Search

Academic debate still exists as to whether and how multi-scale microstructure recovery is linked to creep properties rejuvenation of superalloys. We propose a rejuvenation heat treatment (RHT) for one single-crystal superalloy crept at 1100 °C/120 MPa, by which the degraded phase- and dislocation-microstructure can be recovered to standard heat treatment one. Despite experiencing different plastic deformation, such recovered microstructure leads to nearly a fixed 20% improvement in creep life. Through triple creep-RHT-creep cycle tests, the complete rejuvenation of creep life after special creep time has been validated, while the plastic deformation limit increases, where creep properties recoverability remains.

Carbon use efficiency (CUE) is essential for understanding how climate change impacts carbon fixation by vegetation across diverse ecosystems globally. However, the effects of anthropogenic efforts, such as ecosystem restoration of degraded grasslands via livestock grazing exclusion with fences on the spatiotemporal variation in CUE under ongoing climate change remain poorly evaluated and understood. In this study, we calculated CUE values for fenced and adjacent grazed alpine grasslands in Tibet, China. We considered soil properties, topographical features, and climate conditions as potential predictors to explain the spatial patterns and temporal dynamics of CUE across these grasslands. Our results showed that the annual mean CUE of fenced vs. grazed grasslands were similar with values of 0.6961 and 0.6956 across the whole plateau. However, the annual CUE of fenced grasslands increased at a faster rate (6.89 × 10−5 per year) compared to grazed grasslands (0.23 × 10−5 per year) from 2006 to 2019. CUE also exhibited substantial variation across alpine grassland communities, with the highest values observed in alpine steppe meadows under both fenced and grazed management. Precipitation was identified as the most influential factor controlling the spatial pattern of CUE and showed a significant negative correlation with CUE. Moreover, the presence of fences was found to reduce the sensitivity of CUE to in response to varying precipitation. The effectiveness of fences in enhancing CUE primarily depends on local environmental conditions. Our study sheds light on the interplays between ecological restoration efforts and climate change in shaping the CUE dynamics of alpine grasslands on the Tibetan Plateau and emphasizes the importance of local environmental contexts when programming and implementing restoration projects.

Climate change is one of dominators driving the greening of vegetation worldwide, which is expected to enhance land carbon sink and mitigate global warming. The sensitivity of vegetation greenness to climate change is fluctuant and regulated by other environmental factors. However, the drivers and mechanisms behind remain unclear so far. Here, we hired long-term satellite-based vegetation index (NDVI), climatic variables, nitrogen deposition, and atmospheric CO2 records to investigate variations of greenness climatic sensitivity and its drivers across Eurasia. To obtain the timeseries of temperature (γNDVITEM) and precipitation sensitivity (γNDVIPRE), we applied multi-regression models and regressed temperature and precipitation on NDVI in each 9-year moving windows. The results showed that the area of vegetation greenness limited by low temperatures substantially shrunk, while the area of vegetation greenness limited by precipitation deficit increased during 1982–2015. Specifically, significantly decreasing γNDVITEM and γNDVIPRE accounted for 29.8% and 20.1%, respectively, while remarkably increasing γNDVITEM and γNDVIPRE accounted for about 18.2% and 24.5%, respectively, of the vegetated lands across Eurasia. Declining γNDVITEM was widely observed in most biomes, including tropical and subtropical moist broadleaf forests, temperate broadleaf and mixed forests, temperate coniferous forests, croplands, and deserts and xeric shrublands. Substantially increasing γNDVIPRE was merely found in montane grasslands and shrublands, and tropical and subtropical dry broadleaf forests, while decreasing γNDVIPRE and nonlinear regimes was widely proved in other biome types. Spatially, rather than elevated CO2 and nitrogen deposition, climate factors (temperature, precipitation, and radiation) jointly dominated γNDVITEM and γNDVIPRE variations across nearly 45% and 48% of Eurasia respectively. Our results uncovered the apparent pattern of greenness climate sensitivity changes across Eurasia and highlighted the necessity to unfold the underlying mechanisms based on plant physiology and traits.

The Proton Exchange Membrane Fuel Cell (PEMFC) is a fast-developing battery technology, and the key to its reliability and lifespan improvement lies in the accurate assessment of durability. However, the degradation mechanism of the PEMFC is hard to determine and its internal parameters are highly coupled. Thus, the development of a more accurate life prediction model that meets the actual scenarios is to be investigated urgently. To solve this problem, a multi-feature fusion life prediction method based on the Temporal Convolutional Network-Gated Recurrent Unit (TCN-GRU) is proposed. A TCN algorithm is used as the prediction base model, and two GRU modules are included with the model to strengthen the model’s expression ability and improve its predictive accuracy. Two widely recognized datasets and two operating conditions are utilized for model training and prediction, respectively. Comparisons are made with single-feature parameter models in terms of Root Mean Square Error (RMSE) and the Determination Coefficient (R2). The results show that the prediction accuracy of the TCN-GRU multi-feature fusion model is higher than that of the single-feature models in terms of stability and anti-interference under both operating conditions. The accuracy of the TCN-GRU (three-feature) model is the most optimal in a steady-state condition at 80% of the training set ratio (RMSE = 3.27 × 10−3, R2 = 0.965). Furthermore, with the increase in the input feature parameter, the TCN-GRU model is closer to the real value, which proves once again that the proposed model can meet the accuracy requirements of the life prediction of the PEMFC.

Abstract Background High throughput experiments in cancer and other areas of genomic research identify large numbers of sequence variants that need to be evaluated for phenotypic impact. While many tools exist to score the likely impact of single nucleotide polymorphisms (SNPs) based on sequence alone, the three-dimensional structural environment is essential for understanding the biological impact of a nonsynonymous mutation. Results We present a program, 3DVizSNP, that enables the rapid visualization of nonsynonymous missense mutations extracted from a variant caller format file using the web-based iCn3D visualization platform. The program, written in Python, leverages REST APIs and can be run locally without installing any other software or databases, or from a webserver hosted by the National Cancer Institute. It automatically selects the appropriate experimental structure from the Protein Data Bank, if available, or the predicted structure from the AlphaFold database, enabling users to rapidly screen SNPs based on their local structural environment. 3DVizSNP leverages iCn3D annotations and its structural analysis functions to assess changes in structural contacts associated with mutations. Conclusions This tool enables researchers to efficiently make use of 3D structural information to prioritize mutations for further computational and experimental impact assessment. The program is available as a webserver at https://analysistools.cancer.gov/3dvizsnp or as a standalone python program at https://github.com/CBIIT-CGBB/3DVizSNP .

Improvement of performance and cost reduction are urgent issues for proton exchange membrane water electrolyzers (PEMWEs). This study explored ways to improve electrolyzer performance from the perspective of the catalyst layer (CL) microstructures. The pore network model of the CL was established, and the obtained structural, mass transfer and electrochemical parameters were coupled with the macroscale performance model of PEMWE to get the multi-scale performance model. The mass transfer, heat transfer, and electrochemical processes inside the electrolyzer were considered to improve the model's accuracy. The maximum error between the simulated results by this multi-scale performance model and the experimental data was verified to be only 3.1%. The verified model was then used to predict the electrolyzer performance with various cathode/anode catalyst layer (CCL/ACL) microstructures. The predicted results showed that the electrochemical activity surface area affects the performance of PEMWE to a much greater extent than the conductivity. The performance of PEMWE gradually deteriorated as the catalyst particle radius or pore diameter of the CCL/ACL increased by the same degree, and the catalyst particle radius had a relatively more significant impact on the performance of the electrolyzer. Overall, the variation of ACL structure had a more substantial effect on the electrolyzer performance than that of CCL.

The mass transfer enhanced cathode flow field with little pressure loss is a key factor to proton exchange membrane fuel cell (PEMFC) design. A new type of cathode flow field incorporating ship-shaped baffles which enhances mass transfer while causes little parasitic power is proposed in this study. Effects of length, breadth, molded depth, liquid level height and draft depth of the ship-like baffle on water removal in flow field and PEMFC performance are investigated numerically. Results show that ship-like baffles could accelerate water removal. Slim baffle with big surface helps to break droplets into smaller ones. Ship-like baffles also help to pushed reactant downward and distributed reactant evenly, especially in area under ribs. Sloping “bow” of baffle helps to enhance mass transfer downward and sloping “stern” of baffle helps to further split the droplets already divided by baffles into smaller ones and throw them into the upper part of the channel. In general, the proposed flow field with ship-like baffles shows a good performance in PEMFC mass transfer.

Leukemia is a fatal disease that requires the counting of White Blood Cells (WBCs) in bone marrow for diagnosis. However, bone marrow blood contains many types of leukocytes, some of which have subtle differences. To address this issue, we propose the WBC-GLAformer model, which comprises three parts: Low-level Feature Extractor (LFE), Global–Local Attention based Encoder (GLAE), and Discrimination Part Select (DPS). The LFE uses a convolutional neural network (CNN) to tokenize patches from the extracted low-level features. The GLAE combines the ability of the CNN to extract local features with the ability of the transformer to extract global features, thereby enriching the features of leukocyte images. The DPS improves the accuracy of leukocyte classification by selecting the discriminative regions. Our method achieves state-of-the-art results in the bone marrow leukocyte fine-grained classification dataset. Experimental results demonstrate that the model has good generalization on different datasets and is more robust to the optimizer. And visualization results show that the model can effectively focus on the discriminative parts of different cells. Code is available at https://github.com/ywj1/WBC-GLAformer

Abstract Background Subjective cognitive decline (SCD) is a putative Alzheimer’s disease (AD) precursor without objective neuropsychological deficits. The hippocampus plays an important role in cognitive function and emotional responses and is generally aberrant in SCD. However, previous studies have mainly focused on static functional connectivity (sFC) by resting-state functional magnetic resonance imaging (fMRI) in SCD individuals, and it remains unclear whether hippocampal dynamic functional connectivity (dFC) changes exist in SCD and whether those changes are associated with subtle changes in cognitive function or affect. Methods Seventy SCD patients and 65 healthy controls were recruited. Demographic data, comprehensive neuropsychology assessments, and resting-state fMRI data were collected. The bilateral anterior and posterior hippocampi were selected as seeds to investigate the static and dynamic functional connectivity alterations in SCD. Results Compared to healthy controls, subjects with SCD exhibited: (1) decreased sFC between the left caudal hippocampus and left precuneus; (2) decreased dFC variability between the bilateral caudal hippocampus and precuneus; (3) increased dFC variability between the bilateral rostral hippocampus and caudate nucleus; and (4) increased dFC variability between the left rostral hippocampus and left olfactory cortex. Additionally, the attention scores were positively correlated with dFC variability between the left posterior hippocampus and left precuneus, and the dFC variability between the bilateral anterior hippocampus and caudate nucleus was positively correlated with depression scores and negatively correlated with global cognition scores. Conclusion SCD individuals exhibited abnormal sFC and dFC in the anterior-posterior hippocampus, and abnormal dFC was more widespread than abnormal sFC. A combination of sFC and dFC provides a new perspective for exploring the brain pathophysiological mechanisms in SCD and offers potential neuroimaging biomarkers for the early diagnosis and intervention of AD.

The external excitation caused by random wind load can greatly affect the fatigue life of the wind power transmission system. A four-component model considering the wake effect is used to simulate the random wind speed of a wind farm， and combined with the finite element method， the fatigue life of the wind power planetary gear train is obtained. On this basis， the influence of the depth， length and extension angle of the sun gear single-tooth and double-tooth root cracks on the fatigue strength of wind power planetary gear trains is studied based on the sub-model method. Finally， it is found that the influence degree of the crack size parameters on the fatigue life of the wind power planetary gear train is: crack depth> crack length> crack extension angle. The effect of double root cracks on fatigue life is much greater than that of single root cracks， the fatigue life of the first-engaged tooth in the double-root crack state is much shorter than that of the single-root crack state， and the fatigue life of the later-engaged tooth is slightly larger than that of a single-tooth root crack state. Related research provides a theoretical basis for optimizing the service performance of wind turbines.

In order to solve the problem that the complex structure and operating conditions of planetary gear box lead to the difficulty of signal fault feature extraction， the frequency spectrum feature of gearbox vibration signal with faults is preliminarily deduced by analyzing the vibration mechanism of planetary gear train. The method of harmonic product spectrum （HPS） and sideband product spectrum （SPS） is used to accurately extract the fault characteristic frequencies of the simulation signals under the condition that the noise interference and fault impact are not obvious. The vibration signals of the planetary gearbox under different operating conditions and different fault states are further collected，and the extracted fault features are input into the convolutional neural network for fault identification. The fault information of the gearbox is obtained successfully，which proves the feasibility of the proposed method in fault diagnosis of the planetary gearbox.

By distinguishing between two types of neutralizing antibodies that either exhibit or lack antibody-dependent enhancement (ADE) activity, FcγRIIB and bivalent binding are shown to be required for ADE in SARS-CoV-2 infection.

Abstract Safe, effective, and economical vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are needed to achieve adequate herd immunity and end the pandemic. We constructed a novel SARS-CoV-2 vaccine, CoVac501, which is a self-adjuvanting peptide vaccine conjugated with Toll-like receptor 7 (TLR7) agonists. The vaccine contains immunodominant peptides screened from the receptor-binding domain (RBD) and is fully chemically synthesized. It has been formulated in an optimized nanoemulsion formulation and is stable at 40 °C for 1 month. In non-human primates (NHPs), CoVac501 elicited high and persistent titers of protective neutralizing antibodies against multiple RBD mutations, SARS-CoV-2 original strain, and variants (B.1.1.7 and B.1.617.2). Specific peptides booster immunization against the B.1.351 variant has also been shown to be effective in improving protection against B.1.351. Meanwhile, CoVac501 elicited the increase of memory T cells, antigen-specific CD8+ T-cell responses, and Th1-biased CD4+ T-cell immune responses in NHPs. Notably, at an extremely high SARS-CoV-2 challenge dose of 1 × 107 TCID50, CoVac501 provided near-complete protection for the upper and lower respiratory tracts of cynomolgus macaques.

Abstract Post-traumatic olfactory dysfunction (PTOD) is associated with a significant decrease in quality of life. The present study aimed to explore whether PTOD is associated with depression and changes in sexuality. There were two groups in this case–control study. The patient group consisted of patients with PTOD (n = 55), and the control group comprised healthy individuals without the olfactory disorder (n = 115). Olfactory function, depression, partnership, and sexual satisfaction were assessed using the Iranian version of the Sniffin’ Sticks test (Ir-SST), Beck Depression Inventory (BDI), Enrich Couple Scale (ECS) and Sexual Satisfaction Scale for Women (SSSW). The BDI scores were higher in the patient group than in the control group (p

AIM: To investigate the suitability of a modified Hughes procedure, which consists of conjunctival flap with auricular cartilage grafting in reconstructing large full thickness upper and lower eyelid defect. METHODS: Patients with full thickness eyelid carcinoma involving more than 50% margin length who underwent surgical resection were retrospectively reviewed in the study. The defects were reconstructed using conjunctival flap with auricular cartilage grafting, covered with myocutaneous flap above. Followed-up time ranged from 12 to 24mo. Outcomes were classified as “good”, “fair”, and “poor” by evaluating the margin appearance, eyelid appearance, and complications. RESULTS: A total of 42 patients were enrolled in the study (26 males, 16 females, mean age, 68.6±7.7y, range: 53 to 82y). The mean defect widths measured 23.2±2.9 mm (range, 17 to 28 mm). The mean posterior lamellar defect height was 5.5±1.3 mm (4 to 8 mm). Thirty-seven patients had a “good” outcome (88.1%), 5 patients had a “fair” outcome (11.9%), and no one had a “poor” outcome. CONCLUSION: Conjunctival flap with auricular cartilage grafting and myocutaneous flap grafting is an effective procedure in reconstructing large full thickness upper and lower eyelid defect. It can not only achieve satisfied reconstruction, but also preserve intact tarsal plate of the opposite eyelid, avoiding retraction or entropion.

Since the outbreak of the coronavirus disease 2019 (COVID-19) pandemic, several variants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have emerged and have consistently replaced the previous dominant variant. Therapeutics against variants of SARS-CoV-2 are urgently needed. Ideal SARS-CoV-2 therapeutic antibodies would have high potency in viral neutralization against several emerging variants. Neutralization antibodies targeting SARS-CoV-2 could provide immediate protection after SARS-CoV-2 infection, especially for the most vulnerable populations. In this work, we comprehensively characterize the breadth and efficacy of SARS-CoV-2 RBD-targeting fully human monoclonal antibody (mAb) MW3321. MW3321 retains full neutralization activity to all tested 12 variants that have arisen in the human population, which are assigned as VOC (Variants of Concern) and VOI (Variants of Interest) due to their impacts on public health. Escape mutation experiments using replicating SARS-CoV-2 pseudovirus show that escape mutants were not generated until passage 6 for MW3321, which is much more resistant to escape mutation compared with another clinical staged SARS-CoV-2 neutralizing mAb MW3311. MW3321 could effectively reduce viral burden in hACE2-transgenic mice challenged with either wild-type or Delta SARS-CoV-2 strains through viral neutralization and Fc-mediated effector functions. Moreover, MW3321 exhibits a typical hIgG1 pharmacokinetic and safety profile in cynomolgus monkeys. These data support the development of MW3321 as a monotherapy or cocktail against SARS-CoV-2-related diseases.

BackgroundCognitive impairment in late−life depression (LLD) is considered to be caused by neurodegenerative changes. Elevated homocysteine (Hcy) levels may be linked to cognitive abnormalities associated with LLD. The important role of white matter (WM) damage in cognitive impairment and pathogenesis in patients with LLD has been widely reported. However, no research has explored the interrelationships of these features in patients with LLD.ObjectiveThe goal of the study was to examine the interrelationship between Hcy levels, cognition, and variations in WM microstructure detected by diffusion tensor imaging (DTI) in patients with LLD.MethodsWe recruited 89 healthy controls (HCs) and 113 patients with LLD; then, we measured the plasma Hcy levels of participants in both groups. All individuals performed a battery of neuropsychological tests to measure cognitive ability. Seventy-four patients with LLD and 68 HCs experienced a DTI magnetic resonance imaging (MRI) scan.ResultsPatients with LLD showed significantly lower fractional anisotropy (FA) values in the bilateral inferior longitudinal fasciculus than those of healthy participants. Only in LLD patients was Hcy concentration inversely associated to FA values in the forceps minor. Finally, multiple regression analyses showed that an interaction between Hcy levels and FA values in the right cingulum of the cingulate cortex and right inferior longitudinal fasciculus were independent contributors to the executive function of patients with LLD.ConclusionOur results highlight the complex interplay between elevated homocysteine levels and WM abnormalities in the pathophysiology of LLD-related cognitive impairment, consistent with the neurodegeneration hypothesis.

BackgroundResting-state EEG microstate and omega complexity analyses have been widely used to explore deviant brain function in various neuropsychiatric disorders. This study aimed to investigate the features of microstate dynamics and spatial complexity in patients with late-life schizophrenia (LLS).MethodMicrostate and omega complexity analyses were performed on resting-state EEG data from 39 in patients with LLS and compared with 40 elderly normal controls (NCs).ResultThe duration of microstate classes A and D were significantly higher in patients with LLS compared with NCs. The occurrence of microstate classes A, B, and C was significantly lower in patients with LLS compared with NCs. LLS patients have a lower time coverage of microstate class A and a higher time coverage of class D than NCs. Transition probabilities from microstate class A to B and from class A to C were significantly lower in patients with LLS compared with NCs. Transition probabilities between microstate class B and D were significantly higher in patients with LLS compared with NCs. Global omega complexity and anterior omega complexity were significantly higher in patients with LLS compared with NCs.ConclusionThis study revealed an altered pattern of microstate dynamics and omega complexity in patients with LLS. This may reflect the disturbed neural basis underlying LLS and enhance the understanding of the pathophysiology of LLS.

AIM: To retrospectively compare postoperative outcomes after primary enucleation and placement of a hydroxyapatite (HA) implant without wrapping, wrapped with auricular cartilage or donor sclera. METHODS: Medical records of patients presented as intraocular tumor or severe ocular injury were identified from the electronic medical record system. Cases underwent enucleation and HA orbital implantation were enrolled in this study and were divided into 3 groups according to the wrapping material of HA implant. Cases with autogenous cartilage caps were enrolled in group A (n=11), with donor sclera caps in group B (n=12), and without any wrapping material in group C (n=9). Follow-ups were set at 1, 2wk, 1, 3, 6, and 12mo after surgery. RESULTS: Altogether 32 cases finished the follow-up and were enrolled in this study. Three cases (27.27%) in group A, 4 cases (33.33%) in group B, and 4 cases (44.44%) in group C developed one complication each after surgery. In group A, no HA exposure occurred, but conjunctival inclusion cyst occurred in one and severe conjunctive chemosis in two cases. In group B, one HA exposure occurred, conjunctive inclusion cysts occurred in one, severe conjunctive chemosis occurred in one, and conjunctival granuloma occurred in one case. In group C, one HA exposure occurred, severe conjunctive chemosis occurred in two cases, and conjunctival granuloma occurred in one case. The case of exposure of none-wrapped implant was noted in the first 6mo after placement of the orbital implant. The case of exposure of donor sclera-wrapped implant was noted at the 12mo after placement of the orbital implant. Both exposure cases were treated successfully with conservative treatment. CONCLUSION: With low incidence of implant exposure and mild complications, auricular cartilage can be a good choice of alternative wrapping material of orbit implant with satisfied outcome.

Abstract Early detection of patients with late-life depression (LLD) with a high risk of developing dementia contributes to early intervention. Odor identification (OI) dysfunction serves as a marker for predicting dementia, but whether OI dysfunction increases the risk of dementia in LLD patients remains unclear. The present study aimed to explore the interactive effect of LLD and OI dysfunction on the risk of dementia and its underlying neuroimaging changes. One hundred and fifty-seven LLD patients and 101 normal controls were recruited, and data on their OI, cognition, activity of daily living (ADL), and resting-state functional magnetic resonance imaging were collected. Two × two factorial analyses were used to analyze the interactive effects of LLD and OI dysfunction on neuropsychological and neuroimaging abnormalities. Mediation analyses were used to explore whether abnormalities detected by neuroimaging mediated the the associations between OI and cognition/ADL. The results suggested that LLD and OI dysfunction exhibited additive effects on reduced ADL, global cognition and memory scores, as well as neuroimaging variables including (i) increased fractional amplitude of low-frequency fluctuation (fALFF) in the right orbitofrontal cortex and right precentral cortex, and (ii) increased regional homogeneity (ReHo) in the left hippocampus/fusiform gyrus, etc. In addition, these increased fALFF and ReHo values were associated with reduced neuropsychological scores (ADL, global cognition, memory, and language). Moreover, ReHo of the left hippocampus/fusiform gyrus completely mediated the relationship between OI and ADL, and partially mediated the relationship between OI and global cognition. Overall, mediated by the hypersynchronization of the left hippocampus/fusiform gyrus, OI dysfunction may increase the risk of dementia in LLD patients.

BackgroundLate-life depression (LLD) is a risk factor for cognitive decline in older adults, and odor identification (OI) deficits are an early indicator of cognitive decline with LLD. However, neuropsychiatric symptoms (NPSs) are common in LLD and are associated with OI deficits. In subjects with LLD, when OI deficits forecast cognitive decline, whether and how NPS affects the relationship between OI and cognition still must be further explored.ObjectiveTo comprehensively explore the potential effects of various NPSs on the relationship between OI and cognition in participants with LLD.MethodsThere were 167 patients with LLD and 105 normal elderly (NE) participants. The odor identification test (Sniffin' Sticks), cognitive function assessments (global cognition, memory, executive function, attention, language, visual space), and an NPS assessment (the neuropsychiatric inventory questionnaire) were performed on the subjects. In patients with LLD, the relationship among OI, cognition and NPSs was examined using correlation analysis and moderation analysis.ResultsIn patients with LLD, OI was positively correlated with cognition (global cognition, memory, executive function, attention, language) and negatively associated with NPSs (agitation and aberrant motor behavior). In NE group, OI was correlated with executive function. Moderation analysis showed that there was an interactive effect of agitation and cognitive impairment (language deficit or attention deficit) on OI in patients with LLD.ConclusionThe coexistence of agitation and language or attention deficit was associated with worse OI in subjects with LLD. Agitation should be considered since OI predicts cognitive decline in patients with LLD.

Here the authors characterize a monoclonal antibody from a COVID-19 convalescent patient that interferes with SARS-CoV-2 spike binding to ACE2 and has prophylactic and therapeutic activity in non-human primates. Antibody-dependent enhancement of infection is prevented by mutating the Fc region of the antibody.

Background: Odor identification dysfunction is an early predictor of the development of Alzheimer's disease (AD), but neuropsychiatric symptoms (NPS), which are common in AD and mild cognitive impairment (MCI), are also associated with odor identification dysfunction. Whether NPS affect the specificity of using odor identification dysfunction to predict cognitive decline in AD and MCI remains unclear.Methods: Patients (233 with MCI and 45 with AD) and 45 healthy controls (HCs) underwent assessments of odor identification (Sniffin' Sticks), NPS (Neuropsychiatric Inventory-12), and cognitive function (global cognition, memory, language, executive function, visual-spatial skill, and attention). Structural equation modeling (SEM) with bootstrapping estimation was conducted to explore the relationships between odor identification, NPS, and cognition.Results: Patients with NPS showed significantly worse performance in odor identification and cognition than patients without NPS and HCs. The SEM showed odor identification to be positively associated with cognition, and cognition had special indirect effects on odor identification through affective and psychosis symptoms (two factors extracted from Neuropsychiatric Inventory-12). Additionally, affective and psychosis symptoms partially mediated the effect of cognition on odor identification.Conclusion: Neuropsychiatric symptoms are associated with odor identification dysfunction in patients with AD and MCI. Studies exploring the relationship between odor identification dysfunction and cognitive decline in patients with AD and MCI should include an assessment of affective and psychosis symptoms, and adjust their confounding effects.

Background: Neuropsychiatric symptoms (NPS) and cognitive impairments are both common in patients with late-life depression (LLD). However, the relationship between NPS and cognitive functions in LLD patients remains unclear. The current study aims to explore the effects of NPS on cognitive impairments in LLD patients.Methods: Two hundred and sixty-two LLD patients and 141 normal controls (NC) were recruited. Exploratory factor analysis was used to extract factors from the Neuropsychiatric Inventory (NPI). Correlation, mediation, and moderation analyses were used to explore whether NPS exacerbated the cognitive impairments in LLD and whether NPS exhibited different effects on cognitive impairments in acute-state LLD (aLLD) and recovery-state LLD (rLLD).Results: Three main factors were extracted from the NPI, including emotional, behavioral, and psychotic factors. The patients with LLD exhibited worse cognition and higher NPI scores, and the scores of NPI-total and three extracted factors were negatively associated with cognitive scores. The mediation analyses exhibited that NPI-total and behavioral factor scores increase the difference in cognition scores between LLD and NC groups. The mediation analyses exhibited that behavioral factor score played a greater effect on impairing MMSE in the rLLD group than in the aLLD group. Additionally, behavioral factor score was in a trend to be negatively associated with Mini-Mental State Examination (MMSE) score changes at a one-year follow-up (p = 0.051).Conclusions: NPS, especially behavioral symptoms, exacerbate cognitive impairments in LLD and may contribute to residual cognitive impairment in rLLD patients. Early intervention for behavioral symptoms in LLD patients may be beneficial to their long-term clinical prognosis.

Objectives: Although previous studies have extensively confirmed the cross-sectional relationship between cognitive impairment and depression in depressed elderly patients, the findings of their longitudinal associations are still mixed. The purpose of this study was to explore the two-way causal relationship between depression symptoms and cognition in patients with late-life depression (LLD).Methods: A total of 90 patients with LLD were assessed across two time points (baseline and 1-year follow up) on measures of 3 aspects of cognition and depressive symptoms. The data were then fitted to a structural equation model to examine two cross-lagged effects.Results: Depressive symptoms predicted a decline in executive function (β = 0.864, p = 0.049) but not vice versa. Moreover, depressive symptoms were predicted by a decline in scores of working memory test (β = −0.406, p = 0.023), respectively. None of the relationships between the two factors was bidirectional.Conclusion: These results provide robust evidence that the relationship between cognition and depressive symptoms is unidirectional. Depressive symptoms may be a risk factor for cognitive decline. The decrease of information processing speed predicts depressive symptoms.

Leaf functional traits in drylands are sensitive to environmental changes, which are closely related to plant growth strategies and resource utilization ability and can reflect the balance of substance synthesis and water loss. However, the influence of environmental factors on photosynthetic production traits and water use traits is still unclear in drylands. In this study, nine environmental factors (climatic characteristics and soil physical and chemical properties), leaf net photosynthetic rate (A), transpiration rate (E), and stomatal conductance (GSW) were measured via 60 plant samples and 45 soil samples, which were collected at five sampling sites according to rainfall gradient. Redundancy analysis (RDA), structural equation model (SEM), and regression analysis were used to analyze the influencing mechanism of drought on photosynthetic production traits and water use traits. The results provided the following conclusions: (i) The hydrothermal condition determined A, E, and GSW by affecting the spatial distribution of soil nutrients (SN) and soil salinity (SS); meanwhile, temperature was able to affect A, E, and GSW directly. (ii) The water content (WC) was the key driver of the strength of the synergistic relationship between photosynthetic production traits and water use traits; soil salinity (SS) was the main driver of the synergistic relationship between E and GSW.

Climate models predict the further intensification of global warming in the future. Drylands, as one of the most fragile ecosystems, are vulnerable to changes in temperature, precipitation, and drought extremes. However, it is still unclear how plant traits interact with soil properties to regulate drylands’ responses to seasonal and interannual climate change. The vegetation sensitivity index (VSI) of desert scrubs in the Qaidam Basin (NE Tibetan Plateau) was assessed by summarizing the relative contributions of temperature (SGST), precipitation (SGSP), and drought (temperature vegetation dryness index, STVDI) to the dynamics of the normalized difference vegetation index (NDVI) during plant growing months yearly from 2000 to 2015. Nutrient contents, including carbon, nitrogen, phosphorus, and potassium in topsoils and leaves of plants, were measured for seven types of desert scrub communities at 22 sites in the summer of 2016. Multiple linear and structural equation models were used to reveal how leaf and soil nutrient regimes affect desert scrubs’ sensitivity to climate variability. The results showed that total soil nitrogen (STN) and leaf carbon content (LC), respectively, explained 25.9% and 17.0% of the VSI variance across different scrub communities. Structural equation modeling (SEM) revealed that STN and total soil potassium (STK) mediated desert scrub’s VSI indirectly via SGST (with standardized path strength of −0.35 and +0.32, respectively) while LC indirectly via SGST and SGSP (with standardized path strength of −0.31 and −0.19, respectively). Neither soil nor leave nutrient contents alone could explain the VSI variance across different sites, except for the indirect influences of STN and STK via STVDI (−0.18 and 0.16, respectively). Overall, this study disentangled the relative importance of plant nutrient traits and soil nutrient availability in mediating the climatic sensitivity of desert scrubs in the Tibetan Plateau. Integrating soil nutrient availability with plant functional traits together is recommended to better understand the mechanisms behind dryland dynamics under global climate change.

Abstract Background LncRNA PTCSC3 is a known tumor suppressor, while its roles in other human diseases are unclear. Methods All participants were admitted by The second Affiliated Hospital, School of Medicine, Zhejiang University from January 2016 to January 2018. RT-qPCR, Vectors, cell transfection, In vitro cell proliferation assay and western blot were using to carry out the experiment. Results In this study we found that PTCSC3 was downregulated, while toll-like receptor 4 (TLR4) was upregulated in periodontal ligament stem cells (PDLSCs) isolated from periodontitis affected teeth that in PDLSCs isolated from healthy teeth. Expression levels of PTCSC3 and TLR4 were only significantly and inversely correlated in PDLSCs isolated from periodontitis affected teeth but not in PDLSCs isolated from healthy teeth. PTCSC3 overexpression led to the downregulation of TLR4 in PDLSCs isolated from periodontitis affected teeth, while TLR4 overexpression failed to significantly affect PTCSC3. PTCSC3 overexpression also led to the inhibited proliferation of periodontitis-affected PDLSCs. Conclusions Therefore, lncRNA PTCSC3 may regulate the proliferation of PDLSCs and TLR4 expression to improve periodontitis.

Background: Modular organization reflects the activity patterns of our brain. Different disease states may lead to different activity patterns and clinical features. Early onset depression (EOD) and late onset depression (LOD) share the same clinical symptoms, but have different treatment strategies and prognosis. Thus, explored the modular organization of EOD and LOD might help us understand their pathogenesis.Method: The study included 82 patients with late life depression (EOD 40, LOD 42) and 90 healthy controls. We evaluated the memory, executive function and processing speed and performed resting-stage functional MRI for all participants. We constructed a functional network based on Granger causality analysis and carried out modularity, normalized mutual information (NMI), Phi coefficient, within module degree z-score, and participation coefficient analyses for all the participants.Result: The Granger function network analysis suggested that the functional modularity was different among the three groups (Pauc = 0.0300), and NMI analysis confirmed that the partition of EOD was different from that of LOD (Pauc = 0.0190). Rh.10d.ROI (polar frontal cortex) and Rh.IPS1.ROI (dorsal stream visual cortex) were shown to be the potential specific nodes in the modular assignment according to the Phi coefficient (P = 0.0002, Pfdr = 0.0744 & P = 0.0004, Pfdr = 0.0744).Conclusion: This study reveal that the functional modularity and partition were different between EOD and LOD in Granger function network. These findings support the hypothesis that different pathological changes might exist in EOD and LOD.

The global pandemic of COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in widespread social and economic disruption. Effective interventions are urgently needed for the prevention and treatment of COVID-19. Neutralizing monoclonal antibodies (mAbs) have demonstrated their prophylactic and therapeutic efficacy against SARS-CoV-2, and several have been granted authorization for emergency use. Here, we discover and characterize a fully human cross-reactive mAb, MW06, which binds to both SARS-CoV-2 and SARS-CoV spike receptor-binding domain (RBD) and disrupts their interaction with angiotensin-converting enzyme 2 (ACE2) receptors. Potential neutralization activity of MW06 was observed against both SARS-CoV-2 and SARS-CoV in different assays. The complex structure determination and epitope alignment of SARS-CoV-2 RBD/MW06 revealed that the epitope recognized by MW06 is highly conserved among SARS-related coronavirus strains, indicating the potential broad neutralization activity of MW06. In in vitro assays, no antibody-dependent enhancement (ADE) of SARS-CoV-2 infection was observed for MW06. In addition, MW06 recognizes a different epitope from MW05, which shows high neutralization activity and has been in a Phase 2 clinical trial, supporting the development of the cocktail of MW05 and MW06 to prevent against future escaping variants. MW06 alone and the cocktail show good effects in preventing escape mutations, including a series of variants of concern, B.1.1.7, P.1, B.1.351, and B.1.617.1. These findings suggest that MW06 recognizes a conserved epitope on SARS-CoV-2, which provides insights for the development of a universal antibody-based therapy against SARS-related coronavirus and emerging variant strains, and may be an effective anti-SARS-CoV-2 agent.

In this paper, the model of a proton exchange membrane fuel cell (PEMFC) with single straight channel is established to investigate the effect of dimensionless size factor of baffles on PEMFC performance. The influence of dimensionless length and height of baffles is discussed. Results show that adding baffles could dramatically optimize the mass transfer in PEMFC. The dimensionless length and height of the baffle have much influence on PEMFC performance.

A proton exchange membrane fuel cell (PEMFC) is known as one of the most promising energy sources for electric vehicles. A hydrogen system is required to provide hydrogen to the stack in time to meet the flow and pressure requirements according to the power requirements. In this study, a 1-D model of a hydrogen system, including the fuel cell stack, was established. Two modes, one with and one without a proportion integration differentiation (PID) control strategy, were applied to analyze the pressure characteristics and performance of the PEMFC. The results showed that the established model could be well verified with experimental data. The anode pressure fluctuation with a PID control strategy was more stable, which reduced the damage to the fuel cell stack caused by sudden changes of anode pressure. In addition, the performance of the stack with the PID control mode was slightly improved. There was an inflection point for hydrogen utilization; the hydrogen utilization rate was higher under the mode without PID control when the current density was greater than 0.4 A/cm2. What is more, a hierarchical control strategy was proposed, which made the pressure difference between the anode and cathode meet the stack working requirements, and, more importantly, maintained the high hydrogen utilization of the hydrogen system.

BackgroundOur previous study in animal models revealed that bilirubin could induce Aβ formation and deposition. Bilirubin may be important in neurodegenerative dementia with Aβ deposition. Hence, lowering the concentration of the free bilirubin capable of crossing the blood brain–barrier may benefit the treatment of Alzheimer’s disease (AD).ObjectivesThe objectives of this study were to examine the change in the serum bilirubin and albumin concentrations of dementia patients with Aβ deposition, and to determine the effects of intravenous administration of albumin in the treatment of AD.MethodsBilirubin and albumin concentrations in dementia patients with Aβ deposition were examined. Cell viability and apoptosis were determined in dopaminergic neuron-like cells MN9D treated with bilirubin in the presence of diverse concentrations of serum. Human albumin at a dose of 10 g every 2 weeks for 24 weeks was administered intravenously to AD patients to examine the effect of albumin on AD symptoms.ResultsSignificantly higher indirect bilirubin (IBIL) concentrations, lower albumin concentrations, and higher ratio of IBIL to albumin (IBIL/ALB) were observed in dementia patients with Aβ deposition, including AD, dementia with Lewy bodies, and general paresis of insane. In vitro assays showed that bilirubin-induced injury in cultured dopaminergic neuron-like cells negatively depends on the concentration of serum in the culture medium. General linear model with repeated measures analysis indicated a main effect of group on the change in albumin concentrations and Alzheimer’s Disease Cooperative Study Activities of Daily Living Inventory scale (ADCS-ADL) scores, and the main effect of time and group, and group-by-time interaction on the change of Clinical Dementia Rating Scale–Sum of Boxes (CDR-SB) scores. Analysis of the combined data of the entire 28 weeks of assessment period using the area under curve convincingly showed significantly improvements in the change of albumin concentrations, ADCS-ADL scores, and CDR-SB scores.ConclusionIBIL and the IBIL/ALB ratio are significantly higher in dementia patients with Aβ deposition, and intravenous administration of albumin is beneficial to AD treatment.Trial RegistrationThe intervention study was registered at http://www.chictr.org.cn (ChiCTR-IOR-17011539). Date of registration: June 1, 2017.

(1) Background: Odor identification (OI) dysfunction is a potential predictor of developing dementia in late life depression (LLD). However, it is not clear whether patients with early onset depression (EOD) and late onset depression (LOD) may exhibit different OI dysfunctions. The aim of this study was to compare OI between EOD patients and LOD patients and its relationship with cognitive function. (2) Methods: A total of 179 patients with LLD and 189 normal controls were recruited. Participants underwent clinical assessment, olfactory testing, and comprehensive neuropsychological assessment. The OI scores of EOD patients and LOD patients were compared, and correlation analyses and mediation analyses were used to explore the relationship between OI and cognition. (3) Result: LOD patients exhibited lower OI scores than EOD patients and normal controls (NCs). Additionally, the LOD patients exhibited a higher percentage of OI dysfunction than the EOD patients. Moreover, OI scores were associated with global cognition, memory, language, and visuospatial ability in the EOD group (p < 0.05) but were not associated with any cognitive score in the LOD patients (p > 0.05). Finally, the scores of the Auditory Verbal Learning Test Immediate recall and Boston Naming Test exhibited a partially mediating effect on the difference in OI scores between the EOD and LOD patients. (4) Conclusions: LOD patients exhibited worse OI than EOD patients, and their difference in OI was mediated by their memory and language function.

Abstract Most of the traditional top-k algorithms are based on a single-server setting. They may be highly inefficient and/or cause huge communication overhead when applied to a distributed system environment. Therefore, the problem of top-k monitoring in distributed environments has been intensively investigated recently. This paper studies how to monitor the top-k data objects with the largest aggregate numeric values from distributed data streams within a fixed-size monitoring window W, while minimizing communication cost across the network. We propose a novel algorithm, which adaptively reallocates numeric values of data objects among distributed nodes by assigning revision factors when local constraints are violated and keeps the local top-k result at distributed nodes in line with the global top-k result. We also develop a framework that combines a distributed data stream monitoring architecture with a sliding window model. Based on this framework, extensive experiments are conducted on top of Apache Storm to verify the efficiency and scalability of the proposed algorithm.

Patients with late-life depression (LLD) have a higher incident of developing dementia, especially individuals with memory deficits. However, little is known about the white matter characteristics of LLD with memory deficits (LLD-MD) in the human connectome, especially for the rich-club coefficient, which is an indicator that describes the organization pattern of hub in the network. To address this question, diffusion tensor imaging of 69 participants [15 LLD-MD patients; 24 patients with LLD with intact memory (LLD-IM); and 30 healthy controls (HC)] was applied to construct a brain network for each individual. A full-scale battery of neuropsychological tests were used for grouping, and evaluating executive function, processing speed and memory. Rich-club analysis and global network properties were utilized to describe the topological features in each group. Network-based statistics (NBS) were calculated to identify the impaired subnetwork in the LLD-MD group relative to that in the LLD-IM group. We found that compared with HC participants, patients with LLD (LLD-MD and LLD-IM) had relatively impaired rich-club organizations and rich-club connectivity. In addition, LLD-MD group exhibited lower feeder and local connective average strength than LLD-IM group. Furthermore, global network properties, such as the shortest path length, connective strength, efficiency and fault tolerant efficiency, were significantly decreased in the LLD-MD group relative to those in the LLD-IM and HC groups. According to NBS analysis, a subnetwork, including right cognitive control network (CCN) and corticostriatal circuits, were disrupted in LLD-MD patients. In conclusion, the disease effects of LLD were prevalent in rich-club organization. Feeder and local connections, especially in the subnetwork including right CCN and corticostriatal circuits, were further impaired in those with memory deficits. Global network properties were disrupted in LLD-MD patients relative to those in LLD-IM patients.

T0001 is a recombinant human TNFR-Fc fusion protein mutant; it exhibits higher affinity to TNFα than etanercept and is now being tested in a Phase 1 study in China (ClinicalTrials.gov Identifier: NCT02481180). T0001 can inhibit the binding of soluble TNFα (sTNFα) or membrane-bound TNFα (mTNFα) to TNF receptors. When bound to mTNFα, the Fc-bearing TNFα antagonists have the potential to induce Fc-mediated effects, such as antibody-dependent cellular cytotoxicity (ADCC) and complement-mediated cytotoxicity (CDC) as well as outside-to-inside signals (apoptosis mainly). Recent studies have shown that ADCC may also play an important role in Crohn's disease (CD) and ulcerative colitis (UC). In this study, T0001 presented a higher binding activity on mTNFα than etanercept and similar binding activity with adalimumab and infliximab. Upon the addition of sTNFα, adalimumab and infliximab showed significantly increased binding to FcγRIIIa and C1q than T0001 and etanercept. T0001 exhibited significantly higher ADCC and CDC activity than etanercept, and the potency and the reporter response of T0001 were very close to adalimumab and infliximab in ADCC reporter gene assays. And the similar potency of T0001 was also corroborated by PMBC-based ADCC assay. T0001, but not etanercept could induce apoptosis, while adalimumab and infliximab were more effective. These results suggest that T0001 may not only exert improved efficacy in treating rheumatoid arthritis (RA) because of its high affinity to sTNFα but also has a therapeutic potential in CD and UC due to its increased binding to mTNFα with resultant Fc-associated functions (ADCC, in particular) and improved apoptosis.

Blocking proprotein convertase subtilisin kexin type 9 (PCSK9) binding to low-density lipoprotein receptor (LDLR) can profoundly lower plasma LDL levels. Two anti-PCKS9 monoclonal antibodies (mAbs), alirocumab and evolocumab, were approved by the FDA in 2015. The recommended dose is 75 mg to 150 mg every two weeks for alirocumab and 140mg every two weeks or 420 mg once a month for evolocumab. This study attempted to improve the pharmacokinetic properties of F0016A, an IgG1 anti-PCKS9 mAb, to generate biologically superior molecules. We engineered several variants with two or three amino acid substitutions in the Fc fragment based on prior knowledge. The Fc-modified mAbs exhibited increased binding to FcRn, resulting in prolonged serum half-life and enhanced efficacy in vivo. These results demonstrate that Fc-modified anti-PCKS9 antibodies may enable less frequent or lower dosing of antibodies by improved recycling into the blood.