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Background: To evaluate long-term quality of life and survival in pancreatic ductal adenocarcinoma (PDAC) patients after pancreatoduodenectomy with extended lymphadenectomy (PDEL) and identify candidates., Methods: Patients with resectable PDAC with ≥1 examined lymph node (LN) during pancreatoduodenectomy (PD), and were divided into the PD with standard lymphadenectomy (PDSL) and PDEL groups. Perioperative data, long-term quality of life and survival were compared, and the prognostic effect of LNs ± in every peripancreatic station were analysed., Results: Screening 446 PDAC patients, 237 and 126 were included in the PDSL and PDEL groups, respectively. The PDEL group showed a longer operation time, greater intraoperative blood loss, severe diarrhoea, a higher incidence of grade III complications. Notably, the PDEL patients experienced significant relief from low back pain and diarrhoea, with an obvious survival advantage (p = 0.037), especially in patients with preoperative tumor contact with vascular and pathological N0; however, LNs+ in any station (No. 8p, 12, 14, or 16) were associated with a poorer prognosis. The vascular reconstruction, T and N stage were independent risk factors for survival., Conclusion: PDEL can relieve symptoms and prolong the survival of PDAC patients with acceptable complications, and EL should be performed regardless of preoperative LN enlargement., Competing Interests: Conflict of interest None declared., (Copyright © 2024 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Burns and burn sepsis, characterized by persistent and profound hypercatabolism, cause energy metabolism dysfunction that worsens organ injury and systemic disorders. Glutamine (Gln) is a key nutrient that remarkably replenishes energy metabolism in burn and sepsis patients, but its exact roles beyond substrate supply is unclear. In this study, we demonstrated that Gln alleviated liver injury by sustaining energy supply and restoring redox balance. Meanwhile, Gln also rescued the dysfunctional mitochondrial electron transport chain (ETC) complexes, improved ATP production, reduced oxidative stress, and protected hepatocytes from burn sepsis injury. Mechanistically, we revealed that Gln could activate SIRT4 by upregulating its protein synthesis and increasing the level of Nicotinamide adenine dinucleotide (NAD + ), a co-enzyme that sustains the activity of SIRT4. This, in turn, reduced the acetylation of shock protein (HSP) 60 to facilitate the assembly of the HSP60-HSP10 complex, which maintains the activity of ETC complex II and III and thus sustain ATP generation and reduce reactive oxygen species release. Overall, our study uncovers a previously unknown pharmacological mechanism involving the regulation of HSP60-HSP10 assembly by which Gln recovers mitochondrial complex activity, sustains cellular energy metabolism and exerts a hepato-protective role in burn sepsis.

Background: Hepatic leukemia factor (HLF) is associated with cancer onset, growth, and progression; however, little is known regarding its biological role in pan-cancer. In order to further evaluate the diagnostic and prognostic value of HLF in pan-cancer and colorectal cancer (CRC), we performed comprehensive bioinformatics analyses of the molecular mechanism of HLF in pan-cancer, with subsequent verification in CRC., Methods: We downloaded data (gene expression, clinical data, follow-up duration, and immune-related data) related to 33 solid tumor types from UCSC Xena (University of California Santa Cruz cancer database, https://xena.ucsc.edu/). HLF expression was analyzed in pan-cancer, and its diagnostic efficacy, prognostic value, and correlation with pathological stage and cancer immunity were determined. We also analyzed gene alterations in HLF and biological processes involved in its regulation in pan-cancer. Using CRC data in The Cancer Genome Atlas (TCGA), we assessed correlations between HLF and CRC diagnosis, prognosis, and drug sensitivity and performed functional enrichment analyses. Moreover, we constructed an HLF-related ceRNA regulatory network. Finally, we externally validated HLF expression and diagnostic and prognostic value in CRC using Gene Expression Omnibus (GEO) database, as well as by performing in vitro experiments., Results: HLF expression was downregulated in most tumors, and HLF showed good predictive potential for pan-cancer diagnosis and prognosis. It was closely related to the clinicopathological stages of pan-cancer. Further, HLF was associated with tumor microenvironment and immune cell infiltration in many tumors. Analyses involving cBioPortal revealed changes in HLF amplifications and mutations in most tumors. HLF was also closely associated with microsatellite instability and tumor mutational burden in pan-cancer and involved in regulating various tumor-related pathways and biological processes. In CRC, HLF expression was similarly downregulated, with implications for CRC diagnosis and prognosis. Functional enrichment analysis indicated the association of HLF with many cancer-related pathways. Further, HLF was associated with drug (e.g., oxaliplatin) sensitivity in CRC. The ceRNA regulatory network showed multigene regulation of HLF in CRC. External validation involving GEO databases and quantitative real-time polymerase chain reaction (qRT-PCR) data substantiated these findings., Conclusions: HLF expression generally exhibited downregulation in pan-cancer, contributing to tumor occurrence and development by regulating various biological processes and affecting tumor immune characteristics. HLF was also closely related to CRC occurrence and development. We believe HLF can serve as a reliable diagnostic, prognostic, and immune biomarker for pan-cancer., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tcr.amegroups.com/article/view/10.21037/tcr-23-2274/coif). The authors have no conflicts of interest to declare., (2024 Translational Cancer Research. All rights reserved.)

The SDG 15.3.1 target of Land Degradation Neutrality (LDN) only has 15 years from conception (in 2015) to realization (in 2030). Therefore, investigating the effectiveness and challenges of LDN has become a priority, especially in drylands, where fragile ecosystems intersect with multiple disturbances. In this study, solutions are proposed and validated based on the challenges of LDN. We chose the Northern Slope of the Tianshan Mountains as a case study and set baselines in 2005 and 2010. The region and degree of land change (including degraded, stable, and improved) were depicted at the pixel scale (100 × 100 m), and LDN realization was assessed at the regional scale (including administrative districts and 5000 × 5000 m grids). The results showed a significant disparity between the two baselines. The number of areas that realized the LDN target was rare, regardless of the scale of the administrative districts or grids. Chord plots, Spearman's correlation, and curve estimation were employed to reveal the relationship between LDN and seven natural or socioeconomic factors. We found that substantial degradation was closely related to the expansion of unused, urban, and mining land and reduction in water, glaciers, and forests. Further evidence suggests that agricultural development both positively and negatively affects LDN, whereas urbanization and mining activities are undesirable for LDN. Notably, the adverse effects of glacier melting require additional attention. Therefore, we consider the easy-to-achieve and hard-to-achieve baselines as the mandatory and desirable targets of LDN, respectively, and focus further efforts in three aspects: preventing agricultural exploitation from occupying ecological resources, defining reasonable zones for urbanization and mining, and reducing greenhouse gas emissions to mitigate warming. Overall, this study is expected to be a beneficial addition to existing LDN theoretical systems and serve as a case validation of the challenges of LDN in drylands., Competing Interests: Declaration of competing interest 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., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Mining activities aggravate the ecological degradation and emission of greenhouse gases throughout the world, thereby affecting the global climate and posing a serious threat to the ecological safety. Vegetation restoration is considered to be an effective and sustainable strategy to improve the post-mining soil quality and functions. However, we still have a limited knowledge of the impact of vegetation restoration on carbon sequestration potential in mining areas. In this pursuit, the present study was envisaged to integrate the findings from studies on soil organic carbon (SOC) sequestration in mining areas under vegetation restoration with field monitoring data. The carbon sequestration potential under vegetation restoration in China's mining areas was estimated by using a machine learning model. The results showed that (1) Vegetation restoration exhibited a consistently positive impact on the changes in the SOC reserves. The carbon sequestration potential was the highest in mixed forests, followed by broad-leaved forests, coniferous forests, grassland, shrubland, and farmland; (2) The number of years of vegetation restoration and mean annual precipitation were found to be the important moderating variables affecting the SOC reserves in reclaimed soils in mining areas; (3) There were significant differences in the SOC sequestration potential under different vegetation restoration scenarios in mining areas in China. The SOC sequestration potential reached up to 9.86 million t C a -1 , when the soil was restored to the initial state. Based on the meta-analysis, the maximal attainable SOC sequestration potential was found to be 4.26 million t C a -1 . The SOC sequestration potential reached the highest level of 12.86 million t C a -1 , when the optimal vegetation type in a given climate was restored. The results indicated the importance of vegetation restoration for improving the soil sequestration potential in mining areas. The time lag in carbon sequestration potential for different vegetation types in mining areas was also revealed. Our findings can assist the development of ecological restoration regimens in mining areas to mitigate the global climate change., Competing Interests: Declaration of competing interest 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., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: The global use of plastic materials has undergone rapid expansion, resulting in the substantial generation of degraded and synthetic microplastics and nanoplastics (MNPs), which have the potential to impose significant environmental burdens and cause harmful effects on living organisms. Despite this, the detrimental impacts of MNPs exposure towards host cells and tissues have not been thoroughly characterized., Results: In the present study, we have elucidated a previously unidentified hepatotoxic effect of 20 nm synthetic polystyrene nanoparticles (PSNPs), rather than larger PS beads, by selectively inducing necroptosis in macrophages. Mechanistically, 20 nm PSNPs were rapidly internalized by macrophages and accumulated in the mitochondria, where they disrupted mitochondrial integrity, leading to heightened production of mitochondrial reactive oxygen species (mtROS). This elevated mtROS generation essentially triggered necroptosis in macrophages, resulting in enhanced crosstalk with hepatocytes, ultimately leading to hepatocyte damage. Additionally, it was demonstrated that PSNPs induced necroptosis and promoted acute liver injury in mice. This harmful effect was significantly mitigated by the administration of a necroptosis inhibitor or systemic depletion of macrophages prior to PSNPs injection., Conclusion: Collectively, our study suggests a profound toxicity of environmental PSNP exposure by triggering macrophage necroptosis, which in turn induces hepatotoxicity via intercellular crosstalk between macrophages and hepatocytes in the hepatic microenvironment., (© 2024. The Author(s).)

Background: Prostate cancer (PCa) is one of the leading causes of cancer death in men. About 30% of PCa will develop a biochemical recurrence (BCR) following initial treatment, which significantly contributes to prostate cancer-related deaths. In clinical practice, accurate prediction of PCa recurrence is crucial for making informed treatment decisions. However, the development of reliable models and biomarkers for predicting PCa recurrence remains a challenge. In this study, the aim is to establish an effective and reliable tool for predicting the recurrence of PCa., Methods: We systematically screened and analyzed potential datasets to predict PCa recurrence. Through quality control analysis, low-quality datasets were removed. Using meta-analysis, differential expression analysis, and feature selection, we identified key genes associated with recurrence. We also evaluated 22 previously published signatures for PCa recurrence prediction. To assess prediction performance, we employed nine machine learning algorithms. We compared the predictive capabilities of models constructed using clinical variables, expression data, and their combinations. Subsequently, we implemented these machine learning models into a user-friendly web server freely accessible to all researchers., Results: Based on transcriptomic data derived from eight multicenter studies consisting of 733 PCa patients, we screened 23 highly influential genes for predicting prostate cancer recurrence. These genes were used to construct the Prostate Cancer Recurrence Prediction Signature (PCRPS). By comparing with 22 published signatures and four important clinicopathological features, the PCRPS exhibited a robust and significantly improved predictive capability. Among the tested algorithms, Random Forest demonstrated the highest AUC value of 0.72 in predicting PCa recurrence in the testing dataset. To facilitate access and usage of these machine learning models by all researchers and clinicians, we also developed an online web server (https://urology1926.shinyapps.io/PCRPS/) where the PCRPS model can be freely utilized. The tool can also be used to (1) predict the PCa recurrence by clinical information or expression data with high accuracy. (2) provide the possibility of PCa recurrence by nine machine learning algorithms. Furthermore, using the PCRPS scores, we predicted the sensitivity of 22 drugs from GDSC2 and 95 drugs from CTRP2 to the samples. These predictions provide valuable insights into potential drug sensitivities related to the PCRPS score groups., Conclusion: Overall, our study provides an attractive tool to further guide the clinical management and individualized treatment for PCa., 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., (© 2024 The Authors.)

Background: Prostate cancer is the most common malignant tumor of male genitourinary system, and the gold standard for its diagnosis is prostate biopsy. Focusing on the methods and skills of prostate biopsy, we explored the learning curve and experience of a novel magnetic resonance imaging and transrectal ultrasound (mpMRI-TRUS) image fusion transperineal biopsy (TPB) technique using electromagnetic needle tracking under local anesthesia., Methods: The clinical and pathological data of 92 patients who underwent targeted TPB from January 2023 to July 2023 in our center were prospectively collected. The cumulative sum (CUSUM) analysis method and the best fitting curve were used to analyze the learning curve of this novel technique, and the clinical characteristics, perioperative data and tumor positive rate of prostate biopsy of patients at different stages of the learning curve were compared., Results: With the increase of the number of surgical cases, the overall operative time showed a downward trend. The best fitting curve of CUSUM reached its peak at the twelfth case, which is the minimum cumulative number of surgical cases needed to cross the learning curve of the operation. Taking this as the boundary, the learning curve is divided into two stages: learning improvement stage (group A, 12 cases) and proficiency stage (group B, 80 cases). The surgical time and visual analog scale score during prostate biopsy in group A were significantly higher than those in group B. The visual numerical scale score during prostate biopsy in group A was significantly lower than that in group B. There was no statistically significant difference between group A and group B in the detection rate of csPCa and the incidence of perioperative complications., Conclusion: The novel targeted TPB technique is divided into learning improvement stage and proficiency stage, and 12 cases may be the least cumulative number., 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 Yang, He, Zeng, Lu and Li.)

The industrialization of hydrogen production through dark fermentation of food waste faces challenges, such as low yields and unpredictable fermentation processes. Biochar has emerged as a promising green additive to enhance hydrogen production in dark fermentation. Our study demonstrated that the introduction of Fe-modified biochar (Fe-L600) significantly boosted hydrogen production during thermophilic dark fermentation of food waste. The addition of Fe-L600 led to a remarkable 31.19% increase in hydrogen yield and shortened the time needed for achieving stabilization of hydrogen production from 18 h to 12 h. The metabolite analysis revealed an enhancement in the butyric acid pathway as the molar ratio of acetic acid to butyric acid decreased from 3.09 to 2.69 but hydrogen yield increased from 57.12 ± 1.48 to 76.78 ± 2.77 mL/g, indicating Fe-L600 improved hydrogen yield by regulating crucial metabolic pathways of hydrogen production. The addition of Fe-L600 also promoted the release of Fe 2+ and Fe 3+ and increased the concentrations of Fe 2+ and Fe 3+ in the fermentation system, which might promote the activity of hydrogenase and ferredoxin. Microbial community analysis indicated a substantial increase in the relative abundance of Thermoanaerobacterium after thermophilic dark fermentation. The relative abundances of microorganisms responsible for hydrolysis and acidogenesis were also observed to be improved in the system with Fe-L600 addition. This research provides a feasible strategy for improving hydrogen production of food waste and deepens the understanding of the mechanisms of biochar., Competing Interests: Declaration of competing interest 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., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Atherosclerosis, which is a vascular pathology characterized by inflammation and plaque build-up within arterial vessel walls, acts as the important cause of most cardiovascular diseases. Except for a lipid-depository and chronic inflammatory, increasing evidences propose that epigenetic modifications are increasingly associated with atherosclerosis and are of interest from both therapeutic and biomarker perspectives. The chronic progressive nature of atherosclerosis has highlighted atherosclerosis heterogeneity and the fact that specific cell types in the complex milieu of the plaque are, by far, not the only initiators and drivers of atherosclerosis. Instead, the ubiquitous effects of cell type are tightly controlled and directed by the epigenetic signature, which, in turn, is affected by many proatherogenic stimuli, including low-density lipoprotein, proinflammatory, and physical forces of blood circulation. In this review, we summarize the role of DNA methylation and histone post-translational modifications in atherosclerosis. The future research directions and potential therapy for the management of atherosclerosis are also discussed. Video Abstract., (© 2023. The Author(s).)

Background: FHIP1A-DT is a long non-coding RNA (lncRNA) obtained by divergent transcription whose mechanism in pan-cancer and colorectal cancer (CRC) is unclear. We elucidated the molecular mechanism of FHIP1A-DT through bioinformatics analysis and in vitro experiments., Methods: Pan-cancer and CRC data were downloaded from the University of California, Santa Cruz (UCSC) Genome Browser and the Cancer Genome Atlas (TCGA). We analyzed FHIP1A-DT expression and its relationship with clinical stage, diagnosis, prognosis, and immunity characteristics in pan-cancer. We also analyzed FHIP1A-DT expression in CRC and explored the relationship between FHIP1A-DT and CRC diagnosis and prognosis. Then, we analyzed the correlation between FHIP1A-DT and drug sensitivity, immune cell infiltration, and the biological processes involved in FHIP1A-DT. The competing endogenous RNA (ceRNA) regulatory network associated with FHIP1A-DT was explored. External validation was conducted using external data sets GSE17538 and GSE39582 and in vitro experiments., Results: FHIP1A-DT expression was different in pan-cancer and had excellent diagnostic and prognostic capability for pan-cancer. FHIP1A-DT was also related to the pan-cancer tumor mutation burden (TMB), microsatellite instability (MSI), and immune cell content. FHIP1A-DT was downregulated in CRC, where patients with CRC with low FHIP1A-DT expression had a worse prognosis. A nomogram combined with FHIP1A-DT expression demonstrated excellent predictive ability for prognosis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses indicated that FHIP1A-DT was associated with epigenetic modification and regulated many cancer-related pathways. The ceRNA network demonstrated the potential gene regulation of FHIP1A-DT. FHIP1A-DT was related to many chemotherapeutic drug sensitivities and immune cell infiltration such as CD4 memory resting T cells, monocytes, plasma cells, neutrophils, and M2 macrophages. The FHIP1A-DT expression and prognostic analysis of GSE17538 and GSE39582, and qPCR yielded similar external verification results., Conclusion: FHIP1A-DT was a novel CRC-related lncRNA related to CRC diagnosis, prognosis, and treatment sensitivity. It could be used as a significant CRC biomarker in the future., Competing Interests: Declaration of competing interest 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., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Digestive system cancer and COVID-19 significantly affect the digestive system, but the mechanism of interaction between COVID-19 and the digestive system cancers has not been fully elucidated. We downloaded the gene expression of COVID-19 and seven digestive system cancers (oral, esophageal, gastric, colorectal, hepatocellular, bile duct, pancreatic) from GEO and identified hub differentially expressed genes. Multiple verifications, diagnostic efficacy, prognostic analysis, functional enrichment and related transcription factors of hub genes were explored. We identified 23 common DEGs for subsequent analysis. CytoHubba identified nine hub genes ( CCNA2 , CCNB1 , CDKN3 , ECT2 , KIF14 , KIF20A , KIF4A , NEK2 , TTK ). TCGA and GEO data validated the expression and excellent diagnostic and prognostic ability of hub genes. Functional analysis revealed that the processes of cell division and the cell cycle were essential in COVID-19 and digestive system cancers. Furthermore, six related transcription factors (E2F1, E2F3, E2F4, MYC, TP53, YBX1) were involved in hub gene regulation. Via in vitro experiments, CCNA2 , CCNB1 , and MYC expression was verified in 25 colorectal cancer tissue pairs. Our study revealed the key biomarks and common pathogenesis of digestive system cancers and COVID-19. These may provide new ideas for further mechanistic research.

Mucus forms the first line of defence of the intestinal mucosa barrier, and mucin is its core component. Glutamine is a vital energy substance for goblet cells; it can promote mucus synthesis and alleviate damage to the intestinal mucus barrier after burn injury, but its mechanism is not fully understood. This study focused on the molecular mechanisms underlying the effects of glutamine on the synthesis and modification of mucin 2 (MUC2) by using animal and cellular models of burn sepsis. We found that anterior gradient-2 (AGR2) plays a key role in the posttranslational modification of MUC2. Oxidative stress induced by burn sepsis enhanced the S-glutathionylation of AGR2, interfered with the processing and modification of MUC2 precursors by AGR2 and blocked the synthesis of mature MUC2. Further studies revealed that NADPH, catalysed by glucose-6-phosphate dehydrogenase (G6PD), is a key molecule in inhibiting oxidative stress and regulating AGR2 activity. Glutamine promotes O-linked N-acetylglucosamine (O-GlcNAc) modification of G6PD via the hexosamine pathway, which facilitates G6PD homodimer formation and increases NADPH synthesis, thereby inhibiting AGR2 S-glutathionylation and promoting MUC2 maturation, ultimately reducing damage to the intestinal mucus barrier after burn sepsis. Overall, we have demonstrated that the central mechanisms of glutamine in promoting MUC2 maturation and maintaining the intestinal mucus barrier are the enhancement of G6PD glycosylation and inhibition of AGR2 S-glutathionylation., Competing Interests: Declaration of competing interest All authors declare that they have no competing interests., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

According to the guidelines, transurethral resection of bladder tumor (TURBT) followed by intravesical therapy remains the standard strategy for the management of non-muscle invasive bladder cancer (NMIBC). However, even if patients receive standard strategy, the risk of postoperative recurrence and progression is high. From the clinical perspective, the standard strategy needs to be optimized and improved. Compared to conventional TURBT, the technique of en bloc resection of bladder tumor (ERBT) removes the tumor tissue in one piece, thus following the principles of cancer surgery. Meanwhile, the integrity and spatial orientation of tumor tissue is protected during the operation, which is helpful for pathologists to make accurate histopathological analysis. Then, urologists can make a postoperative individualized treatment plan based on the patient's clinical characteristics and histopathological results. To date, there is no strong evidence that NMIBC patients treated with ERBT achieve better oncological prognosis, which indicates that ERBT alone does not yet improve patient outcomes. With the development of enhanced imaging technology and proteogenomics technology, en bloc resection combined with these technologies will make it possible to achieve precise diagnosis and treatment of bladder cancer. In this review, the authors analyze the current existing shortcomings of en bloc resection and points out its future direction, in order to promote continuous optimization of the management strategy of bladder cancer., 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 Yang, Wang, Li, Lu and Li.)

Background: In cervicothoracic junction, the use of strong fixation device such as pedicle screw placement is often needed., Objective: The current study aimed to evaluate the accuracy and safety of pedicle screw placement using stress conduction analysis in the clinical application., Methods: We retrospectively collected patients who underwent pedicle screw internal fixation in cervicothoracic junction. Patients were divided into conventional nail placement (Group A) and modified pedicle screw implantation under guidance of stress analysis (Group B) according to the methods of pedicle screw placement. The accuracy of pedicle screw placement was assessed by computed tomography (CT) examination, and the success rate was calculated., Results: A total of 80 patients who underwent pedicle screw internal fixation in cervicothoracic junction were included. There were no obvious differences in baseline characteristics between two groups. The success rate of total screw placement, cervical spine screw placement and upper thoracic spine screw placement in Group B was higher than those in Group A (P< 0.001, P= 0.005, P= 0.008). Additionally, Heary Grade I in the Group B was higher than Group A (P= 0.001)., Conclusion: Stress analysis-guided technique can increase the accuracy of pedicle screw placement. Importantly, it meets the requirements of internal fixation of the cervicothoracic junction.

Staphylococcus aureus can survive within phagocytes. Indeed, we confirm in this study that approximately 10% of population persists in macrophages during S. aureus infection, while the rest are eliminated due to bacteriolysis, which is of particular interest to us. Herein, we observe that the bacteriolysis is an early event accompanied by macrophage death during S. aureus infection. Furthermore, the cell death is significantly accelerated following increased intracellular bacteriolysis, indicating that intracellular bacteriolysis induces cell death. Subsequently, we establish that the cell death is not apoptosis or pyroptosis, but AIM2-mediated necroptosis, accompanied by AIM2 inflammasome activation. This finding challenges the classical model that the cell death that accompanies inflammasome activation is always pyroptosis. In addition, we observe that the apoptosis-associated genes are highly inhibited during S. aureus infection. Finally, we establish in vivo that increased bacteriolysis significantly enhances S. aureus pathogenicity by promoting its dissemination to kidney and leading to an inflammatory cytokine storm in AIM2-mediated manner. Collectively, our data demonstrate that bacteriolysis is detrimental when triggered in excess and its side effect is mediated by AIM2. Meanwhile, we propose a potential immune manipulation strategy by which S. aureus sacrifices the minority to trigger a limited necroptosis, thereby releasing signals from dead cells to inhibit apoptosis and other anti-inflammatory cascades of live cells, eventually surviving within host cells and establishing infection.

(1) Background: Nutritional support is one of the most important cornerstones in the management of patients with severe burns, but the carbohydrate-to-fat ratios in burn nutrition therapy remain highly controversial. In this study, we aimed to discuss the effects of different ratios of carbohydrate-fat through enteral nutrition on the metabolic changes and organ damage in burned rats. (2) Methods: Twenty-four burned rats were randomly divided into 5%, 10%, 20% and 30% fat nutritional groups. REE and body weight were measured individually for each rat daily. Then, 75% of REE was given in the first week after burns, and the full dose was given in the second week. Glucose tolerance of the rats was measured on days 1, 3, 7, 10 and 14. Blood biochemistry analysis and organ damage analysis were performed after 7 and 14 days of nutritional therapy, and nuclear magnetic resonance (NMR) and insulin content analysis were performed after 14 days. (3) Results: NMR spectra showed significant differences of glucose, lipid and amino acid metabolic pathways. The energy expenditure increased, and body weight decreased significantly after burn injury, with larger change in the 20%, 5% and 30% fat groups, and minimal change in the 10% fat group. The obvious changes in the level of plasma protein, glucose, lipids and insulin, as well as the organ damage, were in the 30%, 20% and 5% fat groups. In relative terms, the 10% fat group showed the least variation and was closest to normal group. (4) Conclusion: Lower fat intake is beneficial to maintaining metabolic stability and lessening organ damage after burns, but percentage of fat supply should not be less than 10% in burned rats.

Biomass, a globally available resource, is a promising alternative feedstock for fossil fuels, especially considering the current energy crisis and pollution. Biomass-derived diols, such as 2,5-bis(hydroxymethyl)furan, 2,5-bis(hydroxymethyl)-tetrahydrofuran, and 1,6-hexanediol, are a significant class of monomers in the polyester industry. Therefore, the catalytic conversion of biomass to valuable diols has received extensive research attention in the field of biomass conversion and is a crucial factor in determining the development of the polyester industry. 5-Hydroxymethylfurfural (HMF) is an important biomass-derived compound with a C6-furanic framework. The hydroconversion of HMF into diols has the advantages of being simple to operate, inexpensive, environmentally friendly, safe, and reliable. Therefore, in the field of diol synthesis, this method is regarded as a promising approach with significant industrialization potential. This review summarizes recent advances in diol formation, discusses the roles of catalysts in the hydroconversion process, highlights the reaction mechanisms associated with the specificities of each active center, and provides an outlook on the challenges and opportunities associated with the research on biomass-derived diol synthesis., Competing Interests: Authors JL, HC, and YY were employed by the company Chenzhou Gao Xin Material Co., Ltd. The remaining 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 Huang, Wang, Lei, Zhao, Chen, Yang, Xu and Liu.)

Background: Gold nanoparticles (AuNPs) are increasingly utilized in industrial and biomedical fields, thereby demanding a more comprehensive knowledge about their safety. Current toxicological studies mainly focus on the unfavorable biological impact governed by the physicochemical properties of AuNPs, yet the consequences of their interplay with other bioactive compounds in biological systems are poorly understood., Results: In this study, AuNPs with a size of 10 nm, the most favorable size for interaction with host cells, were given alone or in combination with bacterial lipopolysaccharide (LPS) in mice or cultured hepatic cells. The results demonstrated that co exposure to AuNPs and LPS exacerbated fatal acute liver injury (ALI) in mice, although AuNPs are apparently non-toxic when administered alone. AuNPs do not enhance systemic or hepatic inflammation but synergize with LPS to upregulate hepatic apoptosis by augmenting macrophage-hepatocyte crosstalk. Mechanistically, AuNPs and LPS coordinate to upregulate NADPH oxidase 2 (NOX2)-dependent reactive oxygen species (ROS) generation and activate the intrinsic apoptotic pathway in hepatic macrophages. Extracellular ROS generation from macrophages is then augmented, thereby inducing calcium-dependent ROS generation and promoting apoptosis in hepatocytes. Furthermore, AuNPs and LPS upregulate scavenger receptor A expression in macrophages and thus increase AuNP uptake to mediate further apoptosis induction., Conclusions: This study reveals a profound impact of AuNPs in aggravating the hepatotoxic effect of LPS by amplifying ROS-dependent crosstalk in hepatic macrophages and hepatocytes., (© 2022. The Author(s).)

Transurethral resection of bladder tumor (TURBT) followed by intravesical therapy remains the most effective strategy for the management of non-muscle-invasive bladder cancer worldwide. TURBT has two purposes: to remove all visible tumors and to obtain tumor specimens for histopathological analysis. However, the detection of flat and small malignant lesions under white-light cystoscopy is extremely challenging, and residual lesions are still the main reason for the high recurrence rate of bladder cancer. We hypothesized that visual enhancement of malignant lesions using targeted optical molecular imaging could potentially highlight residual tumors in the bladder during surgery, and near-infrared photoimmunotherapy (NIR-PIT) could kill exfoliated cancer cells and residual tumors. A mouse model of complete or partial bladder tumor resection was established under the guidance of optical molecular imaging mediated by indocyanine green and anti-CD47-Alexa Fluor 790, respectively. Once the tumor recurred, mouse model received repeated CD47-targeted NIR-PIT. After complete resection, there was no tumor recurrence. Furthermore, the growth rate of recurrent tumor decreased significantly after repeated NIR-PIT. Therefore, CD47-targeted optical molecular imaging can potentially assist urologists to detect and remove all tumors, and repeated NIR-PIT shows the potential to reduce tumor recurrence rates and inhibit the growth of recurrent tumor., Competing Interests: The authors declare no competing interests., (© 2022 The Authors.)

Present work evaluated the zinc (Zn) concentration in soil, forage, blood plasma, hair, and feces samples of cows, buffaloes, and sheep taken from Mianwali, Punjab, Pakistan. The concentration of Zn was found in the ranged of 21.82-35.09mg/kg, 32.59-42.17mg/kg, 0.927-2.48mg/l, 1.03-2.84mg/kg, and 0.923-1.98mg/kg in soil, forage, blood plasma, hair, and feces samples, respectively. The Zn concentration in soil, forage, blood, hair, and feces was safer compared to standard limits. Statistical analysis described that values for BCF, PLI, EF, DIM, and HRI ranged 1.03-1.57mg/kg, 0.486-0.782mg/kg, 0.457-0.696mg/kg, 0.048-0.08mg/kg, and 0.160-0.272mg/kg, respectively. It can be concluded from the present work that Zn concentration was safe in soil, forages, and animal samples. BCF was noticed as greater than 1 while PLI, EF, DIM, and HRI were found less than 1, so regular heavy metal analysis was required to appraise the contamination level in environment., (© 2021. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.)

Garcinia mangostana L. (mangosteen) is a tropical fruit that has been used for medicinal purposes in Southeast Asia for centuries. With an interest in its applications to treat infection, we sought to investigate the bioactive constituents of mangosteen and identified the phenolic compound procyanidin B2 from the mangosteen pericarp by examining lipopolysaccharide (LPS) binding capacity. The LPS binding and neutralization activities of procyanidin B2 were determined by a combination of biophysical and in silico techniques. The affinity of procyanidin B2 to LPS was 1.61 × 10 -5  M. Procyanidin B2 significantly neutralized LPS and selectively inhibited the LPS-induced release of tumor necrosis factor (TNF)-α from RAW264.7 cells in a dose-dependent manner. Binding thermodynamics revealed favorable hydrogen bonding and hydrophobic interactions between procyanidin B2 and LPS. Molecular simulations suggested that hydrogen bonding and hydrophobic interactions were involved in the binding process. These findings have, for the first time, shed light on the anti-inflammatory properties of procyanidin B2 through LPS binding and neutralization and provided a promising lead for the development of antiendotoxin agents., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Hijacking host ubiquitin pathways is essential for the replication of diverse viruses. However, the role of deubiquitinating enzymes (DUBs) in the interplay between viruses and the host is poorly characterized. Here, we demonstrate that specific DUBs are potent inhibitors of viral proteins from HIVs/simian immunodeficiency viruses (SIVs) that are involved in viral evasion of host restriction factors and viral replication. In particular, we discovered that T cell-functioning ubiquitin-specific protease 8 (USP8) is a potent and specific inhibitor of HIV-1 virion infectivity factor (Vif)-mediated apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3 (APOBEC3)G (A3G) degradation. Ectopic expression of USP8 inhibited Vif-induced A3G degradation and suppressed wild-type HIV-1 infectivity even in the presence of Vif. In addition, specific DUBs repressed Vpr-, Vpu-, and Vpx-triggered host restriction factor degradation. Our study has revealed a previously unrecognized interplay between the host's DUBs and viral replication. Enhancing the antiviral activity of DUBs therefore represents an attractive strategy against HIVs/SIVs., 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 © 2021 Gao, Rui, Li, Zhai, Su, Liu, Zheng, Zheng, Zhang, Yang, Hua and Yu.)

Deep learning approaches to estimating full 3D orientations of objects, in addition to object classes, are limited in their accuracies, due to the difficulty in learning the continuous nature of three-axis orientation variations by regression or classification with sufficient generalization. This paper presents a novel progressive deep learning framework, herein referred to as 3D POCO Net, that offers high accuracy in estimating orientations about three rotational axes yet with efficiency in network complexity. The proposed 3D POCO Net is configured, using four PointNet-based networks for independently representing the object class and three individual axes of rotations. The four independent networks are linked by in-between association subnetworks that are trained to progressively map the global features learned by individual networks one after another for fine-tuning the independent networks. In 3D POCO Net, high accuracy is achieved by combining a high precision classification based on a large number of orientation classes with a regression based on a weighted sum of classification outputs, while high efficiency is maintained by a progressive framework by which a large number of orientation classes are grouped into independent networks linked by association subnetworks. We implemented 3D POCO Net for full three-axis orientation variations and trained it with about 146 million orientation variations augmented from the ModelNet10 dataset. The testing results show that we can achieve an orientation regression error of about 2.5° with about 90% accuracy in object classification for general three-axis orientation estimation and object classification. Furthermore, we demonstrate that a pre-trained 3D POCO Net can serve as an orientation representation platform based on which orientations as well as object classes of partial point clouds from occluded objects are learned in the form of transfer learning.

This investigation was done for the assurance of potassium amassing in four assortments of maize (grains, shoot and root), soil, and water and in seven tissues of chickens (kidney, liver, heart, bone, gizzard, breast meat). The analysis of variance showed significant differences for potassium concentration in water in all sources of water; however, the season and variety significantly influenced the quantity of potassium in cereals. The corn varieties MMRI, Sadaf, and Pearl behaved differently when treated with water from various sources. Water taken from sewage had a higher concentration of potassium compared to canal and groundwater that is why the maize plants irrigated with this water had a higher grouping. Data regarding potassium concentration in different body parts of chicken showed that season and treatment have a significant effect on the potassium concentration in chicken organs. The variety was non-significant for the potassium concentration only in the bone. Season × Variety interaction was only significant in blood, meat heart, and gizzard. Season × Treatment and Variety × Treatment interactions were significant in the heart, kidney, and gizzard. The potassium contents were higher in the chicken body parts that were reared on grains irrigated with sewage water as compared to other groups. The potassium contents were higher in the chicken meat (96.23 ± 0.00) reared on grains of the Pearl variety raised with the sewage water. In a nutshell, the irrigation of grains with sewage water led to accumulation of nutrients greater than those irrigated with ground or canal water., (© 2021. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.)

Vegetation reconstruction and restoration is vital to the health of the mine land ecosystem. Different vegetations might change microbial community structure and function of soil, mediating the biogeochemical cycle and nutrition supply to the soil. To clarify the response of soil microbes to different vegetation reconstruction modes in the mining areas of the Loess Plateau, China, soil microbial community structures and functions were determined by the MiSeq high-throughput sequencing along with PICRUSt2 and FUNGuild tools. The fungal community richness was observed to be the highest in grassland soil and positively correlated with soil organic matter, total nitrogen, and nitrate-nitrogen. The bacterial and fungal community structures were similar in grassland and brushland areas, but were significantly differentiated in the coniferous and broadleaf forest, and the leading factors were soil pH and nitrate-nitrogen. Actinobacteriota, Proteobacteria, and Acidobacteriota were the dominant bacterial phyla under different vegetation reconstruction modes. The dominant phyla of fungi were Ascomycota, Basidiomycota, and Mortierellomycota. Different vegetation reconstruction modes did not affect the bacterial functional communities but shaped different functional groups of fungi. The grassland soil was dominated by saprotrophic fungi, while symbiotrophic fungi dominated the coniferous and broadleaf forests. The results suggested that shifts in vegetation reconstruction modes may alter the mining soil bacterial and fungal community structures and function. These findings improve the understanding of microbial ecology in the reclaimed mine soil and provide a reference for the ecological restoration of fragile mining ecosystems., 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 © 2021 Zhao, Ma, Yang, Yu, Zhang and Chen.)

To improve grain production capacity, many areas in the world are shifting from rainfed agriculture to irrigated agriculture. One example of such land consolidation is dryland-to-paddy conversion. The conversion of land use pattern largely affects the stability of farmland soil, especially the soil carbon cycle. However, the mutual feedback mechanisms between carbon flux variation and environmental factors during the farmland consolidation process are still poorly known. Located in the Huang-Huai-Hai Plain China, Xuzhou is a typical area where dryland-to-paddy conversion are most widely distributed. Therefore, in this study, we have carried out dryland-to-paddy conversion by setting up two isolated rectangular fields one group planting corn in dryland (DL) and another group planting in paddy field (PF) in Xuzhou. Here, we determined the effect of dryland-to-paddy consolidation on soil CO 2 flux in two isolated rectangular fields - the dryland (DL) cultivated with corn and the paddy field (PF) cultivated with rice. Our results showed that the soil carbon flux and temperature followed similar unimodal curves with greater soil CO 2 flux of in PF than in DL. Surprisingly, the land conversion significantly reduced soil microbial biomass carbon and easily oxidized organic carbon by 28.55% and 29.09%, respectively. The structural equation modeling results demonstrated that the changes in soil environmental factors, including temperature, and fungal OTU numbers, were the primary drivers for the soil CO 2 flux and soil carbon pool (P < 0.05). Overall, this study improves the understanding of the ecological impact of dryland-to-paddy conversion, providing insights into low-carbon agriculture and climate mitigation., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Abstract: Epicardial adipose tissue (EAT) dysfunction mediates chronic inflammation by regulating inflammation-related adipokines and cytokines, and it further promotes coronary artery disease (CAD) development. CD40L/CD40 is involved in multiple inflammatory pathways that contribute to various pathophysiological processes. However, the function of CD40L/CD40 in the expression and production of adipokines and cytokines in epicardial adipocytes remains unclear. The purpose of the present study was to explore the role and underlying mechanisms of CD40L/CD40 in adipokine and cytokine expression and production. We isolated adipocytes from EAT tissues of CAD and non-CAD patients. We noticed that CD40 was dramatically increased in EAT tissues of CAD patients. Loss-of-function and gain-of-function studies were performed. The results showed that CD40 silencing reduced recombinant CD40 ligand (rCD40L)-induced upregulation of plasminogen activator inhibitor-1, leptin, interleukin-6, and monocyte chemotactic protein-1 messenger RNA levels and secretion. Overexpression of CD40 displayed the opposite results. In addition, rCD40L triggered mixed lineage leukemia protein-1 (MLL1) expression both in messenger RNA and protein levels. CD40 depletion apparently blocked MLL1 expression, whereas gain of function of CD40 resulted in augmentation of MLL1 levels. Interestingly, chromatin immunoprecipitation-quantitative real-time polymerase chain reaction analysis revealed that CD40 elimination dampened histone H3 lysine 4 trimethylation enrichment at plasminogen activator inhibitor-1, leptin, interleukin-6, and monocyte chemotactic protein-1 promoter regions in the presence of rCD40L. The reverse pattern was observed upon ectopic expression of CD40. Most important, MLL1 silencing effectively reversed the promotive effects of CD40 on adipokine and cytokine secretion. Taken together, our findings suggest that CD40L/CD40 regulates adipokine and cytokine expression by H3 lysine 4 trimethylation modification in adipocytes., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

The use of wastewater in irrigation weakens the beneficial properties of the soil and leads to a threat to food safety standards. The present research was designed to explore the cobalt toxicity associated with the ingestion of wastewater irrigated wheat. Wheat plants of five different varieties were collected from 7 different sites of Punjab, Pakistan, which were irrigated with three different sources of water. The sampling was done in two cropping years. The cobalt values in water, soil and wheat samples (root, shoot, grain) ranged from 0.46 to 1.24 mg/l, 0.15 to 1.20, 0.29 to 1.30, 0.08 to 0.76 and 0.12 to 0.57 mg/kg, respectively. All the water samples showed high cobalt concentration than the maximum permissible value. However, all the soil and wheat plant samples were found within the maximum allowable range. The high cobalt concentration in irrigating water showed that the continuous usage of such type of water may lead to cobalt toxicity in living organisms with the passage of time and may results in severe health risks.

The beneficial effects of antioxidants against oxidative stress have been well described. However, the pharmacological impacts of antioxidants other than inhibiting the production of reactive oxygen species (ROS) remain less understood. This study demonstrated that diphenyleneiodonium (DPI), a canonical NADPH oxidase 2 (NOX2) inhibitor, effectively promoted non-opsonized bacterial phagocytosis. Indeed, DPI abrogated the elevation in the extracellular ATP level of Escherichia coli (E. coli) -infected murine peritoneal macrophages, thereby restoring the association of the purinergic receptor P2X7 with non-muscle myosin heavy chain 9 (MYH9) to upregulate the P2X7 -dependent phagocytosis of E. coli. DPI also suppressed inflammasome activation and reduced necroptosis in E. coli-infected macrophages by decreasing extracellular ATP levels. Mechanistically, DPI upregulated p38 MAPK phosphorylation to suppress the expression and activity of the hemichannel protein connexin 43 (CX43), leading to the inhibition of CX43-mediated ATP efflux in E. coli-infected macrophages. In a murine E. coli infection model, DPI effectively reduced ATP release, decreased bacterial load and inhibited inflammasome activation, thereby improving survival and ameliorating organ injuries in model mice. In summary, our study demonstrates a previously unknown function of DPI in conferring protection against bacterial infection and suggests a putative antimicrobial strategy of modulating CX43 -dependent ATP leakage., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Neutrophil extracellular traps (NETs) are extracellular DNA webs released from neutrophils to mediate the host antimicrobial defense. As NETs could also induce thrombosis and cause organ injury, their release should be strictly controlled; however, the intrinsic mechanisms that prevent unfavorable NETs are not well understood. Herein, an accidental finding of NET release from human peripheral neutrophils was first described in a serum-free culture, which was later determined to be a conserved NET prevention effect of serum. In contrast to canonical NETs induced by phorbol-12-myristate-13-acetate (PMA), NET formation by serum-free culture was rapid and without prevalent NETosis. Next, albumin was screened out as a key serum component that mediated the suppression of NETs. Moreover, NETs induced upon serum or albumin deficiency were independent of the canonical pathway that involves NADPH oxidase 2 (NOX2) activation and cytosol reactive oxygen species (ROS) production. Instead, the generation of mitochondrial ROS (mtROS) was upregulated to promote NET release. Albumin exhibited mtROS scavenging activity and thus inhibited NETs. Serum-free culture also induced the release of NET-bound oxidized mtDNA, which stimulated interferon-β (IFN-β) production. Overall, our research provides new evidence that characterizes the NET production in serum-free culture and determines the mechanisms by which serum albumin inhibits NETs.

Although transurethral resection of bladder tumor is the golden standard for the treatment of non-muscle invasive bladder cancer, this surgical procedure still has some serious drawbacks. For example, piecemeal resection of tumor tissue results in exfoliated tumor cells dissemination and implantation, and fragmented tumor specimens make it difficult for pathologists to accurately assess the pathological stage and histologic grade. En bloc tumor resection follows the basic principle of oncological surgery and provides an intact tumor specimen containing detrusor muscle for pathologists to make accurate histopathological assessment. However, there is no robust clinical evidence that en bloc tumor resection is superior to conventional resection in terms of oncological outcomes. Considering the high recurrence rate, small or occult tumor lesions may be overlooked and incomplete tumor resection may occur during white light cystoscopy-assisted transurethral resection. Molecular fluorescent tracers have the ability to bind tumor cells with high sensitivity and specificity. Optical molecular imaging mediated by it can detect small or occult malignant lesions while minimizing the occurrence of false-positive results. Meanwhile, optical molecular imaging can provide dynamic and real-time image guidance in the surgical procedure, which helps urologists to accurately determine the boundary and depth of tumor invasion, so as to perform complete and high-quality transurethral tumor resection. Integrating the advantages of these two technologies, optical molecular imaging-assisted en bloc tumor resection shows the potential to improve the positive detection rate of small or occult tumor lesions and the quality of transurethral resection, resulting in high recurrence-free and progression-free survival rates., 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 © 2021 Yang, Liu, Yan, Li and Yang.)

Gold nanoparticles (AuNPs) are extensively utilized in biomedical fields. However, their potential interaction with host cells has not been comprehensively elucidated. In this study, we demonstrated a size-dependent effect of AuNPs to synergize with bacterial lipopolysaccharide (LPS) in promoting neutrophil extracellular traps (NETs) release in human peripheral neutrophils. Mechanistically, LPS was more efficient to contact with 10 nm AuNPs and promote their uptake in neutrophils compared to 40 and 100 nm AuNPs, leading to a synergistic upregulation of class A scavenger receptor (SRA) which mediated AuNPs uptake and triggered activation of extracellular regulated protein kinase (ERK) and p38. Blocking SRA or inhibiting ERK and p38 activation remarkably abrogated the effect of AuNPs and LPS to induce NETs formation. Further experiments demonstrated that AuNPs and LPS augmented the production of cytosolic reactive oxygen species (ROS) in p38 and ERK dependent manner, through upregulating and activating NADPH oxidase 2 (NOX2). Accordingly, scavenging of ROS or inhibiting the NOX2 dampened NETs release induced by combined AuNPs and LPS treatment. AuNPs and LPS also synergized to upregulate reactive oxygen species modulator 1 (ROMO1) via activating ERK, thereby increasing mitochondrial ROS generation and promoting the release of NETs. In summary, we provide new evidences about the synergy of AuNPs and LPS to augment cellular responses in neutrophils, which implicates the need to consider the amplifying effect by pathogenic stimuli when utilizing nanomaterials in infectious or inflammatory conditions., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate the safety and efficacy of overnight continuous saline bladder irrigation (CSBI) for patients who have received thulium laser en bloc resection of bladder tumor (TmLRBT) combined with immediate intravesical chemotherapy previously., Methods: From October 2014 to June 2018, 235 patients with newly diagnosed non-muscle invasive bladder cancer (NMIBC) were included in this retrospective study. All patients received intravesical instillation of pirarubicin immediately after TmLRBT. The patients were divided into two groups according to the duration of postoperative bladder irrigation with normal saline. After immediate intravesical chemotherapy, patients in group 1 received overnight CSBI, while patients in group 2 did not receive overnight CSBI. Data on the time of initial tumor recurrence, recurrence-free survival (RFS) and progression-free survival (PFS) rates, and perioperative complications were collected and analyzed., Results: Of 235 included patients (129 in group 1 and 106 in group 2), the median follow-up periods were 42 and 38 months, respectively. There were no significant differences in patients' baseline characteristics between the two groups. The RFS rates of patients in group 1 were 90.7, 82.7, and 76.8% at the end of the first, third, and fifth years, while the corresponding RFS rates of patients in group 2 were 87.7, 78.9, and 73.3%, respectively. Four patients in group 1 and five patients in group 2 experienced tumor progression. No significant differences between the two groups were observed in the time of initial tumor recurrence, RFS, and PFS rates. Only Grade I complications occurred in the two groups, and no significant difference was reached between the two groups., Conclusions: For patients with NMIBC who have previously received TmLRBT combined with immediate intravesical chemotherapy, overnight CSBI may not improve oncological outcomes and reduce perioperative complications., 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 © 2021 Yang, Liu, Yan, Li and Yang.)

Background: To evaluate the surgical safety of en bloc resection of bladder tumor (ERBT) and the effectiveness of ERBT combined with near-infrared (NIR) imaging technique in the diagnosis and treatment of non-muscle invasive bladder cancer (NMIBC)., Methods: From October 2017 to June 2018, 26 patients newly diagnosed with single NMIBC were included in this retrospectively trial. All patients received ERBT with monopolar current. After surgery, the fresh specimen was incubated with anti-CD47-Alexa Fluor 790, and then imaged under NIR imaging technique. Operative details, intraoperative and postoperative complications of ERBT regarded as safety outcomes, the mean fluorescence intensity (MFI) of tumor tissue and adjacent normal background tissue, and 12 months follow-up data were analyzed., Results: Of 26 collected patients, obturator nerve reflex was occurred in six patients during tumor resection, and only one patient was observed with bladder perforation. In NIR gray image, the gray scale of MFI of tumor tissue were 132.31 ± 6.67 and the adjacent normal background tissue were 52.27 ± 12.09. The result showed a significantly higher MFI signals in tumor tissue compared to adjacent normal background tissue (P < 0.001). The recurrence-free survival rate at 12 month was 96.15%., Conclusions: ERBT with monopolar current is a safe and feasible technique to treat patients with NMIBC. A integrated bladder tumor tissue-bound anti-CD47-Alexa Fluor 790 was detected under NIR light, and the NIR image indicates that higher MFI signals in surgical margin is a predictive factor for residual tumor in patients with NMIBC after ERBT.

In the ecological restoration of mine dumps, soil carbon stock (SCS) improvement is an important issue. The type of land use and management approach taken can have a great influence on this issue. On the Loess Plateau, different crops have been cultivated on reclaimed land; however, the effect of long-term crop cultivation on SCS is poorly understood. To address this issue, a field investigation of mine dumps was performed at the Kee Open Pit Mine in Shanxi Province, China. Four sites utilizing different land management methods were analyzed: no reclamation (NR), reclamation with no crop cultivation (NC), and reclamation followed by 11 or 27 years crop cultivation (RC-11 and RC-27, respectively). SCS, associated soil properties (total nitrogen (TN), total phosphorus (TP), total potassium (TK), moisture content (MoiC), and pH), plant community (species composition, plant diversity, and traits), and microbial community operational taxonomic units (OTUs) of fungi and bacteria were determined by field investigation and laboratory analysis. Redundancy analysis was used to show the relationship between SCS and other environmental variables. Results varied by soil depth. At the depth range of 0-20 cm, the SCS of RC-11 was significantly greater compared to that in NR and NC, by 14.64- and 2.25-fold, respectively; whereas compared to RC-27, it was higher by 52.78%. At the depth of 20-40 cm, NC has the largest SCS; the SCS of RC-27 was the lowest, which was less compared to that in NC by 43.64%. Redundancy analysis showed a positive relationship between the SCS and TN, TP, MoiC, as well as average plant coverage, while the bacterial OTUs were negatively related with the SCS. This research suggests the potential of mine dumps for crop cultivation, which could improve the SCS of the mining area on the Loess Plateau., Competing Interests: Declaration of competing interest 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., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The progress of sepsis is increasingly recognized by the transition from early hyperinflammation to long term immunosuppression, which is characterized in innate immune cells by diminished responsiveness termed as lipopolysaccharide (LPS) tolerance. In this study, we investigated the ability of the antimalarial drug artesunate to reverse LPS tolerance and explored the underlying mechanisms. Initially, we detected a dramatic decline in autophagy accompanied by decreased cytokine production and impaired bacterial clearance by LPS tolerant macrophages. Then we demonstrated that artesunate restored cytokine production and enhanced bacterial clearance by inducing autophagy. Moreover, artesunate caused greater suppression of inhibitory phosphorylation than of activating phosphorylation of Unc-51 like autophagy activating kinase 1 (ULK1), a kinase that is essential for initiating autophagy through the inhibition of excessive AMP-activated protein kinase (AMPK) activation. This effect was shown to be achieved by suppression of Ca 2+ /calmodulin-dependent protein kinase II (CaMKII) phosphorylation, resulting in reduction of the inositol 1,4,5-triphate receptor (IP3R) dependent Ca 2+ release from the endoplasmic reticulum (ER) and inhibiting the overactive CaMKKβ-AMPK cascade. Administration of artesunate also upregulated autophagy and reversed the tolerant status in LPS tolerant mice. In summary, our findings reveal a novel immunopharmacological action of artesunate to reverse LPS tolerance by restoring autophagy. Our results may also indicate the significance of autophagy induction for treating immunosuppression in sepsis., Competing Interests: Declaration of Competing Interest 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., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Due to the high recurrence and progression rate of non-muscle invasive bladder cancer after transurethral resection of bladder tumor, some new optical imaging technologies have arisen as auxiliary imaging modes for white light cystoscopy to improve the detection rate of small or occult tumor lesions, such as photodynamic diagnosis, narrow-band imaging, and molecular imaging. White light cystoscopy is inadequate and imperfect for bladder cancer detection, and thus residual tumors or coexisting flat malignant lesions, especially carcinoma in situ , would be ignored during conventional resection. The bladder, a hollow organ with high compliance, provides an ideal closed operation darkroom for endoscopic molecular imaging free from interference of external light sources. Also, intravesical instillation of a molecular fluorescent tracer is simple and convenient before surgery through the urethra. Molecular fluorescent tracer has high sensitivity and specificity to tumor cells, and its mediated molecular imaging allows small or occult tumor lesion detection while minimizing false-positive results. Meanwhile, endoscopic molecular imaging provides a real-time and dynamic image during surgery, which helps urologists to perform high-quality and complete tumor resection through accurate judgment of tumor boundaries and depth of invasion. Photoimmunotherapy is a novel molecular targeted therapeutic pattern of photodynamic therapy that kills malignant cells selectively and minimizes the cytotoxicity to normal tissues. The combination of endoscopic molecular imaging and photoimmunotherapy used in initial treatment may avoid the need of repeat transurethral resection in strictly selected patients and improve oncological outcomes such as recurrence-free survival and overall survival after operation., (© 2020 The Author(s).)

Open-cut coal mining can seriously disturb and reshape natural landscapes which results in a range of impacts on local ecosystems and the services they provide. To address the negative impacts of disturbance, progressive rehabilitation is commonly advocated. However, there is little research focusing on how these impacts affect ecosystem services within mine sites and changes over time. The aim of this study was to assess the cumulative impacts of mining disturbance and rehabilitation on ecosystem services through mapping and quantifying changes at multiple spatial and temporal scales. Four ecosystem services including carbon sequestration, air quality regulation, soil conservation and water yield were assessed in 1989, 1997, 2005 and 2013. Disturbance and rehabilitation was mapped using LandTrendr algorithm with Landsat. We mapped spatial patterns and pixel values for each ecosystem service with corresponding model and the landscape changes were analyzed with landscape metrics. In addition, we assessed synergies and trade-offs using Spearman's correlation coefficient for different landscape classes and scales. The results showed that carbon sequestration, air quality regulation and water yield services were both positively and negatively affected by vegetation cover changes due to mined land disturbance and rehabilitation, while soil conservation service were mainly influenced by topographic changes. There were strong interactions between carbon sequestration, air quality regulation and water yield, which were steady among different spatial scales and landscape types. Soil conservation correlations were weak and changed substantially due to differences of spatial scales and landscape types. Although there are limitations associated with data accessibility, this study provides a new research method for mapping impacts of mining on ecosystem services, which offer spatially explicit information for decision-makers and environmental regulators to carry out feasible policies, balancing mining development with ecosystem services provision., Competing Interests: Declaration of competing interest We declare that we have no actual or potential conflict of interest including any financial, personal or other relationships with other people or organizations within three years of beginning the submitted work that could inappropriately influence, or be perceived to influence, our work., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: To evaluate the surgical safety and quality of transurethral en bloc resection with monopolar current for non-muscle invasive bladder cancer (NMIBC) based on the tumour, node, metastasis (TNM) classification system, and report the midterm oncological outcome., Methods: From October 2015 to June 2017, en bloc resection of bladder tumor (ERBT) and transurethral resection of bladder tumor (TURBT) were performed in 96 and 87 patients clinically diagnosed with NMIBC in the prospective case-control trial, respectively. Operative details, intraoperative and postoperative complications regarded as safety outcomes were documented. The quality of ERBT was judged by the histopathological examination of tumor specimens from initial resection and second TURBT, random bladder biopsy and follow-up recurrence rate., Results: Operative time, obturator nerve reflex, irrigation and catheterization time were similar in the two groups. Bladder perforation was occurred in 2 patients during ERBT and 9 patients during TURBT (2/96 vs. 9/87, P=0.019). Compared with TURBT group, the ratio of detrusor muscle (DM) identified in pathologic T1 tumor specimens was higher (P=0.024), but lower in pathologic Ta tumor specimens in ERBT group (P<0.001). The residual tumor identified in ERBT group was lower than that in TURBT group during second TURBT (2/28 vs. 10/32, P=0.020). The recurrence-free survival rate did not differ significantly between the two groups after 24 months follow-up., Conclusions: ERBT based on TNM system is a safe and feasible technique to treat patients with NMIBC. Besides, ERBT may reduce the proportion of bladder perforation and residual tumor during initial resection., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/tcr.2020.03.48). The authors have no conflicts of interest to declare., (2020 Translational Cancer Research. All rights reserved.)

Microorganisms are the driving force behind the circulation and transformation of the soil substance. The development of soil bacterial communities is critical for ecosystem restoration and evolution. In the Loess Plateau, coal mining activities have aggravated the deterioration of the fragile local ecological environment. The adaptive development of soil bacterial communities in response to different ecological processes caused by coal mining activities was explored through high-throughput sequencing technology and an ecological network analysis of the mining subsidence area of the Daliuta Coal Mine and vegetation rehabilitation area of the Heidaigou Coal Mine in the Loess Plateau. The results showed that while mining subsidence was inhibited, vegetation rehabilitation promoted the soil physicochemical properties. Soil organic matter, available phosphorus and available potassium in the subsidence area decreased significantly ( P < 0.05 ), while soil organic matter, soil water, pH and EC in the vegetation rehabilitation area increased significantly ( P < 0.05 ). The diversity index in the subsidence area decreased by about 20%, while that in the vegetation rehabilitation area increased by 63%. Mining subsidence and vegetation rehabilitation had a distinct influence on the molecular ecological networks of the soil bacteria, which tended to be more complex after the mining subsidence, and the number of connections in the network increased otherwise significantly enhanced interactive relationships. After the vegetation rehabilitation, the number of modules in the ecological network increased, but the contents of modules tended to be simpler. Soil bacterial communities adapted to the changes by changing the relationships between bacteria in response to different ecological processes. This study provides new insights into the monitoring and abatement of the damaged ecological environment in mines.

Enterovirus 71 (EV71) is the causative pathogen of hand, foot, and mouth disease (HFMD). However, no effective antiviral therapy is currently available. Some viruses could escape the host's innate immunity by upregulating suppressor of cytokine signaling (SOCS) proteins. Until now, whether EV71 evades the host immune system by regulating the expression of SOCS proteins remains unknown. In this study, we found that EV71 infection promoted SOCS expression at both mRNA and protein levels in vitro and in vivo. Consistently, the infectivity of EV71 was decreased significantly in the SOCS3 or SOCS1 knockdown cells, suggesting that SOCS1 and especially SOCS3 are crucial for EV71 infection. Further investigation showed that SOCS3 promoted virus infection by inhibiting interferon-induced STAT3 phosphorylation. SOCS1 and SOCS3 mRNA expressions were independent on virus-induced type I interferon expression but were blocked by the inhibitor of NF- κ B. Therefore, EV71 infection stimulates the expression of SOCS proteins in an interferon-independent way and negatively regulates the JAK/STAT signaling pathway, thus escaping host immunity. All these results may add new information to the mechanism of EV71 in fighting against type I interferon responses., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this paper., (Copyright © 2020 Wenying Gao et al.)

Irrigation has been applied on a large scale for the improvement of grain yield per hectare and production stability. However, the dryland-to-paddy conversion affects the ecological environment of areas of long-term dry farming, especially soil microorganisms. Little attention has been paid to the changes in microbial communities and the interactions between their populations in this process. Therefore, in this paper, the compositions and diversity of soil bacterial and fungal communities were explored through a combination of high-throughput sequencing technology and molecular ecological network methods using bacterial 16S rRNA and fungal ITS. The results showed that: (1) both the abundance and diversity of soil bacteria and fungi decreased in a short time, and the abundance of Actinobacteria, Firmicutes and Olpidiomycota varied greatly. (2) Compared to dry land, the modular structure of interaction networks and interspecific relationships of bacterial and fungal communities in paddy soil were simpler, and the network became more unstable. A cooperative relationship dominated in the molecular ecological network of bacteria, while a competitive relationship was dominant in the network of fungi. Actinobacteria and Firmicutes were the dominant bacterial species in dry land and paddy field, respectively. Ascomycota was dominant in the fungal communities of both dry land and paddy field. (3) The change in soil environmental factors, such as pH, electrical conductivity (EC), organic matter (OM) and available potassium (AK), directly affected the soil microbial community structure, showing a significant correlation (p < 0.05). These environmental factors also influenced the dominant microbial species. Microorganisms are the most important link in the carbon and nitrogen cycles of soil, and a large-scale dryland-to-paddy conversion may reduce the ecological stability of regional soil., Competing Interests: The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Objective: To evaluate the accuracy of a novel guidance method of pedicle screw implantation determined by spinal stress., Methods: We retrospectively analyzed patients underwent pedicle screw internal fixation between January 2015 and August 2018 in our hospital. Patients were divided into two groups according to the methods of pedicle screw implantation namely, the conventional nail placement and novel guidance method of pedicle screw implantation determined by spinal stress. Accuracy of spinal pedicle screw placements was evaluated using intraoperative and postoperative X-ray computed tomography (CT) examination and intraoperative touch of nerve root dissection pedicle bone. The success rate of intraoperative one-time screw placement was calculated according to Heary classification I., Results: A total of 785 patients underwent pedicle screw internal fixation were retrospectively analyzed. Among them 384 patients were treated using conventional nail placement (Group A) and 401 patients were treated using the technique according to analysis of spinal stress (Group B). There was no significant difference in terms of the characteristics between two groups. There were significant differences in terms of the success rate of total of screw placement (88.7% vs. 96.2%, P < 0.001) including thoracic screw placement (87.8% vs. 94.5%, P = 0.003) and lumbar screw placement (88.8% vs. 96.5%, P = 0.001) for Group A and Group B, respectively., Conclusions: Using the novel guidance method of pedicle screw implantation determined by spinal stress might improve the accuracy of pedicle screw implantation.