Search

Background: Colorectal cancer (CRC) is a major global health challenge with a need for new biomarkers and therapeutic targets. This work aimed to investigate the biological mechanisms and clinical value of Ly1 antibody reactive (LYAR) in CRC. Methods: We analyzed LYAR mRNA expression across multiple public databases, including genotype-tissue expression, gene expression omnibus, Oncomine, and the cancer genome atlas, alongside in-house immunohistochemical data to evaluate LYAR protein expression in CRC and non-CRC colorectal tissues. Gene set enrichment analysis (GSEA) was used to elucidate LYAR's biological functions, and its impact on the tumor immune microenvironment was assessed using CIBERSORT, ESTIMATE, and single-cell RNA sequencing techniques. In addition, LYAR's association with clinicopathological features and patient prognosis was explored, and its influence on drug sensitivity was investigated using the Connectivity Map database. Results: LYAR was significantly upregulated in CRC tissues compared with non-CRC colorectal counterparts, associated with altered immune cell composition and enhanced RNA processing, splicing, and cell cycle regulation. High LYAR expression correlated with poor disease-free and overall survival, underscoring its prognostic value. GSEA revealed LYAR's involvement in critical cellular processes and pathways, including DNA repair, cell cycle, and mTORC1 signaling. Correlation analysis identified genes positively and negatively associated with LYAR, leading to the discovery of temsirolimus and WYE-354, mTOR inhibitors, as potential therapeutic agents for CRC. Furthermore, LYAR expression predicted increased sensitivity to cetuximab in RAS wild-type metastatic CRC, indicating its utility as a biomarker for treatment responsiveness. Conclusions: LYAR's upregulation in CRC highlights its potential as a biomarker for prognosis and therapeutic targeting, offering insights into CRC pathology and suggesting new avenues for treatment optimization.

Background: The government-led community-based Chinese National Integrated Demonstration Areas for the Prevention and Control of Noncommunicable Diseases programme was launched in 2011, but no rigorous impact evaluation has been conducted to date. We aimed to evaluate the causal effects of this programme on behavioural risk factors., Methods: We used data from the latest five waves of the China Chronic Disease and Risk Factor Surveillance. The primary outcome is a behavioural risk score combining current smoking, passive smoking, drinking in last month, regular exercise, body mass index, and waist circumference. We applied the synthetic difference-in-differences method and constructed synthetic controls from the non-demonstration areas with the outcome. The average treatment effects on the treated were estimated for overall effect and by short- (1-2), medium- (3-4), and long-term (6-7 years) effects., Findings: We identified 26 demonstration areas (N = 72,193) and 100 non-demonstration areas (N = 275,397). Participants in the demonstration areas had higher education and income levels and different pre-implementation trends than non-demonstration areas. Using synthetic controls instead of non-demonstration areas reduced these pre-implementation differences. Compared to the synthetic controls, declines were observed in current smoking (-1.78% [-4.51%, 0.96%]), passive smoking (-8.09% [-14.27%, -1.90%]), and drinking in last month (-4.04% [-8.75%, 0.67%]) but not in the other factors. Behavioural risk score declined by 1.05 short-term (95% CI: -1.84, -0.26), 1.15 medium-term (95% CI: -2.08, -0.22), 2.82 long-term (95% CI: -4.79, -0.85), and 1.54 overall (95% CI: -2.51, -0.56)., Interpretation: The programme improved behavioural risk scores, primarily through reductions in the prevalence of smoking and drinking, and the effect was long-lasting. Our findings provided empirical evidence for utilizing an integrated prevention and control strategy to fight against NCD in China and other countries facing similar challenges., Funding: The China National Key Research and Development Program (2018YFC1315304 and 2017YFC1310902); National Natural Science Foundation of China (81872721)., Competing Interests: We declare no competing interests., (© 2024 The Authors.)

The activation of halogens (X = Cl, Br, I) by N 2 O 5 is linked to NO x sources, ozone concentrations, NO 3 reactivity, and the chemistry of halide-containing aerosol particles. However, a detailed chemical mechanism is still lacking. Herein, we explored the chemistry of the N 2 O 5 ···X - systems at the air-water interface. Two different reaction pathways were identified for the reaction of N 2 O 5 with X - at the air-water interface: the formation of XNO 2 or XONO, along with NO 3 - . In the case of the Cl - system, the ClNO 2 generation pathway is more favorable, while for the Br - and I - systems, the formation of BrONO and IONO is barrierless, making them the predominant products. Furthermore, the mechanisms of formation of X 2 from XNO 2 and XONO were also investigated. The high energy barriers of reactions and the high free energies of the products compared to those of the reactants indicate that ClNO 2 is stable at the air-water interface. Contrary to the widely held belief regarding X 2 producing from the reaction of XNO 2 with X - , our calculations demonstrate that BrONO and IONO initially form stable BrONO···Br - and IONO···I - complexes, which then subsequently react with Br - and I - to form Br 3 - and I 3 - , respectively. Finally, Br 3 - and I 3 - decompose to form Br 2 and I 2. These findings have significant implications for experimental interpretation and offer new insights into halogen cycling in the atmosphere.

Scalable single-use adherent cell-based biomanufacturing platforms are essential for unlocking the full potential of cell and gene therapies. The primary objective of this study is to design and develop a novel fixed bed bioreactor platform tailored specifically for scaling up adherent cell culture. The bioreactor comprises a packed bed of vertically stacked woven polyethylene terephthalate mesh discs, sandwiched between two-fluid guide plates. Leveraging computational fluid dynamics modeling, we optimized bioreactor design to achieve uniform flow with minimal shear stress. Residence time distribution measurements demonstrated excellent flow uniformity with plug flow characteristics. Periodic media sampling coupled with offline analysis revealed minimal gradients of crucial metabolites (glucose, glutamine, lactate, and ammonia) across the bioreactor during cell growth. Furthermore, the bioreactor platform demonstrated high performance in automated cell harvesting, with ≈96% efficiency and ≈98% viability. It also exhibited linear scalability in both operational parameters and performance for cell culture and adeno-associated virus vector production. We developed mathematical models based on oxygen uptake rates to accurately predict cell growth curves and estimate biomass in real-time. This study demonstrates the effectiveness of the developed fixed-bed bioreactor platform in enabling scalable adherent cell-based biomanufacturing with high productivity and process control., (© 2024 The Author(s). Biotechnology Journal published by Wiley‐VCH GmbH.)

Background: There is a dearth of effective treatments to counter retinol-induced skin irritation., Objective: This study aimed to investigate the efficacy of three potential mitigants: (i) phytosteryl/octyldodecyl lauroyl glutamate (PLG), (ii) a physiologic lipid mixture (PLM) comprised of ceramide three and cholesterol, and (iii) niacinamide, in ameliorating irritation instigated by retinol., Methods: An occlusive human patch test, spanning 5 days, was undertaken on 18 Chinese participants aged between 23 and 40. It was designed as a randomized, double-blind, and vehicle-controlled study. Clinician erythema assessment (CEA) and instrumental evaluations were employed pre and post-test. Subsequently, a 4-week consumer in-use test, randomized and double-blind in nature, was executed to substantiate the soothing effects of PLG., Results: Data from CEA and bioengineering assessments revealed that, in comparison to the vehicle control, both 2% PLG and 5% PLM notably curbed retinol-induced skin erythema and inflammation. Notably, PLG outperformed PLM. Conversely, 3% niacinamide did not offer relief against retinol-induced discomfort. The subsequent consumer in-use test affirmed that treatments with 2% PLG were better tolerated than those with the vehicle alone., Conclusion: To the best of our knowledge, this study represents the first confirmation that physiologic lipids effectively mitigate retinol-induced irritation. Given their capacity to counter retinol-induced irritation, physiologic lipids, particularly PLG, are recommended for incorporation in retinol regimens. Additionally, the Visia-CR a* value can serve as a robust objective measure for interpreting patch test outcomes., (© 2024 The Authors. Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

Chlorine oxides play crucial roles in ozone depletion, and the final oxidation steps of chlorine oxide potentially result in the formation of chloric acid (HClO 3 ) or perchloric acid (HClO 4 ). Herein, the solvation and reactive uptake of three stable isomers of chlorine trioxide (Cl 2 O 3 ), namely, ClOCl(O)O, ClClO 3 , and ClOOOCl, at the air-water interface were investigated using classical and hybrid quantum mechanics/molecular mechanics (QM/MM) molecular dynamics (MD) coupled with advanced free energy methods. Two distinct mechanisms were revealed for the hydrolysis of ClOCl(O)O and ClClO 3 : molecular and ionic mechanisms. A comparison of the computed free-energy profiles for the gaseous and air-water interfacial systems indicated that the air-water interface could markedly lower the free-energy barrier for ClO 3 - or HClO 3 formation while stabilizing the product state. In particular, the hydrolysis of ClClO 3 at the air-water interface was barrierless. In contrast, our calculations showed that the hydrolysis of ClOOOCl was very slow, indicating that ClOOOCl was inert to water at the air-water interface. This study provides theoretical evidence for the hypothesis that HClO 3 is a sink for chlorine oxides and for the widespread distributions of HClO 3 recently observed in the Arctic region.

Water tends to wet all hydrophilic surfaces under ambient conditions, and the first water adlayers on solids are important for a broad range of physicochemical phenomena and technological processes, including corrosion, wetting, lubrication, anti-icing, catalysis, and electrochemistry. Unfortunately, challenges in characterizing the first water adlayer in the laboratory have hampered molecular-level understanding of the contact water structure. Herein, we present the first ab initio molecular dynamics simulation evidence of a previously unreported ice-like adlayer structure (named as Ice-AL-II) on a prototype mica surface under ambient conditions. Calculation showed that the newly identified Ice-AL-II structure is more stable than the widely recognized ice-adlayer structure on mica surfaces (named as Ice-AL-I). Ice-AL-II exhibited a face-centered corner-cut tetragon (or a face-centered irregular pentagon) pattern of a hydrogen-bonded network. The center of the corner-cut tetragon was occupied by either a K + cation or a water molecule with two H atoms pinned by the mica (100) via double hydrogen bonds. Our simulation also suggested that bilayer Ice-AL-II favors AA stacking rather than AB stacking. Interestingly, when a graphene sheet was coated on top of the ice-like adlayer, the stability of Ice-AL-II was further enhanced. In contrast, due to its strongly puckered structure, the Ice-AL-I structure could be crushed into a near-Ice-AL-II structure by the graphene coating. Ice-AL-II is thus proposed as a promising candidate for the ice-like structure on a mica surface detected by scanning polarization force microscopy and by atomic force microscopy between a graphene coating and a mica surface.

Large-area transfer-free graphene films prepared via chemical vapor deposition have proved appealing for various applications, with exciting examples in electronics, photonics, and optoelectronics. To achieve their commercialisation, batch production is a prerequisite. Nevertheless, the prevailing scalable synthesis strategies that have been reported are still obstructed by production inefficiencies and non-uniformity. There has also been a lack of reviews in this realm. We present herein a comprehensive and timely summary of recent advances in the batch production of transfer-free graphene. Primary issues and promising approaches for improving the graphene growth rate are first addressed, followed by a discussion of the strategies to guarantee in-plane and batch uniformity for graphene grown on planar plates and wafer-scale substrates, with the design of the target equipment to meet productivity requirements. Finally, potential research directions are outlined, aiming to offer insights into guiding the scalable production of transfer-free graphene.

This study aimed to investigate the mechanisms of LACTB2 in colorectal cancer (CRC). Microarrays and sequencing data of CRC were acquired from UCSC Xena, GTEx, Gene Expression Omnibus, and TCGA. Pooled analysis of the mRNA expression of LACTB2 in CRC was performed using Stata software. The protein expression of LACTB2 in CRC tissues was evaluated by immunohistochemistry. The relationship between immune cell infiltration and LACTB2 expression was investigated using CIBERSORT. The potential signaling pathways and biological mechanisms of LACTB2 were explored using GSEA, KEGG, and GO. Subsequently, further screening of small molecular compounds with potential therapeutic effects on CRC was conducted through the HERB database, followed by molecular docking studies of these compounds with the LACTB2 protein. The integration and analysis of expression data obtained from 2294 CRC samples and 1286 noncancerous colorectal samples showed that LACTB2 was highly expressed in CRC. Immunohistochemistry performed on in-house tissue samples confirmed that LACTB2 protein expression was upregulated in CRC. CIBERSORT revealed lower B cell infiltration levels in the high LACTB2 expression group than in the low expression group. GO, KEGG, and GSEA analyses showed that LACTB2 expression and genes positively correlating with it were mainly related to DNA synthesis and repair, mitochondrial translational elongation and translational termination, phosphorylation, and mTORC1 signaling. Finally, molecular docking simulations confirmed the ability of quercitin to target and bind to LACTB2. This is the first study to demonstrate that LACTB2 is upregulated in CRC. LACTB2 promotes colorectal tumorigenesis and tumor progression., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Microdroplets are a class of soft matter that has been extensively employed for chemical, biochemical, and industrial applications. However, fabricating microdroplets with largely controllable contact-area shape and apparent contact angle, a key prerequisite for their applications, is still a challenge. Here, by engineering a type of surface with homocentric closed-loop microwalls/microchannels, we can achieve facile size, shape, and contact-angle tunability of microdroplets on the textured surfaces by design. More importantly, this class of surface topologies (with universal genus value = 1) allows us to reveal that the conventional Gibbs equation (widely used for assessing the edge effect on the apparent contact angle of macrodroplets) seems no longer applicable for water microdroplets or nanodroplets (evidenced by independent molecular dynamics simulations). Notably, for the flat surface with the intrinsic contact angle ~0°, we find that the critical contact angle on the microtextured counterparts (at edge angle 90°) can be as large as >130°, rather than 90° according to the Gibbs equation. Experiments show that the breakdown of the Gibbs equation occurs for microdroplets of different types of liquids including alcohol and hydrocarbon oils. Overall, the microtextured surface design and topological wetting states not only offer opportunities for diverse applications of microdroplets such as controllable chemical reactions and low-cost circuit fabrications but also provide testbeds for advancing the fundamental surface science of wetting beyond the Gibbs equation., Competing Interests: Competing interests statement:The authors declare no competing interest.

Objective: To study the effect of arctigenin(ARG) on adriamycin(ADM) resistance of leukemia cell line K562/A02 and the underlying mechanism., Methods: Human leukemia cell line K562 and ADM-resistant cell line K562/A02 were cultured and treated with 2.5-50 µmol/L ADM. Cell proliferation was measured using CCK-8 method, and half maximal inhibitory concentration (IC 50 ) was calculated. K562/A02 cells were treated with different concentrations of ARG (1, 2, 4, 8, 16 mmol/L) to detect the effect of ARG on K562/A02 cells, and a suitable concentration (2 mmol/L) was selected for subsequent experiments. K562/A02 cells were treated with 2 mmol/L ARG and 5 µmol/L ADM, and cell apoptosis was detected by flow cytometry, the expression of P-gp, MRP, cleaved caspase-3, Bax, Bcl-2 proteins and the TLR4/NF-κB signaling pathway-related proteins were measured by Western blot. TLR4 overexpression plasmid was transfected into K562/A02 cells which were co-treated with ARG and ADM, then drug sensitivity and cell apoptosis were measured., Results: The IC 50 value of ADM on K562/A02 cells was 36.57 µmol/L, which was significantly higher than that on K562 cells (1.30 µmol/L). ARG with a concentration of ≤2 mmol/L did not have a significant effect on K562/A02 cells. 2 mmol/L ARG significantly reduced the IC 50 of ADM on K562/A02 cells. In 5 µmol/L ADM-treated K562/A02 cells, compared with the control group, the apoptosis rate of K562/A02 cells in the ARG group was significantly increased, the expressions of cleaved caspase-3, Bax proteins were significantly upregulated, the expressions of P-gp, MRP, Bcl-2, TLR4, MyD88, and p-NF-κB proteins were significantly downregulated, and the differences were statistically significant ( P < 0.05). After transfection with TLR4 overexpression plasmid, the sensitivity of ARG-treated K562/A02 cells to ADM was reduced ( P < 0.05), the cell apoptosis was decreased, and the expressions of P-gp, MRP, Bcl-2 and TLR4/NF-κB signaling pathway-related proteins were significantly elevated, while the expressions of cleaved caspase-3 and Bax proteins were significantly decreased (all P < 0.05)., Conclusion: ARG may reverse the resistance of human leukemia cell line K562/A02 to ADM by inhibiting TLR4/NF-κB signaling pathway.

Reactive uptake of dinitrogen pentaoxide (N 2 O 5 ) into aqueous aerosols is a major loss channel for NO x in the troposphere; however, a quantitative understanding of the uptake mechanism is lacking. Herein, a computational chemistry strategy is developed employing high-level quantum chemical methods; the method offers detailed molecular insight into the hydrolysis and ammonolysis mechanisms of N 2 O 5 in microdroplets. Specifically, our calculations estimate the bulk and interfacial hydrolysis rates to be (2.3 ± 1.6) × 10 -3 and (6.3 ± 4.2) × 10 -7 ns -1 , respectively, and ammonolysis competes with hydrolysis at NH 3 concentrations above 1.9 × 10 -4  mol L -1 . The slow interfacial hydrolysis rate suggests that interfacial processes have negligible effect on the hydrolysis of N 2 O 5 in liquid water. In contrast, N 2 O 5 ammonolysis in liquid water is dominated by interfacial processes due to the high interfacial ammonolysis rate. Our findings and strategy are applicable to high-chemical complexity microdroplets., (© 2024. The Author(s).)

Rationale: Post-transplant lymphoproliferative disorder (PTLD) is a well-recognized, but uncommon complication in patients with kidney transplantation, which poses challenges in diagnosis and poor prognosis due to its low incidence and nonspecific clinical manifestations. As a routine follow-up examination method for kidney transplant patients, ultrasound (US) plays a significant role in the diagnosis of PTLD. Therefore, it is critical to evaluate the ultrasonic characteristics of PTLD in transplanted kidney patients for early detection and diagnosis., Patient Concerns: A 59-year-old female patient was unexpectedly found with a mass in the hilum of the transplanted kidney 12th month after transplantation, which gradually grew up in the following 4 months. The latest US examination found hydronephrosis. Contrast-enhanced ultrasound (CEUS) demonstrated a hypo-enhancement pattern in arterial and parenchymal phases and showed a new irregular area lacking perceivable intensification within the mass, which was considered necrosis. Meanwhile, the patient developed an acute increase in serum creatinine from 122 to 195 μmol/L., Diagnosis: A US-guided biopsy was conducted with the final pathological diagnosis of PTLD (polymorphic)., Interventions: After receiving 3 times of rituximab and symptomatic treatment, blood creatinine returned to normal but the mass was still progressing in the patient. Therefore, the treatment approach was modified to immune-chemotherapy., Outcomes: The patient was in a stable condition to date., Lessons: PTLD is a rare complication in a transplanted kidney. US and CEUS are the preferred imaging methods in renal transplant patients due to their good repeatability and no nephrotoxicity. This case demonstrates that continuous dynamic monitoring by using US and CEUS has significant value in the detection and diagnosis of PTLD in a transplanted kidney, suggesting early clinical intervention to avoid further progression., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: This study aimed to explore the diagnostic value of serum adenosine deaminase (ADA) in patients with myelodysplastic syndromes (MDS) and identify potential risk factors for MDS., Methods: Eighty patients with MDS and 80 healthy individuals were included. The serum ADA level was found to be significantly higher in patients with MDS compared with that of healthy controls (p = 0.014)., Results: The receiver operator characteristic curve (ROC) for ADA had an area under curve (AUC) of 0.807 (p = 0.0018). Serum ADA level of 4.5 U/L had a sensitivity of 71.43% and specificity of 80% for MDS diagnosis. The multivariate analysis showed hemoglobin (Hb, OR = 1.322, 95% CI: 1.035 - 2.323, p = 0.039), prothrombin time (PT, OR = 1.524, 95% CI: 1.156 - 3.280, p = 0.042), fibrinogen (OR = 1.335, 95% CI: 1.022 - 2.775, p = 0.027), calculated international normalized ration (INR, OR = 2.212, 95% CI: 1.320 - 3.085, p = 0.038), D-dimer (OR = 2.043, 95% CI: 1.623 - 4.293, p = 0.038), fibrin degradation product (FDP, OR = 2.525, 95% CI: 1.129 - 3.340, p = 0.029), and serum ADA (OR = 2.057, 95% CI: 1.248 - 3.572, p = 0.033) were independently associated with MDS., Conclusions: Serum ADA might be a potential biomarker in the diagnosis of MDS. Serum ADA level, Hb level, PT, fibrinogen level, INR, D-dimer, and FDPs were independent risk factors of MDS.

Age-related macular degeneration (AMD) is a leading cause of vision loss in the elderly, highlighting the need for early and accurate detection. In this study, we proposed DeepDrAMD, a hierarchical vision transformer-based deep learning model that integrates data augmentation techniques and SwinTransformer, to detect AMD and distinguish between different subtypes using color fundus photographs (CFPs). The DeepDrAMD was trained on the in-house WMUEH training set and achieved high performance in AMD detection with an AUC of 98.76% in the WMUEH testing set and 96.47% in the independent external Ichallenge-AMD cohort. Furthermore, the DeepDrAMD effectively classified dryAMD and wetAMD, achieving AUCs of 93.46% and 91.55%, respectively, in the WMUEH cohort and another independent external ODIR cohort. Notably, DeepDrAMD excelled at distinguishing between wetAMD subtypes, achieving an AUC of 99.36% in the WMUEH cohort. Comparative analysis revealed that the DeepDrAMD outperformed conventional deep-learning models and expert-level diagnosis. The cost-benefit analysis demonstrated that the DeepDrAMD offers substantial cost savings and efficiency improvements compared to manual reading approaches. Overall, the DeepDrAMD represents a significant advancement in AMD detection and differential diagnosis using CFPs, and has the potential to assist healthcare professionals in informed decision-making, early intervention, and treatment optimization., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Dinutuximab β can be used to treat children with high-risk neuroblastoma (NB). Due to its high price, whether dinutuximab β is cost-effective for the treatment of high-risk NB remains uncertain. Therefore, assessing the cost-effectiveness of dinutuximab β in children with high-risk NB is of high importance., Methods: The health utilities and economic outcomes in children with high-risk NB were projected using a partitioned survival model. The individual patient data (IPD) of add-on treatment with dinutuximab β (GD2 group) were derived from the literature, while the IPD of traditional therapy (TT group) were obtained from retrospective data of Shanghai Children's Medical Center. Treatment costs included drugs, adverse event-related expenses, and medical resource use. Utility values were obtained from the literature. Costs and quality-adjusted life-years (QALYs) were measured over a 10-year time horizon. Deterministic sensitivity analyses (DSA) and probabilistic sensitivity analyses (PSA) were also conducted., Results: Compared with the TT group, QALY increased in the GD2 group by 0.72 with an increased cost of $171,269.70, leading to an incremental cost-effectiveness ratio of 236,462.75$/QALY. DSA showed that the price of dinutuximab β was the main factor on the results than other parameters. Compared with the TT group, the GD2 group could not be cost-effective in the PSA at the $37,920/QALY threshold., Conclusion: Results found that dinutuximab β is not a cost-effective treatment option for children with high-risk NB unless its price is significantly reduced., (© 2023 Wiley Periodicals LLC.)

Photochemical homolysis of hydrogen peroxide (H 2 O 2 ) occurs widely in nature and is a key source of hydroxyl radicals (·OH). The kinetics of H 2 O 2 photolysis play a pivotal role in determining the efficiency of ·OH production, which is currently mainly investigated in bulk systems. Here, we report considerably accelerated H 2 O 2 photolysis at the air-water interface of microdroplets, with a rate 1.9 × 10 3 times faster than that in bulk water. Our simulations show that due to the trans quasiplanar conformational preference of H 2 O 2 at the air-water interface compared to the bulk or gas phase, the absorption peak in the spectrum of H 2 O 2 is significantly redshifted by 45 nm, corresponding to greater absorbance of photons in the sunlight spectrum and faster photolysis of H 2 O 2 . This discovery has great potential to solve current problems associated with ·OH-centered heterogeneous photochemical processes in aerosols. For instance, we show that accelerated H 2 O 2 photolysis in microdroplets could lead to markedly enhanced oxidation of SO 2 and volatile organic compounds.

In order to improve the dielectric thermal stability of polyvinylidene fluoride (PVDF)-based film, nano silicon nitride (Si 3 N 4 ) was introduced, and hence the energy storage performance was improved. The introduction of nano Si 3 N 4 fillers will induce a phase transition of P(VDF-HFP) from polar β to nonpolar α, which leads to the improved energy storage property. As such, the discharging energy density of Si 3 N 4 /P(VDF-HFP) composite films increased with the amount of doped Si 3 N 4 . After incorporating 10wt% Si 3 N 4 in Si 3 N 4 /P(VDF-HFP) films, the discharging density increased to 1.2 J/cm 3 under a relatively low electric field of 100 MV/m. Compared with a pure P(VDF-HFP) film, both the discharging energy density and thermal dielectric relaxor temperature of Si 3 N 4 /P(VDF-HFP) increased. The working temperature increased from 80 °C to 120 °C, which is significant for ensuring its adaptability in high-temperature energy storage areas. Thus, this result indicates that Si 3 N 4 is a key filler that can improve the thermal stability of PVDF-based energy storage polymer films and may provide a reference for high-temperature capacitor materials.

Background: Rapid advancements in eHealth and mobile health (mHealth) technologies have driven researchers to design and evaluate numerous technology-based interventions to promote smoking cessation. The evolving nature of cessation interventions emphasizes a strong need for knowledge synthesis., Objective: This systematic review and meta-analysis aimed to summarize recent evidence from randomized controlled trials regarding the effectiveness of eHealth-based smoking cessation interventions in promoting abstinence and assess nonabstinence outcome indicators, such as cigarette consumption and user satisfaction, via narrative synthesis., Methods: We searched for studies published in English between 2017 and June 30, 2022, in 4 databases: PubMed (including MEDLINE), PsycINFO, Embase, and Cochrane Library. Two independent reviewers performed study screening, data extraction, and quality assessment based on the GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) framework. We pooled comparable studies based on the population, follow-up time, intervention, and control characteristics. Two researchers performed an independent meta-analysis on smoking abstinence using the Sidik-Jonkman random-effects model and log risk ratio (RR) as the effect measurement. For studies not included in the meta-analysis, the outcomes were narratively synthesized., Results: A total of 464 studies were identified through an initial database search after removing duplicates. Following screening and full-text assessments, we deemed 39 studies (n=37,341 participants) eligible for this review. Of these, 28 studies were shortlisted for meta-analysis. According to the meta-analysis, SMS or app text messaging can significantly increase both short-term (3 months) abstinence (log RR=0.50, 95% CI 0.25-0.75; I 2 =0.72%) and long-term (6 months) abstinence (log RR=0.77, 95% CI 0.49-1.04; I 2 =8.65%), relative to minimal cessation support. The frequency of texting did not significantly influence treatment outcomes. mHealth apps may significantly increase abstinence in the short term (log RR=0.76, 95% CI 0.09-1.42; I 2 =88.02%) but not in the long term (log RR=0.15, 95% CI -0.18 to 0.48; I 2 =80.06%), in contrast to less intensive cessation support. In addition, personalized or interactive interventions showed a moderate increase in cessation for both the short term (log RR=0.62, 95% CI 0.30-0.94; I 2 =66.50%) and long term (log RR=0.28, 95% CI 0.04-0.53; I 2 =73.42%). In contrast, studies without any personalized or interactive features had no significant impact. Finally, the treatment effect was similar between trials that used biochemically verified or self-reported abstinence. Among studies reporting outcomes besides abstinence (n=20), a total of 11 studies reported significantly improved nonabstinence outcomes in cigarette consumption (3/14, 21%) or user satisfaction (8/19, 42%)., Conclusions: Our review of 39 randomized controlled trials found that recent eHealth interventions might promote smoking cessation, with mHealth being the dominant approach. Despite their success, the effectiveness of such interventions may diminish with time. The design of more personalized interventions could potentially benefit future studies., Trial Registration: PROSPERO CRD42022347104; https://www.crd.york.ac.uk/prospero/display&#95;record.php?RecordID=347104., (©Yichen E Fang, Zhixian Zhang, Ray Wang, Bolu Yang, Chen Chen, Claudia Nisa, Xin Tong, Lijing L Yan. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 28.07.2023.)

All-organic, heavy-atom-free photosensitizers based on thionation of nucleobases are receiving increased attention because they are easy to make, noncytotoxic, work both in the presence and absence of molecular oxygen, and can be readily incorporated into DNA and RNA. In this contribution, the DNA and RNA fluorescent probe, thieno[3,4- d ]pyrimidin-4(1 H )-one, has been thionated to develop thieno[3,4- d ]pyrimidin-4(3 H )-thione, which is nonfluorescent and absorbs near-visible radiation with about 60% higher efficiency. Steady-state absorption and emission spectra are combined with transient absorption spectroscopy and CASPT2 calculations to delineate the electronic relaxation mechanisms of both pyrimidine derivatives in aqueous and acetonitrile solutions. It is demonstrated that thieno[3,4- d ]pyrimidin-4(3 H )-thione efficiently populates the long-lived and reactive triplet state generating singlet oxygen with a quantum yield of about 80% independent of solvent. It is further shown that thieno[3,4- d ]pyrimidin-4(3 H )-thione exhibits high photodynamic efficacy against monolayer melanoma cells and cervical cancer cells both under normoxic and hypoxic conditions. Our combined spectroscopic, computational, and in vitro data demonstrate the excellent potential of thieno[3,4- d ]pyrimidin-4(1 H )-thione as a heavy-atom-free PDT agent and paves the way for further development of photosensitizers based on the thionation of thieno[3,4- d ]pyrimidine derivatives. Collectively, the experimental and computational results demonstrate that thieno[3,4- d ]pyrimidine-4(3 H )-thione stands out as the most promising thiobase photosensitizer developed to this date., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Tumor necrosis factor receptor-related factor 7 (TRAF7) can regulate cell differentiation and apoptosis, but its specific functional mechanism in the pathological process of acute myeloid leukemia (AML) closely related to differentiation and apoptosis disorders is largely unclear. In this study, TRAF7 was found to be lowly expressed in AML patients and a variety of myeloid leukemia cells. TRAF7 was overexpressed in AML Molm-13 and chronic myeloid leukemia (CML) K562 cells by transfection with pcDNA3.1-TRAF7. CCK-8 assay and flow cytometry analysis showed that TRAF7 overexpression induced growth inhibition and apoptosis in K562 and Molm-13 cells. Measurements of glucose and lactate suggested that TRAF7 overexpression impaired glycolysis of K562 and Molm-13 cells. Cell cycle analysis indicated that most of K562 and Molm-13 cells were captured in G0/G1 phase by TRAF7 overexpression. PCR and western blot assay revealed that TRAF7 increased Kruppel-like factor 2 (KLF2) expression but decreased 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) expression in AML cells. KLF2 knockdown can counteract TRAF7-triggered PFKFB3 inhibition, and abolish TRAF7-mediated glycolysis inhibition and cell cycle arrest. KLF2 knockdown or PFKFB3 overexpression both can partially neutralize TRAF7-induced growth inhibition and apoptosis of K562 and Molm-13 cells. Moreover, Lv-TRAF7 decreased human CD45 + cells in mouse peripheral blood in the xenograft mice established by NOD/SCID mice. Taken together, TRAF7 exerts anti-leukemia effects by impairing glycolysis and cell cycle progression of myeloid leukemia cells via modulating the KLF2-PFKFB3 axis., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: Early identifying arteriosclerosis in newly diagnosed type 2 diabetes (T2D) patients could contribute to choosing proper subjects for early prevention. Here, we aimed to investigate whether radiomic intermuscular adipose tissue (IMAT) analysis could be used as a novel marker to indicate arteriosclerosis in newly diagnosed T2D patients., Methods: A total of 549 patients with newly diagnosed T2D were included in this study. The clinical information of the patients was recorded and the carotid plaque burden was used to indicate arteriosclerosis. Three models were constructed to evaluate the risk of arteriosclerosis: a clinical model, a radiomics model (a model based on IMAT analysis proceeded on chest CT images), and a clinical-radiomics combined model (a model that integrated clinical-radiological features). The performance of the three models were compared using the area under the curve (AUC) and DeLong test. Nomograms were constructed to indicate arteriosclerosis presence and severity. Calibration curves and decision curves were plotted to evaluate the clinical benefit of using the optimal model., Results: The AUC for indicating arteriosclerosis of the clinical-radiomics combined model was higher than that of the clinical model [0.934 (0.909, 0.959) vs. 0.687 (0.634, 0.730), P < 0.001 in the training set, 0.933 (0.898, 0.969) vs. 0.721 (0.642, 0.799), P < 0.001 in the validation set]. Similar indicative efficacies were found between the clinical-radiomics combined model and radiomics model ( P = 0.5694). The AUC for indicating the severity of arteriosclerosis of the combined clinical-radiomics model was higher than that of both the clinical model and radiomics model [0.824 (0.765, 0.882) vs. 0.755 (0.683, 0.826) and 0.734 (0.663, 0.805), P < 0.001 in the training set, 0.717 (0.604, 0.830) vs. 0.620 (0.490, 0.750) and 0.698 (0.582, 0.814), P < 0.001 in the validation set, respectively]. The decision curve showed that the clinical-radiomics combined model and radiomics model indicated a better performance than the clinical model in indicating arteriosclerosis. However, in indicating severe arteriosclerosis, the clinical-radiomics combined model had higher efficacy than the other two models., Conclusion: Radiomics IMAT analysis could be a novel marker for indicating arteriosclerosis in patients with newly diagnosed T2D. The constructed nomograms provide a quantitative and intuitive way to assess the risk of arteriosclerosis, which may help clinicians comprehensively analyse radiomics characteristics and clinical risk factors more confidently., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 He, Xie, Fu, Yu, Wu, Qiu and Xu.)

The transport of dissolved organic sulfur, including thiols and thioethers, from the ocean surface to the atmosphere through sea spray aerosol (SSA) is of great importance for the global sulfur cycle. Thiol/thioether in SSA undergoes rapid oxidation that is historically linked to photochemical processes. Here, we report the discovery of a non-photochemical, spontaneous path of thiol/thioether oxidation in SSA. Among 10 investigated naturally abundant thiol/thioether, seven species displayed rapid oxidation in SSA, with disulfide, sulfoxide, and sulfone comprising the major products. We suggest that such spontaneous oxidation of thiol/thioether was mainly fueled by thiol/thioether enrichment at the air-water interface and generation of highly reactive radicals by the loss of an electron from ions (e.g., glutathionyl radical produced from ionization of deprotonated glutathione) at or near the surface of the water microdroplet. Our work sheds light on a ubiquitous but previously overlooked pathway of thiol/thioether oxidation, which could contribute to an accelerated sulfur cycle as well as related metal transformation (e.g., mercury) at ocean-atmosphere interfaces.

Background: Artificial intelligence ultrasound of prostate (AIUSP)-targeted biopsy has been used for prostate cancer (PCa) diagnosis. The objective of this prospective multi-center head-to-head clinical randomized comparative trail (RCT) is to compare PCa detection rate in the TRUS-guided 12-core standard systematic biopsy (TRUS-SB) group and cognitive fused mpMRI-guided 12-core biopsy (mpMRI) group against AIUSP group., Methods: Four hundred patients were randomized to three arms and underwent biopsies by TRUS-SB (n = 133), mpMRI (n = 134), and AIUSP (n = 133) between January 2015 and December 2017. In TRUS-SB group, a standard 12-core systematic biopsy was performed. In mpMRI group, mpMRI-suspicious lesions (PI-RADS 3-5) were targeted by 2-core biopsy followed by a 10-core systematic biopsy. Otherwise, 12-core systematic biopsy was performed. In AIUSP group, a 6-core targeted biopsy was performed. The primary endpoint was PCa detection rate., Results: AIUSP detected the highest rate of PCa (66/133, 49.6%) compared to TRUS-SB (46/133, 34.6%, p = 0.036) and mpMRI (48/134, 35.8%, p = 0.052). Compared to TRUS-SB (35/133, 26.3%) and mpMRI (31/134, 23.1%) groups, clinically significant PCa (csPCa) detection rate was 32.3% (43/133) in AIUSP group. Overall biopsy core positive rate in the TRUS-SB group (11.0%, 176/1598) and in the mpMRI group (12.7%, 204/1608) was significantly lower than that in the AIUSP group (22.7%, 181/798, p < 0.001)., Conclusions: AIUSP detected the highest rate of overall and significant PCa compared to TRUS-SB and mpMRI, and could be used as an alternative to systematic biopsy in the future., Registration: This trial was registered in ISRCTN (ISRCTN18033113)., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Our aim was to evaluate the cutoff values of RHE and MRV as markers to diagnose IDA in healthy Han ethnic adults of Chengdu., Methods: A total of 263 Han adults who needed bone marrow aspiration for diagnosis were enrolled according to the inclusive and exclusive criteria. The cutoff values of RHE and MRV were determined by receiver operating curves., Results: According to statistical analysis, the cutoff values of RHE and MRV in male and female groups were 26.75 pg, 89.60 fL and 26.65 pg, 88.55 fL respectively. The areas under the curve (AUC) of RHE and MRV were 0.941, 0.939 and 0.925, 0.909 in male and female groups, respectively., Conclusions: In our study, we explored the cutoff values of RHE and MRV to diagnose IDA in the Han ethnic population in Chengdu for the first time.

Nasopharyngeal carcinoma (NPC) is a highly metastatic and invasive malignant tumor that originates in the nasopharynx. The DNA-binding protein WD repeat and HMG-box DNA-binding protein 1 (WDHD1) are highly expressed in a variety of tumours, but its expression and mechanism of action in NPC have not been reported to date. To investigate the involvement of WDHD1 in NPC, we first mined databases for the gene expression profile of NPC. Immunohistochemistry (IHC) was performed on 338 cases of NPC and 112 non-NPC samples to verify the results. We report that the expression of WDHD1 is significantly elevated in NPC. ChIP-seq was used to show that integrin alpha V (ITGAV) and WDHD1 exhibit a significant binding peak in the promoter region of the ITGAV gene. The expression levels of ITGAV and WDHD1 exhibit a significant positive correlation, and IHC was performed to show that ITGAV is highly expressed in NPC. Expression of ITGAV increased after overexpression of WDHD1, suggesting that ITGAV may be a potential target gene of WDHD1. Pathway analysis showed that both genes were closely related to the cell cycle, and flow cytometry was used to further confirm that decreased expression of WDHD1 significantly increased the number of apoptotic cells. In conclusion, our results suggest that expression of WDHD1 is increased in NPC and is likely to be associated with the NPC cell cycle; thus, we propose that WDHD1 may have the potential as a target gene for primary screening and treatment of NPC., (© 2022 The Authors. FEBS Open Bio published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

Nasopharyngeal carcinoma (NPC) has insidious onset, late clinical diagnosis and high recurrence rate, which leads to poor quality of patient life. Therefore, it is necessary to further explore the pathogenesis and therapy targets of NPC. BUB1 mitotic checkpoint serine/threonine kinase B (BUB1B) was found to be up-regulated in a variety of cancers, but only two previous study showed that BUB1B was overexpressed in NPC and the sample size was small. The clinical role of BUB1B expression and its underlying mechanism in NPC require more in-depth research. Immunohistochemical samples and public RNA-seq data indicated that BUB1B protein and mRNA expression levels were up-regulated in NPC, and summary receiver operating characteristic curve indicated that BUB1B expression level had a strong ability to distinguish NPC tissues from non-NPC tissues. Gene ontology and Kyoto Encyclopedia of genes and genomes were performed and revealed that BUB1B and its related genes were mainly involved in cell cycle and DNA replication. Protein- Protein Interaction were built to interpret the BUB1B molecular mechanism. Histone deacetylase 2 (HDAC2) could be the upstream regulation factor of BUB1B, which was verified by Chromatin Immunoprecipitation Sequencing samples. In summary, BUB1B was highly expressed in NPC, and HDAC2 may affect cell cycle by regulating BUB1B to promote cancer progression., (© 2022. The Author(s).)

Background: Radiation resistance is a challenge that limits the therapeutic benefit of colorectal cancer (CRC) treatment, but the mechanism underlying CRC radiation resistance remains unclear. Andrographolide shows a broad-spectrum anti-tumor effect in various malignancies, including CRC, its effect and how it functions in CRC initiation, and radiation have not been established. This study aimed to explore the mechanism of CRC radiation resistance and the potential mechanisms of andrographolide on CRC radiation., Methods: Two acquired radioresistant cell lines were established and high throughput sequencing was employed to screen out the differentially expressed genes. The expression of AZGP1, which was upregulated in the acquired radioresistant tissues, was verified by microarray data recomputing. The common targets of andrographolide, CRC initiation, and radiation resistance were obtained, and the corresponding functional enrichment and pathway analysis were performed. The interaction between AZGP1 and andrographolide was investigated using molecular docking., Results: AZGP1 was upregulated in both the radioresistant cell model and microarray data. Moreover, AZGP1 was upregulated in cancerous colorectal tissue and displayed a tendency toward elevated expression in patients with an unfavorable prognosis. AZGP1 was identified as the common target of andrographolide, colorectal cancer initiation, and radiotherapy resistance. Ultimately, the protein structure of AZGP1 proved to be closely intertwined with the crystal texture of andrographolide., Conclusion: AZGP1 is recognized as a crucial factor for both CRC initiation and radioresistance. Andrographolide may affect the radioresistance of CRC via the targeting of AZGP1. Thus, the combination of andrographolide and AZGP1 intervention might be a promising strategy for improving the treatment benefit of CRC radiotherapy., Competing Interests: The authors declare that they have no conflicts of interest., (© 2022 Fang et al.)

Background: In children, focal segmental glomerulosclerosis (FSGS) is the main cause of steroid resistant nephrotic syndrome (SRNS). To identify specific candidates and the mechanism of steroid resistance, we examined the formalin-fixed paraffin embedded (FFPE) renal tissue protein profiles via liquid chromatography tandem mass spectrometry (LC-MS/MS)., Methods: Renal biopsies from seven steroid-sensitive (SS) and eleven steroid-resistant (SR) children FSGS patients were obtained. We examined the formalin-fixed paraffin embedded (FFPE) renal tissue protein profiles via liquid chromatography tandem mass spectrometry (LC-MS/MS). Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment and Gene Ontology (GO) analysis, as well as the construction of protein-protein interaction (PPI) network were performed. Two proteins were further valiadated by immunohistochemistry staining in FSGS patients and mice models., Results: In total, we quantified more than 4000 proteins, of which 325 were found to be differentially expressed proteins (DEPs) between the SS and SR group (foldchange ≥2, P<0.05). The results of GO revealed that the most significant up-regulated proteins were primarily related to protein transportation, regulation of the complement activation process and cytolysis. Moreover, clustering analysis showed differences in the pathways (lysosome, terminal pathway of complement) between the two groups. Among these potential candidates, validation analyses for LAMP1 and ACSL4 were conducted. LAMP1 was observed to have a higher expression in glomerulus, while ACSL4 was expressed more in tubular epithelial cells., Conclusions: In this study, the potential mechanism and candidates related to steroid resistance in children FSGS patients were identified. It could be helpful in identifying potential therapeutic targets and predicting outcomes with these proteomic changes for children FSGS patients., (© 2022. The Author(s).)

We present an efficient method based on an extension of metadynamics for exploring complex free energy landscapes (FELs). The method employs two-step metadynamics simulations. In the first step, rapid metadynamics simulations using broad and tall Gaussians are performed to identify a free energy pathway (FEP) connecting the two states of interest. The FEP is then divided into a series of independent subphase spaces that comprise selected discrete images of the system. Using appropriate collective variables (CVs) chosen according to the FEP, the accurate FEL of each subphase space is separately calculated in subsequent divide-and-conquer metadynamics simulations with narrow and low Gaussians. Finally, all FELs calculated in each subphase space are merged to obtain the full FEL. We show that the method greatly improves the performance of the metadynamics approach. In particular, we are able to efficiently model chemical systems with complex FELs, such as chemical reactions at the air/water interface. We demonstrate the performance of this method on two model reactions: the hydrolysis of formaldehyde in the gas phase and at the air/water interface.

Background: The molecular mechanism of laryngeal squamous cell carcinoma (LSCC) is not completely clear, which leads to poor prognosis and treatment difficulties for LSCC patients. To date, no study has reported the exact expression level of zinc finger protein 71 (ZNF71) and its molecular mechanism in LSCC., Methods: In-house immunohistochemistry (IHC) staining (33 LSCC samples and 29 non-LSCC samples) was utilized in analyzing the protein expression level of ZNF71 in LSCC. Gene chips and high-throughput sequencing data collected from multiple public resources (313 LSCC samples and 192 non-LSCC samples) were utilized in analyzing the exact mRNA expression level of ZNF71 in LSCC. Single-cell RNA sequencing (scRNA-seq) data was used to explore the expression status of ZNF71 in different LSCC subpopulations. Enrichment analysis of ZNF71, its positively and differentially co-expressed genes (PDCEGs), and its downstream target genes was employed to detect the potential molecular mechanism of ZNF71 in LSCC. Moreover, we conducted correlation analysis between ZNF71 expression and immune infiltration., Results: ZNF71 was downregulated at the protein level (area under the curve [AUC] = 0.93, p < 0.0001) and the mRNA level (AUC = 0.71, p = 0.023) in LSCC tissues. Patients with nodal metastasis had lower protein expression level of ZNF71 than patients without nodal metastasis (p < 0.05), and male LSCC patients had lower mRNA expression level of ZNF71 than female LSCC patients (p < 0.01). ZNF71 was absent in different LSCC subpopulations, including cancer cells, plasma cells, and tumor-infiltrated immune cells, based on scRNA-seq analysis. Enrichment analysis showed that ZNF71 and its PDCEGs may influence the progression of LSCC by regulating downstream target genes of ZNF71. These downstream target genes of ZNF71 were mainly enriched in tight junctions. Moreover, downregulation of ZNF71 may influence the development and even therapy of LSCC by reducing immune infiltration., Conclusion: Downregulation of ZNF71 may promote the progression of LSCC by reducing tight junctions and immune infiltration; this requires further study., (© 2022. The Author(s).)

Adverse intrauterine and early postnatal environment cause reduced nephron endowment and subsequent hypertension, chronic kidney disease (CKD). Exploring modifiable approaches is particularly important to alleviate the global burden of CKD. Enhanced glomerular progenitor cell apoptosis is a major contributor to renal developmental programming. The differentially expressed protein perlecan, which we previously identified using proteomics, is an important extracellular matrix glycoprotein, and its domain V (endorepellin) can inhibit apoptosis through a paracrine form. In explanted mice embryonic metanephros, we found that endorepellin can rescue glomeruli-deficit phenotype resulting from malnutrition, and this protective effect was also verified in vivo using a renal developmental programming model which was given a low-protein diet during pregnancy. We further demonstrated that endorepellin significantly inhibited glomerular progenitor cell apoptosis which activates ERK1/2 phosphorylation. Our results show that endorepellin rescues the nephron number reduction in renal developmental programming, possibly through the inhibition of progenitor cell apoptosis via the ERK1/2 pathway., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Tang, Sun, Shen, Rao, Yang, Fang, Xiang, Xue, Sun and Xu.)

Objective: To explore the novel biomarkers and therapeutic target candidates related to the stasis-heat syndrome of acute intracerebral hemorrhage (AICH)., Methods: Applying an isobaric tagging for relative and absolute quantitation-(iTRAQ-) based quantitative proteomic approach, plasma samples from AICH patients with stasis-heat, and AICH patients with non-stasis-heat and healthy control subjects were collected and analyzed to distinguish differentially expressed proteins (DEPs) correlated to AICH with stasis-heat in this block design. The standard Western blot was applied to verify DEPs. Additionally, DEPs were analyzed via bioinformatic platforms and further approved via Ingenuity Pathway Analysis (IPA)., Results: A total of 26 DEPs were found among AICH with the stasis-heat, AICH with non-stasis-heat, and healthy control group. The seven DEPs compared with the non-stasis-heat group are closely related to the pathogenesis of stasis heat. These proteins showed three different protein expression patterns. The alpha-1-b glycoprotein (A1BG) and copper-protein (CP) were up-regulated in the stasis-heat group, but down-regulated in the non-stasis-heat group. Compared with the non-stasis-heat group, the expression abundance of actinin, alpha 1 (ACTN1), carbonic anhydrase I (CA1), peroxiredoxin 2 (PRDX2), and vinculin (VCL) is higher in the stasis-heat group, while the CD44 is the opposite. These differences reflect that stasis-heat syndrome has more severe inflammatory immune response, coagulation disorders and damage. Bioinformatics analysis revealed that a wide variety of cellular and metabolic processes and some signaling pathways were involved in the pathophysiology of AICH with stasis-heat. AICH with stasis-heat syndrome showed more severe inflammatory reactions, tissue damage, and coagulation disorders than non-stasis heat syndrome., Conclusions: There are differences in the protein expression patterns between the stasis-heat syndrome and non-stasis-heat syndrome. These differences reflect that stasis-heat syndrome has more severe damage. CD44, CP, ACTN1, CA1, VCL, PRDX2, and A1BG could be the potential biomarkers and therapeutic target candidates of the stasis-heat subtype. This study provides a reasonable explaination for Liangxue Tongyu decoction through anti-inflammatory and brain protection treatment.

In this work, how the excited-state dependent hydrogen bond (H-bond) interactions control photophysical processes have been uncovered by accurate electronic structure calculations for the five lowest-lying states (S 0 , S 1 , S 2 , T 1 , and T 2 ) of three aromatic thioketones and their isomers. The difference in the H-bond nature between S 2 and S 1 gives rise to ultrafast S 2 → S 1 internal conversion via the two-state conical intersection. Strong S 2 fluorescence observed usually in thiocarbonyl compounds is absent in aromatic thioketones with intramolecular H-bonds. Meanwhile, the relatively weak H-bond interactions in S 1 and T 1 states make the S 1 , T 2 , and T 1 states degenerate or quasi-degenerate. As a result, the T 2 state acts as a relay and enables both forward S 1 → T 1 and reverse T 1 → S 1 processes to occur efficiently, which provides new insights into the mechanism of thermally activated delayed fluorescence (TADF), and could be used to improve the design principle of purely organic TADF materials.

Premise: Spatial and temporal resource allocations within inflorescences have been well-studied in many plants based on flowering sequence or floral position. However, there had been few attempts to investigate architectural effects and resource competition in species where the blooming pattern does not follow a linear positional pattern within the inflorescence. Moreover, most flowering plants show female-biased sex allocation in early or basal flowers, but it is unclear in species with inherent and changeless ovule production., Methods: We investigated intra-inflorescence variation in reproductive traits of Salvia przewalskii, a perennial herb with 4-ouvle ovary flowers and flowering sequence-floral position decoupled inflorescences. To detect the effects of resource competition and architectural effects on reproductive success, we manipulated inflorescence (removed floral buds by position and flowering sequence) and pollination (opened and supplemented pollination)., Results: Pollen production and dry mass deceased from bottom to top flowers but did not significantly differ following flowering sequence, resulting in male-biased sex allocation in basal flowers. The seed production, fruit set, and bud development exhibited significant declining trends from proximal to distal positions regardless of the thinning and pollen treatments. Meanwhile, the seed production, fruit set, and bud development success did not significant differ when thinning was conducted according to flowering sequence., Conclusions: Architectural effects plays a crucial role in resource allocation within decoupled flowering inflorescences. Moreover, our results highlighted that inherent floral traits such as changeless ovule production, may modify architectural effects on sex allocation., (© 2022 Botanical Society of America.)

Background: Congenital anomalies of the kidneys and urinary tracts (CAKUT) represent the most prevalent cause for renal failure in children. The RNA epigenetic modification N 6 -methyladenosine (m 6 A) methylation modulates gene expression and function post-transcriptionally, which has recently been revealed to be critical in organ development. However, it is uncertain whether m 6 A methylation plays a role in the pathogenesis of CAKUT. Thus, we aimed to explore the pattern of m 6 A methylation in CAKUT., Methods: Using m 6 A-mRNA epitranscriptomic microarray, we investigated the m 6 A methylomic landscape in the ureter tissue of children with obstructive megaureter (M group) and primary vesicoureteral reflux (V group)., Results: A total of 228 mRNAs engaged in multiple function-relevant signaling pathways were substantially differential methylated between the "V" and "M" groups. Additionally, 215 RNA-binding proteins that recognize differentially methylated regions were predicted based on public databases. The M group showed significantly higher mRNA levels of m 6 A readers/writers (YTHDF1, YTHDF2, YTHDC1, YTHDC2 and WTAP) and significantly lower mRNA levels of m 6 A eraser (FTO) according to real-time PCR. To further investigate the differentially methylated genes, m 6 A methylome and transcriptome data were integrated to identified 298 hypermethylated mRNAs with differential expressions (265 upregulation and 33 downregulation) and 489 hypomethylated mRNAs with differential expressions (431 upregulation and 58 downregulation) in the M/V comparison., Conclusion: The current results highlight the pathogenesis of m 6 A methylation in obstructive and reflux uropathy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Shi, Xiang, Feng, Yang, Li, Fang, Xu, Qi, Shen, Tang, Shen, Wang, Xu and Rao.)

Aim: To investigate the clinical role of transmembrane protease serine 3 (TMPRSS3) in radioresistance and prognosis of colorectal cancer (CRC). Methods: Standardized mean difference (SMD) and summary area under the curve (AUC) of TMPRSS3 were calculated by combining all available high-throughput data globally. The prognostic significance of TMPRSS3 was determined by Kaplan-Meier and Cox regression analyses. Results: TMPRSS3 was remarkably upregulated in 198 CRC radioresistant cases compared with nonradioresistance (SMD = 0.38, AUC = 0.71). Overexpression of TMPRSS3 was observed in 1601 CRC patients compared with control subjects without CRC. TMPRSS3 was a risk factor for disease-free survival of CRC with the summarized hazard ratio 1.28. Conclusion: TMPRSS3 contributes to the radioresistance and unfavorable prognosis of CRC.

Accurate identification of axillary lymph node (ALN) status is crucial for tumor staging procedure and decision making. This retrospective study of 898 participants from two institutions was conducted. The aim of this study is to evaluate the diagnostic performance of clinical parameters combined with collagen signatures (tumor-associated collagen signatures [TACS] and the TACS corresponding microscopic features [TCMF]) in predicting the probability of ALN metastasis in patients with breast cancer. These findings suggest that TACS and TCMF in the breast tumor microenvironment are both novel and independent biomarkers for the estimation of ALN metastasis. The nomogram based on independent clinical parameters combined with TACS and TCMF yields good diagnostic performance in predicting ALN status., (© 2022 Wiley-VCH GmbH.)

Background: Cell division cycle 45 ( CDC45 ) plays an important role in the occurrence and development of numerous carcinomas, but its effect in laryngeal squamous cell carcinoma (LSCC) remains unclear. Materials and Methods: The messenger RNA and protein expression levels of CDC45 in LSCC were evaluated with a t test and the standard mean difference (SMD). The ability of CDC45 expression to distinguish the LSCC was assessed through receiver operating characteristic (ROC) curves. Gene set enrichment analysis (GSEA), protein-protein interaction, public databases, and online tools were used to explore the potential molecular mechanism of CDC45 in LSCC. Results: A high expression of CDC45 was identified in LSCC (SMD = 2.61, 95% confidence interval [1.62-3.61]). Through ROC curves, the expression of CDC45 makes it feasible to distinguish the LSCC group from the non-LSCC counterpart. CDC45 was relevant to the progression-free interval of LSCC patients (log-rank p  = 0.03). GSEAs show that CDC45 is related to the cell cycle. CDC45 , CDC6 , KIF2C , and AURKB were identified as hub genes of LSCC. E2F1 may be the regulatory transcription factor of CDC45 . Conclusions: High expression of CDC45 likely demonstrates carcinogenic effects in LSCC, and CDC45 is a potential target in screening and treatment of LSCC.

Objective: To study the effect of remifentanil and propofol as an anesthesia regimen in patients with high hemodynamics., Methods: From January 2019 to October 2020, 200 patients with high hemodynamics undergoing surgery at the First Affiliated Hospital of Nanchang University in China were selected as study participants, including 100 patients anesthetized with remifentanil and propofol (research group), and 100 patients anesthetized with fentanyl and propofol (control group). Vital signs, hemodynamic changes and recovery time after anesthesia were compared in the 2 groups and any adverse events while under anesthesia were recorded., Results: Both groups had significant fluctuations in vital signs and hemodynamics during anesthesia (P > .05), but the research group showed smaller changes with more stable vital signs and hemodynamics (P < .05). In addition, postoperative recovery time from anesthesia was shorter and the incidence of adverse events was lower in the research group than in the control group (P < .05)., Conclusion: Remifentanil-propofol anesthesia is simple, convenient, safe and reliable in patients with high hemodynamics, and can integrate narcotic drugs with blood pressure control.

Purpose:  To explore the usefulness of liver stiffness measurements (LSMs) by sound touch elastography (STE) and sound touch quantification (STQ) in chronic hepatitis B (CHB) patients for staging fibrosis., Methods:  This prospective multicenter study recruited normal volunteers and CHB patients between May 2018 and October 2019. The volunteers underwent LSM by STE and supersonic shear imaging (SSI) or by STQ and acoustic radiation force impulse imaging (ARFI). CHB patients underwent liver biopsy and LSM by both STE/STQ. The areas under the receiver operating characteristic curves (AUCs) for staging fibrosis were calculated., Results:  Overall, 97 volunteers and 524 CHB patients were finally eligible for the study. The successful STE and STQ measurement rates were both 100 % in volunteers and 99.4 % in CHB patients. The intraclass correlation coefficients (ICCs) for the intra-observer stability of STE and STQ (0.94; 0.90) were similar to those of SSI and ARFI (0.95; 0.87), respectively. STE and STQ showed better accuracy than the aspartate aminotransferase-to-platelet ratio index (APRI) and fibrosis-4 index (FIB-4) (AUC: 0.87 vs 0.86 vs 0.73 vs 0.77) in staging cirrhosis. However, both STE and STQ were not superior to APRI and FIB-4 in staging significant fibrosis (AUC: 0.76 vs 0.73 vs 0.70 vs 0.71, all P-values > 0.05)., Conclusion:  STE and STQ are convenient techniques with a reliable LSM value. They have a similar diagnostic performance and are superior to serum biomarkers in staging cirrhosis in CHB patients., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Herpetospermum pedunculosum (Ser.) C. B. Clarke (Family Cucurbitaceae) is a dioecious plant and has been used as a traditional Tibetan medicine for the treatment of hepatobiliary diseases. The component, content, and difference in volatile compounds in the female and male buds of H . pedunculosum were explored by using headspace solid-phase microextraction-gas chromatography-mass spectrometry (HS-SPME-GC-MS) technology and multivariate statistical analysis. The results showed that isoamyl alcohol was the main compound in both female and male buds and its content in males was higher than that in females; 18 compounds were identified in female buds including 6 unique compounds such as ( E )-4-hexenol and isoamyl acetate, and 32 compounds were identified in male buds, including 20 unique compounds such as ( Z )-3-methylbutyraldehyde oxime and benzyl alcohol. ( Z )-3-methylbutyraldehyde oxime and ( E )-3-methylbutyraldehyde oxime were found in male buds, which only occurred in night-flowering plants. In total, 9 differential volatile compounds between female and male buds were screened out, including isoamyl alcohol, ( Z )-3-methylbutanal oxime, and 1-nitropentane based on multivariate statistical analysis such as principal component analysis (PCA) and orthogonal partial least squares discrimination analysis (OPLS-DA). This is the first time to report the volatile components of H. pedunculosum , which not only find characteristic difference between female and male buds, but also point out the correlation between volatile compounds, floral odor, and plant physiology. This study enriches the basic theory of dioecious plants and has guiding significance for the production and development of H. pedunculosum germplasm resources.

Background: Currently, high expression of WD repeat and HMG-box DNA binding protein 1 (WDHD1) has been found in a variety of tumors; but there is no research has been conducted concerning the expression of WDHD1 in laryngeal squamous cell carcinoma (LSCC). Our purpose is to investigate the expression and the latent mechanism of WDHD1 in LSCC., Methods: Firstly, 9 data sets from the Gene Expression Omnibus (GEO), The Cancer Genome Atlas (TCGA), and ArrayExpress were statistically analyzed to explore the expression of WDHD1 in LSCC; immunohistochemistry was performed in 79 LSCC tissues and 44 non-cancer tissues to further verify the result. In addition, the target gene of WDHD1 was predicted and immunohistochemistry was used to detect the expression of the target gene. The potential mechanism of WDHD1 in LSCC was investigated by Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses and protein-protein interaction network (PPI)., Results: The WDHD1 mRNA was expressed at higher levels in the LSCC tissue than in the normal tissue (SMD=1.90, 95% CI=1.50-2.30); and the results of immunohistochemistry were consistent with the conclusion. Using chip-seq analysis, we found that S-phase kinase-associated protein 2 (Skp2) had a significant binding peak with WDHD1, and the expression of these two genes was significantly positively correlated. Immunohistochemistry showed that Skp2 was also highly expressed in LSCC. In addition, GO and KEGG analysis revealed the WDHD1 positively correlated genes was closely related to cell cycle, and PPI analysis identified 10 hub genes: COL7A1, COL4A2, COL4A1, COL4A6, COL11A1, COL5A2, COL1A1, COL13A1, COL8A1 and COL10A1, which may be critical to the progression of LSCC., Conclusions: WDHD1 was overexpressed in LSCC tissues. Meanwhile, WDHD1 and its target gene Skp2 for transcriptional regulation may play a role in the progression of LSCC by regulating the cell cycle., (Copyright © 2022 The Authors. Published by Elsevier GmbH.. All rights reserved.)

The prognosis of various cardiovascular diseases eventually leads to heart failure (HF). An energy metabolism disorder of cardiomyocytes is important in explaining the molecular basis of HF; this will aid global research regarding treatment options for HF from the perspective of myocardial metabolism. There are many drugs to improve myocardial metabolism for the treatment of HF, including angiotensin receptor blocker-neprilysin inhibitor (ARNi) and sodium glucose cotransporter 2 (SGLT-2) inhibitors. Although Western medicine has made considerable progress in HF therapy, the morbidity and mortality of the disease remain high. Therefore, HF has attracted attention from researchers worldwide. In recent years, the application of traditional Chinese medicine (TCM) in HF treatment has been gradually accepted, and many studies have investigated the mechanism whereby TCM improves myocardial metabolism; the TCMs studied include Danshen yin, Fufang Danshen dripping pill, and Shenmai injection. This enables the clinical application of TCM in the treatment of HF by improving myocardial metabolism. We systematically reviewed the efficacy of TCM for improving myocardial metabolism during HF as well as the pharmacological effects of active TCM ingredients on the cardiovascular system and the potential mechanisms underlying their ability to improve myocardial metabolism. The results indicate that TCM may serve as a complementary and alternative approach for the prevention of HF. However, further rigorously designed randomized controlled trials are warranted to assess the effect of TCM on long-term hard endpoints in patients with cardiovascular disease., (Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Objective: To evaluate the value of ultrasound screening for congenital anomalies of the kidney and urinary tract (CAKUT) during the early postnatal period., Methods: This is a prospective study that enrolled all neonates born from August 2019 to July 2020 at one medical center. Postnatal ultrasound screening was conducted in all neonates at 1, 3, and 6 months old, respectively. Information on antenatal detection and pregnancy was collected. We performed logistic regression analyses and established a predictive model to assess the potential risk factors of abnormal ultrasound screening results., Results: Postnatal ultrasound scanning in 4,877 infants identified 268 cases (5.5%) of anomalies of kidney and urinary tract by primary screening and 92 cases (1.9%) by tertiary screening. A specific diagnosis was identified in 47 cases within the 6-month screening and follow-up program. Logistic regression revealed that preterm birth, oligohydramnios, antenatal ultrasound screening anomalies, and gestational hypothyroidism were independent risk factors for the early detection of CAKUT by postnatal ultrasound screening. The above factors were adopted to develop a predictive model that showed good calibration in predicting ultrasound findings of CAKUT. Decision curve analysis demonstrated good clinical utility., Conclusions: Postnatal ultrasound screening should be conducted in infants with risk factors associated with CAKUT. Further study on prenatal and fetal factors could help establish the predictive model for the early detection of CAKUT., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Liu, Shi, Yu, Xiang, Fang, Xie, Pan, Li, Sun, Zhang, Fu and Rao.)

Background: Colorectal cancer (CRC) represents the third most common malignant tumor in the worldwide. Radiotherapy is the common therapeutic treatment for CRC, but radiation resistance is often encountered. ChIP-seq of Histone H3K27 acetylation (H3K27ac) has revealed enhancers that play an important role in CRC. This study examined the relationship between an active CRC enhancer and claudin-1 (CLDN1), and its effect on CRC radiation resistance., Methods: The target CRC genes of active enhancers were obtained from public H3K27ac ChIP-seq, and the genes highly expressed in radio-resistant CRC were screened and intersected with enhancer-driven genes. The clinical roles of CLDN1 in radiation resistance were examined using the t-test, standard mean deviation (SMD), summary receiver operating characteristic curve and Kaplan-Meier curves. The co-expressed genes of CLDN1 were calculated using Pearson Correlation analysis, and Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes and Gene Set Variation Analysis (GSVA) analyses were used to examine the molecular mechanisms of CLDN1., Results: Total 13 703 CRC genes were regulated by enhancers using 58 H3K27ac ChIP-seq. Claudin-1 (CLDN1) was enhancer-driven and notably up-regulated in CRC tissues compared to non-CRC controls, with a SMD of 3.45 (95 CI % = .56-4.35). CLDN1 expression was increased in radiation-resistant CRC with a SMD of .42 (95% CI = .16-.68) and an area under the curve of .74 (95% CI = .70-.77). The cell cycle and immune macrophage levels were the most significant pathways associated with CLDN1., Conclusion: CLDN1 as an enhancer-regulated gene that can boost radiation resistance in patients with CRC., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2021.)

Hepatocellular carcinoma (HCC) is a leading cause of mortality in cancer patients, but the association between miR-125b-2-3p and the onset and prognosis of HCC has not been reported in previous studies; thus, the clinicopathological implications of miR-125b-2-3p in HCC require elaboration. To examine the expression of miR-125b-2-3p in HCC, both in-house RT-qPCR and public datasets were used to calculate the standard mean difference (SMD) and the summary receiver operating characteristic (sROC). MiR-125b-2-3p was markedly lower in HCC than in non-tumor tissue as assessed by the in-house RT-qPCR which was confirmed by the integrative analysis showing the SMD being -0.69 and the area under the curve (AUC) being 0.84 based on 1,233 cases of HCC and 630 cases of non-HCC controls. To gain a overview of the clinical value of miR-125b-2-3p in HCC, all possible datasets were integrated, and lower miR-125b-2-3p levels could lead to poorer differentiation and a more advanced clinical stage of HCC. The hazard ratio (HR) of miR-125b-2-3p was also calculated using a Cox proportional hazards model, and the miR-125b-2-3p level could act as an protective indication for the survival with the HR being 0.74 based on 586 cases of HCC. Furthermore, the effect of nitidine chloride (NC), a natural bioactive phytochemical alkaloid, on the regulation of miR-125b-2-3p and its potential targets was also investigated. The miR-125b-2-3p level was increased after NC treatment, while the expression of its potential target PRKCA was reduced. Above all, a low-expressed level of miR-125b-2-3p plays a tumor suppressive role in HCC.

Epidemiological studies have demonstrated that the genetic factors partly influence the development of same-sex sexual behavior, but most genetic studies have focused on people of primarily European ancestry, potentially missing important biological insights. Here, we performed a two-stage genome-wide association study (GWAS) with a total sample of 1478 homosexual males and 3313 heterosexual males in Han Chinese populations and identified two genetic loci (rs17320865, Xq27.3, FMR1NB, P meta  = 8.36 × 10 -8 , OR = 1.29; rs7259428, 19q12, ZNF536, P meta  = 7.58 × 10 -8 , OR = 0.75) showing consistent association with male sexual orientation. A fixed-effect meta-analysis including individuals of Han Chinese (n = 4791) and European ancestries (n = 408,995) revealed 3 genome-wide significant loci of same-sex sexual behavior (rs9677294, 2p22.1, SLC8A1, P meta  = 1.95 × 10 -8 ; rs2414487, 15q21.3, LOC145783, P meta  = 4.53 × 10 -9 ; rs2106525, 7q31.1, MDFIC, P meta  = 6.24 × 10 -9 ). These findings may provide new insights into the genetic basis of male sexual orientation from a wider population scope. Furthermore, we defined the average ZNF536-immunoreactivity (ZNF536-ir) concentration in the suprachiasmatic nucleus (SCN) as lower in homosexual individuals than in heterosexual individuals (0.011 ± 0.001 vs 0.021 ± 0.004, P = 0.013) in a postmortem study. In addition, compared with heterosexuals, the percentage of ZNF536 stained area in the SCN was also smaller in the homosexuals (0.075 ± 0.040 vs 0.137 ± 0.103, P = 0.043). More homosexual preference was observed in FMR1NB-knockout mice and we also found significant differences in the expression of serotonin, dopamine, and inflammation pathways that were reported to be related to sexual orientation when comparing CRISPR-mediated FMR1NB knockout mice to matched wild-type target C57 male mice., (© 2021. The Author(s).)