Validated numerical unrestrained occupant-seat crash scenarios for high-speed trains integrating experimental, computational, and inverse methods.

OBJECTIVE: Occupant impact safety is critical for train development. This paper proposes a systematic procedure for developing validated numerical occupant crash scenarios for high-speed trains by integrating experimental, computational, and inverse methods. METHODS: As the train interior is the most potentially injury-causing factor, the material properties were acquired by mechanical tests, and constitutive models were calibrated using inverse methods. The validity of the seat material constitutive model was further verified via drop tower tests. Finite element (FE) and multibody (MB) models of train occupant-seat interactions in frontal impact were established in LS-DYNA and MADYMO software, respectively, using the experimentally acquired materials/mechanical characteristics. Three dummy sled crash tests with different folding table and backrest configurations were conducted to validate the numerical occupant-seat models and to further assess occupant injury in train collisions. The occupant impact responses between dummy tests and simulations were quantitatively compared using a correlation and analysis (CORA) objective rating method. RESULTS: Results indicated that the experimentally calibrated numerical seat-occupant models could effectively reproduce the occupant responses in bullet train collisions (CORA scores >80%). Compared with the train seat-occupant MB model, the FE model could simulate the head acceleration with slightly more acceptable fidelity, however, the FE model CORA scores were slightly less than for the MB models. The maximum head acceleration was 30 g but the maximum HIC score was 17.4. When opening the folding table, the occupant's chest injury was not obvious, but the neck-table contact and "chokehold" may potentially be severe and require further assessment. CONCLUSIONS: This study demonstrates the value of experimental data for occupant-seat model interactions in train collisions and provides practical help for train interior safety design and formulation of standards for rolling stock interior passive safety.

Case report: Efficacy of icotinib treatment in lung adenocarcinoma with esophageal squamous cell carcinoma: a rare case of double primary malignant tumors.

Background: Lung adenocarcinoma with esophageal squamous cell carcinoma is rare and the prognosis is poor, therefore there is an urgent need to improve this situation. The objective of this study was to explore the effect of first-generation tyrosine kinase inhibitors (TKIs) in the patient of the double primary malignant tumors. Case report: We report a case of lung adenocarcinoma with esophageal squamous cell carcinoma treated by icotininb after five-year follow-up. A 71-year-old Chinese woman complaining of swallowing obstruction, heartburn, regurgitation of gastric acid for more than 2 months. An esophageal lesion was found by chest CT scans in T7 vertebral level. The diagnosis by gastroscopic biopsy was squamous cell carcinoma (SCC) with EGFR over-expression. Simultaneously, chest CT showed a 2 cm x 1 cm solitary lesion in the right superior pulmonary. The histological diagnosis by percutaneous lung Biopsy was "adenocarcinoma." Epidermal growth factor receptor (EGFR) gene mutation status was evaluated by Sanger sequencing, and an exon 21 point mutation (L858R) was identified. When the double primary malignant tumors were diagnosed, the patient refused operation and received a tyrosine kinase inhibitor (TKI), icotinib, at the dose of 125 mg, three times per day. All serum tumor biomarkers such as CEA and cancer antigen 125 (CA125) were in the normal range during the treatment period. After five-year follow-up, the patient has no evidence of recurrence or metastasis. The lung cancer was stable, meanwhile the esophageal lesion was almost cured. Conclusion: Icotininb is an effective treatment in the patients of the double primary malignant tumors of lung adenocarcinoma with EGFR gene mutation and esophageal squamous cell carcinoma with EGFR over-expression.

First Report of powdery mildew of Quercus guyavifolia (Fagaceae) Caused by Erysiphe quercicola.

Oaks are the most abundant trees in naturally regenerated forests in China, play a crucial role in preventing soil erosion and maintaining ecological stability (Du et al. 2022). Quercus guyavifolia H. Léveillé (Fagaceae family, Subgenus Cerris, section Ilex), is endemic in China, distributed in the southeastern boundary of the Qinghai-Tibet Plateau, with elevations from 2, 000 - 4, 500 m a.s.l. (Denk et al. 2018; Sun et al. 2016). Powdery mildew is a prevalent disease of oaks with up to 60% of foliage infection, which can induce leaf necrosis or deformation and might contribute to oak decline (Marçais and Desprez-Loustau 2014). In September 2023, we found leaves of Q. guyavifolia near Yunnan Baima Snow Mountain covered with white fungal colonies. Diseased Q. guyavifolia plants were transplanted into a greenhouse at Yunnan University for pathogenicity tests. Conidia from diseased plants were blown into twenty healthy Q. guyavifolia seedlings by cold air blower and five non-inoculated healthy seedlings were used as control. The inoculated seedlings developed powdery mildew symptoms within ten days on both sides of the leaves. Trypan blue staining was used to identify the pathogen that infects Q. guyavifolia (Xiao et al. 2017). Microscopic examination revealed abundant conidia and extensive branched hyphae on leaves, similar to the characteristics of powdery mildew fungi. The mean length and width of conidia were 29.06 ± 3.96 × 9.52 ± 1.36 µm (n = 50). We collected fungi (YNBAIMAXS01) and extracted genomic DNA from five diseased plants (from the same location) using the CTAB method. We amplified and sequenced the ITS (Gardes and Bruns, 1993), MS294, and MS447 (two nuclear protein-encoding genes; Feau et al. 2011; GenBank numbers: PP079015, PP083693, PP083694). BLAST analysis revealed 100% identity of above three sequences with the ITS of Erysiphe quercicola isolate DACA010 (GenBank accession MT569439), MS294 of E. quercicola isolate GEM09_11_FRTB1 (GenBank accession KY348509), and MS447 of E. quercicola isolate A1I1.5 (GenBank accession KY466619). Therefore, the isolate YNBAIMAXS01 was identified as E. quercicola based on its morphological and molecular characteristics. Sequences from the above three regions for YNBAIMAXS01 and five Erysiphe species were used to construct a Maximum likelihood (ML) tree. In addition, we constructed a ML tree using only the ITS region of YNBAIMAXS01 and eight Erysiphe species from GenBank to better distinguish E. quercicola from these species. Both trees were constructed using MEGA X with K2 + G as best model. The ML trees confirmed the powdery mildew fungi isolated from Q. guyavifolia is closely related to E. alphitoides. To date, thirty-four powdery mildew species belonging to genus Erysiphe have been found affecting Quercus and nine oak species can be infected by E. quercicola (https://fungi.ars.usda.gov/). To our knowledge, this is the first report of powdery mildew caused by E. quercicola on Q. guyavifolia, thus the development of control strategies and disease management is urgently needed.

Mex-3 RNA binding family member A (MEX3A)/circMPP6 complex promotes colorectal cancer progression by inhibiting autophagy.

RNA-binding proteins (RBPs)-RNA networks have contributed to cancer development. Circular RNAs (circRNAs) are considered as protein recruiters; nevertheless, the patterns of circRNA-protein interactions in colorectal cancer (CRC) are still lacking. Processing bodies (PBs) formed through liquid-liquid phase separation (LLPS) are membrane-less organelles (MLOs) consisting of RBPs and RNA. Previous evidence suggests a connection between PBs dynamics and cancer progression. Despite the increasingly acknowledged crucial role of RBPs and RNA in the accumulation and maintenance of MLOs, there remains a lack of specific research on the interactions between PBs-related RBPs and circRNAs in CRC. Herein, we identify that MEX-3 RNA binding family member A (MEX3A), frequently upregulated in CRC tissues, predicts poorer patient survival. Elevated MEX3A accelerates malignance and inhibits autophagy of CRC cells. Importantly, MEX3A undergoes intrinsically disordered regions (IDRs)-dependent LLPS in the cytoplasm. Specifically, circMPP6 acts as a scaffold to facilitate the interaction between MEX3A and PBs proteins. The MEX3A/circMPP6 complex modulates PBs dynamic and promotes UPF-mediated phosphodiesterase 5A (PDE5A) mRNA degradation, consequently leading to the aggressive properties of CRC cells. Clinically, CRC patients exhibiting high MEX3A expression and low PDE5A expression have the poorest overall survival. Our findings reveal a collaboration between MEX3A and circMPP6 in the regulation of mRNA decay through triggering the PBs aggregation, which provides prognostic markers and/or therapeutic targets for CRC.

Role of extracellular vesicles in castration-resistant prostate cancer.

Prostate cancer (PCa) is a common health threat to men worldwide, and castration-resistant PCa (CRPC) is the leading cause of PCa-related deaths. Extracellular vesicles (EVs) are lipid bilayer compartments secreted by living cells that are important mediators of intercellular communication. EVs regulate the biological processes of recipient cells by transmitting heterogeneous cargoes, contributing to CRPC occurrence, progression, and drug resistance. These EVs originate not only from malignant cells, but also from various cell types within the tumor microenvironment. EVs are widely dispersed throughout diverse biological fluids and are attractive biomarkers derived from noninvasive liquid biopsy techniques. EV quantities and cargoes have been tested as potential biomarkers for CRPC diagnosis, progression, drug resistance, and prognosis; however, technical barriers to their clinical application continue to exist. Furthermore, exogenous EVs may provide tools for new therapies for CRPC. This review summarizes the current evidence on the role of EVs in CRPC.

Simple-based Dynamic Decentralized Community Detection Algorithm in socially aware networks.

This paper introduces a novel, Simple-based Dynamic Decentralized Community Detection Algorithm (S-DCDA) for Socially Aware Networks. This algorithm aims to address the resource-intensive nature, instabilities and inaccuracies of traditional distributed community detection algorithms. The dynamics of decentralization is evident in the threefold nature of the algorithm: (i) each node of the community is the core of the entire network or community for a certain period of time dependent on their need, (ii) nodes are not centralized around themselves, requiring the consent of the other node to join a community, and (iii) Communities start from a single node to form an initial scale community, the number of nodes and the relationship among them are constantly changing. The algorithm requires low processor performance and memory capacity size of each node, to a certain extent, effectively improve the accuracy and stability of community detection and maintenance. Experimental results demonstrate that in comparison to classical and classical-based improved community detection algorithms, S-DCDA yields superior detection results.

Application of IMB model in preventing venous thromboembolism in elderly lung cancer patients.

Objective: This study aims to explore the effects of the Information-Motivation-Behavioral (IMB) Skills Model on the prevention of Venous Thromboembolism (VTE) in elderly lung cancer patients. Methods: A convenience sampling method was used to select study participants who were hospitalized for treatment between November 2022 and August 2023 at a tertiary hospital in Neijiang and met the inclusion and exclusion criteria. The control group (n = 41) received conventional health education, while the intervention group (n = 40) received health education based on the IMB Skills Model over three months. The scores of the Venous Thrombosis Knowledge, Participation in Thrombosis Prevention Willingness and Behavior Questionnaire, and Quality of Life Measurement Scale (QLQ-C30) were compared before the intervention and after three months. After three months of intervention, the hospital satisfaction and VTE incidence rates in both groups were investigated and compared. Results: After three months of intervention, the scores for the Venous Thrombosis Knowledge, (Participation in Thrombosis Prevention Willingness and Behavior Questionnaire in the intervention group were higher than those in the control group (P < 0.05). The QLQ-C30 scores in the intervention group for physical function, role function, emotional function, insomnia, appetite loss, and overall health status were higher than those in the control group (P < 0.05). The intervention group rated higher in doctor's professional skills, information provision, accessibility; nurse's professional skills, humanistic care, information provision, accessibility; team communication, services of other personnel, overall satisfaction compared to the control group (P < 0.05). The rate of VTE in the intervention group was 2.5%(1/40), and that in the control group was 19.5%(8/41). There was a significant difference (χ2 = 4.336, P = 0.037). Conclusion: Nursing interventions based on the IMB Skills Model for elderly lung cancer patients can enhance patients' understanding of venous thrombosis, increase willingness and active participation in thrombosis prevention, improve quality of life, increase hospital satisfaction, and reduce the incidence of VTE.

Greenhouse gases emissions from aquaculture ponds: Different emission patterns and key microbial processes affected by increased nitrogen loading.

Global aquaculture production is expected to rise to meet the growing demand for food worldwide, potentially leading to increased anthropogenic greenhouse gases (GHG) emissions. As the demand for fish protein increases, so will stocking density, feeding amounts, and nitrogen loading in aquaculture ponds. However, the impact of GHG emissions and the underlying microbial processes remain poorly understood. This study investigated the GHG emission characteristics, key microbial processes, and environmental drivers underlying GHG emissions in low and high nitrogen loading aquaculture ponds (LNP and HNP). The N2O flux in HNP (43.1 ± 11.3 µmol m-2 d-1) was significantly higher than in LNP (-11.3 ± 25.1 µmol m-2 d-1), while the dissolved N2O concentration in HNP (52.8 ± 7.1 nmol L-1) was 150 % higher than in LNP (p < 0.01). However, the methane (CH4) and carbon dioxide (CO2) fluxes and concentrations showed no significant differences (p > 0.05). N2O replaced CH4 as the main source of Global Warming Potential in HNP. Pond sediments acted as a sink for N2O but a source for CH4 and CO2. The △N2O/(△N2O + â–³N2) in HNP (0.015 ± 0.007 %) was 7.7-fold higher than in LNP (0.002 ± 0.001 %) (p < 0.05). The chemical oxygen demand to NO2-N ratio was the most important environmental factor explaining the variability of N2O fluxes. Ammonia-oxidizing bacteria driven nitrification in water was the predominant N2O source, while comammox-driven nitrification and nosZII-driven N2O reduction in water were key processes for reducing N2O emission in LNP but decreased in HNP. The strong CH4 oxidization by Methylocystis and CO2 assimilation by algae resulted in low CH4 emissions and CO2 sink in the aquaculture pond. The Mantel test indicated that HNP increased N2O fluxes mainly through altering functional genes composition in water and sediment. Our findings suggest that there is a significant underestimation of N2O emissions without considering the significantly increased △N2O/(△N2O + â–³N2) caused by increased nitrogen loading.

Direct Z-scheme system of UiO-66 cubes wrapped with Zn0.5Cd0.5S nanoparticles for photocatalytic hydrogen generation synchronized with organic pollutant degradation.

Optimized fabrication of Z-scheme photocatalyst based on MOF materials offers sustainable energy generation and environmental improvement due to their attractive properties. The Z-scheme heterojunctions consisting of UiO-66 cubes covered with Zn0.5Cd0.5S nanoparticles were fabricated by a facile solvothermal method. Thanks to the Z-scheme carrier transport under simulated sunlight irradiation, UiO-66@Zn0.5Cd0.5S exhibited enhanced photocatalytic performance of H2 generation synchronized with organic pollutant degradation in fluoroquinolone antibiotic wastewater. Synergistically, the highest comprehensive performance was obtained in ciprofloxacin solution. The H2 yield reached 224 µmol∙ g-1∙ h-1 and simultaneously the removal efficiency was up to 83.6 %. The degradation pathways revealed that the process of piperazine ring cleavage and decarboxylation also generates H protons, further promoting the production of H2. Therefore, the effective spatial separation and transfer of the photoinduced carriers are attributed to the good band structure, large specific surface area, and cooperative reduction and oxidation reactions of UiO-66@Zn0.5Cd0.5S, resulting in significant photocatalytic activity. The toxicity assessment of antibiotics and intermediate products during the photocatalytic reaction also verifies the reduction of environmental risk. This study highlights a promising way to expand the application of the MOFs-based photocatalyst in clean energy conversion coupling with water remediation.

Patients with hepatocellular carcinoma extrahepatic metastases can benefit from hepatic arterial infusion chemotherapy combined with lenvatinib plus programmed Death-1 inhibitors.

BACKGROUND: Lenvatinib plus Programmed Death-1 (PD-1) inhibitors (LEN-P) have been recommended in China for patients with advanced hepatocellular carcinoma (HCC). However, they provide limited survival benefits to patients with extrahepatic metastases. We aimed to investigate whether combining hepatic arterial infusion chemotherapy (HAIC) with LEN-P could improve its efficacy. MATERIALS AND METHODS: This multi-center cohort study included patients with HCC extrahepatic metastases who received HAIC combined with LEN-P (HAIC-LEN-P group, n=127) or LEN-P alone (n=103) as the primary systemic treatment between January 2019 and December 2022. Baseline data were balanced using a one-to-one propensity score matching (PSM) and inverse probability of treatment weighting (IPTW). RESULTS: After PSM, the HAIC-LEN-P group significantly extended the median overall survival (mOS) and median progression-free survival (mPFS), compared with the LEN-P group (mOS: 27.0 months vs. 9.0 months, P<0.001; mPFS: 8.0 months vs. 3.0 months, P=0.001). After IPTW, the mOS (hazard ratio (HR)=0.384, P<0.001) and mPFS (HR=0.507, P<0.001) were significantly higher in the HAIC-LEN-P group than in the LEN-P group. The HAIC-LEN-P group's objective response rate was twice as high as that of the LEN-P group (PSM cohort: 67.3% vs. 29.1%, P<0.001; IPTW cohort: 66.1% vs. 27.8%, P<0.001). Moreover, the HAIC-LEN-P group exhibited no noticeable increase in the percentages of grade 3 and 4 adverse events compared with the LEN-P group (P>0.05). CONCLUSION: HAIC can improve the efficacy of LEN-P in patients with HCC extrahepatic metastases and may be an alternative treatment for advanced HCC management.

The cost of the perfect body: influence mechanism of internalization of media appearance ideals on eating disorder tendencies in adolescents.

BACKGROUND: Some studies have examined the relationship between internalization of media appearance ideals and eating disorders. However, few have discussed the relationship between eating disorder tendencies. To fill this research gap, this study was to explore the influencing mechanisms of internalization of media appearance ideals on adolescents' eating disorder tendencies in Chinese cultural context. METHOD: The Sociocultural Attitudes Towards Appearance Questionnaire, Eating Attitude Test-26, Physical Self-Description Questionnaire, Body Image Depression Questionnaire and Multidimensional Scale of Perceived Social Support were employed in this study to investigate 1523 adolescents. The collected data were analyzed using SPSS 26.0 and AMOS 24.0. RESULT: The results showed that: (1) internalization of media appearance ideals had a significant positive predictive effect on adolescents' eating disorder tendencies; (2) internalization of media appearance ideals significantly influenced adolescents' eating disorder tendencies through the mediating role of body esteem and body image disturbance respectively, and also influenced eating disorder tendencies through the chain mediating of both; and (3) social support played a moderating role between body image disturbance and eating disorder tendency. CONCLUSION: Our findings suggest distinct pathways through which internalization of media appearance ideals may influence adolescents' eating disorder tendencies. It is suggested that reducing body image disturbance and enhancing social support can help reducing eating disorder tendency.

Summary of the best evidence for the management of dysphagia in elderly patients.

OBJECTIVE: To search for and summarize the best evidence for themanagement of elderly patients with dysphagia. METHODS: Clinical decisions, recommended practices, evidence summaries, clinical practice guidelines, expert consensus, and systematic reviews on the management of dysphagia among elderly patients were systematically reviewed from domestic and foreign guideline websites, association websites, and Chinese and English databases according to the 6S model of evidence-based resources. The search period was between January 1, 2010 and November 1, 2023. Two researchers evaluated the quality of the included literature respectively and extracted evidence. RESULTS: A total of 14 literatures were identified, including 2 guidelines, 2 clinical decisions, 5 evidence summaries, 3 expert consensus statements, and 2 systematic reviews. Twenty-four pieces of evidence from 7 aspects were summarized, including assessment, treatment and rehabilitation, medication care, nutrition management, oral care, complication management, and psychological care. CONCLUSION: The best evidence-based recommendations for the management of dysphagia in elderly patients is summarized, it is suggested that the best evidence should be selected according to the actual situation of patients, and a personalized management plan should be formulated to improve the quality of life of patients and achieve high-quality nursing.

Intestinal adipocytes transdifferentiate into myofibroblast-like cells and contribute to fibrosis in Crohn's disease.

BACKGROUND AND AIMS: Intestinal fibrotic stenosis is a major reason for surgery in Crohn's disease [CD], but the mechanism is unknown. Thus, we asked whether intestinal adipocytes contribute to intestinal fibrosis. Adipocytes were found to transdifferentiate into myofibroblasts and confirmed to be involved in mesenteric fibrosis in our recent study. Here, we investigated the role and possible mechanisms of intestinal adipocytes in intestinal fibrosis in CD. METHODS: The intestinal tissue of patients with CD with or without fibrotic stenosis [CDS or CDN] and normal intestinal tissue from individuals without CD were obtained to assess alterations in submucosal adipocytes in CDS and whether these cells transdifferentiated into myofibroblasts and participated in the fibrotic process. Human primary adipocytes and adipose organoids were used to evaluate whether adipocytes could be induced to transdifferentiate into myofibroblasts and to investigate the fibrotic behaviour of adipocytes. LPS/TLR4/TGF-ß signalling was also studied to explore the underlying mechanism. RESULTS: Submucosal adipocytes were reduced in number or even absent in CDS tissue, and the extent of the reduction correlated negatively with the degree of submucosal fibrosis. Interestingly, submucosal adipocytes in CDS tissue transdifferentiated into myofibroblast-like cells and expressed collagenous components, possibly due to stimulation by submucosally translocated bacteria. LPS-stimulated human primary adipocytes and adipose organoids also exhibited transdifferentiation and profibrotic behaviour. Mechanistically, TLR4-mediated TGF-ß signalling was associated with the transdifferentiation and profibrotic behaviour of intestinal adipocytes in CDS tissue. CONCLUSIONS: Intestinal adipocytes transdifferentiate into myofibroblasts and participate in the intestinal fibrosis process in CD, possibly through LPS/TLR4/TGF-ß signalling.

Ensemble species distribution modeling and multilocus phylogeography provide insight into the spatial genetic patterns and distribution dynamics of a keystone forest species, Quercus glauca.

BACKGROUND: Forests are essential for maintaining species diversity, stabilizing local and global climate, and providing ecosystem services. Exploring the impact of paleogeographic events and climate change on the genetic structure and distribution dynamics of forest keystone species could help predict responses to future climate change. In this study, we combined an ensemble species distribution model (eSDM) and multilocus phylogeography to investigate the spatial genetic patterns and distribution change of Quercus glauca Thunb, a keystone of East Asian subtropical evergreen broad-leaved forest. RESULTS: A total of 781 samples were collected from 77 populations, largely covering the natural distribution of Q. glauca. The eSDM showed that the suitable habitat experienced a significant expansion after the last glacial maximum (LGM) but will recede in the future under a general climate warming scenario. The distribution centroid will migrate toward the northeast as the climate warms. Using nuclear SSR data, two distinct lineages split between east and west were detected. Within-group genetic differentiation was higher in the West than in the East. Based on the identified 58 haplotypes, no clear phylogeographic structure was found. Populations in the Nanling Mountains, Wuyi Mountains, and the southwest region were found to have high genetic diversity. CONCLUSIONS: A significant negative correlation between habitat stability and heterozygosity might be explained by the mixing of different lineages in the expansion region after LGM and/or hybridization between Q. glauca and closely related species. The Nanling Mountains may be important for organisms as a dispersal corridor in the west-east direction and as a refugium during the glacial period. This study provided new insights into spatial genetic patterns and distribution dynamics of Q. glauca.

NADK-mediated proline synthesis enhances high-salinity tolerance in the razor clam.

Euryhaline organisms can accumulate organic osmolytes to maintain osmotic balance between their internal and external environments. Proline is a pivotal organic small molecule and plays an important role in osmoregulation that enables marine shellfish to tolerate high-salinity conditions. During high-salinity challenge, NAD kinase (NADK) is involved in de novo synthesis of NADP(H) in living organisms, which serves as a reducing agent for the biosynthetic reactions. However, the role of shellfish NADK in proline biosynthesis remains elusive. In this study, we show the modulation of NADK on proline synthesis in the razor clam (Sinonovacula constricta) in response to osmotic stress. Under acute hypersaline conditions, gill tissues exhibited a significant increase in the expression of ScNADK. To elucidate the role of ScNADK in proline biosynthesis, we performed dsRNA interference in the expression of ScNADK in gill tissues to assess proline content and the expression levels of key enzyme genes involved in proline biosynthesis. The results indicate that the knock-down of ScNADK led to a significant decrease in proline content (P<0.01), as well as the expression levels of two proline synthetase genes P5CS and P5CR involved in the glutamate pathway. Razor clams preferred to use ornithine as substrate for proline synthesis when the glutamate pathway is blocked. Exogenous administration of proline greatly improved cell viability and mitigated cell apoptosis in gills. In conclusion, our results demonstrate the important role of ScNADK in augmenting proline production under high-salinity stress, by which the razor clam is able to accommodate salinity variations in the ecological niche.

Symmetry breaking and chiral amplification in prebiotic ligation reactions.

The single chirality of biological molecules is a signature of life. Yet, rationalizing how single chirality emerged remains a challenging goal1. Research has commonly focused on initial symmetry breaking and subsequent enantioenrichment of monomer building blocks-sugars and amino acids-that compose the genetic polymers RNA and DNA as well as peptides. If these building blocks are only partially enantioenriched, however, stalling of chain growth may occur, whimsically termed in the case of nucleic acids as "the problem of original syn"2. Here, in studying a new prebiotically plausible route to proteinogenic peptides3-5, we discovered that the reaction favours heterochiral ligation (that is, the ligation of L monomers with D monomers). Although this finding seems problematic for the prebiotic emergence of homochiral L-peptides, we demonstrate, paradoxically, that this heterochiral preference provides a mechanism for enantioenrichment in homochiral chains. Symmetry breaking, chiral amplification and chirality transfer processes occur for all reactants and products in multicomponent competitive reactions even when only one of the molecules in the complex mixture exhibits an imbalance in enantiomer concentrations (non-racemic). Solubility considerations rationalize further chemical purification and enhanced chiral amplification. Experimental data and kinetic modelling support this prebiotically plausible mechanism for the emergence of homochiral biological polymers.

Investigating the impact of HMI on drivers' merging performance in intelligent connected vehicle environment.

Intelligent Connected Vehicle (ICV) is considered one of the most promising active safety technologies to address current transportation challenges. Human-Machine Interface (HMI) plays a vital role in enhancing user driving experience with ICV technology. However, in an ICV environment, drivers may exhibit excessive reliance on HMI, resulting in diminished proactive observation and analysis of the road environment, and subsequently leading to a potential decrease in drivers' situational awareness. This reduced situational awareness may consequently lead to a decline in their overall engagement in driving tasks. Therefore, to comprehensively investigate the impact of HMI on driver performance in various ICV environments, this study incorporates three distinct HMI systems: Control group, Warning group, and Guidance group. The Control group provides basic information, the Warning group adds front vehicle icon and real-time headway information, while the Guidance group further includes speed and voice guidance features. Additionally, the study considers three types of mainline vehicle gaps, namely, 30 m, 20 m, and 15 m. Through our self-developed ICV testing platform, we conducted driving simulation experiments on 43 participants in a freeway interchange merging area. The findings reveal that, drivers in the Guidance group exhibited explicit acceleration while driving on the ramp. Drivers in the Guidance and Warning groups demonstrated smoother speed change trends and lower mean longitudinal acceleration upon entering the acceleration lane compared to the Control group, indicating a preference for more cautious driving strategies. During the pre-merging section, drivers in the Warning group demonstrated a more cautious and smooth longitudinal acceleration. The Guidance group's HMI system assisted drivers in better speed control during the post-merging section. Differences in mainline vehicle gaps did not significantly impact the merging positions of participants across the three HMI groups. Drivers in the Guidance group merged closest to the left side of the taper section, while the Control group merged farthest. The research findings offer valuable insights for developing dynamic human-machine interfaces tailored to specific driving scenarios in the environment of ICVs. Future research should investigate the effects of various HMIs on driver safety, workload, energy efficiency, and overall driving experience. Conducting real-world tests will further validate the findings obtained from driving simulators.

Considerations and anesthetic management of a patient with giant right atrial myxoma: A case report and literature review.

BACKGROUND: Myxoma is a common type of primary cardiac tumor. However, there are few researches to illustrate challenge of safely inducing anesthesia in a patient with a giant right atrial myxoma at moderate altitude. PATIENT CONCERNS AND DIAGNOSES: A 54-year-old female patient lived in a city with an average altitude of 1932 m with scheduled surgical treatment for giant right atrial myxoma, prompting discussions on appropriate anesthesia modalities given her prolonged residence at moderate altitude. METHODS AND RESULTS: Considering the potential impact of moderate altitude on perioperative management, this study emphasizes the necessity of adequate volume preload therapy and the utility of transthoracic echocardiography or transesophageal echocardiography to prevent hemodynamic compromise. Furthermore, it highlights the unique consideration that, post-tumor removal, hypotension may not necessarily lead to decreased oxygen saturation in these patients. CONCLUSION: This case underscores the importance of avoiding hypotension, as pre-tumor resection blood pressure maintenance primarily determines blood oxygen concentration. Additionally, it sheds light on the intriguing observation that post-tumor removal hypotension may not result in decreased oxygen saturation. These findings have significant implications for the perioperative care of patients with giant right atrial myxoma at moderate altitudes.

Prebiotic access to enantioenriched amino acids via peptide-mediated transamination reactions.

The kinetic resolution of racemic amino acids mediated by dipeptides and pyridoxal provides a prebiotically plausible route to enantioenriched proteinogenic amino acids. The enzymatic transamination cycles that are key to modern biochemical formation of enantiopure amino acids may have evolved from this half of the reversible reaction couple. Kinetic resolution of racemic precursors emerges as a general route to enantioenrichment under prebiotic conditions.

The efficacy and safety of fexuprazan in treating erosive esophagitis: a phase III, randomized, double-blind, multicenter study.

BACKGROUND AND AIM: Fexuprazan is a novel potassium-competitive acid blocker (P-CAB). This study aimed to explore the noninferior efficacy and safety of fexuprazan to esomeprazole in treating erosive esophagitis (EE). METHODS: This was a phase III, randomized, double-blind multicenter study. Patients with endoscopically confirmed EE were randomized to receive fexuprazan 40 mg or esomeprazole 40 mg once a daily for 4-8 weeks. The healing rates of EE, symptom response, GERD-health-related quality life (GERD-HRQL), and treatment-emergent adverse events (TEAEs) were compared between fexuprazan group and esomeprazole group. RESULTS: A total of 332 subjects were included in full analysis set (FAS) and 311 in per-protocol set (PPS). The healing rates of fexuprazan and esomeprazole groups at 8 weeks were 88.5% (146/165) and 89.0% (145/163), respectively, in FAS and 97.3% (145/149) and 97.9% (143/146), respectively, in PPS. Noninferiority of fexuprazan compared with esomeprazole according to EE healing rates at 8 weeks was demonstrated in both FAS and PPS analysis. No significant difference was found between groups in EE healing rates at 4 weeks, symptom responses, and changes of GERD-HRQL. The incidence of drug-related AEs was 19.4% (32/165) in fexuprazan arm and 19.6% (32/163) in esomeprazole arm. CONCLUSION: This study demonstrated noninferior efficacy of fexuprazan to esomeprazole in treating EE. The incidence of TEAEs was similar between fexuprazan and esomeprazole. Trial registration number NCT05813561.