Search

Modular integrated construction (MiC) is an innovative construction method that is widely used in practice, but high transportation cost is an obstacle to its wider implementation. This paper is motivated by the real-world need for a scientific approach for MiC transport scheduling, and addresses the practical problem of how to achieve on-time door-to-door MiC delivery in an economical manner. An innovative integer programming model is formulated with the objective of minimising the total transportation costs, including trailer rental, fuel costs, and worker salaries. A case study based on Hong Kong data validates that the developed model can be efficiently solved for problems of practical size. The results also demonstrate that the derived MiC schedule plan can reduce transportation costs by 58.7% compared with a just-in-time (JIT) strategy, thus bringing great economic benefits to off-site construction practitioners. Useful managerial implications related to on-site MiC storage areas are derived through sensitivity analysis. Overall, this paper sets the ground for the application of mathematical programming methodology to the off-site construction field. Future research may be devoted to MiC transport scheduling under uncertainty. [ABSTRACT FROM AUTHOR]

Glass transition, commonly manifested upon cooling a liquid, is continuous and cooling rate dependent. For decades, the thermodynamic basis in liquid–glass transition has been at the center of debate. Here, long-time isothermal annealing was conducted via molecular dynamics simulations for metallic glasses to explore the connection of physical aging in supercooled liquid and glassy states. An anomalous two-step aging is observed in various metallic glasses, exhibiting features of supercooled liquid dynamics in the first step and glassy dynamics in the second step, respectively. Furthermore, the transition potential energy is independent of initial states, proving that it is intrinsic for a metallic glass at a given temperature. We propose that the observed dynamic transition from supercooled liquid dynamics to glassy dynamics could be glass transition manifested isothermally. On this basis, glass transition is no longer cooling rate dependent, but is shown as a clear phase boundary in the temperature-energy phase diagram. Hence, a modified out-of-equilibrium phase diagram is proposed, providing new insights into the nature of glass transition. [ABSTRACT FROM AUTHOR]

Serial CA125 and second line transvaginal ultrasound (TVS) screening in the UKCTOCS indicated a shift towards detection of earlier stage ovarian cancer (OvCa), but did not yield a significant mortality reduction. There remains a need to establish additional biomarkers that can complement CA125 for even earlier and at a larger proportion of new cases. Using a cohort of plasma samples from 219 OvCa cases (59 stage I/II and 160 stage III/IV) and 409 female controls and a novel Sensitivity Maximization At A Given Specificity (SMAGS) method, we developed a blood-based metabolite-based test consisting of 7 metabolites together with CA125 for detection of OvCa. At a 98.5% specificity cutpoint, the metabolite test achieved sensitivity of 86.2% for detection of early-stage OvCa and was able to capture 64% of the cases with low CA125 levels (< 35 units/mL). In an independent test consisting of 65 early-stage OvCa cases and 141 female controls, the metabolite panel achieved sensitivity of 73.8% at a 91.4% specificity and captured 13 (44.8%) out of 29 early-stage cases with CA125 levels < 35 units/mL. The metabolite test has utility for ovarian cancer screening, capable of improving upon CA125 for detection of early-stage disease. [ABSTRACT FROM AUTHOR]

Deficit of oxygen and nutrients in the tumor microenvironment (TME) triggers abnormal angiogenesis that produces dysfunctional and leaky blood vessels, which fail to adequately perfuse tumor tissues. Resulting hypoxia, exacerbation of metabolic disturbances, and generation of an immunosuppressive TME undermine the efficacy of anticancer therapies. Use of carefully scheduled angiogenesis inhibitors has been suggested to overcome these problems and normalize the TME. Here, we propose an alternative agonist-based normalization approach using a derivative of the C-type natriuretic peptide (dCNP). Multiple gene expression signatures in tumor tissues were affected in mice treated with dCNP. In several mouse orthotopic and subcutaneous solid tumor models including colon and pancreatic adenocarcinomas, this well-tolerated agent stimulated formation of highly functional tumor blood vessels to reduce hypoxia. Administration of dCNP also inhibited stromagenesis and remodeling of the extracellular matrix and decreased tumor interstitial fluid pressure. In addition, treatment with dCNP reinvigorated the antitumor immune responses. Administration of dCNP decelerated growth of primary mouse tumors and suppressed their metastases. Moreover, inclusion of dCNP into the chemo-, radio-, or immune-therapeutic regimens increased their efficacy against solid tumors in immunocompetent mice. These results demonstrate the proof of principle for using vasculature normalizing agonists to improve therapies against solid tumors and characterize dCNP as the first in class among such agents. Editor's summary: Tumors often have abnormal and dysfunctional blood vessels that are in part responsible for poor drug delivery and thus reduced efficacy of treatment. Here, Lu et al. have developed a derivative of the C-type natriuretic peptide (dCNP) to normalize vascular structures of tumors to improve therapy efficacy. They demonstrated that this modified dCNP had superior pharmacokinetic and pharmacodynamic properties as compared with native CNP. In addition, administration of dCNP to multiple mouse models remodeled tumor blood vessels and improved antitumorigenic activity of standard monotherapies. This represents a promising compound that could improve therapeutic efficacy of multiple therapies for patients with cancer that requires further study. —Dorothy Hallberg [ABSTRACT FROM AUTHOR]

Background: Tuberculosis (TB) is a major infectious disease with significant public health implications. Its widespread transmission, prolonged treatment duration, notable side effects, and high mortality rate pose severe challenges. This study examines the epidemiological characteristics of TB globally and across major regions, providing a scientific basis for enhancing TB prevention and control measures worldwide. Methods: The ecological study used data from the Global Burden of Disease (GBD) Study 2021. It assessed new incidence cases, deaths, disability-adjusted life years (DALYs), and trends in age-standardized incidence rates (ASIRs), mortality rates (ASMRs), and DALY rates for drug-susceptible tuberculosis (DS-TB), multidrug-resistant tuberculosis (MDR-TB), and extensively drug-resistant tuberculosis (XDR-TB) from 1990 to 2021. A Bayesian age-period-cohort model was applied to project ASIR and ASMR. Results: In 2021, the global ASIR for all HIV-negative TB was 103.00 per 100,000 population [95% uncertainty interval (UI): 92.21, 114.91 per 100,000 population], declining by 0.40% (95% UI: − 0.43, − 0.38%) compared to 1990. The global ASMR was 13.96 per 100,000 population (95% UI: 12.61, 15.72 per 100,000 population), with a decline of 0.44% (95% UI: − 0.61, − 0.23%) since 1990. The global age-standardized DALY rate for HIV-negative TB was 580.26 per 100,000 population (95% UI: 522.37, 649.82 per 100,000 population), showing a decrease of 0.65% (95% UI: − 0.69, − 0.57 per 100,000 population) from 1990. The global ASIR of MDR-TB has not decreased since 2015, instead, it has shown a slow upward trend in recent years. The ASIR of XDR-TB has exhibited significant increase in the past 30 years. The projections indicate MDR-TB and XDR-TB are expected to see significant increases in both ASIR and ASMR from 2022 to 2035, highlighting the growing challenge of drug-resistant TB. Conclusions: This study found that the ASIR of MDR-TB and XDR-TB has shown an upward trend in recent years. To reduce the TB burden, it is essential to enhance health infrastructure and increase funding in low-SDI regions. Developing highly efficient, accurate, and convenient diagnostic reagents, along with more effective therapeutic drugs, and improving public health education and community engagement, are crucial for curbing TB transmission. [ABSTRACT FROM AUTHOR]

Background: The co-infection of human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) and tuberculosis (TB) poses a significant clinical challenge and is a major global public health issue. This study aims to elucidate the disease burden of HIV-TB co-infection in global, regions and countries, providing critical information for policy decisions to curb the HIV-TB epidemic. Methods: The ecological time-series study used data from the Global Burden of Disease (GBD) Study 2021. The data encompass the numbers of incidence, prevalence, mortality, and disability-adjusted life year (DALY), as well as age-standardized incidence rate (ASIR), prevalence rate (ASPR), mortality rate (ASMR), and DALY rate for HIV-infected drug-susceptible tuberculosis (HIV-DS-TB), HIV-infected multidrug-resistant tuberculosis (HIV-MDR-TB), and HIV-infected extensively drug-resistant tuberculosis (HIV-XDR-TB) from 1990 to 2021. from 1990 to 2021. The estimated annual percentage change (EAPC) of rates, with 95% confidence intervals (CIs), was calculated. Results: In 2021, the global ASIR for HIV-DS-TB was 11.59 per 100,000 population (95% UI: 0.37–13.05 per 100,000 population), 0.55 per 100,000 population (95% UI: 0.38–0.81 per 100,000 population), for HIV-MDR-TB, and 0.02 per 100,000 population (95% UI: 0.01–0.03 per 100,000 population) for HIV-XDR-TB. The EAPC for the ASIR of HIV-MDR-TB and HIV-XDR-TB from 1990 to 2021 were 4.71 (95% CI: 1.92–7.59) and 13.63 (95% CI: 9.44–18.01), respectively. The global ASMR for HIV-DS-TB was 2.22 per 100,000 population (95% UI: 1.73–2.74 per 100,000 population), 0.21 per 100,000 population (95% UI: 0.09–0.39 per 100,000 population) for HIV-MDR-TB, and 0.01 per 100,000 population (95% UI: 0.00–0.03 per 100,000 population) for HIV-XDR-TB in 2021. The EAPC for the ASMR of HIV-MDR-TB and HIV-XDR-TB from 1990 to 2021 were 4.78 (95% CI: 1.32–8.32) and 10.00 (95% CI: 6.09–14.05), respectively. Conclusions: The findings indicate that enhancing diagnostic and treatment strategies, strengthening healthcare infrastructure, increasing access to quality medical care, and improving public health education are essential to combat HIV-TB co-infection. [ABSTRACT FROM AUTHOR]

To repair and extend the service life of mobile-contact parts, laser cladding technology was applied to prepare CrB2/Cu coating on Cu–Cr alloy substrate, which was simulated as actual servicing parts, and the current-carrying friction property, including that friction coefficient, wear rate as well as current-carrying efficiency were studied. Results show that most of the CrB2 particles retain while some decompose into CrBx phases during the laser cladding process. With the increase of electric current, the average friction coefficient of CrB2/Cu coating grows first followed by going down. In comparison to the CrB2/Cu coating, the wear rate and average friction coefficient of QCr0.5 substrate always grow with increasing electric current values. When the current is 20A, the COF and wear rate of composite coating are about 0.737 and 1.37 × 10–4 mm3/N•m, which are about 21% and 79% of that of QCr0.5 alloy, respectively, and the major wear mechanism of CrB2/Cu coating is the adhesive wear. Moreover, the CrB2/Cu composite coating has low friction coefficient, low wear rate and high current-carrying efficiency under high electric currents, as a consequence, the CrB2/Cu coating has better current-carrying friction and wear performance under high current conditions. [ABSTRACT FROM AUTHOR]

Background: LARC patients commonly receive adjuvant therapy, however, hidden micrometastases still limit the improvement of OS. This study aims to investigate the impact of VASN in rectal cancer with pulmonary metastasis and understand the underlying molecular mechanisms to guide adjuvant chemotherapy selection. Methods: Sequencing data from rectal cancer patients with pulmonary metastasis from Sun Yat-sen University Cancer Center (SYSUCC) and publicly available data were meticulously analyzed. The functional role of VASN in pulmonary metastasis was validated in vivo and in vitro. Coimmunoprecipitation (co-IP), immunofluorescence, and rescue experiments were conducted to unravel potential molecular mechanisms of VASN. Moreover, VASN expression levels in tumor samples were examined and analyzed for their correlations with pulmonary metastasis status, tumor stage, adjuvant chemotherapy benefit, and survival outcome. Results: Our study revealed a significant association between high VASN expression and pulmonary metastasis in LARC patients. Experiments in vitro and in vivo demonstrated that VASN could promote the cell proliferation, metastasis, and drug resistance of colorectal cancer. Mechanistically, VASN interacts with the NOTCH1 protein, leading to concurrent activation of the NOTCH and MAPK pathways. Clinically, pulmonary metastasis and advanced tumor stage were observed in 90% of VASN-positive patients and 53.5% of VASN-high patients, respectively, and VASN-high patients had a lower five-year survival rate than VASN-low patients (26.7% vs. 83.7%). Moreover, the Cox analysis and OS analysis indicated that VASN was an independent prognostic factor for OS (HR = 7.4, P value < 0.001) and a predictor of adjuvant therapy efficacy in rectal cancer. Conclusions: Our study highlights the role of VASN in decreasing drug sensitivity and activating the NOTCH and MAPK pathways, which leads to tumorigenesis and pulmonary metastasis. Both experimental and clinical data support that rectal cancer patients with VASN overexpression detected in biopsies have a higher risk of pulmonary metastasis and adjuvant chemotherapy resistance. [ABSTRACT FROM AUTHOR]

The exploitation of new green polymerization avenues for the effective synthesis of polymers by reversible-deactivation radical polymerization plays a critical role in pursuing the development of polymeric materials. In this work, serials of deep eutectic solvents (DES) with intermolecular-hydrogen-bonding interaction were constructed as catalysts and medium for actuating reversible complexation-mediated polymerization (RCMP) for the first time, yielding methacrylate polymers with high monomer conversion and narrow dispersion molecular weight in both water and oil systems. The mechanism and elementary reaction of RCMP were explored deeply, revealing that the complexation of initiator with DES to generate radicals was a ratecontrolling step and intermolecular-hydrogen-bond was primary factor to influence polymerization rate. Moreover, the insights of density functional theory calculations revealed that negative electrostatic potential ensured nucleophilic capacity. This investigation demonstrated the considerable potential of DES for RCMP, which is anticipated for other polymerization applications as a novel medium mode. [ABSTRACT FROM AUTHOR]

In this work, the microstructure evolution and corrosion performance of additively manufactured GH4099 superalloy were investigated. The alloy samples were prepared by selective laser melting (SLM) technology with different laser power and scanning speed. The results showed that the GH4099 prepared by SLM had a fine grain structure, and the average grain size of all samples is below 18 μm. The relative density of SLMed samples first rose and then fell as the volume density increased. Under the process conditions of P = 170 W and V = 800 mm/s, sample N2 possessed the highest relative density and the minimum pores. In addition, the electrochemical test results indicated that sample N2 exhibited the best corrosion resistance, and its corrosion potential (ECorr) and corrosion current density (ICorr) were − 0.287 V and 0.149 μA·cm−2, respectively. The relative density and pores of the alloys were the main reason for the difference in corrosion properties. In particular, the irregular pores caused by lack of fusion were regarded as the initiation site of pitting and crack expansion, which has a greater effect on corrosion resistance than spherical pores. According to XPS results, the passivation film mainly consists of oxides and hydroxides of Ni, Cr, Co, and Al. The hydroxides of Ni, Cr, Co, and Al constituted the outer layer of the passivation film. After the dehydration reaction of hydroxides, their oxides formed the inner layer of the passivation film. In addition, the evolution of the passivation film including the formation and breakdown of the passivation film was also discussed. [ABSTRACT FROM AUTHOR]

Net photosynthetic rate (Pn) is a common indicator used to measure the efficiency of photosynthesis and growth conditions of plants. In this study, soybeans under different moisture gradients were selected as the research objects. Fourteen vegetation indices (VIS) and five canopy structure characteristics (CSC) (plant height (PH), volume (V), canopy cover (CC), canopy length (L), and canopy width (W)) were obtained using an unmanned aerial vehicle (UAV) equipped with three different sensors (visible, multispectral, and LiDAR) at five growth stages of soybeans. Soybean Pn was simultaneously measured manually in the field. The variability of soybean Pn under different conditions and the trend change of CSC under different moisture gradients were analysed. VIS, CSC, and their combinations were used as input features, and four machine learning algorithms (multiple linear regression, random forest, Extreme gradient-boosting tree regression, and ridge regression) were used to perform soybean Pn inversion. The results showed that, compared with the inversion model using VIS or CSC as features alone, the inversion model using the combination of VIS and CSC features showed a significant improvement in the inversion accuracy at all five stages. The highest accuracy (R2 = 0.86, RMSE = 1.73 µmol m−2 s−1, RPD = 2.63) was achieved 63 days after sowing (DAS63). [ABSTRACT FROM AUTHOR]

Objective: To assess the efficacy and safety of Bufei Jiedu (BFJD) ranules as adjuvant therapy for patients with multidrug-resistant pulmonary tuberculosis (MDR-PTB). Methods: A large-scale, multi-center, double-blinded, and randomized controlled trial was conducted in 18 sentinel hospitals in China from December 2012 to December 2016. A total of 312 MDR-PTB patients were randomly assigned to BFJD Granules or placebo groups (1:1) using a stratified randomization method, which both received the long-course chemotherapy regimen for 18 months (6 Am-Lfx-P-Z-Pto, 12 Lfx-P-Z-Pto). Meanwhile, patients in both groups also received BFJD Granules or placebo twice a day for a total of 18 months, respectively. The primary outcome was cure rate. The secondary outcomes included time to sputum-culture conversion, changes in lung cavities and quality of life (QoL) of patients. Adverse reactions were monitored during and after the trial. Results: A total of 216 cases completed the trial, 111 in the BFJD Granules group and 105 in the placebo group. BFJD Granules, as an adjuvant treatment, increased the cure rate by 13.6% at the end of treatment, compared with the placebo (58.4% vs. 44.8%, P=0.02), and accelerated the median time to sputum-culture conversion (5 months vs. 11 months). The cavity closure rate of the BFJD Granules group (50.6%, 43/85) was higher than that of the placebo group (32.1%, 26/81; P=0.02) in patients who completed the treatment. At the end of the intensive treatment, according to the 36-item Short Form, the BFJD Granules significantly improved physical functioning, general health, and vitality of patients relative to the placebo group (all P<0.01). Overall, the death rates in the two groups were not significantly different; 5.1% (8/156) in the BFJD Granules group and 2.6% (4/156) in the placebo group. Conclusions: Supplementing BFJD Granules with the long-course chemotherapy regimen significantly increased the cure rate and cavity closure rates, and rapidly improved QoL of patients with MDR-PTB (Registration No. ChiCTR-TRC-12002850) [ABSTRACT FROM AUTHOR]

Tin‐based perovskite solar cells (PSCs) are promising environmentally friendly alternatives to their lead‐based counterparts, yet they currently suffer from much lower device performance. Due to variations in the chemical properties of lead (II) and tin (II) ions, similar treatments may yield distinct effects resulting from differences in underlying mechanisms. In this work, a surface treatment on tin‐based perovskite is conducted with a commonly employed ligand, iso‐butylammonium iodide (iso‐BAI). Unlike the passivation effects previously observed in lead‐based perovskites, such treatment leads to the recrystallization of the surface, driven by the higher solubility of tin‐based perovskite in common solvents. By carefully designing the solvent composition, the perovskite surface is effectively modified while preserving the integrity of the bulk. The treatment led to enhanced surface crystallinity, reduced surface strain and defects, and improved charge transport. Consequently, the best‐performing power conversion efficiency of FASnI3 PSCs increases from 11.8% to 14.2%. This work not only distinguishes the mechanism of surface treatments in tin‐based perovskites from that of lead‐based counterparts, but also underscores the critical role in designing tailor‐made strategies for fabricating efficient tin‐based PSCs. [ABSTRACT FROM AUTHOR]

Objective: Phthalates (PEs) could cause reproductive harm to males. A mixture of three widely used PEs (MPEs) was used to investigate the ameliorative effects of zinc (Zn) and vitamin E (VE) against male reproductive toxicity. Methods: Fifty male SD rats were randomly divided into five groups (n = 10). Rats in MPEs group were orally treated with 160 mg/kg/d MPEs, while rats in MPEs combined Zn and/or VE groups were treated with 160 mg/kg/d MPEs plus 25 mg/kg/d Zn and/or 25 mg/kg/d VE. After intervention for 70 days, it's was measured of male reproductive organs' weight, histopathological observation of sperms and testes, serum hormones, PIWI proteins and steroidogenic proteins. Results: Compared with control, anogenital distance, testes weight, epididymides weight, and sex hormones were significantly decreased, while the sperm malformation rate was markedly increased in MPEs group (p <.05); the testicular tissues were injured in MPEs group with disordered and decreased spermatids, and arrested spermatogenesis. PIWIL1, PIWIL2, StAR, CYP11A1 and CYP19A1 were down‐regulated in MPEs group (p <.05). However, the alterations of these parameters were restored in MPEs combined Zn and/or VE groups (p <.05). Conclusion: Zn and/or VE improved steroid hormone metabolism, and inhibited MPEs' male reproductive toxicity. [ABSTRACT FROM AUTHOR]

Drought stress is a significant factor affecting soybean growth and yield. A lack of suitable high-throughput phenotyping techniques hinders the drought tolerance evaluation of multi-genotype samples. A method for evaluating drought tolerance in soybeans is proposed based on multimodal remote sensing data from an unmanned aerial vehicle (UAV) and machine learning. Hundreds of soybean genotypes were repeatedly planted under well water (WW) and drought stress (DS) in different years and locations (Jiyang and Yazhou, Sanya, China), and UAV multimodal data were obtained in multiple fertility stages. Notably, data from Yazhou were repeatedly obtained during five significant fertility stages, which were selected based on days after sowing. The geometric mean productivity (GMP) index was selected to evaluate the drought tolerance of soybeans. Compared with the results of manual measurement after harvesting, support vector regression (SVR) provided better results (N = 356, R2 = 0.75, RMSE = 29.84 g/m2). The model was also migrated to the Jiyang dataset (N = 427, R2 = 0.68, RMSE = 15.36 g/m2). Soybean varieties were categorized into five Drought Injury Scores (DISs) based on the manually measured GMP. Compared with the results of the manual DIS, the accuracy of the predicted DIS gradually increased with the soybean growth period, reaching a maximum of 77.12% at maturity. This study proposes a UAV-based method for the rapid high-throughput evaluation of drought tolerance in multi-genotype soybean at multiple fertility stages, which provides a new method for the early judgment of drought tolerance in individual varieties, improving the efficiency of soybean breeding, and has the potential to be extended to other crops. [ABSTRACT FROM AUTHOR]

In this work, three coordination polymers (CPs) were synthesized from Zn2+/Cd2+, fluorescent di-9,10-(imidazolyl)-anthracene (dia), and cyclohexane-1,4-dicarboxylic acid (H2cda). The coordination polymer 1, [Zn(dia)(cda2−)0.5(Hcda−)·0.5H2O]n, contained a layered structure. The coordination polymer 2, [Zn(dia)(cda2−)]n, contained a rare 3D network with a self-catenation pattern. The coordination polymer 3, [Cd2(dia)1.5(cda2−)2]n, contained a 3D network of ose topology. Coordination polymers 1, 2 and 3 were all highly fluorescent. Mixed matrix membranes, prepared by dispersing particles of 1, 2 or 3 within a matrix of polymethyl methacrylate, showed high sensitivity, selectivity and recyclability for detecting Cr2O72− in water. [ABSTRACT FROM AUTHOR]

Background: Left ventricular thrombus (LVT) is a serious complication after myocardial infarction. However, due to its asymptomatic nature, early detection is challenging. We aimed to explore the differences in clinical correlates of LVT found in acute to subacute and chronic phases of myocardial infarction. Methods: We collected data from 153 patients who were diagnosed with LVT after myocardial infarction at the Affiliated Hospital of Qingdao University from January 2013 to December 2022. Baseline information, inflammatory markers, transthoracic echocardiograph (TTE) data and other clinical correlates were collected. Patients were categorized into acute to subacute phase group (< 30 days) and chronic phase group (30 days and after) according to the time at which echocardiograph was performed. The resolution of thrombus within 90 days is regarded as the primary endpoint event. We fitted logistic regression models to relating clinical correlates with phase-specific thrombus resolution. Results: For acute to subacute phase thrombus patients: C-reactive protein levels (OR: 0.95, 95% CI: 0.918–0.983, p = 0.003) were significantly associated with thrombus resolution. For chronic phase thrombus patients: anticoagulant treatment was associated with 5.717-fold odds of thrombus resolution (OR: 5.717, 95% CI: 1.543–21.18, p = 0.009). Conclusions: Higher levels of CRP were associated with lower likelihood of LVT resolution in acute phase myocardial infarction; Anticoagulant therapy is still needed for thrombus in the chronic stage of myocardial infarction. [ABSTRACT FROM AUTHOR]

Background: Tumor-infiltrating lymphocyte (TIL) therapy has been restricted by intensive lymphodepletion and high-dose intravenous interleukin-2 (IL-2) administration. To address these limitations, we conducted preclinical and clinical studies to evaluate the safety, antitumor activity, and pharmacokinetics of an innovative modified regimen in patients with advanced gynecologic cancer. Methods: Patient-derived xenografts (PDX) were established from a local recurrent cervical cancer patient. TILs were expanded ex vivo from minced tumors without feeder cells in the modified TIL therapy regimen. Patients underwent low-dose cyclophosphamide lymphodepletion followed by TIL infusion without intravenous IL-2. The primary endpoint was safety; the secondary endpoints included objective response rate, duration of response, and T cell persistence. Results: In matched patient-derived xenografts (PDX) models, homologous TILs efficiently reduced tumor size (p < 0.0001) and underwent IL-2 absence in vivo. In the clinical section, all enrolled patients received TIL infusion using a modified TIL therapy regimen successfully with a manageable safety profile. Five (36%, 95% CI 16.3–61.2) out of 14 evaluable patients experienced objective responses, and three complete responses were ongoing at 19.5, 15.4, and 5.2 months, respectively. Responders had longer overall survival (OS) than non-responders (p = 0.036). Infused TILs showed continuous proliferation and long-term persistence in all patients and showed greater proliferation in responders which was indicated by the Morisita overlap index (MOI) of TCR clonotypes between infused TILs and peripheral T cells on day 14 (p = 0.004) and day 30 (p = 0.004). Higher alteration of the CD8+/CD4+ ratio on day 14 indicated a longer OS (p = 0.010). Conclusions: Our modified TIL therapy regimen demonstrated manageable safety, and TILs could survive and proliferate without IL-2 intravenous administration, showing potent efficacy in patients with advanced gynecologic cancer. Trial registration: NCT04766320, Jan 04, 2021. [ABSTRACT FROM AUTHOR]

Influenza virus is one of the main pathogens causing respiratory diseases in humans. Vaccines are the most effective ways to prevent viral diseases. However, the limited protective efficacy of current influenza vaccines highlights the importance of novel, safe, and effective universal influenza vaccines. With the progress of the COVID-19 pandemic, live-attenuated vaccines delivered through respiratory mucosa have shown robustly protective efficacy. How to obtain a safe and effective live-attenuated vaccine has become a major challenge. Herein, using the influenza virus as a model, we have established a strategy to quickly obtain a live-attenuated vaccine by mutating the cleavage site of the influenza virus. This mutated influenza virus can be specifically cleaved by chymotrypsin. It has similar biological characteristics to the original strain in vitro, but the safety is improved by at least 100 times in mice. It can effectively protect against lethal doses of both homologous H1N1 and heterologous H5N1 viruses post mucosal administration, confirming that the vaccine generated by this strategy has good safety and broad-spectrum protective activities. Therefore, this study can provide valuable insights for the development of attenuated vaccines for respiratory viruses or other viruses with cleavage sites. [ABSTRACT FROM AUTHOR]

Photo‐induced reversible complexation‐mediated polymerization (RCMP) is a green and economical method to prepare polymers with precise molecular weights, narrow molecular weight distributions and functionally active chain ends. Covalent organic frameworks (COFs) are a promising heterogeneous photocatalyst for mediating RCMP due to their adjustable structure, band gap, and porosity. In this work, 1,3,5‐triformylphloroglucinol (Tp) and p‐azoaniline (Azo) were selected to construct 2D β‐ketoenamine linked Tp‐Azo‐COF as a heterogeneous photocatalyst to trigger RCMP under white light irradiation. A series of polymers with controllable molecular weight and narrow molecular weight distribution were successfully prepared by using Tp‐Azo‐COF as photocatalysis. On/off light experiments confirmed the good spatiotemporal control feature, and chain expansion experiments demonstrated the high "activity" of polymer chain ends. Furthermore, the mechanistic research elucidated that electron transfer between Tp‐Azo‐COF and initiator occurred, allowing the formation of reactive radicals to mediate RCMP. Density functional theory calculations revealed that the coordination of iodine on the initiator to catalyst obviously reduced the bond dissociation energy, leading to enhance in the polymerization rate. This work provides a platform for constructing heterogeneous photocatalysts with more efficient and stable to mediate RCMP. [ABSTRACT FROM AUTHOR]

Tumor necrosis factor-α-induced protein 8-like 3 (TNFAIP8L3 or TIPE3) functions as a transfer protein for lipid second messengers. TIPE3 is highly upregulated in several human cancers and has been established to significantly promote tumor cell proliferation, migration, and invasion and inhibit the apoptosis of cancer cells. Thus, inhibiting the function of TIPE3 is expected to be an effective strategy against cancer. The advancement of artificial intelligence (AI)-driven drug development has recently invigorated research in anti-cancer drug development. In this work, we incorporated DFCNN, Autodock Vina docking, DeepBindBC, MD, and metadynamics to efficiently identify inhibitors of TIPE3 from a ZINC compound dataset. Six potential candidates were selected for further experimental study to validate their anti-tumor activity. Among these, three small-molecule compounds (K784-8160, E745-0011, and 7238-1516) showed significant anti-tumor activity in vitro, leading to reduced tumor cell viability, proliferation, and migration and enhanced apoptotic tumor cell death. Notably, E745-0011 and 7238-1516 exhibited selective cytotoxicity toward tumor cells with high TIPE3 expression while having little or no effect on normal human cells or tumor cells with low TIPE3 expression. A molecular docking analysis further supported their interactions with TIPE3, highlighting hydrophobic interactions and their shared interaction residues and offering insights for designing more effective inhibitors. Taken together, this work demonstrates the feasibility of incorporating deep learning and MD simulations in virtual drug screening and provides inhibitors with significant potential for anti-cancer drug development against TIPE3−. [ABSTRACT FROM AUTHOR]

Amorphous alloys or metallic glasses (MGs) thin films have attracted extensive attention in various fields due to their unique functional properties. Here, we use in situ heating transmission electron microscopy (TEM) to investigate the thermal stability and crystallization behavior of Pd-Au-Si thin films prepared by a pulsed laser deposition (PLD) method. Upon heating treatment inside a TEM, we trace the structural changes in the Pd-Au-Si thin films through directly recording high-resolution images and diffraction patterns at different temperatures. TEM observations reveal that the Pd-Au-Si thin films started to nucleate with small crystalline embryos uniformly distributed in the glassy matrix upon approaching the glass transition temperature T g = 625 K , and subsequently, the growth of crystalline nuclei into sub-10 nm Pd-Si nanocrystals commenced. Upon further increasing the temperature to 673 K , the thin films transformed to micro-sized patches of stacking-faulty lamellae that further crystallized into Pd 9 Si 2 and Pd 3 Si intermetallic compounds. Interestingly, with prolonged thermal heating at elevated temperatures, the Pd 9 Si 2 transformed to Pd 3 Si . Simultaneously, the solute Au atoms initially dissolved in glassy alloys and eventually precipitated out of the Pd 9 Si 2 and Pd 3 Si intermetallics, forming nearly spherical Au nanocrystals. Our TEM results reveal the unique thermal stability and crystallization processes of the PLD-prepared Pd-Au-Si thin films as well as demonstrate a possibility of producing a large quantity of pure nanocrystals out of amorphous solids for various applications. [ABSTRACT FROM AUTHOR]

Sea cucumbers frequently expel their guts in response to predators and an aversive environment, a behavior perceived as releasing repellents involved in chemical defense mechanisms. To investigate the chemical nature of the repellent, the viscera of stressed sea cucumbers (Apostichopus japonicus) in the Yellow Sea of China were collected and chemically analyzed. Two novel non-holostane triterpene glycosides were isolated, and the chemical structures were elucidated as 3ꞵ-O-[ꞵ-D-glucopyranosyl-(1→2)-ꞵ-D-xylopyranosyl]-(20S)-hydroxylanosta-7,25-diene-18(16)-lactone (1) and 3ꞵ-O-[ꞵ-D-quinovopyranosyl-(1→2)-ꞵ-D-xylopyranosyl]-(20S)-hydroxylanosta-7,25-diene-18(16)-lactone (2) by spectroscopic and mass-spectrometric analyses, exemplifying a triterpene glycoside constituent of an oligosaccharide containing two sugar-units and a non-holostane aglycone. Zebrafish embryos were exposed to various doses of 1 and 2 from 4 to 96 hpf. Compound 1 exposure showed 96 h-LC50 41.5 µM and an increased zebrafish mortality rates in roughly in a dose- and time-dependent manner. Compound 2, with different sugar substitution, exhibited no mortality and moderate teratogenic toxicity with a 96 h-EC50 of 173.5 µM. Zebrafish embryos exhibited teratogenic effects, such as reduced hatchability and total body length. The study found that triterpene saponin from A. japonicus viscera had acute toxicity in zebrafish embryos, indicating a potential chemical defense role in the marine ecosystem. [ABSTRACT FROM AUTHOR]

Background: Sexual function is an important yet understudied aspect of overall health and well‐being in older adults. We aimed to examine sexual function and its correlates among people 50 years and older in China. Methods: We enrolled people aged 50 years and older recruited from four regions in China between September 2021 and July 2022 in a multicenter cross‐sectional study. Data were collected through an investigator‐administered questionnaire about demographic characteristics, health characteristics, and sexual function status. Logistic regression was used to assess correlates of lower sexual function (the highest quintile of the sex‐specific population distribution of Natsal‐SF scores [i.e., lower functioning compared with the remaining]). Results: A total of 465 women and 832 men who were sexually active in the past year were included in the analysis (mean age: 60.4 ± 7.2) [Correction added after first online publication on 12 Feb 2024. The word "years" has been changed to "year" in this sentence.]. Over a quarter of all participants were dissatisfied with their sex life. Notably, 92 women and 167 men were categorized as having a lower sexual function. Age (in men only), living in urban areas, general health status, being underweight or overweight (in men only), and having depressive symptoms were associated with lower sexual function. Among all participants, 43.1% of men and 54.0% of women experienced sexual response problems lasting 3 months or more. Less than one‐third of all participants had sought help or advice for sex life in the past year. Conclusions: Sexual dysfunction and sexual dissatisfaction are prevalent among older adults in China and are associated with self‐assessed poor health. More efforts are needed to better understand sexual health needs and tailor service provision. [ABSTRACT FROM AUTHOR]

Coloading adjuvant drugs or biomacromolecules with photosensitizers into nanoparticles to enhance the efficiency of photodynamic therapy (PDT) is a common strategy. However, it is difficult to load positively charged photosensitizers and negatively charged adjuvants into the same nanomaterial and further regulate drug release simultaneously. Herein, a single‐component dual‐functional prodrug strategy is reported for tumor treatment specifically activated by tumor microenvironment (TME)‐generated HOCl. A representative prodrug (DHU‐CBA2) is constructed using indomethacin grafted with methylene blue (MB). DHU‐CBA2 exhibited high sensitivity toward HOCl and achieved simultaneous release of dual drugs in vitro and in vivo. DHU‐CBA2 shows effective antitumor activity against lung cancer and spinal metastases via PDT and cyclooxygenase‐2 (COX‐2) inhibition. Mechanistically, PDT induces immunogenic cell death but stimulates the gene encoding COX‐2. Downstream prostaglandins E2 and Indoleamine 2,3 dioxygenase 1 (IDO1) mediate immune escape in the TME, which is rescued by the simultaneous release of indomethacin. DHU‐CBA2 promotes infiltration and function of CD8+ T cells, thus inducing a robust antitumor immune response. This work provides an autoboost strategy for a single‐component dual‐functional prodrug activated by TME‐specific HOCl, thereby achieving favorable tumor treatment via the synergistic therapy of PDT and a COX‐2 inhibitor. [ABSTRACT FROM AUTHOR]

Background: Multiple antigens, autoantibodies (AAb), and antigen-autoantibody (Ag-AAb) complexes were compared for their ability to complement CA125 for early detection of ovarian cancer. Methods: Twenty six biomarkers were measured in a single panel of sera from women with early stage (I-II) ovarian cancers (n = 64), late stage (III-IV) ovarian cancers (186), benign pelvic masses (200) and from healthy controls (502), and then split randomly (50:50) into a training set to identify the most promising classifier and a validation set to compare its performance to CA125 alone. Results: Eight biomarkers detected ≥ 8% of early stage cases at 98% specificity. A four-biomarker panel including CA125, HE4, HE4 Ag-AAb and osteopontin detected 75% of early stage cancers in the validation set from among healthy controls compared to 62% with CA125 alone (p = 0.003) at 98% specificity. The same panel increased sensitivity for distinguishing early-stage ovarian cancers from benign pelvic masses by 25% (p = 0.0004) at 95% specificity. From 21 autoantibody candidates, 3 AAb (anti-p53, anti-CTAG1 and annt-Il-8) detected 22% of early stage ovarian cancers, potentially lengthening lead time prior to diagnosis. Conclusion: A four biomarker panel achieved greater sensitivity at the same specificity for early detection of ovarian cancer than CA125 alone. [ABSTRACT FROM AUTHOR]

Pancreatic ductal adenocarcinoma (PDAC) and low-grade ovarian cancer (LGSOC) are characterized by the prevalence of KRAS oncogene mutations. DIRAS3 is the first endogenous non-RAS protein that heterodimerizes with RAS, disrupts RAS clustering, blocks RAS signaling, and inhibits cancer cell growth. Here, we found that DIRAS3-mediated KRAS inhibition induces ROS-mediated apoptosis in PDAC and LGSOC cells with KRAS mutations, but not in cells with wild-type KRAS, by downregulating NFE2L2/Nrf2 transcription, reducing antioxidants, and inducing oxidative stress. DIRAS3 also induces cytoprotective macroautophagy/autophagy that may protect mutant KRAS cancer cells from oxidative stress, by inhibiting mutant KRAS, activating the STK11/LKB1-PRKAA/AMPK pathway, increasing lysosomal CDKN1B/p27 localization, and inducing autophagic gene expression. Treatment with chloroquine or the novel dimeric chloroquine analog DC661 significantly enhances DIRAS3-mediated inhibition of mutant KRAS tumor cell growth in vitro and in vivo. Taken together, our study demonstrates that DIRAS3 plays a critical role in regulating mutant KRAS-driven oncogenesis in PDAC and LGSOC. Abbreviations: AFR: autophagic flux reporter; ATG: autophagy related; CQ: chloroquine; DCFDA: 2'-7'-dichlorodihydrofluorescein diacetate; DIRAS3: DIRAS family GTPase 3; DOX: doxycycline; KRAS: KRAS proto-oncogene, LGSOC: low-grade serous ovarian cancer; MiT/TFE: microphthalmia family of transcription factors; NAC: N-acetylcysteine; PDAC: pancreatic ductal adenocarcinoma; ROS: reactive oxygen species; TFEB: transcription factor EB [ABSTRACT FROM AUTHOR]

Environmentally cued hatching is prevalent, diverse, and crucial to many animals' survival. Fish embryos use a variety of chemical cues to initiate hatching to avoid potential predators, yet the function of chemical cues released from the predatory consumption of heterospecific prey is largely unknown. Zebra cichlids (Metriaclima estherae) are ferocious predators that can feed on medaka (Oryzias latipes), though it is impossible for this to occur in their natural habitat. Zebrafish (Danio rerio) embryos have been employed as experimental subjects due to their sensitivity to a variety of chemical signals. In this study, zebrafish embryos were subjected to three types of chemical signals: predator cues (PCs, released from cichlids), heterospecific cues (HCs, released from medaka), and heterospecific dietary cues (HDCs, released from cichlids that have ingested medaka). As a result, the hatching times of zebrafish embryos were accelerated by 6.8% and 12.6% by PCs and HDCs, respectively. PCs and HDCs cause significantly reduced morphology in zebrafish embryos, including regarding total length, eye length, dorsal fin length, trunk height, caudal fin height, and body cavity, and increase yolk sac height. The PCs and HDCs diminished the larvae's motion at 120 and 144 h post fertilization (hpf), which could be attributed to non-developmental embryogenesis. Overall, the impacts of HDCs on embryonic hatching, developmental morphology, and locomotor were more pronounced in comparison with PCs. Our findings demonstrate that predators' dietary cues, even those released after predation on heterospecific prey, can modify embryogenesis, highlighting the critical functions of chemical signals in predation risk assessment using embryos. [ABSTRACT FROM AUTHOR]

Melt treatment is well known to have an important influence on the properties of metallic glasses (MGs). However, for the MGs quenched from different melt temperatures with a quartz tube, the underlying physical origin responsible for the variation of properties remains poorly understood. In the present work, we systematically studied the influence of melt treatment on the thermal properties of a Zr50Cu36Al14 glass-forming alloy and unveiled the microscopic origins. Specifically, we quenched the melt at different temperatures ranging from 1.1 T l to 1.5 T l (T l is the liquidus temperature) to obtain melt-spun MG ribbons and investigated the variation of thermal properties of the MGs upon heating. We found that glass transition temperature, T g, increases by as much as 36 K, and the supercooled liquid region disappears in the curve of differential scanning calorimetry when the melt is quenched at a high temperature up to 1.5 T l. The careful chemical analyses indicate that the change in glass transition behavior originates from the incorporation of oxygen and silicon in the molten alloys. The incorporated oxygen and silicon can both enhance the interactions between atoms, which renders the cooperative rearrangements of atoms difficult, and thus enhances the kinetic stability of the MGs. [ABSTRACT FROM AUTHOR]

Currently the main method of mine solid waste disposal and utilization is to apply gangue to underground filling. For the grading characteristics of coal gangue in the hollow zone in underground filling, the state of pressure and the mechanical properties of coal gangue filling materials under different particle sizes. In this paper, through laboratory tests and numerical simulations, the bearing characteristics and deformation damage of gangue are deeply investigated and analyzed from both macroscopic and microscopic perspectives. The results of the study show that when the axial pressure reaches a certain threshold, the strain increases accordingly with the increase in grain size. Under the axial pressure condition of 15MPa, the bearing capacity of gangue with different grain sizes under the lateral pressure of steel cylinder showed obvious positive correlation. In the software PFC3D simulation, as the particle size of gangue particles increases, it has a significant effect on the natural stacking porosity of the specimen, and gangue particles are more prone to force chain instability and failure. Mixed particle size gangue can significantly reduce the natural accumulation porosity of the specimen, thus improving its overall stability. Significant displacement triangles existed in the top and lateral directions of the B1 (0–5 mm), B2 (5–10 mm), and B5 (0–20 mm) specimens under the same circumferential pressure conditions. The results of the study are of great significance for further selection of reasonable gangue gradation and determination of its mechanical properties. [ABSTRACT FROM AUTHOR]

Many traditional fermented foods and beverages industries around the world request the addition of multi‐species starter cultures. However, the microbial community in starter cultures is subject to fluctuations due to their exposure to an open environment during fermentation. A rapid detection approach to identify the microbial composition of starter culture is essential to ensure the quality of the final products. Here, we applied single‐cell Raman spectroscopy (SCRS) combined with machine learning to monitor Oceanobacillus species in Daqu starter, which plays crucial roles in the process of Chinese baijiu. First, a total of six Oceanobacillus species (O. caeni, O. kimchii, O. iheyensis, O. sojae, O. oncorhynchi subsp. Oncorhynchi and O. profundus) were detected in 44 Daqu samples by amplicon sequencing and isolated by pure culture. Then, we created a reference database of these Oceanobacillus strains which correlated their taxonomic data and single‐cell Raman spectra (SCRS). Based on the SCRS dataset, five machine‐learning algorithms were used to classify Oceanobacillus strains, among which support vector machine (SVM) showed the highest rate of accuracy. For validation of SVM‐based model, we employed a synthetic microbial community composed of varying proportions of Oceanobacillus species and demonstrated a remarkable accuracy, with a mean error was less than 1% between the predicted result and the expected value. The relative abundance of six different Oceanobacillus species during Daqu fermentation was predicted within 60 min using this method, and the reliability of the method was proved by correlating the Raman spectrum with the amplicon sequencing profiles by partial least squares regression. Our study provides a rapid, non‐destructive and label‐free approach for rapid identification of Oceanobacillus species in Daqu starter culture, contributing to real‐time monitoring of fermentation process and ensuring high‐quality products. [ABSTRACT FROM AUTHOR]

Expanded polystyrene foam (EPSF), valued for its excellent insulation properties, faces a significant flammability challenge due to its cellular structure. Traditional flame retardant methods such as physical blending and layer‐by‐layer assembly have poor applicability to EPSF. Therefore, it is necessary to find other more effective methods for synthesizing flame‐retardant EPSF. The high internal phase emulsion (HIPE) template is one of the simplest and most commonly used methods for synthesizing porous materials, which have features such as adjustable pore structures and high porosity. In this work, ammonium polyphosphate (APP)/starch was added to the dispersed phase of the HIPE to prepare the flame‐retardant EPSF by one‐pot method. The morphology, thermal stability and flame retardancy of the foams were investigated. When the addition of APP/starch (the weight ratio is 1:1) reached 30 wt.%, the peak heat release rate (PHRR), total heat release (THR), and total smoke release (TSR) of the composite foam decreased by 74.7%, 65.9%, and 24.7%, respectively, compared to the pure PS foam. Meanwhile, its limiting oxygen index (LOI) value reached 25.8%, and the UL‐94 rating reached V‐1 level, indicating significant improvement in flame retardancy. This study provides an effective strategy for synthesizing flame‐retardant porous materials. [ABSTRACT FROM AUTHOR]

Objective To study the mechanism of the intervention of total flavonoids from Zhongjiefeng (sarcandra[twig and leaf]) on immune thrombocytopenia (ITP) using metabolomics techniques. Methods Using Excel random function, 48 male SD rats were randomly divided into the normal control group, the model group, the total flavonoids from Zhongjiefeng low-, medium-, and high-dose groups, and the prednisolone acetate group, with 8 rats in each group. Except for the normal control group, rats in other groups were injected intraperitoneally with rabbit anti-rat platelet serum (5 mL/kg) on days 1, 3, 4, 6, 7, and 8 to replicate an ITP rat model. Rats in the normal control group were injected intraperitoneally with an equal volume of physiological saline. Drug intervention was given on the modeling day once a day. The total flavonoids from Zhongjiefeng low-, medium-, and high-dose groups were gavaged with 31.5, 63.0, and 94.5 mg/kg of total flavonoids from Zhongjiefeng, respectively. The prednisolone acetate group was injected intraperitoneally with 10.0 mg/kg of prednisolone acetate. On days 0, 3, 6, and 9, the number of peripheral platelets in each group of rats was dynamically detected. On day 10, the spleen mass was measured and the spleen index was calculated. Screening and identification of differential metabolites in the spleen of rats in each group were carried out using ultra-high-performance liquid chromatography coupled with four-stage rod time-of-flight mass spectrometry technology and multivariate statistical analysis, and pathway enrichment analysis was conducted. Results Compared with the normal control group, the model group showed a decrease in peripheral blood platelets on days 6 and 9, an increase in spleen mass, and an increase in spleen index(P<0.05). Compared with the model group, the number of peripheral platelets on day 6 and 9 of the total flavonoids from Zhongjiefeng low-, medium-, and high-dose groups were increased, the spleen mass of the total flavonoids from Zhongjiefeng high-dose group was decreased, and the spleen indexes of the total flavonoids from Zhongjiefeng medium- and high-dose groups were decreased (P<0.05). Through metabolomics analysis of the spleen, 24 biomarkers related to ITP were identified. Of these, 21 were reduced in the total flavonoids from Zhongjiefeng high-dose group, which were mainly involved in linoleic acid metabolism, cysteine and methionine metabolism, and glycerol phospholipid metabolism. Conclusion The total flavonoids from Zhongjiefeng may restore the normal regulatory ability of the immune system by regulating spleen linoleic acid metabolism, cysteine and methionine metabolism, and glycerol phospholipid metabolism, in order to inhibit excessive platelet destruction and exert a therapeutic effect on ITP. [ABSTRACT FROM AUTHOR]

Di-(2-ethylhexyl) phthalate (DEHP) is a widely used plasticizer, which can cause damage to male reproductive organs, especially the atrophy of the testis. Meanwhile, DEHP can also lead to a decrease in testicular zinc content, but the role of zinc remains unclear. This study aims to prepare oyster peptide-zinc complex (OPZC) to alleviate DEHP-induced reproductive damage in mice. OPZC was successfully obtained through electron microscopy, X-ray diffraction, and thermogravimetric analysis, with stable structure and high water-solubility. Low dose oyster peptide-zinc complex (OPZCL) significantly reduced the reproductive damage caused by DEHP in mice. Further research had shown that OPZCL restored the content of serum hormones and the activity of oxidative stress kinases to normal, while also normalizing testicular zinc and selenium levels. In addition, it also recovered the disorder of gut microbiota, reduced the proportion of Bacteroides, increased the abundance of Ligilactobacillus, and restored the proportion of Acidobacteriota, Chloroflexi, and Proteobacteria. Therefore, OPZCL can relieve the reproductive damage caused by DEHP in mice by restoring testicular zinc homeostasis and the composition of intestinal microbiota, indicating that OPZCL has a potential protective effect on male reproductive health. [ABSTRACT FROM AUTHOR]

Chronic viral infection induces immunosenescence and systemic low‐grade inflammation, leading to worsened long‐term outcomes. We sought to explore the short‐ and long‐term effects of chronic viral infection on cardiovascular disease (CVD). Based on UK Biobank data, exposed group was identified as individuals who had chronic virus infection‐related hospitalization (IRH). Unexposed group was randomly selected, matched by 5‐year age interval, sex, and Charlson comorbidity index at a ratio up to 1:10. Restricted cubic splines were used to model time‐varying effects of IRH in nonproportional Cox models. A cut‐off value of 5 years was recorded and used in piecewise Cox proportional hazards models as we estimated short‐ and long‐term effects of IRH on CVD. A total of 2826 exposed participants and 28 212 matched unexposed participants were included. Chronic viral IRH was associated with increased risk of CVD (0–5 years: hazard ratio, 1.57 [95% confidence interval: 1.32, 1.87] and 5+ years: 1.31 [1.06, 1.61]). Elevated risk of stroke was only observed within the initial 5‐year follow‐up (0–5 years: 1.91 [1.30, 2.81]). The short‐ and long‐term associations were observed in herpes or hepatitis virus IRH with risk of CVD (all p < 0.05). Subgroup analysis revealed long‐term association between chronic viral IRH and CVD among female (5+ years: 1.68 [1.27, 2.22]) but not among male. The association between chronic viral infection and elevated CVD risk appeared to be stronger among individuals who did not take cholesterol‐lowering medication, antithrombotic medication, or certain antihypertensive medications (all p for interaction < 0.05). The risk of CVD event remained persistently higher within and over 5 years following chronic viral IRH, especially in individuals infected with herpes and hepatitis virus. [ABSTRACT FROM AUTHOR]

The circular saw blade, which is mainly composed of carbon steel, is used to cut the stone. However, the carbon steel is easily corroded in stone processing wastewater, shortening its lifespan. In this study, a new composite inhibitor of sodium nitrite, sodium molybdate, sodium silicate, sodium tungstate, and sodium citrate was investigated firstly, and then, its inhibition efficiency for carbon steel in stone processing wastewater was explored using electrochemical measurements and weight loss measurements. The results showed that the composite inhibitor as a mixed‐type inhibitor displayed good inhibitory performance. Surface analysis including scanning electron microscope, atomic force microscope, X‐ray photoelectron spectroscopy analysis, and contact angle test further revealed the form of protection of the steel surface by composite corrosion inhibitors. The prepared composite inhibitor exhibited excellent corrosion resistance for carbon steel in stone processing wastewater, and it is believed that the composite inhibitor has certain application potential in industries. [ABSTRACT FROM AUTHOR]

Background and aims: The end of the zero-COVID-19 policy placed a large number of older adults in China at increased risk of COVID-19 infection. SARS-CoV-2 rapid antigen testing (RAT) is a promising tool for scaling up testing and ensuring that patient management and public health measures can be implemented without delay. We aimed to understand the knowledge and willingness of RAT, and its correlates among older adults in China. Methods: A nationwide cross-sectional survey on knowledge and willingness about RAT among older adults in China was conducted between January 14 and 28, 2023, shortly after the end of the zero-COVID-19 policy. An online questionnaire was used to collect information on sociodemographic characteristics, health characteristics, sources to access RAT information, and attitudes toward COVID-19 and its RAT. Logistic regression was used to assess correlates of knowledge of RAT and willingness to take RAT among older adults. Results: A total of 1030 older adults (494 women and 536 men, mean age 68.7 ± 7.0 years) were recruited. 49.4% of the participants had a high level of RAT knowledge. After adjusting for sociodemographic characteristics, chronic diseases (0.70, 0.49–0.99), learning RAT from new media (5.46, 3.48–8.68) and traditional media (3.35, 2.13–5.34), and perceiving RAT as convenient (4.03, 2.80–5.85) were associated with levels of RAT knowledge. 53.3% of the participants were willing to take RAT. After adjusting for sociodemographic characteristics, learning RAT from new media (8.46, 5.26–14.0) and traditional media (1.63, 1.04–2.55), perceiving RAT as convenient (2.97, 2.10–4.22), and worrying about (re)infection with COVID-19 (2.12, 1.55–2.92) were associated with willingness to take RAT. Conclusion: The levels of RAT knowledge and willingness to take RAT among older adults in China may hinder the scale-up of RAT. Health education about RAT should be strengthened among older adults. Special efforts should be made to integrate traditional and new media to promote RAT among older adults, specifically, for virus susceptibility and the convenience of RAT. Given the reopening of society, our study could inform our response to future novel infectious diseases and aid in the timely scale-up of RAT. [ABSTRACT FROM AUTHOR]

Lunar glasses with different origins act as snapshots of their formation processes, providing a rich archive of the Moon's formation and evolution. Here, we reveal diverse glasses from Chang'E-5 (CE-5) lunar regolith, and clarify their physical origins of liquid quenching, vapor deposition and irradiation damage respectively. The series of quenched glasses, including rotation-featured particles, vesicular agglutinates and adhered melts, record multiple-scale impact events. Abundant micro-impact products, like micron- to nano-scale glass droplets or craters, highlight that the regolith is heavily reworked by frequent micrometeorite bombardment. Distinct from Apollo samples, the indigenous ultra-elongated glass fibers drawn from viscous melts and the widespread ultra-thin deposited amorphous rims without nanophase iron particles both indicate a relatively gentle impact environment at the CE-5 landing site. The clarification of multitype CE-5 glasses also provides a catalogue of diverse lunar glasses, meaning that more of the Moon's mysteries, recorded in glasses, could be deciphered in future. [ABSTRACT FROM AUTHOR]

Background: The FLT3/ITD mutation exists in many acute myeloid leukemia (AML) patients and is related to the poor prognosis of patients. In this study, we attempted to evaluate the antitumor activity of simvastatin, a member of the statin class of drugs, in vitro and in vivo models of FLT3/ITD AML and to identify the potential mechanisms. Methods: Cell Counting Kit-8 (CCK-8) and Annexin V/propidium iodide (PI) staining kits were used to detect cell viability and apoptosis, respectively. Subsequently, Western blot and rescue experiment were applied to explore the potential molecular mechanism. In vivo anti-leukemia activity of simvastatin was evaluated in xenograft mouse models. Results: In vitro experiments revealed that simvastatin inhibited AML progression in a dose- and time-dependent manner, while in vivo experiments showed that simvastatin significantly reduced tumor burden in FLT3/ITD xenograft mouse models. After simvastatin treatment of FLT3/ITD AML cells, intracellular Rap1 was downregulated and the phosphorylation levels of its downstream targets MEK, ERK and p38 were significantly inhibited. The rescue experiment showed that mevalonate, an intermediate product of the metabolic pathway of mevalonate, and its downstream geranylgeranyl pyrophosphate (GGPP) played a key role in this process. Finally, we demonstrate that simvastatin can induce apoptosis of primary AML cells, while having no effect on peripheral blood mononuclear cells from normal donors. Conclusions: Simvastatin can selectively and effectively eradicate FLT3/ITD AML cells in vitro and in vivo, and its mechanism may be related to the disruption of the HMG-CoA reductase pathway and the downregulation of the MEK/ERK and p38-MAPK signaling pathways. [ABSTRACT FROM AUTHOR]

Data-driven traffic modeling is revolutionizing transportation systems and provides numerous opportunities for achieving high-quality transportation services. A major challenge in optimizing transportation systems is uncertain transportation demand. With the availability of historical data on transportation demand, the uncertain transportation demand can be better modeled, and thereby practitioners can formulate well-informed transportation scheduling decisions. In this paper, we propose three effective and economical transport scheduling strategies using mathematical programming, leveraging big data to extract useful contextual information. Additionally, a perfect-foresight optimization model is proposed to evaluate our proposed data-driven strategies. Results show a negligible optimality gap (i.e., 0.47%) between the optimal solution derived by the perfect-foresight model and the scheduling plans derived by our data-driven strategies. Overall, this paper contributes to the field of transportation engineering by innovatively applying data science, mathematical modeling, and optimization techniques. [ABSTRACT FROM AUTHOR]

The authors have developed a method to estimate the catch efficiency of sampling gear using acoustic information. Since different sampling conditions will cause different sampling results, it is necessary to know more details about catch efficiency to quantitatively catch juvenile fish. In this study, we estimated the catch efficiency of a framed midwater trawl (FMT) for juvenile walleye pollock, and investigated differences in the catch efficiency of the FMT due to various influencing factors. To clarify the effects of different sampling conditions on catch efficiency, we investigated changes in catch efficiency by survey time (daytime and nighttime), net color (black and cyan), and towing speed (2 kt, 3 kt, 4 kt). It was quantitatively shown that the catch efficiency was higher at nighttime than during the daytime, the catch efficiency of black net was higher than that of cyan net, and the catch efficiency was higher at the faster towing speed. Comparing the estimated catch efficiency under different conditions, we found that survey time was the most important influencing factor. [ABSTRACT FROM AUTHOR]

The modifying effects of polymer on bitumen low-temperature performance are substantially compromised by the thermal breakdown of styrene–butadiene rubber (SBR) polymer during bitumen mixture production operations. The efficacy of the utilization of Sasobit/waste cooking oil (Sasobit/WCO) as a warm-mix additive has been demonstrated in mitigating the adverse consequences of thermal aging on SBR-modified bitumen binder (SB) while preserving the binder's original performance characteristics. However, few studies have been conducted to further investigate the rheological properties and aging resistance of SB modified with Sasobit/WCO compounds. In this work, three additives—Sasobit, WCO, and Sasobit/WCO composite—were selected, and their effects on the physical and rheological characteristics of SB as well as the temperatures at which the mixtures were prepared were assessed. In addition, by using dynamic shear rheometers (DSR) and bending beam rheometers (BBR), the effects of this innovative warm-mix addition on the performance grade (PG) and aging resistances of SB were evaluated. According to the results, Sasobit/WCO composites outperform Sasobit and WCO in lowering the mixture preparation temperature. Sasobit/WCO also improves both the high- and low-temperature performance of SB simultaneously. Compared to hot-mix asphalt mixtures, the addition of Sasobit/WCO reduces the preparation temperature of the bitumen mixtures by 19 °C, which in turn helps to minimize the negative effects of temperature aging on the functioning of the SB. Additionally, the Sasobit/WCO composite addition can improve the SB mixture's resistance to thermal cracking. After the introduction of Sasobit/WCO, the high-temperature PG of SB was raised by two levels, regardless of whether the warm-mix impact was taken into account. With the addition of Sasobit/WCO, SB's resilience to short-term aging was enhanced. [ABSTRACT FROM AUTHOR]

Background: The 2018 Australian Heart Failure (HF) guidelines strongly recommended commencing sodium‐glucose co‐transporter‐2 inhibitors (SGLT‐2is) in HF patients with type 2 diabetes mellitus (T2DM). The uptake of SGLT‐2is for HF patients with T2DM in our health service is unknown. Aims: To determine the adoption of the 2018 HF guidelines by assessing the temporal trends of SGLT‐2is' usage in HF patients with T2DM at Metro South Health (MSH) hospitals, in South‐East Queensland. Methods: Retrospective analysis of all HF patients (ejection fraction (EF) < 50%) with T2DM who were managed within MSH hospitals between June 2018 and June 2021. Results: A total of 666 patients met the inclusion criteria with 918 HF encounters. Mean age was 72 years and 71% were male (473/666). Mean EF was 30% (SD ± 11%), and mean estimated glomerular filtration rate was 48 mL/min/1.73 m2 (SD ± 25). Fifty‐four per cent (362/666) had contraindications to SGLT‐2is. Among those without contraindications, there was a five‐fold increase in the utility of SGLT‐2is, 7% (2/29) before versus 38% (103/275) after implementation of the HF guidelines (P < 0.001). Patients on SGLT‐2is were younger (64 years vs 69 years, P = 0.002) and had a lower number of HF hospitalisations (1.1 vs 2.1, P = 0.01). Conclusions: During the study period, 54% of our HF patients with T2DM were not on SGLT‐2is due to prescribing guidelines/limitations in the Australian context. We observed a five‐fold significant increase in the uptake of SGLT‐2is before and after implementation of HF guidelines among patients without contraindications to SGLT‐2is. There were significantly fewer HF hospitalisations among patients on SGLT‐2is compared to those without. [ABSTRACT FROM AUTHOR]