Assessment of chlorine and hydrogen peroxide on airborne bacteria: Disinfection efficiency and induction of antibiotic resistance.

Airborne pathogens severely threaten public health worldwide. Air disinfection is essential to ensure public health. However, excessive use of disinfectants may endanger environmental and ecological security due to the residual disinfectants and their by-products. This study systematically evaluated disinfection efficiency, induction of multidrug resistance, and the underlying mechanisms of disinfectants (NaClO and H2O2) on airborne bacteria. The results showed that airborne bacteria were effectively inactivated by atomized NaClO (>160 µg/L) and H2O2 (>320 µg/L) after 15 min. However, some bacteria still survived after disinfection by atomized NaClO (0-80 µg/L) and H2O2 (0-160 µg/L), and they exhibited significant increases in antibiotic resistance. The whole-genome sequencing of the resistant bacteria revealed distinct mutations that were responsible for both antibiotic resistance and virulence. This study also provided evidences and insights into possible mechanisms underlying the induction of antibiotic resistance by air disinfection, which involved intracellular reactive oxygen species formation, oxidative stress responses, alterations in bacterial membranes, activation of efflux pumps, and the thickening of biofilms. The present results also shed light on the role of air disinfection in inducing antibiotic resistance, which could be a crucial factor contributing to the global spread of antibiotic resistance through the air.

Plasma proteomics analysis of Chinese HIV-1 infected individuals focusing on the immune and inflammatory factors afford insight into the viral control mechanism.

Background: Long-term non-progressors (LTNPs) with HIV infection can naturally control viral replication for up to a decade without antiretroviral therapy (ART), but the underlying mechanisms of this phenomenon remain elusive. Methods: To investigate the relevant immune and inflammatory factors associated with this natural control mechanism, we collected plasma samples from 16 LTNPs, 14 untreated viral progressors (VPs), 17 successfully ART-treated patients (TPs), and 16 healthy controls (HCs). The OLINK immune response panel and inflammation panel were employed to detect critical proteins, and the plasma neutralizing activity against a global panel of pseudoviruses was assessed using TZM-bl cells. Results: The combination of IL17C, IL18, DDX58, and NF2 contributed to discriminating LTNPs and VPs. IL18 and CCL25 were positively associated with CD4+ T cell counts but negatively correlated with viral load. Furthermore, CXCL9 and CXCL10 emerged as potential supplementary diagnostic markers for assessing the efficacy of antiretroviral therapy (ART). Finally, TNFRSF9 displayed positive correlations with neutralization breadth and Geometry Median Titer (GMT) despite the lack of significant differences between LTNPs and VPs. Conclusion: In summary, this study identified a set of biomarkers in HIV-infected individuals at different disease stages. These markers constitute a potential network for immune balance regulation in HIV infection, which is related to the long-term control of HIV by LTNPs. It provides important clues for further exploring the immune regulatory mechanism of HIV.

Plant growth-promoting rhizobacteria (PGPR) improve the growth and quality of several crops.

Plant growth-promoting rhizobacteria (PGPR) are known to have the effect of promoting plant growth. In this paper, three PGPR strains were selected from the previous work, which had plant growth-promoting activities such as phosphate solubilization, nitrogen fixation, phosphorus mobilization, etc. These strains named FJS-3(Burkholderia pyromania), FJS-7(Pseudomonas rhodesiae), and FJS-16(Pseudomonas baetica), respectively, were prepared into solid biological agents. Three widely planted commercial crops (tea plant, tobacco, and chili pepper) were selected for PGPR growth promotion verification. The results showed that the new shoots of tea seedlings under PGPR treatment were much more than the control. We also used tobacco, another important crop in Guizhou, to test the growth-promoting effect of individual bacteria, and the results showed that each of them could promote the growth of tobacco plants, and FJS-3(Burkholderia pyrrocinia) had the best effect. In addition, we carried out experiments on tobacco and pepper using multi-strain PGPR, the tobacco plants' height, fresh, and root weight increased by 30.15 %, 37.36 %, and 54.5 %, respectively, and the pepper plants' increased by 30.10 %, 56.38 % and 43.18 %, respectively, which both showed significantly better effects than that of a single strain. To further test the field performance, field trials were carried out in a mature Longjing43 tea plantation in Guizhou. There were four treatments: no fertilization (T1), combined application of PGPR biological agent and compound fertilizer (T2), only application of PGPR (T3), and only application of compound fertilizer (T4). In terms of yield, grouped with or without PGPR, there was a 15.38 % (T2:T4) and 92.31 % (T3:T1) increase between them, respectively. The tea's yield and tea flavor substances such as tea polyphenols, caffeine, and theanine were detected, and the T2 showed the most significant positive effect on both sides. Especially, an important indicator of Matcha green tea is the color, chlorophyll content was then tested, and PGPR application increased it and improved the appearance. All these results demonstrated that the PGPR we screened could significantly promote plant growth and quality improvement, and had good application potential in crop planting, which could contribute to environmental protection and economic growth.

Psychometric properties of a Mandarin Chinese version of the Body Appreciation Scale-2 among Chinese adolescents.

In the present study, we explored the factor structure and psychometric properties of the Mandarin Chinese BAS-2 among adolescents residing in the Chinese mainland. Exploratory factor analysis in Study 1 (N = 790; 396 girls, 394 boys) supported the unidimensionality of the Mandarin Chinese BAS-2 among Chinese adolescents. Internal consistency reliability was upheld via McDonald's omega. Convergent validity was supported by its moderate-to-strong relationships with body satisfaction, functionality satisfaction, self-esteem, life satisfaction, positive affect, and negative affect, while its small-to-moderate correlation with social desirability provided somewhat weaker discriminant validity support. Criterion-related validity was upheld by its inverse correlation with eating disorder symptomatology and positive correlation with intuitive eating. It explained unique variance in self-esteem (for girls and boys), eating disorder symptomatology (for girls), and intuitive eating (for boys) beyond age, body satisfaction, and functionality satisfaction, providing incremental validity evidence. A subsample of 134 girls and 114 boys completed the Mandarin Chinese BAS-2 again after three months, and test-retest reliability was upheld. The confirmatory factor analysis in Study 2 (N = 337; 192 girls, 145 boys) replicated the unidimensional structure and supported measurement invariance across gender. Collectively, the present study supported the unidimensionality, reliability, and validity of the Mandarin Chinese BAS-2's scores among Chinese adolescents.

Complete long-term monitoring of greenhouse gas emissions from a full-scale industrial wastewater treatment plant with different cover configurations.

The greenhouse gas (GHG) emissions from wastewater treatment plants (WWTPs), consisting mainly of methane (CH4) and nitrous oxide (N2O), have been constantly increasing and become a non-negligible contributor towards carbon neutrality. The precise evaluation of plant-specific GHG emissions, however, remains challenging. The current assessment approach is based on the product of influent load and emission factor (EF), of which the latter is quite often a single value with huge uncertainty. In particular, the latest default Tier 1 value of N2O EF, 0.016 ± 0.012 kgN2O-N kgTN-1, is estimated based on the measurement of 30 municipal WWTPs only, without involving any industrial wastewater. Therefore, to resolve the pattern of GHG emissions from industrial WWTPs, this work conducted a 14-month monitoring campaign covering all the process units at a full-scale industrial WWTP in Shanghai, China. The total CH4 and N2O emissions from the whole plant were, on average, 447.7 ± 224.5 kgCO2-eq d-1 and 1605.3 ± 2491.0 kgCO2-eq d-1, respectively, exhibiting a 5.2- or 3.9-times more significant deviation than the influent loads of chemical oxygen demand (COD) or total nitrogen (TN). The resulting EFs, 0.00072 kgCH4 kgCOD-1 and 0.00211 kgN2O-N kgTN-1, were just 0.36% of the IPCC recommended value for CH4, and 13.2% for N2O. Besides, the parallel anoxic-oxic (A/O) lines of this industrial WWTP were covered in two configurations, allowing the comparison of GHG emissions from different odor control setup. Unit-specific analysis showed that the replacement of enclosed A/open O with enclosed A/O reduced the CH4 EF by three times, from 0.00159 to 0.00051 kgCH4 kgCOD-1, and dramatically decreased the N2O EF by an order of magnitude, from 0.00376 to 0.00032 kgN2O-N kgTN-1, which was among the lowest of all full-scale WWTPs.

Molecular and cellular neurocardiology in heart disease.

This paper updates and builds on a previous White Paper in this journal that some of us contributed to concerning the molecular and cellular basis of cardiac neurobiology of heart disease. Here we focus on recent findings that underpin cardiac autonomic development, novel intracellular pathways and neuroplasticity. Throughout we highlight unanswered questions and areas of controversy. Whilst some neurochemical pathways are already demonstrating prognostic viability in patients with heart failure, we also discuss the opportunity to better understand sympathetic impairment by using patient specific stem cells that provides pathophysiological contextualization to study 'disease in a dish'. Novel imaging techniques and spatial transcriptomics are also facilitating a road map for target discovery of molecular pathways that may form a therapeutic opportunity to treat cardiac dysautonomia.

PRDX1 Interfering Peptide Disrupts Amino Acids 70-90 of PRDX1 to Inhibit the TLR4/NF-κB Signaling Pathway and Attenuate Neuroinflammation and Ischemic Brain Injury.

Ischemic stroke ranks among the leading causes of death and disability in humans and is accompanied by motor and cognitive impairment. However, the precise mechanisms underlying injury after stroke and effective treatment strategies require further investigation. Peroxiredoxin-1 (PRDX1) triggers an extensive inflammatory cascade that plays a pivotal role in the pathology of ischemic stroke, resulting in severe brain damage from activated microglia. In the present study, we used molecular dynamics simulation and nuclear magnetic resonance to detect the interaction between PRDX1 and a specific interfering peptide. We used behavioral, morphological, and molecular experimental methods to demonstrate the effect of PRDX1-peptide on cerebral ischemia-reperfusion (I/R) in mice and to investigate the related mechanism. We found that PRDX1-peptide bound specifically to PRDX1 and improved motor and cognitive functions in I/R mice. In addition, pretreatment with PRDX1-peptide reduced the infarct area and decreased the number of apoptotic cells in the penumbra. Furthermore, PRDX1-peptide inhibited microglial activation and downregulated proinflammatory cytokines including IL-1ß, IL-6, and TNF-α through inhibition of the TLR4/NF-κB signaling pathway, thereby attenuating ischemic brain injury. Our findings clarify the precise mechanism underlying PRDX1-induced inflammation after ischemic stroke and suggest that the PRDX1-peptide can significantly alleviate the postischemic inflammatory response by interfering with PRDX1 amino acids 70-90 and thereby inhibiting the TLR4/NF-κB signaling pathway. Our study provides a theoretical basis for a new therapeutic strategy to treat ischemic stroke.

Prognostic implication of consolidation-to-tumor ratio in early lung adenocarcinoma: a retrospective cross-sectional study.

Background: The threshold value of consolidation-to-tumor ratio (CTR) for distinguishing between ground-glass opacity (GGO)-predominant and solid-predominant ground-glass nodules (GGNs) needs to be clarified, as the lack of clarity has caused the prognostic implications to remain ambiguous. This study aimed to determine the threshold value of CTR for distinguishing between GGO-predominant GGNs and solid-predominant GGNs and elucidate the prognostic implications of the solid-predominant GGNs categorized by CTR on c-stage IA lung adenocarcinoma. Methods: Between January 2016 and October 2018, 764 c-stage IA lung adenocarcinoma cases were assembled from the First Affiliated Hospital of Chongqing Medical University. Of the 764 lesions, 515 (67.4%) were nodules with a GGO component, and 249 (32.6%) were solid nodules (SNs) on thin-section computed tomography (CT). We evaluated the correlation of the 3-dimensional (3D) consolidation component volume ratio with CTR based on the coefficient of determination, r. After receiver operating characteristic (ROC) analysis of 515 GGNs, we defined the nodule with CTR >0.750 as solid-predominant GGN and the nodule with CTR ≤0.750 as GGO-predominant GGN. Subsequently, the prognosis of 439 patients who had follow-up registration was evaluated. Survival curves were calculated using the Kaplan-Meier method, and the log-rank test was employed to compare survival rates among different groups. Cox proportional hazard regression models were applied to evaluate the independent risk factors for recurrence-free survival (RFS). Results: Among 764 patients, 515 (67.4%) were nodules with a GGO component, and 249 (32.6%) were SNs on thin-section CT. For 515 GGNs, the 3D consolidation component volume ratio correlated well with CTR (r=0.888). CTR tended to be slightly larger than the 3D consolidation component volume ratio. A 3D consolidation component volume ratio >50% was best predicted by CTR >0.750, followed by CTR >0.549. CTR >0.750 and CTR >0.549 predicted 3D consolidation component volume ratio >50% with 85% and 99.2% sensitivity and 91.6% and 57.2% specificity, respectively. The 5-year RFS and overall survival (OS) of patients with 0.750< CTR <1 were worse than those of patients with 0≤ CTR ≤0.750 (P<0.001 and P<0.001, respectively) but better than those of patients with CTR =1 (P=0.002 and P=0.03, respectively). Carcinoembryonic antigen (CEA) >2.1 [hazard ratio (HR) =12.516, 95% confidence interval (CI): 1.729-90.598], CTR >0.750 (HR =13.934, 95% CI: 3.341-58.123), larger consolidation component size with diameter more than 20 mm (HR =1.855, 95% CI: 1.242-2.770), poorly differentiated (HR =1.622, 95% CI: 1.056-2.491), lymph node metastasis (HR =2.473, 95% CI: 1.601-3.821), and sublobar resection (HR =2.596, 95% CI: 1.701-3.962) could predict the poor prognosis. Patients with 0≤ CTR ≤0.750 receiving sublobar resection had prognoses comparable to those receiving lobar resection, whether the tumor size ≤2 cm or consolidation component size ≤3 cm. Lobar resection was superior to sublobar resection for non-small cell lung cancer (NSCLC) ≤2 cm with CTR >0.750. Conclusions: Compared to CTR =0.5, the 2-dimensional (2D) CTR =0.750 found using the 3D consolidation component volume ratio as the gold standard better differentiated between solid-predominant GGNs and GGO-predominant GGNs. CTR >0.750 was an independent risk factor associated with the poor prognosis of patients with c-stage IA lung adenocarcinoma. Sublobar resection should be cautiously adopted in GGNs with 0.750< CTR ≤1.

Early enteral nutrition with exclusive donor milk instead of formula milk affects the time of full enteral feeding for very low birth weight infants.

This study investigated the effects of exclusive donor milk or formula in the first 7 days after birth, on the time to full enteral feeding, growth, and morbidity of adverse events related to premature infants. This was a retrospective study carried out from July 2014 to December 2019 at the Department of Neonatology of Shanghai Children's Hospital. All infants with a birth weight < 1,500 g and a gestational age ≤ 32 who received exclusive donor milk or formula in the first 7 days after birth were included in this study. The time to full enteral feeding (defined as 150 mL/kg) in the donor milk group was significantly shorter than in the formula group (18 vs. 22 days, p = 0.01). Donated breast milk was also associated with a lower incidence of NEC (4.4 vs. 7%, p < 0.01), ROP (3.8 vs. 13.2%, p < 0.01), and culture-confirmed sepsis (11 vs. 22.6%, p < 0.01). Using donated breast milk instead of current formula milk for early enteral nutrition can shorten the time to full enteral feeding and reduce the incidence of NEC, ROP, and sepsis.

Evaluating the Effectiveness of Radiofrequency Therapy and Manual Pelvic Fascial Release in Treating Myofascial Pelvic Pain.

INTRODUCTION AND HYPOTHESIS: Myofascial pelvic pain (MFPP), characterized by sensitive trigger points in the pelvic floor muscles, leads to chronic pain and affects various aspects of life. Despite the availability of different treatment modalities, there is limited comparative research on their effectiveness. This study compares radiofrequency (RF) therapy and myofascial manual therapy (MMT) in treating MFPP. We aimed to evaluate pelvic floor muscle strength changes, clinical symptoms, and patient comfort during treatment. METHODS: The study involved 176 participants, divided equally into RF and MMT groups. We assessed pelvic floor pain using the Visual Analogue Scale (VAS), muscle strength using the Modified Oxford Scale (MOS) and surface electromyography (sEMG), clinical symptom improvement through questionnaires, and patient discomfort during treatment. RESULTS: Both RF and MMT groups significantly reduced pelvic floor and paraurethral muscle pain (VAS scores, p < 0.001). RF treatment significantly decreased vaginal laxity in its group (p < 0.001), with no notable change in the MMT group (p = 0.818). RF therapy also resulted in greater patient comfort than MMT (p < 0.001). Although both treatments improved clinical symptoms, there was no significant difference between the two (p = 0.692). MOS scores and pelvic floor sEMG values showed no significant differences between the groups before and after treatment (p > 0.05). CONCLUSIONS: Both RF and MMT effectively alleviate pelvic floor pain and improve clinical symptoms in MFPP patients. RF therapy, however, offers additional benefits in reducing vaginal laxity and enhancing treatment comfort.

How does technological innovation affect the fiscal decentralization of local governments? Evidence from China.

Technological innovation is a pivotal driver of high-quality economic development, and China's distinctive fiscal decentralization model stands out as a crucial institutional factor behind the country's economic growth miracle. Despite its significant academic and practical implications, there is a noticeable scarcity of literature on examining government fiscal decentralization through the lens of technological innovation. This paper addresses fundamental research questions regarding the relationship between technological innovation and fiscal decentralization. Leveraging balanced panel data from 30 provinces in China spanning 2005 to 2020, our findings indicate that technological innovation positively impacts the fiscal decentralization of local governments. Specifically, for each standard deviation increase in technological innovation, there is a corresponding 0.1508 standard deviation in fiscal decentralization. The mechanism driving this relationship lies in technological innovation's ability to enhance enterprise profit levels, increasing tax and non-tax revenues for local governments. Importantly, when non-tax revenue at the central government level surpasses tax revenue, the resulting augmentation in local government revenue contributes to an elevated level of fiscal decentralization. In conclusion, this paper offers valuable insights into the government's endeavors to promote scientific and technological innovation while enhancing local fiscal decentralization. These insights contribute to an improved quality of economic development.

Are spending more time outdoors able to prevent and control myopia in children and adolescents? A meta-analysis.

INTRODUCTION: Spending more time outdoors was treated as a safe and cost-effective method to prevent and control myopia. While prior research has established an inverse association between outdoor time and the risk of myopia onset, the effect of increasing outdoor time in delaying the progression of myopia remains a subject of debate. The present meta-analysis aimed to assess the relationship between outdoor time and the myopia onset, and further examine whether there is a dose-response relationship between outdoor time and the risk of myopia onset. Meanwhile, perform whether the outdoor time is related to delaying the progression of myopia. METHODS: Studies were retrieved from PubMed, Web of Science, Embase, Medline, and the Cochrane Database, spanning from their inception to February 2023. 3 cohort studies and 5 prospective intervention studies were included, with a total of 12,922 participants aged 6 to 16 years. RESULTS: Comparing the highest with the lowest exposure levels of time spent outdoors, the highest outdoor time was strongly associated with a reduced risk of myopia onset (OR: 0.53; 95% CI: 0.34, 0.82). A non-linear dose-response relationship was found between outdoor time and myopia onset risk. Compared to 3.5 hours of outdoor time per week, an increase to 7, 16.3, and 27 hours per week corresponded with a respective reduction in the risk of myopia onset by 20%, 53%, and 69%. Among children and adolescents who were not myopic, spending more time outdoors significantly slowed down the speed of change in spherical equivalent refractive (SER) (WMD=0.10D, 95%CI: 0.07, 0.14) and axial length (AL) (WMD=-0.05mm, 95%CI: -0.06, -0.03). Among children and adolescents who were already myopic, spending more time outdoors did not slow myopia progression. CONCLUSIONS: Overall, spending more time outdoors can prevent the onset of myopia, but it doesn't seem to slow its progression. Further studies are needed to better understand these trends.

DNA vaccine prime and replicating vaccinia vaccine boost induce robust humoral and cellular immune responses against MERS-CoV in mice.

As of December 2022, 2,603 cases laboratory-identified Middle East respiratory syndrome coronavirus (MERS-CoV) infections and 935 associated deaths, with a mortality rate of 36%, had been reported to the World Health Organization (WHO). However, there are still no vaccines for MERS-CoV, which makes the prevention and control of MERS-CoV difficult. In this study, we constructed two vaccine candidates of DNA and replicating Vaccinia Tian Tan (VTT) vector that carried the MERS-CoV Spike (S) protein. Compared with homologous immunization with either vaccine, mice immunized with DNA vaccine prime and VTT vaccine boost exhibited much stronger and durable humoral and cellular immune responses. The mice immunized generated robust binding antibodies and broader neutralizing antibodies against the EMC2012, England1 and KNIH strains of MERS-CoV. Prime-Boost immunization also induced strong MERS-S specific T cells responses, with high memory and poly-functional (CD107a-IFN-γ-TNF-α) effector CD8+ T cells. In conclusion, the research demonstrated that DNA-Prime/VTT-Boost strategy could elicit robust and balanced humoral and cellular immune responses against MERS-CoV-S. This study not only provides a promising set of MERS-CoV vaccine candidates but also proposes a heterologous sequential immunization strategy worthy of further development.

Application of retaining the vessels around the orbicularis oculi muscle in blepharoplasty.

OBJECTIVE: To investigate the effect of retaining the vessels around the orbicularis oculi muscle on reducing local swelling after blepharoplasty. METHODS: A total of 309 patients undergoing blepharoplasty (total incision) were observed and randomly assigned to three groups; (A) conventional operation; (B) preservation of deep vessels; (C) preservation of anterior vessels of orbicularis oculi muscle. The groups were compared based on intraoperative blood loss, operation time, swelling, satisfaction, and complications. RESULTS: Among the 309 patients, 39 were lost to follow-up. c Additionally, A had the shortest operation time, followed by C with slightly longer duration. On the 7th day, 15th day, and 1 month after surgery, both B and C demonstrated significantly lower levels of swelling compared to A. Moreover, patient satisfaction was higher in B and C than in A. CONCLUSION: Retaining either superficial or deep veins of the orbicularis oculi muscle can effectively reduce short-term postoperative swelling. However, when retaining the superficial central group of this muscle during surgery, it is crucial to strictly control the amount of surrounding tissue around vessels.

Evolutionary game analysis of data sharing among large and medium-sized enterprises in the perspective of platform empowerment.

With the swift advancement of the global digital economy, data has emerged as a critical component in fostering the integration of large enterprises with small and medium-sized enterprises (SMEs). Nevertheless, due to disparities in resources and capabilities between these entities, there is a deficiency in the willingness to share data, hindering the full actualization of data's potential value. Hence, it is imperative to facilitate a novel cooperative development paradigm wherein platforms enable data sharing among large enterprises and SMEs. In this paper, we construct a tripartite evolutionary game model encompassing large enterprises, SMEs, and digital platforms, examine the evolutionary stable strategies adopted by these entities in the data sharing, and use numerical simulation to explore the system's evolutionary stability under various influencing factors. Contrasting with prior research, this study considers the heterogeneity of enterprise scale and delves into the data sharing dynamics between large enterprises and SMEs. Simultaneously, it positions the digital platform as a player in the game, examining its impact on data sharing among the enterprises. Findings indicate that: (1) SMEs exhibit greater eagerness for data sharing compared to large enterprises, which display a U-shaped influence during the process; (2) Digital platforms are particularly sensitive to costs, with the platform's initiative and the service quality will affect enterprises strategic choices; (3) Government subsidies positively encourage tripartite cooperation, and robust data security governance framework is crucial for enterprises. Finally, based on the results of the study and combining with the current situation of digital economy development, it puts forward the suggestions for promoting platforms to empower large enterprises and SMEs to realize data sharing and the prospects for future research.

Targeting c-Myc transactivation by LMNA inhibits tRNA processing essential for malate-aspartate shuttle and tumour progression.

BACKGROUND: A series of studies have demonstrated the emerging involvement of transfer RNA (tRNA) processing during the progression of tumours. Nevertheless, the roles and regulating mechanisms of tRNA processing genes in neuroblastoma (NB), the prevalent malignant tumour outside the brain in children, are yet unknown. METHODS: Analysis of multi-omics results was conducted to identify crucial regulators of downstream tRNA processing genes. Co-immunoprecipitation and mass spectrometry methods were utilised to measure interaction between proteins. The impact of transcriptional regulators on expression of downstream genes was measured by dual-luciferase reporter, chromatin immunoprecipitation, western blotting and real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR) methods. Studies have been conducted to reveal impact and mechanisms of transcriptional regulators on biological processes of NB. Survival differences were analysed using the log-rank test. RESULTS: c-Myc was identified as a transcription factor driving tRNA processing gene expression and subsequent malate-aspartate shuttle (MAS) in NB cells. Mechanistically, c-Myc directly promoted the expression of glutamyl-prolyl-tRNA synthetase (EPRS) and leucyl-tRNA synthetase (LARS), resulting in translational up-regulation of glutamic-oxaloacetic transaminase 1 (GOT1) as well as malate dehydrogenase 1 (MDH1) via inhibiting general control nonrepressed 2 or activating mechanistic target of rapamycin signalling. Meanwhile, lamin A (LMNA) inhibited c-Myc transactivation via physical interaction, leading to suppression of MAS, aerobic glycolysis, tumourigenesis and aggressiveness. Pre-clinically, lobeline was discovered as a LMNA-binding compound to facilitate its interaction with c-Myc, which inhibited aminoacyl-tRNA synthetase expression, MAS and tumour progression of NB, as well as growth of organoid derived from c-Myc knock-in mice. Low levels of LMNA or elevated expression of c-Myc, EPRS, LARS, GOT1 or MDH1 were linked to a worse outcome and a shorter survival time of clinical NB patients. CONCLUSIONS: These results suggest that targeting c-Myc transactivation by LMNA inhibits tRNA processing essential for MAS and tumour progression.

Real-world applications of the new grading system in lung adenocarcinoma: A study of 907 patients focusing on revealing the relationship between pathologic grade and genetic status.

BACKGROUND: The status of the lung adenocarcinoma (LUAD) grading system and the association between LUAD differentiation, driver genes, and clinicopathological features remain to be elucidated. METHODS: We included patients with invasive non-mucinous LUAD, evaluated their differentiation, and collected available clinicopathological information, gene mutations, and analyzed clinical outcomes. RESULTS: Among the 907 patients with invasive non-mucinous LUAD, 321 (35.4 %) were poorly differentiated, 422 (46.5 %) were moderately differentiated, and 164 (18.1 %) were well differentiated. EGFR mutation was more common in the LUADs accompanied without CGP (complex glandular pattern) than LUADs with CGP (p < 0.001). Correlation analysis between mutations and clinical characteristics showed that EGFR gene mutation (p < 0.001), KRAS gene mutation (p < 0.05), and ALK gene rearrangement (p < 0.001) were significantly related to the degree of tumor differentiation, and the KRAS and ALK gene mutation frequencies were higher in the low-differentiation group than in the high and medium differentiation groups. The EGFR mutation frequency was higher in the well/moderately differentiated adenocarcinoma group. CONCLUSIONS: Our study adds to the evidence regarding the role of the grading system in prognosis. EGFR, KRAS, and ALK are related to the degree of tumor differentiation.

A potent new-scaffold androgen receptor antagonist discovered on the basis of a MIEC-SVM model.

Prostate cancer (PCa) is the second most prevalent malignancy among men worldwide. The aberrant activation of androgen receptor (AR) signaling has been recognized as a crucial oncogenic driver for PCa and AR antagonists are widely used in PCa therapy. To develop novel AR antagonist, a machine-learning MIEC-SVM model was established for the virtual screening and 51 candidates were selected and submitted for bioactivity evaluation. To our surprise, a new-scaffold AR antagonist C2 with comparable bioactivity with Enz was identified at the initial round of screening. C2 showed pronounced inhibition on the transcriptional function (IC50 = 0.63 µM) and nuclear translocation of AR and significant antiproliferative and antimetastatic activity on PCa cell line of LNCaP. In addition, C2 exhibited a stronger ability to block the cell cycle of LNCaP than Enz at lower dose and superior AR specificity. Our study highlights the success of MIEC-SVM in discovering AR antagonists, and compound C2 presents a promising new scaffold for the development of AR-targeted therapeutics.

Leaders of Peer Groups in Chinese Early Adolescents: The Roles of Social, Academic, and Psychological Characteristics in Group Leadership.

Leadership in peer groups is an important issue in adolescent socioemotional development, yet it has received limited attention in research. This one-year longitudinal study examined peer group leadership and the roles of social, academic, and psychological characteristics in the dynamics of group leadership. Participants included 1061 Chinese students (initial mean age =11.17 years; SD = 6.98 months; 49.4% female). Data were collected from peer assessments, teacher ratings, and self-reports. The longitudinal social network analysis (SIENA) indicated that peer group leadership was fluid with leadership status evolving over time across groups in a hierarchical manner. Adolescents displaying higher social competence and aggression and lower shyness were more likely to become group leaders. Academic performance and loneliness were not significantly associated with the dynamics of peer group leadership. The results help understand peer group leadership and contributions of social behaviors to the attainment of leadership status in peer groups in early adolescence.

Cross-Linking CdSO4-Type Nets with Hexafluorosilicate Anions to Form an Ultramicroporous Material for Efficient C2H2/CO2 and C2H2/C2H4 Separation.

A 44.610.8 topology hybrid ultramicroporous material (HUM), {[Cu1.5F(SiF6)(L)2.5]·G}n, (L = 4,4'-bisimidazolylbiphenyl, G = guest molecules), 1, formed by cross-linking interpenetrated 3D four-connected CdSO4-type nets with hexafluorosilicate anions is synthesized and evaluated in the context of gas sorption and separation herein. 1 is the first HUM functionalized with two different types of fluorinated sites (SiF6 2- and F- anions) lining along the pore surface. The optimal pore size (≈5 Å) combining mixed and high-density electronegative fluorinated sites enable 1 to preferentially adsorb C2H2 over CO2 and C2H4 by hydrogen bonding interactions with a high C2H2 isosteric heat of adsorption (Qst) of ≈42.3 kJ mol-1 at zero loading. The pronounced discriminatory sorption behaviors lead to excellent separation performance for C2H2/CO2 and C2H2/C2H4 that surpasses many well-known sorbents. Dynamic breakthrough experiments are conducted to confirm the practical separation capability of 1, which reveal an impressive separation factor of 6.1 for equimolar C2H2/CO2 mixture. Furthermore, molecular simulation and density functional theory (DFT) calculations validate the strong binding of C2H2 stems from the chelating fix of C2H2 between SiF6 2- anion and coordinated F- anion.