Search

Abstract Climate change and land use change caused by human activities have a profound impact on ecological security. Simulating the spatio-temporal changes in ecosystem service value and ecological security patterns under different carbon emission scenarios in the future is of great significance for formulating sustainable development policies. This study quantified the four major ecosystem services (habitat quality, water retention, soil erosion, and carbon storage) in Northeast China (NC), identified ecological source areas, and constructed a stable ecological security pattern. The results show that the spatial patterns of soil erosion, carbon storage, water retention, and habitat quality, the four major ecosystem services in NC, are relatively stable in the next 30 years, and there is no significant difference from the current spatial pattern distribution. The SSP1–2.6 carbon emission scenario is a priority model for the development of NC in the next 30 years. In this carbon emission scenario, the NC has the largest ecological resources (191,177 km2) and the least comprehensive resistance value (850.006 × 10−4). At the same time, the relative resistance of the corridor in this scenario is the smallest, and the area of the mandatory reserve pinch points is the least. The ecological corridors in the SSP1–2.6 scenario form a network distribution among the ecological sources, connecting several large ecological sources as a whole. This study fills the knowledge gap in building a stable ecological security pattern in NC under the background of global change, and provides a scientific basis for the decision-making of regional ecological security and land resource management.

Abstract Introduction The aim of this study was to assess the efficacy and safety of 15% azelaic acid (AzA) gel in treating acne-induced post-inflammatory erythema (PIE) and post-inflammatory hyperpigmentation (PIH). The effects of 15% AzA gel on acne, skin barrier function, and quality of life were also evaluated. Methods A total of 72 patients with mild to moderate acne were enrolled in a randomized, double-blind, placebo-controlled trial. Patients were divided into two groups: patients in the AzA group applied 15% AzA gel twice daily for 12 weeks, and those in the placebo group applied AzA-free gel. Clinical evaluations using non-invasive skin detection technologies, including VISIA skin analysis, dermoscopy, and skin physiological function tests, were performed at 0, 4, 8, and 12 weeks. Main outcome measures included the post-acne hyperpigmentation index (PAHPI), melanin, hemoglobin, individual typology angle, water content, transepidermal water loss, and sebum. Investigator Global Assessment) and Dermatology Life Quality Index (DLQI) assessments were conducted at weeks 0 and 12. Adverse reactions were recorded. Results Of the 72 patients at study initiation, 60 completed the trial. At 8 and 12 weeks, patients in the AzA group showed significantly reduced PAHPI for PIE lesions compared to baseline and patients receiving placebo (P

Abstract Background The S100 protein family is a group of small molecular EF-hand calcium-binding proteins that play critical roles in various biological processes, including promotion of growth, metastasis and immune evasion of tumor. However, the potential roles of S100 protein family expression in tumor microenvironment (TME) cell infiltration in pan-cancer remain elusive. Methods Herein, we conducted a comprehensive assessment of the expression patterns of the S100 protein family in pan-cancer, meticulously examining their correlation with characteristics of TME cell infiltration. The S100 score was constructed to quantify S100 family expression patterns of individual tumors. Results The S100 family was a potent risk factor in many cancers. Clustering analysis based on the transcriptome patterns of S100 protein family identified two cancer clusters with distinct immunophenotypes and clinical characteristics. Cluster A, with lower S100 expression, exhibited lower immune infiltration, whereas, Cluster B, with higher S100 expression, featured higher immune infiltration. Interestingly, Cluster B had a poorer prognosis, likely due to an immune-excluded phenotype resulting from stromal activation. The analysis revealed robust enrichment of the TGFb and EMT pathways in the cohort exhibiting high S100 score, alongside a positive correlation between the S100 score and Treg levels, suggesting the manifestation of an immune-excluded phenotype in this group. Moreover, S100 families were associated with the prognosis of 22 different cancers and a noteworthy association was observed between high S100 score and an unfavorable response to anti-PD-1/L1 immunotherapy. Consistent findings across two independent immunotherapy cohorts substantiated the advantageous therapeutic outcomes and clinical benefits in patients displaying lower S100score. Conclusion Our analysis demonstrated the role of S100 family in formation of TME diversity and complexity, enabling deeper cognition of TME infiltration characterization and the development of personalized immunotherapy strategies targeting S100 family for unique tumor types.

Abstract Major depressive disorder (MDD), bipolar disorder (BD), and schizophrenia (SCZ) are classified as major mental disorders and together account for the second-highest global disease burden, and half of these patients experience symptom onset in adolescence. Several studies have reported both similar and unique features regarding the risk factors and clinical symptoms of these three disorders. However, it is still unclear whether these disorders have similar or unique metabolic characteristics in adolescents. We conducted a metabolomics analysis of plasma samples from adolescent healthy controls (HCs) and patients with MDD, BD, and SCZ. We identified differentially expressed metabolites between patients and HCs. Based on the differentially expressed metabolites, correlation analysis, metabolic pathway analysis, and potential diagnostic biomarker identification were conducted for disorders and HCs. Our results showed significant changes in plasma metabolism between patients with these mental disorders and HCs; the most distinct changes were observed in SCZ patients. Moreover, the metabolic differences in BD patients shared features with those in both MDD and SCZ, although the BD metabolic profile was closer to that of MDD than to SCZ. Additionally, we identified the metabolites responsible for the similar and unique metabolic characteristics in multiple metabolic pathways. The similar significant differences among the three disorders were found in fatty acid, steroid-hormone, purine, nicotinate, glutamate, tryptophan, arginine, and proline metabolism. Interestingly, we found unique characteristics of significantly altered glycolysis, glycerophospholipid, and sphingolipid metabolism in SCZ; lysine, cysteine, and methionine metabolism in MDD and BD; and phenylalanine, tyrosine, and aspartate metabolism in SCZ and BD. Finally, we identified five panels of potential diagnostic biomarkers for MDD-HC, BD-HC, SCZ-HC, MDD-SCZ, and BD-SCZ comparisons. Our findings suggest that metabolic characteristics in plasma vary across psychiatric disorders and that critical metabolites provide new clues regarding molecular mechanisms in these three psychiatric disorders.

Abstract Wild medicinal plants are prominent in the field of Traditional Chinese Medicine (TCM), but their availability is being impacted by human activities and ecological degradation in China. To ensure sustainable use of these resources, it is crucial to scientifically plan areas for wild plant cultivation. Thesium chinense, a known plant antibiotic, has been overharvested in recent years, resulting in a sharp reduction in its wild resources. In this study, we employed three atmospheric circulation models and four socio-economic approaches (SSP1-2.6, SSP2-4.5, SSP3-7.0, and SSP5-8.5) to investigate the primary environmental factors influencing the distribution of T. chinense. We also examined changes in its suitable area using the Biomod2 package. Additionally, we utilized the PLUS model to project and analyze future land use changes in climate-stable regions for T. chinense. Our planning for wild tending areas of T. chinense was facilitated by the ZONATION software. Over the next century, the climate-stable regions for T. chinense in China is approximately 383.05 × 104 km2, while the natural habitat in this region will progressively decline. Under the current climate conditions, about 65.06% of the habitats in the high suitable areas of T. chinense are not affected by future land use changes in China. Through hotspot analysis, we identified 17 hotspot cities as ideal areas for the wild tending of T. chinense, including 6 core hotspot cities, 6 sub-hotspot cities, and 5 fringe hotspot cities. These findings contribute to a comprehensive research framework for the cultivation planning of T. chinense and other medicinal plants.

Abstract Objective This study investigated the correlation between the pulsatility index (PI) of the middle cerebral artery with the total burden of cerebral small vessel disease and cognitive impairment. Method Information on patients hospitalized in the Department of Neurology was collected retrospectively. These patients had complete clinical and laboratory data. The middle cerebral artery PI was measured using transcranial Doppler, a Mini‐Mental State Examination (MMSE) was used to assess cognitive function, and the total cerebral small vessel disease burden was assessed using magnetic resonance imaging. Patients were grouped according to their scores for total imaging burden of cerebral small vessel disease and cognitive function. Logistic regression analysis assessed the association between the PI, total imaging burden, and cognitive impairment. Spearman analysis was used to evaluate the correlation between the PI and total imaging burden and cognitive impairment, and receiver operating characteristic (ROC) curves were used to determine the predictive value of the PI for cognitive function. Results The PI was higher in the cognitive impairment (CI) group than in the no‐CI group. Binary logistic regression analysis showed that increased PI was an independent risk factor for CI (OR = 1.582; 95% CI: 1.043–2.401; p = .031) and total imaging burden (OR = 1.842; 95% CI: 1.274–2.663; p = .001). Spearman analysis found that the PI correlated negatively with the MMSE score (r = −.627, p

Multiple-valued logics (MVL) have abundant operation functions which can be used for encryption. A reconfigurable MVL operator can perform all MVL functions with a universal circuit structure at fast operation speed, based on which a one-time-pad cryptosystem is expected to be built. However, we find that when the existing MVL encryption method is applied to video data encryption, the color edges in the plaintext image will remain in the ciphertext image, resulting in partial leakage of information. To solve this problem, we propose byte reorganization and random mask strategies, forming an improved MVL encryption method for video streaming. For verifying the effectiveness of the method, we implement an FPGA-based experimental system to encrypt and decrypt real-time video streaming data. In this system, 16-quit reconfigurable quaternary logic operators are implemented to encrypt, decrypt and derive keys. The process of either encryption or decryption only takes 34 clock cycles. The encryption and decryption modules are capable of processing streaming data at a speed of 6.21 Gbit/s, showing that the system has real-time processing capability. For proving that our method is secure, we compare our improved MVL encryption method with existing image encryption methods in terms of common security evaluation metrics. Experimental results show that our method solves the problem of remained color edge and the ciphertext exhibits good statistical properties.

Abstract Background Laparoscopic radical resection of gastrointestinal cancer is associated with a high incidence of postoperative catheter-related bladder discomfort (CRBD). Studies on the benefits of magnesium sulfate intravenous infusion during the perioperative period post-laparoscopic surgery are yet lacking. Methods A total of 88 gastrointestinal cancer male patients scheduled for laparoscopic radical resection were randomly divided into two groups: normal saline (control) and magnesium. In the magnesium group, a 40 mg/kg loading dose of intravenous magnesium sulfate was administered for 10 min just after the induction of anesthesia, followed by continuous intravenous infusion of 15 mg/kg/h magnesium sulfate until the end of the surgery; the control group was administered the same dose of normal saline. Subsequently, 2 μg/kg sufentanil was continuously infused intravenously by a postoperative patient-controlled intravenous analgesia (PCIA) device. The primary outcome was the incidence of CRBD at 0 h after the surgery. The secondary outcomes included incidence of CRBD at 1, 2, and 6 h postsurgery, the severity of CRBD at 0, 1, 2, and 6 h postsurgery. Remifentanil requirement during surgery, sufentanil requirement within 24 h postsurgery, the postoperative numerical rating scale (NRS) score at 48 h after the surgery, magnesium-related side effects and rescue medication (morphine) requirement were also assessed. Results The incidence of CRBD at 0, 1, 2, and 6 h postoperatively was lower in the magnesium group than the control group (0 h: P = 0.01; 1 h: P = 0.003; 2 h: P = 0.001; 6 h: P = 0.006). The incidence of moderate to severe CRBD was higher in the control group at postoperative 0 and 1 h (0 h: P = 0.002; 1 h: P = 0.028), remifentanil requirement during surgery were significantly lower in the magnesium group than the control group. Sufentanil requirements during the 24 h postoperative period were significantly lower in the magnesium group than the control group. The NRS score was reduced in the magnesium group compared to the control group in the early postoperative period. Magnesium-related side effects and rescue medication (morphine) did not differ significantly between the two groups. Conclusions Intravenous magnesium sulfate administration reduces the incidence and severity of CRBD and remifentanil requirement in male patients undergoing radical resection of gastrointestinal cancer. Also, no significant side effects were observed. Trial registration Chictr.org.cn ChiCTR2100053073. The study was registered on 10/11/2021.

ABSTRACTGlycoprotein VI (GPVI) is the major collagen receptor on the platelet surface and is important in mediating granule secretion and atherothrombosis. Sulforaphane (SFN), a dietary isothiocyanate enriched in cruciferous vegetables, exerts multiple biological activities. This study aimed to investigate the efficacy of SFN on GPVI-mediated signaling and platelet granule secretion in vitro. We herein demonstrated that SFN greatly attenuated granule secretion in human gel-filtered platelets in response to collagen, including inhibiting CD62P and CD63 expression and PF4, CCL5, and ATP release. Mechanistically, these inhibitory effects of SFN were mainly mediated by its attenuation of cytosolic phospholipase A2 (cPLA2) phosphorylation and thromboxane A2 (TxA2) generation. Moreover, SFN did not further decrease the inhibitory effects of p38 MAPK inhibitor SB203580 on cPLA2 phosphorylation, TxA2 generation and granule secretion. Thus, SFN attenuates platelet granule secretion via down-regulating GPVI-mediated p38 MAPK/cPLA2/TxA2 signaling, which may play important preventive roles in cardiovascular diseases.

Drought is an important agricultural problem worldwide, which seriously affects the growth and yield of crops. To explore the effects of different degrees of drought on the soluble sugar content of soybeans, this study measured the soluble sugar content of two soybean cultivars at three growth stages under four levels of drought stress. The results showed that drought stress significantly affected the soluble sugar content, and there were differences among different growth stages and cultivars. At the seedling and flowering stages, the sucrose content of both Heinong44 and Heinong65 showed an unimodal trend and reached the maximum value at moderate drought. The increase rate was the highest in the leaves at the flowering stage, which increased by 36.18% and 25.79% compared with CK, respectively. The fructose and glucose contents were the highest during severe drought, and the fructose content increased the most in the leaves at the seedling stage, which increased by 18.05% and 17.67% compared with CK, respectively. The glucose content increased the most in the petioles at the flowering stage, reaching 40.66% and 35.24%. At the pod-filling stage, the three sugar contents of both Heinong44 and Heinong65 were the lowest at severe drought, and the sucrose and fructose contents decreased the most in the petioles, which decreased by 21.66% and 23.94%, 12.58% and 13.49% compared with CK, respectively. The glucose content decreased the most in the stems, which decreased by 11.72% and 9.66%. In addition, at each growth stage and drought treatment, the ratio of the soluble sugar content of Heinong44 was higher than that of Heinong65.

Abstract Memory reconsolidation refers to the process by which the consolidated memory was restored after reactivation (RA). Memory trace becomes labile after reactivation and inhibition of memory reconsolidation may disrupt or update the original memory trace, which provided a new strategy for the treatment of several psychiatric diseases, such as drug addiction and post-traumatic stress disorder. Fat mass and obesity-associated gene (FTO) is a novel demethylase of N6-methyladenosine (m6A) and it has been intensively involved in learning and memory. However, the role of FTO in memory reconsolidation has not been determined. In the present study, the function of FTO in memory reconsolidation was investigated in the novel object recognition (NOR) model in mice. The results showed that RA of NOR memory increased hippocampal FTO expression in a time-dependent manner, while FTO inhibitor meclofenamic acid (MA) injected immediately, but not 6 h after RA disrupted NOR memory reconsolidation. MA downregulated BDNF expression during NOR memory reconsolidation in the hippocampus, while the TrkB agonist 7,8-Dihydroxyflavone (7,8-DHF) reversed the disruptive effects of MA on NOR memory reconsolidation. Furthermore, overexpression of FTO increased BDNF expression via decreasing mRNA m6A in HT22 cells. Taken together, these results indicate that FTO may up-regulate the BDNF-TrkB pathway to promote NOR memory reconsolidation through m6A modification.

Climate change and urbanization have led to an increase in extreme weather and urban heat islands. Green space can help regulate the thermal environment, but previous studies have focused on two-dimensional (2D) indicators, neglecting the intrinsic three-dimensional (3D) characteristics of green space. Therefore, we developed a set of 3D landscape indices to define green space configurations, including characteristic, shape, and compactness, based on landscape ecology and the law of universal gravity, and quantify its benefits for the thermal environment. We collected high-resolution LiDAR point cloud data from Siming Mountain, China, to calculate both 2D and 3D green space landscape patterns and investigate their effects on land surface temperature (LST) using correlation analysis and spatial statistical methods. Our study revealed: (1) All the selected green space landscape indices had a significant negative effect on LST, with a non-linear enhancement when 2D or 3D indices interacted. (2) The 3D compactness index (VCI) could be the most reliable and concise index to explain LST spatial distribution. Adjusting the VCI allowed us to reduce the LST of the study area by up to 3.71 °C in summer and 2.14 °C in winter. However, an overly compact 3D green space above the threshold could lead to higher LST in summer. (3) Terrain had a weaker effect on LST in winter than in summer, and it showed a stronger interaction with the 3D form of green space than with the 2D form. We concluded that the 3D compact form of green space can be utilized as the key factor in maximizing its cooling effect, by taking into account both terrain factors and seasonal variations. Our study can shed light on the scientific planning of green space aiming at optimizing the thermal environment for more sustainable forest and urban habitats.

There are various regulatory mechanisms to coordinate vulnerability disclosure behaviors during crowdsourcing cybersecurity testing. However, in the case of unclear regulatory effectiveness, enterprises cannot obtain sufficient vulnerability information, third-party crowdsourcing cybersecurity testing platforms fail to provide trusted services, and the government lacks strong credibility. We have constructed a tripartite evolutionary game model to analyze the evolutionary process of the equilibrium of {legal disclosure, active operation, strict regulation}, and the paper reveals the impact of three regulatory mechanisms. We find that these participants' positive behaviors are in a stable state. Higher initial willingness accelerates the speed of reaching the evolutionary stability of the system, and this equilibrium is satisfied only if the governmental regulatory benefits are sufficiently high. Regarding the punishment mechanism, increased punishment for enterprises causes them to adopt positive behaviors faster, while the opposite occurs for platforms; increased punishment for platforms drives both participants to adopt positive behaviors faster. Concerning the subsidy mechanism, increased subsidy to enterprises causes them to adopt legal disclosure behaviors faster, while platforms remain unresponsive; increased subsidy to platforms motivates both players to choose their own positive behaviors. In terms of the collaborative disclosure mechanism, excessive collaborative costs reduce the platforms' willingness to operate actively, which decreases the enterprises' incentives to disclose vulnerability legally. These findings guide the government to establish suitable mechanisms to regulate the participants' behavior and promote the healthy development of the cybersecurity crowdsourcing industry.

Abstract Background Adolescent major depressive disorder (MDD) is a prevalent mental health problem with low treatment success rates. Whether fluoxetine or fluoxetine combined with cognitive-behavioural therapy (CBT) is the more effective initial treatment for adolescent MDD remains controversial, and few studies have investigated whether treatment switching or augmentation is preferred when the initial treatment is not working well. Methods We developed a multicentre open-label Sequential Multiple Assignment Randomized Trial (SMART) design, consisting of two phases lasting 8 weeks each. In phase 1 (at baseline), patients will be recruited and grouped in fluoxetine group or fluoxetine combined with CBT group by patient self-selection. In phase 2 (after 8 weeks of treatment), the nonresponders will be randomly assigned to six groups, in which participants will switch to sertraline, vortioxetine, or duloxetine or added aripiprazole, olanzapine, or lithium carbonate to fluoxetine. After the full 16 weeks of treatment, we will assess the long-term sustainability of the treatment effects by evaluating participants during their subsequent naturalistic treatment. The primary outcome will be the response rate, determined by the Children’s Depression Rating Scale-Revised (CDRS-R). Secondary outcomes include the change in scores on the Beck Depression Inventory (BDI), the Screen for Child Anxiety-Related Emotional Disorders (SCARED) and the Safe Assessment. Discussion The results from this study will aid clinicians in making informed treatment selection decisions for adolescents with MDD. Trial registration This protocol was registered at ClinicalTrials.gov with Identifier: NCT05814640.

Abstract The potato (Solanum tuberosum L.) is one of the most important food crops worldwide. Nevertheless, due to food safety concerns, substantial amounts of potatoes are not utilized, resulting in losses. Dormancy development is affected by potato variety, temperature, light, humidity, and so forth. Traditional and novel techniques to detect potato dormancy have been developed based on infrared spectroscopy, hyperspectral, and multispectral imaging systems in combination with simulation verification. This review describes the ability of novel approaches to address the uncertain hazardous issue and delay or inhibit potato dormancy incidence and development. Further, this review describes the role of carbohydrate metabolism and phytohormone regulation involved in potato dormancy, the mechanism of action to address dormancy, and challenges and recommendations moving forward. More work is needed to develop novel approaches toward addressing the problem of potato germination after harvest.

Speech forgery and tampering, increasingly facilitated by advanced audio editing software, pose significant threats to the integrity and privacy of digital speech avatars. Speech resampling is a post-processing operation of various speech-tampering means, and the forensic detection of speech resampling is of great significance. For speech resampling detection, most of the previous works used traditional methods of feature extraction and classification to distinguish original speech from forged speech. In view of the powerful ability of deep learning to extract features, this paper converts the speech signal into a spectrogram with time-frequency characteristics, and uses the feature pyramid network (FPN) with the Squeeze and Excitation (SE) attention mechanism to learn speech resampling features. The proposed method combines the low-level location information and the high-level semantic information, which dramatically improves the detection performance of speech resampling. Experiments were carried out on a resampling corpus made on the basis of the TIMIT dataset. The results indicate that the proposed method significantly improved the detection accuracy of various resampled speech. For the tampered speech with a resampling factor of 0.9, the detection accuracy is increased by nearly 20%. In addition, the robustness test demonstrates that the proposed model has strong resistance to MP3 compression, and the overall performance is better than the existing methods.

The myostatin (MSTN) gene also regulates the developmental balance of skeletal muscle after birth, and has long been linked to age-related muscle wasting. Many rodent studies have shown a correlation between MSTN and age-related diseases. It is unclear how MSTN and age-associated muscle loss in other animals are related. In this study, we utilized MSTN gene-edited bovine skeletal muscle cells to investigate the mechanisms relating to MSTN and muscle cell senescence. The expression of MSTN was higher in older individuals than in younger individuals. We obtained consecutively passaged senescent cells and performed senescence index assays and transcriptome sequencing. We found that senescence hallmarks and the senescence-associated secretory phenotype (SASP) were decreased in long-term-cultured myostatin inactivated (MT-KO) bovine skeletal muscle cells (bSMCs). Using cell signaling profiling, MSTN was shown to regulate the SASP, predominantly through the cycle GMP-AMP synthase-stimulator of antiviral genes (cGAS-STING) pathway. An in-depth investigation by chromatin immunoprecipitation (ChIP) analysis revealed that MSTN influenced three prime repair exonuclease 1 (TREX1) expression through the SMAD2/3 complex. The downregulation of MSTN contributed to the activation of the MSTN-SMAD2/3-TREX1 signaling axis, influencing the secretion of SASP, and consequently delaying the senescence of bSMCs. This study provided valuable new insight into the role of MSTN in cell senescence in large animals.

The security crowd-testing regulatory mechanism is a vital means to promote collaborative vulnerability disclosure. However, existing regulatory mechanisms have not considered multi-agent responsibility boundaries and stakeholders' conflicts of interest, leading to their dysfunction. Distinguishing from previous research on the motivations and constraints of ethical hacks' vulnerability disclosure behaviors from a legal perspective, this paper constructs an evolutionary game model of SRCs, security researchers, and the government from a managerial perspective to propose regulatory mechanisms promoting tripartite collaborative vulnerability disclosure. The results show that the higher the initial willingness of the three parties to choose the collaborative strategy, the faster the system evolves into a stable state. Regarding the government's incentive mechanism, establishing reward and punishment mechanisms based on effective thresholds is essential. However, it is worth noting that the government has an incentive to adopt such mechanisms only if it receives sufficient regulatory benefits. To further facilitate collaborative disclosure, Security Response Centers (SRC) should establish incentive mechanisms including punishment and trust mechanisms. Additionally, publicity and training mechanisms for security researchers should be introduced to reduce their revenue from illegal participation, which promotes the healthy development of security crowd-testing. These findings contribute to improving SRCs' service quality, guiding security researchers' legal participation, enhancing the government's regulatory effectiveness, and ultimately establishing a multi-party collaborative vulnerability disclosure system.

The observational and paleo-ecological records on some shelves (e.g., North Sea, Yellow Sea) have indicated that the proportion of Paralia sulcata in the diatom community has been increasing since the 1980s. Because of its heavily-silicified frustules, this species is considered as an important siliceous organism, which can impact the recycling efficiency of biogenic silicon in the ocean. However, the specific environmental factors driving the increase of P. sulcata remain unclear. In this study, based on seasonal in-situ observations and historical literature in the Yellow Sea, we statistically assessed the importance of different environmental factors in determining P. sulcata abundance. Further, we quantified its optimal realized niches, using the maximum entropy and generalized additive models to predict the fate of this species. P. sulcata indicates a preference for environments with cold temperatures and high nutrient levels. The contribution of sea temperature on cell abundance reaches up to 37.2 %, which is higher than that of the nutrient concentrations (∼ 20.5 %) and salinity (∼ 17.1 %). The optimal realized niches are defined as sea temperature at 6.25 ± 3.50 °C, salinity at 32.8 ± 0.52, the concentrations of dissolved inorganic nitrogen, phosphorus, and silicate at 8.38 ± 5.42 μM, 0.42 ± 0.29 μM, and 5.87 ± 3.53 μM, respectively, and ammonium/nitrate ratio at 1.32 ± 0.19. Based on the multivariate statistical methods, the optimal realized niches indicate that the increased sea temperatures in winter and spring, combined with nitrogen enrichment, especially ammonium enrichment, are key environmental drivers for P. sulcata proliferation in the Yellow Sea.

Abstract Solar‐blind photodetectors have attracted extensive attention due to their advantages such as ultra‐low background noise and all‐weather. In this study, the planar Ti/Ga2O3/Au Schottky avalanche photodetector (APD) is fabricated based on β‐Ga2O3 epitaxial film on the sapphire substrate grown by metal–organic chemical vapor deposition. The Schottky APD exhibits a high responsivity of 9780.23 A W−1, an ultrahigh photo‐to‐dark current ratio of 1.88 × 107, an external quantum efficiency of 4.77 × 106%, a specific detectivity of 9.48 × 1014 Jones, with an ultrahigh gain of 1 × 106 under 254 nm light illumination at 60 V reverse bias, indicating high application potential for solar‐blind imaging. The superior photoresponse performances ascribe to the effective carrier avalanche multiplication, which contributes to the high photocurrent, and the high quality Schottky junction depletion, which leads to the low dark current.

Aspergillus fumigatus, a prevalent saprophytic fungus in the atmosphere, is known to rapidly induce severe invasive aspergillosis (IA) upon inhalation of its conidia by humans or animals. The mortality rate associated with IA exceeds 50%. The misuse of antifungal agents has contributed to the emergence of numerous highly pathogenic drug-resistant strains of A. fumigatus. Our study found that the combination of domiphen and itraconazole had sound synergistic antimicrobial effects against wild-type and itraconazole-resistant A. fumigatus in vivo and in vitro through MIC, FIC, plate inoculation, growth curve experiments, and Galleria mellonella infection model. Drug cytotoxicity and pharmacological tests for acute toxicity assays demonstrated that both itraconazole and domiphen showed minimal cytotoxicity and good biocompatibility. The transcriptome sequencing experiment demonstrated that domiphen exerted a suppressive effect on the expression of various genes, including those involved in drug efflux, redox regulation, and cellular membrane and cell wall remodeling. The present investigation explores the synergistic antimicrobial mechanisms of domiphen and itraconazole, encompassing three key aspects: (i) domiphen inhibited the efflux of itraconazole by reducing the expression of drug efflux-related genes, (ii) the combination has good ability to disrupt the cell membrane and cell wall, (iii) the combination also can remove biofilm more effectively. In summary, the utilization of domiphen as a synergist of itraconazole exhibited disruptive effects on the biofilm, cell wall, and cell membrane of A. fumigatus. This subsequently led to a modified distribution of itraconazole within the fungal organism, ultimately resulting in enhanced antifungal efficacy. The results of this study may provide a new therapeutic strategy for the treatment of IA caused by drug-resistant A. fumigatus.

BackgroundAn ongoing monitoring of national and subnational trajectory of COVID-19 vaccine hesitancy could offer support in designing tailored policies on improving vaccine uptake. ObjectiveWe aim to track the temporal and spatial distribution of COVID-19 vaccine hesitancy and confidence expressed on Twitter during the entire pandemic period in major English-speaking countries. MethodsWe collected 5,257,385 English-language tweets regarding COVID-19 vaccination between January 1, 2020, and June 30, 2022, in 6 countries—the United States, the United Kingdom, Australia, New Zealand, Canada, and Ireland. Transformer-based deep learning models were developed to classify each tweet as intent to accept or reject COVID-19 vaccination and the belief that COVID-19 vaccine is effective or unsafe. Sociodemographic factors associated with COVID-19 vaccine hesitancy and confidence in the United States were analyzed using bivariate and multivariable linear regressions. ResultsThe 6 countries experienced similar evolving trends of COVID-19 vaccine hesitancy and confidence. On average, the prevalence of intent to accept COVID-19 vaccination decreased from 71.38% of 44,944 tweets in March 2020 to 34.85% of 48,167 tweets in June 2022 with fluctuations. The prevalence of believing COVID-19 vaccines to be unsafe continuously rose by 7.49 times from March 2020 (2.84% of 44,944 tweets) to June 2022 (21.27% of 48,167 tweets). COVID-19 vaccine hesitancy and confidence varied by country, vaccine manufacturer, and states within a country. The democrat party and higher vaccine confidence were significantly associated with lower vaccine hesitancy across US states. ConclusionsCOVID-19 vaccine hesitancy and confidence evolved and were influenced by the development of vaccines and viruses during the pandemic. Large-scale self-generated discourses on social media and deep learning models provide a cost-efficient approach to monitoring routine vaccine hesitancy.

ABSTRACT: Mycobacterium iranicum is characterized by rapid growth and orange-pigmented scotochromogenic colonies. However, it is uncommon for M. iranicum to invade the central nervous system. A man nearly 60 years old was referred to our hospital because of a seizure and unconsciousness. After admission, the patient had fever and dizziness without obvious abnormalities in the cerebrospinal fluid, except for an increase in neutrophils. Metagenomic next-generation sequencing and DNA testing were positive for M. iranicum. The patient was treated with imipenem, minocycline, moxifloxacin, and linezolid, and he gradually recovered during follow-up.

Coking wastewater is a typical organic refractory wastewater characterized by high chemical oxygen demand (COD), NH4+-N, and total organic carbon (TOC). Herein, coking wastewater was treated using a heterogeneous electro-Fenton (EF) system comprising a novel iron-loaded needle coke composite cathode (Fe-NCCC) and a dimensionally stable anode. The response surface methodology was used to optimize the reaction conditions. The predicted and actual COD removal rates were 92.13 and 89.96% under optimum conditions of an applied voltage of 4.92 V, an electrode spacing of 2.29 cm, and an initial pH of 3.01. The optimized removal rate of NH4+-N and TOC was 84.12 and 73.44%, respectively. The color of coking wastewater decreased from 250-fold to colorless, and the BOD5/COD increased from 0.126 to 0.34. Gas chromatography–mass spectrometry and Fourier transform infrared spectroscopy show that macromolecular heterocyclic organic compounds decomposed into straight-chain small molecules and even completely mineralized. The energy consumption of the EF process was 23.5 RMB Yuan per cubic meter of coking wastewater. The EF system comprising the Fe-NCCC can effectively remove pollutants from coking wastewater, has low electricity consumption, and can simultaneously reduce various pollution indicators with potential applications in the treatment of high-concentration and difficult-to-degrade organic wastewater. HIGHLIGHTS A novel needle coke composite cathode was fabricated to treat coking wastewater.; The maximum COD removal was ∼90% using an electro-Fenton process.; The COD, -N, and TOC removal rates were optimized using the Box–Behnken design.; Macromolecular organic matter in coking wastewater was degraded after treatment.;

Aedes aegypti (Ae. aegypti) is a major vector of dengue virus (DENV) and Zika virus (ZIKV). Understanding the complex interaction mechanisms between mosquito vectors and arboviruses is essential to interrupt virus transmission. This study constructed CYP4C21 knockout (KO) Aag2 cells (Ae. aegypti cells) and confirmed that CYP4C21 KO reduced DENV2 and ZIKV copies in Aag2 cells, which suggests that CYP4C21 may play an important role in mosquito infection with arboviruses. Furthermore, it is the first report of the CYP4 family related to viral infection, which lays the foundation for exploring the role of the CYP4C21 in the interaction of Ae. aegypti and arbovirus and provides novel insights into the function of cytochrome family proteins.

Abstract Major depressive disorder (MDD) is a highly heterogeneous psychiatric disorder. The pathogenesis of MDD remained unclear, and it may be associated with exposure to different stressors. Most previous studies have focused on molecular changes in a single stress-induced depression model, which limited the identification of the pathogenesis of MDD. The depressive-like behaviors were induced by four well-validated stress models in rats, including chronic unpredictable mild stress, learned helplessness stress, chronic restraint stress and social defeat stress. We applied proteomic and metabolomic to investigate molecular changes in the hippocampus of those four models and revealed 529 proteins and 98 metabolites. Ingenuity Pathways Analysis (IPA) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis identified differentially regulated canonical pathways, and then we presented a schematic model that simulates AKT and MAPK signaling pathways network and their interactions and revealed the cascade reactions. Further, the western blot confirmed that p-AKT, p-ERK12, GluA1, p-MEK1, p-MEK2, p-P38, Syn1, and TrkB, which were changed in at least one depression model. Importantly, p-AKT, p-ERK12, p-MEK1 and p-P38 were identified as common alterations in four depression models. The molecular level changes caused by different stressors may be dramatically different, and even opposite, between four depression models. However, the different molecular alterations converge on a common AKT and MAPK molecular pathway. Further studies of these pathways could contribute to a better understanding of the pathogenesis of depression, with the ultimate goal of helping to develop or select more effective treatment strategies for MDD.

E-20-monooxygenase (E20MO) is an enzymatic product of the shade (shd) locus (cytochrome p450, E20MO). Initially discovered in Drosophila, E20MO facilitates the conversion of ecdysone (E) into 20-hydroxyecdysone (20E) and is crucial for oogenesis. Prior research has implicated 20E in growth, development, and insecticide resistance. However, little attention has been given to the association between the E20MO gene and DENV2 infection. The transcriptome of Ae. aegypti cells (Aag2 cells) infected with DENV2 revealed the presence of the E20MO gene. The subsequent quantification of E20MO gene expression levels in Aag2 cells post-DENV infection was carried out. A CRISPR/Cas9 system was utilized to create an E20MO gene knockout cell line (KO), which was then subjected to DENV infection. Analyses of DENV2 copies in KO and wild-type (WT) cells were conducted at different days post-infection (dpi). Plasmids containing E20MO were constructed and transfected into KO cells, with pre- and post-transfection viral copy comparisons. Gene expression levels of E20MO increased after DENV infection. Subsequently, a successful generation of an E20MO gene knockout cell line and the verification of code-shifting mutations at both DNA and RNA levels were achieved. Furthermore, significantly elevated DENV2 RNA copies were observed in the mid-infection phase for the KO cell line. Viral RNA copies were lower in cells transfected with plasmids containing E20MO, compared to KO cells. Through knockout and plasmid complementation experiments in Aag2 cells, the role of E20MO in controlling DENV2 replication was demonstrated. These findings contribute to our understanding of the intricate biological interactions between mosquitoes and arboviruses.

Statistical depth is widely used as a powerful tool to measure the center-outward rank of multivariate and functional data. Recent studies have introduced the notion of depth to the temporal point process, which exhibits randomness in the cardinality as well as distribution in the observed events. The proposed methods can well capture the rank of a point process in a given time interval, where a critical step is to measure the rank by using inter-arrival events. In this paper, we propose to extend the depth concept to multivariate spatial point process. In this case, the observed process is in a multi-dimensional location and there are no conventional inter-arrival events in the temporal process. We adopt the newly developed depth in metric space by defining two different metrics, namely the penalized metric and the smoothing metric, to fully explore the depth in the spatial point process. The mathematical properties and the large sample theory, as well as depth-based hypothesis testings, are thoroughly discussed. We then use several simulations to illustrate the effectiveness of the proposed depth method. Finally, we apply the new method in a real-world dataset and obtain desirable ranking performance.

In this work, Phragmites australis and Vallisneria natans were selected as the research objects and were cultured for 10 d under 0.10 μg L−1 sulfadiazine (SD) stress in a simulated surface flow wetland reactor. SD degradation was conducted at pH = 7 and 25 °C for 96 h. Each plant group conformed to the first-order kinetic model of degradation, and the degradation rate increased with time, reaching the maximum at 96 h. At 96 h, the degradation rate of P. australis communities was higher than that of V. natans. SD metabolites showed that the degradation pathways in the plant rhizosphere were mainly hydroxylation, aminolation, and S–N bond cleavage. In the analysis of rhizosphere bacterial community structure, the bacterial phyla that could degrade antibiotics accounted for a large proportion. Compared with before degradation, the dominant phylum and genus did not change after degradation (96 h), but their abundance changed to varying degrees, and new genera appeared in the P. australis group. This research provides a reference for the degradation of antibiotics in karst areas and new information on the mechanism of SA degradation in the plant rhizosphere. HIGHLIGHTS Under sulfonamide (SD) stress, the contents of organic acid esters in rhizosphere exudates of P. australis and V. natans increased.; New genera were produced in rhizosphere soil of P. australis group during SD degradation.; Antibiotics in karst wetlands may exist in the form of complexes and be adsorbed in soil or sediments.; After SD degradation, the diversity of bacteria decreased, but the total number of bacteria increased.;

Abstract Background Acid sphingomyelinase deficiency (ASMD) disorder, also known as Niemann–Pick disease (NPD) is a rare genetic disease caused by mutations in SMPD1 gene, which encodes sphingomyelin phosphodiesterase (ASM). Except for liver and spleen enlargement and lung disease, two subtypes (Type A and B) of NDP have different onset times, survival times, ASM activities, and neurological abnormalities. To comprehensively explore NPD’s genotype-phenotype association and pathophysiological characteristics, we collected 144 NPD cases with strict quality control through literature mining. Results The difference in ASM activity can differentiate NPD type A from other subtypes, with the ratio of ASM activity to the reference values being lower in type A (threshold 0.045 (4.45%)). Severe variations, such as deletion and insertion, can cause complete loss of ASM function, leading to type A, whereas relatively mild missense mutations generally result in type B. Among reported mutations, the p.Arg3AlafsX76 mutation is highly prevalent in the Chinese population, and the p.R608del mutation is common in Mediterranean countries. The expression profiles of SMPD1 from GTEx and single-cell RNA sequencing data of multiple fetal tissues showed that high expressions of SMPD1 can be observed in the liver, spleen, and brain tissues of adults and hepatoblasts, hematopoietic stem cells, STC2_TLX1-positive cells, mesothelial cells of the spleen, vascular endothelial cells of the cerebellum and the cerebrum of fetuses, indicating that SMPD1 dysfunction is highly likely to have a significant effect on the function of those cell types during development and the clinicians need pay attention to these organs or tissues as well during diagnosis. In addition, we also predicted 21 new pathogenic mutations in the SMPD1 gene that potentially cause the NPD, signifying that more rare cases will be detected with those mutations in SMPD1. Finally, we also analysed the function of the NPD type A cells following the extracellular milieu. Conclusions Our study is the first to elucidate the effects of SMPD1 mutation on cell types and at the tissue level, which provides new insights into the genotype-phenotype association and can help in the precise diagnosis of NPD.

Aim: Pay-as-you-throw (PAYT) is a recognized waste-charging method commonly used in developed countries to reduce waste effectively and improve resource utilization efficiency. China is currently transitioning from a traditional fixed-fee model to a PAYT model.Method: In this study, a sample of 1,346 urban residents in China is analyzed empirically to investigate their willingness to accept this change and the waste fees they are willing to pay for it.Results: The results indicate that, 1) at present, the proportion of urban residents willing to accept the PAYT charging model is low, accounting for only 54.53%. 2) The average annual cost for residents’ households willing to pay for PAYT is 58.616 RMB, which is relatively low. 3) The main reasons for the residents’ low acceptance of PAYT are behavioral attitudes, social norms, and perceived behavioral control factors. 4) Income and education levels mainly explain the low level of expenses paid by residents.Conclusion: Therefore, we suggest that, in the short term, publicity and education should be used to encourage residents to establish a correct environmental concept and a sense of environmental governance ownership, increase their knowledge of waste recycling and disposal and their awareness of waste charging rules, and thus improve their willingness to accept the PAYT charging model. In the long term, the PAYT charging model should be compatible with the levels of economic development and family education, and residents’ waste charges for PAYT should increase steadily.

The cells of colorectal cancer (CRC) in their microenvironment experience constant stress, leading to dysregulated activity in the tumor niche. As a result, cancer cells acquire alternative pathways in response to the changing microenvironment, posing significant challenges for the design of effective cancer treatment strategies. While computational studies on high-throughput omics data have advanced our understanding of CRC subtypes, characterizing the heterogeneity of this disease remains remarkably complex. Here, we present a novel computational Pipeline for Characterizing Alternative Mechanisms (PCAM) based on biclustering to gain a more detailed understanding of cancer heterogeneity. Our application of PCAM to large-scale CRC transcriptomics datasets suggests that PCAM can generate a wealth of information leading to new biological understanding and predictive markers of alternative mechanisms. Our key findings include: 1) A comprehensive collection of alternative pathways in CRC, associated with biological and clinical factors. 2) Full annotation of detected alternative mechanisms, including their enrichment in known pathways and associations with various clinical outcomes. 3) A mechanistic relationship between known clinical subtypes and outcomes on a consensus map, visualized by the presence of alternative mechanisms. 4) Several potential novel alternative drug resistance mechanisms for Oxaliplatin, 5-Fluorouracil, and FOLFOX, some of which were validated on independent datasets. We believe that gaining a deeper understanding of alternative mechanisms is a critical step towards characterizing the heterogeneity of CRC. The hypotheses generated by PCAM, along with the comprehensive collection of biologically and clinically associated alternative pathways in CRC, could provide valuable insights into the underlying mechanisms driving cancer progression and drug resistance, which could aid in the development of more effective cancer therapies and guide experimental design towards more targeted and personalized treatment strategies. The computational pipeline of PCAM is available in GitHub (https://github.com/changwn/BC-CRC).

Brain metastasis occurs in approximately 30% of patients with lung adenocarcinoma (LUAD) and is closely associated with poor prognosis, recurrence, and death. However, dynamic gene regulation and molecular mechanism driving LUAD progression remain poorly understood. In this study, we performed a comprehensive single-cell transcriptome analysis using data from normal, early stage, advanced stage, and brain metastasis LUAD. Our single-cell-level analysis reveals the cellular composition heterogeneity at different stages during LUAD progression. We identified stage-specific risk genes that could contribute to LUAD progression and metastasis by reprogramming immune-related and metabolic-related functions. We constructed an early advanced metastatic dysregulated network and revealed the dynamic changes in gene regulations during LUAD progression. We identified 6 early advanced (HLA-DRB1, HLA-DQB1, SFTPB, SFTPC, PLA2G1B, and FOLR1), 8 advanced metastasis (RPS15, RPS11, RPL13A, RPS24, HLA-DRB5, LYPLA1, KCNJ15, and PSMA3), and 2 common risk genes in different stages (SFTPD and HLA-DRA) as prognostic markers in LUAD. Particularly, decreased expression of HLA-DRA, HLA-DRB1, HLA-DQB1, and HLA-DRB5 refer poor prognosis in LUAD by controlling antigen processing and presentation and T cell activation. Increased expression of PSMA3 and LYPLA1 refer poor prognosis by reprogramming fatty acid metabolism and RNA catabolic process. Our findings will help further understanding the pathobiology of brain metastases in LUAD.

Nowadays, acute respiratory distress syndrome (ARDS) still has a high mortality rate, and the alleviation and treatment of ARDS remains a major research focus. There are various causes of ARDS, among which pneumonia and non-pulmonary sepsis are the most common. Trauma and blood transfusion can also cause ARDS. In ARDS, the aggregation and infiltration of neutrophils in the lungs have a great influence on the development of the disease. Neutrophils regulate inflammatory responses through various pathways, and the release of neutrophils through neutrophil extracellular traps (NETs) is considered to be one of the most important mechanisms. NETs are mainly composed of DNA, histones, and granuloproteins, all of which can mediate downstream signaling pathways that can activate inflammatory responses, generate immune clots, and cause damage to surrounding tissues. At the same time, the components of NETs can also promote the formation and release of NETs, thus forming a vicious cycle that continuously aggravates the progression of the disease. NETs are also associated with cytokine storms and immune balance. Since DNA is the main component of NETs, DNase I is considered a viable drug for removing NETs. Other therapeutic methods to inhibit the formation of NETs are also worthy of further exploration. This review discusses the formation and mechanism of NETs in ARDS. Understanding the association between NETs and ARDS may help to develop new perspectives on the treatment of ARDS.

GNBPB6, a beta-1,3-glucan-binding protein, was identified in the transcriptome of Aedes aegypti (A. aegypti) with dengue (DENV), Zika (ZIKV), and chikungunya viruses (CHIKV). In this study, we not only clarified that DENV2 and ZIKV regulate the changes in GNBPB6 expression but also identified the relationship of this gene with viral infections. The changes in GNBPB6 expression were quantified and showed a decrease in A. aegypti cells (Aag2 cells) at 2 dpi and 3 dpi and an increase at 4 dpi and 5 dpi (p < 0.05). A significant increase was observed only at 5 dpi after DENV2 infection. Subsequently, a GNBPB6 knockout (KO) cell line was constructed using the CRISPR/Cas9 system, and the DENV2 and ZIKV RNA copies, along with cell densities, were quantified and compared between the KO and wild type (WT) cells at different dpi. The result showed that DENV2 and ZIKV RNA copies were significantly increased in the KO cell line with no significant change in cell growth. Finally, DENV2 copies decreased after GNBPB6 was complemented in the KO. In conclusion, GNBPB6 knockout and complementation in Aag2 cells revealed that GNBPB6 can inhibit the replication of both DENV2 and ZIKV. These results contribute to subsequent research on mosquito–virus interactions.

Battery state of health (SOH) is a significant metric for evaluating battery life and predicting battery safety. Currently, SOH research is largely based on laboratory data, with a dearth of research on electric vehicle (EV) operating data. Due to the difficulty in obtaining complete charge data under EV operating conditions, this study presents a SOH estimation method utilizing deep network adaptation. First, a data-driven approach is employed to extract voltage, current, state of charge (SOC), and incremental capacity (IC) data features. To compensate for the lack of aging information in the EV operation data domain, transfer learning is employed to construct the SOH estimation model. Additionally, to resolve inconsistent data distribution between the source laboratory battery data domain and the target EV operation data domain, an adaptive layer is added to the network, and adaptation of deep network (ADN) is utilized to enhance the model’s performance. Finally, the model is validated using electric bus operational data. Results indicate that this model’s average Mean Absolute Error (MAE) is less than 3.0%, and, compared to support vector machine (SVM) regression and Gaussian Process Regression (GPR) algorithms, the MAE is reduced by 27.7% and 38.4%, respectively.

Human activities and climate change have significantly impacted the quantity and sustainable utilization of medicinal plants. Gentiana manshurica Kitagawa, a high-quality original species of Gentianae Radix et Rhizoma, has significant medicinal value. However, wild resources have experienced a sharp decline due to human excavation, habitat destruction, and other factors. Consequently, it has been classified as an Endangered (EN) species on the IUCN Red List and is considered a third-level national key-protected medicinal material in China. The effects of climate change on G. manshurica are not yet known in the context of the severe negative impacts of climate change on most species. In this study, an optimized MaxEnt model was used to predict the current and future potential distribution of G. manshurica. In addition, land use data in 1980, 2000, and 2020 were used to calculate habitat quality by InVEST model and landscape fragmentation by the Fragstats model. Finally, using the above-calculated results, the priority protection areas and wild tending areas of G. manshurica were planned in ZONATION software. The results show that the suitable area is mainly distributed in the central part of the Songnen Plain. Bio15, bio03, bio01, and clay content are the environmental variables affecting the distribution. In general, the future potential distribution is expected to show an increasing trend. However, the species is expected to become threatened as carbon emission scenarios and years increase gradually. At worst, the high suitability area is expected to disappear completely under SSP585-2090s. Combined with the t-test, this could be due to pressure from bio01. The migration trends of climate niche centroid are inconsistent and do not all move to higher latitudes under different carbon emission scenarios. Over the past 40 years, habitat quality in the current potential distribution has declined yearly, and natural habitat has gradually fragmented. Existing reserves protect only 9.52% of G. manshurica’s priority conservation area. To avoid extinction risk and increase the practicality of the results, we clarified the hotspot counties of priority protection area gaps and wild tending areas. These results can provide an essential reference and decision basis for effectively protecting G. manshurica under climate change.

Carbapenem-resistant Klebsiella pneumoniae (CRKP), particularly those with high virulence, cause invasive disease in clinical settings. An epidemiological investigation was conducted on the evolution, virulence, and antimicrobial resistance of CRKP isolates in two tertiary teaching hospitals in Jiangsu, China from November 2020 to December 2021. There were 31 different CRKP strains discovered. We performed whole genome sequencing (WGS) on 13 SHV, cmlv, and FosA6-producing CRKP to reveal molecular characteristics. Five ST15/ST11 isolates had CRISPR-Cas systems. By conjugation tests, KPC-2 can be transmitted horizontally to E. coil. A conjugative pHN7A8-related multi-resistance plasmid (KPC-2, blaCTX-M-65, blaTEM-1, fosA3, catII, and rmtB) was first discovered in CRKP clinical isolates. Using bacteriological testing, a serum killing assay, and an infection model with Galleria mellonella, three ST11-K64 KPC-2 generating carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP) were identified. These strains harbored a virulent plasmid and an IncFII-family pKPC/pHN7A8 conjugative plasmid, which led to hypervirulence and resistance. One of these CR-hvKPs, which co-harbored KPC-2, NDM-6, SHV-182, SHV-64, and blaCTX-M-122 genes, was first discovered. Importantly, this CR-hvKP strain also produced biofilm and had non-inferior fitness. The widespread use of ceftazidime/avibactam might provide this CR-hvKP with a selective advantage; hence, immediate action is required to stop its dissemination. Another important finding is the novel ST6136 in K. pneumoniae. Finally, the sterilization efficiency rates of Fe2C nanoparticles in CRKP were more than 98%. Furthermore, our novel antibacterial Fe2C nanoparticles may also provide a therapeutic strategy for infections.

Characterized by the accumulation of somatic mutations in blood cell lineages, clonal hematopoiesis of indeterminate potential (CHIP) is frequent in aging and involves the expansion of mutated hematopoietic stem and progenitor cells (HSC/Ps) that leads to an increased risk of hematologic malignancy. However, the risk factors that contribute to CHIP-associated clonal hematopoiesis (CH) are poorly understood. Obesity induces a proinflammatory state and fatty bone marrow (FBM), which may influence CHIP-associated pathologies. We analyzed exome sequencing and clinical data for 47,466 individuals with validated CHIP in the UK Biobank. CHIP was present in 5.8% of the study population and was associated with a significant increase in the waist-to-hip ratio (WHR). Mouse models of obesity and CHIP driven by heterozygosity of Tet2, Dnmt3a, Asxl1, and Jak2 resulted in exacerbated expansion of mutant HSC/Ps due in part to excessive inflammation. Our results show that obesity is highly associated with CHIP and that a proinflammatory state could potentiate the progression of CHIP to more significant hematologic neoplasia. The calcium channel blockers nifedipine and SKF-96365, either alone or in combination with metformin, MCC950, or anakinra (IL-1 receptor antagonist), suppressed the growth of mutant CHIP cells and partially restored normal hematopoiesis. Targeting CHIP-mutant cells with these drugs could be a potential therapeutic approach to treat CH and its associated abnormalities in individuals with obesity.

Soybean is an important grain and oil crop cultivated worldwide. Mepiquat chloride (DPC), a plant growth regulator, is widely used in cotton planting; however, its application in soybean remains rarely studied. Herein, we explored DPC regulation in soybeans using morphology, physiology, and proteomics analyses. Morphological and physiological analyses showed that DPC significantly reduced the plant height and shoot dry weight, promoted the growth of lateral roots in a specific concentration range, increased the activities of the leaf protective enzymes (superoxide dismutase and catalase), and decreased and increased malondialdehyde and total flavonoid contents, respectively. Proteomic analysis of leaves treated with 100 mg/L DPC revealed that multiple proteins related to plant growth and stress resistance were regulated after treatment. The key proteins involved in photosynthesis and cell wall elongation in the two varieties of soybean were significantly downregulated and those related to promoting lateral root growth and stress resistance were significantly upregulated. Overall, DPC inhibited shoot growth and photosynthesis in soybean but promoted lateral root growth, enhanced protective enzyme activity, and improved the ability of plants to resist abiotic stress. This study preliminarily determined the suitable DPC concentration for soybean spraying and provided a theoretical basis for its rational application.

IntroductionSoybean is the world’s most important cultivated crop, and drought can affect their growth and, eventually, yields. Foliar application of mepiquat chloride (MC) can potentially alleviate the damage caused by drought stress in plants; however, the mechanism of MC regulation of soybean drought response has not been studied.MethodsThis study investigated the mechanism of soybean drought response regulation by mepiquat chloride in two varieties of soybean, sensitive Heinong 65 (HN65) and drought-tolerant Heinong44 (HN44), under three treatment scenarios, normal, drought stress, and drought stress + MC conditions.Results and discussionMC promoted dry matter accumulation under drought stress, reduced plant height, decreased antioxidant enzyme activity, and significantly decreased malondialdehyde content. The light capture processes, photosystems I and II, were inhibited; however, accumulation and upregulation of several amino acids and flavonoids by MC was observed. Multi-omics joint analysis indicated 2-oxocarboxylic acid metabolism and isoflavone biosynthetic pathways to be the core pathways by which MC regulated soybean drought response. Candidate genes such as LOC100816177, SOMT-2, LOC100784120, LOC100797504, LOC100794610, and LOC100819853 were identified to be crucial for the drought resistance of soybeans. Finally, a model was constructed to systematically describe the regulatory mechanism of MC application in soybean under drought stress. This study fills the research gap of MC in the field of soybean resistance.

In this experiment, degreased kidney bean protein was used as raw material. The effects of different ultrasonic conditions on the physicochemical properties and antioxidant capacity of kidney bean protein were analyzed by solubility, emulsification and total antioxidant capacity. The results showed that compared with the untreated group, when the ultrasonic time was 20 min and the power was 400 W, the hydrolysis degree and solubility of kidney bean protein reached the maximum value, which increased from 3.34% to 20.10% and 56.83% to 79.63%, respectively. Foamability and foamability stability of kidney bean protein were significantly enhanced after ultrasonic treatment (P

Abstract Background Both Culex quinquefasciatus and Cx. pipiens molestus are sibling species within Cx. pipiens complex. Even though they are hard to distinguish morphologically, they have different physiological behaviors. However, the molecular mechanisms underlying these differences remain poorly understood. Methods Transcriptome sequencing was conducted on antennae of two sibling species. The identification of the differentially expressed genes (DEGs) was performed by the software DESeq2. Database for Annotation, Visualization and Integrated Discovery was used to perform GO pathway enrichment analysis. The protein–protein interaction (PPI) network was constructed with Cytoscape software. The hub genes were screened by the CytoHubba plugin and Degree algorithms. The identified genes were verified by quantitative real-time PCR. Results Most annotated transcripts (14,687/16,005) were expressed in both sibling species. Among 15 identified odorant-related DEGs, OBP10 was expressed 17.17 fold higher in Cx. pipiens molestus than Cx. quinquefasciatus. Eighteen resistance-related DEGs were identified, including 15 from CYP gene family and three from acetylcholinesterase, in which CYP4d1 was 86.59 fold more highly expressed in C. quinquefasciatus. Three reproductive DEGs were indentified with the expression from 5.01 to 6.55 fold. Among eight vision-related DEGs, retinoic acid receptor RXR-gamma in Cx. pipiens molestus group was more expressed with 214.08 fold. Among the 30 hub genes, there are 10 olfactory-related DEGs, 16 resistance-related DEGs, and four vision-related DEGs, with the highest score hub genes being OBP lush (6041148), CYP4C21 (6044704), and Rdh12 (6043932). The RT-qPCR results were consistent with the transcriptomic data with the correlation coefficient R = 0.78. Conclusion The study provided clues that antennae might play special roles in reproduction, drug resistance, and vision, not only the traditional olfactory function. OBP lush, CYP4C21, and Rdh12 may be key hints to the potential molecular mechanisms behind the two sibling species' biological differences. Graphical Abstract

Using defatted adzuki bean protein as raw material, the effects of different ultrasonic power and time on the physical and chemical properties and antioxidant function of adzuki bean protein were studied by using hydrolysis degree, foaming ability and total antioxidant capacity. After treatment with ultrasonic power of 400 W for 20 min, the hydrolysis degree and solubility of adzuki bean protein reached the maximum value, which increased from 3.39% to 21.30% and 46.77% to 79.63%, respectively. Emulsification and emulsification stability were significantly enhanced (P

EAAT2 is an amino acid transporter implicated in glutamate homeostasis in brain and therapy resistance of cancer cells. Here, the authors report cryo-EM structures and reveal inhibitory mechanisms via selective inhibitor WAY213613.

Abstract Circulating tumour DNA (ctDNA) has emerged as an ideal biomarker for the early diagnosis and prognosis of gastric cancer (GC). In this work, a pump-free, high-throughput microfluidic chip coupled with catalytic hairpin assembly (CHA) and hybridization chain reaction (HCR) as the signal cascade amplification strategy (CHA–HCR) was developed for surface-enhanced Raman scattering (SERS) assays of PIK3CA E542K and TP53 (two GC-related ctDNAs). The chip consisted of six parallel functional units, enabling the simultaneous analysis of multiple samples. The pump-free design and hydrophilic treatment with polyethylene glycol (PEG) realized the automatic flow of reaction solutions in microchannels, eliminating the dependence on external heavy-duty pumps and significantly improving portability. In the reaction region of the chip, products generated by target-triggered CHA initiated the HCR, forming long nicked double-stranded DNA (dsDNA) on the Au nanobowl (AuNB) array surface, to which numerous SERS probes (Raman reporters and hairpin DNA-modified Cu2O octahedra) were attached. This CHA–HCR strategy generated numerous active “hot spots” around the Cu2O octahedra and AuNB surface, significantly enhancing the SERS signal intensity. Using this chip, an ultralow limit of detection (LOD) for PIK3CA E542K (1.26 aM) and TP53 (2.04 aM) was achieved, and the whole process was completed within 13 min. Finally, a tumour-bearing mouse model was established, and ctDNA levels in mouse serum at different stages were determined. To verify the experimental accuracy, the gold-standard qRT–PCR assay was utilized, and the results showed a high degree of consistency. Thus, this rapid, sensitive and cost-effective SERS microfluidic chip has potential as an ideal detection platform for ctDNA monitoring.

Abstract Functioning and quality of life (QOL) are typical outcomes assessed in children and adolescents with major depressive disorder (MDD); however, meta-analytical evidence remains scarce. The aim of this meta-analysis was to assess functioning and QOL antidepressant outcomes in this population. Eight electronic databases (PubMed, Cochrane Library, Web of Science, Embase, CINAHL, PsycINFO, LILACS, and ProQuest Dissertation Abstracts) were searched for double-blind randomized controlled trials (RCTs) up to July 31, 2020. RCTs that compared antidepressants with placebo for treating functioning and QOL in children and adolescents with MDD were included. Primary outcomes were mean change scores of functioning and QOL scales from baseline to post-treatment. Subgroup and sensitivity analyses were conducted to examine whether results were affected by moderator variables (e.g., medication type, age, sample size, and treatment duration). From 7284 publications, we included 17 RCTs (all 17 assessed functioning and 4 assessed QOL outcomes) including 2537 participants. Antidepressants showed significant positive effects on functioning (standardized mean difference [SMD] = 0.17, 95% confidence interval [CI] = 0.09–0.25, p

Summary: Evaluation of autophagy flux could be challenging for muscle fibers due to the baseline expression of mCherry-EGFP-LC3 along the Z-line. We established a protocol to overcome this difficulty. We overexpress mChery-EGFP-LC3 in the FDB muscle of an adult mouse via electroporation. Then, we enzymatically digest FDB muscle to yield individual fibers for live cell imaging. Finally, we develop an ImageJ-based program to eliminate the baseline striation pattern and semi-automatically quantify autophagosomes (APs) and autolysosomes (ALs) for autophagy flux analysis. : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.