High throughput sequencing reveals alterations in B cell receptor repertoires associated with the progression of hepatic cirrhosis to hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is developed as a consequence of chronic liver cirrhosis, and both diseases are difficult to diagnose and differentiate. Accurate noninvasive biomarkers for HCC and liver cirrhosis are urgently needed. METHODS: Here we used high-throughput sequencing to characterize the B cell receptor (BCR) repertoires from 36 HCC tumor samples and 10 liver cirrhosis (LC) tissue biopsies to understand the immune alterations during hepatic carcinogenesis. RESULTS: The principal components analysis (PCA) showed that the pattern of BCR in HCC was distinct from that in LC. As measured by Clonality and Shannon indexes, the diversity of BCR repertoire was significantly lower in HCC than in LC (P < 0.01). CONCLUSION: Our results corroborated that the BCR diversity and composition could be closely correlated with hepatic carcinogenesis. And BCR repertoire may be used to predict the progression of HCC and design targeting immunotherapy in the near future.

Clinical and Prognostic Differences in Mild to Moderate COPD With and Without Emphysema.

BACKGROUND: The clinical and prognostic characteristics of mild-to-moderate chronic obstructive pulmonary disease (COPD) with and without emphysema remain inadequately investigated. RESEARCH QUESTION: Do the clinical and prognostic characteristics differ between mild- to-moderate COPD with and without emphysema? STUDY DESIGN AND METHODS: We obtained clinical data of 989 participants with mild-to-moderate COPD from the Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS). They were categorized into two groups based on their baseline %LAA-950 of less than 5% on CT scans: those with emphysema (EC group) and those without emphysema (NEC group). Linear mixed-effects models were utilized to assess the differences in the decline of lung function, health-related quality of life, and quantitative CT indices between these two groups. Zero-inflated negative binomial regressions were employed to evaluate the rates of acute respiratory exacerbations between the groups. RESULTS: Among participants with mild-to-moderate COPD, 428 (43.3%) exhibited emphysema on CT scans. The annual decline in FEV1 was -56.1 mL/year for the EC group and -46.9 mL/year for the NEC group, with a non-significant between-group difference of 9.1 mL/year (95% CI, -24.0 to 5.7 mL/year). The rate of emphysema progression in the EC group was significantly lower than in the NEC group (-0.173%; 95% CI, -0.252 to -0.094). The EC group also showed a more pronounced annual increase in the SGRQ score (0.9 points) compared to the NEC group. The EC group had a higher rate of acute respiratory exacerbations (0.36 per person-year) than the NEC group (0.25 per person-year), with a rate ratio of 1.42 (95% CI, 1.27 to 1.54). INTERPRETATION: Mild-to-moderate COPD with emphysema did not have accelerated rates of decline in FEV1, but they experienced significantly worsen health-related quality of life and a higher rate of acute respiratory exacerbations. The non-emphysema subtype demonstrated increased emphysema progression.

Imaging Spin-Orbit Excitation of Yttrium through High-Energy Collisions with Rare Gas Atoms.

The energy required for spin-orbit excitation plays a critical role in understanding translational-to-electronic energy conversion, particularly in chemical reactions involving changes in spin states. This is particularly important for transition metal atoms possessing d-orbitals, which result in multiple spin-orbit split energy levels at low energies. The accurate identification and characterization of spin-orbit transitions in such species require advanced experimental techniques and theoretical support. In this study, the spin-orbit excited collisions of Y(2D3/2) with rare gas atoms Ne, Ar, and Kr leading to Y(2D5/2) were observed using laser-ablated crossed-beam and time-sliced ion velocity mapping imaging techniques. Through a comparison of the forward angular distributions of Y(2D3/2) to the backward and sideway scattering distributions of Y(2D5/2) from elastic and inelastic collisions of Y(2D) with rare gas atoms, this study reveals that the spin-orbit electronic excitation occurs with high collision energy and low impact parameters from backward and sideway collisions. The effectiveness of the spin-orbit excitation process is strongly dependent on the collision energy or temperature, suggesting that energy requirements of the process have to be considered in chemical reactions involving changes in spin states.

Predicting Acute Exacerbation Phenotype in Chronic Obstructive Pulmonary Disease Patients Using VGG-16 Deep Learning.

INTRODUCTION: Exacerbations of chronic obstructive pulmonary disease (COPD) have a significant impact on hospitalizations, morbidity, and mortality of patients. This study aimed to develop a model for predicting acute exacerbation in COPD patients (AECOPD) based on deep-learning (DL) features. METHODS: We performed a retrospective study on 219 patients with COPD who underwent inspiratory and expiratory HRCT scans. By recording the acute respiratory events of the previous year, these patients were further divided into non-AECOPD group and AECOPD group according to the presence of acute exacerbation events. Sixty-nine quantitative CT (QCT) parameters of emphysema and airway were calculated by NeuLungCARE software, and 2,000 DL features were extracted by VGG-16 method. The logistic regression method was employed to identify AECOPD patients, and 29 patients of external validation cohort were used to access the robustness of the results. RESULTS: The model 3-B achieved an area under the receiver operating characteristic curve (AUC) of 0.933 and 0.865 in the testing cohort and external validation cohort, respectively. Model 3-I obtained AUC of 0.895 in the testing cohort and AUC of 0.774 in the external validation cohort. Model 7-B combined clinical characteristics, QCT parameters, and DL features achieved the best performance with an AUC of 0.979 in the testing cohort and demonstrating robust predictability with an AUC of 0.932 in the external validation cohort. Likewise, model 7-I achieved an AUC of 0.938 and 0.872 in the testing cohort and external validation cohort, respectively. CONCLUSIONS: DL features extracted from HRCT scans can effectively predict acute exacerbation phenotype in COPD patients.

Retraction: circRASSF2 promotes IGF1R and osteosarcoma metastasis via sponging miR-6838-5p.

[This retracts the article DOI: 10.21037/atm-21-6123.].

Can digital economy foster synergistic increases in green innovation and corporate value? Evidence from China.

The rapid evolution of the digital economy has significantly accelerated progress towards achieving green and sustainable processes, particularly in the field of green production. While existing research has delved into the effects of the digital economy on Green Innovation (GI) and the consequences of digital transformation on Corporate Value (CV), there remains a notable gap in the literature regarding the potential for synergistic enhancements in firms' GI&CV through the ongoing digital revolution. This study utilizes an evolutionary game model and employs system dynamics methods to simulate the dynamic evolution trajectory of the influence of the digital economy on the synergy between GI&CV. Subsequently, it empirically assesses the interconnected synergies between GI&CV using a dataset comprising information from Chinese listed firms spanning from 2011 to 2020, examining the impact of the digital economy on these synergies. Moreover, the study delves into the analysis of the transmission mechanism and conducts an extended investigation to further explore this phenomenon. The findings of this paper including: (1) The digital economy acts as a driving force behind the synergistic enhancement of firm GI&CV. Moreover, this effect is further augmented by governmental environmental regulation and green subsidy policies. (2) Drawing upon the information asymmetry theory and the resource-based theory, the regional marketization level and firms' digital transformation play intermediary roles. (3) The heterogeneity test indicate that firms situated in eastern regions and those classified as non-heavily polluted benefitted to a greater extent. This study sheds light on the incentive implications of digital economy for the synergistic upgrading of GI&CV, thereby extending the breadth of study on the consequences of digital economy. Moreover, it offers actionable suggestions for enterprises to leverage digital economy development towards achieving a synergistic improvement of GI&CV.

MATN4 as a target gene of HIF-1α promotes the proliferation and metastasis of osteosarcoma.

BACKGROUND: Osteosarcoma is a highly malignant bone tumor that exhibits rapid growth and early metastasis. Hypoxia plays a pivotal role in promoting the proliferation and metastasis of osteosarcoma through a series of molecular events, which are partially mediated and regulated by HIF-1α. However, the regulatory network associated with HIF-1α in osteosarcoma remains limited. Therefore, the objective of this study was to identify critical hypoxia-associated genes and investigate their effects and molecular mechanisms in osteosarcoma cells. METHODS: Through bioinformatics analysis, matrilin-4 (MATN4) was identified as a crucial gene associated with hypoxia. The expression of MATN4 and HIF-1α was assessed using immunohistochemistry, RT-qPCR, and western blotting. The proliferative capacity of osteosarcoma cells was assessed through the utilization of CCK-8, EDU staining, and colony formation assays. The effects of MATN4 on the mobility of OS cells were evaluated using wound-healing assays and transwell assays. The interaction between MATN4 and HIF-1α was detected through chromatin immunoprecipitation. RESULTS: MATN4 is overexpressed in osteosarcoma tissue and cells, particularly in osteosarcoma cells with high metastatic potential. Knockdown of MATN4 inhibits the proliferation, migration, and invasion abilities of osteosarcoma cells and reverses the promoting effects of hypoxia on these functions. Additionally, HIF-1α binds to MATN4 and upregulates its expression. Interestingly, knockdown of HIF-1α reduces the stimulatory effects of MATN4 overexpression on the proliferation, migration, and invasion of osteosarcoma cells under hypoxic conditions. CONCLUSIONS: Taken together, our results suggest that MATN4 is regulated by HIF-1α and confers a more aggressive phenotype on OS cells. This evidence suggests that MATN4 may act as a potential target for OS diagnosis and treatment.

Imaging Rovibrational Excitation of Scattered YO Molecules in Inelastic Collisions with Kr and Ne.

Energy transfer between atoms and molecules is fundamental to many physical and chemical processes, and understanding the mechanisms and outcomes of energy transfer is crucial for various applications in physics and chemistry. Here, the rovibrational excitation of YO(X 2Σ+) molecules with the collision of Kr and Ne has been studied in the laser-ablation crossed beam and time-sliced ion velocity map imaging setup in combination with the resonance enhanced multiphoton ionization scheme. Significant changes in the angular distribution for different rovibrational excitations of YO molecules are observed with the collision of Kr. The sharp forward distribution for low rovibrational excitation of YO(v' = 0, 1) molecules suggest that the weak attractive potential between Kr and YO is dominant at large impact parameters. Comparatively, the strong sideway distribution for highly rovibrationally excited YO(v' = 1, 2, 3, and 5) is due to rainbow scattering from the stronger attractive potential of Kr···YO at relatively small impact parameters. The more isotropic angular distribution in the highly rovibrationally excited YO(v' = 11) indicates the formation of a short-lived complex. A change in the angular distribution of scattered YO with different rovibrational excitations was also observed in the collisions of Ne. For YO as a heteronuclear diatomic molecule, collisions of the Y- and the O-end of YO with rare gases would affect the contribution of inelastic processes at different impact parameters.

Human genetic associations of the airway microbiome in chronic obstructive pulmonary disease.

Little is known about the relationships between human genetics and the airway microbiome. Deeply sequenced airway metagenomics, by simultaneously characterizing the microbiome and host genetics, provide a unique opportunity to assess the microbiome-host genetic associations. Here we performed a co-profiling of microbiome and host genetics with the identification of over 5 million single nucleotide polymorphisms (SNPs) through deep metagenomic sequencing in sputum of 99 chronic obstructive pulmonary disease (COPD) and 36 healthy individuals. Host genetic variation was the most significant factor associated with the microbiome except for geography and disease status, with its top 5 principal components accounting for 12.11% of the microbiome variability. Within COPD individuals, 113 SNPs mapped to candidate genes reported as genetically associated with COPD exhibited associations with 29 microbial species and 48 functional modules (P < 1 × 10-5), where Streptococcus salivarius exhibits the strongest association to SNP rs6917641 in TBC1D32 (P = 9.54 × 10-8). Integration of concurrent host transcriptomic data identified correlations between the expression of host genes and their genetically-linked microbiome features, including NUDT1, MAD1L1 and Veillonella parvula, TTLL9 and Stenotrophomonas maltophilia, and LTA4H and Haemophilus influenzae. Mendelian randomization analyses revealed a potential causal link between PARK7 expression and microbial type III secretion system, and a genetically-mediated association between COPD and increased relative abundance of airway Streptococcus intermedius. These results suggest a previously underappreciated role of host genetics in shaping the airway microbiome and provide fresh hypotheses for genetic-based host-microbiome interactions in COPD.

Culture and self-construal in the age of globalization: an empirical inquiry based on multiple approaches.

Introduction: There are three main types of culture in human society, namely, individual-oriented, relationship-oriented and social-oriented cultures. In history, there are two main positions on the relationship between culture and self-construal: the cultural determinist position and the interaction position. After analyzing literature critically, we propose that the interaction position is more persuasive than the cultural determinist position. A self-construal model was constructed from an interactionist and polycultural perspective, pointing out the relationship between three cultures and self-construal. We argue that individuals interacting with cultures in the context of globalization can develop a more integrated self-construal. The present study proposes the existence of polycultural self-construal, and aimed to explore how self-construal factors relate to cultures. Methods: Three approaches-psychological tests, priming with cultural icons and content analysis-were used to explore mechanisms between cultures (individual-oriented, relationship-oriented, and social-oriented cultures) and self-construal. In Study 1, we recruited 460 undergraduate students as participants through campus advertising to complete three psychological tests, namely, the Cultural Identity Scale (CIS), the Marlowe-Crowne Social Approval Scale (MC-SDS), and the Polycultural Self-construal Scale (PSCS). In Study 2, we created icon materials that could prime the three cultures. The experimental process was divided into two stages: priming and measurement. First, 165 participants were presented with icon materials on the computer screen to activate the corresponding culture, and then they were asked to complete the PSCS. In Study 3, the experimental procedures were followed as for Study 2. Then the Ten Statements Test (TST) was used. Each of the 178 participants gave 10 different responses to the question of "Who am I?." Each participant's "I am …" narratives were qualitatively processed using content analysis. Results: The individual-oriented culture mainly affects the individuality and equality factor of self-construal. The relationship-oriented culture mainly impacts the relationality factor of self-construal, while the social-oriented culture mainly affects the collectivity and equality factors of self-construal. There were no significant differences in the effects of the three cultures on the autonomy factor of self-construal. The multi-components of the polycultural self-construal are difficult to interpret based on one culture type. All three cultures have specific and shared effects on human self-construal.

pH-responsive interface conversion efficient oral drug delivery platform for alleviating inflammatory bowel disease.

A key challenge for the effective treatment of intestinal diseases, including inflammatory bowel disease (IBD), is to develop an oral drug delivery system that can resist gastric acid erosion and efficiently release drugs after rapid entry into the intestine. In the present work, we developed oral composite nanoparticles (MSZ@PRHS) consisting of a rough mesoporous silica (RHS) loaded with Mesalazine (MSZ) and a CAP polymer membrane for targeted relief of inflammation in colitis. At the pH values of the simulated stomach and small intestine, the release rate of MSZ from MSZ@PRHS was low, while at the pH values of the simulated colon, the release rate of MSZ was high. In dextran sulfate sodium salt (DSS)-induced acute colitis mouse model, compared with oral administration of the drug Mesalazine in the equivalent solution form, oral administration of PRHS loaded with drug-loaded nanoparticles can significantly alleviate the symptoms of inflammatory bowel disease, and improve the therapeutic effect. We propose that the intestinal microenvironment provides an interface for nanocomposites switch and a promising drug delivery platform for the management and treatment of many intestinal diseases, where controlled drug release and prolonged residence time are required.

Negative gallbladder stones: Diagnostic advantages of dual-energy CT and analysis of a unique case.

BACKGROUND: Gallbladder stones are a common digestive system disease, but their diagnosis can be limited in some cases, especially in identifying "negative" stones, which may be difficult to recognize with traditional CT scans. OBJECTIVE: This study aims to explore the advantages of dual-energy CT in diagnosing negative gallbladder stones through a unique case of gallbladder stones. METHODS AND RESULTS: A case of a 31-year-old female is described, who was diagnosed with gallbladder stones during a physical examination two years ago and occasionally experienced pain in the upper right abdomen. Dual-energy CT scanning revealed a mixed-density stone, approximately 2 cm in diameter, in the neck of the gallbladder, consisting of a calcified shell (positive stone) and a homogenous density nucleus (negative stone). Verified by dual-energy CT, single-energy images and spectral curves can very intuitively identify negative stones, demonstrating significantly superior performance compared to traditional CT. CONCLUSION: Dual-energy CT, through single-energy images and spectral curves, intuitively identifies negative gallbladder stones, showcasing significant advantages compared to traditional CT, and offers a valuable approach to enhancing the diagnostic accuracy of gallbladder stones.

The global state of research in stem cells therapy for spinal cord injury (2003-2022): a visualized analysis.

Objective: Our study aimed to visualize the global status and frontiers in stem cell therapy for spinal cord injury by using bibliometric methodology. Methods: Publication citation information related to stem cell therapy for spinal cord injury (SCI) studies between 2003 and 2022 was retrieved from the Web of Science Core Collection database. For the visualized study, VOS viewer software and Graph Pad Prism 9.5 were used to perform bibliometric analysis of included data and publication number statistics in stem cell therapy for the SCI domain. Results: A total of 6,686 publications were retrieved. The USA and China made the highest contributions to global research with the highest number of citations and link strength. The journal Experimental Neurology ranks as the top journal, combining the publication amount and bibliometrics results. The University of Toronto, based in Canada, was the first-ranking institution. The directions of the current study could be divided into five clusters. The research of Transplantation and Regenerative Medicine and Neurosciences Mechanism Research may be the emerging frontiers in this domain. Conclusion: In summary, stem cell therapy for spinal cord injuries is poised for more valuable advances.

Hypoxia inducible factor-1ɑ as a potential therapeutic target for osteosarcoma metastasis.

Osteosarcoma (OS) is a malignant tumor originating from mesenchymal tissue. Pulmonary metastasis is usually present upon initial diagnosis, and metastasis is the primary factor affecting the poor prognosis of patients with OS. Current research shows that the ability to regulate the cellular microenvironment is essential for preventing the distant metastasis of OS, and anoxic microenvironments are important features of solid tumors. During hypoxia, hypoxia-inducible factor-1α (HIF-1α) expression levels and stability increase. Increased HIF-1α promotes tumor vascular remodeling, epithelial-mesenchymal transformation (EMT), and OS cells invasiveness; this leads to distant metastasis of OS cells. HIF-1α plays an essential role in the mechanisms of OS metastasis. In order to develop precise prognostic indicators and potential therapeutic targets for OS treatment, this review examines the molecular mechanisms of HIF-1α in the distant metastasis of OS cells; the signal transduction pathways mediated by HIF-1α are also discussed.

Does incentive-based green governance compensate for green innovation in enterprises? The role of green orientation.

Government-led green governance, as a crucial tool for achieving green and sustainable development, has garnered significant attention among researchers worldwide. Nevertheless, research on incentive-based green governance and green orientation remains insufficient. This study adopts an evolutionary game theory framework to elucidate the mechanisms underlying incentive-based green governance and green orientation in facilitating green innovation. The effectiveness of this framework is then verified through the utilization of propensity score matching (PSM) and difference-in-differences (DID) methods using data from Chinese companies. The main findings include the following: (1) Government incentive-based green governance exhibits a compensatory effect on green innovation, which is validated through robustness testing. (2) Internal green orientation serves as an intermediary factor between incentive-based green governance and green innovation, while external green orientation exerts a positive regulatory effect. (3) Heterogeneity analysis demonstrates that the impact of incentive-based green governance on green innovation is more pronounced in non-high-pollution industries, high-tech corporations, and companies operating in areas with lower governance intensity. This study is conducive to illustrate the compensatory effect of government incentive-based green governance on green innovation and also provides reference for the government to issue targeted green governance policies.

Liquid concrete as a gastrointestinal tract foreign body.

Gastrointestinal foreign bodies present a common clinical challenge. We present an unusual case of a 58-year-old construction worker who ingested liquid concrete that risked solidifying in his stomach. Gastroscopy revealed only partial solidification and pyloric obstruction, which were successfully resolved through endoscopic fragmentation and mechanical removal. To protect the gastric mucosa during elimination, liquid paraffin and a cellulose-based formula were administered. Complete gastrointestinal evacuation was achieved within 3 days, with no complications observed. This case emphasises the urgency of the early removal of concrete.

A global 2A″ state potential energy surface for the Al (2P) + O2 (Σg-3) → AlO (2Σ+) + O (3P) reaction based on the doubly hybrid functional XYG3.

In this paper, a global and full-dimensional potential energy surface at the 2A″ ground state for the Al + O2 → AlO + O reaction was constructed, for the first time, based on extensive electronic structure calculations using the doubly hybrid functional XYG3 and potential energy surface fittings by neural networks. Details of the reaction paths have been analyzed. It was found that both two intermediates, the cyclic-AlO2 and the linear-OAlO, were able to dissociate to the AlO + O products, and the isomerization process between these two intermediates was controlled by conical intersections between two 2A″ states. Ro-vibrational state resolved integral cross sections have also been calculated at collision energies from 1.0 to 10.0 kcal/mol. The results support the harpooning mechanism in this metal-oxidant-involved reaction.