The nucleoside analog 4'-fluorouridine suppresses the replication of multiple enteroviruses by targeting 3D polymerase.

Human enteroviruses are the major pathogens causing hand-foot-and-mouth disease in infants and young children throughout the world, and infection with enterovirus is also associated with severe complications, such as aseptic meningitis and myocarditis. However, there are no antiviral drugs available to treat enteroviruses infection at present. In this study, we found that 4'-fluorouridine (4'-FlU), a nucleoside analog with low cytotoxicity, exhibited broad-spectrum activity against infections of multiple enteroviruses with EC50 values at low micromolar levels, including coxsackievirus A10 (CV-A10), CV-A16, CV-A6, CV-A7, CV-B3, enterovirus A71 (EV-A71), EV-A89, EV-D68, and echovirus 6. With further investigation, the results indicated that 4'-FlU directly interacted with the RNA-dependent RNA polymerase of enterovirus, the 3D pol, and impaired the polymerase activity of 3D pol, hence inhibiting viral RNA synthesis and significantly suppressing viral replication. Our findings suggest that 4'-FlU could be promisingly developed as a broad-spectrum direct-acting antiviral agent for anti-enteroviruses therapy.

An optimized back propagation neural network on small samples spectral data to predict nitrite in water.

Accurate detection of pollutant levels in water bodies using fusion algorithms combined with spectral data has become a critical issue for water conservation. However, the number of samples is too small and the model is unstable, which often leads to poor prediction and fails to achieve the measurement goal well. To address these challenges, this paper proposes a practical and effective method to precisely predict the concentrations of nitrite pollution in aquatic environments. The proposed method consists of three steps. Firstly, the dimension of the spectral data is reduced using Kernel Principal Component Analysis (KPCA), followed by sample augmentation using Generative Adversarial Network (GAN) to reduce calculation cost and increase the diversity and scale of the data. Secondly, several improvement strategies, including multi-cluster competitive and adaptive parameter updating, are introduced to enhance the capability of the Particle Swarm Optimization (PSO) algorithm. The improved PSO algorithm is then applied to optimize the initialization weights and biases of the Back Propagation neural network, thereby improving the model fitting and training performance. Finally, the developed prediction model is employed to predict the test set samples. The result suggests that the R2, RMSE, and MAE values are 0.976290, 0.008626, and 0.006617, which outperform the state-of-the-art and provided a promising model for the prediction of nitrite concentration in water.

The Impact of Postures and Moving Directions in Fire Evacuation in a Low-Visibility Environment.

Walking speed is a significant aspect of evacuation efficiency, and this speed varies during fire emergencies due to individual physical abilities. However, in evacuations, it is not always possible to keep an upright posture, hence atypical postures, such as stoop walking or crawling, may be required for survival. In this study, a novel 3D passive vision-aided inertial system (3D PVINS) for indoor positioning was used to track the movement of 20 volunteers during an evacuation in a low visibility environment. Participants' walking speeds using trunk flexion, trunk-knee flexion, and upright postures were measured. The investigations were carried out under emergency and non-emergency scenarios in vertical and horizontal directions, respectively. Results show that different moving directions led to a roughly 43.90% speed reduction, while posture accounted for over 17%. Gender, one of the key categories in evacuation models, accounted for less than 10% of the differences in speed. The speeds of participants under emergency scenarios when compared to non-emergency scenarios was also found to increase by 53.92-60% when moving in the horizontal direction, and by about 48.28-50% when moving in the vertical direction and descending downstairs. Our results also support the social force theory of the warming-up period, as well as the effect of panic on the facilitating occupants' moving speed.

Carboxylated Poly (p-Phenylene Terephthalamide) Reinforced Polyetherimide for High-Temperature Dielectric Energy Storage.

Dielectric energy storage polymers play a vital role in advanced electronics and electrical systems, due to their high breakdown strength, excellent reliability, and easy fabrication. However, the low dielectric constant and poor thermal resistance of dielectric polymers limit their energy storage density and working temperatures, making them less versatile for broader applications. In this work, a novel carboxylated poly (p-phenylene terephthalamide) (c-PPTA) is synthesized and employed to simultaneously enhance the dielectric constant and thermal resistance of polyetherimide (PEI), leading to a discharged energy density of 6.4 J cm-3 at 150 °C. The introduction of c-PPTA molecules effectively reduces the Πï£¿Π stacking effect and increases the average chain spacing between polymer molecules, which is conducive to improving the dielectric constant. Additionally, c-PPTA molecules with stronger positive charges and high dipole moments can capture electrons, resulting in reduced conduction loss and enhanced breakdown strength at high temperatures. The coiled capacitor fabricated with the PEI/c-PPTA film exhibits superior capacitance performances and higher working temperatures compared to commercial metalized PP capacitors, demonstrating great potential for dielectric polymers in high-temperature electronic and electrical energy storage systems.

Application of Accelerator Mass Spectrometry to Characterize the Mass Balance Recovery and Disposition of AZD4831, a Novel Myeloperoxidase Inhibitor, following Administration of an Oral Radiolabeled Microtracer Dose in Humans.

This study evaluated the mass balance and disposition of AZD4831, a novel myeloperoxidase inhibitor, in six healthy participants using a 14C-labeled microtracer coupled with analysis by accelerator mass spectrometry (AMS). A single oral dose of 10 mg 14C-AZD4831 (14.8 kBq) was administered as a solution, and 14C levels were quantified by AMS in blood, urine, and feces over 336 hours postdose. AZD4831 was rapidly absorbed, and AZD4831 plasma concentrations declined in a biphasic manner, with a long half-life of 52 hours. AZD4831 was eliminated via metabolism and renal excretion. An N-carbamoyl glucuronide metabolite of AZD4831 (M7), formed primarily via UGT1A1, was the predominant circulating metabolite. Presumably, M7 contributed to the long half-life of AZD4831 via biliary elimination and hydrolysis/enterohepatic recirculation of AZD4831. On average, ∼84% of administered 14C-AZD4831 was recovered by 336 hours postdose (urine, 51.2%; feces, 32.4%). Between 32%-44% of the dose was excreted as unchanged AZD4831 in urine, indicating renal elimination as the major excretory route. Only 9.7% of overall fecal recovery was recorded in the first 48 hours, with the remainder excreted over 48%-336 hours, suggesting that most fecal recovery was due to biliary elimination. Furthermore, only 6% of unchanged AZD4831 was recovered in feces. Overall, the fraction of the administered AZD4831 dose absorbed was high. 14C-AZD4831 was well tolerated. These findings contribute to increasing evidence that human absorption, distribution, metabolism, and excretion studies can be performed with acceptable mass balance recovery at therapeutically relevant doses and low radiolabel-specific activity using an AMS-14C microtracer approach. SIGNIFICANCE STATEMENT: In this study, the human absorption, distribution, metabolism, and excretion (hADME) of the novel myeloperoxidase inhibitor AZD4831 was assessed following oral administration. This included investigation of the disposition of M7, the N-carbamoyl glucuronide metabolite. Resolution of challenges highlighted in this study contributes to increasing evidence that hADME objectives can be achieved in a single study for compounds with therapeutically relevant doses and low radiolabel-specific activity by using an AMS-14C microtracer approach, thus reducing the need for preclinical radiolabeled studies.

Machine learning prognosis model based on patient-reported outcomes for chronic heart failure patients after discharge.

BACKGROUND: Patient-reported outcomes (PROs) can be obtained outside hospitals and are of great significance for evaluation of patients with chronic heart failure (CHF). The aim of this study was to establish a prediction model using PROs for out-of-hospital patients. METHODS: CHF-PRO were collected in 941 patients with CHF from a prospective cohort. Primary endpoints were all-cause mortality, HF hospitalization, and major adverse cardiovascular events (MACEs). To establish prognosis models during the two years follow-up, six machine learning methods were used, including logistic regression, random forest classifier, extreme gradient boosting (XGBoost), light gradient boosting machine, naive bayes, and multilayer perceptron. Models were established in four steps, namely, using general information as predictors, using four domains of CHF-PRO, using both of them and adjusting the parameters. The discrimination and calibration were then estimated. Further analyze were performed for the best model. The top prediction variables were further assessed. The Shapley additive explanations (SHAP) method was used to explain black boxes of the models. Moreover, a self-made web-based risk calculator was established to facilitate the clinical application. RESULTS: CHF-PRO showed strong prediction value and improved the performance of the models. Among the approaches, XGBoost of the parameter adjustment model had the highest prediction performance with an area under the curve of 0.754 (95% CI: 0.737 to 0.761) for death, 0.718 (95% CI: 0.717 to 0.721) for HF rehospitalization and 0.670 (95% CI: 0.595 to 0.710) for MACEs. The four domains of CHF-PRO, especially the physical domain, showed the most significant impact on the prediction of outcomes. CONCLUSION: CHF-PRO showed strong prediction value in the models. The XGBoost models using variables based on CHF-PRO and the patient's general information provide prognostic assessment for patients with CHF. The self-made web-based risk calculator can be conveniently used to predict the prognosis for patients after discharge. CLINICAL TRIAL REGISTRATION: URL: http://www.chictr.org.cn/index.aspx ; Unique identifier: ChiCTR2100043337.

Efficacy and safety of broad spectrum penicillin with or without beta-lactamase inhibitors vs first and second generation cephalosporins as prophylactic antibiotics during cesarean section: a systematic review and meta-analysis.

This study assessed the efficacy and safety between broad spectrum penicillin (P2) with or without beta-lactamase inhibitors (P2+) versus first and second generation cephalosporins (C1&C2) in the prevention of post-cesarean infections. Relevant randomized controlled trials (RCTs) were searched in English and Chinese databases: nine RCTs were involved. Six trials compared P2+ vs C1&C2, no differences were found between interventions for endometritis, wound infection, urinary tract infection, febrile morbidity and maternal rashes. Four trials compared P2 vs C1&C2, no differences were found between interventions for endometritis, febrile morbidity, wound infection and urinary tract infection. Postoperative hospitalization was longer for women in P2 than C1&C2. Based on these results, P2/P2+ and C1&C2 may have similar efficacy on postoperative infections after cesarean section, there is no data on infant outcomes. PROSPERO Registration Number: CRD42022345721.

Exploring motivations and resistances for implementing shared decision-making in clinical practice: A systematic review based on a structure-process-outcome model.

OBJECTIVE: Shared decision-making (SDM) as a multicollaborative approach is vital for facilitating patient-centred care. Considering the limited clinical practice, we attempted to synthesize the motivations and resistances, and investigate their mutual relationships for advancing the implementation of SDM. METHODS: A comprehensive systematic review using Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines was performed. 'Shared decision making' was searched as the mesh term through PubMed, Web of Science and EBSCO from 2000 to 2021, and the quality of literature was appraised using the QualSyst Tool. Motivations and resistances were categorized based on content analysis and the 'structure-process-outcome' model. RESULTS: From 8319 potential citations, 105 were included, comprising 53 qualitative studies (the average quality score is 0.92) and 52 quantitative studies (the average quality score is 0.95). A total of 42 categories of factors were identified into 11 themes and further grouped into three dimensions: structure, process and outcome. The structure dimension comprised six themes (71.43%), the process dimension contained four themes (11.01%) and the outcome dimension covered only one theme. Across all categories, decision-making time and patients' decision preparedness in the process dimension were the most reported, followed by physicians' communication skills and health care environment in the structure dimension. Analysis of implementation of SDM among various types of diseases showed that more influencing factors were extracted from chronic diseases and unspecified disease decisions. CONCLUSIONS: The major determinants for the implementation of SDM are focused on the structural dimension, which challenges the health systems of both developed and low- and middle-income countries. Furthermore, we consider it important to understand more about the interactions among the factors to take integrated measures to address the problems and to ensure the effectiveness of implementing SDM. PATIENT OR PUBLIC CONTRIBUTION: Patients, healthcare professionals and other stakeholders articulated their perspectives on the implementation of SDM actively, and these were adopted and analysed in this study. However, the above-mentioned individuals were not directly involved in the process of this study. Protocol was registered on PROSPERO (CRD42021259309).

The Biosynthesis and Transport of Ophiobolins in Aspergillus ustus 094102.

Ophiobolins are a group of sesterterpenoids with a 5-8-5 tricyclic skeleton. They exhibit a significant cytotoxicity and present potential medicinal prospects. However, the biosynthesis and transport mechanisms of these valuable compounds have not been fully resolved. Herein, based on a transcriptome analysis, gene inactivation, heterologous expression and feeding experiments, we fully explain the biosynthesis pathway of ophiobolin K in Aspergillus ustus 094102, especially proved to be an unclustered oxidase OblCAu that catalyzes dehydrogenation at the site of C16 and C17 of both ophiobolin F and ophiobolin C. We also find that the intermediate ophiobolin C and final product ophiobolin K could be transported into a space between the cell wall and membrane by OblDAu to avoid the inhibiting of cell growth, which is proved by a fluorescence observation of the subcellular localization and cytotoxicity tests. This study completely resolves the biosynthesis mechanism of ophiobolins in strain A. ustus 094102. At the same time, it is revealed that the burden of strain growth caused by the excessive accumulation and toxicity of secondary metabolites is closely related to compartmentalized biosynthesis.

Targeted Delivery of CXCL9 and OX40L by Mesenchymal Stem Cells Elicits Potent Antitumor Immunity.

Major obstacles in immunotherapies include toxicities associated with systemic administration of therapeutic agents, as well as low tumor lymphocyte infiltration that hampers the efficacies. In this study, we report a mesenchymal stem cell (MSC)-based immunotherapeutic strategy in which MSCs specifically deliver T/natural killer (NK) cell-targeting chemokine CXCL9 and immunostimulatory factor OX40 ligand (OX40L)/tumor necrosis factor superfamily member 4 (TNFSF4) to tumor sites in syngeneic subcutaneous and azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced spontaneous colon cancer mouse models. This approach generated potent local antitumor immunity by increasing the ratios of tumor-infiltrating CD8+ T and NK cells and production of antitumor cytokines and cytolytic proteins in the tumor microenvironment. Moreover, it improved the efficacy of programmed death-1 (PD-1) blockade in a syngeneic mouse model and significantly suppressed the growth of major histocompatibility complex class I (MHC class I)-deficient tumors. Our MSC-based immunotherapeutic strategy simultaneously recruits and activates immune effector cells at the tumor site, thus overcoming the problems with toxicities of systemic therapeutic agents and low lymphocyte infiltration of solid tumors.

Patient satisfaction with outpatient care in China: a comparison of public secondary and tertiary hospitals.

OBJECTIVE: The aims of this study were to investigate and compare patient satisfaction with outpatient care in public secondary and tertiary hospitals in China and to explore the factors affecting patient satisfaction for improving the quality of outpatient care in public hospitals. METHODS: This cross-sectional study comprised a sample survey of 11 097 adults in 31 provincial cities in China from February to April 2018. A pretested structured questionnaire was used to collect outpatient experience data through a computer-assisted telephone interviewing system. Patient satisfaction was assessed using nine questions answered on a 4-point Likert scale. Multivariate regression models were employed to examine the relationships of patient satisfaction with outpatient services and healthcare provider level and to identify the factors associated with satisfaction. RESULTS: Patient's overall satisfaction score with outpatient care was 27.3 (SD = 3.8), with lower scores observed in tertiary hospitals than in secondary hospitals (27.3 vs. 27.6, P < 0.05). The domain with the highest satisfaction was 'consulting environment', and the domain with the lowest satisfaction was 'patient waiting time in the hospital'. Patients who went to tertiary hospitals reported lower satisfaction in 'patient waiting time in the hospital', 'medical expenses', 'patient length of treatment time' and 'attitudes of other health workers' than patients who went to secondary hospitals (P < 0.05). In secondary hospitals, no significant difference in patient satisfaction was observed between different sociodemographic categories (P > 0.05). In tertiary hospitals, female and single respondents were more likely to have higher satisfaction (P < 0.05), whereas respondents with high school or junior college degrees were more likely to have lower satisfaction (P < 0.05). CONCLUSION: The aforementioned results suggested that tertiary hospitals face larger challenges in patient satisfaction with outpatient care than secondary hospitals. Measures must be adopted to improve patient satisfaction with outpatient care in future healthcare reforms. Patient waiting time, medical expenses and treatment duration especially require improvements in tertiary hospitals.

Evaluating the healthcare practice by defining healthcare principles: An autoregressive integrated moving average model based on time series.

AIM: This study developed a set of health care principles to evaluate the health care practice in China long-term via time series. METHODS: This study was divided into four parts. First, the variables were designed by defining a set of conceptual tools. Second, qualitative text was collected and coded according to the defined conceptual tools. Third, the sampling text was qualitatively analysed. Fourth, the variables were analysed through an autoregressive integrated moving average model based on a time series. Lastly, the qualitative and variable analyses were combined and the basic conclusions of the study were drawn. RESULTS: We found that the health care principle of accessibility was significantly positively affected by abnormal event, policy experimentation and policy authority shift. Quality was found to be significantly positively affected by policy experimentation and policy authority shift, while cost control was significantly positively affected by policy experimentation. CONCLUSION: This study implies that the collective activities of the government and health care practitioners, such as abnormal events, policy failures, policy experimentations and policy authority shifts, as well as health care practice itself, become increasingly interconnected over time.

AGRP Neurons Project to the Medial Preoptic Area and Modulate Maternal Nest-Building.

AGRP (agouti-related neuropeptide) expressing inhibitory neurons sense caloric needs of an animal to coordinate homeostatic feeding. Recent evidence suggests that AGRP neurons also suppress competing actions and motivations to mediate adaptive behavioral selection during starvation. Here, in adult mice of both sexes we show that AGRP neurons form inhibitory synapses onto ∼30% neurons in the medial preoptic area (mPOA), a region critical for maternal care. Remarkably, optogenetically stimulating AGRP neurons decreases maternal nest-building while minimally affecting pup retrieval, partly recapitulating suppression of maternal behaviors during food restriction. In parallel, optogenetically stimulating AGRP projections to the mPOA or to the paraventricular nucleus of hypothalamus but not to the LHA (lateral hypothalamus area) similarly decreases maternal nest-building. Chemogenetic inhibition of mPOA neurons that express Vgat (vesicular GABA transporter), the population targeted by AGRP terminals, also decreases maternal nest-building. In comparison, chemogenetic inhibition of neurons in the LHA that express vesicular glutamate transporter 2, another hypothalamic neuronal population critical for feeding and innate drives, is ineffective. Importantly, nest-building during low temperature thermal challenge is not affected by optogenetic stimulation of AGRP→mPOA projections. Finally, via optogenetic activation and inhibition we show that distinctive subsets of mPOA Vgat+ neurons likely underlie pup retrieval and maternal nest-building. Together, these results show that AGRP neurons can modulate maternal nest-building, in part through direct projections to the mPOA. This study corroborates other recent discoveries and underscores the broad functions that AGRP neurons play in antagonizing rivalry motivations to modulate behavioral outputs during hunger.SIGNIFICANCE STATEMENT In order for animals to initiate ethologically appropriate behaviors, they must typically decide between behavioral repertoires driven by multiple and often conflicting internal states. How neural pathways underlying individual behaviors interact to coherently modulate behavioral outputs, in particular to achieve a proper balance between behaviors that serve immediate individual needs versus those that benefit the propagation of the species, remains poorly understood. Here, by investigating projections from a neuronal population known to drive hunger behaviors to a brain region critical for maternal care, we show that activation of AGRP→mPOA projections in females dramatically inhibits maternal nest-building while leaving mostly intact pup retrieval behavior. Our findings shed new light on neural organization of behaviors and neural mechanisms that coordinate behavioral selection.

Rules governing genetic exchanges among viral types from different Enterovirus A clusters.

The species Enterovirus A (EV-A) consists of two conventional clusters and one unconventional cluster. At present, sequence analysis shows no evidence of recombination between conventional and unconventional EV-A types. However, the factors underlying this genetic barrier are unclear. Here, we systematically dissected the genome components linked to these peculiar phenomena, using the viral reverse genetic tools. We reported that viral capsids of the unconventional EV-A types expressed poorly in human cells. The trans-encapsidation outputs across conventional and unconventional EV-A types were also with low efficiency. However, replicons of conventional types bearing exchanged 5'-untranslated region (UTR) or non-structural regions from the unconventional types were replication-competent. Furthermore, we created a viable recombinant EVA71 (conventional type) with its P3 region replaced by that from EVA89 (unconventional type). Thus, our data for the first time reveal the potential for fertile genetic exchanges between conventional and unconventional EV-A types. It also discloses that the mysterious recombination barriers may lie in uncoordinated capsid expression and particle assembly by different EV-A clusters.

Perilipin LDP1 coordinates lipid droplets formation and utilization for appressorium-mediated infection in Magnaporthe oryzae.

Lipid droplets (LDs) serve as one of the major reservoirs in conidia of Magnaporthe oryzae and are quickly utilized during appressorium formation. Here, we identified a gene, LDP1, encoding a perilipin that is important for LD formation and utilization during appressorium maturation. LDP1 is highly expressed in conidium and immature appressorium. Disruption mutants of LDP1 were significantly reduced in virulence, due to appressorial turgor reduction and difficulty in penetration. LDs were significantly reduced in the Δldp1 mutant, indicating LDP1 was required for LDs formation. LDP1 was colocalized with the LDs in conidium and immature appressorium but was gradually separated during appressorium maturation. A typical intracellular triacylglycerol lipase, TGL1-2, was clearly separated with LDs in conidium and immature appressorium but was well colocalized with LDs during appressorium maturation. The subcellular localization of TGL1-2 was affected by LDP1. These data suggested that LDP1 was bound to LDs for protecting from utilization in conidia and at the early appressorium stage but was separated from LDs for lipase entering and degradation. LDP1 was phosphorylated by CPKA at Thr96, which was essential for its localization and functions. These data indicate perilipin LDP1 can coordinate LD formation and utilization for appressorium-mediated infection of M. oryzae.

Rac1-dependent endocytosis and Rab5-dependent intracellular trafficking are required by Enterovirus A71 and Coxsackievirus A10 to establish infections.

Enterovirus A71 (EVA71) and Coxsackievirus A10 (CVA10) are representative types of Enterovirus A. Dependent on the host cell types, the EVA71 entry may utilize clathrin-, caveola-, and endophilin-A2-mediated endocytosis. However, the cell-entry and intracellular trafficking pathways of CVA10, using KREMEN1 as its receptor, are unclear. Here, we tested the relevant mechanisms through RNA interference (RNAi) and chemical inhibitors. We found that endocytosis of EVA71 and CVA10 in rhabdomyosarcoma (RD) cells engaged multiple pathways, and both viruses required Rac1. Interestingly, while CDC42 and Pak1 participated in EVA71 infection, PI3K played a role in CVA10 infection. The functions of Rab proteins in intracellular trafficking of CVA10 and EVA71 were examined by RNAi. Knockdown of Rab5 and Rab21 significantly reduced CVA10 infectivity, while knockdown of Rab5, Rab7 and Rab9 reduced EVA71 infectivity. Confocal microscopy confirmed the colocalization of CVA10 virions with Rab5 or Rab21, and colocalization of EVA71 virions with Rab5 or Rab7. Additionally, we observed that both CVA10 and EVA71 infections were inhibited by endosome acidification inhibitors, bafilomycin-A1 and NH4Cl. Together, our findings comparatively illustrate the entry and intracellular trafficking processes of representative Enterovirus A types and revealed novel enterovirus intervention targets.

Creg in Hepatocytes Ameliorates Liver Ischemia/Reperfusion Injury in a TAK1-Dependent Manner in Mice.

Hepatic ischemia/reperfusion (I/R) is a major challenge for liver surgery and specific severe conditions of chronic liver disease. Current surgical and pharmacological strategies are limited to improve liver function after hepatic I/R injury. Thus, an in-depth understanding of the liver I/R mechanism is pivotal to develop new therapeutic methods. The cellular repressor of E1A-stimulated genes (Creg), a key regulator of cellular proliferation, exerts protective roles in cardiovascular diseases and participates in lipid accumulation and inflammatory response in the liver. However, the role of Creg in hepatic I/R remains largely unknown. A genetic engineering technique was used to explore the function of Creg in hepatic I/R injury. Hepatocyte-specific Creg knockout (CregΔHep ) and transgenic mice were generated and subjected to hepatic I/R injury, as were the controls. Creg in hepatocytes prevented against liver I/R injury by suppressing cell death and inflammation. In vitro studies were performed using primary hepatocytes isolated from CregΔHep that were challenged by hypoxia/reoxygenation insult. These cells exhibited more cell death and inflammatory cytokines production similar to observations in vivo. Moreover, further molecular experiments showed that Creg suppressed mitogen-activated protein kinase (MAPK) signaling by inhibiting TAK1 (TGF-ß-activated kinase 1) phosphorylation. Inhibiting TAK1 by 5Z-7-ox or mutating the TAK1-binding domain of Creg abolished the protective role of Creg indicating that Creg binding to TAK1 was required for prevention against hepatic I/R injury. Conclusion: These data demonstrate that Creg prevents hepatocytes from liver I/R injury. The Creg-TAK1 interaction inhibited the phosphorylation of TAK1 and the activation of MAPK signaling, which protected against cell death and inflammation during hepatic I/R injury.

A nomogram based on a patient-reported outcomes measure: predicting the risk of readmission for patients with chronic heart failure.

BACKGROUND: Health-related quality of life, as evaluated by a patient-reported outcomes measure (PROM), is an important prognostic marker in patients with chronic heart failure. This study aimed to use PROM to establish an effective readmission nomogram for chronic heart failure. METHODS: Using a PROM as a measurement tool, we conducted a readmission nomogram for chronic heart failure on a prospective observational study comprising of 454 patients with chronic heart failure hospitalized between May 2017 to January 2020. A Concordance index and calibration curve were used to evaluate the discriminative ability and predictive accuracy of the nomogram. A bootstrap resampling method was used for internal validation of results. RESULTS: The median follow-up period in the study was 372 days. After a final COX regression analysis, the gender, income, health care, appetite-sleep, anxiety, depression, paranoia, support, and independence were identified and included in the nomogram. The nomogram showed moderate discrimination, with a concordance index of 0.737 (95% CI 0.673-0.800). The calibration curves for the probability of readmission for patients with chronic heart failure showed high consistency between the probability, as predicted, and the actual probability. CONCLUSIONS: This model offers a platform to assess the risk of readmission for different populations with CHF and can assist clinicians with personalized treatment recommendations.

MOF Decomposition and Introduction of Repairable Defects Using a Photodegradable Strut.

Photoswitchable components can modulate the properties of metal organic frameworks (MOFs); however, photolabile building blocks remain underexplored. A new strut NPDAC (2-nitro-1,4-phenylenediacetic acid) that undergoes photodecarboxylation has been prepared and incorporated into a MOF, using post-synthetic linker exchange (PSLE) from the structural analogue containing PDAC (p-phenylenediacetic acid). Irradiation of NPDAC-MOF leads to MOF decomposition and concomitant formation of amorphous material. In addition to complete linker exchange, MOFs containing a mixture of PDAC and NPDAC can be obtained through partial linker exchange. In NPDAC30-MOF, which contains approximately 30 % NPDAC, the MOF retains crystallinity after irradiation, but the MOF contains defect sites consistent with loss of decarboxylated NPDAC linkers. The defect sites can be repaired by exposure to additional PDAC or NPDAC linkers at a much faster rate than the initial exchange process. The photoremoval and replacement process may lead to a more general approach to customizable MOF structures.

On-demand guest release from MOF-5 sealed with nitrophenylacetic acid photocapping groups.

Recently, we demonstrated that triphenylacetic acid could be used to seal dye molecules within MOF-5, but guest release required the digestion of the framework by treatment with acid. We prepared the sterically bulky photocapping group [bis-(3-nitro-benzyl)-amino]-(3-nitro-phenyl)-acetic acid (PC1) that can prevent crystal violet dye diffusion from inside MOF-5 until removed by photolysis.