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The global incidence of Chronic Kidney Disease (CKD) is steadily escalating, with discernible linkage to the intricate terrain of intestinal microecology. The intestinal microbiota orchestrates a dynamic equilibrium in the organism, metabolizing dietary-derived compounds, a process which profoundly impacts human health. Among these compounds, short-chain fatty acids (SCFAs), which result from microbial metabolic processes, play a versatile role in influencing host energy homeostasis, immune function, and intermicrobial signaling, etc. SCFAs emerge as pivotal risk factors influencing CKD's development and prognosis. This paper review elucidates the impact of gut microbial metabolites, specifically SCFAs, on CKD, highlighting their role in modulating host inflammatory responses, oxidative stress, cellular autophagy, the immune milieu, and signaling cascades. An in-depth comprehension of the interplay between SCFAs and kidney disease pathogenesis may pave the way for their utilization as biomarkers for CKD progression and prognosis or as novel adjunctive therapeutic strategies. [ABSTRACT FROM AUTHOR]

We present the numerical results for the optimization of the pump-to-idler conversion efficiencies of nanosecond idler wavelength tunable cascaded optical parametric oscillators (OPO) in different wavelength tuning ranges, where the primary signals from the OPO process are recycled to enhance the pump-to-idler conversion efficiencies via the simultaneous difference frequency generation (DFG) process by monolithic aperiodically poled, magnesium oxide doped lithium niobate (APMgLN) crystals. The APMgLN crystals are designed with different chirp parameters for the DFG process to broaden their thermal acceptance bandwidths to different extents. The idler wavelength tuning of the cascaded OPO is realized by changing the temperature of the designed APMgLN crystal and the cascaded oscillation is achieved in a single pump pass singly resonant linear cavity. The pump-to-idler conversion efficiencies with respect to the pump pulse duration and ratio of OPO coefficient to DFG coefficient are calculated by numerically solving the coupled wave equations. The optimal working conditions of the tunable cascaded OPOs pumped by pulses with energies of 350 μJ and 700 μJ are compared to obtain the general rules of optimization. It is concluded that the optimization becomes the interplay between the ratio of OPO coefficient to DFG coefficient and the pump pulse duration when the idler wavelength tuning range and the pump pulse energy are fixed. Besides, higher pump pulse energy is beneficial for reaching higher optimal pump-to-idler conversion efficiency as long as the APMgLN crystal is optimized according to this pump condition. To the best of our knowledge, this is the first numerical analysis of idler wavelength tunable cascaded OPOs based on chirp-assisted APMgLN crystals. [ABSTRACT FROM AUTHOR]

We report our recent investigation on the conversion efficiency improvement of a PPMgLN-based single pump pass, singly resonant optical parametric oscillator (OPO) pumped by an acousto-optic Q-switched fiber MOPA. The impacts of the pump pulse duration and signal reflectivity on the pump-to-idler conversion efficiency were studied by numerically solving the coupled wave equations in the first place. The results revealed that longer pulse durations were beneficial to higher conversion efficiencies as long as the signal reflectivity of the OPO cavity was optimized accordingly. Experiments were carried out thereafter utilizing the optimal parameters obtained from the simulation. Idler powers of 4.7 and 3.81 W were achieved at 3.4 and 3.8 μm, respectively, under the highest pump power of 28 W with pump pulse duration of 240 ns. The experimental results were in good agreement with the calculated results. According to our simulation, higher conversion efficiency could be expected when such an OPO was pumped by pulses with even longer duration provided that the signal reflectivity of the output coupler was optimized under that pump condition. [ABSTRACT FROM AUTHOR]

Bone marrow mesenchymal stem cells (BMSCs) are considered the most important seed cells in bone tissue engineering. The present study aimed to investigate the potential of rabbit BMSCs in osteogenesis after the transfection of human BMP-2 and EGFP recombinant adenovirus. Rabbit BMSCs were isolated and the surface stem cell makers, including CD29, CD44 and CD45 were detected by flow cytometry. The expression of BMP-2 mRNA and protein in BMSCs were detected by reverse transcription-quantitative polymerase chain reaction and western blot analysis, respectively. After an induction with osteogenic medium, the alkaline phosphatase (ALK) activity at 7 days, the type I collagen at 14 days, and the calcium nodules at 21 days were performed using an ALK activity kit, immunohistochemical staining and alizarin red S staining, respectively. The expression levels of proteins related to the Wnt signaling pathway were detected by western blot analysis. The positive rates of CD29, CD44 and CD45 were 62.92±1.99, 93.55±0.99 and 0.21±0.12%. The expression of BMP-2 mRNA and protein was significantly upregulated in Ad-BMP-2/EGFP transfected BMSCs. Furthermore, Ad-BMP-2/EGFP induced ALP activity, promoted the production of type I collagen and calcium nodule formation in rabbit BMSCs. The levels of β-catenin, cyclin D1, Runx2 and c-myc were upregulated in Ad-hBMP-2/EGFP transfected BMSCs, while the level of GSK3β was significantly decreased. Results also indicated that the overexpression of BMP-2 by Ad-hBMP-2/EGFP enhanced the osteogenic differentiation ability of cultured rabbit BMSCs via stimulating the Wnt signaling pathway with the accumulation of β-catenin and suppression of GSK3β. The Ad-hBMP-2/EGFP transfected rabbit BMSCs are expected to be a good seed cell in bone tissue engineering. [ABSTRACT FROM AUTHOR]

Background: As an effective measurement for severe acute kidney injury (AKI), the prolonged intermittent renal replacement therapy (PIRRT) received attention. Also, machine learning has advanced and been applied to medicine. This study aimed to establish short-term prognosis prediction models for severe AKI patients who received PIRRT by machine learning. Methods: The hospitalized AKI patients who received PIRRT were assigned to this retrospective case-control study. They were grouped based on survival situation and renal recovery status. To screen the correlation, Pearson's correlation coefficient, partial ETA square, and chi-square test were applied, eight machine learning models were used for training. Results: Among 493 subjects, the mortality rate was 51.93% and the kidney recovery rate was 30.43% at 30 days post-discharge, respectively. The indices related to survival were Sodium, Total protein, Lactate dehydrogenase (LDH), Phosphorus, Thrombin time, Liver cirrhosis, chronic kidney disease stage, number of vital organ injuries, and AKI stage, while Sodium, Total protein, LDH, Phosphorus, Thrombin time, Diabetes, peripherally inserted central catheter and AKI stage were selected to predict the 30-day renal recovery. Naive Bayes has a good performance in the prediction model for survival, Random Forest has a good performance in 30-day renal recovery prediction model, while for 90-day renal recovery prediction model, it's K-Nearest Neighbor. Conclusions: Machine learning can not only screen out indicators influencing prognosis of AKI patients receiving PIRRT, but also establish prediction models to optimize the risk assessment of these people. Moreover, attention should be paid to serum electrolytes to improve prognosis. [ABSTRACT FROM AUTHOR]

Abstract: The geomechanical stability of caprock is critical to the long-term safety of geologic storage of CO2 in depleted oil reservoirs. Based on the theory of rock fracture mechanics in deep formations, we propose a quantitative assessment framework for the resistance of caprock to hydraulic fracturing due to CO2 injection and storage in a sand lens reservoir. By simplifying the sand lens reservoir as a lenticular crack model, we developed a formula for the Mode-I stress intensity factor at the crack tip (pinch-out tip of the sand lens reservoir) and the in situ fracture toughness of the surrounding caprock. We then established a preliminary threshold for assessing the resistance of caprock to hydraulic fracturing. Based on this threshold, the critical hydraulic fracturing pressure at the pinch-out tip of a sand lens reservoir and the allowable injection pressure at the bottom hole of an injection well can be estimated. This quantitative assessment framework has been verified for use in sand lens reservoirs with a case study of the Daqingzijing CO2 storage site in the Jilin oil field, China. These results provide important implications for assessing the resistance to hydraulic fracturing in similar reservoirs with stratigraphic pinch-outs in impermeable formations, preventing caprock fracturing and water or gas channeling during CO2 injection. [Copyright &y& Elsevier]

Objectives: Insulin resistance in chronic kidney disease (CKD) stimulates muscle wasting, but the molecular processes behind the resistance are undetermined. However, inflammation in skeletal muscle is implicated in the pathogenesis of insulin resistance and cachexia. Toll‐like receptors (TLRs) are known to regulate local innate immune responses, and microarray data have shown that Tlr13 is upregulated in the muscles of mice with CKD, but the relevance is unknown. Materials and Methods: We performed in vitro experiments in C2C12 myotubes and constructed a CKD murine model using subtotal nephrectomy to conduct experiments in vivo. Results: Tlr13 expression was stimulated in C2C12 myotubes treated with uremic serum. The expression of Tlr13 was also upregulated in the tibialis anterior muscles of mice with CKD. Tlr13 knockdown with siRNAs in skeletal muscle cells decreased insulin resistance despite the inclusion of uremic serum. This led to increased levels of p‐AKT and suppression of protein degradation. Using immunofluorescence staining and coimmunoprecipitation assay, we found that TLR13 recruits IRF3, which activates Irf3 expression, resulting in decreased AKT activity. Moreover, insulin resistance and proteolysis are re‐induced by Irf3 overexpression under Tlr13 deletion. Conclusions: Our results indicate that TLR13 is involved in CKD‐mediated insulin resistance in muscle. In catabolic conditions where insulin signaling is impaired, targeting TLR13 may improve insulin sensitivity and prevent muscle atrophy. [ABSTRACT FROM AUTHOR]

Background and Purpose: Muscle protein catabolism in patients with diabetic nephropathy (DN) results in striking loss of muscle proteins, which increases morbidity and mortality risks. Evidence shows that short‐chain fatty acids (SCFAs) play an important role in health maintenance and disease development. Recently, the connection between butyrate (a SCFA) and DN has been revealed, although the relationship between butyrate and muscle atrophy remains unclear. Experimental Approach We studied changes in serum butyrate levels in DN patients using metabolomic analyses. In db/db mice, protective effects of butyrate on DN‐induced muscle atrophy. were explored. Inhibition of muscle atrophy by butyrate and the underlying mechanism(s) were studied in C2C12 cells exposed to high glucose/lipopolysaccharide (HG/LPS). Key Results: Butyrate levels in DN patients were significantly decreased. In db/db mice, supplementing normal diet with butyrate improved intestinal barrier function. Concurrently, butyrate alleviated muscle atrophy, promoted PI3K/Akt/mTOR signalling, and suppressed oxidative stress and autophagy in skeletal muscle of db/db mice, and in HG/LPS‐exposed C2C12 cells. Further, FFA2 receptors, key components of SCFA signalling, were decreased in skeletal muscle of db/db mice and in HG/LPS‐exposed C2C12 cells. Overexpression of FFA2 receptors activated PI3K/Akt/mTOR signalling and inhibited oxidative stress and autophagy in HG/LPS‐exposed C2C12 cells. Silencing of FFA2 blocked PI3K/Akt/mTOR signalling that was improved by butyrate, as well as the suppression of oxidative stress and reduction of autophagy. Conclusion and Implication: Butyrate exerts protective effects on muscle atrophy induced by DN by enhancing intestinal barrier function and activating the FFA2 receptor‐mediated PI3K/Akt/mTOR pathway. [ABSTRACT FROM AUTHOR]

Background: Vascular calcification associated with chronic kidney disease (CKD) can increase the risk of mortality. Elevated serum levels of high mobility group box 1 (HMGB1) promotes vascular calcification in CKD via the Wnt/β-catenin pathway. Sirtuin 6 (SIRT6) prevents fibrosis in CKD by blocking the expression of β-catenin target genes through deacetylation. This study aimed to investigate whether the inhibition of vascular calcification by bone marrow mesenchymal stem cell (BMSC)-derived exosomes is related to SIRT6 activity and assess the regulatory relationship between HMGB1 and SIRT6. Methods: CKD characteristics, osteogenic markers, calcium deposition, and the differential expression of HMGB1 and SIRT6 have been measured in a 5/6 nephrectomized mouse CKD model fed a high-phosphate diet to induce aortic calcification. In vitro assays were also performed to validate the in vivo findings. Results: High phosphate promotes the translocation of HMGB1 from the nucleus to the cytosol and induces the expression of Runx2, osteopontin, and Msx2. However, BMSC-derived exosomes were found to alleviate CKD-related fibrosis and the induction of osteogenic genes although less significantly when SIRT6 expression is suppressed. SIRT6 was found to modulate the cytosol translocation of HMGB1 by deacetylation in vascular smooth muscle cells. Conclusion: Our results indicate that BMSC-derived exosomes inhibit high phosphate-induced aortic calcification and ameliorate renal function via the SIRT6–HMGB1 deacetylation pathway. [ABSTRACT FROM AUTHOR]

Water-in-oil (W/O) microemulsions exhibit delivery matrix and exhibit poor lipid solubility. Therefore, increasing the stability of W/O microemulsions is necessary to broaden their applications. In our experiment, a protein microemulsion system was constructed and its stability was investigated. The effects of surfactants, co-surfactants, quality ratio of them (Km) and hydrophilic-lipophilic balance (HLB) values were determined by using the pseudo-ternary phase diagrams and the area of microemulsions (MEs) as the indexes. The results showed that MEs' stability was the best when the limonene was used as oil phase, Tween 20 + span 80 as the surfactant, and anhydrous alcohol as co-surfactant, if and only if HLB = 6.0 and Km = 3:1. Under this condition, the area of micro-emulsion was the largest, and the quality of microemulsion was better when the mass ratio of oil phase and emulsifier was 7:5.The protein microemulsion was a water-in-oil type, with a particle size of 1.41 ± 0.03 μm, containing 1127.37 ± 30.87 μg/g of proteins. Moreover, the temperature, light, and sample observation tests showed that the solution's protein retention rate was lower than those in the microemulsion. Low-concentration NaCl, less than 9% of glucose and maltose exerted no significant influence on the protein microemulsion stability. [ABSTRACT FROM AUTHOR]

Human exposure to pesticides is a topic of public health concern for decades. Pesticide exposures have been assessed through the analysis of urine or blood matrices, but little is known on the accumulation of these chemicals in cerebrospinal fluid (CSF). CSF plays an important role in maintaining physical and chemical balance of the brain and central nervous system and any perturbation can have adverse effects on health. In this study, we investigated the occurrence of 222 pesticides in CSF from 91 individuals using gas chromatography-tandem mass spectrometry (GC-MS/MS). Measured pesticide concentrations in CSF were compared with those in 100 serum and urine specimens from individuals living in the same urban location. Twenty pesticides were found in CSF, serum and urine, at levels above the limit of detection. Three most frequently detected pesticides in CSF were biphenyl (100%), diphenylamine (75%), and hexachlorobenzene (63%). Median concentrations of biphenyl in CSF, serum and urine were 1.11, 10.6, and 1.10 ng/mL, respectively. Six triazole fungicides were found only in CSF, but not in other matrices. To our knowledge, this is the first study to report pesticide concentrations in CSF in a general urban population. [Display omitted] • Pesticide exposure levels in the cerebrospinal fluid of urban populations were tested. • Triazole fungicides were found in cerebrospinal fluid for the first time. • Pesticides in human are mainly from environmental exposure and food chain enrichment. • The pesticides with the highest risk are hexachlorobenzene, biphenyls and p,p′ -DDE. [ABSTRACT FROM AUTHOR]

Desmodium intortum (Mill.) Urb. is an important source of organic fertilizers, but its utilization value has not been developed favorably. The utilization of polyvinyl alcohol is optimized, combined with the film-forming properties of polyvinyl alcohol, to prepare a high-quality composite film. When the nanocellulose content reached 0.8 %, the tensile stress reaches the maximum value, and the composite film is not easily torn. The addition of NCC reduces the crystallinity of the PVA component and increases the initial decomposition temperature of the alcohol-nanocellulose composite film. The thermal decomposition rate of the PVA/NCC composite film is slightly lower than that of the pure PVA film, indicating that the addition of NCC improves the heat resistance of the PVA film. The electron microscope results show that PVA has good compatibility with NCC. The release results of tetracycline hydrochloride showed that when the nanocellulose content reached 0.8 %, the loading rate reached 83.07 %. R2 value of the two materials is 0.99 under the zero-order model fitting, which suggest the release process is transported by Supercase-II transport kinetics. Through the inhibition zone and cytotoxicity, it is proved that this material has a certain bacteriostatic effect and good cytocompatibility. • Preparation of polyvinyl alcohol-nanocellulose composite film by casting method. • Performance characterization of polyvinyl alcohol-nanocellulose composite film. • The composite membrane has bacteriostatic effect and good cytocompatibility. [ABSTRACT FROM AUTHOR]

Cleft palate represents one of the most common congenital birth defects in humans. TGFβsignaling, which is mediated by Smad-dependent and Smad-independent pathways, plays a crucial role in regulating craniofacial development and patterning, particularly in palate development. However, it remains largely unknown whether the Smad-independent pathway contributes to TGFβsignaling function during palatogenesis. In this study, we investigated the function of TGFβactivated kinase 1 (Tak1), a key regulator of Smad-independent TGFβsignaling in palate development. We show that Tak1 protein is expressed in both the epithelium and mesenchyme of the developing palatal shelves. Whereas deletion of Tak1 in the palatal epithelium or mesenchyme did not give rise to a cleft palate defect, inactivation of Tak1 in the neural crest lineage using the Wnt1-Cre transgenic allele resulted in failed palate elevation and subsequently the cleft palate formation. The failure in palate elevation in Wnt1-Cre;Tak1F/F mice results from a malformed tongue and micrognathia, resembling human Pierre Robin sequence cleft of the secondary palate. We found that the abnormal tongue development is associated with Fgf10 overexpression in the neural crest-derived tongue tissue. The failed palate elevation and cleft palate were recapitulated in an Fgf10-overexpressing mouse model. The repressive effect of the Tak1-mediated noncanonical TGFβsignaling on Fgf10 expression was further confirmed by inhibition of p38, a downstream kinase of Tak1, in the primary cell culture of developing tongue. Tak1 thus functions to regulate tongue development by controlling Fgf10 expression and could represent a candidate gene for mutation in human PRS clefting. [ABSTRACT FROM AUTHOR]

Chronic kidney disease (CKD) is an growing public health concern associated with high mortality rates. The occurrences of vascular calcification (VC) increase concordantly with the progression of CKD.With CKD, hyperphosphatemia promotes intermediate VC, a process that is further facilitated by vascular smooth muscle cells (VSMCs) initiating osteogenic transdifferentiation. The purpose of this study was to determine the involvement of CKAP4 in VC progression. Clinical investigations demonstrate that elevated blood CKAP4 and matrix metallopeptidase 2 (MMP2) levels are related with CKD in individuals. As an in vitro model, mouse VSMCs were extracted and treated with high levels of phosphates (2.5 mmol/L Pi). We also created an in vivo mice model of CKD induced by 5/6 nephrophrectomies and a high-protein diet (High Pi diet). The expression of CKAP4 and MMP2 in both in vitro and in vivo models was significantly higher in VSMCs and calcified aorta in both models. Additionally, in vitro tests indicated that CKAP4 modulates YAP phosphorylation. Simultaneous silencing of CKAP4 and calcium content assay revealed a significant reduction in the VSMCs and calcium content of the aorta. Alizarin red staining and calcium content assay reveled that silencing of CKAP4 reduced the VSMCs and aortic calcification, accompanied with reduced expression of YAP and MMP2. Overall, our study demonstrates for the first time that CKAP4 contributes to VC in CKD by modulating YAP phosphorylation and MMP2 expression. • CKAP4 contributes to VC in CKD; • CKAP4 is associated with nuclear translocation and phosphorylation of YAP; • CKAP4 promotes VSMCs calcification via YAP/MMP-2 pathway; [ABSTRACT FROM AUTHOR]

This paper proposes a broadband synthetic aperture imaging lidar based on electro-optic phase modulation, which uses an electro-optic phase modulator to generate a series of broadband chirp signals after the narrow linewidth seed source laser passes through the phase modulator. The de-chirp method is used to achieve pulse compression, and by adopting analogy filters to filter out the interference of multiple harmonics, the near ideal de-chirp signal is attained. The experimental results show that when selecting the first-order sideband signal as the desired signal, we obtain a linear frequency modulated signal with a frequency modulated bandwidth of 3 GHz and a tuning rate of 10 THz/s, and it is achieved the resolution of 0.06 m in the range and 0.02 m in the azimuth. [ABSTRACT FROM AUTHOR]

We report on entanglement-based quantum key distribution between a low-Earth-orbit satellite equipped with a space borne entangled-photon source and a ground observatory. One of the entangled photons is measured locally at the satellite, and the other one is sent via a down link to the receiver in the Delingha ground station. The link attenuation is measured to vary from 29 dB at 530 km to 36 dB at 1000 km. We observe that the two-photon entanglement survives after being distributed between the satellite and the ground, with a measured state fidelity of ≥0.86. We then perform the entanglement-based quantum key distribution protocol and obtain an average final key rate of 3.5 bits/s at the distance range of 530-1000 km. [ABSTRACT FROM AUTHOR]

Background: This study retrospectively evaluated the actual efficacy of Kangxian Yanshen Formula Chinese medicine on renal function-related indicators in chronic kidney disease (CKD) stage 3-4 patients., Methods: In this retrospective cohort study, we collected 212 adult CKD patients with baseline estimated glomerular filtration rate (eGFR) of 15-60 ml/min/1.73 m 2 . All participants received usual care (i.e., Western medications), and participants in the exposure group ( n = 109) were additionally prescribed Kangxian Yanshen Formula Chinese medicine. The primary outcome was an adjusted hazard risk and 95% confidence interval (95% CI) of a 30% decrease in eGFR at month 36 from baseline., Results: In terms of eGFR, among participants treated with additional Kangxian Yanshen Formula, after adjusting for covariates, there was a 57.1% reduction in the risk of a 30% decline from baseline in eGFR among participants in the Kangxian Yanshen Formula group compared with the Western medicine group (adjusted hazard risk: 0.429; 95% CI 0.269-0.682). In addition, participants in the Kangxian Yanshen Formula group had a significantly higher change in eGFR from baseline to month 12 than those in the western medicine group (3.40 ± 11.62 versus -3.87 ± 8.39; between-group difference Δ5.61 [± 2.26 standard deviation] mL/min/1.73 m 2 ; P = 0.014). Participants in both groups showed a decreasing trend in eGFR at months 24 and 36., Conclusion: In patients with stage 3-4 CKD, Kangxian Yanshen Formula Chinese medicine therapy may help delay eGFR decline, but high-quality randomized controlled trials are needed to validate the results further., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Chu, Wei, Liu, Zhang, Zhang, Li, Zheng, Ma, Li, Rong and Zhong.)

Objective: The roles of MTFR1 in the drug resistance of lung adenocarcinoma (LAC) to cisplatin remain unexplored. In this study, the expression, clinical values and mechanisms of MTFR1 were explored, and the relationship between MTFR1 expression and immune microenvironment was investigated in LAC using bioinformatics analysis, cell experiments, and meta-analysis., Methods: MTFR1 expression and clinical values, and the relationship between MTFR1 expression and immunity were explored, through bioinformatics analysis. The effects of MTFR1 on the growth, migration and cisplatin sensitivity of LAC cells were identified using cell counting kit-8, wound healing and Transwell experiments. Additionally, the mechanisms of drug resistance of LAC cells involving MTFR1 were investigated using western blotting., Results: MTFR1 was elevated in LAC tissues. MTFR1 overexpression was associated with sex, age, primary therapy outcome, smoking, T stage, unfavourable prognosis and diagnostic value and considered an independent risk factor for an unfavourable prognosis in patients with LAC. MTFR1 co-expressed genes involved in the cell cycle, oocyte meiosis, DNA replication and others. Moreover, interfering with MTFR1 expression inhibited the proliferation, migration and invasion of A549 and A549/DDP cells and promoted cell sensitivity to cisplatin, which was related to the inhibition of p-AKT, p-P38 and p-ERK protein expression. MTFR1 overexpression was associated with stromal, immune and estimate scores along with natural killer cells, pDC, iDC and others in LAC., Conclusions: MTFR1 overexpression was related to the unfavourable prognosis, diagnostic value and immunity in LAC. MTFR1 also participated in cell growth and migration and promoted the drug resistance of LAC cells to cisplatin via the p-AKT and p-ERK/P38 signalling pathways.

Background: Ubiquitin fold modifier 1 (UFM1) overexpression is associated with cancer cell proliferation, migration and invasion. However, the roles and pathways of UFM1 in oral squamous cell carcinoma (OSCC) has remained undefined., Methods: The expression of UFM1 and the relationship between UFM1 expression and prognosis were investigated using data of OSCC patients from The Cancer Genome Atlas (TCGA) database. The UFM1 co-expressed genes, and the association between the UFM1 expression and immune cells and ubiquitination were explored. The effects of UFM1 expression on the growth and migration of OSCC cells were investigated by siRNA interference, Cell Counting Kit-8 (CCK-8), Transwell, Western blotting, and wound healing experiments., Results: UFM1 was highly expressed in OSCC. UFM1 overexpression was associated with short overall survival, disease-specific survival, and progression-free interval, and was an adverse factor for prognosis in OSCC. UFM1-related nomograms were significantly associated with poor prognosis in OSCC patients. Decreased UFM1 expression could inhibit the proliferation, migration, and invasion of OSCC cells. UFM1 was associated with the immune cells (such as the Th17 cells, T helper cells, and cytotoxic cells) and ubiquitination., Conclusion: Elevated UFM1 expression was associated with poor prognosis, ubiquitination and immune infiltration in OSCC, and inhibition of UFM1 expression delayed OSCC progression, showing that UFM1 could be a biomarker for prognosis and treating OSCC patients.

This study aimed to examine the interaction mechanism of polyphenol protein in a heat-treated aqueous solution system using epigallocatechin gallate (EGCG) and whey protein (WP) as raw materials. Further, we hypothesized the binding characteristics of these two compounds. The results were as follows: The quenching mechanism between WP and EGCG was characterized as static quenching. As the temperature increased, the binding constant and the binding force between EGCG and WP both increased. The number of binding sites (denoted as n ) between WP and EGCG was approximately 1. Hence, WP provided a single site to bind to EGCG to form a complex. The main binding modes between WP and EGCG were hydrophobic and electrostatic interactions, and they were spontaneously combined into complexes (ΔG < 0). This study provided a basis for the interaction between WP and EGCG under different heating conditions and their combination mode., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Author(s).)

Although the expression of autophagy-related 10 (ATG10) is known to be associated with the poor prognosis of cancer patients by enhancing cancer cell growth and migration, the roles of ATG10 in hepatocellular carcinoma (HCC) remains to be determined. In this study, the expression of ATG10 in HCC was analyzed using the data from TCGA databases and was further verified in the clinical samples from our patients. In addition, the relationships of ATG10 expression with clinical features, diagnosis and prognosis, as well as the predictive values of ATG10 expression in overall survival (OS), disease-specific survival (DSS) and progression-free interval (PFI) were explored. Furthermore, the expression and the prognostic values of ATG10 co-expressed genes were also identified in HCC, which was used to construct prognostic nomograms. Our data showed that the expression level of ATG10 was significantly increased in HCC, and the elevated ATG10 expression was associated with poor prognosis. Moreover, cells with ATG10 knockdown were used to investigate the effects of ATG10 on HCC cell proliferation and migration. We found that silencing ATG10 inhibited the proliferation, migration, and invasion of HCC cells, which was related to the protein expression of cyclin B1, CDK1, and CDK2. Similarly, the overexpression of ATG10 co-expressed genes ATG12, LARS1, CWC27, and SLC30A5 in HCC patients were also associated with the OS, DSS, and PFI. The risk models and nomograms based on ATG10 and ATG10 co-expressed genes indicated the correclation between their expression and the dismal prognosis in HCC patients. In conclusion, ATG10 expression was elevated in HCC and was associated with poor prognosis. Inhibition of ATG10 expression could attenuate cancer progression. ATG10-related nomograms and risk models could be used clinically to evaluate the prognosis of HCC patients., Competing Interests: None., (AJCR Copyright © 2023.)

Background: The impact of the degree of worsening renal function (WRF) and B-type natriuretic peptide (BNP) on the prognosis of patients with acute heart failure (AHF) is still debatable. The present study investigated the influence of different degrees of WRF and BNP levels at discharge on 1-year all-cause mortality in AHF., Methods: Hospitalized AHF patients diagnosed with acute new-onset/worsening of chronic heart failure (HF) between January 2015 and December 2019 were included in this study. Patients were assigned into high and low BNP groups based on the median BNP level at discharge (464 pg/ml). According to serum creatinine (Scr) levels, WRF was divided into non-severe WRF (nsWRF) (Scr increased ≥0.3 mg/dl and <0.5 mg/dl) and severe WRF (sWRF) (Scr increased ≥0.5 mg/dl); non-WRF (nWRF) was defined as Scr increased of <0.3 mg/dl). Multivariable cox regression was used to evaluate the association of low BNP value and different degrees of WRF with a all-cause death, as well as testing for an interaction between the two., Results: Among 440 patients in the high BNP group, there was a significant difference in WRF on mortality (nWRF vs. nsWRF vs. sWRF: 22% vs. 23.8% vs. 58.8%, P  < 0.001). Yet, mortality did not significantly differ across the WRF subgroups in the low BNP group (nWRF vs. nsWRF vs. sWRF: 9.1% vs. 6.1% vs. 15.2%, P  = 0.489). In multivariate Cox regression analysis, low BNP group at discharge (HR, 0.265; 95%CI, 0.162-0.434; P  < 0.001) and sWRF (HR, 2.838; 95%CI, 1.756-4.589; P  < 0.001) were independent predictors of 1-year mortality in AHF.There was a significant interaction between low BNP group and sWRF(HR, 0.225; 95%CI, 0.055-0.918; P  < 0.05)., Conclusions: nsWRF does not increase the 1-year mortality in AHF patients, whereas sWRF does. A low BNP value at discharge is associated with better long-term outcomes and mitigates the adverse effects of sWRF on prognosis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Zhao, Gu, Wei, Peng, Yang, Yuan and Rong.)

Tumor hypoxic environment is an inevitable obstacle for photodynamic therapy (PDT) of melanoma. Herein, a multifunctional oxygen-generating hydrogel loaded with hyaluronic acid-chlorin e6 modified nanoceria and calcium peroxide (Gel-HCeC-CaO 2 ) was developed for the phototherapy of melanoma. The thermo-sensitive hydrogel could act as a sustained drug delivery system to accumulate photosensitizers (chlorin e6, Ce6) around the tumor, followed by cellular uptake mediated by nanocarrier and hyaluronic acid (HA) targeting. The moderate sustained oxygen generation in the hydrogel was produced by the reaction of calcium peroxide (CaO 2 ) with infiltrated H 2 O in the presence of catalase mimetic nanoceria. The developed Gel-HCeC-CaO 2 could efficiently alleviate the hypoxia microenvironment of tumors as indicated by the expression of hypoxia-inducible factor -1α (HIF-1α), meeting the "once injection, repeat irradiation" strategy and enhanced PDT efficacy. The prolonged oxygen-generating phototherapy hydrogel system provided a new strategy for tumor hypoxia alleviation and PDT., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhang, Liu, Mao, Rong, Chen, Qi, Cai and Li.)

There is considerable potential for integrating transarterial chemoembolization (TACE), programmed death-(ligand)1 (PD-[L]1) inhibitors, and molecular targeted treatments (MTT) in hepatocellular carcinoma (HCC). It is necessary to investigate the therapeutic efficacy and safety of TACE combined with PD-(L)1 inhibitors and MTT in real-world situations. In this nationwide, retrospective, cohort study, 826 HCC patients receiving either TACE plus PD-(L)1 blockades and MTT (combination group, n = 376) or TACE monotherapy (monotherapy group, n = 450) were included from January 2018 to May 2021. The primary endpoint was progression-free survival (PFS) according to modified RECIST. The secondary outcomes included overall survival (OS), objective response rate (ORR), and safety. We performed propensity score matching approaches to reduce bias between two groups. After matching, 228 pairs were included with a predominantly advanced disease population. Median PFS in combination group was 9.5 months (95% confidence interval [CI], 8.4-11.0) versus 8.0 months (95% CI, 6.6-9.5) (adjusted hazard ratio [HR], 0.70, P = 0.002). OS and ORR were also significantly higher in combination group (median OS, 19.2 [16.1-27.3] vs. 15.7 months [13.0-20.2]; adjusted HR, 0.63, P = 0.001; ORR, 60.1% vs. 32.0%; P < 0.001). Grade 3/4 adverse events were observed at a rate of 15.8% and 7.5% in combination and monotherapy groups, respectively. Our results suggest that TACE plus PD-(L)1 blockades and MTT could significantly improve PFS, OS, and ORR versus TACE monotherapy for Chinese patients with predominantly advanced HCC in real-world practice, with an acceptable safety profile., (© 2022. The Author(s).)

It has been established that long-chain coding RNA (lncRNA) SLC25A25-AS1 is associated with cancer progression. However, the roles and mechanisms of SLC25A25-AS1 in prostate cancer (PC) have not been reported in the literature. The present study explored the relationship between SLC25A25-AS1 expression and PC progression via comprehensive analysis. The pan-cancer expression of SLC25A25-AS1 was identified using data from The Cancer Genome Atlas (TCGA) database and tissue specimens from our hospital. The expression levels of SLC25A25-AS1 in various subgroups based on the clinical features were identified. The prognostic value of SLC25A25-AS1 and SLC25A25-AS1 co-expressed lncRNAs in PC patients was assessed by survival analysis and ROC analysis, and prognosis-related risk models of SLC25A25-AS1 were constructed. The relationship between SLC25A25-AS1 and the PC immune microenvironment was investigated using correlation analysis. SLC25A25-AS1 expression in PC was significantly increased and correlated with the T stage, clinical stage, Gleason score (GS), and dismal prognosis. SLC25A25-AS1 overexpression exhibited good performance in evaluating the prognosis of PC patients. The area under the curves (AUCs) of the 1-, 3-, and 5-year overall survival (OS) for SLC25A25-AS1 was 1, 0.876, and 0.749. Moreover, the AUCs for the 1-, 3-, and 5-year progress free interval (PFI) for SLC25A25-AS1 were 0.731, 0.701, and 0.718. SLC25A25-AS1 overexpression correlated with the infiltration of CD8 T cells, interstitial dendritic cells (IDC), macrophages and other cells. AC020558.2, ZNF32-AS2, AP4B1-AS1, AL355488.1, AC109460.3, SNHG1, C3orf35, LMNTD2-AS1, and AL365330.1 were significantly associated with SLC25A25-AS1 expression, and short OS and PFI in PC patients. The risk models of the SLC25A25-AS1-related lncRNAs were associated with a dismal prognosis in PC. Overall, SLC25A25-AS1 expression was increased in PC and related to the prognosis and PC immune microenvironment. The risk model of SLC25A25-AS1 have huge prospect for application as prognostic tools in PC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhao, Xiang, Chen, Zhang, Zheng, Ke, Shi and Yang.)

Background: Primary hepatic neuroendocrine carcinoma (NEC) is rare, and a combination with hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) is extremely rare. To date, only four combination cases have been reported. The present paper describes the fifth patient., Case Summary: A 32-year-old Chinese man with chronic hepatitis B was hospitalized for persistent upper abdominal pain. Abdominal computed tomography (CT) examination revealed a liver mass. The tumor was located in the 7 th and 8 th segments of the liver, and CT and magnetic resonance imaging findings were consistent with the diagnosis of HCC. Laboratory examinations revealed the following: Alanine aminotransferase, 243 U/L; aspartate aminotransferase, 167 U/L; alpha-fetoprotein, 4519 μg/L. Laparoscopic right lobe hepatectomy was performed on the liver mass. Postoperative pathology showed low differentiation HCC plus medium and low differentiation CCA combined with NEC. One month after the surgery, the patient suffered from epigastric pain again. Liver metastasis was detected by CT, and tumor transcatheter arterial chemoembolization was performed. Unfortunately, the liver tumor was progressively increased and enlarged, and after 1 mo, the patient died of liver failure., Conclusion: This is a rare case, wherein the tumor is highly aggressive, grows rapidly, and metastasizes in a short period. Imaging and laboratory tests can easily misdiagnose or miss such cases; thus, the final diagnosis relies on pathology., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Aim: Nutrition is an important part of the care of patients with chronic kidney disease (CKD). However, there is limited clinical research on the skeletal muscle nutrition of patients with CKD. We carried out this study to find out whether a low-protein diet supplemented with ketoacids (LPD + KA) could improve muscle wasting in patients with CKD., Methods: Patients were enrolled in this non-blind, parallel-group, randomized trial assessing the nutritional status of CKD, randomly assigned to either the LPD + KA group or conventional LPD group. Blood samples such as Hemoglobin, Cystatin C, Creatinine, BUN, Albumin, Pre- Albumin, Glycerin Trilaurate, and Cholesterol were measured at baseline and every 3 months. The parameters of skeletal muscle and other body composition were assessed before and after dietary intervention for 12 months., Results: A total of 58 patients with CKD completed the study and were available for further analysis. The hemoglobin and albumin were observed to be markedly improved in the LPD + KA group during the follow-up as compared to baseline. Body mass index and total body water index of both groups were increased upon follow-up but the increase in the LPD + KA group was comparatively higher. Moreover, an increase in body fat%, skeletal muscle mass index, and appendicular skeletal muscle mass index was observed in both groups between baseline and follow-up, but it was statistically insignificant., Conclusion: This study did not find a significant improvement of KAs on muscle wasting, and a long time or more indices study may need to find the effects of the LPD + KA diets., Clinical Trial Registration: [www.ClinicalTrials.gov], identifier [NCT02568020]., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhang, Gu, Wang, Rong and Yuan.)

Background: Signet ring cell carcinoma (SRCC) is a specific type of mucinous secretory adenocarcinoma, which contains abundant mucus in the cytoplasm and pushes the nucleus to one side of the cell membrane, forming a round or oval, and the nuclear deviations give the cells a signet ring-like appearance. SRCC often originates in the gastrointestinal tract, especially in the stomach. However, primary SRCC of the extrahepatic bile duct is extremely rare. Therefore, little is known about its epidemiology, treatment, and prognosis., Case Summary: An 82-year-old female was admitted with abdominal pain, jaundice, and skin pruritus for 2 mo. She had no specific family history. Physical examination presented normal vital signs, icteric sclera, visible jaundice, and mild tenderness in the right upper abdominal quadrant. Tumor-related cell markers were within normal values. Contrast-enhanced computed tomography revealed a thickened wall of the common bile duct, strengthened with intrahepatic bile duct dilation and multiple round-like lesions in the liver. In addition, the lymph nodes in the hepatic hilum area, the pancreatic head area, and around the abdominal aorta were enlarged. Thus, a preoperative diagnosis of cholangiocarcinoma was established. To alleviate jaundice and prolong the overall survival, percutaneous transhepatic cholangiopancreatic drainage (PTCD) was performed. During the operation, segmental stenosis of the extrahepatic bile duct and a vine-like expansion of the intrahepatic bile duct was observed. Furthermore, a biliary biopsy was performed under fluoroscopy to determine the nature and origin of the lesion. The pathological diagnosis of the biopsy was SRCC. Finally, a diagnosis of primary SRCC of extrahepatic bile duct with distant lymph node metastasis and multiple liver metastases was made based on the radiographic, PTCD, and pathological characteristics. The tumor was diagnosed as T3N1M1 stage IV. Despite our aggressive approach, the patient died of liver failure after 1 mo., Conclusion: This is the only case report on primary SRCC of the extrahepatic bile duct with distant organ metastasis to date., Competing Interests: Conflict-of-interest statement: We have no conflict of interest., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

RNA modification of m6A/m5C/m1A contributes to the occurrence and development of cancer. Consequently, this study aimed to investigate the functions of m6A/m5C/m1A regulated genes in the prognosis and immune microenvironment of hepatocellular carcinoma (HCC). The expression levels of 45 m6A/m5C/m1A regulated genes in HCC tissues were determined. The functional mechanisms and protein-protein interaction network of m6A/m5C/m1A regulated genes were investigated. The Cancer Genome Atlas (TCGA) HCC gene set was categorized based on 45 m6A/m5C/m1A regulated genes, and survival analysis was used to determine the relationship between the overall survival of HCC patients in subgroups. Cox and least absolute shrinkage and selection operator (LASSO) regression analyses were used to construct the risk model and nomogram for m6A/m5C/m1A regulated genes. The relationships between m6A/m5C/m1A regulated gene subsets and risk model and immune cell infiltration were analyzed using CIBERSORT. m6A/m5C/m1A regulated genes were involved in mRNA and RNA modifications, mRNA and RNA methylation, mRNA and RNA stability, and other processes. There was a statistically significant difference between cluster1 and cluster2 groups of genes regulated by m6A/m5C/m1A. The prognosis of cluster1 patients was significantly better than that of cluster2 patients. There were statistically significant differences between the two cluster groups in terms of fustat status, grade, clinical stage, and T stage of HCC patients. The risk model comprised the overexpression of YBX1, ZC3H13, YTHDF1, TRMT10C, YTHDF2, RRP8, TRMT6, LRPPRC, and IGF2BP3, which contributed to the poor prognosis of HCC patients. The high-risk score was associated with prognosis, fustat status, grade, clinical stage, T stage, and M stage and was an independent risk factor for poor prognosis in HCC patients. High-risk score mechanisms included spliceosome, RNA degradation, and DNA replication, among others, and high-risk was closely related to stromal score, CD4 memory resting T cells, M0 macrophages, M1 macrophages, resting mast cells, CD4 memory activated T cells, and follicular helper T cells. In conclusion, the cluster subgroup and risk model of m6A/m5C/m1A regulated genes were associated with the poor prognosis and immune microenvironment in HCC and are expected to be the new tools for assessing the prognosis of HCC patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Li, Li, Zhang, Yang, Mu, Jiang, Shi and Ke.)

Hypoxic environment is a bottleneck of photodynamic therapy (PDT) in tumor treatment, as oxygen is the critical substrate for photosensitivity reaction. Herein, a sustained oxygen supply system based on cerium nanoparticles and hydrogel (GHCAC) was explored for enhanced synergistic PDT and gas therapy. Ceria nanoparticles were prepared as a drug carrier by self-assembly mediated by hyaluronic acid (HA), a targeting for CD44 on cervical cancer cells, followed by photosensitizer and l-arginine (l-Arg) loading. Then, the GHCAC system was developed by incorporating a prepared nanocarrier (HCePA) and O 2 -evolving agent calcium peroxide (CaO 2 ) into the hydrogel (Gel) developed by a poloxamer. Gel in the system could moderately infiltrate H 2 O to react with CaO 2 and generate sustained oxygen using the catalase-like activity of HCePA. The system could efficiently alleviate hypoxia in tumor environments for up to 7 days, meeting the "once injection, repeat irradiation" strategy and enhanced PDT efficacy. Besides, the generated singlet oxygen ( 1 O 2 ) in the PDT process could also oxidize l-Arg into high concentrations of nitric oxide for synergistic gas therapy. The developed oxygen supplied and drug delivery Gel system is a new strategy for synergistic PDT/gas therapy to overcome cervical cancer.

Owing to their excellent characteristics, Pickering emulsions have been widely used in the development and the application of new carriers for embedding and for delivering active compounds. In this study, β-carotene was successfully encapsulated in a Pickering emulsion stabilized using Desmodium intortum protein isolate (DIPI). The results showed that the encapsulation efficiencies of β-carotene in the control group Tween 20 emulsion (TE) and the DIPI Pickering emulsion (DIPIPE) were 46.7 ± 2.5% and 97.3 ± 0.8%, respectively. After storage for 30 days at 25 °C and 37 °C in a dark environment, approximately 79.4% and 72.1% of β-carotene in DIPIPE were retained. Compared with TE, DIPIPE can improve the stability of β-carotene during storage. In vitro digestion experiments showed that the bioaccessibility rate of β-carotene in DIPIPE was less than that in TE. Cytotoxicity experiments showed that DIPI and β-carotene micelles within a specific concentration range exerted no toxic effects on 3T3 cells. These results indicate that DIPIPE can be used as a good food-grade carrier for embedding and transporting active substances to broaden the application of the protein-based Pickering emulsion system in the development of functional foods.

Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant tumour with a poor prognosis and a high mortality rate. It is of great significance to explore sensitive or specific biomarkers for early diagnosis and prognosis. We first examined the metabolome and gut microbiota of resectable and unresectable PDAC patients to comprehensively investigate the characteristics of PDAC at different stages of progression. At the genus level, we found that the relative abundances of Alistipes, Anaerostipes, Faecalibacterium and Parvimonas were reduced in unresectable PDAC patients, whereas Pseudonocardia, Cloacibacterium, Mucispirillum, and Anaerotruncus were increased. Metabolomics analysis showed that the main changed metabolites were amino acids, carnitine derivatives, lipids and fatty acids. ROC analysis showed that Oleic acid, Linoleic acid, Palmitic acid, Linoelaidyl carnitine, 2-Octenedioic acid, 3R, 7R-1,3,7-Octanetriol, LysoPE (P-16:0/0:0) and 3-Hydroxyanthranilic acid had high AUC values (>0.9). Function and network analyses showed that these altered metabolites correlated with NF-kappa B signalling, the FXR/RXR pathway, mitochondrial dysfunction, mTOR signalling and IL-6 signalling. In particular, the abundance of Palmitic acid, Oleic acid, Linoelaidyl carnitine and 2-Octenedioic acid positively correlated with g&#95;Anaerostipes, g&#95;Alistipes, s&#95;indistinctus, s&#95;catus and s&#95;formicigenerans but negatively correlated with g&#95;Cloacibacterium, s&#95;reuteri and s&#95;hathewayi. Meanwhile,We also found that s&#95;catus, s&#95; formicigenerans, s&#95; hathewayi, g&#95; Alistipes, g&#95; Anaerostipes, PE (22:6 (4Z, 7z, 10z, 13z, 16Z, 19Z)/p-18:1 (11z)), (3R, 7R) - 1,3,7-octanetriol and linoelaidyl carnitine were positively correlated with the survival time of patients.These findings may be helpful for the differentiation of resectable and unresectable PDAC based on changes in intestinal flora and metabolites at different stages of PDAC. This study also provides a strategy for preventing the deterioration of PDAC by regulating the gut microbiota and metabolism., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Background: Implanted intravenous infusion port (IVAP) is indicated for patients undergoing chemotherapy, total parenteral nutrition and long-term antibiotic treatment. Among their complications, the rupture and migration of the catheter of an IVAP via internal jugular vein represents a very rare but potentially severe condition., Case Summary: A 43-year-old woman was identified with a spontaneous fracture and migration of catheter of an IVAP via right internal jugular vein after adjuvant chemotherapy for left breast cancer. A computed tomography showed the fractured catheter of the IVAP in the pulmonary artery. Therefore, we conducted an emergency procedure to remove the catheter fragment by a pigtail catheter combined with a gooseneck trap., Conclusion: When the fractured catheter of an IVAP was detected, the special shape of the pigtail catheter in combination with the gooseneck trap successfully facilitated the removal of the dislodged catheter., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflict of interest., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

Highly toxic radicals including reactive oxygen species (ROS) and reactive nitrogen species (RNS) in cigarette smoke play an important role in oxidative damage of the lungs, which cannot be efficiently scavenged by current filter techniques. Herein, a novel alendronate-coated nanoceria (CeAL) nanozyme is explored for cigarette filter modification for ROS/RNS scavenging. The CeAL nanozyme with an adjustable oxidation state and high thermal stability exhibits an excellent superoxide dismutase (SOD)-like activity, hydroxyl radical elimination capacity, catalase-mimicking activity, and nitric oxide radical scavenging ability. These synergistic antioxidant abilities make the CeAL nanozyme a lucrative additive for cigarette filters. The filter incorporated with the CeAL nanozyme can efficiently scavenge ROS/RNS in the hot smoke generated by burned commercial cigarettes, resulting in reduction of oxidative stress-induced pulmonary injury and acute inflammation of mice. The developed CeAL nanozyme opens up new opportunities for cigarette filter modification to decrease the toxicity of cigarette smoke and expands the application fields of nanoceria.

A previous study suggested that pyruvate kinase M2 (PKM2) plays a vital role of metabolic reprogramming in the regulation of the innate inflammatory response, while PKM2 is a sensitive biomarker for nephrotoxicity. In this study, we investigated the role and mechanism of PKM2 in development of LPS-induced acute kidney injury. The AKI model of mice was established using LPS. The serum levels of blood urea nitrogen (Bun), creatinine (Cr), and Cystatin C (CysC) were identified using the enzyme-linked immunosorbent assay (ELISA). Hematoxylin and Eosin staining (H&E) was employed to assess pathological changes in kidney tissues of LPS-induced AKI model. Immunohistochemical staining and Western blot analysis were carried out to determine the expression of apoptosis-related factors at protein levels. We found that Bun, CysC, and Cr were significantly increased in the LPS group compared with the control group. The histopathological assay showed model swollen tubular epithelial cells and the presence of vacuolar degeneration in the LPS-induced AKI. In addition, expression levels of PKM2 significantly increased in the LPS group compared with the control group at both protein and mRNA levels (P<0.01). The inhibition of PKM2 by shikonin notably suppressed the expression of HIF-1α and apoptosis-related factors such as BNIP3, Bax, and Caspase-3, while the inhibition of PKM2 by shikonin significantly improved the histopathological symptoms of LPS-induced AKI. This study demonstrated the potential role of PKM2 in LPS-induced AKI and identified PKM2 as a promising therapeutic target in the treatment of AKI.

Background: Studies assessing prognosis after prolonged intermittent renal replacement therapy (PIRRT) for acute kidney injury (AKI) are scarce., Aim: To assess the impact of PIRRT on AKI and factors associated with short-term prognosis., Methods: In this retrospective nested case-control study, AKI patients administered PIRRT in Shanghai General Hospital from 01/2012 to 10/2018 were assigned to the 30-day survivor and death groups. Surviving patients were further divided into the kidney recovery and non-recovery groups at 30 and 90 days post-discharge, respectively. Propensity score matching was performed., Results: Totally 576 patients were included in the non-matched study population, mortality and kidney recovery rates were 51.7% and 33.4%, respectively. After propensity score matching, there were 250 patients in each of the death and survival groups. Low PIRRT frequency (OR = 2.165, 95% CI = 1.178-3.978), infection (OR = 0.447, 95% CI = 0.251-0.795), number of damaged vital organs (OR = 0.478, 95% CI = 0.346-0.661), sodium (OR = 0.958, 95% CI = 0.928-0.988), total protein (OR = 1.047, 95% CI = 1.022-1.072), pre-dialysis thrombin time (TT; OR = 0.959, 95% CI = 0.936-0.983), pre-discharge glomerular filtration rate (GFR; OR = 1.024, 95% CI = 1.017-1.031) and admission ward [reference: renal ward; intensive care unit (OR = 0.042, 95% CI = 0.008-0.211); surgery (OR = 0.092, 95% CI = 0.018-0.465); medical (OR = 0.049, 95% C% CI = 0.009-0.259); other (OR = 0.097, 95% CI = 0.016-0.572)] independently predicted 30-day mortality. Peripherally inserted central catheter (OR = 13.970, 95% CI = 1.439-135.589), urea nitrogen (OR = 0.961, 95% CI = 0.933-0.990) and pre-discharge GFR (OR = 1.102, 95% CI = 1.067-1.137) independently predicted 30-day kidney recovery. Pre-dialysis Scr (OR = 0.997, 95% CI = 0.995-0.999), urea nitrogen (OR = 0.948, 95% CI = 0.912-0.986) and pre-discharge GFR (OR = 1.137 95% CI = 1.088-1.189) independently predicted 90-day kidney recovery., Conclusions: PIRRT improves survival and kidney function recovery in AKI patients. In patients with previous GFR ≥ 30 mL/(min-1.73 m 2 ) and no prior maintenance dialysis, PIRRT at 3-5 sessions/week might be appropriate., (© 2021 John Wiley & Sons Ltd.)

The hepatoprotection of histone deacetylase sirtuin 1 (SIRT1) has been identified to attenuate ischemia-reperfusion (IR)-triggered inflammation and liver damage. This study was performed to characterize the function of SIRT1 in hepatic IR injury. In in vivo assays on liver-specific knockout mice of SIRT1, we first validated the effect of SIRT1 knockout on liver damage and XBP1/NLRP3 inflammasome activation. Next, we examined whether knockdown of XBP1/NLRP3 or miR-182 agomir could reverse the effect of SIRT1 knockout. In in vitro assays, NCTC1469 cells subjected to hypoxia/reoxygenation (H/R) were transduced with small interfering RNA (siRNA)/activator of SIRT1 or miR-182 agomir to confirm the effect of SIRT1 on NCTC1469 cell behaviors as well as the regulation of miR-182 and the XBP1/NLRP3 signaling pathway. Hepatic IR injury was appreciably aggravated in SIRT1 knockout mice, and SIRT1 knockdown abolished the inhibition of XBP1/NLRP3 inflammasome activation, which was reversed by NLRP3 knockdown, XBP1 knockdown, or miR-182 agomir. Mechanistically, miR-182 expression was positively regulated by SIRT1 in hepatic IR injury in mice, and miR-182 inhibited the expression of XBP1 by binding to the 3' untranslated region (UTR) of XBP1. The histone deacetylase SIRT1 inhibits the downstream XBP1/NLRP3 inflammatory pathway by activating miR-182, thus alleviating hepatic IR injury in mice., (© 2020 The Authors.)

This study compared Sheng Xue Ning (SXN) tablets with ferrous succinate (FS) tablets in terms of their efficacy for the treatment of iron-deficient renal anemia and safety in patients subject to maintenance hemodialysis (MHD). A total of 94 patients undergoing MHD were randomly assigned to an experiment group (receiving oral SXN tablets, SXN group) and a control group (orally given FS tablets, FS group) and followed up for 12 weeks. Erythropoietin (EPO) was used in both groups. The efficacy was assessed by detecting the subsequent changes in hemoglobin (Hb), serum iron (SI), SF and transferrin saturation (TSAT). At the 12th week, Hb and TSAT levels in both groups were significantly increased compared to those in the screening period (P<0.05). However, no significant difference in Hb and TSAT was found between the two groups. The average weekly EPO dosage used was lower in SXN group than in FS group (P<0.05) at the 10th week and the 12th week. Our study showed that SXN tablets can effectively ameliorate renal anemia and keep iron metabolism stable in MHD patients, and its efficacy is virtually close to that of FS tablets. Meanwhile, SXN tablets can reduce the dosage of EPO and have a good safety profile.

Background: P. multocida (Pasteurella multocida) is animal-sourced gram-negative coccobacillus which can be transmitted to human through many animals including household pets. P. multocida induced peritoneal dialysis-related peritonitis has rarely been reported. In recent years, there has been an increase in the incidence of P. multocida induced peritoneal dialysis-related peritonitis, for the reason that patients with PD at home bred household pets. In this study, we present a case of a P. multocida induced peritoneal dialysis-related peritonitis, which is suspected to be caused through intimate contact with a household cat and we have reviewed 28 cases reported before and give suggestions for treatment and the way of prevention., Case Presentation: A 75-year-old man with end-stage renal disease (ESRD) for nearly 5 years on continuous ambulatory peritoneal dialysis (CAPD) was admitted to the nephrology department with a 1-week history of abdominal pain and a cloudy peritoneal dialysis effluent. Based on the history, physical examination and laboratory results with the findings in the peritoneal dialysis fluid, a diagnosis of peritoneal dialysis-related peritonitis was confirmed. The final culture of initial peritoneal effluent results indicated the organism was P. multocida. After a 12-day antibiotic treatment, the condition of patient was not improved. The patient was switched to ampicillin/sulbactam (3 g intravenously) twice every day and the condition was improved significantly. On further inquiring, the patient reported that he had had a cat at home and when the patient did CAPD, the cat was usually playing with the tubing or contacting the patient during CAPD., Conclusion: In our case and reviewed cases, P. multocida induced peritoneal dialysis-related peritonitis could be cured by proper antibiotic treatment. If individuals keep the pet away from the PD process, the infection route may be severed. P. multocida induced peritoneal dialysis-related peritonitis does not need catheter removal and exchange with hemodialysis except long-time intractable peritonitis.

Recently, Glutathione S-transferase M1 (GSTM1), glutathione S-transferase T1 (GSTT1), and their interaction with hypertension risk have been focused on. However, the results of previous studies have been inconsistent. Hence, the present meta-analysis was performed to explore the association. Twenty-two case-control studies met the inclusion criteria for GSTM1 (including 3577 hypertension cases and 3784 controls), twenty-two for GSTT1 (including 3741 cases and 4444 controls), and nine for their combined effects (including 1073 cases and 781 controls). Pooled analyses on the association between GSTM1 present/null polymorphism and hypertension risk were observed to be insignificant in overall and subgroup analyses. The individual who carries the GSTT1 null-genotype had a statistically significant overall population (OR = 1.28, 95% CI: 1.03, 1.60), Indians (OR = 2.45, 95% CI: 1.08, 5.59), and hospital-based controls (OR = 1.53, 95% CI: 1.21, 1.94). For the GSTM1-GSTT1 interaction, we found that the GSTM1/GSTT1 double-null-genotype was significantly associated with hypertension risks (double-null vs. double-present: OR = 2.68, 95% CI: 1.06, 6.81). To summarize, this meta-analysis indicates that Indians with the GSTT1 null-genotype has a raised hypertension risks; the GSTM1 null/GSTT1 null-genotype is association with raised hypertension risks, while the GSTM1 null-genotype is not associated with hypertension risks. In addition, I 2  > 75% cannot be eliminated for GSTM1 in Indians or Asians, hence, it will be very important to explore the GSTM1 null-genotype and hypertension susceptibility in Indians and Asians for a large new sample, on population-based control study.

For this paper, chamber experiments were carried out to investigate the oxidation of secondary organic tracers of toluene and isoprene by ozone under different conditions (relative humidity, mixing state, etc.) using a relative rate constants approach. The uncertainty of the tracer-based method due to the ozone oxidation of secondary organic tracers was also addressed. The results showed that the effective rate constants of analogue of 2-methyl erythritol (AME) and 2,3-dihydroxy-4-oxopentanoic acid (DHOPA) were (4.60±0.66)×10 -19 cm 3 ·(molecule·s) -1 and (6.57±0.51)×10 -19 cm 3 ·(molecule·s) -1 , respectively. Given the instability of the secondary organic tracers caused by the oxidation, the contributions of toluene and isoprene to secondary organic aerosols could be underestimated by 16.5%-44.8% and 18.3%-47.3%, respectively.

Introduction: Increased circulating endothelial progenitor cells (cEPC) have been observed in patients with vascular injury associated with sepsis and acute lung injury. However, a role for cEPC in severe acute pancreatitis (SAP) remains unclear. We therefore conducted a prospective study to study whether the quantities of cEPC can predict persistent organ failure (POF) in patients with predicted SAP., Methods: A total of 42 predicted SAP patients who were admitted within 24 h after symptom onset and 10 healthy control subjects were enrolled in our study. The proportions of cEPC were analyzed based on flow cytometry simultaneously. Vascular endothelial growth factor (VEGF) levels were measured by enzyme-linked immunosorbent assay., Results: The percentage of cEPC was significantly higher in patients with predicted SAP compared with healthy controls. Similarly, the levels of VEGF in peripheral blood were also significantly higher in predicted SAP patients than in the controls. Notably, patients with POF had lower proportion of cEPC compared with patients with transient organ failure (TOF). In contrast, patients with POF had a significantly higher level of VEGF compared with TOF. Of note, the percentages of cEPC were significantly inversely correlated with disease severity scores. More importantly, cEPC showed an excellent discriminative power for predicting POF among predicted SAP patients, whereas plasma VEGF and disease severity scores showed moderate accuracy in predicting future POF., Conclusions: Peripheral EPC as a novel biomarker is elevated and may aid to predict the development of POF in patients with predicted SAP.

Vascular calcification (VC) is common in chronic kidney disease (CKD), where cardiovascular mortality remains the leading cause of death. Here, we examined the role of high-mobility group box1 (HMGB1), a nuclear DNA-binding protein involved in inflammation, in aortic calcification and renal dysfunction induced by high phosphate in a mouse model of CKD induced by 5/6 nephrectomy. HMGB1 and kidney function markers were measured by ELISA in the serum of CKD patients and in CKD mice. Sections of the aortas of mice were analyzed by immunofluorescence and Alizarin red staining, and protein lysates were generated to analyze the expression of related proteins in response to silencing of HMGB1 or β-catenin by western blotting. Our results showed that serum HMGB1 levels were significantly higher in CKD patients than in healthy controls and related to disease stage. High phosphate promoted the translocation of HMGB1 from the nucleus to the cytosol and aortic calcification in CKD mice in vivo , whereas HMGB1 knockdown ameliorated part of renal and vascular function. β-catenin silencing reversed high phosphate-induced calcification and restored renal marker levels. Taken together, our results suggest that HMGB1 is involved in VC associated with CKD via a mechanism involving the β-catenin.

[This corrects the article DOI: 10.1371/journal.pone.0175807.].

Ischemia-reperfusion (I/R) injury of the kidneys is commonly encountered in the clinic. The present study assessed the efficacy of simvastatin in preventing I/R-induced renal injury in a rat model and investigated the corresponding molecular mechanisms. Rats were divided into 3 groups, including a sham, I/R and I/R + simvastatin group. The results revealed that in the I/R group, the levels of blood urea nitrogen, serum creatinine and lactate dehydrogenase were significantly higher than those in the sham group, which was significantly inhibited by simvastatin pre-treatment. I/R significantly decreased superoxide dismutase activity compared with that in the sham group, which was largely rescued by simvastatin. Furthermore, I/R significantly increased the malondialdehyde content compared with that in the sham group, which was reduced by simvastatin. Hematoxylin-eosin staining revealed no obvious morphological abnormalities in the sham group, while I/R led to notable tubular cell swelling, vacuolization, cast formation and tubular necrosis, which was rescued by simvastatin. A terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling assay demonstrated that I/R significantly increased the number of apoptotic cells compared with that in the sham group, which was significantly inhibited by simvastatin. Western blot analysis demonstrated that simvastatin upregulated I/R-induced increases of nuclear factor erythroid-2-related factor 2 (Nrf2) and anti-oxidant enzyme heme oxygenase-1 (HO-1). Reverse-transcription quantitative PCR indicated that changes in the mRNA levels of Nrf2 and HO-1 were consistent with the western blot results. It was concluded that simvastatin treatment led to upregulation of HO-1 protein levels through activating the Nrf2 signaling pathway to ultimately protect the kidneys from I/R-associated oxidative damage.

Background: Skeletal myoblast transplantation seems a promising approach for the repair of myocardial infarction (MI). However, the low engraftment efficacy and impaired angiogenic ability limit the clinical efficiency of the myoblasts. Gene engineering with angiogenic growth factors promotes angiogenesis and enhances engraftment of transplanted skeletal myoblasts, leading to improved infarction recovery in myocardial ischemia. The present study evaluated the therapeutic effects of hepatocyte growth factor (HGF) gene-engineered skeletal myoblasts on tissue regeneration and restoration of heart function in a rat MI model., Methods and Results: The skeletal myoblasts were isolated, expanded, and transduced with adenovirus carrying the HGF gene (Ad-HGF). Male SD rats underwent ligation of the left anterior descending coronary artery. After 2 weeks, the surviving rats were randomized into four groups and treated with skeletal myoblasts by direct injection into the myocardium. The survival and engraftment of skeletal myoblasts were determined by real-time PCR and in situ hybridization. The cardiac function with hemodynamic index and left ventricular architecture were monitored; The adenovirus-mediated-HGF gene transfection increases the HGF expression and promotes the proliferation of skeletal myoblasts in vitro. Transplantation of HGF-engineered skeletal myoblasts results in reduced infarct size and collagen deposition, increased vessel density, and improved cardiac function in a rat MI model. HGF gene modification also increases the myocardial levels of HGF, VEGF, and Bcl-2 and enhances the survival and engraftment of skeletal myoblasts., Conclusions: HGF engineering improves the regenerative effect of skeletal myoblasts on MI by enhancing their survival and engraftment ability.

Objectives: Virtual Touch tissue imaging quantification (VTIQ; Siemens Medical Solutions, Mountain View, CA) is useful for assessing tissue hardness. This study aimed to investigate the value of VTIQ in differential diagnosis of cervical lymph nodes., Methods: We retrospectively analyzed conventional sonograms and VTIQ images of 85 pathologically confirmed patients with superficial lymph node lesions. Conventional sonography was first performed, with 2-dimensional images described. Then VTIQ shear wave velocity (SWV) values of superficial lymph nodes were measured. With pathologic diagnosis as the reference standard, a receiver operating characteristic curve was generated to evaluate VTIQ efficacy in differential diagnosis of metastatic and nonmetastatic cervical lymph nodes., Results: Of the 85 nodes, 44 and 41 were metastatic and nonmetastatic, respectively. The latter group included 24 and 17 hematologic/lymphatic system disease and reactive hyperplastic nodes, respectively. Shear wave velocity values of metastatic nodes were significantly higher than those of their nonmetastatic counterparts (P < .001). With an area under the curve (AUC) of 0.953 and SWV cutoff of 3.27 m/s, accuracy, sensitivity, and specificity were 89.4%, 88.6%, and 90.2%, respectively, for distinguishing metastatic and nonmetastatic nodes. An AUC of 0.943 and SWV cutoff of 3.23 m/s yielded accuracy, sensitivity, and specificity of 88.2%, 88.6%, and 87.5% for differentiating metastatic from hematologic/lymphatic system disease nodes. Finally, an AUC of 0.968 and SWV cutoff of 3.27 m/s yielded accuracy, sensitivity, and specificity of 90.2%, 88.6%, and 94.1% for differentiating metastatic from reactive hyperplastic nodes., Conclusions: Virtual Touch tissue imaging quantification is efficient in differential diagnosis of metastatic and nonmetastatic cervical lymph nodes., (© 2017 by the American Institute of Ultrasound in Medicine.)