Different physiopsychological changes between AMSsusceptible and AMS-resistant pre-selected Antarctic expeditioners in Tibet

Through dynamically monitoring changes of acute mountain sickness (AMS) occurrences, cardiopulmonary function and mood states from Shanghai (4 m) to Lhasa (3650 m) and Yambajan (4300 m), Tibet, we obtained physiopsychological data of the 37th Chinese Antarctic pre-selected expeditioners for Kunlun Station. Through analyzing different physiopsychological changes between AMS-susceptible (AMS-S) and AMS-resistant (AMS-R) expeditioners, we would explore indicators to screen hypoxia-susceptible expeditioners. According to AMS occurrences evaluated by Lake Louise Score (LLS) in Yambajan, we divided the expeditioners (n=24, 31.92±5.76 a) into AMS-S and AMS-R groups. Using a series of medical instruments and questionnaires, we monitored their cardiopulmonary function and mood states, and analyzed the differences of physiopsychological parameters between AMS-S and AMS-R groups. Compared with Shanghai, when expeditioners arrived in Yambajan, in both AMS-S and AMS-R groups, oxygen saturation (SpO2) significantly decreased, and blood pressure significantly increased (P<0.05). As for electrocardiogram (ECG), interval from the beginning to the end of QRS complex wave (QRS), interval from the beginning of QRS complex wave to the end of T wave (QT), interval between 2 adjacent P waves (PP) and interval between 2 adjacent R waves (RR) significantly decreased, heart rate (HR) and HR-corrected QT interval (QTc) significantly increased (P<0.05). Cardiac contractility and pumping function significantly decreased, systemic vascular resistance significantly increased (P<0.05). Pulmonary airway patency significantly increased (P<0.05). Compared with AMS-R group, AMS-S group showed significantly lower SpO2 and higher stroke volume variation (SVV) in Shanghai, however, significantly lower maximal expiratory flow at 75% of forced vital capacity (MEF75), higher levels of anxiety, fatigue and confusion in Yambajan (P<0.05). In conclusion, when expeditioners arrived at 4300 m, their cardiopulmonary function and mood states changed significantly. SpO2, SVV, MEF75, anxiety, fatigue and confusion maybe could be used as clues for screening hypoxia-susceptible individuals

Molecular dynamics simulation of CO2 dissolution-diffusion in multi-component crude oil

In order to study the dissolution-diffusion process and mechanism of CO2 in multi-component crude oil, a model of multi-component crude oil system with octane as the main component and 16 other alkanes as a compound was constructed by using molecular dynamics simulation method. We estimated the CO2 density distribution in crude oil model and the shift in crude oil model volume change. We then investigated the microscopic influence mechanism of CO2 dissolution-diffusion on the volume expansion of crude oil by simulating the action of CO2 dissolution-diffusion in the multi-component crude oil model. Based on the variation law of mean square displacement between crude oil molecules, the dissolution and diffusion coefficients of CO2 were predicted, and the influence of CO2 dissolution-diffusion on crude oil mobility was analyzed. It is found that temperature intensifies the molecular thermal motion and increases the voids between alkane molecules, which promotes the dissolution of CO2 and encourages CO2 molecules to transmit, making the crude oil expand and viscosity decrease, and improving the flow ability of crude oil; with the enhancement of given pressure, the potential energy difference between the inside and outside of the crude oil model becomes larger, and the voids between alkane molecules become larger, which is favorable to the dissolution of CO2. Nevertheless, the action of CO2 molecules’ diffusing in the crude oil sample is significantly limited or even tends to zero, besides, the mobility of crude oil is affected due to the advance of external pressure. The mechanism of CO2 dissolution and diffusion in multi-component crude oil is revealed at the microscopic level, and provides theoretical guidance for the development of CO2 flooding

Machine-Learning-Enabled Virtual Screening for Inhibitors of Lysine-Specific Histone Demethylase 1

A machine learning approach has been applied to virtual screening for lysine specific demethylase 1 (LSD1) inhibitors. LSD1 is an important anti-cancer target. Machine learning models to predict activity were constructed using Morgan molecular fingerprints. The dataset, consisting of 931 molecules with LSD1 inhibition activity, was obtained from the ChEMBL database. An evaluation of several candidate algorithms on the main dataset revealed that the support vector regressor gave the best model, with a coefficient of determination (R2) of 0.703. Virtual screening, using this model, identified five predicted potent inhibitors from the ZINC database comprising more than 300,000 molecules. The virtual screening recovered a known inhibitor, RN1, as well as four compounds where activity against LSD1 had not previously been suggested. Thus, we performed a machine-learning-enabled virtual screening of LSD1 inhibitors using only the structural information of the molecules

MiR-770-5p inhibits cisplatin chemoresistance in human ovarian cancer by targeting ERCC2

In this study, we examined the role of the miRNA miR-770-5p in cisplatin chemotherapy resistance in ovarian cancer (OVC) patients. miR-770-5p expression was reduced in platinum-resistant patients. Using a 6.128-fold in expression as the cutoff value, miR-770-5p expression served as a prognostic biomarker and predicted the response to cisplatin treatment and survival among OVC patients. Overexpression of miR-770-5p in vitro reduced survival in chemoresistant cell lines after cisplatin treatment. ERCC2, a target gene of miR-770-5p that participates in the NER system, was negatively regulated by miR-770-5p. siRNA-mediated silencing of ERCC2 reversed the inhibition of apoptosis resulting from miR-770-5p downreglation in A2780S cells. A comet assay confirmed that this restoration of cisplatin chemosensitivity was due to the inhibition of DNA repair. These findings suggest that endogenous miR-770-5p may function as an anti-oncogene and promote chemosensitivity in OVC, at least in part by downregulating ERCC2. miR-770-5p may therefore be a useful biomarker for predicting chemosensitivity to cisplatin in OVC patients and improve the selection of effective, more personalized, treatment strategies

Evaluating the efficiency of a nomogram based on the data of neurosurgical intensive care unit patients to predict pulmonary infection of multidrug-resistant Acinetobacter baumannii

BackgroundPulmonary infection caused by multidrug-resistant Acinetobacter baumannii (MDR-AB) is a common and serious complication after brain injury. There are no definitive methods for its prediction and it is usually accompanied by a poor prognosis. This study aimed to construct and evaluate a nomogram based on patient data from the neurosurgical intensive care unit (NSICU) to predict the probability of MDR-AB pulmonary infection.MethodsIn this study, we retrospectively collected patient clinical profiles, early laboratory test results, and doctors’ prescriptions (66 variables). Univariate and backward stepwise regression analyses were used to screen the variables to identify predictors, and a nomogram was built in the primary cohort based on the results of a logistic regression model. Discriminatory validity, calibration validity, and clinical utility were evaluated using validation cohort 1 based on receiver operating characteristic curves, calibration curves, and decision curve analysis (DCA). For external validation based on predictors, we prospectively collected information from patients as validation cohort 2.ResultsAmong 2115 patients admitted to the NSICU between December 1, 2019, and December 31, 2021, 217 were eligible for the study, including 102 patients with MDR-AB infections (102 cases) and 115 patients with other bacterial infections (115 cases). We randomly categorized the patients into the primary cohort (70%, N=152) and validation cohort 1 (30%, N=65). Validation cohort 2 consisted of 24 patients admitted to the NSICU between January 1, 2022, and March 31, 2022, whose clinical information was prospectively collected according to predictors. The nomogram, consisting of only six predictors (age, NSICU stay, Glasgow Coma Scale, meropenem, neutrophil to lymphocyte ratio, platelet to lymphocyte ratio), had significantly high sensitivity and specificity (primary cohort AUC=0.913, validation cohort 1 AUC=0.830, validation cohort 2 AUC=0.889) for early identification of infection and had great calibration (validation cohort 1,2 P=0.3801, 0.6274). DCA confirmed that the nomogram is clinically useful.ConclusionOur nomogram could help clinicians make early predictions regarding the onset of pulmonary infection caused by MDR-AB and implement targeted interventions

Decoding the spermatogonial stem cell niche under physiological and recovery conditions in adult mice and humans

The intricate interaction between spermatogonial stem cell (SSC) and testicular niche is essential for maintaining SSC homeostasis; however, this interaction remains largely uncharacterized. In this study, to characterize the underlying signaling pathways and related paracrine factors, we delineated the intercellular interactions between SSC and niche cell in both adult mice and humans under physiological conditions and dissected the niche-derived regulation of SSC maintenance under recovery conditions, thus uncovering the essential role of C-C motif chemokine ligand 24 and insulin-like growth factor binding protein 7 in SSC maintenance. We also established the clinical relevance of specific paracrine factors in human fertility. Collectively, our work on decoding the adult SSC niche serves as a valuable reference for future studies on the aetiology, diagnosis, and treatment of male infertility.</p

BML-111 Reduces Neuroinflammation and Cognitive Impairment in Mice With Sepsis via the SIRT1/NF-κB Signaling Pathway

Sepsis is a life-threatening state of organ dysfunction caused by infection and which can induce severe neurological disorders that lead to neuroinflammation and cognitive impairment. Inflammation has been reported to cause neuronal apoptosis in sepsis, which can finally lead to cognitive impairment. Previous studies have suggested that BML-111 can exhibit anti-inflammatory and proresolution activities. Additionally, silent information regulator 1 (SIRT1) can inhibit the NF-κB signaling pathway in an inflammation state. However, the role of the SIRT1/NF-κB signaling pathway in the protective effects of BML-111 against sepsis-induced neuroinflammation and cognitive impairment remains unclear. This study aimed to determine the effects of BML-111 on neuroinflammation and cognitive impairment induced by sepsis. Male C57BL/6J mice were subjected to cecal ligation and puncture (CLP) or a sham operation. BML-111 was administered via intracerebroventricular injection (0.1 mg/kg) immediately after CLP. Boc-2 (50 μg/kg) was administered intracerebroventricularly 30 min before CLP, and EX527 (10 μg) was administered every 2 days for a total of three times before CLP, also intracerebroventricularly. Some of the surviving mice underwent open-field, novel-object-recognition, and fear-conditioning behavioral tests at 7 days after surgery. Some of the other surviving mice were killed at 24 h after surgery to assess synaptic damage (PSD95 and Synapsin1), markers of inflammation [tumor necrosis factor alpha (TNF-α) and interleukin (IL)-1β], cytoplasmic p65, nuclear p65, Ac- NF-κB and SIRT1. At 48 h after CLP, TUNEL and glia-activation by immunofluorescence investigations were performed on a separate cohort of surviving animals. The results suggested that sepsis resulted in cognitive impairment, which was accompanied by the decreased the expression of PSD95 and Synapsin1, increased amount of TUNEL-positive cells and the activation of glias, increased production of TNF-α and IL-1β, increased expression of nuclear p65, Ac- NF-κB, and decreased expression of SIRT1 and cytoplasmic p65. It is especially notable that these abnormalities could be reduced by BML-111 treatment. EX527, an SIRT1 inhibitor, abolished the effects of BML-111. These results demonstrate that BML-111 can reduce the neuroinflammation and cognitive impairment induced by sepsis via SIRT/NF-κB signaling pathway