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The presence of bacteria and viruses in water has caused many large-scale water disease outbreaks. Cold atmospheric plasma has received much attention as an emerging non-thermal purification technology capable of eliminating micro-organisms, non-ferrous fuels, and heavy metals from water. In this study, a novel gas–liquid diaphragm discharge device that generates air plasma driven by a sinusoidal AC power supply was designed, and its sterilizing effect was investigated. First, the concentrations of reactive oxygen and nitrogen species in the diaphragm discharge were characterized, and the physicochemical properties of activated water were explored. Next, experiments on the inactivation of Pseudomonas aeruginosa were carried out using the device. Finally, pond sewage was treated with the device, and the diversity of micro-organisms in the water was analyzed using 16S rRNA assays to further investigate its applicability. The results showed that the species and quantities of micro-organisms in the water significantly reduced after discharge treatment, with the most significant changes occurring in the Bacillus and Firmicutes species. Thus, this study provides an alternative method for microbial inactivation in sewage treatment. [ABSTRACT FROM AUTHOR]

Summary: SLC17A9 is a vesicular ATP transport protein that plays an important role in determining cell functions and the onset and progression of different diseases. In this study, SLC17A9 was initially identified as a potential diagnostic and prognostic risk biomarker for clear cell renal cell carcinoma (ccRCC). Then, the aberrant expression levels of SLC17A9 were confirmed in both the cell lines and clinical tissues. Mechanistically, SLC17A9 could upregulate the expression of PTHLH, thus promoting epithelial-mesenchymal transition (EMT) in ccRCC. Functionally, SLC17A9 knockdown inhibited the proliferation, migration, and invasion activity of renal cancer cells, whereas its overexpression led to stronger cell viability and more malignant phenotype in vitro. The overexpression of SLC17A9 in vivo could significantly contribute to the growth of tumors. Finally, we found that SLC17A9 might be related to the drug resistance of vorinostat. Cumulatively, this study demonstrated that the SLC17A9-PTHLH-EMT axis could promote the progression of ccRCC.

Background and aimsTetraspanin proteins are closely related to the functional changes of B cells, including antigen presentation, production of cytokines, and transduction. We aim to explore the potential role of Tetraspanin 1 (TSPAN1) in the biological activities of B cells in AIH.Methods and resultsHerein, this study found that numbers of cells expressing TSPAN1 were significantly increased in AIH patients compared to PBC, chronic hepatitis B, and healthy control (P < 0.0001). Moreover, there was a positive correlation between numbers of TSPAN1+ cells and AIH disease severity (P < 0.0001). Immunofluorescence staining further confirmed that TSPAN1 was primarily expressed on CD19+ B cells. Flow-cytometric analysis showed that TSPAN1+ B cells secreted more inflammatory cytokines and expressed higher level of CD86 than TSPAN1- B cells. Furthermore, compared with TSAPN1- cells, the expression of CXCR3 on TSPAN1+ cells was also higher. Meanwhile, CXCL10, the ligand of CXCR3, was significantly elevated in the liver of AIH (P < 0.01) and had positive correlation with the quantities of TSPAN1 (P < 0.05). Interestingly, the numbers of TSPAN1+ B cells were decreased in AIH patients after immunosuppressive therapy.ConclusionsTSPAN1+ B cells in the liver may promote the progression of AIH via secreting cytokines and presenting antigens. The chemotactic movement of TSPAN1+ B cells toward the liver of AIH was possibly due to CXCR3 - CXCL10 interaction.

Researchers have previously described the response of crop productivity and greenhouse gas (GHG) emissions to fertilizer nitrogen (N) additions, but they have not determined how to maximize yields while minimizing GHG emissions. We conducted an experiment at 2293 sites with four N levels to simulate both grain yield and yield-scaled GHG emissions in response to the N addition. The yield-scaled GHG emissions decreased by 16% as the N rate increased from treatments without the N addition to the minimum yield-scaled GHG emissions, which was comparable to the values associated with the maximum grain yields. The sites with both high soil productivity and high crop productivity had the highest yield and lowest yield-scaled GHG emissions, with 43% higher yield and 38% lower yield-scaled GHG emissions than sites with low soil and low crop productivity. These findings are expected to enhance evaluations of wheat production and GHG emissions in China, and thereby contribute to addressing disparities in the global food and GHG budget.

Objective: This study aims to explore the risk signals of osteonecrosis of the jaw induced by antiresorptive drugs and provide references for the clinical safety application.Method: According to the FDA’s Adverse Event Reporting System (FAERS), from January 2004 to September 2021, we chose “Osteonecrosis of the jaw (10064658)” and “Exposed bone in jaw (10071014)” as preferred terms, “antiresorptive drugs” as the target drugs, and primary suspect drug as the drug role code in the dataset. We evaluated the association between drugs and adverse events by using reporting odds ratio (ROR) based on disproportionality analysis. We took the High-Level Terms (HLT) of MedDRA® as the classification level of indications to calculate ROR to compare the signal difference of ONJ in different indications. In addition, patients with antiresorptive-induced osteonecrosis of the jaw and the time of onset of the condition following different antiresorptive medications were collected for the study.Results: The FAERS contained 18,421 reports relating to jaw osteonecrosis from January 2004 to September 2021. A total of eight antiresorptive agents were included in the analysis. From high to low, the ROR of ONJ induced by antiresorptive agents (regardless of indication) is pamidronate (ROR = 494.8), zoledronic acid (ROR = 431.9), denosumab (ROR = 194.8), alendronate (ROR = 151.2), risedronate (ROR = 140.2), etidronic acid (ROR = 64.5), ibandronate (ROR = 40.8), and romosozumab (ROR = 6.4). HLT ROR values for “metabolic bone disorders” were the lowest for each drug, while HLT ROR values were high for “tumor-related indications,” including breast and nipple neoplasms malignant, plasma cell myelomas, and prostatic neoplasms malignant. The onset time for osteonecrosis of the jaw as median (Q1, Q3), osteoporosis-related indications, and the onset time for ONJ were 730 (368, 1268), 489.5 (236.3, 909.8), 722.5 (314, 1055), 761 (368, 1720), and 153 (50, 346) for zoledronic acid, denosumab, ibandronate, risedronate, and romosozumab, respectively. Cancer-related indications: the onset time for ONJ were 680.5 (255.3, 1283), 488 (245, 851), and 696.5 (347, 1087) for zoledronic acid, denosumab, and pamidronate, respectively.Conclusion: When antiresorptive drugs are used for metastasis, they have the largest risk signal, followed by malignancy, and the smallest is osteoporosis. The onset time of ONJ may not be related to the indications. The onset time of ONJ for BPs was about 2 years, denosumab about 1.3 years, and romosozumab less than 1 year, which may be related to sequential treatment. When used according to the instructions, the risk of ONJ caused by denosumab was higher than that of zoledronic acid, regardless of the indication. Based on these findings, researchers will continue to monitor and identify risk factors.

Axenfeld-Rieger syndrome (ARS) is an autosomal dominant disorder that is primarily due to disruption of the development of neural crest cells. The onset of associated symptoms in both eyes accompanied by extraocular developmental defects is referred to as ARS. Cardiac defects associated with ARS have been reported, but the extent of the cardiac defects has yet to be defined. We report a case of a 17-year-old girl with ARS with typical facial malformations and severe mitral and tricuspid valve insufficiency. The patient was diagnosed with secondary glaucoma detected on ophthalmologic examination. Echocardiography showed severe mitral and tricuspid valve insufficiency. This case provides further evidence of the association of ARS with cardiac malformations and extends the reported range of cardiac malformations in patients with ARS.

Background and objectivesAutoimmune hepatitis (AIH) is characterized by the expansion and accumulation of pathogenic T cells in liver. Although CD6 and its ligand activated leukocyte cell adhesion molecule (ALCAM) are involved in the evolution of multiple inflammatory diseases, their roles in the pathogenesis of AIH remain unknown. Herein, we aimed to investigate ALCAM-CD6 axis in AIH development.MethodsImmunohistochemistry was performed to examine hepatic expression of CD6 and ALCAM. The concentration of serum ALCAM was evaluated by ELISA. The phenotypes of liver infiltrating T cells were determined by flow cytometry. Primary human CD4+ T cells were used for functional studies.ResultsOur data showed that patients with AIH exhibited significantly higher expression of CD6 in the liver as compared to primary biliary cholangitis (PBC), chronic hepatitis B (CHB), non-alcoholic liver disease (NAFLD), and healthy controls (HC). In addition, hepatic CD6 expression was strongly correlated with disease severity of AIH. CD6 was mainly expressed on CD4+ T cells in the liver and intrahepatic CD6highCD4+ T cells demonstrated stronger proinflammatory response and proliferation features than CD6low counterparts in both AIH and HC. ALCAM, the ligand of CD6, was highly expressed in the hepatocytes of AIH and serum ALCAM was strongly associated with clinical indices of AIH. Interestingly, close spatial location between CD6+CD4+ T cells and ALCAM+ hepatocytes was observed. Finally, we found that CD6highCD4+ T cells showed enhanced capacity of trans-endothelial migration in vitro, which could be promoted by recombinant ALCAM.ConclusionsOur study found that ALCAM-CD6 axis was upregulated in the AIH liver, suggesting a potential target for alleviating AIH.

The mechanisms underlying neutrophilic inflammation in chronic rhinosinusitis with nasal polyps (CRSwNP) remain poorly investigated. This study aimed to examine the factors that contribute to tissue neutrophilia in CRSwNP. The numbers of neutrophils and active caspase-3-positive apoptotic neutrophils in sinonasal tissues were assessed via immunofluorescence staining. The 95th percentile of tissue neutrophil numbers in control subjects was selected as a cut-off to define neutrophil-high (Neu-high) or neutrophil-low (Neu-low) nasal polyps (NPs). The levels of 34 inflammatory mediators in sinonasal tissues were analyzed using Bio-Plex assay. Purified human peripheral blood neutrophils were incubated with nasal tissue homogenates, and the apoptotic neutrophils were assessed via flow cytometry. The cut-off for Neu-high NPs was >10 myeloperoxidase positive cells/high-power field. Compared with Neu-low NPs, Neu-high NPs had higher tissue levels of IL-1β, IL-1Ra, IL-6, IL-8, G-CSF, MCP-1, and MIP-1α, but lower levels of IL-5, IL-13, IgE, and eosinophils. Principal component and multiple correspondence analyses revealed mixed type 1, type 2, and type 3 endotypes for Neu-low NPs, and predominant type 1 and type 3 endotypes for Neu-high NPs. Neu-high NPs had lower percentages of apoptotic neutrophils than Neu-low NPs. The numbers of neutrophils and the percentages of apoptotic neutrophils correlated with G-CSF and IL-6 levels in the NPs. Tissue homogenates from Neu-high NPs, but not those from Neu-low NPs, suppressed neutrophil apoptosis in vitro, which was reversed by anti-G-CSF treatment. Tissue neutrophil numbers were associated with difficult-to-treat disease in patients with CRSwNP after surgery. We propose that G-CSF promotes neutrophilic inflammation by inhibiting neutrophil apoptosis in CRSwNP. [ABSTRACT FROM AUTHOR]

YOLOv8, as an efficient object detection method, can swiftly and precisely identify objects within images. However, traditional algorithms encounter difficulties when detecting small objects in remote sensing images, such as missing information, background noise, and interactions among multiple objects in complex scenes, which may affect performance. To tackle these challenges, we propose an enhanced algorithm optimized for detecting small objects in remote sensing images, named HP-YOLOv8. Firstly, we design the C2f-D-Mixer (C2f-DM) module as a replacement for the original C2f module. This module integrates both local and global information, significantly improving the ability to detect features of small objects. Secondly, we introduce a feature fusion technique based on attention mechanisms, named Bi-Level Routing Attention in Gated Feature Pyramid Network (BGFPN). This technique utilizes an efficient feature aggregation network and reparameterization technology to optimize information interaction between different scale feature maps, and through the Bi-Level Routing Attention (BRA) mechanism, it effectively captures critical feature information of small objects. Finally, we propose the Shape Mean Perpendicular Distance Intersection over Union (SMPDIoU) loss function. The method comprehensively considers the shape and size of detection boxes, enhances the model's focus on the attributes of detection boxes, and provides a more accurate bounding box regression loss calculation method. To demonstrate our approach's efficacy, we conducted comprehensive experiments across the RSOD, NWPU VHR-10, and VisDrone2019 datasets. The experimental results show that the HP-YOLOv8 achieves 95.11%, 93.05%, and 53.49% in the mAP@0.5 metric, and 72.03%, 65.37%, and 38.91% in the more stringent mAP@0.5:0.95 metric, respectively. [ABSTRACT FROM AUTHOR]

Renal cell carcinoma is one of the most common tumors in the urinary system, among which clear cell renal cell carcinoma is the most common subtype with poor prognosis. As one of the tumors closely related to lipid metabolism, the role of fatty acid metabolism in ccRCC was investigated to predict the prognosis and guide treatment strategies. RNA-seq and clinical information of patients with ccRCC and expression microarray of human renal cell carcinoma cell lines were obtained from TCGA and GEO databases. Fatty acid metabolism–related risk signature was established by the univariate Cox regression and LASSO analysis to predict patient prognosis and response to different treatment modalities. Using the fatty acid metabolism risk signature, the risk score for each sample in the TCGA cohort was calculated and divided into high-risk and low-risk groups, with the cutoff point being the median. Patients with higher risk scores had a poorer prognosis than those with lower risk scores. The response of each sample to immunotherapy was predicted from the “TIDE” algorithm, while the sensitivity of each sample to sunitinib was obtained using the “pRRophetic” R package. Patients with lower risk scores had higher expression of PD-L1 and better efficacy for sunitinib than those in the high-risk group and were less likely to develop drug resistance, while patients with high-risk scores had a strong response to the anti-CTLA4 antibody therapy. A nomogram was constructed by independent prognostic factors to predict the 1-, 3-, and 5-year survival. According to the calibration curves, the nomogram had an excellent ability to predict survival for patients with ccRCC. Therefore, the fatty acid metabolism risk signature we established can not only predict the survival of patients with ccRCC but also predict patient response to targeted therapy and immunotherapy to provide optimal treatment strategies for patients.

PurposeLittle is known about the detailed spectrum of the cause of death associated with prostate cancer (PCa). This study systematically characterized the cause of death among patients with PCa.MethodsPatients aged 40 years and older with primary PCa were identified from the Surveillance, Epidemiology, and End Results program. Mortality rates were estimated. Standardized mortality ratios (SMRs) of non-cancer deaths were calculated to evaluate the risk of death and to compare with the cancer-free population.ResultsThis study included 1,170,489 patients with PCa. There were 501,262 deaths, of which 27.4% were due to PCa and 57.0% were due to non-cancer causes. Non-cancer deaths increased over time from 1975 to 2016, and index cancer death decreased continually. The risk of non-cancer deaths was 1.45 times (SMR, 1.45; 95% confidence interval [CI], 1.45–1.46) that of the general population. Cardiovascular disease was the most common non-cancer cause of death, accounting for 30.2% of all deaths among PCa patients. Alzheimer’s disease (SMR, 3.92; 95% CI, 3.85–4.00) had the highest risk of death. The mortality rate and SMR of non-cancer deaths increased with increased follow-up after diagnosis.ConclusionInstead of the index cancer, non-cancer comorbidities were the leading cause of death among patients with PCa, and the risk of non-cancer deaths was much higher than among the general population. Clinicians and researchers should be aware of this trend to conduct timely and targeted interventions.

To translate the Organ Transplant Symptom and Well-Being instrument (OTSWI) into Chinese and test the reliability and validity of the Chinese version. A total of 259 patients with organ transplants were recruited from The First Affiliated Hospital of China Medical University in Shenyang, from November 2020 to January 2021. Construct validity was evaluated using exploratory factor analysis (EFA) and reliability were assessed using test-retest reliability and internal consistency. The Cronbach's α of the Chinese version of the Organ Transplant Symptom and Well-being instrument was 0.93. EFA demonstrated that 80.785% of the total variance was explained by a seven-factor solution. The criterion validity of the SF-36 was -0.460 (p < .01), while the test-retest reliability was 0.710. The Chinese version of the OTSWI questionnaire is a valid and reliable instrument for assessing the quality of life of organ transplant patients for symptoms and well-being in China.

The mechanisms underlying neutrophilic inflammation in chronic rhinosinusitis with nasal polyps (CRSwNP) remain poorly investigated. This study aimed to examine the factors that contribute to tissue neutrophilia in CRSwNP. The numbers of neutrophils and active caspase-3-positive apoptotic neutrophils in sinonasal tissues were assessed via immunofluorescence staining. The 95th percentile of tissue neutrophil numbers in control subjects was selected as a cut-off to define neutrophil-high (Neu-high) or neutrophil-low (Neu-low) nasal polyps (NPs). The levels of 34 inflammatory mediators in sinonasal tissues were analyzed using Bio-Plex assay. Purified human peripheral blood neutrophils were incubated with nasal tissue homogenates, and the apoptotic neutrophils were assessed via flow cytometry. The cut-off for Neu-high NPs was >10 myeloperoxidase positive cells/high-power field. Compared with Neu-low NPs, Neu-high NPs had higher tissue levels of IL-1β, IL-1Ra, IL-6, IL-8, G-CSF, MCP-1, and MIP-1α, but lower levels of IL-5, IL-13, IgE, and eosinophils. Principal component and multiple correspondence analyses revealed mixed type 1, type 2, and type 3 endotypes for Neu-low NPs, and predominant type 1 and type 3 endotypes for Neu-high NPs. Neu-high NPs had lower percentages of apoptotic neutrophils than Neu-low NPs. The numbers of neutrophils and the percentages of apoptotic neutrophils correlated with G-CSF and IL-6 levels in the NPs. Tissue homogenates from Neu-high NPs, but not those from Neu-low NPs, suppressed neutrophil apoptosis in vitro, which was reversed by anti-G-CSF treatment. Tissue neutrophil numbers were associated with difficult-to-treat disease in patients with CRSwNP after surgery. We propose that G-CSF promotes neutrophilic inflammation by inhibiting neutrophil apoptosis in CRSwNP.

Improving soil organic carbon (SOC) has been considered as a “win-win way” for ensuring high crop productivity and mitigating chemical N input. Improving SOC can achieve higher wheat yield and simultaneously improve nitrogen (N) productivity (defined as kg grain produced per kg total N input from both indigenous and applied N). Two treatments were tested for improving SOC level. The manure treatment involved applying manure for 6 successive years, and the EM treatment involved adding peat and vermiculite once, both combined with optimized in-season N management. The performance of these two systems were compared with a traditional farming system (Control, where only straw was returned each season). N fertilizer input under all three treatments was optimized by in-season N management and was increased by 90.1% and 48.1% under EM and Manure treatments, respectively, as compared with Control. The average wheat yield for the EM and Manure treatments was 9.1 and 9.2 Mg ha–1, respectively, across all three years, which was 18.8% and 19.7% higher, respectively, than that of the Control treatment (7.7 Mg ha–1). The average chemical N application rates for the EM and Manure treatments were 139 and 146 kg ha–1, which were 24.9% and 21.1% lower than those of the Control treatment, respectively. The N productivity was 15.1% and 14.9% which was higher under Manure and EM treatments than that of the Control treatment. The high yield and N productivity were attributed to improved aboveground dry matter and N uptake by wheat, with optimal soil N supply of the root zone. The higher stem number and weight seen in individual plants with increasing SOC resulted in larger spikes and grains at harvest. Our results determined that increasing SOC combined with optimal N management achieve low chemical N input and higher grain yield by increasing productive stems and grains per spike for improving wheat individual growth.

Phosphorous (P) fixation in saline soils is a concern worldwide. To investigate optimization strategies for P fertilizer application that improve P use efficiency (PUE) and crop yield in saline soil, in terms of P sources and rates, we conducted a two year field experiment in the coastal saline area of China to investigate the effects of P rates and sources, including superphosphate (SSP), monoammonium phosphate (MAP) and ammonium polyphosphate (APP) on yield, aboveground P uptake, agronomy efficiency (AEP), and soil available P of winter wheat (Triticum aestivum L.). Wheat yield, under the three P sources, increased with P rates and reached a plateau under 20 kg P ha−1 SSP,18 kg P ha−1 MAP, and 17 kg P ha−1 MAP, respectively. The application of SSP increased the wheat yield by 9–11% compared to MAP and APP. The aboveground P uptake of winter wheat under SSP was 14% and 13% higher than MAP and APP, respectively, under the optimal P application rate. The AEP under SSP was higher than the other two P sources under the same P rate. SSP increased the soil Ca2+ concentration by 20–42%, but decreased the Na+ concentration by 14–18% at the P rate of 26 kg P ha−1 in all soil layers, including 0–20, 20–40, 40–60 cm, compared to CK (0 kg P ha−1). The soil Olsen-P concentration under APP was higher than the other P sources. This study suggests that optimizing P sources and rates can improve wheat yield, PUE, and soil quality in the coastal saline soil.

The discovery of mechanically soft solid‐state materials with fast Mg‐ion conduction is crucial for the development of solid‐state magnesium batteries. In this paper, novel magnesium gallium halide compounds are reported that achieve high ionic conductivity of 0.47 mS cm−1 at room temperature. These Mg‐ion conductors obtained by ball milling Mg and Ga salts exhibit clay‐like mechanical properties, enabling intimate contact at the electrode–electrolyte interface during battery cycling. With a combination of experimental and computational analysis, this study identifies that the soft‐clay formation is induced by partial anion exchange during milling. This partial anion exchange creates undercoordinated magnesium ions in a chlorine‐rich environment, yielding fast Mg‐ion conduction. This work demonstrates the potential of clay‐like halide electrolytes for all‐solid‐state magnesium batteries, with possible further extension to other multivalent battery systems. [ABSTRACT FROM AUTHOR]