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Abstract Current connected vehicle applications, such as platooning require heavy‐load computing capability. Although mobile edge computing (MEC) servers connected to the roadside intelligence facility can assist such separable applications from vehicles, it is a challenge to coordinate the allocation of subtasks among vehicles and MEC servers on the premise of ensuring communication quality. Therefore, an offloading algorithm is proposed based on a double deep Q‐network to solve the placement of subtasks for vehicle to infrastructure and vehicle to vehicle cases. This algorithm considers the randomness of task generation and is model‐free. The MEC server can assist the vehicle in training the neural network and storing relevant state transitions. To improve the performance of the algorithm, the decaying ε−greedy policy is incorporated for faster convergence. The simulation results showed that this algorithm performed well in reducing the dropped subtask rate, average time delay, and total energy consumption.

Abstract Background For patients with steroid-refractory acute graft-versus-host disease (SR-aGVHD), effective second-line regimens are urgently needed. Mesenchymal stromal cells (MSCs) have been used as salvage regimens for SR-aGVHD in the past. However, clinical trials and an overall understanding of the molecular mechanisms of MSCs combined with basiliximab for SR-aGVHD are limited, especially in haploidentical haemopoietic stem cell transplantation (HID HSCT). Methods The primary endpoint of this multicentre, randomized, controlled trial was the 4-week complete response (CR) rate of SR-aGVHD. A total of 130 patients with SR-aGVHD were assigned in a 1:1 randomization schedule to the MSC group (receiving basiliximab plus MSCs) or control group (receiving basiliximab alone) (NCT04738981). Results Most enrolled patients (96.2%) received HID HSCT. The 4-week CR rate of SR-aGVHD in the MSC group was obviously better than that in the control group (83.1% vs. 55.4%, P = 0.001). However, for the overall response rates at week 4, the two groups were comparable. More patients in the control group used ≥ 6 doses of basiliximab (4.6% vs. 20%, P = 0.008). We collected blood samples from 19 consecutive patients and evaluated MSC-derived immunosuppressive cytokines, including HO1, GAL1, GAL9, TNFIA6, PGE2, PDL1, TGF-β and HGF. Compared to the levels before MSC infusion, the HO1 (P = 0.0072) and TGF-β (P = 0.0243) levels increased significantly 1 day after MSC infusion. At 7 days after MSC infusion, the levels of HO1, GAL1, TNFIA6 and TGF-β tended to increase; however, the differences were not statistically significant. Although the 52-week cumulative incidence of cGVHD in the MSC group was comparable to that in the control group, fewer patients in the MSC group developed cGVHD involving ≥3 organs (14.3% vs. 43.6%, P = 0.006). MSCs were well tolerated, no infusion-related adverse events (AEs) occurred and other AEs were also comparable between the two groups. However, patients with malignant haematological diseases in the MSC group had a higher 52-week disease-free survival rate than those in the control group (84.8% vs. 65.9%, P = 0.031). Conclusions For SR-aGVHD after allo-HSCT, especially HID HSCT, the combination of MSCs and basiliximab as the second-line therapy led to significantly better 4-week CR rates than basiliximab alone. The addition of MSCs not only did not increase toxicity but also provided a survival benefit.

Background: Traditional Chinese medicine injection for Activating Blood Circulation (TCMi-ABC), which exhibits comparable anticoagulant and antiplatelet effects, is commonly used as an adjuvant treatment for acute myocardial infarction (AMI) in China. Objective: The aim of this study was to conduct a meta-analysis to assess the efficacy and safety of TCMi-ABC in combination with conventional western medicine in reducing mortality associated with AMI. Methods: We conducted a comprehensive search of PubMed, Cochrane Library, EMBASE, Web of Science, CBM, WanFang Data, and CNKI databases. Randomized controlled trials (RCTs) investigating the use of TCMi-ABC (including Danhong injection, sodium tanshinone IIA sulfonate injection, salvia miltiorrhiza ligupyrazine injection, and puerarin injection) for the treatment of AMI were included. The search included studies published from the inception of the databases up to December 2022. Two authors independently screened RCTs, extracted data, and assessed the risk of bias. Meta-analysis was performed using RevMan 5.3 and Stata 17.0. The quality of evidence was evaluated using the GRADE approach. Results: A total of 52 RCTs involving 5363 patients were included in the analysis, none of which described independent testing of the purity or potency of the TCMi-ABC product used. 19/52 reported random sequence generation. All RCTs lack adequate description of allocation concealment. 51/52 failed to assess blinding. The meta-analysis results demonstrated that the combined application of TCMi-ABC, compared with conventional western medicine treatment alone, significantly reduced in-hospital mortality in AMI patients [RR= 0.41, 95% CI (0.29, 0.59), P 0.05). The GRADE evidence quality classification indicated that the evidence for in-hospital mortality, malignant arrhythmia, and adverse events was of moderate quality, while the evidence for LVEF was of low quality. Conclusion: TCMi-ABC demonstrates additional clinical value in reducing mortality and the risk of malignant arrhythmia in patients with AMI. However, further validation of these findings is warranted through high-quality clinical trials due to methodological weaknesses in randomization, blinding, allocation concealment, and insufficient assessing for the purity/potency of herbs and the gram amount of active constituents.Systematic Review Registration: [INPLASY], identifier [INPLASY202170082]

The excessive accumulation of antibiotic residue in animal-derived foods pose a threat to our heath. Therefore, it is necessary to establish a rapid, simple, effective, safe and highly sensitive lincomycin (LIN) residues detection method by high-performance liquid chromatography equipped with ultraviolet. Here, due to the weak UV absorption of LIN, the p-Toluenesulfonyl isocyanate (PTSI, has a strong UV absorption) was binded to the hydroxyl group of LINs by using pre-column derivatization method, improving the UV absorption of LIN. This 9-min-run analytical method detects and quantifies LIN residues with acceptable validation performance parameters in terms of sensitivity, selectivity, linearity, the limit of quantification, accuracy, and precision.Our result showed that the limits of detection and quantification for LIN in samples were 25–40 μg/kg and 40–60 μg/kg, respectively, under the optimized conditions. Furthermore, the LIN recoveries ranged from 72.4 % to 96.7 %; the determination coefficients were 0.9912–0.9996, and the relative standard deviations were 5.6 %-12.7 %. Therefore, the HPLC-UVD method for detecting LIN residues in animal-derived food products has been established.

Background: Lincomycin (LIN) is extensively used for treating diseases in livestock and promoting growth in food animal farming, and it is frequently found in both the environment and in food products. Currently, most of the methods for detecting lincomycin either lack sensitivity and precision or require the use of costly equipment such as mass spectrometers. Result: In this study, we developed a reliable high-performance liquid chromatography-ultraviolet detection (HPLC-UVD) method and used it to detect LIN residue in 11 types of matrices (pig liver and muscle; chicken kidney and liver; cow fat, liver and milk; goat muscle, liver and milk; and eggs) for the first time. The tissue homogenates and liquid samples were extracted via liquid–liquid extraction, and subsequently purified and enriched via sorbent and solid phase extraction (SPE). After nitrogen drying, the products were derivatized with p-toluene sulfonyl isocyanic acid (PTSI) (100 µL) for 30 min at room temperature. Finally, the derivatized products were analyzed by HPLC at 227 nm. Under the optimized conditions, the method displayed impressive performance and demonstrated its reliability and practicability, with a limit of detection (LOD) and quantification (LOQ) of LIN in each matrix of 25–40 μg/kg and 40–60 μg/kg, respectively. The recovery ranged from 71.11% to 98.30%. Conclusions: The results showed that this method had great selectivity, high sensitivity, satisfactory recovery and cost-effectiveness—fulfilling the criteria in drug residue and actual detection requirements—and proved to have broad applicability in the field of detecting LIN in animal-derived foods.

Tea plants have a long cultivation history in the world, but there are few studies on polysaccharides from fresh tea leaves. In this study, tea polysaccharides (TPSs) were isolated from fresh tea leaves. Then, we investigated the characteristics of TPSs during in vitro simulated digestion and fermentation; moreover, the effects of TPSs on gut microbiota were explored. The results revealed that saliva did not significantly affect TPSs’ molecular weight, monosaccharide composition, and reducing sugar content, indicating that TPSs cannot be digested in the oral cavity. However, TPSs were partially decomposed in the gastrointestinal tract after gastric and intestinal digestion, resulting in the release of a small amount of free glucose monosaccharides. Our in vitro fermentation experiments demonstrated that TPSs are degraded by gut microbiota, leading to short-chain fatty acid (SCFA) production and pH reduction. Moreover, TPSs increased the abundance of Bacteroides, Lactobacillus, and Bifidobacterium but reduced that of Escherichia, Shigella, and Enterococcus, demonstrating that TPSs can regulate the gut microbiome. In conclusion, TPSs are partially decomposed by gut microbiota, resulting in the production of SCFAs and the regulation of gut microbiota composition and function. Therefore, TPSs may be used to develop a prebiotic supplement to regulate the gut microbiome and improve host health.

Amoxicillin and sulbactam are widely used in animal food compounding. Amoxicillin–sulbactam hybrid molecules are bicester compounds made by linking amoxicillin and sulbactam with methylene groups and have good application prospects. However, the residual elimination pattern of these hybrid molecules in animals needs to be explored. In the present study, the amoxicillin–sulbactam hybrid molecule (AS group) and a mixture of amoxicillin and sulbactam (mixture group) were administered to rats by gavage, and the levels of the major metabolites of amoxicillin, amoxicilloic acid, amoxicillin diketopiperazine, and sulbactam were determined by UPLC–MS/MS. The residue elimination patterns of the major metabolites in the liver, kidney, urine, and feces of rats in the AS group and the mixture group were compared. The results showed that the total amount of amoxicillin, amoxicilloic acid, amoxicillin diketopiperazine, and the highest concentration of sulbactam in the liver and kidney samples of the AS group and the mixture group appeared at 1 h after drug withdrawal. Between 1 h and 12 h post discontinuation, the total amount of amoxicillin, amoxicilloic acid, and amoxicillin diketopiperazine in the two tissues decreased rapidly, and the elimination half-life of the AS group was significantly higher than that in the mixture group (p < 0.05); the residual amount of sulbactam also decreased rapidly, and the elimination half-life was not significantly different (p > 0.05). In 72 h urine samples, the total excretion rates were 60.61 ± 2.13% and 62.62 ± 1.73% in the AS group and mixture group, respectively. The total excretion rates of fecal samples (at 72 h) for the AS group and mixture group were 9.54 ± 0.26% and 10.60 ± 0.24%, respectively. These results showed that the total quantity of amoxicillin, amoxicilloic acid, and amoxicillin diketopiperazine was eliminated more slowly in the liver and kidney of the AS group than those of the mixture group and that the excretion rate through urine and feces was essentially the same for both groups. The residual elimination pattern of the hybrid molecule in rats determined in this study provides a theoretical basis for the in-depth development and application of hybrid molecules, as well as guidelines for the development of similar drugs.

Methicillin-resistant Staphylococcus aureus (MRSA) has evolved into a dangerous pathogen resistant to beta-lactam antibiotics (BLAs) and has become a worrisome superbug. In this study, a strategy in which shikimic acid (SA), which has anti-inflammatory and antibacterial activity, is combined with BLAs to restart BLA activity was proposed for MRSA treatment. The synergistic effects of oxacillin combined with SA against oxacillin resistance in vitro and in vivo were investigated. The excellent synergistic effect of the oxacillin and SA combination was confirmed by performing the checkerboard assay, time-killing assay, live/dead bacterial cell viability assay, and assessing protein leakage. SEM showed that the cells in the control group had a regular, smooth, and intact surface. In contrast, oxacillin and SA or the combination treatment group exhibited different degrees of surface collapse. q-PCR indicated that the combination treatment group significantly inhibited the expression of the mecA gene. In vivo, we showed that the combination treatment increased the survival rate and decreased the bacterial load in mice. These results suggest that the combination of oxacillin with SA is considered an effective treatment option for MRSA, and the combination of SA with oxacillin in the treatment of MRSA is a novel strategy.

Abstract The distributed blocking flowshop scheduling problem (DBFSP) with new job insertions is studied. Rescheduling all remaining jobs after a dynamic event like a new job insertion is unreasonable to an actual distributed blocking flowshop production process. A deep reinforcement learning (DRL) algorithm is proposed to optimise the job selection model, and local modifications are made on the basis of the original scheduling plan when new jobs arrive. The objective is to minimise the total completion time deviation of all products so that all jobs can be finished on time to reduce the cost of storage. First, according to the definitions of the dynamic DBFSP problem, a DRL framework based on multi‐agent deep deterministic policy gradient (MADDPG) is proposed. In this framework, a full schedule is generated by the variable neighbourhood descent algorithm before a dynamic event occurs. Meanwhile, all newly added jobs are reordered before the agents make decisions to select the one that needs to be scheduled most urgently. This study defines the observations, actions and reward calculation methods and applies centralised training and distributed execution in MADDPG. Finally, a comprehensive computational experiment is carried out to compare the proposed method with the closely related and well‐performing methods. The results indicate that the proposed method can solve the dynamic DBFSP effectively and efficiently.

Abstract Background Both extracellular vesicles from mesenchymal stromal cell-derived human umbilical cords (hUC-EVs) and arsenic trioxides (ATOs) have been demonstrated to treat acute graft-versus-host disease (aGVHD) via immunomodulation. Apart from immunomodulation, hUC-EVs have a unique function of drug delivery, which has been proposed to enhance their efficacy. In this study, we first prepared ATO-loaded hUC-EVs (hUC-EVs-ATO) to investigate the therapeutic effect and potential mechanisms of hUC-EVs-ATO in a mouse model of aGVHD after allogeneic hematopoietic stem cell transplantation (HSCT). Methods An aGVHD model was established to observe the therapeutic effects of hUC-EVs-ATO on aGVHD. Target organs were harvested for histopathological analysis on day 14 after transplantation. The effects of hUC-EVs-ATO on alloreactive CD4+ were evaluated by flow cytometry in vivo and in vitro. Flow cytometry, RT-PCR, immunofluorescence colocalization analysis and Western blot (Wb) analysis were performed to examine macrophage polarization after hUC-EV-ATO treatment. The cytokines in serum were measured by a cytometric bead array (CBA). TEM, confocal microscopy and Wb were performed to observe the level of autophagy in macrophages. A graft-versus-lymphoma (GVL) mouse model was established to observe the role of hUC-EVs-ATO in the GVL effect. Results The clinical manifestations and histological scores of aGVHD in the hUC-EVs-ATO group were significantly reduced compared with those in the ATO and hUC-EVs groups. The mice receiving hUC-EVs-ATO lived longer than the control mice. Notably, hUC-EVs-ATO interfering with alloreactive CD4+ T cells differentiation were observed in aGVHD mice but not in an in vitro culture system. Additional studies showed that depletion of macrophages blocked the therapeutic effects of hUC-EVs-ATO on aGVHD. Mechanistically, hUC-EVs-ATO induced autophagic flux by inhibiting mammalian target of rapamycin (mTOR) activity to repolarize M1 to M2 macrophages. Additionally, using a murine model of GVL effects, hUC-EVs-ATO were found not only to reduce the severity of aGVHD but also to preserve the GVL effects. Taken together, hUC-EVs-ATO may be promising candidates for aGVHD treatment. Conclusions hUC-EVs-ATO enhanced the alleviation of aGVHD severity in mice compared with ATO and hUC-EVs without weakening GVL activity. hUC-EVs-ATO promoted M1 to M2 polarization via the mTOR-autophagy pathway. hUC-EVs-ATO could be a potential therapeutic approach in aGVHD after allo-HSCT.

Abstract The Industrial Internet of Things (IIoT), along with 5G and beyond networks, is driving a new era of revolution in intelligent manufacturing. However, the integration of more heterogeneous entities and intricate communication protocols complicates the enhanced manufacturing system, posing challenges for quantitatively assessing its complexity. To tackle this issue, a complexity assessment framework for the IIoT‐enabled collaborative manufacturing system is proposed by combining the complex network and information entropy theory. Firstly, industrial entities in the physical space are mapped into a two‐tier complex network taking into account the weights of various access communications. Secondly, an importance‐aware structure entropy is introduced to capture the complexity of industrial networks from the communication perspective in the system. The experiments conducted on various network topological structures validate the proposed method and provide guidance for system design.

Pleurotus tuber-regium is an edible and medicinal sclerotium-producing mushroom. The sclerotia of this mushroom also serve as food and folk medicine. Based on the description of its monokaryon genome, sequenced with Illumina and PacBio sequencing technologies, comparative transcriptomic analysis using RNA sequencing (RNA-seq) was employed to study its mechanism of sclerotium formation. The de novo assembled genome is 35.82 Mb in size with a N50 scaffold size of 4.29 Mb and encodes 12,173 putative proteins. Expression analysis demonstrated that 1,146 and 1,249 genes were upregulated and downregulated with the formation of sclerotia, respectively. The differentially expressed genes were associated with substrate decomposition, the oxidation-reduction process, cell wall synthesis, and other biological processes in P. tuber-regium. These genomic and transcriptomic resources provide useful information for the mechanism underlying sclerotium formation in P. tuber-regium.

Antibiotics are widely used for infectious diseases and feed additives for animal health and growth. Antibiotic resistant caused by overuse of antibiotics poses a global health threat. It is urgent to choose safe and environment-friendly alternatives to antibiotics to promote the ecological sustainable development of the pig industry. Phytochemicals are characterized by little residue, no resistance, and minimal side effects and have been reported to improve animal health and growth performance in pigs, which may become a promising additive in pig production. This paper summarizes the biological functions of recent studies of phytochemicals on growth performance, metabolism, antioxidative capacity, gut microbiota, intestinal mucosa barrier, antiviral, antimicrobial, immunomodulatory, detoxification of mycotoxins, as well as their action mechanisms in pig production. The review may provide the theoretical basis for the application of phytochemicals functioning as alternative antibiotic additives in the pig industry.

Temperature lapse rate (TLR) is an important parameter for simulations of snow/glacier melts in alpine watersheds. However, the traditional scheme estimates TLR mainly based on a limited number of stations and may not be suitable for alpine watersheds with scarce observations. To overcome this problem, this study developed a new basin-oriented TLR scheme based on Moderate Resolution Imaging Spectroradiometer (MODIS) land surface temperature data which was applied in a typical glacierized watershed on the northern slope of the Himalayas. The new TLR scheme was evaluated by comparison with the station-based traditional TLR scheme in terms of performance in simulations of both snow cover area and runoff using the same hydrological model. The results showed that the monthly TLRs estimated by the new scheme presented a more reasonable seasonal pattern than those estimated by the traditional scheme. The model using the new TLR scheme showed better performance in discharge simulations of low-runoff months than that using the traditional TLR scheme. The R-squared value of multiyear mean monthly snow cover area of the former (0.82) was also higher than that of the latter (0.56). This study provides an efficient framework for estimating TLR based on remote sensing for alpine watersheds with scarce observations.

In the post-genomic era, gene function analysis has attracted much attention. Transformation is often needed to investigate gene function. In this study, an easy, rapid, reliable, and cost-effective colony polymerase chain reaction (PCR) method for screening mushroom transformants was developed: picking up a suitable amount of transformant’s tissue (1–10 μg) to 20 μl 0.25% Lywallzyme solution, and vortexing for 10 s followed by incubation at 34 °C for 15 min. Finally, 2 μl of the suspension was used as templates to perform PCR and single target bands were successfully amplified from respective transformants of Tremella fuciformis, Pleurotus ostreatus, and Pleurotus tuber-regium. This procedure could be widely employed for screening transformants in mushroom transformation experiments.

Agrobacterium tumefaciens-mediated transformation (ATMT), as a simple and versatile method, achieves successful transformation in the yeast-like cells (YLCs) of Tremella fuciformis with lower efficiency. Establishment of a more efficient transformation system of YLCs is important for functional genomics research and biotechnological application. In this study, an enzymolysis-assisted ATMT method was developed. The degradation degree of YLCs depends on the concentration and digestion time of Lywallzyme. Lower concentration (≤0.1%) of Lywallzyme was capable of formation of limited wounds on the surface of YLCs and has less influence on their growth. In addition, there is no significant difference of YLCs growth among groups treated with 0.1% Lywallzyme for different time. The binary vector pGEH under the control of T. fuciformis glyceraldehyde-3-phosphate dehydrogenase gene (gpd) promoter was utilized to transform the enzymolytic wounded YLCs with different concentrations and digestion time. The results of PCR, Southern blot, quantitative real-time PCR (qRT-PCR) and fluorescence microscopy revealed that the T-DNA was integrated into the YLCs genome, suggesting an efficient enzymolysis-assisted ATMT method of YLCs was established. The highest transformation frequency reached 1200 transformants per 106 YLCs by 0.05% (w/v) Lywallzyme digestion for 15 min, and the transformants were genetically stable. Compared with the mechanical wounding methods, enzymolytic wounding is thought to be a tender, safer and more effective method.

The dynamics analysis of a planetary gear set transmissions requires the creation of completely different models for different gears, which is very tedious. In this paper, a generalized dynamics modeling process is proposed for a three planetary gear set transmissions, and a generalized dynamic model for multiple gears is established by using the lumped mass method. The analysis of meshing force characteristics is carried out for the second gear position, and the meshing frequency coupling phenomenon between the meshing forces of the three planetary gear sets is investigated. The results show that, for the current gear set of meshing force, the meshing frequency components of other gear sets only appear in a part of the speed, and with the increase in speed, certain low-frequency components of other sets that exist at low speed will decrease or even disappear, and the coupling relationship between the meshing forces of different planetary gear sets is not symmetrical.

In this work, a biomedical Ti-6Al-4V (TC4)/Zn composite with gradient microstructures was successfully prepared by friction stir processing (FSP). The microstructures and mechanical properties of the composite were systematically studied using scanning electron microscope (SEM), X-ray diffractometer (XRD), transmission electron microscope (TEM), atom probe tomography (APT), and microhardness test. The results show that TC4/Zn composite can be successfully prepared, and gradient microstructures varying from coarse grain to nanocrystalline is formed from the bottom to the upper surface. During FSP, adding Zn can accelerate the growth of β phase region, and the grain size significantly increases with the increasing rotation rate. The grain combination is the main mechanism for grain growth of β phase region. The deformation mechanisms gradually change from dislocation accumulations and rearrangement to dynamic recrystallization from the bottom to the upper surface (1.5 mm−150 μm from the upper surface). The composite exhibits slightly higher microhardness compared with the matrix. This paper provides a new method to obtain a TC4/Zn composite with gradient surface microstructures for potential applications in the biomedical field.

Marine environment monitoring has attracted more and more attention due to the growing concern about climate change. During the past couple of decades, advanced information and communication technologies have been applied to the development of various marine environment monitoring systems. Among others, the Internet of Things (IoT) has been playing an important role in this area. This paper presents a review of the application of the Internet of Things in the field of marine environment monitoring. New technologies including advanced Big Data analytics and their applications in this area are briefly reviewed. It also discusses key research challenges and opportunities in this area, including the potential application of IoT and Big Data in marine environment protection.