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Abstract Cisplatin (CP), a chemotherapy drug commonly used in cancers treatment, causes serious reproductive toxicity. With younger cancer patients and increasing survival rates, it is important to preserve their reproductive capacity. NME8 is highly expressed in testis and contains thioredoxin and NDPK domains, suggesting it may be a target against the CP-induced reproductive toxicity. We deleted exons 6–7 of the Nme8 in mice based on human mutation sites and observed impaired transcript splicing. In mice, Nme8 was not essential for spermatogenesis, possibly due to functional compensation by its paralog, Nme5. Nme8 expression was elevated and translocated to the nucleus in response to two weeks of CP treatment. Under CP treatment, Nme8 deficiency further impaired antioxidant capacity, induced lipid peroxidation and increased ROS level, and failed to activate autophagy, resulting in aggravated DNA damage in testes and sperm. Consequently, the proliferation and differentiation of spermatogonia and the meiosis of spermatocyte were almost completely halted, and sperm motility was impaired. Our research indicates that NME8 protects against CP-induced testis and sperm damage. This may provide new insights into the physiological functions of the Nme family and potential targets for preserving fertility in young male cancer patients.

The production of androst-4-ene-3,17-dione (AD) by the steroidal microbial cell factory requires transcription factors (TFs) to participate in metabolic regulation. However, microbial cell factory lacks effective TFs that can respond to AD in its metabolic pathway. Additionally, finding and obtaining natural TFs that specifically respond to AD is a complex and onerous task. In this study, we devised an artificial TF that responds to AD, termed AdT, based on structure-guided molecular dynamics (MD) simulation. According to MD analysis of the conformational changes of AdT after binding to AD, an LBD in which the N- and C-termini exhibited convergence tendencies was used as a microswitch to guide the assembly of a DNA-binding domain lexA, a linker (GGGGS)2, and a transcription activation domain B42 into an artificial TF. As a proof of design, a AD biosensor was designed and constructed in yeast on the basis of the ligand-binding domain (LBD) of hormone receptor. In addition, the transcription factor activity of AdT was increased by 1.44-fold for its variant F320Y. Overall, we created non-natural TF elements for AD microbial cell factory, and expected that the design TF strategy will be applied to running in parallel to the signaling machinery of the host cell.

Orchidaceae are one of the largest families of angiosperms in terms of species richness. In the last decade, numerous studies have delved into reconstructing the phylogenetic framework of Orchidaceae, leveraging data from plastid, mitochondrial and nuclear sources. These studies have provided new insights into the systematics, diversification and biogeography of Orchidaceae, establishing a robust foundation for future research. Nevertheless, pronounced controversies persist regarding the precise placement of certain lineages within these phylogenetic frameworks. To address these discrepancies and deepen our understanding of the phylogenetic structure of Orchidaceae, we provide a comprehensive overview and analysis of phylogenetic studies focusing on contentious groups within Orchidaceae since 2015, delving into discussions on the underlying reasons for observed topological conflicts. We also provide a novel phylogenetic framework at the subtribal level. Furthermore, we examine the tempo and mode underlying orchid species diversity from the perspective of historical biogeography, highlighting factors contributing to extensive speciation. Ultimately, we delineate avenues for future research aimed at enhancing our understanding of Orchidaceae phylogeny and diversity.

Abstract Background Patients with pancreatic ductal adenocarcinoma (PDAC) display an altered oral, gastrointestinal, and intra-pancreatic microbiome compared to healthy individuals. However, knowledge regarding the bile microbiome and its potential impact on progression-free survival in PDACs remains limited. Methods Patients with PDAC (n = 45), including 20 matched pairs before and after surgery, and benign controls (n = 16) were included prospectively. The characteristics of the microbiomes of the total 81 bile were revealed by 16 S-rRNA gene sequencing. PDAC patients were divided into distinct groups based on tumor marker levels, disease staging, before and after surgery, as well as progression free survival (PFS) for further analysis. Disease diagnostic model was formulated utilizing the random forest algorithm. Results PDAC patients harbor a unique and diverse bile microbiome (PCoA, weighted Unifrac, p = 0.038), and the increasing microbial diversity is correlated with dysbiosis according to key microbes and microbial functions. Aliihoeflea emerged as the genus displaying the most significant alteration among two groups (p

Abstract The exploration of post-Lithium (Li) metals, such as Sodium (Na), Potassium (K), Magnesium (Mg), Calcium (Ca), Aluminum (Al), and Zinc (Zn), for electrochemical energy storage has been driven by the limited availability of Li and the higher theoretical specific energies compared to the state-of-the-art Li-ion batteries. Post-Li metal||S batteries have emerged as a promising system for practical applications. Yet, the insufficient understanding of quantitative cell parameters and the mechanisms of sulfur electrocatalytic conversion hinder the advancement of these battery technologies. This perspective offers a comprehensive analysis of electrode parameters, including S mass loading, S content, electrolyte/S ratio, and negative/positive electrode capacity ratio, in establishing the specific energy (Wh kg−1) of post-Li metal||S batteries. Additionally, we critically evaluate the progress in investigating electrochemical sulfur conversion via homogeneous and heterogeneous electrocatalytic approaches in both non-aqueous Na/K/Mg/Ca/Al||S and aqueous Zn||S batteries. Lastly, we provide a critical outlook on potential research directions for designing practical post-Li metal||S batteries.

Since the outbreak of the new coronavirus, point-of-care diagnostics based on nucleic acid testing have become a requirement for the development of pathogen diagnostics, which require the ability to accurately, rapidly, and conveniently detect pathogens. Conventional nucleic acid amplification techniques no longer meet the requirements for pathogen detection in low-resource, low-skill environments because they require specialist equipment, complex operations, and long detection times. Therefore, recombinant polymerase amplification (RPA) is becoming an increasingly important method in today’s nucleic acid detection technology because it can amplify nucleic acids in 20–30 minutes at a constant temperature, greatly reducing the dependence on specialist equipment and technicians. RPA products are primarily detected through methods such as real-time fluorescence, gel electrophoresis, lateral flow assays (LFAs), and other techniques. Among these, LFAs allow for the rapid detection of amplification products within minutes through the visualization of results, offering convenient operation and low cost. Therefore, the combination of RPA with LFA technology has significant advantages and holds broad application prospects in point-of-care (POC) diagnostics, particularly in low-resource settings. Here, we focus on the principles of RPA combined with LFAs, their application to pathogen diagnosis, their main advantages and limitations, and some improvements in the methods.

Objectives: This study conducted a network meta-analysis comparing linezolid, teicoplanin, daptomycin, tigecycline, and ceftaroline fosamil with vancomycin for treating MRSA-related diseases, addressing the lack of comprehensive evaluations in existing research on antibiotic therapy for MRSA infections. Methods: We systematically searched databases including PubMed, Embase, Web of Science, the Cochrane Librar up to August 22, 2023. All eligible randomized controlled trials of the six antibiotics were included in the NMA, and their effectiveness and safety were compared across various MRSA-related diseases. Categorical data were used for the odds ratio (OR), and continuous data were used for mean difference (SMD). The surface under the cumulative ranking (SUCRA) was employed to evaluate the incidence rate. Results: According to SUCRA results, daptomycin was the most effective treatment (73.0%) in bloodstream infections. In pulmonary infections and skin and soft tissue infections, linezolid out-performed other antibiotics in effectiveness rate (90.6% and 86.3%), microbial killing rate (93.3% and 93.1%). Vancomycin showed lower adverse reactions than teicoplanin, with less hepatotoxicity compared to linezolid and tigecycline. Linezolid had higher thrombocytopenia risk but lower nephrotoxicity risk than others. Vancomycin was less effective in microbial killing rates than linezolid across various infections. Conclusion: The present research suggests that in pulmonary infections and skin and soft tissue infections, linezolid may be a better option for treating MRSA-related diseases. However, caution is warranted due to the association of linezolid with thrombocytopenia. Trial registration: Our study protocol was registered with the International Prospective Register of SystematicReviews (PROSPERO); Registration number: CRD42024535142.

Abstract The increase in the emergence of antimicrobial resistance has led to great challenges in controlling porcine extraintestinal pathogenic Escherichia coli (ExPEC) infections. Combinations of antimicrobial peptides (AMPs) and antibiotics can synergistically improve antimicrobial efficacy and reduce bacterial resistance. In this study, we investigated the antibacterial activity of porcine myeloid antimicrobial peptide 36 (PMAP-36) in combination with tetracycline against porcine ExPEC PCN033 both in vitro and in vivo. The minimum bactericidal concentrations (MBCs) of AMPs (PMAP-36 and PR-39) against the ExPEC strains PCN033 and RS218 were 10 μM and 5 μM, respectively. Results of the checkerboard assay and the time-kill assay showed that PMAP-36 and antibiotics (tetracycline and gentamicin) had synergistic bactericidal effects against PCN033. PMAP-36 and tetracycline in combination led to PCN033 cell wall shrinkage, as was shown by scanning electron microscopy. Furthermore, PMAP-36 delayed the emergence of PCN033 resistance to tetracycline by inhibiting the expression of the tetracycline resistance gene tetB. In a mouse model of systemic infection of PCN033, treatment with PMAP-36 combined with tetracycline significantly increased the survival rate, reduced the bacterial load and dampened the inflammatory response in mice. In addition, detection of immune cells in the peritoneal lavage fluid using flow cytometry revealed that the combination of PMAP-36 and tetracycline promoted the migration of monocytes/macrophages to the infection site. Our results suggest that AMPs in combination with antibiotics may provide more therapeutic options against multidrug-resistant porcine ExPEC.

Immune checkpoints inhibitors are effective but it needs more precise biomarkers for patient selection. We explored the biological significance of LINC00862 in pan-cancer by bioinformatics. And we studied its regulatory mechanisms using chromatin immunoprecipitation and RNA immunoprecipitation assays etc. TCGA and single-cell sequencing data analysis indicated that LINC00862 was overexpressed in the majority of tumor and stromal cells, which was related with poor prognosis. LINC00862 expression was related with immune cell infiltration and immune checkpoints expression, and had a high predictive value for immunotherapy efficacy. Mechanistically, LINC00862 competitively bound to miR-29c-3p to unleash SIRT1’s tumor-promoting function. SIRT1 inhibitor-EX527 were screened by virtual screening and verified by in vitro and vivo assays. Notably, acetyltransferase P300-mediated super-enhancer activity stimulated LINC00862 transcription. Collectively, LINC00862 could be a diagnostic and prognostic biomarker. LINC00862 could also be a predictive biomarker for immunotherapy efficacy. Super-enhancer activity is the driver for LINC00862 overexpression in cervical cancer and gastric cancer.

Lgl1 protein plays a critical role in neurodevelopment, including hippocampus, olfactory bulb, and Purkinje cell. However, the specific mechanism of LGL1 function in the midbrain remains elusive. In this study, we generated Lgl1 conditional knockout mice using Pax2-Cre, which is expressed in the midbrain, and examined the functions of Lgl1 in the midbrain. Histological analysis exhibited abnormal midbrain development characterized by enlarged ventricular aqueduct and thinning tectum cortex. Lgl1 deletion caused excessive proliferation and heightened apoptosis of neural progenitor cells in the tectum of LP cko mice. BrdU labeling studies demonstrated abnormal neuronal migration. Immunofluorescence analysis of Nestin demonstrated an irregular and clustered distribution of glial cell fibers, with the adhesion junction marker N-cadherin employed for immunofluorescent labeling, unveiling abnormal epithelial connections within the tectum of LP cko mice. The current findings suggest that the deletion of Lgl1 leads to the disruption of the expression pattern of N-cadherin, resulting in abnormal development of the midbrain.

Abstract Glutarate is a key monomer in polyester and polyamide production. The low efficiency of the current biosynthetic pathways hampers its production by microbial cell factories. Herein, through metabolic simulation, a lysine-overproducing E. coli strain Lys5 is engineered, achieving titer, yield, and productivity of 195.9 g/L, 0.67 g/g glucose, and 5.4 g/L·h, respectively. Subsequently, the pathway involving aromatic aldehyde synthase, monoamine oxidase, and aldehyde dehydrogenase (AMA pathway) is introduced into E. coli Lys5 to produce glutarate from glucose. To enhance the pathway’s efficiency, rational mutagenesis on the aldehyde dehydrogenase is performed, resulting in the development of variant Mu5 with a 50-fold increase in catalytic efficiency. Finally, a glutarate tolerance gene cbpA is identified and genomically overexpressed to enhance glutarate productivity. With enzyme expression optimization, the glutarate titer, yield, and productivity of E. coli AMA06 reach 88.4 g/L, 0.42 g/g glucose, and 1.8 g/L·h, respectively. These findings hold implications for improving glutarate biosynthesis efficiency in microbial cell factories.

Abstract Glutathione synthetase (GSS) catalyzes the final step in the synthesis of glutathione (GSH), a well-established antioxidant. Research on the specific roles of the Gss gene during spermatogenesis remains limited due to the intricate structure of testis. In this study, we identified pachytene spermatocytes as the primary site of GSS expression and generated a mouse model with postnatal deletion of Gss using Stra8-Cre (S8) to investigate the role of GSS in germ cells. The impact of Gss knockout on reducing male fertility is age-dependent and caused by ferroptosis in the testis. The 2-month-old S8/Gss −/− male mice exhibited normal fertility, due to a compensatory increase in GPX4, which prevented the accumulation of ROS. With aging, there was a decline in GPX4 and an increase in ALOX15 levels observed in 8-month-old S8/Gss −/− mice, resulting in the accumulation of ROS, lipid peroxidation, and ultimately testicular ferroptosis. We found that testicular ferroptosis did not affect spermatogonia, but caused meiosis disruption and acrosome heterotopia. Then the resulting aberrant sperm showed lower concentration and abnormal morphology, leading to reduced fertility. Furthermore, these injuries could be functionally rescued by inhibiting ferroptosis through intraperitoneal injection of GSH or Fer-1. In summary, Gss in germ cells play a crucial role in the resistance to oxidative stress injury in aged mice. Our findings deepen the understanding of ferroptosis during spermatogenesis and suggest that inhibiting ferroptosis may be a potential strategy for the treatment of male infertility.

Special environmental microorganisms are considered to be of great industrial application value because of their special genotypes, physiological functions and metabolites. The research and development of special environmental microorganisms will certainly bring about some innovations in biotechnology processes and change the face of bioengineering. The Special Environmental Microbial Database (DSEMR) is a comprehensive database that provides information on special environmental microbial resources and correlates them with synthetic biological parts. DSEMR aggregates information on specific environmental microbial genomes, physiological properties, culture media, biological parts, and metabolic pathways, and provides online tool analysis data, including 5268 strains from 620 genera, 31 media, and 42,126 biological parts. In short, DSEMR will become an important resource for the study of microorganisms in special environments and actively promote the development of synthetic biology.

A new type of SiCf/TiC-Ti3SiC2 composite was prepared by the Spark Plasma Sintering (SPS) method in this work. The phase transformation and interface cracking of this composite under ion irradiation (single Xe, Xe + He, and Xe + He + H ions) and subsequent annealing were analyzed using transmission electron microscopy (TEM), mainly focusing on the interface regions. Xe ion irradiation resulted in the formation of high-density stacking faults in the TiC coatings and the complete amorphization of SiC fibers. The implanted H ions exacerbated interface coarsening. After annealing at 900 °C for 2 h, the interface in the Xe + He + H ion-irradiated samples was seriously damaged, resulting in the formation of large bubbles and cracks. This damage occurred because the H atoms reduced the surface free energy, thereby promoting the nucleation and growth of bubbles. Due to the absorption effect of the SiCf/TiC interface on defects, the SiC fiber areas near the interface recovered back to the initial nano-polycrystalline structure after annealing.

Highlights A humanoid intelligent display platform (HIDP) is created using stretchable and resilient ionotronic materials, and can be applicable in extreme environments and complex mechanical stimulations. HIDP links sound amplitude and brightness through machine learning for audiovisual interaction. HIDP identifies and displays animal species and corresponding frequencies in real-time.

Biomimetic structures often endow materials with excellent performance. In order to explore the impact of biomimetic structures on the performance of energetic materials, the sedum multiceps-like bionic structure dihydroxylammonium 5,5′-bistetrazole-1,1′-diolate (TKX-50) was constructed by self-assembly technology, and controllable particle size adjustment was achieved. Moreover, the effects of solvent ratio, solute content, stirring flow field, and temperature on the quality of sedum multiceps-like TKX-50 crystals were explored, and the formation mechanism of sedum multiceps-like TKX-50 crystals was analyzed. Then, the crystal morphology, crystal form and particle size distribution of sedum multiceps-like TKX-50 were characterized, furthermore, the thermal properties and mechanical sensitivity of sedum multiceps-like TKX-50 were emphatically studied. The results showed that the sedum multiceps-like biomimetic structure TKX-50 was assembled from needle shaped or sheet shaped small particle crystals, and the sedum multiceps-like structure did not change the explosive crystal form of TKX-50. What's more, the thermal decomposition activation energy of the prepared sedum multiceps-like TKX-50 crystal was at least 157.30 kJ⋅mol−1 and at most 185.27 kJ⋅mol−1, and the thermal energy was greatly affected by particle size. In addition, the minimum and maximum ultimate impact energy of the sedum multiceps-like TKX-50 crystals are 20 J and 55 J. The ultimate impact energy of the sedum multiceps-like TKX-50 crystal with different particle sizes is higher than that of the raw TKX-50 (15 J). As a consequence, the sedum multiceps-like bionic structure effectively improves the energy release of TKX-50, reduces the impact sensitivity, and improves the uniformity of particle size distribution.

In this paper, a practical discrete-time control method with adaptive image feature prediction for the image-based visual servoing (IBVS) scheme is presented. In the discrete-time IBVS inner-loop/outer-loop control architecture, the time delay caused by image capture and computation is noticed. Considering the dynamic characteristics of a 6-DOF manipulator velocity input system, we propose a linear dynamic model to describe the motion of a robot end effector. Furthermore, for better estimation of image features and smoothing of the robot’s velocity input, we propose an adaptive image feature prediction method that employs past image feature data and real robot velocity data to adopt the prediction parameters. The experimental results on a 6-DOF robotic arm demonstrate that the proposed method can ensure system stability and accelerate system convergence.

In recent years, the clinical cases of ENTV-2 infection have increased and become prevalent in several provinces of China. In this study, we reported the occurrence of ENTV-2 in one goat farm in Chongqing, southwest China. The complete genome of an emerged ENTV-2 isolate (designated as CQ2) was sequenced with 7468 bp in length. Phylogenetic analysis revealed that ENTV-2 consisted of two main lineages. Lineage 1 was composed of Chinese strains and could be subdivided into five sublineages. CQ2 and the other six recent isolates from China were clustered in sublineage 1.5; however, CQ2 was significantly different from the other six isolates. Furthermore, recombination analysis suggested that CQ2 might be a recombinant variant derived from sublineage 1.5 and sublineage 1.2 strains, with the recombination region in areas of pro and pol genes. In conclusion, we sequenced and analyzed the complete genome of a potential ENTV-2 recombinant, which may contribute to our understanding of the genetic variation and evolution of ENTV-2 in China.

Abstract Objectives The clinical features of aseptic meningitis associated with amoxicillin are unknown. The main objective of this study was to investigate the clinical characteristics of amoxicillin-induced aseptic meningitis (AIAM) and provide a reference for clinical diagnosis and treatment. Methods AIAM-related studies were collected by searching the relevant databases from inception to October 31, 2022. Results AIAM usually occurred 3 h to 7 days after amoxicillin administration in 13 males and 9 females. Twenty-one patients (95.5%) had recurrent AIAM with a total of 62 episodes. Fever (19 cases, 86.4%) and headache (18 cases, 81.8%) were the most common symptoms. Typical cerebrospinal fluid (CSF) findings were leukocytosis (100%) with lymphocytic predominance (14 cases, 63.6%), elevated protein (20 cases, 90.1%), normal glucose (21 cases, 95.5%) and negative culture (21 cases, 100%). Brain magnetic resonance imaging showed mild meningeal enhancement in one patient. The symptoms resolved mainly within 1–4 days after drug discontinuation in all patients. Conclusion Clinical attention should be given to the adverse effects of AIAM. The medication history of patients with suspected meningitis should be investigated to avoid unnecessary examination and antibiotic treatment.

Abstract Streptococcus suis serotype 2 (SS2) is an important zoonotic pathogen with the characteristics of high mortality and morbidity, which brings great challenges to prevent and control epidemic disease in the swine industry. Cathelicidins (CATH) are antimicrobial peptides with antimicrobial and immunomodulatory activities. In this study, bactericidal and anti-inflammatory effects of chicken cathelicidin-1 (CATH-1) were investigated in vitro and in vivo against SS2 infection. The results show that CATH-1 exhibited a better bactericidal effect compared to other species’ cathelicidins including chickens (CATH-2, -3, and -B1), mice (CRAMP) and pigs (PMAP-36 and PR-39), which rapidly killed bacteria in 20 min by a time-killing curve assay. Furthermore, CATH-1 destroyed the bacterial morphology and affected bacterial ultrastructure as observed under electron microscopy. Moreover, CATH-1 antibacterial activity in vivo shows that CATH-1 increased survival rate of SS2-infected mice by 60% and significantly reduced the bacterial load in the lungs, liver, spleen, blood, and peritoneal lavage as well as the release of SS2-induced inflammatory cytokines including IL-1α, IL-1β, IL-12, and IL-18. Importantly, CATH-1 did not show severe histopathological changes in mice. Further studies on the mechanism of anti-inflammatory activity show that CATH-1 not only reduced the inflammatory response through direct neutralization, but also by regulating the TLR2/4/NF-κB/ERK pathway. This study provides a scientific basis for the research and development of antimicrobial peptides as new antimicrobial agents.

The external influencing factors, the thermal interface material, load-bearing brick weight, and temperature difference, of a thermoelectric generator (TEG) device were experimentally examined. The micro heat pipe array (MHPA), as one novel thermal interface material, was investigated. The multi-variable coupling approach is used to analyze the intrinsic coupling correlation of the external influencing factors. The dimensionless synthesis economic factor index was proposed to analyze the improvement of thermoelectric characteristics, which can quickly assess the contact thermal resistance of different thermal interface materials. The results showed that the load power and load voltage generally increase with increased temperature differences. The contact thermal resistance decreases with increased load-bearing brick weight, but the decrement gradually decreases. The thermal interface material plays an important role in thermoelectric characteristics. The load-bearing brick weight performs little impact on the non-thermal interface material (NTIM) scheme. The two thermal conductive silicone grease schemes noticeably reveal better thermoelectric characteristics than those of the graphite paper schemes, although the thermal conductivity of thermal conductive silicone grease are much lower than that of graphite paper. The MHPA scheme exhibit the best thermoelectric characteristics, and its dimensionless synthesis economic factor index can be up to 371.81 %.

Abstract In addition to being an important intermediate in the TCA cycle, L‐malate is also widely used in the chemical and beverage industries. Due to the resulting high demand, numerous studies investigated chemical methods to synthesize L‐malate from petrochemical resources, but such approaches are hampered by complex downstream processing and environmental pollution. Accordingly, there is an urgent need to develop microbial methods for environmentally‐friendly and economical L‐malate biosynthesis. The rapid progress and understanding of DNA manipulation, cell physiology, and cell metabolism can improve industrial L‐malate biosynthesis by applying intelligent biochemical strategies and advanced synthetic biology tools. In this paper, we mainly focused on biotechnological approaches for enhancing L‐malate synthesis, encompassing the microbial chassis, substrate utilization, synthesis pathway, fermentation regulation, and industrial application. This review emphasizes the application of novel metabolic engineering strategies and synthetic biology tools combined with a deep understanding of microbial physiology to improve industrial L‐malate biosynthesis in the future.

Abstract Background Recently, accumulating studies have unveiled that circRNAs exert critical function in a variety of tumor biological processes including chemoresistance. Our previous study has found circACTR2 is significantly down-regulated in acquired gemcitabine (GEM)- resistant pancreatic cancer (PC) cells, which has not been well-explored. Our study aimed to research the function and molecular mechanism of circACTR2 in PC chemoresistance. Methods qRT-PCR and western blot analysis was performed to detect gene expression. The effect of circACTR2 on PC GEM resistance were examined by CCK-8 and flow cytometry assays. Whether circACTR2 could sponge miR-221-3p and regulate PTEN expression were determined by bioinformatics analysis, RNA pull-down, and Dual-luciferase reporter assay. Results circACTR2 was notably down-regulated in a panel of GEM-resistant PC cells lines, and negatively associated with aggressive phenotype and poor prognosis of PC. circACTR2 downregulation contributed to GEM chemoresistance of PC cells with decreased S phase ratio of cell cycle and cell apoptosis, as confirmed by gain- and loss-of-function assays in vitro. In addition, circACTR2 overexpression retarded GEM resistance in vivo. Further, circACTR2 acted as a ceRNA against miR-221-3p, which directly targeted PTEN. The mechanistic studies revealed that loss of circACTR2 promoted GEM resistance in PC through activating the PI3K/AKT signaling pathway by downregulating PTEN expression in a miR-221-3p dependent manner. Conclusions circACTR2 reversed the chemoresistance of PC cells to GEM through inhibiting PI3K/AKT signaling pathway by sponging miR-221-3p and upregulating PTEN expression.

Abstract Structural biomimicry is an intelligent approach for developing lightweight, strong, and tough materials (LSTMs). Current fabrication technologies, such as 3D printing and two‐photon lithography often face challenges in constructing complex interlaced structures, such as the sinusoidal crossed herringbone structure that contributes to the ultrahigh strength and fracture toughness of the dactyl club of peacock mantis shrimps. Herein, bioinspired LSTMs with laminated or herringbone structures is reported, by combining textile processing and silk fiber “welding” techniques. The resulting biomimetic silk LSTMs (BS‐LSTMs) exhibit a remarkable combination of lightweight with a density of 0.6–0.9 g cm−3, while also being 1.5 times stronger and 16 times more durable than animal horns. These findings demonstrate that BS‐LSTMs are among the toughest natural materials made from silk proteins. Finite element simulations further reveal that the fortification and hardening of BS‐LSTMs arise primarily from the hierarchical organization of silk fibers and mechanically transferable meso‐interfaces. This study highlights the rational, cost‐effective, controllable mesostructure, and transferable strategy of integrating textile processing and fiber “welding” techniques for the fabrication of BS‐LSTMs with advantageous structural and mechanical properties. These findings have significant implications for a wide range of applications in biomedicine, mechanical engineering, intelligent textiles, aerospace industries, and beyond.

Future rainfall and land use are two important factors for flood management since they both directly and indirectly affect the functionality and performance of urban stormwater drainage infrastructures. Although some studies have already examined the coupled effects of future rainfall and land use conditions, they have not concluded how such effects on both surface runoff and flood areas would change with regional surface elevation variation and infrastructure conditions. This paper analyzed the coupled effects of future rainfall and land use on urban drainage systems in terms of surface runoff quantity and flood area changes using EPA SWMM. Future downscaled and bias-corrected precipitation projections for 2040–2060 and 2080–2099 from “Downscaled CMIP3 and CMIP5 Climate and Hydrology Projections” Archive and future land use for 2050 s and 2090 s from EPA ICLUS project were used for the City of Tampa in Florida (USA). It was shown that potential runoff volume and flood area changes ranged from −40% to 160%, and −40% to 400% due to rainfall change, while potential changes induced by land use change ranged from 0% to 3.5%, and 0% to 18% respectively. Additionally, this study examined the coupled effects of future rainfall and land use changes on flood area variations, considering the capacity of drainage infrastructure and elevation variation of study site. Results showed that flood area variations are not solely influenced by runoff quantity changes due to the two external drivers, but also by other factors. Specifically, in low-relief areas with inadequate drainage infrastructure and less elevation variation, these two drivers have no additive effects on the percentage of flood area changes. In contrast, in areas with adequate drainage infrastructure and greater surface elevation variation, there are additive effects from rainfall and land use changes on flood area expansions. These findings have important implications for stakeholders involved in city planning and flooding control, particularly for urban areas facing future precipitation and urbanization challenges.

Abstract Background Advanced DNA synthesis, biosensor assembly, and genetic circuit development in synthetic biology and metabolic engineering have reinforced the application of filamentous bacteria, yeasts, and fungi as promising chassis cells for chemical production, but their industrial application remains a major challenge that needs to be solved. Results As important chassis strains, filamentous microorganisms can synthesize important enzymes, chemicals, and niche pharmaceutical products through microbial fermentation. With the aid of metabolic engineering and synthetic biology, filamentous bacteria, yeasts, and fungi can be developed into efficient microbial cell factories through genome engineering, pathway engineering, tolerance engineering, and microbial engineering. Mutant screening and metabolic engineering can be used in filamentous bacteria, filamentous yeasts (Candida glabrata, Candida utilis), and filamentous fungi (Aspergillus sp., Rhizopus sp.) to greatly increase their capacity for chemical production. This review highlights the potential of using biotechnology to further develop filamentous bacteria, yeasts, and fungi as alternative chassis strains. Conclusions In this review, we recapitulate the recent progress in the application of filamentous bacteria, yeasts, and fungi as microbial cell factories. Furthermore, emphasis on metabolic engineering strategies involved in cellular tolerance, metabolic engineering, and screening are discussed. Finally, we offer an outlook on advanced techniques for the engineering of filamentous bacteria, yeasts, and fungi.

Abstract Pasteurella multocida (P. multocida) can cause severe respiratory disease in cattle, resulting in high mortality and morbidity. Inflammasomes are multiprotein complexes in the cytoplasm that recognize pathogens and play an important role in the host defense against microbial infection. In this study, the mechanism of P. multocida-induced NLRP6 inflammasome activation was investigated in vitro and in vivo. Firstly, P. multocida induced severe inflammation with a large number of inflammatory cells infiltrating the lungs of WT and Nlrp6 −/− mice. Nlrp6 −/− mice were more susceptible to P. multocida infection and they had more bacterial burden in the lungs. Then, the recruitment of macrophages and neutrophils in the lungs was investigated and the results show that the number of immune cells was significantly decreased in Nlrp6 −/− mice. Subsequently, NLRP6 was shown to regulate P. multocida-induced inflammatory cytokine secretion including IL-1β and IL-6 both in vivo and in vitro while TNF-α secretion was not altered. Moreover, NLRP6 was found to mediate caspase-1 activation and ASC oligomerization, resulting in IL-1β secretion. Furthermore, NLRP6 inflammasome mediated the gene expression of chemokines including CXCL1, CXCL2 and CXCR2 which drive the activation of NLRP3 inflammasomes. Finally, NLRP3 protein expression was detected to be abrogated in P. multocida-infected Nlrp6 −/− macrophages, indicating the synergic effect of NLRP6 and NLRP3. Our study demonstrates that NLRP6 inflammasome plays an important role in the host against P. multocida infection and contributes to the development of immune therapeutics against P. multocida.

Abstract Chicken cathelicidin-2 (CATH-2) as a host defense peptide has been identified to have potent antimicrobial and immunomodulatory activities. Here, we reported the mechanism by which CATH-2 modulates NLRP3 inflammasome activation. Our results show that CATH-2 and ATP as a positive control induced secretion of IL-1β and IL-1α in LPS-primed macrophages but did not affect secretion of IL-6, IL-12 and TNF-α. Furthermore, CATH-2 induced caspase-1 activation and oligomerization of apoptosis-associated speck-like protein containing a carboxy- terminal caspase recruitment domain (ASC), which is essential for NLRP3 inflammasome activation. However, CATH-2 failed to induce IL-1β secretion in Nlrp3−/−, Asc−/− and Casp1−/− macrophages. Notably, IL-1β and NLRP3 mRNA expression were not affected by CATH-2. In addition, CATH-2-induced NLRP3 inflammasome activation was mediated by K+ efflux but independent of the P2X7 receptor that is required for ATP-mediated K+ efflux. Gene interference of NEK7 kinase which has been identified to directly interact with NLRP3, significantly reduced IL-1β secretion and caspase-1 activation induced by CATH-2. Furthermore, confocal microscopy shows that CATH-2 significantly induced lysosomal leakage with the diffusion of dextran fluorescent signal. Cathepsin B inhibitors completely abrogated IL-1β secretion and caspase-1 activation as well as attenuating the formation of ASC specks induced by CATH-2. These results all indicate that CATH-2-induced activation of NLRP3 inflammasome is mediated by K+ efflux, and involves the NEK7 protein and cathepsin B. In conclusion, our study shows that CATH-2 acts as a second signal to activate NLRP3 inflammasome. Our study provides new insight into CATH-2 modulating immune response.

Summary: National key protected wild plants (NKPWPs) are considered flagship species for plant diversity conservation in China. Using data for 1101 species, we characterized NKPWPs distribution patterns in China and assessed conservation effectiveness and conservation gaps. In total, 4880 grid cells at a 20 × 20 km resolution were filled with occurrence records for NKPWPs. We identified 444 hotspot grid cells and 27 diversity hotspot regions, containing 92.37% of NKPWPs. However, 43.24% of these hotspot grid cells were fully or partially covered by national nature reserves (NNRs), where 70.21% of species were distributed. Approximately 61.49% of the NKPWPs species were protected by NNRs, but the populations or habitats of 963 species were partially or fully outside of NNRs. With global warming, the overall change in the extent of suitable habitats for NKPWPs is expected to be small, however, habitat quality in some areas with a high habitat suitability index will decrease.

Bovine parainfluenza virus type 3 (BPIV-3), also known as bovine respirovirus 3, is a common respiratory pathogen associated with bovine respiratory disease (BRD). BPIV-3 has currently circulated worldwide; however, data on the prevalence and genetic characteristics of BPIV-3 are still scarce and limited. In this study, the BPIV-3 strain SC was identified and isolated from cattle presenting with clinical signs of BRD in China. Animal experiments indicated that BPIV-3 SC can successfully infect C57BL/6 mice and induce weight loss, lung inflammatory cell infiltration, and inflammatory cytokine expression in mice. In addition, the complete genome of BPIV-3 SC was obtained using next-generation sequencing and was 15,473 bp in length. Phylogenetic analysis indicated that BPIV-3 SC belonged to genotype C, which clustered in the same large clade consisting of a population of Chinese genotype C strains but was found to be different from the other strains upon further differentiation. Compared to other Chinese genotype C strains, the BPIV-3 SC showed 70 unique nucleotide mutations and 13 unique amino acid mutations in the HN, P, and L proteins, suggesting a unique genetic evolution of BPIV-3 SC. In conclusion, we isolated and characterized a differential Chinese genotype C BPIV-3, which contributed to an understanding of the prevalence and evolution of BPIV-3 in China.

Beef potentiator is an important flavour enhancer in the food industry, while it is prone to generating insufficient compounds with umami and sweet tastes and compounds with a fishy odour during enzymatic hydrolysis of beef, resulting in poor flavour of beef potentiator. It has been extensively reported that sonication is capable of improving food flavour. However, the effect of sonication on the flavour of enzymatically hydrolysed beef liquid (EHBL) was scarcely reported. Herein, we investigated the effect of sonication on the flavour of EHBL using quantitative descriptive analysis (QDA), physicochemical analysis and SPME-GC-olfactometry/MS. QDA showed that sonication had a significant effect on taste improvement and off-odour removal of EHBL. Compared with the control, sonication (40 kHz, 80 W/L) increased the contents of total nitrogen, formaldehyde nitrogen, total sugars, reducing sugars, free amino acids (FAAs) and hydrolysis degree of EHBL by 19.25%, 19.80%, 11.83%, 9.52%, 14.37% and 20.45%. Notably, sonication markedly enhanced the contents of sweet FAAs, umami FAAs and bitter FAAs of EHBL by 19.66%, 14.04% and 9.18%, respectively, which contributed to the taste improvement of EHBL. SPME-GC-olfactometry/MS analysis showed that aldehydes and alcohols were the main contributors to aroma compounds of EHBL, and sonication significantly increased the contents of key aroma compounds and alcohols (115.88%) in EHBL. Notably, sonication decreased the contents of fishy odorants, hexanoic acid and nonanal markedly by 35.29% and 26.03%, which was responsible for the aroma improvement of EHBL. Therefore, sonication could become a new potential tool to improve the flavour of EHBL.

Zn dendrite growth and water-related side reactions have been criticized to hinder actual applications of aqueous Zn-ion batteries. To address these issues, a series of Zn interfacial modifications of building solid/electrolyte interphase (SEI) and nucleation layers have been widely proposed, however, their effectiveness remains debatable. Here, we report a boron nitride (BN)/Nafion layer on the Zn surface to efficiently solve Zn problems through combining the hybrid working mechanisms of SEI and nucleation layers. In our protective layer, Nafion exhibits the SEI mechanism by blocking water from the Zn surface and providing abundant channels for rapid Zn2+ transmission, whilst BN nanosheets induce Zn deposition underneath with a preferred (002) orientation. Accordingly, dendrite-free and side-reaction-free Zn electrode with (002) deposition under the protective layer is realized for the first time, as reflected by its high reversibility with average Coulombic efficiency of 99.2% for > 3000 ​h. The protected Zn electrode also shows excellent performance in full cells when coupling with polyaniline cathode under the strict condition of lean electrolyte addition. This work highlights insights for designing highly reversible metal electrodes towards practical applications.

A type II band aligned BaTiO3/CeO2 photocatalysts was constructed by a simple one-step solution synthesis method. The BaTiO3/CeO2 photocatalysts contain only cubic phase BaTiO3 and CeO2, and the particles are approximately spherical with a small amount of adhesion and agglomeration, and the average particle size is about 50 nm. Transmission electron microscopy (TEM) observation and element Mapping characterization confirmed the formation of special heterojunction between BaTiO3 and CeO2 and the presence of a large number of oxygen vacancies, which resulted in high visible optical absorption coefficient. The BaTiO3/CeO2 photocatalysts demonstrated high photocatalytic activity for the degradation of oxytetracycin hydrochloride, and the optimal drug concentration, catalyst content and pH value are 50 mg/L, 1 g/L and 7, respectively. Simultaneously, the BaTiO3/CeO2 photocatalysts were selective for degradation of aureomycin hydrochloride, doxycycline hydrochloride and tetracycline hydrochloride. Other photocatalytic experiments show that the BaTiO3/CeO2 photocatalysts have high chemical and cyclic stability, and the synergistic effect of holes, hydroxyl radicals and superoxide radicals plays an important role in the whole photocatalytic process. This simple synthesis route provides a technical reference for constructing other wide-band gap semiconductors to respond to simulated sunlight.

IntroductionBovine ephemeral fever virus (BEFV), belonging to the genus Ephemerovirus under the family Rhabdoviridae, is the etiological cause for the bovine ephemeral fever (BEF) in cattle and water buffalo.MethodsIn this study, we report recent BEF outbreaks in Southwest China and sequence the complete genome sequence of one BEFV isolate BEFV/CQ1/2022.Results and DiscussionComparative genomic analyses between BEFV/CQ1/2022 and isolates available in GenBank revealed remarkable inter-isolate divergence. Meanwhile, the sequence divergence was related to the evolutionary relationships and geographical distribution of the isolates. Phylogenetic analysis indicated that the global BEFV isolates can be divided into 4 distinct lineages. The East Asia lineage was the most diverse and could be subdivided into 4 sublineages. Notably, BEFV/CQ1/2022 and other 10 recent isolates from Mainland China were found to be clustered in sublineage 2. Additionally, recombination analysis provided evidence of BEFV recombination among East Asian isolates for the first time. Taken together, a novel sublineage of the East Asian BEFV emerged in Southwest China, and large divergence and potential recombination among BEFV strains were investigated in this study, which may improve understanding of BEFV epidemiology and evolution.

A dual fluidized bed (DFB) reactor is the main operating system of various energy-efficient and clean utilization technologies. The gas-solid flow characteristics of the DFB reactor greatly affect the efficiency of various technologies. A large-scale DFB reactor with a maximum height of 21.6 m was built and relevant cold mode tests were carried out in this study. The effects of the superficial gas velocity of both beds, static bed height and particle size on the distribution of both pressure and solid suspension density, solid circulation rate, solid inventory distribution ratio and other characteristics were studied. For 282 μm-particles, the solid suspension density in the dense phase zone of the two beds was 100–400 and 400–800 kg/m3, respectively, when the static bed height was 0.65 m; the solid circulation rate was about 0.87–1.75, 1.04–3.04 and 1.13–3.69 kg/(m2s) when the static bed height was 0.65, 0.95 and 1.25 m, respectively. The solid circulation rate was positively correlated with the static bed height and the superficial gas velocity of both beds, yet negatively correlated with the particle size. Additionally, the empirical equation of solid circulation rate and the empirical equation of solid inventory distribution ratio were proposed, respectively. The material control method of the DFB reactor is put forward.

Objective: Based on the expression changes in the TGF-β/ALK5/Smad2/3 signal transduction pathway, the repair of cartilage injury in the rabbit knee joint was investigated and evaluated by oral administration of naringin in combination with acellular dermal matrix implantation. Methods: First, twenty New Zealand white rabbits were randomly divided into five groups: a sham operation group (Sham group), a model group (Mod group), a naringin group (Nar group), an acellular dermal matrix group (ADM group), a naringin ​+ ​acellular dermal matrix group (Nar/ADM group). After the 12th week, the repaired tissues were assessed for histomorphology and repair content of the repaired site by observing the morphological characteristics of articular cartilage. The International Cartilage Repair Society (ICRS)'s macroscopic evaluation of the cartilage repair scale and the quantitative scoring repair effect of the modified O'Driscoll grading system were used as evaluation criteria. In addition, the structure of the rabbit knee joint was evaluated by micro-CT scan, histological staining (H & E staining, Alcian blue staining, Safranin-O staining) and immunohistochemical staining (TGF-β2 immunostaining, TGF-β3 immunostaining, Sox-9 immunostaining). Results: ① The observation of the repair morphology of joint defect tissues showed that the repair effects of the Nar and ADM groups were better than that of the Mod group, and the repair effect of Nar/ADM group was the best (P

Geosmin is one of the most common earthy-musty odor compounds, which is mainly produced by Streptomyces. Streptomyces radiopugnans was screened in radiation-polluted soil, which has the potential to overproduce geosmin. However, due to the complex cellular metabolism and regulation mechanism, the phenotypes of S. radiopugnans were hard to investigate. A genome-scale metabolic model of S. radiopugnans named iZDZ767 was constructed. Model iZDZ767 involved 1,411 reactions, 1,399 metabolites, and 767 genes; its gene coverage was 14.1%. Model iZDZ767 could grow on 23 carbon sources and five nitrogen sources, which achieved 82.1% and 83.3% prediction accuracy, respectively. For the essential gene prediction, the accuracy was 97.6%. According to the simulation of model iZDZ767, D-glucose and urea were the best for geosmin fermentation. The culture condition optimization experiments proved that with D-glucose as the carbon source and urea as the nitrogen source (4 g/L), geosmin production could reach 581.6 ng/L. Using the OptForce algorithm, 29 genes were identified as the targets of metabolic engineering modification. With the help of model iZDZ767, the phenotypes of S. radiopugnans could be well resolved. The key targets for geosmin overproduction could also be identified efficiently.

ObjectiveThis study aimed to explore the clinical characteristics and differential diagnosis of patients with autoimmune pancreatitis (AIP) and pancreatic cancer to prevent misdiagnosis and mistreatment.MethodsThe clinical data of patients with AIP with suspected pancreatic or bile duct malignancy and pancreatic cancer were retrospectively analyzed. The risk factors and the diagnostic value of IgG4 and Tbil levels before treatment for AIP was investigated. Moreover, the imaging features and response to hormone therapy were analyzed.ResultsAIP was commonly observed in men. Compared to patients with pancreatic cancer, the incidence of poor appetite and weight loss and carbohydrate antigen 19-9 (CA19-9) level was lower in patients with AIP, while the immunoglobulin G4 (IgG4) level was higher (p

Incomplete conversion of sodium polysulfides represents a significant issue in room-temperature sodium-sulfur batteries. Here, the authors propose Mo5N6 as an electrocatalyst for efficient Na2S electrodeposition and improved cell cycling performances.

Abstract The fusion (F) and haemagglutinin-neuraminidase (HN) proteins of Newcastle disease virus (NDV) are viral entry proteins and are recognized as the major virulence determinants. Previously, a lentogenic NDV virus (CE16) was derived from a mesogenic strain (CI10) through sequential passages in chick embryos. Whole-genome sequence analysis revealed that the two homologous strains shared the same F protein but differed in HN with two amino acid (aa) substitutions (A215G and T430A). To elucidate the molecular reasons for virulence attenuation, two original plasmids (HN-CI10 and HN-CE16) and two single-point mutants (G215A and A430T) reverse-mutated from HN-CE16 were constructed to analyse the known biological functions of HN. The results showed that the A430T substitution significantly weakened the haemadsorption (HAd) activity, increased the neuraminidase (NA) activity, improved the fusion-promoting activity, and enhanced the cleavage-promoting activity of HN-CE16. However, G215A failed to induce obvious functional changes. Therefore, the aa residue HN430 may play a key role in determining virulence. To test this hypothesis, further studies on A430T were conducted through reverse genetics using an infectious cDNA clone. At the viral level, the A430T-mutated virus showed dramatic promotion of viral plaque formation, propagation, and pathogenicity in vitro and in vivo. This study demonstrates a new virulence site associated with HN protein functions, viral propagation, and pathogenicity. All these findings could lay a foundation for illuminating the molecular mechanism of NDV virulence.

The sulfur cathode in metal-sulfur batteries normally undergoes electrochemical reduction to form metal sulfides. Here, the authors demonstrate the electrochemical oxidation of sulfur in ionic liquid for high-voltage aluminium-sulfur batteries.

Abstract To understand the distribution of biodiversity and its determinants, particularly that of ecologically sensitive ones, has long been intriguing to the science community and will help formulate conservation strategies under future climate changes. To this end, we conducted extensive field surveys on the distribution of orchid flora in the Beipan River Basin in Guizhou Province, which is one of the biodiversity conservation priorities in China. The data we acquired, together with those published previously, were converted into orchid species richness for each of the 3 km × 3 km grid cells covering the study region. Redundancy analysis (RDA) and geographically weighted regression (GWR) were then applied to determine which of the 30 environmental factors are potentially critical for the spatial distribution of orchid flora we have observed. Despite a moderate spatial extent, we found that the Beipan River Basin harbors about 249 native orchid species belonging to 74 genera, equivalent to 14.5% of orchid flora of China. Orchid species richness in this area follows a descending gradient from the southeast to the northwest, 70.41% of its variation among grid cells can be explained by environmental factors and spatial variables, and spatial variables accounted for 63.90% of the spatial variation of orchid distribution, indicating that spatial variables played a dominant role in the distribution of wild Orchidaceae species richness. In addition, the main environmental driver is the mean temperature of the wettest quarter. Our study provides a good example for revealing the main drivers of orchid distribution characteristics and has a certain reference value for the development of orchid conservation strategies.

The variability and heterogeneity of tumor antigens and the tumor-driven development of immunosuppressive mechanisms leading to tumor escape from established immunological surveillance. Here, the tumor cells were genetically modified to achieve an inducible overexpression of the N-terminal domain of gasdermin D (GSDMD-NT) and effectively cause pyroptosis under a strict control. Pyroptotic tumor cells release damage-associated molecular patterns (DAMPs) and inflammatory cytokines to promote the maturation and migration of bone marrow-derived dendritic cells (BMDCs). Furthermore, local tumor delivery, and preventive or therapeutic subcutaneous immunization of the modified cells, followed by the induction of GSDMD-NT expression, significantly stimulated both the systemic and local responses of antitumor immunity, and reprogrammed the tumor microenvironment, leading to the dramatic suppression of tumor growth in mice. This study has explored the application potency of inducing the pyroptosis of tumor cells in the field of tumor immunotherapy, especially for developing a new and promising personalized tumor vaccine.

As a value-led entity, the nonprofit depends on its staff for the delivery of the brand value outsides and thus promoting the brand inside is crucial to the development of the nonprofits. Using a sample of 290 full-time staff working in 270 nonprofits in China, two related studies were conducted. Study 1 aimed to develop and validate a new scale for internal branding in the nonprofit context, while Study 2 aimed to investigate the linking mechanism between internal branding and brand performance with the mediating roles (including chain mediation) of the person–organization fit (POF) and intent to stay with the brand (IntSB). As predicted, the results revealed that: (1) the nonprofit internal branding (NIB) scale is a three-dimensional construct that is composed of brand-centered training, internal brand communication, and brand-oriented leadership, (2) internal branding positively predicts POF, IntSB, and brand performance, and (3) POF and IntSB sequentially mediate the internal branding–brand performance relationship. The implications of our findings for internal branding in the nonprofit context are discussed.

With the increasing bacterial resistance to traditional antibiotics, there is an urgent need for the development of alternative drugs or adjuvants of antibiotics to enhance antibacterial efficiency. The combination of antimicrobial peptides (AMPs) and traditional antibiotics is a potential alternative to enhance antibacterial efficiency. In this study, we investigated the synergistic bactericidal effect of AMPs, including chicken (CATH-1,−2,−3, and -B1), mice (CRAMP), and porcine (PMAP-36 and PR-39) in combination with conventional antibiotics containing ampicillin, tetracycline, gentamicin, and erythromycin against Staphylococcus aureus, Salmonella enteritidis, and Escherichia coli. The results showed that the minimum bactericidal concentration (MBC) of CATH-1,−3 and PMAP-36 was lower than 10 μM, indicating that these three AMPs had good bacterial activity against S. aureus, S. enteritidis, and E. coli. Then, the synergistic antibacterial activity of AMPs and antibiotics combination was determined by the fractional bactericidal concentration index (FBCI). The results showed that the FBCI of AMPs (CATH-1,−3 and PMAP-36) and erythromycin was lower than 0.5 against bacterial pathogens, demonstrating that they had a synergistic bactericidal effect. Furthermore, the time-killing kinetics of AMPs (CATH-1,−3 and PMAP-36) in combination with erythromycin showed that they had a continuous killing effect on bacteria within 3 h. Notably, the combination showed lower hemolytic activity and cytotoxicity to mammal cells compared to erythromycin and peptide alone treatment. In addition, the antibacterial mechanism of CATH-1 and erythromycin combination against E. coli was studied. The results of the scanning electron microscope showed that CATH-1 enhanced the antibacterial activity of erythromycin by increasing the permeability of bacterial cell membrane. Moreover, the results of bacterial migration movement showed that the combination of CATH-1 and erythromycin significantly inhibits the migration of E. coli. Finally, drug resistance analysis was performed and the results showed that CATH-1 delayed the emergence of E. coli resistance to erythromycin. In conclusion, the combination of CATH-1 and erythromycin has synergistic antibacterial activity and reduces the emergence of bacterial drug resistance. Our study provides valuable information to develop AMPs as potential substitutes or adjuvants for traditional antibiotics.

Postoperative cognitive dysfunction (POCD), an important postoperative neurological complication, is very common and has an elevated incidence in elderly patients. Sevoflurane, an inhaled anesthetic, has been demonstrated to be associated with POCD in both clinical and animal studies. However, how to prevent POCD remains unclear. Minocycline, a commonly used antibiotic can cross the blood-brain barrier and exert an inhibitory effect on inflammation in the central nervous system. The present work aimed to examine the protective effect and mechanism of minocycline on sevoflurane-induced POCD in aged mice. We found that 3% sevoflurane administered 2 h a day for 3 consecutive days led to cognitive impairment in aged animals. Further investigation revealed that sevoflurane impaired synapse plasticity by causing apoptosis and neuroinflammation and thus induced cognitive dysfunction. However, minocycline pretreatment (50 mg/kg, i.p, 1 h prior to sevoflurane exposure) significantly attenuated learning and memory impairments associated with sevoflurane in aged animals by suppressing apoptosis and neuroinflammation. Moreover, a mechanistic analysis showed that minocycline suppressed sevoflurane-triggered neuroinflammation by inhibiting Notch signaling. Similar results were also obtained in vitro. Collectively, these findings suggested minocycline may be an effective drug for the prevention of sevoflurane-induced POCD in elderly patients.

Highlights Wearable and smart textiles are constructed by integrating embroidery technology and 5G cloud communication, showing promising applications in temperature management and real-time dynamic textile displays. Thermochromism is introduced into the natural silk to produce high-performance thermochromic silks (TCSs) through a low cost, sustainable, efficient, and scalable strategy. The interfacial bonding of the continuously produced TCSs is in situ analyzed and improved through pre-solvent treatment and is confirmed using synchrotron Fourier transform infrared microspectroscopy. Abstract Silks have various advantages compared with synthetic polymer fibers, such as sustainability, mechanical properties, luster, as well as air and humidity permeability. However, the functionalization of silks has not yet been fully developed. Functionalization techniques that retain or even improve the sustainability of silk production are required. To this end, a low-cost, effective, and scalable strategy to produce TCSs by integrating yarn-spinning and continuous dip coating technique is developed herein. TCSs with extremely long length (> 10 km), high mechanical performance (strength of 443.1 MPa, toughness of 56.0 MJ m−3, comparable with natural cocoon silk), and good interfacial bonding were developed. TCSs can be automatically woven into arbitrary fabrics, which feature super-hydrophobicity as well as rapid and programmable thermochromic responses with good cyclic performance: the response speed reached to one second and remained stable after hundreds of tests. Finally, applications of TCS fabrics in temperature management and dynamic textile displays are demonstrated, confirming their application potential in smart textiles, wearable devices, flexible displays, and human–machine interfaces. Moreover, combination of the fabrication and the demonstrated applications is expected to bridge the gap between lab research and industry and accelerate the commercialization of TCSs.

Objective: Vancomycin combined with β-lactams (Combo therapy) has been encouraged in the treatment of methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infections (BSIs) in recent years, but its efficacy and safety have not been systematically evaluated. This is a systematic review and meta-analysis to clarify the efficacy and safety of Combo therapy in patients with MRSA BSIs. Methods: Relevant articles reporting on the clinical or microbiology outcomes of Combo treatment in adult patients with MRSA bacteraemia throughout November 2019 were searched in PubMed, EMBASE and Cochrane Library databases. Summary odds ratios (ORs) or mean differences (MDs) and 95% confidence intervals (CIs) were evaluated using a fixed- or random-effects model. Results: Six articles (806 patients) consisting of one RCT and five retrospective cohort studies were included in this study. The pooled data showed that Combo therapy could significantly reduce the risk of microbiological failure (OR = 0.54, 95% CI 0.35–0.83, I2 40%, P = 0.005) and persistent bacteraemia (OR=0.48, 95% CI 0.30–0.77, I2 13%, P = 0.002), as well as shorten the duration of bacteraemia (MD = −1.06, 95% CI −1.53 to −0.60, I2 0%, P < 0.00001). In addition, it did not significantly increase the incidence of nephrotoxicity (OR = 1.17, 95% CI 0.64–2.13, I2 0%, P = 0.61). However, no significant difference was detected between the groups regarding 28/30-day mortality, MRSA-related mortality, bacteraemia relapse or length of hospitalization. Conclusions: These results demonstrate that Combo therapy clears the pathogenic bacteria of MRSA bacteraemia but does not improve the clinical prognosis. As the sample size was small and most of the studies were retrospective cohort studies with substantial heterogeneity, there is a need for further studies encompassing large-scale multicentre RCTs to validate our results.