The clinical trajectory of peripheral blood immune cell subsets, T-cell activation, and cytokines in septic patients.

OBJECTIVE AND DESIGN: Changes in the immune status of patients with sepsis may have a major impact on their prognosis. Our research focused on changes in various immune cell subsets and T-cell activation during the progression of sepsis. METHODS AND SUBJECTS: We collected data from 188 sepsis patients at the First Affiliated Hospital of Zhejiang University School of Medicine. The main focus was on the patient's immunocyte subset typing, T-cell activation/Treg cell analysis, and cytokine assay, which can indicate the immune status of the patient. RESULTS: The study found that the number of CD4+ T cells, CD8+ T cells, NK cells, and B cells decreased early in the disease, and the decrease in CD4+ and CD8+ T cells was more pronounced in the death group. T lymphocyte activation was inhibited, and the number of Treg cells increased as the disease progressed. T lymphocyte inhibition was more significant in the death group, and the increase in IL-10 was more significant in the death group. Finally, we used patients' baseline conditions and immunological detection indicators for modeling and found that IL-10, CD4+ Treg cells, CD3+HLA-DR+ T cells, and CD3+CD69+ T cells could predict patients' prognosis well. CONCLUSION: Our study found that immunosuppression occurs in patients early in sepsis. Early monitoring of the patient's immune status may provide a timely warning of the disease.

Structural and Property Characterizations of Dual-Responsive Core-Shell Tecto Dendrimers for Tumor Penetration and Gene Delivery Applications.

Core-shell tecto dendrimers (CSTDs) with excellent physicochemical properties and good tumor penetration and gene transfection efficiency have been demonstrated to have the potential to replace high-generation dendrimers in biomedical applications. However, their characterization and related biological properties of CSTDs for enhanced tumor penetration and gene delivery still lack in-depth investigation. Herein, three types of dual-responsive CSTDs are designed for thorough physicochemical characterization and investigation of their tumor penetration and gene delivery efficiency. Three types of CSTDs are prepared through phenylborate ester bonds of phenylboronic acid (PBA)-decorated generation 5 (G5) poly(amidoamine) (PAMAM) dendrimers as cores and monose (galactose, glucose, or mannose)-conjugated G3 PAMAM dendrimers as shells and thoroughly characterized via NMR and other techniques. It is shown that the produced CSTDs display strong correlation signals between the PBA and monose protons, similar hydrodynamic diameters, and dual reactive oxygen species- and pH-responsivenesses. The dual-responsive CSTDs are proven to have structure-dependent tumor penetration property and gene delivery efficiency in terms of small interference RNA for gene silencing and plasmid DNA for gene editing, thus revealing a great potential for different biomedical applications.

Mangiferin alleviates diabetic pulmonary fibrosis in mice via inhibiting endothelial-mesenchymal transition through AMPK/FoxO3/SIRT3 axis.

Diabetes mellitus results in numerous complications. Diabetic pulmonary fibrosis (DPF), a late pulmonary complication of diabetes, has not attracted as much attention as diabetic nephropathy and cardiomyopathy. Mangiferin (MF) is a natural small molecular compound that exhibits a variety of pharmacological effects including anti-inflammatory, anti-cancer, anti-diabetes, and anti-fibrosis effects. In this study, we investigated whether long-term diabetes shock induces DPF, and explored whether MF had a protective effect against DPF. We first examined the lung tissues and sections of 20 diabetic patients obtained from discarded lung surgical resection specimens and found that pulmonary fibrosis mainly accumulated around the pulmonary vessels, accompanied by significantly enhanced endothelial-mesenchymal transition (EndMT). We established a mouse model of DPF by STZ injections. Ten days after the final STZ injection, the mice were administered MF (20, 60 mg/kg, i.g.) every 3 days for 4 weeks, and kept feeding until 16 weeks and euthanized. We showed that pulmonary fibrotic lesions were developed in the diabetic mice, which began around the pulmonary vessels, while MF administration did not affect long-term blood glucose levels, but dose-dependently alleviated diabetes-induced pulmonary fibrosis. In human umbilical vein endothelial cells (HUVECs), exposure to high glucose (33.3 mM) induced EndMT, which was dose-dependently inhibited by treatment with MF (10, 50 µM). Furthermore, MF treatment promoted SIRT3 expression in high glucose-exposed HUVECs by directly binding to AMPK to enhance the activity of FoxO3, which finally reversed diabetes-induced EndMT. We conclude that MF attenuates DPF by inhibiting EndMT through the AMPK/FoxO3/SIRT3 axis. MF could be a potential candidate for the early prevention and treatment of DPF.

Study on the dynamic effects of plateau hypoxic and cold environment on the thermal adaptation of short-term sojourners in Xizang.

The plateau hypoxic environment can affect the thermoregulation process of the human body, and due to the different acclimatization ability to the hypoxic environment, the thermal requirements among the people who enter Xizang at different times may be different. Accordingly, this study aims to clarify how plateau hypoxic environments influence the physiological and subjective responses of people entering Xizang at different times. And field experiments were conducted in Xi'an and Lhasa, respectively, to compare the thermal responses and oxygen responses of the subjects under different temperature conditions on the plain, the first day of entering Xizang and the 15th day of entering Xizang. The results showed that under the hypoxic environment, the thermal sensation of the subjects decreased. With the extension of the time entering Xizang, the influence of the hypoxic environment on thermal comfort was gradually weakened, but under the low temperature environment, the effect of hypoxia on thermal response was not significantly reduced. The results of this study can help to reveal how plateau hypoxic environments affect human thermal comfort and provide a theoretical basis for the design of indoor thermal environment parameters suitable for sojourners entering Xizang at different times.

Hydroxycitric Acid Alleviated Lung Ischemia-Reperfusion Injury by Inhibiting Oxidative Stress and Ferroptosis through the Hif-1α Pathway.

Lung ischemia-reperfusion injury (LIRI) is a prevalent occurrence in various pulmonary diseases and surgical procedures, including lung resections and transplantation. LIRI can result in systemic hypoxemia and multi-organ failure. Hydroxycitric acid (HCA), the primary acid present in the peel of Garcinia cambogia, exhibits anti-inflammatory, antioxidant, and anticancer properties. However, the effects of HCA on LIRI remain unknown. To investigate the impact of HCA on LIRI in mice, the mice were randomly divided into four groups: the control group, the I/R model group, and the I/R + low- or high-dose HCA groups. Human umbilical vein endothelial cells (HUVECs) were subjected to hypoxia for 12 h followed by reoxygenation for 6 h to simulate in vitro LIRI. The results demonstrated that administration of HCA effectively attenuated lung injury, inflammation, and edema induced by ischemia reperfusion. Moreover, HCA treatment significantly reduced malondialdehyde (MDA) and reactive oxygen species (ROS) levels while decreasing iron content and increasing superoxide dismutase (SOD) levels after ischemia-reperfusion insult. Mechanistically, HCA administration significantly inhibited Hif-1α and HO-1 upregulation both in vivo and in vitro. We found that HCA could also alleviate endothelial barrier damage in H/R-induced HUVECs in a concentration-dependent manner. In addition, overexpression of Hif-1α counteracted HCA-mediated inhibition of H/R-induced endothelial cell ferroptosis. In summary, these results indicate that HCA alleviated LIRI by inhibiting oxidative stress and ferroptosis through the Hif-1α pathway.

Multifunctional Proximity Labeling Strategy for Lipid Raft-Specific Sialic Acid Tracking and Engineering.

Lipid raft-specific glycosylation has been implicated in many biological processes, including intracellular trafficking, cell adhesion, signal transduction, and host-pathogen interactions. The major predicament in lipid raft-specific glycosylation research is the unavailability of tools for tracking and manipulating glycans on lipid rafts at the microstructural level. To overcome this challenge, we developed a multifunctional proximity labeling (MPL) platform that relies on cholera toxin B subunit to localize horseradish peroxidase on lipid rafts. In addition to the prevailing electron-rich amino acids, modified sialic acid was included in the horseradish peroxidase-mediated proximity labeling substrate via purposefully designed chemical transformation reactions. In combination with sialic acid editing, the self-renewal of lipid raft-specific sialic acid was visualized. The MPL method enabled tracking of lipid raft dynamics under methyl-ß-cyclodextrin and mevinolin treatments; in particular, the alteration of lipid rafts markedly affected cell migration. Furthermore, we embedded functional molecules into the method and implemented raft-specific sialic acid gradient engineering. Our novel strategy presents opportunities for tailoring lipid raft-specific sialic acids, thereby regulating interactions associated with lipid raft regions (such as cell-virus and cell-microenvironment interactions), and can aid in the development of lipid raft-based therapeutic regimens for tumors.

Tripterygium wilfordii Hook.f. ameliorates paraquat-induced lung injury by reducing oxidative stress and ferroptosis via Nrf2/HO-1 pathway.

Paraquat (PQ) poisoning can induce acute lung injury and fibrosis and has an extremely high mortality rate. However, no effective treatments for PQ poisoning have been established. In this study, the potential efficacy of Tripterygium wilfordii Hook.f. (TwHF) in alleviating PQ-induced lung injury and fibrosis was investigated in a mouse model. Mice were randomly assigned to the control, PQ, PQ + TwHF1 (pretreatment before inducing poisoning), and PQ + TwHF2 (treatment after poisoning) groups. The mice in the PQ + TwHF1 group were pretreated with TwHF for 5 days before receiving one dose of PQ (120 mg/kg) and then received a daily oral gavage of the indicated dosages of TwHF until sacrifice. The mice in the PQ + TwHF2 group were treated with TwHF 2 h after PQ exposure until sacrifice. The pathological analysis and Fapi PET/CT showed that treatment with TwHF attenuated lung injury. And TwHF reduced pulmonary oxidative stress, as indicated by the reduction in, malondialdehyde (MDA), glutathione (GSH), and reactive oxygen species (ROS) levels, as well as by the increase in superoxide dismutase (SOD) levels. Accordingly, the Perls DAB staining showed increased iron concentrations and western blotting revealed a decreased GPX4 expression after PQ exposure, as well as the mitigation of the overexpression of Nrf2 and HO-1 induced by PQ. In conclusion, our study demonstrated the potential of TwHF as a treatment for PQ-induced lung injury and fibrosis. The protective mechanism of this medicinal herb may involve the regulation of ferroptosis.

Dry response and acclimated characteristics of people ascending the Tibetan Plateau.

Due to a long period of low humidity, exposure to the dry environment of the Tibetan Plateau can cause skin and respiratory diseases and threaten human health. To examine the characteristics of acclimatization response to humidity comfort in visitors to the Tibetan Plateau based on an examination of the targeted effect and mechanism of the dry environment. A scale corresponding to local dryness symptoms was proposed. Eight participants were selected to conduct a two-week plateau experiment and a one-week plain experiment under six humidity ratios, respectively, to explore the characteristics of dry response and acclimatization of people entering the plateau. The results indicate that duration has a significant effect on human dry response. On the sixth day after entering Tibet, the degree of dryness reached the maximum, and acclimatization to the plateau environment began on the 12th day. The sensitivity of different body parts to the change in a dry environment was different. When the indoor humidity ratio increased from 9.04 g/kg to 21.77 g/kg, the symptoms of dry skin were most significantly relieved by 0.5 units of scale. After de-acclimatization, the degree of dryness in the eyes was most significantly alleviated, reducing by nearly one scale. The analysis of human symptom indicators in a dry environment shows that subjective and physiological indices are influential and essential in measuring human comfort in a dry environment. This study extends our understanding of dry environment responses and cognition of human comfort and lays a solid foundation for humid built environments in the plateau.

Dendrimer-Based Nanogels for Cancer Nanomedicine Applications.

Recent advances in the field of nanotechnology bring an alternative approach to personalized medicine in cancer treatment. Nanogels (NGs) are among the nanosized superconstructs composed of amphiphilic or hydrophilic polymer networks. The design of different types of biodegradable polymer-based NGs in various biomedical applications has received extensive attention, due to their unique physicochemical properties such as highly porous structure, stimuli-responsiveness, and mimicking of some biological properties. In this review, we concisely surveyed the synthesis of dendrimer-based NGs synthesized via different methods including covalent conjugation, inverse nanoprecipitation, physical cross-linking, or self-assembly for various cancer nanomedicine applications, particularly for drug delivery, gene delivery, photothermal therapy, and combination therapy, as well as for biological imaging-guided chemotherapy. Additionally, we provide herein future perspective toward the new design of dendrimer-based NGs for different cancer nanomedicine uses.

Synthesis and Shaping of Core-Shell Tecto Dendrimers for Biomedical Applications.

In recent years, the use of poly(amidoamine) (PAMAM) dendrimers of different generations as building blocks or reactive modules to construct core-shell tecto dendrimers (CSTDs) that are superior to the performance of single-generation dendrimers has received great attention in the field of biomedical applications. The CSTDs are always based on high-generation dendrimers as the core and low-generation dendrimers as the shell; not only do they have excellent properties similar to single high-generation dendrimers, but they also have overcome some of the shortcomings (e.g., limited drug loading capacity or enhanced permeability and retention effect due to small size) of single-generation dendrimers in biomedical applications. Herein, the recent advances of CSTDs synthesized by different approaches as nanoplatforms for different biomedical applications, particularly for chemotherapy, gene delivery, and combination therapy, as well as biological imaging, are summarized. In addition, the current challenges and future perspectives of CSTDs are also discussed.

Core-Shell Tecto Dendrimers Enable Enhanced Tumor MR Imaging through an Amplified EPR Effect.

Development of nanoplatforms that can amplify the passive tumor targeting effect based on enhanced permeability and retention (EPR) effect is crucial for precision cancer nanomedicine applications. Herein, we present the development of core-shell tecto dendrimers (CSTDs) as a platform for enhanced tumor magnetic resonance (MR) imaging through an amplified EPR effect. In this work, poly(amidoamine) (PAMAM) dendrimers of generation 5 (G5) were decorated with ß-cyclodextrin (CD) and then assembled with G3 PAMAM dendrimers premodified with adamantane (Ad) via supramolecular recognition of CD and Ad. The formed G5-CD/Ad-G3 CSTDs were conjugated with tetraazacyclododecane tetraacetic acid (DOTA)-Gd(III) chelators and further acetylated to neutralize the remaining CSTD periphery amines. We reveal that the formed CSTD.NHAc-DOTA(Gd) (CSTD-D-Gd) complexes have a narrow size distribution and satisfactory colloidal stability, and are cytocompatible within the concentration range studied. Compared to the single dendrimer counterpart of G5.NHAc-DOTA(Gd) (G5-D-Gd) complexes, the CSTD-D-Gd complexes with a higher molecular weight and volume possess a longer rotation correlation time, hence having a longitudinal relaxivity (r1) of 7.34 mM-1 s-1, which is 1.5 times larger than that of G5-D-Gd complexes (4.92 mM-1 s-1). More importantly, the CSTD-D-Gd complexes display better permeability in the three-dimensional (3D) cell spheroids in vitro through fluorescence imaging and a more significant EPR effect for improved tumor MR imaging in vivo than the G5-DOTA-Gd complexes. The generated CSTD-D-Gd complexes may be adopted for enhanced tumor MR imaging through an amplified passive EPR effect and also be further extended for different cancer theranostic applications.

Dynamic and quantitative characterization of antagonism within disinfectant mixtures by a modified area-concentration ratio method.

The coexistence of various typical disinfectant pollutants has the potential to produce toxicity interaction towards organisms in the environment. A suitable model is necessary to evaluate the interaction quantitatively. Hence, the area-concentration ratio (ACR) method was modified (MACR) by combing confidence intervals to dynamically and quantitatively evaluate the toxicity interactions within disinfectant mixture pollutants. Disinfectant mixtures were designed by the direct equipartition design ray method using three guanidine disinfectants, chlorhexidine diacetate (CD), chlorhexidine (CHL), and polyhexamethylene biguanidine (POL) and one chlorine-containing disinfectant calcium hypochlorite (CAL). The toxicities of the four disinfectants and their mixtures towards Vibrio qinghaiensis sp.-Q67 (Q67) were determined by the time-dependent toxicity microplate analysis method. And the toxicity mechanism was analyzed by determining the effects of four disinfectants and their binary mixtures on the structure of cell, DNA and proteins (Pro) for Q67. The results show that the toxicities of CD and CHL to Q67vary little with time, but POL and CAL show the obvious time-dependent toxicity. The toxicities of CD, CHL and POL to Q67 are significantly stronger than that of CAL at the same exposure time. The toxicities of three binary mixture systems don't have significant difference in different exposure time. MACR can dynamically, quantitatively and accurately characterize toxicity interactions compared with ACR. According to MACR, the antagonism intensity dynamically changes with the prolongation of exposure time for binary mixture rays of three guanidine disinfectants and CAL, and linearly correlates with the components' concentration ratios. Four disinfectants all can destroy cell membrane and cause desaturation DNA of test organism, and CAL even can destroy the structure of DNA and protein. The probably reason for the antagonism within binary mixtures is the reaction between guanidine group and ClO-, which is called chemical antaogism.

Role of routine check-up in the prognosis of patients with pancreatic cancer: A puzzling phenomenon.

BACKGROUND: The high coverage of annual routine health check-up in China is a unique phenomenon throughout the world. However, its clinical value is controversial. In this cohort study, we chose pancreatic cancer as a disease model to explore the role of routine check-up in the prognosis of patients with pancreatic cancer. METHODS: Data from 157 patients who were diagnosed with pancreatic cancer between January 2010 and April 2014 were collected. Patients were divided into two groups depending on how their disease was detected. Group A (n = 85): Patients were diagnosed with pancreatic cancer in clinic visits. Group B (n = 72): Patients were diagnosed with pancreatic cancer in routine check-ups. We compared their prognosis. RESULTS: The tumor stage in group B was earlier than that in group A. The 1-year survival rate in group B was significantly higher than that in group A (74.6% vs. 42.4%, P < 0.001), while the 3- and 5-year survival rates of the two groups showed no significant difference (P > 0.05). The difference of overall survival time between the two groups was not significant (22.0 vs. 9.0 months, P = 0.078). CONCLUSIONS: The stage of pancreatic cancer diagnosed in routine check-ups was earlier and therefore, the intervention was earlier which improved short-term survival rate. However, early intervention did not improve overall survival in the long-term.

Alternating Hemiplegia of Childhood Caused by ATP1A3 Mutations: A Report of Two Cases.

Alternating hemiplegia of childhood is a rare neurodevelopmental disorder. Most cases are reported as sporadic disorder due to de novo variants, and few with family members involved. Two boys were hospitalized due to epileptic seizures occurred initially at age of six to seven months. During the course of the disease, there were repeated episodes of paroxysmal weakness or paralysis affecting one side of the body. Genetic testing showed that both patients carried heterozygous missense mutations in theATP1A3 gene (OMIM: 614820): c.3025 (exon 22) A>G (p.K1009E) and c.2443 (exon 18) G>A (p.E815K). Flunarizine can significantly improve the paroxysmal motor symptoms of pediatric patients with alternating hemiplegia.

N-3-oxo-octanoyl-homoserine lactone-mediated priming of resistance to Pseudomonas syringae requires the salicylic acid signaling pathway in Arabidopsis thaliana.

BACKGROUD: Many Gram-negative bacteria use N-acyl-homoserine lactones (AHLs) to communicate each other and to coordinate their collective behaviors. Recently, accumulating evidence shows that host plants are able to sense and respond to bacterial AHLs. Once primed, plants are in an altered state that enables plant cells to more quickly and/or strongly respond to subsequent pathogen infection or abiotic stress. RESULTS: In this study, we report that pretreatment with N-3-oxo-octanoyl-homoserine lactone (3OC8-HSL) confers resistance against the pathogenic bacterium Pseudomonas syringae pv. tomato DC3000 (PstDC3000) in Arabidopsis. Pretreatment with 3OC8-HSL and subsequent pathogen invasion triggered an augmented burst of hydrogen peroxide, salicylic acid accumulation, and fortified expression of the pathogenesis-related genes PR1 and PR5. Upon PstDC3000 challenge, plants treated with 3OC8-HSL showed increased activities of defense-related enzymes including peroxidase, catalase, phenylalanine ammonialyase, and superoxide dismutase. In addition, the 3OC8-HSL-primed resistance to PstDC3000 in wild-type plants was impaired in plants expressing the bacterial NahG gene and in the npr1 mutant. Moreover, the expression levels of isochorismate synthases (ICS1), a critical salicylic acid biosynthesis enzyme, and two regulators of its expression, SARD1 and CBP60g, were potentiated by 3OC8-HSL pretreatment followed by pathogen inoculation. CONCLUSIONS: Our data indicate that 3OC8-HSL primes the Arabidopsis defense response upon hemibiotrophic bacterial infection and that 3OC8-HSL-primed resistance is dependent on the SA signaling pathway. These findings may help establish a novel strategy for the control of plant disease.

Identification of local thermal conditions for sleeping comfort improvement in neutral to cold indoor thermal environments.

The effect of the thermal environment on sleep quality has attracted considerable attention, as sleep forms one-third of human lifetime and the occupied space is largely constrained during sleep. With an increasing development of partial space regulation and task air conditioning systems and devices, thermal comfort demand concerning local thermal conditions has attracted more and more attention. In the present study, experiment was conducted and data mining technologies were performed to investigate correlations between local thermal conditions and whole body thermal comfort in sleeping state. The identification of local thermal condition included two steps: the first step was to clarify thermal sensation links between local and covered body, and the second step was to identify local thermal sensation inclination towards different thermal comfort levels. Thermal sensation correlations among local body parts and covered body were obtained. Back, face, and thigh were identified as three dominant linear-correlated local parts with weighting factors 0.488, 0.388, and 0.152, respectively; in addition, chest, arm, leg and foot were found as non-negligible local parts in the estimation of covered body thermal sensation. By dividing the sleeping human body into three parts as head, trunk and extremity, the proper local thermal sensations and their coupling relationships for whole body sleeping thermal comfort have been elaborated by three rules. The present study provides implications in sleeping thermal environment regulation in neutral to cold indoor conditions.

Genome-wide analysis reveals alcohol dehydrogenase 1C and secreted phosphoprotein 1 for prognostic biomarkers in lung adenocarcinoma.

To seek out novel promising biomarkers for predicting lung adenocarcinoma (LUAD) prognosis, we conducted this study. First, 279 upregulated and 37 downregulated differentially expressed genes were obtained from LUAD and para-carcinoma tissues by the Affymetrix GeneChip Human Transcriptome Array. Then, we randomly classified samples of LUAD data set GSE31210 as training and testing sets in a 1:1 ratio. Alcohol dehydrogenase 1C (ADH1C) and secreted phosphoprotein 1 (SPP1) were finally identified correlating with the LUAD survival through least absolute shrinkage and selection operator penalized Cox proportion hazards regression model, and applied to build a 2-gene signature related to prognosis in training set. Univariate and multivariable survival analyses suggested that overall survival (OS) and relapse-free survival (RFS) in the 2-gene signature low-risk group were better than the high-risk group. Kaplan-Meier curves proved that elevated ADH1C expression and reduced SPP1 expression were related to better OS and RFS. Besides, the SPP1 expressed higher in LUAD than para-carcinoma tissues using quantitative reverse transcription polymerase chain reaction assay. Finally, the association between the two genes and clinicopathological parameters in 80 LUAD were analyzed, it is suggested that SPP1 was relevant to epidermal growth factor receptor mutation. These findings indicated that ADH1C and SPP1 might be novel promising biomarkers for predicting LUAD prognosis.

Design and Synthesis of Fluorinated Amphiphile as (19)F MRI/Fluorescence Dual-Imaging Agent by Tuning the Self-Assembly.

Both (19)F MRI and optical imaging are powerful noninvasive molecular imaging modalities in biomedical applications. To integrate these two complementary imaging modalities, the design and synthesis of a novel (19)F MRI/fluorescence dual-modal imaging agent is reported herein. Through Sonogashira coupling reaction between the fluorinated phenylacetylene and 1,2,4,5-tetraiodobenzene, a fluorophore with 48 symmetrical fluorines at its periphery was constructed with high efficacy. High aqueous solubility was achieved by PEGylation of the fluorophore with monodisperse PEGs. However, an unexpected self-assembly of the PEGylated amphiphilic fluorophore in water "turned off" the (19)F NMR signal. However, hydrogenation of the triple bonds or introduction of branched monodisperse PEGs was able to efficiently tune the self-assembly, resulting in the "turning on" of the (19)F NMR signal. One of these amphiphiles combines the advantages of label-free fluorescence, high (19)F MRI sensitivity, biocompatibility, and excellent aqueous solubility. The results demonstrate the great potential of such amphiphiles for real-time (19)F MRI and fluorescence dual-modality imaging.

Indole-3-acetic acid reverses the harpin-induced hypersensitive response and alters the expression of hypersensitive-response-related genes in tobacco.

Harpin proteins stimulate hypersensitive response (HR) in plants. However, the mechanism by which HR is regulated is not clear. The role of the auxin, indole-3-acetic acid (IAA), in the control of harpin-stimulated HR was investigated. IAA was used to inhibit HR that was stimulated by purified fusion harpin(Xoo) protein in tobacco. Semi-quantitative PCR and qRT-PCR were employed to detect the expression of HR related genes. IAA at 100 µM reversed harpin-induced HR which was inhibited by 500 µM 2,3,5-triiodobenzoic acid (TIBA). Semi-quantitative PCR and qRT-PCR showed the combined application of 100 µM IAA and harpin protein from Xanthomonas oryzae enhanced the expression of HR marker gene, hsr203J, but weakened the expression of the disease-defense gene, chia5. TIBA also decreased the expression of hsr203J but increased the expression of chia5. Thus, the auxin can reverse harpin(Xoo)-induced HR.

Machine learning models for early prediction of potassium lowering effectiveness and adverse events in patients with hyperkalemia.

The aim of this study was to develop a model for early prediction of adverse events and treatment effectiveness in patients with hyperkalemia. We collected clinical data from patients with hyperkalemia in the First Hospital of Zhejiang University School of Medicine between 2015 and 2021. The least absolute shrinkage and selection operator (LASSO) and multivariate logistic regression were used to analyze the predictors on the full dataset. We randomly divided the data into a training group and a validation group, and used LASSO to filter variables in the training set. Six machine learning methods were used to develop the models. The best model was selected based on the area under the curve (AUC). Shapley additive exPlanations (SHAP) values were used to explain the best model. A total of 1074 patients with hyperkalemia were finally enrolled. Diastolic blood pressure (DBP), breathing, oxygen saturation (SPO2), Glasgow coma score (GCS), liver disease, oliguria, blood sodium, international standardized ratio (ISR), and initial blood potassium were the predictors of the occurrence of adverse events; peripheral edema, estimated glomerular filtration rate (eGFR), blood sodium, actual base residual, and initial blood potassium were the predictors of therapeutic effect. Extreme gradient boosting (XGBoost) model achieved the best performance (adverse events: AUC = 0.87; therapeutic effect: AUC = 0.75). A model based on clinical characteristics was developed and validated with good performance.