted whole genome deep sequencing of 81 Cambodian aborigines from eight ethnic groups. Through a genome-wide scan of selective sweeps, we discovered key genes harboring Cambodian-enriched mutations that may contribute to their phenotypes, including two hair morphogenesis genes (TCHH and TCHHL1), one nasal morphology gene (PAX3) and a set of genes (such as ENTPD1-AS1) associated with short stature. The identified new genes and novel mutations suggest an independent origin of the distinct phenotypes in Cambodian aborigines through parallel evolution, refuting the long-standing argument on the common ancestry of these phenotypes among the worldwide rainforest hunter-gatherers. Notably, our discovery reveals that various types of molecular mechanisms, including antisense transcription and epigenetic regulation, contribute to human morphogenesis, providing novel insights into the genetics of human environmental adaptation.