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Abstract Background Patients with Turner syndrome (TS) face an increased risk of developing aortic dilatation (AD), but diagnosing AD in children presents greater complexity compared to adults. This study aimed to investigate the application of various assessment indicators of AD in Chinese children and adolescents with TS. Methods This study included TS patients admitted to Shenzhen Children’s Hospital from 2017 to 2022. Cardiovascular lesions were diagnosed by experienced radiologists. Patients without structural heart disease were divided into different body surface area groups, then the Chinese TS population Z-score (CHTSZ-score) of the ascending aorta was calculated and compared with other indicators such as aortic size index (ASI), ratio of the ascending to descending aortic diameter (A/D ratio), and TSZ-score (Quezada’s method). Results A total of 115 TS patients were included, with an average age of 10.0 ± 3.7 years. The incidences of the three most serious cardiovascular complications were 9.6% (AD), 10.4% (coarctation of the aorta, CoA), and 7.0% (bicuspid aortic valve, BAV), respectively. The proportion of developing AD in TS patients aged ≥ 10 years was higher than that in those

PurposeA systematic review and meta-analysis were conducted to evaluate the diagnostic precision of radiomics in the differential diagnosis of parotid tumors, considering the increasing utilization of radiomics in tumor diagnosis. Although some researchers have attempted to apply radiomics in this context, there is ongoing debate regarding its accuracy.MethodsDatabases of PubMed, Cochrane, EMBASE, and Web of Science up to May 29, 2024 were systematically searched. The quality of included primary studies was assessed using the Radiomics Quality Score (RQS) checklist. The meta-analysis was performed utilizing a bivariate mixed-effects model.ResultsA total of 39 primary studies were incorporated. The machine learning model relying on MRI radiomics for diagnosis malignant tumors of the parotid gland, demonstrated a sensitivity of 0.80 [95% CI: 0.74, 0.86], SROC of 0.89 [95% CI: 0.27-0.99] in the validation set. The machine learning model based on MRI radiomics for diagnosis malignant tumors of the parotid gland, exhibited a sensitivity of 0.83[95% CI: 0.76, 0.88], SROC of 0.89 [95% CI: 0.17-1.00] in the validation set. The models also demonstrated high predictive accuracy for benign lesions.ConclusionThere is great potential for radiomics-based models to improve the accuracy of diagnosing benign and malignant tumors of the parotid gland. To further enhance this potential, future studies should consider implementing standardized radiomics-based features, adopting more robust feature selection methods, and utilizing advanced model development tools. These measures can significantly improve the diagnostic accuracy of artificial intelligence algorithms in distinguishing between benign and malignant tumors of the parotid gland.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42023434931.

BackgroundHeart failure is a common cause of adverse cardiovascular outcomes in patients with chronic kidney disease (CKD). Left atrial (LA) characteristics are thought to be involved in the development of heart failure. However, LA assessment is complex. Though a variety of parameters have been defined, there is no single parameter that best defines LA function. Pilot data indicate that left atrial volumetric/mechanical coupling index (LACI) may be useful, but data with CKD are lacking.AimThe objective of this study was to define LACI in a cohort of patients with CKD and to assess its value in evaluating LA function and predicting heart failure.MethodsA cohort of patients with CKD was enrolled at our hospital between 2021 and 2023. Follow-up was performed for heart failure. LACI is a volumetric to mechanical coupling index, calculated as the ratio of the LA volume index to the tissue-Doppler myocardial velocity at atrial contraction. Spearman’s rank correlation or Pearson’s correlation was used to calculate the correlation between LACI and echocardiographic/hemodynamic variables. Receiver operating characteristic curve (ROC) analysis was utilised to derive the area under the curve (AUC) for LACI, LVGLS, LASr, LASct and LASI for the detection of heart failure. Kaplan-Meier survival curves were employed to compare clinical outcomes based on LACI thresholds. A multivariable logistic regression analysis was employed to assess the relationship between risk factors and elevated LACI. Cox proportional hazards regression was used to identify risk factors for heart failure.ResultsLACI showed a positive correlation with NT-proBNP, CK-MB, LAVI, E/e’ and LASI (r = 0.504, 0.536, 0.856, 0.541 and 0.509, p 5.0 (log-rank test: P 5.0 was an independent predictor of heart failure [OR: 0.121, 95% CI (0.020–0.740), p = 0.022].ConclusionLACI may prove to be a valuable tool for assessing LA function in patients with CKD, and could be integrated into the routine assessment of LA for the purpose of prognostic assessment and clinical decision-making in patients with CKD.

This study reported a case of early-onset parkinsonism associated with a novel variant of the PLA2G6 gene. The boy first started showing symptoms at the age of 11, with gait instability and frequent falls. As the disease progressed, his gait instability worsened, and he developed difficulties with swallowing and speaking, although there was no apparent decline in cognitive function. An MRI of the head revealed significant atrophy of the cerebellum. The initial diagnosis for the boy was early-onset parkinsonism, classified as Hoehn-Yahr grade 5.Genomic sequencing of the patient indicated that he had compound heterozygous variations in the PLA2G6 gene: c.1454G>A (p.Gly485Glu) and c.991G>T (p.Asp331Tyr). Pedigree analysis revealed that his younger brother also carried the same variant, albeit with milder symptoms. The patient's unaffected mother was found to be a carrier of the c.991G>T variant. Additionally, this study reviewed 62 unrelated families with PLA2G6 gene-related early-onset parkinsonism. The analysis showed a higher proportion of female probands, with a mean age of onset of ~23.0 years. Primary symptoms were predominantly bradykinesia and psychosis, with tremors being relatively rare. Cerebellar atrophy was observed in 41 patients (66.1%). Among the reported mutations, the most common mutation was c.991G>T, presenting in 21 families (33.9%), followed by c.2222G>A in eight families (12.9%). Other mutations were less common. Notably, the c.991G>T mutation was exclusive to Chinese families and was a prevalent mutation among this population. The initial symptoms varied significantly among patients with different mutations.

ABSTRACTHuman adenovirus (HAdV) infects the respiratory system, thus posing a threat to health. However, immunodiagnostic reagents for human adenovirus are limited. This study aimed to develop efficient diagnostic reagents based on monoclonal antibodies for diagnosing various human adenovirus infections. Evolutionary and homology analyses of various human adenoviral antigen genes revealed highly conserved antigenic fragments. The prokaryotic expression system was applied to recombinant penton, hexon, and IVa2 conserved fragments of adenovirus, which were injected into BALB/c mice to prepare human adenovirus-specific monoclonal antibodies. Enzyme-linked immunosorbent assay (ELISA), indirect immunofluorescence assay (IFA), and Western blotting were used to determine the immune specificity of the monoclonal antibodies. Indirect ELISA showed that monoclonal antibodies 1F10, 8D3, 4A1, and 9B2 were specifically bound to HAdV-3 and HAdV-55 and revealed high sensitivity and low detection limits for various human adenoviruses. Western blotting showed that 1F10 and 8D3 specifically recognized various human adenovirus types, including HAdV-1, HAdV-2, HAdV-3, HAdV-4, HAdV-5, HAdV-7, HAdV-21, and HAdV-55, and 4A1 specifically recognized HAdV-1, HAdV-2, HAdV-3, HAdV-5, HAdV-7, HAdV-21, and HAdV-55. IFAs showed that 1F10, 8D3, and 4A1 exhibited highly selective localization to A549 cells infected with HAdV-3 and HAdV-55. Finally, two antibody pairs that could detect hexon antigens HAdV-3 and HAdV-55 at low concentrations were developed. The monoclonal antibodies developed in this study show potential for detecting human adenoviruses.IMPORTANCEIn this study, we selected the three most conserved antigenic fragments of human adenovirus to prepare a murine monoclonal antibody for the first time, and human adenovirus antigenic fragments with heretofore unheard of degrees of conservatism were isolated. The three monoclonal antibodies with the ability to recognize human respiratory adenovirus over a broad spectrum were screened by hybridoma and monoclonal antibody preparation. Human adenovirus infections are serious; however, therapeutic drugs and diagnostic reagents are scarce. Thus, to reduce the serious consequences of human viral infections and adenovirus pneumonitis, early diagnosis of infection is required. The present study provides three monoclonal antibodies capable of recognizing a wide range of human adenoviruses, thereby offering guidance for subsequent research and development.

Abstract International innovation cooperation is crucial to the enhancement of national technological innovation capabilities in the context of globalization. Does the Belt and Road Initiative (BRI), as a major international initiative, promote innovation cooperation between China and BRI partner countries? Taking the top 80 global countries in innovation capability as the research sample, this paper uses the DID method to answer this question. The empirical results show that the BRI indeed promoted innovation cooperation between them to a certain extent. Specifically, it significantly increased the proportion of their cooperative patents in China’s total patents, and the promotion effect was more obvious for countries with better economic foundations. Furthermore, the mechanism tests indicate that shortening the institutional distance, strengthening the exchange of scientific and technological talents, and stimulating cultural differences were important mechanisms promoting their innovation cooperation. Although the BRI did not significantly increase the proportion of cooperative patents in BRI partner countries’ total patents, it effectively improved their innovation foundations and capabilities.

This paper proposes a generalized partially functional linear model with interaction terms. It is suitable for cases where the response variable is scalar, and the predictor variables include a mix of functional and scalar types, while considering the correlations among functional predictor variables. The model uses principal component analysis for dimensionality reduction, employs maximum likelihood estimation to obtain parameter values, proves the asymptotic properties of the estimates, and validates the model’s accuracy through data simulation experiments. Finally, the proposed model was applied to investigate the influence of air quality, climate factors, and medical and social indicators, along with their interactions, on cancer incidence, which is a binary response.

Abstract To evaluate the relationship between factors of metastatic intraparotid lymph node (IPLN) and distant metastasis in parotid adenoid cystic carcinoma (ACC). Patients with surgically treated parotid ACC were retrospectively enrolled, and primary outcome variable was distant metastasis free survival (DMFS). The effect of factors of metastatic IPLN on DMFS was evaluated using Cox model. In total, 232 patients were included. Extranodal extension of IPLN and cervical lymph nodes did not impact the DMFS, and the 7th but not 8th AJCC N stage was associated with DMFS. Groups of 0 and 1 metastatic IPLN had comparable DMFS, but presence of 2+ positive IPLN was related to increased worse DMFS (p = 0.034, HR 2.09). A new N stage (0 vs 1–2 vs 3+) based on total positive lymph node number exhibited better C-index than traditional N stage. IPLN metastasis increased the risk of distant metastasis, and the impact was mainly determined by the number of metastatic IPLN. Our proposed N stage provided better DMFS prediction than the 8th AJCC N classification.

Abstract Background Standard treatment of locally advanced rectal cancer (LARC) was neoadjuvant chemoradiotherapy (CRT), followed by total mesorectal excision (TME). Total neoadjuvant treatment (TNT), a new concept, attempts to deliver both systemic chemotherapy and neoadjuvant CRT prior to surgery. Patients treated with neoadjuvant chemotherapy were more likely to show higher tumor regression. The objective of this trial was to increase complete clinical rate (cCR) for LARC patients by optimizing tumor response, using TNT regimen as compared to conventional chemoradiotherapy. TESS, a prospective, open‐label, multicenter, single‐arm, phase 2 study, is underway. Methods Main inclusion criteria include cT3‐4aNany or cT1‐4aN+ rectal adenocarcinoma aged 18‐70y; Eastern Cooperative Oncology Group (ECOG) performance 0–1; location ≤5 cm from anal verge. Ninety‐eight patients will receive 2 cycles of neoadjuvant chemotherapy Capeox (capecitabine + oxaliplatin) before, during, and after radiotherapy 50Gy/25 fractions, before TME (or other treatment decisions, such as Watch and Wait strategy) and adjuvant chemotherapy capecitabine 2 cycles. Primary endpoint is the cCR rate. Secondary endpoints include ratio of sphincter preservation strategy; pathological complete response rate and tumor regression grade distribution; local recurrence or metastasis; disease‐free survival; locoregional recurrence‐free survival; acute toxicity; surgical complications; long‐term anal function; late toxicity; adverse effect, ECOG standard score, and quality of life. Adverse events are graded per Common Terminology Criteria for Adverse Events V5.0. Acute toxicity will be monitored during antitumor treatment, and late toxicity will be monitored for 3 years from the end of the first course of antitumor treatment. Discussion The TESS trial aims to explore a new TNT strategy, which is expected to increase the rate of cCR and sphincter preservation rate. This study will provide new options and evidence for a new sandwich TNT strategy in patients with distal LARC.

Abstract Based on the soil arching effect theory, the magnitude and distribution of sidewall earth pressure on open caissons when the embedded depth is large was analyzed by using theory of non-limit state earth pressure theory and horizontal differential element method. The theoretical formula was deduced. The theoretical calculation results are compared with the field test results and centrifugal model test results respectively. The results show that when the embedded depth of the open caisson is large, the distribution of earth pressure on the side wall of the open caisson first increases with the increase of embedded depth, reaches a peak value, and then sharply decreases. The peak point is located at 2/3 ~ 4/5 of the embedded depth. In engineering practice, when the embedded depth of the open caisson is 40 m, the relative error between the field test value and the theoretical calculation value is − 55.8% ~ 1.2%, with an average error of 13.8%. When the equivalent embedded depth of the open caisson in the centrifugal model test is 36 m, the relative error between the centrifugal model test value and the theoretical calculation value is − 20.1% ~ 68.0%, with an average error of 10.6%, The results are consistent well. The results of this article provides reference for the design and construction of open caisson.

Background: There is a rapidly increasing incidence of early-onset colorectal cancer (EO-CRC) which threatens the survival of young people, while aging also represents a challenging clinical problem. Objectives: We aimed to investigate the differences in the clinical characteristics and prognosis in stage III rectal cancer (RC), to help optimize treatment strategies. Design and methods: This study included 757 patients with stage III RC, all of whom received neoadjuvant chemoradiotherapy and total mesorectal excision. The whole cohort was categorized as very early onset (VEO, ⩽30 years old), early onset (EO, >30 years old, ⩽50 years old), intermediate onset (IO, >50 years, ⩽70 years), or late onset (LO, >70 years old). Results: There were more female VEO patients than males, more mucinous adenocarcinoma, signet-ring cell carcinoma, pre-treatment cT4 stage, and higher pre-treatment serum carbohydrate antigen 19-9 compared with the other three groups. VEO patients had the worst survival with the highest RC-related mortality (34.5%), recurrence (13.8%), and metastasis (51.7%). LO patients had the highest non-RC-related mortality rate (16.6%). The Cox regression model showed VEO was a negative independent prognostic factor for disease-free survival [DFS, hazard ratio (HR): 2.830, 95% confidence interval (CI): 1.633–4.904, p < 0.001], distant metastasis-free survival (DMFS, HR: 2.969, 95% CI: 1.720–5.127, p < 0.001), overall survival (OS, HR: 2.164, 95% CI: 1.102–4.249, p = 0.025), and cancer-specific survival (CSS, HR: 2.321, 95% CI: 1.145–4.705, p = 0.020). LO was a negative independent factor on DFS (HR: 1.800, 95% CI: 1.113–2.911, p = 0.017), DMFS (HR: 1.903, 95% CI: 1.150–3.149, p = 0.012), OS (HR: 2.856, 95% CI: 1.745–4.583, p < 0.001), and CSS (HR: 2.248, 95% CI: 1.282–3.942, p = 0.005). VEO patients had better survival in the total neoadjuvant therapy-like (TNT-like) pattern on DFS ( p = 0.039). IO patients receiving TNT-like patterns had better survival on DFS, OS, and CSS ( p = 0.006, p = 0.018, p = 0.006, respectively). Conclusion: In stage III RC, VEO patients exhibited unique clinicopathological characteristics, with VEO a negative independent prognostic factor for DFS, DMFS, OS, and CSS. VEO and IO patients may benefit from a TNT-like treatment pattern.

Objectives To explore the association between non-high-density lipoprotein (non-HDL) and mortality risk, both short-term and long-term, in Chinese people.Design A prospective cohort study.Setting The National Basic Public Health Service (BPHS) in China.Participants Including 621 164 elderly individuals around Hunan Province who underwent healthcare management receiving check-ups in China BPHS from 2010 to 2020. Exclusion criteria: (1) missing information on gender; (2) missing records of lipid screening; (3) missing information on key covariates; and (4) missing records of comorbidities (cardiovascular disease, hypertension, diabetes, cancer.)Primary and secondary outcome measures The study’s primary endpoint was all-cause and cause-specific mortality, sourced from Hunan’s CDC(Center for Disease Control and Prevention)-operated National Mortality Surveillance System, tracking participants until 24 February 2021.Results 26 758 (4.3%) deaths were recorded, with a median follow-up of 0.83 years. Association between non-HDL and mortality was non-linear after multivariable adjustment, with the optimum concentration (OC) being 3.29 and 4.85 mmol/L. Compared with OC, the risk increased by 1.12-fold for non-HDL

The worldwide outbreak of the monkeypox virus (MPXV) has become a “Public Health Emergency of International Concern” (PHEIC). Severe monkeypox virus infection can be fatal, however, effective therapeutic methods are yet to be developed. Mice were immunized with A35R protein and A29L protein of MPXV, and the binding and neutralizing activities of the immune sera against poxvirus-associated antigens and viruses were identified. A29L protein and A35R protein-specific monoclonal antibodies (mAbs) were generated and their antiviral activities of these mAbs were characterized in vitro and in vivo. Immunization with the MPXV A29L protein and A35R protein induced neutralizing antibodies against the orthopoxvirus in mice. None of the mAbs screened in this study against A35R could effectively neutralize the vaccinia virus (VACV), while three mAbs against A29L protein, 9F8, 3A1 and 2D1 were confirmed to have strong broad binding and neutralizing activities against orthopoxvirus, among which 9F8 showed the best neutralizing activity. 9F8, 3A1, and 2D1 recognized different epitopes on MPXV A29L protein, showing synergistic antiviral activity in vitro against the VACV Tian Tan and WR strains; the best activity was observed when the three antibodies were combined. In the vivo antiviral prophylactic and therapeutic experiments, 9F8 showed complete protective activity, whereas 3A1 and 2D1 showed partial protective activity. Similarly, the three antibodies showed synergistic antiviral protective activity against the two VACVs. In conclusion, three mAbs recognized different epitopes on MPXV A29L protein were developed and showed synergistic effects against orthopoxvirus.

Aerosol transmission is an important disease transmission route and has been especially pertinent to hospital and biosafety laboratories during the SARS-CoV-2 pandemic. The thermal resistance of airborne SARS-CoV-2 is lower than that of Bacillus subtilis spores, which are often used to test the effectiveness of SARS-CoV-2 and other pathogen disinfection methods. Herein, we propose a new method to test the disinfection ability of a flowing air disinfector (a digital electromagnetic induction air heater) using B. subtilis spores. The study provides an alternative air disinfection test method. The new test system combined an aerosol generator and a respiratory filter designed in-house and could effectively recover spores on the filter membrane at the air outlet after passing through the flowing air disinfector. The total number of bacterial spores used in the test was within the range of 5 × 105–5 × 106 colony-forming units (CFUs) specified in the technical standard for disinfection. The calculation was based on the calculation method in Air Disinfection Effect Appraisal Test in Technical Standard for Disinfection (2002 Edition). At an air speed of 3.5 m/s, we used a digital electromagnetic induction air heater to disinfect flowing air containing 4.100 × 106 CFUs of B. subtilis spores and determined that the minimum disinfection temperature was 350 °C for a killing rate of 99.99%. At 400 °C, additional experiments using higher spore concentrations (4.700 × 106 ± 1.871 × 105 CFU) and a higher airspeed (4 m/s) showed that the killing rate remained>99.99%. B. subtilis spores, as a biological indicator for testing the efficiency of dry-heat sterilization, were killed by the high temperatures used in this system. The proposed method used to test the flowing air disinfector is simple, stable, and effective. This study provides a reference for the development of test systems that can assess the disinfection ability of flowing air disinfectors.

Grouting sleeves are widely used in the field of assembled construction. The present study aims to investigate the reliability of grouting sleeves under large-deformation repeated tension and compression after high temperature, considering the influences of steel bar diameter, the cooling method, and the protective layer. Through experimentation on 28 test pieces, we analyzed the bonding performance of the test pieces at different high temperatures. The results indicate that within the temperature range of 20–800 °C, the bond performance of the test pieces declines by no more than 9.8%. However, upon reaching a temperature of 1000 °C, the bond performance of the test pieces decreases by over 33.7%, with the compressive strength of the grout material reduced to only 27.50% of that kept at 20 °C. Employing larger-diameter steel bars is advantageous for maintaining the bond performance of the test pieces. Natural cooling shows relatively good bond performance, although its influence is not significant. Furthermore, the protective layer effectively attenuates the heating rate of the test pieces, thus safeguarding their bond performance. Scanning electron microscopy (SEM) analysis reveals that the decomposition of C-H and C-S-H phases is the primary cause of high-temperature degradation of the grouting material. Finally, a recommendation for the correlation coefficient (k) between the average bond strength and the compressive strength of the grout material is proposed, with a suggested value of k ≤ 2.58.

X chromosome dosage compensation (XDC) refers to the process by which X-linked genes acquire expression equivalence between two sexes. Ohno proposed that XDC is achieved by two-fold upregulations of X-linked genes in both sexes and by silencing one X chromosome (X chromosome inactivation, XCI) in females. However, genes subject to two-fold upregulations as well as the underlying mechanism remain unclear. It’s reported that gene dosage changes may only affect X-linked dosage-sensitive genes, such as protein complex coding genes (PCGs). Our results showed that in human PCGs are more likely to escape XCI and escaping PCGs (EsP) show two-fold higher expression than inactivated PCGs (InP) or other X-linked genes at RNA and protein levels in both sexes, which suggest that EsP may achieve upregulations and XDC. The higher expressions of EsP possibly result from the upregulations of the single active X chromosome (Xa), rather than escaping expressions from the inactive X chromosome (Xi). EsP genes have relatively high expression levels in humans and lower dN/dS ratios, suggesting that they are likely under stronger selection pressure over evolutionary time. Our study also suggests that SP1 transcription factor is significantly enriched in EsP and may be involved in the up-regulations of EsP on the active X. Finally, human EsP genes in this study are enriched in the toll-like receptor pathway, NF-kB pathway, apoptotic pathway, and abnormal mental, developmental and reproductive phenotypes. These findings suggest misregulations of EsP may be involved in autoimmune, reproductive, and neurological diseases, providing insight for the diagnosis and treatment of these diseases.

In this investigation, a U-shaped connection (U-C) was introduced for a prefabricated steel plate shear wall with beam-only connections. This design replaces a portion of shear bolts with tension bolts to enhance bolt efficiency and reduce the overall bolt count, and it is suitable for a prefabricated high-rise steel structure. Four 1/3 scale specimens were designed, and an array of performance aspects including failure modes, hysteretic behavior, skeleton curves, energy dissipation capacity, stiffness degradation, and key performance indicators were systematically investigated through a combination of quasi-static tests and finite element analyses. The results showed that the combination arrangement of tensile and shear bolts in U-C effectively reduced the usage of bolts used and reduced installation costs; under low cycle reciprocating loads, the ultimate bearing capacity and energy dissipation capacity of a beam-only-connected prefabricated steel plate shear wall with U-shaped connection (BPSW-U) had slightly decreased compared with the prefabricated steel plate shear wall with discontinuous cover-plate connection (DCPC). Nevertheless, the BPSW-U excelled in preserving the integrity of the frame beams, channeling structural plastic deformations primarily into the infilled steel plate. This design feature ensures that post-earthquake functionality recovery can be achieved by simply replacing the infilled steel plate.

For local advanced rectal cancer (LARC), total neoadjuvant treatment (TNT) has shown more complete response (CR), reduced risk of distant metastasis (DM) and increase of the sphincter preservation rate. Now it is the one and only recommendation for high-risk group of LARC according to National Comprehensive Cancer Network (NCCN) rectal cancer guideline, while it is also preferentially recommended for low-risk group of LARC. TNT is also beneficial for distant rectal cancer patients who have need for organ preservation. Even though the prognostic value of programmed cell death-ligand 1 (PD-L1) in the neoadjuvant chemoradiotherapy (NACRT) of LARC patients is undetermined yet, the combination of NACRT and programmed cell death-1 (PD-1)/PD-L1 antibodies seem bring new hope for mismatch repair proficient (pMMR)/microsatellite stable (MSS) LARC patients. Accumulating small sample sized studies have shown that combining NACRT with PD-1/PD-L1 antibody yield better short-term outcomes for pMMR/MSS LARC patients than historic data. However, ideal total dose and fractionation of radiotherapy remains one of unresolved issues in this combination setting. Thorough understanding the impact of radiotherapy on the tumor microenvironment and their interaction is needed for in-depth understanding and exquisite design of treatments combination model.

Declined regenerative potential and aggravated inflammation upon aging create an inappropriate environment for arterial regeneration. Macrophages are one of vital effector cells in the immune microenvironment, especially during biomaterials mediated repairing process. Here, we revealed that the macrophage autophagy decreased with aging, which led to aggravated inflammation, thereby causing poor vascular remodeling of artificial grafts in aging body. Through loading the autophagy-targeted drugs, rapamycin and 3-MA (3-methyladenine), in PCL (polycaprolactone) sheath of the PGS (poly glycerol sebacate) - PCL vascular graft, the essential role of macrophage autophagy was confirmed in regulating macrophage polarization and biomaterial degradation. Moreover, the utilization of rapamycin promoted anti-inflammatory polarization of macrophage by activating autophagy, which further promoted myogenic differentiation of vascular progenitor cells and accelerated endothelialization. Our study elucidated the contribution of pharmacological manipulation of macrophage autophagy in promoting regeneration of small caliber artery, which may pave a new avenue for clinical translation of vascular grafts in aging body.

In existing models with an unknown link function, the issue of predictors containing both multiple functional data and multiple scalar data has not been studied. To fill this gap, we propose a generalized partially functional linear model, which not only models the relationship between multiple scalar and functional predictors and responses, but also automatically estimates the link function. Specifically, we use the functional principal component analysis method to reduce the dimensionality of functional predictors, estimate the regression coefficients using the maximum likelihood estimation method, estimate the link function using the method of local linear regression, iteratively obtain the final estimator, and establish the asymptotic normality of the estimator. The asymptotic normality is illustrated through simulation experiments. Finally, the proposed model is applied to study the influence of environmental, economic, and medical levels on life expectancy in China. In the study, functional predictors are the daily air quality index, temperature, and humidity of 58 cities in 2020, and scalar predictors are GDP and the number of beds in hospitals. The experimental results indicate that the unknown link function model has a smaller prediction error and better performance than both the model with the known link function and the model without a link function.

ObjectiveSepsis is a life-threatening condition secondary to infection that evolves into a dysregulated host response and is associated with acute organ dysfunction. Sepsis-induced cardiac dysfunction is one of the most complex organ failures to characterize. This study performed comprehensive metabolomic profiling that distinguished between septic patients with and without cardiac dysfunction.MethodPlasma samples collected from 80 septic patients were analysed by untargeted liquid chromatography-mass spectrometry (LC-MS) metabolomics. Principal component analysis (PCA), partial least squares discrimination analysis (PLS-DA), and orthogonal partial least square discriminant analysis (OPLS-DA) were applied to analyse the metabolic model between septic patients with and without cardiac dysfunction. The screening criteria for potential candidate metabolites were as follows: variable importance in the projection (VIP) >1, P < 0.05, and fold change (FC) > 1.5 or < 0.7. Pathway enrichment analysis further revealed associated metabolic pathways. In addition, we constructed a subgroup metabolic analysis between the survivors and non-survivors according to 28-day mortality in the cardiac dysfunction group.ResultsTwo metabolite markers, kynurenic acid and gluconolactone, could distinguish the cardiac dysfunction group from the normal cardiac function group. Two metabolites, kynurenic acid and galactitol, could distinguish survivors and non-survivors in the subgroup analysis. Kynurenic acid is a common differential metabolite that could be used as a candidate for both diagnosis and prognosis for septic patients with cardiac dysfunction. The main associated pathways were amino acid metabolism, glucose metabolism and bile acid metabolism.ConclusionMetabolomic technology could be a promising approach for identifying diagnostic and prognostic biomarkers of sepsis-induced cardiac dysfunction.

Receptor activity modifying protein 1 (RAMP1) facilitates the localization of the calcitonin-like receptor (CLR) to the plasma membrane, but its role in osteosarcoma (OS) remains unclear. We evaluated the RAMP1 expression and prognostic value across different cancers, studying tumor immune infiltration. The prognostic value was analyzed using the GSE39058 and TARGET datasets. Differential gene expression was evaluated. a protein-protein interaction network was constructed, and gene set enrichment analysis was performed. The function of RAMP1 in the tumor microenvironment was analyzed, and its expression in OS cell lines was validated using quantitative real-time PCR. High RAMP1 expression correlated with poor prognosis relative to low RAMP1 expression (p < 0.05). Low RAMP1 expression correlated with an abundance of CD4+ memory-activated T cells. whereas a high expression level correlated with a high proportion of gamma-delta T cells (γδ T cells). Differentially expressed genes from TARGET was enriched in olfactory transduction pathways (normalized enrichment scores [NES] = 1.6998, p < 0.0001). RAMP1 expression negatively correlated with CD44 expression but positively correlated with TNFSF9 expression. The RAMP1 gene is substantially expressed in OS cells compared to the normal osteoblast cell line hFOB1.19. Thus, RAMP1 may be a prognostic biomarker and potential therapeutic target in OS.

Abstract In this paper, a generalized partially functional linear regression model is proposed and the asymptotic property of the proposed estimated coefficients in the model is established. Extensive simulation experiment results are consistent with the theoretical result. Finally, two application examples of the model are given. One is sleep quality study where we studied the effects of heart rate, percentage of sleep time on total sleep in bed, wake after sleep onset and number of wakening during the night on sleep quality in 22 healthy people. The other one is mortality rate where we studied the effects of air quality index, temperature, relative humidity, GDP per capita and the number of beds per thousand people on the mortality rate across 80 major cities in China.

Abstract Background The optimal treatment of stage IV rectal cancer remains controversial. The purpose of this study was to assess the treatment outcomes and toxicity of neoadjuvant chemotherapy and radiotherapy followed by local treatment of all tumor sites and subsequent adjuvant chemotherapy in stage IV rectal cancer patients with potentially resectable metastases. Methods Adult patients diagnosed with locally advanced rectal adenocarcinoma with potentially resectable metastases, who received neoadjuvant chemotherapy and radiotherapy from July 2013 and September 2019 at Sun Yat-sen University cancer center, were included. Completion of the whole treatment schedule, pathological response, treatment-related toxicity and survival were evaluated. Results A total of 228 patients were analyzed with a median follow-up of 33 (range 3.3 to 93.4) months. Eventually, 112 (49.1%) patients finished the whole treatment schedule, of which complete response of all tumor sites and pathological downstaging of the rectal tumor were observed in three (2.7%) and 90 (80.4%) patients. The three-year overall survival (OS) and progression-free survival (PFS) of all patients were 56.6% (50.2 to 63.9%) and 38.6% (95% CI 32.5 to 45.8%), respectively. For patients who finished the treatment schedule, 3-year OS (74.4% vs 39.2%, P

Small peptides provide the easily utilized nitrogen for rumen microbial and promote acetate generation for milk fat synthesis. However, the impacts of peptide supplements on lipometabolic processes were still unclear. Therefore, a total of 800 multiparous dairy herds (with an average live weight of 667.6 ± 39.4 kg, an average lactation of 89.3 ± 18.8 days, and an average calving parity of 2.76 ± 0.47) were randomly allocated to the control (CON) and the small peptide (SP) supplement (100 g/day for each cow) treatments, respectively. A 35-day-long feeding procedure that includes a 7-day-long pretreatment test and a 28-day-long treatment test was followed for all cows. Dry matter intake (DMI) was recorded every day and calculated by the deviation between the supply and residue, while the daily milk production was automatically recorded through the rotary milking facilities. Milk samples were collected from each replicate on the last day, followed by the milk quality and milk lipid composition measurement. Rumen fluid samples were collected on the last day through esophageal tubing 3 h after morning feeding for the determination of the underlying mechanism of the small peptide on lipid metabolism through the measurement of rumen lipometabolic-related metabolites and rumen bacterial communities. Results indicated that dry matter intake showed an increasing trend, while milk production and the milk fat content remarkably increased after SP supplement (P < 0.05). Further detailed detection showed the mainly increased milk composition focused on monounsaturated fatty acid (MUFA) and polyunsaturated fatty acid (PUFA). Acetate-producing microbes, such as Acetitomaculum, Bifidobacterium, Succiniclasticum, and Succinivibrio, and butyrate-producing microbes, such as Shuttleworthia and Saccharofermentans, significantly proliferated, which causatively brought the increased ruminal content of acetate, isobutyrate, and butyrate after SP supplement (P < 0.05) compared with CON. Lipometabolic metabolites such as phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylinositol (PI), phosphatidylserine (PS), triacylglycerol (TG), and Acetyl-CoA also significantly increased after SP supplement. In summary, SP supplements help to increase milk fat content through the proliferation of rumen bacterial communities, which provided more acetate and butyrate for milk fat synthesis combined with the promotion of ruminal lipometabolism.

BackgroundThe pathological T3N0M0 (pT3N0M0) rectal cancer is the earliest stage and has the best prognosis in the locally advanced rectal cancer, but the optimal treatment remains controversial. A reliable prognostic model is needed to discriminate the high-risk patients from the low-risk patients, and optimize adjuvant chemotherapy (ACT) treatment decisions by predicting the likelihood of ACT benefit for the target population.Patients and methodsWe gathered and analyzed 276 patients in Sun Yat-sen University Cancer Center from March 2005 to December 2011. All patients underwent total mesorectal excision (TME), without preoperative therapy, and were pathologically proven pT3N0M0 rectal cancer with negative circumferential resection margin (CRM). LASSO regression model was used for variable selection and risk factor prediction. Multivariable cox regression was used to develop the predicting model. Optimum cut-off values were determined using X-Tile plot analysis. The 10-fold cross-validation was adopted to validate the model. The performance of the nomogram was evaluated with its calibration, discrimination and clinical usefulness.ResultsA total of 188 patients (68.1%) had ACT and no patients had adjuvant radiotherapy. Age, monocyte percentage, carbohydrate antigen 19–9, lymph node dissection numbers and perineural invasion (PNI) were identified as significantly associated variables that could be combined for an accurate prediction risk of Cancer Specific Survival (CSS) for pT3N0M0 patients. The model adjusted for CSS showed good discrimination with a C-index of 0.723 (95% CI: 0.652–0.794). The calibration curves showed that the nomogram adjusted for CSS was able to predict 3-, 5-, and 10-year CSS accurately. The corresponding predicted probability was used to stratify high and low-risk patients (10-year CSS: 69.1% vs. 90.8%, HR = 3.815, 95%CI: 2.102–6.924, P < 0.0001). ACT improved overall survival (OS) in the low-risk patients (10-year OS: 91.9% vs. 83.3%, HR = 0.338, 95% CI: 0.135–0.848, P < 0.0001), while it did not exhibit a significant benefit in the high-risk patients.ConclusionThe present study showed that age, monocyte percentage, carbohydrate antigen 19–9, lymph node dissection numbers and PNI were independent prognostic factors for pT3N0M0 rectal cancer patients. A nomogram based on these prognostic factors effectively predicts CSS in patients, which can be conveniently used in clinical practice. ACT may improve overall survival in the low-risk patients. But the benefit of ACT was not seen in the high-risk patients.

In recent years, misinformation sharing has become the focus of public debate and academic research. We aim to explore whether individuals prefer to share accurate information or not, and discover what factors increase people’s preferences for sharing accurate information. Combining behavioral economics experiments and psychology experiments, we construct “an information search—information sharing—information feedback experiment” to examine individuals’ behavior of sharing accurate information and its influencing factors. A total of 210 students are recruited for the laboratory experiment. Our results show that when individuals can control the accuracy of the information they obtain through their efforts, they are more willing to share accurate information with others. We also find that positive feedback from information receivers can promote the accuracy of information shared by individuals, and this effect works through reciprocity norms. Individuals with higher reciprocity are more willing to share accurate information, especially in the treatment with the role of reciprocity norms enhanced by feedback. These findings indicate that individuals who are willing to obtain accurate information prefer to share information, and information feedback can enhance this preference through reciprocity norms. This study captures individuals’ behavior and preference characteristics with regard to the accuracy of the information they share in the era of highly developed network interaction.

BackgroundAnal canal squamous cell carcinoma (ACSCC) is an exceedingly rare malignant neoplasm with challenges in sphincter preservation, treatment toxicities and long-term survival. Little is known concerning the activity of PD-1 antibodies in locally advanced ACSCC. This study reports on the efficacy and toxicities of a neoadjuvant PD-1 blockade combined with chemotherapy followed by concurrent immunoradiotherapy in ACSCC patients, and describes biomarkers expression and mutation signatures.MethodsIn this cohort study, patients were treated as planned, including four cycles of neoadjuvant PD-1 antibody toripalimab combined with docetaxol and cisplatin, followed by radiotherapy and two cycles of concurrent toripalimab. Multiplex immunofluorescence staining (mIHC) with PD-L1, CD8, CD163, Pan-Keratin and DAPI was performed with the pretreatment tumor tissue. Whole exome sequencing was performed for the primary tumor and peripheral blood mononuclear cells. The primary endpoint was the complete clinical response (cCR) rate at 3 months after overall treatment. Acute and late toxicities graded were assessed prospectively.ResultsFive female patients with a median age of 50 years old (range, 43-65 years old), finished treatment as planned. One patient had grade 3 immune related dermatitis. Two patients had grade 3 myelosuppression during neoadjuvant treatment. No severe radiation-related toxicities were noted. Four patients with PD-L1 expression >1% achieved a cCR after neoadjuvant treatment. and the other patient with negative PD-L1 expression also achieved a cCR at 3 months after radiotherapy. All the patients were alive and free from disease and had a normal quality of life, with 19.6-24 months follow up. Inconsistent expression of PD-L1 and CD163 was detected in 3 and 5 patients, respectively. TTN, POLE, MGAM2 were the top mutation frequencies, and 80 significant driver genes were identified. Pathway analysis showed enrichment of apoptosis, Rap1, Ras, and pathways in cancer signaling pathways. Eight significantly deleted regions were identified.ConclusionsThis small cohort of locally advanced ACSCC patients had quite satisfactory cCR and sphincter preservation rate, after neoadjuvant PD-1 antibody toripalimab combined with chemotherapy followed by concurrent immunoradiotherapy, with mild acute and long-term toxicities.

PurposeImmune checkpoint blockade has led to a significant improvement of patient survival in metastatic colorectal cancer (CRC) with DNA mismatch repair-deficiency (dMMR)/microsatellite instability-high (MSI-H). However, not all these patients are sensitive to monoimmunotherapy. We firstly presented a case series of advanced dMMR/MSI-H CRCs treating with PD-1 inhibitor-based chemoradioimmunotherapy (CRIT).Methods and MaterialsWe assessed the short-term efficacy and safety of CRIT in advanced dMMR/MSI-H CRCs, and also did next-generation sequencing (NGS) assays.ResultsOur analysis included five advanced dMMR/MSI-H CRCs who have received toripalimab-based CRIT. Toripalimab was given 240mg every three weeks, and the radiation dose was 45-50 gray in 25 fractions. Chemotherapy regimens consisted of CAPOX in three patients, capecitabine in one patient, and mFOLFOX6 in one patient. Initially, two patients displayed complete response (CR), and three patients achieved partial response (PR) on imaging findings. Afterwards, one PR patient was confirmed pathological complete response after surgery, leading to three CR cases in total. Hematological toxicity was the most common adverse effect, and only two patients developed mild immune-related adverse effects besides. All the treatment-related adverse events were under control. Based on the NGS results, the median intratumor heterogeneity was 0.19 (range 0-0.957), which was less in CR patients than PR patients (P = 0.019). Genetic mutations at DNA damage repair genes and the JAK1 gene were also observed.ConclusionsFor advanced dMMR/MSI-H CRC, anti-PD-1 based CRIT is effective and safe. Further studies are required to better clarify the potential role and mechanism of CRIT as a viable therapeutic strategy in this population.

Sleep quality is related to people’s physical and mental health, so an accurate assessment of sleep quality is key to recognizing sleep disorders and taking effective interventions. To address the shortcomings of traditional manual and automatic staging methods, such as being time-consuming and having low classification accuracy, an automatic sleep staging method based on the null space pursuit (NSP) decomposition algorithm of single-channel electroencephalographic (EEG) signals is proposed, which provides a new way for EEG signal decomposition and automatic identification of sleep stages. First, the single-channel EEG signal data from the Sleep-EDF database, DREAMS Subject database, and Sleep Heart Health Study database (SHHS), available on PhysioNet, were preprocessed, respectively. Second, the preprocessed single-channel EEG signals were decomposed by the NSP algorithm. Third, we extracted nine features in the time domain of the nonlinear dynamics and statistics from the original EEG signal and the six simple signals that were decomposed. Finally, the extreme gradient boosting (XGBOOST) algorithm was used to construct a classification model to classify and identify the 63 extracted EEG signal features for automatic sleep staging. The experimental results showed that, on the Sleep-EDF database, the accuracy of four and five categories were 93.59% and 92.89%, respectively; on the DREAMS Subject database, the accuracy rates of four and five categories were 91.32% and 90.01%, respectively; on the SHHS database, the accuracy rates of four and five categories were 90.25% and 88.37%, respectively. The experimental results show that the automatic sleep staging model proposed in this work has high classification accuracy and efficiency, as well as strong applicability and robustness.

Abstract Profiling heterologous cell types within tumors is essential to decipher tumor microenvironment that shapes tumor progress and determines the outcome of therapeutic response. Here, we comprehensively characterized transcriptomes of 34,037 single cells obtained from 12 treatment‐naïve patients with colorectal cancer. Our comprehensive evaluation revealed attenuated B‐cell antigen presentation, distinct regulatory T‐cell clusters with different origin and novel polyfunctional tumor associated macrophages associated with CRC. Moreover, we identified expanded XCL1+ T‐cell clusters associated with tumor mutational burden high status. We further explored the underlying molecular mechanisms by profiling epigenetic landscape and inferring transcription factor motifs using single‐cell ATAC‐seq. Our dataset and analysis approaches herein provide a rich resource for further study of the impact of immune cells and translational research for human colorectal cancer.

Background/Aims: Glioblastoma multiforme (GBM) is a malignant and aggressive central nervous system (CNS) tumor with high mortality and low survival rate. Effective treatment of GMB is a challenge worldwide. Temozolomide (TMZ) is a drug used to treat GBM, while the survival period of GBM patients with positive treatment remains less than 15 months. Reactivating p53 and Inducing Tumor Apoptosis (RITA) is a novel potential anti-cancer small molecular drug. Thus, it is essential to discover novel targets or develop effective drugs combination strategy to treat GBM. Methods: The U87 cells and U251 cells (p53 mutated) were treated with DMSO and 1, 5,10, 20 μM RITA, TMZ, RITA+TMA or PFT-α. The cell proliferation was measured using the MTS cell proliferation assay. The cell apoptosis was analyzed by Annexin V-FITC/PI Apoptosis Detection Kit. The key protein expression level was evaluated by WB. Molecular docking and molecular dynamics (MD) simulation methods were applied to simulate the interaction between RITA and ASK1. Results: Herein, we found that combination RITA and TMZ effectively inhibited the proliferation of U87 cells and promoted the apoptosis of U87 cells. Then the mechanism of RITA and TMZ treating GBM were further studied by detecting the expression of the proteins associating with p53 pathway, such as ASK1, Bax, and so on. RITA bound to the amino acids residues in the activation domain of the ASK1, then induced the conformation change of ASK1 receptor, activated ASK1 and caused a series of signal transduction, further resulted in the physiological effects. Conclusion: Taken together, the RITA suppressed the cell proliferation in glioblastoma via targeting ASK1.

Oridonin (ORI) has been shown to inhibit tumor cell growth and proliferation in vitro, while its optimum anti-tumor activity in vivo is limited due to the poor aqueous solubility and bioavailability. In this study, to improve the bioavailability, we developed a nanoparticle-based drug delivery system to facilitate delivery of ORI to breast tumor. ORI was encapsulated in biodegradable nanoparticles (NPs) based on poly-lactic-co-glycolic acid (PLGA) and polyethylene glycol (PEG) to form ORI NPs (ORI-NPs). The resulting ORI-NPs exhibited a mean particle diameter of 100 nm and displayed an efficient cellular uptake by human breast cancer MCF-7 cells. Compared to free ORI that showed no effects on tumor cell proliferation, the ORI-NPs showed significant cytotoxicity and delayed endothelial cell migration, tube formation and angiogenesis. Pharmacokinetics studies showed that ORI-NPs significantly increased the half-life of ORI in the blood circulation. In the nude mouse xenograft model, ORI-NPs markedly inhibited tumor growth and angiogenesis, while ORI did not show any inhibitory effects on the growth of tumor xenografts. The mechanism experiments showed that the antitumor activity of ORI-NPs against breast cancer might be through ROS related Nrf2/HO-1 signaling pathway. Together, these results demonstrated that ORI-loaded PEG-PLGA NPs enhanced bioactivity and bioavailability in vivo over ORI, indicating that ORI-NPs may represent a promisingly effective candidate against breast cancer.

This article proposes an Analytic Hierarchy Process Dempster-Shafer (AHP-DS) and similarity-based network selection algorithm for the scenario of dynamic changes in user requirements and network environment; combines machine learning with network selection and proposes a decision tree-based network selection algorithm; combines multiattribute decision-making and genetic algorithm to propose a weighted Gray Relation Analysis (GRA) and genetic algorithm-based network access decision algorithm. Firstly, the training data is obtained from the collaborative algorithm, and it is used as the training set, and the network attributes are used as the attribute set, and the continuous attributes are discretized by dichotomization, and the attribute that can make the greatest information gain is selected as the division feature, and a decision tree with strong generalization ability is finally obtained, which is used as the decision basis for network access selection. The simulation results show that the algorithm proposed in this thesis can effectively improve user service quality under three services, and the algorithm is simple and effective with low complexity. It first uses AHP-DS hierarchical analysis to establish a recursive hierarchy for the network selection problem and obtains the subjective weights of network attributes through the judgment matrix. Then, it uses a genetic algorithm to adjust the subjective weight, defines the fitness function in the genetic algorithm-based on gray correlation analysis, adjusts the weights of the selection operator, crossover operator, and variation operator in the genetic algorithm, and gets the network with the largest fitness as the target network, which can effectively improve the user service quality.

In this study, the effect of 8% UEA the reason why the UEA content is 8% is as follows: the expansion agent content in the actual mix proportion of the project is 8%, which is selected in this test to fit the reality better. expansion agent on the compressive strength, chloride ion penetration resistance, and carbonation resistance of civil air defense concrete were studied by simulating the rapid carbonation and chloride solution immersion of concrete structure in coastal civil air defense engineering environment. The results of this study show that the early compressive strength of concrete decreased by adding the UEA expansion agent and was also affected by the curing time. Moreover, the addition of UEA expansion agent decreased the content of free chloride ions and calcium carbonate in concrete and reduced the early compressive strength of concrete.

Cr and Al coating were respectively deposited on Zr-4 alloy by magnetron sputtering and high temperature oxidation (HTO) tests were conducted in air environment at 1200 °C for 3 h for Cr-coated and Al-coated specimens. The morphology and phase composition of the specimens were detected by SEM, EDS and XRD. The adhesion properties were characterized by scratch test. The XRD results revealed that the two coatings were crystalline with preferred orientation. The results of scratch testing showed that critical load of Cr coating was higher than that of Al coating. After HTO test, the Cr-coated specimen was intact without cracking and spalling off, only the outermost layer of Cr coating was oxidized to a Cr2O3 layer of about 4 μm thick with a residual Cr layer of about 4 μm thick, and the internal zirconium alloy was not oxidized. For Al-coated specimen, besides the complete oxidation of the Al coating, there were also about 500 μm Zr-4 alloy oxidized on each side, and there were a lot of voids and cracks in the specimen. The EDS results indicated that a thickness of about 5 μm Cr-Zr diffusion layer developed at the interface between Cr coating and Zr-4 alloy for the Cr-coated Zr-4 specimen. While, for the Al-coated Zr-4 specimen, Al diffused into the specimen to a depth of about 100 μm, and Zr diffused almost to the outermost layer. Moreover, Sn in the Zr-4 alloy is concentrated at the interface between the residual Zr-4 alloy and ZrO2 layer. The obtained results manifested that Cr coating shows better oxidation resistance than Al coating.

Radiotherapy (RT) is a key component of neoadjuvant chemoradiotherapy to treat locally advanced rectal cancer (LARC). However, the therapeutic effect is limited due to radioresistance. Investigating the biomarkers of radioresistance might assist in the development of more effective therapeutic strategies for LARC.In this study, we investigated the different gene expressions in tumor samples from 110 patients using transcriptome analysis and immunohistochemistry (IHC), and identified serum- and glucocorticoid-regulated kinase 1 (SGK1) as a modulator of LARC radioresistance. We evaluated the impact of genetic and pharmacologic inhibition of the gene associated with radioresistance in vitro and in vivo. We found that the expression of SGK1 was upregulated in non-pathological complete response (non-pCR) patients. A high SGK1 expression was associated with radioresistance, whereas the genetic or pharmacologic inhibition of SGK1 expression reduced the radioresistance. We found that activate transcription factor 3 (ATF3) is a regulator of SGK1 in radioresistance.In conclusion, our findings indicate that SGK1 is a key player in LARC radioresistance, and drives radioresistance in an ATF3 dependent manner, which provides insights for future radio-sensitizer design.

CD47 is an immunoglobulin that is overexpressed on the surface of many types of cancer cells. CD47 forms a signaling complex with signal-regulatory protein α (SIRPα), enabling the escape of these cancer cells from macrophage-mediated phagocytosis. In recent years, CD47 has been shown to be highly expressed by various types of solid tumors and to be associated with poor patient prognosis in various types of cancer. A growing number of studies have since demonstrated that inhibiting the CD47-SIRPα signaling pathway promotes the adaptive immune response and enhances the phagocytosis of tumor cells by macrophages. Improved understanding in this field of research could lead to the development of novel and effective anti-tumor treatments that act through the inhibition of CD47 signaling in cancer cells. In this review, we describe the structure and function of CD47, provide an overview of studies that have aimed to inhibit CD47-dependent avoidance of macrophage-mediated phagocytosis by tumor cells, and assess the potential and challenges for targeting the CD47-SIRPα signaling pathway in anti-cancer therapy.

Seed dormancy and germination are important agronomic traits in wheat (Triticum aestivum L.) because they determine pre-harvest sprouting (PHS) resistance and thus affect grain production. These processes are regulated by Gibberellic Acid-Stimulated Regulator (GASR) genes. In this study, we identified 37 GASR genes in common wheat, which were designated TaGASR1-37. Moreover, we identified 40 pairs of paralogous genes, of which only one had a Ka/Ks value greater than 1, indicating that most TaGASR genes have undergone negative selection. Chromosomal location and duplication analysis revealed 25 pairs of segmentally duplicated genes and seven pairs of tandemly duplicated genes, suggesting that large-scale duplication events may have contributed to the expansion of TaGASR gene family. Microarray analysis of the expression of 18 TaGASR genes indicated that these genes play diverse roles in different biological processes. Using wheat varieties with contrasting seed dormancy phenotypes, we investigated the expression patterns of TaGASR genes and the corresponding seed germination index phenotypes in response to water imbibition, exogenous ABA and GA treatment, and low- and high-temperature treatment. Based on these data, we identified the TaGASR34 gene as potentially associated with seed dormancy and germination. Further, we used a SNP mutation of the TaGASR34 promoter (-16) to develop the CAPS marker GS34-7B, which was then used to validate the association of TaGASR34 with seed dormancy and germination by evaluating two natural populations across environments. Notably, the frequency of the high-dormancy GS34-7Bb allele was significantly lower than that of the low-dormancy GS34-7Ba allele, implying that the favorable GS34-7Bb allele has not previously been used in wheat breeding. These results provide valuable information for further functional analysis of TaGASR genes and present a useful gene and marker combination for future improvement of PHS resistance in wheat.

Estimating the changes in the spatial–temporal characteristics of extreme temperature events under future climate scenarios is critical to provide reference information to help mitigate climate change. In this study, we analyzed 16 extreme temperature indices calculated based on downscaled data from 28 Global Climate Models (GCMs) that were obtained from Coupled Model Intercomparison Project Phase 5 (CMIP5) under Representative Concentration Pathway (RCP) 4.5 and 8.5 scenarios in the Han River Basin (HRB). The results indicate that the downscaled data from 28 GCMs reproduced a consistent sign of recent trends for all extreme temperature indices except the DTR for the historical period (1961–2013). We found significantly increasing trends for the warm extreme indices (i.e., TXx, TNx, TX90p, TN90p, SU, TR, and WSDI) and considerably decreasing trends for the cold extreme indices (i.e., TX10p, TN10p, CSDI, FD, ID) under both the RCP4.5 and 8.5 scenarios for 2021–2100. Spatially, great changes in warm extremes will occur in the west and southeast of the HRB in the future. The projected changes in extreme temperatures will impact the eco-environment and agricultural production. Our findings will help regional managers adopt countermeasures and strategies to adapt to future climate change, especially extreme weather events.

Titanium nitride (TiN) coatings were deposited on Zr-4 substrate by direct current magnetron sputtering. The microstructural property of the as-deposited coating was studied by means of x-ray diffraction (XRD). The microstructural parameters, such as crystal size, lattice strain, lattice deformation stress and lattice deformation energy density, were investigated in detail by employed modified Debye–Scherrer method (MDS) and Williamson-Hall methods by assuming three models namely uniform deformation model, uniform stress deformation model and uniform energy density deformation model. And the effects of sputtering power, substrate temperature and substrate bias on microstructural parameters were investigated. The results show that TiN coating deposited by magnetron sputtering presents lattice compressive strain, except for sample X3 - 1 which is prepared by substrate bias of −50 V. It is also shown that sputtering power, substrate temperature and substrate bias have great influence on crystal size, lattice strain, lattice deformation stress and lattice deformation energy density of the as-deposited TiN coating. Especially the influence of substrate bias is very significant.

IntroductionTo evaluate the prognostic value of gross tumor volume (TV) in patients with locally recurrent, nonmetastatic nasopharyngeal carcinoma.MethodsBetween 2001 and 2012, 291 consecutive patients with locally recurrent, nonmetastatic nasopharyngeal carcinoma underwent salvage IMRT were retrospectively reviewed. The correlations between TV and recurrent T classification were analyzed. Survival analyses were performed. Receiver operating characteristic (ROC) curves were calculated to identify cut-off point of TV. The Akaike information criterion and Harrell's concordance index (c-index) were utilized to test the prognostic value.ResultsThe median TV significantly increased with advancing recurrent T classification (PConclusionsOur data suggests TV is a significant prognostic factor for predicting the distant metastasis, overall survival and toxicity-related death of patients with locally recurrent, nonmetastatic nasopharyngeal carcinoma after salvage IMRT. TV should be considered when designing personalized salvage treatments for these patients. For patients with bulky local recurrent tumor, radiation may need to be de-emphasized in favor of systemic treatment or best supportive care.

Radiation therapy (RT) continues to be one of the most popular treatment options for localized prostate cancer (CaP). The purpose of the study was to investigate the in vitro effect of LBH589 alone and in combination with RT on the growth and survival of CaP cell lines and the possible mechanisms of radiosensitization of this combination therapy. The effect of LBH589 alone or in combination with RT on two CaP cell lines (PC-3 and LNCaP) and a normal prostatic epithelial cell line (RWPE-1) was studied by MTT and clonogenic assays, cell cycle analysis, western blotting of apoptosis-related and cell check point proteins, and DNA double strand break (DSB) repair markers. The immunofluorescence staining was used to further confirm DSB expression in treated CaP cells. Our results indicate that LBH589 inhibited proliferation in both CaP and normal prostatic epithelial cells in a time-and-dose-dependent manner; low-dose of LBH589 (IC20) combined with RT greatly improved efficiency of cell killing in CaP cells; compared to RT alone, the combination treatment with LBH589 and RT induced more apoptosis and led to a steady increase of sub-G1 population and abolishment of RT-induced G2/M arrest, increased and persistent DSB, less activation of non-homologous end joining (NHEJ)/homologous recombination (HR) repair pathways and a panel of cell cycle related proteins. These results suggest that LBH589 is a potential agent to increase radiosensitivity of human CaP cells. LBH589 used either alone, or in combination with RT is an attractive strategy for treating human CaP.

CD44 and CD147 are associated with cancer metastasis and progression. Our purpose in the study was to investigate the effects of down-regulation of CD44 or CD147 on the metastatic ability of prostate cancer (CaP) cells, their docetaxel (DTX) responsiveness and potential mechanisms involved in vitro and in vivo. CD44 and CD147 were knocked down (KD) in PC-3M-luc CaP cells using short hairpin RNA (shRNA). Expression of CD44, CD147, MRP2 (multi-drug resistance protein-2) and MCT4 (monocarboxylate tranporter-4) was evaluated using immunofluorescence and Western blotting. The DTX dose-response and proliferation was measured by MTT and colony assays, respectively. The invasive potential was assessed using a matrigel chamber assay. Signal transduction proteins in PI3K/Akt and MAPK/Erk pathways were assessed by Western blotting. An in vivo subcutaneous (s.c.) xenograft model was established to assess CaP tumorigenecity, lymph node metastases and DTX response. Our results indicated that KD of CD44 or CD147 decreased MCT4 and MRP2 expression, reduced CaP proliferation and invasive potential and enhanced DTX sensitivity; and KD of CD44 or CD147 down-regulated p-Akt and p-Erk, the main signal modulators associated with cell growth and survival. In vivo, CD44 or CD147-KD PC-3M-luc xenografts displayed suppressed tumor growth with increased DTX responsiveness compared to control xenografts. Both CD44 and CD147 enhance metastatic capacity and chemoresistance of CaP cells, potentially mediated by activation of the PI3K and MAPK pathways. Selective targeting of CD44/CD147 alone or combined with DTX may limit CaP metastasis and increase chemosensitivity, with promise for future CaP treatment.

In this study, a vibration equation for axially moving truncated conical thin shells made of functionally gradient materials with uniformly and non-uniformly distributed pores has been established based on classical thin shell theory. The free vibration and dynamic response solutions are obtained using the Galerkin method. The effects of axial velocity, half cone angle, ceramic material mass composition, material component index, and internal porosity on the free vibration and dynamic response of mentioned shells were analyzed and discussed. The results show that the increase of axial velocity, half cone angle, and material composition index all decrease the natural frequency of the truncated conical shell but amplify its dynamic response, and the rise of the mass fraction of the ceramic material increases the natural frequency of the truncated conical shell but reduces the dynamic response. The results also demonstrate that compared with non-uniformly distributed pores, the effects of uniformly distributed pores on the shells’ dynamic responses are more evident under axial motion. [ABSTRACT FROM AUTHOR]