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Abstract Streets and roads have been constantly identified as key spaces to improve walkability and—by extension—the entire urban environment. Such improvements lie on planning and design theories that are often supported by qualitative evidence and as such, tend to remain highly speculative on how street design influences walkability in more deterministic ways. Drawbacks in further exploring this street-walkability correlation are partly defined by an explicit rejection to ‘spatial determinism’ in urban morphology and social sciences, but also because combining differing epistemological approaches for understanding social processes linked to the physical aspects of the space is complex. In this paper, it is proposed that qualitative (social-based) theories of the space and quantitative (positivist) understandings of people’s behaviour can complement each other to elaborate upon ‘spatial determinism’ with focus on streetscapes and pedestrian behaviour. By using Agent-Based Modelling (ABMs), morphological components of streets linked to population characteristics are analysed to understand walkability from the perspective of spatial determinism. The findings suggest that the street settings directly affect pedestrian behaviour, and that changes in the built environment result in changes on walkability patterns. Ultimately, the modelling exercise shed light on street design and walkability, but also on wider debates on how urban design and social processes correlate in more deterministic and, therefore, predictable ways.

Abstract Background Renal cell carcinoma (RCC) is a type of cancer that can develop at any point in adulthood, spanning the range of age-related changes that occur in the body. However, the specific molecular mechanisms underlying the connections between age and genetic mutations in RCC have not been extensively investigated. Methods Clinical and genetic data from patients diagnosed with RCC were collected from two prominent medical centers in China as well as the TCGA dataset. The patients were categorized into two groups based on their prognosticated age: young adults (YAs) and older adults (OAs). Univariate and multivariate analysis were employed to evaluate the relationships between age and genetic mutations. Furthermore, a mediation analysis was conducted to assess the association between age and overall survival, with genetic disparities serving as a mediator. Results Our analysis revealed significant differences in clinical presentation between YAs and OAs with RCC, including histopathological types, histopathological tumor stage, and sarcomatoid differentiation. YAs were found to have lower mutation burden and significantly mutated genes (SMGs) of RCC. However, we did not observe any significant differences between the two groups in terms of 10 canonical oncogenic signaling pathways-related genes mutation, telomerase-related genes (TRGs) mutation, copy number changes, and genetic mutations associated with clinically actionable targeted drugs. Importantly, we demonstrate superior survival outcomes in YAs, and we confirmed the mediating effect of genetic disparities on these survival outcome differences between YAs and OAs. Conclusion Our findings reveal previously unrecognized associations between age and the molecular underpinnings of RCC. These associations may serve as valuable insights to guide precision diagnostics and treatments for RCC.

Abstract Molecular weight (MW) of organics was one of the important factors influencing membrane fouling propensity. This study identified critical foulants of reverse osmosis (RO) membranes in reclaimed water by MW fractionation. MW > 10 kDa component was identified as the critical fouling contributor (CFC) in secondary effluent (SE), which accounted for only 13 ± 5% of dissolved organic carbon (DOC) but contributed to 86 ± 11% of flux decline. Throughout 12-month monitoring, SE and MW > 10 kDa component showed a similar fouling variation tendency: apparently higher fouling potential in winter and lower in summer, while MW 10 kDa component and glean valuable insights into RO fouling mechanisms of reclaimed water in practical application.

Abstract Objectives Endocardial trabeculae undergo varicose changes and hyperplasia in response to hemodynamic influences and are a variable phenotype reflecting changes in disease. Fractal analysis has been used to analyze the complexity of endocardial trabeculae in a variety of cardiomyopathies. The aim of this paper was to quantify the myocardial trabecular complexity through fractal analysis and to investigate its predictive value for the diagnosis of heart failure with preserved ejection fraction (HFpEF) in patients with multivessel coronary artery disease (CAD). Methods The retrospective study population consisted of 97 patients with multivessel CAD, 39 of them were diagnosed with HFpEF, while 46 healthy volunteers were recruited as controls. Fractal dimension (FD) was obtained through fractal analysis of endocardial trabeculae on LV short-axis cine images. Logistic regression analyses were used to confirm the predictors and compare different prediction models. Results Mean basal FD was significantly higher in patients with HFpEF than in patients without HFpEF or in the healthy group (median: 1.289; IQR: 0.078; p

Abstract To improve the precision of defect categorization and localization in images, this paper proposes an approach for detecting surface defects in hot-rolled steel strips. The approach uses an improved YOLOv5 network model to overcome the issues of inadequate feature extraction capacity and suboptimal feature integration when identifying surface defects on steel strips. The proposed method achieves higher detection accuracy and localization precision, making it more competitive and applicable in real production. Firstly, the multi-scale feature fusion (MSF) strategy is utilized to fuse shallow and deep features effectively and enrich detailed information relevant to target defects. Secondly, the CSPLayer Res2Attention block (CRA block) residual module is introduced to reduce the loss of defect information during hierarchical transmission, thereby enhancing the extraction of fine-grained features and improving the perception of details and global features. Finally, the experimental results indicate that the mAP on the NEU-DET and GC10-DET datasets approaches 78.5% and 67.3%, respectively, which is 4.9% and 2.1% higher than that of the baseline. Meanwhile, it has higher precision and more precise localization capabilities than other methods. Furthermore, it also achieves 59.2% mAP on the APDDD dataset, indicating its potential for growth in further domains.

Background: To explore the median effective dose (ED50) and 95% effective dose (ED95) of remimazolam besylate combined with alfentanil for adult gastroscopy. Methods: This prospective studyenrolled 31 patients scheduled to painless gastroscopy at Anhui No. 2 Provincial People's Hospital between April and May, 2022. 5 µg.kg−1 of alfentanil hydrochloride was used for pre-analgesia. The initial single loading dose of remimazolam besylate was 0.12 mg.kg−1, increased or reduced by 0.01 mg.kg−1 for the next patient with modified Dixon sequential method. The modified Observer's Assessment of Alertness/Sedation Scale (MOAA/S) was used to assess sedation. Results: Combined with alfentanil, the ED50 of remimazolam besylate was 0.147 mg.kg−1 (95% CI: 0.138-0.160 mg.kg−1) and ED95 0.171 mg.kg−1 (95% CI: 0.159-0.245 mg.kg−1). The induction time after injection of remimazolam besylate was 70 ± 25 s, with the anesthesia recovery time and the observation time in resuscitation room 5.13 ± 2.13 min and 2.32 ± 1.6 min, respectively. Twenty nine patients’ vital signs were within acceptable limits during gastroscopy. Conclusions: The ED50 of remimazolam besylate combined with alfentanil for painless gastroscopy was 0.147 mg.kg−1, and the ED95 was 0.171 mg.kg−1.

Leakage failure occurred in the reheater pipe of a subcritical unit after 9 years operation, but didn't reach the design lifespan. Multi test and analysis methods were applied to find the failure reason and mechanism. The results show that the main failure mode is the thinning of the pipe wall caused by high temperature corrosion, the metal loss of the pipe wall is more than 25 %. Through the analysis of the structure and composition of the corrosion products, it is found that the corrosion products of the pipe wall are divided into three layers, while a large number of pores exist between the corrosion products and base material, hereby, the corrosive substances can continuously reach the surface of the base material. The content of sulfur and oxygen in the corrosion layer on the side of pipe wall is high, and the percentage reaches 20.95 % and 49.17 % respectively. It is proved that sulfur is the main factor affecting the high temperature corrosion of reheater pipes, and sulfate is produced by the combined action of sulfur and oxygen. Under the continuous action of high temperature sulfur corrosion, the local pipe wall of the pipeline is thinned and eventually leaks.

Abstract Background Coronary artery disease (CAD) is a complex disease that is influenced by environmental and genetic factors. In this study, we aimed to investigate the relationship between coding variants in lipid metabolism-related genes and CAD in a Chinese Han population. Methods A total of 252 individuals were recruited for this study, including 120 CAD patients and 132 healthy control individuals. Rare and common coding variants in 12 lipid metabolism-related genes (ANGPTL3, ANGPTL4, APOA1, APOA5, APOC1, APOC3, CETP, LDLR, LIPC, LPL, PCSK9 and SCARB1) were detected via next-generation sequencing (NGS)-based targeted sequencing. Associations between common variants and CAD were evaluated by Fisher’s exact test. A gene-based association test of rare variants was performed by the sequence kernel association test-optimal (SKAT-O test). Results We found 51 rare variants and 17 common variants in this study. One common missense variant, LIPC rs6083, was significantly associated with CAD after Bonferroni correction (OR = 0.47, 95% CI = 0.29–0.76, p = 1.9 × 10− 3). Thirty-three nonsynonymous rare variants were identified, including two novel variants located in the ANGPTL4 (p.Gly47Glu) and SCARB1 (p.Leu233Phe) genes. We did not find a significant association between rare variants and CAD via gene-based analysis via the SKAT-O test. Conclusions Targeted sequencing is a powerful tool for identifying rare and common variants in CAD. The common missense variant LIPC rs6083 confers protection against CAD. The clinical relevance of rare variants in CAD aetiology needs to be investigated in larger sample sizes in the future.

Abstract Domestic attempts to advance the Sustainable Development Goals (SDGs) in a country can have synergistic and/or trade-off effects on the advancement of SDGs in other countries. Transboundary SDG interactions can be delivered through various transmission channels (e.g., trade, river flow, ocean currents, and air flow). This study quantified the transboundary interactions through these channels between 768 pairs of SDG indicators. The results showed that although high income countries only comprised 14.18% of the global population, they contributed considerably to total SDG interactions worldwide (60.60%). Transboundary synergistic effects via international trade were 14.94% more pronounced with trade partners outside their immediate geographic vicinity than with neighbouring ones. Conversely, nature-caused flows (including river flow, ocean currents, and air flow) resulted in 39.29% stronger transboundary synergistic effects among neighboring countries compared to non-neighboring ones. To facilitate the achievement of SDGs worldwide, it is essential to enhance collaboration among countries and leverage transboundary synergies.

AbstractBackground Venetoclax monotherapy is an effective option for patients with acute myeloid leukemia (AML). Venetoclax has also been used in non-myeloablative conditioning allogeneic hematopoietic stem cell transplantation (allo-HSCT) for high-risk AML with a tolerable toxicity profile. However, the efficacy and safety of a venetoclax-containing myeloablative conditioning (MAC) allo-HSCT regimen for high-risk AML have not been evaluated.Objective To evaluate the safety and efficacy of a MAC regimen containing venetoclax for high-risk AML.Study design From 25 February 2021 to 4 September 2022, a total of 31 patients with high-risk AML who underwent allo-HSCT and a MAC regimen with venetoclax were analyzed.Results At the time of transplantation, 21 patients were in first complete remission (CR1), 4 were in a second complete remission (CR2), and 6 in non-remission (NR). Twenty-four patients (77.4%) were minimal residual disease (MRD)-positive before transplant. The FLT3-ITD gene mutation was present in 51.6% of patients. NUP98 rearrangement, MLL rearrangement or MLL-PTD and DEK::CAN fusion genes were found in 5 (16.1%), 7(22.6%) and 2 (6.5%) patients, respectively. Twenty-nine (93.6%) patients underwent haploidentical allo-HSCT. The median follow-up time was 278 days (range: 52–632 days). The 100-day cumulative incidence of grade 3 to 4 acute graft-versus-host disease (aGVHD) was 16.1% (95%CI, 7.2–36.0%). The 180-day cumulative incidence of moderate to severe chronic graft-versus-host disease (cGVHD) was 7.1% (95%CI, 1.9–26.9%). Cumulative incidence of 100-day cytomegalovirus (CMV) viraemia and 100-day Epstein-Barr virus (EBV) viraemia was 61.6% (95%CI, 46.5–81.4%) and 3.2% (95%CI, 0.4–22.2%), respectively. The 600-day overall survival (OS) and leukemia-free survival (LFS) were 80.9% (95%CI, 63.5–93.6%) and 81.3% (95%CI, 64.2–93.7%), respectively. The 600-day relapse incidence (RI) and non-relapse mortality (NRM) was 6.9% (95%CI, 1.8–26.3%) and 11.7% (95%CI, 3.9–35.0%).Conclusion Our study shows that the addition of venetoclax to a MAC allo-HSCT was feasible, safe and effective for high-risk AML patients.

Abstract The inflammatory damage caused by thrombus formation and dissolution can increase the risk of thrombotic complications on top of cell death and organ dysfunction caused by thrombus itself. Therefore, a rapid and precise thrombolytic therapy strategy is in urgent need to effectively dissolve thrombus and resist oxidation simultaneously. In this study, Ce‐UiO‐66, a cerium‐based metal–organic framework (Ce‐MOF) with reactive oxygen species (ROS) scavenging properties, encapsulated by low‐immunogenic mesenchymal stem cell membrane with inflammation‐targeting properties, is used to construct a targeted nanomedicine Ce‐UiO‐CM. Ce‐UiO‐CM is applied in combination with external ultrasound stimulation for thrombolytic therapy in rat femoral artery. Ce‐UiO‐66 has abundant Ce (III)/Ce (IV) coupling sites that react with hydrogen peroxide (H2O2) to produce oxygen, exhibiting catalase (CAT) activity. The multi‐cavity structure of Ce‐UiO‐66 can generate electron holes, and its pore channels can act as micro‐reactors to further enhance its ROS scavenging capacity. Additionally, the porous structure of Ce‐UiO‐66 and the oxygen produced by its reaction with H2O2 may enhance the cavitation effects of ultrasound, thereby improving thrombolysis efficacy.

The increase in UV-B radiation at the Earth’s surface due to the depletion of the stratospheric ozone layer is a notable facet of contemporary climate change patterns. The macroalgae inhabiting the intertidal zone exhibit a diverse array of adaptive strategies to cope with dramatic environmental changes. In this study, we integrated physiological, transcriptomic and metabolomic data from energy metabolism perspective to elucidate the responses and recovery mechanism of N. haitanensis to UV-B radiation exposure. UV-B radiation has a harmful impact on the photosynthetic performance of N. haitanensis. However, an increase in photosynthetic performance and upregulated expression of genes related to photosynthesis were observed during recovery, suggesting that the effect of UV-B on N. haitanensis was dynamic photoinhibition. Recovery experiments revealed that most genes and metabolites related to glycolysis were significantly upregulated, suggesting that glycolysis was activated to promote energy production. In addition, the TCA cycle was also activated, as evidenced by the increase in key substances and the upregulated expression of key enzyme-encoding genes during recovery. Correspondingly, ATP was also abundantly accumulated. These results suggested that the TCA cycle provided ATP for N. haitanensis to repair UV-B damage. Meanwhile, amino acid metabolism was enhanced during recovery as a source of intermediates for the TCA cycle. Therefore, photosynthesis, glycolysis, the TCA cycle, and amino acid metabolism synergistically cooperate to provide material and energy for recovery after UV-B radiation. This study is important for understanding the adaptive strategies of intertidal macroalgae in response to UV-B radiation.

Abstract MicroRNAs (miRNAs) have been reported to serve as potential biomarkers in bladder cancer and play important roles in cancer progression. This study aimed to investigate the biological role of miR-205-3p in bladder cancer. We showed that miR-205-3p was significantly down-regulated in bladder cancer tissues and cells. Moreover, overexpression of miR-205-3p inhibited bladder cancer progression in vitro. Then we confirmed that GLO1, a downstream target of miR-205-3p, mediated the effect of miR-205-3p on bladder cancer cells. In addition, we found that miR-205-3p inhibits P38/ERK activation through repressing GLO1. Eventually, we confirmed that miR-205-3p inhibits the occurrence and progress of bladder cancer by targeting GLO1 in vivo by nude mouse tumorigenesis and immunohistochemistry. In a word, miR-205-3p inhibits proliferation and metastasis of bladder cancer cells by activating the GLO1 mediated P38/ERK signaling pathway and that may be a potential therapeutic target for bladder cancer.

Abstract Background After the eradication of smallpox in China in 1979, vaccination with the vaccinia virus (VACV) Tiantan strain for the general population was stopped in 1980. As the monkeypox virus (MPXV) is rapidly spreading in the world, we would like to investigate whether the individuals with historic VACV Tiantan strain vaccination, even after more than 40 years, could still provide ELISA reactivity and neutralizing protection; and whether the unvaccinated individuals have no antibody reactivity against MPXV at all. Results We established serologic ELISA to measure the serum anti-MPXV titer by using immunodominant MPXV surface proteins, A35R, B6R, A29L, and M1R. A small proportion of individuals (born before 1980) with historic VACV Tiantan strain vaccination exhibited serum ELISA cross-reactivity against these MPXV surface proteins. Consistently, these donors also showed ELISA seropositivity and serum neutralization against VACV Tiantan strain. However, surprisingly, some unvaccinated young adults (born after 1980) also showed potent serum ELISA activity against MPXV proteins, possibly due to their past infection by some self-limiting Orthopoxvirus (OPXV). Conclusions We report the serum ELISA cross-reactivity against MPXV surface protein in a small proportion of individuals both with and without VACV Tiantan strain vaccination history. Combined with our serum neutralization assay against VACV and the recent literature about mice vaccinated with VACV Tiantan strain, our study confirmed the anti-MPXV cross-reactivity and cross-neutralization of smallpox vaccine using VACV Tiantan strain. Therefore, it is necessary to restart the smallpox vaccination program in high risk populations.

Plate turning is an essential step in the plate rolling process. The traditional control mode relies on the manual observation of billets and mainly manual operation. Manual plate turning becomes an external disturbance of the automatic control system of plate mills, which reduces the reproducibility and accuracy of the rolling process. The automatic plate turning function is urgently needed to improve the control level of the rolling line. In this paper, based on the improved image processing algorithm, the position and angle information of the billet conversion process are detected in real time, and the real-time processing of detection data in a complex production environment is realized. Based on the change in the billet rotation angle in the actual plate turning process, a mathematical model is constructed to simulate the plate turning process. On this basis, the digital model and optimization algorithm for automatic plate turning based on reinforcement learning are established, and the automatic optimization of plate turning speed and accuracy is completed. The field application of data-driven plate turning systems replaces manual plate turning control. The plate turning angle detection error of the system is ≤2°. The average plate turning time of each billet is greatly shortened compared with manual plate turning mode, and the fastest time can be shortened by more than 1 s, which greatly improves the production efficiency and is of great significance for improving the automatic control level and digital upgrade of plate mills.

Germline mutations in genes involved in perforin-granzyme-mediated cytotoxicity such as PRF1, UNC13D, STX11, and STXBP2 were known to cause familial hemophagocytic lymphohistiocytosis (FHL). In this study, we reported a unique group of 3 patients with germline mutations of UNC13D and STX11 genes and presented as adult-onset peripheral T-cell lymphoma (PTCL) with cytotoxic T-cell phenotype and atypical lymphoma presentations. CD107a degranulation assay and NK-cell activity analysis demonstrated impaired cytotoxic function of the NK/T-cells of the patients with FHL-related mutations. Gene expression profile study revealed that up-regulated genes of the cytotoxic T-cells were enriched in autoimmune-related pathways. It was possible that impaired cytotoxic lymphocyte-mediated immune surveillance and autoantigen stimulation may both participate in PTCL oncogenesis. Germline defects of FLH-related genes may represent a novel predisposing factor for PTCLs.

The occurrence of a co-infection involving four distinct respiratory pathogens could be underestimated. Here, we report the case of a 72-year-old woman who presented to a community hospital with a cough productive of sputum as her main clinical manifestation. Antibody detection of common respiratory pathogens revealed potential co-infection with influenza A, influenza B, respiratory syncytial virus, and Chlamydia pneumoniae. We treated her with 75 mg oseltamivir phosphate administered orally twice daily for 5 days, 0.5 g azithromycin administered orally for 5 days, and 0.3 g acetylcysteine aerosol inhaled twice daily for 3 days. The patient showed a favorable outcome on the eighth day after early diagnosis and treatment. Since co-infection with these four pathogens is rare, we performed an extensive PubMed search of similar cases and carried out a systematic review to analyze the epidemiology, clinical manifestations, transmission route, susceptible population, and outcomes of these four different pathogens. Our report highlights the importance for general practitioners to be vigilant about the possibility of mixed infections when a patient presents with respiratory symptoms. Although these symptoms may be mild, early diagnosis and timely treatment could improve outcomes. Additionally, further research is warranted to explore the potential influence of SARS-CoV-2 infection on the co-occurrence of multiple respiratory pathogens.

Transients in hydraulic systems are normally simulated by one-dimensional (1D) method of characteristics (MOC). When local three-dimensional (3D) flow patterns have crucial impacts on the hydraulic system characteristics, 3D computational fluid dynamics (CFD) simulation should be incorporated. Since simulating an entire long system by the 3D CFD method is unrealistic, we have proposed several 1D-3D coupled simulation methods. However, the coupled methods are difficult to apply and popularise because most CFD codes are inaccessible and implementation details are unclear. Consequently, we utilised the open source toolbox OpenFOAM to develop a 1D-3D coupled simulation method and proved its feasibility by applying it to analysing practical problems. This paper describes the implementations of water compressibility, 1D-3D coupling, gas-liquid flow simulation, and dynamic mesh; shows their verifications of accuracy by benchmark cases; demonstrates the simulations of the closing and opening processes of a 194 km long water conveyance system. The gas-liquid flow patterns in the gate chamber and the maximum/minimum water head envelopes along the tunnels, which support the design optimisation of the project, are presented. It is shown that the method is computationally efficient and accurate, and can be applied to hydraulic transient analyses for water conveyance systems, pumped-storage power stations, etc.

Abstract Objective This study aims to demonstrate the cellular composition and underlying mechanisms in subchondral bone marrow lesions (BMLs) of knee osteoarthritis (OA). Methods BMLs were assessed by MRI Osteoarthritis Knee Score (MOAKS)≥2. Bulk RNA-sequencing (bulk-seq) and BML-specific differentially expressed genes (DEGs) analysis were performed among subchondral bone samples (including OA-BML=3, paired OA-NBML=3; non-OA=3). The hub genes of BMLs were identified by verifying in independent datasets and multiple bioinformatic analyses. To further estimate cell-type composition of subchondral bone, we utilized two newly developed deconvolution algorithms (MuSiC, MCP-counter) in transcriptomic datasets, based on signatures from open-accessed single-cell RNA sequencing (scRNA-seq). Finally, competing endogenous RNA (ceRNA) and transcription factor (TF) networks were constructed through multiple predictive databases, and validated by public non-coding RNA profiles. Results A total of 86 BML-specific DEGs (up 79, down 7) were identified. IL11 and VCAN were identified as core hub genes. The “has-miR-424-5p/lncRNA PVT1” was determined as crucial network, targeting IL11 and VCAN, respectively. More importantly, two deconvolution algorithms produced approximate estimations of cell-type composition, and the cluster of heterotopic-chondrocyte was discovered abundant in BMLs, and positively correlated with the expression of hub genes. Conclusion IL11 and VCAN were identified as the core hub genes of BMLs, and their molecular networks were determined as well. We profiled the characteristics of subchondral bone at single-cell level and determined that the heterotopic-chondrocyte was abundant in BMLs and was closely linked to IL11 and VCAN. Our study may provide new insights into the microenvironment and pathological molecular mechanism of BMLs, and could lead to novel therapeutic strategies.

Abstract Objectives Entropy is a new late gadolinium enhanced (LGE) cardiac magnetic resonance (CMR)–derived parameter that is independent of signal intensity thresholds. Entropy can be used to measure myocardial tissue heterogeneity by comparing full pixel points of tissue images. This study investigated the incremental prognostic value of left ventricular (LV) entropy in patients with hypertrophic cardiomyopathy (HCM). Methods This study enrolled 337 participants with HCM who underwent 3.0-T CMR. The LV entropy was obtained by calculating the probability distribution of the LV myocardial pixel signal intensities of the LGE sequence. Patients who underwent CMR imaging were followed up for endpoints. The primary endpoint was defined as readmission to the hospital owing to heart failure. The secondary endpoint was the composite of the primary endpoint, sudden cardiac death and non-cardiovascular death. Results During the median follow-up of 24 months ± 13 (standard deviation), 43 patients who reached the primary and secondary endpoints had a higher entropy (6.20 ± 0.45, p

Abstract Germ cell tumors complicated by hematological malignancy (HM) are a rare clinical phenomenon. Allogeneic hematopoietic stem cell transplantation (allo‐HSCT) is a potentially effective therapy, but graft‐versus‐host disease (GVHD) is a life‐threatening complication. We report a case of a 13‐year‐old female patient diagnosed with germ cell tumors followed by acute lymphoblastic leukemia. After chemotherapy, she received allo‐HSCT and her chimerism rate decreased rapidly to near zero by 6 months without evidence of HM recurrence. However, she developed severe, multiorgan GVHD‐like manifestations. DNA analysis revealed the pathogenesis of GVHD to be loss of HLA heterozygosity in recipient hematopoietic cells.

Objective: This study aimed to develop polysaccharide-based composite antibacterial films with excellent antibacterial and physicochemical properties to effectively improve the shelf life of food. Methods: Carrageenan, agar, konjac gum and pectin were used as film-forming substrates and natamycin and nano-MgO were used as antibacterialagents to investigate the effects of adding antimicrobial agents on the physical, mechanical and antibacterial properties of the films and the preservation of grapes. Results: After the addition of antibacterial agents, the film thickness, tensile strength and haze increased, air permeability increased and elongation at break decreased, water solubility, swelling and moisture permeability decreased, light transmission and gloss decreased and the color tended to yellow-green, good compatibility with the film filler. It can effectively inhibit the growth and reproduction of Trichoderma, Rhizopus, Aspergillus, Staphylococcus aureus, Escherichia coli, Shigella and Salmonella, among which carrageenan/natamycin/nano-MgO composite membrane （CNM） and agar/natamycin/nano-MgO composite membrane （ANM） with good indicators can delay the water loss rate of grapes, improve the decline in hardness and the reduction of soluble solids content, and ensure the appearance and nutritional quality of grapes. Conclusion: ANM and CNM films are suitable for use as antibacterial packaging materials to extend the shelf life of food products, and are expected to be developed into fruit and vegetable preservation films with antibacterial preservation functions.

Objective: The research aimed to reveal the changes of biogenic amines in cheese made from different refrigerated milk during ripening and evaluate its quality safety. Methods: The hard cheese made from yak milk refrigerated for 24, 48 and 72 hours was taken as the research object, and the biogenic amines in cheese during ripening were determined by high performance liquid chromatography. Results: During the ripening period from 0 to 6 months, the content of biogenic amine in hard cheese made from different refrigerated yak milk showed an increasing trend. When the cold storage time of yak milk was extended from 24 h to 72 h, total biogenic amines, 2-phenylethylamine, cadaverine, tyramine and putrescine in cheese also increased in turn. The biogenic amines in the cheese made from raw milk refrigerated for 72 hours after ripening for 4 months were significantly higher than those in the other two groups of cheese. The contents of total biogenic amines and tyramine yak milk hard cheese matured for 6 months were （212.94±8.03） mg/kg and （81.04±3.92） mg/kg respectively. Conclusion: With the prolongation of the cold storage time of raw milk and the ripening time of cheese, the biogenic amine content in cheese increased. However, when the cold storage time of raw milk was less than 72 h, the biogenic amine content in its cheese was lower than the content recommended by scholars.

Background: Patients undergoing cardiothoracic surgery frequently encounter perioperative neurocognitive disorders (PND), which can include postoperative delirium (POD) and postoperative cognitive decline (POCD). Currently, there is not enough evidence to support the use of electroencephalograms (EEGs) in preventing POD and POCD among cardiothoracic surgery patients. This meta-analysis examined the importance of EEG monitoring in POD and POCD. Methods: Cochrane Library, PubMed, and EMBASE databases were searched to obtain the relevant literature. This analysis identified trials based on the inclusion and exclusion criteria. The Cochrane tool was used to evaluate the methodological quality of the included studies. Review Manager software (version 5.3) was applied to analyze the data. Results: Four randomized controlled trials (RCTs) were included in this meta-analysis, with 1096 participants. Our results found no correlation between EEG monitoring and lower POD risk (relative risk (RR): 0.81; 95% CI: 0.55–1.18; p = 0.270). There was also no statistically significant difference between the EEG group and the control group in the red cell transfusions (RR: 0.86; 95% CI: 0.51–1.46; p = 0.590), intensive care unit (ICU) stay (mean deviation (MD): –0.46; 95% CI: –1.53–0.62; p = 0.410), hospital stay (MD: –0.27; 95% CI: –2.00–1.47; p = 0.760), and mortality (RR: 0.33; 95% CI: 0.03–3.59; p = 0.360). Only one trial reported an incidence of POCD, meaning we did not conduct data analysis on POCD risk. Conclusions: This meta-analysis did not find evidence supporting EEG monitoring as a potential method to reduce POD incidence in cardiothoracic surgery patients. In the future, more high-quality RCTs with larger sample sizes are needed to validate the relationship between EEG monitoring and POD/POCD further.

Abstract Reverse osmosis (RO) is widely used in wastewater reclamation to alleviate the increasingly global water shortage. However, it has an inconvenient defect of biofouling. Some disinfection processes have been reported to select certain undesirable disinfection-residual bacteria (DRB), leading to severe long-term biofouling potential. To provide constructive guidance on biofouling prevention in RO systems, this study performed a 32-day experiment to parallelly compared the biofouling characteristics of RO membranes of DRB after five mature water disinfection methods (NaClO, NH2Cl, ClO2, UV, and O3) and two recently developed water disinfection methods (K2FeO4 and flow-through electrode system). As a result, the DRB biofilm of K2FeO4 and O3 caused a slight normalised flux drop (22.4 ± 2.4% and 23.9 ± 1.7%) of RO membrane compared to the control group (non-disinfected, ~27% normalised flux drop). FES, UV, NaClO and ClO2 caused aggravated membrane flux drop (29.1 ± 0.3%, 33.3 ± 7.8%, 34.6 ± 6.4%, and 35.5 ± 4.0%, respectively). The biofouling behaviour showed no relationship with bacterial concentration or metabolic activity (p > 0.05). The thickness and compactness of the biofilms and the organics/bacterial number ratio in the biofilm, helped explain the difference in the fouling degree between each group. Moreover, microbial community analysis showed that the relative abundance of typical highly EPS-secretory and biofouling-related genera, such as Pseudomonas, Sphingomonas, Acinetobacter, Methylobacterium, Sphingobium, and Ralstonia, were the main reasons for the high EPS secreting ability of the total bacteria, resulting in aggravation of biofouling degree (p

Abstract The effects of increased UV-B radiation on macroalgae have been widely studied, but knowledge concerning the response of communities of algal epiphytic bacteria to increased UV-B radiation and differences between male and female algae is still lacking. Via 16S rDNA high-throughput sequencing technology, changes in the epiphytic bacterial communities on male and female S. thunbergii under increased UV-B radiation were studied in the lab. Under different UV-B radiation intensities, although the α diversity and community composition of epiphytic bacteria changed little, the β diversity indicated that the community structure of bacteria on S. thunbergii was obviously clustered, and the relative abundance of dominant bacteria and indicator species changed considerably. There were unique bacteria in each experimental group, and the bacteria whose abundance obviously changed were members of groups related to environmental resistance or adaptability. The variation in the abundance of epiphytic bacteria was different in male and female S. thunbergii, and the bacteria whose abundance greatly changed were mainly related to algal growth and metabolism. The abundance of genes with predicted functions related to metabolism, genetic information processing, environmental adaptation and infectious diseases changed with increased UV-B radiation, and those variations differed between epiphytic bacteria on male and female S. thunbergii. This study found that the algal epiphytic bacteria were influenced by the increase in UV-B radiation and underwent certain adaptations through adjustments to community structure and function, and this response was also affected by the sex of the macroalgae. These results are expected to serve as experimental basis and provide reference for further understanding of the response of algae epiphytic bacteria to enhanced UV-B radiation caused by the thinning of the ozone layer and the resulting changes in the relationship between algae and bacteria, which may change the community of the marine ecosystem and affect important marine ecological process.

Double-crystal monochromators (DCMs) are one of the most critical optical devices in beamlines at synchrotron sources, directly affecting the quality of the beam energy and position. As the performance of synchrotron light sources continues to improve, higher demands are placed on the stability of DCMs. This paper proposes a novel adaptive vibration control method combining variational modal decomposition (VMD) and filter-x normalized least mean squares (FxNLMS), ensuring DCM stability under random engineering disturbance. Firstly, the sample entropy of the vibration signal is selected as the fitness function, and the number of modal components k and the penalty factor α are optimized by a genetic algorithm. Subsequently, the vibration signal is decomposed into band frequencies that do not overlap with each other. Eventually, each band signal is individually governed by the FxNLMS controller. Numerical results have demonstrated that the proposed adaptive vibration control method has high convergence accuracy and excellent vibration suppression performance. Furthermore, the effectiveness of the vibration control method has been verified with actual measured vibration signals of the DCM.

IntroductionAllogeneic hematopoietic stem cell transplantation (allo-HCT) is a standard treatment for relapsed/refractory B-cell acute lymphoblastic leukemia (r/r B-ALL). However, about 30-40% of patients still relapse after HCT. Chimeric antigen receptor-modified T-cell (CAR-T) therapy has been proven effective in the treatment of relapsed or refractory B-ALL.Patients and methodsWe report a cohort of 30 B-ALL patients, who relapsed after HCT and were enrolled in the 4SCAR2.0 study, receiving CD19 CAR-Ts alone (20 patients), or two types of CAR-Ts targeting CD19, CD22, CD38 or CD123 antigens (10 patients), depending on the tumor antigen expression profile. These patients had extramedullary (EM) relapse or bone marrow (BM) relapse, or both. Based on the GVHD history, donor chimerism, and the available T-cell source, 25 patients received allogeneic donor CAR-Ts, and 5 patients received autologous CAR-T treatment. ResultsAll 20 patients receiving a single CD19 CAR-T infusion achieved a minimal residual disease (MRD) remission within 60 days. The remaining 10 patients, due to low CD19 antigen expression profile, received 2 CAR-T products given on the same day, and 9 of 10 achieved complete remission (CR) and one had disease progression within 60 days. After CAR-T infusion, no cytokine release syndrome (CRS) was observed in 14 patients, and 16 patients experienced grade 1 CRS, and there was no neurotoxicity. Seventeen of the 30 patients who achieved remission (57%) remained in continuous remission following CAR-T treatment with a median follow-up period of 2 years and a median duration of remission of 12 months (range: 2.8 months - 67 months). Twelve out of 29 patients (41%) who achieved remission, subsequently relapsed at a median of 6.3 months (range: 2.8 months - 22.3 months) after CAR-T treatment. In summary, 29 patients (97%) achieved MRD negative remission within 60 days of therapy with a single or double CAR-T infusion, and seven patients remained in durable remission (7/30, 23%) after more than 2 years of follow-up. DiscussionThe tumor antigen profile-guided precision 4SCAR2.0 regimen for the treatment of r/r B-ALL after allo-HCT was highly effective with low toxicity. This approach warrants extended follow-up and further studies. Clinical trial registrationClinicalTrials.gov, identifier NCT03125577.

Abstract The regulation of inflammatory response at the site of injury and macrophage immunotherapy is critical for tissue repair. Chiral self‐assemblies are one of the most ubiquitous life cues, which is closely related to biological functions, life processes, and even the pathogenesis of diseases. However, the role of supramolecular chiral self‐assemblies in the regulation of immune functions in the internal environment of tissues has not been fully explored yet. Herein, 3D supramolecular chiral self‐assembling matrixes are prepared to regulate the polarization of macrophages and further enhance the repair of myocardial infarction (MI). Experiments studies show that M‐type (left‐handed) self‐assembling matrixes significantly inhibit inflammation and promote damaged myocardium repair by upregulating M2 macrophage polarization and downstream immune signaling compared with P‐type (right‐handed), and R‐type (non‐chirality) self‐assembling matrixes. Classical molecular dynamics (MD) simulation demonstrates that M‐type self‐assembling matrixes display higher stereo‐affinity to cellular binding, which enhances the clustering of mechanosensitive integrin β1 (Itgβ1) and activates focal adhesion kinase (FAK) and Rho‐associated protein kinase (ROCK), as well as downstream PI3K/Akt1/mTOR signaling axes to promote M2 polarization. This study of designing a 3D chiral self‐assembling matrixes microenvironment suitable for regulating the polarization of macrophages will provide devise basis for immunotherapy with biomimetic materials.

The blood–brain barrier (BBB) is a functional phenotype exhibited by the neurovascular unit (NVU). It is maintained and regulated by the interaction between cellular and non-cellular matrix components of the NVU. The BBB plays a vital role in maintaining the dynamic stability of the intracerebral microenvironment as a barrier layer at the critical interface between the blood and neural tissues. The large contact area (approximately 20 m2/1.3 kg brain) and short diffusion distance between neurons and capillaries allow endothelial cells to dominate the regulatory role. The NVU is a structural component of the BBB. Individual cells and components of the NVU work together to maintain BBB stability. One of the hallmarks of acute ischemic stroke is the disruption of the BBB, including impaired function of the tight junction and other molecules, as well as increased BBB permeability, leading to brain edema and a range of clinical symptoms. This review summarizes the cellular composition of the BBB and describes the protein composition of the barrier functional junction complex and the mechanisms regulating acute ischemic stroke-induced BBB disruption.

Abstract Background Seagrasses are a polyphyletic group of monocotyledonous angiosperms that have evolved to live entirely submerged in marine waters. Thus, these species are ideal for studying plant adaptation to marine environments. Herein, we sequenced the chloroplast (cp) genomes of two seagrass species (Zostera muelleri and Halophila ovalis) and performed a comparative analysis of them with 10 previously published seagrasses, resulting in various novel findings. Results The cp genomes of the seagrasses ranged in size from 143,877 bp (Zostera marina) to 178,261 bp (Thalassia hemprichii), and also varied in size among different families in the following order: Hydrocharitaceae > Cymodoceaceae > Ruppiaceae > Zosteraceae. The length differences between families were mainly related to the expansion and contraction of the IR region. In addition, we screened out 2,751 simple sequence repeats and 1,757 long repeat sequence types in the cp genome sequences of the 12 seagrass species, ultimately finding seven hot spots in coding regions. Interestingly, we found nine genes with positive selection sites, including two ATP subunit genes (atpA and atpF), three ribosome subunit genes (rps4, rps7, and rpl20), one photosystem subunit gene (psbH), and the ycf2, accD, and rbcL genes. These gene regions may have played critical roles in the adaptation of seagrasses to diverse environments. In addition, phylogenetic analysis strongly supported the division of the 12 seagrass species into four previously recognized major clades. Finally, the divergence time of the seagrasses inferred from the cp genome sequences was generally consistent with previous studies. Conclusions In this study, we compared chloroplast genomes from 12 seagrass species, covering the main phylogenetic clades. Our findings will provide valuable genetic data for research into the taxonomy, phylogeny, and species evolution of seagrasses.

Mesenchymal stem cells (MSCs) therapy shows the potential benefits to relieve clinical symptoms of osteoarthritis (OA), but it is uncertain if it can repair articular cartilage lesions — the main pathology of OA. Here, we prepared biomimetic cupper sulfide@phosphatidylcholine (CuS@PC) nanoparticles (NPs) loaded with plasmid DNA (pDNA) encoding transforming growth factor-beta 1 (TGF-β1) to engineer MSCs for enhanced OA therapy via cartilage regeneration. We found that the NPs not only promoted cell proliferation and migration, but also presented a higher pDNA transfection efficiency relative to commercial transfection reagent lipofectamine 3000. The resultant CuS/TGF-β1@PC NP-engineered MSCs (termed CTP-MSCs) were better than pure MSCs in terms of chondrogenic gene expression, glycosaminoglycan deposition and type II collagen formation, favoring cartilage repair. Further, CTP-MSCs inhibited extracellular matrix degradation in interleukin-1β-induced chondrocytes. Consequently, intraarticular administration of CTP-MSCs significantly enhanced the repair of damaged cartilage, whereas pure MSCs exhibited very limited effects on cartilage regeneration in destabilization of the medial meniscus (DMM) surgical instability mice. Hence, this work provides a new strategy to overcome the limitation of current stem cell therapy in OA treatment through developing more effective nanoengineered MSCs.

Abstract Background Increasing evidence has supported a link between obstructive sleep apnea (OSA) and cognition, and blood-brain barrier (BBB) dysfunction which can be reflected by paroxysmal slow wave events (PSWEs) may be a potential mechanism. The purpose of our study was to investigate the correlation between the PSWEs and cognitive impairment in patients with OSA, with a focus on the possible mechanism. Methods In total, 339 subjects with subjective snoring complaints from the Sleep Medicine Center underwent magnetic resonance imaging and whole-night polysomnography. OSA was defined as apnea-hypopnea index (AHI) ≥ 5 events/h. MCI was defined as the MoCA < 26 and met the criteria: (1) subjective cognitive impairment; (2) objective impairment in one or more cognitive domains; (3) slightly impaired complex instrumental daily abilities, but independent daily living abilities; and (4) no dementia. The PSWEs calculated by self-developed Python scripts were defined for EEG recordings as a median power frequency of < 6 Hz for more than five consecutive seconds. Serum cyclophilin A (CyPA) and matrix metalloproteinase-9 (MMP-9) levels and amyloid-β 42 levels in neuron-derived exosomes were determined. The participants who received continuous positive airway pressure (CPAP) were followed up and their PSWEs were recalculated after 1 year of treatment. Results A total of 339 participants were divided into the OSA+MCI group (n = 157), OSA-MCI group (n = 118), and controls (normal cognitive state without OSA) (n = 64). The total PSWEs and the occurrence per minute of PSWEs at stage REM in the OSA+MCI group were higher than those in the OSA-MCI and control groups. The duration ratio of PSWEs at stage REM in the OSA+MCI group significantly increased. The total PSWEs and PSWEs at the F4-M1, O1-M2, and O2-M1 channels in stage REM were independently associated with cognitive impairment in OSA patients. There were positive correlations between the PSWEs and serum CyPA and MMP-9 levels in patients with OSA. The mediation analysis showed that the relationship between mean SaO2 and percentage of sleep time spent with oxygen saturation

Abstract Background Seagrasses are higher marine flowering plants that evolved from terrestrial plants, but returned to the sea during the early evolution of monocotyledons through several separate lineages. Thus, they become a good model for studying the adaptation of plants to the marine environment. Sequencing of the mitochondrial (mt) genome of seagrasses is essential for understanding their evolutionary characteristics. Results In this study, we sequenced the mt genome of two endangered seagrasses (Zostera japonica and Phyllospadix iwatensis). These data and data on previously sequenced mt genomes from monocotyledons provide new evolutionary evidence of genome size reduction, gene loss, and adaptive evolution in seagrasses. The mt genomes of Z. japonica and P. iwatensis are circular. The sizes of the three seagrasses (including Zostera marine) that have been sequenced to date are smaller than that of other monocotyledons. Additionally, we found a large number of repeat sequences in seagrasses. The most abundant long repeat sequences were 31–40 bp repeats. Our study also found that seagrass species lost extensive ribosomal protein genes during evolution. The rps7 gene and the rpl16 gene of P. iwatensis are exceptions to this trend. The phylogenetic analysis based on the mt genome strongly supports the previous results. Furthermore, we identified five positive selection genes (atp8, nad3, nad6, ccmFn, and matR) in seagrasses that may be associated with their adaptation to the marine environment. Conclusions In this study, we sequenced and annotated the mt genomes of Z. japonica and P. iwatensis and compared them with the genome of other monocotyledons. The results of this study will enhance our understanding of seagrass adaptation to the marine environment and can inform further investigations of the seagrass mt genome.

Early warning of safety risks downstream of small reservoirs is directly related to the safety of people’s lives and property and the economic and social development of the region. The lack of data and low collaboration in downstream safety management of small reservoirs makes the existing safety risk warning methods for small reservoirs no longer fully applicable. The data from flood control and drought relief departments, small reservoir operation and management departments, etc., are used comprehensively. A machine learning model suitable for a large number of samples, a small amount of data, and the condition of incomplete information is applied and innovated, and from the holistic perspective of ‘upstream reservoir—downstream region’, the safety risk factors of the upstream reservoir are identified with the help of the Granger causality test. The risk losses of the disaster behavior are predicted with the three-dimensional k~ε two-equation model coupled with the VOF (Volume of fluid) method and the neural network model. The safety risk dynamics prediction, the prediction of the disaster-causing environment, and the prediction of the risk losses are integrated to construct the early warning method of the downstream safety risk of small reservoirs, and the simulation effect is verified with the example of the J Reservoir. The results show that the model can clarify the causal relationships and time lag dependencies between hydro-meteorological factors and the water level of small reservoirs, and calculate the inundation depth, inundation range, and flood velocity downstream of small reservoirs. The downstream safety warning model of small reservoirs constructed in this article can effectively integrate upstream and downstream information, further improve the timeliness and accuracy of warning, and provide a reference for downstream safety risk management of small reservoirs.

Summary: The selective production of C4 bulk chemicals from biomass is significant to replace the traditional method from petroleum resource. In this work, the succinic anhydride (SAN) is directly prepared from bio-based furanic platform compounds utilizing the visible light-induced oxygenation process, in which m-tetraphenyl porphyrin (H2TPP) and molecular oxygen was employed as the photocatalyst and terminal oxidant, respectively. Under optimal conditions, a 99.9% conversion with 97.8% selectivity of SAN was obtained from furoic acid (FAC) at room temperature. Moreover, the transformation of furfural and furfuryl alcohol with this system can also generate SAN, and the product selectivity is controllable by tuning light intensity and time. Furthermore, the EPR detection, isotope labeling, and control experiments exhibited that the generation of singlet oxygen plays a crucial role and 5-hydroxy-2(5H)-furanone is the main intermediate during the reaction. Finally, a possible reaction mechanism for the production of SAN from furanic compound is proposed.

ObjectivesOur aim was to describe the molecular characteristics of Renal Cell Carcinoma (RCC) and develop a small panel of RCC-associated genes from a large panel of cancer-related genes.Materials and methodsClinical data of 55 patients with RCC diagnosed in four hospitals from September 2021 to August 2022 were collected. Among the 55 patients, 38 were diagnosed with clear cell RCC (ccRCC), and the other 17 were diagnosed with non-clear cell RCC (nccRCC), including 10 cases of papillary renal cell carcinoma, 2 cases of hereditary leiomyomatosis and RCC syndrome (HLRCC), 1 eosinophilic papillary RCC, 1 tubular cystic carcinoma, 1 TFE3 gene fusion RCC, and 2 RCC with sarcomatoid differentiation. For each patient, 1123 cancer-related genes and 79 RCC-associated genes were analyzed.ResultsThe most frequent mutations in a large panel of 1123 cancer-related genes in the overall population of RCC patients were VHL (51%), PBRM1 (35%), BAP1 (16%), KMT2D (15%), PTPRD (15%), and SETD2 (15%). For ccRCC patients, mutations in VHL, PBRM1, BAP1, and SERD2 can reach 74%, 50%, 24%, and 18%, respectively, while for nccRCC patients, the most frequent mutation was FH (29%), MLH3 (24%), ARID1A (18%), KMT2D (18%), and CREBBP (18%). The germline mutation rate in all 55 patients reached 12.7% (five with FH, one with ATM, and one with RAD50). The small panel containing only 79 RCC-associated genes demonstrated that mutations of VHL, PBRM1, BAP1, and SETD2 in ccRCC patients were 74%, 50%, 24%, and 18% respectively, while for the nccRCC cohort, the most frequent mutations were FH (29%), ARID1A (18%), ATM (12%), MSH6 (12%), BRAF (12%), and KRAS (12%). For ccRCC patients, the spectrum of mutations by large and small panels was almost the same, while for nccRCC patients, the mutation spectrum showed some differences. Even though the most frequent mutations (FH and ARID1A) in nccRCC were both demonstrated by large panels and small panels, other less frequent mutations such as MLH3, KMT2D, and CREBBP were not shown by the small panel.ConclusionOur study revealed that nccRCC is more heterogeneous than ccRCC. For nccRCC patients, the small panel shows a more clear profile of genetic characteristics by replacing MLH3, KMT2D, and CREBBP with ATM, MSH6, BRAF, and KRAS, which may help predict prognosis and make clinical decisions.

Osteoarthritis (OA) is the most prevalent musculoskeletal disease characterized by multiple joint structure damages, including articular cartilage, subchondral bone and synovium, resulting in disability and economic burden. Bone marrow lesions (BMLs) are common and important magnetic resonance imaging (MRI) features in OA patients. Basic and clinical research on subchondral BMLs in the pathogenesis of OA has been a hotspot. New evidence shows that subchondral bone degeneration, including BML and angiogenesis, occurs not only at or after cartilage degeneration, but even earlier than cartilage degeneration. Although BMLs are recognized as important biomarkers for OA, their exact roles in the pathogenesis of OA are still unclear, and disputes about the clinical impact and treatment of BMLs remain. This review summarizes the current basic and clinical research progress of BMLs. We particularly focus on molecular pathways, cellular abnormalities and microenvironmental changes of subchondral bone that contributed to the formation of BMLs, and emphasize the crosstalk between subchondral bone and cartilage in OA development. Finally, potential therapeutic strategies targeting BMLs in OA are discussed, which provides novel strategies for OA treatment.

ABSTRACTHydraulic excitation causes abnormal head-cover vibration in some pump-turbines, particularly as design heads continue to rise. Pump-turbines with heads exceeding 600 m have reported such vibrations in pump mode, and it is urgent to reveal the reasons. A study was conducted on a head-cover of a pump-turbine with a maximum head of 660 m by 3D computational fluid dynamics (CFD) and finite element method (FEM) numerical simulations to investigate the hydraulic excitation source and vibration mechanism. Results show that the intensive vibration is related to the coincidence of frequency and mode between abnormal pressure pulsations with frequency 6–8fn and the low-order wet mode of the head-cover. A new flow pattern termed the rolling vortex was discovered in the vaneless space under high-head pumping conditions. The 6–8fn pressure pulsations result from the interaction between rolling vortices and guide-vanes, similar to the rotor-stator interaction. The flow mechanism of the rolling vortices is that the outflow velocity near the hub at the runner outlet is higher than that near the shroud, due to the positive blade lean angle and the X-shape distorted blades. Suppressing rolling vortices may help eliminate the abnormal head-cover vibration, which will be attempted in further study.

Introduction In this study, we aimed to investigate the role of miRNA-21 and the regulating pathway that promotes the differentiation of bone marrow mesenchymal stem cells (BMSCs). Material and methods We used miR-21-OE, miR-21-KD, ajuba-OE and ajuba-KD plasmids to infect BMSCs. The expression of miRNA-21, ajuba, Isl1 and cTnI was detected by RT-qPCR, WB and immunofluorescence staining in groups. Results MiRNA-21 over-expression increased the expression of Isl1, and vice versa. Ajuba over-expression decreased the expression of Isl1, and vice versa. Ajuba negatively regulated the differentiation of BMSCs into cardiomyocyte-like cells. Conclusions MiRNA-21 could regulate differentiation of bone marrow mesenchymal stem cells (BMSCs) to cardiomyocyte-like cells through the ajuba/Isl1 axis pathway.

Deep learning-based methods have been proposed to substitute CT-based PET attenuation and scatter correction to achieve CT-free PET imaging. Here, the authors present a simple way to integrate domain knowledge in deep learning for CT-free PET imaging.

Abstract Background Tumorigenic phenotype of M2 tumor-associated macrophages promote tumor progression in response to exosomes cues imposed by tumor cells. However, the effect and underlying mechanisms of clear cell renal cell carcinoma (ccRCC)-derived exosomes (ccRCC-exo) on instructing macrophages phenotype remains unclear. Methods Macrophages were cocultured with ccRCC-exo and then evaluate the polarization of macrophages and migration of ccRCC cells. The effect and mechanism of lncRNA AP000439.2 overexpressed or deleted exosomes on macrophages M2 polarization were examined. Xenograft tumor mice model was used for in vivo validation. Results The ccRCC-exo significantly activated macrophages to M2 phenotype presented by increased expression of transforming growth factor-beta (TGF-β) and interleukin 10 (IL-10) at mRNA and protein levels, and these M2 macrophages in turn facilitating the migration of ccRCC cells. LncRNA AP000439.2 was highly enriched in the ccRCC-exo. Overexpression of exosomal AP000439.2 promoted M2 macrophage polarization whereas AP000439.2-deficient exosome had the opposite effects. Nuclear-localized AP000439.2 directly interacted with signal transducer and activator of transcription 3 (STAT3) proteins and phosphorylated STAT3 in macrophages. RNA-Seq results showed overexpression of AP000439.2 activated NF-κB signaling pathway. Silencing of STAT3 suppressed overexpression of AP000439.2-induced up-regulation of TGF-β and IL-10 expression, and p65 phosphorylation. AP000439.2-deleted exosome inhibited tumor growth in vivo. Conclusion Exosomes from ccRCC deliver AP000439.2 to promote M2 macrophage polarization via STAT3, thus enhancing ccRCC progression, indicating exosomal AP000439.2 might be a novel therapeutic target in ccRCC. Video Abstract

The power industry involves people’s livelihood. While ensuring the normal operation of the power system, power companies also need to consider strengthening line loss management to promote grid efficiency. Through grounded theory, 19 factors affecting regional distribution network line loss are extracted from the management and technical perspectives. The Apriori algorithm is used to analyze the data of Chuzhou distribution network line loss rate, and the connection between different influencing factors and line loss rate is analyzed. Association rules are used to filter out the key influencing factors. Finally, the calculation results of the Apriori algorithm and the interpretation structure model (ISM) are combined to make up for the shortcomings of ISM’s strong subjectivity and draw the influence path diagram of the regional distribution network line loss rate based on Apriori-ISM. The results show that measurement errors, the number of strain-resistant sections, the total number of special transformers, the cross-sectional area of conductors, the number of aging transformers, load switching, power theft, and operating time are the direct factors affecting the line loss rate of the regional distribution network, whose confidence levels are 100%, 81.06%, 91.76%, 89.36%, 89.38%, 83.23%, 84.39% and 90.53% respectively, and the correlation is strong.

Objective To investigate the effect of Traditional Chinese Medicine (TCM) nursing technology in prevention and treatment of chemotherapy-induced nausea and vomiting in patients with breast cancer, and its effect in relief of negative emotion. Methods Totally 80 hospitalized patients with breast cancer were randomly divided into the control group and study group, with 40 cases in each group. All patients received anti-nausea drugs treatment and routine care, and those in the study group were given TCM nursing interventions. The gastrointestinal reactions of patients were recorded during the chemotherapy, and the efficacy of intervention in control of chemotherapy-induced nausea and vomiting was evaluated. The Self-rating Anxiety Scale (SAS) was used to evaluate patient anxiety. Results The effective rate of controlling chemotherapy-induced nausea and vomiting in the study group was higher than that in the control group (P＜0. 01). The VAS score dropped in both two groups after intervention, and VAS score in the study group was lower than that in the control group (P＜0. 01). Conclusion Based on the anti-nausea drugs treatment and routine care, the TCM nursing is able to further improve the efficiency in control of nausea and vomiting and relief of anxiety in patients undergoing chemotherapy for breast cancer (目的 探讨中医护理技术防治乳腺癌化疗所致恶心呕吐的效果, 以及对患者不良情绪的改善作用。方法 将住院治疗的80例乳腺癌化疗患者随机分为对照组与研究组, 各40例。对照组采用常规药物治疗和护理, 研究组在对照组基础上增加中医护理干预。记录两组化疗期间消化道反应, 评价干预后恶心呕吐控制效果, 采用焦虑自评量表(VAS)评价患者焦虑程度。结果 治疗10 d后, 研究组恶心呕吐程度较对照组轻, 差异有统计学意义(P＜0. 01)。干预后, 两组VAS评分均较干预前下降, 且研究组VAS评分低于对照组, 差异有统计学意义(P＜0. 01)。结论 在常规止吐治疗和护理的基础上, 中医护理干预能够进一步改善乳腺癌患者化疗所致恶心、呕吐程度, 同时缓解患者焦虑情绪。)

Soybean mosaic virus (SMV) is a member of the genus Potyvirus that extensively impairs global soybean production. The full-length coding sequence of the MADS-box transcription factor GmCAL was cloned from the SMV-resistant soybean cultivar Kefeng 1. SMV-induced expression analysis indicated that GmCAL responded quickly to SMV-SC8 infection in Kefeng 1 but not in NN1138-2. GmCAL was expressed at high levels in flowers and pods but at lower levels in leaves. The gene was localized to the nucleus by subcellular localization assay. Virus-induced gene silencing did not increase the accumulation of SMV in GmCAL-silenced Kefeng 1 plants (with silencing efficiency ∼ 80%) after SC8 inoculation. GmCAL-silencing plants still conferred resistance to SC8 that might be owing to incomplete silencing of genes with lower expression. SMV content decreased significantly in GmCAL-overexpressing NN1138-2 plants after SMV-SC3, SMV-SC7, and SMV-SC8 inoculation in comparison with a vector control, showing that overexpression of GmCAL conferred broad-spectrum resistance to multiple SMV strains. These results confirm that GmCAL, a key regulator but not a specific SC8 resistance gene (Rsc8), is a positive regulatory transcription factor involved in soybean resistance to SMV.

Summary: Striking antibody evasion by emerging circulating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants drives the identification of broadly neutralizing antibodies (bNAbs). However, how a bNAb acquires increased neutralization breadth during antibody evolution is still elusive. Here, we identify a clonally related antibody family from a convalescent individual. One of the members, XG005, exhibits potent and broad neutralizing activities against SARS-CoV-2 variants, while the other members show significant reductions in neutralization breadth and potency, especially against the Omicron sublineages. Structural analysis visualizing the XG005-Omicron spike binding interface reveals how crucial somatic mutations endow XG005 with greater neutralization potency and breadth. A single administration of XG005 with extended half-life, reduced antibody-dependent enhancement (ADE) effect, and increased antibody product quality exhibits a high therapeutic efficacy in BA.2- and BA.5-challenged mice. Our results provide a natural example to show the importance of somatic hypermutation during antibody evolution for SARS-CoV-2 neutralization breadth and potency.

BackgroundThe occurrence of abdominal aortic aneurysms (AAAs) is related to the disorder of immune microenvironment. Cuprotosis was reported to influence the immune microenvironment. The objective of this study is to identify cuprotosis-related genes involved in the pathogenesis and progression of AAA.MethodsDifferentially expressed lncRNAs (DElncRNAs) and mRNAs (DEmRNAs) in mouse were identified following AAA through high-throughput RNA sequencing. The enrichment analyses of pathway were selected through Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG). The validation of cuprotosis-related genes was conducted through immunofluorescence and western blot analyses.ResultsTotally, 27616 lncRNAs and 2189 mRNAs were observed to be differentially expressed (|Fold Change| ≥ 2 and q< 0.05) after AAA, including 10424 up-regulated and 17192 down-regulated lncRNAs, 1904 up-regulated and 285 down-regulated mRNAs. Gene ontology and KEGG pathway analysis showed that the DElncRNAs and DEmRNAs were implicated in many different biological processes and pathways. Furthermore, Cuprotosis-related genes (NLRP3, FDX1) were upregulated in the AAA samples compared with the normal one.ConclusionCuprotosis-related genes (NLRP3,FDX1) involved in AAA immune environment might be critical for providing new insight into identification of potential targets for AAA therapy.

Objective: To assess the causal effect of systemic iron status by using four biomarkers (serum iron; transferrin saturation; ferritin; total iron-binding capacity) on knee osteoarthritis (OA), hip OA, total knee replacement, and total hip replacement using 2-sample Mendelian randomization (MR) design.Methods: Three instrument sets were used to construct the genetic instruments for the iron status: Liberal instruments (variants associated with one of the iron biomarkers), sensitivity instruments (liberal instruments exclude variants associated with potential confounders), and conservative instruments (variants associated with all four iron biomarkers). Summary-level data for four OA phenotypes, including knee OA, hip OA, total knee replacement, and total hip replacement were obtained from the largest genome-wide meta-analysis with 826,690 individuals. Inverse-variance weighted based on the random-effect model as the main approach was conducted. Weighted median, MR-Egger, and Mendelian randomization pleiotropy residual sum and outlier methods were used as sensitivity MR approaches.Results: Based on liberal instruments, genetically predicted serum iron and transferrin saturation were significantly associated with hip OA and total hip replacement, but not with knee OA and total knee replacement. Statistical evidence of heterogeneity across the MR estimates indicated that mutation rs1800562 was the SNP significantly associated with hip OA in serum iron (odds ratio, OR = 1.48), transferrin saturation (OR = 1.57), ferritin (OR = 2.24), and total-iron binding capacity (OR = 0.79), and hip replacement in serum iron (OR = 1.45), transferrin saturation (OR = 1.25), ferritin (OR = 1.37), and total-iron binding capacity (OR = 0.80).Conclusion: Our study suggests that high iron status might be a causal factor of hip OA and total hip replacement where rs1800562 is the main contributor.

Seed development is a crucial phase in the life cycle of seed-propagated plants. As the only group of angiosperms that evolved from terrestrial plants to complete their life cycle submerged in marine environments, the mechanisms underlying seed development in seagrasses are still largely unknown. In the present study, we attempted to combine transcriptomic, metabolomic, and physiological data to comprehensively analyze the molecular mechanism that regulates energy metabolism in Zostera marina seeds at the four major developmental stages. Our results demonstrated that seed metabolism was reprogrammed with significant alteration of starch and sucrose metabolism, glycolysis, the tricarboxylic acid cycle (TCA cycle), and the pentose phosphate pathway during the transition from seed formation to seedling establishment. The interconversion of starch and sugar provided energy storage substances in mature seeds and further acted as energy sources to support seed germination and seedling growth. The glycolysis pathway was active during Z. marina germination and seedling establishment, which provided pyruvate for TCA cycle by decomposing soluble sugar. Notably, the biological processes of glycolysis were severely inhibited during Z. marina seed maturation may have a positive effect on seed germination, maintaining a low level of metabolic activity during seed maturation to preserve seed viability. Increased acetyl-CoA and ATP contents were accompanied with the higher TCA cycle activity during seed germination and seedling establishment, indicating that the accumulations of precursor and intermediates metabolite that can strengthen the TCA cycle and facilitate energy supply for Z. marina seed germination and seedling growth. The large amount of oxidatively generated sugar phosphate promotes fructose 1,6-bisphosphate synthesis to feed back to glycolysis during seed germination, indicating that the pentose phosphate pathway not only provides energy for germination, but also complements the glycolytic pathway. Collectively, our findings suggest these energy metabolism pathways cooperate with each other in the process of seed transformation from maturity to seedling establishment, transforming seed from storage tissue to highly active metabolic tissue to meet the energy requirement seed development. These findings provide insights into the roles of the energy metabolism pathway in the complete developmental process of Z. marina seeds from different perspectives, which could facilitate habitat restoration of Z. marina meadows via seeds.

In regard to membrane-based technologies of wastewater reclamation, the reported key foulants were faced with dilemma that they could not be effectively separated and extracted from reclaimed water for thorough investigation. In this study, the crucial foulants were proposed as “critical minority fraction (FCM)”, representing the fraction with molecular weight (MW) > 100 kDa which could be easily separated by physical filtration using MW cut-off membrane of 100 kDa with fairly high recovery ratio. FCM with low dissolved organic carbon (DOC) concentration (∼1 mg/L) accounted for less than 20% of the total DOC in reclaimed water, while contributed to more than 90% of the membrane fouling, and thus FCM could be considered as a “perfect criminal” causing membrane fouling. Furthermore, pivotal fouling mechanism was attributed to the significant attractive force between FCM and membranes, which led to severe fouling development due to the aggregation of FCM on membrane surface. Fluorescent chromophores of FCM were concentrated in regions of proteins and soluble microbial products, with proteins and polysaccharides accounted for 45.2% and 25.1% of the total DOC, specifically. FCM was further fractionated into six fractions, among which hydrophobic acids and hydrophobic neutrals were the dominant components in terms of DOC content (∼80%) as well as fouling contribution. Regarding to these pronounced properties of FCM, targeted fouling control strategies including ozonation and coagulation were applied and proved to achieve remarkable fouling control effect. High-performance size-exclusion chromatography results suggested that ozonation achieved distinct transformation of FCM into low MW fractions, while coagulation removed FCM directly, thus leading to effective fouling alleviation. Therefore, the investigation of the critical foulants was expected to help glean valuable insight into the fouling mechanism and develop targeted fouling control technologies in practical applications.