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Introduction: Neurological dysfunction induced by fluoride contamination is still one of major concern worldwide. Recently, neuroprotective roles of silent information regulator 1 (SIRT1) focusing on mitochondrial function have been highlighted. However, what roles SIRT1 exerts and the underlying regulative mechanisms, remain largely uncharacterized in such neurotoxic process of fluoride. Objectives: We aimed at evaluating the regulatory roles of SIRT1 in human neuroblastoma SH-SY5Y cells and Sprague-Dawley rats with fluoride treatment, and to further identify potential miRNA directly targeting SIRT1. Methods: Pharmacological suppression of SIRT1 by nicotinamide (NIC) and promotion of SIRT1 by adenovirus (Ad-SIRT1) or resveratrol (RSV) were employed to assess the effects of SIRT1 in mitochondrial dysfunction induced by fluoride. Also, miRNAs profiling and bioinformatic prediction were used to screen the miRNAs which can regulate SIRT1 directly. Further, chemical mimic or inhibitor of chosen miRNA was applied to validate the modulation of chosen miRNA. Results: NIC exacerbated defects in mitochondrial network dynamics and cytochrome c (Cyto C) release-driven apoptosis, contributing to fluoride-induced neuronal death. In contrast, the ameliorative effects were observed when overexpressing SIRT1 by Ad-SIRT1 in vitro or RSV in vivo. More importantly, miR-708-3p targeting SIRT1 directly was identified. And interestingly, moreover, treatment with chemically modified miR-708-3p mimic aggravated, while miR-708-3p inhibitor suppressed fluoride-caused neuronal death. Further confirmedly, overexpressing SIRT1 effectively neutralized miR-708-3p mimic-worsened fluoride neuronal death via correcting mitochondrial network dynamics. On contrary, inhibiting SIRT1 counteracted the promotive effects of miR-708-3p inhibitor against neurotoxic response by fluoride through aggravating abnormal mitochondrial network dynamics. Conclusion: These data underscore the functional importance of SIRT1 to mitochondrial network dynamics in neurotoxic process of fluoride and further screen a novel unreported neuronal function of miR-708-3p as an upstream regulator of targeting SIRT1, which has important theoretical implications for a potential therapeutic and preventative target for treatment of neurotoxic progression by fluoride.

Background: The brominated flame retardant 2, 2′, 4, 4′-tetrabromodiphenyl ether (PBDE-47) is well known as a developmental neurotoxicant, yet the underlying mechanisms remain elusive. Increasing evidence has demonstrated that brain glucose metabolism perturbation plays a role in neural impairments. Nevertheless, whether this disturbance is involved in PBDE-47-induced neurotoxicity remains unknown. Objectives: To explore the impacts of perinatal PBDE-47 exposure on brain glucose metabolism, and its link to thyroid hormones (THs) levels as well as neurobehavioral changes. Methods: Female Sprague-Dawley rats were orally exposed to PBDE-47 at environmentally relevant levels (0.1, 1.0, and 10.0 mg/kg bw) from pre-pregnancy through weaning of offspring. The male offspring were continued to raise to 88 days after birth for follow-up experiments. Morris water maze and Open field tests were performed to assess the neurobehavioral alterations. The brain glucose metabolism was evaluated using 18F-labeled fluorodeoxyglucose (18F-FDG) positron emission tomography. Serum THs levels were measured via enzyme-linked immunosorbent assay. Results: Perinatal exposure to PBDE-47 induced neurobehavioral impairments in adult male rats as evidenced by learning and memory impairments, hyperactivity and anxiety-like behavior. Moreover, positron emission tomography showed that the glucose metabolism in the whole and the specific brain regions were markedly declined. Interestingly, variations in brain glucose metabolism were associated with the increased serum triiodothyronine (T3) levels, and both were linked to neurobehavioral disorders. Conclusion: Exposure to environmentally related levels of PBDE-47 at critical developmental stages lowers glucose metabolism in the whole brain and in various brain regions, which is associated with behavioral and cognitive deficits in adult male rats. Moreover, the association may be influenced by the disturbance of T3 homeostasis.

Abstract Liposomal irinotecan has shown promising antitumor activity in patients with advanced or metastatic pancreatic ductal adenocarcinoma (PDAC) who have undergone prior gemcitabine-based therapies. This randomized, double-blind, parallel-controlled, multicenter phase 3 study (NCT05074589) assessed the efficacy and safety of liposomal irinotecan HR070803 combined with 5-fluorouracil (5-FU) and leucovorin (LV) in this patient population. Patients with unresectable, locally advanced, or metastatic PDAC who had previously received gemcitabine-based therapies were randomized 1:1 to receive either HR070803 (60 mg/m2 anhydrous irinotecan hydrochloride, equal to 56.5 mg/m2 free base) or placebo, both in combination with 5-FU (2000 mg/m2) and LV (200 mg/m2), all given intravenously every two weeks. The primary endpoint of the study was overall survival (OS). A total of 298 patients were enrolled and received HR070803 plus 5-FU/LV (HR070803 group, n = 149) or placebo plus 5-FU/LV (placebo group, n = 149). Median OS was significantly improved in the HR070803 group compared to the placebo group (7.4 months [95% CI 6.1–8.4] versus 5.0 months [95% CI 4.3–6.0]; HR 0.63 [95% CI 0.48–0.84]; two-sided p = 0.0019). The most common grade ≥ 3 adverse events in the HR070803 group were increased gamma-glutamyltransferase (19.0% versus 11.6% in placebo group) and decreased neutrophil count (12.9% versus 0 in placebo group). No treatment-related deaths occurred in the HR070803 group, while the placebo group reported one treatment-related death (abdominal infection). HR070803 in combination with 5-FU/LV has shown promising efficacy and manageable safety in advanced or metastatic PDAC in the second-line setting, representing a potential option in this patient population.

Abstract People often change their evaluations upon learning about their peers’ evaluations, i.e., social learning. Given sleep’s vital role in consolidating daytime experiences, sleep may facilitate social learning, thereby further changing people’s evaluations. Combining a social learning task and the sleep-based targeted memory reactivation technique, we asked whether social learning-induced evaluation updating can be modulated during sleep. After participants had indicated their initial evaluation of snacks, they learned about their peers’ evaluations while hearing the snacks’ spoken names. During the post-learning non-rapid-eye-movement sleep, we re-played half of the snack names (i.e., cued snack) to reactivate the associated peers’ evaluations. Upon waking up, we found that the social learning-induced evaluation updating further enlarged for both cued and uncued snacks. Examining sleep electroencephalogram (EEG) activity revealed that cue-elicited delta-theta EEG power and the overnight N2 sleep spindle density predicted post-sleep evaluation updating for cued but not for uncued snacks. These findings underscore the role of sleep-mediated memory reactivation and the associated neural activity in supporting social learning-induced evaluation updating.

This study explores the biological effects and mechanisms of Lily extract on LPS-induced pneumonia mice. Research has found that after 48 h of treatment with low-dose and high-dose lily extract (100 mg/kg, 200 mg/kg), there was a significant reduction in inflammatory cell infiltration, mRNA expression levels of pro-inflammatory factors (IL-6, IL-1β, TNF-α), protein levels of inflammation-related proteins (IL-6, NF-κB P65) in the lung tissue. In addition, lily extract significantly improved the function of cilia assembly and movement. The expression levels of cilia-related genes (Ttc21a, Cfap45, etc.) and proteins were significantly upregulated. Among them, the high-dose treatment group had tightly arranged cilia and good growth conditions, which was significantly better than the LPS pneumonia model and low-dose treatment group. This found providing novel insights into the pathogenesis and progression of pneumonia. This has important implications for the prevention and treatment of pneumonia, as well as the development of natural agents.

The flow field structure for aero-engine combustor is one of the most important factors for combustion performance. To investigate how the rotating direction of dual-axial swirlers affects the flow field and combustion characteristics, particle image velocimetry (PIV) experiments were conducted in the primary combustion and intermediate zones. Additionally, planar laser induced fluorescence (PLIF) was used to map the distribution of kerosene and OH in the primary combustion zone. The results show that the swirling jets in co-swirl exhibit greater jet momentum, resulting in a longer primary recirculation zone and a larger deflection angle of the primary jets. This ultimately leads to a higher recirculation rate compared to counter-swirl. The primary jets define the boundary of the flow field structure. The rotating direction primarily affects the flow field structure upstream of the primary jets, exerts a relatively weaker influence on the intermediate zone, which is mainly affected by the deflection direction of the primary jets, and essentially has no impact on the dilution jets. Co-swirl has a relatively stable flow field than counter-swirl, whereas the flow field in counter-swirl is more chaotic, featuring a greater number of vortex cores in the primary recirculation zone. The coupling between the primary and swirling jets affects the mass transfer direction in the intermediate zone, which is reflected in the fact that the mass transfer is from top-left to bottom-right in co-swirl, while it is in the opposite direction in counter-swirl. OH is predominantly found in the swirling shear layers, the primary and secondary combustion zones, whereas kerosene is mainly concentrated in the shear layers of swirling jets. The kerosene distribution in co-swirl shows a larger and more concentrated expansion angle compared to counter-swirl. In contrast, the OH distribution downstream of counter-swirl is broader, with more intense combustion due to enhanced kerosene decomposition and fuel-air mixing. The smaller primary recirculation zone in counter-swirl forces the primary combustion zone to extend downstream, leading to a more intense reaction in the secondary recirculation zone.

Introduction: Vitexin is a natural flavonoid compound extracted from Vitex leaves or seeds, exhibiting various pharmacological activities including anticancer, antihypertensive, anti-inflammatory, and spasmolytic effects. However, its protective effects on hypertensive nephropathy (HN) and the underlying mechanisms remain unclear. Methods: Spontaneous hypertension rats were fed a high-sugar and high-fat diet for 8 weeks to induce the disease HN model. From the 5th week, the rats were administered vitexin via gavage. Blood pressure was measured bi-weekly using the tail-cuff method. Histopathological changes were assessed using HE staining, and biochemical analyses were performed to evaluate the effects of vitexin on HN rats. The underlying mechanisms of vitexin treatment were investigated through western blotting. Results: The data demonstrated that vitexin significantly lowered systolic, diastolic, and mean arterial pressures, and ameliorated histopathological changes in HN rats. Biochemical analyses revealed that vitexin reduced the levels of creatinine (Cr), blood urea nitrogen (BUN), total cholesterol (TC), triglycerides (TG), total protein (TP), low-density lipoprotein cholesterol (LDL-C), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), malondialdehyde (MDA), and advanced glycation end products (AGEs), while increasing the levels of albumin (ALB) and superoxide dismutase (SOD). Western blotting results indicated that vitexin treatment decreased the expression of TNF-α, IL-6, and nuclear factor kappa-B (NF-κB), while increasing the expression of SOD. Conclusion: The findings of this study suggest that vitexin exerts protective effects against HN, providing pharmacological evidence for its potential use in HN treatment.

Subgroup 4 (Sg4) members of the R2R3-MYB are generally known as negative regulators of the phenylpropanoid pathway in plants. Our previous research showed that a R2R3-MYB Sg4 member from Camellia sinensis (CsMYB4a) inhibits expression of some genes in the phenylpropanoid pathway, but its physiological function in the tea plant remained unknown. Here, CsMYB4a was found to be highly expressed in anther and filaments, and participated in regulating filament growth. Transcriptome analysis and exogenous auxin treatment showed that the target of CsMYB4a might be the auxin signal pathway. Auxin/indole-3-acetic acid 4 (AUX/IAA4), a repressor in auxin signal transduction, was detected from a yeast two-hybrid screen using CsMYB4a as bait. Gene silencing assays showed that both CsIAA4 and CsMYB4a regulate filament growth. Tobacco plants overexpressing CsIAA4 were insensitive to exogenous α-NAA, consistent with overexpression of CsMYB4a. Protein-protein interaction experiments revealed that CsMYB4a interacts with N-terminal of CsIAA4 to prevent CsIAA4 degradation. Knock out of the endogenous NtIAA4 gene, a CsIAA4 homolog, in tobacco alleviated filament growth inhibition and α-NAA insensitivity in plants overexpressing CsMYB4a. All results strongly suggest that CsMYB4a works synergistically with CsIAA4 and participates in regulation of the auxin pathway in stamen.

The multidrug and toxic compound extrusion (MATE) family is the latest class of novel secondary transporters discovered in plants. However, there is currently no comprehensive analysis of the MATE gene family in the tea plant. In this study, 68 CsMATE genes were identified from the tea plant genome using bioinformatic methods. In general, we analyzed the evolutionary relationships, intron–exon structure, distribution in chromosomes, conserved domains, and gene expression patterns in different tissues and stresses of the CsMATE gene family. The 68 CsMATEs were phylogenetically divided into four major clusters (Class I to Class IV). The CsMATE genes within the same class exhibit similar structural features, while displaying certain distinctions across different classes. Evolutionary analysis indicated that the CsMATE gene family expanded mainly through gene duplication events, in addition to proximal duplication. Through the analysis of cis-acting elements, it was found that CsMATE genes may be involved in the growth, development, and stress response. Furthermore, we observed that certain CsMATE genes could be induced to exhibit expression under abiotic stress conditions such as low temperature, high salinity (NaCl), osmotic stress (PEG), and methyl jasmonate treatment (MeJA). The findings presented herein offer a crucial theoretical foundation for elucidating the biological functions of CsMATE genes, particularly in response to abiotic stress, and furnish valuable potential genetic resources for tea plant resistance breeding.

IntroductionCoastal nations heavily rely on their sea areas to achieve sustainable socioeconomic development. Sea areas offer abundant marine ecosystem products and services that are difficult to substitute with industrial goods. Although considerable research has been performed to evaluate the contribution offrom the marine ecosystems to human well-being, systematic and measurable indices are lacking.MethodsTo address this knowledge gap, ecosystem service theory was used to establish a framework for assessing the gross ecosystem product (GEP) of a sea area, which represents the total monetary value of final ecosystem products directly and indirectly used by people within a specific administrative jurisdiction in one year. To evaluate marine GEP, three primary indices, i.e., material products, regulating products, and cultural products, were employed, and they consist of eight secondary indices. Material products in the sea area include aquatic products and oxygen products; regulating products include carbon sequestration, climate regulation, waste treatment, and coastal protection; and cultural products include leisure and recreation, and seascape-added value. The marine GEP was calculated for the administrative sea areas of Changdao County, which is located in the Yellow Sea-Bohai Sea transitional zone.Results and discussionOur analysis indicated that from 2017 to 2019, the marine GEP in Changdao ranged between 32.59 and 33.35 billion Chinese yuan (CNY). Regulating products contributed two-thirds of this total value. However, over the three-year period, the marine GEP underwent a 5.64% decrease in Changdao. Specifically, the value of material products increased by 38.85% while that of regulating and cultural products decreased by 9.16% and 15.87%, respectively. Notably, the spatial distribution of ecosystem product values in Changdao displayed two prominent trends: (1) higher values along the coastal sea areas of islands and lower values in offshore sea areas; and (2) higher values in coastal areas of southern islands and lower values in coastal areas of northern islands. Marine GEP may serve as a comprehensive indicator for assessing the sustainability of marine ecosystem. Combining the assessment of both marine and terrestrial GEP facilitates an understanding of how marine and terrestrial ecosystems interact in coastal regions. Furthermore, the combined use of marine GEP and GDP helps better evaluate and sort the level of green development of coastal nations and regions.

ObjectiveTo investigate the molecular and biological characteristics of Vibrio vulnificus （V. vulnificus）isolated from Guangzhou.MethodsThirty-eight strains of V. vulnificus were collected from Guangzhou， and whole-genome sequences were obtained. The population structure of V. vulnificus was inferred by utilizing 50 publicly available genome sequences obtained from NCBI. FineSTRUCTURE software was employed for this analysis. Antibiotic resistance and virulence factors were identified using CARD， ResFinder， and VFDB databases.ResultsFour well-supported phylogenetic groups or lineages （L1-L4） were identified， and all genomes of the strains in Guangzhou were classified into L1 （47%） and L2 （53%）. The predominant ST were ST357， ST157， ST136， ST139， ST345， ST303， and so on， which showed regional aggregation. Multiple genome identification of V. vulnificus revealed 11 drug resistance genes： acrF， CRP， catB9， rpoC， ugd， and others. MCR genes related to polymyxin resistance were identified in V. vulnificus for the first time. The species also carries 23 virulence genes in five classes encoding flagellin， type Ⅱ secretory system protein， capsular polysaccharide， RtxA toxin， iron overload， and other virulence-related genes.ConclusionVibrio vulnificus in Guangzhou undergoes highly homologous recombination and carries a variety of antimicrobial resistance genes and virulence-related genes. Therefore， monitoring and management of Vibrio vulnificus should be strengthened.

The utilization of unmanned sailboats as a burgeoning instrument for ocean exploration and monitoring is steadily rising. In this study, a dual sail configuration is put forth to augment the sailboats’ proficiency in its wind-catching ability and adapt to the harsh environment of the sea. This proposition is based on a thorough investigation of sail aerodynamics. The symmetric rigid wing sails NACA 0020 and NACA 0016 are selected for use as the mainsail and trailing wing sail, respectively, after considering the operational environment of unmanned sailboats. The wing sail structure is modeled using SolidWorks, and computational fluid dynamics (CFD) simulations are conducted using ANSYS Fluent 2022R1 software to evaluate the aerodynamic performance of the sails. Key aerodynamic parameters, including lift, drag, lift coefficient, drag coefficient, and thrust coefficient, are obtained under different angles of attack. Furthermore, the effects of mainsail aspect ratios, mainsail taper ratios, and the positional relationship between the mainsail and trailing sail on performance are analyzed to determine the optimal structure. The thrust provided by the sail to the boat is mainly generated by the decomposition of lift, and the lift coefficient is used to measure the efficiency of an object in generating lift in the air. The proposed sail structure demonstrates a 37.1% improvement in the peak lift coefficient compared to traditional flexible sails and exhibits strong propulsion capability, indicating its potential for widespread application in the marine field.

Unmanned aerial vehicles (UAVs) play a critical role in various fields, including logistics, agriculture, and rescue operations. Effective identity authentication and key agreement schemes are vital for UAV networks to combat threats. Current schemes often employ algorithms like elliptic curve cryptography (ECC) and Rivest–Shamir–Adleman (RSA), which are vulnerable to quantum attacks. To address this issue, we propose LIGKYX, a novel scheme combining the quantum-resistant Kyber algorithm with the hash-based message authentication code (HMAC) for enhanced security and efficiency. This scheme enables the mutual authentication between UAVs and ground stations and supports secure session key establishment protocols. Additionally, it facilitates robust authentication and key agreement among UAVs through control stations, addressing the critical challenge of quantum-resistant security in UAV networks. The proposed LIGKYX scheme operates based on the Kyber algorithm and elliptic curve Diffie–Hellman (ECDH) key exchange protocol, employing the HMAC and pre-computation techniques. Furthermore, a formal verification tool validated the security of LIGKYX under the Dolev–Yao threat model. Comparative analyses on security properties, communication overhead, and computational overhead indicate that LIGKYX not only matches or exceeds existing schemes but also uniquely counters quantum attacks effectively, ensuring the security of UAV communication networks with a lower time overhead for authentication and communication.

Abstract Wounds can lead to skin and soft tissue damage and their improper management may lead to the growth of pathogenic bacteria at the site of injury. Identifying better ways to promote wound healing is a major unmet need and biomedical materials with the ability to promote wound healing are urgently needed. Here, we report a thermosensitive black phosphorus hydrogel composed of black phosphorus nano-loaded drug silver sulfadiazine (SSD) and chitosan thermosensitive hydrogel for wound healing. The hydrogel has temperature-sensitive properties and enables the continuous release of SSD under near-infrared irradiation to achieve synergistic photothermal and antibacterial treatment. Additionally, it exerts antibacterial effects on Staphylococcus aureus. In a rat skin injury model, it promotes collagen deposition, boosts neovascularization, and suppresses inflammatory markers. In summary, the excellent thermosensitivity, biocompatibility, and wound-healing-promoting qualities of the reported thermosensitive hydrogel make it suitable as an ideal wound dressing in the clinic.

Plant flavonoids have various physiological functions beneficial to human health, but their content in plants is not high and usually exists in form of flavonoid glycosides with low bioavailability. This study used ultrasonic assisted ethanol extraction to extract flavonoids from common and tartary buckwheat, the total flavonoid content increased significantly. After treated with β-glucosidase, flavonoid aglycones of common and tartary buckwheat increased by 27.51 % and 29.58 % respectively. Blood glucose of diabetic mice was significantly reduced by 38.20–47.20 % after receiving extracts for 4 weeks, of which tartary buckwheat extract treated with β-glucosidase had the best efficacy (47.20 %), which was 94.70 % of metformin hydrochloride group. The extracts could effectively restore serum and liver biochemical indicators and organ index, which may be related to regulating IRS-1/PI3K/AKT-1/mTOR and PI3K/AKT-1/GSK-3β signaling pathways. Our findings suggested that buckwheat extracts rich in flavonoid aglycones and glycosides could significantly improve hypoglycemic effect and alleviate insulin resistance in T2DM.

[Objective] The oil and gas conveyed in transmission pipelines are highly flammable and explosive. During natural disasters,these pipelines are susceptible to technological accidents such as fire, explosion, and environmental pollution, i.e. Natural Hazards Triggering Technological Accidents(Natech). Rapid and accurate identification of weak segments of oil and gas pipelines in Natech events is particularly critical for disaster prevention and mitigation and emergency decision-making of pipelines. [Methods] Vulnerability is often employed as a metric to assess the safety risk level of complex systems. It can also be used to characterize the disparity in the safety levels of oil and gas pipeline during Natech events. Based on the characteristic parameters of oil and gas pipeline segmentation and initial natural disasters, as well as the functional model method commonly used in vulnerability assessment research, a vulnerability assessment model for oil and gas pipeline in Natech events was created. The design concept of a vulnerability assessment system for oil and gas pipeline segments in Natech events was proposed from the aspects of system architecture design, database design, and function module design, and the functions of the assessment system were realized based on the B/S architecture, ArcGIS technology, Editable Table technology, Localstorage technology, and Lay-UI component technology. [Results] The new assessment system was used in an oil pipeline project in South China. The practical results show that the vulnerability assessment system of oil and gas pipeline in Natech events can not only quickly solve the vulnerability assessment results to simplify the application process of the vulnerability assessment method, but also help users identify the root causes of vulnerability differences according to the data acquisition module, providing a clear solution for reducing the vulnerability level of pipeline segments, visually displaying the vulnerability assessment results, and effectively improving the production efficiency of the vulnerability zoning map. [Conclusion] The research results provide a reference for the prevention and control of Natech events of oil and gas pipelines, the identification of key vulnerable targets, and the development of information systems.

Abstract Background Recurrence after resection is the main factor for poor survival. The relationship between clinicopathological factors and recurrence after curative distal pancreatectomy for PDAC has rarely been reported separately. Methods Patients with PDAC after left‑sided pancreatectomy between May 2015 and August 2021 were retrospectively identified. Results One hundred forty-one patients were included. Recurrence was observed in 97 patients (68.8%), while 44 (31.2%) patients had no recurrence. The median RFS was 8.8 months. The median OS was 24.9 months. Local recurrence was the predominant first detected recurrence site (n = 36, 37.1%), closely followed by liver recurrence (n = 35, 36.1%). Multiple recurrences occurred in 16 (16.5%) patients, peritoneal recurrence in 6 (6.2%) patients, and lung recurrence in 4 (4.1%) patients. High CA19-9 value after surgery, poor differentiation grade, and positive lymph nodes were found to be independently associated with recurrence. The patients receiving adjuvant chemotherapy had a decreased likelihood of recurrence. In the high CA19-9 value cohort, the median PFS and OS of the patients with or without chemotherapy were 8.0 VS. 5.7 months and 15.6 VS. 13.8 months, respectively. In the normal CA19-9 value cohort, there was no significant difference in PFS with or without chemotherapy (11.7 VS. 10.0 months, P = 0.147). However, OS was significantly longer in the patients with chemotherapy (26.4 VS. 13.8 months, P = 0.019). Conclusions Tumor biologic characteristics, such as T stage, tumor differentiation and positive lymph nodes, affecting CA19-9 value after surgery are associated with patterns and timing of recurrence. Adjuvant chemotherapy significantly reduced recurrence and improved survival. Chemotherapy is strongly recommended in patients with high CA199 after surgery.

Understanding how individual memories are reactivated during sleep is essential in theorizing memory consolidation. Here, we employed the targeted memory reactivation (TMR) paradigm to unobtrusively replaying auditory memory cues during human participants' slow-wave sleep (SWS). Using representational similarity analysis (RSA) on cue-elicited electroencephalogram (EEG), we found temporally segregated and functionally distinct item-specific neural representations: the early post-cue EEG activity (within 0 to 2,000 ms) contained comparable item-specific representations for memory cues and control cues, signifying effective processing of auditory cues. Critically, the later EEG activity (2,500 to 2,960 ms) showed greater item-specific representations for post-sleep remembered items than for forgotten and control cues, indicating memory reprocessing. Moreover, these later item-specific neural representations were supported by concurrently increased spindles, particularly for items that had not been tested prior to sleep. These findings elucidated how external memory cues triggered item-specific neural representations during SWS and how such representations were linked to successful long-term memory. These results will benefit future research aiming to perturb specific memory episodes during sleep.

Research on vacancy analysis and spatial layout of protected natural areas has been carried out for many years around the world, but most of the research objects are land-type protected natural areas, while studies on Marine protected natural areas are relatively rare, and there are few cases to carry out integrated optimization research on spatial layout of protected natural areas. This study will take Changdao in Yantai, Shandong Province, China as an example, from the protection of how much? How representative? Where is it protected? Starting from the three problems, the vacancy analysis is carried out, and the integrated optimization research is carried out based on the existing spatial layout, aiming at the rescue protection, coordinated protection and forward-looking protection. The results show that the integrated and optimized Changdao protected area eliminates the protection vacancy, integrates the overlapping protected areas, optimizes the unreasonable protected space, alleviates the contradiction between protection and development, promotes the coordinated development of ecology and economy and society, and can provide a scientific reference for the integrated and optimized spatial layout of Marine protected areas.

Lignocellulose recalcitrance hampers its utilization for the production of biofuels and biosourced chemicals. Here, the authors reveal that the amorphous cellulose is the breakpoint of interact microfibrils and propose OsFC16/CESA9 as the engineering target to increase saccharification ability.

Abstract Background The root systems of higher plants play an important role in plant growth and development. In our present study, it was found that poly-γ-glutamic acid (γ-PGA), an environmentally friendly biomacromolecule, significantly improved root development in maize. Results After treatment with γ-PGA for 7 days, the fresh weight of maize roots was significantly increased and the differences between γ-PGA treated group and control group were mainly caused by the number (higher by 71.87% compared to the control) and length of lateral roots. RNAseq and RT-PCR analyses showed that γ-PGA treatment upregulated the expression of genes related to the synthesis of auxins and auxin signal in maize roots. In addition, γ-PGA promoted the accumulation of plant growth-promoting bacteria, such as Azospirillum, Azohydromonas, Ramlibacter, and Sphingobium (Proteobacteria), Streptomyces (Actinobacteria), Parasegetibacter (Bacteroidetes), and Gemmatimonas (Gemmatimonadetes) in rhizosphere soil and the secretion of auxins. The results of this study deepened our understanding of the effects and mechanism of γ-PGA on maize root development, and as well as highlighted the possibility of using γ-PGA to improve crop growth and soil environment. Conclusions γ-PGA promotes early growth and development of maize roots by inducing the secretion and accumulation of auxin in roots and in rhizosphere soil, and increasing the abundance of plant growth promoting bacteria.

The electric capacitance tomography (ECT) technique has been widely used in phase distribution reconstruction, while the practical application raised nonideal noise and other errors for cryogenic conditions, requiring a more accurate algorithm. This paper develops a new image reconstruction algorithm for ECT by coupling the traditional Landweber algorithm with the least square support vector regression (LSSVR) for cryogenic fluids. The performance of the algorithm is quantitatively evaluated by comparing the inversion images with the experimental results for both the room temperature working medium with the dielectric constant ratio close to cryogenic fluid and the cryogenic fluid of liquid nitrogen/nitrogen vapor (LN2-VN2). The inversion images based on the conventional LBP and Landweber algorithms are also presented for comparison. The benefits and drawbacks of the developed algorithms are revealed and discussed, according to the results. It is demonstrated that the correlated coefficients of the images based on the developed algorithm reach more than 0.88 and a maximum of 0.975. In addition, the minimum void fraction error of the algorithm is reduced to 0.534%, which indicates the significant optimization of the LSSVR coupled method over the Landweber algorithm.

Abstract Background Immunotherapy has demonstrated a limited clinical efficacy in approximately 5% of cholangiocarcinoma. The main challenges for an effective immunotherapy response in cholangiocarcinoma arise from the tumor microenvironment, which is poorly understood. Methods For a comprehensive analysis of the tumor microenvironment in cholangiocarcinoma, we performed multiplex immunohistochemistry with two 15-marker immune panels and Nanostring assays for a comprehensive analysis of 104 surgically resected cholangiocarcinomas including intrahepatic, hilar, and distal cholangiocarcinoma. We also validated some key findings with a batch integration analysis of published single cell RNA sequencing data. Results This study found that natural killer cells occupy the largest immune cell compartment in cholangiocarcinoma. Granzyme-B+CD8+ effector T cells are significantly associated with better overall survival in both intrahepatic and distal cholangiocarcinoma. Above 85% of intrahepatic cholangiocarcinomas with higher density of PD-1−EOMES−CD8+ effector T cells are associated with long-term survival. However, only the density of PD-1−EOMES−CD8+ T cells in the tumor areas, but not in the peripheries of the tumors, is prognostic. In all three cholangiocarcinoma subtypes, T regulator cells are significantly associated with a poor prognosis; however, M1 and M2 tumor-associated macrophages or PD-L1+ tumor-associated macrophage demonstrate different prognostic values. Combining PD-L1+ M1 or M2, PD-L1− M1 or M2 tumor-associated macrophages, and T regulator cells to subgroup intrahepatic and distal cholangiocarcinoma, the prognosis is significantly better distinguished. Moreover, PD-L1− M2 tumor-associated macrophages is associated with a good prognosis in intrahepatic and distal cholangiocarcinoma, suggesting this subtype of M2 tumor-associated macrophages may be antitumoral. Interestingly, lower densities of various types of immunosuppressive cells are associated with decreased infiltration of effector T cells in distal and hilar cholangiocarcinoma, but not in intrahepatic cholangiocarcinoma. In intrahepatic cholangiocarcinoma, PD-L1+ tumor-associated macrophages exert their immunosuppressive function likely through promoting T cell exhaustion. Conclusions This study suggests that the densities of Granzyme-B+CD8+ effector T cells and non-exhausted PD-1−EOMES−CD8+ T cells and the PD-L1 status in the tumor-associated macrophages are prognostic makers in cholangiocarcinomas. The study also supports targeting PD-L1+ tumor-associated macrophages as the immunotherapy for cholangiocarcinoma.

The 2020 Mw6.4 Nima earthquake is one of the largest normal-faulting earthquakes recently occurring north of the Banggong suture zone in remote central Tibet, where geologic investigation of active faults is extremely limited. We analyze jointly InSAR and GNSS observations over 9 months after the Nima earthquake and calculate the coseismic and postseismic displacement. The optimal coseismic slip model suggests this event is the result of moderate-angle down-dip slip on a complex reversed “S-shape” three-segmented structure at fault junctions of the West Yibu-Chaka fault, the Heishi fault, and an unmapped blind fault, with a small component of left-lateral slip. The superposition of seismic waves from faults with different strikes and dips accounted for a large non-double-couple component in the long-period point-source solutions. The geodetic moment released by the mainshock is 6.4 × 1018 N⋅m, equivalent to Mw 6.42. Coseismic rupture concentrated at a depth of 4–15 km, with a peak slip of 1.36 m at 8.5 km depth. The cumulative afterslip moment within 9 months after the mainshock is 1 × 1018 N m, about 15.6% of that released by the mainshock coseismic slip. The afterslips contributed largely to the release of additional strain energy. In addition, shallow creep on the northern part of the blind fault, and deep uplift on the east normal fault system are promoted by stress perturbations. A significant proportion of down-dip coseismic slip spreading to more than 20 km beneath the surface, and deep up-slip afterslip have implications for the rheology of down-dip extension of the dipping faults in northern Tibet. Two obvious stress loading zones of more than 1 bar highlight seismic hazards in the region, especially in the junction between normal faults and ends of the large-size sinistral Riganpei-Co and Jiangai-Zangbu faults. It is necessary to forecast accurately by longer-term afterslip observation over timescales of years for the faults. Compared with previous studies, our results suggest a more complex subsurface fault geometry linking the normal and strike-slip faults and dynamic stress adjustment in this poorly-known region of Tibet.

Heavy metal immobilization using poly-γ-glutamic acid-producing bacteria is a novel and environmentally friendly technique for the remediation of heavy metal-contaminated soil. However, only a few studies have investigated the effects of γ-PGA-producing bacteria on the Cd uptake of wheat plants and the Cd distribution in soil aggregates in Cd-polluted soils. In this study, solution culture and pot experiments were used to investigate the Cd immobilization effect and mechanism of the γ-PGA-producing bacteria Bacillus subtilis W7 and Bacillus amyloliquefaciens W25. In the two bacteria-inoculated culture media, the concentration of Cd decreased, whereas the pH, cell growth, γ-PGA production and cell-immobilized Cd significantly increased over time. Strain W25 exhibited a higher ability to produce γ-PGA and immobilize Cd than strain W7. In the pot experiments, the grain Cd content of wheat was reduced by 24–35% and the DTPA-Cd content was decreased by 22–37% in the rhizosphere soils inoculated with both strains compared to the control. Furthermore, strain W25 had a greater ability to decrease the grain Cd uptake than strain W7. Inoculation with the two strains significantly increased the pH, organic matter content, and urease activity and promoted the migration of Cd from large fractions (>0.25 mm) to small fractions (

Abstract Background As a major component of plant cell walls, cellulose provides the most abundant biomass resource convertible for biofuels. Since cellulose crystallinity and polymerization have been characterized as two major features accounting for lignocellulose recalcitrance against biomass enzymatic saccharification, genetic engineering of cellulose biosynthesis is increasingly considered as a promising solution in bioenergy crops. Although several transcription factors have been identified to regulate cellulose biosynthesis and plant cell wall formation, much remains unknown about its potential roles for genetic improvement of lignocellulose recalcitrance. Results In this study, we identified a novel rice mutant (Osfc9/myb103) encoded a R2R3-MYB transcription factor, and meanwhile generated OsMYB103L-RNAi-silenced transgenic lines. We determined significantly reduced cellulose levels with other major wall polymers (hemicellulose, lignin) slightly altered in mature rice straws of the myb103 mutant and RNAi line, compared to their wild type (NPB). Notably, the rice mutant and RNAi line were of significantly reduced cellulose features (crystalline index/CrI, degree of polymerization/DP) and distinct cellulose nanofibers assembly. These alterations consequently improved lignocellulose recalcitrance for significantly enhanced biomass enzymatic saccharification by 10–28% at p

Lignin contributes to plant resistance to biotic and abiotic stresses and is dominantly regulated by enzymes which catalyze the generation of metabolites intermediates in lignin synthesis. However, the response of lignin and its key regulatory factors to high temperature stress are poorly understood. Here, this finding revealed that the content of lignin in poplar (Populus spp) stem increased after 3 days of high temperature stress treatment. In fourteen metabolic intermediates of lignin biosynthetic pathway with targeted metabolomics analysis, caffeate and coniferaldehyde increased evidently upon heat stress. C3’H (p-Coumaroylshikimate 3-hydroxylase) and CCR (Cinnamoyl-CoA reductase) are recognized to catalyze the formation of caffeate and coniferaldehyde, respectively. Transcriptome data and RT-qPCR (reverse transcription-quantitative real-time polymerase chain reaction) analysis uncovered the high transcriptional level of PtrMYBs (PtrMYB021, PtrMYB074, PtrMYB85, PtrMYB46), PtrC3’H1 (Potri.006G033300) and PtrCCR2 (Potri.003G181400), suggesting that they played the vital role in the increase of lignin and its metabolic intermediates were induced by high temperature. The discovery of key regulators and metabolic intermediates in lignin pathway that respond to high temperature provides a theoretical basis for quality improvement of lignin and the application of forest resources.

BackgroundLaparoscopic radical antegrade modular pancreatosplenectomy (LRAMPS) is a validated surgical treatment for patients with left-sided pancreatic ductal adenocarcinoma (PDAC). In addition, laparoscopic distal pancreatectomy (LDPS) has purported benefits. However, there is a limited analysis comparing the results between LRAMPS and LDPS. Thus, this study aims to compare the short-term and long-term outcomes of patients who underwent LRAMPS and LDPS for PDAC treatment.MethodsPatients with left-sided PDAC that underwent LRAMPS or LDPS from 2015 to 2021 were retrospectively identified. Demographic and clinic pathologic data were collected. Disease-free survival (DFS) and overall survival (OS) probabilities were obtained.ResultsThe number of lymph nodes retrieved was significantly greater in the LRAMPS group than in the LDPS group. Several clinicopathological factors, including CA19-9 levels greater than 37 U/ml, positive lymph nodes, moderate to poor tumor differentiation, and peripancreas fat invasion, were associated with DFS. Moderate with poor tumor differentiation was associated with poor DFS (HR 0.568; 95% CI 0.373–0.921; P = 0.021). Levels of CA19-9 greater than 37 U/ml, CEA levels greater than 5 μg/ml, larger tumor size, positive lymph nodes, moderate with poor tumor differentiation, peripancreas fat invasion, and adjuvant chemotherapy were all associated with OS. LRAMPS nearly improved OS but did not reach statistical significance. Serum carcinoembryonic antigen (CEA) levels greater than 5 ug/ml (HR 1.693; 95% CI 1.200–1.132; P = 0.001), and positive lymph nodes (HR 2.410; 95% CI 1.453–3.995; P = 0.001) were independently associated with poor OS. Treatment with adjuvant chemotherapy was associated with improved OS (HR 0.491; 95% CI 0.248–0.708; P = 0.001).ConclusionsThe LRAMPS procedure achieved comparable results to standard LDPS in terms of postoperative outcomes. Treatment with chemotherapy is important for the prognosis of patients with left-sided pancreatic cancer.

ObjectiveTo investigate the etiology of a small outbreak of gastroenteritis caused by Vibrio parahaemolyticus in Guangzhou, 2017.MethodsSerotype identification, antimicrobial susceptibility test, polymerase chain reaction (PCR) test of virulence genes (tdh, trh, tlh), toxRS/new gene, orf8 gene, pulsed field gel electrophoresis (PFGE) and multilocus sequence typing (MLST) were analyzed.ResultsThe serotype O8∶K21 was identified. All isolates were sensitive to ceftriaxone, ciprofloxacin, chloramphenicol, cotrimoxazole, sulfonamide complex, amikacin, nalidixic acid, streptomycin, tetracycline and gentamicin, and resistant to ampicillin and trimethoprim. The PCR detection of virulence gene showed that all the strains were positive for tdh (thermostable direct hemolysin) and tlh (themolabile hemolysin), but negative for trh (tdh-related hemolysin), and carried toxRS/new and orf8 genes. According to PFGE cluster analysis, they were considered to be a highly related strains. According to MLST analysis, the results were all ST479 type.ConclusionThe reason for the small outbreak of gastroenteritis was due to Vibrio parahaemolyticus O8∶K21, which shared common genetic characteristics. It harbored the tdh gene which was the key characteristic of pandemic strains, and additional surveillance should be conducted to facilitate control of the transmission of this pathogen.

In order to study the ignition process and response characteristics of cast polymer-bonded explosives (PBX) under the action of friction, HMX-based cast PBX explosives were used to carry out friction ignition experiments at a 90° swing angle and obtain the critical ignition loading pressure was 3.7 MPa. Combined with the morphology characterization results of HMX-based cast PBX, the friction temperature rise process was numerically simulated at the macro and micro scale, and the ignition characteristics were judged. The accuracy of the numerical simulation results was ensured based on the experiment. Based on the thermal–mechanical coupling algorithm, the mechanical–thermal response of HMX-based cast PBX tablet under friction was analyzed from the macro scale. The results show that the maximum temperature rise is 55 °C, and the temperature rise of the whole tablet is not enough to ignite the explosive. Based on the random circle and morphology characterization results of tablet, the mesoscopic model of HMX-based cast PBX was constructed, and the microcrack friction formed after interface debonding was introduced into the model. The temperature rise process at the micro scale shows that HMX crystal particles can be ignited at a temperature of 619 K under 4 MPa hydraulic pressure loaded by friction sensitivity instrument. The main reason for friction ignition of HMX-based cast PBX is the friction hot spot generated by microcracks formed after interface damage of the tablet mesoscopic model, and the external friction heat between cast PBX tablet and sliding column has little effect on ignition. External friction affects the ignition of HMX-based cast PBX by influencing the formation of internal cracks and the stress at microcracks.

In this paper, a finite control set model predictive direct power control (FCS-MPDPC) method based on satisfactory optimization, for single-phase three-level PWM rectifier, is proposed to achieve global optimization that takes into account all its objectives and constraints. Satisfaction optimization aims to obtain the satisfactory solution after coordination of multiple goals, instead of the optimal solution of a single goal. By replacing “optimal” with “satisfaction”, more control degrees of freedom are acquired, so that low-priority auxiliary control objectives can participate in the optimization process. Meanwhile, in order to enhance the description accuracy of FCS-MPDPC method for the future trend of PWM rectifier, the prediction time domain is extended from the traditional single-step to multi-step, and the average switching frequency model is established to realize the low switching frequency control. The satisfactory optimized FCS-MPDPC method proposed in this paper is compared, through simulation and experimental results, with the standard FCS-MPDPC method, which verifies the effectiveness and superiority of the proposed algorithm.

The single-phase phase-locked loop (PLL) is essential for the stable operation and control of single-phase grid-connected converters. However, in practical applications, the grid voltage is usually affected by harmonics and dc offset, which will cause errors in the output of the PLL. Therefore, using sliding discrete Fourier transform filter (SDFT) as a prefilter, this paper proposes an improved single-phase synchronous reference frame PLL with a fixed sampling frequency, which can accurately and quickly obtain the grid parameters under distorted grid conditions. Most importantly, the paper theoretically analyzes phase and amplitude errors generated by SDFT for the first time and a quantitative compensation method is proposed, which is straightforward to be used by a reader. Finally, the proposed PLL is compared with other PLLs through simulation and experiments. The experimental results show the effectiveness and practicability of the proposed method.

Abstract Background The characteristics of elephant grass, especially its stem lignocellulose, are of great significance for its quality as feed or other industrial raw materials. However, the research on lignocellulose biosynthesis pathway and key genes is limited because the genome of elephant grass has not been deciphered. Results In this study, RNA sequencing (RNA-seq) combined with lignocellulose content analysis and cell wall morphology observation using elephant grass stems from different development stages as materials were applied to reveal the genes that regulate the synthesis of cellulose and lignin. A total of 3852 differentially expressed genes (DEGs) were identified in three periods of T1, T2, and T3 through RNA-seq analysis. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of all DEGs showed that the two most abundant metabolic pathways were phenylpropane metabolism, starch and sucrose metabolism, which were closely related to cell wall development, hemicellulose, lignin and cellulose synthesis. Through weighted gene co-expression network analysis (WGCNA) of DEGs, a ‘blue’ module highly associated with cellulose synthesis and a ‘turquoise’ module highly correlated with lignin synthesis were exhibited. A total of 43 candidate genes were screened, of which 17 had function annotations in other species. Besides, by analyzing the content of lignocellulose in the stem tissues of elephant grass at different developmental stages and the expression levels of genes such as CesA, PAL, CAD, C4H, COMT, CCoAMT, F5H and CCR, it was found that the content of lignocellulose was related to the expression level of these structural genes. Conclusions This study provides a basis for further understanding the molecular mechanisms of cellulose and lignin synthesis pathways of elephant grass, and offers a unique and extensive list of candidate genes for future specialized functional studies which may promote the development of high-quality elephant grass varieties with high cellulose and low lignin content.

Abstract Background Methylxanthines, including caffeine, theobromine and theophylline, are natural and synthetic compounds in tea, which could be metabolized by certain kinds of bacteria and fungi. Previous studies confirmed that several microbial isolates from Pu-erh tea could degrade and convert caffeine and theophylline. We speculated that these candidate isolates also could degrade and convert theobromine through N-demethylation and oxidation. In this study, seven tea-derived fungal strains were inoculated into various theobromine agar medias and theobromine liquid mediums to assess their capacity in theobromine utilization. Related metabolites with theobromine degradation were detected by using HPLC in the liquid culture to investigate their potential application in the production of 3-methylxanthine. Results Based on theobromine utilization capacity, Aspergillus niger PT-1, Aspergillus sydowii PT-2, Aspergillus ustus PT-6 and Aspergillus tamarii PT-7 have demonstrated the potential for theobromine biodegradation. Particularly, A. sydowii PT-2 and A. tamarii PT-7 could degrade theobromine significantly (p

Abstract Background Caffeine, theobromine and theophylline are main purine alkaloid in tea. Theophylline is the downstream metabolite and it remains at a very low level in Camellia sinensis. In our previous study, Aspergillus sydowii could convert caffeine into theophylline in solid-state fermentation of pu-erh tea through N-demethylation. In this study, tea-derived fungi caused theophylline degradation in the solid-state fermentation. The purpose of this study is identify and isolate theophylline-degrading fungi and investigate their application in production of methylxanthines with theophylline as feedstock through microbial conversion. Results Seven tea-derived fungi were collected and identified by ITS, β-tubulin and calmodulin gene sequences, Aspergillus ustus, Aspergillus tamarii, Aspergillus niger and A. sydowii associated with solid-state fermentation of pu-erh tea have shown ability to degrade theophylline in liquid culture. Particularly, A. ustus and A. tamarii could degrade theophylline highly significantly (p

All-pass-filter-based single-phase phase-locked loop (APF-PLL) is a widely used grid synchronization method in grid-connected power converters. However, the performance of APF-PLL degrades under distorted grid conditions and the estimated phase and frequency will contain low-frequency oscillation terms, which is not conducive to practical application. To deal with this problem, this paper proposes two advanced APF-PLLs, which have good ability to suppress harmonics and dc offset interference without sacrificing the dynamic response of the system. In the first one, a band-pass filter (BPF) is used as the prefilter of APF-PLL to process the input voltage signal, and in the second one, the APF-PLL input signal is processed by using a harmonic decoupling network (HDN) and multiple prefilters. In addition, their parameter design procedure is also described in detail and is easy to follow. The experimental results presented in this paper finally verify the superiority and effectiveness of the two proposed methods.

Purpose: Computer-aided diagnostic methods were used to compare the characteristics of the Original COVID-19 and its Delta Variant.Methods: This was a retrospective study. A deep learning segmentation model was applied to segment lungs and infections in CT. Three-dimensional (3D) reconstruction was used to create 3D models of the patient’s lungs and infections. A stereoscopic segmentation method was proposed, which can subdivide the 3D lung into five lobes and 18 segments. An expert-based CT scoring system was improved and artificial intelligence was used to automatically score instead of visual score. Non-linear regression and quantitative analysis were used to analyze the dynamic changes in the percentages of infection (POI).Results: The POI in the five lung lobes of all patients were calculated and converted into CT scores. The CT scores of Original COVID-19 patients and Delta Variant patients since the onset of initial symptoms were fitted over time, respectively. The peak was found to occur on day 11 in Original COVID-19 patients and on day 15 in Delta Variant patients. The time course of lung changes in CT of Delta Variant patients was redetermined as early stage (0–3 days), progressive and peak stage (4–16 days), and absorption stage (17–42 days). The first RT-PCR negative time in Original COVID-19 patients appeared earlier than in Delta Variant patients (22 [17–30] vs. 39 [31–44], p < 0.001). Delta Variant patients had more re-detectable positive RT-PCR test results than Original COVID-19 patients after the first negative RT-PCR time (30.5% vs. 17.1%). In the early stage, CT scores in the right lower lobe were significantly different (Delta Variant vs. Original COVID-19, 0.8 ± 0.6 vs. 1.3 ± 0.6, p = 0.039). In the absorption stage, CT scores of the right middle lobes were significantly different (Delta Variant vs. Original COVID-19, 0.6 ± 0.7 vs. 0.3 ± 0.4, p = 0.012). The left and the right lower lobes contributed most to lung involvement at any given time.Conclusion: Compared with the Original COVID-19, the Delta Variant has a longer lung change duration, more re-detectable positive RT-PCR test results, different locations of pneumonia, and more lesions in the early stage, and the peak of infection occurred later.

Cellulosic ethanol is regarded as a perfect additive for petrol fuels for global carbon neutralization. As bioethanol conversion requires strong biomass pretreatment and overpriced enzymatic hydrolysis, it is increasingly considered in the exploration of biomass processes with fewer chemicals for cost-effective biofuels and value-added bioproducts. In this study, we performed optimal liquid-hot-water pretreatment (190 °C for 10 min) co-supplied with 4% FeCl3 to achieve the near-complete biomass enzymatic saccharification of desirable corn stalk for high bioethanol production, and all the enzyme-undigestible lignocellulose residues were then examined as active biosorbents for high Cd adsorption. Furthermore, by incubating Trichoderma reesei with the desired corn stalk co-supplied with 0.05% FeCl3 for the secretion of lignocellulose-degradation enzymes in vivo, we examined five secreted enzyme activities elevated by 1.3–3.0-fold in vitro, compared to the control without FeCl3 supplementation. After further supplying 1:2 (w/w) FeCl3 into the T. reesei-undigested lignocellulose residue for the thermal-carbonization process, we generated highly porous carbon with specific electroconductivity raised by 3–12-fold for the supercapacitor. Therefore, this work demonstrates that FeCl3 can act as a universal catalyst for the full-chain enhancement of biological, biochemical, and chemical conversions of lignocellulose substrates, providing a green-like strategy for low-cost biofuels and high-value bioproducts.

Aiming at the problem of unstable output power of wireless charging systems for autonomous underwater vehicles (AUVs), a magnetic coupler (MC) with an arc-shaped core structure is introduced and an output power stabilization control strategy based on mutual inductance identification algorithm is proposed. Firstly, an arc-shaped MC with high tolerances, excellent magnetic coupling and weak electromagnetic interference (EMI) is designed for the cylinder-shaped AUV. Based on ANSYS Maxwell simulation, an analysis of the magnetic field and comparative misalignment tests are carried out for the arc-shaped and the double dipole core structures. Secondly, a mathematical model of the LCC-S type magnetically coupled resonant wireless power transfer (MCR-WPT) system is developed, and a particle swarm parameter identification algorithm with adaptive inertia weights is proposed. Finally, the output power is steadily controlled by real-time adaptation of the duty cycle for the Buck-Boost circuit. The results show there is a maximum error within 2.5% in mutual inductance identification when the load is changed from 0 Ω to 12 Ω and the mutual inductance is changed from 25 μH to 50 μH. The system output power is steady at around 680 W with a maximum fluctuation rate of 4.90%, which verifies the efficiency of the power stabilization control strategy.

The wireless charging system (WCS) is widely employed to solve the problem of underwater charging of autonomous underwater vehicles (AUVs). However, the AUV is prone to misalignment caused by the tidal currents, which directly leads to fluctuations in transmission efficiency and output power. For this reason, a circular-arc-type (CA-type) magnetic coupler with strong misalignment tolerance was proposed in this article. Compared with the ring-type magnetic coupler, the proposed magnetic coupler had better magnetic field convergence and lower weight. Further, the effect of dimensional parameters on the CA-type magnetic coupler performance was analyzed by ANSYS Maxwell, with which the parameters of the magnetic coupler were optimized, and its coupling coefficient could finally reach 0.671. To analyze the influence of misalignment on the CA-type magnetic coupler, EE-type and UI-type magnetic cores are compared. Within the same range of rotation misalignment [−10°, 10°] and axial misalignment [−30, 30 mm], the CA-type magnetic core has stronger misalignment adaptability, and it can achieve a stable output power of 575 W and DC-DC efficiency of 92.51% when rotational misalignment occurs. A WCS experimental prototype is built based on one of the magnetic couplers and its experimental results verify the correctness of the theoretical analysis and simulation results.

Maternal gut microbiota play an important role in the modulation of offspring disease susceptibility and gut microbiota dysbiosis has been proposed as a mechanism through which toxic environmental chemicals exert their adverse impacts on health. The brominated flame retardants polybrominated diphenyl ethers (PBDEs) are developmental toxicants and induce dysbiotic gut microbiota in offspring. Yet, whether and how PBDEs impact the maternal gut microbiota remain unclear. Here, we sought to investigate the effect of 2,2′,4,4′-tetrabromodiphenyl ether (PBDE-47) exposure from preconception through lactation cessation on maternal gut microbiota and its link to host serum metabolic consequences. Female Sprague-Dawley rats were daily exposed to 10 mg/kg PBDE-47 via oral gavage from ten days before conception until offspring were weaned on postnatal day 21, then maternal fecal and blood samples were collected for microbiome and metabolome analyses by using 16S ribosomal RNA gene sequencing and gas chromatography-mass spectrometry, respectively. Maternal exposure to PBDE-47 showed a distinct profile in gut microbiota compared to control dams, as evidenced by increased Actinobacteria phylum and genera Blautia, Gemella and Phascolarctobacterium, and decreased genera AF12 and Oscillospira. Additionally, global metabolomics analysis identified 26 differential serum metabolites to distinguish PBDE-47 from controls, which were mainly involved in amino acid, lipid, carbohydrate and energy metabolism, further confirmed by pathway analysis. Importantly, the differential serum metabolites are closely correlated with the disturbed gut microbiota in response to PBDE-47. Collectively, our results suggest that maternal gut microbial dysbiosis may serve as a potential mechanism underlying PBDE-47-elicited health hazards to mothers or even offspring.

Flavonoids, including flavonol derivatives, are the main astringent compounds of tea and are beneficial to human health. Many researches have been conducted to comprehensively identify and characterize the phenolic compounds in the tea plant. However, the biological function of tea flavonoids is not yet understood, especially those accumulated in floral organs. In this study, the metabolic characteristics of phenolic compounds in different developmental stages of flower buds and various parts of the tea flower were investigated by using metabolomic and transcriptomic analyses. Targeted metabolomic analysis revealed varying accumulation patterns of different phenolic polyphenol compounds during flowering; moreover, the content of flavonol compounds gradually increased as the flowers opened. Petals and stamens were the main sites of flavone and flavonol accumulation. Compared with those of fertile flowers, the content of certain flavonols, such as kaempferol derivatives, in anthers of hybrid sterile flowers was significantly low. Transcriptomic analysis revealed different expression patterns of genes in the same gene family in tea flowers. The CsFLSb gene was significantly increased during flowering and was highly expressed in anthers. Compared with fertile flowers, CsFLSb was significantly downregulated in sterile flowers. Further functional verification of the three CsFLS genes indicated that CsFLSb caused an increase in flavonol content in transgenic tobacco flowers and that CsFLSa acted in leaves. Taken together, this study highlighted the metabolic properties of phenolic compounds in tea flowers and determined how the three CsFLS genes have different functions in the vegetative and reproductive organs of tea plants. Furthermore, CsFLSb could regulated flavonol biosynthesis in tea flowers, thus influencing fertility. This research is of great significance for balancing the reproductive growth and vegetative growth of tea plants.

The ubiquitin/26S proteasome pathway is a critical protein-degradation pathway in plant growth and development as well as in nearly all biological and abiotic stress processes. Although as a member of the ubiquitin/26S proteasome pathway, the E3 ubiquitin ligase family has been shown to be essential for the selective degradation of downstream target proteins, it has been rarely reported in tea plants (Camellia sinensis). In this study, through database searches and extensive manual deduplication, 335 RING finger family proteins were selected from the Tea Plant Information Archive. These proteins were divided into six categories by the difference of RING finger domain: RING-H2, RING-HCa, RING-HCb, RING-C2, RING-v, and RING-G. Stress-induced differential gene expression analysis showed that 53 proteins in RING finger family can respond to selected exogenous stress. In vitro ubiquitination assays indicated that TEA031033, which was named CsMIEL1, exhibited the activity of E3 ubiquitin ligases. CsMIEL1-overexpressing transgenic Arabidopsis thaliana seedlings were resistant to some exogenous abiotic stresses, such as salt and drought stress but sensitive to exogenous methyl jasmonate treatment. Furthermore, CsMIEL1 reduced the accumulation of anthocyanin in transgenic plants in response to low temperature treatment. The results of this article provide basic date for studying the role of ubiquitin/26S proteasome pathway in tea plants response to stresses.

Cold stress restricts the growth and development of plants. Lignin plays an important role in stress resistance. However, there are few studies on lignin mechanisms regulation under low-temperature stress. In this study, the contents of both acid-soluble and -insoluble lignin were reduced after a short period of cold treatment. A targeted metabolomics analysis showed that the contents of caffeate, ferulic acid, coniferaldehyde, and p-coumaraldehyde decreased after cold stress, while the contents of L-phenylalanine and sinapaldehyde increased. The C3′H (p-coumaroylshikimate 3-hydroxylase) and COMT (caffeic acid O-methyltransferase) families, which catalyze the formation of caffeate and coniferaldehyde, were analyzed. Among them, the transcriptional levels of PtrC3′H1, PtrCOMTL4, and PtrCOMT1 were positively correlated with the decreased lignin after cold stimulation. The lignin-related transcription factor PtrMYBs, such as PtrMYB021, PtrMYB074, PtrMYB125/85, and PtrMYB103/46, were clearly induced by cold stress. The reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR) further verified that the level of transcription of key genes was consistent with the transcriptomic data. The identified key genes and metabolic intermediates in lignin synthesis provide a foundation for the functional characterization of the molecular mechanism of lignin biosynthesis under cold stress, which should help to efficiently utilize lignin in forest resources.

Axisymmetric resonators are key elements of Coriolis vibratory gyroscopes (CVGs). The performance of a CVG is closely related to the stiffness and damping symmetry of its resonator. The stiffness symmetry of a resonator can be effectively improved by electrostatic tuning or mechanical trimming, both of which need an accurate knowledge of the azimuth angles of the two stiffness axes of the resonator. Considering that the motion of a non-ideal axisymmetric resonator can be decomposed as two principal oscillations with two different natural frequencies along two orthogonal stiffness axes, this paper introduces a novel high-precision method of stiffness axes identification. The method is based on measurements of the phase difference between the signals detected at two orthogonal sensing electrodes when an axisymmetric resonator is released from all the control forces of the force-to-rebalance mode and from different initial pattern angles. Except for simplicity, our method works with the eight-electrodes configuration, in no need of additional electrodes or detectors. Furthermore, the method is insensitive to the variation of natural frequencies and operates properly in the cases of either large or small frequency splits. The introduced method is tested on a resonator gyroscope, and two stiffness axes azimuth angles are obtained with a resolution better than 0.1°. A comparison of the experimental results and theoretical model simulations confirmed the validity of our method.

Abstract Background The bioconversion of lignocellulose to fermentable C5/C6-saccharides is composed of pretreatment and enzymatic hydrolysis. Lignin, as one of the main components, resists lignocellulose to be bio-digested. Alkali and organosolv treatments were reported to be able to delignify feedstocks and loose lignocellulose structure. In addition, the use of additives was an alternative way to block lignin and reduce the binding of cellulases to lignin during hydrolysis. However, the relatively high cost of these additives limits their commercial application. Results This study explored the feasibility of using elephant grass (Pennisetum purpureum) and reed straw (Phragmites australis), both of which are important fibrous plants with high biomass, no-occupation of cultivated land, and soil phytoremediation, as feedstocks for bio-saccharification. Compared with typical agricultural residues, elephant grass and reed straw contained high contents of cellulose and hemicellulose. However, lignin droplets on the surface of elephant grass and the high lignin content in reed straw limited their hydrolysis performances. High hydrolysis yield was obtained for reed straw after organosolv and alkali pretreatments via increasing cellulose content and removing lignin. However, the hydrolysis of elephant grass was only enhanced by organosolv pretreatment. Further study showed that the addition of bovine serum albumin (BSA) or thioredoxin with His- and S-Tags (Trx-His-S) improved the hydrolysis of alkali-pretreated elephant grass. In particular, Trx-His-S was first used as an additive in lignocellulose saccharification. Its structural and catalytic properties were supposed to be beneficial for enzymatic hydrolysis. Conclusions Elephant grass and reed straw could be used as feedstocks for bioconversion. Organosolv and alkali pretreatments improved their enzymatic sugar production; however, the increase in hydrolysis yield of pretreated elephant grass was not as effective as that of reed straw. During the hydrolysis of alkali-pretreated elephant grass, Trx-His-S performed well as additive, and its structural and catalytic capability was beneficial for enzymatic hydrolysis.

Abstract Background Caffeine is one of the most abundant methylxanthines in tea, and it remains stable in processing of general teas. In the secondary metabolism of microorganism, theophylline is the main conversion product in caffeine catabolism through demethylation. Microorganisms, involved in the solid-state fermentation of pu-erh tea, have a certain impact on caffeine level. Inoculating an appropriate starter strain that is able to convert caffeine to theophylline would be an alternative way to obtain theophylline in tea. The purpose of this study was to isolate and identify the effective strain converting caffeine to theophylline in pu-erh tea, and discuss the optimal conditions for theophylline production. Results Caffeine content was decreased significantly (p

Abstract Background Immune checkpoint inhibitors are not effective for pancreatic ductal adenocarcinoma (PDAC) as single agents. Vaccine therapy may sensitize PDACs to checkpoint inhibitor treatments. Annexin A2 (ANXA2) is a pro-metastasis protein, previously identified as a relevant PDAC antigen that is expressed by a GM-CSF-secreting allogenic whole pancreatic tumor cell vaccine (GVAX) to induce an anti-ANXA2 antibody response in patients with PDAC. We hypothesized that an ANXA2-targeting vaccine approach not only provokes an immune response but also mounts anti-tumor effects. Methods We developed a Listeria-based, ANXA2-targeting cancer immunotherapy (Lm-ANXA2) and investigated its effectiveness within two murine models of PDAC. Results We show that Lm-ANXA2 prolonged the survival in a transplant model of mouse PDACs. More importantly, priming with the Lm-ANXA2 treatment prior to administration of anti-PD-1 antibodies increased cure rates in the implanted PDAC model and resulted in objective tumor responses and prolonged survival in the genetically engineered spontaneous PDAC model. In tumors treated with Lm-ANXA2 followed by anti-PD-1 antibody, the T cells specific to ANXA2 had significantly increased INFγ expression. Conclusions For the first time, a listeria vaccine-based immunotherapy was shown to be able to induce a tumor antigen-specific T cell response within the tumor microenvironment of a “cold” tumor such as PDAC and sensitize the tumor to checkpoint inhibitor therapy. Moreover, this combination immunotherapy led to objective tumor responses and survival benefit in the mice with spontaneously developed PDAC tumors. Therefore, our study supports developing Lm-ANXA2 as a therapeutic agent in combination with anti-PD-1 antibody for PDAC treatment.

Abstract Background Genetic modification of plant cell walls has been implemented to reduce lignocellulosic recalcitrance for biofuel production. Plant glycoside hydrolase family 9 (GH9) comprises endo-β-1,4-glucanase in plants. Few studies have examined the roles of GH9 in cell wall modification. In this study, we independently overexpressed two genes from GH9B subclasses (OsGH9B1 and OsGH9B3) and examined cell wall features and biomass saccharification in transgenic rice plants. Results Compared with the wild type (WT, Nipponbare), the OsGH9B1 and OsGH9B3 transgenic rice plants, respectively, contained much higher OsGH9B1 and OsGH9B3 protein levels and both proteins were observed in situ with nonspecific distribution in the plant cells. The transgenic lines exhibited significantly increased cellulase activity in vitro than the WT. The OsGH9B1 and OsGH9B3 transgenic plants showed a slight alteration in three wall polymer compositions (cellulose, hemicelluloses, and lignin), in their stem mechanical strength and biomass yield, but were significantly decreased in the cellulose degree of polymerization (DP) and lignocellulose crystalline index (CrI) by 21–22%. Notably, the crude cellulose substrates of the transgenic lines were more efficiently digested by cellobiohydrolase (CBHI) than those of the WT, indicating the significantly increased amounts of reducing ends of β-1,4-glucans in cellulose microfibrils. Finally, the engineered lines generated high sugar yields after mild alkali pretreatments and subsequent enzymatic hydrolysis, resulting in the high bioethanol yields obtained at 22.5% of dry matter. Conclusions Overproduction of OsGH9B1/B3 enzymes should have specific activity in the postmodification of cellulose microfibrils. The increased reducing ends of β-1,4-glucan chains for reduced cellulose DP and CrI positively affected biomass enzymatic saccharification. Our results demonstrate a potential strategy for genetic modification of cellulose microfibrils in bioenergy crops.

BackgroundAdenocarcinoma of the ampulla of Vater (AAV) is standardly treated using a complex operation, a pancreatoduodenectomy (PD), to remove the tumor. However, dicision-making in AAV clinical treatment remains difficult due to the broad range of AAV types, outcomes, and responses to special chemotherapeutics. Thus, this study aimed to explore clinicopathological prognostic factors associated with overall survival, as well as post-chemotherapeutic effects related to curative resection of AAV.MethodsWe retrospectively reviewed data for clinicopathological outcome of 47 patients diagnosed with AAV that had underwent a PD. Overall survival probabilities were obtained using the Kaplan–Meier estimate method and a Cox proportional hazards model.ResultsForty-five patients underwent LPD (laparoscopic pancreatoduodenectomy) and two patients underwent PD. The patient group was composed of 31 males (66%) and 16 females (34%) with a mean age of 65(34–91)years. We selected 45 patients for long-term survival analysis. One- and three-year overall survival rates after resection were 97.6% and 58.9% respectively. The median survival was 37.7 months for the intestinal-type and 26.9 months in pancreatobiliary-type ampullary tumors. Serum carbohydrate antigen (CA) 19-9 greater than 37 U/ml (HR 0.140, P = 0.007), perineural invasion (HR 0.141, P = 0.003), and classification as pancreatobiliary-type (HR 6.633, P = 0.006) were independently associated with poor survival. Serum carcinoembryonic antigen (CEA) greater than 5 µg/ml (P = 0.031), serum CA 19-9 greater than 37 U/ml (P = 0.002), tumor sizes greater than 2.5cm (P=0.002), and positive perineural invasion (P=0.003) were all associated with a poor prognosis in the histopathological subgroup. Serum CA 19-9 greater than 37 U/ml (P=0.002) and positive perineural invasion (P=0.001) were significantly associated with poor survival in of patients with intestinal-type ampullary tumors. Serum CEA greater than 5 µg/ml (P=0.013) and tumor sizes greater than 2.5cm (P=0.002) were significantly associated with poor survival in patients with pancreatobiliary-type ampullary tumors.ConclusionsPancreatobiliary-type ampullary tumors were associated with poor survival. Serum CA 19-9 in the intestinal-type and CEA in the pancreatobiliary-type were significantly associated with poor survival. Ajuvant chemotherapy could not predict the survival of AAV patients.