Search

Abstract CRISPR diagnostics are effective but suffer from low signal transduction efficiency, limited sensitivity, and poor stability due to their reliance on the trans-cleavage of single-stranded nucleic acid fluorescent reporters. Here, we present CrisprAIE, which integrates CRISPR/Cas reactions with “one to more” aggregation-induced emission luminogen (AIEgen) lighting-up fluorescence generated by the trans-cleavage of Cas proteins to AIEgen-incorporated double-stranded DNA labeled with single-stranded nucleic acid linkers and Black Hole Quencher groups at both ends (Q-dsDNA/AIEgens-Q). CrisprAIE demonstrates superior performance in the clinical nucleic acid detection of norovirus and SARS-CoV-2 regardless of amplification. Moreover, the diagnostic potential of CrisprAIE is further enhanced by integrating it with spherical nucleic acid-modified AIEgens (SNA/AIEgens) and a portable cellphone-based readout device. The improved CrisprAIE system, utilizing Q-dsDNA/AIEgen-Q and SNA/AIEgen reporters, exhibits approximately 80- and 270-fold improvements in sensitivity, respectively, compared to conventional CRISPR-based diagnostics. We believe CrisprAIE can be readily extended as a universal signal generation strategy to significantly enhance the detection efficiency of almost all existing CRISPR-based diagnostics.

Abstract Accurate and sensitive near‐infrared (NIR) luminescent lateral flow immunoassay (LFIA) has attracted considerable attention in the field of point‐of‐care testing (POCT). However, the detection accuracy and sensitivity are often compromised by the low fluorescence quantum efficiency ( 800 nm) completely eliminated background interference and allowed highly accurate and sensitive detection without any pre‐treatment steps. The limits of detection (LODs) for aflatoxin B1 (AFB1) in soy sauce, alpha hemolysin (Hla) of Staphylococcus aureus biomarker in joint fluid, and C‐reactive protein (CRP) in human haemolysed samples were 0.01 ng mL−1, 0.02 µg mL−1, and 0.156 mg L−1, respectively, commensurating with those of the corresponding gold standard assays and covering the detection range of interests. It is anticipated that the ultrabright NIR AIEgen nanoparticles will serve as a universally applicable signal probe for NIR‐LFIA diagnostics, promising to expand the range of applications for quantitative detection of complex samples.

Abstract Dendritic mechanisms driving input-output transformation in starburst amacrine cells (SACs) are not fully understood. Here, we combine two-photon subcellular voltage and calcium imaging and electrophysiological recording to determine the computational architecture of mouse SAC dendrites. We found that the perisomatic region integrates motion signals over the entire dendritic field, providing a low-pass-filtered global depolarization to dendrites. Dendrites integrate local synaptic inputs with this global signal in a direction-selective manner. Coincidental local synaptic inputs and the global motion signal in the outward motion direction generate local suprathreshold calcium transients. Moreover, metabotropic glutamate receptor 2 (mGluR2) signaling in SACs modulates the initiation of calcium transients in dendrites but not at the soma. In contrast, voltage-gated potassium channel 3 (Kv3) dampens fast voltage transients at the soma. Together, complementary mGluR2 and Kv3 signaling in different subcellular regions leads to dendritic compartmentalization and direction selectivity, highlighting the importance of these mechanisms in dendritic computation.

Abstract Lipoprotein(a) [Lp(a)] is a risk factor for cardiovascular disease (CVD) and aortic stenosis. However, the data on the relationship between Lp(a) and mildly reduced estimated glomerular filtration rate (eGFR) has been disputed. This study was conducted to assess the relationship between Lp(a) concentrations and mildly reduced eGFR in healthy subjects.This community-based, cross-sectional study enrolled 1,064 volunteers aged ≥ 40 years who lived in Yonghong Community, Zhonglou District, Changzhou, China, between December 2016 and December 2017. A mildly reduced eGFR was defined as eGFR between 60 and 90 mL/min/1.73m2. A standardized questionnaire and biochemical measurements were used to gather information about participants. The serum concentration of Lp(a) was determined using the latex-enhanced immunoturbidimetric test. Of the total study population, 34.8% (n = 370) were men, and the mean age was 66.8 ± 8.5 years. A significant association existed between Lp(a) levels and the risk of mildly reduced eGFR. Individuals with the highest tertile of Lp(a) had higher odds of mildly reduced eGFR after adjusting for various confounders (adjusted odds ratio [OR]: 1.80, 95% confidence interval [CI]: 1.24–2.60, P = 0.0025) compared to those with the lowest tertile of Lp(a). Multivariable logistic regression of studies in which Lp(a) was presented as continuous variables showed consistent results (adjusted OR: 1.23 for 1-SD increment of Ln-Lp(a), 95% CI: 1.05–1.43). Subgroup analyses showed that study characteristics such as age, sex, obesity, diabetes, and hypertension status did not significantly affect the association (P for all interactions > 0.05). These results suggest that higher serum Lp(a) level was an independent risk factor for mildly reduced eGFR.

Abstract Immunity-and-matrix-regulatory cells (IMRCs) derived from human embryonic stem cells have unique abilities in modulating immunity and regulating the extracellular matrix, which could be mass-produced with stable biological properties. Despite resemblance to mesenchymal stem cells (MSCs) in terms of self-renew and tri-lineage differentiation, the ability of IMRCs to repair the meniscus and the underlying mechanism remains undetermined. Here, we showed that IMRCs demonstrated stronger immunomodulatory and pro-regenerative potential than umbilical cord MSCs when stimulated by synovial fluid from patients with meniscus injury. Following injection into the knees of rabbits with meniscal injury, IMRCs enhanced endogenous fibrocartilage regeneration. In the dose-escalating phase I clinical trial (NCT03839238) with eighteen patients recruited, we found that intra-articular IMRCs injection in patients was safe over 12 months post-grafting. Furthermore, the effective results of magnetic resonance imaging (MRI) of meniscus repair and knee functional scores suggested that 5 × 107 cells are optimal for meniscus injury treatment. In summary, we present the first report of a phase I clinical trial using IMRCs to treat meniscus injury. Our results demonstrated that intra-articular injection of IMRCs is a safe and effective therapy by providing a permissive niche for cartilage regeneration.

Numerous studies have demonstrated that under low-velocity, low-energy impact conditions, although the surface damage to fiber-reinforced composite laminates may be minimal, significant internal damage can occur. Consequently, a progressive damage finite element model was specifically developed for thermoplastic carbon fiber-reinforced composite laminates subjected to low-speed impact loads, with the objective of analyzing the damage behavior of laminates under impacts of varying energy levels. The model utilizes a three-dimensional Hashin criterion for predicting intralayer damage initiation, with cohesive elements based on bilinear traction–separation law for predicting interlaminar delamination initiation, and incorporates a damage constitutive model based on equivalent displacement to characterize fiber damage evolution, along with the B-K criterion for interlaminar damage evolution. The impact response of laminates at energy levels of 5 J, 10 J, 15 J, 20 J, and 25 J was analyzed through numerical simulation, drop-hammer experiments, and XCT non-destructive testing. The results indicated that the simulation outcomes closely correspond with the experimental findings, with both the predicted peak error and absorbed energy error maintained within a 5% margin, and the trends of the mechanical response curves aligning closely with the experimental data. The damage patterns predicted by the numerical simulations were consistent with the results obtained from XCT scans. The study additionally revealed that the impact damage of the laminates primarily stems from interlaminar delamination and intralayer tensile failure. Initial damage typically presents as internal delamination; hence, enhancing interlaminar bonding performance can significantly augment the overall load-bearing capacity of the laminate.

Several exogenous probiotics are applicable in fish culture; however, challenges in isolation and verification have hindered the full utilization of numerous host probiotics. Therefore, this study aimed to apply the host probiotic Exiguobacterium acetylicum G1-33 to hybrid grouper (Epinephelus fuscoguttatus ♀ × Epinephelus lanceolatus ♂) cultures and explore its mechanism of action. In total, 360 hybrid grouper were divided into four groups, which were fed the following for 60 days: three received commercial feed with varying concentrations of E. acetylicum G1-33 (106, 108, and 1010 CFU/g), while a control group received commercial feed. The results showed that supplementation with 106 and 108 CFU/g of E. acetylicum G1-33 enhanced gut morphology, upregulated growth-related genes (ghr1, igf-2, s6k1, tor), and promoted growth, with supplementation with 108 CFU/g resulting in the most notable enhancement. However, supplementation with 1010 CFU/g inhibited growth, possibly because of changes in intestinal morphology. Additionally, supplementation with E. acetylicum G1-33 upregulated the expression of immune-related genes (c3, myd88, Cu/Zn-sod, tlr3, and tnf2) in the liver and head kidney but led to an increase in malondialdehyde content, as well as a decrease in alkaline phosphatase and acid phosphatase activities, in the liver and serum, indicating increased oxidative stress. Moreover, supplementation with 106 and 108 CFU/g E. acetylicum G1-33 enhanced the widespread expression of immune-related genes in the head kidney and liver, respectively, and improved resistance to Vibrio harveyi, whereas supplementation with 1010 CFU/g weakened this resistance. In conclusion, E. acetylicum G1-33, particularly at 108 CFU/g, emerged as an effective probiotic, optimizing growth performance and immunity in hybrid grouper. This research is pioneering in its application of E. acetylicum in mariculture, potentially broadening the range of probiotic strategies in aquaculture.

The gut microbiota participates in a wide range of biological processes of host, such as growth, feeding and immunity. The rabbitfish (Siganus oramin) is a popular table fish with good taste and rich nutrition. However, there are many potential unknown risks in artificial cultivation process. In this study, for the first time, we performed a 16 s rDNA sequencing analysis of gut microbiota in rabbitfish growing in different environments including marine cage, cement pond and wild environment. The most abundant phylum in all conditions was Proteobacteria, especially in individuals cultured in cement pond, and the relative abundance of Firmicutes, Fusobacteria and Bacteroidetes was obviously higher in marine-cage and wild individuals. At the genus level, Burkholderia-Caballeronia-Paraburkholderia was the most abundant in rabbitfish cultivated in cement pond environment. Moreover, Lipid biosynthesis proteins, Carotenoid biosynthesis, Proximal tubule bicarbonate reclamation, Dioxin degradation and Xylene degradation pathways were found to be highly abundant in rabbitfish cultivated in cement pond, while Sphingolipid metabolism, Plant-pathogen interaction and Glycosphingolipid biosynthesis-globo series pathways were scarce. Interestingly, no obvious difference of gut microbiota was found between marine-cage and wild rabbitfish. All these results would lay a good foundation for developing a microbiota based strategy for artificial cultivation of rabbitfish.

Abstract Fluorescent‐magneto nanoemitters have gained considerable attention for their applications in mechanical controlling‐assisted optical signaling. However, the incompatibility between magnetic and fluorescent components often leads to functional limitations in traditional magneto@fluorescence nanostructure. Herein, we introduce a new compact‐discrete spatial arrangement on a “fluorescence@magneto” core–shell nanostructure consisting of a close‐packed aggregation‐induced emission luminogen (AIEgen) core and a discrete magnetic shell. This structural design effectively eliminates the optical and magnetic interferences between the dual components by facilitating AIEgens loading in core region and reducing the magnetic feeding amount through effective exposure of the magnetic units. Thereby, the resulting magneto‐AIEgen nanoparticle (MANP) demonstrates “win‐win” performances: (i) high fluorescent intensity contributed by AIEgens stacking‐enhanced photoluminescence and reduced photons loss from the meager magnetic shell; (ii) marked magnetic activity due to magneto extraposition‐minimized magnetic shielding. Accordingly, the dual functions‐retained MANP provides a proof of concept for construction of an immunochromatographic sensing platform, where it enables bright fluorescent labeling after magnetically enriching and separating procalcitonin and lipoarabinomannan in clinical human serum and urine, respectively, for the clinical diagnosis of bacterial infections‐caused inflammation and tuberculosis. This study not only inspires the rational design of magnetic‐fluorescent nanoemitter but also highlights promising potential in magneto‐assisted point‐of‐care test and biomedicine applications.

Abstract ‘Urban Dry (Wet) Islands’ (UDI/UWI) represents microclimate change that impacts ecosystems and human well-being. However, causes of the UDI (UWI) phenomena are not fully understood due to the lack of empirical data. Here, we quantify UDI (UWI) using global observations of atmospheric humidity, evapotranspiration (ET), and land surface characteristics across 25 large urban agglomerations. We show that UDI (17) and UWI (8) are closely tied to local ET, global warming, and ‘Urban Heat Islands’ through intertwined linkages with water and energy balances. UDI is most pronounced in humid vegetated regions where mean urban-rural annual ET differences are as high as 215 mm, whereas UWI is found in arid regions or in climates with dry summers. We conclude that ET can be used as a single variable to explain emerging urban environmental changes. Our study supports a concerted strategy of restoring nature’s ET power as effective ‘Nature-based Solutions’ to mitigate the negative environmental effects of urbanization.

Potential evapotranspiration (PET), as an indicator of atmospheric evaporative demand, is a critical hydrological and meteorological factor to reflect regional and global hydrological cycles and environmental change. Understanding these nuanced responses of PET to environmental changes is important for agricultural production and water demand estimation. This study rigorously evaluated fluctuations in PET using the Penman–Monteith model over a 50-year span from 1970 to 2020 in the Sichuan–Chongqing region, an area notably susceptible to climate change. The changing characteristics of PET and local meteorological factors were detected by integrating the Mann–Kendall method and Pettitt test. Furthermore, the contribution and sensitivity of key meteorological variables to the observed variation in PET were also thoroughly investigated. Breakpoint analysis revealed that abrupt changes appeared in 1996 for annual PET. The detrending method indicated that substantial decreases in net radiation and wind speed (p < 0.01) were responsible for the decrease in annual PET from 1970 to 1996. Marked increases in minimum temperature and wind speed were the driving forces behind the uptick in annual PET in 1997–2020. At seasonal scales, wind speed and net radiation predominantly influenced PET in 1970–1996 in general. However, from 1997 to 2020, the factors controlling PET fluctuations displayed considerable seasonal variation. Sensitivity analysis showed that Ws and Tmin were the second-most sensitive factors. By exploring the impacts of PET changes and shifts, attention must be paid when allocating water resources reasonably under the background of ongoing climate change and likelihood of future drought.

This study investigated the effects of the dietary replacing fishmeal (FM) with fermented cottonseed meal (FCSM) on growth performance, body coloration, serum biochemistry, muscle quality, and liver antioxidant capacity of juvenile golden pompano (Trachinotus ovatus). Fish were fed with five experimental diets (0 (FM), 12.5% (CSM12.5), 25% (CSM25), 50% (CSM50), and 100% (CSM100) replacement levels) for 8 weeks. The weight gain rate (WGR), specific growth rate (SGR), and condition factor (CF) in fish fed with CSM25 were significantly higher than those of the FM (P0.05). The relative gene expression of Nrf2 of fish fed with CSM25 diet was higher than that of the other groups (P0.05). Based on these results, we recommend that of FCSM in the diet of golden pompano, whereas the optimal level of FCSM should be carefully evaluated. In conclusion, the optimum level of dietary replacing FM with FCSM in T. ovatus diet was 24.74%−29.38% based on SGR and WGR.

Abstract Background Inflammatory bone resorption is a prominent risk factor for implantation failure. Simvastatin (SIM) has anti‐inflammatory effects independent of cholesterol lowering and reduces osteoclastogenesis by decreasing both the number and activity of osteoclasts. However, the specific mechanism of inflammatory bone loss alleviation by SIM remains to be elucidated. We hypothesized that SIM relieves inflammatory bone loss by modulating autophagy and suppressing the NOD‐like receptor family pyrin domain‐containing protein 3 (NLRP3) signaling pathway. Methods and results RAW264.7 cells were stimulated by lipopolysaccharide (LPS) after being pretreated with various concentrations of SIM. Osteoclast (OC) differentiation, formation and activity were evaluated by tartrate‐resistant acid phosphatase staining, F‐actin ring staining and bone resorption pit assays, respectively. We observed autophagosomes by transmission electron microscopy. Then NLRP3 inhibitor MCC950 was used to further explore the corresponding molecular mechanism underlying anti‑inflammatory bone resorption, the expression of autophagy‐related proteins and NLRP3 signaling pathway factors in pre‐OCs were evaluated by western blot analysis, and the expression of OC‑specific molecules was analyzed using reverse transcription‑quantitative polymerase chain reaction. The results showed that SIM decreased the expression of tumor necrosis factor‐α, whereas increased Interleukin‐10. In addition, SIM inhibited LPS‐induced OC differentiation, formation, bone resorption activity, the level of autophagosomes, and OC‑specific markers. Furthermore, SIM significantly suppressed autophagy by downregulating LC3II, Beclin1, ATG7, and NLRP3‐related proteins expression while upregulating P62 under inflammatory conditions. Conclusions SIM may reduce autophagy secretion to attenuate LPS‐induced osteoclastogenesis and the NLRP3 signaling pathway participates in this process, thus providing theoretical basis for the application of this drug in peri‐implantitis.

Abstract Background The impact of metabolically healthy obesity (MHO) on kidney dysfunction remains debatable. Moreover, few studies have focused on the early stages of kidney dysfunction indicated by hyperfiltration and mildly reduced eGFR. Thus, we aimed to investigate the association between the MHO and early kidney dysfunction, which is represented by hyperfiltration and mildly reduced estimated glomerular filtration rate (eGFR), and to further explore whether serum uric acid affects this association. Methods This cross-sectional study enrolled 1188 residents aged ≥ 40 years old from Yonghong Communities. Metabolically healthy phenotypes were categorized based on Adult Treatment Panel III criteria. Obesity was defined as body mass index (BMI) ≥ 25 kg/m2. Mildly reduced eGFR was defined as being in the range 60 95th percentile after adjusting for sex, age, weight, and height. Results Overall, MHO accounted for 12.8% of total participants and 24.6% of obese participants. Compared to metabolically healthy non-obesity (MHNO), MHO was significantly associated with an increased risk of mildly reduced eGFR (odds ratio [OR] = 1.85, 95% confidence interval [CI] 1.13–3.01) and hyperfiltration (OR = 2.28, 95% CI 1.03–5.09). However, upon further adjusting for uric acid, the association between the MHO phenotype and mildly reduced eGFR was reduced to null. Compared with MHNO/non-hyperuricemia, MHO/non-hyperuricemia was associated with an increased risk of mildly reduced eGFR (OR = 2.04, 95% CI 1.17–3.58), whereas MHO/hyperuricemia was associated with an observably increased risk (OR = 3.07, 95% CI 1.34–7.01). Conclusions MHO was associated with an increased risk of early kidney dysfunction, and the serum uric acid partially mediated this association. Further prospective studies are warranted to clarify the causality.

The rabbitfish, Siganus oramin, is a commercially important table fish in southeastern China. However, there have been few studies on its gonad development and reproduction regulation. Comparative transcriptome analysis was first performed on adult male and female gonads of S. oramin. In total, 47,070 unigenes were successfully assembled and 22,737 unigenes were successfully annotated. Through comparative transcriptome analysis of male and female gonads, a total of 6722 differentially expressed genes were successfully identified, with 3528 upregulated genes and 3154 downregulated genes in the testes. In addition, 39 differentially expressed reproduction-related genes were identified. Finally, quantitative real-time PCR was used to validate the expression levels of several differentially expressed genes. These results provide important data for further studying the function of reproduction-related genes and the molecular mechanism regulating gonad development and reproduction in S. oramin.

The rabbitfish Siganus oramin is an important naturally caught and aquaculture fish species. Intestinal microbiota can affect the metabolism and immunity of fish, which is closely related to the habitat of the host. In this study, we collected the wild fry S. oramin from a natural sea area, and cultured them in outdoor and indoor ponds, respectively, and investigated the changes in serum biochemical indexes and intestinal microbial community in three different habitats. The results showed that compared with the wild population, the serum total protein content of the outdoor culture population increased significantly. The indoor culture population had significantly higher triglyceride and total cholesterol contents than that of the outdoor culture population. Additionally, the intestinal microbial richness indexes ACE and Chao1 of the cultured population were higher than those of the wild population, especially the indoor culture, but Shannon and Simpson had no obvious changes. The relative abundances of Firmicutes, Spirochaetae and Bacteroidetes increased in the outdoor culture population, but decreased in the indoor culture population; those of Proteobacteria and Cyanobacteria were completely the opposite. Some putative beneficial bacteria (Lactobacillus, Clostridium sensu stricto 1, and Intestinibacter) and harmful bacteria (Vibrio, Photobacterium, Desulfovibrio, Streptococcus) all decreased in the intestines of the cultured population when compared with the wild population, while Akkermansia and Faecalibacterium were enriched in the outdoor culture population. These results reveal that a change in habitat environment, whether an outdoor or an indoor pond, positively influenced the intestinal microbiota of the rabbitfish, which is beneficial to the healthy culture of the fish from the perspective of microbial community.

Abstract Retinal degeneration, characterized by the progressive loss of retinal neurons, is the leading cause of incurable visual impairment. Retinal progenitor cells (RPCs)‐based transplantation can facilitate sight restoration, but the clinical efficacy of this process is compromised by the imprecise neurogenic differentiation of RPCs and undermining function of transplanted cells surrounded by severely oxidative retinal lesions. Here, it is shown that ultrathin niobium carbide (Nb2C) MXene enables performance enhancement of RPCs for retinal regeneration. Nb2C MXene with moderate photothermal effect markedly improves retinal neuronal differentiation of RPCs by activating intracellular signaling, in addition to the highly effective RPC protection by scavenging free radicals concurrently, which has been solidly evidenced by the comprehensive biomedical assessments and theoretical calculations. A dramatically increased neuronal differentiation is observed upon subretinal transplantation of MXene‐assisted RPCs into the typical retinal degeneration 10 (rd10) mice, thereby contributing to the efficient restoration of retinal architecture and visual function. The dual‐intrinsic function of MXene synergistically aids RPC transplantation, which represents an intriguing paradigm in vision‐restoration research filed, and will broaden the multifunctionality horizon of nanomedicine.

Abstract Metastasis and chemical resistance are the most serious problems in the treatment of highly aggressive uveal melanoma (UM). The newly identified lncRNA OUM1 is overexpressed in UM, functions as a catalyst and regulates protein tyrosine phosphatase (PTP) activity by binding to PTP receptor type Z1 (PTPRZ1), which plays an important role in cell proliferation, metastasis and chemotherapy resistance in the UM microenvironment. Hence, siRNAs that selectively knocking down the lncRNA OUM1 (siOUM1) and its target gene PTPRZ1 (siPTPRZ1) were designed to inhibit the OUM1/PTPRZ1 pathway to reduce PTP activity, and this reduction in activity interrupts protein tyrosine phosphorylation, suppresses UM proliferation and metastasis and improves cisplatin sensitivity in UM cells. Then, to overcome the limitations of the difficulty of drug administration and traditional therapeutics, the indocyanine green (ICG)-labeled manganese metal–organic framework (MOF) nanoparticles (NPs) were fabricated and linked with arginine-glycine-aspartate (RGD) peptide to carry siOUM1/siPTPRZ1 and cisplatin to achieve targeted siRNA interference-mediated therapy, enhanced cisplatin therapy and chemodynamic therapy. This NP system also has a dual-modal imaging ability because ICG is a near-infrared region fluorescent dye and manganese has the potential to be used in magnetic resonance imaging. This study verifies the significance of the newly discovered lncRNA OUM1 as a new therapeutic target for aggressive UM and provides a drug delivery NP system for precise treatment of UM accompanied with a dual-modal imaging ability. Graphical Abstract

Abstracts: This trial was performed to investigate the effects of Clostridium butyricum on growth and intestinal health of hybrid groupers (Epinephelus lanceolatus♂ × E. fuscoguttatus♀). 300 hybrid groupers were fed five diets containing C. butyricum at 0, 1 × 107, 2 × 107, 3 × 107, 4 × 107 CFU/g for 8 weeks. The results revealed that dietary C. butyricum significantly increased weight gain rate (WGR), specific growth rate (SGR) and relative feed intake (RFI) (P

IntroductionThe aim of this study was to describe appetite and glucose fluctuation in type 2 diabetes mellitus patients initiating treatment with dulaglutide combined with insulin degludec.MethodsThis retrospective study of patients identified adults starting treatment with once-weekly (QW) dulaglutide combined with insulin degludec (experimental group) or insulin degludec alone (control group). Patients were followed for up to 6 months from treatment initiation. The clinical characteristics of patients, treatment patterns, CGM data, and appetite scores were obtained for the two groups.ResultsA total of 236 patients were included in this study. SDBG, MAGE, LAGE, and PPGE of the experimental group were lower than the control group’s (P < 0.05). The proportions of patients achieving a time in range (TIR) of ≥70% in the experimental group were higher than in the control group, with 43% and 10% on the second day, 88% and 47% on the fourth day, 95% and 47% on the seventh day, and 100% and 67% on the tenth day, respectively. Significant associations existed between TIR and the prevalence of islet function. At six months, 89.2% of patients in the experimental group were still using dulaglutide. Appetite decreased significantly at 1 week and increased at 3 months after treatment with dulaglutide.ConclusionDulaglutide combined with insulin degludec significantly reduces glucose fluctuations in patients with type 2 diabetes mellitus and improves the TIR rate. However, the treatment on appetite could decrease in the first three months.

Due to increasing anthropogenic pressure, over half of the world’s tropical forests are reforested or afforested secondary forests or plantations. The recovery pace and potential of these forests depend largely on soil microbially-mediated biogeochemical cycling. Here we measured soil extracellular enzyme activities and quantified microbial metabolic limitations using a vector analysis in a bare land (BL, representing the original state before restoration), two afforested sites [i.e. a restored secondary forest (MF) and a managed Eucalyptus exserta plantation (EP)] and a nearby undisturbed forest (UF) in south China. Results showed that soil microbial metabolisms were co-limited by carbon (C) and phosphorus (P) across the four forests. Both microbial C and P limitations were higher in BL than UF. Microbial C limitation significantly reduced after restoration only in MF when compared to BL, but it was still higher than that in UF. Interestingly, microbial P limitation significantly enhanced after restoration in both EP and MF when compared to BL, and it did not differ between the two restored forests. Structural equation modeling (SEM) showed that microbial C limitation was primarily attributed to microbial C use efficiency, while microbial P limitation was co-driven by plant biomass, microbial C use efficiency and soil P availability. These findings suggest microbial C limitation could be gradually recovered after forest restoration in southern China, which would facilitate soil organic carbon accumulation. However, the enhanced microbial P limitation after forest restoration underlines the necessity to develop optimal P management in these restored forests.

BackgroundBecause it is one of the important pathways for promoting motor recovery after cortical injury, the function of the reticulospinal tract (RST) has received increasing attention in recent years. However, the central regulatory mechanism of RST facilitation and reduction of apparent response time is not well understood.ObjectivesTo explore the potential role of RST facilitation in the acoustic startle priming (ASP) paradigm and observe the cortical changes induced by ASP reaching tasks.MethodsTwenty healthy participants were included in this study. The reaching tasks were performed with their left and right hands. Participants were instructed to get ready after the warning cue and complete the reach as soon as they heard the Go cue. Half of the testing trials were set as control trials with an 80-dB Go cue. The other half of the trials had the Go cue replaced with 114-dB white noise to evoke the StartleReact effect, inducing reticulospinal tract facilitation. The response of the bilateral sternocleidomastoid muscle (SCM) and the anterior deltoid was recorded via surface electromyography. Startle trials were labeled as exhibiting a positive or negative StartleReact effect, according to whether the SCM was activated early (30–130 ms after the Go cue) or late, respectively. Functional near-infrared spectroscopy was used to synchronously record the oxyhemoglobin and deoxyhemoglobin fluctuations in bilateral motor-related cortical regions. The β values representing cortical responses were estimated via the statistical parametric mapping technique and included in the final analyses.ResultsSeparate analyses of data from movements of the left or right side revealed significant activation of the right dorsolateral prefrontal cortex during RST facilitation. Moreover, left frontopolar cortex activation was greater in positive startle trials than in control or negative startle trials during left-side movements. Furthermore, decreased activity of the ipsilateral primary motor cortex in positive startle trials during ASP reaching tasks was observed.ConclusionThe right dorsolateral prefrontal cortex and the frontoparietal network to which it belongs may be the regulatory center for the StartleReact effect and RST facilitation. In addition, the ascending reticular activating system may be involved. The decreased activity of the ipsilateral primary motor cortex suggests enhanced inhibition of the non-moving side during the ASP reaching task. These findings provide further insight into the SE and into RST facilitation.

The present study was conducted to investigate the effects of dietary fermented cottonseed meal (FCSM) substitution for fish meal on intestinal enzymatic activity, inflammatory and physical-barrier-related gene expression, and intestinal microflora of juvenile golden pompano. The 375 golden pompanos were divided into 15 groups of 25 fish each, with three replicates for each experimental group. The fish were fed five experimental diets (0 (FM), 12.5% (CSM12.5), 25% (CSM25), 50% (CSM50), and 100% (CSM100) substitution levels) for 8 weeks. The fish were reared and fed the experimental diets under a natural-day light cycle. Compared with the control group, the activities of AMY (amylase) enzymes in the CSM12.5 group and all other groups were elevated (p < 0.05). The CSM25 group exhibited a considerable up-regulation of IL-10 (Interleukin-10) expression relative to the FM group (p < 0.05). With an increase in dietary FM substitution with FCSM from 0 to 25%, the relative expressions of NF-κB (Nuclear factor kappa-B), IL-1β (Interleukin-1 beta), and IL-8 (Interleukin-8) were down-regulated. In this study, the relative expressions of ZO-1 (zonula occluden-1) and Occludin were up-regulated, and those of Claudin-3 and Claudin-15 significantly up-regulated, when the FCSM substitution ratio was 25%. The results of high-throughput sequencing of the intestinal microflora showed that ACE indices the lowest in the CSM25 group, which was significantly different from those in the CSM100 group (p < 0.05). The CSM50 group had the highest Shannon and Simpson indices and the highest community diversity. In addition, replacing a high percentage of fish meal with FCSM can negatively affect the intestinal flora of fish. In this study, the 25% substitution ratio improved nutrient absorption, reduced intestinal inflammation, improved intestinal physical barrier damage, did not affect intestinal microecology, and had no adverse effects on fish. However, substitution of a high proportion of FM with FCSM negatively affects the intestinal microflora and nutrient absorption capacity of fish.

Abstract Acoustic emission (AE) characterization is an effective technique to indirectly capture the failure process of quasi brittle rock. In previous studies, both experiments and numerical simulations were adopted to investigate the AE characteristics of rocks. However, as the most popular numerical model, the moment tensor model (MTM) cannot be constrained by the experimental result because there is a gap between MTM and experiments in principle, signal processing and energy analysis. In this paper, we developed a particle-velocity-based model (PVBM) that enabled direct monitoring and analysis of the particle velocity in the numerical model and had good robustness. The PVBM imitated the actual experiment and could fill in gaps between the experiment and MTM. AE experiments of marine shale under uniaxial compression were carried out, and the results were simulated by MTM. In general, the variation trend of the experimental result could be presented by MTM. Nevertheless, the magnitudes of AE parameters by MTM presented notable differences of more than several orders of magnitude compared with those by the experiment. We sequentially used PVBM as a proxy to analyse these discrepancies and systematically evaluate the AE characterization of rocks from the experiment to numerical simulation, considering the influence of wave reflection, energy geometrical diffusion, viscous attenuation, particle size and progressive deterioration of rock material. The combination of MTM and PVBM could reasonably and accurately acquire AE characteristics of the actual AE experiment of rocks by making full use of their respective advantages.

Highlight 1. We developed a new DLS immunosensing technology for the rapid and sensitive detection of glycoprotein NT-proBNP. 2. The boronate affinity recognition amplified nanoparticle aggregation was designed to enable highly sensitive DLS transduction. 3. The fabricated DLS immunosensor exhibited ultrahigh sensitivity with an LOD of 7.4 fg mL−1, fast response time (

ObjectivesThe triglyceride-glucose (TyG) index has been identified as a reliable and simple surrogate of insulin resistance. In this study, we sought to determine the association between TyG index and cardiac function among asymptomatic individuals with type 2 diabetes (T2DM) without history of any cardiovascular disease.Materials and methodsThe cross-sectional study enrolled 180 T2DM patients without cardiac symptoms. Heart failure with preserved ejection fraction (HFpEF) was defined as Heart Failure Association (HFA)-PEFF score ≥ 5 points.ResultsA total of 38 (21.1%) diabetic patients were identified with HFpEF. Compared with the low-TyG group (TyG index

Abstract Background Probiotics are widely used to promote host health. Compared to mammals and terrestrial invertebrates, little is known the role of probiotics in aquatic invertebrates. In this study, eighteen tanks with eight hundred of shrimp post-larvae individuals each were randomly grouped into three groups, one is shrimps administered with E. faecium as probiotic (Tre) and others are shrimps without probiotic-treatment (CK1: blank control, CK2: medium control). We investigated the correlations between a kind of commercial Enterococcus faecium (E. faecium) powder and microbiota composition with function potentials in shrimp post-larvae gut. Results We sequenced the 16S rRNA gene (V4) of gut samples to assess diversity and composition of the shrimp gut microbiome and used differential abundance and Tax4Fun2 analyses to identify the differences of taxonomy and predicted function between different treatment groups. The ingested probiotic bacteria (E. faecium) were tracked in gut microbiota of Tre and the shrimps here showed the best growth performance especially in survival ratio (SR). The distribution of SR across samples was similar to that in PCoA plot based on Bray-Curits and two subgroups generated (SL: SR

BackgroundThe setup accuracy plays an extremely important role in the local control of tumors. The purpose of this study is to verify the feasibility of "Sphere-Mask" Optical Positioning System (S-M_OPS) for fast and accurate setup.MethodsFrom 2016 to 2021, we used S-M_OPS to supervise 15441 fractions in 1981patients (with the cancer in intracalvarium, nasopharynx, esophagus, lung, liver, abdomen or cervix) undergoing intensity-modulated radiation therapy (IMRT), and recorded the data such as registration time and mask deformation. Then, we used S-M_OPS, laser line and cone beam computed tomography (CBCT) for co-setup in 277 fractions, and recorded laser line-guided setup errors and S-M_OPS-guided setup errors with CBCT-guided setup result as the standard.ResultsS-M_OPS supervision results: The average time for laser line-guided setup was 31.75s. 12.8% of the reference points had an average deviation of more than 2 mm and 5.2% of the reference points had an average deviation of more than 3 mm. Co-setup results: The average time for S-M_OPS-guided setup was 7.47s, and average time for CBCT-guided setup was 228.84s (including time for CBCT scan and manual verification). In the LAT (left/right), VRT (superior/inferior) and LNG (anterior/posterior) directions, laser line-guided setup errors (mean±SD) were -0.21±3.13mm, 1.02±2.76mm and 2.22±4.26mm respectively; the 95% confidence intervals (95% CIs) of laser line-guided setup errors were -6.35 to 5.93mm, -4.39 to 6.43mm and -6.14 to 10.58mm respectively; S-M_OPS-guided setup errors were 0.12±1.91mm, 1.02±1.81mm and -0.10±2.25mm respectively; the 95% CIs of S-M_OPS-guided setup errors were -3.86 to 3.62mm, -2.53 to 4.57mm and -4.51 to 4.31mm respectively.ConclusionS-M_OPS can greatly improve setup accuracy and stability compared with laser line-guided setup. Furthermore, S-M_OPS can provide comparable setup accuracy to CBCT in less setup time.

The performance indicators of concrete are mainly determined by the interface characteristics between cement hydration slurry and aggregates. In this study, molecular dynamics technology was used to evaluate the effect of the interfacial water content on the evolution of the interface structure, interaction energy, and mechanical properties of calcium silicate hydrate (C-S-H) and silicon dioxide (SiO2) systems, and the weakening mechanism of the C-S-H/SiO2 interface in a humid environment was revealed. The results showed that all stress–strain curves of C-S-H/SiO2 were divided into the elastic stage and the failure stage. As the interfacial water layer thickened, the molecular weight of the water invading the C-S-H gradually increased, and the desorption of Ca2+ ions in the surface region became significant, while the amount of Ca2+ ions entering the water-layer region increased. The interaction energy of the C-S-H/SiO2 progressively became larger, and the energy ratio (ER) significantly decreased; the tensile strength σc and residual strength σr of C-S-H/SiO2 both showed a downward trend. In summary, a lower water content had a limited impact on the interfacial bonding strength, while the weakening effect enhanced with an increase in the interfacial water content. This phenomenon was also demonstrated in concrete interfacial bond strength experiments.

Potential rockfall source areas are widely distributed in the high mountain areas of the Tibetan Plateau, posing significant hazards to human lives, infrastructures, and lifeline facilities. In a combination of field investigation, high-precision aerial photogrammetry, and numerical simulation, we took the Maoyaba basin as an example to explore a rapid identification method for high-altitude rockfall sources. An automatic potential rockfall source identification (PRSI) procedure was introduced to simplify the process of rockfall source identification. The study revealed that rockfall sources are concentrated in areas with intense frost weathering. Our identification results were validated using rockfall inventory data detection from remote sensing images and field investigation. Of the rockfall source areas identified by the PRSI procedure, 80.85% overlapped with the remote sensing images result. The accuracy assessment using precision, recall, and F1 score was 0.91, 0.81, and 0.85, respectively, which validates the reliability and effectiveness of the PRSI procedure. Meanwhile, we compared the rockfall source distribution of five DEMs with different resolutions and four neighborhood areas. We discovered that, in addition to high-resolution DEMs (i.e., 1 m and 2 m), medium-resolution DEMs (i.e., 5 m, 12.5 m) also perform well in identifying rockfall sources. Finally, we conducted a hazard assessment based on Culmann’s two-dimensional slope stability model and rockfall hazard vector method. Appropriate protective measures should be taken at high-hazard sections to safeguard pedestrians, vehicles, and related infrastructure from rockfalls.

Abstract Background Walking and running are the most common means of locomotion in human daily life. People have made advances in developing separate exoskeletons to reduce the metabolic rate of walking or running. However, the combined requirements of overcoming the fundamental biomechanical differences between the two gaits and minimizing the metabolic penalty of the exoskeleton mass make it challenging to develop an exoskeleton that can reduce the metabolic energy during both gaits. Here we show that the metabolic energy of both walking and running can be reduced by regulating the metabolic energy of hip flexion during the common energy consumption period of the two gaits using an unpowered hip exoskeleton. Methods We analyzed the metabolic rates, muscle activities and spatiotemporal parameters of 9 healthy subjects (mean ± s.t.d; 24.9 ± 3.7 years, 66.9 ± 8.7 kg, 1.76 ± 0.05 m) walking on a treadmill at a speed of 1.5 m s−1 and running at a speed of 2.5 m s−1 with different spring stiffnesses. After obtaining the optimal spring stiffness, we recruited the participants to walk and run with the assistance from a spring with optimal stiffness at different speeds to demonstrate the generality of the proposed approach. Results We found that the common optimal exoskeleton spring stiffness for walking and running was 83 Nm Rad−1, corresponding to 7.2% ± 1.2% (mean ± s.e.m, paired t-test p

Abstract Background Adiponectin is an adipocytokine that plays a key regulatory role in glucose and lipid metabolism in obesity. The prevalence of obesity has led to an increase in the incidence of obesity-related glomerulopathy (ORG). This study aimed to identify the protective role of adiponectin in ORG. Methods Small-interfering RNA (siRNA) against the gene encoding adiponectin was transfected into podocytes. The oxidative stress level was determined using a fluorometric assay. Apoptosis was analyzed by flow cytometry. The expressions of podocyte markers and pyrin domain containing protein 3 (NLRP3) inflammasome-related proteins were measured by qRT-PCR, immunohistochemistry, and Western blot. Results Podocytes treated with palmitic acid (PA) showed downregulated expressions of podocyte markers, increased apoptosis, upregulated levels of NLRP3 inflammasome-related proteins, increased production of inflammatory cytokines (IL-18 and IL-1β), and induced activation of NF-κB as compared to the vehicle-treated controls. Decreased adiponectin expression was observed in the serum samples from high fat diet (HFD)-fed mice. Decreased podocin expression and upregulated NLRP3 expression were observed in the kidney samples from high fat diet (HFD)-fed mice. Treatment with adiponectin or the NLRP3 inflammasome inhibitor, MCC950, protected cultured podocytes against podocyte apoptosis and inflammation. Treatment with adiponectin protected mouse kidney tissues against decreased podocin expression and upregulated NLRP3 expression. The knockout of adiponectin gene by siRNA increased ROS production, resulting in the activation of NLRP3 inflammasome and the phosphorylation of NF-κB in podocytes. Pyrrolidine dithiocarbamate, an NF-κB inhibitor, prevented adiponectin from ameliorating FFA-induced podocyte injury and NLRP3 activation. Conclusions Our study showed that adiponectin ameliorated PA-induced podocyte injury in vitro and HFD-induced injury in vivo via inhibiting the ROS/NF-κB/NLRP3 pathway. These data suggest the potential use of adiponectin for the prevention and treatment of ORG.

ABSTRACT Introduction: There are few circulating biomarkers for valvular heart disease. Angiopoietin (Ang) 1, Ang2, and vascular endothelial growth factor are important inflammation-associated cytokines. The aim of this study was to investigate the clinical significance and association of Ang1, Ang2, and vascular endothelial growth factor in valvular heart disease. Methods: This is a retrospective study; a total of 62 individuals (valvular heart disease patients [n=42] and healthy controls [n=20]) were included. Plasma levels of Ang1, Ang2, and vascular endothelial growth factor were detected by enzyme-linked immunosorbent assays. We retrospectively collected the baseline characteristics and short-term outcomes; logistic regression was performed to identify predictor for short-term mortality. Results: Ang2 was significantly decreased in the valvular heart disease group compared with the healthy control group (P=0.023), while no significant difference was observed in the Ang1 and vascular endothelial growth factor levels. The Ang2 level of New York Heart Association (NYHA) I/II patients — but not NYHA III/IV patients — was significantly decreased compared with that of healthy control individuals (NYHA I/II: P=0.017; NYHA III/IV: P=0.485). Univariable logistic regression analysis indicated that Ang2 was a significant independent predictor for short-term mortality (odds ratio 18.75, P=0.033, 95% confidence interval 8.08-102.33). Ang1 was negatively correlated with Ang2 (P=0.032, Pearson’s correlation coefficient =-0.317) and was positively correlated with vascular endothelial growth factor (P=0.019, Pearson’s correlation coefficient = 0.359). Conclusion: Ang2 might serve as a therapeutic and prognostic target for valvular heart disease.

ObjectiveThe current study aimed to assess the efficacy and safety of percutaneous nephrolithotomy (PCNL) in obese and overweight individuals based on body mass index (BMI).MethodsWe electronically explored the databases of PubMed, CENTRAL, ScienceDirect, Embase, and Google Scholar databases for all types of comparative studies investigating the role of BMI on PCNL outcomes. Only studies defining obesity as >30 kg/m2 were included. Efficacy outcomes were stone-free rates and operating time while safety outcomes were complications and length of hospital stay (LOS).ResultsEighteen studies with 101,363 patients were included. We noted no difference in the stone-free rates after PCNL for morbid obese vs normal BMI patients (OR: 0.78 95% CI, 0.57, 1.08 I2 = 7% p = 0.13), overweight vs normal (OR: 1.01 95% CI, 0.89, 1.15 I2 = 1% p = 0.83) and obese vs normal patients (OR: 1.00 95% CI, 0.87, 1.16 I2 = 0% p = 0.95). PCNL operative time was significantly increased in morbid obese (MD: 9.36 95% CI, 2.85, 15.88 I2 = 76% p = 0.005) and obese patients as compared with normal patients (MD: 2.15 95% CI, 1.20, 3.10 I2 = 0% p

This study was conducted to investigate the impacts of potassium diformate (KDF) on growth performance, fillet quality, plasma indices, immune response and intestinal morphology of juvenile Trachinotus ovatus. Six diets with 0 (KDF1), 3.00 (KDF2), 6.00 (KDF3), 9.00 (KDF4), 12.00 (KDF5) and 15.00 (KDF6) g/kg KDF were formulated to feed T. ovatus (average fish weight: 5.87 ± 0.03 g) for 8 weeks. The results indicated that 3.00 g/kg and 6.00 g/kg KDF significantly increased the growth parameters of juvenile T. ovatus (P

ObjectiveTo evaluate the safety, walking efficiency, physiological cost, don and doff time cost, and user satisfaction of Ai-robot.DesignProspective, multi-center, and cross-over trial.SubjectsParaplegic subjects (n = 40) with T6–L2 level spinal cord injury.MethodsSubjects who could walk independently using Aiwalker, Ailegs, and hip knee ankle foot orthosis (HKAFO) for 6 min within 30 days of training underwent 10 sets of tests. In each set, they completed three 6-min walk test (6MWT) sessions using the three aids in random order.ResultsSkin lesions, pressure sores, and fractures, were the main adverse events, likely due to a lack of experience in using exoskeleton systems. The average 6MWT distances of the Aiwalker, Ailegs, and HKAFO groups were 134.20 ± 18.74, 79.71 ± 18.06, and 48.31 ± 19.87 m, respectively. The average heart rate increases in the Aiwalker (4.21 ± 8.20%) and Ailegs (41.81 ± 23.47%) groups were both significantly lower than that in the HKAFO group (62.33 ± 28.32%) (both p < 0.001). The average donning/doffing time costs for Ailegs and Aiwalker were significantly shorter than that of HKAFO (both p < 0.001). Satisfaction was higher in the Ailegs and Aiwalker groups (both p < 0.001).ConclusionSubjects with paraplegia below T6 level were able to ambulate safely and efficiently with Ai-robot. The use of Ai-robot should be learned under the guidance of experienced medical personnel.

Abstract Background Stroke produces multiple symptoms, including sensory, motor, cognitive and psychological dysfunctions, among which motor deficit is the most common and is widely recognized as a major contributor to long-term functional disability. Robot-assisted training is effective in promoting upper extremity muscle strength and motor impairment recovery after stroke. Additionally, action observation treatment can enhance the effects of physical and occupational therapy by increasing neural activation. The AOT-EXO trial aims to investigate whether action observation treatment coupled with robot-assisted training could enhance motor circuit activation and improve upper extremity motor outcomes. Methods The AOT-EXO trial is a multicentre, prospective, three-group randomized controlled trial (RCT). We will screen and enrol 132 eligible patients in the trial implemented in the Department of Rehabilitation Medicine of Tongji Hospital, Optical Valley Branch of Tongji Hospital and Hubei Province Hospital of Integrated Chinese & Western Medicine in Wuhan, China. Prior to study participation, written informed consent will be obtained from eligible patients in accordance with the Declaration of Helsinki. The enrolled stroke patients will be randomized to three groups: the CT group (conventional therapy); EXO group (exoskeleton therapy) and AOT-EXO group (action observation treatment-based exoskeleton therapy). The patients will undergo blinded assessments at baseline, post-intervention (after 4 weeks) and follow-up (after 12 weeks). The primary outcome will be the Fugl-Meyer Assessment for Upper Extremity (FMA-UE). Secondary outcomes will include the Action Research Arm Test (ARAT), modified Barthel Index (MBI), kinematic metrics assessed by inertial measurement unit (IMU), resting motor threshold (rMT), motor evoked potentials (MEP), functional magnetic resonance imaging (fMRI) and safety outcomes. Discussion This trial will provide evidence regarding the feasibility and efficacy of the action observation treatment-based exoskeleton (AOT-EXO) for post-stroke upper extremity rehabilitation and elucidate the potential underlying kinematic and neurological mechanisms. Trial registration Chinese Clinical Trial Registry ChiCTR1900026656 . Registered on 17 October 2019.

Ion doping, an effective way to modify the nature of materials, is beneficial for the improvement of material properties. Mn doping exhibits gain of piezoelectric properties in KTa1−xNbxO3 (KTN). However, the impact mechanism of Mn ions on properties remains unclear. Here, the effects of Mn doping on local heterogeneity and piezoelectric properties in KTN are studied. The electric field-induced strain of Mn-doped KTN is ∼0.25% at 10 kV cm−1, 118% higher than that of pristine KTN. Meanwhile, as a result of Mn doping, the dielectric permittivity was tripled and the ferroelectricity was modified. The changes in A1(2TO), B1 + E(3TO) and E(4TO) vibrations characterized by Raman spectra indicate increased local polarization, weak correlation of dipoles and distorted lattices in Mn-doped KTN, respectively. First-principles calculations demonstrate stronger local heterogeneity introduced by Mn dopants, which weakens the dipole correlations and reduces domain sizes. As a result, the decreased domain sizes, combined with the larger ratio of lattice parameters c and a of the Mn-contained portion, are responsible for the higher piezoelectricity. This work reveals the impact on properties of KTN from Mn dopants and the prominent role of local heterogeneity in improving piezoelectricity, being valuable for the optimization and design of material properties.

Hg2+ contamination in sewage can accumulate in the human body through the food chains and cause health problems. Herein, a novel aggregation-induced emission luminogen (AIEgen)-encapsulated hydrogel probe for ultrasensitive detection of Hg2+ was developed by integrating hydrophobic AIEgens into hydrophilic hydrogels. The working mechanism of the multi-fluorophore AIEgens (TPE-RB) is based on the dark through-bond energy transfer strategy, by which the energy of the dark tetraphenylethene (TPE) derivative is completely transferred to the rhodamine-B derivative (RB), thus resulting in intense photoluminescent intensity. The spatial networks of the supporting hydrogels further provide fixing sites for the hydrophobic AIEgens to enlarge accessible reaction surface for hydrosoluble Hg2+, as well create a confined reaction space to facilitate the interaction between the AIEgens and the Hg2+. In addition, the abundant hydrogen bonds of hydrogels further promote the Hg2+ adsorption, which significantly improves the sensitivity. The integrated TPE-RB-encapsulated hydrogels (TR hydrogels) present excellent specificity, accuracy and precision in Hg2+ detection in real-world water samples, with a 4-fold higher sensitivity compared to that of pure AIEgen probes. The as-developed TR hydrogel-based chemosensor holds promising potential as a robust, fast and effective bifunctional platform for the sensitive detection of Hg2+.

This paper studies the local optimality condition for the widely applied concave piecewise linear network flow problem (CPLNFP). Traditionally, for CPLNFP the complexity of checking the local optimality condition is exponentially related to the number of active arcs (i.e., arcs in which the flow is at the breakpoints). When the scale of CPLNFP is large, even local optimality is unverifiable and the corresponding local algorithms are inefficient. To overcome this shortcoming, a new local optimality condition is given. This new condition is based on the concavity and piecewise linearity of the cost function and makes full use of the network structure. It is proven that the complexity of the new condition is polynomial. Therefore, using the new condition to verify the local optimality is far superior to using the traditional condition, especially when there are many active arcs.

Abstract Background Spinal manipulative therapy is commonly used in the treatment of adolescent idiopathic scoliosis. Some therapists also rely on physiotherapeutic scoliosis-specific exercise (PSSE). Combining these two modalities seems reasonable, but the effectiveness of this combination has never been rigorously tested. Here, a protocol for a pilot study is proposed to determine the feasibility of conducting a larger randomized trial. The pilot study was designed to test the hypothesis that spinal manipulative therapy followed by PSSE is more effective than PSSE alone in improving the Cobb angle, sensorimotor integration, the angle of trunk rotation (ATR), body symmetry, and quality of life. Methods The protocol describes a randomized controlled pilot trial with 40 subjects divided into study and control groups. Both groups will receive 8 weeks of PSSE, but the study group will also receive spinal manipulative therapy during the first 2 weeks before PSSE. The primary outcome will be an estimate of the feasibility of conducting a full-scale experiment. The influencing factors will be the time to complete enrollment, the recruitment rate, subject retention, and adherence to the treatment allocations. The secondary outcomes that will be used to assess the efficacy of treatment will include the Cobb angle, somatosensory evoked potentials, ATR, three-dimensional postural parameters, and scores on the 22-item Scoliosis Research Society outcomes questionnaire. The Cobb angle will be measured at baseline and at the end of 8 weeks of training. The somatosensory evoked potentials will be measured at baseline and at the end of 2 weeks of training. The ATR, three-dimensional postural parameters, and scores on the 22-item Scoliosis Research Society outcomes questionnaire will be measured at baseline and at 2 weeks, 4 weeks, and 8 weeks of treatment. Discussion This study will inform the design of a future full-scale trial. The outcomes will provide preliminary data about the efficacy of the combination of spinal manipulative therapy and exercise in treating scoliosis. Trial registration Prospectively registered at Chinese clinical trial registry, ChiCTR1900027037 . Registered on 29 October 2019. http://www.chictr.org.cn/edit.aspx?pid=44954&htm=4

In the intensive care unit(ICU), excessive false alarms burden medical staff greatly, and cause a waste of medical resources as well. In order to alleviate false alarming in ICU, we constructed classification models based on convolutional neural network, which can directly deal with time series and avoid manually extracting features. Combining with grouping strategy, we tried two basic network structures, i.e. deep group convolutional neural network(DGCN) and embedded deep group convolutional network(EDGCN). After that, based on EDGCN, which was proved better, ensemble networks were constructed to elevate the performance further. Considering of the limited sample size, various data expansions were also tried. For comparison, we used a widely adopted index ‘Score’, which is defined as $100\times $ (TP+TN)/(TP+TN+FP $+ 5\times $ FN), as performance evaluation. Finally, we tested our model in the online sandbox, and got a score of 80.68. Although it is slightly lower than the best scores that have been reported, our models are end-to-end, which means the original time series can be automatically mapped into a binary output, without manual feature extraction. In addition, the innovative adoption of group convolution makes full use of information from multi-channel signals. Besides, this work provides ideas for relating network parameter selection with physiological or physical natures of signals. In the end, after further discussion, we also proposed potential elevation solutions.

Biomass-based carbon dots (Bio-CDs) were prepared from dehydroabietic acid using a one-step hydrothermal process. Characterization by TEM, XPS and FTIR spectroscopy showed that the Bio-CDs are spherical nanoparticles containing mainly C, N and O elements, with functional groups such as amino and carbonyl groups on their surface. The optical properties of the Bio-CDs were studied in detail. A solution of Bio-CDs exhibited excitation-dependent blue fluorescence emission. The solution showed excellent photostability under ultraviolet light and the fluorescence intensity could be enhanced by decreasing the temperature. The intensity of fluorescence emission of the solution was essentially unchanged over the pH range 3.91–8.69, and in the presence of different anions and cations, other than Fe3+ and Pb2+. Fe3+ and Pb2+ ions, respectively, quenched and enhanced the intensity of the fluorescence emission of the solution, allowing sensitive and selective detection of Fe3+ (LOD = 2.33 μM, Em = 437 nm) and of Pb2+ (LOD = 0.27 μM, Em = 437 nm and LOD = 0.33 μM, Em = 500 nm). As a further demonstration of potential applications, the Bio-CDs were shown to have low cytotoxicity and to stain cell nuclei as effectively as the commonly used nuclear stain 4′,6-diamino-2-phenylindole (DAPI), demonstrating their promise in the field of cell imaging.

This paper proposes a novel siamese cross contrast neural network (SCCNN) to classify the hepatocellular carcinoma (HCC) and the intrahepatic cholangiocarcinoma (ICC) on computed tomography (CT) images. This method is inspired from cross contrast neural networks (CCNN) which is based on tailored CNN and information based similarity(IBS) theory. A new IBS-based measurement named as discriminative IBS(DisIBS) is designed for SCCNN. SCCNN is composed of two main parts including siamese feature extractors with DisIBS operator and MLP classifiers. Siamese networks extract features with DisIBS calculated by DisIBS operator as metric at the top. MLP classifiers are connected with but gradient-stop to feature extractors deriving classification results. We assign different loss functions with different parts to make better practice, specially DisIBS-based loss for feature extractors and softmax-based for MLP classifiers. SCCNN preserves the advantages of CCNN that can fit the insufficient medical images and small lesions. Furthermore, it extends CCNN with the siamese mechanism and gradient-stop MLP classifiers to accept the random inputs and predict like traditional CNN. To present the effectiveness of SCCNN empirically, we apply this method on a 234-person (157/77 for train/test) dataset and achieve better results than other classic CNN and CCNN methods. We try different base models of siamese structures and display prediction accuracy in two levels (slice/patient). The highest slice/patient accuracy which we have achieved on three-categories classification (HCC/ICC/Normal) is 90.22%/94.92% and the accuracy rises to 94.17%/97.44% on binary classification(HCC/ICC).

Objectives: To demonstrate the task-specificities of anticipatory muscle activations (AMAs) among different forward-reaching tasks and to explore the StartleReact Effect (SE) on AMAs in occurrence proportions, AMA onset latency or amplitude within these tasks in both healthy and stroke population.Methods: Ten healthy and ten stroke subjects were recruited. Participants were asked to complete the three forward-reaching tasks (reaching, reaching to grasp a ball or cup) on the left and right hand, respectively, with two different starting signals (warning-Go, 80 dB and warning-startle, 114 dB). The surface electromyography of anterior deltoid (AD), flexor carpi radialis (FCR), and extensor carpi radialis (ECR) on the moving side was recorded together with signals from bilateral sternocleidomastoid muscles (SCM), lower trapezius (LT), latissimus dorsi (LD), and tibialis anterior (TA). Proportions of valid trials, the incidence of SE, AMA incidence of each muscle, and their onset latency and amplitude were involved in analyses. The differences of these variables across different move sides (healthy, non-paretic, and paretic), normal or startle conditions, and the three tasks were explored. The ECR AMA onset was selected to further explore the SE on the incidence of AMAs.Results: Comparisons between move sides revealed a widespread AMA dysfunction in subacute stroke survivors, which was manifested as lower AMA onset incidence, changed onset latency, and smaller amplitude of AMAs in bilateral muscles. However, a significant effect of different tasks was only observed in AMA onset latency of muscle ECR (F = 3.56, p = 0.03, η2p = 0.011), but the significance disappeared in the subsequent analysis of the stroke subjects only (p > 0.05). Moreover, the following post-hoc comparison indicated significant early AMA onsets of ECR in task cup when comparing with reach (p < 0.01). For different stimuli conditions, a significance was only revealed on shortened premotor reaction time under startle for all participants (F = 60.68, p < 0.001, ηp2 = 0.056). Furthermore, stroke survivors had a significantly lower incidence of SE than healthy subjects under startle (p < 0.01). But all performed a higher incidence of ECR AMA onset (p < 0.05) than with normal signal. In addition, the incidence of ECR AMAs of both non-paretic and paretic sides could be increased significantly via startle (p ≤ 0.02).Conclusions: Healthy people have task-specific AMAs of muscle ECR when they perform forward-reaching tasks with different hand manipulations. However, this task-specific adjustment is lost in subacute stroke survivors. SE can improve the incidence of AMAs for all subjects in the forward-reaching tasks involving precision manipulations, but not change AMA onset latency and amplitude.

Summary: Continuous theta-burst stimulation (cTBS), a non-invasive brain stimulation technique, can induce long-lasting changes in synaptic plasticity, vital for memory reconsolidation. For this study, a total of 170 participants completed four experiments by a randomized controlled design. Succeeding fear conditioning, the subjects received cTBS over the right dorsolateral prefrontal cortex (dlPFC) or vertex (control) with or without exposure to the conditioned stimulus to reactivate the original fear memory, and then underwent fear response tests. Compared with cTBS over the vertex and without memory reactivation, only cTBS over the right dlPFC after reactivation decreased the fear response for both recent and remote fear memories. This procedure was effective only during the reconsolidation window. The disruptive effect of cTBS over the right dlPFC on fear memory reconsolidation was delay-dependent. These findings demonstrate that cTBS time-dependently and delay-dependently prevents the return of fear and may have clinical potential for treating fear-related disorders.

Analyzing the primary factors of potential evapotranspiration (PET) dynamic is fundamental to accurately estimating crop yield, evaluating environmental impacts, and understanding water and carbon cycles. Previous studies have focused on regionally average regional PET and its dominant factors. Spatial distributions of PET trends and their main causes have not been fully investigated. The Mann-Kendall test was used to determine the significance of long-term trends in PET and five meteorological factors (net radiation, wind speed, air temperature, vapor pressure deficit, relative humidity) at 56 meteorological stations in the Sichuan-Chongqing region from 1970 to 2020. Furthermore, this present study combining and quantitatively illustrated sensitivities and contributions of the meteorological factors to change in annual and seasonal PET. There was a positive trend in PET for approximately 58%, 68%, 38%, 73% and 73% of all surveyed stations at annual, spring, summer, autumn and winter, respectively. Contribution analysis exhibited that the driving factors for the PET variation varied spatially and seasonally. For stations with an upward PET trend, vapor pressure deficit was a dominant factor at all time scales. For stations with a downward PET trend, annual changes in PET mainly resulted from decreased wind speed, as did changes in spring, autumn and winter; decreasing net radiation was the dominant factor in summer. The positive effect of the vapor pressure deficit offset the negative effects of wind speed and net radiation, leading to the increasing PET in this area as a whole. Sensitivity analysis showed that net radiation and relative humidity were the two most sensitive variables for PET, followed by vapor pressure deficit in this study area. Results from the two mathematical approaches were not perfect match, because the change magnitude of the meteorological factors is also responsible for the effects of meteorological factors on PET variation to some extent. However, conducting sensitivity and contribution analysis in this study can avoid the uncertainties from using a single method and provides detailed and well-understood information for interpreting the influence of global climate change on the water cycle and improving local water management.

Staphylococcal enterotoxin A (SEA) has presented enormous difficulties in dairy food safety and the sensitive detection of SEA provides opportunities for effective food safety controls and staphylococcal food poisoning tracebacks. Herein, a novel aggregation-induced emission (AIE)-based sandwich lateral flow immunoassay (LFIA) was introduced to detect SEA by using red-emissive AIE nanoparticles (AIENPs) as the fluorescent nanoprobe. The nanoprobe was constructed by directly immobilising antibodies on boronate-tagged AIENPs (PBA-AIENPs) via a boronate affinity reaction, which exhibited a high SEA-specific affinity and remarkable fluorescent performance. Under optimal conditions, the ultrasensitive detection of SEA in pasteurised milk was achieved within 20 min with a limit of detection of 0.04 ng mL−1. The average recoveries of the PBA-AIENP-LFIA ranged from 91.3% to 117.6% and the coefficient of variation was below 15%. It was also demonstrated that the PBA-AIENP-LFIA had an excellent selectivity against other SE serotypes. Taking advantage of the excellent sensitivity of this approach, real chicken and salad samples were further analysed, with a high versatility and accuracy. The proposed PBA-AIENP-LFIA platform shows promise as a potent tool for the identification of additional compounds in food samples as well as an ideal test method for on-site detections.

Lateral flow immunoassay (LFIA) based on fluorescent microbeads has attracted much attention for its use in rapid and accurate food safety monitoring. However, conventional fluorescent microbeads are limited by the aggregation-caused quenching effect of the loaded fluorophores, thus resulting in low signal intensity and insufficient sensitivity of fluorescent LFIA. In this study, a green-emitting fluorophore with an aggregation-induced emission (AIE) characteristic was encapsulated in polymer nanoparticles via an emulsification technique to form ultrabright fluorescent microbeads (denoted as AIEMBs). The prepared AIEMBs were then applied in a competitive LFIA (AIE-LFIA) as signal reporters for the rapid and highly sensitive screening of fumonisin B1 (FB1) in real corn samples. High sensitivity with a detection limit of 0.024 ng/mL for FB1 was achieved by the developed AIE-LFIA. Excellent selectivity, good accuracy, and high reliability of the AIE-LFIA were demonstrated, indicating a promising platform for FB1 screening.

During the guided drilling process as part of shale gas exploration and development, shale is damaged by a polycrystalline diamond compact (PDC) bit cutter. It is essential to carry out research on rock breaking by a PDC cutter. In this paper, we study the mechanism of shale fragmentation by a PDC cutter based on the discrete element method. Additionally, we consider the effects of bedding angle, bedding thickness, cutting depth and cutting rate on the rock-breaking efficiency of a PDC cutter. The results show the following: (1) With the increase in bedding angle, the number and area of microcracks first increase and then decrease, and the proportion of tension cracks is relatively unchanged; there is no significant change in the morphology of the failure zone, and the average particle size of the cutting fragments first decreases and then increases. (2) With the increase in the bedding thickness, microcracks continue to extend in a horizontal direction, the total number of cracks shows a fluctuated change, and the proportion of tension cracks increases. The failure zone extends in a conical shape in the horizontal direction, and the average size of the cutting fragments gradually increases. (3) With the increase in cutting depth and cutting rate, the number and area of microcracks increase, and the proportion of shear cracks increases; the area of the failure zone increases and the size of the cutting fragment decreases.