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Abstract Crowdsourced package delivery (CPD) has gained great interest from the logistics industry and academe due to its signficant economic and environmental impact. A number of progresses have been reported; however, dynamic pricing, as a special and significant part of the uncertain CPD markets, is far less explored. To address the problem, a novel Delaunay Triangulation (DT) based pricing strategy is proposed for dealing with the imbalanced demand and supply in local markets with the aim to maximizing the profit of the CPD platform. To cater to drivers’ wishes further, the hyperbolic temporal discounting function is applied to estimate their psychological rewards in order to increase the possibility of package acceptance. A three‐stage framework consisting of the DT‐based pricing, the matching pruning and the package assigning algorithm is proposed, to figure out the best‐possible package‐driver matching. With the dataset generated by Brinkhoff road network generator in the city of Jinan and Luoyang, China, a series of experiments is conducted to evaluate the proposed approach against several representative baseline approaches. Experimental results show that the approach significantly outperforms the other approaches in terms of effectiveness and efficiency.

The hybrids (BY) derived from blunt snout bream (Megalobrama amblycephala, BSB, ♀) and Bleeker's yellow tai (Xenocypris davidi Bleeker, YT, ♂) have a fast growth rate and body thickness. However, the molecular mechanisms underlying the growth advantage of BY are still unclear. MSTN, a member of the TGF-β superfamily, is a negative regulator of muscle growth and development. MYOD, a member of the myogenic regulatory factor family (MRFs), is a positive regulator of muscle growth and development. MSTN and MYOD interact to co-regulate muscle growth and development. In this study, we cloned the full-length cDNAs of mstn and myod in BY, analyzed differential expression of the two genes in muscle of BY and its parents, and observed the localization of the two genes during embryonic development of BY. Multiple sequence alignment of amino acids and phylogenetic analysis showed that mstn and myod were highly conserved in BY, BSB, YT, and other carp family fishes. Quantitative Real-time PCR (qRT-PCR) showed that mstn and myod were primarily expressed in muscle of BY, and there were significant differences in the expression of the two genes in the red and white muscles of BY, BSB, and YT at different age. The results of in situ hybridization of embryos showed an overlap in the temporal and spatial expression of mstn and myod in BY embryo development, suggesting that the two genes might interact to co-regulate embryo growth and development. This study provides a theoretical basis for further research on the mechanisms of mstn and myod in muscle growth of hybrid fishes.

Distant hybridization often results in the generation of naturally gynogenic offspring. However, there are currently few reports about fertile natural gynogenetic bream. In this study, we established a natural gynogenetic blunt snout bream (NGBSB-YT, F1) through distant hybridization from female blunt snout bream (Megalobrama amblycephala, BSB) × male Bleeker's yellow tail (Xenocypris davidi Bleeker, YT), and further obtained NGBSB1-YT (F2) by self-cross. Except for the morphological characteristics, the DNA content, chromosome numbers, and 5 S rDNA sequences of NGBSB1-YT had no significant difference compared to those of BSB. The results of gonad sections showed that NGBSB1-YT was bisexual. The NGBSB2-YT (F3) obtained by self-cross further proved the fertility of NGBSB1-YT. Interestingly, the results of microsatellite (prime XD007) analysis and sox9 sequence analysis confirmed that paternal DNA fragments were inserted in NGBSB1-YT. This study has established a lineage of natural gynogenetic bream(F1-F3), that provides a reference for improvement of the theory of natural gynogenesis in fish. The NGBSB-YT lineage can be used as a new type of germplasm resource of bream.

BackgroundAnkle sprains are prevalent in sports, often causing complex injuries to the lateral ligaments. Among these, anterior talofibular ligament (ATFL) injuries constitute 85%, and calcaneofibular ligament (CFL) injuries comprise 35%. Despite conservative treatment, some ankle sprain patients develop chronic lateral ankle instability (CLAI). Thus, this study aimed to investigate stress response and neural control alterations during landing in lateral ankle ligament injury patients.MethodThis study recruited twenty individuals from a Healthy group and twenty CLAI patients performed a landing task using relevant instruments to collect biomechanical data. The study constructed a finite element (FE) foot model to examine stress responses in the presence of laxity of the lateral ankle ligaments. The lateral ankle ligament was modeled as a hyperelastic composite structure with a refined representation of collagen bundles and ligament laxity was simulated by adjusting material parameters. Finally, the validity of the finite element model is verified by a high-speed dual fluoroscopic imaging system (DFIS).ResultCLAI patients exhibited earlier Vastus medialis (p < 0.001) and tibialis anterior (p < 0.001) muscle activation during landing. The FE analysis revealed that with laxity in the ATFL, the peak von Mises stress in the fifth metatarsal was 20.74 MPa, while with laxity in the CFL, it was 17.52 MPa. However, when both ligaments were relaxed simultaneously, the peak von Mises stress surged to 21.93 MPa. When the ATFL exhibits laxity, the CFL is subjected to a higher stress of 3.84 MPa. Conversely, when the CFL displays laxity, the ATFL experiences a peak von Mises stress of 2.34 MPa.ConclusionThis study found that changes in the laxity of the ATFL and the CFL are linked to shifts in metatarsal stress levels, potentially affecting ankle joint stability. These alterations may contribute to the progression towards CLAI in individuals with posterolateral ankle ligament injuries. Additionally, significant muscle activation pattern changes were observed in CLAI patients, suggesting altered neural control strategies post-ankle ligament injury.

Aiming to address the issue of mapping failure resulting from unsmooth motion during SLAM (Simultaneous Localization and Mapping) performed by a quadruped robot, a tightly coupled SLAM algorithm that integrates LIDAR and IMU sensors is proposed in this paper. Firstly, the IMU information, after undergoing deviation correction, is utilized to remove point cloud distortion and serve as the initial value for point cloud registration. Subsequently, a registration algorithm based on Normal Distribution Transform (NDT) and sliding window is presented to ensure real-time positioning and accuracy. Then, an error function combining IMU and LIDAR is formulated using a factor graph, which iteratively optimizes position, attitude, and IMU deviation. Finally, loop closure detection based on Scan Context is introduced, and loop closure factors are incorporated into the factor graph to achieve effective mapping. An experimental platform is established to conduct accuracy and robustness comparison experiments. Results showed that the proposed algorithm significantly outperforms the LOAM algorithm, the NDT-based SLAM algorithm and the LeGO-LOAM algorithm in terms of positioning accuracy, with a reduction of 65.08%, 22.81%, and 37.14% in root mean square error, respectively. Moreover, the proposed algorithm exhibits superior robustness compared to LOAM, NDT-based SLAM and LeGO-LOAM.

AbstractBackground Acute respiratory failure (ARF) is a common clinical critical syndrome with substantial mortality. Extracorporeal carbon dioxide removal (ECCO2R) has been proposed for the treatment of ARF. However, whether ECCO2R could provide a survival advantage for patients with ARF is still controversial.Methods Electronic databases (PubMed, Embase, Web of Science, and the Cochrane database) were searched from inception to 30 April 2022. Randomized controlled trials (RCTs) and observational studies that examined the following outcomes were included: mortality, length of hospital and ICU stay, intubation and tracheotomy rate, mechanical ventilation days, ventilator-free days (VFDs), respiratory parameters, and reported adverse events.Results Four RCTs and five observational studies including 1173 participants with ARF due to COPD or ARDS were included in this meta-analysis. Pooled analyses of related studies showed no significant difference in overall mortality between ECCO2R and control group, neither in RCTs targeted ARDS or acute hypoxic respiratory failure patients (RR 1.05, 95% CI 0.83 to 1.32, p = 0.70, I2 =0.0%), nor in studies targeted patients with ARF secondary to COPD (RR 0.80, 95% CI 0.58 to 1.11, p = 0.19, I2 =0.0%). A shorter duration of ICU stay in the ECCO2R group was only obtained in observational studies (WMD −4.25, p

This paper comprehensively analyses the first-ever monkeypox outbreak in Shenzhen, China, encompassing clinical symptomatology, therapeutic approaches, epidemiological research, and comprehensive laboratory tests, aiming to establish a robust reference for future monkeypox mitigation and management strategies. The investigation involved a thorough investigation of all identified positive cases, including extensive molecular analysis by nucleic acid detection and whole-genome sequencing of the monkeypox virus. Contact tracing and containment of the infected individuals were also undertaken. Three distinct monkeypox cases were identified in this unique outbreak, exhibiting mild and atypical clinical manifestations, primarily fever and rash. All cases were associated with a single transmission chain, primarily facilitated through close contact and homosexual behavior, indicative of a high-risk factor for monkeypox transmission.

BackgroundMelanocortin-3 and -4 receptors (MC3R and MC4R), G protein-coupled receptors, play vital roles in the regulation of energy homeostasis. To understand the functions of mc3r and mc4r in the energy homeostasis of red crucian carp (Carassius auratus red var., RCC), we cloned mc3r and mc4r, analyzed the tissue expression and localization of the genes, and investigated the effects of knockout of mc3r (mc3r+/-) and mc4r (mc4r+/-) in RCC. ResultsThe full-length cDNAs of RCC mc3r and mc4r were 1459 base pairs (bp) and 1894 bp, respectively. qRT-PCR indicated that mc3r and mc4r were profusely expressed in the brain, but lower expressed in the periphery tissues. ISH revealed that mc3r and mc4r were located in NPP, NPO, NAPv, NSC, NAT, NRL, NLTl, and NLTp of the brain, suggesting that mc3r and mc4r might regulate many physiological and behavioral aspects in RCC. To further verify the roles of mc3r and mc4r in energy homeostasis, the mc3r+/- and mc4r+/- fish were obtained by the CRISPR/Cas9 system. The average body weights, total lengths, body depths, and food intake of mc4r+/- fish were significantly higher than those of mc3r+/- and the normal wild-type (WT) fish, but there was no difference between the mc3r+/- and WT fish, indicating that the RCC phenotype and food intake were mainly influenced by mc4r but not mc3r. Interestingly, mc4r+/- fish displayed more visceral fat mass than mc3r+/- and WT fish, and mc3r+/- fish also exhibited slightly more visceral fat mass compared to WT. RNA-seq of the liver and muscle revealed that a large number of differentially expressed genes (DEGs) differed in WT vs. mc3r+/-, WT vs. mc4r+/-, and mc3r+/- vs. mc4r+/-, mainly related to lipid, glucose, and energy metabolism. The KEGG enrichment analysis revealed that DEGs were mainly enriched in pathways such as steroid biosynthesis, fatty acid metabolism, fatty acid biosynthesis, glycolysis/gluconeogenesis, wnt signaling pathway, PPAR signaling pathway, and MAPK signaling pathway, thereby affecting lipid accumulation and growth. ConclusionIn conclusion, these results will assist in the further investigation of the molecular mechanisms in which MC3R and MC4R were involved in the regulation of energy homeostasis in fish.

Abstract Background Continuous renal replacement therapy (CRRT) is a widely used standard therapy for critically ill patients with acute kidney injury (AKI). Despite its effectiveness, treatment is often interrupted due to clot formation in the extracorporeal circuits. Anticoagulation is a crucial strategy for preventing extracorporeal circuit clotting during CRRT. While various anticoagulation options are available, there were still no studies synthetically comparing the efficacy and safety of these anticoagulation options. Methods Electronic databases (PubMed, Embase, Web of Science, and the Cochrane database) were searched from inception to October 31, 2022. All randomized controlled trials (RCTs) that examined the following outcomes were included: filter lifespan, all-cause mortality, length of stay, duration of CRRT, recovery of kidney function, adverse events and costs. Results Thirty-seven RCTs from 38 articles, comprising 2648 participants with 14 comparisons, were included in this network meta-analysis (NMA). Unfractionated heparin (UFH) and regional citrate anticoagulation (RCA) are the most frequently used anticoagulants. Compared to UFH, RCA was found to be more effective in prolonging filter lifespan (MD 12.0, 95% CI 3.8 to 20.2) and reducing the risk of bleeding. Regional-UFH plus Prostaglandin I2 (Regional-UFH + PGI2) appeared to outperform RCA (MD 37.0, 95% CI 12.0 to 62.0), LMWH (MD 41.3, 95% CI 15.6 to 67.0), and other evaluated anticoagulation options in prolonging filter lifespan. However, only a single included RCT with 46 participants had evaluated Regional-UFH + PGI2. No statistically significant difference was observed in terms of length of ICU stay, all-cause mortality, duration of CRRT, recovery of kidney function, and adverse events among most evaluated anticoagulation options. Conclusions Compared to UFH, RCA is the preferred anticoagulant for critically ill patients requiring CRRT. The SUCRA analysis and forest plot of Regional-UFH + PGI2 are limited, as only a single study was included. Additional high-quality studies are necessary before any recommendation of Regional-UFH + PGI2. Further larger high-quality RCTs are desirable to strengthen the evidence on the best choice of anticoagulation options to reduce all-cause mortality and adverse events and promote the recovery of kidney function. Trial registration The protocol of this network meta-analysis was registered on PROSPERO ( CRD42022360263 ). Registered 26 September 2022.

The detection of the spine is crucial in automating the measurement of the Cobb Angle. While various segmentation models have been employed for vertebrae segmentation in X-ray images, there is a need to enhance segmentation performance. This paper proposes a comprehensive automatic measurement method for the Cobb angle. The RetinaNet model is employed to detect the region of interest corresponding to the spine, while the W-Net model is developed for accurate vertebrae segmentation. To address the issue of adjacent vertebrae adhesion in the segmented image, a post-processing technique is applied. Experimental results demonstrate that the W-Net model achieves superior performance, with a mean Intersection over Union (MIoU) of 0.9073 ± 0.0021, Dice Coefficient of 0.9446 ± 0.0139, and Precision of 0.9390 ± 0.0190. The post-processing step reduces adhesion at one end by approximately 83.4% and adhesion at both ends by approximately 83.6%. The reliability of the proposed method is evaluated through intra-group correlation coefficients (ICC) of 0.902 and 0.915, respectively, between two observers, both exceeding 0.9. The mean absolute deviation (MAD) is 3.08° and 2.91°, respectively. Therefore, the proposed method achieves automatic detection of the Cobb angle without the need for manual cropping or additional human intervention, while maintaining good reliability.

Abstract. Background:. Whether high cut-off (HCO) membranes are more effective than high-flux (HF) membranes in patients requiring renal replacement therapy (RRT) remains controversial. The aim of this systematic review was to investigate the efficacy of HCO membranes regarding the clearance of inflammation-related mediators, β2-microglobulin and urea; albumin loss; and all-cause mortality in patients requiring RRT. Methods:. We searched all relevant studies on PubMed, Embase, Web of Science, the Cochrane Library, and China National Knowledge Infrastructure, with no language or publication year restrictions. Two reviewers independently selected studies and extracted data using a prespecified extraction instrument. Only randomized controlled trials (RCTs) were included. Summary estimates of standardized mean differences (SMDs) or weighted mean differences (WMDs) and risk ratios (RRs) were obtained by fixed-effects or random-effects models. Sensitivity analyses and subgroup analyses were performed to determine the source of heterogeneity. Results:. Nineteen RCTs involving 710 participants were included in this systematic review. Compared with HF membranes, HCO membranes were more effective in reducing the plasma level of interleukin-6 (IL-6) (SMD −0.25, 95% confidence interval (CI) −0.48 to −0.01, P = 0.04, I2 = 63.8%); however, no difference was observed in the clearance of tumor necrosis factor-α (TNF-α) (SMD 0.03, 95% CI −0.27 to 0.33, P = 0.84, I2 = 4.3%), IL-10 (SMD 0.22, 95% CI −0.12 to 0.55, P = 0.21, I2 = 0.0%), or urea (WMD −0.27, 95% CI −2.77 to 2.23, P = 0.83, I2 = 19.6%). In addition, a more significant reduction ratio of β2-microglobulin (WMD 14.8, 95% CI 3.78 to 25.82, P = 0.01, I2 = 88.3%) and a more obvious loss of albumin (WMD −0.25, 95% CI −0.35 to −0.16, P

Distant hybridization can integrate parental advantages to produce new varieties, which may also improve the fish meat quality. Fish is considered to be one of the healthiest meats because it can provide rich protein sources and high levels of omega-3 long-chain polyunsaturated fatty acids. Two types of hybrid bream (BBTB and BTBB) were obtained by the two rounds of backcrossing with an established hybrid lineage of blunt snout bream (Megalobrama amblycephala, BSB, ♀) ​× ​topmouth culter (Culter alburnus, TC, ♂). In the present study, the muscle nutrients, including moisture, fat, protein and ash contents, as well as amino acid and fatty acid compositions, in BBTB, BTBB and their parent BSB with the age of four months were investigated and analyzed by biochemical methods. The results showed that the moisture content of BTBB (76.6%) was lower than that of BSB (77.4%) and BBTB (77.3%), while the protein content of BBTB (17.1%) and BTBB (17.6%) was higher than that of BSB (16.3%). Seventeen amino acids were detected in the muscles from three kinds of fish, among which total amino acids, essential amino acids and delicious amino acids in BTBB and BBTB were all to different degrees higher than those of BSB. Further analysis of fatty acids revealed that BTBB and BBTB exhibited higher levels of unsaturated fatty acids (UFAs) content and the sum content of eicosapentaenoic acid (EPA, C20:5 n-3) and docosahexaenoic acid (DHA, C22:6 n-3) in muscle than BSB. Taken together, the results showed the advantages of BBTB and BTBB in nutritional value and taste, which provided theoretical support for their production application.

Abstract Major depressive disorder (MDD) is a severe brain disease associated with a significant risk of suicide. Identification of suicidality is sometimes life-saving for MDD patients. We aimed to explore the use of dynamic functional network connectivity (dFNC) for suicidality detection in MDD patients. A total of 173 MDD patients, including 48 without suicide risk (NS), 74 with suicide ideation (SI), and 51 having attempted suicide (SA), participated in the present study. Thirty-eight healthy controls were also recruited for comparison. A sliding window approach was used to derive the dFNC, and the K-means clustering method was used to cluster the windowed dFNC. A linear support vector machine was used for classification, and leave-one-out cross-validation was performed for validation. Other machine learning methods were also used for comparison. MDD patients had widespread hypoconnectivity in both the strongly connected states (states 2 and 5) and the weakly connected state (state 4), while the dysfunctional connectivity within the weakly connected state (state 4) was mainly driven by suicidal attempts. Furthermore, dFNC matrices, especially the weakly connected state, could be used to distinguish MDD from healthy controls (area under curve [AUC] = 82), and even to identify suicidality in MDD patients (AUC = 78 for NS vs. SI, AUC = 88 for NS vs. SA, and AUC = 74 for SA vs. SI), with vision-related and default-related inter-network connectivity serving as important features. Thus, the dFNC abnormalities observed in this study might further improve our understanding of the neural substrates of suicidality in MDD patients.

Abstract Objectives This study was designed to evaluate the specific imaging features of ovarian sclerosing stromal tumor (SST), improve its accuracy as well as the specificity of imaging diagnosing, and prevent overestimation of malignancy to reduce unnecessary surgical procedures. Methods Eight patients with magnetic resonance imaging (MRI) and six with computed tomography (CT) images were analyzed in this retrospective observational study. All the cases were confirmed by postoperative pathological examination as those of ovarian SST. Imaging and pathological features were also evaluated. Results All the 14 masses displayed cystic and solid components with outer surface of tumors contained a capsular and complete smooth rim. Eight tumors of MRI exhibited “lake-island” sign on T2 weighted imaging (T2WI). Two of the 6 CT cases displayed a flaky calcification. One case showed as a multiloculated cystic mass with irregularly thickened septae and the tumor wall. The solid components in other 13 masses were comb- or wheel-like enhanced. After injection of contrast agent, the solid components in 8 cases (57.1%) appeared as early enhancement, whereas the other 6 cases (42.9%) appeared as progressive enhanced, and the cystic components of all the cases had no enhancement in the whole course. Vascular flow signals or/and marked enhancement of the blood vessels were found in 12 lesions (85.7%). Pathological examination demonstrated pseudolobule patterns, round to spindle shaped cells, collagenous areas, edematous hypocellular areas and prominent vasculatures. Conclusions The results demonstrated that MRI with “lake-island” signs on T2WI and MRI/CT dynamic enhancement could potentially play a critical role in facilitating appropriate diagnosis preoperatively.

Chimeric antigen receptor (CAR) T cells have been proven effective for the treatment of B-cell-mediated malignancies. Currently, the development of efficient tools that supply CAR T cells for the treatment of other malignancies would have great impact. In this study, interleukin (IL)-15 and C-C motif chemokine ligand 19 (CCL19) were introduced into natural killer group 2D (NKG2D)-based CARs to generate 15×19 CAR T cells, which remarkably increased T-cell expansion and promoted the production of central memory T (Tcm) cells. 15×19 CAR T cells showed greater cytotoxicity to gastric cell lines than conventional CAR T cells and produced higher levels of IL-15 and CCL-19, which resulted in increased responder T cell chemotaxis and reduced expression of T cell exhaustion markers. A live zebrafish model was used for single-cell visualization of local cytotoxicity and metastatic cancers. Administration of 15×19 CAR T cells resulted in significant shrinking of gastric cancer xenograft tumors and expansion of 15×19 CAR T cells in zebrafish models. Taken together, these findings demonstrate that 15×19 CAR T cells are highly efficient in killing gastric cancer cells, are effective to avoid off-target effects, and migrate to local and metastatic sites for long-term surveillance of cancers.

Abstract Crowdsourced package delivery has gained great interest from the logistics industry and academe due to its significant economic and environmental impact. However, there are few research achievements about incentive mechanism to motivate people to participate. A novel domain‐of‐influence based pricing strategy for crowdsourced delivery is proposed. The three‐stage package delivery framework is extended with the proposed pricing algorithm, which can iteratively figure out the price that represents a state of balance between the package demand and driver supply. To create better matching, even hyperbolic temporal discounting function is employed to estimate the driver's perceived reward to accept the package. The performance is evaluated using the Jinan dataset and real delivery data. Results show that economic utility and stable assignment rate have been increased by over 9% and over 6%, respectively, while the average delivery time and average delivery price have also been improved.

The aluminium alloy front subframe of an automobile was developed through multi-operating condition topology optimization and multi-objective optimization methods. By considering the influences of loads on the strength, static stiffness, and modal of the aluminium alloy front subframe under typical operating conditions, the performance parameters of the aluminium alloy front subframe after topology optimization were obtained. After topology optimization was performed, the parametric model of the aluminium alloy front subframe was established. Based on the Isight optimization platform, sample points were generated with the optimal Latin hypercube test method, and the response surface approximate model was constructed. The minimum mass and maximum first-order frequency were taken as the objectives, the stress under typical working conditions did not exceed the set target value, and the maximum displacement of the installation point was taken as the constraint condition. The multi-objective particle swarm optimization algorithm was used to optimize the aluminium alloy front subframe. The error of the free modal and finite element free modal analysis of the aluminium alloy front subframe samples was less than 15%. The optimized aluminium alloy front subframe was 2.4 kg lighter than the original subframe under the premise of satisfying various performance indices, and the lightweight rate was up to 12%.

Traditional manual measurement of Cobb angle is a time-consuming process and leads to different results. To address this issue, this paper proposes a deep learning-based method of locating the vertebral center points. The whole X-ray can be input into the network for prediction, without worrying about the detection of cervical vertebrae with similar characteristics to the thoracic and lumbar vertebrae. First, key points predicting and noise points filtering operations are employed to obtain vertebral center points for fitting. Then, the spine curve is fitted, and the slope of the normal line of the spine curve is adjusted according to an empirical formula. Finally, the Cobb angle allowed by the error is calculated. Through the reliability analysis of the traditional manual measurement method and the automatic detection method in this paper, ICC (intraclass correlation coefficient) with the two observers was 0.897 and 0.901, respectively, and MAD (mean absolute deviation) was 3.13° and 3.04° respectively. This indicates that the automatic detecting method by computer has good reliability. Therefore, this method can be used to detect scoliosis quickly and effectively.

Blindness studies are important models for the comprehension of human brain development and reorganization, after visual deprivation early in life. To investigate the global and local topologic alterations and to identify specific reorganized neural patterns in early-blind adolescents (EBAs), we applied diffusion tensor tractography and graph theory to establish and analyze the white matter connectivity networks in 21 EBAs and 22 age- and sex-matched normal-sighted controls (NSCs). The network profiles were compared between the groups using a linear regression model, and the associations between clinical variables and network profiles were analyzed. Graph theory analysis revealed “small-world” attributes in the structural connection networks of both EBA and NSC cohorts. The EBA cohort exhibited significant lower network density and global and local efficiency, as well as significantly elevated shortest path length, compared to the NSC group. The network efficiencies were markedly reduced in the EBA cohort, with the largest alterations in the default-mode, visual, and limbic areas. Moreover, decreased regional efficiency and increased nodal path length in some visual and default-mode areas were strongly associated with the period of blindness in EBA cohort, suggesting that the function of these areas would gradually weaken in the early-blind brains. Additionally, the differences in hub distribution between the two groups were mainly within the occipital and frontal areas, suggesting that neural reorganization occurred in these brain regions after early visual deprivation during adolescence. This study revealed that the EBA brain structural network undergoes both convergent and divergent topologic reorganizations to circumvent early visual deprivation. Our research will add to the growing knowledge of underlying neural mechanisms that govern brain reorganization and development, under conditions of early visual deprivation.

Research on light modulation has typically examined the wavelength, intensity, and exposure time of light, and measured rhythm, sleep, and cognitive ability to evaluate the regulatory effects of light variables on physiological and cognitive functions. Although the frequency of light is one of the main dimensions of light, few studies have attempted to manipulate it to test the effect on brain activation and performance. Recently, 40-Hz light stimulation has been proven to significantly alleviate deficits in gamma oscillation of the hippocampus caused by Alzheimer’s disease. Although this oscillation is one of the key functional characteristics of performing memory tasks in healthy people, there is no evidence that 40-Hz blue light exposure can effectively regulate brain activities related to complex cognitive tasks. In the current study, we examined the difference in the effects of 40-Hz light or 0-Hz light exposure on brain activation and functional connectivity during a recognition memory task. Through joint augmentation of visual area activation, 40-Hz light enhanced brain areas mostly in the limbic system that are related to memory, such as the hippocampus and thalamus. Conversely, 0-Hz light enhanced brain areas mostly in the prefrontal cortex. Additionally, functional connection analysis, with the hippocampus as the seed point, showed that 40-Hz light enhanced connection with the superior parietal lobe and reduced the connection with the default network. These results indicate that light at a frequency of 40 Hz can change the activity and functional connection of memory-related core brain areas. They also indicate that in the use of light to regulate cognitive functions, its frequency characteristics merit attention.

Anaerobic digestion is used to treat diverse waste classes, and polycyclic aromatic hydrocarbons (PAHs) are a class of refractory compounds that common in wastes treated using anaerobic digestion. In this study, a microbial consortium with the ability to degrade phenanthrene under methanogenesis was enriched from paddy soil to investigate the cometabolic effect of glucose on methane (CH4) production and phenanthrene (a representative PAH) degradation under methanogenic conditions. The addition of glucose enhanced the CH4 production rate (from 0.37 to 2.25mg⋅L−1⋅d−1) but had no influence on the degradation rate of phenanthrene. Moreover, glucose addition significantly decreased the microbial α-diversity (from 2.59 to 1.30) of the enriched consortium but showed no significant effect on the microbial community (R2=0.39, p=0.10), archaeal community (R2=0.48, p=0.10), or functional profile (R2=0.48, p=0.10). The relative abundance of genes involved in the degradation of aromatic compounds showed a decreasing tendency with the addition of glucose, whereas that of genes related to CH4 synthesis was not affected. Additionally, the abundance of genes related to the acetate pathway was the highest among the four types of CH4 synthesis pathways detected in the enriched consortium, which averagely accounted for 48.24% of the total CH4 synthesis pathway, indicating that the acetate pathway is dominant in this phenanthrene-degrading system during methanogenesis. Our results reveal that achieving an ideal effect is diffcult via co-metabolism in a single-stage digestion system of PAH under methanogenesis; thus, other anaerobic systems with higher PAH removal efficiency should be combined with methanogenic digestion, assembling a multistage pattern to enhance the PAH removal rate and CH4 production in anaerobic digestion.

Numerical simulations of hypersonic magnetohydrodynamics (MHD) flow over a typical sphere–cone blunt body are carried out based on the assumption of a low magnetic Reynolds number. The effects of an external dipole magnetic field on the surface heat flux are analyzed in detail, and multiple mechanisms of the MHD heat flux mitigation are revealed systematically for the first time. The following is found: (1) The external magnetic field can effectively reduce the stagnation point heat flux, and the increase in the boundary layer thickness due to the effect of counter-flow Lorentz force, which is equivalent to adding an adverse pressure gradient, is the main reason. (2) In the head region of the blunt body, the relative surface heat flux shows a complex trend of rising and falling because there are two mechanisms which could produce the opposite effects on the surface heat flux. One is that the counter-flow Lorentz force results in an increase in the boundary layer thickness, and the other is that the Joule heating increases the static temperature behind the shock wave. (3) In the shoulder region of the blunt body, the Lorentz force component, normal to streamline, could change the flow direction of the fluid elements, causing the streamline to deviate from the wall or even separate, thus affecting the surface heat flux. (4) In the large area downstream of the blunt body, the surface heat flux could still be reduced by more than 30% due to the “upstream historical effect”.

Background: Breast cancer (BC) is one of the most frequently diagnosed malignancies among females. As a huge heterogeneity of malignant tumor, it is important to seek reliable molecular biomarkers to carry out the stratification for patients with BC. We surveyed immune- associated lncRNAs that may be used as potential therapeutic targets in BC.Methods: LncRNA expression data and clinical information of BC patients were downloaded from the TCGA database for a comprehensive analysis of candidate genes. A model consisting of immune-related lncRNAs enriched in BC cancerous tissues was established using the univariate Cox regression analysis and the iterative Lasso Cox regression analysis. The prognostic performance of this model was validated in two independent cohorts (GSE21653 and BC-KR), and compared with known prognostic biomarkers. A nomogram that integrated the immune-related lncRNA signature and clinicopathological factors was constructed to accurately assess the prognostic value of this signature. The correlation between the signature and immune cell infiltration in BC was also analyzed.Results: The Kaplan-Meier analysis showed that the OS of Patients in the low-risk group had significantly better survival than those in the high-risk group, Clinical subgroup analysis showed that the predictive ability was independent of clinicopathological factors. Univariate/multivariate Cox regression analysis showed immune lncRNA signature is an important prognostic factor and an independent prognostic marker. In addition, GSEA and GSVA analysis as well as comprehensive analysis of immune cells showed that the signature was significantly correlated with the infiltration of immune cells.Conclusion: We successfully constructed an immune-associated lncRNA signature that can accurately predict BC prognosis.

Although evidence from studies on blind adults indicates that visual deprivation early in life leads to structural and functional disruption and reorganization of the brain, whether young blind people show similar patterns remains unknown. Therefore, this study is aimed at exploring the structural and functional alterations of the brain of early-blind adolescents (EBAs) compared to normal-sighted controls (NSCs) and investigating the effects of residual light perception on brain microstructure and function in EBAs. We obtained magnetic resonance imaging (MRI) data from 23 EBAs (8 with residual light perception (LPs), 15 without light perception (NLPs)) and 21 NSCs (age range 11-19 years old). Whole-brain voxel-based analyses of diffusion tensor imaging metrics and region-of-interest analyses of resting-state functional connectivity (RSFC) were performed to compare patterns of brain microstructure and the corresponding RSFC between the groups. The results showed that structural disruptions of LPs and NLPs were mainly located in the occipital visual pathway. Compared with NLPs, LPs showed increased fractional anisotropy (FA) in the superior frontal gyrus and reduced diffusivity in the caudate nucleus. Moreover, the correlations between FA of the occipital cortices or mean diffusivity of the lingual gyrus and age were consistent with the development trajectory of the brain in NSCs, but inconsistent or even opposite in EBAs. Additionally, we found functional, but not structural, reorganization in NLPs compared with NSCs, suggesting that functional neuroplasticity occurs earlier than structural neuroplasticity in EBAs. Altogether, these findings provided new insights into the mechanisms underlying the neural reorganization of the brain in adolescents with early visual deprivation.

Some studies identified hypo-connectivity, while others showed hyper-connectivity of the insula in the autism spectrum disorders (ASD). These contradictory findings leave open the question of whether and to what extent functional connectivity of the insula is altered and how functional connectivity of the insula is associated with the severity of ASD. A newly emerging insular atlas that comprises multiple functionally differentiated subregions provides a new framework to interpret the functional significance of insular findings and uncover the mechanisms underlying the severity of ASD. Using the new insular atlas, the present study aimed to investigate the distinct functional connectivity of the insular subregions and their associations with ASD severity in a cohort of 49 children with ASD and 33 typically developing (TD) subjects. We found that compared with TD group, the ASD group showed different connectivity patterns in the left ventral agranular insula, right ventral dysgranular and granular insula, and dorsal dysgranular insula, characterized by significant hyper-connectivity and/or hypo-connectivity with special brain regions. Furthermore, both the hypo-connectivity and hyper-connectivity patterns of the insular subregions were significantly associated with the severity of ASD symptoms. Our research demonstrated distinct functional connectivity patterns of the insular subregions and emphasized the importance of the subdivisions within the insula to the potential impact of functional difference in children with ASD. Moreover, these results might help us to better understand the mechanisms underlying the symptoms in children with ASD and might elucidate potential biomarkers for clinical applications.

BACKGROUND:By performing identical studies in humans and rats, we attempted to distinguish vulnerability factors for addiction from neurobiological effects of chronic drug exposure. We focused on the GABAergic system within the hippocampus, a brain region that is a constituent of the memory/conditioning neuronal circuitry of addiction that is considered to be important in drug reinforcement behaviors in animals and craving and relapse in humans. METHODOLOGY:Using RNA-Seq we quantified mRNA transcripts in postmortem total hippocampus from alcoholics, cocaine addicts and controls and also from alcohol-naïve, alcohol preferring (P) and non-preferring (NP) rats selectively bred for extremes of alcohol-seeking behavior that also show a general addictive tendency. A pathway-targeted analysis of 25 GABAergic genes encoding proteins implicated in GABA synthesis, metabolism, synaptic transmission and re-uptake was undertaken. PRINCIPAL FINDINGS:Directionally consistent and biologically plausible overlapping and specific changes were detected: 14/25 of the human genes and 12/25 of the rat genes showed nominally significant differences in gene expression (global p values: 9×10⁻¹⁴, 7×10⁻¹¹ respectively). Principal FDR-corrected findings were that GABBR1 was down-regulated in alcoholics, cocaine addicts and P rats with congruent findings in NSF, implicated in GABAB signaling efficacy, potentially resulting in increased synaptic GABA. GABRG2, encoding the gamma2 subunit required for postsynaptic clustering of GABAA receptors together with GPHN, encoding the associated scaffolding protein gephryin, were both down-regulated in alcoholics and cocaine addicts but were both up-regulated in P rats. There were also expression changes specific to cocaine addicts (GAD1, GAD2), alcoholics (GABRA2) and P rats (ABAT, GABRG3). CONCLUSIONS/SIGNIFICANCE:Our study confirms the involvement of the GABAergic system in alcoholism but also reveals a hippocampal GABA input in cocaine addiction. Congruent findings in human addicts and P rats provide clues to predisposing factors for alcohol and drug addiction. Finally, the results of this study have therapeutic implications.