Biodegradation of poly(ethylene terephthalate) through PETase surface-display: From function to structure.

Polyethylene terephthalate (PET) is one of the most used plastics which has caused some environmental pollution and social problems. Although many newly discovered or modified PET hydrolases have been reported at present, there is still a lack of comparison between their hydrolytic capacities, as well as the need for new biotechnology to apply them for the PET treatment. Here, we systematically studied the surface-display technology for PET hydrolysis using several PET hydrolases. It is found that anchoring protein types had little influence on the surface-display result under T7 promoter, while the PET hydrolase types were more important. By contrast, the newly reported FAST-PETase showed the strongest hydrolysis effect, achieving 71.3% PET hydrolysis in 24 h by pGSA-FAST-PETase. Via model calculation, FAST-PETase indeed exhibited higher temperature tolerance and catalytic capacity. Besides, smaller particle size and lower crystallinity favored the hydrolysis of PET pellets. Through protein structure comparison, we summarized the common characteristics of efficient PET-hydrolyzing enzymes and proposed three main crystal structures of PET enzymes via crystal structural analysis, with ISPETase being the representative and main structure. Surface co-display of FAST-PETase and MHETase can promote the hydrolysis of PET, and the C-terminal of the fusion protein is crucial for PET hydrolysis. The results of our research can be helpful for PET contamination removal as well as other areas involving the application of enzymes. SYNOPSIS: This research can promote the development of better PET hydrolase and its applications in PET pollution treatment via bacteria surface-display.

Highly efficient sulfur-doped Ni3Fe electrocatalysts for overall water splitting: Rapid synthesis, mechanism and driven by sustainable energy.

Designing efficient electrocatalysts and insight into their electrocatalytic mechanisms are significantly important for storing and converting the intermittent sustainable energy sources into clean hydrogen. In this study, we synthesize the bifunctional sulfur-doped Ni3Fe (NiFeS) electrocatalysts by a simple electrodeposition method only taking 30 s. After optimizing the components, it was found that the synthesized NiFeS electrocatalysts exhibit the excellent hydrogen and oxygen evolution reaction performances in 1.0 M potassium hydroxide solution. The results of experimental and theoretical calculations reveal that the introduced sulfur could optimize the electronic distribution, which make Ni electron-rich and Fe electron-deficient, thereby weakening the energy barriers of potential-determining steps, i.e. the absorption of H2O molecule on Ni sites for HER and formation of *OOH on Fe sites for OER, respectively. Besides, the NiFeS electrocatalysts are used as the bifunctional electrodes to water splitting, which only need 1.51 V to reach 10 mA·cm-2, and exhibits excellent durability and a >95% Faraday efficiency. Furthermore, the intermittent kinetic, wind and solar energies are used to power the assembled electrolyzer with NiFeS bi-electrodes to verify their great application potential. This work not only proved a deep insight into mechanism of the boosted electrocatalytic activities of NiFeS, but also the synthesized NiFeS electrocatalysts have great application prospect in the conversion of intermittent and sustainable energy sources into hydrogen by water electrocatalysis.

Isolating micro/nanoplastics from organic-rich wastewater: Co/PMS outweighs Fenton system.

Rapid isolation of microplastics is the prerequisite for correct and in-depth understanding of their environmental impacts and human health threats. And Fenton's reagent (Fe/H2O2 system, FHS) has been proven to be a viable way to isolate microplastics from wastewater, but it is limited because of harsh reaction conditions, long reaction time and low efficiency. Herein, it's proven that the Fenton-like system, which is using Cobalt (II) salts to decompose potassium peroxymonosulfate (Co/PMS system, CPS) with generation of 1O2, can offer shorter time (within 30 min) in complex sample isolation. The experimental results showed that the isolation time of micro/nanoplastics from pollutants with CPS in only 30 min, while it was at least more than 5 h with FHS. Via a serious of experiments of comparison and characterization between FHS and CPS, whether from the point of view of reaction time or isolation effect, CPS is superior to FHS. On this basis, we validate the applicability of this system (CPS) in different reaction conditions (concentration, pH), different sizes (from microns to nanometers) and types of plastic (PS, PA, PE, PP, PVC). In addition, the CPS can also preserve the integrity of the plastic itself and reduce the impact on the quality of samples evidenced by a variety of characterization of physicochemical structure like UV-vis, TEM, AFM, FTIR and XPS. CPS is proved to be faster, higher, stronger for enhancing the isolation of micro/nanoplastics from complex matrix. In a word, this study provides a promising solution for the efficient isolation of microplastics from wastewater without causing additional harm to the plastics.

Polystyrene microplastics enhance oxidative dissolution but suppress the aquatic acute toxicity of a commercial cadmium yellow pigment under simulated irradiation.

Commercial cadmium yellow (CdS) pigment widely coexist with microplastics (MPs) in surface water, thus it is important to understand how MPs affect CdS pigment stability and toxicity under irradiation. Herein, the dissolution of CdS pigment (krelease = 0.118 h-1) under irradiation was visibly increased to 0.144 h-1 by polystyrene (PS) MPs, due to reactive species generation such as 1O2, •OH and 3PS* , while O2•- was unimportant to this process. The O2, humic acid, photoaging status of PS MPs could promote PS MPs-related CdS pigment dissolution rate by modifying reactive species generation. However, the CO32-, PO43- and alkaline condition significantly decreased the dissolution rate to 0.091, 0.053 and 0.094 h-1, respectively, through modifying free Cd2+ stability. Comparably, PS MPs-related CdS pigment dissolution was relatively slow in natural water samples (krelease = 0.075 h-1). PS MPs at environmental concentration can also promote CdS pigment dissolution and Cd2+ release, but suppress acute toxicity of CdS pigment to zebrafish larvae as increasing 10 h survival from 65% to 85% by adsorbing the Cd2+ and decreasing Cd2+ bioavailability. This study emphasized the environmental risks and human safety of CdS pigment should be carefully evaluated in the presence of PS MPs in aquatic environments.

Safety of Sonazoid in Assisting High-Intensity Focused Ultrasound Ablation Therapy for Advanced Liver Malignant Lesions: A Single-Arm Clinical Study.

OBJECTIVE: The aim of the study described here was to evaluate the safety of Sonazoid-assisted high-intensity focused ultrasound (HIFU) in the treatment of advanced malignant liver lesions. METHODS: A single-arm study was designed to enroll participants who were diagnosed with advanced primary liver cancer or liver metastases and proposed to receive Sonazoid assistance during HIFU treatment. Serological examination was conducted within 1 wk, and side effects in each patient were monitored for 1 mo. To evaluate therapeutic efficacy, the contrast-enhanced magnetic resonance imaging was performed 1 mo after treatment, and short-term follow-up was conducted a year later. RESULTS: A total of 17 participants (12 male, 5 female) with an average age of 58 y (range: 46-73 y) were enrolled, including 11 patients with hepatocellular carcinoma, 2 patients with hepatic metastasis and 4 patients with cholangiocarcinoma. The total volume of tumor mass was 111.82 (11.01-272.30) cm3. The average total ablation time for a patient was 2021 ± 1030 s, and the energy efficiency factor was 5979.7 (3108.0, 45634.5) J/cm3. Immediately after HIFU treatment, 1 patient (5.9%) achieved complete response (CR), 4 patients (23.5%) had a moderate response, 8 patients (47.1%) had partial reperfusion and 4 patients (23.5%) had stable disease (SD). The average ablation rate for all the tumors was 51.5 ± 26.7%. The level of glutamic-pyruvic transaminase (ALT) was mildly increased in 71.6% (12/17) of patients after HIFU therapy. Mean ALT values before and after treatment were 22 (14, 35) U/L and 36 (25, 41) U/L, respectively (Z = 1.947, p = 0.051). Mild or obvious edema in skin and subcutaneous soft tissues were observed in 76.5% of patients, but no serious side effects were found. Twelve months after treatment, the follow-up results revealed that 1 patient (5.8%) achieved a CR, 8 patients (47.1%) had SD and 8 patients (47.1%) had progressive disease. The estimated median time to progression was 11 mo after treatment, with a 95% confidence interval of 6, 11 for all involved patients. CONCLUSION: Use of Sonazoid is safe and feasible for improving HIFU ablation efficiency during the treatment of advanced malignant liver lesions. The therapeutic efficacy of Sonazoid-assisted HIFU needs to be explored in additional controlled clinical investigations.

Environmental exposure to legacy and emerging per- and polyfluoroalkyl substances and endometriosis in women of childbearing age.

Per- and polyfluoroalkyl substances (PFAS) are man-made chemicals known for their adverse effects on humans. Growing concern has risen regarding the reproductive toxicity of PFAS, but whether PFAS affect endometriosis remains to be explored. This hospital-based case-control study included 240 laparoscopic-confirmed endometriosis cases and 334 normal controls in China from 2014 to 2018. Concentrations of thirty-three legacy and emerging PFAS were measured in the plasma samples. Associations between single PFAS and endometriosis were estimated by binary logistic regression. The elastic net regression (ENR) model was used to identify dominant PFAS related to endometriosis. The joint effect of the PFAS mixture on endometriosis was assessed by principal component analysis (PCA), Bayesian kernel machine regression (BKMR), and quantile-based g-computation (q-gcomp). In the single-PFAS model, significant positive associations of PFOA [adjusted odds ratio (95 % CI): 1.22 (1.00, 1.51)], total PFOS [1.19 (1.05, 1.34)] and two branched PFOS isomers [1.16 (1.09, 1.22) for 1m-PFOS; 1.18 (1.04, 1.34) for 6m-PFOS] with increased endometriosis odds were observed. Mixture models showed that the joint effect of PFAS mixture on endometriosis was significant [1.24 (1.05, 1.48)], mainly driven by 1m-PFOS. The PFOS isomers profile suggested a PFOS precursor biotransformation source of 1m-PFOS in our population. Our study suggests that branched isomers of PFOS may be associated with endometriosis.

METTL3 regulates the proliferation, metastasis and EMT progression of bladder cancer through P3H4.

Bladder cancer, the most common malignant tumor in the urinary system, exhibits significantly up-regulated expression of P3H4, which is associated with pathological factors. The objective of this study was to elucidate the underlying mechanism of P3H4 in bladder cancer. Initially, we analyzed P3H4 gene expression using the TCGA database and evaluated P3H4 levels in clinical samples and various bladder cell lines. P3H4 was found to be markedly overexpressed in bladder cancer samples. Subsequently, bladder cancer cells were transfected with shRNA targeting P3H4 (sh-P3H4), sh-METTL3, and P3H4 overexpression vectors (P3H4 OE). Viability, migration, and invasion of bladder cancer cells were assessed using CCK-8, wound healing, and transwell assays. Western blot analysis was performed to determine the levels of EMT-associated proteins, while RNA stability assays determined the half-life of P3H4. Knockdown of P3H4 resulted in inhibition of bladder cancer cell proliferation, migration, invasion, and EMT progression. Mechanistically, METTL3 was found to regulate the mRNA stability of P3H4 in bladder cancer. Moreover, overexpression of P3H4 reversed the inhibitory effects of METTL3 knockdown on bladder cancer cell behaviors. Stable cell lines were established by infecting EJ cells with lentiviral vectors containing sh-METTL3 or P3H4 OE. These cells were then implanted into the skin of BALB/c nude mice, and IHC analysis was used to analyze the expression levels of EMT-associated proteins. In vivo studies demonstrated that inhibition of METTL3 suppressed bladder cancer growth and EMT through P3H4. In conclusion, our findings suggest that METTL3 regulates the proliferation, metastasis, and EMT progression of bladder cancer through P3H4, highlighting its potential as a therapeutic target.

Logarithmic total variation regularization via preconditioned conjugate gradient method for sparse reconstruction of bioluminescence tomography.

BACKGROUND AND OBJECTIVE: Bioluminescence Tomography (BLT) is a powerful optical molecular imaging technique that enables the noninvasive investigation of dynamic biological phenomena. It aims to reconstruct the three-dimensional spatial distribution of bioluminescent sources from optical measurements collected on the surface of the imaged object. However, BLT reconstruction is a challenging ill-posed problem due to the scattering effect of light and the limitations in detecting surface photons, which makes it difficult for existing methods to achieve satisfactory reconstruction results. In this study, we propose a novel method for sparse reconstruction of BLT based on a preconditioned conjugate gradient with logarithmic total variation regularization (PCG-logTV). METHOD: This PCG-logTV method incorporates the sparsity of overlapping groups and enhances the sparse structure of these groups using logarithmic functions, which can preserve edge features and achieve more stable reconstruction results in BLT. To accelerate the convergence of the algorithm solution, we use the preconditioned conjugate gradient iteration method on the objective function and obtain the reconstruction results. We demonstrate the performance of our proposed method through numerical simulations and in vivo experiment. RESULTS AND CONCLUSIONS: The results show that the PCG-logTV method obtains the most accurate reconstruction results, and the minimum position error (LE) is 0.254mm, which is 26%, 31% and 34% of the FISTA (0.961), IVTCG (0.81) and L1-TV (0.739) methods, and the root mean square error (RMSE) and relative intensity error (RIE) are the smallest, indicating that it is closest to the real light source. In addition, compared with the other three methods, the PCG-logTV method also has the highest DICE similarity coefficient, which is 0.928, which means that this method can effectively reconstruct the three-dimensional spatial distribution of bioluminescent light sources, has higher resolution and robustness, and is beneficial to the preclinical and clinical studies of BLT.

Correlation of immediate prevalence of cervical squamous cell precancers and cancers with HPV genotype and age in women with LSIL cytology: A retrospective analysis of 1617 cases.

AIMS: To evaluate the immediate risk of cervical squamous cell precancers and cancers in women with low-grade squamous intraepithelial lesion (LSIL) cytology according to different high-risk human papillomavirus (hrHPV) results and age stratification. METHODS: The study included 1617 women with LSIL cytology and underwent simultaneous Aptima HPV genotyping (E6/E7 mRNA test) followed by cervical biopsy. RESULTS: Among 1317 hrHPV positive cases, other 11 types of hrHPV were the most frequent (68.8%), followed by HPV16 (11.1%), HPV18/45 (4.1%), and HPV16/HPV18/45 (0.5%). Compared to other groups, HPV18/45 positive group and other 11 types of hrHPV group showed significantly higher prevalence of intraepithelial neoplasia grade (CIN)1 (p < .0001), while HPV16 positive and HPV16/HPV18/45 dual positive groups showed significantly higher prevalence of CIN2/3 (p < .0001). In addition, hrHPV positive, 25-39 years-old age group showed a significantly higher prevalence of CIN1 (p = .032) than the other age groups. Furthermore, CIN1 prevalence was significantly higher in patients under 40 or 50 years of age than in those over 40 or 50 years of age (p = .005 and p = .011, respectively). However, there was no significant difference among the different age groups in CIN2/3 prevalence in women with LSIL cytology. CONCLUSION: In southern Chinese women population, LSIL cytology carries very low immediate risk of high-grade squamous intraepithelial lesions (HSIL) (CIN2/3) in general. However, HPV16 positive and HPV16/HPV18/45 dual positive indicated a higher immediate risk of high-grade squamous intraepithelial lesions (HSIL) (CIN2/3). Age is not an immediate risk factor in this patient population for high-grade squamous lesions or SCC. These results are similar to data from cytology laboratories in the United States and other international settings, therefore strongly support the usage of ASCCP guidelines in this patient population.

HSP90ß regulates EAAT2 expression and participates in ischemia­reperfusion injury in rats.

Cerebrovascular diseases (CVDs) have become a global public health problem and ischemia­reperfusion injury, the major cause of neurological impairment exacerbation, is closely related to excitotoxicity. The present study aimed to investigate the effects of changes in heat shock protein (HSP)90ß expression and verify whether HSP90ß regulates EAAT2 expression in a cerebral ischemia­reperfusion injury model. Healthy adult Sprague­Dawley (SD) male rats were used to establish a control group, sham­operated group, middle cerebral artery occlusion (MCAO) group, empty virus group and lentivirus group. A model of cerebral ischemia­reperfusion was established using the MCAO method. Lentivirus construction and injection were used to interfere with the expression of HSP90ß. The modified neurological severity score was used to assess neurological deficits. Triphenyltetrazolium chloride staining was used to detect infarct areas. Immunofluorescence was used to detect HSP90ß expression localization and the expression levels of HSP90ß and EAAT2 were determined using western blotting and reverse transcription­quantitative PCR. An MCAO model was successfully established and it was found that HSP90ß, but not HSP90α, was upregulated after MCAO. HSP90ß expression coincided with astrocyte markers in the ischemic penumbra area, while no expression was observed in microglia. Inhibition of HSP90ß expression improved neurological deficits and alleviated brain injury by increasing EAAT2 expression. These results suggested that HSP90ß is involved in the process of cerebral ischemia­reperfusion injury in rats and that inhibition of HSP90ß expression increases EAAT2 levels, conferring a neuroprotective effect in MCAO model rats.

A clean method for gallium recovery and the coproduction of silica-potassium compound fertilizer and zeolite F from brown corundum fly ash.

Brown corundum fly ash (BCFA) is a solid waste from the brown corundum smelting process that contains abundant Ga, K, Si, and Al, but effectively extracting Ga can be challenging since most of it is located inside the particles. This study proposes a comprehensive utilization method of BCFA that combines hydrothermal leaching and alkali regeneration to extract Ga efficiently while producing silica-potassium compound fertilizer (SPCF) and zeolite F. By utilizing the transformation of phase and structure in the hydrothermal leaching process, Ga extraction is efficiently achieved. The results showed that under the conditions of 210 g/L KOH concentration, a liquidsolid ratio of 25 mL/g, and 160 °C hydrothermal leaching for 60 min, the extraction efficiencies of Ga, K, and Si were 95.91 %, 51.78 %, and 69.57 %, respectively. The solid product's effective SiO2 and K2O contents increased to 24.72 wt% and 17.74 wt%, respectively, which can be further used as SPCF for agricultural production. The hydrothermal leaching solution was regenerated by adjusting the Al/Si molar ratio and crystalizing at 160 °C for 24 h. The Si was recovered in the form of high value-added zeolite F, with only a 3.60 % loss of Ga.

Polyfluoroalkyl phosphate esters (PAPs) as PFAS substitutes and precursors: An overview.

Polyfluoroalkyl phosphate esters (PAPs) are emerging substitutes for legacy per- and polyfluoroalkyl substances (PFAS), which are widely applied in consumer products and closely related to people's daily lives. Increasing concern has been raised about the safety of PAPs due to their metabolism into perfluorooctanoic acid (PFOA) and other perfluorinated carboxylates (PFCAs) in vivo. This review summarizes the current knowledge on PAPs and highlights the knowledge gaps. PAPs dominated the PFAS profiles in wastewater, sludge, household dust, food-contact materials, paper products, paints, and cosmetics. They exhibit biomagnification due to their higher levels in top predators. PAPs have been detected in human blood worldwide, with the highest mean levels being found in the United States (1.9 ng/mL) and China (0.4 ng/mL). 6:2 diPAP is the predominant PAP among all identified matrices, followed by 8:2 diPAP. Toxicokinetic studies suggest that after entering the body, most PAPs undergo biotransformation, generating phase Ⅰ (i.e., PFCAs), phase II, and intermediate products with toxicity to be verified. Several epidemiological and toxicological studies have reported the antiandrogenic effect, estrogenic effect, thyroid disruption, oxidative damage, and reproductive toxicity of PAPs. More research is urgently needed on the source and fate of PAPs, human exposure pathways, toxicity other than reproductive and endocrine systems, toxic effects of metabolites, and mixed exposure effects.

Estimating atmospheric nitrogen deposition within a large river basin using moss nitrogen and isotope signatures.

Assessing flux and primary sources of the atmospheric nitrogen (N) deposition with high spatial resolution remained challenging. The epilithic moss is considered a suitable biological monitor to explore N deposition. Our study presented a detailed analysis of flux and major source contributions of ammonium (NH4+) and nitrate (NO3-) deposition using N and δ15N signatures of epilithic moss collected densely from the Yangtze River basin. The results showed a more negative δ15N and higher N concentration of the moss in cropland and urban area than in forest and grassland of the basin. A gradient of the estimated N deposition (9.6-34.0 kg ha-1 yr-1) occurred from the Tibetan Plateau to lower reaches, with amount of NH4+ was approximately three times higher than NO3- deposition. The contribution from volatilization to NH4+ deposition (33.28 ± 8.10%) was less than the contribution from combustion (66.72 ± 8.10%), inconsistent with the traditional findings that N fertilizer and livestock waste are the principal sources of NH3 emissions. Fossil fuel was the dominant sources of NO3- deposition, accounted for 70.22 ± 18.67%. From 2006 to 2019, the source contribution of N deposition in forest remained unchanged, while NH3 volatilization and fossil fuel emitted NOx in urban areas have increased. Our findings highlighted the importance of combustion sources to N deposition in the Yangtze River basin.

Efficient degradation of imidacloprid by surface discharge cold plasma: Mechanism of interaction between ROS and molecular structure and evaluation of residual toxicity.

Incorrect use of neonicotinoid pesticides poses a serious threat to human and pollinator health, as these substances are commonly present in bee products and even drinking water. To combat this threat, the study developed a new method of degrading the pesticide imidacloprid using surface discharge cold plasma oxidation technology. The study showed that this method achieved a very high efficiency of imidacloprid degradation of 91.4%. The main reactive oxygen species (H2O2, O3, ·OH, O2-, 1O2) effectively participated in the decomposition reaction of imidacloprid. Reactive oxygen species were more sensitive to the structure of the nitroimine group. Density functional theory (DFT) further explored the sites of reactive oxygen species attack on imidacloprid and revealed the process of energy change of attacking imidacloprid. In addition, a degradation pathway for imidacloprid was proposed, mainly involving reactive oxygen species chemisorption, a ring-opening intermediate, and complete cleavage of the nitroimine group structure. Model predictions indicated that acute oral and developmental toxicity were significantly reduced after cold plasma treatment, as confirmed by insect experiments. Animal experiments have shown that plasma treatment reduces imidacloprid damage to mice hippocampal tissue structure and inhibits the reduction of brain-derived neurotrophic factor content, thus revealing the detoxification mechanism of the body.

Epigenetically upregulated NSUN2 confers ferroptosis resistance in endometrial cancer via m5C modification of SLC7A11 mRNA.

Endometrial cancer (EC) is a prevalent gynecological malignancy worldwide, and 5-methylcytosine (m5C) modification of mRNA is a crucial epigenetic modification associated with the development and occurrence of several cancers. However, the precise function of m5C modification in EC remains elusive. This study aimed to investigate the expression and clinical significance of the primary m5C modification writer, NSUN2, in EC. Our findings indicated that NSUN2 exhibited a substantial up-regulation in EC as a result of an epigenetic augmentation in H3K4me3 levels within the promoter region, which was triggered by the down-regulation of KDM5A. Moreover, gain- and loss-of-function experiments revealed the role of NSUN2 in enhancing m5C modification of mRNA, thereby promoting EC cell proliferation. RNA bisulfite sequencing and transcriptomic sequencing were employed to elucidate the involvement of NSUN2 in the regulation of ferroptosis. Subsequent in vitro experiments confirmed that the knockdown of NSUN2 significantly up-regulated the levels of lipid peroxides and lipid ROS in EC cells, thereby augmenting the susceptibility of EC to ferroptosis. Mechanistically, NSUN2 stimulated the m5C modification of SLC7A11 mRNA, and the m5C reader YBX1 exhibited direct recognition and binding to the m5C sites on SLC7A11 mRNA via its internal cold shock domain (CSD), leading to an increase in SLC7A11 mRNA stability and elevated levels of SLC7A11. Additionally, rescue experiments showed that NSUN2 functioned as a suppressor of ferroptosis, which was dependent on SLC7A11. Overall, targeting the NSUN2/SLC7A11 axis inhibited tumor growth by increasing lipid peroxidation and ferroptosis of EC cells both in vitro and in vivo. Therefore, our study provides new insight into the role of NSUN2, suggesting that NSUN2 may serve as a prognostic biomarker and therapeutic target in patients with EC.

Using HFACS to understand human error in railway dispatcher performance: a study of proactive safety inspection records.

This study analyzes 4,095 proactive safety inspection records obtained from a large dispatching center by utilizing the HFACS framework. These proactive safety inspection records offer comprehensive documentation of incidents, capturing major accidents and numerous minor discrepancies and lapses that often go unnoticed in accident reports. The analysis revealed that most incidents were attributed to unsafe actions, primarily skill-based errors and poor decision-making. Additionally, contributing factors such as adverse mental states, personal readiness, and crew resource management were found to play a significant role as preconditions for unsafe acts. Path analyses further established a significant correlation between factors such as unsafe supervision, preconditions for unsafe acts, and the occurrence of unsafe acts. In our discussion, we critically evaluate the strengths and limitations of proactive safety inspection records in safety research. Moreover, we emphasize these findings' potential to enhance safety within the railway industry.

Based on a substantial dataset comprising proactive safety inspection records of railway dispatchers rather than the incident reports utilized in prior studies, this paper presents a causal model of human error among railway dispatchers in combination with HFACS and critically evaluates the strengths and limitations of active safety inspection records.

Safety and Immunogenicity of Homologous Recombinant Adenovirus Type 5-Vectored COVID-19 Vaccine Booster Dose in Healthy Adults Aged 18-60 Years: a Single-Center, Open-Label Trial.

INTRODUCTION: The waning antibody levels several months after prime vaccination and the persistent epidemics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) around the world have generated great interest in the evaluation of a booster dose. We aimed to assess the safety and immunogenicity of a homologous booster dose of the recombinant adenovirus type 5-vectored coronavirus disease 2019 (COVID-19) vaccine (Ad5-nCoV). METHODS: In this trial, we recruited healthy adults aged 18-60 years who had received one dose of Ad5-nCoV vaccine (low, middle, or high dose) in the previous phase 1 trial approximately 6 months earlier, and then all participants received a booster dose of 5 × 1010 viral particles (low dose) intramuscularly. The primary outcome was the incidence of adverse reactions within 14 days after booster vaccination. The specific binding antibodies were measured by enzyme-linked immunosorbent assay and the neutralizing antibody responses were assessed with live SARS-CoV-2 and pseudovirus neutralization assay. The cellular immune responses were analyzed by enzyme-linked immunospot assay and intracellular cytokine staining. RESULTS: From September 26 to 28, 2020, 108 volunteers were recruited and 89 eligible participants (52% male) were enrolled and received a booster dose of Ad5-nCoV vaccine: 28 (31%) had received a low prime dose, 30 (34%) a middle prime dose, and 31 (35%) a high prime dose in the previous phase 1 trial. All participants were included in the safety analysis and immunogenicity was assessed in 88 (99%) participants. Twenty-three (82%) participants in the low prime dose group, 23 (77%) participants in the middle prime dose group, and 26 (84%) participants in the high prime dose group reported at least one adverse reaction within the first 14 days post booster. Pain at the injection site and fatigue were the most common adverse reactions. Most adverse reactions were mild or moderate in all groups and no vaccine-related severe adverse event was noted within 12 months after booster vaccination. Neutralizing antibodies increased moderately at day 14 and peaked at 28 days post booster. T cell responses were also boosted at 14 days after vaccination. CONCLUSIONS: A homologous booster of Ad5-nCoV vaccine is well tolerated and immunogenic in healthy adults aged 18-60 years who had received a priming dose of Ad5-nCoV 6 months previously. The neutralizing antibodies against SARS-CoV-2 peaked at day 28 and specific T cell responses were noted at day 14 after booster. Ad5-nCoV vaccine can be considered as a homologous booster 6 months after a priming dose. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04568811.

Identifying TYMP as an Immune Prognostic Marker in Clear Cell Renal Cell Carcinoma.

BACKGROUND: In clear cell renal cell carcinoma (ccRCC), only some patients can benefit from immunotherapy therapy, and it is urgent to find immune-related molecular markers and targets. METHODS: Thymidine phosphorylase (TYMP) expression level and predictive value in pan-cancers were analyzed using TIMER, GEPIA2, and The Human Protein Atlas. We obtained ccRCC tissues to verify the differential expression of TYMP and confirmed the biological function in vitro. Subsequently, Gene Ontology, Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) are used to explore the potential mechanism of TYMP. Finally, TIMER was used to analyze the infiltration levels and prognostic value of different immune cells. RESULTS: TYMP is upregulated in various cancers, including ccRCC, and there is a certain degree of causality between high expression and poor prognosis in ccRCC. It was confirmed that TYMP knockdown could suppress cell aggressiveness, and cause cell death. Differential analysis showed that 55 differential genes were upregulated in the high-expression groups of TYMP. KEGG and GSEA analyses suggested that TYMP was linked to immune cell invasion, fatty acid metabolism, and P53 signaling pathway. Further investigation revealed that the expression level of TYMP linked positively to T-cell follicular helper and Tregs, but negatively with mast cell activation. Finally, a Nomogram was established on the base of expression level of TYMP and the clinical characteristics of ccRCC patients to predict prognosis. CONCLUSIONS: Patient survival is poor and immune cell infiltration is abnormal when TYMP is highly expressed in ccRCC, suggesting that ccRCC patients could benefit from using TYMP as a molecular diagnostic and therapeutic target.

Association between serum polyunsaturated fatty acids and bone mineral density in US adults: NHANES 2011-2014.

Objective: The purpose of this study was to investigate the association between serum polyunsaturated fatty acids (PUFAs) and bone mineral density (BMD). Methods: We performed a cross-sectional study based on data from the National Health and Nutrition Examination Survey (NHANES) 2011-2014. The weighted multiple linear regression model was utilized to determine the association between serum PUFAs and BMD. Further smoothed curve fitting and threshold effect analysis were conducted. Finally, we performed a subgroup analysis. Results: In total, 1979 participants aged 20-59 years were enrolled. After adjusting for all covariates, we found that serum docosapentaenoic acid (DPA) was positively associated with head BMD (ß = 0.0015, 95% Cl: 0.0004, 0.0026, P = 0.008296) and lumbar spine BMD (ß = 0.0005, 95% Cl: 0.0000, 0.0010, P = 0.036093), and serum eicosadienoic acid (EDA) was negatively associated with thoracic spine BMD (ß = -0.0008, 95% Cl: -0.0016, -0.0000, P = 0.045355). Smoothed curve fitting revealed a nonlinear positive association between serum DPA and lumbar spine BMD. Threshold effect analysis indicated that the threshold of serum DPA was 81.4 µmol/L. Subgroup analysis revealed a positive correlation between serum DPA and head BMD in the subgroup aged 50-59 years (ß = 0.0025, 95% Cl: 0.0002, 0.0049, P = 0.035249) and females (ß = 0.0026, 95% Cl: 0.0008, 0.0044, P = 0.005005). There was a positive relationship between serum DPA and lumbar spine BMD in females (ß = 0.0008, 95% Cl: 0.0001, 0.0015, P = 0.017900) and a negative association between serum EDA and thoracic spine BMD in the subgroup aged 30-39 years (ß = -0.0016, 95% Cl: -0.0031, -0.0001, P = 0.041331), males (ß = -0.0012, 95% Cl: -0.0023, -0.0001, P = 0.039364) and other races (ß = -0.0021, 95% Cl: -0.0037, -0.0006, P = 0.008059). Conclusion: This study demonstrated a linear positive relationship between serum DPA and head BMD, a nonlinear positive association between serum DPA and lumbar spine BMD, and a linear negative correlation between serum EDA and thoracic spine BMD in US adults.