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Background. gcrR gene acts as a negative regulator related to sucrose-dependent adherence in S. mutans. It is constructive to test the potential capacity of mutans with gcrR gene deficient in bacteria replacement therapy. Methods. In this study, we constructed the mutant by homologous recombination. The morphological characteristics of biofilms were analyzed by confocal laser scanning microscopy. S. mutans UA159 and the mutant MS-gcrR-def were inoculated, respectively, or together for competitive testing in vitro and in rat model. Results. Adhesion assay showed that the adhesion ability of the mutant increased relative to the wild type, especially in the early stage. MS-gcrR-def out-competed S. mutans UA159 in vitro biofilm, and correspondingly coinfection displayed significantly fewer caries in vivo. The former possessed both a lower level of acid production and a stronger colonization potential than S. mutans UA159. Conclusion. These findings demonstrate that MS-gcrR-def appears to be a good candidate for replacement therapy.

Abstract For linear time varying (LTV) multiple input multiple output (MIMO) systems with vector relative degree, an open‐closed‐loop iterative learning control (ILC) strategy is developed in this article, where the time interval of operation is iteration dependent. To compensate the missing tracking signal caused by iteration dependent interval, the feedback control is introduced in ILC design. As the tracking signal of many continuous iterations is lost in a certain interval, the feedback control part can employ the tracking signal of current iteration for compensation. Under the assumption that the initial state vibrates around the desired initial state uniformly in mathematical expectation sense, the expectation of ILC tracking error can converge to zero as the number of iteration tends to infinity. Under the circumstance that the initial state varies around the desired initial state with a bound, as the number of iteration tends to infinity, the expectation of ILC tracking error can be driven to a bounded range, whose upper bound is proportional to the fluctuation. It is revealed that the convergence condition is dependent on the feedforward control gains, while the feedback control can accelerate convergence speed by selecting appropriate feedback control gains. As a special case, the controlled system with integrated high relative degree is also addressed by proposing a simplified iteration dependent interval based open‐closed‐loop ILC method. Finally, the effectiveness of the developed iteration dependent interval based open‐closed‐loop ILC is illustrated by a simulation example with two cases on initial state.

Abstract An undescribed pyrrole acid, 1-(4′-methoxy-4′-oxobutyl)-1 H-pyrrole-2,5-dicarboxylic acid (1) and one known pyrrole acid (2) were isolated from the fruits of Phyllanthus emblica. The structures of these compounds were elucidated via the comprehensive analyses of IR, HRESIMS, 1D and 2D spectroscopic data. A series of biological assays revealed that compounds 1 and 2 could inhibit LPS-induced over-production of nitric oxide (NO), interleukin-6 (IL-6), monocyte chemotactic protein 1 (MCP-1) and tumor necrosis factor-α (TNF-α) by reducing the phosphorylation of extracellular regulated protein kinases (ERK) and c-Jun N-terminal kinases (JNK) in RAW 264.7 cells. Additionally, compounds 1 and 2 were found to reduce lipid deposition and increase the mRNA expression of ATP-binding cassette transporter A1 in oxidized low-density lipoprotein-treated RAW264.7 macrophages. Graphical abstract

A new species of Primulina, P. pingnanensis, from the Guangxi Zhuangzu Autonomous Region, China, is described and illustrated here. It is morphologically similar to P. orthandra but has significant differences in the bracts, corolla tube and lobes shape, as well as in the indumentum of the outer surface of the corolla, the filaments, the staminodes and the anthers. Colorful photographs and essential information of this new taxon are also provided, including detailed taxonomic description, distribution, habitat, the comparison table, and the IUCN conservation status. We also discuss a validation of new combination P. crassifolia and Chirita crassifolia.

Alzheimer’s disease (AD), an irreversible neurodegenerative disease that progressively impairs memory and cognitive judgment, severely affects the quality of life and imposes a heavy burden on the healthcare system. No cure is currently available for AD, in part because the pathogenesis of this disease has not been established. Animal models are essential for investigating AD pathogenesis and evaluating potential therapeutic strategies for AD. Some phenotypic and neuropathologic changes in AD patients can be recapitulated with genetic and pharmacologic approaches in animals. This article systematically reviews the animal models available for AD research, including transgenic, chemical- or drug-induced, and spontaneous animal models, and the characteristics of these animal models. In this review we also discuss the challenges and constraints when using AD animal models. Although no single animal model can reproduce all pathologic aspects and behavioral features in AD patients, the currently available AD models are valuable tools for deciphering the pathogenic mechanisms underlying AD and developing new anti-AD therapeutics.

Abstract Background Diffuse large B‐cell lymphoma (DLBCL) is a non‐Hodgkin lymphoma with high mortality rates. Small nucleolar RNAs (snoRNAs) are tumor‐specific biological markers, but there are few studies on the role of snoRNAs in DLBCL. Materials and Methods Survival‐related snoRNAs were selected to construct a specific snoRNA‐based signature via computational analyses (Cox regression and independent prognostic analyses) to predict the prognosis of DLBCL patients. To assist in clinical applications, a nomogram was built by combining the risk model and other independent prognostic factors. Pathway analysis, gene ontology analysis, transcription factor enrichment, protein–protein interactions, and single nucleotide variant analysis were used to explore the potential biological mechanisms of co‐expressed genes. Results Twelve prognosis‐correlated snoRNAs were selected from the DLBCL patient cohort of microarray profiles, and a three‐snoRNA signature consisting of SNORD1A, SNORA60, and SNORA66 was constructed. DLBCL patients could be divided into high‐risk and low‐risk cohorts using the risk model, and the high‐risk group and activated B cell‐like (ABC) type DLBCL were linked with disappointing survival. In addition, SNORD1A co‐expressed genes were inseparably linked to the biological functions of the ribosome and mitochondria. Potential transcriptional regulatory networks have also been identified. MYC and RPL10A were the most mutated SNORD1A co‐expressed genes in DLBCL. Conclusion Put together, our findings explored the potential biological effects of snoRNAs in DLBCL, and provided a new predictor for DLBCL prediction.

Abstract Background Alzheimer’s disease (AD) is a chronic neurodegenerative disease characterized by progressive cognitive dysfunctions and behavioral impairments. Patchouli alcohol (PA), isolated from Pogostemonis Herba, exhibits multiple pharmacological properties, including neuroprotective effects. This study aimed to investigate the therapeutic effects of PA against AD using the TgCRND8 transgenic AD mouse model, and to explore the underlying mechanisms targeting CCAAT/enhancer-binding protein β/asparagine endopeptidase (C/EBPβ/AEP) signaling pathway. Methods After genotyping to confirm the transgenicity, drug treatments were administered intragastrically once daily to 3-month-old TgCRND8 mice for 4 consecutive months. Several behavioral tests were applied to assess different aspects of neurological functions. Then the brain and colon tissues were harvested for in-depth mechanistic studies. To further verify whether PA exerts anti-AD effects via modulating C/EBPβ/AEP signaling pathway in TgCRND8 mice, adeno-associated virus (AAV) vectors encoding CEBP/β were bilaterally injected into the hippocampal CA1 region in TgCRND8 mice to overexpress C/EBPβ. Additionally, the fecal microbiota transplantation (FMT) experiment was performed to verify the potential role of gut microbiota on the anti-AD effects of PA. Results Our results showed that PA treatment significantly improved activities of daily living (ADL), ameliorated the anxiety-related behavioral deficits and cognitive impairments in TgCRND8 mice. PA modulated the amyloid precursor protein (APP) processing. PA also markedly reduced the levels of beta-amyloid (Aβ) 40 and Aβ42, suppressed Aβ plaque burdens, inhibited tau protein hyperphosphorylation at several sites and relieved neuroinflammation in the brains of TgCRND8 mice. Moreover, PA restored gut dysbiosis and inhibited the activation of the C/EBPβ/AEP signaling pathway in the brain and colon tissues of TgCRND8 mice. Interestingly, PA strikingly alleviated the AD-like pathologies induced by the overexpression of C/EBPβ in TgCRND8 mice. Additionally, the FMT of fecal microbiota from the PA-treated TgCRND8 mice significantly alleviated the cognitive impairments and AD-like pathologies in the germ-free TgCRND8 mice. Conclusion All these findings amply demonstrated that PA could ameliorate the cognitive deficits in TgCRND8 mice via suppressing Aβ plaques deposition, hyperphosphorylation of tau protein, neuroinflammation and gut dysbiosis through inhibiting the activation of C/EBPβ/AEP pathway, suggesting that PA is a promising naturally occurring chemical worthy of further development into the pharmaceutical treatment of AD.

Abstract Purpose To analyse and summarize branching pattern types of the interlobar portion of right pulmonary arteries (RPA) through chest thin-slice CT scans and three-dimensional reconstruction. Methods A total of 179 patients (58 males and 121 females, with an average age of 53.9 years) at the Thoracic Surgery Department of Ningbo First Hospital were retrospectively included from December 2020 to December 2021. All patients completed preoperative thin-slice CT scans and three-dimensional reconstructions of the chest. The clinical data and branching patterns were collected. Data were analysed using SPSS 21.0. Results The branching pattern types of the interlobar portion of RPA were divided into 4 types according to the order and number of branches: Type I (145/179, 81.0%), Asc. A2, MA, A6; Type II (28/179, 15.6%), Asc. A2 deletion, MA, A6; Type III (5/179, 2.8%), Asc. A2, A6, MA; and Type IV (1/179, 0.6%), MA, Asc. A2, A6. Type I was the most common pattern. Furthermore, according to the number of branches of MA and A6, this pattern can be subdivided into 15 subcategories. Conclusion Chest thin-slice CT scans and 3D reconstructions can provide surgeons with accurate lung anatomy, which helps surgeons perform preoperative planning and complete surgery successfully.

Abstract Oral squamous cell carcinoma (OSCC) is one of the most frequent malignancies found in head and neck cancers. Dysregulation of lncRNAs has been proposed to be related to the development of OSCC. Here, we investigated the function and probable mechanisms of lncRNA DLEU1 in OSCC. OSCC cell lines and human oral keratinocytes (HOKs) were cultured, while SCC‐25 and CAL‐27 cells were transfected with the corresponding plasmids. Reverse transcription quantitative PCR (RT‐qPCR) and western blot were carried out to measure the RNA and protein levels. Cell proliferation, migration and invasion were evaluated using MTT assays, wound healing and Transwell assays. The StarBase database predicted the interactions between DLEU1 and miR‐126‐5p, as well as miR‐126‐5p and GAB1, which were further validated using a dual‐luciferase reporter assay. Our results indicated that DLEU1 and GAB1 were upregulated, while miR‐126‐5p was downregulated in OSCC cells. Silencing DLEU1 reduced OSCC cell proliferation, migration, and invasion, while DLEU1 overexpression had the opposite effects. DLEU1 mediated biological effects in OSCC through binding to miR‐126‐5p, which directly targeted GAB1. miR‐126‐5p knockdown rescued the inhibitory function of DLEU1 depletion on proliferation, migration and invasion. Meanwhile, the miR‐126‐5p mimic exerted suppressive functions in the progression of OSCC, which were neutralized after GAB1 overexpression. In summary, lncRNA DLEU1 targets the miR‐126‐5p/GAB1 axis to aggravate OSCC progression, providing a novel target for treating OSCC.

2D transition metal ditellurides exhibit nontrivial topological phases, but the controlled bottom-up synthesis of these materials is still challenging. Here, the authors report the layer-by-layer growth of large-area bilayer and trilayer 1T’ MoTe2 films, showing thickness-dependent ferroelectricity and nonlinear Hall effect.

The plasmon-exciton interaction between gap-mode nanocavities and A excitons of MoS2 is investigated, and the longitudinal distribution of the plasmon-exciton interactions is obtained at ~1 nm spatial resolution.

Post-collisional alkaline intrusive rocks from the Dabie orogen were studied for their whole-rock major-trace elements and Sr-Nd-Hf-Pb isotopes, as well as zircon U-Pb ages and Hf-O isotopes. The results provide geochemical constraints on the nature of their mantle sources and thus insight into crust-mantle interaction in the continental collision zone. The alkaline intrusive rocks are composed of syenite and nepheline syenite. Syn-magmatic zircon U-Pb dating by LA-ICP-MS for them yielded Early Cretaceous ages of 131.3 ± 1.4 Ma to 122.6 ± 0.6 Ma, coeval with the post-collisional magmatism in the Dabie orogen. One relict zircon with U-Pb age of 211 Ma is consistent with the timing of metamorphism for the ultrahigh-pressure (UHP) metamorphic rocks in this orogen. They have arc-like trace element distribution patterns, such as enrichment in LILE (large ion lithophile element) and LREE (light rare earth element) but depletion in HFSE (high field strength element), and enriched whole-rock Sr-Nd-Hf isotope compositions with high (87Sr/86Sr)i ratios of 0.7077–0.7131 but negative εNd(t) values of −16.0 to −9.4 and εHf(t) values of −17.5 to −12.7. Their syn-magmatic zircons have three groups of Hf-O isotope compositions comparable to those of UHP metamorphic rocks in Central-South Dabie and North Dabie, which represent the upper and middle continental crust of the subducted South China Block, respectively. In this regard, slab–mantle interaction is evident during the Triassic continental collision. We suggest that the melts derived from the subducted South China Block reacted with the lithospheric mantle wedge of the North China Block, resulting in phlogopite-bearing metasomatites, whose partial melting would generate the post-collisional alkaline intrusive rocks during the Early Cretaceous.

Abstract There have been an increasing number of patients with degenerative disc diseases due to the aging population. In light of this, studies on the pathogenesis of intervertebral disc degeneration have become a hot topic, and gene knockout mice have become a valuable tool in this field of research. With the development of science and technology, constitutive gene knockout mice can be constructed using homologous recombination, zinc finger nuclease, transcription activator‐like effector nuclease technology and clustered regularly interspaced short palindromic repeats/Cas9 (CRISPR/Cas9) system, and conditional gene knockout mice can be constructed using the Cre/LoxP system. The gene‐edited mice using these techniques have been widely used in the studies on disc degeneration. This paper reviews the development process and principles of these technologies, functions of the edited genes in disc degeneration, advantages, and disadvantages of different methods and possible targets of the specific Cre recombinase in intervertebral discs. Recommendations for the choice of suitable gene‐edited model mice are presented. At the same time, possible technological improvements in the future are also discussed.

IntroductionPasteurella multocida is a widespread respiratory pathogen in pigs, causing swine pneumonia and atrophic rhinitis, and the capsular serogroups A and D are the main epidemic serogroups in infected animals. This study investigated the protective effects of serogroup A and D bacterins against current circulating P. multocida strains, to better understand the immunity generated by bacterins.Method13 serogroup A (seven A: L3 and six A: L6 strains) and 13 serogroup D (all D: L6 strains) P. multocida strains were isolated, and used as inactivated whole cell antigen to prepare P. multocida bacterins. Mice were immunized with these bacterins at 21-day interval and intraperitoneally challenged with the homologous and heterologous P. multocida strains, respectively. The antibody titer levels and immunization protective efficacy of vaccines were evaluated.ResultsAll of the bacterins tested induced high titer levels of immunoglobulin G antibodies against the parental bacterial antigen in mice. Vaccination with the six A: L6 bacterins provided no protection against the parent strain, but some strains did provide heterologous protection against A: L3 strains. Vaccination with the seven A: L3 bacterins provided 50%–100% protection against the parent strain, but none gave heterologous protection against the A:L6 strains. Immunization with the thirteen D: L6 bacterins offered 60%–100% protection against the parent strain, and almost all D: L6 strains gave cross-protection.DiscussionThis study found that the cross-protectivity of serogroup A strains was poor, while serogroup D strains was effective, which provided some insights for P. multocida vaccine development.

Study on turbine blades is crucial due to their critical role in ensuring the efficient and reliable operation of aircraft engines. Nickel-based single crystal superalloys are extensively used in the hot manufacturing of turbine blades due to their exceptional high-temperature mechanical properties. The hot manufacturing of single crystal blades involves directional solidification and heat treatment. Experimental manufacturing of these blades is time-consuming, capital-intensive, and often insufficient to meet industrial demands. Numerical simulation techniques have gained widespread acceptance in blade manufacturing research due to their low energy consumption, high efficiency, and rapid turnaround time. This article introduces the modeling and simulation of hot manufacturing in single crystal blades. The discussion outlines the prevalent mathematical models employed in numerical simulations related to blade hot manufacturing. It encapsulates the advancements in research concerning macro to micro-level numerical simulation techniques for directional solidification and heat treatment processes. Furthermore, potential future trajectories for the numerical simulation of single crystal blade hot manufacturing are also discussed. [ABSTRACT FROM AUTHOR]

In the existing robust iterative learning control (ILC) for 2-D discrete systems, they typicallly require to satisfy a core hypothesis that the strict repetitiveness of tracking reference trajectory and system model should be satisfied. This paper first investigates the robustness and convergence of a P-type ILC law and a high-order ILC law for 2-D linear nonrepetitive discrete systems (LNDS) with arbitrarily bounded reference trajectory and iteration-dependent reference trajectory described by a high order internal model (HOIM) operator in iteration domain, respectively. It is theoretically proved by using the 2-D linear nonrepetitive inequalities that the ILC tracking error and the control input robustly converge to a bounded range, the bound of which depends continuously on the bounds of all the nonrepetitive uncertainties. If these uncertainties are progressively convergent along the iteration domain, a precise tracking on the 2-D reference trajectory can be achieved. Two illustrative examples are provided to demonstrate the validity of the presented ILC law. Additionally, some comparative result on the practical dynamical processes is given.

PurposeHead and neck squamous cell carcinoma (HNSCC) ranks sixth among all cancers globally regarding morbidity, and it has a poor prognosis, high mortality, and highly aggressive properties. In this study, we established a model for predicting prognosis based on immunohistochemical (IHC) scores.MethodsData on 402 HNSCC cases were collected, the glmnet Cox proportional hazards model was used, risk factors were analyzed for predicting the prognosis of survival, and the IHC score was established. We used the IHC score to predict disease-free survival (DFS) using training and independent validation cohorts, including 264 cases in total. Additionally, the accuracy of the IHC score and the TNM system (8th edition) was compared. A DFS prediction nomogram was established by combining the prognostic factors.ResultsThe IHC scores included CK, Ki-67, p16, and p40 staining intensity. The concordance index and the Kaplan-Meier survival analysis showed that the IHC scores had high predictive power for HNSCC. Our results showed that the IHC score is an independent factor that can predict prognosis in a multivariate Cox regression analysis. When predicting DFS, the IHC score had a significantly higher value for the area under the ROC curve (AUC) than that of the TNM system. A nomogram was established and included the IHC score, age, tumor location, and the TNM stage. The calibration curves exhibited high consistency between the prognosis predicted by our nomogram and the actual prognosis.ConclusionsThe IHC score was more accurate than the eighth edition of the TNM system in predicting HNSCC prognosis. Therefore, combining the two methods can facilitate individualized patient consultation and care.

Abstract Nitrate, a common pollutant in water, can be used as a nitrogen source for electrocatalytic ammonia production. Bismuth oxide (Bi2O3) is a promising electrocatalyst because of earth‐abundance and high hydrogen overpotential. However, it also has the disadvantages of easy agglomeration and poor charge transfer. This study demonstrated that the high dispersion of Bi2O3 nanosheets can be achieved through in‐situ growth on Ti3C2Tx MXene nanosheets that improved the efficiency of charge transmission, and thus improving the electrocatalytic ammonia production performance. A NH3 yield rate of ∼7.00 mg h−1 cm−2 with faradic efficiency of 91.1 % could be achieved on 11 % Bi2O3/MXene. Density functional theory (DFT) calculations, electrochemical active surface area (ECSA) and electrochemical impedance spectroscopy (EIS) proved that the excellent ammonia production performance came from the fact that bismuth oxide itself could inhibit hydrogen evolution, and in situ growth on MXene enabled high active site exposure and enhanced charge transfer capacity.

Abstract Background There is a lack of clinical-radiological predictive models for the small (≤ 20 mm) solitary pulmonary nodules (SPNs). We aim to establish a clinical-radiological predictive model for differentiating malignant and benign small SPNs. Materials and methods Between January 2013 and December 2018, a retrospective cohort of 250 patients with small SPNs was used to construct the predictive model. A second retrospective cohort of 101 patients treated between January 2019 and December 2020 was used to independently test the model. The model was also compared to two other models that had previously been identified. Results In the training group, 250 patients with small SPNs including 156 (62.4%) malignant SPNs and 94 (37.6%) benign SPNs patients were included. Multivariate logistic regression analysis indicated that older age, pleural retraction sign, CT bronchus sign, and higher CEA level were the risk factors of malignant small SPNs. The predictive model was established as: X = − 10.111 + [0.129 × age (y)] + [1.214 × pleural retraction sign (present = 1; no present = 0)] + [0.985 × CT bronchus sign (present = 1; no present = 0)] + [0.21 × CEA level (ug/L)]. Our model had a significantly higher region under the receiver operating characteristic (ROC) curve (0.870; 50% CI: 0.828–0.913) than the other two models. Conclusions We established and validated a predictive model for estimating the pre-test probability of malignant small SPNs, that can help physicians to choose and interpret the outcomes of subsequent diagnostic tests.

ObjectiveThe study aimed to determine the prevalence and pathogens of invasive fungal infection (IFI) among intensive care unit (ICU) patients. The next goal was to investigate the association between empirical antifungal treatment and mortality in ICU patients.MethodsUsing microbiological events, we identified all ICU patients with IFI and then retrieved electronic clinical data from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. The data were statistically analyzed using t-tests, chi-square tests, log-rank tests, and Cox regression.ResultsThe most commonly reported fungi were Candida (72.64%) and Aspergillus (19.08%). The most frequently prescribed antifungal medication was fluconazole (37.57%), followed by micafungin (26.47%). In the survival study of ICU patients and patients with sepsis, survivors were more likely to receive empirical antifungal treatment. In contrast, non-empirical antifungal therapy was significantly associated with poor survival in patients with positive blood cultures. We found that the current predictive score makes an accurate prediction of patients with fungal infections challenging.ConclusionsOur study demonstrated that empirical antifungal treatment is associated with decreased mortality in ICU patients. To avoid treatment delays, novel diagnostic techniques should be implemented in the clinic. Until such tests are available, appropriate empirical antifungal therapy could be administered based on a model that predicts the optimal time to initiate antifungal therapy. Additional studies should be conducted to establish more accurate predictive models in the future.

Nonalcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease, associated with an outcome of hepatic fibrosis/cirrhosis and hepatocellular carcinoma. However, limited exploration of the underlying mechanisms hinders its prevention and treatment. To investigate the mechanisms of epigenetic regulation in NAFLD, the expression profile of circular RNA (circRNA) of rodents in which NAFLD was induced by a high-fat, high-cholesterol (HFHC) diet was studied. Modeling of the circRNA-microRNA (miRNA) -mRNA regulatory network revealed the functional characteristics of NAFLD-specific circRNAs. The targets and effects in the liver of such NAFLD-specific circRNAs were further assessed. Our results uncovered that the downregulation of 28 annotated circRNAs characterizes HFHC diet-induced NAFLD. Among the downregulated circRNAs, long intergenic non-protein coding RNA, P53 induced transcript (LNCPINT) -derived circRNAs (circ_0001452, circ_0001453, and circ_0001454) targeted both miR-466i-3p and miR-669c-3p. Their deficiency in NAFLD abrogated the circRNA-based inhibitory effect on both miRNAs, which further inactivated the AMPK signaling pathway via AMPK-α1 suppression. Inhibition of the AMPK signaling pathway promotes hepatic steatosis, depending on the transcriptional and translational upregulation of lipogenic genes, such as those encoding sterol regulatory element-binding protein 1 (SREBP1) and fatty acid synthase (FASN) in hepatocytes. The levels of LNCPINT-derived circRNAs displayed a negative association with hepatic triglyceride (TG) concentration. These findings suggest that loss of LNCPINT-derived circRNAs may underlie NAFLD via miR-466i-3p- and miR-669c-3p-dependent inactivation of the AMPK signaling pathway.

The feasibility of laser‐engineered fluorescence emission from carbon black (CB) with three laser sources of different wavelengths—660 nm (red), 532 nm (green), and 405 nm (blue) is demonstrated. From which the 660 nm focused laser beam produces the most intense fluorescence. Detailed systematic studies on how the laser‐engineered fluorescence emission from CB depends on laser power, laser patterning speed, and environmental control during the laser modification process are carried out. From the systematic studies, the CB samples in ambience undergo most noticeable modifications with a laser power of ≈7 mW and patterning speed of ≈12 μms−1. The fluorescence emission is attributed to the creation of complex defects states into the oxidized form of the pristine system by the formation of 1) C60 fullerene and fullerites; 2) ZnO; 3) Zn2SiO4, and more complex hybrid such as 4) carbon‐induced mid‐gap states in Zn2SiO4, and 5) Ca‐induced defects in ZnO. Such incorporations resulted in the formation of intermediate states in the large bandgap materials. As a result, distinct multicolored fluorescence is emitted by these laser‐quenched material systems. Accordingly, multicolored fluorescence designs can be created with elaborative control of focused laser treatment in an ambient and helium environment.

Abstract Background Hepatocellular carcinoma (HCC), the second leading cause of cancer death worldwide, alone accounts for over half (466,100) of new cancer cases and 422,100 deaths based on the average year incidence rates of 2009 to 2011 in China. Due to unclear and complex underlying mechanisms for HCC development, effective therapy for HCC is still unavailable. The Wnt–β-catenin pathway is a critical contributor of HCC pathogenesis: 40–70% of HCCs from patients harbor the nuclear accumulation of β-catenin protein. However, the mechanisms for β-catenin activation are not fully understood. Methods The deletion of EHMT2 in Hep3B and Huh1 cells was achieved by transiently transfecting cells with pX459 plasmids, which carry EHMT2 specific small guide RNA (sgRNA) sequences for Cas9 protein. All experiments were performed in triplicate and repeated more than three times. Results In the present study, we observed that EHMT2 (but not EHMT1) mRNA and protein levels were significantly elevated in HCC compared with normal controls. Next, the results of Ki67 staining, as well as MTT, soft-agar and xenograft assays, in wild-type and EHMT2 −/− Hep3B and Huh1 cancer stem cells collectively revealed that the elevation of EHMT2 expression is required for the tumorigenesis of HCC. Meanwhile, we found that elevated EHMT2 expression contributes to the activation of Wnt–β-catenin signaling: deletion of EHMT2 in Hep3B or Huh1 cells promoted the cytoplasmic localization of β-catenin and restrained the expression of Wnt–β-catenin signaling targets such as Myc, CCND1, MMP-7, etc. We demonstrated that EMHT2 directly mediates the H3K9me2 methylation of the APC promoter to epigenetically silence its expression. More intriguingly, our findings also showed that UNC0642, a specific inhibitor of EHMT2, exhibits anti-tumorigenesis effects in HCC both in vitro and in vivo, which were largely abolished by deletion of EHMT2 or overexpression of APC in Hep3B and Huh1 cells. Conclusion Altogether, our observations emphasize that the EHMT2–APC axis is a critical contributor to Wnt–β-catenin pathway activation in HCC, and UNC0642 may be a potential candidate for target drug treatment of HCC.

Abstract Objectives The study aims to analyze the clinical characteristics of head and neck mucosal melanoma (MMHN) and the effects of multiple treatment modalities on distant metastasis, recurrence and survival rates to provide a reference for the individualized treatment of MMHN. Methods We retrospectively reviewed 262 patients with stage III–IVb MMHN treated from March 1986 to November 2018 at our cancer center. Results The median follow-up time was 34.0 months (range 1–262 months). The 5-year overall survival (OS), distant metastasis-free survival (DMFS) and disease-free survival (DFS) probabilities were 37.7%, 30.2%, and 20.3%, respectively. The 5-year OS rates for patients with stage III, stage IVA, and stage IVB MMHN were 67.0%, 24.1% and 8.3%, respectively (P

Seeking a scientific and reasonable population structure is the key to realizing low-carbon and green development of urban agglomerations. Based on the coupled coordination degree model and exploratory spatial data analysis (ESDA), this paper studied the spatiotemporal differences of population spatial equilibrium in Changsha-Zhuzhou-Xiangtan urban agglomeration, and constructed a nonlinear dynamic panel econometric model and quantile regression model to empirically test the carbon emission reduction effect and its heterogeneity of the population spatial equilibrium. The research conclusions are as follows: First, the population spatial equilibrium index of Changsha-Zhuzhou-Xiangtan urban agglomeration shows an upward trend in time, but the overall level is not high and the internal gap is obvious. In space, it presents a situation of concentration in the central urban area of Changsha. Second, the carbon emissions of Changsha-Zhuzhou-Xiangtan urban agglomeration have obvious dynamic inertia and path-dependent characteristics. That is, the carbon emissions of the previous period will significantly promote the carbon emissions of the current period. Third, the carbon emission reduction effect of population spatial equilibrium has the characteristics of an inverted “U” shape, and the population spatial equilibrium index in most areas is too low to achieve carbon emission reduction. Fourth, the legal environment helps to promote the spatial balance of population, thereby reducing the regional total carbon emissions, per capita carbon emissions and carbon emissions per unit area. Last, Changsha-Zhuzhou-Xiangtan urban agglomeration needs to improve the level of economic development and government expenditure to realize the carbon emission reduction effect. In general, Changsha-Zhuzhou-Xiangtan urban agglomeration should take into account the development of economy and environment in the process of improving the level of population space balance, so as to achieve a win-win situation for economy and environment.

Locusta migratoria manilensis is one of the most important agricultural pests in China. The locust has high fecundity and consumes large quantities of food, causing severe damage to diverse crops such as corn, sorghum, and rice. Immunity against pathogens and reproductive success are two important components of individual fitness, and many insects have a trade-off between reproduction and immunity when resources are limited, which may be an important target for pest control. In this study, adult females L. migratoria manilensis were treated with different concentrations (5 × 106 spores/mL or 2 × 107 spores/mL) of the entomopathogenic fungus Paranosema locustae. Effects of input to immunity on reproduction were studied by measuring feeding amount, enzyme activity, vitellogenin (Vg) and vitellogenin receptor (VgR) production, ovary development, and oviposition amount. When infected by P. locustae, feeding rate and phenol oxidase and lysozyme activities increased, mRNA expression of Vg and VgR genes decreased, and yolk deposition was blocked. Weight of ovaries decreased, with significant decreases in egg, length and weight.Thus, locusts used nutritive input required for reproduction to resist invasion by microsporidia. This leads to a decrease in expression of Vg and VgR genes inhibited ovarian development, and greatly decreased total fecundity. P. locustae at 2 × 107 spores/mL had a more obvious inhibitory effect on the ovarian development in migratory locusts. This study provides a detailed trade-off between reproduction and immune input of the female, which provides a reliable basis to find pest targets for biological control from those trade-off processes.

Abstract Objectives We aimed to understand the clinical characteristics and better predict the prognosis of patients with mucosal melanoma of the head and neck (MMHN) using a nomogram. Methods Three hundred patients with nometastatic MMHN were included. Multivariable Cox regression was performed to analyze independent prognostic factors for overall survival (OS), disease-free survival (DFS), distant metastasis-free survival (DMFS), and locoregional relapse-free survival (LRRFS), and these factors were used to develop a nomogram. Concordance indexes (C-indexes), calibration plots, and receiver operating characteristic (ROC) analysis were performed to test the predictive performance of the nomogram in both the primary (n = 300) and validation cohorts (n = 182). Results The primary tumor site, T stage and N stage were independent risk factors for survival and were included in the nomogram to predict the 3- and 5-year OS, DFS, DMFS, and LRRFS in the primary cohort. The C-indexes (both > 0.700), well-fit calibration plots, and area under the ROC curve (both > 0.700) indicated the high diagnostic accuracy of the nomogram, in both the primary and validation cohorts. The patients were divided into three groups (high-risk, intermediate-risk, and low-risk groups) according to their nomogram scores. The survival curves of OS, DFS, DMFS, and LRRFS were well separated by the risk groups in both cohorts (all P

The paper presents an improved hybrid tri-stable cantilever piezoelectric energy harvester based on rotational motion, thus providing a new perspective for achieving higher efficiency in energy capture for rotational motion. The proposed system comprises a piezoelectric cantilever beam with an innovative dynamic amplifier installed at the edge of a vehicle's wheel hub. Through theoretical analysis and numerical simulations, the influence of parameters such as the mass of the tip magnetic on the piezoelectric beam, the wheel hub radius, rotational speed, and the ratio of the dynamic amplifier's spring stiffness are investigated with respect to the system's steady-state dynamic response and time-domain performance. A comparative analysis is also conducted with traditional tri-stable piezoelectric energy harvesters. The results demonstrate that the hybrid tri-stable piezoelectric energy harvester exhibits superior performance in capturing vibrational energy during rotational motion, compared to traditional tri-stable piezoelectric energy harvesters. Proper adjustments to the mass of the tip magnetic and the internal spring stiffness of the dynamic amplifier can enhance the system's output voltage and the rotational speed range of inter-well motion. Additionally, the rotational speed range of inter-well motion increases with the expansion of the wheel hub radius. However, when the rotational speed is below 100 rpm, the influence of varying the wheel hub radius on the system's output voltage is minimal. [ABSTRACT FROM AUTHOR]

Polypropylene is commonly used as a binder for ceramic injection molding, and rapid cooling is often encountered during processing. However, the crystallization behavior of polypropylene shows a strong dependence on cooling rate due to its semi-crystalline characteristics. Therefore, the influence of cooling rate on the quality of final product cannot be ignored. In this study, the fast differential scanning calorimetry (FSC) test was performed to study the influence of cooling rate on the non-isothermal crystallization behavior and non-isothermal crystallization kinetics of a copolymer polypropylene (PP BC03B). The results show that the crystallization temperatures and crystallinity decrease as the cooling rate increases. In addition, two exothermic peaks occur when cooling rate ranges from 30 to 300 K·s-1, indicating the formation of another crystal phase. Avrami, Ozawa and Mo equations were used to explore the non-isothermal crystallization kinetics, and it can be concluded that the Mo method is suitable for this study. [ABSTRACT FROM AUTHOR]

Tumor necrosis factor alpha-induced protein 8 (TNFAIP8) is implicated in the tumor progression and prognosis of triple-negative breast cancer (TNBC), but the detailed regulatory mechanism of TNFAIP8 in cisplatin tolerance in TNBC has not yet been investigated. TNFAIP8 was evidently upregulated in TNBC tumor tissues and cell lines. Knocking down TNFAIP8 led to impaired proliferation and elevated apoptosis of TNBC cells upon cisplatin (DDP) treatment. Mechanistic studies revealed that TNFAIP8 repressed the expression of p53 and p53-promoted microRNA (miR)-205-5p; moreover, miR-205-5p targeted multiple genes required for the cell cycle and repressed Akt phosphorylation, which thus inhibited the proliferation of TNBC cells. In addition, silencing of TNFAIP8 led to the upregulation of miR-205-5p and the restraint of the TRAF2-NF-κB pathway, which thus enhanced the suppressive effects of DDP on tumor growth in nude mice. This study revealed that TNFAIP8 was essential in the DDP tolerance formation of TNBC cells by reducing p53-promoted miR-205-5p expression. Thus, targeting TNFAIP8 might become a promising strategy to suppress TNBC progression.

In this study, two patients with papillary thyroid carcinoma and lymph node metastasis were treated by Dr. Shurong Wang’s team and are reported. The two patients refused surgery and underwent microwave ablation (MWA) of the thyroid and lymph node lesions. Ultrasound review 2 days after MWA revealed internal jugular vein thrombosis. Patient #1 received low molecular weight heparin calcium injection, Xueshuantong injection, Xiangdan injection, and rivaroxaban. Patient #2 was treated with enoxaparin sodium injection, Xueshuantong injection, urokinase, and warfarin sodium tablet. The thrombus was successfully managed in each patient using anticoagulant treatment. Such complication of MWA has not been reported in many cases before. According to the relevant literature, thrombosis after thyroid cancer ablation might be related to subclinical hypothyroidism, increased heme oxidase 1 (HO-1) levels in the blood of patients with papillary thyroid cancer, and increased platelet content and mean platelet volume in patients with thyroid cancer. No specific cause of thrombosis was identified in the two cases reported here. No recurrence was observed after 1 (patient #1) and 4 (#2) years of follow-up. In conclusion, patients with papillary thyroid carcinoma and lymph node metastasis should undergo color Doppler ultrasound of the neck after MWA of thyroid lesions and neck metastasis.

Abstract Memristors are a new type of circuit element with a resistance that is tunable to discrete levels by a voltage/current and sustainable after removal of power, allowing for low‐power computation and multilevel information storage. Many organic‐inorganic lead perovskites are reported to demonstrate memristive behavior, but few have been considered for use as a multilevel memory; also, their potential application has been hindered by the toxicity of lead ions. In this article, lead‐free perovskite MASnBr3 was utilized in memristors for quaternary information storage. Indium tin oxide (ITO)/MASnBr3/Au memristors were fabricated and showed reliable memristive switching with well‐separated ON/OFF states of a maxima resistance ratio of 102 to 103. More importantly, four resistive states can be distinguished and repeatedly written/read/erased with a retention time of 104 seconds and an endurance of 104 pulses. By investigating the current‐electrode area relationship, Br distribution in the ON/OFF states by in situ Raman and scanning electron microscopy, and temperature‐dependent current decay, the memristive behavior was explicitly attributed to the forming/breaking of conductive filaments caused by the migration of Br− under an electric field. In addition, poly(ethylene terephthalate)‐ITO/MASnBr3/Au devices were found to retain their multiresistance state behavior after being bent for 1000 times, thus demonstrating good device flexibility. Our results will inspire more lead‐free perovskite work for multilevel information storage, as well as other memristor‐based electronics.

Abstract Background Long non-coding RNA H19 (lncRNA H19) has been implicated in tumorigenesis and metastasis of breast cancer through regulating epithelial to mesenchymal transition (EMT); however, the underlying mechanisms remain elusive. Methods LncRNA H19 and TNFAIP8 were identified by qRT-PCR and western blotting. CCK-8 assay, clone formation assay, transwell assay, and flow cytometry assay were performed to determine cell proliferation, migration, invasion and cell cycle of breast cancer respectively. Western blotting and immunohistochemistry (IHC) were utilized to evaluate the protein expression levels of p53, TNFAIP8, and marker proteins of EMT cascades in vivo. Dual luciferase reporter assay and RNA pull down assay were conducted to evaluate the interactions of lncRNA H19, p53 and TNFAIP8. Results The expression of lncRNA H19 and TNFAIP8 was up-regulated in breast cancer tissues and cell lines, especially in triple-negative breast cancer (TNBC). Functionally, knockdown of lncRNA H19 or TNFAIP8 coused the capacities of cell proliferation, migration, and invasion were suppressed, and cell cycle arrest was induced, as well as that the EMT markers were expressed abnormal. Mechanistically, lncRNA H19 antagonized p53 and increased expression of its target gene TNFAIP8 to promote EMT process. Furthermore, silencing of lncRNA H19 or TNFAIP8 also could inhibit tumorigenesis and lymph node metastases of MDA-MB-231 cells in xenograft nude mouse models. Conclusions Our findings provide insight into a novel mechanism of lncRNA H19 in tumorigenesis and metastases of breast cancer and demonstrate H19/p53/TNFAIP8 axis as a promising therapeutic target for breast cancer, especially for TNBC.

Abstract. Epigenetic regulation includes changes of DNA methylation and modifications of histone proteins and is essential for normal physiologic functions, especially for controlling gene expression. Epigenetic dysregulation plays a key role in disease pathogenesis and progression of some malignancies, including acute myeloid leukemia (AML). Epigenetic therapies, including hypomethylating agents (HMAs) and histone deacetylase (HDAC) inhibitors, were developed to reprogram the epigenetic abnormalities in AML. However, the molecular mechanisms and therapeutic effects of the two agents alone or their combination remain unknown. An overview of these epigenetic therapies is given here. A literature search was conducted through PubMed database, looking for important biological or clinical studies related to the epigenetic regimens in the treatment of AML until October 15th, 2019. Various types of articles, including original research and reviews, were assessed, identified, and eventually summarized as a collection of data pertaining the mechanisms and clinical effects of HMAs and HDAC inhibitors in AML patients. We provided here an overview of the current understanding of the mechanisms and clinical therapeutic effects involved in the treatment with HMAs and HDAC inhibitors alone, the combination of epigenetic therapies with intensive chemotherapy, and the combination of both types of epigenetic therapies. Relevant clinical trials were also discussed. Generally speaking, the large number of studies and their varied outcomes demonstrate that effects of epigenetic therapies are heterogeneous, and that HMAs combination regimens probably contribute to significant response rates. However, more research is needed to explore therapeutic effects of HDAC inhibitors and various combinations of HMAs and HDAC inhibitors.

The objective of this study was to investigate the effect of lactic acid bacteria (LAB) inoculums on fermentation quality and in vitro digestibility of corn stover silage. Corn stover was ensiled without (control) or with Lactobacillus plantarum (LP), Enterococcus faecalis (EF), and Enterococcus mundtii (EM) for 45 days. The fermentation characteristics were assessed, and subsequent in vitro dry matter digestibility (DM-D), neutral detergent fiber digestibility (NDF-D), volatile fatty acids (VFA), methane (CH4) production, cellulolytic bacteria proportions and their activities per corn stover silage were also determined. There was no significant difference (P>0.05) among the silage pH, lactic acid, crude protein (CP), water soluble carbohydrates (WSC) and lignocelluloses contents of different treatments. The relative proportions of Ruminococcus flavefaciens and Fibrobacter succinogenes, carboxymethyl-ocellulose and β-glycosidase activities, DM-D, NDF-D, and VFA production of in vitro incubation was higher (P

Aim: The aim of this study was to investigate the predictive role of lymphocyte subsets and other laboratory measurements in patients with COVID-19. Methods: Electronic medical records of adult patients with confirmed diagnosis of COVID-19 from the Shanghai Public Health Clinical Center were reviewed retrospectively to obtain relevant data. Results: The mean age of patients was 40.98 ± 15.95 years, with 58% of the patients being males. The cutoff values at the intensive care unit (ICU) admission, mechanical ventilation, and mortality were CD4+ cells (267, 198, and 405), CD8+ cells (263, 203, and 182), and CD4+ /CD8+ cells (1.4, 1.8, and 1.4). The cutoffs below these values indicate the higher chances of disease progression. Higher CD4+ cell count led to lesser chances for ICU admission [odds ratio (OR) (95% confidence interval (CI): 0.994 (0.991, 0.997); p = 0.0002] and mortality [OR (95% CI): 0.988 (0.979, 0.99); p = 0.001], higher CD8+ count was an independent risk factor for ICU admission. T-cell count positively correlated with total lymphocyte count and platelets, while negatively correlated with D-dimer and lactate dehydrogenase (LDH). Among patients with non-severe COVID-19, median CD8+ T cell, CD4+ T cell, total lymphocyte count, and platelets were 570, 362, 1.45, and 211, respectively, while median values decreased to 149, 106, 0.64, and 172, respectively, in patients with severe COVID-19. Conclusion: Lower T lymphocyte subsets were significantly associated with higher admission to ICU, mechanical ventilation, and mortality among patients with COVID-19. A cutoff value of ICU admission, mechanical ventilation, and mortality below CD4+ cells (267, 198, and 405), CD8+ cells (263, 203, 182), and CD4+/CD8+ cells (1.4, 1.8, 1.4) may help identify patients at high risk of disease progression. The continuous evaluation of laboratory indices may help with dismal prognosis and prompt intervention to improve outcomes.

Introduction and objectives: Chronic hepatitis B virus (HBV) infection exerts an impact on lipid metabolism, but its interaction with dysmetabolism-based non-alcoholic fatty liver disease (NAFLD) remains uncertain. The purpose of the study was to investigate the effects of HBV infection on lipid metabolism, hepatic steatosis and related impairments of NAFLD patients. Methods: Biopsy-proven Chinese NAFLD patients with (NAFLD-HBV group, n = 21) or without chronic HBV infection (NAFLD group, n = 41) were enrolled in the case-control study. Their serum lipidomics was subjected to individual investigation by ultra-performance liquid chromatography–tandem mass spectrometry. Steatosis, activity, and fibrosis (SAF) scoring revealed the NAFLD-specific pathological characteristics. Results: Chronic HBV infection was associated with global alteration of serum lipidomics in NAFLD patients. Upregulation of phosphatidylcholine (PCs), choline plasmalogen (PC-Os) and downregulation of free fatty acids (FFAs), lysophosphatidylcholine (LPCs) dominated the HBV-related lipidomic characteristics. Compared to those of NAFLD group, the levels of serum hepatoxic lipids (FFA16:0, FFA16: 1, FFA18:1, FFA18:2) were significantly lowered in the NAFLD-HBV group. These low-level FFAs demonstrated correlation to statistical improvements in aspartate aminotransferase activity (FFA16:0, r = 0.33; FFA16:1, r = 0.37; FFA18:1, r = 0.32; FFA18:2, r = 0.42), hepatocyte steatosis (FFA16: 1, r = 0.39; FFA18:1, r = 0.39; FFA18:2, r = 0.32), and ballooning (FFA16:0, r = 0.30; FFA16:1, r = 0.45; FFA18:1, r = 0.36; FFA18:2, r = 0.30) (all P

Both free and glycosidically bound forms of volatile compounds in Vidal grapes from the Shangri-La high-altitude region during the on-vine non-destructive dehydration process were investigated by headspace solid-phase micro-extraction (HS-SPME) combined with gas chromatography–mass spectrometry (GC-MS), following which the data were processed by multivariate statistical analysis. Fatty-acid-derived volatiles (FADs), amino-acid-derived volatiles (AADs), and isoprene-derived volatiles (IPDs), which occurred mainly in bound forms, were the three major volatiles in dehydrated Vidal grapes. Water-loss concentration, biosynthesis, and biodegradation all occurred during dehydration, eventually modifying some volatiles significantly, especially some powerful odorants such as hexanal, trans-2-hexenal, 2-phenethyl acetate, β-myrcene, linalool, geraniol, cis-rose oxide, and β-damascenone. 1-Octen-3-ol was relatively stable during the non-destructive on-vine dehydration process and its content in grape juice was mainly determined by the concentration effect. 2,4-Di-tert-butylphenol, 2-phenethyl acetate, 2-methyl-1-propanol, and hexanol were screened as some of the most important metabolic markers to discriminate grapes at different dehydration degrees. Our study also highlights the fundamental importance of the expression of volatile content in the metabolomic study of grape berries.

An adaptive fuzzy iterative learning control (ILC) algorithm is designed for the iterative variable reference trajectory problem of nonlinear discrete-time systems with input saturations and unknown control directions. Firstly, an adaptive fuzzy iterative learning controller is constructed by combining with the fuzzy logic system (FLS), which can compensate the loss caused by input saturation. Then, the discrete Nussbaum gain technique is adopted along the iteration axis, which can be embedded to the learning control method to identify the control direction of the system. Finally, based on the nonincreasing Lyapunov-like function, it is proven that the adaptive iterative learning controller can converge asymptotically when the number of iterations tends to infinity, and the system signals always remain bounded in the learning process. A simulation example verifies the feasibility and effectiveness of the learning control method.

PurposeWe aimed to develop a prognostic immunohistochemistry (IHC) signature for patients with head and neck mucosal melanoma (MMHN).MethodsIn total, 190 patients with nonmetastatic MMHN with complete clinical and pathological data before treatment were included in our retrospective study.ResultsWe extracted five IHC markers associated with overall survival (OS) and then constructed a signature in the training set (n=116) with the least absolute shrinkage and selection operator (LASSO) regression model. The validation set (n=74) was further built to confirm the prognostic significance of this classifier. We then divided patients into high- and low-risk groups according to the IHC score. In the training set, the 5-year OS rate was 22.0% (95% confidence interval [CI]: 11.2%- 43.2%) for the high-risk group and 54.1% (95% CI: 41.8%-69.9%) for the low-risk group (P

Based on real data, a new parameterized model of the Main Drift Chamberresponse is proposed. In this model, we tune the ratio of good hits and theresidual distribution separately. The difference between simulation and data intrack reconstruction efficiency reduces from 1% to 0.5%, and the momentumresolution agreement improves significantly.

Among the existing adaptive iterative learning control (ILC) work concerning unknown control direction problem, no result is available for the two-dimensional (2-D) dynamical systems. In this paper, an adaptive ILC is developed for a class of 2-D dynamical systems described by the Fornasini-Marchesini model (FMM). Notably, the 2-D FMM system under investigation possesses not only random uncertainties in boundary condition and reference trajectory, but also unknown control direction. Even so, the constructed adaptive ILC combining with a modification mechanism can still guarantee the precise tracking of iteration-variant reference trajectory and the boundedness of all the system signals, as iteration number k tends to infinity. Theoretical analysis and simulation study are given to demonstrate the effectiveness of the developed adaptive ILC.

Insect ecdysis triggering hormone (ETH) receptors (ETHRs) are rhodopsin-like G protein-coupled receptors. Upon binding its ligand ETH, ETHR initiates a precisely programed ecdysis behavior series and physiological events. In Drosophila melanogaster, the ethr gene produces two functionally distinct splicing isoforms, ethra and ethrb. ETH/ETHRA activates eclosion hormone (EH), kinin, crustacean cardioactive peptide (CCAP), and bursicon (burs and pburs) neurons, among others, in a rigid order, to elicit the behavioral sequences and physiological actions for ecdysis at all developmental stages, whereas ETH/ETHRB is required at both pupal and adult ecdysis. However, the role of ETHRB in regulation of molting has not been clarified in any non-drosophila insects. In the present paper, we found that 20-hydroxyecdysone (20E) signaling triggers the expression of both ethra and ethrb in a Coleopteran insect pest, the Colorado potato beetle Leptinotarsa decemlineata. RNA interference (RNAi) was performed using double-stranded RNAs (dsRNAs) targeting the common (dsethr) or isoform-specific (dsethra, dsethrb) regions of ethr. RNAi of dsethr, dsethra, or dsethrb by the final-instar larvae arrested larva development. The arrest was not rescued by feeding 20E. All the ethra depleted larvae stopped development at prepupae stage; the body cavity was expanded by a large amount of liquid. Comparably, more than 80% of the ethrb RNAi larvae developmentally halted at the prepupae stage. The remaining Ldethrb hypomorphs became pupae, with blackened wings and highly-expressed burs, pburs and four melanin biosynthesis genes. Therefore, ETHRA and ETHRB play isoform-specific roles in regulation of ecdysis during larva-pupa transition in L. decemlineata.

The continuing emergence and development of pathogenic microorganisms that are resistant to antibiotics constitute an increasing global concern, and the effort in new antimicrobials discovery will remain relevant until a lasting solution is found. A new bacterial strain, designated JFL21, was isolated from seafood and identified as B. amyloliquefaciens. The antimicrobial substance produced by B. amyloliquefaciens JFL21 showed low toxicity to most probiotics but exhibited strong antimicrobial activities against multidrug-resistant foodborne pathogens. The partially purified antimicrobial substance, Anti-JFL21, was characterized to be a multiple lipopeptides mixture comprising the families of surfactin, fengycin, and iturin. Compared with commercially available polymyxin B and Nisin, Anti-JFL21 not only could exhibit a wider and stronger antibacterial activity toward Gram-positive pathogens but also inhibit the growth of a majority of fungal pathogens. After further separation through gel filtration chromatography (GFC), the family of surfactin, fengycin, and iturin were obtained, respectively. The results of the antimicrobial test pointed out that only fengycin family presented marked antimicrobial properties against the indicators of L. monocytogenes, A. hydrophila, and C. gloeosporioides, which demonstrated that fengycins might play a major role in the antibacterial and antifungal activity of Anti-JFL21. Additionally, the current study also showed that the fengycins produced by B. amyloliquefaciens JFL21 not only maintained stable anti-Listeria activity over a broad pH and temperature range, but also remained active after treatment with ultraviolet sterilization, chemical reagents, and proteolytic enzymes. Therefore, the results of this study suggest the new strain and its antimicrobials are potentially useful in food preservation for the biological control of the multidrug-resistant foodborne pathogens.

This study evaluated the potential effects of adding acidifiers to the drinking water on the growth performance, complete blood count, antioxidant indicators, and diversity of gastrointestinal microbiota for weaned pigs. A total of 400 weaned pigs were randomly divided into four treatments. Pigs were fed the same basal diet and given either water (no acidifier was added, control) or water plus blends of different formulas of acidifiers (acidifier A1, A2, or A3) for 35 days. On d 18 and 35 of the experimental period, 64 pigs (four pigs per pen) were randomly selected to collect blood for a CBC test (n = 128) and an antioxidant indicators test (n = 128); 24 pigs (six pigs per group) were randomly selected to collect fresh feces (n = 48) from the rectum for 16S rRNA gene sequencing. Compared to the control, supplementing the drinking water with acidifiers improved the growth performance and survival rate of weaned pigs. Acidifier groups also increased serum catalase (CAT) and total antioxidant capacity (T-AOC) activities, while also displaying a decreased malondialdehyde (MDA) concentration compared to the control. The relative abundance of Firmicutes in the acidifier A1 group was greater than that in the control group (p < 0.05) on d 35; the relative abundance of Lactobacillus in the acidifier A1 group was greater than that in the control group (p < 0.05) on d 18 and 35. The microbial species Subdoligranulum or Ruminococcaceae_UCG-005 had significantly positive correlations with ADG and ADFI or with serum antioxidant indicators, respectively. These findings suggest that supplementing the drinking water with an acidifier has a potential as an antioxidant, which was reflected in the improvement of growth performance, immunity, antioxidant capacity, and intestinal flora.