Targeting EZH2 attenuates the ferroptosis-mediated osteoblast-osteoclast imbalance in rheumatoid arthritis.

OBJECTIVE: The enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2) can regulate osteogenesis and osteoclastogenesis. This study aimed to further explore the effects of EZH2 modification on ferroptosis and the osteoblast-osteoclast balance in rheumatoid arthritis (RA) in vitro and in vivo. METHODS: Bone marrow mesenchymal stromal cells were transfected with EZH2 overexpression (oeEZH2) and EZH2 shRNA (shEZH2) plasmids with or without ferrostatin-1 (Fer-1) treatment and subjected to an osteoblast differentiation assay. The cells were then cocultured with bone marrow-derived macrophages and subjected to an osteoclast differentiation assay. Collagen-induced arthritis (CIA) mice were generated and injected with shEZH2 adeno-associated virus (AAV). RESULTS: OeEZH2 repressed osteoblast differentiation, as reflected by decreased ALP and Alizarin Red S staining and increased OPN, RUNX2, OPG and RANKL; however, shEZH2 had the opposite effects. Besides, oeEZH2 promoted osteoblast ferroptosis, as suggested by increased MDA, Fe2+, ROS, and PTGS2 but decreased GPX4 and SLC7A11; these effects could be attenuated by Fer-1 treatment. In contrast, shEZH2 ameliorated osteoblast ferroptosis. OeEZH2 subsequently increased osteoclast differentiation, as indicated by increased TRAP+ multinucleated cells, NFATC1, CTSK, and c-FOS; however, shEZH2 had the opposite effect, except that it did not regulate CTSK. In CIA mice, shEZH2 AAV decreased the clinical symptom score, histological score of cartilage, and systemic inflammation (TNF-α and IL-6) and repressed bone ferroptosis and restored the osteoblast-osteoclast balance to some extent, as reflected by immunohistochemical staining of related markers. CONCLUSION: Targeting EZH2 attenuates the ferroptosis-mediated osteoblast-osteoclast imbalance in RA, revealing its potential as a treatment target.

Clinical and genetic characteristics of Chinese pediatric and adult patients with hereditary spherocytosis.

OBJECTIVE: This study aimed to investigate the clinical features, pathogenic gene variants, and potential genotype-phenotype correlations in Chinese patients with hereditary spherocytosis (HS). METHODS: Retrospective analysis of clinical data and molecular genetic characteristics was conducted on patients diagnosed with HS at Jiangxi Provincial Children's Hospital, the Second Affiliated Hospital of Nanchang University, Pingxiang People's Hospital and The Third People's Hospital of Jingdezhen between November 2017 and June 2023. Statistical analyses were performed to compare and analyze the red blood cell (RBC), hemoglobin (HB), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin concentration (MCHC) data between and within groups based on different mutations and age groups (< 14 and ≥ 14 years). RESULTS: A total of 34 HS patients were included in this study, comprising 22 children (64.70%) and 12 adults (35.30%). The probands who underwent genetic testing were derived from 34 unrelated families. Thirty-two variants were tested and 9 of them are novel. Eighteen cases had ANK1 variants, 15 had SPTB variants, and 1 had SLC4A1 variant. 25 patients performed core family members underwent genetic testing, 17 (68.0%, 17/25) were de novo, 5 (20.0%, 5/25) were maternally inherited, and 3 (12.0%, 3/25) were paternally inherited. ANK1-HS patients exhibited more severe anemia compared to cases with SPTB-HS, showing lower levels of RBC and HB (P < 0.05). Anemia was more severe in patients diagnosed in childhood than in those diagnosed in adulthood. Within the ANK1-HS group, MCH levels in adult patients was significantly higher than those in children (P < 0.05), while there were no significant differences in RBC, HB, MCV, and MCHC levels between two groups. Adult patients with SPTB-HS had significantly higher levels of RBC, HB, and MCH than pediatric patients (P < 0.05), while MCV and MCHC levels showed no significant statistical differences. CONCLUSION: This study conducted a comparative analysis of phenotypic characteristics and molecular genetics in adult and pediatric patients diagnosed with HS, confirming that pediatric ANK1-HS patients exhibit a more severe anemic phenotype compared to SPTB-HS patients, while the severity of HS in adults does not significantly differ between different causative genes.

Rapid and sustained response to luspatercept and eltrombopag combined treatment in one case of clonal cytopenias of undetermined significance with prior failure to cyclosporin and androgen therapy: a case report.

Clonal cytopenia of undetermined significance (CCUS) has the characteristics of high-risk transformation into myelodysplastic syndromes. At present, there are few effective treatments for CCUS, and there is no consensus or evidence-based recommendation. We present a case demonstrating a rapid, significant and sustained response to combined treatment with luspatercept and eltrombopag, following the failure of cyclosporin and androgen therapy. Even after discontinuing luspatercept for 10 months, trilineage haematopoiesis remained normal with the use of cyclosporin and other haematopoietic stimulants. This case suggests that the inhibition of transforming growth factor-ß could potentially have an immunomodulatory effect, thereby promoting the recovery of haematopoietic function. Luspatercept, along with Acalabrutinib or Cyclosporine, may synergistically stimulate haematopoiesis.

Application of hybrid multi-criteria decision-making approach to analyze wastewater microalgae culture systems for bioenergy production.

Bioenergy generation from microalgae can significantly contribute to climate mitigation and renewable energy production. In this regard, several multi-criteria decision-making method were employed to prioritize appropriate microalgae culture system for bioenergy production. Entropy weight, Criteria Importance Through Intercriteria Correlation (CRITIC) and Technique for Order of Preference by Similarity to Ideal Solution (TOPSIS) were the employed MCDA method. Fourteen microalgae culture systems were selected as a case study, which contain teen monoculture and four dual-culture. Initially, through ans in-depth review of the literature and expert views, four categories total eight indicators were selected as the evaluation indices of the study, namely 1) Proliferation: Half growth cycle and Max growth rate,2) Biomass output: Bio-crude yield and Lipid yield, 3) Nutrient utilization: residual concentration of total Nitrogen and total Phosphorus, and, 4) Stability: coefficient of variation of Bio-crude yield and Lipid yield. The result indicated that "Pediastrum sp. & Micractinium sp." was identified as the most bioenergy potential microalgae culture system, and the evaluation results of entropy weight method and CRITIC method are similar. It is pertinent to note that 1)the entropy weight method exhibits lower sample size requirements, 2) the critic method excels when dealing with larger sample sizes, and 3) the TOPSIS method necessitates the incorporation of appropriate weighting methods to ensure credible results. In the application stage, the key indicators related to cost can be further included in the evaluation indices.

Pilot-scale membrane-covered composting of food waste: Initial moisture, mature compost addition, aeration time and rate.

The impact of different operational parameters on the composting efficiency and compost quality during pilot-scale membrane-covered composting (MCC) of food waste (FW) was evaluated. Four factors were assessed in an orthogonal experiment at three different levels: initial mixture moisture (IMM, 55 %, 60 %, and 65 %), aeration time (AT, 6, 9, and 12 h/d), aeration rate (AR, 0.2, 0.4, and 0.6 m3/h) and mature compost addition ratio (MC, 2 %, 4 %, and 6 %). Results indicated that 55 % IMM, 6 h/d AT, 0.4 m3/h AR, and 4 % MC addition ratio simultaneously provided the compost with the maximum cumulative temperature and the minimum moisture. It was shown that the IMM was the driving factor of this optimum composting process. On contrary, the optimal parameters for reducing carbon and nitrogen loss were 65 % IMM, 6 h/d AT, 0.4 m3/h AR, and 2 % MC addition ratio. The AR had the most influence on reducing carbon and nitrogen losses compared to all other factors. The optimal conditions for compost maturity were 55 % IMM, 9 h/d AT, 0.2 m3/h AR, and 6 % MC addition ratio. The primary element influencing the pH and electrical conductivity values was the AR, while the germination index was influenced by IMM. Protein was the main organic matter limiting the composting efficiency. The results of this study will provide guidance for the promotion and application of food waste MCC technology, and contribute to a better understanding of the mechanisms involved in MCC for organic solid waste treatment.

Effect of different bulking agents on fed-batch composting and microbial community profile.

The current study focused on analyzing the effect of different types of bulking agents and other factors on fed-batch composting and the structure of microbial communities. The results indicated that the introduction of bulking agents to fed-batch composting significantly improved composting efficiency as well as compost product quality. In particular, using green waste as a bulking agent, the compost products would achieve good performance in the following indicators: moisture (3.16%), weight loss rate (85.26%), and C/N ratio (13.98). The significant difference in moisture of compost products (p < 0.05) was observed in different sizes of bulking agent (green waste), which was because the voids in green waste significantly affected the capacity of the water to permeate. Meanwhile, controlling the size of green waste at 3-6 mm, the following indicators would show great performance from the compost products: moisture (3.12%), organic matter content (63.93%), and electrical conductivity (EC) (5.37 mS/cm). According to 16S rRNA sequencing, the relative abundance (RA) of thermophilic microbes increased as reactor temperature rose in fed-batch composting, among which Firmicutes, Proteobacteria, Basidiomycota, and Rasamsonia were involved in cellulose and lignocellulose degradation.

Reducing nitrogen loss from farmland by layered double hydroxide-supported carbon dots-enhanced ammonium immobilization.

It remains a significant challenge to develop a kind of cost-effective and eco-friendly adsorbent with strong immobilization capabilities for ammonium in farmland. In this work, we employed Ca/Al layered double hydroxide-supported carbon dots (CDs@Ca/Al-LDHs) as a novel and efficient adsorbent for ammonium immobilization both in aqueous and soil environments. Such a composite could exhibit a high adsorption capacity towards ammonium in solution, which was four times higher than zeolite and three times higher than biochar under the same conditions. The mechanism investigations revealed that electrostatic interactions between the negatively charged CDs and the positively charged ammonium played a key role in the adsorption. In 30-day leaching experiments, the fabricated composite cumulatively reduced ammonium and nitrate by 6.3% and 9.7%, respectively at a dosage of 0.1% (w/w). Incubation experiments further confirmed that the developed composite could effectively inhibit ammonia volatilization and nitrification by immobilizing the ammonium within soil matrices. Our results demonstrated that CDs@Ca/Al-LDHs represented a promising candidate for cost-effective and eco-friendly immobilization of excess ammonium from over-fertilized farmland.

Transcranial magnetic stimulation effects on cognitive enhancement in mild cognitive impairment and Alzheimer's disease: a systematic review and meta-analysis.

Introduction: Transcranial magnetic stimulation (TMS) is a non-invasive intervention that holds promise for improving cognitive function in individuals with Alzheimer's disease (AD). However, the effectiveness of this therapy and the optimal TMS parameters has not reached a consensus. The purpose of the meta-analysis was to systematically discern the effectiveness of different components of TMS protocols on cognitive improvement in patients with mild cognitive impairment (MCI) and AD. Methods: The meta-analysis was preregistered on Prospero (registration number: CRD42022345482). PubMed, Web of Science, Science Direct, and Cochrane Library databases were used to search, screen and identify eligible studies with the following keywords: Transcranial Magnetic Stimulation OR TMS OR theta burst stimulation AND Alzheimer OR Alzheimers OR Alzheimer's OR mild cognitive impairment OR MCI. Randomized controlled trials (RCTs) of participants with accepted standardized diagnostic criteria were searched by two authors independently. The risk of bias was assessed using an adapted Cochrane Risk of Bias tool. Standardized mean difference (SMD) and 95% confidence interval (CI) were calculated using the random-effects models. Subgroup analyses were performed to investigate the influential factors. Results: A total of 21 studies and 25 trials were included in this meta-analysis. The findings revealed a significant overall cognition improvement of real stimulation compared with sham stimulation (short-term effects: SMD, 0.91; 95% CI 0.44-1.38; P < 0.01; long-lasting effects: SMD, 0.91; 95% CI 0.27-1.55; P < 0.01). Subgroup analysis demonstrated that stimulation of the left dorsolateral prefrontal cortex and bilateral cerebellums, as well as moderate frequency stimulation (5 Hz and 10 Hz) on mild and moderate cognitive impairment patients, were more effective than other TMS protocols. However, the additional application of cognitive training showed no significant improvement. Conclusion: Cognitive improvement effect of TMS was demonstrated in MCI and AD patients in both short-term assessment and long-lasting outcomes, and the efficiency of TMS is affected by the stimulation frequency, stimulation site, and participant characteristics. Further RCTs are needed to validate the findings of our subgroup analysis. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022345482, identifier: CRD42022345482.

Features of event-related potentials during retrieval of episodic memory in patients with mild cognitive impairment due to Alzheimer's disease.

Objective: To provide a rigorous comparison between patients with mild cognitive impairment due to Alzheimer's disease (MCI-AD) and healthy elderly, as well as to assess the value of electroencephalography (EEG) in terms of early diagnosis, we conducted a neutral image recognition memory task involving individuals with positive biomarkers including ß amyloid deposition, pathologic tau or neurodegeneration. Methods: The task involving study and test blocks was designed to evaluate participants' recognition memory. Electroencephalogram was recorded synchronously to elicit event-related potentials in patients with MCI-AD and healthy control subjects. We further analyzed differences between groups or conditions in terms of behavioral performance, time domain, and time-frequency domain. Results: The MCI-AD cohort showed a slower response time to old/new images and had low accuracy regarding behavioral performance. The amplitude of the late positive complex for the old/new effects was significantly suppressed in the MCI-AD cohort when compared with that in the HC cohort. The amplitude of the late old/new effects was correlated with the Auditory Verbal Learning Test recognition score in all participants. The time-frequency domain analysis revealed that correct recognition of old items elicited a decrease in beta power, mainly limited to the HC cohort. Moreover, the combination of behavioral (processing speed and accuracy) and electrophysiological (average amplitude and relative power of delta band) measures contributes to classifying patients with MCI-AD from healthy elderly people. Conclusion: Changes of old/new effects, accuracy and response time are sensitive to the impairment of recognition memory in patients with MCI-AD and have moderate value in predicting the incipient stage of AD.

Comparison of methods for detecting protein extracted from excess activated sludge.

The protein contents of hydrolyzed sludge supernatant are commonly determined with the Kjeldahl method, but this method suffers from complicated operations, long process times, and large quantities of chemicals consumed. In this paper, the Lowry, bicinchoninic acid (BCA), and Bradford methods were used to test the precision and spiked recovery of proteins from sludge supernatants hydrolyzed by alkaline-thermal hydrolysis (ATH), enzymatic hydrolysis (EH), and ultrasound-assisted enzymatic hydrolysis (UEH), and the results were compared with those obtained with the Kjeldahl method. For all the hydrolytic processes, the sludge protein values determined with the three tested methods were within 0.05 of each other, which met the experimental requirement for accuracy. Both the Lowry and BCA methods had recovery rates of 95-105%, while the Bradford method showed large deviations and was not highly reliable. The three protein determination methods showed significant differences with the Kjeldahl method (P<0.05). However, the relative deviation between the Kjeldahl and BCA methods was the smallest (3-5%), followed by those between the Kjeldahl and the Lowry (11-21%) and Bradford methods (21-90%), and the causes of the deviations were analyzed based on the protein hydrolysate components and the mechanisms for the different detection methods. On the basis of these results, the BCA method was chosen as the most appropriate quantification method for use with sludge protein extraction, and it was used to analyze the protein contents extracted from residual sludge samples obtained from two sewage treatment plants. The reliability of the method was verified, and this lays a foundation for the extraction and reclamation of sludge proteins.

Optimization of protein recovery from sewage sludge via controlled and energy-saving ultrasonic-alkali hydrolysis.

The abundant protein in excess sludge can be recovered to prepare high value-added products. However, this sustainable treatment method still has large challenges, such as high energy consumption. In this work, the classical batch operation (BO) and semi-batch operation (SBO) modes were adopted and compared for ultrasonic-alkali hydrolysis. The results showed that the reaction time of SBO significantly decreased to half of that of BO with the same efficiency (ca. 70 %), indicating that SBO was much more energy-efficient. Moreover, analysis of the nitrogen solubility index and trichloroacetic acid-soluble nitrogen index demonstrated that the further proteolysis of protein under SBO was limited. Furthermore, the first-order reaction model fitted the hydrolysis data well (R2 ≥ 0.91) for both modes, in which the rate constant of SBO (k = 0.44 min-1) was 2.3 times that of BO. Finally, the properties of both products met the standards of foaming extinguishers.

Preparation of a sulfonated coal@ZVI@chitosan-acrylic acid composite and study of its removal of groundwater Cr(VI).

In this research, a new composite adsorbent (SC@ZVI@CS-AA) was designed and synthesized, and its application for the removal of Cr(VI) in groundwater was investigated. The interaction between SC@ZVI@CS-AA and Cr(VI) conformed to a pseudo-second-order model, and the adsorption process was dominated by chemisorption. The effects of material ratios, pH, temperature, SC@ZVI@CS-AA dosage, and coexisting ions on the removal of Cr(VI) were investigated. The removal efficiency of Cr(VI) by SC@ZVI@CS-AA reached 95%, and the reaction was significantly inhibited when SO42- was present. Thermodynamically, the adsorption of Cr(VI) proceeded spontaneously above 35 °C (ΔGθ < 0). According to scanning electron microscopy, X-ray photoelectron spectroscopy, Fourier transform infrared spectrometry, and synchronous thermal analysis, the removal mechanism of Cr(VI) by SC@ZVI@CS-AA was attributed to electrostatic attraction and reduction. In addition, SC@ZVI@CS-AA had good cyclic adsorption performance. Overall, the SC@ZVI@CS-AA composite showed great potential in the remediation of Cr(VI)-contaminated groundwater.

Osmoprotectants boost adaptation and protect methanogenic microbiome during ammonia toxicity events in continuous processes.

Different osmoprotectants were used to counteract ammonia toxicity in continuous anaerobic reactors. The anaerobic microbiome osmoadaptation process and its role to the methanogenic recovery are also assessed. Three osmoprotectants (i.e., glycine betaine, MgCl2 and KCl) were respectively introduced in continuous reactors at high ammonia levels, namely RGB, RMg, RK, while a control reactor (RCtrl) was also used. After ammonia was introduced, the RGB, RMg, RK and RCtrl suffered 39.0%, 36.6%, 39.9% and 36.2% methane production loss, respectively. Osmoprotectants addition recovered significantly methane production by up to 68.9%, 54.3% and 32.2% for RGB, RMg and RK, respectively contrary to RCtrl, where production increased only by 13.6%. The recovered methane production was maintained in RGB and RMg for at least four HRTs, even after the addition of osmoprotectants was stopped, due to the formed methanogenic microbiota by osmoadaptation process, with Methanoculleus sp. as the dominant species.

Intracellular and extracellular sources, transformation process and resource recovery value of proteins extracted from wastewater treatment sludge via alkaline thermal hydrolysis and enzymatic hydrolysis.

Excess sludge contains a large amount of protein and can be recycled to prepare industrial foaming agents, foliar fertilizers and other high value-added products. The optimization and effects of sludge protein extraction using the common processes of alkaline thermal hydrolysis (ATH) and enzymatic hydrolysis (EH) have been widely studied. This study focused on the protein extraction mechanisms of ATH and EH by comparing the ratio of intracellular to extracellular proteins extracted and the transformation of protein during the hydrolysis process. The extracellular protein content was 82.6 ± 5.07 mg/g VSS, and the content of intracellular protein extracted using ATH and EH was 376.9 mg/g VSS and 127.9 mg/g VSS, respectively. The ratio of intracellular to extracellular proteins extracted by ATH and EH was 4.5 and 1.5, respectively, indicating that ATH had a much better wall-breaking effect that allowed it to extract abundant intracellular proteins. The protein content obtained from ATH continuously increased over time, and approximately 38 % of proteins were further hydrolyzed to polypeptides. In contrast, the relatively low protein content extracted by EH possibly limited subsequent polypeptide hydrolysis, but subsequent hydrolysis to amino acids was not noticeably affected and was linearly correlated with the amount of protein extracted. An analysis of the recycling convenience and value of extracted proteins showed that the sludge dewatering performance increased by 86.7 % and 45.5 % after ATH and EH treatment, respectively, which was conducive to the subsequent separation of the protein solution. The protein extracted by ATH, with a large amount of peptides, would be beneficial to prepare industrial foaming agents, while the protein extracted by EH was rich in free amino acids and could be used to prepare foliar fertilizer.

Effects of coronavirus disease 2019 lockdown on metabolic syndrome and its components among Chinese employees: A retrospective cohort study.

Objective: Coronavirus disease 2019 (COVID-19) and the accompanying isolation have changed resident life rhythms and behaviors. This study investigated the effects of the COVID-19 pandemic on metabolic syndrome (MetS) and its components in employees in southwestern China. Methods: This retrospective cohort study included 3,777 employees of five institutions who underwent physical examinations at the Affiliated Hospital of Southwest Medical University for three consecutive years from 2018 to 2020. We collected data on participant age and sex and measured the component indices of metabolic syndrome, including waist circumference, blood pressure (systolic and diastolic), fasting blood glucose level, and blood lipid (triglyceride and high-density lipoprotein cholesterol) level. We applied t-, chi-square, Mann-Whitney U, and Friedman's M tests to compare metabolic variables at different times. Results: The incidence of MetS in 2020 was 18.6%, significantly higher than the prevalence of 15.7% before the epidemic. The number of abnormal MetS components following the COVID-19 lockdown was much greater than those in 2018 (P < 0.001) and 2019 (P < 0.001), with no significant variations between the two years (P = 0.142). All metabolic parameters, except for fasting blood glucose, were significantly worse than those pre-lockdown. The increase in the prevalence of MetS and all its abnormal components except for fasting glucose from 2019 to 2020 was significantly higher than that from 2018 to 2019. The change values between 2019-2020 and 2018-2019 for all indices except for diastolic blood pressure did not differ significantly between men and women. For all component indicators except for waist circumference, we observed no significant age differences in the growth differentials between the two periods (2019-2020 and 2018-2019). Conclusions: COVD-19 lockdown have increased metabolic health risks among Chinese adults. Targeted measures, such as health education, are urgently needed to address poor metabolic health caused by the COVID-19 pandemic.

Preparation and mechanical optimization of a two-layer silk/magnesium wires braided porous artificial nerve guidance conduit.

Peripheral nerve injures have long been a tricky problem in surgery and a feasible treatment is the transplantation of nerve guidance conduits (NGCs). This study presents a two-layer composite NGC with fair mechanical properties and good biocompatibility. The inner layer was made of degummed silk yarns/magnesium wires using braiding technology, and the outer layer was made from mixed solution of silk fibroin/chitosan (SF/CS) using freeze-drying treatment. Orthogonal experimental design was applied to rationally design the braided structural layer and obtain the optimal combination of technical process parameters. Meanwhile, the SF/CS porous outer layer was optimized from three concentrations of SF/CS solution. In vitro and in vivo study suggested that the textile-forming scaffold exhibited good biocompatibility and no toxicity. During 4 weeks' degradation, the skeleton of conduits retained its shape, and magnesium ions released from degraded magnesium wires contributed to sustainable release and uniform dispersion, proliferation and adhesion of Schwann cells, indicating potential approach in the development of NGCs.

Acid/alkali pretreatment enhances the formation of vivianite during anaerobic fermentation of waste activated sludge.

Phosphorus (P) recovery from waste activated sludge (WAS) of wastewater treatment plants is significant in the world suffering from P shortage. Recently, vivianite crystallization has been regarded as an essential method of recovering P from anaerobic fermentation (AF) of WAS. This study performed acid/alkali pretreatment (pH 3/pH 10) on AF of WAS to improve iron reduction and vivianite formation. The results showed that the maximum iron reduction rate (Rmax) in the pH 3 and pH 10 groups was increased by 1.9 and 1.7 times compared with that in the Control-Fe group, and the iron reduction efficiency (EFe) was increased by 17.5% and 12.0% respectively. The Fe bound P (Fe-P) proportion in the sludge in the pH 3 and pH 10 groups increased by 50.0% and 33.7%, respectively. Furthermore, the relative abundance of the iron-reducing bacteria Clostridium_sensusensu in the pH 3 group was higher; and the Fe-P proportion in the sludge and the size of vivianite crystal after AF were larger. With these results, pH 3 pretreatment was preferred for promoting Fe2+ release and vivianite formation during AF.

Effect of cerebellum stimulation on cognitive recovery in patients with Alzheimer disease: A randomized clinical trial.

INTRODUCTION: Evidence indicates that the cerebellum is involved in cognitive processing. However, the specific mechanisms through which the cerebellum repetitive transcranial magnetic stimulation (rTMS) contributes to the cognitive state are unclear. METHODS: In the current randomized, double-blind, sham-controlled trial, 27 patients with Alzheimer's disease (AD) were randomly allotted to one of the two groups: rTMS-real or rTMS-sham. We investigated the efficacy of a four-week treatment of bilateral cerebellum rTMS to promote cognitive recovery and alter specific cerebello-cerebral functional connectivity. RESULTS: The cerebellum rTMS significantly improves multi-domain cognitive functions, directly associated with the observed intrinsic functional connectivity between the cerebellum nodes and the dorsolateral prefrontal cortex (DLPFC), medial frontal cortex, and the cingulate cortex in the real rTMS group. In contrast, the sham stimulation showed no significant impact on the clinical improvements and the cerebello-cerebral connectivity. CONCLUSION: Our results depict that 5 Hz rTMS of the bilateral cerebellum is a promising, non-invasive treatment of cognitive dysfunction in AD patients. This cognitive improvement is accompanied by brain connectivity modulation and is consistent with the pathophysiological brain disconnection model in AD patients.

Enhancing enzyme activity via low-intensity ultrasound for protein extraction from excess sludge.

Rich protein within excess sludge could be recovered to prepare high value-added products such as liquid fertilizer and foaming agents. Low-intensity ultrasonication was adopted to help extract sludge protein by improving enzyme activity. Alkaline protease was added to the sludge for ultrasonic irradiation, and the maximum enzyme activity at 3500 kJ/kg TS was approximately 21% higher than that without ultrasonication. The protein extraction effect, specific resistance of sludge (SRS) and economics of low-intensity ultrasound-assisted enzymatic hydrolysis (LUEH) were compared with those of single enzymatic hydrolysis (EH) and HUEH under optimal conditions. The protein extraction rates of HUEH and LUEH were both higher than that of EH. Although the protein extraction rate of LUEH was 13.6% lower than that of HUEH, the amino acid content was similar because the low-intensity ultrasonic radiation promoted the enzyme activity and thereby enhanced the protein hydrolysis capacity. After hydrolysis, the SRS of LUEH was lower than that of HUEH, indicating that LUEH possessed a better dewatering performance, which was beneficial to the subsequent separation of the protein solution. The amount consumed by LUEH was approximately 20% lower than that consumed by HUEH and 17.3% lower than that consumed by EH. In addition, the enzyme dosage was reduced by approximately 38.5% with LUEH. Therefore, the total cost of LUEH was less than that of EH and HUEH, indicating that LUEH is more economically feasible for the extraction of protein from excess sludge.

Drug repositioning based on multi-view learning with matrix completion.

Determining drug indications is a critical part of the drug development process. However, traditional drug discovery is expensive and time-consuming. Drug repositioning aims to find potential indications for existing drugs, which is considered as an important alternative to the traditional drug discovery. In this article, we propose a multi-view learning with matrix completion (MLMC) method to predict the potential associations between drugs and diseases. Specifically, MLMC first learns the comprehensive similarity matrices from five drug similarity matrices and two disease similarity matrices based on the multi-view learning (ML) with Laplacian graph regularization, and updates the drug-disease association matrix simultaneously. Then, we introduce matrix completion (MC) to add some positive entries in original association matrix based on low-rank structure, and re-execute the multi-view learning algorithm for association prediction. At last, the prediction results of the above two operations are integrated as the final output. Evaluated by 10-fold cross-validation and de novo tests, MLMC achieves higher prediction accuracy than the current state-of-the-art methods. Moreover, case studies confirm the ability of our method in novel drug-disease association discovery. The codes of MLMC are available at https://github.com/BioinformaticsCSU/MLMC. Contact: jxwang@mail.csu.edu.cn.