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AbstractAutoimmune thyroiditis (AIT), also known as Hashimoto’s thyroiditis (HT), is an autoimmune disease that is characterised by elevated thyroid-specific antibody titres. The incidence of AIT is increasing year over year, making it urgent to establish a suitable animal model for this condition, in order to better explore its pathogenesis and potential pharmaceutical mechanisms for treatment. Owing to a lack of basic research on this disease, problems such as disparate modelling methods with unclear and varying success rates make it difficult for researchers to obtain effective information on AIT in the short term. This report summarises and analyzes the current literature on AIT and combines actual operability to explain the selection and specific implementation processes behind the uses of different modelling approaches, to provide a better overall understanding of autoimmune thyroid diseases.

Abstract Cardiac magnetic resonance imaging (CMR) has emerged as a valuable diagnostic tool for cardiac diseases. However, a significant drawback of CMR is its slow imaging speed, resulting in low patient throughput and compromised clinical diagnostic quality. The limited temporal resolution also causes patient discomfort and introduces artifacts in the images, further diminishing their overall quality and diagnostic value. There has been growing interest in deep learning-based CMR imaging algorithms that can reconstruct high-quality images from highly under-sampled k-space data. However, the development of deep learning methods requires large training datasets, which have so far not been made publicly available for CMR. To address this gap, we released a dataset that includes multi-contrast, multi-view, multi-slice and multi-coil CMR imaging data from 300 subjects. Imaging studies include cardiac cine and mapping sequences. The ‘CMRxRecon’ dataset contains raw k-space data and auto-calibration lines. Our aim is to facilitate the advancement of state-of-the-art CMR image reconstruction by introducing standardized evaluation criteria and making the dataset freely accessible to the research community.

Abstract Previous reports have established that rESWT fosters angiogenesis, yet the mechanism by which rESWT promotes cerebral angiogenesis remains elusive. rESWT stimulated HUVECs proliferation as evidenced by the CCK-8 test, with an optimal dosage of 2.0 Bar, 200 impulses, and 2 Hz. The tube formation assay of HUVECs revealed that tube formation peaked at 36 h post-rESWT treatment, concurrent with the lowest expression level of Bach1, as detected by both Western blot and immunofluorescence. The expression level of Wnt3a, β-catenin, and VEGF also peaked at 36 h. A Bach1 overexpression plasmid was transfected into HUVECs, resulting in a decreased expression level of Wnt3a, β-catenin, and VEGF. Upon treatment with rESWT, the down-regulation of Wnt3a, β-catenin, and VEGF expression in the transfected cells was reversed. The Wnt/β-catenin inhibitor DKK-1 was utilized to suppress Wnt3a and β-catenin expression, which led to a concurrent decrease in VEGF expression. However, rESWT treatment could restore the expression of these three proteins, even in the presence of DKK-1. Moreover, in the established OGD model, it was observed that rESWT could inhibit the overexpression of Bach1 and enhance VEGF and VEGFR-2 expression under the OGD environment.

Abstract Zintl phases typically exhibit low lattice thermal conductivity, which are extensively investigated as promising thermoelectric candidates. While the significance of Zintl anionic frameworks in electronic transport properties is widely recognized, their roles in thermal transport properties have often been overlooked. This study delves into KCdSb as a representative case, where the [CdSb4/4]− tetrahedrons not only impact charge transfer but also phonon transport. The phonon velocity and mean free path, are heavily influenced by the bonding distance and strength of the Zintl anions Cd and Sb, considering the three acoustic branches arising from their vibrations. Furthermore, the weakly bound Zintl cation K exhibits localized vibration behaviors, resulting in strong coupling between the high‐lying acoustic branch and the low‐lying optical branch, further impeding phonon diffusion. The calculations reveal that grain boundaries also contribute to the low lattice thermal conductivity of KCdSb through medium‐frequency phonon scattering. These combined factors create a glass‐like thermal transport behavior, which is advantageous for improving the thermoelectric merit of zT. Notably, a maximum zT of 0.6 is achieved for K0.84Na0.16CdSb at 712 K. The study offers both intrinsic and extrinsic strategies for developing high‐efficiency thermoelectric Zintl materials with extremely low lattice thermal conductivity.

Abstract The objective of this study is to investigate the expression and influence of adenosine triphosphate-sensitive potassium channel (KATP) in human umbilical arterial smooth muscle cells (HUASMCs) of patients with hypertensive disorders of pregnancy (HDP). Western blotting was used to detect the protein expression levels of KATP inwardly rectifying potassium channel (Kir)6.1 and sulphonylurea receptor (SUR)2B subunits in HUASMCs from patients with normal parturients (NP), gestational hypertension (GH), chronic hypertension (CH), preeclampsia (PE) and chronic hypertension with superimposed preeclampsia (CHSP), respectively. There was no significant difference in the protein expression of Kir6.1 subunit in NP group, GH group, CH group, PE group and CHSP group (P > 0.05). The protein expression of SUR2B subunit was gradually decreased in NP group, GH group, CH group, PE group and CHSP group, with statistically significant difference among the groups (P

Abstract We aimed to investigate the characteristics of intestinal metabolomics and non-invasive biomarkers for early diagnosis of late-onset sepsis (LOS) by analyzing gut metabolites in preterm infants with LOS. We collected stool samples from septic and healthy preterm infants for analysis by liquid chromatography–mass spectrometry. 123 different metabolites were identified and 13 pathways were mainly involved. Glycine, serine, and threonine metabolism; glyoxylate and dicarboxylic acid metabolism; glutathione metabolism; primary bile acid biosynthesis; steroid synthesis; pentose and glucuronic acid interconversion may be involved in the pathogenesis of LOS in preterm infants. The significant changes of N-Methyldopamine, cellulose, glycine, gamma-Glutamyltryptophan, N-Ribosylnicotinamide and 1alpha, 25-dihydroxycholecalciferol showed specific diagnostic values and as non-invasive biomarkers for LOS.

Large Seebeck coefficients induced by high degeneracy of conduction band minimum, and low intrinsic lattice thermal conductivity originated from large lattice vibrational anharmonicity render Mg3Sb2 as a promising n-type thermoelectric material. Herein, we demonstrated unique concentration-dependent occupation behaviors of Cu in Mg3.4Sb1.5Bi0.49Te0.01 matrix, evidenced by structural characterization and transport property measurements. It is found that Cu atoms prefer to enter the interstitial lattice sites in Mg3Sb2 host with low doping level (Mg3.4Sb1.5Bi0.49Te0.01 + x% Cu, x

Abstract The regulation of PD‐L1 is the key question, which largely determines the outcome of the immune checkpoint inhibitors (ICIs) based therapy. However, besides the transcription level, the protein stability of PD‐L1 is closely correlated with its function and has drawn increasing attention. In this study, EZH2 inhibition enhances PD‐L1 expression and protein stability, and the deubiquitinase ubiquitin‐specific peptidase 22 (USP22) is identified as a key mediator in this process. EZH2 inhibition transcriptionally upregulates USP22 expression, and upregulated USP22 further stabilizes PD‐L1. Importantly, a combination of EZH2 inhibitors with anti‐PD‐1 immune checkpoint blockade therapy improves the tumor microenvironment, enhances sensitivity to immunotherapy, and exerts synergistic anticancer effects. In addition, knocking down USP22 can potentially enhance the therapeutic efficacy of EZH2 inhibitors on colon cancer. These findings unveil the novel role of EZH2 inhibitors in tumor immune evasion by upregulating PD‐L1, and this drawback can be compensated by combining ICI immunotherapy. Therefore, these findings provide valuable insights into the EZH2‐USP22‐PD‐L1 regulatory axis, shedding light on the optimization of combining both immune checkpoint blockade and EZH2 inhibitor‐based epigenetic therapies to achieve more efficacies and accuracy in cancer treatment.

Abstract Background Clinicians agree that obtaining and retaining good treatment results for missing maxillary central incisors owing to trauma is not easy. Management of adult patients with permanent maxillary central incisor loss who visit the clinic with high expectations for aesthetics and function pose a significant diagnostic dilemma. Therefore, esthetic and functional outcomes should be taken into consideration when deciding the proper treatment method. The treatment described in this study aimed to reestablish smile esthetics by proposing an effective multidisciplinary clinical approach that includes orthodontic-prosthetic-periodontal procedures, optimally reduced lip protrusion, center dental midlines, and establishment of stable occlusion. Case presentation The patient was a 19-year-old adult female with bimaxillary arch protrusion who had been wearing removable dentures for several years since the loss of her maxillary central permanent incisors. A multidisciplinary treatment including the extraction of two mandibular primary premolars was adopted. The treatment plan consisted of orthodontic space closure by shifting the adjacent teeth towards the central incisor spaces combined with appropriate morphologic remodeling and gingival reshaping to obtain good aesthetic and functional results. The duration to complete the orthodontic treatment was 35 months. Clinical and radiographic results after treatment suggested smile harmony with an improvement in the facial profile, good function of the occlusion, and a positive effect on bone remodeling in the area of the missing incisors during orthodontic tooth movement. Conclusions This clinical case illustrated the necessity for using multidisciplinary methods involving orthodontic, prosthodontic, and periodontic procedures to treat an adult female patient with bimaxillary arch protrusion and long-term absence of anterior teeth due to severe trauma.

In previous studies, we found radial extracorporeal shock wave (rESW), can promote the proliferation of neural stem cells (NSCs). Emerging evidence suggests that lncRNA NEAT1 can regulate NSCs proliferation. Whether lncRNA NEAT1 plays a role in the proliferation of NSC induced by shock waves is unclear. Cell Counting Kit-8（CCK 8) method was used to detect the proliferation of NSCs, and the relative protein and mRNA expression of related genes of Nestin, Cyclin D1 and P21 were detected by Western Blot and Quantitative real-time PCR (RT-qPCR) respectively. Immunofluorescence staining was used to observe the changes in the number of BrdU/nestin positive cells. Overexpression of NEAT1 and let 7 b in cells were used to explore whether rESW can rescue the decreased number of NSCs.We found that the optimal dose of R15 transmitter promoting NSCs proliferation is 1.5 bar, 500 pulse, 2 Hz. 1.2–1.5 bar showed a dose-dependent effect on the proliferation of NSCs, but it was negatively correlated with the proliferation effect of NSC when it was more than 1.5 bar. We revealed that let 7 b-P21 axis was involved in regulating the inhibition of NSC proliferation which was activated by NEAT1 in NSCs. In addition, we demonstrated that rESW treatment resulted in the decrease of NEAT1 expression, which was accompanied by the improved biological function including proliferation. Our results confirm that low-intensity rESW (1.5 bar，500 pulse，2 Hz) can promote the proliferation of NSCs through NEAT1-let 7 b-P21 axis.

The hardening or softening behaviors of the Ni-W based alloys, that can be applied in metal forming, high-speed impact, and penetration mechanics industries, are different from other traditional alloys under high strain rates (higher than 1000 s−1) or at high temperatures. The quasi-static and dynamic mechanical properties of a Ni-W-Co-C alloy, as well as the corresponding deformation behaviors and microstructure evolution, is studied herein. Further investigations and discussions on the constitutive relationships corresponding to dynamic deformations are carried out in this paper. The strain hardening behaviors are found varying with increasing temperatures, i.e., obvious enhancement of strength with increasing strains at 300–500 °C, but apparent softening behaviors at 700 °C. No dynamic softening behaviors are observed in the compressed specimens under high strain rates in range of 1000–3000 s−1, but with more very refined deformation twins under higher strain rates, suggesting the strain rate hardening effect may be enhanced. A feasible constitutive model is established by modifying the Johnson-Cook model, i.e., introducing a constant of λ′ to describe the variation of strength with the increasing temperatures and strains, providing a theoretical basis for the promising applications of this alloy.

Here, Wang and colleagues combine short and long sequencing reads to characterize structural variations, prophage and CRISPR spacer elements in human gut microbiomes, and reveal functional differences at a finer level of bacterial strains.

In this paper a typical tension/compression asymmetry (TCA) behavior of a Ni48W35Co17 alloy is found by quai-static and dynamic mechanical tests and then systematically investigated by in-situ tensile and compression tests equipped with SEM, EBSD, TEM, etc. The true stress obtained by compression of this alloy is found increasing to 2500 MPa or even larger with strain over 0.5, which is almost twice of the value of tension. In tension, a little increase of reinforcement coefficient is found with increasing strain rates, from 0.36 to 0.56 max. In compression, reinforcement coefficient is found increased apparently from 0.76 to 1.24 according to the exponential stress-strain relationship. The TCA behavior of this alloy is related to the dislocation nucleation stress asymmetry. The TCA of yield strength is related to the formation of textures on [111] and [110] directions, since a larger nucleation stress is required in uniaxial compression than tension. TCA is also promoted by the formation of twin boundaries or sub-grain boundaries due to the higher average nucleation stress tilt grain boundaries in compression than intension. TCA behavior of this alloy in dynamic deformation is attributed to the high dislocation densities due to the formation of very thin deformation twins.

This paper presents a pilot study that focuses on the exploratory and rapid prototyping within the human-in-the-loop control of a self-constructed and developed educational robot in assisting communicative English learning in primary Education in Madrid, Spain. The study sample was composed of 37 3rd graders that attended four English learning program sessions in November 2021, in which robot integration plays a leading role as learning material. To achieve the above, an easy-to-build, programmed and economical LEGO Education Mindstorms EV3 package was optioned. Pre-and-post questionnaires, classroom observations, and an evaluation sheet that measures self-evaluation, peer evaluation, and teacher evaluation were applied. The result reveals students’ perception of the pioneering robot and although preliminary, presents validation of the technology for English class assistance. Another finding suggests that students’ stress generated from communication in English among peers was reduced with the companion of the robot. Due to the nature of a pilot study, both the number of sessions and the sample size are limited to determine if the robot is helpful in students’ vocabulary acquisition in the long run. Further study is to be conducted with the pioneer model to teach vocabularies of different categories for a longer period. The findings of this pilot study will serve as a reference in the attempt to develop and reproduce promising robots to assist English teaching and learning that are accessible to public schools.

Atrial fibrillation (AF), one of the most common arrhythmias, is associated with chronic emotional disorder. Chronic pain represents a psychological instability condition related to cardiovascular diseases, but the mechanistic linkage connecting chronic pain to AF occurrence remains unknown. Wild-type C57BL/6J male mice were randomly divided into sham and chronic pain groups. Autonomic nerve remodeling was reflected by the increased atrial parasympathetic tension and muscarinic acetylcholine receptor M2 expression. AF susceptibility was assessed through transesophageal burst stimulation in combination with electrocardiogram recording and investigating AERP in Langendorff perfused hearts. Our results demonstrated the elevated protein expression of muscarinic acetylcholine receptor M2 in the atria of mice subjected to chronic pain stress. Moreover, chronic pain induced the increase of atrial PR interval, and atrial effective refractory periods as compared to the sham group, underlying the enhanced susceptibility of AF. Thus, autonomic cholinergic nerve may mediate mice AF in the setting of chronic pain.

Sulfate and chloride in the marine environment threaten the lifespan of concrete structures. Predicting the strength of concrete under different degrees of ion erosion is essential for marine structure design and maintenance. In this paper, a novel method was developed to predict the compressive strength evolution due to sulfate and chloride attack. The degradation and ion diffusion behavior of cement-based materials was investigated by analyzing the visual appearance, compressive strength, porosity, and ion distributions of mortar soaked in sulfate and chloride solutions with different concentrations. The damage degree was observed to increase with sulfate concentration and decrease with chloride concentration. Additionally, it was discovered that chloride and sulfate ions inhibited the diffusion of each other, and a higher concentration resulted in a more substantial inhibition effect. The total effective sulfate and chloride intrusions were proposed to describe the erosion degree of mortar based on the evaluation of the ion distributions with Fick’s second law. A compressive strength assessment method was established based on the analysis of the correlation between the strength contribution of sulfate reaction and the total effective chloride and sulfate intrusions. This method exhibits the potential for estimating the concrete strength of actual marine structures damaged by sulfate and chloride with accelerated laboratory tests.

EZH2 inhibitors (EZH2i), a class of small-molecule inhibitors that target EZH2 to exert anti-tumor functions, have just been approved by the US Food and Drug Administration (FDA) in treatment of adults and adolescents with locally advanced or metastatic epithelioid sarcoma. The application of EZH2i in several solid tumors is still in different stages of clinical trials and needs to be further validated. As a key epigenetic regulator, besides its role in controlling the proliferation of tumor cells, EZH2 has been implicated in the regulation of various immune cells including macrophages. But there are still controversial research results at present. Colorectal cancer (CRC) is a common malignant tumor that highly expresses EZH2, which has the third highest incidence and is the second leading cause of cancer-related death worldwide. Studies have shown that the numbers of M2-type tumor-associated macrophages (TAMs) are highly associated with the progression and metastasis of CRC. In the current study, we aim to investigate how EZH2 modulates the polarization of macrophages in the tumor microenvironment (TME) of CRC, and compare the role of two different EZH2 inhibitors, EPZ6438 and GSK126. We applied a 3D culture method to demonstrate that EZH2i did indeed suppress the proliferation of CRC cells in vitro. In vivo, we found that the percentage of CD206+ macrophages of the TME was decreased under the treatment of EPZ6438, but it increased upon GSK126 treatment. Besides, in the co-culture system of macrophages and CRC cells, EPZ6438 led to significant elevation of M1 markers and reduction of M2 markers. Furthermore, mechanistic studies validated by ChIP-qPCR demonstrated that EZH2i inhibit EZH2-mediated H3K27me3 levels on the promoters of STAT3, an essential transcription factor for M1 macrophage polarization. Therefore, our data suggested that EZH2i not only suppress CRC cell proliferation directly, but also regulate macrophage by skewing M2 into effector M1 macrophage to exert a tumor suppressive effect. Moreover, our study provided new insight for better understanding of the role of two kinds of EZH2i: EPZ6438 and GSK126, which may pave the way in treating CRC by targeting cancer cells and immune cells via this epigenetic approach in the future.

Abstract Background Kinesin superfamily proteins (KIFs) can transport membranous organelles and protein complexes in an ATP-dependent manner. Kinesin family member 15 (KIF15) is overexpressed in various cancers. However, the function of KIF15 in gastric cancer (GC) is still unclear. Methods GC patients’ data from The Cancer Genome Atlas (TCGA) were analyzed by bioinformatics methods. The expression of KIF15 was examined in GC and paracarcinoma tissues from 41 patients to verify the analysis results. The relationship between KIF15 expression and clinical characteristics were also observed by bioinformatics methods. Kaplan–Meier survival analysis of 122 GC patients in our hospital was performed to explore the relationship between KIF15 expression levels and GC patients’ prognosis. KIF15 was downregulated in GC cell lines AGS and SGC-7901 by transfecting a lentivirus-mediated shRNA plasmid targeting KIF15. In vitro, GC cell proliferation and apoptosis were detected by MTT assay, colony formation assay, and Annexin V-APC staining. In vivo, xenograft experiments were used to verify the in vitro results. Furthermore, Human Apoptosis Antibody Array kit was used to screen possible targets of KIF15 in GC cell lines. Results The bioinformatics results showed that KIF15 expression levels were higher in GC tissues than in normal tissues. IHC showed same results. High expression of KIF15 was statistical correlated with high age and early histologic stage. Kaplan–Meier curves indicated that high KIF15 expression predict poor prognosis in patients with GC. MTT assay and colony formation assay showed that KIF15 promote GC cell proliferation. Annexin V-APC staining found that KIF15 can inhibit GC cell apoptosis. Xenograft experiments reveal that downregulating KIF15 can inhibit GC tumor growth and promote GC apoptosis. Through detection of 43 anti-apoptotic proteins by the Human Apoptosis Antibody Array kit, it was confirmed that knocking down KIF15 can reduce seven anti-apoptotic proteins expression. Conclusions Taken together, our study revealed a critical role for KIF15 to inhibit GC cell apoptosis and promote GC cell proliferation. KIF15 may decrease anti-apoptotic proteins expression by regulating apoptosis pathways. High expression of KIF15 predicts a poor prognosis in patients with GC. KIF15 might be a novel prognostic biomarker and a therapeutic target for GC.

Abstract Background Circular RNAs (circRNAs) are a novel type of noncoding RNAs and play important roles in tumorigenesis, including gastric cancer (GC). However, the functions of most circRNAs remain poorly understood. In our study, we aimed to investigate the functions of a new circRNA circ-DONSON in GC progression. Methods The expression of circ-DONSON in gastric cancer tissues and adjacent normal tissues was analyzed by bioinformatics method, qRT-PCR, Northern blotting and in situ hybridization (ISH). The effects of circ-DONSON on GC cell proliferation, apoptosis, migration and invasion were measured by using CCK8, colony formation, EdU, immunofluorescence (IF), FACS and Transwell assays. qRT-PCR and Western blotting were utilized to validate how circ-DONSON regulates SOX4 expression. ChIP, DNA fluorescence in situ hybridization (DNA-FISH) and DNA accessibility assays were used to investigate how circ-DONSON regulates SOX4 transcription. The interaction between circ-DONSON and NURF complex was evaluated by mass spectrum, RNA immunoprecipitation (RIP), pulldown and EMSA assays. Xenograft mouse model was used to analyze the effect of circ-DONSON on GC growth in vivo. Results Elevated expression of circ-DONSON was observed in GC tissues and positively associated with advanced TNM stage and unfavorable prognosis. Silencing of circ-DONSON significantly suppressed the proliferation, migration and invasion of GC cells while promoting apoptosis. circ-DONSON was localized in the nucleus, recruited the NURF complex to SOX4 promoter and initiated its transcription. Silencing of the NURF complex subunit SNF2L, BPTF or RBBP4 similarly attenuated GC cell growth and increased apoptosis. circ-DONSON knockdown inhibited GC growth in vivo. Conclusion circ-DONSON promotes GC progression through recruiting the NURF complex to initiate SOX4 expression.

In this paper, a sparse optimization model with ℓ0-norm and the squared ℓ2-norm as the objective function is proposed for energy-efficient timetabling in subway systems by means of improving the regenerative braking energy utilization. Optimality analysis is addressed for the proposed sparse optimization problem. Specifically, the local minimizer is shown to be a KKT point without any additional constraint qualification. Moreover, based on the hard-thresholding operator, we yield an explicit formula for the Lagrangian dual problem for the proposed non-convex discontinuous optimization problem and achieve the strong duality under the stationarity condition. To evaluate the effectiveness of our proposed model for the energy-efficient timetabling, we design a hard-thresholding based alternating direction method of multipliers for solving the proposed model. The case study on Beijing Metro Yizhuang Line is conducted and the comparison to some recent existing approaches illustrates the effectiveness of our model in terms of energy saving rate and the efficiency of our proposed algorithm in terms of computation time.

We present a new approach, based on a multi-parameter back-propagation neural network (BPNN) model, to simultaneously retrieve sea surface wind speed, sea surface temperature, near-surface air temperature, and dewpoint temperature over the global oceans from the Advanced Microwave Scanning Radiometer 2 (AMSR2) onboard the Global Change Observation Mission 1st-Water (GCOM-W1). The model is trained and validated with the collocations of AMSR2 multi-channel (6.9–36.5 GHz) brightness temperatures, under both clear and cloudy conditions, and National Data Buoy Center (NDBC) and Tropical Atmosphere Ocean Project (TAO) buoy measurements along with ECMWF ERA5 reanalysis data. The root-mean-square (rms) errors of BPNN-retrieved sea surface wind speed, sea surface temperature, near-surface air temperature, and dewpoint temperature are 1.13 m/s, 1.02 °C, 1.20 °C, and 1.57 °C, respectively. The first three retrieved geophysical parameters and the estimated relative humidity from near-surface air temperature and dewpoint temperature are used to compute the sensible heat flux (SHF) and latent heat flux (LHF), using an improved bulk flux parametrization. The rms errors of the estimated SHF and LHF from BPNN-derived air–sea interface variables, and those from buoy and reanalysis data, are 18.13 W/m2 and 39.56 W/m2. We also compare SHF and LHF estimates with the Yongxing air–sea flux tower measurements in the northern South China Sea. The estimated SHF and LHF in summer and autumn periods are closer to observations than in winter and spring. The proposed method has potential to derive instantaneous air–sea interface atmospheric and oceanic parameters as well as surface sensible and latent heat fluxes from AMSR2 along-track wide swath observations.

Herbal medicines (HMs) are a major subset of complementary and alternative medicine. They have been employed for the efficient clinical management of type 2 diabetes mellitus (T2DM) for centuries. However, the related underlying mechanisms still remain to be elucidated. It has been found out that microbiota is implicated in the pathogenesis and treatment of T2DM. An interplay between gut microbiota and host occurs mainly at the gastrointestinal mucosal barrier. The host movements influence the composition and abundance of gut microbiota, whereas gut microbiota in turn modulate the metabolic and immunological activities of the host. Intestinal dysbiosis, endotoxin-induced metabolic inflammation, immune response disorder, bacterial components and metabolites, and decreased production of short-chain fatty acids are considered significant pathogenic mechanisms underlying T2DM. The interaction between gut microbiota and HMs during T2DM treatment has been investigated in human, animal, and in vitro studies. HMs regulate the composition of beneficial and harmful bacteria and decrease the inflammation caused by gut microbiota. Furthermore, the metabolism of gut microbiota modulates HM biotransformation. In this review, we have summarized such research findings, with the aim to improve our understanding of the pathogenesis and potential therapeutic mechanisms of HMs in T2DM and to provide new insights into specific targeted HM-based therapies and drug discovery.

ABSTRACT Accumulating evidence implicates gut microbiota as promising targets for the treatment of type 2 diabetes mellitus (T2DM). With a randomized clinical trial, we tested the hypothesis that alteration of gut microbiota may be involved in the alleviation of T2DM with hyperlipidemia by metformin and a specifically designed herbal formula (AMC). Four hundred fifty patients with T2DM and hyperlipidemia were randomly assigned to either the metformin- or AMC-treated group. After 12 weeks of treatment, 100 patients were randomly selected from each group and assessed for clinical improvement. The effects of the two drugs on the intestinal microbiota were evaluated by analyzing the V3 and V4 regions of the 16S rRNA gene by Illumina sequencing and multivariate statistical methods. Both metformin and AMC significantly alleviated hyperglycemia and hyperlipidemia and shifted gut microbiota structure in diabetic patients. They significantly increased a coabundant group represented by Blautia spp., which significantly correlated with the improvements in glucose and lipid homeostasis. However, AMC showed better efficacies in improving homeostasis model assessment of insulin resistance (HOMA-IR) and plasma triglyceride and also exerted a larger effect on gut microbiota. Furthermore, only AMC increased the coabundant group represented by Faecalibacterium spp., which was previously reported to be associated with the alleviation of T2DM in a randomized clinical trial. Metformin and the Chinese herbal formula may ameliorate type 2 diabetes with hyperlipidemia via enriching beneficial bacteria, such as Blautia and Faecalibacterium spp. IMPORTANCE Metabolic diseases such as T2DM and obesity have become a worldwide public health threat. Accumulating evidence indicates that gut microbiota can causatively arouse metabolic diseases, and thus the gut microbiota serves as a promising target for disease control. In this study, we evaluated the role of gut microbiota during improvements in hyperglycemia and hyperlipidemia by two drugs: metformin and a specifically designed Chinese herbal formula (AMC) for diabetic patients with hyperlipidemia. Both drugs significantly ameliorated blood glucose and lipid levels and shifted the gut microbiota. Blautia spp. were identified as being associated with improvements in glucose and lipid homeostasis for both drugs. AMC exerted larger effects on the gut microbiota together with better efficacies in improving HOMA-IR and plasma triglyceride levels, which were associated with the enrichment of Faecalibacterium spp. In brief, these data suggest that gut microbiota might be involved in the alleviation of diabetes with hyperlipidemia by metformin and the AMC herbal formula.

Background and Aim. Studies have shown an increasing number of type 2 diabetes (T2D) patients with concomitant obesity and hyperlipidemia syndromes, resulting from relevant metabolic disorders. However, there are few medications and therapies, which can thoroughly address these issues. Therefore, the current study evaluated the efficacy and safety of using JTTZ, a Chinese herbal formula, to treat T2D with obesity and hyperlipidemia. Methods. A total of 450 participants with T2D (HbA1c ≥ 7.0%; waist circumference ≥ 90 cm and 80 cm in males and females, resp.; and triglycerides (TG) ≥ 1.7 mmol/L) were randomly assigned, in equal proportions, to two groups in this multicenter randomized, positive-controlled, open-label trial. One group received JTTZ formula, and the other received metformin (MET) for 12 consecutive weeks. The primary efficacy outcomes were changes in HbA1c, TG, weight, and waist circumference. Adverse reactions and hypoglycemia were monitored. Results. HbA1c decreased by 0.75 ± 1.32% and 0.71 ± 1.2% in the JTTZ and MET groups, respectively, after 12 weeks of treatment. TG levels in the JTTZ and MET groups were reduced by 0.64 ± 2.37 mmol/L and 0.37 ± 2.18 mmol/L, respectively. Weight was decreased by 2.47 ± 2.71 kg in the JTTZ group and by 2.03 ± 2.36 kg in the MET group. JTTZ also appeared to alleviate insulin resistance and increase HOMA-β. In addition, symptoms were significantly relieved in participants in the JTTZ group compared to those in the MET group. One case of hypoglycemia was reported in the MET group. No severe adverse events were reported in either group. Conclusions. The JTTZ formula led to safe and significant improvements in the blood glucose, blood lipids, and weight levels; relieved symptoms; and enhanced β cell function for T2D patients with obesity and hyperlipidemia. The JTTZ formula has shown that it could potentially be developed as an alternative medicine for patients with T2D, particularly those who cannot tolerate metformin or other hypoglycemic drugs. This trial was registered with Clinicaltrials.gov NCT01471275.

A 41-wk growth trial was conducted to evaluate the effects of dietary protein levels on the long-term growth response and fitting growth models of gibel carp (Carassius auratus gibelio) with an initial body weight of 1.85 ± 0.17 g. The dietary protein levels were designed at 320 (P32), 360 (P36), 400 (P40), and 440 g/kg (P44), respectively. The growth curves of the gibel carp for each group were fitted and analyzed with four nonlinear regression models (Gompertz, logistic, von Bertalanffy and Richards). The final body weights (mean ± SD) of the fish were 226 ± 6, 231 ± 7, 242 ± 2, and 236 ± 2 g for P32, P36, P40, and P44, respectively. Feed conversion ratio of P40 and P44 groups was significantly lower than that of P32 and P36 groups (P

The quick growth of energy consumption in urban rail transit has drawn much attention due to the pressure of both operational cost and environmental responsibilities. In this paper, the timetable is optimized with respect to the system cost of urban rail transit, which pays more attention to energy consumption. Firstly, we propose a Mixed-Integer Non-Linear Programming (MINLP) model including the non-linear objective and constraints. The objective and constraints are linearized for an easier process of solution. Then, a Mixed-Integer Linear Programming (MILP) model is employed, which is solved using the commercial solver Gurobi. Furthermore, from the viewpoint of system cost, we present an alternative objective to optimize the total operational cost. Real Automatic Fare Collection (AFC) data from the Changping Line of Beijing urban rail transit is applied to validate the model in the case study. The results show that the designed timetable could achieve about a 35% energy reduction compared with the maximum energy consumption and a 6.6% cost saving compared with the maximum system cost.

Urotensin II (UII), a somatostatin-like cyclic peptide, is involved in tumor progression due to its mitogenic effect. Our previous study demonstrated that UII and its receptor UT were up-regulated in human hepatocellular carcinoma (HCC), and exogenous UII promoted proliferation of human hepatoma cell line BEL-7402. Hepatic progenitor cell (HPCs) are considered to be one of the origins of liver cancer cells, but their relationship with UII remains unclear. In this work, we aimed to investigate the effect of UII on ROS generation in HPCs and the mechanisms of UII-induced ROS in promoting cell proliferation. Human HCC samples were used to examine ROS level and expression of NADPH oxidase. Hepatic oval cell line WB-F344 was utilized to investigate the underlying mechanisms. ROS level was detected by dihydroethidium (DHE) or 2', 7'-dichlorofluorescein diacetate (DCF-DA) fluorescent probe. For HCC samples, ROS level and expression of NADPH oxidase were significantly up-regulated. In vitro, UII also increased ROS generation and expression of NADPH oxidase in WB-F344 cells. NADPH oxidase inhibitor apocynin pretreatment partially abolished UII-increased phosphorylation of PI3K/Akt and ERK, expression of cyclin E/cyclin-dependent kinase 2. Cell cycle was then analyzed by flow cytometry and UII-elevated S phase proportion was inhibited by apocynin pretreatment. Finally, bromodeoxyuridine (Brdu) incorporation assay showed that apocynin partially abolished UII induced cell proliferation. In conclusion, this study indicates that UII-increased ROS production via the NADPH oxidase pathway is partially associated with activation of the PI3K/Akt and ERK cascades, accelerates G1/S transition, and contributes to cell proliferation. These results showed that UII plays an important role in growth of HPCs, which provides novel evidence for the involvement of HPCs in the formation and pathogenesis of HCC.

Esophageal cancer is associated with high mortality rates and is one of the cancers with the worst prognosis. Its incidence has significant regional specificity, particularly in China where it is much higher than in other countries. Moreover, effective diagnostic markers, therapeutic targets, and molecular subtyping biomarkers are currently lacking for esophageal cancer. Nevertheless, large-scale omics studies have identified dozens of robust genetic risk loci and prognosis-related loci, drawn genomic, epigenomic, and transcriptomic maps of esophageal cancer at multiple molecular levels, and described significant differences between esophageal squamous cell carcinoma and adenocarcinoma. These studies are of great significance for exploring the occurrence and development mechanism of esophageal cancer, guiding clinical treatment, and improving patient prognosis. This review, from the perspective of multi-omics, discusses the analytical strategies employed in these studies and summarizes their core findings. It emphasizes that the integration and analysis of multi-omics data is a key focus and development trend in the precise medical research of esophageal cancer, and has broad research and application prospects. [ABSTRACT FROM AUTHOR]