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Non-Volatile Memory (NVM) offers byte-addressability and persistency Because NVM can be plugged into memory and provide low latency, it offers a new opportunity to build new database systems with a single-layer storage design. A single-layer NVM-Native DataBase (N2DB) provides zero copy and log freedom. Hence, all data are stored in NVM and there is no extra data duplication and logging during execution. N2DB avoids complex data synchronization and logging overhead in the two-layer storage design of disk-oriented databases and in-memory databases. Garbage Collection (GC) is critical in such an NVM-based database because memory leaks on NVM are durable. Moreover, data recovery is equally essential to guarantee atomicity, consistency, isolation, and durability properties. Without logging, it is a great challenge for N2DB to restore data to a consistent state after crashes and recoveries. This paper presents the GC and data recovery mechanisms for N2DB. Evaluations show that the overall performance of N2DB is up to 3.6× higher than that of InnoDB. Enabling GC reduces performance by up to 10%, but saves storage space by up to 67%. Moreover, our data recovery requires only 0.2% of the time and half of the storage space of InnoDB.

Background Internal hospital infection is one of the major public health concerns worldwide. To investigate the etiological characteristics and risk factors of infections after colorectal cancer(CRC) surgery and the formulation of targeted infection control strategies. Methods This is a retrospective analysis of 1500 patients from colorectal cancer patients from General Surgery between March 2018 and March 2022，Anyang Tumor Hospital. Based on pathogen distribution and results of drug sensitivity testing, pattern of pathogens and drug resistance in infection in hospitalized patients with with colonic malignancy were analyzed. We conducted univariate and multivariate logistic regression analyses to determine the risk factors of infections that are associated with postoperative colorectal cancer. Results Infection cases were noted in 5.20% of all 1500 cases (78 of 1500 CRC patients). Drug resistance pattern showed that 88.89% of the implicated coagulase-negative staphylococci species and 40% of the implicated Acinetobacter species were meropenem-resistant. Considering all infection sites, age >60 years (OR=2.190, P=0.002), diabetes mellitus (OR=2.044, P=0.005), operation time >3h (OR=2.178, P=0.002) ), hospitalization time >10d (OR=1.793, P=0.017), parenteral nutrition (OR=2.797, P=0.000), indwelling catheter (OR=1.699, P=0.038), mechanical ventilation (OR=2.294, P=0.001) and the usage of drainage tube (OR=3.455, P=0.000) were risk factors at multivariate analysis. Conclusions: Post-operative infections may negatively affect surgical outcomes. Based on the greatest available evidence,important preoperative risk factors for postoperative colorectal cancer infections have been identified. Knowledge on risk factors may influence treatment and procedure-related decisions, and possibly reduce the postoperative infection rate.

To improve the accuracy of detection of arrhythmia in patients with atrial fibrillation (AF) and to enable the scientific management and assessment of AF, a comprehensive management tool for AF is proposed, which is helpful for medical staff to systematically evaluate and manage patients with AF.A professional view of atrial fibrillation (AF View) was designed to unify the statistical information of AF event, and display the statistical distribution data of AF events and trend data of other physiological parameters or characteristics such as heart rate, blood pressure and ST value during the patient monitoring period in a centralized manner. A multi-dimensional summary information was obtained from AF View. In addition, the monitoring period and monitoring parameters or characteristics in the AF View can be adjusted so as to obtain the summary information under different periods and parameters or characteristics, and get the condition of AF of the patient.Accurate detection and comprehensive management of AF were achieved.The application of AF comprehensive management proposed in this study is helpful for medical staff to know the condition of AF patients in real time and adjust the treatment plan in time.

Dysfunction of Tumour Suppressor Genes (TSGs) is a common feature in carcinogenesis. Epigenetic abnormalities including DNA hypermethylation or aberrant histone modifications in promoter regions have been described for interpreting TSG inactivation. However, in many instances, how TSGs are silenced in tumours are largely unknown. Given that miRNA with low expression in tumours is another recognized signature, we hypothesize that low expression of miRNA may reduce the activity of TSG related enhancers and further lead to inactivation of TSG during cancer development. Here, we reported that low expression of miRNA in cancer as a recognized signature leads to loss of function of TSGs in breast cancer. In 157 paired breast cancer and adjacent normal samples, tumour suppressor gene GPER1 and miR-339 are both downregulated in Luminal A/B and Triple Negative Breast Cancer subtypes. Mechanistic investigations revealed that miR-339 upregulates GPER1 expression in breast cancer cells by switching on the GPER1 enhancer, which can be blocked by enhancer deletion through the CRISPR/Cas9 system. Collectively, our findings reveal novel mechanistic insights into TSG dysfunction in cancer development, and provide evidence that reactivation of TSG by enhancer switching may be a promising alternative strategy for clinical breast cancer treatment.

Leaf senescence reduces the photosynthetic capacity of leaves, thus significantly affecting the growth, development, and yield formation of cotton. Melatonin (MT) is a multipotent substance proven to delay leaf senescence. However, its potential mechanism in delaying leaf senescence induced by abiotic stress remains unclear. This study aimed to explore the effect of MT on delaying drought-induced leaf senescence in cotton seedlings and to clarify its morphological and physiological mechanisms. Drought stress upregulated the leaf senescence marker genes, destroyed the photosystem, and led to excessive accumulation of reactive oxygen species (ROS, e.g., H2O2 and O2−), thus accelerating leaf senescence. However, leaf senescence was significantly delayed when 100 μM MT was sprayed on the leaves of the cotton seedlings. The delay was embodied by the increased chlorophyll content, photosynthetic capacity, and antioxidant enzyme activities, as well as decreased H2O2, O2−, and abscisic acid (ABA) contents by 34.44%, 37.68%, and 29.32%, respectively. MT significantly down-regulated chlorophyll degradation-related genes and senescence marker genes (GhNAC12 and GhWRKY27/71). In addition, MT reduced the chloroplast damage caused by drought-induced leaf senescence and maintained the integrity of the chloroplast lamellae structure under drought stress. The findings of this study collectively suggest that MT can effectively enhance the antioxidant enzyme system, improve photosynthetic efficiency, reduce chlorophyll degradation and ROS accumulation, and inhibit ABA synthesis, thereby delaying drought-induced leaf senescence in cotton.

SummaryBackgroundWe previously found that human identical sequences (HIS) of SARS-CoV-2 promote the clinical progression of COVID-19 by upregulating hyaluronan (HA). As one of the drugs for hyaluronan inhibition, hymecromone was chosen for evaluating its therapeutic effects on COVID-19.MethodsELISA was performed to detect the level of HA in COVID-19 patients. We first analyzed the correlation between the level of plasma HA and clinical parameters (lymphocytes, C-reactive protein, D-dimer, and fibrinogen). We then assessed the correlation between the plasma HA level and pulmonary lesions, which were quantified by using artificial intelligence based on chest CT scans, including ground-glass opacity (GGO) and consolidation. Furthermore, we assessed the effect of hyaluronan treatment on the formation of pulmonary lesions in mice and evaluated the role of hymecromone on hyaluronan production in cultured cells. Finally, 94 of the 144 confirmed COVID-19 patients received oral hymecromone in addition to standard care, whereas the others with only standard care were treated as control. Abnormal serological markers in two groups were selected to determine the efficacy of hymecromone.FindingsPlasma HA was closely relevant to clinical parameters, including lymphocytes (n = 158;r= -0.50;P< 0.0001), CRP (n = 156;r= 0.55;P< 0.0001), D-dimer (n = 154;r= 0.38;P< 0.0001), and fibrinogen (n = 152;r= 0.37;P< 0.0001), as well as the mass (n = 120;r= 0.30;P= 0.0008) and volume (n = 120;r= 0.30;P= 0.0009) of GGO, the mass (n = 120;r= 0.34;P= 0.0002) and volume (n = 120;r= 0.35;P< 0.0001) of consolidation. Mice experiment further verified that hyaluronan could cause pulmonary lesions directly. Hymecromone remarkably reduced HA via downregulatingHAS2/HAS3expression. Accordingly, the number of lymphocytes recovered more quickly as the fold change of lymphocytes per day was higher in hymecromone-treated patients (n = 8) than the control group (n = 5) (P< 0.01). Moreover, 89% patients with hymecromone treatment had pulmonary lesion absorption while only 42% patients in control group had pulmonary lesion absorption (P< 0.0001).InterpretationHyaluronan is closely correlated with COVID-19 progression and can serve as a plasma biomarker. As a promising treatment for COVID-19, hymecromone deserves our further efforts to determine its effect in a larger cohort of COVID-19 patients.FundingNational Key R&D Program of China, Major Special Projects of Basic Research of Shanghai Science and Technology Commission, and Shanghai Science and Technology Innovation Action Plan, Medical Innovation Research Special Project, Research of early identification and warning of acute respiratory infectious diseases.Research in contextEvidence before this studyOur previous study revealed that human identical sequences (HIS) of SARS-CoV-2 promotes hyaluronan production in COVID-19 patients. We searched PubMed for studies associated with hyaluronan and COVID-19 using the search terms (“hyaluronan” OR “hyaluronic acid” OR “hymecromone”) AND (“COVID-19” OR “SARS-CoV-2”) without any language restrictions from inception up to May 27, 2021. The studies showed that hyaluronan was present in lung alveoli of severe COVID-19 and SARS-CoV-2 infection-induced hyaluronan. Meanwhile, one report showed that hyaluronan was related to the severity of COVID-19 based on the research of 32 COVID-19 cases. As the inhibitor of hyaluronan synthesis, hymecromone is already an approved drug for patients with biliary spasms in Europe and Asia. However, it is unclear whether hymecromone is an effective therapeutic drug for COVID-19.Added value of this studyWe found significant correlations between hyaluronan and clinical parameters (lymphocytes, C-reaction protein, D-dimer, fibrinogen, and pulmonary lesions) in COVID-19 patients. Hyaluronan is the essential material for the induction of ground-glass opacity formation in the lung of COVID-19 patients. The lymphopenia of COVID-19 may be due to T cell exhaustion caused by hyaluronan. Notably, we demonstrated that hymecromone could accelerate the recovery of lymphopenia and pulmonary lesion absorption of COVID-19 in clinical sets.Implications of all the available evidenceOur finding shows that hymecromone could significantly improve the clinical manifestations, especially in severe COVID-19 patients. Reducing hyaluronan using specific drugs could be a promising and alternative therapeutic strategy for COVID-19, especially for the treatment of patients with lymphopenia and pulmonary lesion.x

Using a highly specific “lock and key” fluorescent Cys probe, we confirmed that targeting Cys metabolism to deplete intracellular Cys is a more potent strategy to sensitize cancer cells to chemotherapies., To probe the regulatory roles of cysteine (Cys) in cancer cell survival, a highly selective and sensitive fluorescent Cys probe SiR was developed by employing a novel “lock and key” strategy, which allows Cys to be detected without any interference or probe consumption caused by the intracellular high concentration of glutathione (GSH). Using SiR, we confirmed that inhibiting cystine (Cys2) transporter system xc– to deplete intracellular Cys is more efficient than inhibiting glutamate–cysteine ligase GCL to deplete intracellular GSH for sensitizing cancer cells to chemotherapy. Moreover, with the probe, a possible self-protection mechanism of cancer cells was indicated: when extracellular Cys sources are blocked, cancer cells could still survive by multidrug resistance protein transporter (Mrp1)-mediated export of intracellular GSH/GSSG as sources to supply intracellular Cys for resisting detrimental oxidative stress. Based on this finding, we further confirmed that abrogating the self-protection mechanism is an even more efficient strategy for sensitizing cancer cells to chemotherapy.

In order to ameliorate alarm fatigue, three optimization strategies are proposed to reduce false alarms and repetitive non-actionable true alarms. The four-lead arrhythmia analysis, multi-parameter fusion and intelligent threshold reminder are adopted and evaluated in multi-center clinic study. The four-lead arrhythmia analysis algorithm includes lead optimization, beat matching, detection and classification combinations. The multi-parameter fusion algorithm aggregates the information obtained from ECG, SpO 2 and IBP wave signals. The intelligent threshold reminder can help medical staff to adjust and recover alarm limits appropriately. The results show that more than 50% of false alarms can be reduced by the four-lead analysis and the multi-parameter fusion analysis. In some specific occasions, the intelligent threshold reminder can reduce repetitive non-actionable true alarms significantly. And no further false-negative events are generated after using the strategies in our experiments. We demonstrate that increasing the dimensionality of parametric analysis and controlling the alarm limits is beneficial for reducing alarm fatigue in intensive care units.

Ballistocardiography (BCG), the noninvasive measurement of the reaction forces of the body to the cardiac ejection of blood, is one of few methods available for unobtrusively assessing the mechanical aspects of cardiovascular health outside clinical settings. In this study, two sizes of piezoelectric film sensors were installed into the seat cushion of a chair and the foot insole, respectively, to acquire local BCG signals in sitting and standing positions. The design and engineering implementation of the signal processing circuit and data transmission system are discussed below. Although wearable BCG measurement devices have been extensively researched to date, to the authors’ knowledge, they have never been tested in regards to power consumption and electrostatic discharge (ESD) immunity. In this work, comprehensive experiments were conducted to show the low power consumption and high reliability of the proposed system. The shapes and the amplitudes of measured signals were examined in detail. The results suggest that the proposed system can feasibly and reliably be used to continuously record and evaluate cardiovascular changes occurring throughout an individual’s daily life.