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Polymyxins are the last line of defense against multidrug-resistant (MDR) Gram-negative bacterial infections. However, this last resort has been threatened by the emergence of superbugs carrying the mobile colistin resistance gene-1 (mcr-1). Given the high concentration of matrix metalloproteinase 3 (MMP-3) in bacterial pneumonia, limited plasma accumulation of colistin (CST) in the lung, and potential toxicity of ionic silver (Ag+), we designed a feasible clinical transformation platform, an MMP-3 high-performance lung-targeted bio-responsive delivery system, which we named “CST&Ag@CNMS”. This system exhibited excellent lung-targeting ability (>80% in lungs), MMP-3 bio-responsive release property (95% release on demand), and synergistic bactericidal activity in vitro (2–4-fold minimum inhibitory concentration reduction). In the mcr-1+ CST-resistant murine pneumonia model, treatment with CST&Ag@CNMS improved survival rates (70% vs. 20%), reduced bacteria burden (2–3 log colony-forming unit [CFU]/g tissue), and considerably mitigated inflammatory response. In this study, CST&Ag@CNMS performed better than the combination of free CST and AgNO3. We also demonstrated the superior biosafety and biodegradability of CST&Ag@CNMS both in vitro and in vivo. These findings indicate the clinical translational potential of CST&Ag@CNMS for the treatment of lung infections caused by CST-resistant bacteria carrying mcr-1.

Abstract Photothermal therapy is favored by cancer researchers due to its advantages such as controllable initiation, direct killing and immune promotion. However, the low enrichment efficiency of photosensitizer in tumor site and the limited effect of single use limits the further development of photothermal therapy. Herein, a photo-responsive multifunctional nanosystem was designed for cancer therapy, in which myeloid-derived suppressor cell (MDSC) membrane vesicle encapsulated decitabine-loaded black phosphorous (BP) nanosheets (BP@ Decitabine @MDSCs, named BDM). The BDM demonstrated excellent biosafety and biochemical characteristics, providing a suitable microenvironment for cancer cell killing. First, the BDM achieves the ability to be highly enriched at tumor sites by inheriting the ability of MDSCs to actively target tumor microenvironment. And then, BP nanosheets achieves hyperthermia and induces mitochondrial damage by its photothermal and photodynamic properties, which enhancing anti-tumor immunity mediated by immunogenic cell death (ICD). Meanwhile, intra-tumoral release of decitabine induced G2/M cell cycle arrest, further promoting tumor cell apoptosis. In vivo, the BMD showed significant inhibition of tumor growth with down-regulation of PCNA expression and increased expression of high mobility group B1 (HMGB1), calreticulin (CRT) and caspase 3. Flow cytometry revealed significantly decreased infiltration of MDSCs and M2-macrophages along with an increased proportion of CD4+, CD8+ T cells as well as CD103+ DCs, suggesting a potentiated anti-tumor immune response. In summary, BDM realizes photothermal therapy/photodynamic therapy synergized chemotherapy for cancer.

Background: The predictive value of growth differentiation factor-15 (GDF-15) in coronary microvascular dysfunction (CMD) following primary percutaneous coronary intervention (PPCI) in ST-segment elevation myocardial infarction (STEMI) patients is unclear. Methods: This study continuously recruited STEMI patients treated with PPCI at the Chest Pain Center of Qilu Hospital of Shandong University from April 2023 to December 2023. Blood samples were taken before PPCI and the level of circulating GDF-15 was measured by enzyme-linked immunosorbent assay (ELISA), and the patients were divided into CMD and Control group according to angiographic microvascular resistance (AMR) (cut-off value 2.50 mmHg*s/cm). The differences in GDF-15 expression levels between the two groups were compared, and the predictive value of GDF-15 for CMD was systematically evaluated. Results: A total of 134 patients, with an average age of 59.78 ± 12.69 years and 75.37 % being male, were included in this study. Multivariable logistic regression revealed a significant association between GDF-15 and CMD (adjusted OR = 2.505, 95 % CI: 1.661–3.779, P

Objectives The objective of the study was to assess the clinical predictive value of the dynamics of absolute lymphocyte count (ALC) for 90-day all-cause mortality in sepsis patients in intensive care unit (ICU).Design Retrospective cohort study using big data.Setting This study was conducted using the Medical Information Mart for Intensive Care IV database V.2.0 database.Primary and secondary outcome measures The primary outcome was 90-day all-cause mortality.Participants Patients were included if they were diagnosed with sepsis on the first day of ICU admission. Exclusion criteria were ICU stay under 24 hours; the absence of lymphocyte count on the first day; extremely high lymphocyte count (>10×109/L); history of haematolymphatic tumours, bone marrow or solid organ transplants; survival time under 72 hours and previous ICU admissions. The analysis ultimately included 17 329 sepsis patients.Results The ALC in the non-survivors group was lower on days 1, 3, 5 and 7 after admission (p

AimsClostridium perfringens is one of the major anaerobic pathogen causing food poisoning and animal enteritis. With the rise of antibiotic resistance and the restrictions of the use of antibiotic growth promoting agents (AGPs) in farming, Clostridium enteritis and food contamination have become more common. It is time-consuming and labor-intensive to confirm the detection by standard culture methods, and it is necessary to develop on-site rapid detection tools. In this study, a combination of recombinase polymerase amplification (RPA) and lateral flow biosensor (LFB) was used to visually detect C. perfringens in chicken meat and milk.Methods and resultsTwo sets of primers were designed for the plc gene of C. perfringens, and the amplification efficiency and specificity of the primers. Selection of primers produces an amplified fragment on which the probe is designed. The probe was combined with the lateral flow biosensor (LFB). The reaction time and temperature of RPA-LFB assay were optimized, and the sensitivity of the assay was assessed. Several common foodborne pathogens were selected to test the specificity of the established method. Chicken and milk samples were artificially inoculated with different concentrations (1 × 102 CFU/mL to 1 × 106 CFU/mL) of C. perfringens, and the detection efficiency of RPA-LFB method and PCR method was compared. RPA-LFB can be completed in 20 min and the results can be read visually by the LFB test strips. The RPA-LFB has acceptable specificity and the lowest detection limit of 100 pg./μL for nucleic acid samples. It was able to stably detect C. perfringens contamination in chicken and milk at the lowest concentration of 1 × 104 CFU/mL and 1 × 103 CFU/mL, respectively.ConclusionIn conclusion, RPA-LFB is specific and sensitive. It is a rapid, simple and easy-to-visualize method for the detection of C. perfringens in food and is suitable for use in field testing work.

The prevalence of calcific aortic valve disease (CAVD) remains substantial while there is currently no medical therapy available. Forkhead box O1 (FOXO1) is known to be involved in the pathogenesis of cardiovascular diseases, including vascular calcification and atherosclerosis; however, its specific role in calcific aortic valve disease remains to be elucidated. In this study, we identified FOXO1 significantly down-regulated in the aortic valve interstitial cells (VICs) of calcified aortic valves by investigating clinical specimens and GEO database analysis. FOXO1 silencing or inhibition promoted VICs osteogenic differentiation in vitro and aortic valve calcification in Apoe−/− mice, respectively. We identified that FOXO1 facilitated the ubiquitination and degradation of RUNX2, which process was mainly mediated by SMAD-specific E3 ubiquitin ligase 2 (SMURF2). Our discoveries unveil a heretofore unacknowledged mechanism involving the FOXO1/SMURF2/RUNX2 axis in CAVD, thereby proposing the potential therapeutic utility of FOXO1 or SMURF2 as viable strategies to impede the progression of CAVD.

Abstract Background Whether distributions and prognostic values of high-sensitivity cardiac troponin (hs-cTn) T and I are different across normoglycemic, prediabetic, and diabetic populations is unknown. Methods 10127 adult participants from the National Health and Nutrition Examination Survey 1999–2004 with determined glycemic status and measurement of at least one of hs-cTn assays were included, from whom healthy participants and presumably healthy diabetic and prediabetic participants were selected to investigate pure impacts of glycemic status on distributions of hs-cTn. The nonparametric method and bootstrapping were used to derive the 99th upper reference limits of hs-cTn and 95% CI. Participants with available follow-up and hs-cTn concentrations of all 4 assays were included in prognostic analyses. Associations of hs-cTn with all-cause and cardiac-specific mortality were modeled by Cox proportional hazard regression under the complex survey design. The incremental value of hs-cTn to an established risk score in predicting cardiac-specific mortality was assessed by the 10-year area under time-dependent receiver operating characteristic curve (AUC) using the Fine-Grey competing risk model. Results Among 9714 participants included in prognostic analyses, 5946 (61.2%) were normoglycemic, 2172 (22.4%) prediabetic, and 1596 (16.4%) diabetic. Hyperglycemic populations were older than the normoglycemic population but sex and race/ethnicity were similar. During the median follow-up of 16.8 years, hs-cTnT and hs-cTnI were independently associated with all-cause and cardiac-specific mortality across glycemic status. In the diabetic population, adjusted hazard ratios per 1-standard deviation increase of log-transformed hs-cTnT and hs-cTnI (Abbott) concentrations were 1.77 (95% CI 1.48–2.12; P

The DC micro-grid system, as a new generation of shipboard DC micro-grid system, has the advantages of integrating renewable energy and enhancing the stability and reliability of the power system. For the energy distribution problem of energy storage battery charging and discharging in shipboard DC micro-grid, P-V voltage droop control and SOC-I current droop control methods are proposed. The SOC-I control method incorporated in the battery charging and discharging process can effectively balance the SOC and output power of the energy storage battery. For the on/off-grid process of shipboard power converter and onshore power, the control method of voltage and current control mode switching is proposed, which realizes the fast response of output voltage in off-grid mode and the controllable transfer of power interacting with the grid in grid-connected mode. Secondly, a pre-synchronized control based on amplitude and frequency modulation achieves a flexible on-grid/off-grid connection of the power converter. A method based on the parallel connection of multiple reduced-order generalized integrator (ROGI) is introduced to achieve suppression of output voltage unbalance as well as $5th$ and $7th$ harmonics. Finally, the efficiency and correctness of the proposed control method has been successfully evaluated an level 750KVA shipboard micro-grid system.

Introduction: Breast cancer is the most common cancer among women. The surgical treatment of breast cancer has transitioned progressively from radical mastectomy to breast-conserving surgery. In this meta-analysis, we are aiming to compare oncoplastic breast-conserving surgery (OS) with conventional breast-conserving surgery (BCS) in terms of efficacy and safety. Methods: We searched Medline, Web of Science, Embase, Cochrane databases, Clinicaltrial.gov, and CNKI until April 30, 2024. Data from cohort studies and randomized controlled trials (RCTs) were included. Outcomes included primary outcomes (re-excision, local recurrence, positive surgical margin, mastectomy), secondary outcomes and safety outcomes. The Cochrane Risk of Bias Assessment Tool and Newcastle-Ottawa Scale were used to evaluate the quality of outcomes. Results: Our study included 52 studies containing 46,835 patients. Primary outcomes comprise re-excision, local recurrence, positive surgical margin, and mastectomy, there were significant differences favoring OS over BCS (RR 0.68 [0.56, 0.82], RR 0.62 [0.47, 0.82], RR 0.76 [0.59, 0.98], RR 0.66 [0.44, 0.98] respectively), indicating superior efficacy of OS. Additionally, OS demonstrated significant aesthetic benefits (RR 1.17 [1.03, 1.33] and RR 1.34 [1.18, 1.52]). While total complications were significantly fewer in the OS group (RR 0.70 [0.53, 0.94]), the differences in specific complications were not significant. Furthermore, subgroup analyses were conducted based on nationality, sample size, quality, and type. Conclusion: OS demonstrates either superior or at least comparable outcomes across various aspects when compared to BCS.

Programmed cell death 2 (PDCD2) is related to cancer progression and chemotherapy sensitivity. The role of PDCD2 in solid cancers (excluding hematopoietic malignancies) and their diagnosis and prognosis remains unclear. The TCGA, CGGA, GEPIA, cBioPortal, and GTEx databases were analyzed for expression, prognostic value, and genetic modifications of PDCD2 in cancer patients. Functional enrichment analysis, CCK8, colony formation assay, transwell assay, and xenograft tumor model were undertaken to study the PDCD2's biological function in glioma (GBMLGG). The PDCD2 gene was associated with solid cancer progression. In the functional enrichment analysis results, PDCD2 was shown to participate in several important GBMLGG biological processes. GBMLGG cells may be inhibited in their proliferation, migration, invasion, and xenograft tumor growth by knocking down PDCD2. Our research can provide new insights into solid cancer prognostic biomarkers of PDCD2.

Background: Cisplatin (DDP) is the principal agent used for chemotherapy in patients with non-small cell lung cancer (NSCLC). Nevertheless, DDP resistance is an essential cause for a worse prognosis of patient. Therefore, this study proposes to discover features of miR-424-5p in DDP resistance of NSCLC. Method: After exogenous modulation of miR-424-5p expression, A549 cell activity was measured using CCK-8 and flow cytometry. A549/DDP and A549/DDP-associated subcutaneous tumor model were constructed to investigate the effect of miR-424-5p on DDP resistance in NSCLC in vivo. TargetScan and JASPAR databases predicted the potential molecular mechanism of miR-424-5p. A549-and A549/DDP-derived exosomes were isolated and characterized using a transmission electron microscope and nanoparticle tracking analysis. Result: Overexpression of miR-424-5p facilitated proliferation and DDP resistance in A549 cells, and knockdown of miR-424-5p did the opposite. Knockdown of miR-424-5p enhanced DDP restriction on tumor weight and volume. Moreover, SOCS5 and SOCS56 (SOCS5/6) were downstream targets of miR-424-5p. miR-424-5p down-regulated SOCS5/6 expression to activate JAK2/STAT3 and PI3K/AKT pathways. Notably, tumor protein p53 (TP53) is a transcription factor for the miR-424-5p host gene, as confirmed by the dual-luciferase reporter gene. Cellular and animal experiments indicated that TP53 limited the regulatory function of miR-424-5p on NSCLC growth, DDP resistance, and related molecules. Interestingly, miR-424-5p was markedly enriched in A549/DDP cell-derived exosomes than in A549 cell-derived exosomes, and TP53 down-regulated miR-424-5p expression in A549/DDP cell-derived exosomes. Conclusion: DDP-resistant cell-derived exosome miR-424-5p contributes to NSCLC growth and DDP resistance by targeting SOCS5 and SOCS6 to activate JAK2/STAT3 and PI3K/AKT pathways, which are blocked by TP53.

In this paper, we demonstrated a distributed feedback fiber-laser- (DFB-FL) based ultrasound detection system with a high signal-to-noise ratio (SNR), high sensitivity and wide frequency response range. The DFB-FL was fabricated by UV-inscribing a π phase-shifted grating in the Erbium–Ytterbium co-doped fiber using the phase mask method. The theory of DFB-FL and the sensing principle has been discussed and analyzed. The sensing signal was demodulated via an unbalanced Mach–Zehnder interferometer (MZI) system. The experimental results showed that the sensitivity of the sensor reached 75.18 mV/kPa and the flat frequency response range covered over 30 MHz, which covered the ultrasonic detection frequency range of abnormal discharge in the electric power system. The SNR of this DFB-FL was 42.9 dB, and the corresponding noise-equivalent pressure was calculated as 0.12 kPa.

Abstract Diastolic dysfunction is a major cardiac dysfunction, and an important predisposing factor is age. Although exercise training is often used for the prevention and treatment of cardiovascular disease nowadays, little is currently known about whether exercise interventions associated with the slowing of cardiac aging are related to mtp‐related pathways. In the present study, the UAS/Tub‐Gal4 system was used to knockdown whole‐body mtp expression levels in Drosophila, which underwent 2 weeks of endurance training. By conducting different assays and quantifying different indicators, we sought to investigate the relationship between mtp, exercise, and age‐related diastolic dysfunction. We found that (1) Drosophila in the mtpRNAi youth group exhibited age‐related diastolic dysfunction and had a significantly shorter mean lifespan. (2) Endurance exercise could improve diastolic dysfunction and prolong lifespan in aged Drosophila. (3) Endurance exercise could increase the expression levels of apolpp and Acox3, and decrease the levels of TC, LDL‐C, and TG in the aged group. In summary, aging causes age‐associated diastolic dysfunction in Drosophila, and systemic knockdown of mtp causes premature age‐associated diastolic dysfunction in young Drosophila. Besides, endurance exercise improves age‐related diastolic dysfunction and prolongs lifespan.

BackgroundBoth psoriasis and metabolic dysfunction-associated steatotic liver disease (MASLD) are immune-mediated chronic inflammatory diseases. Psoriasis manifests itself mainly as skin damage, while MASLD mainly involves the liver promoting liver fibrosis, which has a significant impact on patient health and quality of life. Some clinical studies have shown that there are mutually reinforcing mechanisms between these two diseases, but they are not clearly defined, and this paper aims to further explore their common pathogenesis.MethodsGene expression profiling datasets (GSE30999, GSE48452) and single cell datasets (GSE151177, GSE186328) for psoriasis and MASLD were downloaded from the Gene Expression Omnibus (GEO) database. Common differential gene sets were obtained by gene differential analysis, and then functional enrichment of differential genes was performed to find associated transcription factors and PPI protein network analysis. Single-cell datasets were validated for gene expression and explored for cellular communication, gene set differential analysis and immune infiltration analysis.ResultsWe identified seven common differential genes, all of which were upregulated.The IL-17 pathway, tumor necrosis factor (TNF-α) pathway were shown in strong association with both diseases, and five transcription factors regulating the differential genes were predicted. Two key genes (MMP9, CXCL10) and three key transcription factors (TF) (IRF1, STAT1, NFKB1) were obtained by PPI protein network analysis. Single cell dataset verified the expression of key genes, and combined with gene set differential analysis, immune infiltration revealed that CD4+ T cells, NK cells and macrophages were heavily infiltrated in both diseases. IL-17, IL-1 and cGAS-STING pathways were highly expressed in both diseases, and both diseases share a similar immune microenvironment.ConclusionsOur study reveals the common pathogenesis of psoriasis and MASLD from gene expression to immune cell similarities and differences, identifies key genes and regulatory pathways common to both, and elucidates the similarities in the immune microenvironment of both diseases, providing new ideas for subsequent studies on targeted therapy.

BackgroundIncreasing evidence suggests that alterations in gut microbiota are associated with a variety of skin diseases. However, whether this association reflects a causal relationship remains unknown. We aimed to reveal the causal relationship between gut microbiota and skin diseases, including psoriasis, atopic dermatitis, acne, and lichen planus.MethodsWe obtained full genetic association summary data for gut microbiota, psoriasis, atopic dermatitis, acne, and lichen planus from public databases and used three methods, mainly inverse variance weighting, to analyze the causal relationships between gut microbiota and these skin diseases using bidirectional Mendelian randomization, as well as sensitivity and stability analysis of the results using multiple methods.ResultsThe results showed that there were five associated genera in the psoriasis group, seven associated genera were obtained in the atopic dermatitis group, a total of ten associated genera in the acne group, and four associated genera in the lichen planus group. The results corrected for false discovery rate showed that Eubacteriumfissicatenagroup (P = 2.20E-04, OR = 1.24, 95%CI:1.11-1.40) and psoriasis still showed a causal relationship. In contrast, in the reverse Mendelian randomization results, there was no evidence of an association between these skin diseases and gut microbiota.ConclusionWe demonstrated a causal relationship between gut microbiota and immune skin diseases and provide a new therapeutic perspective for the study of immune diseases: targeted modulation of dysregulation of specific bacterial taxa to prevent and treat psoriasis, atopic dermatitis, acne, and lichen planus.

Summary: Here, we present a protocol for generating LtCas12a protein recognizing distinct TTNA (N represented A, T, C, G) protospacer adjacent motif sequence. We describe steps for transforming and harvesting bacterial cells and protein purification including nickel affinity chromatography and dialysis. We then detail procedures for verification of LtCas12a with cis- and trans-cleavage activities.For complete details on the use and execution of this protocol, please refer to Chen et al. (2023).1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Abstract It remains a great challenge to engineer materials with strong and stable interactions for the simultaneously mechanical-robust and room temperature phosphorescence-efficient materials. In this work, we demonstrate a covalent cross-linking strategy to engineer mechanical-robust room temperature phosphorescence materials through the B–O click reaction between chromophores, polyvinyl alcohol matrix and inorganic layered double hydroxide nanosheets. Through the covalent cross-linkage between the organic polyvinyl alcohol and inorganic layered double hydroxide, a polymeric composite with ultralong lifetime up to 1.45 s is acquired based on the inhibited non-radiative transition of chromophores. Simultaneously, decent mechanical strength of 97.9 MPa can be realized for the composite materials due to the dissipated loading stress through the covalent-bond-accommodated interfacial interaction. These cross-linked composites also exhibit flexibility, processability, scalability and phosphorescence responses towards the mechanical deformation. It is anticipated that the proposed covalent click reaction could provide a platform for the design and modulation of composites with multi-functionality and long-term durability.

Abstract Sepsis involves endothelial cell (EC) dysfunction, which contributes to multiple organ failure. To improve therapeutic prospects, elucidating molecular mechanisms of vascular dysfunction is of the essence. ATP-citrate lyase (ACLY) directs glucose metabolic fluxes to de novo lipogenesis by generating acetyl-Co-enzyme A (acetyl-CoA), which facilitates transcriptional priming via protein acetylation. It is well illustrated that ACLY participates in promoting cancer metastasis and fatty liver diseases. Its biological functions in ECs during sepsis remain unclear. We found that plasma levels of ACLY were increased in septic patients and were positively correlated with interleukin (IL)-6, soluble E-selectin (sE-selectin), soluble vascular cell adhesion molecule 1 (sVCAM-1), and lactate levels. ACLY inhibition significantly ameliorated lipopolysaccharide challenge-induced EC proinflammatory response in vitro and organ injury in vivo. The metabolomic analysis revealed that ACLY blockade fostered ECs a quiescent status by reducing the levels of glycolytic and lipogenic metabolites. Mechanistically, ACLY promoted forkhead box O1 (FoxO1) and histone H3 acetylation, thereby increasing the transcription of c-Myc (MYC) to facilitate the expression of proinflammatory and gluco-lipogenic genes. Our findings revealed that ACLY promoted EC gluco-lipogenic metabolism and proinflammatory response through acetylation-mediated MYC transcription, suggesting ACLY as the potential therapeutic target for treating sepsis-associated EC dysfunction and organ injury.

DNAzymes have attracted increasing interest in developments of gene tools, therapies, and biosensors. Among them, G-quadruplexes are widely used as the key structure elements of DNAzymes to activate the catalytic competency of specific cofactors, such as hemin, but there is a great demand to diversify DNAzymes using other more straightforward DNA structures such as fully matched duplex (FM-DNA). However, the perfect base pairs in duplex limit the DNAzyme activity. In this work, a photocatalytic DNAzyme was developed by introducing an abasic site (AP site) into duplex (AP-DNA) to switch its photocatalytic activity. Palmatine (PAL), a photosensitizer from natural isoquinoline alkaloids, served as a cofactor of the DNAzyme by binding at the AP site. The AP site provides a less polarized environment to favor the PAL fluorescence. As a result, dissolved oxygen was converted into singlet oxygen (1O2) via energy transfer from the excited PAL. The oxidation of substrates by the in situ photogenerated 1O2 served as a readout for the DNAzyme. In addition, the duplex-based DNAzyme was engineered from FM-DNA by the cascade uracil-DNA glycosylase to generate AP-DNA. Our work provides a new way to construct duplex-based DNAzymes.

In this work we discussed the safety of the electric field environment in the No.3 carriage where the pantograph is located. DSA380 pantograph, CRH5 EMU carriage and passengers’ models were established to study the electric field exposure of passengers at different positions. The results showed that Emax in the carriage without passengers is 1.173 x 10 6 mV/m. Then we set the passengers’ positions according to the electric field distribution in the carriage without passengers and obtained that Emax in the carriage with passengers is 3.195 x 10 6 mV/m. It can be seen that the maximum induced electric field intensity of passengers at different positions appears on the soles of shoes, the maximum value is 3.028 x 105 mV/m, the maximum induced current density occurs at the ankle, its maximum value is 3.476 x 10 -5 A/m 2. It can be concluded that the maximum induced electric field intensity of passenger’s head appears in the cerebrospinal fluid area, with a maximum value of 202.817 mV/m, and the maximum induced electric field intensity of passenger’s head at the door is larger than that in the middle of the carriage. The maximum values of the induced electric field intensity in all tissues of passengers are much smaller than the basic limits of electromagnetic exposure to the public set by the International Commission on Non-Ionizing Radiation Protection (ICNIRP). This study indicated that the pantograph has little influence on the electric field environment in the carriage under working state, and will not cause any health hazard to the passengers in this working frequency electric field environment.

This is a paper in the field of mining engineering. With the increasing demands for energy conservation and consumption reduction in mineral processing plants, ball mill load measurement is the key technology to realize mill control and optimize the grinding process. This paper summarizes the measurement methods of mill load in the recent years: differential pressure method, grinding sound method, vibration method, power method, ultrasonic method, indirect detection method based on multi-source signal fusion. Moreover, it summarizes and analyzes the mill load modeling methods that have emerged inrecent years. In the future, the indirect methods of multi-source information fusion will still be the main methods to detect mill load, modeling methods based on improvement of neural network and new online detection methods, as well as the establishment of efficient and accurate load detection models will be the main development direction of mill load detection.

Flood control operation of cascade reservoirs is an important technology to reduce flood disasters and increase economic benefits. Flood forecast information can help reservoir managers make better use of flood resources and reduce flood risks. In this paper, a hierarchical pre-release flood operation rule considering the flood forecast and its uncertainty information is proposed for real-time flood control. A many-objective optimization model considering the cascade reservoir’s power generation objective, flood control objective, and navigation objective is established. Then, a region search evolutionary algorithm is applied to optimize the many-objective optimization model in a real-world case study upstream of the Yangtze River basin. The optimization experimental results show that the region search evolutionary algorithm can balance convergence and diversity well, and the HV value is 40% higher than the MOEA/D algorithm. The simulation flood control results of cascade reservoirs upstream of the Yangtze River demonstrate that the optimized flood control rule can increase the average multi-year power generation of cascade reservoirs by a maximum of 27.72 × 108 kWh under the condition of flood control safety. The rules proposed in this paper utilize flood resources by identifying runoff forecast information, and pre-release to the flood limit level 145 m before the big flood occurs, so as to ensure the safety downstream and the dam’s own flood control and provide reliable decision support for reservoir managers.

Abstract Background Delayed neutrophil apoptosis during sepsis may impact neutrophil organ accumulation and tissue immune homeostasis. Elucidating the mechanisms underlying neutrophil apoptosis may help identify potential therapeutic targets. Glycolysis is critical to neutrophil activities during sepsis. However, the precise mechanisms through which glycolysis regulates neutrophil physiology remain under-explored, especially those involving the non-metabolic functions of glycolytic enzymes. In the present study, the impact of programmed death ligand-1 (PD-L1) on neutrophil apoptosis was explored. The regulatory effect of the glycolytic enzyme, pyruvate kinase M2 (PKM2), whose role in septic neutrophils remains unaddressed, on neutrophil PD-L1 expression was also explored. Methods Peripheral blood neutrophils were isolated from patients with sepsis and healthy controls. PD-L1 and PKM2 levels were determined by flow cytometry and Western blotting, respectively. Dimethyl sulfoxide (DMSO)-differentiated HL-60 cells were stimulated with lipopolysaccharide (LPS) as an in vitro simulation of septic neutrophils. Cell apoptosis was assessed by annexin V/propidium iodide (annexin V/PI) staining, as well as determination of protein levels of cleaved caspase-3 and myeloid cell leukemia-1 (Mcl-1) by Western blotting. An in vivo model of sepsis was constructed by intraperitoneal injection of LPS (5 mg/kg) for 16 h. Pulmonary and hepatic neutrophil infiltration was assessed by flow cytometry or immunohistochemistry. Results PD-L1 level was elevated on neutrophils under septic conditions. Administration of neutralizing antibodies against PD-L1 partially reversed the inhibitory effect of LPS on neutrophil apoptosis. Neutrophil infiltration into the lung and liver was also reduced in PD-L1−/− mice 16 h after sepsis induction. PKM2 was upregulated in septic neutrophils and promoted neutrophil PD-L1 expression both in vitro and in vivo. In addition, PKM2 nuclear translocation was increased after LPS stimulation, which promoted PD-L1 expression by directly interacting with and activating signal transducer and activator of transcription 1 (STAT1). Inhibition of PKM2 activity or STAT1 activation also led to increased neutrophil apoptosis. Conclusion In this study, a PKM2/STAT1-mediated upregulation of PD-L1 on neutrophils and the anti-apoptotic effect of upregulated PD-L1 on neutrophils during sepsis were identified, which may result in increased pulmonary and hepatic neutrophil accumulation. These findings suggest that PKM2 and PD-L1 could serve as potential therapeutic targets.

Abstract Estimation of ore grade is very important for the value evaluation of ore deposits, and it directly affects the development of mineral resources. To improve the accuracy of the inverse distance weighting (IDW) method in ore grade estimation and reduce the smoothing effect of the IDW method in grade estimation, the weight calculation method involved in the IDW method was improved. The length parameter of the ore sample was used to calculate the weight of the IDW method. The length of the ore samples was used as a new factor of the weighting calculation. A new method of IDW integrated with sample length weighting (IDWW) was proposed. The grade estimation of Li, Al, and Fe in porcelain clay ore was used as a case study. A comparative protocol for grade estimation via the IDWW method was designed and implemented. The number of samples involved in the estimation, sample combination, sample grade distribution, and other factors affecting the grade estimation were considered in the experimental scheme. The grade estimation results of the IDWW and the IDW methods were used for comparative analysis of grades of the original and combined samples. The estimated results of the IDWW method were also compared with those of the IDW method. The deviation analysis of the estimated grade mainly included the minimum, maximum, mean, and coefficient of variation of the ore grade. The estimation effect of IDWW method was verified. The minimum deviations of the estimated grade of Li, Al, and Fe were between 9.129% and 59.554%. The maximum deviations were between 4.210 and 22.375%. The mean deviations were between − 1.068 and 7.187%. The deviations in the coefficient of variation were between 3.076 and 36.186%. The deviations in the maximum, minimum, mean, and coefficients of variation of the IDWW were consistent with those of the IDW, demonstrating the accuracy and stability of the IDWW method. The more the samples involved in the estimation, the greater the estimation deviations of IDW and IDWW methods. The estimated deviations of Li, Al, and Fe were affected by the shape of the grade distribution, when the same estimation parameters were used. The grade distribution pattern of the samples significantly influenced the grade estimation results. The IDWW method offers significant theoretical advantages and addresses the adverse effects of uneven sample lengths on the estimates. The IDWW method can effectively reduce the smoothing effect and improves the utilization efficiency of the original samples.

Background: Semantic segmentation is crucial in medical image diagnosis. Traditional deep convolutional neural networks excel in image classification and object detection but fall short in segmentation tasks. Enhancing the accuracy and efficiency of detecting high-level cervical lesions and invasive cancer poses a primary challenge in segmentation model development. Methods: Between 2018 and 2022, we retrospectively studied a total of 777 patients, comprising 339 patients with high-level cervical lesions and 313 patients with microinvasive or invasive cervical cancer. Overall, 1554 colposcopic images were put into the DeepLabv3+ model for learning. Accuracy, Precision, Specificity, and mIoU were employed to evaluate the performance of the model in the prediction of cervical high-level lesions and cancer. Results: Experiments showed that our segmentation model had better diagnosis efficiency than colposcopic experts and other artificial intelligence models, and reached Accuracy of 93.29 %, Precision of 87.2 %, Specificity of 90.1 %, and mIoU of 80.27 %, respectively. Conclution: The DeepLabv3+ model had good performance in the segmentation of cervical lesions in colposcopic post-acetic-acid images and can better assist colposcopists in improving the diagnosis.

The space reactor is the primary energy supply for future space vehicles and space stations. The radiator is one of the essential parts of a space reactor. Therefore, the research on radiators can improve the heat dissipation power, reduce the quality of radiators, and make the space reactor smaller. Based on MOOSE multi-physics numerical calculation platform, a simulation program for the combination of heat pipe and fin at the end of heat pipe radiator is developed. It is verified that the calculation result of this program is accurate and the calculation speed is fast. Analyze the heat transfer characteristics of the combination with heat pipe and fin, and obtain its internal temperature field. Based on the calculation results, the influence of structural parameters on the heat dissipation power is analyzed. The results show that when the fin width is 0.25 m, fin thickness is 0.002 m, condensing section length is 0.5425 m and heat pipe radius is 0.014 m, the power-mass ratio is the highest. When the temperature is 700K–900K, the heat dissipation power increases 41.12% for every 100K increase in the operating temperature. Smaller fin width and thinner fin thickness can improve the power-mass ratio and reduce the radiator quality.

Objectives: The current study aims to assess the effectiveness of acupuncture in improving the live birth rate (LBR), ongoing pregnancy rate (OPR), clinical pregnancy rate (CPR), biochemical pregnancy rate (BPR), and pregnancy loss (early abortion rate, late abortion rate, ectopic pregnancy rate) in patients with recurrent implantation failure (RIF). Design: This retrospective study compares the outcomes of patients with RIF who underwent frozen embryo transfer (FET) with or without acupuncture. Setting: The medical records of patients diagnosed with RIF and visiting Chengdu Xi'nan Gynecological Hospital between January 2018 and June 2021 were reviewed. The Chengdu Xi'nan Gynecological Hospital Ethics Committee approved this retrospective study (No. 2021–029). Participants: A total of 923 patients with RIF who underwent FET were included in this study. The patients were divided into two groups: the Acupuncture (n = 303) and the Non-acupuncture groups (n = 620). Exposure: The Acupuncture group consisted of 303 RIF patients who received acupuncture therapy in addition to standard hormone replacement therapy (HRT)/delayed hormone replacement therapy (d-HRT) for FET. The Non-acupuncture group consisted of 620 RIF patients who received only standard HRT/d-HRT for FET. Primary and secondary outcome measures: The primary outcome was the LBR. The secondary outcome referred to OPR, CPR, BPR, and pregnancy loss. Results: The Acupuncture group had significantly higher BPR (P = 0.08) and CPR (P = 0.049) than the Non-acupuncture group. A potentially higher LBR (P = 0.16) and OPR (P = 0.248) were observed in the Acupuncture group than in the Non-acupuncture group. However, the survival analysis did not show that acupuncture significantly promoted live birth. Conclusions: Acupuncture is an appropriate adjunctive technique in the in vitro fertilization process as it improves biochemical and clinical pregnancies. Therefore, it is necessary to be cautious about the role of acupuncture throughout the whole pregnancy cycle.

Background There was limited high‐quality evidence that illuminated the efficiency of cerebral embolic protection (CEP) use during transcatheter aortic valve replacement (TAVR) for bicuspid aortic valve (BAV) stenosis. Methods and Results In this retrospective cohort study, patients with BAV stenosis undergoing TAVR with or without CEP were identified by querying the National Inpatient Sample database. The primary end point was any stroke during the hospitalization. The composite safety end point included any in‐hospital death and stroke. We applied propensity score–matched analysis to minimize standardized mean differences of baseline variables and compare in‐hospital outcomes. From July 2017 to December 2020, 4610 weighted hospitalizations with BAV stenosis undergoing TAVR were identified, of which 795 were treated with CEP. There was a significant increase in the CEP use rate for BAV stenosis (P‐trend

The herbicide paraquat is an agonist of Stromal Interaction Molecule 1 (STIM1), leading to extracellular calcium entry observed in epithelial-mesenchymal transition in alveolar cells during pulmonary fibrosis.

Abstract Background Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and has an extremely poor prognosis. We aimed to determine the latent relationships between TRIM36 regulation of apoptosis and the Wnt/β-catenin pathway in HCC. Methods Immunohistochemistry and western blotting were used to characterize the aberrant expression of TRIM36 in HCC and adjacent tissues. Clinical information was analyzed using Kaplan–Meier and Cox methods. RNA-seq of potential targets was conducted to detect the regulation of TRIM36. Apoptosis assays and cellular proliferation, invasion and migration were conducted in a loss- and gain-of-function manner in cultured cells to determine the biological functions of TRIM36. A rescue experiment was conducted to confirm the role of Wnt/β-catenin signaling in TRIM36 regulation. Finally, in vivo experiments were conducted using cell line-derived xenografts in nude mice to validate the central role of TRIM36 in HCC. Results TRIM36 expression was significantly downregulated in HCC tissues compared to adjacent non-tumor tissues. TRIM36 repressed the proliferation, migration, and invasion of Huh7 and HCCLM3 cells, whereas it stimulated apoptosis. Wnt/β-catenin signaling was inhibited by TRIM36, and rescue experiments highlighted its importance in HCC proliferation, migration, and invasion. In vivo experiments further confirmed the effects of sh-TRIM36 on HCC tumorigenesis, inhibition of apoptosis, and promotion of Wnt/β-catenin signaling. Conclusion Our study is the first to indicate that TRIM36 acts as a tumor suppressor in HCC. TRIM36 activates apoptosis and inhibits cellular proliferation, invasion, and migration via the Wnt/β-catenin pathway, which may serve as an important biomarker and promising therapeutic target for HCC.

Background: Effective antiplatelet therapy is critical for patients with ST-segment elevation myocardial infarction (STEMI) and receiving primary percutaneous coronary interventions (PPCI). Intracoronary (IC) and intravenous (IV) administration of tirofiban are commonly used during the procedure of PPCI. However, which is the better administration route of tirofiban have not been fully evaluated. Methods: A comprehensive literature search of RCTs that comparing IC with IV tirofiban in STEMI patients undergoing PPCI was conducted, which were published as of May 7, 2022, in PubMed, Embase, Cochrane Library, Web of Science, Scopus and ClinicalTrials.gov. The primary efficacy endpoint was 30-day major adverse cardiovascular events (MACE) and the primary safety endpoint was in-hospital bleeding events. Results: This meta-analysis included 9 trials involving 1177 patients. IC tirofiban significantly reduced the incidence of 30-day MACE (RR 0.65, 95% CI: 0.44 to 0.95, P = 0.028) and improved the rate of the thrombolysis in myocardial infarction (TIMI) grade 3 flow in high-dose (25 μg/kg) group (RR = 1.13, 95% CI: 0.99–1.30, P = 0.001), in-hospital (WMD 2.03, 95% CI: 1.03 to 3.02, P

Virtual Touch Tissue Quantification (VTQ) offers several advantages in the diagnosis of various lung diseases. Chemokine expression levels, such as CXCL13, play a vital role in the occurrence and development of tumors and aid in the diagnosis process. The purpose of this study was to evaluate the combined value of VTQ and changes in CXCL13 expression levels for the diagnosis of lung tumors. A total of 60 patients with thoracic nodules and pleural effusion were included, with 30 of them having malignant pleural effusion (based on pathology) and the remaining 30 having benign thoracic nodules and pleural effusion. The relative expression level of CXCL13 was measured in the collected pleural effusions using Enzyme-Linked Immunosorbent Assay (ELISA). The relationship between CXCL13 expression levels and various clinical features was analyzed. A Receiver Operating Characteristic (ROC) curve analysis was conducted on the VTQ results and relative expression levels of CXCL13, and the areas under the curve, critical values, sensitivity, and specificity were calculated. Multivariate analysis incorporating multiple indicators was performed to determine the accuracy of lung tumor diagnosis. The results showed that the expression levels of CXCL13 and VTQ were significantly higher in the lung cancer group compared to the control group (P < 0.05). In the Non-Small Cell Lung Cancer (NSCLC) group, CXCL13 expression levels increased with later TNM staging and poorer tumor differentiation. The expression level of CXCL13 in adenocarcinoma was higher than that in squamous cell carcinoma. The ROC curve analysis revealed that CXCL13 had an area under the curve (AUC) of 0.74 (0.61, 0.86) with an optimal cut-off value of 777.82 pg/ml for diagnosing lung tumors. The ROC curve analysis of VTQ showed an AUC of 0.67 (0.53, 0.82) with a sensitivity of 60.0% and a specificity of 83.3%, and an optimal diagnostic cut-off of 3.33 m/s. The combination of CXCL13 and VTQ for diagnosing thoracic tumors had an AUC of 0.842 (0.74, 0.94), which was significantly higher than either factor alone. The results of the study demonstrate the strong potential of combining VTQ results with chemokine CXCL13 expression levels for lung tumor diagnosis. Additionally, the findings suggest that elevated relative expression of CXCL13 in cases of malignant pleural effusion caused by non-small cell lung cancer may indicate a poor prognosis. This provides promising potential for using CXCL13 as a screening tool and prognostic indicator for patients with advanced lung cancer complicated by malignant pleural effusion.

Previous camera self-calibration methods have exhibited certain notable shortcomings. On the one hand, they either exclusively emphasized scene cues or solely focused on vehicle-related cues, resulting in a lack of adaptability to diverse scenarios and a limited number of effective features. Furthermore, these methods either solely utilized geometric features within traffic scenes or exclusively extracted semantic information, failing to comprehensively consider both aspects. This limited the comprehensive feature extraction from scenes, ultimately leading to a decrease in calibration accuracy. Additionally, conventional vanishing point-based self-calibration methods often required the design of additional edge-background models and manual parameter tuning, thereby increasing operational complexity and the potential for errors. Given these observed limitations, and in order to address these challenges, we propose an innovative roadside camera self-calibration model based on the Transformer architecture. This model possesses a unique capability to simultaneously learn scene features and vehicle features within traffic scenarios while considering both geometric and semantic information. Through this approach, our model can overcome the constraints of prior methods, enhancing calibration accuracy and robustness while reducing operational complexity and the potential for errors. Our method outperforms existing approaches on both real-world dataset scenarios and publicly available datasets, demonstrating the effectiveness of our approach.

Obesity is a prevalent metabolic disorder associated with various diseases, including cardiovascular conditions. While exercise is recognized as an effective approach for preventing and treating obesity, its underlying molecular mechanisms remain unclear. This study aimed to explore the impact of regular exercise on high-fat-diet-induced obesity and cardiac dysfunction in Drosophila, shedding light on its molecular mechanisms by identifying its regulation of the dfoxo and dsrebp signaling pathways. Our findings demonstrated that a high-fat diet leads to weight gain, fat accumulation, reduced climbing performance, and elevated triglyceride levels in Drosophila. Additionally, cardiac microfilaments in these flies exhibited irregularities, breakages, and shortening. M-mode analysis revealed that high-fat-diet-fed Drosophila displayed increased heart rates, shortened cardiac cycles, decreased systolic intervals, heightened arrhythmia indices, reduced diastolic diameters, and diminished fractional shortening. Remarkably, regular exercise effectively ameliorated these adverse outcomes. Further analysis showed that regular exercise reduced fat synthesis, promoted lipolysis, and mitigated high-fat-diet-induced cardiac dysfunction in Drosophila. These results suggest that regular exercise may mitigate high-fat-diet-induced obesity and cardiac dysfunction in Drosophila by regulating the dfoxo and dsrebp signaling pathways, offering valuable insights into the mechanisms underlying the beneficial effects of exercise on obesity and cardiac dysfunction induced by a high-fat diet.

It is currently difficult to synthesise NIR-II probes with good quantum yields, biocompatibility and pharmacokinetics. Here the authors report a strategy to alter these properties by modifying the protein coatings with biofunctional molecules, and generate long-wavelength fluorophores for in vivo imaging.

A genome editing tool targeting the high-risk human papillomavirus (HPV) oncogene is a promising therapeutic strategy to treat HPV-related cervical cancer. To improve gene knockout efficiency, we developed a gene knockout chain reaction (GKCR) method for continually generating mutagenic disruptions and used this method to disrupt the HPV18 E6 and E7 genes. We verified that the GKCR Cas9/guide RNA (gRNA) cassettes could integrated into the targeted loci via homology-independent targeted insertion (HITI). The qPCR results revealed that the GKCR method enabled a relatively higher Cas9/gRNA cassette insertion rate than a control method (the common CRISPR-Cas9 strategy). Tracking of Indels by DEcomposition (TIDE) assay results showed that the GKCR method produced a significantly higher percentage of insertions or deletions (indels) in the HPV18 E6 and E7 genes. Furthermore, by targeting the HPV18 E6/E7 oncogenes, we found that the GKCR method significantly upregulated the P53/RB proteins and inhibited the proliferation and motility of HeLa cells. The GKCR method significantly improved the gene knockout efficiency of the HPV18 E6/E7 oncogenes, which might provide new insights into treatment of HPV infection and related cervical cancer.

Gene editing tools have tremendous potential for biomedical and basic research. Here the authors report a Cas9 from Faecalibaculum rodentium (FrCas9) that achieves efficient and specific gene editing in human cells with a NNTA palindrome PAMs for targeting optimal sites at TATA-boxes to enhance CRISPRa/i screening.

The current epidemiological status of the new coronary pneumonia epidemic in China is being explored to prevent and control the localized dissemination of aggregated outbreaks. This study analyzed the characteristics of new outbreaks of coronavirus disease 2019 (COVID-19) at three stages of aggregated outbreaks in Jilin Province, China, to provide a reference for the prevention and control of aggregated outbreaks. Case information were collected from all patients in Jilin Province from January 12, 2020 to the present. The epidemic was divided into three stages according to the time of onset. The first stage comprised 97 cases reported from January 12, 2020 to February 19, 2020, during which 17 aggregated outbreaks occurred. The second comprised 43 cases reported from April 25, 2020 and May 23, 2020, involving one aggregated outbreak. The third comprised 435 cases reported on January 10, 2021 and February 9, 2021, involving one aggregated outbreak. The relationship between aggregated and non-aggregated cases in the first phase of the outbreak and the difference between imported and local cases during the aggregated outbreak were assess using statistical analysis, and the differences in the baseline information between the three phases were analyzed. The incubation periods of the three phases were 10 days, 8 days, and 5 days. The number of aggregated epidemic events in Jilin Province tended to increase and then decrease over time. The clustered events in Jilin Province were divided into four categories: household contact (14 times, 51 cases); household contact and public places (one time, three cases); household contact, public places, and gatherings (one time, six cases); and household contact, public places, gatherings, and work (three times, 495 cases). Clustered events occurred mainly between January 22, 2020, and February 4, 2020. Among all cases in the first phase of the outbreak, the method of detection and the time from diagnosis to discharge were longer in aggregated cases than in non-aggregated cases, and that the source of infection and renewal cases were more frequent and more likely to be detected in the outpatient clinics during aggregated outbreaks than the imported cases. The second phase of the epidemic showed significant spatial variability (Moran's I

Systemic lupus erythematosus (SLE) is a common multisystem, multiorgan heterozygous autoimmune disease. The main pathological features of the disease are autoantibody production and immune complex deposition. Autophagy is an important mechanism to maintain cell homeostasis. Autophagy functional abnormalities lead to the accumulation of apoptosis and induce the autoantibodies that result in immune disorders. Therefore, improving autophagy may alleviate the development of SLE. For SLE, glucocorticoids or immunosuppressive agents are commonly used in clinical treatment, but long-term use of these drugs causes serious side effects in humans. Immunosuppressive agents are expensive. Traditional Chinese medicines (TCMs) are widely used for immune diseases due to their low toxicity and few side effects. Many recent studies found that TCM and its active ingredients affected the pathological development of SLE by regulating autophagy. This article explains how autophagy interferes with immune system homeostasis and participates in the occurrence and development of SLE. It also summarizes several studies on TCM-regulated autophagy intervention in SLE to generate new ideas for basic research, the development of novel medications, and the clinical treatment of SLE.

Insufficient available phosphorus in soil has become an important limiting factor for the improvement of yield and quality in soybean. The mining of QTLs and candidate genes controlling soybean phosphorus utilization related traits is a necessary strategy to solve this problem. In this study, 11 phosphorus utilization related traits of a natural population of 281 typical soybean germplasms and a recombinant inbred line (RIL) population of 270 lines were evaluated under different phosphorus conditions at two critical stages: the four-leaf stage as the seedling critical stage was designated as the T1 stage, and the six-leaf stage as the flowering critical stage was designated as the T2 stage. In total, 200 single nucleotide polymorphism (SNP) loci associated with phosphorus utilization related traits were identified in the natural population, including 91 detected at the T1 stage, and 109 detected at the T2 stage. Among these SNP loci, one SNP cluster (s715611375, ss715611377, ss715611379 and ss715611380) on Gm12 was shown to be significantly associated with plant height under the low phosphorus condition at the T1 stage, and the elite haplotype showed significantly greater plant height than the others. Meanwhile, one pleiotropic SNP cluster (ss715606501, ss715606506 and ss715606543) on Gm10 was found to be significantly associated with the ratio of root/shoot, root and total dry weights under the low phosphorus condition at the T2 stage, and the elite haplotype also presented significantly higher values for related characteristics under the phosphorus starvation condition. Furthermore, four co-associated SNP loci (ss715597964, ss715607012, ss715622173 and ss715602331) were identified under the low phosphorus condition at both the T1 and T2 stages, and 12 QTLs were found to be consistent with these genetic loci in the RIL population. More importantly, 14 candidate genes, including MYB transcription factor, purple acid phosphatase, sugar transporter and HSP20-like chaperones superfamily genes, etc., showed differential expression levels after low phosphorus treatment, and three of them were further verified by qRT-PCR. Thus, these genetic loci and candidate genes could be applied in marker-assisted selection or map-based gene cloning for the genetic improvement of soybean phosphorus utilization.

Abstract Background Effective removal of pathogenic bacteria is key to improving the prognosis of sepsis. Polymorphonuclear neutrophils (PMNs) are the most important components of innate cellular immunity and play vital roles in clearing pathogenic bacteria. However, the metabolic characteristics and immunomodulatory pathways of PMNs during sepsis have not been investigated. In the present study, we explored the immune metabolism characteristics of PMNs and the mechanism by which neutrophilic glycolysis is regulated during sepsis. Methods Metabolomics analysis was performed on PMNs isolated from 14 septic patients, 26 patients with acute appendicitis, and 19 healthy volunteers. Transcriptome analysis was performed on the PMNs isolated from the healthy volunteers and the patients with sepsis to assess glycolysis and investigate its mechanism. Lipopolysaccharide (LPS) was used to stimulate the neutrophils isolated from the healthy volunteers at different time intervals to build an LPS-tolerant model. Chemotaxis, phagocytosis, lactate production, oxygen consumption rate (OCR), and extracellular acidification rate (ECAR) were evaluated. Results Transcriptomics showed significant changes in glycolysis and the mTOR/HIF-1α signaling pathway during sepsis. Metabolomics revealed that the Warburg effect was significantly altered in the patients with sepsis. We discovered that glycolysis regulated PMNs’ chemotaxis and phagocytosis functions during sepsis. Lactate dehydrogenase A (LDHA) downregulation was a key factor in the inhibition of glycolysis in PMNs. This study confirmed that the PI3K/Akt-HIF-1α pathway was involved in the LDHA expression level and also influenced PMNs’ chemotaxis and phagocytosis functions. Conclusions The inhibition of glycolysis contributed to neutrophil immunosuppression during sepsis and might be controlled by PI3K/Akt-HIF-1α pathway-mediated LDHA downregulation. Our study provides a scientific theoretical basis for the management and treatment of patients with sepsis and promotes to identify therapeutic target for the improvement of immune function in sepsis.

Zinc-finger nucleases (ZFNs), transcription activator-like endonucleases (TALENs), and CRISPR-associated Cas9 endonucleases are three major generations of genome editing tools. However, no parallel comparison about the efficiencies and off-target activity of the three nucleases has been reported, which is critical for the final clinical decision. We for the first time developed the genome-wide unbiased identification of double-stranded breaks enabled by sequencing (GUIDE-seq) method in ZFNs and TALENs with novel bioinformatics algorithms to evaluate the off-targets. By targeting human papillomavirus 16 (HPV16), we compared the performance of ZFNs, TALENs, and SpCas9 in vivo. Our data showed that ZFNs with similar targets could generate distinct massive off-targets (287–1,856), and the specificity could be reversely correlated with the counts of middle “G” in zinc finger proteins (ZFPs). We also compared the TALENs with different N-terminal domains (wild-type [WT]/αN/βN) and G recognition modules (NN/NH) and found the design (αN or NN) to improve the efficiency of TALEN inevitably increased off-targets. Finally, our results showed that SpCas9 was more efficient and specific than ZFNs and TALENs. Specifically, SpCas9 had fewer off-target counts in URR (SpCas9, n = 0; TALEN, n = 1; ZFN, n = 287), E6 (SpCas9, n = 0; TALEN, n = 7), and E7 (SpCas9, n = 4; TALEN, n = 36). Taken together, we suggest that for HPV gene therapies, SpCas9 is a more efficient and safer genome editing tool. Our off-target data could be used to improve the design of ZFNs and TALENs, and the universal in vivo off-target detection pipeline for three generations of artificial nucleases provided useful tools for genome engineering-based gene therapy.

Transition metal sulphide electrocatalytic materials possess the bright overall water-splitting performance of practical electrocatalytic technologies. In this study, an amethyst-like MoS2@Ni9S8/Co3S4 rod electrocatalyst was constructed via a one-step hydrothermal method with in-situ-grown ZIF-67 nanoparticles on nickel foam (NF) as a precursor. The rational design and synthesis of MoS2@Ni9S8/Co3S4 endow the catalyst with neat nanorods morphology and high conductivity. The MoS2@Ni9S8/Co3S4/NF with the amethyst-like rod structure exposes abundant active sites and displays fast electron-transfer capability. The resultant MoS2@Ni9S8/Co3S4/NF exhibits outstanding hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) electrocatalytic activities, with low overpotentials of 81.24 mV (HER) at 10 mA cm−2 and 159.67 mV (OER) at 50 mA cm−2 in 1.0 M KOH solution. The full-cell voltage of overall water splitting only achieves 1.45 V at 10 mA cm−2. The successful preparation of the amethyst-like MoS2@Ni9S8/Co3S4 rod electrocatalyst provides a reliable reference for obtaining efficient electrocatalysts for overall water splitting.

In this paper, the effect of melting characteristics of CuO/paraffin wax composite phase change material in a spherical heat storage unit in a constant temperature water bath is investigated. Experiments were conducted in three different water bath temperatures (65 °C, 70 °C, and 75 °C). The inner surface of the sphere was fixed with two, four, and six pin-shaped fins 3 mm in diameter. The spheres were filled with different mass fractions of CuO nanoparticles/paraffin phase change materials. Experimental CCD was used to model and optimize the spherical thermal storage unit. Regression models were developed to predict the effects of various operational factors on the melting time of the composite PCM. The factors in the model included the number of pin fins in the spherical heat storage unit, the water bath temperature, and the content of added CuO nanoparticles in the PCM, and ANOVA was used to statistically validate the regression model. The results showed that the interaction between the water bath temperature and the number of pin fins had the most significant effect on the melting time. With the melting time of the phase change material as the optimized objective function, the optimized optimal working condition was six pin fins, a water bath temperature of 75 °C, and the addition of 5 wt% CuO nanoparticles/paraffin phase change material, and the actual melting time under this condition was 78.9 min, which was lower than the predicted value of 79.4 min, with an error of 0.63% between them.

Due to nonlinear components in the charging piles of electric vehicles, harmonics and nonstationary signals in the electric vehicle charging load bring voltage and current distortion, seriously affecting the accuracy of the power-related calculation in nonsinusoidal environments. This paper proposed a new approach to calculate the active power and root mean square values from decomposed components using the adaptive chirp mode decomposition (ACMD) method on voltage and current. The advantage of the ACMD-based method is that it correctly provides the power-related quantities of harmonics or nonstationary components for the electric vehicle charging load. The performance of the proposed method was verified using synthetic signals and simulation tests. The experimental results presented better estimations for each quantity defined in IEEE Standard 1459-2010, compared with the discrete wavelet transform approach.

Rechargeable aqueous Zn-metal batteries have attracted widespread attention owing to their safety and low cost beyond Li-metal batteries. However, due to the lack of the solid electrolyte interphase, problems such as dendrites, side reactions and hydrogen generation severely restrict their commercial applications. Herein, a quasi-liquid interphase (QLI) with a “solid–liquid” property is constructed to stabilize the Zn-metal anode. The synergistic effect of solid and liquid behavior ensures the stable existence of QLI and simultaneously enables the interphase dynamic and self-adaptive to the anode evolution. Electrolyte erosion, Zn2+ diffusion and side reactions are inhibited during long-term cycling after introducing QLI, significantly improving the cycling stability and capacity retention of the symmetric and full cells modified with QLI (Zn@QLI), respectively. Constructing an interphase with a quasi-liquid state represents a promising strategy to stabilize the metal anodes in aqueous electrolytes and even extend to organic electrolytes.

The mass fraction of 0.01 wt% ZnO nanofluid was prepared via the two-step method. The measurement verifies that ZnO nanofluids have better transmission characteristics in the frequency division window range of 400–1200 nm. At the same time, it has good absorption characteristics in ultraviolet and near-infrared bands, which meets the application conditions of the spectral beam-splitting module of the PV/T system. A spectral beam-splitting module of the PV/T system was designed. The simplified physical model was established in ANSYS 14.0. The flow field and convective heat transfer were simulated for different arrangements of the interlayer inlet to obtain a more ideal and uniform temperature distribution to improve the system’s comprehensive efficiency. The results show that the fluid flow in the interlayer under case II is more uniform, and the temperature field distribution is better than other arrangements. Hence, this work could provide a reference for optimising nanofluid flow within a spectral beam-splitting module.

The COVID-19 pandemic has created an urgent need for volunteers to complement overwhelmed public health systems. This study aims to explore Chinese people’s attitudes toward volunteerism amid the COVID-19 pandemic. To this end, we identify the latent topics in volunteerism-related microblogs on Weibo, the Chinese equivalent of Twitter using the topic modeling analysis via Latent Dirichlet Allocation (LDA). To further investigate the public sentiment toward the topics generated by LDA, we also conducted sentiment analysis on the sample posts using the open-source natural language processing (NLP) technique from Baidu. Through an in-depth analysis of 91,933 Weibo posts, this study captures 10 topics that are, in turn, distributed into five factors associated with volunteerism in China as motive fulfillment (n = 31,661, 34.44%), fear of COVID-19 (n = 22,597, 24.58%), individual characteristic (n = 17,688, 19.24%), government support (n = 15,482, 16.84%), and community effect (n = 4,505, 4.90%). The results show that motive fulfillment, government support, and community effect are the factors that could enhance positive attitudes toward volunteerism since the topics related to these factors report high proportions of positive emotion. Fear of COVID-19 and individual characteristic are the factors inducing negative sentiment toward volunteerism as the topics related to these factors show relatively high proportions of negative emotion. The provision of tailored strategies based on the factors could potentially enhance Chinese people’s willingness to participate in volunteer activities during the COVID-19 pandemic.