Talaromyces marneffei endocarditis initially detected by Next Generation Sequencing: A case report.

BACKGROUND: Talaromyces marneffei (T. marneffei) is a thermal dimorphic fungus, which can cause lung or blood stream infection in patients, often life-threatening. However, endocarditis caused by T. marneffei has not been reported. For elderly patients with implanted cardiac devices or artificial valves, the prevention and treatment of infective endocarditis should not be ignored. METHODS: This is a descriptive study of a T. marneffei endocarditis by joint detection of cardiac ultrasound examination, peripheral blood DNA metagenomics Next Generation Sequencing (mNGS), and in vitro culture. RESULTS: We describe an 80-year-old female patient with an unusual infection of T. marneffei endocarditis. After intravenous drip of 0.2 g voriconazole twice a day for antifungal treatment, the patient showed no signs of improvement and their family refused further treatment. CONCLUSION: Infective endocarditis is becoming more and more common in the elderly due to the widely use of invasive surgical procedures and implantation of intracardiac devices. The diagnosis and treatment of T. marneffei endocarditis is challenging because of its rarity. Here, we discussed a case of T. marneffei endocarditis, and emphasized the role of mNGS in early diagnosis, which is of great significance for treatment and survival rate of patients.

Rational and design of prophylactic cranial irradiation (PCI) and brain MRI surveillance versus brain MRI surveillance alone in patients with limited-stage small cell lung cancer achieving complete remission (CR) of tumor after chemoradiotherapy: a multicenter prospective randomized study.

BACKGROUND: Prophylactic cranial irradiation (PCI) is part of standard care in limited-stage small cell lung cancer (SCLC) at present. As evidence from retrospective studies increases, the benefits of PCI for limited-stage SCLC are being challenged. METHODS: A multicenter, prospective, randomized controlled study was designed. The key inclusion criteria were: histologically or cytologically confirmed small cell carcinoma, age ≥ 18 years, KPS ≥ 80, limited-stage is defined as tumor confined to one side of the chest including ipsilateral hilar, bilateral mediastinum and supraclavicular lymph nodes, patients have received definitive thoracic radiotherapy (regardless of the dose-fractionation of radiotherapy used) and chemotherapy, evaluated as complete remission (CR) of tumor 4-6 weeks after the completion of chemo-radiotherapy. Eligible patients will be randomly assigned to two arms: (1) PCI and brain MRI surveillance arm, receiving PCI (2.5 Gy qd to a total dose of 25 Gy in two weeks) followed by brain MRI surveillance once every three months for two years; (2) brain MRI surveillance alone arm, undergoing brain MRI surveillance once every three months for two years. The primary objective is to compare the 2-year brain metastasis-free survival (BMFS) rates between the two arms. Secondary objectives include 2-year overall survival (OS) rates, intra-cranial failure patterns, 2-year progression-free survival rates and neurotoxicity. In case of brain metastasis (BM) detect during follow-up, stereotactic radiosurgery (SRS) will be recommended if patients meet the eligibility criteria. DISCUSSION: Based on our post-hoc analysis of a prospective study, we hypothesize that in limited-stage SCLC patients with CR after definitive chemoradiotherapy, and ruling out of BM by MRI, it would be feasible to use brain MRI surveillance and omit PCI in these patients. If BM is detected during follow-up, treatment with SRS or whole brain radiotherapy does not appear to have a detrimental effect on OS. Additionally, this approach may reduce potential neurotoxicity associated with PCI.

Neuroprotective Effects of CXCR2 Antagonist SB332235 on Traumatic Brain Injury Through Suppressing NLRP3 Inflammasome.

The inflammatory process mediated by nucleotide-binding oligomerization domain (NOD)-like receptor family pyrin domain comprising 3 (NLRP3) inflammasome plays a predominant role in the neurological dysfunction following traumatic brain injury (TBI). SB332235, a highly selective antagonist of chemokine receptor 2 (CXCR2), has been demonstrated to exhibit anti-inflammatory properties and improve neurological outcomes in the central nervous system. We aimed to determine the neuroprotective effects of SB332235 in the acute phase after TBI in mice and to elucidate its underlying mechanisms. Male C57BL/6J animals were exposed to a controlled cortical impact, then received 4 doses of SB332235, with the first dose administered at 30 min after TBI, followed by additional doses at 6, 24, and 30 h. Neurological defects were assessed by the modified neurological severity score, while the motor function was evaluated using the beam balance and open field tests. Cognitive performance was evaluated using the novel object recognition test. Brain tissues were collected for pathological, Western blot, and immunohistochemical analyses. The results showed that SB332235 significantly ameliorated TBI-induced deficits, including motor and cognitive impairments. SB332235 administration suppressed expression of both CXCL1 and CXCR2 in TBI. Moreover, SB332235 substantially mitigated the augmented expression levels and activation of the NLRP3 inflammasome within the peri-contusional cortex induced by TBI. This was accompanied by the blocking of subsequent production of pro-inflammatory cytokines. Additionally, SB332235 hindered microglial activity induced by TBI. These findings confirmed the neuroprotective effects of SB332235 against TBI, and the involved mechanisms were in part due to the suppression of NLRP3 inflammasome activity. This study suggests that SB332235 may act as an anti-inflammatory agent to improve functional outcomes in brain injury when applied clinically.

Pathological prognostic factors of rectal cancer based on diffusion-weighted imaging, intravoxel incoherent motion, and diffusion kurtosis imaging.

OBJECTIVES: To explore diffusion-weighted imaging (DWI), intravoxel incoherent motion (IVIM), and diffusion kurtosis imaging (DKI) for assessing pathological prognostic factors in patients with rectal cancer. MATERIALS AND METHODS: A total of 162 patients (105 males; mean age of 61.8 ± 13.1 years old) scheduled to undergo radical surgery were enrolled in this prospective study. The pathological prognostic factors included histological differentiation, lymph node metastasis (LNM), and extramural vascular invasion (EMVI). The DWI, IVIM, and DKI parameters were obtained and correlated with prognostic factors using univariable and multivariable logistic regression. Their assessment value was evaluated using receiver operating characteristic (ROC) curve analysis. RESULTS: Multivariable logistic regression analyses showed that higher mean kurtosis (MK) (odds ratio (OR) = 194.931, p < 0.001) and lower apparent diffusion coefficient (ADC) (OR = 0.077, p = 0.025) were independently associated with poorer differentiation tumors. Higher perfusion fraction (f) (OR = 575.707, p = 0.023) and higher MK (OR = 173.559, p < 0.001) were independently associated with LNMs. Higher f (OR = 1036.116, p = 0.024), higher MK (OR = 253.629, p < 0.001), lower mean diffusivity (MD) (OR = 0.125, p = 0.038), and lower ADC (OR = 0.094, p = 0.022) were independently associated with EMVI. The area under the ROC curve (AUC) of MK for histological differentiation was significantly higher than ADC (0.771 vs. 0.638, p = 0.035). The AUC of MK for LNM positivity was higher than f (0.770 vs. 0.656, p = 0.048). The AUC of MK combined with MD (0.790) was the highest among f (0.663), MK (0.779), MD (0.617), and ADC (0.610) in assessing EMVI. CONCLUSION: The DKI parameters may be used as imaging biomarkers to assess pathological prognostic factors of rectal cancer before surgery. CLINICAL RELEVANCE STATEMENT: Diffusion kurtosis imaging (DKI) parameters, particularly mean kurtosis (MK), are promising biomarkers for assessing histological differentiation, lymph node metastasis, and extramural vascular invasion of rectal cancer. These findings suggest DKI's potential in the preoperative assessment of rectal cancer. KEY POINTS: Mean kurtosis outperformed the apparent diffusion coefficient in assessing histological differentiation in resectable rectal cancer. Perfusion fraction and mean kurtosis are independent indicators for assessing lymph node metastasis in rectal cancer. Mean kurtosis and mean diffusivity demonstrated superior accuracy in assessing extramural vascular invasion.

PKM2 interacts with and phosphorylates PHB2 to sustain mitochondrial quality control against septic cerebral-cardiac injury.

Sepsis induces profound disruptions in cellular homeostasis, particularly impacting mitochondrial function in cardiovascular and cerebrovascular systems. This study elucidates the regulatory role of the Pyruvate Kinase M2 (PKM2)- Prohibitin 2 (PHB2) axis in mitochondrial quality control during septic challenges and its protective effects against myocardial and cerebral injuries. Employing LPS-induced mouse models, we demonstrate a significant downregulation of PKM2 and PHB2 in both heart and brain tissues post-sepsis, with corresponding impairments in mitochondrial dynamics, including fission, fusion, and mitophagy. Overexpression of PKM2 and PHB2 not only restores mitochondrial function, as evidenced by normalized ATP production and membrane potential but also confers resistance to oxidative stress by mitigating reactive oxygen species generation. These cellular mechanisms translate into substantial in vivo benefits, with transgenic mice overexpressing PKM2 or PHB2 displaying remarkable resistance to sepsis-induced cardiomyocyte and neuronal apoptosis, and organ dysfunction. Our findings highlight the PKM2-PHB2 interaction as a novel therapeutic target for sepsis, providing a foundation for future research into mitochondrial-based interventions to treat this condition. The study's insights into the molecular underpinnings of sepsis-induced organ failure pave the way for potential clinical applications in the management of sepsis and related pathologies.

The impact of residential environment on older people's capabilities to live independently: a survey in Beijing.

BACKGROUND: Studies have shown how environmental factors influence older people's health and functional limitations, which are crucial for achieving healthy aging. However, such a healthy aging model has been criticized for defining health as an absence of disease, because chronic conditions cannot be reversed through medical treatments. In response to such critiques, this study refers to Huber's positive health definition, arguing that health should not be defined as the absence of disease but as the ability to adapt and self-manage in the face of social, physical, and emotional challenges. There is a need to develop a community-based approach to healthy aging that considers how the residential environment enables older people to adapt and self-manage. Drawing on Sen's capability approach, this study proposes that such a community-based approach should provide a supportive environment to enable older people's capabilities to live independently. METHODS: Using hierarchical multiple regression analysis of data from 650 older people (60 years and older) surveyed in Beijing, we unravel which features of the residential environment support older people' s capabilities to live independently and how these impacts differ depending on older people's frailty levels. RESULTS: The results show that four environmental factors, namely perceived accessibility (B = 0.238, p < 0.001 for physical capability, B = 0.126, p < 0.001 for social capability, B = 0.195, p < 0.001 for psychological capability), pleasant surroundings (B = 0.079, p < 0.05 for physical capability, B = 0.065, p < 0.05 for social capability), meeting opportunities (B = 0.256, p < 0.001 for social capability, B = 0.188, p < 0,001 for psychological capability, and life convenience B = 0.089, p < 0.05 for physical capability, B = 0.153, p < 0.001 for psychological capability) positively affect older people's capabilities to live independently. These four environmental factors cause differences in older people's capabilities between different neighborhood types. Moderation analysis shows that meeting opportunities are more relevant for frail older people (B = 0.090, p < 0.001 for social capability, B = 0.086, p < 0.01 for psychological capability). CONCLUSIONS: This study contributes to the literature by emphasizing the role of supportive residential environments in enabling older people to live independently. Furthermore, we identify four environmental factors that support older people's capabilities. Results can be used to develop effective community-based environmental support to enable older people to live independently.

Vulnerability Analysis Method Based on Network and Copula Entropy.

With the deepening of the diversification and openness of financial systems, financial vulnerability, as an endogenous attribute of financial systems, becomes an important measurement of financial security. Based on a network analysis, we introduce a network curvature indicator improved by Copula entropy as an innovative metric of financial vulnerability. Compared with the previous network curvature analysis method, the CE-based curvature proposed in this paper can measure market vulnerability and systematic risk with significant advantages.

[Mechanism of miR-221-3p inhibiting cadmium-induced apoptosis of TM3 cells through DDIT4].

OBJECTIVE: To investigate the mechanism of DNA-damage-inducible transcript 4(DDIT4)targeting miR-221-3p in microRNA(miRNA) on cadmium-induced apoptosis of mouse testicular stromal cells. METHODS: The activity of mouse testicular interstitial cells(TM3) was detected by CCK-8 after exposure to different concentrations of cadmium(0, 10, 20, 30, 40 µmol/L). Total RNA was extracted from cadmium-treated TM3 cells, and the significantly differentially expressed miRNA was screened with fold change(FC)>1.2 and P<0.05 as the criterion. TM3 cells were divided into blank control group, negative control group, cadmium exposure group(CdCl_2, 20 µmol/L), and cadmium+miR-221-3p mimic group. miR-221-3p mimic group was transfected into TM3 cells first, combined with cadmium exposure for 24 hours. The cell morphology was detected by Hoechst staining, and the apoptosis rate was analyzed by flow cytometry. Quantitative real-time PCR(qRT-PCR) and Western blot were used to detect DDIT4 expression. Dual luciferase reporter gene assay verified the binding of miR-221-3p to DDIT4. The function of DDIT4 and its relationship with apoptosis were analyzed by bioinformatics. The expression levels of B-cell lymphoma-2(Bcl-2) and Bcl-2 associated X protein(BAX) were observed after overexpression of miR-221-3p. RESULTS: Cadmium treatment of TM3 cells could reduce cell activity and there was a dose-effect relationship. The cell morphology showed that compared with the control group, the cells were wrinkled and the nuclei were heavily stained, and the apoptosis rate increased to 19.66%±0.45%(P<0.01). Compared with the cadmium exposure group, the normal morphologic cells increased in the cadmium exposure +miR-221-3p mimic group, and the apoptosis rate decreased to 13.76%±0.37%(P<0.05). The expression level of miR-221-3p was down-regulated(P<0.01), and the expression level of DDIT4 was up-regulated(P<0.05). Bioinformatics analysis and dual luciferase report analysis showed that DDIT4 was one of the target genes of miR-221-3p. Compared with the cadmium exposure group, the expression level of DDIT4 in the cadmium+miR-221-3p mimic group was down-regulated(P<0.05), and the ratio of Bcl-2/BAX was increased from 0.54±0.03 to 0.71±0.04. CONCLUSION: miR-221-3p inhibits cadmium-induced apoptosis of TM3 cells by targeting DDIT4.

Understanding the Institutional Logics of China's Community-Based Intervention for Older People.

Community-based policies have gained global popularity, signaling a paradigm shift from individual responsibility for healthy aging to an approach involving community-based intervention. Learning from Western experience, China has also experimented with this form of intervention. It has policy interventions aimed at providing community-based facilities and services that enable older people to age in place. However, the institutional foundations of Chinese communities differ greatly from those in Western countries. Implementing a critical realist case study focusing on a community-based program in Beijing, this study aims to examine the institutional logics that contribute toward a contextually appropriate community-based policy intervention in China. We identified three institutional logics. First, the Confucian moral obligation of benevolence requires authorities to provide social welfare for vulnerable citizens. Second, China's community-based interventions are state-led territorialized provisions prioritizing communities rather than individuals. Third, community-based social policies are subordinate to economic growth objectives. This study contributes to the understanding of contextually appropriate community-based policy interventions in China.

A nomogram to predict the cumulative risk for brain metastases in patients with limited-stage small cell lung cancer without prophylactic cranial irradiation.

OBJECTIVE: Patients with small cell lung cancer (SCLC) have a high risk of developing brain metastases (BM). Prophylactic cranial irradiation (PCI) is a standard therapy for limited-stage SCLC (LS-SCLC) patients who achieved complete or partial response after thoracic chemoradiotherapy (Chemo-RT). Recent studies have indicated that a subgroup of patients with a lower risk of BM can avoid PCI, and the present study therefore tries to construct a nomogram to predict the cumulative risk of development of BM in LS-SCLC patients without PCI. METHODS: After screening of 2298 SCLC patients who were treated at the Zhejiang Cancer Hospital from December 2009 to April 2016, a total of 167 consecutive patients with LS-SCLC who received thoracic Chemo-RT without PCI were retrospectively analyzed. The paper analyzed clinical and laboratory factors that may be correlated with BM, such as response to treatment, pretreatment serum neuron-specific enolase (NSE) and lactate dehydrogenase (LDH) levels, and TNM stage. Thereafter, a nomogram was constructed to predict 3­ and 5­year intracranial progression-free survival (IPFS). RESULTS: Of 167 patients with LS-SCLC, 50 developed subsequent BM. Univariate analysis showed that pretreatment LDH (pre-LDH) ≥ 200 IU/L, an incomplete response to initial chemoradiation, and UICC stage III were positively correlated to a higher risk of BM (p < 0.05). Multivariate analysis identified pretreatment LDH level (hazard ratio [HR] 1.90, 95% confidence interval [CI] 1.08-3.34, p = 0.026), response to chemoradiation (HR 1.87, 95% CI 1.04-3.34, p = 0.035), and UICC stage (HR 6.67, 95% CI 1.03-49.15, p = 0.043) as independent predictors for the development of BM. A nomogram model was then established, and areas under the curve of 3­year and 5­year IPFS were 0.72 and 0.67, respectively. CONCLUSION: The present study has developed an innovative tool that is able to predict the individual cumulative risk for development of BM in LS-SCLC patients without PCI, which is beneficial for providing personalized risk estimates and facilitating the decision to perform PCI.

Incidence and clinical features of HHV-7 detection in lower respiratory tract in patients with severe pneumonia: a multicenter, retrospective study.

PURPOSE: The significance of detecting human herpesvirus 7 (HHV-7) in the lower respiratory tract of patients with severe pneumonia is unclear. This study aims to evaluate the clinical characteristics and prognosis of detecting HHV-7 in the lower respiratory tract of patients with severe pneumonia. METHODS: Patients with severe pneumonia requiring invasive mechanical ventilation and underwent commercial metagenomic next-generation sequencing (mNGS) testing of bronchoalveolar lavage fluid from January 2019 to March 2023 were enrolled in 12 medical centers. Clinical data of patients were collected retrospectively, and propensity score matching was used for subgroup analysis and mortality assessment. RESULTS: In a total number of 721 patients, 45 cases (6.24%) were identified with HHV-7 positive in lower respiratory tract. HHV-7 positive patients were younger (59.2 vs 64.4, p = 0.032) and had a higher rate of co-detection with Cytomegalovirus (42.2% vs 20.7%, p = 0.001) and Epstein-Barr virus (35.6% vs 18.2%, p = 0.008). After propensity score matching for gender, age, SOFA score at ICU admission, and days from ICU admission to mNGS assay, there was no statistically significant difference in the 28-day mortality rate between HHV-7 positive and negative patients (46.2% vs 36.0%, p = 0.395). Multivariate Cox regression analysis adjusting for gender, age, and SOFA score showed that HHV-7 positive was not an independent risk factor for 28-day mortality (HR 1.783, 95%CI 0.936-3.400, p = 0.079). CONCLUSION: HHV-7 was detected in the lungs of 6.24% of patients with severe pneumonia. The presence of HHV-7 in patients with severe pneumonia requiring invasive mechanical ventilation is associated with a younger age and co-detected of Cytomegalovirus and Epstein-Barr virus. While HHV-7 positivity was not found to be an independent risk factor for mortality in this cohort, this result may have been influenced by the relatively small sample size of the study.

Cadmium influence on lipid metabolism in Sprague-Dawley rats through linoleic acid and glycerophospholipid metabolism pathways.

Cadmium (Cd) is widely distributed in the environment and easy adsorbed by living organisms with adverse effects. Exposure to Cd-contaminated food may disrupt lipid metabolism and increase human health risk. To study the perturbation effect of Cd on lipid metabolism in vivo, 24 male Sprague-Dawley (SD) rats were randomly assigned four groups and treated by Cd chloride solution (0, 1.375 mg/kg, 5.5 mg/kg, 22 mg/kg) for 14 days. The characteristic indexes of serum lipid metabolism were analyzed. Afterwards, untargeted metabolomics analysis was applied to explore the adverse effects of Cd on rats by liquid chromatography coupled with mass spectrometry (LC-MS). The results revealed that Cd exposure obviously decreased the average serum of triglycerides (TG) and low-density lipoprotein cholesterol (LDL-C) and caused an imbalance of endogenous compounds in the 22 mg/kg Cd-exposed group. Compared with the control group, 30 metabolites with significant differences were identified in the serum. Our results indicated that Cd caused lipid metabolic disorders in rats by disrupting linoleic acid and glycerophospholipid metabolism pathways. Furthermore, there were three kinds of remarkable differential metabolites-9Z,12Z-octadecadienoic acid, PC(20:4(8Z,11Z,14Z,17Z)/0:0), and PC(15:0/18:2(9Z,12Z)), which enriched the two significant metabolism pathways and could be the potential biomarkers.

Construction of Carbon Dots with Wavelength-Tunable Electrochemiluminescence and Enhanced Efficiency.

Tuning the electrochemiluminescence (ECL) wavelength of carbon dots (CDs) with enhanced efficiency is essential for multiplexed biosensing, bioimaging, and energy applications but remains challenging. Herein, we reported a facile route to finely modulate the ECL wavelength of CDs from 425 to 645 nm, the widest range ever reported, along with a more than 5-fold enhancement of ECL efficiency via phosphorous (P) incorporation. The molecular mechanism was explored experimentally and theoretically, which revealed the unusual dual roles of P dopants in the form of P-C and P-O bonding, that is, importing shallow trapping states and promoting an effective intramolecular charge transfer. This work would allow unlocking the key factors of ECL kinetics for heteroatom-doped CDs appearing out of reach and open a new avenue for the rational design of nanocarbon for desirable applications.

Serum lactate dehydrogenase predicts brain metastasis and survival in limited-stage small cell lung cancer patients treated with thoracic radiotherapy and prophylactic cranial irradiation.

BACKGROUND: Small cell lung cancer (SCLC) is characterized by a high risk of brain metastasis and poor survival. This study aims to assess the prognostic role of lactate dehydrogenase (LDH) in limited-stage small cell lung cancer (LS-SCLC) treated with thoracic radiotherapy (TRT) and prophylactic cranial irradiation (PCI). METHODS: This study retrospectively evaluated 197 consecutive patients who underwent TRT and PCI for LS-SCLC between November 2005 and October 2017. Both pretreatment and maximal serum LDH levels (mLDH) during treatment were checked, and an increased LDH level was defined as more than 240 IU/ml. Clinical factors were tested for associations with intracranial progression-free survival (IPFS) and overall survival (OS) after PCI. The Kaplan-Meier method was used to calculate survival rates, and multivariate Cox regression analyses were carried out to identify variables associated with survival. RESULTS: Of the total patients, 28 had higher pretreatment LDH levels and mLDH levels were increased in 95 patients during treatment. In patients in the normal and elevated mLDH groups, the 1­, 2­, and 5­year IPFS rates were 96.7% vs. 90.1%, 91.7% vs. 73.8%, and 87.8% vs. 61.0% (P < 0.01), respectively. Compared to those with normal LDH levels, patients with increased mLDH levels had a higher cumulative risk of intracranial metastasis (hazard ratio [HR] 3.87; 95% confidence interval [CI] 1.73-8.63; P < 0.01) and worse overall survival (HR 2.59; 95% CI 1.67-4.04; P < 0.01). The factors LDH level at baseline or changes between pretreatment level and maximum level during treatment failed to predict brain metastases or OS with statistical significance. In the multivariate analyses, both mLDH during treatment (HR 3.53; 95% CI 1.57-7.92; P = 0.002) and patient age ≥ 60 (HR 2.46; 95% CI 1.22-4.94; P = 0.012) were independently associated with worse IPFS. Factors significantly associated with worse OS included mLDH during treatment (HR 2.45; 95% CI 1.56-3.86; P < 0.001), IIIB stage (HR 1.75; 95% CI 1.06-2.88; P = 0.029), and conventional radiotherapy applied in TRT (HR 1.66; 95% CI 1.04-2.65; P = 0.034). CONCLUSION: The mLDH level during treatment predicts brain metastasis and survival in LS-SCLC patients treated with TRT and PCI, which may provide valuable information for identifying patients with poor survival outcomes and possible candidates for treatment intensification.

Inferring network structure with unobservable nodes from time series data.

Network structures play important roles in social, technological, and biological systems. However, the observable nodes and connections in real cases are often incomplete or unavailable due to measurement errors, private protection issues, or other problems. Therefore, inferring the complete network structure is useful for understanding human interactions and complex dynamics. The existing studies have not fully solved the problem of the inferring network structure with partial information about connections or nodes. In this paper, we tackle the problem by utilizing time series data generated by network dynamics. We regard the network inference problem based on dynamical time series data as a problem of minimizing errors for predicting states of observable nodes and proposed a novel data-driven deep learning model called Gumbel-softmax Inference for Network (GIN) to solve the problem under incomplete information. The GIN framework includes three modules: a dynamics learner, a network generator, and an initial state generator to infer the unobservable parts of the network. We implement experiments on artificial and empirical social networks with discrete and continuous dynamics. The experiments show that our method can infer the unknown parts of the structure and the initial states of the observable nodes with up to 90% accuracy. The accuracy declines linearly with the increase of the fractions of unobservable nodes. Our framework may have wide applications where the network structure is hard to obtain and the time series data is rich.

A Dual Functional Self-Enhanced Electrochemiluminescent Nanohybrid for Label-Free MicroRNA Detection.

The development of electrochemiluminescent (ECL) emitters with both intense ECL and excellent film-forming properties is highly desirable for biosensing applications. Herein, a facile one-pot preparation strategy was proposed for the synthesis of a self-enhanced ECL emitter by co-doping Ru(bpy)32+ and (diethylaminomethyl)triethoxysilane (DEAMTES) into an in situ-produced silica nanohybrid (DEAMTES@RuSiO2). DEAMTES@RuSiO2 not only possessed improved ECL properties but also exhibited outstanding film-forming ability, which are both critical for the construction of ECL biosensors. By coupling branched catalytic hairpin assembly with efficient signal amplification peculiarity, a label-free ECL biosensor was further constructed for the convenient and highly sensitive detection of miRNA-21. The as-fabricated ECL biosensor displayed a detection limit of 8.19 fM, much lower than those in previous reports for miRNA-21 and showed superior reliability for detecting miRNA-21-spiked human serum sample, demonstrating its potential for applications in miRNA-associated fundamental research and clinical diagnosis.

Targeting lactate dehydrogenase a improves radiotherapy efficacy in non-small cell lung cancer: from bedside to bench.

BACKGROUND: Lactate dehydrogenase A (LDHA) is overexpressed and associated with poor prognosis in many kinds of cancer. In the current study, we evaluated the prognostic value of LDHA expression in non-small cell lung cancer (NSCLC), and tested whether LDHA inhibition might improve radiotherapy efficacy in NSCLC. METHODS: LDHA expression was investigated in NSCLC patients, using online database and further verified by immunohistochemistry. The prognostic value of LDHA was evaluated using Kaplan-Meier plotter database. In vitro, two NSCLC cell lines were pretreated with oxamate, an inhibitor of LDHA, and colony formation method was performed to determine cellular radiosensitivity. Comet assay was used to detect DNA damage after irradiation. Flow cytometry was applied to test cell cycle progression and apoptosis, and monodansylcadaverine (MDC) staining was used to examine cell autophagy. RESULTS: Both mRNA and protein levels of LDHA expression were up-regulated in NSCLC tissues. High LDHA expression was a poor prognostic factor and associated with radioresistance in NSCLC patients. LDHA inhibition by oxamate remarkably increased radiosensitivity in both A549 and H1975 cancer cells, and enhanced ionizing radiation (IR)-induced apoptosis and autophagy, accompanied by cell cycle distribution alternations. Furthermore, LDHA inhibition induced reactive oxygen species (ROS) accumulation and cellular ATP depletion, which might increase DNA injury and hinder DNA repair activity. CONCLUSIONS: Our study suggests that inhibition of LDHA may be a potential strategy to improve radiotherapy efficacy in NSCLC patients, which needs to be further tested by clinical trials.

Effect of proanthocyanidins on blood pressure: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Hypertension is a common chronic disease that can lead to serious health problems. Previous studies have not drawn a consistent conclusion about the effect of proanthocyanidins (PCs) on blood pressure (BP). This systematic review and meta-analysis aims to evaluate the effect of PCs supplementation on blood pressure (BP). METHODS: A comprehensive literature search was performed in 6 databases (Pubmed, Scopus, ISI Web of Science, the Cochrane Library, Embase and Google Scholar) to identify the randomized controlled trials (RCTs) that evaluated the BP-lowering effect of PCs. Subgroup and sensitivity analyses were conducted to evaluate the potential heterogeneity. Meta-regression analysis was used to evaluate dose effects of PCs on BP. RESULTS: A total of 6 studies comprising 376 subjects were included in our meta-analysis to estimate the pooled effect size. This meta-analysis suggested that PCs supplementation could significantly reduce systolic blood pressure (SBP) (WMD: -4.598 mmHg; 95 % CI: -8.037, -1.159; I2 = 33.7 %; p = 0.009), diastolic blood pressure (DBP) (WMD: -2.750 mmHg; 95 % CI: -5.087, -0.412; I2 = 0.0 %; p = 0.021) and mean arterial pressure (MAP) (WMD: -3.366 mmHg; 95 % CI: -6.719, -0.041 mmHg; I2 = 0.0 %; p = 0.049), but had no significant effect on pulse pressure (PP) (WMD: -2.131 mmHg; 95 % CI: -6.292, 2.030; I2 = 0.0 %; p = 0.315). When the studies were stratified according to the duration of the study, there was a significant reduction on SBP in the subset of the trials with <12 weeks of duration. On the contrary, there was a significant reduction on DBP in the subset of the trials with ≥12 weeks of duration. The Subgroup analysis by BMI indicated that a significant reduction on SBP for people with a higher BMI (BMI ≥ 25) and a significant reduction on DBP for people with a lower BMI (BMI < 25). Additional subgroup analysis revealed low-dose-PCs (<245 mg/day) could significantly reduce SBP, DBP and MAP. The meta-regression analyses did not indicate the dose effects of PCs on SBP, DBP, PP and MAP. CONCLUSION: Based on the current findings, PCs supplementation may be a useful treatment of hypertensive patients as well as a preventive measure in the prehypertensive and healthy subjects. However, further investigation is needed to confirm these results.

Sporadic hand, foot, and mouth disease cases associated with non-C4 enterovirus 71 strains in Xiamen, China, from 2009 to 2018.

Enterovirus 71 (EV71) has caused large hand, foot, and mouth disease (HFMD) epidemics among young children, and EV71 infection is the leading cause of severe HFMD cases and deaths. In mainland China, the prevalence and risk factors of non-C4 EV71 strains are still unclear. In this study, we monitored non-C4 strains over a 10-year HFMD epidemiological surveillance period in Xiamen. The 5'UTR and VP1 coding region of EV71 strains were amplified by RT-nested PCR and sequenced. Thirty-two non-C4 EV71 strains were identified during 2009-2018. This study provides important information about the prevalence of EV71 in China that will be applicable for development of vaccines and diagnostic reagents as well as establishment of policies for HFMD prevention and control.

The interaction between reward and the task-irrelevant emotional context in memory.

Reward improves task performance while the emotional contexts irrelevant to the task impair task performance. An interaction between reward and the task-irrelevant emotional context has been discovered by some studies using perceptual tasks. However, it is unclear that how memory performance would be affected by both variables. This study aimed to answer this question and explore the role of arousal induced by emotional stimuli, to which was seldomly paid attention by previous studies. We conducted two experiments with the study-test paradigm. The first difference between the experiments was the way that the emotional stimuli were presented. They were presented with the words (Experiment 1) or separately (Experiment 2). The second difference was that the manipulation of the emotional arousal was phasic (Experiment 1) or tonic (Experiment 2). Both experiments showed that the reward effect was greater in emotional context compared to the neutral context, which is not only due to the poorer memory of no reward-associated words but also the better memory of reward-associated words in emotional contexts especially in negative one. These results supported the view that emotional arousal enhanced the memory of high priority stimuli (reward-associated words) and impaired the memory of low priority stimuli (no reward-associated words).