Ubiquitylation activates a peptidase that promotes cleavage and destabilization of its activating E3 ligases and diverse growth regulatory proteins to limit cell proliferation in Arabidopsis.

The characteristic shapes and sizes of organs are established by cell proliferation patterns and final cell sizes, but the underlying molecular mechanisms coordinating these are poorly understood. Here we characterize a ubiquitin-activated peptidase called DA1 that limits the duration of cell proliferation during organ growth in Arabidopsis thaliana The peptidase is activated by two RING E3 ligases, Big Brother (BB) and DA2, which are subsequently cleaved by the activated peptidase and destabilized. In the case of BB, cleavage leads to destabilization by the RING E3 ligase PROTEOLYSIS 1 (PRT1) of the N-end rule pathway. DA1 peptidase activity also cleaves the deubiquitylase UBP15, which promotes cell proliferation, and the transcription factors TEOSINTE BRANCED 1/CYCLOIDEA/PCF 15 (TCP15) and TCP22, which promote cell proliferation and repress endoreduplication. We propose that DA1 peptidase activity regulates the duration of cell proliferation and the transition to endoreduplication and differentiation during organ formation in plants by coordinating the destabilization of regulatory proteins.

Identification and characterization of circular RNAs involved in the fertility stability of cotton CMS-D2 restorer line under heat stress.

BACKGROUND: As a vital type of noncoding RNAs, circular RNAs (circRNAs) play important roles in plant growth and development and stress response. However, little is known about the biological roles of circRNAs in regulating the stability of male fertility restoration for cytoplasmic male sterility (CMS) conditioned by Gossypium harknessii cytoplasm (CMS-D2) cotton under high-temperature (HT) stress. RESULTS: In this study, RNA-sequencing and bioinformatics analysis were performed on pollen grains of isonuclear alloplasmic near-isogenic restorer lines NH [N(Rf1rf1)] and SH [S(Rf1rf1)] with obvious differences in fertility stability under HT stress at two environments. A total of 967 circRNAs were identified, with 250 differentially expressed under HT stress. We confirmed the back-splicing sites of eight selected circRNAs using divergent primers and Sanger sequencing. Tissue-specific expression patterns of five differentially expressed circRNAs (DECs) were also verified by RT-PCR and qRT-PCR. Functional enrichment and metabolic pathway analysis revealed that the parental genes of DECs were significantly enriched in fertility-related biological processes such as pollen tube guidance and cell wall organization, as well as the Pentose and glucuronate interconversions, Steroid biosynthesis, and N-Glycan biosynthesis pathways. Moreover, we also constructed a putative circRNA-mediated competing endogenous RNA (ceRNA) network consisting of 21 DECs, eight predicted circRNA-binding miRNAs, and their corresponding 22 mRNA targets, especially the two ceRNA modules circRNA346-miR159a-MYB33 and circRNA484-miR319e-MYB33, which might play important biological roles in regulating pollen fertility stability of cotton CMS-D2 restorer line under HT stress. CONCLUSIONS: Through systematic analysis of the abundance, characteristics and expression patterns of circRNAs, as well as the potential functions of their parent genes, our findings suggested that circRNAs and their mediated ceRNA networks acted vital biological roles in cotton pollen development, and might be also essential regulators for fertility stability of CMS-D2 restorer line under heat stress. This study will open a new door for further unlocking complex regulatory mechanisms underpinning the fertility restoration stability for CMS-D2 in cotton.

Sex-specific phosphorus acquisition strategies and cycling in dioecious Populus euphratica forests along a natural water availability gradient.

Soil phosphorus (P) availability affects plant growth and distribution. However, it is still unknown how sex-specific variation in functional traits affects plants' P acquisition and soil P transformation. On wet sites, female poplars had a greater specific root length (SRL), and a higher diversity of arbuscular mycorrhizal fungi (AMF) and phosphate-solubilizing bacteria (PSB). Male poplars living on wet sites increased the abundance of AMF and PSB communities and enhanced moderately labile and highly resistant organic P mineralisation via increased phosphatase activity. In contrast, on the dry site, the abundance and diversity of AMF and PSB communities increased in females, enhancing moderately labile and highly resistant organic P mineralisation via elevating phosphatase activities. Males maintained greater SRL and promoted Ca-P mobilisation via the release of root carboxylic acids and rhizosphere acidification on the dry site. The AMF community diversity followed a similar pattern as that of the PSB community when altering the P availability of different-sex plants. Our results indicated that organic P and Ca-P are the major sources of plant-available P in natural P. euphratica forests. Seasonal shifts and geographic locations affected the share of organic and inorganic P pools, and AMF and PSB diversities, ultimately altering sex-specific P acquisition strategies of plants.

Obinutuzumab may be an effective and safe option for adult minimal change disease and focal segmental glomerulosclerosis patients after multitarget therapy including rituximab.

INTRODUCTION: Rituximab has proven effective and safe in pediatric and adult minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS) patients with frequently relapsing nephrotic syndrome (FRNS). However, its efficacy diminishes in several patients who experience nephrotic syndrome relapsing in short durations or failing to achieve remission. We aimed to explore the efficacy and safety of obinutuzumab, a novel anti-CD20 antibody, in these patients. METHODS: A retrospective case series study at our center included 11 adult MCD or FSGS patients who presented with nephrotic syndrome characterized by short-duration relapses or lack of remission after multitarget therapy, including rituximab. Primary outcomes included the first relapse-free time, relapse rate during follow-up, and the use of immunosuppressants after obinutuzumab. All adverse events were recorded. RESULTS: Eleven adult patients (median age 26.0 years, 81.9% males) received an average obinutuzumab dose of 2.0 (1.0, 2.0) g during a median follow-up period of 17.0 (12.0, 22.0) months. The first relapse-free time was 12.1 (10.8, 18.9) months. Two patients with FSGS experienced relapses, while the remaining maintained remission by the end of follow-up. Six patients (54.5%) achieved cessation of corticosteroids and immunosuppressants within three months after obinutuzumab. Adverse events were mostly mild. CONCLUSION: Obinutuzumab may be an efficient and safe option for inducing remission in adult MCD and FSGS patients who presented with nephrotic syndrome relapsing in short durations or failed to achieve remission after multitarget therapy, including rituximab. It was effective in maintaining remission in MCD patients, while its efficacy in maintaining remission in FSGS patients remained uncertain.

The Effect of Mindfulness on Death Escape Acceptance in Young People: Emotion Regulation as a Mediator.

Few studies have examined young people's attitudes toward death escape acceptance and its relationship to mindfulness. This study addressed this issue and examined the mediating role of emotion regulation. In Study 1, 61 undergraduate students aged 19-22 years participated in a mindfulness intervention program, and the results showed that increasing young people's levels of mindfulness could improve their attitudes toward death escape acceptance. The Study 2, which recruited 440 young people aged 18-26 years to complete a cross-sectional survey, replicated the main effect and showed that young people's difficulty in emotion regulation fully mediated the coping effect of mindfulness. These findings suggest that individuals with high levels of mindfulness may have low levels of difficulty in emotion regulation and in turn promote healthy attitudes toward death escape acceptance.

The efficacy of rituximab plus belimumab or telitacicept in refractory lupus nephritis.

OBJECTIVE: Lupus nephritis is a severe and common complication of systemic lupus erythematosus (SLE). The pathogenesis of lupus nephritis is characterized by B-cell activation and autoantibody formation. Rituximab and belimumab, as well as telitacicept, target B cells through different mechanisms, potentially exerting a synergistic effect in the treatment of lupus nephritis. This study aims to investigate the efficacy and safety of treatment with rituximab followed by belimumab or telitacicept in the management of refractory lupus nephritis. METHODS: We conducted a single-center, open-label, retrospective study, including 25 patients with refractory lupus nephritis. All patients received combination therapy with rituximab in individualized dosages to achieve peripheral B-cell depletion, and then followed by belimumab or telitacicept. The follow-up period was at least 12 months, and the primary end point was renal remission rate at the last follow-up. RESULTS: During a median follow-up of 19 (13, 29) months, 20 of 25 (80%) patients achieved objective remission (OR), including 19 (76%) patients achieved complete renal response (CRR). After rituximab (712 ± 416mg in average), 18 patients received belimumab and seven patients received telitacicept. In the rituximab plus telitacicept group, all patients achieved CRR; while in the rituximab plus belimumab group, 12 (66.7%) patients achieved CRR and 13 (72.2%) patients achieved OR. The mean SLEDAI-2K score decreased from 15 ± 6 to 6 ± 6, representing an average reduction of 60%. At the last follow-up, 18/25 (72%) had prednisone ≤ 5 mg/d or even discontinued prednisone use. Adverse effects were mainly immunoglobulin deficiency, respiratory tract infection, urinary tract infections, and rash. No death occurred. CONCLUSIONS: Rituximab followed by belimumab or telitacicept may be effective in inducing remission in refractory lupus nephritis, with tolerable adverse effects.

Amyloid Protein Cross-Seeding Provides a New Perspective on Multiple Diseases In Vivo.

Amyloid protein cross-seeding is a peculiar phenomenon of cross-spreading among different diseases. Unlike traditional infectious ones, diseases caused by amyloid protein cross-seeding are spread by misfolded proteins instead of pathogens. As a consequence of the interactions among misfolded heterologous proteins or polypeptides, amyloid protein cross-seeding is considered to be the crucial cause of overlapping pathological transmission between various protein misfolding disorders (PMDs) in multiple tissues and cells. Here, we briefly review the phenomenon of cross-seeding among amyloid proteins. As an interesting example worth mentioning, the potential links between the novel coronavirus pneumonia (COVID-19) and some neurodegenerative diseases might be related to the amyloid protein cross-seeding, thus may cause an undesirable trend in the incidence of PMDs around the world. We then summarize the theoretical models as well as the experimental techniques for studying amyloid protein cross-seeding. Finally, we conclude with an outlook on the challenges and opportunities for basic research in this field. Cross-seeding of amyloid opens up a new perspective in our understanding of the process of amyloidogenesis, which is crucial for the development of new treatments for diseases. It is therefore valuable but still challenging to explore the cross-seeding system of amyloid protein as well as to reveal the structural basis and the intricate processes.

The predictive value of Berden's classification versus renal risk score for renal survival of Chinese patients with myeloperoxidase-anti-neutrophil cytoplasmic antibody-associated glomerulonephritis.

OBJECTIVES: This study aims to compare the prognostic values of two histopathological classification, Berden's classification versus renal risk score (RRS) by Brix et al. for predicting renal survival in Chinese patients with myeloperoxidase-anti-neutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis (MPO-AAGN). METHODS: The medical records of 225 patients with MPO-AAGN diagnosed in our centre between February 2004 and December 2020 were retrospectively analysed. The predictive model of Berden's classification or RRS was established by Cox regression, respectively. The above two models were compared on aspects of discrimination, calibration, and decision curve analysis for predicting the 0.5-, 1-, 3-, and 5-year renal survival. RESULTS: After a median follow up of 38.99 months, 32.44% of patients developed end-stage renal disease (ESRD). In the Kaplan-Meier analysis, there were significant differences in renal survival among groups according to Berden's classification or RRS (both log-rank p<0.001). According to time-dependent receiver operating characteristic (ROC) curve analysis, the model based on RRS showed better discrimination ability than the model based on Berden's classification for predicting 0.5-, 1-, and 3-year renal survival. For calibration analysis, the model based on RRS showed worse calibration than the model based on Berden's classification for predicting 1- and 3-year renal survival. According to the decision curve analysis, the clinical decisions based on RRS could achieve more clinical benefits than those based on Berden's classification in predicting 0.5-, 1-, and 3-year renal survival. CONCLUSIONS: The model based on RRS has better predictive value for renal survival than Berden's classification in aspect of discrimination and clinical decision from 0.5- to 3-year renal survival.

Emotional problems mediate the association between attention deficit/hyperactivity disorder and obesity in adolescents.

BACKGROUND: Attention deficit/hyperactivity disorder (ADHD) has been identified as a risk factor for obesity in both children and adolescents. However, the mechanisms underlying the relationship between ADHD and obesity are still unclear. This study aimed to test a theoretical model of whether anxiety/depression is an intermediary factor in the ADHD-obesity relationship. METHODS: Data were derived from the National Health Interview Survey (NHIS), a principal source of information on the health of the civilian noninstitutionalized population of the United States. A total of 35,108 adolescents aged 12-17 years old from 2010-2015 NHIS and 2016-2018 NHIS representing 46,550,729 individuals in the weighted population, had a parent-reported previous ADHD diagnosis, emotional problems, and height and weight data. Mediation analyses were used to explore whether anxiety/depression is an intermediary factor in the relationship between ever having ADHD and obesity. Mediation analyses were performed using multiple logistic regressions. RESULTS: The findings showed that ADHD was a predictor of obesity. This relationship was partially mediated by depression(2010-2015: ß=0.28, 95%CI:0.13-0.43; 2016-2018: ß=0.26, 95%CI:0.03-0.49), as well as anxiety (2010-2015: ß=0.28, 95%CI:0.18-0.38). CONCLUSIONS: Our study suggests the hypothetical role of depression and anxiety as underlying mechanisms in the association between ever having ADHD and obesity in adolescents. When treating children with ADHD, clinicians need to be particularly attentive to whether they show emotional problems and use interventions to eliminate anxiety/depression to protect against obesity.

Heat-responsive microRNAs participate in regulating the pollen fertility stability of CMS-D2 restorer line under high-temperature stress.

Anther development and pollen fertility of cytoplasmic male sterility (CMS) conditioned by Gossypium harknessii cytoplasm (CMS-D2) restorer lines are susceptible to continuous high-temperature (HT) stress in summer, which seriously hinders the large-scale application of "three-line" hybrids in production. Here, integrated small RNA, transcriptome, degradome, and hormone profiling was performed to explore the roles of microRNAs (miRNAs) in regulating fertility stability in mature pollens of isonuclear alloplasmic near-isogenic restorer lines NH and SH under HT stress at two environments. A total of 211 known and 248 novel miRNAs were identified, of which 159 were differentially expressed miRNAs (DEMs). Additionally, 45 DEMs in 39 miRNA clusters (PmCs) were also identified, and most highly expressed miRNAs were significantly induced in SH under extreme HT, especially four MIR482 and six MIR6300 family miRNAs. PmC28 was located in the fine-mapped interval of the Rf1 gene and contained two DEMs, gra-miR482_L-2R + 2 and gma-miR2118a-3p_R + 1_1ss18TG. Transcriptome sequencing identified 6281 differentially expressed genes, of which heat shock protein (HSP)-related genes, such as HSP70, HSP22, HSP18.5-C, HSP18.2 and HSP17.3-B, presented significantly reduced expression levels in SH under HT stress. Through integrating multi-omics data, we constructed a comprehensive molecular network of miRNA-mRNA-gene-KEGG containing 35 pairs of miRNA/target genes involved in regulating the pollen development in response to HT, among which the mtr-miR167a_R + 1, tcc-miR167c and ghr-miR390a, tcc-miR396c_L-1 and ghr-MIR169b-p3_1ss6AG regulated the pollen fertility by influencing ARF8 responsible for the auxin signal transduction, ascorbate and aldarate metabolism, and the sugar and lipid metabolism and transport pathways, respectively. Further combination with hormone analysis revealed that HT-induced jasmonic acid signaling could activate the expression of downstream auxin synthesis-related genes and cause excessive auxin accumulation, followed by a cascade of auxin signal transduction, ultimately resulting in pollen abortion. The results provide a new understanding of how heat-responsive miRNAs regulate the stability of fertility restoration for CMS-D2 cotton under heat stress.

A possible combined appraisal pattern: predicting the prognosis of patients after esophagectomy.

OBJECTIVE: To investigate the predictive merit of combined preoperative nutritional condition and systemic inflammation on the prognosis of patients receiving esophagectomy, with the assessment of model construction to extract a multidisciplinary phantom having clinical relevance and suitability. METHODS: The software of R 4.1.2 was utilized to acquire the survival optimal truncation value and the confusion matrix of survival for the continuity variables. SPSS Statistics 26 was employed to analyze the correlation of parameters, where including t-test, ANOVA and the nonparametric rank sum test shall. Pearson chi-square test was used for categorical variables. The survival curve was retrieved by Kaplan-Meier method. Univariate analysis of overall survival (OS) was performed through log-rank test. Cox analysis was for survival analyze. The performance of the prediction phantom through the area under curve (AUC) of receiver operating characteristic curve (ROC), decision curve analysis (DCA), nomogram and clinical impact curve (CIC) was plotted by R. RESULTS: The AUC value of albumin-globulin score and skeletal muscle index (CAS) is markedly superior. Patients with diminished AGS and greater SMI were associated with improved overall survival (OS) and recurrence-free survival (RFS) (P < 0.01). The CAS composite evaluation model was calibrated with better accuracy and predictive performance. The DCA and CIC indicated a relatively higher net revenue for the prediction model. CONCLUSIONS: The prediction model including the CAS score has excellent accuracy, a high net revenue, and favorable prediction function.

Positive effects of the COVID-19 pandemic on depression and anxiety in Chinese adolescents.

The potential impact on mental health of home schooling and social isolation due to COVID-19 lockdowns has led to widespread concern, particularly for adolescents. However, studies including pre-pandemic data from longitudinal cohorts with an assessment of the longer-term impact of the Covid-19 pandemic beyond the first months of 2020 are scarce. This longitudinal study of 1534 adolescents attending a secondary school in Hunan province investigated self-reported symptoms of anxiety and depression using two validated scales (Screen for Child Anxiety Related Disorders, Child Mood and Feelings Questionnaire) at six time points before, during, and after the 2020 national lockdown restrictions in China. Perceived COVID-related stress was assessed by an author-developed scale at two timepoints during the lockdown. We investigated trends in symptoms over time with a fixed effects model and multiple imputations of missing data. Counter to our expectations, depressive and anxiety symptoms were reduced during the 2020 lockdown relative to pre-lockdown (depression: b = - 3.37, SE = 0.345, Cohen's d = - 0.25, p < 0.0001; anxiety: b = - 4.55, SE = 0.382, Cohen's d = - 0.30, p < 0.0001). Symptoms remained significantly reduced even after lockdown restrictions eased. Higher symptom levels during lockdown were associated with greater self-reported COVID-related stress (depression: b = 0.11, SE = 0.026, p < 0.0001; anxiety: b = 0.11, SE = 0.036, p < 0.0001). Although COVID-related stresses correlated with higher levels of anxiety and depression, the lockdown period was associated with improved symptom levels in the adolescents taking part in our study. School closures may have improved the mental health of adolescents in China. We speculate this beneficial effect of lockdown can be explained by the adverse effects of attending school itself such as exposure to bullying and achievement pressures.

Reconstruction of Gap-Free Land Surface Temperature at a 100 m Spatial Resolution from Multidimensional Data: A Case in Wuhan, China.

Land surface temperatures (LST) are vital parameters in land surface-atmosphere interactions. Constrained by technology and atmospheric interferences, LST retrievals from various satellite sensors usually return missing data, thus negatively impacting analyses. Reconstructing missing data is important for acquiring gap-free datasets. However, the current reconstruction methods are limited for maintaining spatial details and high accuracies. We developed a new gap-free algorithm termed the spatial feature-considered random forest regression (SFRFR) model; it builds stable nonlinear relationships to connect the LST with related parameters, including terrain elements, land coverage types, spectral indexes, surface reflectance data, and the spatial feature of the LST, to reconstruct the missing LST data. The SFRFR model reconstructed gap-free LST data retrieved from the Landsat 8 satellite on 27 July 2017 in Wuhan. The results show that the SFRFR model exhibits the best performance according to the various evaluation metrics among the SFRFR, random forest regression and spline interpolation, with a coefficient of determination (R2) reaching 0.96, root-mean-square error (RMSE) of 0.55, and mean absolute error (MAE) of 0.55. Then, we reconstructed gap-free LST data gathered in Wuhan from 2016 to 2021 to analyze urban thermal environment changes and found that 2020 presented the coolest temperatures. The SFRFR model still displayed satisfactory results, with an average R2 of 0.91 and an MAE of 0.63. We further discuss and discover the factors affecting the visual performance of SFRFR and identify the research priority to circumvent these disadvantages. Overall, this study provides a simple, practical method for acquiring gap-free LST data to help us better understand the spatiotemporal LST variation process.

Effects of Pretreated Phosphogypsum and Granulated Blast-Furnace Slag on the Rheological Properties of the Paste Excited by NaOH.

The main component of phosphogypsum (PG) is CaSO4·2H2O. PG contains a few impurities, heavy metals, and radioisotopes, which limit the use of PG and pose a danger to the environment. In this study, under the excitation of a sodium hydroxide solution, the rheological properties of a paste with granulated blast-furnace slag (GGBS) and PG treated with ultrasonic water washing were investigated. Experimental results showed that the ratio of GGBS to PG and the amount of sodium hydroxide solution significantly affect the density and viscosity of the paste, but the effect patterns of both are different. The maximum viscosity was 498 mPa·s when the ratio of GGBS to PG was 4:1. When the ratio changed from 3:2 to 1:4, the viscosity of the paste gradually decreased by 15.5%, 32.1%, 36.1%, and 46.8%, respectively. In contrast, the ratio of GGBS to PG had a greater effect on the viscosity than the amount of sodium hydroxide solution in terms of the standard consistency water consumption, viscosity, and water release ratio. The larger the PG ratio, the smaller the density, viscosity, and water release ratio of the paste. The variation in the ratio of GGBS to PG had a significant effect on the water film thickness of the paste, demonstrating that the larger the PG mixture, the larger the water film thickness of the paste, which reached 1.122 µm, 2.31 times the minimum water film thickness of the paste. At the same time, the water film thickness of the paste was negatively correlated with the water consumption of the standard consistency, viscosity, and water release ratio, and was positively correlated with the fluidity.

Diazulenorubicene as a Non-benzenoid Isomer of peri-Tetracene with Two Sets of 5/7/5 Membered Rings Showing Good Semiconducting Properties.

Non-benzenoid polycyclic aromatic hydrocarbons (PAHs) have received a lot of attention because of their unique optical, electronic, and magnetic properties, but their synthesis remains challenging. Herein, we report a non-benzenoid isomer of peri-tetracene, diazulenorubicene (DAR), with two sets of 5/7/5 membered rings synthesized by a (3+2) annulation reaction. Compared with the precursor containing only 5/7 membered rings, the newly formed five membered rings switch the aromaticity of the original heptagon/pentagon from antiaromatic/aromatic to non-aromatic/antiaromatic respectively, modify the intermolecular packing modes, and lower the LUMO levels. Notably, compound 2 b (DAR-TMS) shows p-type semiconducting properties with a hole mobility up to 1.27 cm2  V-1 s-1 . Moreover, further extension to larger non-benzenoid PAHs with 19 rings was achieved through on-surface chemistry from the DAR derivative with one alkynyl group.

[A Novel Single-arm Single-port Micro-traumatic Laparoscopic Robotic Surgical System].

As the robotic assisted single port surgery arousing attention, a novel single-arm single-port micro-traumatic laparoscopic robotic surgical system is proposed in this study. From the perspective of the mechanics, joints with high rigidity and high reliability were utilized to realize the remote center of motion (RCM). Besides, the cost of consumables was reduced by adding the support of the rigid endoscope. From the perspective of the algorithm, high-precision motion control method and feedback force protection mechanism were implemented. The effectiveness of the aforementioned characteristics were verified by five clinical experiments of cholecystectomy. The results showed that the system is able to reduce the amount of bleeding, accelerate the patient recovery, reduce the infection risk and shorten the learning period. The robotic surgical system had significant clinical application value.

The survival nomograms for anti-neutrophil cytoplasmic antibody-associated glomerulonephritis patients with a follow-up of more than one year.

OBJECTIVES: Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis with kidney injury, manifested as ANCA-associated glomerulonephritis (AAGN), often portends a poor prognosis of renal function and life survival in long term. METHODS: A cohort of 339 AAGN patients were enrolled retrospectively. These patients survived and were followed up for at least 12 months after diagnosis in our centre. Multivariate Cox regression analysis and nomogram models were performed to determine the risk factors associated with renal survival and patient survival. RESULTS: The median follow-up time of all 339 patients was 65.2 (IQR 45.1, 91.3) months and the median age was 61(IQR 53, 69) years. In order to analyse the impact of the factors on renal survival, we divided the patients into 2 groups: non-dialysis group (204 patients without dialysis at the final visit) and dialysis group (135 patients with maintaining dialysis). The patients in dialysis group had lower haemoglobin level, lower eGFR level, lower platelets count, more daily urine protein, and higher Birmingham Vasculitis Activity Score (BVAS) at admission than those in non-dialysis group. Multivariate Cox regression revealed that low haemoglobin (HR=0.977, 95%CI 0.965-0.990, p<0.001), low eGFR (HR=0.957, 95%CI 0.941-0.973, p<0.001) and high proteinuria (HR=1.139, 95%CI 1.055-1.230, p=0.001) at admission were independent risk factors for developing maintaining dialysis. A nomogram was established based on the results of multivariate Cox analysis and the internal bootstrap resampling approach showed the C-index of the nomogram was 0.83. Then we divided all patients into death group (n=99) and survival group (n=240). The patients in death group had older age, more hypertension, more chronic lung disease, lower platelets count, lower serum albumin, higher BVAS and lower eGFR at admission than those in survival group. Multivariate Cox regression revealed that the status of maintaining dialysis (HR 3.51, 95% CI 1.91-6.47, p<0.001) and old age (HR 1.07, 95% CI 1.04-1.09, p<0.001) were independent risk factors for all-cause mortality. Again, a nomogram was established and the C-index was 0.74. CONCLUSIONS: We analysed the independent risk factors for maintaining dialysis and all-cause mortality in AAGN patients with a follow-up of more than 12 months. The two proposed nomograms were of predictive value.

McKeown esophagectomy: robot-assisted versus conventional minimally invasive technique-systematic review and meta-analysis.

BACKGROUND AND PURPOSE: This meta-analysis assesses the surgical outcomes between robot-assisted minimally-invasive McKeown esophagectomy and conventional one. METHOD: This meta-analysis searched the Web of Science, PUBMED, and EMBASE from the database's inception to January 2022. Altogether, 1073 records were identified in the literature search. Studies that evaluated the outcomes between robot-assisted minimally-invasive McKeown esophagectomy and conventional one among postoperative patients with oesophageal neoplasms were included. The assessed outcomes involved complications and clinical outcomes. In addition, heterogeneity was analyzed, and evidence quality was evaluated. RESULT: Evidence indicated that RAMIE (minimally-invasive esophagectomy assisted with robot) decreased incidences of lung complications and hospital stay as well as increased harvested lymph nodes. CONCLUSIONS: There was currently little evidence from randomized studies depicting that robot surgery manifested a clear overall advantage, but there was growing evidence regarding the clinical benefits of robot-assisted minimally invasive McKeown esophagectomy over conventional one.

Bursal peptide BP-IV as a novel immunoadjuvant enhances the protective efficacy of an epitope peptide vaccine containing T and B cell epitopes of the H9N2 avian influenza virus.

Short peptide antigens covering conserved T or B cell epitopes have been investigated in influenza vaccines. Bursal pentapeptide V (BPP-V) and bursal peptide IV (BP-IV) are small molecular peptides that were isolated and identified from the bursa of Fabricius (BF) and induce a strong immune response at both the humoural and cellular levels. To explore the molecular adjuvant potential of BPP-V and BP-IV with an epitope vaccine, an epitope peptide (HA284-298, GNCVVQCQTERGGLN) rich in T and B cell epitopes for the H9N2 avian influenza virus (AIV) haemagglutinin (HA) protein was selected. BPP-V and BP-IV were coupled with the epitope peptide sequence to form BPP-V and BP-IV-epitope vaccines, respectively. The immunoefficacy of BPP-V and BP-IV-epitope peptide vaccines was evaluated. The results showed that the epitope peptide had weak immunogenicity. The BPP-V-epitope peptide vaccine promoted only the secretion of anti-HA IgG and IgG1 antibodies. The BP-IV-epitope peptide vaccine not only promoted the production of anti-HA IgG and IgG1 antibodies but also significantly induced the production of the IgG2a antibody. The BP-IV-epitope peptide vaccine significantly promoted the production of interleukin (IL-4) and interferon-γ (IFN-γ) (the BPP-V epitope peptide vaccine promoted only the production of IL-4), enhanced the cytotoxic T lymphocyte (CTL) response, and increased the proportion of CD3+ T lymphocytes. Moreover, the BP-IV-epitope peptide vaccine promoted a cell-mediated immune response similar to that of the AIV vaccine group. Furthermore, BPP-V and BP-IV-epitope peptide vaccines could also accelerate the clearance of pulmonary virus and reduce pathological damage after the challenge with H9N2 AIV. This study demonstrates the potential of BP-IV as an effective adjuvant for the epitope peptide vaccine for the H9N2 AIV.

Searching for conditions of protein self-assembly by protein crystallization screening method.

The self-assembly of biomacromolecules is an extremely important process. It is potentially useful in the fields of life science and materials science. To carry out the study on the self-assembly of proteins, it is necessary to find out the suitable self-assembly conditions, which have always been a challenging task in practice. Inspired by the screening technique in the field of protein crystallization, we proposed using the same screening technique for seeking suitable protein self-assembly conditions. Based on this consideration, we selected 5 proteins (ß-lactoglobulin, hemoglobin, pepsin, lysozyme, α-chymotrypsinogen (II) A) together with 5 screening kits (IndexTM, BML, Morpheus, JCSG, PEG/Ion ScreenTM) to investigate the performance of these crystallization screening techniques in order to discover new optimized conditions of protein self-assembly. The screens were all kept at 293 K for certain days, and were analyzed using optical microscope, scanning electron microscope, transmission electron microscope, atomic force microscope, fluorescence microscope, and atomic absorption spectroscope. The results demonstrated that the method of protein crystallization screening can be successfully applied in the screening of self-assembly conditions. This method is fast, high throughput, and easily implemented in an automated system, with a low protein consumption feature. These results suggested that such strategy can be applied to finding new conditions or forms in routine research of protein self-assembly. KEY POINTS: • Protein crystallization screening method is successfully applied in the screening of self-assembly conditions. • This screening method can be applied on various kinds of proteins and possess a feature of low protein consumption. • This screening method is fast, high throughput, and easily implemented in an automated system.