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We address the problem of resource allocation with multi-attribute demand considering heterogeneous servers in mobile edge computing (MEC). A mobile device (MD) may be within the coverage area of multiple access points and can get resources from any server that can establish direct communication. However, the configurations of heterogeneous servers are different, so the demand for each MEC server is different. We tackle this problem and consider multi-attribute demand, where each MD is assigned exactly one of multiple demands. We formulate the allocation problem in an auction-based setting to provide server scalability. We propose a family of greedy mechanisms to solve the resource allocation problem. However, each MD is self-interested and may try to manipulate the system to maximize its utility. We show our mechanisms are truthful, and they drive the system into an equilibrium where no MD can declare an untrue value to obtain higher utility. We also analyze the approximation ratios of our greedy mechanisms. Experimental results demonstrate that the greedy mechanisms obtain the near-optimal allocation in a short period while benefiting MDs and edge cloud providers. [ABSTRACT FROM AUTHOR]

Aging has made stroke a top killer and disabler, with post-stroke sarcopenia worsening disability and quality of life. While resistance training benefits the elderly, its impact on stroke patients is understudied. This study evaluates the potential of a 4-week unilateral resistance training (URT) program to prevent sarcopenia in stroke patients. It assesses the impact of URT on hand grip strength (HG), muscle thickness (MT), upper limb functionality, and the psychological status of the patients. The study aims to quantitatively analyze these indicators to inform evidence-based post-stroke rehabilitation practices. This study employed a randomized controlled trial (RCT) involving 77 eligible stroke survivors, equally allocated into a control group (n = 39) and an intervention group (n = 38). The control group received standard rehabilitation, while the intervention group additionally underwent a 4-week URT program. The primary outcomes were unaffected side HG and MT, measuring muscle mass and function. Secondary outcomes included the Fugl-Meyer Assessment of the Upper Extremity (FMA-UE) for upper limb functionality and the Hamilton Depression Rating Scale (HAMD) for psychological well-being changes. Statistical analysis showed significant differences (p < 0. 05) in all measured parameters between the intervention and control groups after the 4-week period. Intra-group comparisons also indicated substantial improvements (p < 0. 05). Unilateral resistance training significantly mitigates muscle atrophy in stroke patients, preventing sarcopenia and enhancing upper limb function. It also ameliorates depressive symptoms, improving rehabilitation outcomes and overall quality of life. [ABSTRACT FROM AUTHOR]

Satellite cloud image sequences contain rich spatial and temporal information, and forecasting future cloud image sequences is of great significance for meteorological research. Traditional satellite cloud image prediction methods usually ignore nonlinear variations in cloud masses, leading to large errors in prediction results and low prediction efficiency. The use of existing video prediction methods for satellite cloud image sequence prediction also suffers from problems of blurred prediction images and the accumulation of sequence errors. To address these issues, we propose a Multi-feature Extraction and High-resolution Generative Network (MEHGNet) for the prediction of satellite cloud image sequences, which consists of an encoder, a translator, a decoder, and a generator. To learn the spatial features and spatiotemporal dependencies of cloud images, 2D convolution multi-head attention mechanisms and local residue connections are introduced to the encoder and decoder. The generator preserves detailed features and improves the resolution of the predicted images using the generative ability of generative adversarial networks. In addition, a motion-aware loss function is proposed to learn high-level features of motion variations among cloud image sequences. Experiments on satellite datasets demonstrate that the proposed method is superior compared to other prediction methods. [ABSTRACT FROM AUTHOR]

Enrofloxacin (EF) is a broad-spectrum and highly efficient antibiotic commonly used for treating diseases in aquatic animals. However, its abuse in aquaculture applications often leads to excess residue in tissues of grass carp (Ctenopharyngodon idella). Hence, this study aimed to estimate the withdrawal time (WT) of EF and its metabolite of ciprofloxacin (CF) administered medicated feed in natural culture environments and conduct a risk assessment. Plasma and tissue samples were gathered at appropriate time points and detected by high-performance liquid chromatography. The data homogeneity was evaluated by Bartlett's test and Cochran's test. The linearity of the regressed line was evaluated by visual inspection and F test. Outliers were estimated on a normal probability scale by plotting the standardized residual versus their cumulative frequency distribution. Finally, the WT was calculated to be 51 days in muscle + skin based on the maximum residue limit of 100 µg/kg. After 51 days, the concentration of EF and CF fell below 10 µg/kg. The estimated daily intake was calculated to be 0.009 µg/kg/d. Hazard quotient was computed to be 0.002, which was far below one. These results suggested that calculated WT of EF could ensure the safety of products from grass carp for humans. [ABSTRACT FROM AUTHOR]

Key message: The major irregular chromosome pairing and mis-segregation were detected during meiosis through unambiguous chromosome identification and found that allotriploid Brassica can undergo meiosis successfully and produce mostly viable aneuploid gametes. Triploids have played a crucial role in the evolution of species by forming polyploids and facilitating interploidy gene transfer. It is widely accepted that triploids cannot undergo meiosis normally and predominantly produce nonfunctional aneuploid gametes, which restricts their role in species evolution. In this study, we demonstrated that natural and synthetic allotriploid Brassica (AAC), produced by crossing natural and synthetic Brassica napus (AACC) with Brassica rapa (AA), exhibits basically normal chromosome pairing and segregation during meiosis. Homologous A chromosomes paired faithfully and generally segregated equally. Monosomic C chromosomes were largely retained as univalents and randomly entered daughter cells. The primary irregular meiotic behaviors included associations of homoeologs and 45S rDNA loci at diakinesis, as well as homoeologous chromosome replacement and premature sister chromatid separation at anaphase I. Preexisting homoeologous arrangements altered meiotic behaviors in both chromosome irregular pairing and mis-segregation by increasing the formation of A-genomic univalents and A-C bivalents, as well as premature sister chromatid separation and homologous chromosome nondisjunction. Meiotic behaviors depended significantly on the genetic background and heterozygous homoeologous rearrangement. AAC triploids mainly generated aneuploid gametes, most of which were viable. These results demonstrate that allotriploid Brassica containing an intact karyotype can proceed through meiosis successfully, broadening our current understanding of the inheritance and role in species evolution of allotriploid. [ABSTRACT FROM AUTHOR]

When managing resource flexibility in service systems, the conventional wisdom is that server flexibility is beneficial due to the resource pooling effect. However, in practice, flexibility often incurs some additional costs, which makes how much flexibility is optimal and how to best utilize the flexible resource a nontrivial question. In this paper, we study the joint staffing and scheduling problem in service systems with two classes of customers and dedicated and flexible servers. The specific feature we consider is that the flexible server may incur a higher staffing cost or a loss of efficiency. We study how flexibility is best utilized in two scenarios: one with deterministic arrival rates and the other with random/uncertain arrival rates. We utilize a heavy-traffic asymptotic framework to develop structural insights. Our results show that the size of the flexible server pool is of a smaller order than the size of the dedicated server pools, and the flexible servers are mostly used to hedge against system stochasticity or demand uncertainty, depending on which source of randomness dominates. The proposed staffing and scheduling policies are easy to implement and achieve near-optimal performance. [ABSTRACT FROM AUTHOR]

Purpose: α2-adrenoceptor agonist dexmedetomidine (DEX) has been reported to promote tumorigenesis. Stem-cell protein Piwil2 is associated with cancer progression. Whether Piwil2 plays a role in tumor-promoting effects of DEX is unknown. Methods: We examined the expression of Piwil2 in human colorectal cancer (CRC) cell lines with/without DEX treatment. We also studied the roles of Piwil2 in proliferation, invasion, migration, as well as expressions of epithelial-mesenchymal transition (EMT)-related proteins in DEX-treated in vitro and in vivo CRC models. And the experiments with genetic and pharmacological treatments were conducted to investigate the underlying molecular mechanism. Results: RNA-sequencing (RNA-seq) analysis found Piwil2 is one of most upregulated genes upon DEX treatment in CRC cells. Furthermore, Piwil2 protein levels significantly increased in DEX-treated CRC cancer cells, which promoted proliferation, invasion, and migration in both CRC cell lines and human tumor xenografts model. Mechanistically, DEX increased nuclear factor E2-related factor 2 (Nrf2) expression, which enhanced Piwil2 transcription via binding to its promoter. Furthermore, in vitro experiments with Piwil2 knockdown or Siah2 inhibition indicated that DEX promoted EMT process and tumorigenesis through Siah2/PHD3/HIF1α pathway. The experiments with another α2-adrenoceptor agonist Brimonidine and antagonists yohimbine and atipamezole also suggested the role of Piwil2 signaling in tumor-promoting effects via an α2 adrenoceptor-dependent manner. Conclusion: DEX promotes CRC progression may via activating α2 adrenoceptor-dependent Nrf2/Piwil2/Siah2 pathway and thus EMT process. Our work provides a novel insight into the mechanism underlying tumor-promoting effects of α2-adrenoceptor agonists. [ABSTRACT FROM AUTHOR]

A novel 3D nitrogen-doped porous carbon supported Fe-Cu bimetallic nanoparticles composite (Fe-Cu-N-PC) was prepared via direct pyrolysis by employing black liquor lignin as a main precursor, and it was utilized as a novel catalyst for PMS activation in degrading naphthalene. Under the optimum experimental conditions, the naphthalene degradation rate was up to 93.2% within 60 min in the Fe-Cu-N-PC/PMS system. The porous carbon framework of Fe-Cu-N-PC could facilitate the quick molecule diffusion of reactants towards the inner bimetallic nanoparticles and enriched naphthalene molecules from the solution by a specific adsorption, which increased the odds of contact between naphthalene and reactive oxygen species and improved the reaction efficiency. The quenching reaction proved that the non-free radical pathway dominated by 1O2 was the main way in naphthalene degradation, while the free radical pathway involving SO4·− and ·OH only played a secondary role. Moreover, owing to its high magnetization performance, Fe-Cu-N-PC could be magnetically recovered and maintained excellent naphthalene degradation rate after four degradation cycles. This research will offer a theoretical basis for the construction of facile, efficient, and green technologies to remediate persistent organic pollutants in the environment. [ABSTRACT FROM AUTHOR]

Ultrastrong and deep-strong coupling are two coupling regimes rich in intriguing physical phenomena. Recently, hybrid magnonic systems have emerged as promising candidates for exploring these regimes, owing to their unique advantages in quantum engineering. However, because of the relatively weak coupling between magnons and other quasiparticles, ultrastrong coupling is predominantly realized at cryogenic temperatures, while deep-strong coupling remains to be explored. In our work, we achieve both theoretical and experimental realization of room-temperature ultrastrong magnon-magnon coupling in synthetic antiferromagnets with intrinsic asymmetry of magnetic anisotropy. Unlike most ultrastrong coupling systems, where the counter-rotating coupling strength g2 is strictly equal to the co-rotating coupling strength g1, our systems allow for highly tunable g1 and g2. This high degree of freedom also enables the realization of normalized g1 or g2 larger than 0.5. Particularly, our experimental findings reveal that the maximum observed g1 is nearly identical to the bare frequency, with g1/ω0 = 0.963, indicating a close realization of deep-strong coupling within our hybrid magnonic systems. Our results highlight synthetic antiferromagnets as platforms for exploring unconventional ultrastrong and even deep-strong coupling regimes, facilitating the further exploration of quantum phenomena.Deep-strong coupling in hybrid magnonic systems is yet to be explored. Here, the authors unveil unconventional coupling properties in synthetic antiferromagnets. The systems’ high degree of freedom enables a near-realization of deep-strong coupling. [ABSTRACT FROM AUTHOR]

Multiple myeloma (MM) is a heterogenous plasma cell malignancy, for which the established prognostic models exhibit limitations in capturing the full spectrum of outcome variability. Leveraging single-cell RNA-sequencing data, we developed a novel plasma cell gene signature. We evaluated and validated the associations of the resulting plasma cell malignancy (PBM) score with disease state, progression and clinical outcomes using data from five independent myeloma studies consisting of 2115 samples (1978 MM, 65 monoclonal gammopathy of undetermined significance, 35 smoldering MM, and 37 healthy controls). Overall, a higher PBM score was significantly associated with a more advanced stage within the spectrum of plasma cell dyscrasias (all p < 0.05) and a shorter overall survival in MM (hazard ratio, HR = 1.72; p < 0.001). Notably, the prognostic effect of the PBM score was independent of the International Staging System (ISS) and Revised ISS (R-ISS). The downstream analysis further linked higher PBM scores with the presence of cytogenetic abnormalities, TP53 mutations, and compositional changes in the myeloma tumor immune microenvironment. Our integrated analyses suggest the PBM score may provide an opportunity for refining risk stratification and guide decisions on therapeutic approaches to MM. [ABSTRACT FROM AUTHOR]

Purpose: The air health index (AHI) captures the combined effects of air pollution and non-optimal temperatures and helps assess the atmospheric environment's overall health risk. Shandong Province is a crucial industrial base in China, and the health effects of air pollution and non-optimal temperature cannot be ignored. To construct an AHI for Shandong Province and assess the district-level mortality burden due to AHI in the study area. Methods: Daily district-specific mortality, meteorological, and air pollution data over 2013–2018 were collected in Shandong Province, China. The AHI construction eventually incorporated PM2.5 and NO2, O3, and non-optimal temperatures. Attributable fraction (AF) and attributable number (AN) were used to estimate the district-specific mortality burden attributable to AHI. Results: The average AHI value observed in Shandong Province was 6. Our research revealed a positive association between the total AHI and total mortality, with an overall trend of a slow increase followed by a rapid increase. The exposure–response curves, when stratified by gender, age, and cause of death, were approximately consistent with the overall trend. The provincial attributable fraction (AF) was 5.31% (95% CI 4.58%, 5.91%), and the attributable number (AN) was 188,246 (95% CI 162,396, 209,533). Overall, higher ANs mainly appeared in the southwestern area, while higher values of AF were observed in the central-eastern and central-northern areas. Conclusions: The air health index performs well in predicting death burden and can convey health risks related to exposure to the ambient environment to the public. [ABSTRACT FROM AUTHOR]

Key message: Homoeolog expression bias and the gene dosage effect induce downregulation of genes on chromosome A7, causing a significant increase in the plant height of resynthesized allopolyploid Brassica napus. Gene expression levels in allopolyploid plants are not equivalent to the simple average of the expression levels in the parents and are associated with several non-additive expression phenomena, including homoeolog expression bias. However, hardly any information is available on the effect of homoeolog expression bias on traits. Here, we studied the effects of gene expression-related characteristics on agronomic traits using six isogenic resynthesized Brassica napus lines across the first ten generations. We found a group of genes located on chromosome A7 whose expression levels were significantly negatively correlated with plant height. They were expressed at significantly lower levels than their homoeologous genes, owing to allopolyploidy rather than inheritance from parents. Homoeolog expression bias resulted in resynthesized allopolyploids with a plant height similar to their female Brassica oleracea parent, but significantly higher than that of the male Brassica rapa parent. Notably, aneuploid lines carrying monosomic and trisomic chromosome A7 had the highest and lowest plant heights, respectively, due to changes in the expression bias of homoeologous genes because of alterations in the gene dosage. These findings suggest that the downregulation of the expression of homoeologous genes on a single chromosome can result in the partial improvement of traits to a significant extent in the nascent allopolyploid B. napus. [ABSTRACT FROM AUTHOR]

A series of 1,3,4-oxadiazole derivatives were synthesized starting from substituted phenylacetic acids, and their structures were confirmed by IR, NMR, and HRMS data. The synthesized compounds showed potent in vitro cholinesterase inhibitory activities with IC50 values of 8.59 μM against butyrylcholinesterase (6a) and 7.12 μM against acetylcholinesterase (6f). Molecular docking studies indicated that compound 6f could interact with the peripheral anion that binds to acetylcholinesterase. Moreover, compound 6c also exhibited strong anti-inflammatory effect. This compound could significantly reduce LPS-induced secretion of inflam-matory cytokines IL-6, IL-1β, and TNF-α in RAW 264.7 cells. These results suggested that 1,3,4-oxadiazole derivatives may be promising lead compounds for the treatment of Alzheimer's disease. [ABSTRACT FROM AUTHOR]

In China, the northeastern region has preserved many valuable modern built heritage buildings, which are undergoing difficult exploratory protection during the industrial and urbanisation process. Taking Dalian city as a case study, this article retraces the history of Dalian's opening up and colonial management from the perspective of urban planning and historic district protection and management systems. This article sorts out the influence of national and local institutional policies on Dalian's urban construction and development to analyse the past evolution, current problems and internal causes of the renovation and protection of Dalian's typical historic districts. This influence is mainly reflected in the lack of protection and damage done to unofficial heritage, the disconnection between historic districts and the surrounding environments and urban textures, and the Chinese-style transformation and economic decline of exotic areas. This paper calls for attention to and the rapid clarification of the built heritage list, the improvement of planning and protection systems and related supporting policies, and a focus on the protection of the authenticity of colonial heritage. This paper provides strategic guidance for improving the protection of historic districts in Dalian in Northeast China and hopes to serve as a reference for the protection of built heritage in other nonfamous historic and cultural cities. [ABSTRACT FROM AUTHOR]

Purpose: To assess the effect of esketamine nasal spray on patient-reported outcomes (PROs) in patients with major depressive disorder having active suicidal ideation with intent (MDSI). Methods: Patient-level data from two phase 3 studies (ASPIRE I; ASPIRE II) of esketamine + standard of care (SOC) in patients (aged 18–64 years) with MDSI, were pooled. PROs were evaluated from baseline through end of the double-blind treatment phase (day 25). Outcome assessments included: Beck Hopelessness Scale (BHS), Quality of Life (QoL) in Depression Scale (QLDS), European QoL Group-5-Dimension-5-Level (EQ-5D-5L), and 9-item Treatment Satisfaction Questionnaire for Medication (TSQM-9). Changes in BHS and QLDS scores (baseline to day 25) were analyzed using a mixed-effects model for repeated measures (MMRM). Results: Pooled data for esketamine + SOC (n = 226; mean age: 40.5 years, 59.3% females) and placebo + SOC (n = 225; mean age: 39.6 years, 62.2% females) were analyzed. Mean ± SD change from baseline to day 25, esketamine + SOC vs placebo + SOC (least-square mean difference [95% CI] based on MMRM): BHS total score, − 7.4 ± 6.7 vs − 6.8 ± 6.5 [− 1.0 (− 2.23, 0.21)]; QLDS score, − 14.4 ± 11.5 vs − 12.2 ± 10.8 [− 3.1 (− 5.21, − 1.02)]. Relative risk (95% CI) of reporting perceived problems (slight to extreme) in EQ-5D-5L dimensions (day 25) in esketamine + SOC vs placebo + SOC: mobility [0.78 (0.50, 1.20)], self-care [0.83 (0.55, 1.27)], usual activities [0.87 (0.72, 1.05)], pain/discomfort [0.85 (0.69, 1.04)], and anxiety/depression [0.90 (0.80, 1.00)]. Mean ± SD changes from baseline in esketamine + SOC vs placebo + SOC for health status index: 0.23 ± 0.21 vs 0.19 ± 0.22; and for EQ-Visual Analogue Scale: 24.0 ± 27.2 vs 19.3 ± 24.4. At day 25, mean ± SD in domains of TSQM-9 scores in esketamine + SOC vs placebo + SOC were: effectiveness, 67.2 ± 25.3 vs 56.2 ± 26.8; global satisfaction, 69.9 ± 25.2 vs 56.3 ± 27.8; and convenience, 74.0 ± 19.4 vs 75.4 ± 18.7. Conclusion: These PRO data support the patient perspective of the effect associated with esketamine + SOC in improving health-related QoL in patients with MDSI. Trial registration: ClinicalTrials.gov Identifier: ASPIRE I, NCT03039192 (Registration date: February 1, 2017); ASPIRE II, NCT03097133 (Registration date: March 31, 2017). [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the splenic tissue damage of environmental biological drug avermectin to freshwater cultured carp and to evaluate the effect of silybin on the splenic tissue damage of carp induced by avermectin. A total of 60 carp were divided into 4 groups with 15 carp in each group, including the control group fed with basic diet, experimental group fed with basal diet and exposed to avermectin (avermectin group), experimental group fed with basal diet supplement silybin (silybin group), and experimental group fed with basal diet supplement silybin and exposed to avermectin (silybin + avermectin group). The whole test period lasted for 30 days, and spleen tissue was collected for analysis. In this study, H&E staining, mitochondrial purification and membrane potential detection, ATP detection, DHE staining, biochemical tests, qPCR, immunohistochemistry, and apoptosis staining were used to evaluate the biological processes of spleen tissue injury, mitochondrial function, oxidative stress, apoptosis, and endoplasmic reticulum stress. The results show that silybin protected carp splenic tissue damage caused by chronic avermectin exposure, decreased mitochondrial membrane potential, decreased ATP content, ROS accumulation, oxidative stress, apoptosis, and endoplasmic reticulum stress. Silybin may ameliorate the splenic tissue damage of cultured freshwater carp caused by environmental biopesticide avermectin by alleviating mitochondrial dysfunction and inhibiting PERK-ATF4-CHOP-driven mitochondrial apoptosis. Adding silybin into the diet becomes a feasible strategy to resist the pollution of avermectin and provides a theoretical basis for creating a good living environment for freshwater carp. [ABSTRACT FROM AUTHOR]

Key message: MeJA supplementation enhanced the chilling tolerance and gene expression of PpMsrA1. PpMYB105 protein positively regulated the PpMsrA1 promoter. PpMYB105 mediated the MeJA-boosted chilling tolerance by regulating PpMsrA1. Cold storage can maintain the quality of postharvest fruit. However, peaches easily suffer from chilling injury (CI) during cold storage, leading to economic loss. Results showed that methyl jasmonate (MeJA) supplementation reduced the CI severity, and enhanced the gene expression of methionine sulfoxide reductase A1 (PpMsrA1). It was found that MeJA application elevated the MsrA activity and methionine (Met) content, and reduced the methionine-S-sulfoxide (Met-S-SO) content and reactive oxygen species (ROS) production afterwards. Moreover, PpMYB105 could activate the transcription of PpMsrA1 by binding to the MYB binding element in its promoter. The gene expression of PpMYB105 was up-regulated by MeJA application. Overexpression of PpMYB105 in tomatoes enhanced the chilling tolerance and gene expression of SlMsrA1. Virus-induced gene silencing of PpMYB105 in peaches resulted in the increase in CI severity and the decrease in gene expression of PpMsrA1. Thus, PpMYB105 was involved in the MeJA-boosted chilling tolerance by regulating PpMsrA1. [ABSTRACT FROM AUTHOR]

Purpose: Volatile organic compounds (VOCs) have shown great potential as novel biomarkers for cancer detection; however, comprehensive quantitative analysis is lacking. In this study, we performed a bibliometric analysis of non-invasive cancer diagnosis using VOCs to better characterise international trends and to predict future hotspots in this field, and then we focussed on human studies to analyse clinical characteristics for presenting the current controversies and future perspectives of further clinical work. Methods: Publications, from 2002 to 2022, were retrieved from the Web of Science Core Collection database. CiteSpace and VOSviewer were used to generate network maps and identify the annual publications, top countries, authors, institutions, journals, references, and keywords. Then, we further screened clinical trials, and the key information was extracted into Microsoft Excel for further systematical analysis. Results: Six hundred and forty-one articles were identified to evaluate research trends, of which 301 clinical trials were selected for further systematical analysis. Overall, the annual publications in this area increased, with an overall upward trend, while the quality of clinical research remains remarkably uneven. Conclusion: The study of non-invasive cancer diagnosis using VOCs would continue to be an active field. However, without stringent clinical design criteria, most suitable acquisition and analysis devices and statistical approaches, a list of exclusive, specific, reliable and reproducible VOCs to identify a disease and these VOCs appearing in a breath at detectable levels at early stage disease, the clinical utility of VOC tests will be difficult to have any breakthroughs. [ABSTRACT FROM AUTHOR]

We aimed to test the effects of connexin43 (Cx43) on ischemic neurogenesis and examined whether it was dependent on aquaporin-4 (AQP4). We detected the expression of Cx43 and AQP4 in the ipsilateral subventricular zone (SVZ) and peri-infarct cortex after middle cerebral artery occlusion (MCAO). Also, we examined neurogenesis in the above regions via co-labeling of 5-bromo-2-deoxyuridine (BrdU)/neuronal nuclear antigen (NeuN) and BrdU/doublecortin (DCX). The effects of Cx43 and AQP4 were investigated by using two transgenic animals: heterozygous Cx43 (Cx43±) mice and AQP4 knockout (AQP4−/−) mice, and connexin mimetic peptide (CMP), a selective Cx43 blocker. We demonstrated AQP4 and Cx43 were co-expressed in the astrocytes after MCAO and the expression was highly increased in ipsilateral SVZ and peri-infarct cortex. Cx43± mice had larger infarction volumes and worse neurological function. Both BrdU/NeuN and BrdU/DCX co-labeled cells in the two regions were reduced in Cx43± and AQP4−/− mice compared to wild-type (WT) mice, suggesting Cx43 and AQP4 participated in neurogenesis of neural stem cells. Moreover, CMP decreased AQP4 expression and inhibited neurogenesis in WT mice, while the latter failed to be observed in AQP4−/− mice. Besides, higher levels of IL-1β and TNF-α were detected in the SVZ and peri-infarct cortex of AQP4−/− and Cx43± mice than those in WT mice. In conclusion, our data suggest that Cx43 elicits neuroprotective effects after cerebral ischemia through promoting neurogenesis in the SVZ to regenerate the injured neurons, which is AQP4 dependent and associated with down-regulation of inflammatory cytokines IL-1β and TNF-α. [ABSTRACT FROM AUTHOR]

Background: Treatment-resistant depression (TRD) is a chronic illness requiring long-term treatment. Esketamine nasal spray (ESK) has been studied in several long-term trials of patients with TRD, including SUSTAIN-1 (NCT02493868) and SUSTAIN-3 (NCT02782104). This subgroup analysis of SUSTAIN-3 evaluated patients with TRD who received a second induction (IND) and maintenance treatment with ESK plus oral antidepressant (AD) after a relapse in SUSTAIN-1. Methods: Patients aged 18–64 years who achieved stable remission or response with ESK and subsequently relapsed after randomization to continue ESK or switch to placebo nasal spray (PBO) in SUSTAIN-1 and entered the IND phase of SUSTAIN-3 were included in this interim analysis. Response (≥50% improvement in total score from baseline for Montgomery–Åsberg Depression Rating Scale [MADRS] and Patient Health Questionnaire 9-item [PHQ-9]), remission (MADRS score ≤12; PHQ-9 total score <5), changes in depression rating scores (measured as mean change from baseline), and safety were evaluated (incidence of treatment-emergent and serious adverse events [AE]). Results: Of the 96 eligible patients who entered IND in SUSTAIN-3, 32 (33.3%) were taking ESK+AD at the time of relapse in SUSTAIN-1 and 64 (66.7%) were taking AD+PBO. Substantial improvements in depressive symptoms were observed over the second IND phase in both groups and were maintained over the optimization/maintenance (OP/M) phase. MADRS response rates following a second IND were 71.9% and 73.4% for previously relapsed (PR) ESK+AD and PR-AD+PBO, respectively; remission rates were 62.5% and 60.9%, respectively. During the IND and OP/M phases, 58.3% and 83.3% of patients experienced a treatment-emergent AE, respectively. No patients discontinued due to an AE during the second IND. Conclusions: Patients with TRD benefitted from receiving a second IND and maintenance treatment with ESK and no new safety signals were identified. [ABSTRACT FROM AUTHOR]

The discovery of magnetic order in atomically-thin van der Waals materials has strengthened the alliance between spintronics and two-dimensional materials. An important use of magnetic two-dimensional materials in spintronic devices, which has not yet been demonstrated, would be for coherent spin injection via the spin-pumping effect. Here, we report spin pumping from Cr2Ge2Te6 into Pt or W and detection of the spin current by inverse spin Hall effect. The magnetization dynamics of the hybrid Cr2Ge2Te6/Pt system are measured, and a magnetic damping constant of ~ 4–10 × 10−4 is obtained for thick Cr2Ge2Te6 flakes, a record low for ferromagnetic van der Waals materials. Moreover, a high interface spin transmission efficiency (a spin mixing conductance of 2.4 × 1019/m2) is directly extracted, which is instrumental in delivering spin-related quantities such as spin angular momentum and spin-orbit torque across an interface of the van der Waals system. The low magnetic damping that promotes efficient spin current generation together with high interfacial spin transmission efficiency suggests promising applications for integrating Cr2Ge2Te6 into low-temperature two-dimensional spintronic devices as the source of coherent spin or magnon current. Spin-pumping experimental technique where a DC or AC spin current is generated, and typically transferred to a heavy metal layer where it can be detected via electrical measurements. While well established in conventional materials, coherent spin-pumping in van der Waals magnetic materials is challenging due to the low damping and high-quality interface requirements. Here, Xu et al demonstrate coherent spin pumping in the van der Waals magnet Cr2Ge2Te6. [ABSTRACT FROM AUTHOR]

Multimodal medical volumetric image fusion is a hot topic in medical image processing. Currently, most multi-scale based medical image fusion methods are put forward in two-dimensional space. However, they often fail to deal with multimodal medical volumetric image fusion due to the inaccurate image representation caused by ignoring the correlation between adjacent slices and the inappropriate design of fusion rule based on individual feature. To overcome the above drawbacks, a novel multimodal fusion method using 3-D Shearlet transform and T-S fuzzy reasoning is proposed, named as 3DSTSF. Firstly, the low frequency subbands and high frequency subbands of multimodal medical volumetric images are obtained by using the 3-D Shearlet transform. For comprehensive interpretation of source image, a contextual hidden Markov model is established for 3-D Shearlet transform high frequency subbands to model multiple dependency relationship among coefficients. Then, a fuzzy reasoning rule based on contextual hidden Markov model statistical characteristics, interval type-2 fuzzy entropy and region energy of high-frequency coefficients is designed to fuse high frequency subbands, which can accurately describe volumetric images and avoid introducing false information. Besides, a novel and simple local energy based fusion rule is performed on low frequency subbands to ensure the visual quality of fused image. Finally, the fused medical volumetric image is reconstructed by the inverse 3-D Shearlet transform. A series of experimental results demonstrate the superiority of 3DSTSF. [ABSTRACT FROM AUTHOR]

Preterm premature rupture of membranes (pPROM) is a common pregnancy disease closely related to inflammation. The formyl peptide receptor 2 (FPR2), a member of the G protein-coupled receptor family involved in defense responses, inflammation, and disturbances in glucose and lipid metabolism, is associated with pregnancy diseases. Lipoxin A4 (LXA4) can activate FPR2 and inhibit the inflammatory signals. Exosomes derived from mesenchymal stem cells are good materials for anti-inflammatory and tissue repair. This study aims to investigate the anti-inflammatory and tissue repair effects of the combined application of exosomes derived from human umbilical cord mesenchymal stem cells and FPR2 agonist LXA4. In this study, LPS was used to establish the inflammation model of pregnant mice and HTR8 cells, and LXA4 and exosome treatment were carried out to observe the fetal membranes' tissue repair. The scanning and transmission electron microscopy of fetal membrane tissue indicated that the structure of pPROM tissue was disordered, and the cell gap was significantly increased. The results of the inflammatory mice model suggested that LPS can cause damage to the fetal membrane structure. LXA4 combined with exosome treatment can inhibit the production of MMP2 and MMP9, and promote neovascularization by inhibiting the p38 MAPK/Nuclear factor kB p65 (NFkB) pathway in the inflammation model of HTR8 cells and pregnant mice, thus helping to control inflammation and tissue repair. [ABSTRACT FROM AUTHOR]

To evaluate the relationships between maternal particulate matter exposure and offspring birth weight. Studies were categorized into three subgroups: term low birth weight (TLBW) among full-term births and all births (regardless of gestational age) and low birth weight (LBW) among all births, based on the search results of MEDLINE and the Web of Science from the inception of the database to April 2022. Subgroup analyses were conducted based on the economic status, region, exposure assessment, risk of bias, and adjustment. Sixty-one studies involving 34,506,975 singleton live births in 15 countries were analyzed. Overall, the risk of bias for most studies (75%) was low. In 39 of 47 term birth studies, the pooled odds ratio of TLBW among term births for per interquartile range (IQR) increases throughout the entire pregnancy was 1.02 (1.01 to 1.03) for PM2.5 and 1.03 (1.01 to 1.05) for PM10 after adjustment for covariates. No significant relevance was detected across each trimester period for PM2.5. A stronger effect was observed during the second trimester (1.03, 1.01 to 1.06) for PM10. There was no increased risk of TLBW in all births associated with IQR increases in PM2.5 and PM10. LBW was associated with PM2.5 exposure in 4 of 7 studies, but statistical heterogeneity was considerable. In the TLBW subgroup analysis, the effects of PM2.5 and PM10 were both greater in studies conducted in advanced countries, studies with low bias, and studies that adjusted for maternal age, infant sex, and parity. Stronger effects were present for PM2.5 exposure collected from monitoring stations and PM10 exposure interpolated from the inverse distance weighting model. TLBW may be associated with prenatal exposure to particulate matter, but no critical windows were identified. Stronger associations were observed in advanced countries. Future original study designs need to consider the impact of different exposure assessment modalities and all possible confounding factors. [ABSTRACT FROM AUTHOR]

Outbreaks of Microcystis blooms can affect growth of submerged plants, which in turn can inhibit cyanobacterial growth. Microcystin (MC)-producing and non-MC-producing Microcystis strains typically coexist in Microcystis-dominated blooms. However, the interaction between submerged plants and Microcystis at strain level is not clear. This study was aimed at assessing the effects of a submerged macrophyte Myriophyllum spicatum on one MC-producing versus one non-MC-producing strains of the cyanobacterium Microcystis using plant-Microcystis co-culture experiments. The impacts of Microcystis on M. spicatum were also examined. It showed that the MC-producing Microcystis strain had a higher resistance to negative impacts by the cocultured submerged plant M. spicatum than the non-MC-producing strain. By contrast, the plant M. spicatum was impacted more by the MC-producing Microcystis than the non-MC-producer. The associated bacterioplankton community was affected more by the MC-producing Microcystis than the cocultured M. spicatum. The MC cell quotas were significantly higher in the coculture treatment (the PM + treatment, p < 0.05), indicating that the production and release of MCs might be a key factor responsible for the reduced impact of M. spicatum. The higher concentrations of dissolved organic and reducing inorganic compounds might eventually exacerbate the recovering capacity of coexisting submerged plants. Overall, this study indicated that the capacity to produce MCs, as well as the density of Microcystis, should be taken into account when attempting to reestablish submerged vegetation to undertake remediation works. [ABSTRACT FROM AUTHOR]

Measurement of thermal forces is an important process that aids in reducing the maintenance cost of continuous welded rails (CWRs). But it is still a very challenging problem. Axial force can be measured through vibration modal changes, and vibration measurement methods have several merits compared to conventional measurement methods using piles, strain sensors, magnetoelastic and acoustoelastic effect sensors, and X-rays. Vibration measurement methods have the ability to measure the absolute thermal force in a local interval and are robust against abrasion, surface residual stress, and material grains. However, they are affected by both axial force and track parameters, thereby restricting their engineering applications. To address these limitations, this study proposes a novel method called 'modal utilization method of periodic structure' (MUMPS). Its novelty lies in proving that variations in frequency constitute a random sequence satisfying the constraints of Chebyshev's law of large numbers. It can determine the influence of track parameters on the vibration modes by averaging across different eigenfrequencies without investigating what they correspond to respectively. First, MUMPS is introduced through a hypothesis that the mean value of the natural frequency variations caused by the track parameter variations approaches a stable value. Second, MUMPS is validated using finite element simulation results, which show that the probability density function of the measurement error of the neutral temperature obey N(0.5,2.6). Finally, the accuracy of MUMPS is investigated through experiments, the results are compared with the strain-gauge method results, and they show good agreement. The experimental results show that as the number of the eigenfrequencies reaches 12, the mean value becomes stable, and the measurement error of neutral temperature is less than 4 ∘ C . Engineering applicability of MUMPS is demonstrated by conducting real-time measurements on railway tracks. The results show that the proposed method is simple, as sophisticated instruments are not employed to determine the axial forces on railway tracks. [ABSTRACT FROM AUTHOR]

To explore the leaching behavior and potential degree of pollution that can result from the backfilling of goafs with different types of coal gangue (CG), fresh CG from the Hongqi Coal Mine goaf and surface CG (weathered for 1 year) were selected as the research objects in this study. A series of leaching experiments were carried out using the Ordovician limestone karst waters of the mining areas as the soaking solution. A comparative study on the dissolution characteristics of Fe3+, Mn2+, and SO42− and on the traditional water quality parameters of the two types of CG was conducted. The results showed that the soaked, weathered CG displayed a higher ion dissolution value than fresh CG. The ratio of each ion was as follows: Fe3+ was 1, Mn2+ was 2.86 ~ 68.18, and SO42− was 1.34 ~ 2.09. Over time, the ion concentration of water samples that initially contained high ion concentration values showed a decreasing trend after CG was soaked in these waters, but the values were still in the range of high ion release concentrations. The pH and oxidation‒reduction potential (ORP) values of the leachate of both CG types indicated that the leachates were weakly alkaline and weakly oxidizing, and the overall change in total dissolved solids (TDS) was small and consistent with the SO42− trend. SO42− in the leachate of the weathered CG showed a more significant correlation with the pH and TDS of the soaking solution, and it was the major pollutant. According to the geoaccumulation index evaluation, weathered CG had higher pollution potential than fresh CG. Fe3+ presented a slight and moderate risk for contamination. [ABSTRACT FROM AUTHOR]

Von Willebrand factor (VWF) is an adhesive ligand critical for maintaining hemostasis. However, it has also been increasingly recognized for its role in cancer development because it has been shown to mediate the adhesion of cancer cells to endothelial cells, promote the epithelial–mesenchymal transition, and enhance angiogenesis. We have previously shown that gastric cancer cells synthesize VWF, which mediates the interaction between the cancer and endothelial cells to promote cancer growth. Here, we report results from a clinical observational study that demonstrate the association of VWF in plasma and on the surface of extracellular vesicles (EVs) with the pathological characteristics of gastric cancer. We found that patients with gastric cancer had elevated and intrinsically hyperadhesive VWF in their peripheral blood samples. VWF was detected on the surface of EVs from cancer cells, platelets, and endothelial cells. Higher levels of these VWF-bound EVs were associated with cancer aggression and poor clinical outcomes for patients. These findings suggest that VWF+ EVs from different cell types serve collectively as a new class of biomarkers for the outcome assessment of gastric cancer patients. [ABSTRACT FROM AUTHOR]

Through neodymium-mediated coordinative chain transfer copolymerizaiton (CCTcoP), polyisoprenes bearing dual hydroxylated mini-blocky chain-ends were prepared via a three-step strategy. Kinetic studies revealed that, the polymerization demonstrated typical features of CCTcoP across the whole polymerization process, i.e., quasi-living polymerization characteristic, tunable molecular weights, narrow molecular weight distributions, and atom economies. Comparing to previously reported CCTP homopolymerization systems, the presence of oxygen-containing IpOAl polar comonomer slowed down chain transfer rates obviously, rendering slightly higher molecular weights of the resultant PIps and smaller Np (number of polymer chains per Nd atom) values. Moreover, to mimic the structure of natural rubber, the hydroxyl end groups can be facilely modified into phosphonate, amide, and UPy, whose structures were further confirmed by NMR spectra. Incorporation these functionalities could greatly improve the hydrophilic properties of the polymers, as revealed from the significantly reduced static water contact angles. [ABSTRACT FROM AUTHOR]

Rasagiline has a certain potential in neuroprotection and delaying the progression of Parkinson's disease (PD). However, the poor pharmacokinetics (PK) characteristics of conventional oral tablets and poor medication compliance limit the optimal efficacy of rasagiline. Based on this, we designed and optimized a sustained-release rasagiline in situ gel based on in vitro release and in vivo PK results. Among them, we found for the first time that aluminum hydroxide can effectively shorten the lag phase and promote early and late release, making the daily release more uniform. After subcutaneous administration of the optimized gel formulation at a monthly dose, the Cmax (64 ng/ml) was lower than that of free rasagiline (494 ng/ml) administered subcutaneously at a daily dose and comparable to that of oral administration of Azilect® (59.1 ng/ml) at a daily dose. In the meantime, the plasma concentration of rasagiline was mainly maintained at 5–10 ng/ml for about 1 month, and the active metabolite 1-aminoindane in plasma was also able to maintain a steady state. The rasagiline in situ gel has suitable viscosity and injectability, good repeatability of subcutaneous injection, and controllable impurities and can achieve sustained release in vivo with small burst release, which may have the clinical application advantages of maximizing the disease-modifying effect of rasagiline and improving medication compliance. The rasagiline in situ gel was optimized through the feedback of in vitro release and in vivo pharmacokinetics (PK), in which the addition of aluminum hydroxide had a modulating effect on uniform release. The gel has low burst release and maintains steady-state blood drug concentration for about 1 month. [ABSTRACT FROM AUTHOR]

Interspecific interaction are playing vital roles in shaping phytoplankton structure and affecting the food webs in freshwater ecosystems. However, the responses of green algae to allelochemically competition with submerged macrophytes were mainly focused on the growth, whereas, the algal morphology changes were usually ignored. In the present study, according to co-cultivation experimentation of submerged macrophyte Egeria densa and green alga Scenedesmus obliquus with gradient initial algal density, it was demonstrated that E. densa could allelochemically suppress the growth of S. obliquus, but the shading effects should also be considered when the algal density was low. In addition, small colonies of S. obliquus with large amount were induced in the presence of E. densa. The suppressing expression of photosynthesis-related genes LhcbM and PS II D1 might lead the reduction of cell division in S. obliquus. The small but not large colonies formation might be interpreted as the inhibitory cell division and promotion of polysaccharide by allelochemicals from E. densa. Owing to the ecological significance, much more emphasis should be placed on the morphological changes induced by interspecific competition. The results would be of great help in the prediction of phytoplankton composition and structure in freshwater ecosystems. [ABSTRACT FROM AUTHOR]

This study seeks to propose and compare different quantitative evaluation methods for identifying patients with peri-device leak (PDL) using cardiac computed tomography angiography (CCTA). Patients who had undergone left atrial appendage (LAA) closure and both transesophageal echocardiography (TEE) and CCTA were enrolled. Hounsfield units (HU) were measured in the proximal and distal regions of the left atrial appendage (p-LAA, d-LAA) on the CCTA, and the average of the two was determined (a-LAA). The relative HU ratios of the LAA to the center of the left atrium (LA) were calculated (p-LAA/c-LA, d-LAA/c-LA, a-LAA/c-LA). The area under the curve (AUC) for the LAA HU and the LAA/LA HU ratio were analyzed and compared. Fifty-one patients were included in this study. Pairwise comparisons showed a statistically significant difference (p = 0.029) in diagnostic performance between the d-LAA (AUC = 0.868) and a-LAA (AUC = 0.972). There were no significant differences between the a-LAA and p-LAA (p = 0.549) or between the d-LAA and p-LAA (p = 0.053). At the optimal cutoff for a-LAA of 115.5 HU, the sensitivity was 100%, the specificity was 88%. At the optimal cutoff for p-LAA of 109 HU, the sensitivity was 100%, the specificity was 84%. The LAA/LA HU ratio did not exhibit better diagnostic performance than HU attenuation in the LAA (p > 0.05). The a-LAA > 115.5 is useful in identifying PDL. Due to its convenience and intuitiveness, p-LAA > 109.0 can also be used as an alternative protocol for a-LAA. [ABSTRACT FROM AUTHOR]

As the most common cancer disease in the world, breast cancer is the main cause of death of female cancer patients. The number of women in China is far greater than that in other countries. Therefore, the absolute death toll is often high. Even a small increase in incidence rate will lead to a severe increase in deaths. Therefore, accurate preoperative diagnosis of benign and malignant breast cancer and the status prediction of various clinical indicators are urgently needed in clinical practice. Deep learning based on neural network has been widely used in diagnosis. Therefore, this paper attempts to explore the influence of deep learning on the auxiliary diagnosis technology of small tumor in mammography. In this paper, 200 cases of breast disease patients in a hospital of our city were taken as the research object, and the artificial neural network model was established. Through the experimental simulation, the results showed that the diagnostic sensitivity, specificity and overall accuracy of BP neural network for test set samples were 95.3%, 96.7 and 96.2%, respectively. The experimental results confirmed its generalization ability. In this paper, the core idea of multi feature kernel hash, combined with a variety of features and deep kernel hash network framework, constructs a new multi feature based deep learning network, which can effectively express the image features of breast tumor, and complete the task of breast micro tumor detection with good performance. [ABSTRACT FROM AUTHOR]

As filter-feeders, bivalves naturally come into direct contact with microcystins (MCs) in eutrophic water bodies suffering from cyanobacteria blooms. To date, however, no studies have quantified the dynamics of microcystin accumulation and depuration in the edible freshwater bivalve Corbicula fluminea when exposed to dense bloom concentrations of Microcystis aeruginosa, while considering dynamic changes of biochemical indexes and feeding structure. In the present study, the bioaccumulation and detoxification of microcystin-LR (MC-LR) in C. fluminea were investigated. Our results showed that C. fluminea would graze equally efficiently on green algae and M. aeruginosa, irrespective of whether the M. aeruginosa strains were toxic or non-toxic. MCs could be accumulated and depurated by C. fluminea efficiently. In addition, linear and exposure time-dependent MC-LR accumulation patterns were observed in C. fluminea. Activities of biotransformation (glutathione S-transferase, GST) and antioxidant enzymes (superoxide dismutase, SOD, and catalase, CAT) and malondialdehyde (MDA) contents in various tissues of treated clams were stimulated by MCs in a tissue-specific manner. Our findings indicated that C. fluminea hepatopancreas was the primary target organ for MC-LR detoxification processes, as evidenced by a significant increase in GST activity. Besides, gills and mantle were more sensitive than the other tissues to oxidative stress in the initial microcystin exposure period with a significant increase in SOD activity. The scanning electron microscopy (SEM) observations revealed that the lateral cilia in the gill aperture were well developed during the MCs exposure period, which could perform the filter-feeding function instead of the damaged frontal cilium. This study provides insight into the possible tolerance of C. fluminea exposed to dense bloom concentrations of M. aeruginosa. [ABSTRACT FROM AUTHOR]

The functional group (FG) system sensu Colin S. Reynolds of freshwater phytoplankton has been widely applied in many aspects of freshwater ecological assessments. However, there is no current consensus as to how and to why some functional coda shows multiple habitat templates in different water bodies. To test whether there are multiple habitat templates for some functional coda in the FG system, we used two mesotrophic deep reservoirs in China as examples, analysing phytoplankton taxonomic and environmental data collected in 4 seasons over two years. Results showed that a large proportion of the indicators had similar habitat templates within the FG system, whilst some species had multiple or different habitat templates according to their niche differentiation. The random forest (RF) model filtered a minimum set of environmental conditions and provided two potential habitat templates for Oocystis lacustris. One explanatory habitat template of clear water provided by the FG system was verified in the Nanwan Reservoir, and the other habitat template of high dissolved inorganic nitrogen (DIN) was found in the Nianyushan Reservoir. Further studies of the potential multiple habitat templates for some functional coda are recommended for its proper use. [ABSTRACT FROM AUTHOR]

Key message: Map-based cloning, subcellular localization, virus-induced-gene-silencing and transcriptomic analysis reveal HvTUB8 as a candidate gene with pleiotropic effects on barley spike and leaf development via ethylene and chlorophyll metabolism. Barley lateral spikelet morphology and grain shape play key roles in grain physical quality and yield. Several genes and QTLs for these traits have been cloned or fine mapped previously. Here, we report the phenotypic and genotypic analysis of a barley mutant with round lateral spikelet (rls) from cv. Edamai 934. rls had round lateral spikelet, short but round grain, shortened awn, thick glume and dark green leaves. Histocytologic and ultrastructural analysis revealed that the difference of grain shape of rls was caused by change of cell arrangement in glume, and the dark leaf color resulted from enlarged chloroplast. HvTUBULIN8 (HvTUB8) was identified as the candidate gene for rls by combination of RNA-Seq, map-based-cloning, virus-induced-gene-silencing (VIGS) and protein subcellular location. A single G-A substitution at the third exon of HvTUB8 resulted in change of Cysteine 354 to tyrosine. Furthermore, the mutant isoform Hvtub8 could be detected in both nucleus and cytoplasm, whereas the wild-type protein was only in cytoplasm and granular organelles of wheat protoplasts. Being consistent with the rare phenotype, the “A” allele of HvTUB8 was only detected in rls, but not in a worldwide barley germplasm panel with 400 accessions. VIGS confirmed that HvTUB8 was essential to maintain spike integrity. RNA-Seq results suggested that HvTUB8 may control spike morphogenesis via ethylene homeostasis and signaling, and control leaf color through chlorophyll metabolism. Collectively, our results support HvTUB8 as a candidate gene for barley spike and leaf morphology and provide insight of a novel mechanism of it in barley development. [ABSTRACT FROM AUTHOR]

Diabetic retinopathy (DR) is a diabetes mellitus (DM) complication that causes visual acuity impairment and loss of sight in the working population, mainly in developed countries. According to the WHO, DR accounts for 5% of the world's 37 million blind people. The prevalence of diabetic retinopathy was highest in Africa, followed by North America and the Caribbean and South and Central America. Hyperglycemia can generate excessive ROS that activates multiple pathways, which can damage the cells. Oxidative stress and inflammatory process are intricate in the DR pathological mechanism. Bilobalide is the main bioactive compound isolated from the Ginkgo biloba, a plant utilized in folklore medicine. Bilobalide, a sesquiterpene trilactone, exhibits excellent antioxidant activity. But the molecular mechanisms associated with such effects, especially the antioxidant-related mechanism, have not been documented. Hence, this investigation explored whether bilobalide may attenuate DR in streptozotocin (STZ)-prompted diabetic rats. The effects of bilobalide on parameters of antioxidant content, oxidative stress, and inflammatory factors in the retinal tissues were evaluated by ELISA, RT-PCR, and immunohistochemistry methods. Bilobalide improved caloric management by reducing food consumption and increasing body weight. Furthermore, the administration of bilobalide decreases the blood glucose level and glycosylated (HbA1c) hemoglobin. The anti-retinopathy activity of bilobalide was established by the increase in the total retina thickness (TRT), inner nuclear layer (INL), and outer nuclear layer (ONL) in diabetic rats. Additionally, the serum level of MDA was decreased. In contrast, the antioxidant enzyme (SOD and CAT) levels were increased with TAC plus lower Keap1 and higher Nrf2 expression in the retina when associated with the DM rats. Moreover, bilobalide increased the nuclear factor erythroid 2-related factor 2 (Nrf2) and Heme oxygenase-1 (HO-1) expression level and inflammatory mediators (NF-κβ p65, TNF-α, IL-1β, and VEGF), thus inhibiting oxidative stress. Bilobalide can be effective against DR, and the possible mechanism may be relatively elucidated by decreasing oxidative stress and anti-inflammatory activities. But the further investigation should be directed to expose the precise mechanism. [ABSTRACT FROM AUTHOR]

The responses of Ceratophyllum demersum to gradient concentrations (0, 0.8, 3.2, and 10 µg/L) of microcystin-LR (MC-LR) were comprehensively investigated by laboratory simulation experiments. The high reduction and accumulation efficiency of MC-LR by C. demersum were verified in this study. Results showed that the reduction ratio of MC-LR in the cultivation medium was up to 99% after 14 days of exposure, and the accumulation of MC-LR in C. demersum was highest at an exposure concentration of 10 μg/L, the value of which was 0.9 ng/g fresh weight (FW). Meanwhile, a series of negative effects on C. demersum was detectable, accompanied by a significant biomass reduction of the plant and changes in microbial community composition. In particular, this study indicated that the amount of Flavobacteria was elevated under the stress of MC-LR, provoking great threats to aquatic ecosystems. Moreover, oxidative damage was evidenced by the changes in total antioxidant capacity, superoxide dismutase, and glutathione. The results also demonstrated significant increases in sugar (0.025 mg/g FW), protein (0.3 mg/g FW), and carotenoids (0.6 mg/g FW) in C. demersum stressed by 10 μg/L of MC-LR, compared with the control without microcystins, which were among the defense strategies for dealing with adverse conditions. These results verified the good potential of submerged macrophytes as an eco-friendly strategy for controlling cyanobacterial blooms. However, the negative effects of MC-LR on the macrophytes themselves were also demonstrated, which would be considered in future practice and management. [ABSTRACT FROM AUTHOR]

Theskeleton structure of human body is a natural undirected graph. Being applied to 3D body pose estimation, graph convolutional network (GCN) has achieved good results. However, the vanilla GCN ignores the differences between joints and the connections between joints with different distances. Based on the above two problems, we propose High-order Local Connection Network (HLCN) for 3D human pose estimation. On one hand, different filters for different joints are assigned to produce different weights. On the other hand, the feature of multi-hop joints synthetically is gathered into HLCN. Furthermore, we study different methods of fusing these multi-hop features and compare their performance. The new network not only takes the differences between the joints in the human skeleton into consideration, but also captures the remote dependencies between human joints. The experiment suggests that this method is superior to vanilla GCN and achieve state-of-the-art performance. The average error on the H36M dataset is 50.9 mm. [ABSTRACT FROM AUTHOR]

The present work comprehensively investigated the responses of submerged Ceratophyllum demersum to exudates and extracts of toxic Microcystis aeruginosa at the exponential (EU, ET) or declining phase (DU, DT). The highest amount of MC-LR was detected in medium with DT, the value of which reached 6.36 μg/l, and C. demersum exhibited the highest absorption of MC-LR with a value of 1.73 ng/g FW upon exposure to DU. Significant negative effects on C. demersum was detected under the treatment with EU of toxic M. aeruginosa, expressed with the reduction of freshweight, Chla/Chlb, and the Superoxide Dismutase (SOD) activity. Meanwhile, increased carotenoid/total chlorophyll ratio might be employed by submerged C. demersum as the defense strategy to EU of toxic M. aeruginosa. In addition, under EU treatment, the microorganisms Flavobacterium Bergey, and Chryseobacterium Vandamme, which exert negative effects on aquatic organisms, increased, whereas the Rhizobacter Goto & Kuwata, Limnothrix Meffert, and Pseudanabaena Lauterborn, which are beneficial to the growth of the plants, were lower. The research highlighted the significance of toxic cyanobacterial bloom development and different growth phases on submerged macrophytes, providing more insights for the allelopathic interaction between submerged macrophytes and toxic cyanobacteria in natural freshwater ecosystems. [ABSTRACT FROM AUTHOR]

To explore how decomposed Microcystis-dominant cyanobacterial blooms affect submerged macrophytes, the submerged plant Myriophyllum spicatum was exposed to cell extracts from microcystin (MC)- and non-MC-producing Microcystis strains in a laboratory experiment. Results showed that both Microcystis cell extracts exerted obvious damages to plant biomass, photosynthesis, primary and secondary metabolism measures, and resistance of plant antioxidant systems, with MC-producing Microcystis having stronger effects due to the presence of MCs. Cyanotoxins other than MCs responsible for the negative effects from both Microcystis strains needs further identification. The Shannon diversity and Chao1 indices of epiphytic and planktonic bacteria were decreased by the cell extracts from both Microcystis strains. However, epiphytic and planktonic bacterial communities responded differently to Microcystis cell extracts at the genus level. The dominant genera of planktonic bacteria including Enterobacter, Pseudomonas, and Novosphingobium from phylum Proteobacteria, Chryseobacterium from phylum Bacteroidetes, and Microbacterium from Actinobacteriota in the treatments with cell extracts were previously reported to have strains with algicidal and MC-degrading capabilities. Bacterial genes associated with energy production and conversion, amino acid transport and metabolism, and inorganic ion transport and metabolism, were more abundant in both treatments than the control for planktonic bacteria, but less abundant for epiphytic bacteria. We speculate that planktonic bacterial communities have the potential to use and degrade substances derived from Microcystis cell extracts, which may be beneficial for M. spicatum to alleviate damages from Microcystis. Further research is needed to verify the structure and function dynamics of epiphytic and planktonic bacteria in the interaction between cyanobacteria and submerged macrophytes. [ABSTRACT FROM AUTHOR]

Background: Major depressive disorder (MDD) directly impacts patients' lives including symptoms, functioning and health-related quality-of-life (HRQoL). Patient-reported outcomes can capture these impacts, however interpretation of clinical meaningfulness of these measurements are often not readily available. Meaningful change thresholds (MCTs) can be derived for clinical outcome assessments to quantify the change in symptoms that is meaningful to the patient following pharmacologic treatment or other interventions. The objective of this analysis was to determine the within-patient MCT of the self-reported Quality-of-Life in Depression Scale (QLDS) among patients with MDD and active suicidal ideation with intent (MDSI) using an anchor-based approach. Methods: Data from 2 randomized phase-3 trials of esketamine nasal spray (ASPIRE I and ASPIRE II) were analyzed. The Montgomery–Åsberg Depression Rating Scale (MADRS) was the primary anchor with three different severity criteria. Other anchor variables utilized were Clinical Global Impression of Severity of Suicidality-revised version, Clinical Global Impression of Imminent Suicide Risk, and EuroQol Visual Analog Scale [EQ-VAS]. Spearman correlation coefficients between the change in QLDS and anchor variables were calculated. The mean change in QLDS score at Day 25 from baseline was calculated based on the categorical change in the anchor. Coefficient yield from linear regression of the mean changes in EQ-VAS and QLDS, and distribution-based approach with ½ SD of change in QLDS were considered. Results: In ASPIRE I, mean (SD) improvement in QLDS score among patients with one category improvement in MADRS from baseline to Day 25 was − 8.22 (8.87), − 8.30 (9.01), and − 8.20 (8.92) using severity criteria #1, #2, and #3, respectively. Patients who achieved a 7-point improvement (MCT) in EQ-VAS yielded a mean − 9.69-point improvement in QLDS at Day 25. The ½ SD of change in QLDS was 5.63. Similar results were obtained for ASPIRE II. The MCTs identified using multiple anchors across both trials ranged from − 11.4 to − 6.7 and had an overall mean of − 7.90 (ASPIRE I) and − 7.92 (ASPIRE II). Thus, an 8-point change was recommended as the MCT for QLDS. Conclusion: The recommended MCT will help quantify within-person changes in HRQoL using patient-reported QLDS and determine meaningful treatment benefit in an MDD patient population with acute suicidal ideation or behavior. Trial registration: Name of the registry: ClinicalTrials.gov. Trial registration number: ASPIRE I (NCT03039192), ASPIRE II (NCT03097133). Date of registration: February 01, 2017; March 31, 2017. URL of trial registry record: https://clinicaltrials.gov/ct2/show/NCT03039192; https://clinicaltrials.gov/ct2/show/NCT03097133. [ABSTRACT FROM AUTHOR]

Objectives: To compare the performance of spleen stiffness measurement (SSM) and liver stiffness measurement (LSM) by sound touch elastography (STE) for the diagnosis of cirrhosis at different alanine aminotransferase (ALT) levels, and to compare the applicability and repeatability of SSM with LSM performed by STE, a new two-dimensional shear wave elastography technology. Methods: This prospective multicenter study included 25 centers and recruited chronic hepatitis B (CHB) patients with liver biopsy between May 2018 and November 2019. All patients underwent LSM and SSM by STE. Success and reliability rates were calculated and compared. Intra-observer agreement was assessed using intraclass correlation coefficients (ICCs). Differences between areas under the receiver operating characteristic curves (AUCs) of LSMs and SSMs at different ALT levels were compared using the Delong test. Results: Among 603 CHB patients, the success and reliability rates of SSM were 94.53% (570/603) and 85.74% (517/603), respectively, which were similar to those of LSM (p > 0.05), respectively. The ICC for intra-observer agreements of SSM was 0.964 (p < 0.001). In the total cohort, ALT ≤ 2 × upper limit of normal (ULN) group, and A0–1 group, the AUCs of SSMs were significantly lower than those of LSMs for the diagnosis of cirrhosis (p < 0.001). In the ALT > 2 × ULN group and A2–3 group, the AUC of SSM improved and was not significantly different from that of LSM (p = 0.342, p = 0.510, respectively). Conclusions: SSM by STE achieved applicability and repeatability equivalent to those of LSM. SSM might be a good substitute to LSM in patients with high ALT levels. Key Points: • Spleen stiffness measurement performed by sound touch elastography was proven to have similar applicability and repeatability to liver stiffness measurement in this prospective multicenter study. • Spleen stiffness measurement demonstrated a poorer diagnostic performance for cirrhosis compared with liver stiffness measurement in the total cohort and low ALT level group, yet it showed a similar diagnostic performance to liver stiffness measurement in patients with high ALT levels. [ABSTRACT FROM AUTHOR]