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Abstract Background Early-life exposure to famine may influence the occurrence of chronic diseases and aging in midlife among those exposed. This study aims to explore the relationship between exposure to the Chinese Great Famine and aging in middle-aged individuals. Methods Participants born in 1963–1965 (unexposed), 1959–1961 (in utero exposure), and 1955–1957 (childhood exposure) from the Kailuan Study were included. Their biological age at 2010, 2014, and 2018 was investigated, and age acceleration (biological age minus actual age) was calculated to assess aging. Logistic regression analysis was employed to describe the relationship between famine exposure and the aging risk. Subgroup and sensitivity analysis were conducted to explore differences and stability in this relationship among different groups. Results A total of 17,543 participants were included in this study. Among them, 12,762 (72.7%) were male, and 4,781 (27.3%) were female, with 2,543 participants experiencing aging events. Compared to unexposed participants, those exposed during childhood and in utero exhibited a 1.69-fold (OR = 1.69, 95%CI: 1.53–1.87) and 1.22-fold (OR = 1.22, 95%CI: 1.08–1.37) increased risk of aging. Subgroup analysis revealed an interaction with income (P for interaction = 0.008), and additional interaction analysis suggested that increasing income could partially mitigate the detrimental effects of early-life famine exposure. Furthermore, experiencing famine in severely affected regions exacerbated the risk of aging (OR = 1.41, 95%CI: 1.21–1.63). Conclusion Exposure to famine in utero or during childhood may elevate the risk of midlife aging among exposed individuals, and these relationships are influenced by the severity of famine exposure. Increasing income may also help mitigate these effects. Trial registration: Kailuan study, ChiCTRTNRC11001489. Registered July 19, 2015 Retrospectively registered, https//www.chictr.org.cn/showprojEN.html?proj=8050&u_atoken=af46a0dee8d73f320bb5459ab7bbcfa9&u_asig=1a0c381017255295896468605e00cf .

Abstract Depression is a significant mental health issue with extensive economic implications, and recent studies suggest it may be transmitted between individuals. However, the mechanisms of this contagion remain unclear, and the social buffering effect has been understudied. This research employs three rodent models, including stress crossover, cohabitation-induced, and non-contact induced depression contagion models, to explore these mechanisms. Here, we report that that naive mice cohabiting with depressed mice showed increased corticosterone levels and depressive behaviors, unlike those with stressed mice, who did not exhibit these changes and even mitigated desperation in stressed mice. Non-contact cohabitation did not produce significant behavioral differences, but exposure to bedding from depressed mice reduced sucrose preference in naive mice. This study introduces reliable models of depression contagion, suggesting it operates independently of stress transmission. The interplay between depression contagion and social buffering may vary in different contexts. These findings provide new insights into the mechanisms of depression contagion and potential strategies for preventing depressive disorders.

The COVID-19 global pandemic exposed healthcare system vulnerabilities, further endangering patient safety. This article explores perspectives on resilience and patient safety among healthcare workers using data from the Taiwan Patient Safety Culture Survey (TPSCS) and implementing Patient Safety Leadership Walkrounds (PSLWs) at E-Da Hospital. In 2021 and 2022, 1340 and 1114 staff members from clinical departments completed TPSCS questionnaires, respectively. 89 leaders from clinical departments participated in PSLWs in 2022. Among the four job categories, scores of Safety Attitude Questionnaire (SAQ) were lower among nurses and medical technicians, while perceptions of resilience and work-life balance were lowest among nurses. Between the two-year surveys, nurses exhibited significant decreases in SAQ in 2022 compared to 2021, while perceptions of work condition and work-life balance significantly declined among pharmacists. Resilience perception significantly decreased among all job categories except physicians during the pandemic. Mediation analyses showed teamwork climate, job satisfaction, management, work condition, and work-life balance were directly associated with safety climate, while resilience acts as a mediator, indirectly potentiating these relationships. Through PSLWs, we identified concerns about patient safety, including workforce, systems, processes, equipment, and work environment. Among these, workforce shortages and unsatisfactory pay emerged as the most pressing challenges. Strong leadership was recognized as a crucial factor in enhancing resilience and patient safety. This study suggests that TPSCS and PSLWs are worth regularly promoting among hospital institutions. Additionally, our findings highlight the urgency of healthcare organizations and governmental agencies to undertake policy reforms to improve healthcare workers’ well-being.

Abstract The COVID-19 pandemic has highlighted the urgent need to address vaccine coverage inequality. Despite calls from scientists and national organizations, progress in ensuring equitable access to vaccines has been slow. This study aims to reveal the COVID-19 vaccine coverage inequality and investigate the predictive effect of attitudes toward science and religion on real-word vaccination uptake. We draw on three high-quality, large-scale databases to unveil real-world vaccine coverage, which stood at an average of 53% of the population by mid-2022. The vaccination rate varies based on a country’s income, with higher-income nations having higher vaccination rates and faster vaccination speed. Regression models and a multiverse analysis reveal that both country-level attitudes towards science and religion, as well as religious faith, are linked to vaccination rate at the country level. Countries where a higher proportion of the population prioritize religious beliefs over scientific evidence when the two come into conflict tend to have lower vaccination coverage rates and slower vaccination speeds. These findings suggest that scientists and policymakers must take into account social and cultural characteristics of populations when addressing vaccine inequality.

Bone defects caused by trauma or tumor led to high medical costs and poor life quality for patients. The exosomes, micro vesicles of 30–150 nm in diameter, derived from macrophages manipulated bone regeneration. However, the role of hydrogen sulfide (H2S) in the biogenesis and function of exosomes and its effects on bone regeneration remains elusive. In this study, we used H2S slow releasing donor GYY4137 to stimulate macrophages and found that H2S promoted the polarization of M2 macrophages to increase bone regeneration of MSCs in vitro and in vivo. Moreover, we developed the H2S pre-treated M2 macrophage exosomes and found these exosomes displayed significantly higher capacity to promote bone regeneration in calvarial bone defects by re-establishing the local immune microenvironment. Mechanically, H2S treatment altered the protein profile of exosomes derived from M2 macrophages. One of the significantly enriched exosomal proteins stimulated by H2S, moesin protein, facilitated the exosomes endocytosis into MSCs, leading to activated the β-catenin signaling pathway to promote osteogenic differentiation of MSCs. In summary, H2S pretreated M2 exosomes promoted the bone regeneration of MSCs via facilitating exosomes uptake by MSCs and activate β-catenin signaling pathway. This study not only provides new strategies for promoting bone regeneration, but also provides new insights for the effect and mechanism of exosomes internalization.

Objective: and design Mild vascular inflammation promotes the pathogenesis of hypertension. Asprosin, a newly discovered adipokine, is closely associated with metabolic diseases. We hypothesized that asprosin might led to vascular inflammation in hypertension via NLRP3 inflammasome formation. This study shows the importance of asprosin in the vascular inflammation of hypertension. Methods: Primary vascular smooth muscle cells (VSMCs) were obtained from the aorta of animals, including spontaneously hypertensive rats (SHR), Wistar–Kyoto rats (WKY), NLRP3−/− and wild-type mice. Studies were performed in VSMCs in vitro, as well as WKY and SHR in vivo. Results: Asprosin expressions were up-regulated in VSMCs and media of arteries in SHR. Asprosin overexpression promoted NLRP3 inflammasome activation via Toll-like receptor 4 (TLR4), accompanied with activation of NFκB signaling pathway in VSMCs. Exogenous asprosin protein showed similar roles in promoting NLRP3 inflammasome activation. Knockdown of asprosin restrained NLRP3 inflammasome and p65-NFκB activation in VSMCs of SHR. NLRP3 inhibitor MCC950 or NFκB inhibitor BAY11-7082 attenuated asprosin-caused VSMC proliferation and migration. Asprosin-induced interleukin-1β production, proliferation and migration were attenuated in NLRP3−/− VSMCs. Local asprosin knockdown in common carotid artery of SHR attenuated inflammation and vascular remodeling. Conclusions: Asprosin promoted NLRP3 inflammasome activation in VSMCs by TLR4-NFκB pathway, and thereby stimulates VSMCs proliferation, migration, and vascular remodeling of SHR.

In this study, electrochemical corrosion and wear experiments were conducted to clarify the role of cryogenic treatment on the microstructural morphology and resistance to corrosion and wear of high-manganese austenitic steel. Heat treatment of the solution (950 °C) and annealing (500 °C and 600 °C) were performed on the hot-rolled specimens. Cryogenic treatment was applied to hot-rolled, hot-rolled + heat treated specimens. Cryogenic treatment is a practical technology for eliminating the strip morphology of hot-rolled specimens and improves the wear resistance of heat-treated specimens. However, it plays different role on the corrosion resistance of tested specimens related with production process. The wear mechanism differs due to the cryogenic treatment. A schematic model of the wear mechanism is proposed based on the experimental results. Cryogenic treatment coarsens the grain size regardless of the production process.

Abstract Background Previous studies have shown that insomnia affects human prefrontal function and that there are specific patterns of brain activation to counteract sleep and improve cognition. However, the effects of insomnia on the prefrontal cortex of MDD (major depressive disorder) patients and the patterns of activation to counteract sleep in MDD patients remain unclear. The aim of this study is to examine this using fNIRS (functional near-infrared spectroscopy). Methods Eighty depressed patients and 44 healthy controls were recruited for this study. fNIRS was used to assess changes in the concentration of oxygenated hemoglobin ([oxy-Hb]) in the prefrontal cortex of all participants during the VFT (verbal fluency test) and to record the number of words created to assess cognitive ability. The Pittsburgh Sleep Quality Index was used to assess sleep quality, and the Hamilton Rating Scale for Depression (24-item) and Hamilton Rating Scale for Anxiety (14-item) were used to assess the severity of depression and anxiety. Results When comparing patients, the healthy control group had significantly higher [oxy-Hb] values in the bilateral prefrontal cortex during VFT than the MDD group. In the MDD group, the [oxy-Hb] values in all brain regions except the right DLPFC were significantly higher in the group with insomnia than in the group without insomnia, but their VFT performance was significantly lower than in the group without insomnia and the healthy group. PSQI scores were positively correlated with [oxy-Hb] values in some left-brain regions, whereas HAMD and HAMA scores were not correlated with [oxy-Hb] values. Conclusion The PFC was significantly less active during VFT in those with MDD than in healthy controls. All brain regions, except the right DLPFC, were significantly more active in MDD patients with insomnia than in those without insomnia, suggesting that sleep quality needs to be an important indicator in fNIRS screening. In addition, there was a positive correlation between the severity of insomnia in the left VLPFC and the level of activation, suggesting a role for the left brain region in the neurophysiology of overcoming sleepiness in MDD patients. these findings may provide new ideas for the treatment of MDD patients in the future. Trial registration Our experiment was registered in the China Clinical Trial Registry (registration number ChiCTR2200065622) on November 10.( The first patient was recruited in 10/11/2022.)

Objective Imaging measurements allow assessment of the mechanical alignment before and after total knee arthroplasty (TKA). The changes in radiographic parameters in each period of time within 1 year after TKA has been poorly understood. The purpose of this study was to examine the timing and causes of imaging changes in lower extremity force lines after total knee arthroplasty with mechanical alignment. Methods A total of 93 mechanically‐aligned TKA were radiographically examined before, 3 days, 3 months, and 1 year after surgery. Radiographic parameters included hip‐knee angle (HKA), lateral distal femoral angle (LDFA), medial proximal tibial angle (MPTA), knee joint line orientation (KJLO), ankle joint line orientation (AJLO), the knee joint line relative to ankle joint line angle (KJLTA) and midpoints of the ankle distance (MAD). Paired t‐test were used to analyze the changes of these imaging parameters, By establishing a simple tibial model, the time points of changes in the imaging parameters after TKA was determined, with an attempt to understand the post‐TKA changes in these imaging parameters. Results Statistically significant differences were found between the preoperative data and the data measured 3 days after surgery in HKA, LDFA, MPTA, MAD, KJLTA, AJLO (P 0.05). Significant differences were revealed between the data measured 3 months and those collected 1 year after surgery in LDFA, MPTA, AJLO, KJLTA (P 0.05). The tibial model was made to look into the changes in postoperative imaging parameters. ΔMAD and postoperative AJLO were calculated to verify the model and hypothesis. Conclusions Postoperative changes in radiographic parameters and tibial models showed that the lower extremities were in an unnatural state within 1 year after TKA. The changes in the lower extremities force line were the results of the gradual adaptation of the lower extremities to TKA and the lateral swing of the extremities (3°) after surgery. Imaging data 1 year after surgery should be taken into account in the explanation of post‐TKA changes in lower limb force lines.

Hemihydrate phosphogypsum (HPG), as a cementing material for mine filling, will spontaneously transform into phosphogypsum (PG) in the stockpiling state. The gelling activity decreases, and meeting the requirements of mechanical properties required for long-distance mine filling becomes difficult. The key measure in expanding the industrial application radius of HPG as a filling cementitious material is the prevention of the spontaneous conversion of HPG to PG. In-depth research on the conversion process of HPG in the storage state is required to achieve a breakthrough in the HPG resource utilization technology. In the storage process, the HPG chemical reaction will release the heat of hydration, causing the temperature and chemical fields in the system to interact with each other and promote the conversion of HPG to PG. Therefore, the HPG hydration heat release process is accurately calculated, analyzed, and simulated. This is a prerequisite to effectively inhibit the conversion of HPG. This article seeks a model of the heat release of the HPG hydration reaction during the storage process to understand the change of its gelation performance and guide on-site industrial applications. The monitoring of the free water mass fraction and the temperature of HPG stacks with initial temperatures of 35 °C, 40 °C, 60 °C, and 80 °C reveals that the HPG free water mass fraction change law conforms to the first-order reaction kinetic model. Based on thermodynamics and chemical reaction kinetics, a thermal kinetic model of the HPG hydration reaction on the relationship between the storage temperature and time is proposed. Using the COMSOL Multiphysics numerical simulation software, the HPG hydration reaction thermokinetic equation was then embedded in the heat transfer and ODE modules, and the HPG reactor temperature was numerically simulated. The simulated reactor temperature curve was more consistent with experimental results, and the reliability of the proposed model was verified. This model can provide guidance for the later design of the delaying HPG conversion plan and has very important practical significance for the promotion and application of HPG.

Abstract Objective Minimal invasive approach has been increasingly used in total knee arthroplasty (TKA) and more is expected of early rehabilitation in terms of pain release and recovery of knee function. The approach type is one of the major factors that determines the early rehabilitation after TKA. The purpose of this study is to determine whether mini‐subvastus approach (MSVA) is superior to the traditional medial parapatellar approach (MPA) in TKA. Methods From 2018 to 2019, a randomized double‐blinded prospective study was conducted on 58 patients who underwent simultaneous bilateral TKA. The subjects included eight men and 50 women, with an average age of 65 years. One side was randomized using MSVA and the other side using MPA. Visual analog scale (VAS), operative duration, recovery time to straight leg raising (SLR), range of motion (ROM), HSS score, release rate of lateral retinaculum, satisfaction rate were recorded and compared. Paired‐samples T test were used for quantitative data and chi‐square test for qualitative data. Results There was no statistical difference in the ratio of left and right sides, preoperative ROM, VAS, HSS score, muscular strength of lower limbs, KL grade, operative order, and operative duration between the two groups. The average ROM (118.91 ± 8.21 vs. 107.60 ± 7.99, t = 14.320, p = 0.0000) and HSS score (72.03 ± 4.55 vs. 61.22 ± 4.36, t = 13.095, p = 0.0000) on POD 3, VAS in rest and motion on POD 1 and 3, the recovery time to SLR (1.17 ± 0.38 vs. 3.09 ± 0.76, t = 19.902, p = 0.0000), and the satisfaction rate on POD 1 (96.55% vs. 74.14%, χ2 = 9.9251, p = 0.0016) were superior in the MSVA group over MPA group. ROM in rest and motion and HSS score on POD 30 had no difference. The release rate of lateral retinaculum was less in the MSVA group than in the MPA group. The mean value of HKA, FFC, and FTC and the proportion of outliers did not differ significantly between the two groups. Conclusions Compared with MPA, MSVA can make ROM of knee and SLR recover earlier, reduce postoperative pain after TKA, improve the early postoperative satisfaction and reduce the lateral release rate. MSVA can be used as a favorable measure in the concept of enhanced recovery after surgery (ERAS).

Abstract The spongy moth Lymantria dispar, formerly known as the gypsy moth, is a forest pest that occurs as two different biotypes: the European spongy moth (ESM), Lymantria dispar dispar, which is distributed in Europe and North America; and the Asian spongy moth (ASM), which consists of subspecies Lymantria dispar asiatica and Lymantria dispar japonica and is distributed in China, Russia, Korea, and Japan. The Asian biotype is classified as a quarantine pest by the U.S. Department of Agriculture because of the superior flight ability of adult females compared to females of the European biotype. To identify genes that potentially account for differences in female flight capability between the two biotypes, we assembled and compared transcriptional profiles of two North American populations of ESM and two Chinese populations of ASM, including samples of unmated female adults and females after mating and oviposition. Of 129,286 unigenes identified, 306 were up-regulated in ASM samples relative to ESM, including genes involved in egg production. In contrast, 2309 unigenes were down-regulated in ASM samples, including genes involved in energy production. Although a previous study found that ASM female flight was reduced after oviposition, a comparison of gene expression before and after mating and oviposition did not reveal any genes which were consistently up- or down-regulated in the two ASM populations.

A significant challenge facing heliospheric models is the lack of full Sun observational coverage. The lack of information about the farside photospheric magnetic field necessitates the use of various techniques to approximate the structure and appearance of this field. However, a recently developed technique that uses He ii 304 Å emission observed by the Solar Terrestrial Relations Observatory (STEREO) enables developing a magnetic flux proxy by imaging of active regions on the far side of the Sun. Incorporating information about these active regions on the far side of the Sun may have the potential to drastically improve heliospheric models. In this work, we run multiple heliospheric models with and without farside information obtained from STEREO observations of He ii 304 Å emission and compare the predicted in situ measurements from the models with real in situ data from STEREO and Earth. We find that although there are noticeable quantitative differences between the in situ predictions from the two models, they are dwarfed by the overall disagreement between the heliospheric model and the actual in situ data. Nevertheless, our results indicate that active regions that significantly change the ratio of open-to-closed and open-to-total flux create the biggest change in the predicted in situ measurements.

Summary Pseudomonas sp. strain 166 was isolated from soil samples from Changbai Mountains. A novel bacteriocin PA166 from Pseudomonas sp. 166 was purified using ammonium sulfate, dextran gel chromatography column and Q‐Sepharose column chromatography successively. The molecular mass of bacteriocin PA166 was found to be 49.38 kDa by SDS‐PAGE and liquid chromatography–mass spectrometry (MS)/MS. Bacteriocin PA166 showed stability at a wide range of pH (2–10), and thermal stability (40, 60, 80 and 100°C). The bacteriocin PA166 antimicrobial activity was slightly inhibited by Ca2+, K+ and Mg2+. The minimum bactericidal concentrations of bacteriocin PA166 against five Pasteurella multocida strains ranged from 2 to 8 μg ml−1. Bacteriocin PA166 showed low cytotoxicity and a higher treatment index (TI = 82.51). Fluorescence spectroscopy indicated that bacteriocin PA166 destroyed the cell membrane to exert antimicrobial activity. In summary, bacteriocin PA166 had strong antibacterial activity, high TI and low toxicity, and hence could serve as a potential clinical therapeutic drug.

Whether domestic or foreign, the utilization of phosphogypsum (PG) resources is not satisfactory. A chemical plant in Guizhou produces phosphoric acid through a semi-aqueous process to obtain the byproduct hemihydrate phosphogypsum (HPG), which has a certain gelling activity. If this feature of HPG can be fully utilized, it can replace cement as a cementing material to prepare mine-filling materials. Utilizing HPG for goaf filling can not only reduce the environmental protection problems caused by the surface discharge of PG but also eliminate the hidden safety hazards in the goaf. At present, when HPG is used to prepare mine-filling cementitious materials, HPG will be consolidated into a block and lose its gelling activity when it is stacked for a certain period of time. The gelling performance of the HPG in the storage state appears to decline. Based on the indoor HPG crystal water detection and uniaxial compression test and setting four different storage temperatures (20 ℃, 40 ℃, 60 ℃, and 80 ℃), this study explored the changes in the mass fraction of the crystal water of HPG samples under different storage temperatures. The compressive strength development law of HCM prepared after storage and microscopic analysis methods, such as scanning electron microscopy, were used to study the influence mechanism of the storage temperature on its strength. Results show that the stacking temperature has a significant effect on the gelling performance of HPG. A high stacking temperature will speed up the conversion of free water in the HPG sample to crystal water and inhibit the strength development of the HCM prepared after stacking. Data standardization was used to predict the compressive strength of samples after storage at different temperatures, which is confirmed to be in good agreement with the measured values. The microscopic analysis found that the storage temperature mainly affects the supersaturation of the system, and the microscopic morphology of the HCM prepared after storage at different temperatures is different.

Tailings and waste rock produced in metal mines are the most common industrial solid wastes all over the world, resulting in serious environmental and safety issues. Cemented paste backfill (CPB) is widely used for tailings management and stope treatment. CPB of total solid waste (TSW-CPB) was proposed on the basis of CPB of full-tailings. In the TSW-CPB process, thickened full-tailings, waste rock, and slag are mixed to prepare a paste that is filled into the stope. TSW-CPB can avoid the collapse of a stope, failure of the tailings storage facility, and landslide of a waste-rock yard, achieving the goal of “total waste to cure three harms.” The effects of solid fraction (SF), waste rock dosage (WRD), and glue powder dosage (GPD) on the slump (S), yield stress (τ0), uniaxial compressive strength (UCS), and bleeding rate (BR) were investigated through orthogonal experiments. According to the scope of technical indicators specified in the National Standard of the People’s Republic of China “Technical specification for the total tailings paste backfill (GB/T 39489—2020),” the overall desirability function approach was used to conduct multiple response optimization of key TSW-CPB performance indicators. TSW-CPB was shown to have similar fluidity, transportation performance, mechanical properties, and bleeding performance to the CPB of full-tailings. The SF, WRD, and GPD affect the S, τ0, UCS, and BR of TSW-CPB considerably. The SF has the most important influence on S and τ0, while GPD has the most substantial impact on UCS and BR. Multiple response optimization yielded SF = 79.31%, WRD = 18.86%, and GPD = 3:20, with S = 25.45 cm, τ0 = 100.49 Pa, UCS = 3.55 MPa, and BR = 1.50% as the corresponding responses. The optimal results can provide references for practical application, and the overall desirability function approach can be used in other mines to optimize multi objective CPB.

The real-time inline monitoring technologies of focused beam reflectance measurement (FBRM) and particle video microscopy (PVM) were used to analyze the aggregate structure evolution during the operation of a dynamic thickening system. The tailings dewatering studies were performed under two series of conditions: (i) rake rotation speeds of 0, 0.1, 1, and 10 r·min−1 and an initial mud bed height of 75 cm and (ii) initial mud bed heights of 75, 45, and 25 cm and a rake rotation speed of 0.1 r·min−1. The aggregate diameter, particle size distribution, and real-time images of the tailings thickening process were obtained. The results show that with the increase in the shearing time, the diameter and counts of aggregate first increase, then decrease, and then become stable. According to the aggregate diameter variation, the aggregate evolution can be divided into three stages: growth, reconstruction, and densification periods. The condition of a shear rate of 0.1 r·min−1 and an initial mud bed height of 75 cm has the best effects on the aggregate growth, structure breaking acceleration, aggregate reconstruction, and aggregate densification improvement, as determined in the laboratory; however, high shear rate has a degrading effect on the aggregate structure evolution. The aggregate diameter progressively decreases with the increase in the shear rate. The longer the aggregate growth period, the larger the maximum aggregate diameter, and a longer reconstruction period is observed at higher initial mud bed heights. Moreover, the aggregate diameter increases with the increase in the initial mud bed height. The fractal dimension of tailings aggregate reflects the change characteristics of the aggregate structure. According to the calculation of fractal dimension and porosity of the PVM image, the dynamic equilibrium relastionship between the breaking force and cohesive force of aggregates was analyzed, the influence on the aggregate breaking was analyzed. The aggregate densification rule in the tailings thickening process was revealed analyzed, based on the dynamic equilibrium relationship between the breaking force and cohesive force of aggregates.

With the advantages of efficiency and economy, deep-cone thickener (DCT) has been increasingly applied in tailings management. The rake in the DCT is essential for obtaining high-concentration underflow slurry; thus, more emphasis was placed on the effects of rakes on the underflow concentration. However, high concentration means high yield stress, which may lead to rake blockage. Therefore, this study investigated the effects of flocculation and sedimentation on the yield stress of thickened ultrafine tailings slurry. First, flocculation and sedimentation experiments were conducted under a pH range of 8 to 11 and flocculant dosage of 0 to 45 g·t−1 to obtain different thickened ultrafine tailings slurries. Then, the yield stress was measured through an in situ test. Finally, the amount of flocculant adsorbed on the tailings particle surface was analyzed by total organic carbon analysis. The amount of flocculant adsorbed on the tailings particles surface increased with the pH and flocculant dosage over the entire experiment range. Then, the yield stress increased with the increase in the amount of adsorbed flocculant, indicating that flocculation sedimentation has a significant influence on the yield stress. Based on the flocculation sedimentation behavior and yield stress, the optimal conditions were a pH of 8 and flocculant dosage of 15 g·t−1. Under these conditions, the initial settling rate of the solid–liquid interface was 0.4565 mm·s−1, supernate turbidity was 143 NTU, solid mass fraction of sediment was 51.56%, and yield stress was 243.18 Pa. The relationship between yield stress and the amount of flocculant adsorbed and yield stress was investigated, and an empirical model for yield stress based on flocculant adsorption was established. It was found that the yield stress increased with the amount of flocculant adsorbed, providing a reference for the control of flocculation sedimentation parameters in actual production.

BackgroundDiabetic Foot (DF) is one of the most common complications of diabetes, and it is characterized by high morbidity, disability, lethality and low cure rate. Traditional Chinese medicine treatment has certain characteristics and advantages in diabetic foot. Due to selective reporting bias and heterogeneity of research results, on the one hand, relevant clinical studies are of low quality and poor practicability, and on the other hand, similar studies cannot be included in meta-analysis to form high-quality evidence-based evidence and evaluate the value of studies. Therefore, the development of a core set of outcomes (COS-TCM-DF) for traditional Chinese medicine for the treatment of diabetic foot is an important way to address these issues.MethodsThe COS-TCM-DF project will refer to the developed COS methodology and the steps are divided into four stages: (1) a scoping review and analysis of enrolled research protocols to collect and analyze all existing outcomes that have been used in trials on the prevention or treatment of diabetic foot with Chinese Medicine; (2) qualitative interviews with Diabetic foot patient and attendants to Collect additional outcomes related to them; (3) Gather opinionest and obtain initial consensus from key stakeholders, including patients, clinicians, researchers, and pharmaceutical company staff, through a Delphi survey; (4) a consensus meeting was held to develop the final COS-TCM-DF.DiscussionCurrently, there is no COS on measuring or monitoring diabetic foot with TCM in trials or clinical practice. The COS-TCM-DF will be developed to advance the synthesis of evidence regarding the prevention and treatment of diabetic foot in TCM and to promote the standardized and consistent application of results in future studies in this field.Trial registrationRegistered with the Core Outcome Measures in Effectiveness Trials (COMET) database, December 2019 https://www.comet-initiative.org/Studies/Details/1553.

The Rcs phosphorelay system is present in many members of the Enterobacteriaceae. The aim of this study was to illustrate the possible mechanisms of eugenol on ultimate targets of Klebsiella pneumoniae (K. pneumoniae) Rcs phosphorelay, rcsB, and impact on biofilm formation. The minimum inhibitory concentration (MIC) of eugenol against K. pneumoniae KP1 and KP1 ΔrcsB strain was determined using the 2-fold micro-dilution method. Biofilm was measured by crystal violet staining. Transcriptome sequencing was performed to investigate sub-MIC eugenol on K. pneumoniae, and gene expression at mRNA level was analyzed by RT-qPCR. In vitro biofilm formation test and molecular docking were used to evaluate the effect of eugenol and to predict potential interactions with RcsB. MicroScale Thermophoresis (MST) was conducted for further validation. MIC of eugenol against K. pneumoniae KP1 and KP1 ΔrcsB strain was both 200 μg/ml. Transcriptome sequencing and RT-qPCR results indicated that rpmg, degP, rnpA, and dapD were downregulated, while rcsB, rcsD, rcsA, yiaG, and yiaD were upregulated in the eugenol-treated group. ΔrcsB exhibited a weakened biofilm formation capacity. Additional isopropyl-β-d-thiogalactoside (IPTG) hinders biofilm formation, while sub-MIC eugenol could promote biofilm formation greatly. Docking analysis revealed that eugenol forms more hydrophobic bonds than hydrogen bonds. MST assay also showed a weak binding affinity between eugenol and RcsB. These results provide significant evidence that rcsB plays a key role in K. pneumoniae biofilm formation. Sub-MIC eugenol facilitates biofilm formation to a large extent instead of inhibiting it. Our findings reveal the potential risk of natural anti-biofilm ingredients at sub-MIC to treat drug-resistance bacteria.

Cemented paste backfill (CPB) technology is a significant approach for the development of green mining in metal mines and can provide safe, environmentally friendly, and efficient technical support for deep underground mining. As the theoretical basis of paste backfill, the rheological concepts, characteristics, and models of paste had been systematically reviewed, and the rheological measurement methods were analyzed herein. Rheological measurement enables the quantitative characterization of the rheological behavior of paste, and on this basis, a series of studies, such as the rheological constitutive equations of paste, evaluation of the influence of both internal and external factors on paste rheology, and quality control of CPB, was conducted. Generally, the rheology of paste is influenced by certain constituents, including solids concentration, particle size distribution, density, and cement hydration, and various external conditions, such as shear stress and temperature. The rheological properties of paste differ significantly, and currently, a unified method is not yet available for the rheological measurement of paste. Hence, comprehensive knowledge of rheological measurement is essential to achieve a better combination of rheology and CPB engineering, particularly in consideration of the specific physical and chemical properties of tailings and the common practice in the mining field. Therefore, the principles and applications of commonly used approaches, including the vane rheometer, slump cone, L-shaped tube, inclined pipe, and loop facility, were summarized, with emphasis on the measurement of yield stress because of its influence on the paste, that is, a non-Newtonian fluid. Furthermore, the applicability of the aforementioned measurement methods was comprehensively discussed. Given that rheological measurement has a profound effect on the development of paste rheology theory and paste backfill technology, the key problems were discussed by emphasizing the importance of the establishment of rheological measurement standards and the application of rheological measurement to paste backfill processes in real time. The development trend of research on paste rheology was also explored.

Abstract Background The clinical characteristics of Parkinson’s disease (PD) differ between men and women, and late- and early-onset patients, including motor symptoms and some nonmotor symptoms, such as cognition, anxiety, and depression. Objective To explore the features of excessive daytime sleepiness (EDS) and night-time sleep quality in PD patients of different sexes and age at onset (AAO). Methods Demographic data and clinical characteristics of 586 PD patients were collected. Epworth Sleepiness Scale (ESS) and Pittsburgh Sleep Quality Index (PSQI) were used to investigate the daytime drowsiness and nocturnal sleep. Multivariate logistic regression analysis was used to explore the risk factors of EDS and poor night-time sleep quality. Results Sleep disorders were common in PD patients. EDS was more prominent in men than in women. There was no significant difference in ESS scores between late-onset PD (LOPD) and early-onset PD. LOPD patients had a higher probability of poor night-time sleep quality. Male sex, disease duration, and depression were risk factors for EDS. In all patients of both sexes and all AAO, depression was a risk factor for poor night-time sleep. Conclusion More attention should be paid to sleep disorders of PD patients, especially male LOPD patients. Depression is a common risk factor for EDS and poor sleep quality in PD patients.

The spongy moth virus Lymantria dispar iflavirus 1 (LdIV1), originally identified from a Lymantria dispar cell line, was detected in 24 RNA samples from female moths of four populations from the USA and China. Genome-length contigs were assembled for each population and compared with the reference genomes of the first reported LdIV1 genome (Ames strain) and two LdIV1 sequences available in GenBank originating from Novosibirsk, the Russian Federation. A whole-genome phylogeny was generated for these sequences, indicating that LdIV1 viruses observed in North American (flightless) and Asian (flighted) spongy moth lineages indeed partition into clades as would be expected per their host’s geographic origin and biotype. A comprehensive listing of synonymous and non-synonymous mutations, as well as indels, among the polyprotein coding sequences of these seven LdIV1 variants was compiled and a codon-level phylogram was computed using polyprotein sequences of these, and 50 additional iflaviruses placed LdIV1 in a large clade consisting mostly of iflaviruses from other species of Lepidoptera. Of special note, LdIV1 RNA was present at very high levels in all samples, with LdIV1 reads accounting for a mean average of 36.41% (ranging from 1.84% to 68.75%, with a standard deviation of 20.91) of the total sequenced volume.

Quantum mechanics/molecular mechanics (QM/MM) simulations offer an efficient way to model reactions occurring in complex environments. This study introduces a specialized set of charge and Lennard-Jones parameters tailored for electrostatically embedded QM/MM calculations, aiming to accurately model both adsorption processes and catalytic reactions in zirconium-based metal-organic frameworks (Zr-MOFs). To validate our approach, we compare adsorption energies derived from QM/MM simulations against experimental results and Monte Carlo simulation outcomes. The developed parameters showcase the ability of QM/MM simulations to represent long-range electrostatic and van der Waals interactions faithfully. This capability is evidenced by the prediction of adsorption energies with a low root mean square error of 1.1 kcal mol-1 across a wide range of adsorbates. The practical applicability of our QM/MM model is further illustrated through the study of glucose isomerization and epimerization reactions catalyzed by two structurally distinct Zr-MOF catalysts, UiO-66 and MOF-808. Our QM/MM calculations closely align with experimental activation energies. Importantly, the parameter set introduced here is compatible with the widely used universal force field (UFF). Moreover, we thoroughly explore how the size of the cluster model and the choice of density functional theory (DFT) methodologies influence the simulation outcomes. This work provides an accurate and computationally efficient framework for modeling complex catalytic reactions within Zr-MOFs, contributing valuable insights into their mechanistic behaviors and facilitating further advancements in this dynamic area of research. [ABSTRACT FROM AUTHOR]

Abstract Background The undergraduate program of psychiatry has been widely established in recent years to improve the education and recruitment of psychiatrists in China. We aim to investigate the career choice of medical students majoring in psychiatry in China and the influential factors. Method This multicenter study was conducted in 26 medical schools in China from May to October of 2019. Participants included 4610 medical students majoring in psychiatry and 3857 medical students majoring in clinical medicine. Multivariable logistic regression was used to investigate the influential factors of students’ choices of psychiatry at matriculation and as a career. Results 44.08% of psychiatry majored students gave psychiatry as a first choice at matriculation, and 56.67% of them would choose psychiatry as a career, which was in sharp contrast to the proportion of clinical medicine majored students who would choose psychiatry as a career (0.69%). Personal interest (59.61%), suggestions from family members (27.96%), and experiencing mental problems (23.19%) were main reasons for choosing psychiatry major at matriculation. Personal interest (odds ratio [OR] = 2.12, 95% confidence interval [CI] = 1.87–2.40), experiencing a psychiatry clerkship (OR = 1.99, 95% CI = 1.28–3.08), being female (OR = 1.50, 95% CI = 1.30–1.68), experiencing mental problems (OR = 1.33, 95% CI = 1.28–1.56), and suggestions from family members (OR = 1.25, 95% CI = 1.08–1.46) correlated positively with students’ choice of psychiatry as career. Students who lacked psychiatry knowledge (OR = 0.49, 95% CI = 0.29–0.85) or chose psychiatry because of lower admission scores (OR = 0.80, 95% CI = 0.63–0.97) were less likely to choose psychiatry as a career. Conclusion More than half of psychiatry majored medical school students planned to choose psychiatry as their career, whereas very few students in the clinic medicine major would make this choice. Increasing students’ interest in psychiatry, strengthening psychiatry clerkships, and popularizing psychiatric knowledge are modifiable factors to increase the psychiatry career intention. The extent to which medical students’ attitudes toward psychiatry can be changed through medical school education and greater exposure to psychiatry will need further investigation.

Liver cirrhosis represents a type of end-stage liver disease with few effective therapies, which was characterized by damaged functional liver tissue due to long-term inflammation. Gasdermin D (GSDMD)-executed programmed necrosis is reported to be involved in inflammation. However, the role of GSDMD in liver cirrhosis remains unclear. In this study, we used a CCl4-induced cirrhosis model and found stem cells from human exfoliated deciduous teeth (SHED) infusion showed profound therapeutic effects for liver cirrhosis. Mechanistically, NLRP3 inflammasome-activated GSDMD and its pyroptosis were upregulated in liver cirrhosis, while SHED infusion could suppress the expression of GSDMD and Caspase-1, resulting in reduced hepatocyte pyroptosis and inflammatory cytokine IL-1β release. Consistently, SHED could inhibit the elevated expression of NLRP3, GSDMD and Caspase-1 induced by CCl4 treatment in vitro co-culture system, which was mediated by decreasing reactive oxygen species (ROS) generation. Moreover, the pyroptosis inhibitor disulfiram showed similar therapeutic effects for liver cirrhosis as SHED. In conclusion, SHED alleviates CCl4-induced liver cirrhosis via inhibition of hepatocytes pyroptosis. Our findings could provide a potential treatment strategy and novel target for liver cirrhosis.

Red mud is a solid waste produced in the process of bauxite refining alumina, with high alkali content, and its treatment methods are mainly stacking and ocean dumping, which not only occupy a large amount of cultivated land and pollute land and water sources, but also have high safety risk. The preparation of red mud-based filling materials to fill the underground goaf can improve the utilization rate of mineral resources and reduce the harm of red mud to the environment, which has the effect of killing two birds with one stone. In view of the problems of low utilization rate of bayer red mud in mine filling system, low strength, bleeding and shrinkage in filling materials slurry with low concentration, the effects of the addition ratio of fly ash, desulfurization gypsum, lime and initiator on the early strength and volume stability were studied in this paper. Scanning electron microscope- energy dispersive spectroscope (SEM-EDS) and X-ray diffraction (XRD) were used to analyze the hydration mechanism of the filling materials. The results show that when the ratio of red mud to fly ash is 4∶6, the mechanical properties of the filling material are the best. Desulfurized gypsum promotes the formation of ettringite. Lime promotes the pozzolanic effect of fly ash. The composite activator can accelerate the hydration process of red mud and fly ash. All of this enhance the red mud backfill strength. The filling materials 28 d compressive strength is 3.35 MPa, and the initial and 60 min fluidity are above 200 mm. Microscopic test results show that the hydration products of hardened paste are ettringite, lawsonite, silica aluminate gel, which fill the pores and improve the strength of slurry. Through adding activator, activating red mud activity and designing low concentration filling material, it is the direction of mass and green utilization of red mud, desulfurization gypsum and other solid wastes. The utilization ratio of solid waste of red mud filling materials reaches 92%, no bleeding, no shrinkage, and has high economic value and environmental value.

Abstract Purpose The gross tumor volume (GTV) could be an independent prognostic factor for unresectable locally advanced non-small cell lung cancer (LANSCLC). We aimed to develop and validate a novel integrated GTV-TNM stratification system to supplement LANSCLC sub-staging in patients treated with concurrent chemoradiotherapy (CCRT). Methods We performed a retrospective review of 340 patients with unresectable LANSCLC receiving definitive CCRT. All included patients were divided into two randomized cohorts. Then the Kaplan–Meier method and Cox regression were calculated to access the prognostic value of the integrated GTV-TNM stratification system, which was further validated by the area under the receiver operating characteristic curve (AUC) score and F1-score. Results The optimal outcome-based GTV cut-off values (70 and 180 cm3) of the modeling cohort were used to determine each patient’s integrated GTV-TNM stratum in the whole cohort. Our results indicated that a lower integrated GTV-TNM stratum could had better overall survival and progression-free survival (all P

Abstract Proper bone age assessment is crucial for the clinical diagnosis and evaluation of treatment responses. We investigated the applicability of Greulich and Pyle (GP), and Tanner and Whitehouse 3 (TW3) methods for children in modern Taiwan, using computer‐aided diagnosis. Hand and wrist radiographs were obtained from 611 children (3‐17 years) who came to our emergency department due to trauma. Ages 0 to 2 years old were excluded because of a limited number of cases. Skeletal maturation was assessed using the BoneXpert (version 2.5.4.1 automated software), which determines GP and TW3 bone age. The two scoring systems were evaluated for comparing the chronological ages in each subgroup. In boys, mean GP bone age vs mean chronological ages were delayed for ages 3 to 11 and advanced for age 12 to 17. In girls, mean GP bone age vs mean chronological ages was delayed for ages 4 to 8 and 17, and advanced for ages 3 and 9 to 17. In boys, the mean TW3 bone ages vs mean chronological ages were delayed for ages 5 to 10 except age 8, and advanced for ages 3 to 4, 8, and 11 to 15. In girls, the mean TW3 bone ages vs mean chronological ages were delayed for ages 4 to 12, and advanced for ages 3 and 13 to 14. By using the BoneXpert automatic software, we established bone age reference standards for children in Taiwan. Clinical application of GP and TW3 scoring methods can be adjusted according to our results to better assess bone age.

Phosphorus slag (PS) is an industrial waste discharged during the refining of yellow phosphorus by a high-temperature electric furnace. The slag is generally deposited on the surface in situ, and this uses up considerable areas of land and causes environmental pollution problems. The glass phase content in electric furnace PS is over 90%, indicating that the PS has potential cementitious property. As a cement admixture, PS has a retarding effect on cement, thus, its application to cement has become less adopted. Based on the hydration characteristics of PS and the application conditions of mine filling, the feasibility of alkali-activated cement–PS used as cementitious material (CPCM) to cement sulfur tailings was studied. Quicklime, NaOH, and Na2SiO3 were used as the activators to investigate the CPCM curing performance in a laboratory, and the compatibility of CPCM with sulfur tailings was evaluated. The results show that when the PS-to-cement mole ratio is 1∶1, quicklime is 3% of PS, the final setting time of CPCM is 300 min, and the CPCM strength for 28 days is 40.6 MPa, indicating that the material can replace P.O 42.5 cement in the subsequent filling process. When the Na2SiO3 is 4% of PS, the final setting time of CPCM is 39.3% less than that of cement, and its strength for 7 days is 31.1% higher than that of cement. Compared with cement, CPCM shortens the setting time of backfill by 8 hours, and its strength does not deteriorate after curing for 28 days. Therefore, CPCM is suitable for cementing sulfur tailings. X-ray diffraction (XRD), scanning electron microscopy (SEM), and energy-dispersive X-ray spectroscopy (EDS) analyses show that the CPCM hydration products are mainly Ca(OH)2 and C−S−H. Moreover, the PS hydration resulted in a decrease in the Ca(OH)2 content, and a compact C−S−H gel with a low Ca/Si mole ratio is formed. This not only improves the later strength of CPCM but also prevents the strength deterioration of the backfill.

The cemented paste backfill (CPB) technology provides a safe, green and efficient access to deep underground mining and sustainable exploitation of mineral resources, and it has become one of the research focuses and development trends in the mining field. The CPB technology mainly includes four key processes, namely, the thickening of unclassified tailings, homogeneous mixing of multi-scale materials, pipeline transportation of fresh CPB, and its consolidation in the mined-out underground stopes. As a relatively new material that is comprised of various constituents, typically the tailings, cement, and water, as well as a high solid concentration, CPB tends to show complicated behaviors under the effects of surroundings. Therefore, understanding CPB behaviors is of practical significance for the development of the technology, since knowledge of CPB behavior is essential in the preliminary backfill system design and operation. It has been pointed out that the use of solid-liquid two-phase flows shows some limitations for the paste. In comparison, the rheology which targets on the flow and deformation of the paste under the influence of external shearing can provide a theoretical basis for the whole processes of paste backfill technology and deeply affect its development. Based on the characteristics of the paste materials, the necessity, particularity and complexity of the research on paste rheology were systematically discussed. Typical rheological properties of paste and the latest achievements were analyzed with the summarized results from rheological experiments. The commonly used rheological models of yielding non-Newtonian fluids were reviewed, and the applicability of corresponding constitutive equations to paste slurry was discussed with reasonable suggestions provided for its practical application. Meanwhile, the key influence factors of paste rheological properties were summarized. According to the research status, the priorities and difficulties of research on paste rheology were summarized and proposed, with emphases on test standards, constitutive equations, microscopic mechanisms and engineering applications.

Abstract Background Polycystic ovary syndrome (PCOS) is a complex endocrine syndrome with poorly understood mechanisms. To provide patients with PCOS with individualized therapy, it is critical to precisely diagnose the phenotypes of the disease. However, the criteria for diagnosing the different phenotypes are mostly based on symptoms, physical examination and laboratory results. This study aims to compare the accuracy and efficacy of diagnosing PCOS by integrating metabolomic markers with common clinical characteristics. Methods This is a prospective, multicenter, analyst-blinded, randomized controlled trial. Participants will be grouped into (1) people without PCOS (healthy control group), (2) patients diagnosed with PCOS based on clinical indices (experimental group 1), and (3) patients diagnosed with PCOS based on metabolomic indices (experimental group 2). A total of 276 participants, including 60 healthy people and 216 patients with PCOS, will be recruited. The 216 patients with PCOS will be randomly assigned to the two experimental groups in a 1:1 ratio, and each group will receive a different 6-month treatment. The primary outcome for the experimental groups will be the effect of PCOS treatment. Discussion The results of this trial should help to determine whether using metabolomic indices is more accurate and effective than using clinical characteristics in diagnosing the phenotypes of PCOS. The results could provide a solid foundation for the accurate diagnosis of different PCOS subgroups and for future research on individualized PCOS therapy. Trial registration Chinese Clinical Trial Registry, ID: ChiCTR-INR-1800016346. Registered 26 May 2018.

With the development of integrated circuits according to Moore’s law, traditional silicon-based devices have gradually reached their performance limitation. Nanoelectronics based on carbon nanomaterials provides a broad prospect for the continuation of Moore’s law. In particular, in the field of optoelectronic devices, it is necessary to further develop new types of nano-optoelectronic devices. Carbon nanotubes (CNTs) are one of the representative materials of nanoelectronics with excellent electrical and optical properties, e.g., high mobility, suitable band structure, and good infrared absorption. The application of CNTs in optoelectronic devices is a very attractive research topic, which has been developed rapidly in recent years. Until now, various prototypes of CNT-based optoelectronic devices have been developed. In this Review, we briefly introduce the structure and photoelectric properties of CNTs. Then, according to different photo-electron coupling mechanisms, four types of CNTs based on optoelectronic devices are introduced in detail, namely, solar cells, photodetectors, light-emitting diodes, and lasers. Intrinsic and composite CNT-based optoelectronic devices are presented in order to describe the development of CNT-based optoelectronic devices. Finally, different material preparation, separation, and mixing methods of CNTs are discussed, which are the methods for basic material preparation for the fabrication of high performance CNT-based optoelectronic devices. An in-depth study of the development trend of CNT-based optoelectronic devices will contribute to the future development of novel high-performance nanoelectronic devices.

Glucagon-like peptide-1 (GLP-1) and its analogs are widely used for diabetes treatment. The paraventricular nucleus (PVN) is crucial for regulating cardiovascular activity. This study aims to determine the roles of GLP-1 and its receptors (GLP-1R) in the PVN in regulating sympathetic outflow and blood pressure. Experiments were carried out in male normotensive rats and spontaneously hypertensive rats (SHR). Renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) were recorded. GLP-1 and GLP-1R expressions were present in the PVN. PVN microinjection of GLP-1R agonist recombinant human GLP-1 (rhGLP-1) or EX-4 increased RSNA and MAP, which were prevented by GLP-1R antagonist exendin 9-39 (EX9-39) or GLP-1R antagonist 1, superoxide scavenger tempol, antioxidant N-acetylcysteine, NADPH oxidase (NOX) inhibitor apocynin, adenylyl cyclase (AC) inhibitor SQ22536 or protein kinase A (PKA) inhibitor H89. PVNmicroinjection of rhGLP-1 increased superoxide production, NADPH oxidase activity, cAMP level, AC, and PKA activity, which were prevented by SQ22536 or H89. GLP-1 and GLP-1R were upregulated in the PVN of SHR. PVN microinjection of GLP-1 agonist increased RSNA and MAP in both WKY and SHR, but GLP-1 antagonists caused greater effects in reducing RSNA and MAP in SHR than in WKY. The increased superoxide production and NADPH oxidase activity in the PVN of SHR were augmented by GLP-1R agonists but attenuated by GLP-1R antagonists. These results indicate that activation of GLP-1R in the PVN increased sympathetic outflow and blood pressure via cAMP-PKA-mediated NADPH oxidase activation and subsequent superoxide production. GLP-1 and GLP-1R upregulation in the PVN partially contributes to sympathetic overactivity and hypertension. [ABSTRACT FROM AUTHOR]

Abstract Bacterial enteritis is the most important disease in lamb for breeding greatly affects the growth of animals. Changes in the community of intestinal flora can cause the disorder of the colonic environment induced diarrhea. This study aimed to investigate the relationship between the incidence of bacterial enteritis and the number of intestinal microbiome, then the prevalence of drug-resistant genes was detected. Fecal samples were collected at five fattening sheep farms with different incidence of bacterial enteritis, pathogenic bacteria were isolated and identified, drug sensitivity tests were performed. Then, changes in number and structure of intestinal flora were compared by 16S rDNA V3-V4 region high-throughput sequencing, and the ARGs were detected using high-throughput real-time PCR. Our results revealed that the microbial communities were positively correlated with the incidence of bacterial enteritis in different farms. Bacterial communities were higher in YJ (with highest incidence of diarrhea) than any other farms. However, the ARGs seemed not to be more affected by the incidence of bacterial enteritis, but one of the significant findings to emerge from this study is that MCR-1 and NDM are detected in manure. This study has provided an insight of the changes occurring in intestinal flora and AGRs in fattening sheep farms with diverse incidence of bacterial enteritis.

Background: Frequent overdose of paracetamol (APAP) has become the major cause of acute liver injury. The present study was designed to evaluate the potential protective effects of ginsenoside Rk1 on APAP-induced hepatotoxicity and investigate the underlying mechanisms for the first time. Methods: Mice were treated with Rk1 (10 mg/kg or 20 mg/kg) by oral gavage once per d for 7 d. On the 7th d, all mice treated with 250 mg/kg APAP exhibited severe liver injury after 24 h, and hepatotoxicity was assessed. Results: Our results showed that pretreatment with Rk1 significantly decreased the levels of serum alanine aminotransferase, aspartate aminotransferase, tumor necrosis factor, and interleukin-1β compared with the APAP group. Meanwhile, hepatic antioxidants, including superoxide dismutase and glutathione, were elevated compared with the APAP group. In contrast, a significant decrease in levels of the lipid peroxidation product malondialdehyde was observed in the ginsenoside Rk1-treated group compared with the APAP group. These effects were associated with a significant increase of cytochrome P450 E1 and 4-hydroxynonenal levels in liver tissues. Moreover, ginsenoside Rk1 supplementation suppressed activation of apoptotic pathways by increasing Bcl-2 and decreasing Bax protein expression levels, which was shown using western blotting analysis. Histopathological observation also revealed that ginsenoside Rk1 pretreatment significantly reversed APAP-induced necrosis and inflammatory infiltration in liver tissues. Biological indicators of nitrative stress, such as 3-nitrotyrosine, were also inhibited after pretreatment with Rk1 compared with the APAP group. Conclusion: The results clearly suggest that the underlying molecular mechanisms in the hepatoprotection of ginsenoside Rk1 in APAP-induced hepatotoxicity may be due to its antioxidation, antiapoptosis, anti-inflammation, and antinitrative effects. Keywords: anti-inflammation, anti-apoptosis, APAP-induced hepatotoxicity, ginsenoside Rk1, oxidative stress

Preparation of reduced graphene oxide (RGO) from abundant and inexpensive low-grade coal is regarded as one of the most promising methods for utilizing this resource in a high-value and environmentally sustainable manner. As the main precursor for the fabrication of RGO, graphene oxide (GO) can be extracted from low-grade coal such as lignite, but its size is just in the range of tens to hundreds of nanometers, which limits its practical application. Herein, we demonstrate that large-size RGO sheets can be prepared in large quantities by the pretreatment of lignite using the high temperature–high pressure (HTHP) method. The RGO electrode after the reduction reaction by 50 mM NaBH4 at 105 °C features porosity and high conductivity, which can facilitate high electrochemical reaction efficiency. Thus, we also demonstrate the use of lignite-derived RGO for supercapacitor electrode materials with high performance. The lignite-derived RGO supercapacitor can deliver outstanding volumetric capacitance (30.6 F cm−3), high energy density (4.2 mW h cm−3), excellent flexibility (79.5% retention of the initial capacitance at 180° bending), and a long lifespan (112.3% retention of the initial capacitance after 20,000 cycles). It is believed that the proposed large-size RGO based on reasonable optimization of inferior lignite will offer a new prospect for next-generation energy storage applications.

Background: To explore the prognostic value of radiomics-based and digital pathology-based imaging biomarkers from macroscopic magnetic resonance imaging (MRI) and microscopic whole-slide images for patients with nasopharyngeal carcinoma (NPC). Methods: We recruited 220 NPC patients and divided them into training ( n = 132), internal test ( n = 44), and external test ( n = 44) cohorts. The primary endpoint was failure-free survival (FFS). Radiomic features were extracted from pretreatment MRI and selected and integrated into a radiomic signature. The histopathological signature was extracted from whole-slide images of biopsy specimens using an end-to-end deep-learning method. Incorporating two signatures and independent clinical factors, a multi-scale nomogram was constructed. We also tested the correlation between the key imaging features and genetic alternations in an independent cohort of 16 patients (biological test cohort). Results: Both radiomic and histopathologic signatures presented significant associations with treatment failure in the three cohorts (C-index: 0.689–0.779, all p

Abundant and cheap lignite is regarded as inferior fuel due to its disadvantages such as low heat and high moisture. In order to realize the high value and clean, non-fuel utilization of lignite, we used lignite as precursor to prepare high-quality synthetic graphite through graphitization treatment using the high temperature–high pressure (HTHP) method, and afterwards characterized the samples by XRD, Raman, FTIR, SEM-EDS, and HRTEM, and systematically analyzed the effect of P-T conditions on the structure evolution of lignite. Our results demonstrated that temperature dominates the graphitization of lignite, and high pressure accelerates the graphitization process of lignite. Under HTHP treatment, the aromatic layer of lignite accelerates directional rearrangement; the ordered domain increases rapidly, and the ductility and stacking degree of the carbon sheets of the lignite sample are greatly enhanced. Compared with the traditional high-temperature graphitization method, the HTHP method greatly reduces the graphitization temperature and shortens the graphitization time. Remarkably, the as-prepared graphite with a graphitization degree of 91.87% superior to graphite fabricated by the conventional high-temperature processing were rapidly prepared from lignite at 6 GPa and 1300 °C in 20 min. This study demonstrates that the HTHP method is a feasible and effective method to realize the green, efficient, and high value utilization of lignite.

Abstract Background Bacterial infections have become more challenging to treat due to the emergence of multidrug-resistant pathogenic bacteria. Combined antibiotics prove to be a relatively effective method to control such resistant strains. This study aim to investigate synergistic activity of eugenol combined with colistin against a collection of clinical isolated Escherichia coli (E.coli) strains, and to evaluate potential interaction. Methods Antimicrobial susceptibility, minimum inhibitory concentration (MIC) and fractional inhibitory concentration index (FICI) of the bacteria were determined by disk diffusion assay, broth microdilution method and checkerboard assay, respectively. The mcr-1 mRNA expression was measured by Real-time PCR. To predict possible interactions between eugenol and MCR-1, molecular docking assay was taken. Results For total fourteen strains including eight colistin-resistant strains, eugenol was determined with MIC values of 4 to 8 μg/mL. Checkerboard dilution test suggested that eugenol exhibited synergistic activity when combined with colistin (FICI ranging from 0.375 to 0.625). Comparison analysis of Real-time PCR showed that synergy could significantly down-regulate expression of mcr-1 gene. A metal ion coordination bond with catalytic zinc atom and a hydrogen bond with crucial amino acid residue Ser284 of MCR-1 were observed after molecular docking, indicating antibacterial activity and direct molecular interactions of eugenol with MCR-1 protein. Conclusions Our results demonstrated that eugenol exhibited synergistic effect with colistin and enhanced its antimicrobial activity. This might further contribute to the antibacterial actions against colistin-resistant E.coli strains. Graphical abstract Synergistic effect of eugenol with colistin against colistin-resistant Escherichia coli isolates.