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IntroductionBetula tianschanica Rupr. is distributed in regions such as China, Kyrgyzstan, and Tajikistan. Owing to the impacts of climate change, it is increasingly threatened by habitat fragmentation, resulting in a precipitous decline in its population. Currently listed as endangered on the Red List of Trees of Central Asia, this species is predominantly found in the Tianshan Mountains. Examining the influence of climate change on the geographical distribution pattern of Betula tianschanica is crucial for the management and conservation of its wild resources.MethodsThis study employed two models, maximum entropy (MaxEnt) and random forest (RF), combined with 116 distribution points of Betula tianschanica and 27 environmental factor variables, to investigate the environmental determinants of the distribution of Betula tianschanica and project its potential geographical distribution areas.ResultsThe MaxEnt model and the RF model determined the primary environmental factors influencing the potential distribution of Betula tianschanica. The MaxEnt model showed that the percentage of gravel volume in the lower soil layer and elevation are the most significant, while the RF model considered elevation and precipitation of the wettest quarter to be the most crucial. Both models unanimously asserted that elevation is the pivotal environmental element affecting the distribution of Betula tianschanica.The mean area under the curve (AUC) scores for the MaxEnt model and RF were 0.970 and 0.873, respectively, revealing that the MaxEnt model outperformed the RF model in predictive accuracy. Consequently, the present study employed the estimated geographical area for Betula tianschanica modeled by the MaxEnt model as a reference. Following the MaxEnt model’s projected outcomes, Betula tianschanica is mainly located in territories such as the Tianshan Mountains, Ili River Basin, Lake Issyk-Kul, Turpan Basin, Irtysh River, Ulungur River, Bogda Mountains, Kazakh Hills, Lake Balkhash, Amu River, and the middle reaches of the Syr River.Within the MaxEnt model, the total suitable habitat area exhibits growth across all scenarios, with the exception of a decline observed during the 2041–2060 period under the SSP2-4.5 scenario. Remarkably, under the SSP58.5 scenario for the same timeframe, this area expands significantly by 42.7%. In contrast, the RF model demonstrated relatively minor fluctuations in the total suitable habitat area, with the highest recorded increase being 12.81%. This paper recommends establishing protected areas in the Tianshan Mountains, conducting long-term monitoring of its population dynamics, and enhancing international cooperation. In response to future climate change, climate refuges should be established and adaptive management implemented to ensure the survival and reproduction of Betula tianschanica.

Chlorophyll-a (Chl-a) plays a vital role in assessing environmental health and understanding the response of marine ecosystems to physical factors and climate change. In situ sampling, remote sensing, and moored buoys or floats are commonly employed methods for obtaining Chl-a in marine science research. Although in situ sampling, buoys, and floats could provide accurate data, they are limited by the spatial and temporal resolution. Remote sensing offers continuous and broad spatial coverage, while it is often hindered by cloud cover in the South China Sea (SCS). This study discussed the feasibility of a predictive model by linking the physical factors [e.g., wind field, surface currents, sea surface height (SSH), and sea surface temperature (SST)] with surface Chl-a in the SCS based on the ResUnet. The ResUnet architecture performs well in capturing non-linear relationships between variables, with the model achieving a prediction accuracy exceeding 90%. The results indicate that (1) the combination of oceanic dynamical and meteorological data could effectively estimate the Chl-a based on deep learning methods; (2) the combination of meteorological and SST effectively reproduces Chl-a in the northern SCS, while adding surface currents and SSH improves model performance in the southern SCS; (3) With the addition of surface currents and SSH, the model effectively captures the high Chl-a patches induced by eddies. This research presents a viable method for estimating surface Chl-a concentrations in regions where they are highly correlated with dynamic factors, using deep learning and comprehensive oceanic and atmospheric data.

ObjectiveAddressing the rising prevalence of pain disorders and limitations of current analgesics, our study explores repurposing antihypertensive drugs for pain management, inspired by the link between hypertension and pain. We leverage a drug-target Mendelian Randomization (MR) approach to explore their dual benefits and establish causal connections.MethodsA comprehensive compilation of antihypertensive drug classes was undertaken through British National Formulary, with their target genes identified using the DrugBank database. Relevant single nucleotide polymorphisms (SNPs) associated with these targets were selected from published genomic studies on systolic blood pressure (SBP) as genetic instruments. These SNPs were validated through MR against acute coronary artery disease (CAD) to ensure genes not linked to CAD were excluded from acting as proxies for antihypertensive drugs. An MR analysis of 29 pain-related outcomes was conducted using the FinnGen R10 database employing the selected and validated genetic instruments. We utilized the Inverse Variance Weighted (IVW) method for primary analysis, applying Bonferroni correction to control type I error. IVW’s multiplicative random effects (MRE) addressed heterogeneity, and MR-PRESSO managed pleiotropy, ensuring accurate causal inference.ResultsOur analysis differentiates strong and suggestive evidence in linking antihypertensive drugs to pain disorder risks. Strong evidence was found for adrenergic neuron blockers increasing migraine without aura risk, loop diuretics reducing panniculitis, and vasodilator antihypertensives lowering limb pain risk. Suggestive evidence suggests alpha-adrenoceptor blockers might increase migraine risk, while beta-adrenoceptor blockers could lower radiculopathy risk. Adrenergic neuron blockers also show a potential protective effect against coxarthrosis (hip osteoarthritis) and increased femgenpain risk (pain and other conditions related to female genital organs and menstrual cycle). Additionally, suggestive links were found between vasodilator antihypertensives and reduced radiculopathy risk, and both alpha-adrenoceptor blockers and renin inhibitors possibly decreasing dorsalgianas risk (unspecified dorsalgia). These findings highlight the intricate effects of antihypertensive drugs on pain disorders, underlining the need for further research.ConclusionThe findings indicate that antihypertensive medications may exert varied effects on pain management, suggesting a repurposing potential for treating specific pain disorders. The results advocate for further research to confirm these associations and to explore underlying mechanisms, to optimize pain management practices.

BackgroundInfection is the main cause of death for patients after allogeneic hematopoietic stem cell transplantation (HSCT). However, pathogen profiles still have not been reported in detail due to their heterogeneity caused by geographic region.ObjectiveTo evaluate the performance of metagenomic next-generation sequencing (mNGS) and summarize regional pathogen profiles of infected patients after HSCT.MethodsFrom February 2021 to August 2022, 64 patients, admitted to the Department of Hematology of The First Hospital of Jilin University for HSCT and diagnosed as suspected infections, were retrospectively enrolled.ResultsA total of 38 patients were diagnosed as having infections, including bloodstream (n =17), pulmonary (n =16), central nervous system (CNS) (n =4), and chest (n =1) infections. Human betaherpesvirus 5 (CMV) was the most common pathogen in both bloodstream (n =10) and pulmonary (n =8) infections, while CNS (n =2) and chest (n =1) infections were mainly caused by Human gammaherpesvirus 4 (EBV). For bloodstream infection, Mycobacterium tuberculosis complex (n =3), Staphylococcus epidermidis (n =1), and Candida tropicalis (n =1) were also diagnosed as causative pathogens. Furthermore, mNGS combined with conventional tests can identify more causative pathogens with high sensitivity of 82.9% (95% CI 70.4-95.3%), and the total coincidence rate can reach up to 76.7% (95% CI 64.1-89.4%).ConclusionsOur findings emphasized the importance of mNGS in diagnosing, managing, and ruling out infections, and an era of more rapid, independent, and impartial diagnosis of infections after HSCT can be expected.

IntroductionThis study aimed to analyze how authoritative parenting affects behavioral problems among primary, junior high, and secondary high school students. Today, parental educational anxiety and parent–child relationship conflicts are common in China and are resulting in a high incidence of child behavioral problems. High-quality family education is becoming increasingly important in China. This study sought to provide a reference for developing responsive family education services.MethodsA total of 10,441 parents in Hubei Province, including urban and rural areas, were evaluated using the Parents’ Education Anxiety Questionnaire, Parental Authority Parenting Questionnaire, Parent–Child Relationship Scale, and Self-Made Behavior Problem Scale to determine the internal mechanisms of child behavioral problems in the family system. To make the sample more representative, this study collected data from primary and secondary schools representative of the southeast, northwest, and center of Hubei Province; further, the number of parents involved in each school was controlled at approximately 300 to ensure that the final sample had analytical value.ResultsEducational anxiety directly affected children’s behavioral problems and indirectly affected them through the conflicts between parent and child. This conflict partially mediated educational anxiety and child behavioral problems, and authoritative parenting played a significant regulatory role in this relationship.DiscussionHigher levels of educational anxiety among parents increased the likelihood of a depressed family environment. This can lead to deteriorating parent–child relationships, which can result in children’s problem behaviors. Parents can address these problems by changing their approach to education and adjusting their emotions accordingly.

The evolution of power system is a dynamic and complex process. Whether the evolution of power system can adapt to the macro environment and develop with all subsystems within the system depends on the matching and integration development among different evolutionary subjects. Based on the dissipation theory and Brusselator model, this paper constructs an evolutionary synergy model of the power system, and quantitatively analyzes the evolutionary synergy relationship between the evolving subjects of the power system and the overall evolutionary process of the power system. Then, from the socio-technical system transformation theory, we analyze the evolutionary elements of macro-environmental level, meso-institutional level and micro-beneficial level in the process of system transformation in China and the interaction among them. Finally, by comparing the entropy changes of the evolutionary participant subjects and the overall power system at each stage, the endogenous mechanism of the power system, the external elements and their interactions on the system development are studied in order to reveal the evolutionary synergistic law of China’s power system and make suggestions for the development of the new power system.

The present work investigates whether and how decisions in real-world online shopping scenarios can be predicted based on brain activation. Potential customers were asked to search through product pages on e-commerce platforms and decide, which products to buy, while their EEG signal was recorded. Machine learning algorithms were then trained to distinguish between EEG activation when viewing products that are later bought or put into the shopping card as opposed to products that are later discarded. We find that Hjorth parameters extracted from the raw EEG can be used to predict purchase choices to a high level of accuracy. Above-chance predictions based on Hjorth parameters are achieved via different standard machine learning methods with random forest models showing the best performance of above 80% prediction accuracy in both 2-class (bought or put into card vs. not bought) and 3-class (bought vs. put into card vs. not bought) classification. While conventional EEG signal analysis commonly employs frequency domain features such as alpha or theta power and phase, Hjorth parameters use time domain signals, which can be calculated rapidly with little computational cost. Given the presented evidence that Hjorth parameters are suitable for the prediction of complex behaviors, their potential and remaining challenges for implementation in real-time applications are discussed.

ObjectiveThis study aimed to explore the potential causal link between three specific types of occupational exposure on rheumatoid arthritis (RA) and ankylosing spondylitis (AS).MethodA Two-sample Mendelian randomization (TSMR) analysis, comprising univariate MR (UVMR) and multivariate MR (MVMR) analyses, was performed to investigate the potential causal association between three types of occupational exposures, jobs involving mainly walking or standing (JWS), jobs involving heavy manual or physical work (JMP), and jobs involving shift work(JSW) on RA and AS. Genetic variants for genome-wide association studies (GWAS) of occupational exposure and AS were obtained from the UK Biobank. GWAS summary data for RA were obtained from FinnGen Biobank analysis. For UVMR, six methods of Inverse Variance Weighted (IVW), MR-Egger, Weighted Mode, Weighted Median, Simple Mode, MR pleiotropy residual sum, and outlier (MR-PRESSO) were used for the analysis. The MVMR was analyzed using the IVW model as well as the MR-Egger model.ResultsThe UVMR suggested no causal relationship between the three occupational exposure and RA [IVW: P=0.59,0.21,0.63] or AS [IVW: P=0.43,0.57,0.04], as did the bidirectional MR [IVW: P=0.73,0.70,0.16], [IVW: P=0.65,0.68,0.74]. Although unadjusted MVMR suggested a causal relationship between JMP and AS [IVW: OR = 1.01, 95% CI = 1.00- 1.02, p = 0.02], the adjusted MVMR denied this relationship and concluded that there was no causal relationship between the other occupational exposure and either RA or AS.ConclusionOur MR analysis did not establish a direct causal relationship between certain occupational exposures and either RA or AS.

Introduction: Understanding and tracking changes in crop water requirements is crucial for effective irrigation, water planning, and future decisions. Determining the reference evapotranspiration (ETO) and crop evapotranspiration (ETC) of China cotton is essential for water resource management.Methods: This study analyzed the spatiotemporal changes in ETO and ETC at 248 standard stations in cotton production regions of China from 1960 to 2019, and the ETO and ETC of each station were quantified by using the CropWat 8.0 and non-parametric Mann-Kendall test. The impacts of climate change on ETO and ETC were evaluated by analyzing the contribution rate and sensitivity coefficient of climate change.Discussion: The results revealed distinct distributions of ETO and ETC across various growth stages and spatial scales in the cotton production regions of China. In the Huanghe Valley, the rate of decline for ETO decreased from 787.23 mm to 769.84 mm, while in the Yangtze Valley cotton region, it decreased from 749.19 mm to 735.01 mm. Similarly, in the Northwest inland cotton regions, the rate of decline for ETO reduced from 991.19 mm to 982.70 mm. As for ETC, the rate of decline decreased from 677.62 mm to 654.33 mm in the Huanghe Valley, from 653.02 mm to 625.50 mm in the Yangtze Valley, and from 916.25 mm to 886.74 mm in the Northwest inland cotton regions. ETO was highly sensitive to maximum air temperature (Tmax), followed by relative humidity (RH), sunshine duration (SD), wind speed at 2 m height (WS), and minimum air temperature (Tmin). WS was the most influential climate variable associated with ETO change, followed by Tmax, SD, RH, and Tmin. Significant declines in WS and SD were indicated in the decrease in ETO in the Huanghe Valley and Yangtze Valley cotton regions. WS showed a significant decrease in ETO in the northwestern inland cotton region. However, decreased RH and increased temperature commonly reversed the trend of ETO from 2000 to 2019, and the northwestern inland cotton region had the most significant upward trend. Amidst high temperatures and drought stress, the irrigation needs of cotton were rising, posing a significant threat to both cotton production and water resources.

MicroRNAs (miRNAs) are small non-coding RNAs with the unique ability to degrade or block specific RNAs and regulate many cellular processes. Neuroinflammation plays the pivotal role in the occurrence and development of multiple central nervous system (CNS) diseases. The ability of miRNAs to enhance or restrict neuroinflammatory signaling pathways in CNS diseases is an emerging and important research area, including neurodegenerative diseases, stroke, and traumatic brain injury (TBI). In this review, we summarize the roles and regulatory mechanisms of recently identified miRNAs involved in neuroinflammation-mediated CNS diseases, aiming to explore and provide a better understanding and direction for the treatment of CNS diseases.

ObjectiveTo describe the characteristics of large vestibular aqueduct syndrome (LVAS) in wideband acoustic immittance (WAI) and to explore whether inner ear deformity has an impact on WAI results.MethodsSubjects with typical LVAS (LVAS group) and control subjects with a normal anatomical structure of the inner ear (control group) were screened from pediatric patients with cochlear implants using thin-slice computed tomography (CT) images of the temporal bone. With inflammation of the auditory canal and middle ear excluded by routine ear examination and 226 Hz acoustic immittance, WAI data were acquired. Then, the maximum absorbance as the major observation indicator on the mean tympanogram was compared between the LVAS group and control group, and a descriptive comparison of the mean tympanogram and frequency-absorbance curve at peak pressure was performed between the two groups.ResultsThe LVAS group included 21 cases (38 ears), and the control group included 27 cases (45 ears). All LVAS subjects met the Valvassori criteria, and the VA at the horizontal semicircular canal displayed flared expansion. On the mean tympanogram, the maximum absorbance in the LVAS group (0.542 ± 0.087) was significantly higher than that in the control group (0.455 ± 0.087) (p < 0.001). The tympanogram in the LVAS group showed an overall elevation, and the absorbance at all pressure sampling points was significantly higher than that in the control group (p < 0.001). The frequency-absorbance curve at peak pressure first increased and then decreased in both groups, and the LVAS group showed higher absorbance than the control group in the frequency range below 2,828 Hz. The absorbance at 343–1,124 Hz was significantly different between the two groups (p < 0.001), and 343–1,124 Hz was the major frequency range at which the maximum absorbance on the mean tympanogram increased in the LVAS group.ConclusionLarge vestibular aqueduct syndrome (LVAS) shows increased absorbance in low and medium frequency ranges in WAI. The maximum absorbance on the mean tympanogram can serve as a reliable evaluation indicator. Inner ear factors must be considered when middle ear lesions are analyzed by WAI.

IntroductionMost previous studies focused on the effects of fathers’ presence on adolescent development, but rarely examined the mechanisms underlying the presence of fathers on adolescent development. Moreover, previous studies ignored the impact of fathers’ way of being present on adolescent interpersonal relationships. Based on social identity theory, the present study introduced adolescents’ social responsibility as a mediating variable to explore the influence of father’s presence style on adolescents’ interpersonal. This study examined the mechanism of fathers’ way of being present on father’s presence, adolescents’ social responsibility, and their quality of interpersonal relationships; if fathers adopt a democratic approach to be present, the study examines whether teenagers are more likely to enhance their sense of social responsibility and achieve harmonious interpersonal relationships.MethodsParticipants were 1,942 senior high school and college students who responded to the Fatherhood Questionnaire, Social Responsibility Questionnaire, and Interpersonal Relationship Quality Diagnosis Scale. This study used PROCESS macro of SPSS 24.0 and Amos 26.0 to examine the hypotheses.ResultsEmpirical results demonstrated that (a) fathers’ presence is directly and positively related to adolescents’ social responsibility, (b) fathers’ presence is indirectly and positively related to the quality of adolescents’ interpersonal relationships through social responsibility, and (c) parenting styles played a moderating role in the first half of the fathers’ presence on social responsibility and the quality of interpersonal relationships. Results demonstrated that more harmonious interpersonal relationships were present among teenagers when fathers adopted a democratic upbringing, and this interaction effect on interpersonal relationships was mediated by teenagers’ sense of social responsibility.DiscussionThe findings of this study enrich the literature by exploring the significance of emphasizing fathers’ democratic presence on teenagers’ sense of social responsibility and interpersonal relationships. The practical implications of this study are that society should encourage more fathers to be present and guide them to adopt a democratic parenting style that will benefit adolescents’ development and family well-being.

ObjectiveTo assess the usefulness of gray-scale ultrasound (US) and shear wave elastography (SWE) in assessing the condition of the skeletal muscles in patients with chronic heart failure (CHF).MethodsWe prospectively compared 20 patients with clinically diagnosed CHF and a control population of 20 normal volunteers. The gastrocnemius medialis (GM) of each individual in the rest and the contraction position was assessed using gray-scale US and SWE. The quantitative US parameters including the fascicle length (FL), pinnation angle (PA), echo intensity (EI), and Young's modulus of the muscle were measured.ResultsIn the CHF group compared with the control group, in the rest position, there was a significant difference in EI, PA, and FL of the GM (P 0.05); however, in the contraction position, all parameters were statistically different between the two groups (P

Meibomian gland dysfunction (MGD) is caused by abnormalities of the meibomian glands (MG) and is one of the causes of evaporative dry eye (DED). Precise MG segmentation is crucial for MGD-related DED diagnosis because the morphological parameters of MG are of importance. Deep learning has achieved state-of-the-art performance in medical image segmentation tasks, especially when training and test data come from the same distribution. But in practice, MG images can be acquired from different devices or hospitals. When testing image data from different distributions, deep learning models that have been trained on a specific distribution are prone to poor performance. Histogram specification (HS) has been reported as an effective method for contrast enhancement and improving model performance on images of different modalities. Additionally, contrast limited adaptive histogram equalization (CLAHE) will be used as a preprocessing method to enhance the contrast of MG images. In this study, we developed and evaluated the automatic segmentation method of the eyelid area and the MG area based on CNN and automatically calculated MG loss rate. This method is evaluated in the internal and external testing sets from two meibography devices. In addition, to assess whether HS and CLAHE improve segmentation results, we trained the network model using images from one device (internal testing set) and tested on images from another device (external testing set). High DSC (0.84 for MG region, 0.92 for eyelid region) for the internal test set was obtained, while for the external testing set, lower DSC (0.69–0.71 for MG region, 0.89–0.91 for eyelid region) was obtained. Also, HS and CLAHE were reported to have no statistical improvement in the segmentation results of MG in this experiment.

ObjectiveThis study aimed to investigate the differences in intra-regional brain activity and inter-regional functional connectivity between patients with recent-onset tinnitus (ROT) and persistent tinnitus (PT) using resting-state functional magnetic resonance imaging (rs-fMRI), including the amplitude of low-frequency fluctuations (ALFF), regional homogeneity (ReHo), and voxel-wise functional connectivity (FC).MethodWe acquired rs-fMRI scans from 82 patients (25 without recent-onset tinnitus, 28 with persistent tinnitus, and 29 healthy controls). Age, sex, and years of education were matched across the three groups. We performed ALFF, ReHo, and voxel-wise FC analyses for all patients.ResultsCompared with the control group, participants with ROT and PT manifested significantly reduced ALFF and ReHo activity within the left and right dorsolateral superior frontal gyrus (SFG) and gyrus rectus (GR). Additional voxel-wise FC revealed decreased connectivity between the dorsolateral SFG (left and right) and the right superior parietal gyrus (SPG), right middle frontal gyrus (MFG), and left medial superior frontal gyrus (mSFG) within these two groups. Significant differences were observed between the ROT and PT groups, with the ROT group demonstrating reduced FC.ConclusionOur data suggest that patients with PT have more difficulty monitoring external stimuli and reorienting attention than patients with ROT. In addition, patients who perceive higher levels of disruption from tinnitus are more likely to develop persistent and debilitating tinnitus once the tinnitus lasts longer than six months. Therefore, we strongly recommend that clinicians implement effective tinnitus management strategies in patients with ROT as soon as possible.

Guanylate binding protein 2 (GBP2) is a member of the guanine binding protein family, and its relationship with prognostic outcomes and tumor immune microenvironments in glioma remains elusive. We found GBP2 were increased in glioma tissues at both mRNA and protein levels. Kaplan-Meier curves revealed that high GBP2 expression was linked with worse survival of glioma patients, and multivariate Cox regression analysis indicated that high GBP2 expression was an independent prognostic factor for glioma. Combined analysis in immune database revealed that the expression of GBP2 was significantly related to the level of immune infiltration and immunomodulators. Single-cell analysis illustrated the high expression of GBP2 in malignant glioma cells showed the high antigen presentation capability, which were confirmed by real-time polymerase chain reaction (qRT-PCR) data. Additionally, the hsa-mir-26b-5p and hsa-mir-335-5p were predicted as GBP2 regulators and were validated in U87 and U251 cells. Our results first decipher immune-related characteristics and noncoding regulators of GBP2 in glioma, which may provide insights into associated immunotherapies and prognostic predictor.

BackgroundThe incidence of perioperative neurocognitive disorders (PNDs) is reportedly higher in older patients. Mitochondrial and synaptic dysfunctions have consistently been demonstrated in models of aging and neurodegenerative diseases; nonetheless, their role in PND is not well understood.MethodsThe Morris water maze and elevated plus maze tests were used to assess the learning and memory abilities of both C57BL/6 and 3×Tg-AD mice of different ages (8 and 18 months). PND was induced by laparotomy in C57BL/6 mice and 3×Tg-AD mice (8 months old). Markers associated with neuroinflammation, mitochondrial function, synaptic function, and autophagy were assessed postoperatively. The roles of protein kinase C (PKC) and double-stranded RNA-dependent protein kinase (PKR) were further demonstrated by using PKC-sensitive inhibitor bisindolylmaleimide X (BIMX) or PKR−/− mice.ResultsSignificant cognitive impairment was accompanied by mitochondrial dysfunction and autophagy inactivation in both aged C57BL/6 and 3×Tg-AD mice. Laparotomy induced a significant neuroinflammatory response and synaptic protein loss in the hippocampus. Cognitive and neuropathological changes induced by aging or laparotomy were further exacerbated in 3×Tg-AD mice. Deficits in postoperative cognition, hippocampal mitochondria, autophagy, and synapse were significantly attenuated after pharmacological inhibition of PKC or genetic deletion of PKR.ConclusionsOur findings suggest similar pathogenic features in aging, Alzheimer's disease, and PND, including altered mitochondrial homeostasis and autophagy dysregulation. In addition, laparotomy may exacerbate cognitive deficits associated with distinct neuronal inflammation, mitochondrial dysfunction, and neuronal loss independent of genetic background. The dysregulation of PKC/PKR activity may participate in the pathogenesis of these neurodegenerative diseases.

Inflammation is an innate immune response to infection, and it is the main factor causing bodily injury and other complications in the pathological process. Ginsenoside Rh4 (G-Rh4), a minor ginsenoside of Panax ginseng C. A. Meyer and Panax notoginseng, has excellent pharmacological properties. However, many of its major pharmacological mechanisms, including anti-inflammatory actions, remain unrevealed. In this study, network pharmacology and an experimental approach were employed to elucidate the drug target and pathways of G-Rh4 in treating inflammation. The potential targets of G-Rh4 were selected from the multi-source databases, and 58 overlapping gene symbols related to G-Rh4 and inflammation were obtained for generating a protein–protein interaction (PPI) network. Molecular docking revealed the high affinities between key proteins and G-Rh4. Gene ontology (GO) and pathway enrichment analyses were used to analyze the screened core targets and explore the target–pathway networks. It was found that the JAK-STAT signaling pathway, TNF signaling pathway, NF-κB signaling pathway, and PI3K-Akt signaling pathway may be the key and main pathways of G-Rh4 to treat inflammation. Additionally, the potential molecular mechanisms of G-Rh4 predicted from network pharmacology analysis were validated in RAW264.7 cells. RT-PCR, Western blot, and ELISA analysis indicated that G-Rh4 significantly inhibited the production of pro-inflammatory cytokines such as TNF-α, IL-6, and IL-1β, as well as inflammation-related enzymes in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. Moreover, in vitro experiments evaluated that Ginsenoside Rh4 exerts anti-inflammatory effects via the NF-κB and STAT3 signaling pathways. It is believed that our study will provide the basic scientific evidence that G-Rh4 has potential anti-inflammatory effects for further clinical studies.

Background: Renal fibrosis is a key pathological change that occurs in the progression of almost all chronic kidney diseases . CKD has the characteristics of high morbidity and mortality. Its prevalence is increasing each year on a global scale, which seriously affects people’s health and quality of life. Natural products have been used for new drug development and disease treatment for many years. The abundant natural products in R. ribes L. can intervene in the process of renal fibrosis in different ways and have considerable therapeutic prospects.Purpose: The etiology and pathology of renal fibrosis were analyzed, and the different ways in which the natural components of R. ribes L. can intervene and provide curative effects on the process of renal fibrosis were summarized. Methods: Electronic databases, such as PubMed, Life Science, MEDLINE, and Web of Science, were searched using the keywords ‘R. ribes L.’, ‘kidney fibrosis’, ‘emodin’ and ‘rhein’, and the various ways in which the natural ingredients protect against renal fibrosis were collected and sorted out.Results: We analyzed several factors that play a leading role in the pathogenesis of renal fibrosis, such as the mechanism of the TGF-β/Smad and Wnt/β-catenin signaling pathways. Additionally, we reviewed the progress of the treatment of renal fibrosis with natural components in R. ribes L. and the intervention mechanism of the crucial therapeutic targets.Conclusion: The natural components of R. ribes L. have a wide range of intervention effects on renal fibrosis targets, which provides new ideas for the development of new anti-kidney fibrosis drugs.

When fish are under oxidative stress, levels of reactive oxygen species (ROS) are chronically elevated, which play a crucial role in fish innate immunity. In the present study, the mechanism by which betaine regulates ROS production via Wnt10b/β-catenin signaling was investigated in zebrafish liver. Our results showed that betaine enrichment of diet at 0.1, 0.2 and 0.4 g/kg induced Wnt10b and β-catenin gene expression, but suppressed GSK-3β expression in zebrafish liver. In addition, the content of superoxide anion (O2·−), hydrogen peroxide (H2O2) and hydroxyl radical (·OH) was decreased by all of the experimental betaine treatments. However, betaine enrichment of diet at 0.1, 0.2 and 0.4 g/kg enhanced gene expression and activity of superoxide dismutase (SOD), glutathione peroxidase (GSH-PX) and catalase (CAT) in zebrafish liver. In addition, Wnt10b RNA was further interfered in zebrafish, and the results of Wnt10b RNAi indicated that Wnt10b plays a key role in regulating ROS production and antioxidant enzyme activity. In conclusion, betaine can inhibit ROS production in zebrafish liver through the Wnt10b/β-catenin signaling pathway.

ObjectiveTo assess the diagnostic performance of US and MRI in predicting malignancy of soft tissue masses by using a scoring system.MethodsA total of 120 cases of pathologically confirmed soft tissue masses (71 cases of malignant lesions and 49 cases of benign lesions) were enrolled. All patients underwent ultrasound and MRI examination prior to biopsy or surgical excision. A scoring system based on the parameters of conventional US and MRI to distinguish malignant and benign masses was established by the regression model. The receiver operating characteristic (ROC) analysis was used to evaluate the diagnostic performance of US and MRI.ResultsMultivariate analysis showed that margin, maximum diameter, and vascular density were independent predictors for malignancy found by US, while maximum diameter, margin, and affected peripheral soft tissue were independent predictors for malignancy found by MRI. The mean scores of the benign and malignant groups were 2.8 ± 1.6, 5.1 ± 1.1 on US and 1.3 ± 1.2, 3.5 ± 0.9 on MRI. Based on the cut-off score of 3.5 and 2.5 calculated by ROC analysis, US and MRI had 92% and 87% sensitivity, 72% and 76% specificity, 86% and 89% accuracy, respectively. The combination of these two modalities achieved the sensitivity of 91%, specificity of 82%, and accuracy of 93%.ConclusionsBoth US and MRI can provide valuable information about the differential diagnosis between benign and malignant soft tissue masses. The combination of the two imaging-based scoring systems can increase the diagnostic performance, especially in specificity.

For improving solubility and bioaccessibility of phytosterols (PS), phytosterol nanoparticles (PNPs) were prepared by emulsification–evaporation combined high-pressure homogenization method. The organic phase was formed with the dissolved PS and soybean lecithin (SL) in anhydrous ethanol, then mixed with soy protein isolate (SPI) solution, and homogenized into nanoparticles, followed by the evaporation of ethanol. The optimum fabrication conditions were determined as PS (1%, w/v): SL of 1:4, SPI content of 0.75% (w/v), and ethanol volume of 16 ml. PNPs were characterized to have average particle size 93.35 nm, polydispersity index (PDI) 0.179, zeta potential −29.3 mV, and encapsulation efficiency (EE) 97.3%. The impact of temperature, pH, and ionic strength on the stability of fabricated PNPs was determined. After 3-h in vitro digestion, the bioaccessibility of PS in nanoparticles reached 70.8%, significantly higher than the 18.2% of raw PS. Upon freeze-drying, the particle size of PNPs increased to 199.1 nm, resulting in a bimodal distribution. The solubility of PS in water could reach up to 2.122 mg/ml, ~155 times higher than that of raw PS. Therefore, this study contributes to the development of functional PS-food ingredients.

Understanding the genetic basis of trait variations and their coordination between relative species or populations distributing in different environmental conditions is important in evolutionary biology. In marine ectotherms, growth-defense trade-offs are a common ecological and evolutionary phenomenon. However, the biochemical and molecular mechanisms that govern these trade-offs in marine ectotherms in the evolutionary perspective remain poorly investigated. Oysters are among the most important species in global aquaculture. Crassostrea gigas (C. gigas) and Crassostrea angulata (C. angulata) are two allopatric congeneric dominant oyster species that inhabit the northern and southern intertidal areas of China. Wild C. gigas and C. angulata were spawned, and their F1 progeny were cultured in the same sites to reduce the environmental effects. Untargeted metabolomics and transcriptomics, together with phenotypic parameters including morphological traits (growth performance), nutritional content (glycogen, crude fat, and fatty acid content), physiology (normalized oxygen consumption rate and total antioxidant capacity) were applied to assess metabolic and transcript divergences between C. gigas and C. angulata. Integrated analyses of metabolites and transcriptomes showed that C. gigas allocated more energy to storage and defense by suppressing glycolysis, fatty acid oxidation and by upregulating fatty acid synthesis, antioxidant gene expression, and related metabolites. The metabolic and transcript results were further confirmed by the phenotypic data that C. gigas has higher glycogen and crude fat content and fatty acid unsaturation and stronger antioxidant capacity than C. angulata. In contrast, C. angulata exhibited better growth performance and a higher oxygen consumption rate. These findings suggest that C. angulata allocates more energy to growth, which is embodied in its stronger aerobic capacity and higher levels of protein synthesis genes, metabolites, and growth-related biomarkers. This study will help to enlighten the evolutionary patterns and genetic basis of growth-defense trade-offs in marine ectotherms and the biochemical and molecular mechanisms underlying energy allocation. Also, the key genes and metabolites of glycogen and fatty acids pathway identified in this study will be applied for meat quality improvement in the oyster industry.

Neomycin is a common ototoxic aminoglycoside antibiotic that causes sensory hearing disorders worldwide, and monosialotetrahexosylganglioside (GM1) is reported to have antioxidant effects that protect various cells. However, little is known about the effect of GM1 on neomycin-induced hair cell (HC) ototoxic damage and related mechanism. In this study, cochlear HC-like HEI-OC-1 cells along with whole-organ explant cultures were used to establish an in vitro neomycin-induced HC damage model, and then the apoptosis rate, the balance of oxidative and antioxidant gene expression, reactive oxygen species (ROS) levels and mitochondrial membrane potential (MMP) were measured. GM1 could maintain the balance of oxidative and antioxidant gene expression, inhibit the accumulation of ROS and proapoptotic gene expression, promoted antioxidant gene expression, and reduce apoptosis after neomycin exposure in HEI-OC-1 cells and cultured cochlear HCs. These results suggested that GM1 could reduce ROS aggregation, maintain mitochondrial function, and improve HC viability in the presence of neomycin, possibly through mitochondrial antioxidation. Hence, GM1 may have potential clinical value in protecting against aminoglycoside-induced HC injury.

Sensorineural hearing loss (SNHL) affects approximately 466 million people worldwide, which is projected to reach 900 million by 2050. Its histological characteristics are lesions in cochlear hair cells, supporting cells, and auditory nerve endings. Neurological disorders cover a wide range of diseases affecting the nervous system, including Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), autism spectrum disorder (ASD), etc. Many studies have revealed that neurological disorders manifest with hearing loss, in addition to typical nervous symptoms. The prevalence, manifestations, and neuropathological mechanisms underlying vary among different diseases. In this review, we discuss the relevant literature, from clinical trials to research mice models, to provide an overview of auditory dysfunctions in the most common neurological disorders, particularly those associated with hearing loss, and to explain their underlying pathological and molecular mechanisms.

Background: Consensus is lacking with regard to whether hearing loss is an independent risk factor for dementia. We therefore conducted a meta-analysis to clarify the relationship of hearing loss and dementia.Methods: Prospective cohort studies investigating the association between hearing loss and the incidence of dementia in a community-derived population were included by searching electronic databases that included PubMed, Embase, and Cochrane's Library. A random-effects model was adopted to combine the results.Results: Fourteen cohorts including 726,900 participants were analyzed. It was shown that hearing loss was independently associated with dementia [adjusted hazard ratio (HR): 1.59, 95% confidence interval (CI): 1.37 to 1.86, p < 0.001; I2 = 86%]. Sensitivity analysis sequentially excluding any of the individual studies included showed similar results. Subgroup analysis according to the diagnostic methods for hearing loss, validation strategy for dementia, follow-up duration, and adjustment of apolipoprotein E genotype also showed consistent results (p-values for subgroup differences all > 0.05). Meta-analysis with five studies showed that hearing loss was also connected to higher risk of Alzheimer's disease (adjusted HR: 2.24, 95% CI: 1.32 to 3.79, p = 0.003; I2 = 2%).Conclusions: Hearing loss may increase the risk of dementia in the adult population. Whether effective treatment for hearing loss could reduce the incidence of dementia should be explored in the future.

ObjectivesTo explore the relationship between ultrasound (US) features and Ki-67 labeling index (LI) of soft tissue sarcoma (STS).MethodsForty-six patients with 47 STS lesions, between September 2014 and April 2020, were enrolled in the study. Point-biserial correlation analysis and Spearman’s correlation analysis were utilized to examining the relationship between the US features and the Ki-67 LI of STS. The differences of US features between high and low Ki-67 proliferation groups were statistically analyzed by independent t test, Wilcoxon rank-sum test, and Fisher’s exact test. The optimal cut-off points of US features revealing significant differences were estimated by the maximum Youden index.ResultsA moderate correlation between the vascular density grade and the Ki-67 LI (ρ = 0.409, P = 0.004) was found in this study. In addition, other ultrasound features were irrelevant to the Ki-67 LI. The cut-off for differentiating low- and high-proliferation groups was grade II according to the best Youden index. The area under receiver operating characteristic (ROC) curve was 0.74 (p = 0.011) with a sensitivity of 60.6% and specificity of 78.6%.ConclusionsOnly the vascular density grade of STS had a weak positive correlation with Ki-67 LI, and might be capable of predicting the proliferation of STS. Other ultrasonographic features of STS such as shape and tumor margin have no correlation with Ki-67 LI.

Medicago and its relatives, Trigonella and Melilotus comprise the most important forage resources globally. The alfalfa selected from the wild relatives has been cultivated worldwide as the forage queen. In the Flora of China, 15 Medicago, eight Trigonella, and four Melilotus species are recorded, of which six Medicago and two Trigonella species are introduced. Although several studies have been conducted to investigate the phylogenetic relationship within the three genera, many Chinese naturally distributed or endemic species are not included in those studies. Therefore, the taxonomic identity and phylogenetic relationship of these species remains unclear. In this study, we collected samples representing 18 out of 19 Chinese naturally distributed species of these three genera and three introduced Medicago species, and applied an integrative approach by combining evidences from population-based morphological clusters and molecular data to investigate species boundaries. A total of 186 individuals selected from 156 populations and 454 individuals from 124 populations were collected for genetic and morphological analyses, respectively. We sequenced three commonly used DNA barcodes (trnH-psbA, trnK-matK, and ITS) and one nuclear marker (GA3ox1) for phylogenetic analyses. We found that 16 out of 21 species could be well delimited based on phylogenetic analyses and morphological clusters. Two Trigonella species may be merged as one species or treated as two subspecies, and Medicago falcata should be treated as a subspecies of the M. sativa complex. We further found that major incongruences between the chloroplast and nuclear trees mainly occurred among the deep diverging lineages, which may be resulted from hybridization, incomplete lineage sorting and/or sampling errors. Further studies involving a finer sampling of species associated with large scale genomic data should be employed to better understand the species delimitation of these three genera.

Purpose: Nutritional intervention was always implemented based on “one-size-fits-all” recommendation instead of personalized strategy. We aimed to develop a machine learning based model to predict the optimal dose of a botanical combination of lutein ester, zeaxanthin, extracts of black currant, chrysanthemum, and goji berry for individuals with eye fatigue.Methods: 504 features, including demographic, anthropometrics, eye-related indexes, blood biomarkers, and dietary habits, were collected at baseline from 303 subjects in a randomized controlled trial. An aggregated score of visual health (VHS) was developed from total score of eye fatigue symptoms, visuognosis persistence, macular pigment optical density, and Schirmer test to represent an overall eye fatigue level. VHS at 45 days after intervention was predicted by XGBoost algorithm using all features at baseline to show the eye fatigue improvement. Optimal dose of the combination was chosen based on the predicted VHS.Results: After feature selection and parameter optimization, a model was trained and optimized with a Pearson's correlation coefficient of 0.649, 0.638, and 0.685 in training, test and validation set, respectively. After removing the features collected by invasive blood test and costly optical coherence tomography, the model remained good performance. Among 58 subjects in test and validation sets, 39 should take the highest dose as the optimal option, 17 might take a lower dose, while 2 could not benefit from the combination.Conclusion: We applied XGBoost algorithm to develop a model which could predict optimized dose of the combination to provide personalized nutrition solution for individuals with eye fatigue.

Natural selection and isolation are both important for understanding the geographic distribution of marine species and environmental responses to changing climate. In this study, we revealed distinct genetic variation in Crassostrea ariakensis by comparing the COI gene segment sequence in northern and southern oysters partitioned by the Yangtze River estuary. Reciprocal hybridization and intrapopulation crosses clarified their taxonomic status as the same species. There was no heterosis in the survival and growth of the hybrids, while the maternal effect was observed in larvae from eggs in the native habitat that showed higher fitness. Both the northern and southern F1 progenies exhibited positive performance in fitness traits, including survivorship, respiration rate, and growth, in their native habitats compared to that in their non-native habitats, indicating a strong signature of local adaptation. The oysters dwelling in the warm/southern habitats evolved a higher thermotolerance of LT50, while the oysters inhabiting the high-salinity/northern habitats had a 2.43‰ higher LS50 than that of their southern counterparts. After strong natural selection in the northern environments, the higher survival of the F1 progenies from the southern oysters under heat shock indicates an evolved genetic basis for its higher thermal tolerance. Strong environmental gradients, especially for temperature and salinity, and geographic isolation by the interaction between coastal currents and the Yangtze River estuary potentially contribute to shaping the distribution pattern and adaptive divergence of C. ariakensis in China.

Rheumatoid arthritis (RA) is characterized by synovial hyperplasia and cartilage/bone destruction, which results in a high disability rate on human health and a huge burden on social economy. At present, traditional therapies based on drug therapy still cannot cure RA, in accompany with the potential serious side effects. Based on the development of nanobiotechnology and nanomedicine, energy conversion-based nanotherapy has demonstrated distinctive potential and performance in RA treatment. This strategy employs specific nanoparticles with intrinsic physiochemical properties to target lesions with the following activation by diverse external stimuli, such as light, ultrasound, microwave, and radiation. These nanoagents subsequently produce therapeutic effects or release therapeutic factors to promote necrotic apoptosis of RA inflammatory cells, reduce the concentration of related inflammatory factors, relieve the symptoms of RA, which are expected to ultimately improve the life quality of RA patients. This review highlights and discusses the versatile biomedical applications of energy conversion-based nanotherapy in efficient RA treatment, in together with the deep clarification of the facing challenges and further prospects on the final clinical translations of these energy conversion-based nanotherapies against RA.

Investigating responses of organisms to stressful or new environments with selection pressure is one of the crucial problems in evolutionary biology, and it is of importance to understand the phenotypic and molecular mechanism underlying thermal tolerance under the context of the climate change. The Pacific oyster, Crassostrea gigas, inhabiting the environment with high variation in temperature, is a worldwide aquaculture species. However, summer mortality relevant to the high temperature is one of the problems challenging the oyster industry. An artificial selective breeding program was initiated to select for the thermal tolerance of oysters in an attempt to increase the summer survival rates since 2017 in our study. Parents of thermotolerance oyster selection is are based on acute thermal tolerance under controlled heat stress to strengthen the selection intensity. Furthermore, the phenotypic and the genotypic response to extreme high temperature were investigated based on the comparison of the F1 progeny of the selected and natural populations in growth, physiology, mortality rate post heat stress, genetic structure, and gene expression. The parameter of growth showed no significant change between the selected and natural populations for the 6-month-old oysters. The selected population exhibited a higher survival rate after exposure to heat stress in the laboratory, which is in line with result of the filed experience that summer mortality of selected population was significantly lower than that of natural population. Further, the respiration rate of the selected population increased at 38°C, while it increased at 35°C in the natural population. Simultaneously, metabolism-related enzymes (PK, SOD) showed higher activity levels in the selected population. Furthermore, phylogenetic analysis, population structure, and principal component analysis (PCA) suggested that the selected and natural populations exhibited genetic divergence, with eight genes (IF4A2, IF6, EIF3A, MANBA, DDX43, RECS, CAT2, and BAG4) in the selected regions showing differential expression patterns in response to heat stress in the two populations. This study suggests that artificial selection has a significant effect on phenotype and genome structure for the oyster, our study providing an alternative way to reveal the mechanism underlying thermotolerance that plays an important role to predict the potential adaptation to the climate change.

Background: Attention-deficit hyperactivity disorder (ADHD) is a typical neuropsychiatric disorder characterized by inattention, impulsivity, and hyperactivity, particularly in children. Recent studies demonstrated a close relationship between the development of ADHD and surgery under general anesthesia. However, few studies illustrated if ADHD symptoms changed after surgery. Meanwhile, whether these individuals with natural neural impairment were sensitive to postoperative neurocognitive disorder (PND) still remain unclear.Methods: Spontaneously hypertensive rats (SHR) were utilized as spontaneous ADHD animal model and Wistar-Kyoto (WKY) rats as non-ADHD animal model. We evaluated the variation of neurocognitive function and locomotor activity of the rats undergoing experimental laparotomy with general anesthesia by isoflurane. Neurocognitive function was assessed by fear conditioning test for contextual memory and Morris water maze (MWM) for spatial memory. Depressive-like behavior after surgery was detected by forced swim test, and open-field test and elevated plus maze test were utilized to evaluate locomotor activities and anxiety. Furthermore, we compared electroencephalogram (EEG) signal in ADHD and WKY rats under free-moving conditions. Afterward, c-Fos staining was also utilized to detect the excitatory activity of neurons in these rats to explore the neural mechanism.Results: Locomotor activity of SHR assessed by average speed and number of line crossings in the open-field test decreased 1 week after surgery under general anesthesia, but there was no difference concerning anxiety levels between SHR and WKY rats after surgery. This phenomenon was also paralleled with the change in EEG signal (delta band 0∼3 Hz). Surgery under general anesthesia had no effect on spatial and contextual memory, while it improved spontaneous depression in SHR. The expression of c-Fos was downregulated for at least 1 week in the nucleus accumbens (NAc) area of ADHD rats’ brain after surgery.Conclusion: ADHD rats were not sensitive to PND. Surgery with general anesthesia could partly improve the hyperactivity symptom of ADHD rats. This mechanism was related to the suppression of neural activity in the cerebral NAc of ADHD rats induced by general anesthetics.

Investigating the physiological mechanisms of closely related species that exhibit distinct geographic distributions and thermal niches is essential for understanding their thermal tolerance capacities and local adaptations in view of climate warming. The variations in upper thermal limits (LT50) under acute heat shock and cardiac activity, standard metabolic rate (SMR), anaerobic metabolite production and molecular responses (expression of molecular chaperones and glycolysis metabolism genes) under increasing temperatures in two oyster subspecies were studied. The populations of two oyster subspecies, Crassostrea gigas gigas and C. gigas angulata, exhibit different latitudinal distributions along the northern and southern coastlines of China, respectively, which experience different environmental conditions. The LT50 was significantly higher, by ∼1°C, in the southern than in the northern oysters. In both subspecies, temperature increases had powerful effects on heart rate, SMR and gene expression. The southern oysters had the highest Arrhenius breakpoint temperatures for heart rate (31.4 ± 0.17°C) and SMR (33.09°C), whereas the heart rate (28.86 ± 0.3°C) and SMR (29.22°C) of the northern oysters were lower. The same patterns were observed for the Q10 coefficients. More thermal sensitivity was observed in the northern oysters than in their southern counterparts, as the heat-shock proteins (HSPs) in the northern oysters were expressed first and had a higher induction at a lower temperature than those of southern oysters. Furthermore, different expression patterns of energetic metabolism genes (HK, PK, and PEPCK) were observed. In the northern oysters, increasing anaerobic glycolysis genes (PEPCK) and end products (succinate) were found at 36–43°C, indicating a transition from aerobic to anaerobic metabolism and a lower aerobic scope compared with the southern oysters. These two subspecies experience different environmental conditions, and their physiological performances suggested species-specific thermal tolerance windows in which the southern oysters, with mild physiological flexibility, had a higher potential capability to withstand heat stress. Overall, our results indicate that comparing and unifying physiological and molecular mechanisms can provide a framework for understanding the likely effects of global warming on marine ectotherms in intertidal regions.

Lung cancer is one of leading causes of cancer death all over the world. Non-small cell lung cancer (NSCLC) is the most predominant subtype of lung cancer. Molecular targeting therapy has been shown great success in the treatment of advanced NSCLC. Thus, an easy, sensitive, and specific way of recognizing therapeutic gene targets would help to select effective treatments, to improve physical condition and increase patient survival. In this study, we recruited and followed up a female NSCLC patient, whose plasma ctDNAs (circulating tumor DNAs), blood cell DNAs, psDNAs (pleural effusion supernatant DNAs), and ppDNAs (pleural effusion pellet DNAs), were collected and analyzed over periodic time points by methods of next generation sequencing (NGS), droplet digital PCR (ddPCR), and Amplification Refractory Mutation System (ARMS). In addition, pleural effusion pellets were stained by IHC (immunohistochemistry). The investigation results showed that EGFR L858R mutation was recognized by methods of NGS, ddPCR, and ARMS, while EGFR T790M mutation was only identified by methods of NGS and ddPCR but not ARMS, indicating that ARMS as an auxiliary clinical diagnostic method, is less sensitive and less reliable than NGS and ddPCR. In summary, the non-invasive and sensitive way of collecting ctDNAs for NGS and/or ddPCR screenings offers patients new diagnosis and therapeutic options.

Fine-scale adaptive evolution is always constrained by strong gene flow at vertical level in marine organisms. Rapid environmental fluctuations and phenotypic plasticity through optimization of fitness-related traits in organisms play important roles in shaping intraspecific divergence. The coastal systems experience strong variations in multiple abiotic environmental factors, especially the temperature. We used a typical intertidal species, Pacific oyster (Crassostrea gigas), to investigate the interaction between plasticity and adaptive evolution. We collected intertidal and subtidal oysters from two ecological niches and carried out common garden experiments for one generation. We identified fine-scale vertical adaptive divergence between intertidal and subtidal F1 progeny at both sites, based on different hierarchical phenotypes, including morphological, physiological, and molecular traits. We further quantified the global plasticity to thermal stress through transcriptomic analysis. The intertidal oysters exhibited slow growth rate. However, they showed high survival and metabolic rates under heat stress, indicating vertically fine-scale phenotypic adaptive mechanisms and evolutionary trade-offs between growth and thermal tolerance. Transcriptomic analysis confirmed that the intertidal oysters have evolved high plasticity. The genes were classified into three types: evolutionarily divergent, concordantly plastic, and adaptive plastic genes. The evolved divergence between intertidal and subtidal oysters for these gene sets showed a significant positive correlation with plastic changes of subtidal populations in response to high temperature. Furthermore, the intertidal oysters exhibited delayed large-scale increase in expressional plasticity than that in subtidal counterparts. The same direction between plasticity and selection suggests that the oysters have evolved adaptive plasticity. This implies that adaptive plasticity facilitates the oyster to adapt to severe intertidal zones. The oysters exposed to strong environmental variability are thermal tolerant and have high adaptive potential to face the current global warming. Our findings will not only provide new insights into the significant role of plasticity in adaptive evolution that can be extended to other marine invertebrates, but also provide basic information for oyster resources conservation and reef reestablishment.

An-Gong-Niu-Huang Wan (AGNH) is a well-known traditional Chinese medicine (TCM) recipe containing cinnabar (HgS) and realgar (As2S2). However, the application of AGNH is limited by the hepato- and nephrotoxicity of cinnabar and realgar. It should be noted that cinnabar and realgar in AGNH are not used alone, but rather combined with other herbs as formula to use. In this study, the protective effects and mechanisms of the other herbs in AGNH against the hepatorenal toxicity induced by cinnabar and realgar were investigated. The combination use of the other herbs in AGNH alleviated inflammatory cell infiltration and damage in the liver and kidney and restored the disturbed serum metabolic profile induced by cinnabar and realgar insults. By UPLC/Q-TOFMS combined with pattern recognition approaches, we identified 41 endogenous metabolites in the sera of mice that were related to the hepatorenal toxicity of cinnabar and realgar, 36 of which were restored to normal levels when various kinds of herbs were combined as compound recipe. These metabolites function as modulators in inflammation-associated glycerophospholipid, arachidonic acid, linoleic acid, sphingolipid, and ether lipid metabolic pathways. Notably, lysophosphatidylcholines (LysoPCs) were the most elevated among all of the metabolites detected after cinnabar and realgar treatment, while these LysoPCs did not show overt differences between the AGNH and saline control groups, which was associated with relatively unaffected or even up-regulated expression of lysophosphatidylcholine acyltransferase 1 (LPCAT1) and autotaxin (ATX). These findings indicated that other herbs in AGNH could have a protective effect against cinnabar- and realgar-induced hepatic and renal damage via modulating the disordered homeostasis of the glycerophospholipid, arachidonic acid, linoleic acid, ether lipid, and sphingolipid metabolism.

The present work investigates whether and how decisions in real-world online shopping scenarios can be predicted based on brain activation. Potential customers were asked to search through product pages on e-commerce platforms and decide, which products to buy, while their EEG signal was recorded. Machine learning algorithms were then trained to distinguish between EEG activation when viewing products that are later bought or put into the shopping card as opposed to products that are later discarded. We find that Hjorth parameters extracted from the raw EEG can be used to predict purchase choices to a high level of accuracy. Above-chance predictions based on Hjorth parameters are achieved via different standard machine learning methods with random forest models showing the best performance of above 80% prediction accuracy in both 2-class (bought or put into card vs. not bought) and 3-class (bought vs. put into card vs. not bought) classification. While conventional EEG signal analysis commonly employs frequency domain features such as alpha or theta power and phase, Hjorth parameters use time domain signals, which can be calculated rapidly with little computational cost. Given the presented evidence that Hjorth parameters are suitable for the prediction of complex behaviors, their potential and remaining challenges for implementation in real-time applications are discussed. [ABSTRACT FROM AUTHOR]

Brain parcellation divides the brain’s spatial domain into small regions, which are represented by nodes within the network analysis framework. While template-based parcellations are widely used, the parcels on the template do not necessarily match individual’s functional nodes. A new method is developed to overcome the inconsistent network analysis results by by-passing the difficulties of parcellating the brain into functionally meaningful areas. First, roughly equal-sized parcellations are obtained. Second, these random parcellations are applied to individual subjects multiple times and a pseudo-bootstrap (PBS) of the network is obtained for statistical inferences. It was found that the variation of mean global network metrics from PBS sampling is smaller compared with inter-subject variation or within-subject variation between two diffusion MRI scans. Using the mean global network metrics from PBS sampling, the intra-class correlation is always higher than the average obtained from using a single random parcellation. As one application, the PBS method was tested on the Human Connectome Project resting state dataset to identify individuals across scan sessions based on the mean functional connectivity (FC)—a trivial network property that has little information about the connectivity between nodes. An accuracy rate of ∼90% was achieved by simply finding the maximum correlation of mean FC of PBS samples between two scan sessions.

Low-intensity focused ultrasound (LIFU) has been shown to provide effective activation of the spinal cord neurocircuits. The aim of this study was to investigate the effects of LIFU in order to alleviate spasticity following spinal cord injury (SCI) by activating the spinal neurocircuits and increasing the expression of the neuronal K-Cl cotransporter KCC2. Adult male Sprague Dawley (SD) rats (220–300 g) were randomly divided into a sham control group, a LIFU− group, and a LIFU+ group. The mechanical threshold hold (g) was used to evaluate the behavioral characteristics of spasm. Electromyography (EMG) was used to assess activation of the spinal cord neurocircuits and muscle spontaneous contraction. Spasticity was assessed by frequency-dependent depression (FDD). The expression of KCC2 of the lumbar spinal cord was determined via western blot (WB) and immunofluorescence (IF) staining. The spinal cord neurocircuits were activated by LIFU simulation, which significantly reduced the mechanical threshold (g), FDD, and EMG recordings (s) after 4 weeks of treatment. WB and IF staining both demonstrated that the expression of KCC2 was reduced in the LIFU− group (P < 0.05). After 4 weeks of LIFU stimulation, expression of KCC2 had significantly increased (P < 0.05) in the LIFU+ group compared with the LIFU− group. Thus, we hypothesized that LIFU treatment can alleviate spasticity effectively and upregulate the expression of KCC2 in the L4–L5 section of SCI rats. [ABSTRACT FROM AUTHOR]

Increasing evidence indicates that inflammatory responses may influence brain neurochemical pathways, inducing depressive-like behaviors. Ultrasound stimulation (US) is a promising non-invasive treatment for neuropsychiatric diseases. We investigated whether US can suppress inflammation and improve depressive-like behaviors. Mice were intraperitoneally injected with lipopolysaccharide to induce depressive-like behaviors. Ultrasound wave was delivered into the prefrontal cortex (PFC) for 30 min. Depressive- and anxiety-like behaviors were evaluated through the forced swimming test (FST), tail suspension test (TST), and elevated plus maze (EPM). Biochemical analyses were performed to assess the expression of inflammatory cytokines in the PFC and serum. The results indicated that US of the PFC significantly improved depressive-like behaviors in the TST (p < 0.05) and FST (p < 0.05). Anxiety-like behaviors also improved in the EPM (p < 0.05). Furthermore, the lipopolysaccharide-mediated upregulation of IL-6, IL-1β, and TNF-α in the PFC was significantly reduced (p < 0.05) by US. In addition, no tissue damage was observed. Overall, US of PFC can effectively improve lipopolysaccharide-induced depressive-like behaviors, possibly through the downregulation of inflammatory cytokines in the PFC. US may be a safe and promising tool for improvement of depression. [ABSTRACT FROM AUTHOR]

A central challenge in pharmaceutical research is to investigate genetic variation in response to drugs. The Collaborative Cross (CC) mouse reference population is a promising model for pharmacogenomic studies because of its large amount of genetic variation, genetic reproducibility, and dense recombination sites. While the CC lines are phenotypically diverse, their genetic diversity in drug disposition processes, such as detoxification reactions, is still largely uncharacterized. Here we systematically measured RNA-sequencing expression profiles from livers of 29 CC lines under baseline conditions. We then leveraged a reference collection of metabolic biotransformation pathways to map potential relations between drugs and their underlying expression quantitative trait loci (eQTLs). By applying this approach on proximal eQTLs, including eQTLs acting on the overall expression of genes and on the expression of particular transcript isoforms, we were able to construct the organization of hepatic eQTL-drug connectivity across the CC population. The analysis revealed a substantial impact of genetic variation acting on drug biotransformation, allowed mapping of potential joint genetic effects in the context of individual drugs, and demonstrated crosstalk between drug metabolism and lipid metabolism. Our findings provide a resource for investigating drug disposition in the CC strains, and offer a new paradigm for integrating biotransformation reactions to corresponding variations in DNA sequences. [ABSTRACT FROM AUTHOR]