Tripartite motif-containing protein 31 confers protection against nonalcoholic steatohepatitis by deactivating mitogen-activated protein kinase kinase kinase 7.

BACKGROUND AIMS: As a global health threat, NASH has been confirmed to be a chronic progressive liver disease that is strongly associated with obesity. However, no approved drugs or efficient therapeutic strategies are valid, mainly because its complicated pathological processes is underestimated. APPROACH RESULTS: We identified the RING-type E3 ubiquitin transferase-tripartite motif-containing protein 31 (TRIM31), a member of the E3 ubiquitin ligases family, as an efficient endogenous inhibitor of transforming growth factor-beta-activated kinase 1 (mitogen-activated protein kinase kinase kinase 7; MAP3K7), and we further confirmed that TRIM31 is an MAP3K7-interacting protein and promotes MAP3K7 degradation by enhancing ubiquitination of K48 linkage in hepatocytes. Hepatocyte-specific Trim31 deletion blocks hepatic metabolism homeostasis, concomitant with glucose metabolic syndrome, lipid accumulation, up-regulated inflammation, and dramatically facilitates NASH progression. Inversely, transgenic overexpression, lentivirus, or adeno-associated virus-mediated Trim31 gene therapy restrain NASH in three dietary mice models. Mechanistically, in response to metabolic insults, TRIM31 interacts with MAP3K7 and conjugates K48-linked ubiquitination chains to promote MAP3K7 degradation, thus blocking MAP3K7 abundance and its downstream signaling cascade activation in hepatocytes. CONCLUSIONS: TRIM31 may serve as a promising therapeutic target for NASH treatment and associated metabolic disorders.

Accurate and Robust Static Hydrophobic Contact Angle Measurements Using Machine Learning.

We present a machine learning (ML) approach to static contact angle measurement, trained on a large data set (>7.2 million) of half drop contours based on solutions to the Young-Laplace equation where the contact angle is known a priori (removing all sources of error from human input). The data set included the effects of surface roughness, gravity, the size of drop relative to the image, and reflections of the drop on the surface. The presented ML model (valid for contact angles >110°), in combination with a new automated image and contour processing approach, is shown to be more accurate than other methods when benchmarked against an experimental data set, with an estimated error of 1°. The ML model is also 2 orders of magnitude faster at predicting contact angles than Young-Laplace fitting (the current best practice approach). The accuracy and speed of the presented approach provides a viable pathway toward robust and reproducible high-throughput contact angle analysis. This approach, Conan-ML, is open-source and provided for the use and development of new approaches to goniometry.

Prediction Model of Coal Gas Permeability Based on Improved DBO Optimized BP Neural Network.

Accurate measurement of coal gas permeability helps prevent coal gas safety accidents effectively. To predict permeability more accurately, we propose the IDBO-BPNN coal body gas permeability prediction model. This model combines the Improved Dung Beetle algorithm (IDBO) with the BP neural network (BPNN). First, the Sine chaotic mapping, Osprey optimization algorithm, and adaptive T-distribution dynamic selection strategy are integrated to enhance the DBO algorithm and improve its global search capability. Then, IDBO is utilized to optimize the weights and thresholds in BPNN to enhance its prediction accuracy and mitigate the risk of overfitting to some extent. Secondly, based on the influencing factors of gas permeability, effective stress, gas pressure, temperature, and compressive strength, they are chosen as the coupling indicators. The SPSS 27 software is used to analyze the correlation among the indicators using the Pearson correlation coefficient matrix. Additionally, the Kernel Principal Component Analysis (KPCA) is employed to extract the original data. Then, the original data is divided into principal component data for the model input. The prediction results of the IDBO-BPNN model are compared with those of the PSO-BPNN, PSO-LSSVM, PSO-SVM, MPA-BPNN, WOA-SVM, BES-SVM, and DPO-BPNN models. This comparison assesses the capability of KPCA to enhance the accuracy of model predictions and the performance of the IDBO-BPNN model. Finally, the IDBO-BPNN model is tested using data from a coal mine in Shanxi. The results indicate that the predicted outcome closely aligns with the actual value, confirming the reliability and stability of the model. Therefore, the IDBO-BPNN model is better suited for predicting coal gas permeability in academic research writing.

Use of T-Scan III in analyzing occlusal changes in molar fixed denture placement.

BACKGROUND: This study aims to analyze the longitudinal variation of occlusal force distribution prior to and after fixed restoration for molar full-crowns with T-SCAN III which provide reference for occlusal adjustment and long-term maintenance. METHODS: We enrolled a total of 20 patients who received conventional restorative treatment for molars. The occlusion examination was conducted in 3 stages (before placement, immediately after placement, and 3 months after placement) using T-SCAN III (Tekscan South Boston, MA, USA, 10.0) to examine and measure the occlusal contact areas of the full dentition. RESULTS: The results indicated that the occlusal force distribution in the molar region of the patients changed before and after the fixed restoration, but the percentages of occlusal force in the dental arch of the molar did not differ significantly before and after the restoration (P > 0.05). Three months after the fixed restoration, the percentage of occlusal force in the restored dental arches of lateral teeth increased significantly (P < 0.05). CONCLUSION: The results of this study indicated that the occlusal forces of the patients changed with tooth movement and adaptation, which is mainly reflected in the increasing occlusal force. Quantitative occlusal force analysis using T-SCAN III occlusal analyzer can provide more objective and accurate data to effectively guide clinical occlusion adjustments.

Effectiveness of binocular therapy as a complementary treatment of part-time patching in older amblyopic children: a randomized clinical trial.

PURPOSE: To assess the effectiveness of combined use of stereoscopic 3D video movies and part-time patching in treating older amblyopic children with poor response or compliance to traditional patching treatments and comparing this combined treatment with patching alone. METHODS: Thirty-two children aged 5-12 years with amblyopia associated with anisometropia, strabismus, or both were recruited in a randomized clinical trial. Eligible participants were assigned randomly to the combined and patching groups. Here, binocular treatment refers to using the Bangerter filter to blur the fellow eye and subsequently watching a close-up 3D movie with large parallax. The primary outcome was amblyopic eye (AE) best-corrected visual acuity (BCVA) improvement at six weeks. In addition, secondary outcomes included BCVA of AE improvement at three weeks and change of stereoacuity. RESULTS: Of 32 participants, mean (SD) age was 6.63 (1.46) years, and 19 (59%) were female. At 6 weeks, mean (SD) amblyopic eye VA improved by 0.17 ± 0.08 logMAR (2-sided 95% CI, 0.13 to 0.22; F = 57.2, p < 0.01) and 0.05 ± 0.04 logMAR (2-sided 95% CI, 0.05 to 0.09; F = 8.73, p = 0.01) in the combined and patching groups, respectively. The difference was statistically significant (mean difference, 0.13 logMAR [1.3 line]; 95% CI, 0.08-0.17 logMAR [0.8-1.7 lines]; t25 = 5.65, p < 0 .01). After treatment, only the combined group had significantly improved stereoacuity, such as binocular function score (median [interquartile range], 2.30 [2.23 to 2.68] vs. 1.69 [1.60 to 2.30] log arcsec; paired, z = -3.53, p < 0.01), and mean stereoacuity gain was 0.47 log arcsec (± 0.22). Changes in other types of stereoacuity were similar. CONCLUSION: Our laboratory-based binocular treatment strategy engaged a high level of compliance that led to a substantial gain in visual function after a short period of treatment for older amblyopic children having poor response or compliance to traditional patching treatments. Notably, the improving stereoacuity showed a greater advantage.

SCRE serves as a unique synaptonemal complex fastener and is essential for progression of meiosis prophase I in mice.

Meiosis is a specialized cell division for producing haploid gametes from diploid germ cells. During meiosis, synaptonemal complex (SC) mediates the alignment of homologs and plays essential roles in homologous recombination and therefore in promoting accurate chromosome segregation. In this study, we have identified a novel protein SCRE (synaptonemal complex reinforcing element) as a key molecule in maintaining the integrity of SC during meiosis prophase I in mice. Deletion of Scre (synaptonemal complex reinforcing element) caused germ cell death in both male and female mice, resulting in infertility. Our mechanistic studies showed that the synapses and SCs in Scre knockout mice were unstable due to the lack of the SC reinforcing function of SCRE, which is sparsely localized as discrete foci along the central elements in normal synaptic homologous chromosomes. The lack of Scre leads to meiosis collapse at the late zygotene stage. We further showed that SCRE interacts with synaptonemal complex protein 1 (SYCP1) and synaptonemal complex central element 3 (SYCE3). We conclude that the function of SCRE is to reinforce the integrity of the central elements, thereby stabilizing the SC and ensuring meiotic cell cycle progression. Our study identified SCRE as a novel SC fastener protein that is distinct from other known SC proteins.

Molecular mechanisms governing shade responses in maize.

Light is one of the most important environmental factors affecting plant growth and development. Plants use shade avoidance or tolerance strategies to adjust their growth and development thus increase their success in the competition for incoming light. To investigate the mechanism of shade responses in maize (Zea mays), we examined the anatomical and transcriptional dynamics of the early shade response in seedlings of the B73 inbred line. Transcriptome analysis identified 912 differentially expressed genes, including genes involved in light signaling, auxin responses, and cell elongation pathways. Grouping transcription factor family genes and performing enrichment analysis identified multiple types of transcription factors that are differentially regulated by shade and predicted putative core genes responsible for regulating shade avoidance syndrome. For functional analyses, we ectopically over-expressed ZmHB53, a type II HD-ZIP transcription factor gene significantly induced by shade, in Arabidopsis thaliana. Transgenic Arabidopsis plants overexpressing ZmHB53 exhibited narrower leaves, earlier flowering, and enhanced expression of shade-responsive genes, suggesting that ZmHB53 might participates in the regulation of shade responses in maize. This study increases our understanding of the regulatory network of the shade response in maize and provides a useful resource for maize genetics and breeding.

Use of a Cyclometalated Iridium(III) Complex Containing a N∧C∧N-Coordinating Terdentate Ligand as a Catalyst for the α-Alkylation of Ketones and N-Alkylation of Amines with Alcohols.

A cyclometalated iridium(III) complex containing a N∧C∧N-coordinating terdentate ligand [Ir(dpyx-N,C,N)Cl(µ-Cl)]2 was found to be a general and highly effective catalyst for the α-alkylation of ketones and N-alkylation of amines with alcohols. In the presence of catalyst (1 mol % Ir) and base (0.2-0.5 equiv), a variety of desirable products were obtained in good yields under an air atmosphere. Notably, this research exhibited the new potential of Ir(III) complexes bearing non-Cp* ligand and will facilitate the progress of the hydrogen autotransfer process.

Characterization and distribution of poly(3-hexylthiophene) phases in an annealed blend film.

The characteristic absorption spectra of three kinds of phases, the isolated, ordered, and disordered phases, in a solvent-vapor annealed poly(3-hexylthiophene)/[6,6]-phenyl-C61 -butyric acid methyl ester (P3HT/PCBM) blend film were studied by means of spectroelectrochemistry (SEC) and time-resolved absorption spectroscopy (TAS). The results reveal that the content of three phases are 12 % isolated, 37 % ordered, and 51 % disordered for the annealed P3HT neat film, and 25 % isolated, 31 % ordered, and 44 % disordered for the annealed P3HT/PCBM blend film. The vertical distribution of the different phases in the blend film was studied by SEC, and the results show that the ordered and isolated phases are mainly distributed in the top and in the bottom of the annealed films, respectively, while the disordered phase is mainly distributed in the middle and the bottom of the films.

Coal and gas protrusion risk evaluation based on cloud model and improved combination of assignment.

The proposed study presents an enhanced combination weighting cloud model for accurate assessment of coal and gas outburst risks. Firstly, a comprehensive evaluation index system for coal and gas outburst risks is established, consisting of primary indicators such as coal rock properties and secondary indicators including 13 factors. Secondly, the improved Analytic Hierarchy Process (IAHP) based on the 3-scale method and the improved CRITIC based on indicator correlation weight determination method are employed to determine subjective and objective weights of evaluation indicators respectively. Additionally, the Lagrange multiplier method is introduced to fuse these weights in order to obtain optimal weights. Subsequently, a prominent danger assessment model is developed based on cloud theory. Finally, using a mine in Hebei Province as an example, the results obtained from IAHP combined with improved CRITIC weighting method are compared with those from traditional AHP method and AHP-CRITIC combination weighting method. The findings demonstrate that among all methods considered, IAHP combined with improved CRITIC exhibits superior performance in terms of distribution expectation Ex, entropy value En, and super entropy He within cloud digital features; thus indicating that the risk level of coal and gas outbursts in this particular mine can be classified as general risk. These evaluation results align well with actual observations thereby validating the effectiveness of this approach. Consequently, this constructed model enables rapid yet accurate determination of coal and gas outburst risks within mines.

Prediction model of spontaneous combustion risk of extraction borehole based on PSO-BPNN and its application.

The feasibility and accuracy of the risk prediction of gas extraction borehole spontaneous combustion is improved to avoid the occurrence of spontaneous combustion in the gas extraction borehole. A gas extraction borehole spontaneous combustion risk prediction model (PSO-BPNN model) coupling the PSO algorithm with BP neural network is established through improving the connection weight and threshold values of BP neural network by the particle swarm optimization (PSO) algorithm. The prediction results of the PSO-BPNN model are compared and analyzed with that of the BP neural network model (BPNN model), GA-BPNN model, SSA-BPNN model and MPA-BPNN model. The results showed as follows: the average relative error of the PSO-BPNN model was 4.38%; the average absolute error was 0.0678; the root mean square error was 0.0934; and the determination coefficient was 0.9874. Compared with the BPNN model, the average relative error, average absolute error and root mean square error decreased by 9.35%, 0.1707 and 0.2056 respectively; and the determination coefficient increased by 0.1169. Compared with the GA-BPNN model, the average relative error, average absolute error and root mean square error decreased by 3.19%, 0.0602 and 0.0821 respectively; and the determination coefficient increased by 0.0320. Compared with the SSA-BPNN model, the average relative error, average absolute error and root mean square error decreased by 5.70%, 0.0820 and 0.1100 respectively; and the determination coefficient increased by 0.0474. Compared with the MPA-BPNN model, the average relative error, average absolute error and root mean square error decreased by 3.50%, 0.0861 and 0.1125 respectively; and the determination coefficient increased by 0.0488, proving that the PSO-BPNN model is more accurate than the BPNN model, GA-BPNN model, SSA-BPNN model and MPA-BPNN model as for prediction. When the PSO-BPNN model was applied to three extraction boreholes A, B, and C in a coal mine of Shanxi, the prediction results were better than the BPNN model, GA-BPNN model, SSA-BPNN model and MPA-BPNN model, proving the accuracy and stability of the PSO-BPNN model in predicting risk of borehole spontaneous combustion in other mine.

Mine water inrush source discrimination model based on KPCA-ISSA-KELM.

In order to ensure the safety of coal mine production, a mine water source identification model is proposed to improve the accuracy of mine water inrush source identification and effectively prevent water inrush accidents based on kernel principal component analysis (KPCA) and improved sparrow search algorithm (ISSA) optimized kernel extreme learning machine (KELM). Taking Zhaogezhuang mine as the research object, firstly, Na+, Ca2+, Mg2+, Cl-, SO2- 4 and HCO- 3 were selected as evaluation indexes, and their correlation was analyzed by SPSS27 software, with reducing the dimension of the original data by KPCA. Secondly, the Sine Chaotic Mapping, dynamic adaptive weights, and Cauchy Variation and Reverse Learning were introduced to improve the Sparrow Search Algorithm (SSA) to strengthen global search ability and stability. Meanwhile, the ISSA was used to optimize the kernel parameters and regularization coefficients in the KELM to establish a mine water inrush source discrimination model based on the KPCA-ISSA-KELM. Then, the mine water source data are input into the model for discrimination in compared with discrimination results of KPCA-SSA-KELM, KPCA-KELM, ISSA-KELM, SSA-KELM and KELM models. The results of the study show as follows: The discrimination results of the KPCA-ISSA-KELM model are in agreement with the actual results. Compared with the other models, the accuracy of the KPCA-ISSA-KELM model is improved by 8.33%, 12.5%, 4.17%, 21.83%, and 25%, respectively. Finally, when these models were applied to discriminate water sources in a coal mine in Shanxi, and the misjudgment rates of each model were 28.57%, 19.05%, 14.29%, 23.81%, 9.52% and 4.76%, respectively. From this, the KPCA-ISSA-KLEM model is the most accurate about discrimination and significantly better than other models in other evaluation indicators, verifying the universality and stability of the model. It can be effectively applied to the discrimination of inrush water sources in mines, providing important guarantees for mine safety production.

Side-chain effects on the solution-phase conformations and charge photogeneration dynamics of low-bandgap copolymers.

Solution-phase conformations and charge photogeneration dynamics of a pair of low-bandgap copolymers based on benzo[1,2-b:4,5-b(')]dithiophene (BDT) and thieno[3,4-b]thiophene (TT), differed by the respective carbonyl (-C) and ester (-E) substituents at the TT units, were comparatively investigated by using near-infrared time-resolved absorption (TA) spectroscopy at 25 °C and 120 °C. Steady-state and TA spectroscopic results corroborated by quantum chemical analyses prove that both PBDTTT-C and PBDTTT-E in chlorobenzene solutions are self-aggregated; however, the former bears a relatively higher packing order. Specifically, PBDTTT-C aggregates with more π-π stacked domains, whereas PBDTTT-E does with more random coils interacting strongly at the chain intersections. At 25 °C, the copolymers exhibit comparable exciton lifetimes (~1 ns) and fluorescence quantum yields (~2%), but distinctly different charge photogeneration dynamics: PBDTTT-C on photoexcitation gives rise to a branching ratio of charge separated (CS) over charge transfer (CT) states more than 20% higher than PBDTTT-E does, correlating with their photovoltaic performance. Temperature and excitation-wavelength dependent exciton∕charge dynamics suggest that the CT states localize at the chain intersections that are survivable up to 120 °C, and that the excitons and the CS states inhabit the stretched strands and the also thermally robust orderly stacked domains. The stable self-aggregation structures and the associated primary charge dynamics of the PBDTTT copolymers in solutions are suggested to impact intimately on the morphologies and the charge photogeneration efficiency of the solid-state photoactive layers.

Evaluation of the Efficacy and Safety of Topical 0.05% Cyclosporine Eye Drops (II) in the Treatment of Dry Eye Associated with Primary Sjögren's Syndrome.

PURPOSE: To evaluate the efficacy and safety of 0.05% cyclosporine eye drops (II) for the treatment of primary Sjögren's syndrome-associated dry eye (PSSDE). METHODS: Sixty patients with PSSDE were randomly divided into three groups, received treatment with 0.05% cyclosporine (C group), artificial tears (S group) or their combination (CS group). The evaluation indicators were evaluated at baseline and at weeks 2, 4 and 12. RESULTS: The symptoms of C and CS groups were reduced significantly. The signs [schirmer I test (F = 4.838, p = .011), ocular staining score (F = 7.961, p = .001) and tear break-up time (F = 9.283, p < .001)] were significantly different between S and C groups as well as S and CS groups. The tear meniscus height (F = 3.197, p = .048) was significantly different between S and CS groups. No serious adverse events occurred. CONCLUSION: 0.05% cyclosporine is an effective and safe treatment for patients with PSSDE.

The health-related quality of life for hemiarthroplasty and total hip arthroplasty in the elderly: A meta-analysis.

Purpose: What constitutes the optimal surgical plan for femoral neck fractures (FNFs) in elderly patients is controversial. The European quality of life 5-Dimension Questionnaire (EU-5Q) is an international scale used to measure the health-related quality of life (HRQoL) after surgery. We aim to verify the hip arthroplasty effect in elderly patients by analyzing HRQoL scores in the EU-5Q scale. Methods: We searched the EBSCO, Embase, PubMed, Ovid, Cochrane Library, and Web of Science databases using strict searching from established to 30 November 2022; used the Cochrane Library's Risk of Bias Assessment Tool and the Newcastle-Ottawa Scale to evaluate the literature; and used RevMan5.4.1 software to perform a meta-analysis. All the included studies used the EU-5Q scale to validate the overall outcomes for elderly hip arthroplasty. Results: The final included literature is composed of four RCTs, two cohort studies, three case-control trials, and three cross-sectional surveys. This study compared HRQoL scores measured by the EU-5Q scale, including 328 elderly patients with total hip arthroplasty (THA) and 323 elderly patients with hemiarthroplasty, which is statistically significant (OR = 0.05; 95% CI, 0.02~0.08; P = 0.002). The subgroups were as follows: unipolar vs. bipolar and cemented vs. uncemented hemiarthroplasty (OR = 0.06; 95% CI, 0.03~0.08; P < 0.001), follow-up time and age arthroplasty (OR = 0.16; 95% CI, 0.11~0.22; P < 0.001), molecular exercise and enhanced recovery after surgery (ERAS) (OR = 0.02; 95% CI,-0.03~0.07; P = 0.38), and analysis of hemiarthroplasty with cognitive dysfunction vs. the normal group (OR = 0.17; 95% CI, 0.08~0.26; P < 0.001). The outcome analysis was consistent with the included studies, and HRQoL of the EU-5Q scale is sensitive to surgical outcomes between THA and hemiarthroplasty. Conclusion: Surgeons still need to further evaluate and verify whether the hip arthroplasty surgical program or effect in elderly patients is optimal. Hemiarthroplasty operations in elderly patients have pointed toward a new direction for clinical treatment, and HRQoL scores measured by the EU-5Q can sensitively reflect the rehabilitation status after hip arthroplasty surgery. Moreover, the extensive correlation between surgical outcomes and perioperative neurocognitive function should be further investigated.

Circ_UTRN ameliorates caerulein-induced acute pancreatitis in vitro via reducing inflammation and promoting apoptosis through miR-320-3p/PTK2 axis.

OBJECTIVES: Circular RNAs (circRNAs) have been demonstrated to play important roles in acute pancreatitis (AP). Herein, this study aimed to investigate the role and mechanism of circRNAs utrophin (circ_UTRN) in AP. METHODS: In vitro cultured rat pancreatic acinar cell line AR42J was exposed to caerulein (10 nmol/L) to mimic an AP cell model. The levels of circ_UTRN and microRNA (miR)-320-3p and protein tyrosine kinase 2 (PTK2) were examined using quantitative real-time polymerase chain reaction and Western blot assays. Cell apoptosis was analysed by flow cytometry and Western blot assays. ELISA was employed to detect the levels of tumour necrosis factor-α (TNF-α), IL-1ß and IL-6. The binding interaction between miR-320-3p and circ_UTRN or PTK2 was verified using dual-luciferase reporter assay. KEY FINDINGS: The expression of circ_UTRN was decreased by caerulein in pancreatic acinar cells, ectopic overexpression of circ_UTRN reduced inflammation and promoted apoptosis in caerulein-mediated pancreatic acinar cells. In a mechanical study, circ_UTRN served as a sponge of miR-320-3p, and miR-320-3p directly targeted PTK2. Rescue assay suggested that the promotion of apoptosis and inhibition of inflammation induced by circ_UTRN re-expression in caerulein-mediated pancreatic acinar cells were partially abolished by miR-320-3p overexpression or PTK2 knockdown. Besides that, miR-320-3p inhibition impaired caerulein-induced cell apoptosis arrest and inflammation via targeting PTK2. CONCLUSIONS: Up-regulation of circ_UTRN in pancreatic acinar cells attenuates caerulein-evoked cell apoptosis arrest and inflammation enhancement via miR-320-3p/PTK2, suggesting that circ_UTRN/miR-320-3p/PTK2 axis might be engaged in caerulein-induced AP.

Association of neutralizing breadth against SARS-CoV-2 with inoculation orders of heterologous prime-boost vaccines.

BACKGROUND: Emerging evidence suggests heterologous prime-boost COVID-19 vaccination as a superior strategy than homologous schedules. Animal experiments and clinical observations have shown enhanced antibody response against influenza variants after heterologous vaccination; however, whether the inoculation order of COVID-19 vaccines in a prime-boost schedule affects antibody response against SARS-CoV-2 variants is not clear. METHODS: We conducted immunological analyses in a cohort of health care workers (n = 486) recently vaccinated by three types of inactivated COVID-19 vaccines under homologous or heterologous prime-boost schedules. Antibody response against ancestral SARS-CoV-2 (Wuhan-Hu-1) was assessed by total antibody measurements, surrogate virus neutralization tests, and pseudovirus neutralization assays (PNA). Furthermore, serum neutralization activity against SARS-CoV-2 variants of concern was also measured by PNA. FINDINGS: We observed strongest serum neutralization activity against the widely circulating SARS-CoV-2 variant B.1.617.2 among recipients of heterologous BBIBP-CorV/CoronaVac and WIBP-CorV/CoronaVac. In contrast, recipients of CoronaVac/BBIBP-CorV and CoronaVac/WIBP-CorV showed significantly lower B.1.617.2 neutralization titers than recipients of reverse schedules. Laboratory tests revealed that neutralizing activity against common variants but not the ancestral SARS-CoV-2 was associated with the inoculation order of heterologous prime-boost vaccines. Multivariable regression analyses confirmed this association after adjusting for known confounders. CONCLUSIONS: Our data provide clinical evidence of inoculation order-dependent expansion of neutralizing breadth against SARS-CoV-2 in recipients of heterologous prime-boost vaccination and call for further studies into its underlying mechanism. FUNDING: National Key R&D Program of China, National Development and Re-form Commission of China, National Natural Science Foundation of China, Shenzhen Science and Technology Innovation Commission, and US Department of Veterans Affairs.

Lycium barbarum polysaccharide protects ARPE­19 cells against H2O2­induced oxidative stress via the Nrf2/HO­1 pathway.

Age­related macular degeneration (AMD) is a global health problem. Lycium barbarum polysaccharide (LBP), a traditional Chinese herbal medicine, has been proven to be effective against several eye diseases. However, only a few studies have investigated the effectiveness of LBP for AMD. In the present study, the human retinal epithelial cell line, ARPE­19, was pretreated with LBP for 24 h before exposure to H2O2 (500 µM). Cell viability was assessed, and a series of oxidative and antioxidant indicators were evaluated to determine the influence of LBP on H2O2­triggered oxidative stress. The present study also determined the apoptosis status, as well as the expression levels of apoptotic proteins and nuclear factor erythroid 2­related factor 2 (Nrf2)/heme oxygenase­1 (HO­1) pathway proteins. The present study aimed to determine the protective role for LBP pretreatment and its underlying molecular mechanism. The results of the present study suggest that pretreatment of ARPE­19 cells with LBP exhibit high efficacy at reducing oxidative damage and inhibiting cell apoptosis. Furthermore, LBP may modulate the expression of proteins involved in the apoptotic pathway and activate the Nrf2 signaling pathway.

SARS-CoV-2 immunity and functional recovery of COVID-19 patients 1-year after infection.

The long-term immunity and functional recovery after SARS-CoV-2 infection have implications in preventive measures and patient quality of life. Here we analyzed a prospective cohort of 121 recovered COVID-19 patients from Xiangyang, China at 1-year after diagnosis. Among them, chemiluminescence immunoassay-based screening showed 99% (95% CI, 98-100%) seroprevalence 10-12 months after infection, comparing to 0.8% (95% CI, 0.7-0.9%) in the general population. Total anti-receptor-binding domain (RBD) antibodies remained stable since discharge, while anti-RBD IgG and neutralization levels decreased over time. A predictive model estimates 17% (95% CI, 11-24%) and 87% (95% CI, 80-92%) participants were still 50% protected against detectable and severe re-infection of WT SARS-CoV-2, respectively, while neutralization levels against B.1.1.7 and B.1.351 variants were significantly reduced. All non-severe patients showed normal chest CT and 21% reported COVID-19-related symptoms. In contrast, 53% severe patients had abnormal chest CT, decreased pulmonary function or cardiac involvement and 79% were still symptomatic. Our findings suggest long-lasting immune protection after SARS-CoV-2 infection, while also highlight the risk of immune evasive variants and long-term consequences for COVID-19 survivors.

Diagnostic values of conventional tumor markers and their combination with chest CT for patients with stageⅠA lung cancer / 中华肿瘤杂志

Objective: To investigate the diagnostic efficiency of conventional serum tumor markers and their combination with chest CT for stage ⅠA lung cancer. Methods: A total of 1 155 patients with stage ⅠA lung cancer and 200 patients with benign lung lesions (confirmed by surgery) treated at the Cancer Hospital, Chinese Academy of Medical Sciences from January 2016 to October 2020 were retrospectively enrolled in this study. Six conventional serum tumor markers [carcinoembryonic antigen (CEA), carbohydrate antigen 125 (CA125), squamous cell carcinoma associated antigen (SCCA), cytokeratin 19 fragment (CYFRA21-1), neuron-specific enolase (NSE), and gastrin-releasing peptide precursor (ProGRP)] and chest thin-slice CT were performed on all patients one month before surgery. Pathology was taken as the gold standard to analyze the difference of positivity rates of tumor markers between the lung cancer group and the benign group, the moderate/poor differentiation group and the well differentiation group, the adenocarcinoma group and the squamous cell carcinoma group, the lepidic and non-lepidic predominant adenocarcinoma groups, the solid nodule group and the subsolid nodule group based on thin-slice CT, and subgroups of ⅠA1 to ⅠA3 lung cancers. The diagnostic performance of tumor markers and tumor markers combined with chest CT was analyzed using the receiver operating characteristic curve. Results: The positivity rates of six serum tumor markers in the lung cancer group and the benign group were 2.32%-20.08% and 0-13.64%, respectively; only the SCCA positivity rate in the lung cancer group was higher than that in the benign group (10.81% and 0, P=0.022). There were no significant differences in the positivity rates of other serum tumor markers between the two groups (all P>0.05). The combined detection of six tumor markers showed that the positivity rate of the lung cancer group was higher than that of the benign group (40.93% and 18.18%, P=0.004), and the positivity rate of the adenocarcinoma group was lower than that of the squamous cell carcinoma group (35.66% and 47.41%, P=0.045). The positivity rates in the poorly differentiated group and moderately differentiated group were higher than that in the well differentiated group (46.48%, 43.75% and 22.73%, P=0.025). The positivity rate in the non-lepidic adenocarcinoma group was higher than that in lepidic adenocarcinoma group (39.51% and 21.74%, P=0.001). The positivity rate of subsolid nodules was lower than that of solid nodules (30.01% vs 58.71%, P=0.038), and the positivity rates of stageⅠA1, ⅠA2 and ⅠA3 lung cancers were 33.33%, 48.96% and 69.23%, respectively, showing an increasing trend (P=0.005). The sensitivity and specificity of the combined detection of six tumor markers in the diagnosis of stage ⅠA lung cancer were 74.00% and 56.30%, respectively, and the area under the curve (AUC) was 0.541. The sensitivity and specificity of the combined detection of six serum tumor markers with CT in the diagnosis of stage ⅠA lung cancer were 83.0% and 78.3%, respectively, and the AUC was 0.721. Conclusions: For stage ⅠA lung cancer, the positivity rates of commonly used clinical tumor markers are generally low. The combined detection of six markers can increase the positivity rate. The positivity rate of markers tends to be higher in poorly differentiated lung cancer, squamous cell carcinoma, or solid nodules. Tumor markers combined with thin-slice CT showed limited improvement in diagnostic efficiency for early lung cancer.