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ABSTRACTNeuroblastoma (NB) is a type of neuroectodermal tumor that originates from primitive sympathetic ganglion cells. Although many risk factors contributing to the occurrence of NB have been reported in recent years, the role of the gut microbiota in its development remains unclear. A bidirectional Mendelian randomization (MR) analysis was conducted to elucidate the causal relationship between the gut microbiota and NB. In the MR analysis, we employed the inverse-variance weighted (IVW) method as the primary criterion for assessing causality, while also utilizing three additional approaches, including MR-Egger, weighted median model, and weighted mode, for comprehensive evaluation. For gut microbiota that were causally associated with NB, a reverse MR was also used to assess the stability of this causal relationship. Finally, we also used external cohorts for validation and performed a meta-analysis of the results. The IVW results indicated a causal relationship between six gut microbiota and NB. Among the six gut microbiota, genus Lachnospiraceae [IVW odds ratio (OR): 2.66, 95% confidence interval (CI): 1.09–6.51, P value: 0.03] exhibited a detrimental effect against NB. On the other hand, the class Actinobacteria (IVW OR: 0.24, 95% CI: 0.07–0.77, P value: 0.02), the family Bifidobacteriaceae (IVW OR: 0.40, 95% CI: 0.17–0.96, P value: 0.04), the genus Desulfovibrio (IVW OR: 0.50, 95% CI: 0.25–0.97, P value: 0.04), the genus Bifidobacterium (IVW OR: 0.39, 95% CI: 0.16–0.92, P value: 0.03), and the genus Howardella (IVW OR: 0.55, 95% CI: 0.31–0.97, P value: 0.04) displayed a protective effect on NB. A reverse MR analysis did not reveal a causality between NB and the six gut microbiota. Meta-analysis showed that genus Bifidobacterium (meta OR: 0.41, 95% CI: 0.22–0.75, P < 0.01) and genus Lachnospiraceae (meta OR: 2.20, 95% CI: 1.01–4.79, P < 0.05) were still significant.IMPORTANCEBidirectional Mendelian randomization was used to explore the causality between gut microbiota and neuroblastoma (NB). The results showed that there is a causal relationship between the six gut microbiota and NB, of which two gut microbiota were further confirmed in the meta-analysis. This may provide a new perspective on the prevention and treatment of NB.

Abstract Pyroelectric energy harvesting has received increasing attention due to its ability to convert low-grade waste heat into electricity. However, the low output energy density driven by low-grade temperature limits its practical applications. Here, we show a high-performance hybrid BNT-BZT-xGaN thermal energy harvesting system with environmentally friendly lead-free BNT-BZT pyroelectric matrix and high thermal conductivity GaN as dopant. The theoretical analysis of BNT-BZT and BNT-BZT-xGaN with x = 0.1 wt% suggests that the introduction of GaN facilitates the resonance vibration between Ga and Ti, O atoms, which not only contributes to the enhancement of the lattice heat conduction, but also improves the vibration of TiO6 octahedra, resulting in simultaneous improvement of thermal conductivity and pyroelectric coefficient. Therefore, a thermoelectric coupling enhanced energy harvesting density of 80 μJ cm−3 has been achieved in BNT-BZT-xGaN ceramics with x = 0.1 wt% driven by a temperature variation of 2 oC, at the optical load resistance of 600 MΩ.

Polycrystalline diamond compact (PDC) cutters, the most widely used cutting tool in oil and gas drilling, often fail very quickly because of excessive wear and poor impact toughness in hard and complex formations. In this study, dense PDC samples doped with SiC whiskers (SiCw) were successfully synthesized under high pressure and high temperature (HPHT) conditions. The microstructures, elemental distributions, and phase compositions of the PDC samples were systematically investigated. The mechanical properties including the Vickers hardness, wear resistance, impact toughness and thermal stability, were tested. The introduction of SiCw reduced the Co content in the polycrystalline diamond layer. The testing results showed that the hardness of PDC doped with 0.5 wt% SiCw was 75.25 GPa, wear ratio was 145.6 × 104 and impact toughness reached 4020 J, which were 12.2%, 30.9%, and 142.2% higher than those of the control group (CG), respectively. The PDC-0.5 wt% SiCw had the lowest thermal expansion value, with a 57.5% reduction compared with the CG. In addition, the strengthening mechanism of SiCw was explored. SiCw partially replaced the weakening cobalt phase in the binder phase, thus improving the hardness, wear resistance, and thermal stability of the PDC. The introduction of SiCw inhibited the abnormal growth of WC at the interface of the cemented carbide substrate and changed the fracture mode from intergranular to transgranular, which were the main mechanisms responsible for the significant increase in the impact toughness of PDC.

Abstract Three-dimensional (3D) frictional contact model of functionally graded magneto-electro-elastic (FGMEE) material with a conducting spherical punch under electromagnetic fields is presented. Two types of imperfect bonding interface of layers, dislocation-like interface and force-like interface, are considered. Frequency response functions (FRFs) for multilayered MEE material with imperfect interface subjected to unit mechanical, electric, and magnetic loads are derived. The FRFs are used with the semi-analytical method (SAM) to solve present multiphysical contact problem. The present model is verified by comparing with literatures and the finite element method (FEM) and used to study the contact problem of FGMEE film imperfectly bonded on homogenous MEE half-space under electromagnetic fields. Parametric studies are conducted to reveal the effects of imperfect interfaces and also film properties including gradient index and thickness.

Abstract Background Mechanical ventilation may cause pulmonary hypertension in patients with acute lung injury (ALI), but the underlying mechanism remains elucidated. Methods ALI was induced in rabbits by a two-hit injury, i.e., hydrochloric acid aspiration followed by mechanical ventilation for 1 h. Rabbits were then ventilated with driving pressure of 10, 15, 20, or 25 cmH2O for 7 h. Clinicopathological parameters were measured at baseline and different timepoints of ventilation. RNA sequencing was conducted to identify the differentially expressed genes in high driving pressure ventilated lung tissue. Results The two-hit injury induced ALI in rabbits was evidenced by dramatically decreased PaO2/FiO2 in the ALI group compared with that in the control group (144.5 ± 23.8 mmHg vs. 391.6 ± 26.6 mmHg, P

The frequent occurrence of the pantograph–catenary (PC) arc seriously threatens the safe and stable operation of electric multiple units (EMUs). In order to investigate the primary factors affecting the electrical characteristics of the PC arc, this paper first reveals the mechanism of arc generation when EMUs leave the split-zone insulator according to the actual mechanical structure of the PC articulated split-zone insulator. Then, based on the Habedank black box arc model, considering the dynamic changes in arc length during the actual operation of EMUs, a numerical simulation model suitable for describing the PC articulated split-zone insulator arc is established. Furthermore, by comparing with existing research results, the effectiveness of the proposed model is verified. Next, a series of simulation experiments were conducted to analyze the influence of different operating parameters of the EMUs on the electrical characteristics of the PC arc. More importantly, the paper proposes using the entropy weight method to calculate the impact strength of different operating parameters of the EMUs on the arc duration time of the contact wire split-zone region. The research results of this paper can provide some technical references for reducing the erosion of the PC contact wire and slide caused by arcs when the EMUs pass through the split-zone insulator.

With the rapid development of marine engineering in recent years, offshore operations have become increasingly common, making wave compensation platforms crucial for safe operations at sea. This paper presents a pendulum-type wave compensation platform specifically designed for wave compensation applications. The main components of this wave compensation platform include a chassis, support base, hydraulic cylinders, telescopic rods, upper platform, three sets of balancing mechanisms, three sets of tilt angle sensors, and a control system. Firstly, to thoroughly understand the compensatory motion of the pendulum-type three-degree-of-freedom wave compensation platform, kinematic analysis of the entire system was conducted, and the motion inverse solution curves of the mechanism were obtained through simulation using motion simulation software. Secondly, to enhance the compensatory response performance of the platform, a fuzzy PID control algorithm was employed to control the system and achieve attitude control of the platform. Finally, through control system simulation, compared to PID control, fuzzy PID reduces system response delay and successfully meets the expected technical requirements and application needs.

Solar energy, as a clean and renewable energy source, holds significant promise for addressing water shortages. Utilizing solar energy for water evaporation is seen as an effective solution in this regard. While many existing interfacial photothermal water evaporation systems rely on nanoparticles or graphene as photothermal or support materials, this study introduced polydopamine (PDA) as a photothermal material due to its environmental friendliness and excellent photon absorption characteristics that closely match the solar spectrum. Polystyrene (PS) was also introduced as a support material for its porous structure and density similar to water, enabling it to float on water. The resulting PS-PDA composite porous structure solar evaporator exhibited a photothermal conversion efficiency comparable to nanoparticles (over 75%), yet with lower production costs and minimal environmental impact. This innovative approach offers a scalable solution for water-scarce regions, providing a cost-effective and efficient means to address water scarcity. The use of PDA and PS in this context highlights the potential for utilizing common materials in novel ways to meet pressing environmental challenges.

Soil salinization and nutrient deficiency limit agricultural production in the Yellow River Delta region. This study investigates the green manure-forage grass rotation on soil quality and productivity. A two-year field experiment was conducted to investigate the effects of different varieties of Sesbania cannabina and ᵡTriticosecale Wittm rotations on soil properties, biological characteristics, and adaptability in coastal saline-alkali land. Four cropping rotation systems were set: Gaoyuan 2 - Lujing 2 (G2L2), Gaoyuan 2 - Lujing 5 (G2L5), Gaoyuan 1640 - Lujing 2 (G1640L2), and Gaoyuan 1640 - Lujing 5 (G1640L5). The G2L5 rotation demonstrated superior enhancement of soil quality. The soil organic matter increased by 35.8%, and the soil electric conductivity (CEC) increased by 20.2%. Compared with T. Wittm, S. cannabina had a significant positive effect on soil physical and chemical properties. S. cannabina L5 showed improved performance in mass density, fresh weight of stem, leaf and aboveground part, etc. After S. cannabina returned to the field, T. Wittm G2 had greater plant height, thousand-grain weight, and stem weight, and the yield reached 322 kg per 667 m2. In conclusion, G2L5 is the recommended planting model in saline-alkali soil. This research offers valuable insight for the efficient planting and sustainable development of coastal saline-alkali land.

In response to the problems of large deformation, fracture closure and poor permeability of the surrounding rocks in the weak rock roadways of the 1 000 m or deeper coal mines, it is required that the grouting material has good injectability, fast solidification speed, high early strength, and strong bonding performance. A new method of synergistic preparation of inorganic grouting materials was designed using “component optimization + ultra-fine + nano-reinforcement + organic modification”. An inorganic grouting material with an optimum composition ratio of 50∶40∶10 for the ternary cementing system of calcium sulphate aluminate, gypsum and lime was developed. After ultra grinding, the compressive strength of the concretion increased by 163.0% within 4 hours, achieving initial early strength and rapid solidification. A nano-lithium-aluminium hydrotalcite reinforcement material with synergistic effects of nano-nucleation-induced crystallization and lithium ion promotion was developed, resulting in a 183.7% increase in the 2 h strength of the ultra grinding grouting material. The organic modifier with directional coupling effect at the coal-rock interface was synthesized, which formed a bridge through bonding with the grout and coal interface, significantly improving the bonding between the slurry concretion and the coal rock interface. The synergistically prodeuced inorganic-organic composite grouting reinforcement materials has small particle size (D95

Abstract Non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutation often obtain de novo resistance or develop secondary resistance to EGFR tyrosine kinase inhibitors (EGFR-TKIs), which restricts the clinical benefit for the patients. The activation of phosphatidylinositol 3-kinase (PI3K)/AKT signal pathway is one of the most important mechanisms for the EGFR-TKIs resistance beyond T790M mutation. There are currently no drugs simultaneously targeting EGFR and PI3K signal pathways, and combination of these two pathway inhibitors may be a possible strategy to reverse theses resistances. To test whether this combinational strategy works, we investigated the therapeutic effects and mechanisms of combining BYL719, a PI3Kα inhibitor, with gefitinib, an EGFR-TKI inhibitor in EGFR-TKIs resistance NSCLC models induced by PI3K/AKT activation. Our results demonstrated that PIK3CA mutated cells showed increased growth rate and less sensitive or even resistant to gefitinib, associated with increased PI3K/AKT expression. The combination of BYL719 and gefitinib resulted in synergistic effect compared with the single agents alone in EGFR-mutated NSCLC cells with PI3K/AKT activation. The inhibition of AKT phosphorylation by BYL719 increased the antitumor efficacy of gefitinib in these cell lines. Moreover, the combined effect and mechanism of gefitinib and BYL719 were also confirmed in the NSCLC cells and patient-derived organoids under 3D culture condition, as well as in vivo. Taken together, the data indicate that PIK3CA mutation induces more aggressive growth and gefitinib resistance in NSCLC cells, and the combination treatment with gefitinib and BYL719 is a promising therapeutic approach to overcoming EGFR-TKIs resistance induced by PI3K/AKT activation.

In order to solve the security problems caused by collusion of malicious vehicles in the open Internet of vehicles environment, a collusion node detection method based on fuzzy evaluation density clustering was designed.The method realized vehicle reputation update through subjective recommendation trust, objective data trust and historical reputation.Two rounds malicious node detection method was designed to detect malicious vehicles, in the first round, fuzzy comprehensive evaluation was used to screen out a single malicious vehicle node, and in the second round, the conspiracy malicious vehicle nodes were searched by the improved density clustering method according to a single malicious vehicle node to ensure the sustainable development of network environment security.Experimental results show that the proposed method has a high recognition rate for malicious vehicles, and when the proportion of malicious vehicles reaches 30%, the detection accuracy can still remain above 90%.At the same time, under the proportion of different malicious vehicles, the detection recall rate and detection F value still remain higher value, indicating that the proposed method has a high stability.For the change of total vehicle nodes, the performance evaluation index shows a small fluctuation and remain within the range from 80% to 100%.

Abstract Acute respiratory distress syndrome (ARDS) has a ~ 40% mortality rate with an increasing prevalence exacerbated by the COVID-19 pandemic. Mechanical ventilation is the primary means for life-saving support to buy time for lung healing in ARDS patients, however, it can also lead to ventilator-induced lung injury (VILI). Effective strategies to reduce or prevent VILI are necessary but are not currently delivered. Therefore, we aim at evaluating the current imaging technologies to visualize where pressure and volume being delivered to the lung during mechanical ventilation; and combining plasma biomarkers to guide management of mechanical ventilation. We searched PubMed and Medline using keywords and analyzed the literature, including both animal models and human studies, to examine the independent use of computed tomography (CT) to evaluate lung mechanics, electrical impedance tomography (EIT) to guide ventilation, ultrasound to monitor lung injury, and plasma biomarkers to indicate status of lung pathophysiology. This investigation has led to our proposal of the combination of imaging and biomarkers to precisely deliver mechanical ventilation to improve patient outcomes in ARDS.

Aiming at the problem that the current batch authentication and key agreement protocol were relied on semi-trusted road side unit (RSU) and were not suitable for key update in large-scale Internet of vehicles (IoV), a ring-based efficient batch authentication and group key agreement protocol with anonymity in IoV was proposed.The anonymity was ensured by the pseudonym mechanism.The authentication key pairs were constructed by the chaotic map, and the batch authentication for many vehicles was quickly completed by a small number of bilinear maps.The joining and leaving of vehicles in large-scale IoV scenario were fully considered, a ring session group was efficiently constructed by using the semi-group property of chaotic maps, and a group key establishment and update mechanism suitable for large-scale vehicles was designed.In addition, a pseudonym update mechanism and an anonymous tracing mechanism were designed to ensure a more secure session process.At the same time, the BAN logic model was used to prove the semantic security of the protocol.The security analysis and simulation results show that the proposed protocol has multiple security attributes and certain efficiency advantages.

Hypoxic exercise is an effective intervention for obesity, because it promotes weight loss by regulating fatty acid (FA) metabolism. The regulation of peroxisome proliferator-activated receptor β (PPARβ) by miR-122 may be involved in this process, but the detailed mechanisms are unknown. In order to address this issue, we probed how miR-122 affected the expression of factors associated with FA metabolism in skeletal muscle of obese rats undergoing hypoxic training. By injecting adeno-associated virus 9 containing miR-122 overexpression vector or miR-122 inhibitor into skeletal muscles of rats with a 4-week hypoxic exercise regimen, the miR-122 expression level can be regulated. Body composition and blood lipid levels were analyzed, and PPARβ, carnitine palmitoyltransferase 1b (CPT1b), acetylCoA carboxylase 2 (ACC2), and FA synthase (FAS) mRNA and protein levels were evaluated using quantitative reverse transcription quantitative PCR(RT-qPCR) and Western blot analysis. We found that miR-122 overexpression increased low-density lipoprotein cholesterol (LDL-C) and triglyceride (TG) levels and decreased PPARβ, ACC2, and FAS expression. Conversely, miR-122 inhibition decreased TG level, increased high-density lipoprotein cholesterol (HDL-C) level, and upregulated PPARβ, ACC2, FAS, and CPT1b. These data indicated that the negative regulation of PPARβ by miR-122 promotes FA metabolism by altering the levels of the factors related to FA metabolism in skeletal muscle of obese rat under hypoxic training, thus providing molecular-level insight into the beneficial effects of this intervention.

Abstract Along with the demand for further miniaturization of high and pulsed power devices, it becomes more and more important to realize ultrahigh recoverable energy storage density (Wrec) with high energy storage efficiency (η) and ultrahigh discharge energy storage density (Wd) accompanied by high power density (Pd) in dielectrics. To date, it remains, however, a big challenge to achieve high Wrec or Wd in glass ceramics compared to other dielectric energy storage materials. Herein, a strategy of defect formation modulation is applied to form “amorphous‐disordered‐ordered” microstructure in BaTiO3‐based glass ceramics so as to achieve a high Wrec of 12.04 J cm−3 with a high η of 81.1% and an ultrahigh Wd of 11.98 J cm−3 with a superb Pd of 973 MW cm−3. This work demonstrates a feasible route to obtain glass ceramics with an outstanding energy storage performance and proves the enormous potential of glass ceramics in high and pulsed power applications.

Based on the observed biological activity of 1,2,4-triazin-5-one derivatives and their cyclic analogues, a novel series of 7H-thiazolo[3,2-b]-1,2,4-triazin-7-one derivatives that contain ester moiety compounds 3a-3g, carboxylic acid moiety compounds 4a-4g and piperazine amide moiety compounds 5a-5k at position-3 of the thiazolotriazinone scaffold were synthesized. The intermolecular cyclization occurred regioselectively at N2-position of 1,2,4-triazine ring was characterized by X-ray single-crystal diffraction analysis. The in vitro biological activities of the target compounds were assayed against some bacterial strains. Compared with ciprofloxacin, compounds 3g and 4g exhibited more excellent antibacterial activity, especially the activity against Staphylococcus aureus and Escherichia coli, showing that the fluorine at the para position of the benzyl group would be the best choice. In addition, compounds 4e-4g with carboxylic acid moiety can enhance the antibacterial activity. Compounds 5g-5k containing bulky 1-(substituted phenyl)piperazine moiety were found with slightly less biological activity. Similar to ciprofloxacin, the docking result of target compounds with DNA topoisomerase II indicates the carboxyl group of the target compounds with carboxylic acid moiety has a crucial salt bridge interaction with Mg2+ in the protein.

BackgroundThe clinical prognosis of mitral valve surgery at morning, afternoon, and evening is not yet clear. The aim of the study is to investigate the impact of different time periods of surgery in the morning, afternoon and evening on the short-term and long-term results of mitral valve surgery.MethodsFrom January 2018 to December 2020, 947 patients with mitral valve surgery in our department were selected. These patients were divided into 3 groups according to the starting time of surgery. Morning group (operation start time 8:00–10:30, n = 231), afternoon group (operation start time 12:00–14:30, n = 543), and evening group (operation start time 17:30–20:00, n = 173). The short-term and long-term results of the three groups were compared.ResultsThere were no significant difference in the long-term mortality, long-term risk of stroke and reoperation. And there were no significant difference in in-hospital outcomes, including mortality, stroke, cardiopulmonary bypass time, aortic cross clamp time, mitral valve repair convert to mitral valve replacement, number of aortic cross clamp ≥2 times, unplanned secondary surgery during hospitalization (including thoracotomy hemostasis, thoracotomy exploration, redo mitral valve surgery, and debridement), intra-aortic balloon pump, extracorporeal membrane oxygenation, continuous renal replacement therapy, mechanical ventilation time, and intensive care unit length of stay.ConclusionThere is no significant difference in the risk of short-term and long-term survival and adverse events after mitral valve surgery at different time periods in the morning, afternoon, and evening. Mitral valve surgery at night is safe.

PurposeThis study aimed to develop and validate a clinicopathological model to predict pathological complete response (pCR) to neoadjuvant chemotherapy (NAC) in breast cancer patients and identify key prognostic factors.MethodsThis retrospective study analyzed data from 279 breast cancer patients who received NAC at Zhejiang Provincial People’s Hospital from 2011 to 2021. Additionally, an external validation dataset, comprising 50 patients from Lanxi People’s Hospital and Second Affiliated Hospital, Zhejiang University School of Medicine from 2022 to 2023 was utilized for model verification. A multivariate logistic regression model was established incorporating clinical, ultrasound features, circulating tumor cells (CTCs), and pathology variables at baseline and post-NAC. Model performance for predicting pCR was evaluated. Prognostic factors were identified using survival analysis.ResultsIn the 279 patients enrolled, a pathologic complete response (pCR) rate of 27.96% (78 out of 279) was achieved. The predictive model incorporated independent predictors such as stromal tumor-infiltrating lymphocyte (sTIL) levels, Ki-67 expression, molecular subtype, and ultrasound echo features. The model demonstrated strong predictive accuracy for pCR (C-statistics/AUC 0.874), especially in human epidermal growth factor receptor 2 (HER2)-enriched (C-statistics/AUC 0.878) and triple-negative (C-statistics/AUC 0.870) subtypes, and the model performed well in external validation data set (C-statistics/AUC 0.836). Incorporating circulating tumor cell (CTC) changes post-NAC and tumor size changes further improved predictive performance (C-statistics/AUC 0.945) in the CTC detection subgroup. Key prognostic factors included tumor size >5cm, lymph node metastasis, sTIL levels, estrogen receptor (ER) status and pCR. Despite varied pCR rates, overall prognosis after standard systemic therapy was consistent across molecular subtypes.ConclusionThe developed predictive model showcases robust performance in forecasting pCR in NAC-treated breast cancer patients, marking a step toward more personalized therapeutic strategies in breast cancer.

ObjectiveCarcinoid syndrome (CS) commonly results from neuroendocrine tumors. While active substances are recognized as the main causes of the typical symptoms such as diarrhea and skin flush, the cause-and-effect relationship between gut microbiota abundance and CS remains unclear.MethodsThe Single Nucleotide Polymorphisms (SNPs) related to gut microbiota abundance and CS were obtained from the GWAS summary data. The inverse variance weighted (IVW) method was used to assess the causal relationship between gut microbiota abundance and CS. Additionally, the MR-Egger, Weighted Median model, and Weighted model were employed as supplementary approaches. The heterogeneity function of the TwoSampleMR package was utilized to assess whether SNPs exhibit heterogeneity. The Egger intercept and Presso test were used to assess whether SNPs exhibit pleiotropy. The Leave-One-Out test was employed to evaluate the sensitivity of SNPs. The Steiger test was utilized to examine whether SNPs have a reverse causal relationship. A bidirectional mendelian randomization (MR) study was conducted to elucidate the inferred cause-and-effect relationship between gut microbiota abundance and CS.ResultsThe IVW results indicated a causal relationship between 6 gut microbiota taxa and CS. Among the 6 gut microbiota taxa, the genus Anaerofilum (IVW OR: 0.3606, 95%CI: 0.1554–0.8367, p-value: 0.0175) exhibited a protective effect against CS. On the other hand, the family Coriobacteriaceae (IVW OR: 3.4572, 95%CI: 1.0571–11.3066, p-value: 0.0402), the genus Enterorhabdus (IVW OR: 4.2496, 95%CI: 1.3314–13.5640, p-value: 0.0146), the genus Ruminiclostridium6 (IVW OR: 4.0116, 95%CI: 1.2711–12.6604, p-value: 0.0178), the genus Veillonella (IVW OR: 3.7023, 95%CI: 1.0155–13.4980, p-value: 0.0473) and genus Holdemanella (IVW OR: 2.2400, 95%CI: 1.0376–4.8358, p-value: 0.0400) demonstrated a detrimental effect on CS. The CS was not found to have a reverse causal relationship with the above 6 gut microbiota taxa.ConclusionSix microbiota taxa were found to have a causal relationship with CS, and further randomized controlled trials are needed for verification.

Aiming at the security problems caused by the low efficiency and accuracy of malicious vehicle identification in Internet of vehicles, a distributed trust management scheme based on blockchain in Internet of vehicles was proposed.A false information identification strategy was designed by aggregating the scoring information of vehicles, combined with Bayesian inference model.A reputation value updating algorithm was designed by combining the historical interaction information of vehicles and traffic information, malicious vehicles were identified by the reputation threshold.A blockchain was constructed roadside units to realize the distributed storage of traffic data and vehicle reputation values.The traditional proof of work consensus mechanism was improved to dynamically change the difficulty of miner node generating a block through the event level and the number of vehicles involved in scoring, and the waiting mechanism was used to temporarily stop the nodes that had recently blocked from participating in the election process of miner nodes, thus reducing the resource consumption caused by repeated calculations.The simulation results show that the proposed scheme can effectively identify false information, resist the deceptive behavior of malicious vehicles, improve the identification efficiency of malicious vehicles, reduce resource consumption, and is effective and feasible in distributed trust management for Internet of vehicles.

Abstract The relationship between total lymphocyte counts (TLCs) and survival is not well documented in rectal cancer. This study aimed to investigate the association between TLCs and disease-free survival (DFS) and identify factors associated with lymphopenia in locally advanced rectal cancer patients receiving chemoradiotherapy. Thirty-six patients with locally advanced rectal cancer were retrospectively analyzed. TLCs were evaluated before surgery (pre-S), before radiotherapy (pre-RT), and during concurrent chemoradiotherapy (CCRT). The relationship between TLCs and DFS was analyzed by univariate and multivariate analysis. Potential clinical factors associated with lymphopenia were also evaluated. Median TLC declined significantly during radiotherapy. Severe lymphopenia during CCRT was significantly associated with poorer DFS on Kaplan–Meier analysis (p = 0.01), univariate regression analysis (p = 0.036), and multivariate regression analysis (p = 0.038). Pre-S TLCs (p = 0.009) and pre-RT TLCs (p = 0.042) were significantly associated with severe lymphopenia on univariate regression analysis; however, only pre-S TLCs (p = 0.026) were significantly associated with severe lymphopenia on multivariate regression analysis. Severe lymphopenia was a predictor of poorer DFS in patients with locally advanced rectal cancer receiving adjuvant chemoradiotherapy. Pre-S TLCs were predictors of severe lymphopenia. Further study is warranted to reduce the rate of severe lymphopenia.

In the present paper, the fast pulse loading at high temperature (FPLHT) was conducted on Stellite 6 coatings with and without the interlayer, and exerted great effects on the microstructure, distribution of elements, and mechanical property of the two coatings. The evident crack occurred in the coating without the interlayer in the 400-cycle condition, which was induced by the diffusion of the Fe, the formation of reprecipitation carbides, the coarsening grain, and the formation of Laves phase. The mechanisms of the formation of the Fe–Co phase was revealed by transmission electron microscopy, binary phase diagram, and diagrammatic sketch. To specify the functions of fast pulse loading on the diffusion of Fe and the transformation of the microstructure, the Stellite 6 coating without the interlayer aged for 2880 h was employed for comparison with that in the 400-cycle condition. The softened phenomena occurred in the Stellite 6 coating without the interlayer and the Stellite 6 with the interlayer, the former resulting from the diffusion of Fe and the latter resulting from the diffusion of Ni. The Stellite 6 coating with the interlayer exhibited no crack during the FPLHT, and the disparity of deformation between Stellite 6 coatings with and without the interlayer in the 100-cycle condition was less than that in the 400-cycle condition owing to the difference of diffusion speed between Fe and Ni.

Purpose: We aimed to investigate the mechanism of phenotypic transformation of corporal cavernosum smooth muscle cells (CCSMCs) under hypoxic conditions in vitro. Materials and Methods: In this study, a hypoxia model was established using cobalt chloride (CoCl2). CCSMCs were treated with different concentrations of CoCl2 for varying time periods, and cell viability was assessed. Hypoxia-inducible factor-1α (HIF-1α), myocardin (Myocd) and phenotypic markers were detected in the CCSMCs. We also transfected the CCSMCs with si-HIF-1α and Ad-Myocd and evaluated the effects on phenotypic modulation of CCSMCs and the relationship between HIF- 1α and Myocd was evaluated. Results: CoCl2 inhibited the viability of CCSMCs in a dose- and time-dependent manner, and treatment with 300 μM CoCl2 for 48 hours were the optimal conditions for establishing the hypoxia model. The results showed increased expression levels of HIF-1α and osteopontin and decreased Myocd, alpha-smooth muscle actin, and calponin levels in CCSMCs under hypoxia. HIF-1α knockdown reversed hypoxia-induced phenotypic transformation with elevated Myocd expression. Overexpression of Myocd also reversed the effect of hypoxia on the phenotypic switch, but did not affect HIF-1α expression. Conclusions: Our findings showed that HIF-1α was involved in the effect of hypoxia induced by CoCl2 on CCSMC phenotypic modulation, and Myocd overexpression could inhibit this process. Thus, Myocd might be a potential therapeutic target for erectile dysfunction under hypoxia or HIF-1α activation.

Abstract Stage III non‐small cell lung cancer (NSCLC) encompasses a group of diseases with high heterogeneity. Such patients should actively receive comprehensive treatments. It is imperative for all stage III NSCLC patients to receive consultation with a multiple disciplinary team, which allows the development of a proposal for clinical diagnosis and treatment. In this consensus, stage III NSCLC is divided into two types (operable and inoperable) according to different clinical conditions. Resectable NSCLC is further subdivided into two conditions (with or without driver genes). For each clinical scenario, this consensus emphasizes that the foundation of any medical decisions regarding the optimal diagnostic or therapy procedure is scientific evidence from clinical research. Finally, based on the level of evidence and strength of recommendations, this consensus provides recommendations for the management of stage III NSCLC from six perspectives. The objective of this consensus is to help clinicians choose the best treatment and promote the standardization of stage III NSCLC diagnosis and treatment in China.

Advancements in contact mechanics play an important role in the design of modern mechanical and bio-medical systems, enhancing their efficiency, power density, and reliability [...]

2-Phenylethanol (2-PE) and indole-3-acetic acid (IAA) are important secondary metabolites produced by microorganisms, and their production are closely linked to the growth state of microorganisms and environmental factors. Enterobacter CGMCC 5087 can produce both 2-PE and IAA depending on α-ketoacid decarboxylase KDC4427. This study aimed to investigate the effects of different environment factors including osmotic pressure, temperature, and pH on the synthesis of 2-PE and IAA in Enterobacter sp. CGMCC 5087. The bacteria exhibited an enhanced capacity for 2-PE synthesis while not affecting IAA synthesis under 5% NaCl and pH 4.5 stress conditions. In an environment with pH 9.5, the synthesis capacity of 2-PE remained unchanged while the synthesis capacity of IAA decreased. The synthesis ability of 2-PE was enhanced with an increase in temperature within the range of 25 °C to 37 °C, while the synthesis capacity of IAA was not affected significantly. Additionally, the expression of KDC4427 varied under stress conditions. Under 5% NaCl stress and decreased temperature, expression of the KDC4427 gene was increased. However, altering pH did not result in significant differences in gene expression levels, while elevated temperature caused a decrease in gene expression. Furthermore, molecular docking and molecular dynamics simulations suggested that these conditions may induce fluctuation in the geometry shape of binding cavity, binding energy, and especially the dαC-C- value, which played key roles in affecting the enzyme activity. These results provide insights and strategies for the synthesis of metabolic products 2-PE and IAA in bacterial fermentation, even under unfavorable conditions.

Carbon fiber fabric-reinforced poly(ether ether ketone) (CFF-PEEK) composites exhibit exceptional mechanical properties, and their flexibility and conformability make them a promising alternative to traditional prepregs. However, the formation of the CFF-PEEK composite is trapped in the high viscosity of PEEK, the smooth surface, and tightly interwoven bundles of CFF. It is more difficult for the resin to flow through the fibers of complex textile structures. Here, a simple film stacking method using the hot-pressing process of plain-woven CFF-PEEK thermoplastic composites is discussed. The uniform distribution of PEEK resin between each layer of CFF reduces the flow distance during the molding process, preventing defects in the composite material effectively. Four process parameters, including molding temperature (370, 385, 400, and 415 °C), molding pressure (1, 2, 4, 8, and 10 MPa), molding time (10, 20, 30, 40, 60, and 90 min), and pre-compaction process, are considered. Interlaminar shear strength (ILSS), tensile strength, and flexural strength of CFF/PEEK composites are evaluated to optimize the process parameters. Moreover, ultrasonic scanning microscopy and scanning electron microscopy are employed to observe the formation quality and microscopic failure modes of CFF/PEEK composites, respectively. The ultimate process parameters are a molding temperature of 410 °C, molding pressure of 10 MPa, molding time of 60 min, and the need for the pre-compaction process. Under the best process parameters, the ILSS is 62.5 MPa, the flexural strength is 754.4 MPa, and the tensile strength is 796.1 MPa. This work provides valuable insight for studying the process parameters of fiber fabric-reinforced thermoplastic polymer composites and revealing their impact on mechanical properties.

The accurate estimation of forest aboveground biomass is of great significance for forest management and carbon balance monitoring. Remote sensing instruments have been widely applied in forest parameters inversion with wide coverage and high spatiotemporal resolution. In this paper, the capability of different remote-sensed imagery was investigated, including multispectral images (GaoFen-6, Sentinel-2 and Landsat-8) and various SAR (Synthetic Aperture Radar) data (GaoFen-3, Sentinel-1, ALOS-2), in aboveground forest biomass estimation. In particular, based on the forest inventory data of Hangzhou in China, the Random Forest (RF), Convolutional Neural Network (CNN) and Convolutional Neural Networks Long Short-Term Memory Networks (CNN-LSTM) algorithms were deployed to construct the forest biomass estimation models, respectively. The estimate accuracies were evaluated under the different configurations of images and methods. The results show that for the SAR data, ALOS-2 has a higher biomass estimation accuracy than the GaoFen-3 and Sentinel-1. Moreover, the GaoFen-6 data is slightly worse than Sentinel-2 and Landsat-8 optical data in biomass estimation. In contrast with the single source, integrating multisource data can effectively enhance accuracy, with improvements ranging from 5% to 10%. The CNN-LSTM generally performs better than CNN and RF, regardless of the data used. The combination of CNN-LSTM and multisource data provided the best results in this case and can achieve the maximum R2 value of up to 0.74. It was found that the majority of the biomass values in the study area in 2018 ranged from 60 to 90 Mg/ha, with an average value of 64.20 Mg/ha.

Introduction The strategy for initiating antithrombotic therapy to prevent bioprosthetic valve thrombosis (BPVT) after transcatheter aortic valve replacement (TAVR) remains uncertain. There is still lacking evidence on the efficacy and safety of early 6 months usage of single-antiplatelet therapy (SAPT) or oral anticoagulant (OAC) after TAVR in patients without anticoagulant indications.Methods and analysis This is a multicentre, randomised controlled, open-label trial, and 650 patients undergoing TAVR from 13 top TAVR centres in China will be recruited. Each eligible participant will be randomly assigned to two groups (1:1 ratio) as (1) SAPT (aspirin 75–100 mg for 6 months) group or (2) OAC group (warfarin, therapeutic international normalised ratio at 1.8–2.5 for 6 months), both followed by sequential aspirin 75–100 mg for 6 months. Participants in both groups will be invited for three follow-up visits of 1, 6 and 12 months after discharge. We will use both the net clinical benefit endpoint (composite of all-cause mortality, myocardial infarction, stroke/transient ischaemic attacks, peripheral artery thrombosis, intracardiac thrombosis and major bleeding and disabling or life-threatening bleeding) and the BPVT endpoint evaluated by four-dimensional CT as our primary endpoints. P value of

Background and objectives: Safe and effective management of cancer-related pain is a worldwide challenge. In the search for treatment options, natural products used in Chinese herbal medicines (CHMs) have received attention in clinical studies for their effects on cancer-related pain. The objective of this systematic review is to evaluate the clinical evidence for topically applied CHMs as adjunctive treatments for cancer pain management. Methods: Nine biomedical databases and 4 clinical trial registries were searched for randomized-controlled trials (RCTs) that reported measures of pain and/or quality of life. Risk of bias was assessed using the Cochrane tool. Meta-analysis employed mean difference (MD) with 95% confidence intervals (random effects). Results: Twenty (20) RCTs (1636 participants) met the inclusion criteria. Meta-analyses were grouped based on the comparisons and outcome measures. For pain intensity, there was a greater reduction in the topical CHM group versus placebo (MD −0.72 [−1.04, −0.40]), no difference when compared to tramadol (MD −0.15 [−0.38, 0.08]), and a greater reduction when topical CHMs were combined with conventional analgesic medications (MD −0.67 [−0.93, −0.40]). Analgesic onset time was reduced in the CHM group compared to tramadol (MD −26.02 [−27.57, −24.47] minutes), and for CHMs combined with conventional medications (MD −19.17 [−21.83, −16.52] minutes). When CHMs were combined with analgesic medications, improvements were found for duration of analgesia (MD 1.65 [0.78, 2.51] hours), analgesic maintenance dose (MD −31.72 [−50.43, −13.01] milligrams/day), and quality of life. Conclusion: Addition of topical CHMs to conventional analgesic medications was associated with improved outcomes for pain intensity, some other pain-related outcomes, and measures of quality of life. Limitations included methodological issues in some studies and considerable heterogeneity in some pooled results.

Predicting the risk for general psychopathology (the p factor) requires the examination of multiple factors ranging from brain to cognitive skills. While an increasing number of findings have reported the roles of the cerebral cortex and executive functions, it is much less clear whether and how the cerebellum and cognitive flexibility (a core component of executive function) may be associated with the risk for general psychopathology. Based on the data from more than 400 children aged 6–12 in the Children School Functions and Brain Development (CBD) Project, this study examined whether the left cerebellar lobule VIIb and its connectivity within the cerebellum may prospectively predict the risk for general psychopathology one year later and whether cognitive flexibility may mediate such predictions in school-age children. The reduced gray matter volume in the left cerebellar lobule VIIb and the increased connectivity of this region to the left cerebellar lobule VI prospectively predicted the risk for general psychopathology and was partially mediated by worse cognitive flexibility. Deficits in cognitive flexibility may play an important role in linking cerebellar structure and function to the risk for general psychopathology.

Summary: Background: Pre-procedural computed tomography (CT) imaging assessment of the aortic valvular complex (AVC) is essential for the success of transcatheter aortic valve replacement (TAVR). However, pre-TAVR assessment is a time-intensive process, and the visual assessment of anatomical structures at the AVC shows interobserver variability. This study aimed to develop and validate a deep learning-based algorithm for pre-TAVR CT assessment and anatomical risk factor detection. Methods: This retrospective, multicentre study used AVC CT scans to develop a deep learning-based, fully automated algorithm, which was then internally and externally validated. After loading CT scans into the algorithm, it automatically assessed the essential anatomical structure data required for TAVR planning. CT scans of 1252 TAVR candidates continuously enrolled from Fuwai Hospital were used to establish training and internal validation datasets, while CT scans of 100 patients with aortic valve disease across 19 Chinese hospitals served as an external validation dataset. The validation focused on segmentation performance, localisation and measurement accuracy of key anatomical structures, detection ability of specific anatomical risk factors, and improvement in assessment efficiency. Findings: Relative to senior observers, our algorithm achieved significant consistent performance with remarkable accuracy, efficiency and ease in segmentation, localisation, and the assessment of the aortic annulus perimeter-derived diameter, and other basic planes, coronary ostia height, calcification volume, and aortic angle. The intraclass correlation coefficient values for the algorithm in the internal and external validation datasets were up to 0.998 (95% confidence interval 0.998–0.998), respectively. Furthermore, the algorithm demonstrated high alignment in detecting specific anatomical risk factors, with accuracy, sensitivity, and specificity up to 0.989 (95% CI 0.973–0.996), 0.979 (95% CI 0.936–0.995), 0.986 (95% CI 0.945–0.998), respectively. Interpretation: Our algorithm efficiently performs pre-TAVR assessments by using AVC CT imaging with accuracy comparable to senior observers, potentially improving TAVR planning in clinical practice. Funding: National Key R&D Program of China (2020YFC2008100), CAMS Innovation Fund for Medical Sciences (2022-I2M-C&T-B-044).

Abstract Special separation membranes are widely employed for separation and purification purposes under challenging operating conditions due to their low energy consumption, excellent solvent, and corrosion resistance. However, the development of membranes is limited by corrosion‐resistant polymer substrates and precise interfacial separation layers. Herein, polyaniline (PANI) is employed to achieve insitu anchoring of multiple interfaces, resulting in the fabrication of polyaniline@graphene oxide/polyether ether ketone (PANI@GO/PEEK) membranes. Insitu growth of PANI achieves the adequate bonding of the PEEK substrate and GO separation interface, which solves the problem of solution processing of PEEK and the instability of GO layers. By bottom‐up confined polymerization of aniline, it could control the pore size of the separation layer, correct defects, and anchor among polymer, nano‐separation layer, and nano‐sheet. The mechanism of membrane construction within the confined domain and micro‐nano structure modulation is further explored. The membranes demonstrate exceptional stability realizing over 90% rejection in 2 m HCl, NaOH, and high temperatures. Additionally, –membranes exhibit remarkable durability after 240 days immersion and 100 h long‐term operation, which display the methanol flux of 50.2 L m−2 h−1 and 92% rejection of AF (585 g mol−1). This method substantially contributes to special separation membranes by offering a novel strategy.

Numerous antibiotic resistance genes (ARGs) and virulence factors (VFs) found in animal manure pose significant risks to human health. However, the effects of graphene sodium selenite (GSSe), a novel chemical nano-Selenium, and biological nano-Selenium (BNSSe), a new bioaugmentation nano-Se, on bacterial Se metabolism, chemotaxis, ARGs, and VFs in animal manure remain unknown. In this study, we investigated the effects of GSSe and BNSSe on ARGs and VFs expression in broiler manure using high-throughput sequencing. Results showed that BNSSe reduced Se pressure during anaerobic fermentation by inhibiting bacterial selenocompound metabolism pathways, thereby lowering manure Selenium pollution. Additionally, the expression levels of ARGs and VFs were lower in the BNSSe group compared to the Sodium Selenite and GSSe groups, as BNSSe inhibited bacterial chemotaxis pathways. Co-occurrence network analysis identified ARGs and VFs within the following phyla Bacteroidetes (genera Butyricimonas, Odoribacter, Paraprevotella, and Rikenella), Firmicutes (genera Lactobacillus, Candidatus_Borkfalkia, Merdimonas, Oscillibacter, Intestinimonas, and Megamonas), and Proteobacteria (genera Desulfovibrio). The expression and abundance of ARGs and VFs genes were found to be associated with ARGs-VFs coexistence. Moreover, BNSSe disruption of bacterial selenocompound metabolism and chemotaxis pathways resulted in less frequent transfer of ARGs and VFs. These findings indicate that BNSSe can reduce ARGs and VFs expression in animal manure by suppressing bacterial selenocompound metabolism and chemotaxis pathways.

A robust distributed state estimation algorithm for AC/DC system with AC tie lines and high voltage direct current (LCC-HVDC) tie lines is proposed. The proposed algorithm consists of robust DC state estimation in the coordinator and robust distributed AC state estimation, and implements sequential solving by exchanging coupling variables of the AC/DC system. For AC state estimation, a distributed state estimation algorithm based on the bilinear algorithm is designed, which can achieve the same accuracy as the centralized algorithm. Robust state estimator based on the exponential absolute value function and exponential square function is suitable for reducing the influence of outliers and can reduce the operation scale by simplifying the nonlinear iterative process in distributed state estimation. Finally, the correctness and effectiveness of the algorithm is verified by simulation of three IEEE 118 bus systems interconnected through AC/DC hybrid tie lines.

To investigate the effect of the dynamic deflection process of a two-dimensional vector nozzle on its actuator load and engine performance, a comprehensive modeling method of two-dimensional vector nozzle/actuator load/turbofan engine is proposed. Firstly, based on the two-dimensional vector nozzle spatial motion model, combined with force and moment analysis, the mechanical model of vector nozzle actuation system is established; The load spectrum of the actuating system under different working conditions and deflection angles is obtained by CFD numerical simulation results; Using AMESim, the hydraulic actuation system model of two-dimensional vector nozzle is established. Finally, a two-dimensional vector nozzle/actuator/turbofan engine comprehensive model is established based on the component-level model of turbofan engine. The comprehensive model can accurately calculate the changes of main performance parameters such as engine rotor speed, thrust and pre-turbine temperature when the nozzle vector deflects. The simulation results show that the load on the nozzle actuator is positively correlated with the deflection angle, and the load change will lead to the fluctuation of the output displacement of the hydraulic actuation system. During vector deflection, due to the change of engine circulation capacity and thrust coefficient, the performance parameters such as engine low-pressure rotor speed and surge margin fluctuate greatly.

An initial-rectification adaptive iterative learning control scheme is proposed to solve the angle tracking problem of robot manipulators with input deadzone under nonzero initial errors. Lyapunov approach is utilized to design the controller. First, the initial-rectification auxiliary reference signal is constructed to overcome the obstacle caused by nonzero initial errors during ILC design. Second, adaptive ILC strategy and robust control strategy are adopted for dealing with deadzone nonlinearity. In addition, adaptive learning neural network is applied to approximate for uncertainties. The stability of closed-loop robotic system is rigorously proven by theoretical analysis. In the end, numerical simulation results are provided to verify the effectiveness of the proposed adaptive iterative learning control scheme.

Abstract An industrial robot with a six-axis force/torque sensor is usually used to produce a zero-gravity environment for testing space robotic operations. However, using traditional force control methods, such as admittance control, causes position-controlled industrial robots to undergo from force divergence owing to intrinsic time delay. In this paper, a new force control method is proposed to eliminate the force divergence. A hardware-in-the-loop (HIL) simulator with an industrial robot is first presented. The free-floating satellite dynamics and the motion mapping from the satellites to simulator are both established. Thus, the effects of measurement delay and dynamic response delay on contact velocity and force are investigated. After that, a real-time estimation method for contact stiffness and damping is proposed based on the adaptive Kalman filter. The measurement delay is compensated by a phase lead model. Moreover, the identified contact parameters are adopted to modify contact forces, and thus the dynamics response delay can be compensated for. Finally, a co-simulation and experiments were conducted to verify the force control method. The results show that contact stiffness and damping could be identified exactly and that the simulation divergence could be prevented. This paper proposes an active compliance control method that can deal with force constrained tasks of a position-controlled robot in unknown environments.

Abstract Background To our knowledge, carbon loaded with nano-ZnO (NZnOC) represents a new nutritional additive for the animal husbandry industry. However, the mechanism by which NZnOC mediates beef cattle growth and intestinal health is not fully understood. This study aimed to investigate the effects of carbon loaded with nano-ZnO (NZnOC) supplementation on growth performance, gut microbiota, bile acid (BAs) metabolism and intestinal immunity in fattening cattle. Twenty cattle (16 ± 0.95 months) were randomly assigned to two dietary groups: CON (control, without feed additive) and NZnOC (diet supplemented with 80 mg NZnOC/kg diet dry matter basic) for 60 d. The colon digesta microbiota composition and BAs concentration were determined by microbiota metagenomics and gas chromatography methods, respectively. Results The results showed that the NZnOC-supplemented cattle had greater final weight, average daily gain and gain-to-feed ratio than those in the CON group. Cattle fed the NZnOC diet had a higher relative abundance of the secondary BAs synthesizing phyla Firmicutes, Tenericutes and Actinobacteria than those fed the CON diet. Dietary supplementation with NZnOC increased the relative abundance of the secondary BAs synthesis microbiota genera Clostridium, Ruminococcus, Eubacterium, and Brevibacillus in colon digesta. Cattle fed the NZnOC diet had increased activities of 3α-hydroxysteroid dehydrogenase (EC: 1.1.1.52) and bile acid-CoA ligase BaiB (EC: 6.2.1.7) in the colon digesta compared with those fed the CON diet. The primary BAs taurocholic acid, taurochenodeoxycholic acid and taurodeoxycholate acid were significantly decreased by dietary NZnOC supplementation, while the secondary BAs deoxycholic acid, taurolithocholic acid, beta-muricholic acid, 12-ketolithocholic acid and ursodeoxycholic acid were significantly increased. Dietary supplementation with NZnOC increased the mRNA abundance of G protein-coupled bile acid receptor 1, protein kinase cAMP-activated catalytic subunit alpha, cyclic-AMP response element binding protein 1 and interleukin (IL)-10 in the colon mucosa of cattle, while the mRNA abundance of tumor necrosis factor and IL-1β were significantly decreased. Conclusions In summary, dietary supplementation with NZnOC can facilitate the growth performance and intestinal immune function of cattle by improving BAs metabolism. NZnOC can be supplemented in the diet as a safe regulator of gut microbiota and as a feed additive in the ruminants industry.

Abstract Background Colon cancer is one of the most common diagnosed malignancies. Despite the use of surgery, chemotherapy, radiotherapy, targeted therapy, immunotherapy, and other comprehensive treatments, distant metastasis is still one of the main causes for dying of colon cancer. The common metastatic site of colon cancer is the liver, lung, and bone. In this article, we report a rare case of breast metastasis of signet ring cell carcinoma from the colon. Case presentation A 44-year-old woman was diagnosed with colon cancer and received a radical surgery of colon cancer in 2019. Combined with postoperative pathological and computed tomography (CT) images, a diagnosis of cT3N2M0 mucinous adenocarcinoma of colon (according to AJCC cancer staging manual, Version 8) was established. Adjuvant chemotherapy (XELOX: oxaliplatin 130 mg/m2 on day 1 plus capecitabine 1000 mg/m2 twice daily on days 1 to 14 every 3 weeks for 18 weeks) was performed followed by surgical resection. Fourteen months later, the patient underwent mastectomy for breast mass, which was diagnosed pathologically as metastasis of signet ring cell carcinoma from the colon. XELOX chemotherapy regimen (oxaliplatin 130 mg/m2 on day 1 plus capecitabine 1000 mg/m2 twice daily on days 1 to 14 every 3 weeks for 24 weeks) combined with bevacizumab (7.5 mg/kg on day 1) was used after the mastectomy. The patient had stable disease according to her last examination (RECIST criteria). Conclusion It is rare to find a report of a patient of colon cancer that metastasizes to breast. We hope to increase treatment experience for patients with this rare metastasis.

Abstract Cases of vaccine breakthrough, especially in variants of concern (VOCs) infections, are emerging in coronavirus disease (COVID-19). Due to mutations of structural proteins (SPs) (e.g., Spike proteins), increased transmissibility and risk of escaping from vaccine-induced immunity have been reported amongst the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Remdesivir was the first to be granted emergency use authorization but showed little impact on survival in patients with severe COVID-19. Remdesivir is a prodrug of the nucleoside analogue GS-441524 which is converted into the active nucleotide triphosphate to disrupt viral genome of the conserved non-structural proteins (NSPs) and thus block viral replication. GS-441524 exerts a number of pharmacological advantages over Remdesivir: (1) it needs fewer conversions for bioactivation to nucleotide triphosphate; (2) it requires only nucleoside kinase, while Remdesivir requires several hepato-renal enzymes, for bioactivation; (3) it is a smaller molecule and has a potency for aerosol and oral administration; (4) it is less toxic allowing higher pulmonary concentrations; (5) it is easier to be synthesized. The current article will focus on the discussion of interactions between GS-441524 and NSPs of VOCs to suggest potential application of GS-441524 in breakthrough SARS-CoV-2 infections.

A truncating variant of 17β-hydroxysteroid dehydrogenase-13 (17β-HSD13), a lipid droplet -associated protein, associates with lower risk of chronic liver disease. Here the authors identify a phosphorylation site in 17β-HSD13 which promotes lipolysis, and report that a knock-in mouse with a 17β-HSD13 mutant defective for phosphorylation is more susceptible to nonalcoholic steatohepatitis.

In order to explore the effect of the compound probiotic powder of Lactobacillus rhamnosus and Bifidobacterium lactis on the immunity of mice and its food safety. In this study, low, medium and high doses (1.00, 0.67, 0.34g/kg BW) of compound probiotic powder were orally administered to mice to observe the organ/weight ratio, cellular immune function, humoral immune function, monocyte-macrophage function, NK cell activity and other indicators, comprehensively evaluate the effect of compound probiotic powder on the immune function of mice for 30 d. In addition, rat acute toxicity test, genetic toxicity test (mouse bone marrow cell micronucleus test, mouse sperm deformity test, Ames test) and 30-day feeding test for rats were used for food safety research. The results showed that, compared with the negative control group, the high-dose group mice had significantly increased delayed-type hypersensitivity (DTH), antibody cell production (PFC), serum hemolysin levels, and the phagocytosis index of carbon clearance in mice (P0.05). The growth and development of rats were good, and there was no significant difference in each index compared with the solvent control group (P>0.05). Therefore, the compound probiotic powder of Lactobacillus rhamnosus and Bifidobacterium lactis could enhance immunity without acute toxicity, genetic toxicity and subacute toxicity, and had high edible safety.

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are life-threatening lung diseases with high mortality rates, predominantly attributable to acute and severe pulmonary inflammation. Lomerizine (LMZ) is a calcium channel blocker previously used in preventing and treating migraine. Here, we found that LMZ inhibited inflammatory responses and lung pathological injury by reducing pulmonary edema, neutrophil infiltration and pro-inflammatory cytokine production in lipopolysaccharide (LPS)-induced ALI mice. In vitro experiments, upon treating with LMZ, the expression of interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α was attenuated in macrophages. The phosphorylation of p38 MAPK, ERK1/2, JNK, and NF-κB p65 was inhibited after LMZ treatment. Furthermore, LPS-induced Ca2+ influx was reduced by treating with LMZ, which correlated with inhibition of pro-inflammatory cytokine production. And L-type Ca2+ channel agonist Bay K8644 (BK) could restore cytokine generation. In conclusion, our study demonstrated that LMZ alleviates LPS-induced ALI and is a potential agent for treating ALI/ARDS.

Summary: Despite similar infection rates, COVID-19 has resulted in more deaths in men than women. To understand the underlying mechanisms behind this sex-biased difference in disease severity, we infected K18-human angiotensin converting enzyme 2 (ACE2) mice of both sexes with SARS-CoV-2. Our study revealed a unique protein expression profile in the lung microenvironment of female mice. As a result, they were less vulnerable to severe infection, with higher ACE2 expression and a higher estrogen receptor α (ERα)/androgen receptor (AR) ratio that led to increased antiviral factor levels. In male mice, inhaling recombinant ACE2 neutralized the virus and maintained the ERα/AR ratio, thereby protecting the lungs. Our findings suggest that inhaling recombinant ACE2 could serve as a decoy receptor against SARS-CoV-2 and protect male mice by offsetting ERα-associated protective mechanisms. Additionally, our study supports the potential effectiveness of recombinant ACE2 therapy in human lung organoids infected with the Delta variant.

Cyclin-dependent kinase 16 (CDK16) is an orphan “cyclin-dependent kinase” (CDK) involved in the cell cycle, vesicle trafficking, spindle orientation, skeletal myogenesis, neurite outgrowth, secretory cargo transport, spermatogenesis, glucose transportation, cell apoptosis, cell growth and proliferation, metastasis, and autophagy. Human CDK16 is located on chromosome Xp11.3 and is related to X-linked congenital diseases. CDK16 is commonly expressed in mammalian tissues and may act as an oncoprotein. It is a PCTAIRE kinase in which Cyclin Y or its homologue, Cyclin Y-like 1, regulates activity by binding to the N- and C- terminal regions of CDK16. CDK16 plays a vital role in various cancers, including lung cancer, prostate cancer, breast cancer, malignant melanoma, and hepatocellular carcinoma. CDK16 is a promising biomarker for cancer diagnosis and prognosis. In this review, we summarized and discussed the roles and mechanisms of CDK16 in human cancers.

Potentially toxic elements (PTEs) in cultivated lands pose serious threats to the environment and human health. Therefore, improving the understanding of their distinct sources and environmental risks by integrating various methods is necessary. This study investigated the distribution, sources, and environmental risks of eight PTEs in cultivated soils in Lishui City, eastern China, using digital soil mapping, positive matrix factorisation (PMF), isotopic tracing, and Monte Carlo simulation. The results showed that Pb and Cd are the main pollutants, which posed higher ecological risks in the study area than the other PTEs. Natural, mining, traffic, and agricultural sources were identified as the four determinants of PTE accumulation via a PMF model combined with Pearson correlation analysis, showing that their contribution rates were 22.6 %, 45.7 %, 15.2 %, and 16.5 %, respectively. Stable isotope analysis further confirmed that local mining activities affected the HM accumulation. Additionally, non-carcinogenic and carcinogenic risk values for children were 3.18 % and 3.75 %, respectively, exceeding their acceptable levels. We also identified that mining activities were the most important sources of human health risks (55.7 % for adults and 58.6 % for children) via Monte Carlo simulations coupled with the PMF model. Overall, this study provides insights into the PTE pollution management and health risk control in cultivated soils.

BackgroundWith technological advancements, the incidence of most transcatheter aortic valve implantation (TAVI)-related complications, with the exception of conduction disturbances, has decreased. Bicuspid aortic valve (BAV) is also no longer considered a contraindication to TAVI; however, the effect of BAV on postoperative conduction disturbances after TAVI is unknown.MethodsWe collected information on patients who met the indications for TAVI and successfully underwent TAVI at our center between January 2018 and January 2021. Patients with preoperative pacemaker implantation status or conduction disturbances (atrioventricular block, bundle branch block, and intraventricular block) were excluded. Based on imaging data, the patients were categorized into the BAV group and the tricuspid aortic valve (TAV) group. The incidence of new perioperative conduction disturbances was compared between the two groups.ResultsA total of 187 patients were included in this study, 64 (34.2%) of whom had BAV. The incidence of third-degree block in the BAV group was 1.6%, which was lower than that (13.0%) in the TAV group (P 0.05).ConclusionThe present study found that patients with BAV had a lower rate of third-degree conduction disturbances after TAVI than patients with TAV.

Abstract Histones are DNA‐binding basic proteins found in chromosomes. After the histone translation, its amino tail undergoes various modifications, such as methylation, acetylation, phosphorylation, ubiquitination, malonylation, propionylation, butyrylation, crotonylation, and lactylation, which together constitute the “histone code.” The relationship between their combination and biological function can be used as an important epigenetic marker. Methylation and demethylation of the same histone residue, acetylation and deacetylation, phosphorylation and dephosphorylation, and even methylation and acetylation between different histone residues cooperate or antagonize with each other, forming a complex network. Histone‐modifying enzymes, which cause numerous histone codes, have become a hot topic in the research on cancer therapeutic targets. Therefore, a thorough understanding of the role of histone post‐translational modifications (PTMs) in cell life activities is very important for preventing and treating human diseases. In this review, several most thoroughly studied and newly discovered histone PTMs are introduced. Furthermore, we focus on the histone‐modifying enzymes with carcinogenic potential, their abnormal modification sites in various tumors, and multiple essential molecular regulation mechanism. Finally, we summarize the missing areas of the current research and point out the direction of future research. We hope to provide a comprehensive understanding and promote further research in this field.