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In this investigation, a Fe–20Mn–9Al-1.5C lightweight austenitic steel has been developed through strategic alloying with Ni and Cr elements coupled with the employment of a thermo-mechanical processing technique featuring ultra-fast cooling. This composition and treatment synergistically transcend the conventional trade-off between strength and ductility, positioning the mechanical performance of this steel notably above that of comparable low-density austenitic steels previously reported. The coordinated incorporation of Ni and Cr is key to modulating the precipitation threshold for nanoscale κ-carbides and LRO domains, achieving an optimal size for precipitate-induced strengthening. The incorporation of Cr specifically contributes to a dual enhancement mechanism: it fosters the generation of high-density dislocation arrays (HDDA) and refines the dynamic slip band (DSBR) during deformation, which in turn, elevates the strain hardenability and ductility. The remarkable synergy in strength and ductility is attributed to a combination of mechanisms including grain boundary reinforcement, solid solution hardening, the precipitation strengthening effect of nanoscale precipitates, and the activation of secondary slip system dislocations. This synergy is quantitatively reflected in the material's yield strength (YS) exceeding 1100 MPa, ultimate tensile strength (UTS) surpassing 1200 MPa, and a total elongation (TEL) exceeding 45%. The insights gained from this research provide critical guidance for the design and creation of austenitic low-density steels that do not compromise between strength and ductility, thereby offering superior overall performance.

Fretting wear is the main factor restricting the application of titanium alloy as compressor blades. Preparing a kind of high entropy alloy (HEA) coating is an effective way to improve the fretting wear resistance under high temperature conditions. Thus, in the present work, the FeCrAlMoxNby HEA coating was fabricated on a Ti-64 substrate by the laser cladding technology. The phase composition, microstructure and fretting wear resistance of the coating at high temperatures (200 °C, 300 °C and 400 °C) were investigated. It was demonstrated that the laser cladding FeCrAlMoxNby HEA coatings exhibited dense and uniform microstructures consisting of a BCC phase and a Laves phase (Cr2Nb). In addition, the changing trend of phase content of BCC and Laves phase is the same as the trend of atomic content of Mo and Nb respectively. The presence of the Laves phase increases the hardness of the coating. Due to its high hardness and the formation of a protective oxide layer, the coating demonstrated significantly superior resistance to high-temperature fretting wear compared to the substrate. The lowest wear rate is Mo0·5Nb0.5 coating at 300 °C, only 1.3 × 10−6 mm3/N·m. The current results provide a new method to protect titanium alloy's surface from fretting wear damage in high-temperature service environments.

Summary: Background: In non-high-risk individuals, risk-category-based atherosclerotic cardiovascular disease (ASCVD) screening strategies may be more cost-effective than one-size-fits-all approaches. However, current decisions are constrained by a lack of research evidence. We aimed to explore appropriate risk-category-based screening interval strategies for non-high-risk individuals in ASCVD primary prevention in the Chinese population. Methods: We used data from 28,624 participants in the China Kadoorie Biobank (CKB) who had completed at least two field surveys. The risk assessment tools were the 10-year ASCVD risk prediction models developed based on the CKB cohort. We constructed multistate Markov models to model disease progression and estimate transition probabilities between different risk categories. The total person-years spent unidentified in the high-risk state over a 10-year period were calculated for each screening interval protocol. We also estimated the number of ASCVD events prevented, quality-adjusted life years (QALYs) gained, and costs saved when compared to the 3-yearly screening protocol. Findings: When compared to the uniform 3-yearly protocol, most risk-category-based screening interval protocols would identify more high-risk individuals timely, thus preventing more ASCVD events and gaining QALYs. A few of them would reduce total health-care costs. The protocol, which used 6-year, 3-year, and 2-year screening intervals for low-risk, intermediate-low-risk, and intermediate-high risk individuals, was optimal, and would reduce the person-years spent unidentified in the high-risk category by 17.9% (95% CI: 13.1%–21.9%), thus preventing an estimated 113 thousand (95% CI: 83–138) hard ASCVD events for Chinese adults aged 30–79 over a 10-year period. When using a lower cost of statin therapy, more screening protocols would gain QALYs while saving costs. Interpretation: For the primary prevention of ASCVD, risk-category-based screening protocols outperformed the one-size-fits-all approach in the Chinese population. Funding: This work was supported by National Natural Science Foundation of China (82192904, 82388102, 82192900) and grants (2023YFC2509400) from the National Key R&D Program of China. The CKB baseline survey and the first re-survey were supported by a grant from the Kadoorie Charitable Foundation in Hong Kong. The long-term follow-up is supported by grants from the UK Wellcome Trust (212946/Z/18/Z, 202922/Z/16/Z, 104085/Z/14/Z, 088158/Z/09/Z), grants (2016YFC0900500) from the National Key R&D Program of China, National Natural Science Foundation of China (81390540, 91846303, 81941018), and Chinese Ministry of Science and Technology (2011BAI09B01).

Background: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common urinary system disease that is prone to recurrence. It typically leads to varying degrees of pelvic pain and discomfort, as well as symptoms related to the urinary system in affected patients. QianLieJinDan tablets (QLJD), a traditional Chinese medicine, have shown promising therapeutic effects on CP/CPPS in clinical practice, but the underlying mechanisms of QLJD in treating CP/CPPS have not been determined. Objective: To reveal the phytochemical characterization and multitarget mechanism of QLJD on CP/CPPS. Methods: The concentrations of the components of QLJD were determined using UHPLC-Q Exactive Orbitrap-MS. Utilizing network pharmacology approaches, the potential components, targets, and pathways involved in the treatment of CP/CPPS caused by QLJD were screened. Molecular docking calculations were employed to assess the affinity between the components of the QLJD and potential targets, revealing the optimal molecular conformation and binding site. Finally, the therapeutic efficacy and potential underlying mechanisms of QLJD were investigated through pharmacological experiments. Results: In this study, a total of 35 components targeting 29 CP-related genes were identified, among which quercetin, baicalin, icariin, luteolin, and gallic acid were the major constituents. Enrichment analysis revealed that the potential targets were involved mainly in the regulation of cytokines, cell proliferation and apoptosis, and the oxidative stress response and were primarily associated with the cytokine‒cytokine receptor interaction pathway, the IL-17 signaling pathway, the Th17 cell differentiation pathway, and the JAK-STAT signaling pathway. In vivo experiments demonstrated that QLJD effectively attenuated the infiltration of CD3+ T cells and the expression of ROS in a CP/CPPS model rat prostate tissue. Furthermore, through the inhibition of IL-6 and STAT3 expression, QLJD reduced the differentiation of Th17 cells, thereby ameliorating pathological injury and prostatic index in prostate tissue. Conclusion: The potential of QLJD as an anti-CP/CPPS agent lies in its ability to interfere with the expression of IL-6 and STAT3, inhibit Th17 cell differentiation, reduce inflammatory cell infiltration in rat prostate tissue, and alleviate oxidative stress damage through its multi-component, multi-target, and multi-pathway effects.

Summary: Background: Previous observational studies established a positive relationship between snoring and stroke. We aimed to investigate the causal effect of snoring on stroke. Methods: Based on 82,339 unrelated individuals with qualified genotyping data of Asian descent from the China Kadoorie Biobank (CKB), we conducted a Mendelian randomization (MR) analysis of snoring and stroke. Genetic variants identified in the genome-wide association analysis (GWAS) of snoring in CKB and UK Biobank (UKB) were selected for constructing genetic risk scores (GRS). A two-stage method was applied to estimate the associations of the genetically predicted snoring with stroke and its subtypes. Besides, MR analysis among the non-obese group (body mass index, BMI

Due to the vulnerable ecosystem environments, plateau lakes in the southwest of China face high eutrophication risks. Excessive nitrogen input is an important driver of eutrophication in plateau lakes. However, it is lacked of accurate analysis of spatial and temporal distribution characteristics of nitrogen sources for plateau lakes, which restricts local water environment management. Taking a typical plateau lake, Erhai Lake, as an example, this study applied the MARINA (Model to Assess River Inputs of Nutrients to seAs)-Lakes model to 26 sub-basins of Erhai Lake to analyze the temporal (1998–2016) characteristics of nitrogen inputs and identify the main pollution sources in different sub-basins. The results showed that the most obvious decreasing trends in river export of nitrogen occurred in 2016. It decreased from 2.9 in 2010–2.3 Mg in 2016, which is associated with the series of water quality protection measures implemented. By distinguish nitrogen forms, we found that dissolved inorganic nitrogen was mainly from diffuse source (synthetic fertilizer) whereas point source (directly discharge of animal manure) was the dominant source for dissolved organic nitrogen. The highest river export of nitrogen was from Zhonghe sub-basin in the western areas with high population density and intensive agricultural system, and the lowest was from Mijuhe sub-basin in the northern areas. Tourism was the dominant source of river export of nitrogen in several sub-basins, including Zhonghe, Meitao, Haidongqin, Boluo, and Jinli. Our study developed an explicit spatial analysis approach to quantify river export of nitrogen by sources at sub-basin scale. Based on the primary sources of nitrogen within each sub-basin, we could divide Erhai Lake basin into different management zones. These results can not only help decision-makers formulate accurate and effective lake protection policies for Erhai Lake, but also provide new insights for other plateau lakes.

The abundant lignocellulosic biomass has great potential as a renewable energy source. Due to its resistant nature, lignocellulosic biomass requires pretreatment to increase its accessibility to cellulase. Currently, the main types of pretreatments include physical, chemical, and biological pretreatment, of which biological pretreatment is favored for its advantages of mild conditions, nonpolluting, and low energy consumption. Still, disadvantages such as time-consuming and low efficiency limit its large-scale application. This review focuses on the advantages and disadvantages of various pretreatment methods, highlighting the advances in research on bio-coordinated physicochemical pretreatment to improve the enzymatic hydrolysis rate of lignocellulosic biomass. By bio-coordinating different pretreatment methods, biological pretreatment time has been shortened, and enzymatic sugar yield has been increased by more than 30% in general compared with pretreatment alone, which has a broad application prospect in industrial production. However, research gaps related to the economic-technical analysis and combined pretreatment energy efficiency still remain.

Crushed rock layers (CRLs), ventilation ducts (VDs) and thermosyphons are air-cooling structures (ACSs) widely used for maintaining the long-term stability of engineered infrastructures in permafrost environments. These ACSs can effectively cool and maintain the permafrost subgrade’s frozen state under climate warming by facilitating heat exchange with ambient air in cold seasons. As convection is a crucial working mechanism of these ACSs, it is imperative to understand the near-surface wind flow (NSWF) across a constructed infrastructure, such as an embankment. This article describes a yearlong field observation of the NSWF across an experimental expressway embankment, the first of its kind on the Qinghai–Tibet Plateau (QTP). The wind speed and direction along a transect perpendicular to the embankment on both the windward and leeward sides and at four different heights above the ground surface were collected and analyzed. The results showed that the embankment has a considerable impact on the NSWF speed within a distance of up to ten times its height, and in the direction on the leeward side. A power law can well describe the speed profiles of NSWF across the embankment, with the power-law indices (PLIs) varying from 0.14 to 0.40. On an annual basis, the fitted NSWF PLI far away from the embankment was 0.19, which differs substantially from the values widely used in previous thermal performance evaluations of ACSs on the QTP. Finally, the significance of the NSWF to the thermal performance of the ACSs, particularly the CRLs and VDs, in linear transportation infrastructure is discussed. It is concluded that underestimating the PLI and neglecting wind direction variations may lead to unconservative designs of the ACSs. The results reported in this study can provide valuable guidance for infrastructure engineering on the QTP and other similar permafrost regions.

Language teaching is by nature a complex and social practice with numerous personal and contextual aspects. It hinges upon how teachers perceive themselves, the way they are perceived by others, and their roles and positioning in the classroom and its occurring interactions. Despite the proliferation of research on English as a foreign language (EFL) teachers' professional identity, its association to agency and positioning has been widely ignored in academia. Urged by this backdrop, the current study was a bid to theoretically explore the relationship among teachers’ professional identity, agency, and positioning in language education. To do so, the theoretical and empirical underpinnings of this line of research are reviewed referring to different definitions, dimensions, approaches, and conceptualizations of each construct. Additionally, to approve their strong linkage, scientific findings from previous studies are built upon. Furthermore, the implications of this line of inquiry for different stakeholders in EFL contexts, especially teachers are presented in detail. Finally, the study enumerates a number of research gaps in this domain and suggests some future directions for enthusiastic scholars.

Wound healing and angiogenesis remain challenges for both clinical and experimental research worldwide. Periosteum-derived extracellular vesicles (P-sEVs) delivered by hydrogel dressings provide a potential strategy for wound defects to promote fast healing. In this study, we designed a NAGA/GelMA/Laponite/glycerol hydrogel wound dressing that can release P-sEVs to accelerate angiogenesis and wound healing (named P-sEVs@hydrogel) (N-acryloyl glycinamide, NAGA). The wound dressing showed multiple functions, including efficient angiogenesis, tissue adhesion and a physical barrier. P-sEVs significantly enhanced the proliferation, migration, and tube formation of endothelial cells in vitro. The results of in vivo experiments showed that P-sEVs@hydrogel accelerates the healing of a full-thickness defect wound model by stimulating the angiogenic process. The improved cell proliferation, tissue formation, remodeling, and re-epithelialization possibly resulted in the fast healing. This study shows that multifunctional hydrogel dressing combined with bioactive molecules can achieve fast and satisfactory wound healing in full-thickness wound defects and other related wounds.

The pump-driven two-phase loop is a promising thermal management technology for avionics, but its dynamic characteristics and control strategy are not clear. A prototype of a pump-driven two-phase loop with a single/dual evaporator for cooling of avionics was developed and its dynamic characteristic under different heat loads and flow rates were studied. It was found that after the evaporator outlet reached saturation, increasing the flow rate would instead reduce the performance, due to the increasing flow resistance of the gas tube and pump power consumption. Based on this, a control strategy of controlling the vapor quality at the evaporator outlet to 0.9–0.95, by adjusting the speed of the pump, was proposed and verified under dynamic heat loads. The results showed that this control strategy ensured optimal system heat transfer performance while reduced the power consumption of the pump. In the experiments of the pump-driven two-phase loop with dual evaporators, it was found that the branch with the larger heat load had a lower flow rate, and was more likely to be superheated. Therefore, in the control of a pump-driven two-phase loop with multiple evaporators, the branch with the maximum heat load should be taken as the control object.

One of the most important reasons underlying the resistance of tumors is the immune suppression induced by cancer cells. Myeloid-derived suppressor cells (MDSCs), which exerts pivotal functions in immunosuppression, is a key participator in tumor microenvironment and a novel target for cancer therapy. Here curcumin (Cur) was employed as a specific MDSCs repressor to inhibit the number and function of MDSCs. Moreover, a novel self-assembled nano-filament system was generated through the conjugation of Cur and a self-assembled peptide. In vivo study demonstrated the powerful antitumor effect of curcumin-loaded nano-filaments (Nano-Cur) with delayed tumor growth and longer survival. The immune status of tumor microenvironment (TME) was well improved by Nano-Cur treatment with increased T cell proliferation and activation as well as enhanced production of inflammatory mediators such as GM-CSF and IL-6, which revealed that Nano-Cur contributed to relieve the tumor burden by regulating and improving the TME. Furthermore, flow cytometry analysis implied the lower MDSCs levels under Nano-Cur treatment, which indicated that the anticancer effect of Nano-Cur may be associated with the inhibition of recruitment and accumulation of MDSCs in the TME. Therefore, Nano-Cur may be a novel therapeutic approach for lung cancer, and extensive studies of mechanisms are required to better understand how TME affects tumor progression and provide new insights into anticancer therapeutics.

The repair of cartilage and subchondral bone defects, especially the former, remains a challenge in clinical practice. An increasing number of studies have shown that the use of biomaterials has great advantages in regulating tissue repair, with lower cost and risk than the use of cytokines or cells. However, great challenges remain because of the marked differences between cartilage and subchondral bone. Here, biphasic osteochondral scaffolds with layer-specific differentiation were designed and developed. Hyaluronic acid (HA) was used as the matrix in the upper and lower layers, and differences in physicochemical properties and biological properties between the two layers were realized by different chemical crosslinking methods. The cartilage regeneration layer exhibited stress relaxation from the HA hydrazone crosslinking dynamics. Additionally, a porous HA hydrogel with dominant elasticity was prepared for subchondral bone repair. Importantly, a 3D-printed scaffold bracket could keep close integration of two layers and provided mechanical support, aiding the long-term tissue regeneration process. The in vitro and in vivo results indicated that the HA-base bilayer scaffold consisting of a dynamic HA layer and a porous HA layer realized the simultaneous integrated regeneration of articular cartilage and subchondral bone. Such scaffolds represent potential new materials for osteochondral regeneration.

Different temperature enamel firings were applied on a Ti-containing hot rolled enamel steel. The microstructure, mechanical properties and resistance to fish-scaling were characterized by optical microscopy, transmission electron microscopy, tensile test and hydrogen permeation test. The results show that both ferrite grain size and TiC particles size were increased after enamel firing. The yield strength, tensile strength and resistance to fish-scaling of experimental steel decrease with increasing firing temperature, which can be attributed to the increase in ferrite grain size and TiC particles size. TiC precipitates significantly affect the resistance to fish-scaling, and small sized TiC particles are beneficial for the high resistance to fish-scaling.

Stress-strain behavior of four types of polyethylene (PE), i.e. low-density polyethylene (LDPE), linear low-density polyethylene (LLDPE), medium-density polyethylene (MDPE) and high-density polyethylene (HDPE), under a wide strain rate ranging from 0.001 to 1000 s−1, and the crystalline structures of corresponding fractured PEs were investigated. Results demonstrated that when the strain rate was less than 1 s−1, PE exhibited ductile fracture with a rougher section. While at strain rates larger than 1 s−1, the damage was manifested as brittle fracture with a smooth fracture surface. For all PE specimens, the yield strength increased with strain rate, but the increasing dependency of yield stress on strain rate was diverse in various strain rate ranges. Under the same strain rate, due to the largest molecular weight and lowest branching degree, HDPE showed the highest values in yield strength, crystallinity, crystal orientation degree, and crystallite size. At the appropriate stain rate, i.e. 10 s−1, HDPE with less branched structure is more likely to obtain higher crystallinity and molecular chain orientation degree.

Atherosclerosis (AS) is the leading cause of heart attacks, stroke, and peripheral vascular disease. Berberine (BBR), a botanical medicine, has diversified anti-atherosclerotic effects but with poor absorption. The aim of this study was to develop an effective BBR-entrapped nano-system for treating AS in high-fat diet (HFD)-fed Apoe(−/−) mice, and also explore the possible underlying mechanisms involved. Three d-α-tocopherol polyethylene glycol (PEG) succinate (TPGS) analogues with different PEG chain lengths were synthesized to formulate BBR-entrapped micelles. HFD-fed Apoe(−/−) mice were administered with optimized formula (BBR, 100 mg/kg/day) orally for 5 months. The artery plaque onset and related metabolic disorders were evaluated, and the underlying mechanisms were studied. Our data showed that, BT1500M increased BBR deposition in liver and adipose by 107.6% and 172.3%, respectively. In the Apoe(−/−) mice, BT1500M ameliorated HFD-induced hyperlipidemia and lipid accumulation in liver and adipose. BT1500M also suppressed HFD-induced chronic inflammation as evidenced by the reduced liver and adipose levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β); and decreased plasma level of TNF-α, IL-6, IL-1β, interferon-γ (IFN-γ), monocyte chemotactic protein (MCP), and macrophage inflammatory factor (MIP). The mechanism study showed that BT1500M changed Ampk and Nf-κb gene expression, and interrupted a crosstalk process between adipocytes and macrophages. Further investigation proved that BT1500M decreased endothelial lesion and subsequent macrophage activation, cytokines release, as well as cholesteryl ester gathering in the aortic arch, resulting in ameliorated artery plaque build-up. Our results provide a practical strategy for treating AS using a BBR-entrapped nano-system.

Although various dressings currently used have the effect of promoting wound healing, they still cannot meet the requirements of clinically efficient treatment. Recently, parathyroid hormone (PTH) and its pathway have been shown as the new target for wound repair. However, using PTH in clinical wound treatment can be a question. This study is to develop a novel PTHrP-2 loaded cellulose acetate nanofiber mat (CAP) via electrospinning to benefit wound repair. By observing the effects of prepared CAP on cell proliferation, migration, tube formation, and wound healing in the rat models, we have evaluated the safety and effectiveness of CAP. With the extract of CAP, the viability of human umbilical vein endothelial cells and fibroblasts was enhanced. It also could significantly increase the movement rate of human umbilical vein endothelial cells and promote tube formation. The wound closure speed of CAP treatment was significantly faster than the cellulose acetate group. In conclusion, CAP has a promoting effect in angiogenesis, collagen formation and re-epithelialization, thereby it can accelerate wound healing. CAP is a promising translational nanocomposite material, which might be transferred into a new type of wound dressing.

Summary: Despite the high incidence of male infertility, only 30% of infertile men receive a causative diagnosis. To explore the regulatory mechanisms governing human germ cell function in normal and impaired spermatogenesis (crypto), we performed single-cell RNA sequencing (>30,000 cells). We find major alterations in the crypto spermatogonial compartment with increased numbers of the most undifferentiated spermatogonia (PIWIL4+). We also observe a transcriptional switch within the spermatogonial compartment driven by increased and prolonged expression of the transcription factor EGR4. Intriguingly, the EGR4-regulated chromatin-associated transcriptional repressor UTF1 is downregulated at transcriptional and protein levels. This is associated with changes in spermatogonial chromatin structure and fewer Adark spermatogonia, characterized by tightly compacted chromatin and serving as reserve stem cells. These findings suggest that crypto patients are disadvantaged, as fewer cells safeguard their germline’s genetic integrity. These identified spermatogonial regulators will be highly interesting targets to uncover genetic causes of male infertility.

China has a long history of planting ginkgo trees, and there are many large old ginkgo trees in rural and urban areas of China. Those large old ginkgo trees have aesthetic and cultural values and play an important role in regulating landscape and ecological functions. However, the geographical distribution and its determinants of large old ginkgo trees in China are still unexplored. In this study, we first collected from published references the county-level distribution data of ginkgo trees older than 100-year in China. Then we used generalized linear regression and random forest models to analyze the influence of 18 variables representing macroclimate, topography, soil conditions, and intensity of human activity on the occurrence and density of old ginkgo trees. We found that 66,184 old ginkgo trees were distributed in 818 counties of 23 provinces with the county-level average density of 0.11 ± 0.04 trees per km2. Old ginkgo trees were mainly distributed east of the Hu Huanyong line where the climate is humid and human population density is high. The probability of occurrence of old ginkgo trees was predominately affected by macroclimate and soil conditions. It significantly decreased with increasing proportion of soil sand content, soil pH, and climate stability, and significantly increased with increasing temperature and precipitation. In contrast, the density of old ginkgo trees was predominately affected by human activity, significantly increasing with human activity intensity (i.e., human population density, gross domestic product, and night-time light intensity). In conclusion, the occurrences of old ginkgo tree were constrained by macroclimate and soil conditions, while their density was mainly driven by human activity.

Inspired by the process of bone reconstruction, porous scaffolds with robust osteogenesis and biodegradability would provide an ideal bone substitute for clinical practice. In this study, a novel porous Mg–Nd–Zn–Zr (JDBM) alloy scaffold coated with brushite (i.e., DCPD), denoted as JDBM-DCPD, is fabricated using a special patent template technique, which forms the main spherical pores (400–450 μm) and smaller pores (150–250 μm) interconnected between the adjacent main pores, facilitating nutrient penetration and cell in-growth, exhibiting sufficient mechanical properties. In vitro results demonstrate that JDBM-DCPD scaffolds promote cell in-growth and osteogenic differentiation, which significantly enhance mineralization, osteogenesis and angiogenesis-related genes expression when cultured with bone marrow mesenchymal stem cells. After implanting in vivo, JDBM-DCPD scaffolds effectively stimulate angiogenesis, osteogenesis, and remodeling with the degradation of JDBM-DCPD, and perfectly repair large bone defect in rat and rabbit models. Results from the present study provide the solid evidence that porous biodegradable Mg-based scaffolds whose pore structure can be precisely regulated by a spacer-selection technique may be a promising tissue engineering scaffolds for large bone defect repair clinically, free from any extra growth factors and live cells, such advances will make scaffold-based bone tissue repair safer, more convenient and more cost-effective. Keywords: Biodegradable Mg–Nd–Zn–Zr alloy scaffold, DCPD coating, Osteogenesis, Angiogenesis, Bone tissue engineering

Esophageal squamous cell carcinoma (ESCC) is one of the most common cancers in China, accompanied by an extremely high mortality rate. Chlorogenic acid (CGA) is a small-molecule compound, that has been shown to have a wide range of biological activities, including antitumor. However, the efficacy and molecular mechanism of CGA on ESCC remains unknown. In this study, we confirmed the inhibition of proliferation by CGA in ESCC cells, as well as the reduction of ESCC xenograft volume by CGA in vivo. In addition, CGA also suppressed both the migration and invasion of ESCC cells in vitro. In a carcinogen-induced murine model of ESCC, hyperplasia of the esophagus was slowed by CGA, while mice suffering from ESCC that were treated with CGA had longer survival times than mice in the control group. The measurement of pluripotency factors (BMI1, SOX2, OCT4 and Nanog) that are related to poor prognosis revealed reduced expression of both BMI1 and SOX2, but not of OCT4 or Nanog, in ESCC cells, in both a dose- and time-dependent manner. Together, our initial findings demonstrate that CGA suppresses ESCC progression, downregulates the expression of BMI1 and SOX2, and provide an anti-tumor candidate for ESCC therapy.

Objectives: Men who have sex with men are at risk of tenofovir nephrotoxicity due to its wide use in both treatment and prophylaxis for human immunodeficiency virus infection, but little is known about the urinary biomarkers of early renal dysfunction in this population. This study aims to identify useful biomarkers of early renal dysfunction among human immunodeficiency virus-infected men who have sex with men exposed to tenofovir. Methods: In a cross-sectional study urinary alpha1-microglobulin, beta2-microglobulin, N-acetyl-β-d-glucosaminidase and albumin were measured and expressed as the ratio-to-creatinine in 239 human immunodeficiency virus-infected men who have sex with men who were treatment naïve or receiving antiretroviral therapy with tenofovir-containing or non-tenofovir-containing regimens. Additionally, 56 patients in the non-antiretroviral therapy group started a tenofovir-containing regimen and were assessed after 3 and 6 months on antiretroviral therapy. Results: Both the frequency of alpha1-microglobulin proteinuria (alpha1-microglobulin-creatinine ratio >25.8 mg/g) and the median urinary alpha1-microglobulin-creatinine ratio were higher in the tenofovir disoproxil fumarate group than the other two groups (all p 0.68 mg/g) was also observed in the tenofovir group (28.9%) compared to the non-tenofovir group (13.6%, p = 0.024). There were no significant differences between groups for N-acetyl-β-d-glucosaminidase and albumin. In the longitudinal study, the median urinary alpha1-microglobulin-creatinine ratio after 3 and 6 months on tenofovir-containing therapy (16.8 and 17.3 mg/g) was higher than baseline (12.3 mg/g, p = 0.023 and 0.011, respectively), while no statistically important changes were observed in urinary beta2-microglobulin-creatinine ratio or in the other biomarkers after 3 and 6 months on antiretroviral therapy (all p > 0.05). Conclusion: Urinary alpha1-microglobulin seems to be a more sensitive and stable indicator of tubular dysfunction than urinary beta2-microglobulin for assessing tenofovir-related nephrotoxicity and can be significantly altered after tenofovir exposure. Keywords: Alpha1-microglobulin, Beta2-microglobulin, Tenofovir, Human immunodeficiency virus

A highly crystalline LiCoPO4/C cathode material has been synthesized without noticeable impurities via a single step solid-state reaction using CoHPO4·xH2O nanoplate as a precursor obtained by a simple precipitation route. The LiCoPO4/C cathode delivered a specific capacity of 125 mAhg−1 at a charge/discharge rate of C/10. The nanoplate precursor and final LiCoPO4/C cathode have been characterized using X-ray diffraction, thermogravimetric analysis − differential scanning calorimetry (TGA-DSC), transmission electron microscopy (TEM), and scanning electron microscopy (SEM) and the electrochemical cycling stability has been investigated using different electrolytes, additives and separators.

The COVID-19 outbreak has garnered significant global attention due to its impact on human health. Despite its relatively low fatality rate, the virus affects multiple organ systems, resulting in various symptoms such as palpitations, headaches, muscle pain, and hearing loss among COVID-19 patients and those recovering from the disease. These symptoms impose a substantial physical, psychological, and social burden on affected individuals. On February 15, 2020, the Chinese government advised incorporating antimalarial drugs into the guidelines issued by the National Health Commission of China for preventing, diagnosing, and treating COVID-19 pneumonia. We examine the adverse effects of Chloroquine (CQ) in treating COVID-19 complications to understand why it is no longer the primary treatment for the disease.

Background: The interaction between cancer cells and the tumor microenvironment is of critical importance in liver cancer. Jiedu Granule formula (JDF) has been shown to minimize the risk of recurrence and metastasis following liver cancer resection. Investigating the mechanism underlying the therapeutic effects of JDF can extend its field of application and develop novel treatment approaches. Methods: We established a rat liver orthotopic transplantation tumor model, and recorded the prognostic effects of JDF adjuvant therapy on the recurrence and metastasis of liver cancer. Liver and lung tissues were collected for immunofluorescence staining and H&E staining, respectively. In addition, THP-1 cells were incubated with PMA and IL-4 to induce them to differentiate into M2 macrophages. CSF-1 expression was knocked down using lentivirus to determine the function of CSF-1. Liver cancer cells were cultured with a conditioned medium (CM) or co-cultured with macrophages. Cell viability was determined using the MTT assay. The levels of CSF-1, CSF-1R, E-cadherin, N-cadherin, PI3K, AKT, and cleaved caspase-3 were detected using ELISA, Western blotting and qPCR. The ability of cells to migrate was assessed using cell scratch and transwell assays. Apoptosis was evaluated using flow cytometry. Results: The JDF treatment decreased the risk of liver cancer metastasis after surgery and the infiltration of CD206/CD68 cells in liver cancer tissue. In cell experiments, JDF showed effects in suppressing M2 macrophages activity and downregulating the expression of CSF-1 and CSF-1R. The concentration of CSF-1 in the supernatant was also lower in the JDF-treated group. Futhermore, M2-CM was found to promote cancer cell migration and epithelial-mesenchymal transition (EMT); however, these effects were weakened after administering JDF. Knocking down endogenous CSF-1 in M2 macrophages resulted in a comparable suppression of cancer cell migration and EMT. Additionally, JDF treatment inhibited activation of the PI3K/AKT pathway, thus promoting the apoptosis of M2 macrophages. Conclusions: Treatment with JDF reduced the EMT and migratory capacity of liver cancer cells, which might be attributed to the inhibition of M2 macrophage infiltration and interruption of the CSF-1/PI3K/AKT signaling pathway. This mechanism may hold significant implications for mitigating the risk of metastatic spread in the aftermath of hepatic surgery.

Summary: The role of fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), and triglyceride-glucose index (TyG index) in predicting all-cause and cause-specific mortalities remains elusive. This study included 384,420 adults from the Shanghai cohort and the UK Biobank (UKB) cohort. After multivariable adjustment in the Cox models, FPG ≥7.0 mmol/L or HbA1c ≥ 6.5% increased the risk of all-cause mortality, FPG ≥5.6 mmol/L or HbA1c ≥ 6.5% increased CVD-related mortality, and higher or lower TyG index increased all-cause and CVD-related mortalities in the Shanghai cohort; FPG ≥5.6 mmol/L, HbA1c ≥ 5.7%, TyG index

Large-size pure titanium ingots melted by single electron beam cold hearth melting (EBCHM)) could be rolled into large-width and heavy-weight titanium strip coils using short process without forging. It is crucial to study the large-span refinement mechanism from highly coarse grains, whose sizes are in the order of ∼cm, to micronmeter. In this study, the recrystallization mechanism and texture evolution of pure titanium with a size of 1570 × 200 × > 8000 mm was investigated by multi-pass simulated rolling and experimental rolling. The results indicated the hot deformation can result in marked reduction in grain size of the as-cast grain, from 3 to 5 cm to 17–23 μm. The discontinuous dynamic recrystallization (DDRX) mechanism of a pure titanium ingot during direct multi-pass hot deformation causes the reconstruction of as-cast microstructure and refinement of hot rolling microstructure. Furthermore, DDRX occurred, during hot deformation, and was accompanied with weakening of deformation texture. Raising the initial hot deformation temperature results in a modification of the texture type of the {0001} crystal plane. The strength of the texture experiences a decrease initially and then eventually an increase. This alteration in strength is inversely related to the degree of dynamic recrystallization. Based on the simulated rolling experiment, the results of experimental rolling also found the coarse as-cast grains was broken and reconstructed. It has strength (average yield strength: 334 MPa, ultimate tensile strength: 371 MPa), ductility (total elongation: 30 %). Such a combination of mechanical properties makes the hot rolling plate a potential choice for sheet practical application.

Summary: The causality between circulating proteins and thyroid cancer (TC) remains unclear. We employed five large-scale circulating proteomic genome-wide association studies (GWASs) with up to 100,000 participants and a TC meta-GWAS (nCase = 3,418, nControl = 292,703) to conduct proteome-wide Mendelian randomization (MR) and Bayesian colocalization analysis. Protein and gene expressions were validated in thyroid tissue. Through MR analysis, we identified 26 circulating proteins with a putative causal relationship with TCs, among which NANS protein passed multiple corrections (PBH = 3.28e-5, 0.05/1,525). These proteins were involved in amino acids and organic acid synthesis pathways. Colocalization analysis further identified six proteins associated with TCs (VCAM1, LGMN, NPTX1, PLEKHA7, TNFAIP3, and BMP1). Tissue validation confirmed BMP1, LGMN, and PLEKHA7’s differential expression between normal and TC tissues. We found limited evidence for linking circulating proteins and the risk of TCs. Our study highlighted the contribution of proteins, particularly those involved in amino acid metabolism, to TCs.

Background: Epidemiological studies have reported associations between heavy metals and renal function. However, longitudinal studies are required to further validate these associations and explore the interactive effects of heavy metals on renal function and their directional influence. Method: This study, conducted in Northeast China from 2016 to 2021, included a four-time repeated measures design involving 384 participants (1536 observations). Urinary concentrations of chromium (Cr), cadmium (Cd), manganese (Mn), and lead (Pb) were measured, along with renal biomarkers including urinary microalbumin (umAlb), urinary albumin-to-creatinine ratio (UACR), N-acetyl-β-D-glucosaminidase (NAG), and β2-microglobulin (β2-MG) levels. Estimated glomerular filtration rate (eGFR) was calculated. A Linear Mixed Effects Model (LME) examined the association between individual metal exposure and renal biomarkers. Subsequently, Quantile g-computation and Bayesian Kernel Machine Regression (BKMR) models assessed the overall effects of heavy metal mixtures. Marginal Effect models examined the directional impact of metal interactions in the BKMR on renal function. Result: Results indicate significant impacts of individual and combined exposures of Cr, Cd, Pb, and Mn on renal biomarkers. Metal interactions in the BKMR model were observed, with synergistic effects of Cd-Cr on NAG, umAlb, UACR; Cd-Pb on NAG, UACR; Pb-Cr on umAlb, UACR, eGFR-MDRD, eGFR-EPI; and an antagonistic effect of Mn-Pb-Cr on UACR. Conclusion: Both individual and combined exposures to heavy metals are associated with renal biomarkers, with significant synergistic interactions leading to renal damage. Our findings elucidate potential interactions among these metals, offering valuable insights into the mechanisms linking multiple metal exposures to renal injury.

Objective: To investigate the vaginal and gut microbes changes during the carcinogenesis of cervical and the auxiliary diagnostic value. To investigate the effect of microbiome-specific metabolites butyric on cervical cancer cells. Methods: We studied 416 vaginal 16S rRNA sequencing data and 116 gut sequencing data. Reads were processed using VSEARCH. We used Shannon index, Chao1 index, Simpson diversity index, β diversity index, Linear discriminant analysis Effect Size (LEfSe), co-abundance network and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis to explore microbiome differences between groups. We constructed random forest models based on genus and verified its discriminant effect. Finally, we used the cell counting kit-8 (CCK-8) method to detect cell proliferation capacity and flow cytometry to detect apoptosis and induction of cell cycle progression. Results: Compared to the non-cancerous population, patients with cervical cancer had unique microbial community characteristics in both vaginal and gut ecological niches. Our predictive model based on genus in two ecological regions achieved high accuracy in the diagnosis of cervical cancer (vaginal model AUC=91.58 %; gut model AUC=99.95 %). Butyric inhibited cervical cancer cell proliferation in a concentration-dependent manner and promoted apoptosis of cancer cells. Conclusion: Significant differences were found in vaginal and gut microbes in patients with cervical cancer compared to the non-cancerous population. The prediction models constructed at the genus level in both ecological sites have good diagnostic value. Microorganisms may be involved in cervical cancer progression in a metabolite-dependent way, and targeting butyric may provide therapeutic options for cervical cancer.

Background: The impact of heavy metals on liver function has been examined in numerous epidemiological studies. However, these findings lack consistency and longitudinal validation. Methods: In this study, we conducted three follow-up surveys with 426 participants from Northeast China. Blood and urine samples were collected, along with questionnaire information. Urine samples were analyzed for concentrations of four metals (chromium [Cr], cadmium [Cd], lead [Pb], and manganese [Mn]), while blood samples were used to measure five liver function indicators (alanine aminotransferase [ALT], aspartate aminotransferase [AST], albumin [ALB], globulin [GLB], and total protein [TP]). We utilized a linear mixed-effects model (LME) to explore the association between individual heavy metal exposure and liver function. Joint effects of metal mixtures were investigated using quantile g-computation and Bayesian kernel machine regression (BKMR). Furthermore, we employed BKMR and Marginal Effect models to examine the interaction effects between metals on liver function. Results: The LME results demonstrated a significant association between urinary heavy metals (Cr, Cd, Pb, and Mn) and liver function markers. BKMR results indicated positive associations between heavy metal mixtures and ALT, AST, and GLB, and negative associations with ALB and TP, which were consistent with the g-comp results. Synergistic effects were observed between Cd-Cr on ALT, Mn-Cr and Cr-Pb on ALB, while an antagonistic effect was found between Mn-Pb and Mn-Cd on ALB. Additionally, synergistic effects were observed between Mn-Cr on GLB and Cd-Cr on TP. Furthermore, a three-way antagonistic effect of Mn-Pb-Cr on ALB was identified. Conclusion: Exposure to heavy metals (Cr, Cd, Mn, Pb) is associated with liver function markers, potentially leading to liver damage. Moreover, there are joint and interaction effects among these metals, which warrant further investigation at both the population and mechanistic levels.

ABSTRACT: The aim of the experiment was to evaluate the status of innate immunity, oxidative status and lipid accumulation in ducklings exhibiting varying susceptibilities to DHAV-3 infection. In the experiment, ducklings with different DHAV-3 susceptibilities were used. Samples were collected at 6, 12, 15, and 24 h post infection (hpi), with 5 samples per time point. Plasma biochemistry, antioxidant enzyme activities, lipid content of liver and kidney were detected in the experiment. Elevated plasma level of total bilirubin, direct bilirubin, and creatinine indicated the injury of liver and kidney in susceptible ducklings (P < 0.05). The histopathological sections showed the injury in kidney. During the infection time, there was an increase in the concentrations of reactive oxygen species and oxidative damage markers (malondialdehyde and nitric oxide) in plasma of susceptible ducklings, particularly at 24 hpi (P < 0.05). Compared with the resistant ducklings, DHAV-3 infection resulted in a significant increase in the plasma total triglyceride (TG) level and a decrease in glucose level in susceptible ducklings. Gene expression of the innate immune response was both investigated in liver and kidney. In resistant ducklings, the expressions levels of pattern recognition receptors RIG-I, MDA5 remained constant. In contrast, the gene expressions peaked at 24 hpi in the susceptible ducklings. DHAV-3 infection promoted the expression of IFN, IL6, IL12β, caspase-8 or caspase-9 in both liver and kidney of susceptible ducklings. In conclusion, DHAV-3 infection led to the mobilization of antioxidant defenses, alterations in lipid metabolism, and oxidative stress in susceptible ducklings during DHAV-3 infection.

Background and aim: Standard deep learning methods have been found inadequate in distinguishing between intestinal tuberculosis (ITB) and Crohn's disease (CD), a shortcoming largely attributed to the scarcity of available samples. In light of this limitation, our objective is to develop an innovative few-shot learning (FSL) system, specifically tailored for the efficient categorization and differential diagnosis of CD and ITB, using endoscopic image data with minimal sample requirements. Methods: A total of 122 white-light endoscopic images (99 CD images and 23 ITB images) were collected (one ileum image from each patient). A 2-way, 3-shot FSL model that integrated dual transfer learning and metric learning strategies was devised. Xception architecture was selected as the foundation and then underwent a dual transfer process utilizing oesophagitis images sourced from HyperKvasir. Subsequently, the eigenvectors derived from the Xception for each query image were converted into predictive scores, which were calculated using the Euclidean distances to six reference images from the support sets. Results: The FSL model, which leverages dual transfer learning, exhibited enhanced performance metrics (AUC 0.81) compared to a model relying on single transfer learning (AUC 0.56) across three evaluation rounds. Additionally, its performance surpassed that of a less experienced endoscopist (AUC 0.56) and even a more seasoned specialist (AUC 0.61). Conclusions: The FSL model we have developed demonstrates efficacy in distinguishing between CD and ITB using a limited dataset of endoscopic imagery. FSL holds value for enhancing the diagnostic capabilities of rare conditions.

IL-37 is a newly discovered member of the IL-1 cytokine family which plays an important role in regulating inflammation and maintaining physiological homeostasis. IL-37 showed a close relationship with IL-18, another key cytokine in inflammation regulation and cancer development. IL-37 affects the function of IL-18 either by binding to IL-18Rα, a key subunit of both IL-37 and IL-18 receptor, or by drastically neutralizing the IL-18 protein expression of IL-18 binding protein, an important natural inhibitory molecule of IL-18. Moreover, as another subunit receptor of IL-37, IL-1R8 can suppress IL-18Rα expression, functioning as a surveillance mechanism to prevent overactivation of both IL-18 and IL-37 signaling pathways. While IL-18 and IL-37 share the same receptor subunit, IL-18 would in turn interfere with IL-37 signal transduction by binding to IL-18Rα. It is also reported that IL-18 and IL-37 demonstrated opposing effects in a variety of cancers, such as glioblastoma, lung cancer, leukemia, and hepatocellular cancer. Although the mutual regulation of IL-18 and IL-37 and their diametrically opposed effects in cancers has been reported, IL-18 has not been taken into consideration when interpreting clinical findings and conducting mechanism investigations related to IL-37 in cancer. We aim to review the recent progress in IL-18 and IL-37 research in cancer and summarize the correlation between IL-18 and IL-37 in cancer based on their expression level and underlying mechanisms, which would provide new insights into elucidating the conflicting roles of IL-18 and IL-37 in cancer and bring new ideas for translational research related to IL-18 and IL-37.

Background: Abnormal cardiac metabolism is a key factor in the development of cardiovascular diseases. Consequently, there has been considerable emphasis on researching and developing drugs that regulate metabolism. This study employed bibliometric methods to comprehensively and objectively analyze the relevant literature, offering insights into the knowledge dynamics in this field. Methods: The data source for this study was the Web of Science Core Collection (WoSCC), from which the collected data were imported into bibliometric software for analysis. Results: The United States was the leading contributor, accounting for 38.33 % of publications. The University of Washington and Damian J. Tyler were the most active institution and author, respectively. The American Journal of Physiology-Heart and Circulatory Physiology, Journal of Molecular and Cellular Cardiology, Cardiovascular Research, Circulation Research, and American Journal of Physiology-Endocrinology and Metabolism were highly influential journals that published numerous high-quality articles on cardiac metabolism. Common keywords in this research area included heart failure, insulin resistance, skeletal muscle, mitochondria, as well as topic words such as cardiac metabolism, fatty acid oxidation, glucose metabolism, and myocardial metabolism. Co-citation analysis has shown that research on heart failure and in vitro modeling of cardiovascular disease has gained prominence in recent years and making it a research hotspot. Conclusion: Research on cardiac metabolism is steadily growing, with a specific focus on heart failure and the interplay between mitochondrial dysfunction, insulin resistance, and cardiac metabolism. An emerging trend in this field involves the enhancement of maturation in human induced pluripotent stem cell-derived cardiomyocyte (hiPSC-CM) through the manipulation of cardiac metabolism.

Background: Neuroendocrine neoplasms (NENs) are tumors that originate from secretory cells of the diffuse endocrine system and typically produce bioactive amines or peptide hormones. This paper describes the development and validation of a predictive model of the risk of lymph node metastasis among gastric NEN patients based on machine learning platform. Methods: In this investigation, data from 1256 patients were used, of whom 119 patients from the First Affiliated Hospital of Soochow University in China and 1137 cases from the surveillance epidemiology and end results (SEER) database were combined. Six machine learning algorithms, including the logistic regression model (LR), random forest (RF), decision tree (DT), Naive Bayes (NB), support vector machine (SVM), and k-nearest neighbor algorithm (KNN), were used to build the predictive model. The performance of the models was evaluated using the area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, and specificity. Results: Among the 1256 patients with gastric NENs, 276 patients (21.97 %) developed lymph node metastasis. T stage, tumor size, degree of differentiation, and sex were predictive factors of lymph node metastasis. The RF model achieved the best predictive performance among the six machine learning models, with an AUC, accuracy, sensitivity, and specificity of 0.81, 0.78, 0.76, and 0.82, respectively. Conclusion: The RF model provided the best prediction and can help physicians determine the lymph node metastasis risk of gastric NEN patients to formulate individualized medical strategies.

Chronic kidney disease (CKD) is a public health concern worldwide, and chromium exposure may be a risk factor due to its potential nephrotoxicity. However, research on the association between chromium exposure and kidney function especially the potential threshold effect of chromium exposure is limited. A repeated-measures study involving 183 adults (641 observations) was conducted from 2017 to 2021 in Jinzhou, China. Urinary albumin-to-creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR) were measured as kidney function biomarkers. Generalized mixed models and two-piecewise linear spline mixed models were used to assess the dose-response relationship and potential threshold effect of chromium on kidney function, respectively. Temporal analysis was conducted by the latent process mixed model to depict the longitudinal change of kidney function over age. Urinary chromium was associated with CKD (odds ratio [OR] = 1.29; 95 % confidence interval [CI], 6.41, 14.06) and UACR (Percent change = 10.16 %; 95 % CI, 6.41 %, 14.06 %), and we did not find significant association between urinary chromium and eGFR (Percent change = 0.06 %; 95 % CI, −0.80 %, 0.95 %). The threshold analyses suggested the existence of threshold effects of urinary chromium, with inflection points at 2.74 μg/L for UACR and 3.95 μg/L for eGFR. Furthermore, we found that chromium exposure exhibited stronger kidney damage over age. Our study provided evidence for the threshold effects of chromium exposure on kidney function biomarkers and the heightened nephrotoxicity of chromium in older adults. More attention should be paid to the supervision of chromium exposure concentrations for preventing kidney damage, especially in older adults.

The human gut microbiome has primarily been studied through the use of fecal samples, a practice that has generated vital knowledge on the composition and functional capacities of gastrointestinal microbial communities. However, this reliance on fecal materials limits the investigation of microbial dynamics in other locations along the gastrointestinal tract (in situ), and the infrequent availability of fecal samples prevents analysis at finer temporal scales (e.g., hours). In our study, we utilized colonic transendoscopic enteral tubing, a technology originally developed for fecal microbiota transplantation, to sample the ileocecal microbiome twice daily; metagenomic and metatranscriptomic analyses were then conducted on these samples. A total of 43 ileocecal and 28 urine and fecal samples were collected from five healthy volunteers. The ileocecal and fecal microbiomes, as profiled in the five volunteers, were found to be similar in metagenomic profiling, yet their active genes (metatranscriptome) were found to be highly distinct. Both microbiomes were perturbed after laxative exposure; over time, they exhibited reduced dissimilarity to their pre-treatment state, thereby demonstrating resilience as an innate property of the gut microbiome, although they did not fully recover within our observation time window. Sampling of the ileocecal microbiome during the day and at night revealed the existence of diurnal rhythms in a series of bacterial species and functional pathways, particularly those related to short-chain fatty acid production, such as Propionibacterium acnes and coenzyme A biosynthesis II. Autocorrelation analysis and fluctuations decomposition further indicated the significant periodicity of the diurnal oscillations. Metabolomic profiling in the fecal and urine samples mirrored the perturbance and recovery in the gut microbiome, indicating the crucial contribution of the gut microbiome to many key metabolites involved in host health. This study provides novel insights into the human gut microbiome and its inner resilience and diurnal rhythms, as well as the potential consequences of these to the host.