The adsorption of petroleum hydrocarbons by soils in the unsaturated zone determines the amount that goes into the groundwater. However, the intricate behavior of petroleum hydrocarbon adsorption in ...soil media under the influence of freeze–thaw conditions in globally prevalent seasonally frozen regions remains unclear. Alkanes as a non-polar compound are an important part of petroleum hydrocarbons. We conducted field-scale seasonal freeze-thaw experiments using n-dodecane to quantify the dynamic patterns and influencing factors of the physicochemical properties of soil media and their adsorption capacity for petroleum hydrocarbons during different freeze–thaw cycles. Our findings demonstrated that, as the number of natural freeze–thaw cycles increased, the proportion of soil micro-agglomerates rose rapidly, thereby expanding the available adsorption sites and enhancing the adsorption capacity for non-polar organic pollutants. The rise in sorption capacity for the outdoor freeze–thaw experimental group surpassed that of the indoor room-temperature control group by an impressive 75.57%, showing the enhancement of the adsorption capacity for non-polar organic pollutants. Conversely, the decline in soil organic matter content during the later stages of the freeze–thaw process hampered its adsorption performance for non-polar organic pollutants. The decrease in sorption capacity for the outdoor freeze–thaw experimental group surpassed that of the indoor room temperature control group by 77.97%. By shedding light on the adsorption mechanisms of non-polar organic pollutants in soils subjected to freeze–thaw conditions, our research facilitated a comprehensive understanding and predictive modeling of this process. Furthermore, our study provided a scientific foundation for exploring the convergence and migration transformation patterns of other organic compounds in petroleum-contaminated areas within seasonally frozen regions.
Large rivers without hydrological data from remote sensing observations have recently become a hot research topic. The Irrawaddy River is among the major tropical rivers worldwide; however, published ...hydrological data on this river have rarely been obtained in recent years. In this paper, based on the existing measured the total suspended matter flux (FTSM) and discharge data for the Irrawaddy River, an inversion model of the total suspended matter concentration (CTSM) is constructed for the Irrawaddy River, and the CTSM and FTSM from 1990 to 2020 are estimated using the L1 products of Landsat-8 OLI/TIRS and Landsat-5 TM. The results show that over the last 30 years, the FTSM of the Irrawaddy River decreased at a rate of 3.9 Mt/yr, which is significant at the 99% confidence interval. An increase in the vegetation density of the Irrawaddy Delta has increased the land conservation capacity of the region and reduced the inflow of land-based total suspended matter (TSM). The FTSM of the Irrawaddy River was estimated by fusing satellite data and data measured at hydrological stations. The research method employed in this paper provides a new supplement to the existing hydrological data for large rivers.
Rheumatoid arthritis (RA) is an autoimmune disease that significantly impacts quality of life by disrupting CD4+ T cell immune homeostasis. The identification of a low-side-effect drug for RA ...treatment is urgently needed. Our previous study suggests that Trichinella spiralis paramyosin (Ts-Pmy) has immunomodulatory effects, but its potential effect on CD4+ T cell response in RA remains unclear. In this study, we used a murine model to investigate the role of rTs-Pmy in regulating CD4+ T cell differentiation in collagen-induced arthritis (CIA). Additionally, we assessed the impact of rTs-Pmy on CD4+ T cell differentiation towards the Th1 and Th17 phenotypes, which are associated with inflammatory responses in arthritis, using in vitro assays. The results demonstrated that rTs-Pmy administration reduced arthritis severity by inhibiting Th1 and Th17 response while enhancing Treg response. Prophylactic administration of Ts-Pmy showed superior efficacy on CIA compared to therapeutic administration. Furthermore, in vitro assays demonstrated that rTs-Pmy could inhibit the differentiation of CD4+ T cells into Th1 and Th17 while inducing the production of Tregs, suggesting a potential mechanism underlying its therapeutic effects. This study suggests that Ts-Pmy may ameliorate CIA by restoring the immune balance of CD4+ T cells and provides new insights into the mechanism through which helminth-derived proteins exert their effects on autoimmune diseases.
Abstract
To establish a high-quality, easy-to-use, and effective risk prediction model for hepatic encephalopathy, to help healthcare professionals with identifying people who are at high risk of ...getting hepatic encephalopathy, and to guide them to take early interventions to reduce the occurrence of hepatic encephalopathy. Patients (n = 1178) with decompensated cirrhosis who attended the First Affiliated Hospital of Guangxi University of Chinese Medicine between January 2016 and June 2022 were selected for the establishment and validation of a nomogram model for risk prediction of hepatic encephalopathy. In this study, we screened the risk factors for the development of hepatic encephalopathy in patients with decompensated cirrhosis by univariate analysis, LASSO regression and multifactor analysis, then established a nomogram model for predicting the risk of getting hepatic encephalopathy for patients with decompensated cirrhosis, and finally performed differentiation analysis, calibration analysis, clinical decision curve analysis and validation of the established model. A total of 1178 patients with decompensated cirrhosis who were hospitalized and treated at the First Affiliated Hospital of Guangxi University of Chinese Medicine between January 2016 and June 2022 were included for modeling and validation. Based on the results of univariate analysis, LASSO regression analysis and multifactor analysis, a final nomogram model with age, diabetes, ascites, spontaneous peritonitis, alanine transaminase, and blood potassium as predictors of hepatic encephalopathy risk prediction was created. The results of model differentiation analysis showed that the AUC of the model of the training set was 0.738 (95% CI 0.63–0.746), while the AUC of the model of the validation set was 0.667 (95% CI 0.541–0.706), and the two AUCs indicated a good discrimination of this nomogram model. According to the Cut-Off value determined by the Jorden index, when the Cut-Off value of the training set was set at 0.150, the sensitivity of the model was 72.8%, the specificity was 64.8%, the positive predictive value was 30.4%, and the negative predictive value was 91.9%; when the Cut-Off value of the validation set was set at 0.141, the sensitivity of the model was 69.7%, the specificity was 57.3%, the positive predictive value was 34.5%, and the negative predictive value was 84.7%. The calibration curve and the actual events curve largely overlap at the diagonal, indicating that the prediction with this model has less error. The Hosmer–Lemeshow test for goodness of fit was also applied, and the results showed that for the training set, χ
2
= 1.237587,
P
= 0.998, and for the validation set, χ
2
= 31.90904,
P
= 0.0202, indicating that there was no significant difference between the predicted and actual observed values. The results of the clinical decision curve analysis showed that the model had a good clinical benefit, compared with the two extreme clinical scenarios (all patients treated or none treated), and the model also had a good clinical benefit in the validation set. This study showed that aged over 55 years, complications of diabetes, ascites, and spontaneous bacterial peritonitis, abnormal glutamate aminotransferase and abnormal blood potassium are independent risks indicators for the development of hepatic encephalopathy in patients with decompensated cirrhosis. The nomogram model based on the indicators mentioned above can effectively and conveniently predict the risk of developing hepatic encephalopathy in patients with decompensated cirrhosis. The nomogram model established on this study can help clinical healthcare professionals to timely and early identify patients with high risk of developing hepatic encephalopathy.
Helminth-modulated macrophages contribute to attenuating inflammation in inflammatory bowel diseases. The programmed death 1 (PD-1) plays an important role in macrophage polarization and is essential ...in the maintenance of immune system homeostasis. Here, we investigate the role of PD-1-mediated polarization of M2 macrophages and the protective effects of excretory/secretory products from
adult worms (AES) on DSS-induced colitis in mice. Colitis in mice was induced by oral administration of dextran sodium sulfate (DSS) daily. Mice with DSS-induced colitis were treated with
AES intraperitoneally, and pathological manifestations were evaluated. Macrophages in mice were depleted with liposomal clodronate. Markers for M1-type (iNOS, TNF-α) and M2-type (CD206, Arg-1) macrophages were detected by qRT-PCR and flow cytometry. Macrophage expression of PD-1 was quantified by flow cytometry; RAW 264.7 cells and peritoneal macrophages were used for
tests, and PD-1 gene knockout mice were used for
investigation of the role of PD-1 in AES-induced M2 macrophage polarization. Macrophage depletion was found to reduce DSS-induced colitis in mice. Treatment with
AES significantly increased macrophage expression of CD206 and Arg-1 and simultaneously attenuated colitis severity. We found
AES to enhance M2 macrophage polarization; these findings were confirmed studying
cultures of RAW264.7 cells and peritoneal macrophages from mice. Further experimentation revealed that AES upregulated PD-1 expression, primarily on M2 macrophages expressing CD206. The AES-induced M2 polarization was found to be decreased in PD-1 deficient macrophages, and the therapeutic effects of AES on colitis was reduced in PD-1 knockout mice. In conclusion, the protective effects of
AES on DSS-induced colitis were found to associate with PD-1 upregulation and M2 macrophage polarization. Thus, PD-1-mediated M2 macrophage polarization is a key mechanism of helminth-induced modulation of the host immune system.
In-hospital cardiac arrest (IHCA) is an acute disease with a high fatality rate that burdens individuals, society, and the economy. This study aimed to develop a machine learning (ML) model using ...routine laboratory parameters to predict the risk of IHCA in rescue-treated patients.
This retrospective cohort study examined all rescue-treated patients hospitalized at the First Medical Center of the PLA General Hospital in Beijing, China, from January 2016 to December 2020. Five machine learning algorithms, including support vector machine, random forest, extra trees classifier (ETC), decision tree, and logistic regression algorithms, were trained to develop models for predicting IHCA. We included blood counts, biochemical markers, and coagulation markers in the model development. We validated model performance using fivefold cross-validation and used the SHapley Additive exPlanation (SHAP) for model interpretation.
A total of 11,308 participants were included in the study, of which 7779 patients remained. Among these patients, 1796 (23.09%) cases of IHCA occurred. Among five machine learning models for predicting IHCA, the ETC algorithm exhibited better performance, with an AUC of 0.920, compared with the other four machine learning models in the fivefold cross-validation. The SHAP showed that the top ten factors accounting for cardiac arrest in rescue-treated patients are prothrombin activity, platelets, hemoglobin, N-terminal pro-brain natriuretic peptide, neutrophils, prothrombin time, serum albumin, sodium, activated partial thromboplastin time, and potassium.
We developed a reliable machine learning-derived model that integrates readily available laboratory parameters to predict IHCA in patients treated with rescue therapy.
Salt stress is a critical limiting factor for rice growth and production. Although numerous salt-tolerant genes have been identified, the mechanism underlying salt stress tolerance in rice remains ...unclear. This study reports the need for an uncharacterized WRKY transcription factor OsWRKY54 for rice salt-tolerance. Salt stress resulted in a rapid induction of OsWRKY54 expression in roots. Immunostaining analysis showed that it was mainly expressed in the stele. The loss of OsWRKY54 resulted in greater Na accumulation in shoots and enhanced sensitivity of rice plants to salt stress. The real-time quantitative PCR (qRT-PCR) and transcriptome analysis revealed that OsWRKY54 regulated the expression of some essential genes related to salt tolerance, such as OsNHX4 and OsHKT1;5. Furthermore, OsWRKY54 was found to regulate OsHKT1;5 expression by directly binding to the W-box motif in its promoter. Thus, these results indicated that OsWRKY54 was a critical regulatory factor in salt tolerance in rice.
Acid sphingomyelinase (ASM) is a lysosomal phosphodiesterase that catalyzes the hydrolysis of sphingomyelin to produce ceramide and phosphocholine. While other lysosomal sphingolipid hydrolases ...require a saposin activator protein for full activity, the ASM polypeptide incorporates a built-in N-terminal saposin domain and does not require an external activator protein. Here, we report the crystal structure of human ASM and describe the organization of the three main regions of the enzyme: the N-terminal saposin domain, the proline-rich connector, and the catalytic domain. The saposin domain is tightly associated along an edge of the large, bowl-shaped catalytic domain and adopts an open form that exposes a hydrophobic concave surface approximately 30Å from the catalytic center. The calculated electrostatic potential of the enzyme is electropositive at the acidic pH of the lysosome, consistent with the strict requirement for the presence of acidic lipids in target membranes. Docking studies indicate that sphingomyelin binds with the ceramide-phosphate group positioned at the binuclear zinc center and molecular dynamic simulations indicate that the intrinsic flexibility of the saposin domain is important for monomer-dimer exchange and for membrane interactions. Overall, ASM uses a combination of electrostatic and hydrophobic interactions to cause local disruptions of target bilayers in order to bring the lipid headgroup to the catalytic center in a membrane-bound reaction.
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•Crystal structure of human acid sphingomyelinase (ASM).•The ASM saposin domain and connector regions are tightly associated with the metallophosphatase catalytic domain.•The saposin domain undergoes hinge-opening and maintains its association with the catalytic domain upon membrane binding.•Membrane binding by the saposin domain guides the active site of the catalytic domain to the headgroups of the bilayer.•The model for ASM membrane binding provides structural insight into saposin-hydrolase complexes at bilayer surfaces.
A robust and practical difluoroalkylation synthon, α,α‐difluoroenol species, which generated in situ from trifluoromethyl diazo compounds and water in the presence of dirhodium complex, is disclosed. ...As compared to the presynthesized difluoroenoxysilane and in situ formed difluoroenolate under basic conditions, this difluoroenol intermediate displayed versatile reactivity, resulting in dramatically improved enantioselectivity under mild conditions. As demonstrated in catalytic asymmetric aldol reaction and Mannich reactions with ketones or imines in the presence of chiral organocatalysts, quinine‐derived urea, and chiral phosphoric acid (CPA), respectively, this relay catalysis strategy provides an effective platform for applying asymmetric fluorination chemistry. Moreover, this method features a novel 1,2‐difunctionalization process via installation of a carbonyl motif and an alkyl group on two vicinal carbons, which is a complementary protocol to the metal carbene gem‐difunctionalization reaction.
An enantioselective three‐component difluoroalkylation reaction using an in situ formed α,α‐difluoroenol species as the key difluorinated synthon is reported. This method features a 1,2‐difunctionalization process, which is a complementary protocol to the metal carbene gem‐difunctionalization reaction. The disclosed relay catalysis strategy provides an effective platform for expanding asymmetric fluorination chemistry.
Colorectal cancer (CRC) is a gastrointestinal malignancy originating from either the colon or the rectum. A growing number of researches prove that the unfolded protein response (UPR) is closely ...related to the occurrence and progression of colorectal cancer. The UPR has three canonical endoplasmic reticulum (ER) transmembrane protein sensors: inositol requiring kinase 1 (IRE1), pancreatic ER eIF2α kinase (PERK), and activating transcription factor 6 (ATF6). Each of the three pathways is closely associated with CRC development. The three pathways are relatively independent as well as interrelated. Under ER stress, the activated UPR boosts the protein folding capacity to maximize cell adaptation and survival, whereas sustained or excessive ER triggers cell apoptosis conversely. The UPR involves different stages of CRC pathogenesis, promotes or hinders the progression of CRC, and will pave the way for novel therapeutic and diagnostic approaches. Meanwhile, the correlation between different signal branches in UPR and the switch between the adaptation and apoptosis pathways still need to be further investigated in the future.
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