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Abstract Background Small cell lung cancer (SCLC) stands as one of the most lethal malignancies, characterized by a grim diagnosis and prognosis. The emergence of multi-drug resistance poses a significant hurdle to effective therapy. Although previous studies have implicated the long noncoding RNA LYPLAL1-DT in the tumorigenesis of SCLC, the precise role of the highly expressed LYPLAL1-DT in SCLC chemoresistance and the underlying mechanism remain inadequately understood. Methods cDDP-, VP-16- and PTX-resistant SCLC cells lines were established. The viabilities of SCLC cells were assessed by CCK-8 assay in vitro and xenograft tumor formation assay in vivo. Apoptosis was evaluated by FACS, Western blot and JC-1 fluorescence staining, while autophagy was explored via autophagic flux detection under confocal microscopy and autophagic vacuole investigation under transmission electron microscopy (TEM). The functional role and mechanism of LYPLAL1-DT were further investigated by gain- and loss-of-function assays in vitro. Furthermore, the therapeutic efficacy of the combination of venetoclax and HCQ with cDDP, VP-16 or PTX was evaluated by cell line, cell-derived xenograft (CDX) and patient-derived xenograft (PDX) mice model. Results Our findings revealed that LYPLAL1-DT is upregulated in chemoresistant SCLC cell lines. Gain- and loss-of-function assays demonstrated that LYPLAL1-DT impairs sensitivity to cDDP, VP-16, or PTX both in vitro and in vivo. Overexpression of LYPLAL1-DT significantly enhanced autophagy and inhibited apoptosis in SCLC cells. Further analyses, including RIP and RNA pull-down assays, revealed that LYPLAL1-DT promotes the expression of BCL2 by sponging miR-204-5p and is implicated in the assembly of the autophagy-specific complex (BECN1/PtdIns3K complex). Combining venetoclax and HCQ with cDDP, VP-16, or PTX effectively mitigated chemoresistance in SCLC cells and suppressed tumor growth in CDX and PDX models without inducing obvious toxic effects. Conclusions Our findings demonstrate that upregulation of LYPLAL1-DT sequesters apoptosis through the LYPLAL1-DT/miR-204-5p/BCL2 axis and promotes autophagy by facilitating the assembly of the BECN1/PtdIns3K complex, thereby mediating multi-drug resistance of SCLC. The triple combination of venetoclax, HCQ, in conjunction with cDDP, VP-16 or PTX overcomes refractory SCLC, shedding light on a potential therapeutic target for combating SCLC chemoresistance.

Abstract A radial basis function neural network PID controller under fuzzy rules (FUZZY-RBF-PID) was designed for the electro-hydraulic position servo system under the influence of uncertain factors such as load mutation, and load stiffness change. Firstly, the mathematical model of the system is established, and the frequency domain and time domain analysis of the system are carried out. Secondly, based on the analysis results, a radial basis function (RBF) neural network PID controller is designed, and fuzzy rules are innovatively used to adjust the learning rate of PID parameters in the RBF neural network learning algorithm in real time. Thirdly, the simulation results show that under the action of the FUZZY-RBF-PID controller, the unit step response of the system has high steady-state accuracy, fast response speed, and under the condition of large load stiffness, the system can recover to the steady-state value faster after being disturbed. At the same time, when the input signal is the sinusoidal signal of 10 HZ, the system under the action of the FUZZY-RBF-PID controller has no obvious phase lag phenomenon, and the tracking error is minimal. The proposed method can effectively improve the comprehensive performance of the electro-hydraulic position servo system under the influence of uncertain factors.

ABSTRACT Helicobacter pylori is a microaerophilic Gram-negative bacterium that resides in the human stomach and is classified as a class I carcinogen for gastric cancer. Numerous studies have demonstrated that H. pylori infection plays a role in regulating the function of host cells, thereby contributing to the malignant transformation of these cells. However, H. pylori infection is a chronic process, and short-term cellular experiments may not provide a comprehensive understanding of the in vivo situation, especially when considering the lower oxygen levels in the human stomach. In this study, we aimed to investigate the mechanisms underlying gastric cell dysfunction after prolonged exposure to H. pylori under hypoxic conditions. We conducted a co-culture experiment using the gastric cell line GES-1 and H. pylori for 30 generations under intermittent hypoxic conditions. By closely monitoring cell proliferation, migration, invasion, autophagy, and apoptosis, we revealed that sustained H. pylori stimulation under hypoxic conditions significantly influences the function of GES-1 cells. This stimulation induces epithelial-mesenchymal transition and contributes to the propensity for malignant transformation of gastric cells. To confirm the in vitro results, we conducted an experiment involving Mongolian gerbils infected with H. pylori for 85 weeks. All the results strongly suggest that the Nod1 receptor signaling pathway plays a crucial role in H. pylori-related apoptosis and autophagy. In summary, continuous stimulation by H. pylori affects the functioning of gastric cells through the Nod1 receptor signaling pathway, increasing the likelihood of cell carcinogenesis. The presence of hypoxic conditions further exacerbates this process.IMPORTANCEDeciphering the collaborative effects of Helicobacter pylori infection on gastric epithelial cell function is key to unraveling the development mechanisms of gastric cancer. Prior research has solely examined the outcomes of short-term H. pylori stimulation on gastric epithelial cells under aerobic conditions, neglecting the bacterium’s nature as a microaerophilic organism that leads to cancer following prolonged stomach colonization. This study mimics a more genuine in vivo infection scenario by repeatedly exposing gastric epithelial cells to H. pylori under hypoxic conditions for up to 30 generations. The results show that chronic exposure to H. pylori in hypoxia substantially increases cell migration, invasion, and epithelial-mesenchymal transition, while suppressing autophagy and apoptosis. This highlights the significance of hypoxic conditions in intensifying the carcinogenic impact of H. pylori infection. By accurately replicating the in vivo gastric environment, this study enhances our comprehension of H. pylori’s pathogenic mechanisms in gastric cancer.

Abstract We use an automated research platform combined with machine learning to assess and understand the resilience against air and light during production of organic photovoltaic (OPV) devices from over 40 donor and acceptor combinations. The standardized protocol and high reproducibility of the platform results in a dataset of high variety and veracity to deploy machine learning models to encounter links between stability and chemical, energetic, and morphological structure. We find that the strongest predictor for air/light resilience during production is the effective gap Eg,eff which points to singlet oxygen rather than the superoxide anion being the dominant agent in degradation under processing conditions. A similarly good prediction of air/light resilience can also be achieved by considering only features from chemical structure, that is, information which is available prior to any experimentation.

Abstract Background The Mongolian gerbil is an excellent laboratory animal for preparing the cerebral ischemia model due to its inherent deficiency in the circle of Willis. However, the low incidence and unpredictability of symptoms are caused by numerous complex variant types of the circle. Additionally, the lack of an evaluation system for the cerebral ischemia/reperfusion (I/R) model of gerbils has shackled the application of this model. Methods We created a symptom‐oriented principle and detailed neurobehavioral scoring criteria. At different time points of reperfusion, we analyzed the alteration in locomotion by rotarod test and grip force score, infarct volume by triphenyltetrazolium chloride (TTC) staining, neuron loss using Nissl staining, and histological characteristics using hematoxylin–eosin (H&E) straining. Results With a successful model rate of 56%, 32 of the 57 gerbils operated by our method harbored typical features of cerebral I/R injury, and the mortality rate in the male gerbils was significantly higher than that in the female gerbils. The successfully prepared I/R gerbils demonstrated a significant reduction in motility and grip strength at 1 day after reperfusion; formed obvious infarction; exhibited typical pathological features, such as tissue edema, neuronal atrophy and death, and vacuolated structures; and were partially recovered with the extension of reperfusion time. Conclusion This study developed a new method for the unilateral common carotid artery ligation I/R model of gerbil and established a standardized evaluation system for this model, which could provide a new cerebral I/R model of gerbils with more practical applications.

Abstract The scanning vibration mirror system drives the scanning mirror fixed to it through the oscillation of the motor shaft, so as to control the reflected light to form a dynamic variable light path. The vibration mirror scanning system has higher controllability than the fixed optical path system and has been widely used.In this dissertation, after establishing the models of the core components of the scanning vibration mirror system, the mathematical model of the whole system is established.On this basis, simulation and theoretical analysis show that the system has some shortcomings, such as small bandwidth, low dynamic tracking accuracy, and the comprehensive dynamic performance of the system is easily affected by the input of external interference branches. A series correction controller and three closed-loop controller are designed for the above problems, respectively, and the control effects of the two controllers on the scanning vibration mirror system are studied through simulation experiments. By comparing the output response results of the system under the action of sinusoidal signals of different frequencies, it can be seen that the comprehensive effect of the three closed-loop controllers is better. Under the action of step signals, the overshoot of the three closed-loop correction controller correction system is 21.5% higher than that of the series controller correction system, the adjustment time is 82.7% less, and the steady-state error is significantly smaller. Therefore, it indicates that the three closed-loop correction system has good rapidity and steady-state accuracy.

Aflatoxin B1 (AFB1) contamination in food and feed is a global health and economic threat, necessitating the immediate development of effective strategies to mitigate its negative effects. This study focuses on the isolation and characterization of Enterococcus faecium HB2-2 (E. faecium HB2-2) as a potent AFB1-degrading microorganism, using morphological observation, biochemical profiling, and 16S rRNA sequence analysis. An incubation of E. faecium HB2-2 at 32 °C for 96 h in a pH 10 nutrient broth (NB) medium resulted in a remarkable degradation rate of 90.0% for AFB1. Furthermore, E. faecium HB2-2 demonstrated 82.9% AFB1 degradation rate in the peanut meal, reducing AFB1 levels from 105.1 to 17.9 μg/kg. The AFB1 degradation ability of E. faecium HB2-2 was found to be dependent on the fermentation supernatant. The products of AFB1 degradation by E. faecium HB2-2 were analyzed by liquid chromatography–mass spectrometry (LC-MS), and a possible degradation mechanism was proposed based on the identified degradation products. Additionally, cytotoxicity assays revealed a significant reduction in the toxicity of the degradation products compared to the parent AFB1. These findings highlight the potential of E. faecium HB2-2 as a safe and effective method for mitigating AFB1 contamination in food and feed.

BackgroundThe effect of different non-cardiac surgical methods on islet and renal function remains unclear. We conducted a preliminary investigation to determine whether different surgical methods affect islet function or cause further damage to renal function.MethodsIn this prospective cohort study, the clinical data of 63 adult patients who underwent non-cardiac surgery under general anesthesia were evaluated from February 2019 to January 2020. Patients were divided into the abdominal surgery group, the laparoscopic surgery group, and the breast cancer surgery group. The primary outcome was the difference between the effects of different surgical methods on renal function.ResultsIslet and renal function were not significantly different between the groups. The correlation analysis showed that hematocrit (HCT) and hemoglobin (HB) were negatively correlated with fasting plasma glucose (FPG) (p

Conclusions: Our study, which may be considered a pilot investigation, suggests that the interaction of adipocytokines and inflammation factors in different adipose depots could play diverse roles in the development of diabetes or obesity.

In the current computing environment, the significance of distributed heterogeneous systems has gained prominence. The research on scheduling problems in distributed systems that consider energy consumption has garnered substantial attention due to its potential to enhance system stability, achieve energy savings, and contribute to environmental preservation. However, efficient scheduling in such systems necessitates not only the consideration of energy consumption but also the ability to adapt to the dynamic nature of the system. To tackle these challenges, we propose an online energy-aware scheduling algorithm for deadline-constrained applications in distributed heterogeneous systems, leveraging dynamic voltage and frequency scaling (DVFS) techniques. First, the algorithm models the continuously arriving applications and heterogeneous processors and proposes a novel task-sorting method to prioritize tasks, ensuring that more applications are completed within their respective deadlines. Second, the algorithm controls the selection range of processors based on the task’s subdeadline and assigns the task to the processor with the minimum energy consumption. Through experiments conducted with randomly generated applications, our approach consistently exhibits superior performance when compared to similar scheduling algorithms.

Abstract Acute kidney injury (AKI) is one of the serious clinical syndromes with high morbidity and mortality. Despite substantial progress in understanding the mechanism of AKI, no effective drug is available for treatment or prevention. In this study, we identified that a ligand-activated transcription factor aryl hydrocarbon receptor (AhR) was abnormally increased in the kidneys of cisplatin-induced AKI mice or tubular epithelial TCMK-1 cells. The AhR inhibition by BAY2416964 and tubular conditional deletion both alleviated cisplatin-induced kidney dysfunction and tubular injury. Notably, inhibition of AhR could improve cellular senescence of injured kidneys, which was indicated by senescence-associated β-galactosidase (SA-β-gal) activity, biomarker p53, p21, p16 expression, and secretory-associated secretory phenotype IL-1β, IL-6 and TNFα level. Mechanistically, the abnormal AhR expression was positively correlated with the increase of a methyltransferase EZH2, and AhR inhibition suppressed the EZH2 expression in cisplatin-injured kidneys. Furthermore, the result of ChIP assay displayed that EZH2 might indirectly interact with AhR promoter region by affecting H3K27me3. The direct recruitment between H3K27me3 and AhR promoter is higher in the kidneys of control than that of cisplatin-treated mice, suggesting EZH2 reversely influenced AhR expression through weakening H3K27me3 transcriptional inhibition on AhR promoter. The present study implicated that AhR and EZH2 have mutual regulation, which further accelerated tubular senescence in cisplatin-induced AKI. Notably, the crucial role of AhR is potential to become a promising target for AKI.

Highlights 4-Terminal inorganic perovskite/organic tandem solar cells were made by using semi-transparent inorganic perovskite solar cells and narrow-bandgap organic solar cells as the sub-cells, yielding a power conversion efficiency of 22.34%, which is the highest efficiency for inorganic perovskite/organic tandem solar cells. Inorganic perovskite solar cells made by drop-coating (self-spreading) gave much higher power conversion efficiency than the cells made by spin-coating, enabling perovskite/organic tandem solar cells with higher efficiency.

Long operational stability is essential to commercialisation of organic solar cells. Here, the authors investigate the thermal degradation of inverted photovoltaic devices based on PM6:Y6 non-fullerene system to reveal that trap-induced transport resistance is primarily responsible for the drop in fill factor.

Abstract Long noncoding RNAs (lncRNAs) are involved in diabetes related diseases. However, the role of lncRNAs in the pathogenesis of type 2 diabetes with macrovascular complication (DMC) has seldomly been recognized. This study screened lncRNA profiles of leukocytes from DMC patients and explored protective role of lncRNA LYPLAL1-DT in endothelial cells (EC) under high glucose (HG) and inflammatory conditions (IS). Between DMC and healthy controls, 477 differential expression lncRNAs (DE-lncRNAs) were identified. The enrichment and pathway analysis showed that most of the DE-lncRNAs belonged to inflammatory, metabolic, and vascular diseases. A total of 12 lncRNAs was validated as significant DE-lncRNAs in expanding cohorts. Furthermore, these DE-lncRNAs were shown to be significantly related to hypoxia, HG, and IS in EC, especially lncRNA LYPLAL1-DT. LYPLAL1-DT overexpression results in the promotion of the proliferation, and migration of EC, as well as an elevation of autophagy. Overexpressed LYPLAL1-DT reduces the adhesion of monocytes to EC, boosts anti-inflammation, and suppresses inflammatory molecules secreted in the medium. Mechanistically, LYPLAL1-DT acts as competing endogenous RNA (ceRNA) by downregulating miR-204-5p, therefore enhancing SIRT1 and protecting EC autophagy function; thus, alleviating apoptosis. Finally, exosome sequencing revealed LYPLAL1-DT expression was 4 times lower in DMC cells than in healthy samples. In general, we identified LYPLAL1-DT having protective effects on EC as ceRNA mediated through the miR-204-5p/SIRT1 pathway. Therefore, it inhibits the autophagy of EC as well as modulating systemic inflammation. This approach could be regarded as a new potential therapeutic target in DMC.

Objectives: This study aimed to develop a self-management behavior questionnaire for Chinese enterostomy patients and examine its reliability and validity. Methods: Guided by the theory of self-management, an initial questionnaire was generated through literature review, group meetings, and two rounds of an expert consultation. Finally, the reliability and validity of the questionnaire were validated through a questionnaire survey of 200 enterostomy patients were selected from the Affiliated Hospital of Medical University from June 2016 to March 2017. Results: The content validity index was 0.80–1.00. The exploratory factor analysis yielded a five-factor (dietary behavior, psychosocial behavior, symptom management behavior, medical compliance behavior, information management behavior), consisting of 40 items. The cumulative variance contribution rate was 65.42%. The Cronbach’s α coefficient for the total questionnaire was 0.972, and for the five factors ranged from 0.797 to 0.939, indicating a good internal consistency. The test-retest reliability was 0.867 (P

An increasing number of railway tunnels are afflicted with railway tunnel lining diseases. Through on-site detection of lining diseases in double-track railway tunnels, this paper analyzed its causative factors and developed a section steel arch frame lining reinforcement. Through a simulation of its mechanical performance, both the steel plate and concrete met the tensile strength code requirements for railway tunnel design (TB 10003-2016). It effectively repaired the damage from lining diseases under narrow-site and short maintenance “window” time conditions without affecting the normal operation of catenary and power supply facilities. This reinforcement has great practical significance and broad application prospects.

According to the principle of system identification, the least squares algorithm and MATLAB system identification toolbox is used to identify the model of the test bench of the vibration mirror swing scan system with the step signal and the vibration mirror swing-sweep angular displacement as the input and output quantities. Taking the identification model as the object, a sliding mode variable structures composite controller of fuzzy switching gain adjustment is designed. In the controller, according to the actual conditions achieved by the sliding mode, the switching gain is effectively estimated, so as to eliminate the interference of uncertain factors and high-frequency vibration. At the same time, the sliding mode function and sliding mode controller of the system needs to be designed. The switching hyperplane of the system is designed using the fuzzy switching method and the desired dynamic characteristics of the system, to ensure the smooth transition of the system state from outside the hyperplane to the convergence of the switching hyperplane. The simulation results show that: the new composite control method eliminates the shortcomings of PD series control, improves the response speed and tracking accuracy of the vibration mirror swing scan system, and improves the overall performance of the system. And it has a strong ability to inhibit the adverse effects caused by changes in the parameters of the controlled object.

Abstract Background Microsatellite instability (MSI) is a biomarker for better outcomes in colorectal cancer (CRC). However, this conclusion is controversial. In addition, MSs can be a useful marker for loss of heterozygosity (LOH) of genes, but this finding has not been well studied. Here, we aimed to clarify the predictive value of MSI/LOH within tumor-related genes in CRC. Methods We detected MSI/LOH of MSs in tumor-related genes and the Bethesda (B5) panel by STR scanning and cloning/sequencing. We further analyzed the relationship between MSI/LOH status and clinical features or outcomes by Pearson’s Chi-square test, Fisher’s exact test and the Kaplan–Meier method. Results The findings indicated that the MSI rates of B5 loci were all higher than those of loci in tumor-related genes. Interestingly, MSI/LOH of 2 loci in the B5 panel and 12 loci in tumor-related genes were associated with poorer outcomes, while MSI/LOH of the B5 panel failed to predict outcomes in CRC. MSI of BAT25, MSI/LOH of BAT26 and MSI of the B5 panel showed closer relationships with mucinous carcinoma. In addition, LOH-H of the B5 panel was associated with increased lymphatic metastasis. Conclusions In summary, MSI/LOH of certain loci or the whole panel of B5 is related to clinical features, and several loci within tumor-related genes showed prognostic value in the outcomes of CRC.

ObjectivesThis study aimed to develop a score including novel putative predictors for predicting the risk of sICH and outcomes after thrombolytic therapy with intravenous (IV) recombinant tissue-type plasminogen activator (r-tPA) in acute ischemic stroke patients.MethodsAll patients with acute ischemic stroke treated with IV r-tPA at three university-based hospitals in Chongqing, China, from 2014 to 2019 were retrospectively studied. Potential risk factors associated with sICH (NINDS criteria) were determined with multivariate logistic regression, and we developed our score according to the magnitude of logistic regression coefficients. The score was validated in another independent cohort. Area under the receiver operating characteristic curve (AUC-ROC) was used to assess the performance of the score. Calibration was evaluated using the Hosmer–Lemeshow goodness-of-fit method.ResultsThe SON2A2 score (0 to 8 points) consisted of history of smoking (no = 1, yes = 0, β = 0.81), onset-to-needle time (≥3.5 = 1,10 = 2, ≤10 = 0, β = 1.22), neutrophil percentage (≥80.0% = 1, 11 = 0, β = 1.30), and age (>65 years = 1, ≤65 years = 0, β = 0.89). The SON2A2 score was strongly associated with sICH (OR 1.98; 95%CI 1.675–2.34) and poor outcomes (OR 1.89; 95%CI 1.68–2.13). AUC-ROC in the derivation cohort was 0.82 (95%CI 0.77–0.86). Similar results were obtained in the validation cohort. The Hosmer–Lemeshow test revealed that predicted and observed event rates in derivation and validation cohorts were very close.ConclusionThe SON2A2 score is a simple, efficient, quick, and easy-to-perform scale for predicting the risk of sICH and outcome after intravenous r-tPA thrombolysis within 4.5 h in patients with ischemic stroke, and risk assessment using this test has the potential for early and personalized management of this disease in high-risk patients.

BackgroundNumerous genetic studies have shown that genes are related to the pathogenesis of coronary heart disease (CHD). The main aim of this study was to confirm whether fibronectin type III domain containing 1 (FNDC1) polymorphisms correlate with the risk of CHD.MethodsIn this study, in order to assess the association between three FNDC1 single nucleotide polymorphisms (SNPs) and the risk of CHD, we conducted a case-control study involving 630 patients with CHD and 568 healthy controls using Agena MassARRAY (Agena Bioscience, San Diego, CA, USA). Genotype distribution in case and control groups was analyzed by Chi square test. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by logistic regression models adjusted for age, sex, smoking, and alcohol consumption to assess the correlation between SNPs and CHD risk.ResultsOur results indicated that FNDC1-rs420137, -rs386360, and -rs7763726 played important roles in enhancing the risk of CHD. Subgroup analysis revealed that rs420137 increased the susceptibility to CHD in males, smokers, and patients aged ≤62 years. Rs360 had an increased risk of CHD in males, patients at aged ≤62 years, smokers, and non-drinkers. Furthermore, the association of rs7763726 with increased CHD risk was also observed in males, patients aged ≤62 years, smokers, and drinkers. Last but not least, these three SNPs we selected were protective factors against hypertension in CHD individuals.ConclusionOur research suggest that FNDC1-rs420137, -rs386360, and -rs7763726 variants may be regarded as novel biomarkers for predicting CHD risk and other specific mechanisms of action of CHD need to be further studied.

Organizational ambidexterity has been employed in the study of international business. Existing studies advocate an ambidextrous internationalization strategy for multinational enterprises in emerging markets (EM MNEs). However, the performance effect and moderating mechanism of international ambidexterity have not been fully explored yet. This study expands the combinative view of organizational learning and institutional perspective, and examines the impact and moderating mechanism of international ambidexterity on firm performance based on 387 Chinese multinationals. This study adopts the questionnaire survey method to obtain the research sample and tests the relationships among variables through multiple regression analysis. The conclusions indicate that both the balanced and combined dimensions of international ambidexterity positively impact innovation performance. Additionally, EM MNEs operating in countries with well-developed institutions are more innovative than those operating in countries with underdeveloped institutions. This study not only promotes the development of internationalization and institutional theories but also guides managers of EM MNEs to formulate internationalization strategies.

Current view of the impact of A-site cation on the stability of perovskite materials and devices is derived from accelerated ageing tests at high temperature, which is beyond normal operation range. Here, the authors reveal the great impact of ageing condition on assessing the photothermal stability of mixed-cation perovskites using high-throughput robot system coupled with machine learning.

Cardiovascular diseases (CVD) are the leading cause of death worldwide, wherein myocardial infarction (MI) is the most dangerous one. Promoting angiogenesis is a prospective strategy to alleviate MI. Our previous study indicated that profilin 2 (PFN2) may be a novel target associated with angiogenesis. Further results showed higher levels of serum PFN2 and exosomal PFN2 in patients, mice, and pigs with MI. In this study, we explored whether PFN2 and endothelial cell (EC)-derived exosomal PFN2 could increase angiogenesis and be beneficial for the treatment of MI. Serum PFN2, exosomes, and exosomal PFN2 were elevated in rats with MI. PFN2 and exosomes from PFN2-overexpressing ECs (OE-exo) enhanced EC proliferation, migration, and tube formation ability. OE-exo also significantly increased the vessel number in zebrafish and protected the ECs from inflammatory injury. Moreover, OE-exo-treated mice with MI showed improvement in motor ability, ejection fraction, left ventricular shortening fraction, and left ventricular mass, as well as increased vessel numbers in the MI location, and decreased infarction volume. Mechanistically, PI3K might be the upstream regulator of PFN2, while ERK might be the downstream regulator in the PI3K-PFN2-ERK axis. Taken together, our findings demonstrate that PFN2 and exosomal PFN2 promote EC proliferation, migration, and tube formation through the PI3K-PFN2-ERK axis. Exosomal PFN2 may be a valuable target in the repair of MI injury via angiogenesis.

Previous studies suggest that in people with major depressive disorder (MDD), there exists a perturbation of the normal balance between the excitatory and inhibitory neurotransmitter systems in the visual cortex, indicating the possibility of altered visual cortical excitability. However, investigations into the neural activities of the visual cortex in MDD patients yielded inconsistent findings. The present study aimed to evaluate the visual cortical excitability utilizing a paired-pulse stimulation paradigm in patients with MDD and to access the paired-pulse behavior of recording visual evoked potentials (VEPs) as a marker of MDD. We analyzed the amplitudes of VEPs and paired-pulse suppression (PPS) at four different stimulus onset asynchronies (SOAs) spanning 93 ms to 133 ms. Further, the relationship between PPS and the symptom severity of depression was investigated using Spearman's correlation. We found that, whereas the first VEP amplitude remained unchanged, the second VEP amplitude was significantly higher in the MDD group compared to the healthy controls. As a result, the amplitude ratio (second VEP amplitude/first VEP amplitude) increased, indicating reduced PPS and thus increased excitability in the visual cortex. Moreover, we found the amplitude ratios had a significantly positive correlation with the symptom severity of depression in MDD, indicating a clinically useful biomarker for MDD. Our findings provide new insights into the changes in the excitation-inhibition balance of visual cortex in MDD, which could pave the way for specific clinical interventions.

Non-fullerene acceptors are crucial for realising efficient charge transport and high power conversion in organic solar cells, yet the relationship of molecular packing and carrier transport is not well-understood. Here, the authors study the effect of side-chain engineering on the backbone assembly and the corresponding charge transport pathway.

Y6, as a non-fullerene acceptor for organic solar cells, has attracted intensive attention because of the low voltage loss and high charge generation efficiency. Here, Zhang et al. find that the delocalization of exciton and electron wavefunction due to strong π-π packing of Y6 is the key for the high performance.

As one of the latest market-oriented resource provisioning paradigms, cloud computing has been widely adopted by a growing number of consumers due to its powerful computing ability and storage ability. Although cloud computing can achieve effective cost reduction and convenience enhancement in the development of large-scale applications, it results in a complex cost optimization problem for data-dependent tasks represented by a workflow. All tasks in a workflow should be scheduled according to a proper strategy such that the cost is minimized and the precedence constraints and timing requirements are satisfied. In this paper, we study the cost optimization problem of deadline constrained workflows on cloud computing, and propose two list scheduling algorithms named Look-back Workflow Scheduling (LBWS) and Structure Aware Workflow Scheduling (SAWS) to solve the problem. LBWS distributes the deadline over the workflow as sub-deadlines to tasks in different levels, and schedules the tasks according to their priorities to the resources which meet their sub-deadlines and the best time-cost trade off requirements. Compared with LBWS, SAWS considers tasks allocated to the same level at a time and provisions resources with minimum cost to these tasks. Experiments on scientific workflow applications with different data and computational characteristics are conducted to show that, the proposed approaches can achieve better performance in terms of success rate and monetary cost.

In order to realize rapid service-oriented construction of resources and efficient supply-demand matching in avionics systems, an ontology-based resource modeling and matching framework in avionics systems is proposed. First, this paper constructs a hierarchical resource organization framework based on virtual resource pool, covering dispersed and heterogeneous avionics resources and shielding the differences and diversity of resources; next, introduces ontology technology into resource modeling and encapsulates resources as services using the idea of “resource as a service,” facilitating the access and control of resources; in addition, proposes a matching framework which takes into account the energy consumption, in which it firstly tries to find a list of resources which can meet task requirements by a stepwise intelligent matching strategy based on semantic similarity, and the resources in the list will then be sorted according to the energy consumption. Finally, a radar detection case is taken to demonstrate that the proposed model and method are feasible and effective.

Long noncoding RNAs (lncRNAs) have been reported to have multiple functions and can be used as markers of various diseases, including diabetes. This study was conducted to determine the lncRNA profile in leukocytes from patients with type 2 diabetes (T2D). Differential expression of lncRNAs in T2D and type 1 diabetes (T1D) was also examined. RNA sequencing was performed in a critically grouped sample of leukocytes from T2D patients and healthy persons. A total of 845 significantly differentially expressed lncRNAs were identified, with 260 downregulated and 585 upregulated lncRNAs in T2D. The analysis of functions of DE-lncRNA and constructed co-expression networks (CNC) showed that 21 lncRNAs and 117 mRNAs harbored more than 10 related genes in CNC. Fourteen of 21 lncRNAs were confirmed to be significantly differentially expressed was detected by qPCR between the T2D and control validation cohorts. We also identified a panel of 4 lncRNAs showing significant differences in expression between T1D and T2D. Collectively, hundreds of novel DE-lncRNAs we identified in leukocytes from T2D patients will aid in epigenetic mechanism studies. Fourteen confirmed DE-lncRNAs can be regarded as diagnostic markers or regulators of T2D, including 4 lncRNAs that chould distinguish T1D and T2D in clinical practice to avoid misdiagnosis.

Stroke is a brain system disease with a high fatality rate and disability rate. About 80% of strokes are ischemic strokes. Cerebral ischemia-reperfusion injury (CIRI) caused by ischemic stroke seriously affects the prognosis of stroke patients. The purpose of this study is to investigate the effect of sufentanil (SUF) on CIRI model rats. We used middle cerebral artery occlusion (MCAO) to make the CIRI model in rats and monitored region cerebral blood flow (rCBF) to ensure that blood flow was blocked and recanalized. We used ELISA and RT-PCR to detect the expression of inflammatory factors in rat serum and brain tissue. In addition, we detected the expression of metalloproteinase (MMP) 2, MMP9 and collagen IV in brain tissues and performed Evans blue (EB) assay to determine the permeability of the blood-brain barrier (BBB). Finally, we clarified the apoptosis of brain tissue through the TUNEL staining and the detection of caspase3, Bcl2 and Bax. Various concentrations of SUF, especially 5, 10 and 25 μg/kg of SUF, all alleviated the infarct size, neurological function and brain edema of MCAO rats. SUF pretreatment also effectively reduced the expression of inflammatory cytokines in MCAO rats, including interleukin (IL)-1β, IL-4, IL-6, IL-8, IL-10 and tumor necrosis factor (TNF)-α. In addition, SUF also inhibited MMP2 and MMP9 and promoted the expression of collagen IV, indicating that SUF attenuated the destruction of the BBB. SUF also inhibited caspase3 and Bax rats and promoted Bcl2 in MCAO rats, thus inhibiting cell apoptosis. SUF pretreatment effectively improved the neurological function and cerebral infarction of MCAO rats, inhibited excessive inflammation in rats, protected the BBB, and inhibited cell apoptosis in brain tissue.

The innovation performance of the manufacturing industry in the Wuhan city circle is evaluated based on the relevant data from 2018 to 2020 in 9 cities of Hubei Province within the Wuhan city circle using the DEA-BCC model, the DEA-Malmquist index method, and the location quotient method. This article measures the agglomeration level of innovation elements in the Wuhan city circle, constructs a performance evaluation index system including two input indicators: R&D expenditure and R&D personnel, and two output indicators: new product sales revenue and number of patent applications; evaluates the innovation performance of 27 manufacturing industries in the Wuhan city circle from five aspects: technical efficiency change (effch), technical progress change (techch), pure technical efficiency change (pech), scale efficiency change (sech), and total factor productivity change (tfpch), and compares and analyzes the innovation performance of Wuhan, Xianning, Xiantao, and Tianmen using the DEA-BCC model and DEAP 2.1. The results show that the agglomeration level of talent elements in the Wuhan city circle is between 0.24 and 1.75, and the agglomeration level of capital elements is between 0.23 and 1.52. The differences between regions are obvious, the degree of coordination is low, and the radiation effect of Wuhan is insufficient. The average value of technological progress is 1.274, which is vital to enhance the innovation performance of the Wuhan manufacturing industry. The technical efficiency dropped by 65%, but the total factor productivity fell only 13%, indicating that the technical efficiency value is not the main factor affecting the innovation performance of Wuhan. The innovation performance of high-tech and high-value-added industries such as computer, communication, and other electronic equipment manufacturing industries is relatively high, while the innovation performance of low-tech and low-value-added industries such as agricultural and sideline food processing industry and textile industry is relatively low. The innovation performance of Xianning, Xiantao, and Tianmen is higher, while the relative technological inefficiency caused by the low-scale efficiency value adversely affects the innovation performance of Wuhan. The results indicate that increasing the scale of manufacturing innovation investment can effectively enhance the innovation performance of the Wuhan city circle manufacturing industry.

Summary: Converting checkpoint inhibitor (CPI)-resistant individuals to being responsive requires identifying suppressive mechanisms. We identify TREM2+ tumor-associated macrophages (TAMs) as being correlated with exhausted CD8+ tumor-infiltrating lymphocytes (TILs) in mouse syngeneic tumor models and human solid tumors of multiple histological types. Fc domain-enhanced anti-TREM2 monoclonal antibody (mAb) therapy promotes anti-tumor immunity by elimination and modulation of TAM populations, which leads to enhanced CD8+ TIL infiltration and effector function. TREM2+ TAMs are most enriched in individuals with ovarian cancer, where TREM2 expression corresponds to disease grade accompanied by worse recurrence-free survival. In an aggressive orthotopic ovarian cancer model, anti-TREM2 mAb therapy drives potent anti-tumor immunity. These results highlight TREM2 as a highly attractive target for immunotherapy modulation in individuals who are refractory to CPI therapy and likely have a TAM-rich tumor microenvironment.

Avionics systems, which determine the performance, stability, and safety of aircraft, are a crucial part of aircraft. With the rapid development of the aviation industry, there are many serious problems in the process of the traditional simulation and verification of avionics systems, especially in the aspects of poor reusability of the hardware and software, poor real-time data interaction, and the high cost of development. In order to solve these problems, a simulation and verification platform for avionics systems based on the Future Airborne Capability Environment (FACE) architecture has been designed by using component and memory database technology. First, a general architecture is designed by referencing the FACE architecture, which allows flexible access to software and hardware resources of avionics systems. Second, the key technologies involved in the platform are described in detail, including scheduling management, communication management, and configuration management, which provide technical support for the simulation and verification of avionics systems. Finally, the simulation and verification environment of avionics systems is established, which realizes data interaction and management of various models, and improves the efficiency of the development and implementation of avionics systems.

The stability of an open-pit slope is an extremely important factor related to the safe production of an open-pit mine. It is the first safety technical problem encountered and should be solved in the process of mine design and production. By the means of an engineering geology and hydrogeological investigation of the waste dump area of the Nayuan open-pit coal mine and numerical simulation research, this paper analyzes and studies the slope stability of the stope and waste dump of the Nayuan open-pit coal mine in detail and puts forward measures such as slope prevention and automatic monitoring to achieve the goal of protecting the slope of the stope and waste dump and the surrounding environment. The main research results are as follows: (1) The geotechnical physical and mechanical indexes of stope and waste dump are collected and analyzed, and the geotechnical mechanical indexes in this report were determined, which basically meet the requirements of slope stability analysis. (2) The limit equilibrium method and finite element method were used to analyze and evaluate the current slope stability of the Nayuan open-pit coal mine. It was concluded that the foundation of the waste dump is basically stable, and the potential landslide modes of the slope are arc-shaped sliding surface and arc-shaped straight-line sliding surface. The numerical simulation and checking results showed that the current stope and waste dump slope are stable. (3) According to the analysis and evaluation results of slope stability, feasible slope prevention measures are put forward. The research results are of great significance to the safety of important facilities in open-pit mines and provide a basis for the design and safety implementation of open-pit slope engineering.

Abstract The Mongolian gerbil has been widely used in many research fields and has been reported to be a diurnal laboratory animal. The circadian rhythmicity of these gerbils was investigated in the present study by measuring two hormones that show daily oscillations, cortisol and ACTH, in serum using ELISA kits. The levels of the two hormones were highest at 8:00 am and their rhythmic changes were similar to those in humans. In addition, the influence of stress of handling and blood collection on the physiological parameters of the gerbils was examined. After adaptation to handling for 1 week, some serum parameters in the animals changed. Handling and blood collection did not impact significantly on the following parameters: creatine kinase (CK), lactate dehydrogenase (LD), alanine aminotransferase (ALT), aspartate transaminase (AST), blood urea nitrogen (BUN), and albumin (ALB). However, blood glucose (GLU), total protein (TP) and globulin (GLB) significantly increased while creatinine (CRE) and albumin/globulin (A/G) significantly decreased after adaptation. This work further confirms that the Mongolian gerbil is a diurnal animal and also indicates that a suitable adaptation procedure is necessary for getting reliable results when performing experiments using these animals.

In situ stress is the natural stress existing in the stratum without engineering disturbance, also known as initial stress, absolute stress, or original rock stress. In order to master the in situ stress of the Manmushu Tunnel and Mamo Tunnel in Southwest China, the casing stress solution method is adopted in this paper. Through the combination of field measurement and laboratory test, the basic data such as initial strain during stress relief are collected, and the in situ stress values are analyzed in combination with indoor temperature compensation test, confining pressure calibration, and relevant rock mechanics tests. The measured results show the following: (1) the maximum horizontal principal stress σh.max ranges from 6.44 MPa to 19.74 MPa; the vertical principal stress σv ranges from 4.11 MPa to 13.48 MPa; and the minimum horizontal principal stress ranges from 4.32 MPa to 11.22 MPa. (2) The maximum horizontal principal stress directions of the five measuring points are all located in the NW direction, which is basically consistent with the maximum principal stress direction of the regional tectonic stress field. The maximum horizontal principal stress (σh.max), the minimum horizontal principal stress (σh.min), and the vertical principal stress (σv) all increase with the increase of buried depth, and the relationship is approximately linear. It is suggested that, in the actual construction process, the construction method and construction parameters should be optimized scientifically and reasonably to reduce the disturbance of blasting on the tunnel surrounding rock. After tunnel excavation, support measures should be taken quickly, timely, and scientifically to reduce and control the deformation of the surrounding rock.

For a long time, cracks can appear on the surface of concrete, resulting in a number of safety problems. Traditional manual detection methods not only cost money and time but also cannot guarantee high accuracy. Therefore, a recognition method based on the combination of convolutional neural network and cluster segmentation is proposed. The proposed method realizes the accurate identification of concrete surface crack image under complex background and improves the efficiency of concrete surface crack identification. The research results show that the proposed method not only classifies crack and noncrack efficiently but also identifies cracks in complex backgrounds. The proposed method has high accuracy in crack recognition, which is at least 97.3% and even up to 98.6%.

Helicobacter pylori is designated as a class I carcinogen of human gastric cancer following long-term infection. During this process, H. pylori bacteria persist in proliferation and death, and release bacterial components that come into contact with gastric epithelial cells and regulate host cell function. However, the impact of long-term exposure to H. pylori lysate on the pathological changes of gastric cells is not clear. In this study, we aimed to investigate the regulation and mechanisms involved in gastric cell dysfunction following continuous exposure to H. pylori lysate. We co-cultured gastric cell lines GES-1 and MKN-45 with H. pylori lysate for 30 generations, and we found that sustained exposure to H. pylori lysate inhibited GES-1 cell invasion, migration, autophagy, and apoptosis, while it did not inhibit MKN-45 cell invasion or migration. Furthermore, Mongolian gerbils infected with H. pylori ATCC 43504 strains for 90 weeks confirmed the in vitro results. The clinical and in vitro data indicated that sustained exposure to H. pylori lysate inhibited cell apoptosis and autophagy through the Nod1-NF-κB/MAPK-ERK/FOXO4 signaling pathway. In conclusion, sustained exposure to H. pylori lysate promoted proliferation of gastric epithelial cells and inhibited autophagy and apoptosis via Nod1-NF-κB/MAPK-ERK/FOXO4 signaling pathway. In the process of H. pylori-induced gastric lesions, H. pylori lysate plays as an “accomplice” to carcinogenesis.

The Mongolian gerbil (Meriones unguiculatus), a well-known “multifunctional” experimental animal, plays a crucial role in the research of hearing, cerebrovascular diseases and Helicobacter pylori infection. Although the whole-genome sequencing of Mongolian gerbils has been recently completed, lack of valid gene-editing systems for gerbils largely limited the further usage of Mongolian gerbils in biomedical research. Here, efficient targeted mutagenesis in Mongolian gerbils was successfully conducted by pronuclear injection with Cas9 protein and single-guide RNAs (sgRNAs) targeting Cystatin C (Cst3) or Apolipoprotein A-II (Apoa2). We found that 22 h after human chorionic gonadotropin (hCG) injection, zygote microinjection was conducted, and the injected zygotes were transferred into the pseudopregnant gerbils, which were induced by injecting equine chorionic gonadotropin (eCG) and hCG at a 70 h interval and being caged with ligated male gerbils. We successfully obtained Cst3 and Apoa2 gene knockout gerbils with the knockout efficiencies of 55 and 30.9%, respectively. No off-target effects were detected in all knockout gerbils and the mutations can be germline-transmitted. The absence of CST3 protein was observed in the tissues of homozygous Cst3 knockout (Cst3-KO) gerbils. Interestingly, we found that disruption of the Cst3 gene led to more severe brain damage and neurological deficits after unilateral carotid artery ligation, thereby indicating that the gene modifications happened at both genetic and functional levels. In conclusion, we successfully generated a CRISPR/Cas9 system based genome editing platform for Mongolian gerbils, which provided a foundation for obtaining other genetically modified gerbil models for biomedical research.

Milk casein and triglyceride content are important production traits in goats. Studies on mechanisms in milk casein secretion and mammary gland development is essential for milk goat breeding. miRNAs play an important role in goat lactation. While novel-miR-3880 is highly expressed at goat peak lactation stage, its molecular mechanism has not been studied. The purpose of the present study was to explore the relationship between novel-miR-3880 and lactation, as well as to construct a network among novel-miR-3880, ciRNA13761, and E74 like ETS transcription factor 2 (ELF2), thus further exploring their potential roles in milk components and mammary gland development. ELF2 was previously proven to be important in cell survival and proliferation, and 3′-UTR of ELF2 was predicted to have binding sites of novel-miR-3880. Our study found that the overexpression of novel-miR-3880 exerted anti-apoptotic and proliferative roles in GMEC, induced a boost in triglyceride synthesis, and caused a decrease in α s1-, α s2-, and β-casein, but an increase in κ-casein secretion. Furthermore, treatment in mice indicated that novel-miR-3880 could promote mammary gland development and extend the lactation period, while novel-miR-3880 expression was found to be suppressed by ciRNA13761 as a miRNA sponge. The present study explores a mechanism of triglyceride synthesis and casein secretion, and reveals a crosstalk between ciRNA13761/novel-miR-3880/ELF2 axis and PI3K/AKT/mTOR/S6K1 pathway, to gain a better understanding of lactation traits in dairy goats.

AimsThis study aimed to examine the association of different anatomical forms of obesity with adipose tissue insulin resistance and to assess the diagnostic value and contribution of obesity to adipose tissue insulin resistance.MethodsThis cross-sectional study included a total of 499 subjects aged 50 years or over. Multivariate regression analysis was conducted to clarify the association of different forms of obesity with adipose tissue insulin resistance (calculated as fasting insulin level×fasting free fatty acids level). Receiver operating characteristic cure analyses were used to assess the diagnostic value of each anthropometric indicator for adipose tissue insulin resistance. Attributable risk per cent and population attributable risk per cent were calculated to assess the contribution of obesity to adipose tissue insulin resistance.ResultsAfter adjustment for potential confounders, we showed that anthropometric indicators were all positively associated with adipose tissue insulin resistance. In males, waist circumference (WC) was the strongest associated factor (OR, 3.43 (95% CI 2.03 to 5.82)) and indicator (area under the curve (AUC): 0.79) of adipose tissue insulin resistance among those indicators. Here, abdominal obesity (WC≥90 cm) accounted for 64.9% of adipose tissue insulin resistance in the abdominal obese males. Accordingly, body mass index (BMI) was the strongest associated factor (OR,3.08 (95% CI 2.04 to 4.66)) and indicator (AUC: 0.78) of adipose tissue insulin resistance in females. Here, general obesity of BMI≥25 kg/m2 accounted for 66.2% of the adipose tissue insulin resistance in the general obese females. We further demonstrated that adipose tissue insulin resistance was associated or trended to be associated with the metabolic diseases of cardiovascular disease, type 2 diabetes and fatty liver in subjects with normal BMI and WC.ConclusionsMaintaining WC in males and BMI in females to a normal range could be an important strategy to significantly reduce the occurrence of adipose tissue insulin resistance and the subsequent metabolic diseases.

ObjectiveWe aimed to investigate the effects of prediabetes and its phenotypes of impaired fasting glucose (IFG), impaired glucose tolerance (IGT) and elevated glycated hemoglobin A1c (EHbA1c) on chronic kidney disease (CKD) occurrence, and define the cut-off point of each glycemic index that significantly increases the risk of CKD.Research design and methodsIn this prospective cohort study, 6446 non-diabetic subjects aged 40 years and over were followed over a period of 3 years to track the new onset of CKD. Cox regression was used to assess the association of prediabetes and its phenotypes with CKD. Receiver operating characteristic curves were used to define the cut-off point of each glycemic index that significantly increases the occurrence of CKD. Population attributable risk percent was calculated to estimate the contribution of prediabetes to CKD.ResultsCompared to subjects with normal glucose tolerance, patients with prediabetes significantly increased the risk of development of CKD (HR=2.33 (1.19–4.55)). Specifically, this increased risk of CKD development was observed in patients with IFG, IGT and EHbA1c. The cut-off points shown to significantly increase the risk of CKD are fasting plasma glucose of 5.63 mmol/L, 2-hour plasma glucose of 6.80 mmol/L and HbA1c of 5.6%. The contribution of prediabetes to CKD occurrence in the study population was 60.6%.ConclusionsThis result suggests that the stricter criteria might be needed to define normal plasma glucose level in China that would not be predisposed to diabetic complications, particularly CKD.

Long noncoding RNAs (lncRNAs) regulate gene expression at different levels in various diseases, including type 1 diabetes (T1D). However, the expression of circulating lncRNAs in leukocytes in T1D has not been well documented. To identify differentially expressed lncRNAs between T1D patients and healthy controls, RNA sequencing was performed on samples of leukocytes collected from both healthy persons and T1D patients. The categories, enriched pathways, coexpression networks, and the characteristics of novel lncRNAs were analyzed to provide an extensive profile. qPCR was adopted to validate the differential expression of lncRNAs in the validation cohort. A total of 14,930 lncRNAs and 16,063 mRNAs were identified in the peripheral blood leukocyte of T1D patients. After optimization using an adjusted p value (threshold of

Abstract Therapies based on monoclonal antibodies (mAbs) have delivered an impressive success in the clinics due to their exquisite specificity, potential for agonistic or antagonistic responses, tunable effector function, and optimal pharmacokinetic properties. Building on these inherent antibody properties, the design and development of antibody-drug conjugates (ADCs) with improved or gained therapeutic activity and safety has been successfully demonstrated in oncological applications. There is enormous potential for this new type of hybrid biologics but there are also significant engineering, manufacturing and bioanalytical challenges. In this manuscript, we highlight the range and diversity of assays that are critical to characterize the individual components of ADCs-linker, carrier, and payload. We discuss a series of in vitro and in vivo preclinical experimental approaches we implemented to characterize two anti-inflammatory steroid bearing ADCs, and an ADC bearing a modified glucagon-like peptide 1 receptor/glucagon receptor co-agonist peptide.

Polymorphic melanism in insects is a conspicuous phenotype which is derived from specific genotypes, and might be central to speciation processes via assortative sexual selection. At the molecular level, melanism in insects is attributed to the melanin pathway. DOPA decarboxylase (DDC) protein encoded by the DDC gene plays a central role in dopamine-melanin synthesis, the main component of melanin in insects. Although the mechanism of melanism has been elucidated in holometabolous insects, other physiological processes coupled with melanin synthesis are unknown. Herein, we identified DDC from the Asian multi-colored ladybird (Harmonia axyridis), an ideal holometabolous insect for studies of melanization due to highly variable color on their elytra. Analyses revealed that HaDDC (the DDC gene of H. axyridis) was constitutively expressed throughout all developmental stages. We performed RNAi technique to examine the melanin synthesis pathway of elytra in H. axyridis. The transcript levels of HaDDC were significantly suppressed after the injection of double-strand RNA of HaDDC (dsHaDDC) at 300 ng/individual in third instar larvae. Silencing HaDDC in third instar larvae did not result in mortality nor significantly affect pupation and eclosion. We further demonstrated that all adults of H. axyridis (forms succinea, spectabilis, and conspicua) with HaDDC silenced in third larvae showed abnormal phenotype which emerged as decreased elytra melanin. However, melanin was still observed in other parts of the adults such as head or pronotum. These results demonstrate for the first time that dopamine-derived melanin is the main contributor in elytra melanization in H. axyridis. Additionally, we provide evidence for DDC in regulating fecundity by showing that silencing of HaDDC in third instar larvae significantly reduced female egg-laying and egg hatching. As such, DDC is likely pleiotropic in respect of its role in melanin production and fecundity processes. These findings bring novel insights into melanin production in holometabolous insects, and contribute to the framework on which further studies may be conducted on the mechanism of pigment production and patterning in various types of insect coloration.

Brachymystax lenok tsinlingensis is an endangered freshwater fish which is endemic to part of China. To investigate its genetic diversity and population structure, mitochondrial cytochrome b gene and D-loop control region were used to analyze samples from five different locations. Fifteen haplotypes were identified; however, no shared haplotypes were observed among different streams. The analysis of molecular variance (AMOVA) results indicated that 77.38% of total variation was attributed to differentiation between populations, whereas 22.62% from variation within populations. The high genetic differentiation among the populations would provide useful information for building natural reserves and artificially releasing cultured juveniles in the future.