DRP1 inhibition-mediated mitochondrial elongation abolishes cancer stemness, enhances glutaminolysis, and drives ferroptosis in oral squamous cell carcinoma.

BACKGROUND: Mitochondrial dynamics play a fundamental role in determining stem cell fate. However, the underlying mechanisms of mitochondrial dynamics in the stemness acquisition of cancer cells are incompletely understood. METHODS: Metabolomic profiling of cells were analyzed by MS/MS. The genomic distribution of H3K27me3 was measured by CUT&Tag. Oral squamous cell carcinoma (OSCC) cells depended on glucose or glutamine fueling TCA cycle were monitored by 13C-isotope tracing. Organoids and tumors from patients and mice were treated with DRP1 inhibitors mdivi-1, ferroptosis inducer erastin, or combination with mdivi-1 and erastin to evaluate treatment effects. RESULTS: Mitochondria of OSCC stem cells own fragment mitochondrial network and DRP1 is required for maintenance of their globular morphology. Imbalanced mitochondrial dynamics induced by DRP1 knockdown suppressed stemness of OSCC cells. Elongated mitochondria increased α-ketoglutarate levels and enhanced glutaminolysis to fuel the TCA cycle by increasing glutamine transporter ASCT2 expression. α-KG promoted the demethylation of histone H3K27me3, resulting in downregulation of SNAI2 associated with stemness and EMT. Significantly, suppressing DRP1 enhanced the anticancer effects of ferroptosis. CONCLUSION: Our study reveals a novel mechanism underlying mitochondrial dynamics mediated cancer stemness acquisition and highlights the therapeutic potential of mitochondria elongation to increase the susceptibility of cancer cells to ferroptosis.

Acetyl-11-keto-beta-boswellic acid inhibits cell proliferation and growth of oral squamous cell carcinoma via RAB7B-mediated autophagy.

Natural products can overcome the limitations of conventional chemotherapy. Acetyl-11-keto-beta-boswellic acid (AKBA) as a natural product extracted from frankincense, exhibited chemotherapeutic activities in different cancers. However, whether AKBA exerts inhibiting effect of oral squamous cell carcinoma (OSCC) cells growth and the mechanism need to be explored. We attempted to investigate the therapeutic effects of AKBA against OSCC and explore the mechanism involved. Here we attempt to disclose the cell-killing effect of AKBA on OSCC cell lines and try to figure out the specifical pathway. The presence of increase autophagosome and the production of mitochondrial reactive oxygen species were confirmed after the application of AKBA on OSCC cells, and RAB7B inhibition enhanced autophagosome accumulation. Though the increase autophagosome was detected induced by AKBA, autophagic flux was inhibited as the failure fusion of autophagosome and lysosome. Cal27 xenografts were established to verify the role of anti-OSCC cells of AKBA in vivo. Based above findings, we speculate that natural product AKBA suppresses OSCC cells growth via RAB7B-mediated autophagy and may serve as a promising strategy for the therapy of OSCC.

The impact of chemical properties of the solid-liquid-adsorbate interfaces on the entropy-enthalpy compensation involved in adsorption.

Despite extensive studies on the thermodynamic mechanism governing molecular adsorption at the solid-water interface, a comprehensive understanding of the crucial role of interface properties in mediating the entropy-enthalpy compensation during adsorption is lacking, particularly at a quantitative level. Herein, we employed two types of surface models (hydroxyapatite and graphene) along with a series of amino acids to successfully elucidate how distinct interfacial features dictate the delicate balance between entropy and enthalpy variations. The adsorption of all amino acids on the hydroxyapatite surface is an enthalpy-dominated process, where the water-induced enthalpic component of the free energy and the surface-adsorbate electrostatic interaction term alternatively act as the driving force for adsorption in different regions of the surface. Although favorable interactions are observed between amino acids and the graphene surface, the entropy-enthalpy compensation exhibits dependence on the molecular size of the adsorbates. For small amino acids, favorable enthalpy changes predominantly determine their adsorption behavior; however, larger amino acids tend to bind more tightly with the graphene surface, which is thermodynamically dominated by the entropy variations despite the structural characteristics of amino acids. This study reveals specific entropy-enthalpy mechanisms underlying amino acid adsorption at the solid-liquid interface, providing guidance for surface design and synthesis of new biomolecules.

The role of Ca2+ signalling and InsP3R in the pathogenesis of intrahepatic cholestasis of pregnancy.

BACKGROUND: In order to contribute new insights for future prevention and treatment of intrahepatic cholestasis of pregnancy (ICP), and to promote positive pregnancy outcomes, we evaluated serum Ca2+ levels and inositol 1,4,5-trisphosphate receptor (InsP3R) expression in the liver tissue of a rat ICP model. METHODS: After establishing the model by injection of oestradiol benzoate and progesterone into pregnant rats, animals were divided into normal control (n = 5) and ICP model groups (n = 5). The expression of InsP3R protein in the liver, and serum levels of Ca2+, glycocholic acid and bile acid were detected. RESULTS: InsP3R mRNA and protein were significantly lower in the ICP model group compared to the normal group, as determined by qPCR and immunohistochemistry, respectively. Serum enzyme-linked immunosorbent assay results revealed significantly higher levels of glycocholic acid and bile acid in the ICP model group compared to the normal group, while Ca2+ levels were significantly lower. The levers of Ca2+ were significantly and negatively correlated with the levels of glycocholic acid. The observed decrease in Ca2+ was associated with an increase in total bile acids, but there was no significant correlation. CONCLUSIONS: Our results revealed that the expression of InsP3R and serum Ca2+ levels was significantly decreased in the liver tissue of ICP model rats. Additionally, Ca2+ levels were found to be negatively correlated with the level of glycocholic acid.

This study investigated the relationship between serum Ca²⁺ levels, inositol 1,4,5-trisphosphate receptor (InsP3R) expression and intrahepatic cholestasis of pregnancy (ICP) in a rat model. The results indicated a significant decrease in InsP3R expression and Ca²⁺ in the disease group compared to the control group, alongside elevated levels of glycocholic acid and bile acid. The levels of Ca²⁺ exhibited a negative correlation with the levels of glycocholic acid. These findings indicated that the decrease of InsP3R expression and Ca²⁺ levels may be related to the pathogenesis of ICP. The study provides further insight into the treatment of this disease.

[An ensemble model for assisting early Alzheimer's disease diagnosis based on structural magnetic resonance imaging with dual-time-point fusion].

Alzheimer's Disease (AD) is a progressive neurodegenerative disorder. Due to the subtlety of symptoms in the early stages of AD, rapid and accurate clinical diagnosis is challenging, leading to a high rate of misdiagnosis. Current research on early diagnosis of AD has not sufficiently focused on tracking the progression of the disease over an extended period in subjects. To address this issue, this paper proposes an ensemble model for assisting early diagnosis of AD that combines structural magnetic resonance imaging (sMRI) data from two time points with clinical information. The model employs a three-dimensional convolutional neural network (3DCNN) and twin neural network modules to extract features from the sMRI data of subjects at two time points, while a multi-layer perceptron (MLP) is used to model the clinical information of the subjects. The objective is to extract AD-related features from the multi-modal data of the subjects as much as possible, thereby enhancing the diagnostic performance of the ensemble model. Experimental results show that based on this model, the classification accuracy rate is 89% for differentiating AD patients from normal controls (NC), 88% for differentiating mild cognitive impairment converting to AD (MCIc) from NC, and 69% for distinguishing non-converting mild cognitive impairment (MCInc) from MCIc, confirming the effectiveness and efficiency of the proposed method for early diagnosis of AD, as well as its potential to play a supportive role in the clinical diagnosis of early Alzheimer's disease.

The origin and evolution of emerged swine acute diarrhea syndrome coronavirus with zoonotic potential.

Swine acute diarrhea syndrome coronavirus (SADS-CoV) is a newly discovered alphacoronavirus with zoonotic potential that causes diarrhea and vomiting mainly in piglets. Having emerged suddenly in 2017, the prevailing opinion is that the virus originated from HKU2, an alphacoronavirus whose primary host is bats, and at some unknown point achieved interspecies transmission via some intermediate. Here, we further explore the evolutionary history and possible cross-species transmission event for SADS-CoV. Coevolutionary analysis demonstrated that HKU2 may have achieved host switch via SADS-related (SADSr)-CoV, which was isolated from the genus Rhinolophus in 2017. SADS-CoV, HKU2, and SADSr-CoV share similar codon usage patterns and showed a lower tendency to use CpG, which may reflect a method of immune escape. The analyses of virus-host coevolution and recombination support SADSr-CoV is the direct source of SADS-CoV that may have undergone recombination events during its formation. Structure-based spike glycoprotein variance analysis revealed a more nuanced evolutionary pathway to receptor recognition for host switch. We did not find a possible positive selection site, and the dN/dS of the S gene was only 0.29, which indicates that the current SADS-CoV is slowly evolving. These results provide new insights that may help predict future cross-species transmission, and possibly surveil future zoonotic outbreaks and associated public health emergencies.

The Wet Suction Technique Enhances the Diagnostic Efficacy and Aspirate Quality of EUS-FNA for Solid Lesions: A Multicenter Retrospective Study in China.

GOALS: To comprehensively compare the wet suction technique with the conventional dry suction technique for endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) in solid lesions. BACKGROUND: Optimal suction techniques for EUS-FNA remain uncertain when approaching solid lesions. STUDY: We performed a retrospective study of EUS-FNA at 3 medical centers in China. A total of 203 patients were enrolled who received 2 passes of EUS-FNA with 22-G needles. If the first pass underwent dry suction, the second pass was wet suction. Otherwise, the order of suction technique is opposite. Diagnostic accuracy, sample quality (including cellularity and blood contamination), and sample quantity (including specimen adequacy, the maximum intact specimen length, and the total specimen length) were compared between wet-suction and dry-suction techniques. RESULTS: The patients included 143 pancreatic lesions and 60 nonpancreatic lesions. Compared with the dry suction technique, the wet suction technique yielded a significantly higher diagnostic accuracy (85.22% vs. 72.41%, P =0.002), better specimen adequacy score and cellularity score ( P <0.0001), and lower blood contamination score ( P <0.0001). In the subgroup analysis, wet suction provided significantly higher diagnostic accuracy in pancreatic cancer without chronic pancreatitis ( P <0.05), and better cellularity score and specimen adequacy score, lower blood contamination score, and longer maximum intact specimen length and total specimen length in various lesions than that in dry suction. CONCLUSIONS: The wet suction technique resulted in significantly higher diagnostic accuracy in pancreatic cancer without chronic pancreatitis, and better cellularity and histologic specimen in most of solid lesions.

Changes in gene expression and enzyme activity related to glucose metabolism in the livers of Brandt's voles (Lasiopodomys brandtii) exposed to hypoxia.

Brandt's vole (Lasiopodomys brandtii) is a hypoxia-tolerant species, and the metabolic characteristics of hypoxia-tolerant species have become a focus of recent research. However, insights into the anaerobic and aerobic metabolism of the livers of Brandt's voles under hypoxia remain limited. In this study, Brandt's voles and hypoxia-intolerant Kunming mice (Mus musculus, control species) were exposed to hypoxia conditions (Brandt's voles, 10% and 7.5% O2; Kunming mice, 10% O2) for 24 h, and changes in gene expression and enzyme activity related to anaerobic and aerobic metabolism in the livers were evaluated. Phosphofructokinase 1 (PFK1), phosphofructokinase 2 (PFK2), pyruvate kinase muscle (PKM), hexokinase 2 (HK2), and lactate dehydrogenase (LDH) related to anaerobic metabolism in the livers of Brandt's voles were increased under 7.5% O2. Regarding gene expression and enzyme activity for aerobic metabolism in Brandt's voles under 7.5% and 10% O2, pyruvate dehydrogenase kinase 1 (PDK1) expression was up-regulated, and succinate dehydrogenase (SDH) activity was decreased. In the livers of Kunming mice, gene expression related to anaerobic and aerobic metabolism was increased at the late stage of 10% O2, and SDH activity was enhanced at 6 h and reduced at 18 h. In addition, PFK1,PKM, PDK1 expression and SDH activity in Brandt's voles were significantly correlated with HIF-1a expression. PFK1, PKM, LDHand PDK1 expression in Kunming mice were significantly correlated with HIF-1a expression. These findings indicate that the livers of Brandt's voles have a certain tolerance to hypoxia, and metabolic changes play important roles in hypoxia tolerance.

[Alzheimer's disease classification based on nonlinear high-order features and hypergraph convolutional neural network].

Alzheimer's disease (AD) is an irreversible neurodegenerative disorder that damages patients' memory and cognitive abilities. Therefore, the diagnosis of AD holds significant importance. The interactions between regions of interest (ROIs) in the brain often involve multiple areas collaborating in a nonlinear manner. Leveraging these nonlinear higher-order interaction features to their fullest potential contributes to enhancing the accuracy of AD diagnosis. To address this, a framework combining nonlinear higher-order feature extraction and three-dimensional (3D) hypergraph neural networks is proposed for computer-assisted diagnosis of AD. First, a support vector machine regression model based on the radial basis function kernel was trained on ROI data to obtain a base estimator. Then, a recursive feature elimination algorithm based on the base estimator was applied to extract nonlinear higher-order features from functional magnetic resonance imaging (fMRI) data. These features were subsequently constructed into a hypergraph, leveraging the complex interactions captured in the data. Finally, a four-dimensional (4D) spatiotemporal hypergraph convolutional neural network model was constructed based on the fMRI data for classification. Experimental results on the Alzheimer's Disease Neuroimaging Initiative (ADNI) database demonstrated that the proposed framework outperformed the Hyper Graph Convolutional Network (HyperGCN) framework by 8% and traditional two-dimensional (2D) linear feature extraction methods by 12% in the AD/normal control (NC) classification task. In conclusion, this framework demonstrates an improvement in AD classification compared to mainstream deep learning methods, providing valuable evidence for computer-assisted diagnosis of AD.

Three-Dimensional Quantitative Coherent Diffraction Imaging of Staphylococcus aureus Treated with Peptide-Mineralized Au-Cluster Probes.

Characterizing interactions between microbial cells and their specific inhibitory drugs is essential for developing effective drugs and understanding the therapeutic mechanism. Functional metal nanoclusters can be effective inhibitory agents against microorganisms according to various characterization methods, but quantitative three-dimensional (3D) spatial structural analysis of intact cells is lacking. Herein, using coherent X-ray diffraction imaging, we performed in situ 3D visualization of unstained Staphylococcus aureus cells treated with peptide-mineralized Au-cluster probes at a resolution of ∼47 nm. Subsequent 3D mass-density mapping and quantitative structural analyses of S. aureus in different degrees of destruction showed that the bacterial cell wall was damaged and cytoplasmic constituents were released from cells, confirming the significant antibacterial effects of the Au-cluster probe. This study provides a promising nondestructive approach for quantitative imaging and paves the way for further research into microbe-inhibitor drug interactions.

64-Pixel Mo80Si20 superconducting nanowire single-photon imager with a saturated internal quantum efficiency at 1.5 µm.

A superconducting nanowire single-photon imager (SNSPI) uses a time-multiplexing method to reduce the readout complexity. However, due to the serial connection, the nanowire should be uniform so that a common bias can set all segments of the nanowire to their maximum detection efficiency, which becomes more challenging as the scalability (i.e., the length of the nanowire) increases. Here, we have developed a 64-pixel SNSPI based on amorphous Mo80Si20 film, which yielded a uniform nanowire and slow transmission line. Adjacent detectors were separated by delay lines, giving an imaging field of 270 µm × 240 µm. Benefiting from the high kinetic inductance of Mo80Si20 films, the delay line gave a phase velocity as low as 4.6 µm/ps. The positions of all pixels can be read out with a negligible electrical cross talk of 0.02% by using cryogenic amplifiers. The timing jitter was 100.8 ps. Saturated internal quantum efficiency was observed at a wavelength of 1550 nm. These results demonstrate that amorphous film is a promising material for achieving SNSPIs with large scalability and high efficiency.

Gonadotropin-releasing hormone agonist downregulation combined with hormone replacement therapy improves the reproductive outcome in frozen-thawed embryo transfer cycles for patients of advanced reproductive age with idiopathic recurrent implantation failure.

BACKGROUND: To determine whether gonadotropin-releasing hormone (GnRH) agonist downregulation combined with hormone replacement therapy (HRT) can improve the reproductive outcomes in frozen-thawed embryo transfer cycles for older patients (aged 36-43 years) with idiopathic recurrent implantation failure (RIF). METHODS: This retrospective cohort study involved 549 older patients undergoing their third cleavage-stage embryo or blastocyst transfer over a 5-year period (January 2015-December 2020) at Northwest Women's and Children's Hospital after in vitro fertilization/intracytoplasmic sperm injection cycles. Patients with known endometriosis or adenomyosis were excluded from the study. The patients were divided into three groups according to the endometrial preparation protocol: the natural cycle (NC) group (n = 65), the HRT group (n = 194), and the GnRH agonist downregulation combined with HRT cycle (GnRH agonist-HRT) group (n = 290). The primary outcome was the live birth rate, and the secondary outcomes were the clinical pregnancy, miscarriage, and ongoing pregnancy rates. RESULTS: The live birth rate in the GnRH agonist-HRT group (36.55%) was higher than that in the HRT group (22.16%) and NC group (16.92%) (P < 0.0001). Similarly, a logistic regression model adjusting for potential confounders showed that the live birth rate was higher in the GnRH agonist-HRT group than in the HRT group (odds ratio, 0.594; 95% confidence interval, 0.381-0.926; P = 0.021) and NC group (odds ratio, 0.380; 95% confidence interval, 0.181-0.796; P = 0.010). CONCLUSIONS: The GnRH agonist-HRT protocol improves the live birth rate in frozen-thawed embryo transfer cycles for patients of advanced reproductive age with RIF. We hypothesize that the GnRH agonist-HRT protocol enhances implantation-related factors and promotes optimal endometrial receptivity, leading to an improved live birth rate. These findings are also useful for further investigating the underlying mechanism of the GnRH agonist-HRT protocol in improving the reproductive outcomes for patients of advanced reproductive age with RIF. TRIAL REGISTRATION: This research protocol was approved by the hospital institutional ethics committee (No. 2021002).

Clinical-pathological characteristics and prognostic factors for malignant peritoneal mesothelioma in the elderly.

BACKGROUND: Malignant peritoneal mesothelioma (MPM) is a rare disease characterized by atypical symptoms, difficult diagnosis, variable course and poor prognosis, and it develops mainly in elderly individuals. The authors aimed to identify the clinical-pathological characteristics, prognosis, and prognostic factors in elderly MPM patients. METHODS: From the National Cancer Institute Surveillance Epidemiology End Results (SEER) database, 1492 patients with MPM from 1975 to 2016 were selected and divided into the elderly group (≥ 65) and the adult group (< 65). We compared the clinical-pathological characteristics and treatment methods of the elderly group (N = 665) and the adult group (N = 827). At the same time, we analysed specific selected clinicopathological parameters and prognostic factors for elderly MPM patients. RESULTS: Compared with the adult group, the elderly group had higher percentages of male patients (P = 0.017) and white patients (P = 0.043) and lower proportions of insured patients (P < 0.001) married patients (P < 0.001), patients with peritoneal tumours (P = 0.006) and patients who underwent surgery (P < 0.001) and chemotherapy (P < 0.001). There was a significant difference in the differentiation grade between the two groups (P = 0.003). Elderly patients had a shorter median survival time than adult patients (6 months vs. 19 months). Uninsured (hazard ratio (HR): 5.187, P = 0.005), sarcomatoid type (HR 3.913, P < 0.001), poorly differentiated (HR 3.900, P < 0.001), distant metastasis (HR 1.735, P = 0.001), no cancer-directed surgery (HR 1.733, P < 0.001), and no chemotherapy (HR 1.532, P < 0.001) were independently associated with poorer prognosis in elderly MPM patients. CONCLUSION: Compared with adult patients, elderly MPM patients had a higher male ratio, poor differentiation and relatively conservative treatment. The cancer-specific survival (CSS) rate of elderly MPM patients was significantly lower than that of adult patients. Insurance status, histology type, differentiation grade, stage, surgery status, and chemotherapy status were all independent prognostic factors for elderly MPM patients.

Can campaign-style enforcement facilitate water pollution control? Learning from China's Environmental Protection Interview.

The effectiveness of campaign-style enforcement (CSE) on water pollution, especially the long-term effectiveness, is controversial, and little knowledge is known about the channels through which the effectiveness happens. We take advantage of China's Environmental Protection Interview (EPI)- a distinguished form of CSE launched in 2014, as a natural experiment to estimate the short-term and long-term effects of CSE on water pollution. Using a time-varying difference-in-differences model based on city panel data from 2006 to 2018, we find that EPI can lead to an average 14.5% reduction in water pollution, and this effect is still persistent in the long term. Mechanism analysis shows that EPI reduces water pollution mainly through the pressure effect on the government, the penalty effect on the firms, and the mobilization effect on the public. Heterogeneity analysis shows that the effect of EPI on water pollution is more significant in cities with high initial pollution, low public complaints, and low economic levels. Further cost-benefit analysis based on the estimated value of water pollution reduction shows that the upper health benefit of EPI is $520.97 billion, which is 4.87 times higher than its estimated cost of $107.05 billion.

[The Association between the Level of Plasma D-dimer and Disease Severity and Prognosis of Mycoplasma pneumoniae Pneumonia in Children].

OBJECTIVE: To explore the association between the levels of plasma D-dimer and the disease severity and prognosis of Mycoplasma pneumoniae pneumonia (MPP) in children. METHODS: We retrospectively analyzed the clinical data of pediatric MPP patients who were admitted in our hospital between January 1, 2016 and December 31, 2018. According to the peak value of D-dimer, patients were divided into the normal group (D-dimer<0.55 mg/L) and the elevated group (D-dimer≥0.55 mg/L). Information regarding the demographics, clinical manifestations, auxiliary examinations and treatments of patients in the two groups was compared. RESULTS: Of the 231 MPP patients included in the study, 70 were in the normal group and 161 were in the elevated group. The age of patients in the D-dimer elevated group was significantly higher than that of the normal group ( P<0.01). Compared with the normal group, the elevated group had longer lengths of fever, hospital stay and antibiotic therapy, and more severe radiographic manifestations (all P<0.01). In addition, the incidence of extrapulmonary complications, refractory MPP and severe MPP in the elevated group were significantly higher than those in the normal group ( P<0.01). As for the laboratory data, we found that neutrophils, C-reactive protein, lactate dehydrogenase, interleukin-6, interleukin-10 and interferon-γ were significantly higher in the elevated group than those in the normal group ( P<0.05). After treatments, all patients showed improvement and were discharged, but the proportions of patients requiring glucocorticoids, bronchoscopy, thoracentesis were significantly higher in the elevated group than those in the normal group ( P<0.05). Follow-up findings showed that the absorption rate of lung lesions 4 weeks after admission was significantly higher, the time needed for lung lesions absorption was significantly shorter, and the incidence of pulmonary sequelae was significantly lower in the normal group than those in the elevated group (all P<0.05). Correlation analysis showed that D-dimer level was positively correlated with the severity of pneumonia ( r=0.272, P=0.000) and the incidence of pulmonary sequelae ( r=0.235, P=0.000). CONCLUSION: Pediatric patients of MPP who had elevated plasma D-dimer had clinical manifestations that were more severe, required longer duration of treatment and longer recovery time for lung lesions, and were more likely to have pulmonary sequelae.

A Superconducting Binary Encoder with Multigate Nanowire Cryotrons.

Many classic and quantum devices need to operate at cryogenic temperatures, demanding advanced cryogenic digital electronics for processing the input and output signals on a chip to extend their scalability and performance. Here, we report a superconducting binary encoder with ultralow power dissipation and ultracompact size. We introduce a multigate superconducting nanowire cryotron (nTron) that functions as an 8-input OR gate within a footprint of approximately 0.5 µm2. Four cryotrons compose a 4-bit encoder that has a bias margin of 18.9%, an operation speed greater than 250 MHz, an average switching jitter of 75 ps, and a power dissipation of less than 1 µW. We apply this encoder to read out a superconducting-nanowire single-photon detector array whose pixel location is digitized into a 4-bit binary address. The small size of the nanowire combined with the low power dissipation makes nTrons promising for future monolithic integration.

[Early diagnosis of Alzheimer's disease based on three-dimensional convolutional neural networks ensemble model combined with genetic algorithm].

The pathogenesis of Alzheimer's disease (AD), a common neurodegenerative disease, is still unknown. It is difficult to determine the atrophy areas, especially for patients with mild cognitive impairment (MCI) at different stages of AD, which results in a low diagnostic rate. Therefore, an early diagnosis model of AD based on 3-dimensional convolutional neural network (3DCNN) and genetic algorithm (GA) was proposed. Firstly, the 3DCNN was used to train a base classifier for each region of interest (ROI). And then, the optimal combination of the base classifiers was determined with the GA. Finally, the ensemble consisting of the chosen base classifiers was employed to make a diagnosis for a patient and the brain regions with significant classification capability were decided. The experimental results showed that the classification accuracy was 88.6% for AD vs. normal control (NC), 88.1% for MCI patients who will convert to AD (MCIc) vs. NC, and 71.3% for MCI patients who will not convert to AD (MCInc) vs. MCIc. In addition, with the statistical analysis of the behavioral domains corresponding to ROIs (i.e. brain regions), besides left hippocampus, medial and lateral amygdala, and left para-hippocampal gyrus, anterior superior temporal sulcus of middle temporal gyrus and dorsal area 23 of cingulate gyrus were also found with GA. It is concluded that the functions of the selected brain regions mainly are relevant to emotions, memory, cognition and the like, which is basically consistent with the symptoms of indifference, memory losses, mobility decreases and cognitive declines in AD patients. All of these show that the proposed method is effective.

Monocyte to high-density lipoprotein ratio and cardiovascular events in patients on peritoneal dialysis.

BACKGROUND AND AIMS: The monocyte to high-density lipoprotein cholesterol ratio (MHR) is associated with multiple cardiovascular diseases. However, the role of the MHR in predicting cardiovascular diseases in patients on peritoneal dialysis remains unclear. METHODS AND RESULTS: Eight hundred and eighty incident peritoneal dialysis patients were enrolled from November 1, 2005, to February 28, 2017, and followed until May 31, 2017. Primary outcomes were cardiovascular events. Using the X-tile program, these patients were divided into three groups according to the MHR. Kaplan-Meier method and Cox regressions were used for survival analysis. During a median follow-up period of 26 months (interquartile range: 12-39 months), 139 cardiovascular events were recorded. After multiple adjustment, the high MHR group was associated with a 1.97-fold increase in the cardiovascular events hazard compared to that of the low group in the overall population (hazard ratio: 1.97; 95% CI, 1.19-3.28; P = 0.009). Subgroup analysis demonstrated that the association between the MHR and a higher risk of cardiovascular events was strongest in the subgroup of patients with diabetes (P for interaction = 0.004). In this subgroup, the high MHR group was found to be associated with a higher risk of cardiovascular events compared to the low group (hazard ratio: 7.69; 95% CI, 2.76-21.47). CONCLUSION: This study suggests that the MHR is independently associated with the risk of cardiovascular events in patients undergoing peritoneal dialysis, and diabetes status can influence the association between the MHR and the risk of cardiovascular events.

An innovative method to enhance protease tolerance of nisin in endogenous proteases.

Nisin, a natural peptide produced by Lactococcus lactis cultivation in milk whey, is widely used as a preservative in industrial production. However, nisin can be degraded by endogenous enzymes in foods. In this study, we investigated the antibacterial activity of nisin-soybean protein and nisin-egg white protein and compared them with that of free nisin in cantaloupe juice, which was used as a model of endogenous protease environment. Results showed that endogenous proteases in the model resulted in a loss of nisin activity, but combining nisin with protein (soybean or egg white) resulted in greater protection of its antimicrobial activity by inhibiting endogenous proteases. The microbial addition experiment (Staphylococcus aureus and Micrococcus luteus) and preservation experiment in the food model showed that the antibacterial activity of nisin combined with either of the 2 proteins was higher than that of nisin alone in an endogenous protease environment. In summary, soybean protein and egg white protein improved the protease tolerance of nisin, expanding the application scope of nisin in food.

Efficiency evaluation of urban wastewater treatment: Evidence from 113 cities in the Yangtze River Economic Belt of China.

To resolve the increasing water pollution crisis, scientifically evaluating the urban wastewater treatment efficiency (UWTE) is an essential prerequisite to ensure the success of any policies aiming to decrease water pollution. Using 113 city-level panel data in the Yangtze River Economic Belt (YREB)-the biggest economic belt in China, during 2008-2017, this study aims to evaluate the UWTE based on a Bootstrap-DEA and to measure the efficiency changes through a Malmquist index model. The results show that the overall UWTE is at a low level, evidenced by the fact the average efficiency score is 0.51 during 2008-2017, and no cities have an efficiency score equal to 1. The UWTE is in the trend of decreasing, which is mainly caused by the decline of technical progress change. 69.02% of cities are in the state of decreasing returns to scale. The UWTE shows considerable disparities both between regions and city sizes, with the highest efficiency score observed in the midstream area and large-sized cities, the lowest efficiency score observed in the downstream area and small-sized cities. The findings of this study are expected to have great practical significance for governing wastewater pollution.