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The high mortality rate in sepsis patients is related to sepsis-associated liver injury (SALI). We sought to develop an accurate forecasting nomogram to estimate individual 90-day mortality in SALI patients. Data from 34,329 patients were extracted from the public Medical Information Mart for Intensive Care (MIMIC-IV) database. SALI was defined by total bilirubin (TBIL) > 2 mg/dL and the occurrence of an international normalized ratio (INR) > 1.5 in the presence of sepsis. Logistic regression analysis was performed to establish a prediction model called the nomogram based on the training set (n = 727), which was subsequently subjected to internal validation. Multivariate logistic regression analysis showed that SALI was an independent risk factor for mortality in patients with sepsis. The Kaplan‒Meier curves for 90-day survival were different between the SALI and non-SALI groups after propensity score matching (PSM) (log rank: P < 0.001 versus P = 0.038), regardless of PSM balance. The nomogram demonstrated better discrimination than the sequential organ failure assessment (SOFA) score, logistic organ dysfunction system (LODS) score, simplified acute physiology II (SAPS II) score, and Albumin–Bilirubin (ALBI) score in the training and validation sets, with areas under the receiver operating characteristic curve (AUROC) of 0.778 (95% CI 0.730–0.799, P < 0.001) and 0.804 (95% CI 0.713–0.820, P < 0.001), respectively. The calibration plot showed that the nomogram was sufficiently successful to predict the probability of 90-day mortality in both groups. The DCA of the nomogram demonstrated a higher net benefit regarding clinical usefulness than SOFA, LODS, SAPSII, and ALBI scores in the two groups. The nomogram performs exceptionally well in predicting the 90-day mortality rate in SALI patients, which can be used to assess the prognosis of patients with SALI and may assist in guiding clinical practice to enhance patient outcomes.

During labor, a variety of coordinated physiological and biochemical events cause the myometrium to transition from a quiescent to contractile state; the molecular mechanisms responsible for this transition, however, remain unclear. To better understand this transition at a molecular level, the global transcriptome and proteome of human myometrial samples in labor and those not in labor were investigated through RNA sequencing (RNA-seq) and quantitative liquid chromatography–tandem mass spectrometry (LC-MS/MS) via data-independent acquisition (DIA) and parallel reaction monitoring (PRM) methods. Furthermore, an integrated proteotranscriptomic analysis was performed to explore biological processes and pathway alterations during labor; this analysis identified 1,626 differentially expressed mRNAs (1,101 upregulated, 525 downregulated) and 135 differentially expressed proteins (97 upregulated, 38 downregulated) in myometrium between nonlabor and in labor groups. The comprehensive results of these analyses showed that the upregulated mRNAs and proteins increased inflammation under hypoxia stress in the myometrium under labor, and related proteins and cytokines were validated by PRM and Luminex assays. Our study confirmed the biological process of inflammation and hypoxia in laboring myometrium at the transcriptome and proteome levels and provided recourse to discover new molecular and biological changes during labor.

Regular uterine contractions were the common characteristics in spontaneous labor at term or PTL. [...]effective decrease or suppression of myometrial contraction could prevent preterm delivery. Combined with bioinformatics and in vitro experiments, miR-206 directly targeted the 3΄ UTR of GJA1 and decreased its expression, confirming GJA1 as a target of miR-206. Since miR-206 suppresses the expression of contraction-associated protein GJA1, we tried to determine the therapeutic role of miR-206 in RU486-induced PTL mice model by injecting RU486 or miR-206 agomir. Specifically, on day 8, no significant differences were observed in the timing of eye-opening, hair growth, and nail and tooth eruptions of the offspring in the two groups [Supplementary Figure 2G, http://links.lww.com/CM9/B758]. Under the condition of the hypoxia-reoxygenation cycle, two indexes of the myometrial contractility, the area under the curve (AUC) and amplitude of contractions, in the control and miR-NC group gradually increased at each hypoxia-reoxygenation cycle.

Cancer stem cells (CSCs) are predicted to be critical drivers of tumor progression due to their “stemness”, but the molecular mechanism of CSCs in regulating metastasis remains to be elucidated. Epithelial‐mesenchymal transition (EMT), hypoxia‐inducible factor (HIF)‐1α, and miR‐21, all of which contribute to cell migration for metastasis, are interrelated with CSCs. In the present study, third‐sphere forming (3‐S) CSC‐like cells, which showed elevated CSC surface markers (ALDH1+ and CD44+/CD24−/low) and sphereforming capacity as well as migration and invasion capacities, were cultured and isolated from breast cancer MCF‐7 parental cells, to evaluate the role of miR‐21 in regulating the CSC‐like cell biological features, especially EMT. EMT, which was assessed by overexpression of mesenchymal cell markers (N‐cadherin, Vimentin, alpha‐smooth muscle actin [α‐SMA]) and suppression of epithelial cell marker (E‐cadherin), was induced in 3‐S CSC‐like cells. Moreover, both of HIF‐1α and miR‐21 were upregulated in the CSC‐like cells. Interestingly, antagonism of miR‐21 by antagomir led to reversal of EMT, downexpression of HIF‐1α, as well as suppression of invasion and migration, which indicates a key role of miR‐21 involved in regulate CSC‐associated features. In conclusion, we demonstrated that the formation of CSC‐like cells undergoing process of EMT‐like associated with overexpression of HIF‐1α, both of which are regulated by miR‐21. (Cancer Sci 2012; 103: 1058–1064)

Our previous studies have shown that the maternal hyperinflammatory response in pre-eclampsia lowered the eclampsia-like seizure threshold. Cyclosporin A (CsA), which is an effective immunosuppressant, could attenuate the inflammatory responses in LPS-induced pre-eclampsia rats. Here, we hypothesized that CsA may ameliorate seizure severity through reducing systemic inflammation in pre-eclampsia/eclampsia. In the current study, the effects of CsA on pre-eclampsia manifestation, eclampsia-like seizure activities and systemic inflammation were examined in a pre-eclampsia model. Pregnant rats were given an intraperitoneal injection of the epileptogenic drug pentylenetetrazol (PTZ) following a tail vein injection of lipopolysaccharide to establish the eclampsia-like seizure model. CsA (5 mg/kg) was administered intravenously through the tail after LPS infusion. Mean systolic blood pressure and proteinuria in pre-eclampsia were detected. After PTZ injection, seizure activity was assessed, inflammatory responses were determined and pregnancy outcomes were analyzed. The results showed that CsA treatment significantly decreased blood pressure and proteinuria and increased the fetal and placental weight (P < 0.01). Meanwhile, CsA treatment significantly reduced serum IL-1β, TNF-α, and IL-17 levels (P < 0.01), decreased the seizure scores and prolonged the latency to seizure (P < 0.01). CsA effectively attenuated pre-eclampsia manifestation and eclampsia-like seizure severity. In addition, CsA treatment significantly reduced the inflammatory cytokine levels and improved pregnancy outcomes following eclampsia-like seizures. The decreased inflammatory cytokines in pre-eclampsia are coincident with attenuated pre-eclampsia manifestation after CsA treatment, suggesting that CsA treatment might decrease the eclampsia-like seizure severity through decreasing systemic inflammation in pre-eclasmpsia/eclampsia.

Coenzyme Q10 (CoQ10) exists in two forms, an oxidized form and a reduced form. Ubiquinol is the fully reduced form of CoQ10. Compared to the oxidized form, ubiquinol has a much higher biological absorption and better therapeutic effect. However, ubiquinol has an important stability problem which hampers its storage and formulation. It can be easily transformed into its oxidized form—ubiquinone—even at low temperature. In this work, we designed, synthesized, and characterized a new cocrystal of ubiquinol with vitamin B3 nicotinamide (UQ-NC). Compared to the marketed ubiquinol form, the cocrystal exhibited an excellent stability, improved dissolution properties, and higher bioavailability. The cocrystal remained stable for a long period, even when stored under stressed conditions. In the dissolution experiments, the cocrystal generated 12.6 (in SIF) and 38.3 (in SGF) times greater maximum ubiquinol concentrations above that of the marketed form. In addition, in the PK studies, compared to the marketed form, the cocrystal exhibited a 2.2 times greater maximum total coenzyme Q10 concentration and a 4.5 times greater AUC than that of the marketed form.

Objective This study was performed to investigate the predilection sites of acute vestibular syndrome (AVS) and episodic vestibular syndrome (EVS) caused by acute infarcts. Methods This retrospective cohort study was performed at a stroke center in a tertiary teaching hospital. We diagnosed patients with AVS/EVS caused by acute ischemic stroke using diffusion-weighted imaging (DWI) and magnetic resonance angiography. Results Among all patients with AVS/EVS, 68 had DWI-positive ischemic events and 113 had DWI-negative ischemic events. Of the 68 patients with positive DWI findings, 42.6% had acute infarcts in the anterior circulation and 41.2% had acute infarcts in the posterior circulation. The main stroke predilection sites were the insular cortex (22.1%) and posterior thalamus (11.8%). Large vessel stenosis/occlusion (odds ratio, 0.12; 95% confidence interval, 0.04–0.36) and focal neurological symptoms/signs (odds ratio, 0.27; 95% confidence interval, 0.10–0.72) were significantly associated with the risk of AVS/EVS in patients with acute ischemic stroke. Conclusions The main predilection sites of AVS/EVS caused by ischemic stroke are the insular cortex and posterior thalamus. The risk of AVS/EVS is associated with large vessel stenosis and focal symptoms.

To reduce hydrogen consumption by hydrogen fuel cell vehicles (HFCVs), an adaptive power-following control strategy based on gated recurrent unit (GRU) neural network operating condition recognition was proposed. The future vehicle speed was predicted based on a GRU neural network and a driving cycle condition recognition model was established based on k-means cluster analysis. By predicting the speed over a specific time horizon, feature parameters were extracted and compared with those of typical operating conditions to determine the categories of the parameters, thus the adjustment of the power-following control strategy was realized. The simulation results indicate that the proposed control strategy reduces hydrogen consumption by hydrogen fuel cell vehicles (HFCVs) by 16.6% with the CLTC-P driving cycle and by 4.7% with the NEDC driving cycle, compared to the conventional power-following control strategy. Additionally, the proposed strategy effectively stabilizes the battery’s state of charge (SOC).

In spinal degenerative disease, an injectable liquid hydrogel can fill in defect entirely, lessen the danger of implant relocation and following loss of disc height, minimizing the operative trauma. Here, we propose an injectable in-situ chemically cross-linked hydrogel by a two-component reaction of liquid silk fibroin with liquid polyurethane at physiological temperature conditions. Confined compression tests and fatigue tests were reported to assess physical properties of the hydrogel. Impact of different diameter on the biomechanical behaviours was tested to evaluate the clinical potentiality of the hydrogel for replacing nucleus pulposus. Degradation behaviours in different solutions and animal experiments were also investigated to examine the tissue biocompatibility of the hydrogel. The hydrogel modulus was affected by the hydrogel geometrical (diameter) parameters. SF/PU composite hydrogel can survive a million cycles, unconstrained fatigue resistance. More importantly, in vivo biocompatibility using New Zealand white rabbits, showed good biocompatibility over a three-month period in culture. Particularly, they showed the significant clinical merit of providing stronger axial compressive stiffness on confined compression test. Based on the outcomes of the present research, the SF/PU composite hydrogel may provide significant advantages for use in future clinical application in replacing nucleus pulposus field.

Osteosarcoma (OS) is the common primary bone cancer that affects mostly children and young adults. To augment the standard-of-care chemotherapy, we examined the possibility of protein-based therapy using mesenchymal stem cells (MSCs)-derived proteomes and OS-elevated proteins. While a conditioned medium (CM), collected from MSCs, did not present tumor-suppressing ability, the activation of PKA converted MSCs into induced tumor-suppressing cells (iTSCs). In a mouse model, the direct and hydrogel-assisted administration of CM inhibited tumor-induced bone destruction, and its effect was additive with cisplatin. CM was enriched with proteins such as calreticulin, which acted as an extracellular tumor suppressor by interacting with CD47. Notably, the level of CALR transcripts was elevated in OS tissues, together with other tumor-suppressing proteins, including histone H4, and PCOLCE. PCOLCE acted as an extracellular tumor-suppressing protein by interacting with amyloid precursor protein, a prognostic OS marker with poor survival. The results supported the possibility of employing a paradoxical strategy of utilizing OS transcriptomes for the treatment of OS.