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Fetal alcohol spectrum disorder (FASD) encompasses neurodevelopmental disabilities and physical birth defects associated with prenatal alcohol exposure. Previously, we attempted to identify epigenetic biomarkers for FASD by investigating the genome-wide DNA methylation (DNAm) profiles of individuals with FASD compared to healthy controls. In this study, we generated additional gene expression profiles in a subset of our previous FASD cohort, encompassing the most severely affected individuals, to examine the functional integrative effects of altered DNAm status on gene expression. We identified six differentially methylated regions (annotated to the SEC61G, REEP3, ZNF577, HNRNPF, MSC, and SDHAF1 genes) associated with changes in gene expression (p-value < 0.05). To the best of our knowledge, this study is the first to assess whole blood gene expression and DNAm-gene expression associations in FASD. Our results present novel insights into the molecular footprint of FASD in whole blood and opens opportunities for future research into multi-omics biomarkers for the diagnosis of FASD.

To assess value of placental vascularization indices (PVIs) for predicting preeclampsia (PE) and fetal growth restriction (FGR) in different stages of pregnancy in high-risk women.PVIs derived from 3-dimensional power doppler(3DPD) imaging were measured at seven stages of pregnancy: 11-13Adverse outcomes occurred in 10.9% of pregnancies. Statistical differences appeared in 32-36VI and VFI were valuable for predicting PE and FGR at the 32-36

Background and AimsHistone deacetylase inhibitors [HDACi] exert potent anti-inflammatory effects. Because of the ubiquitous expression of HDACs, clinical utility of HDACi is limited by off-target effects. Esterase-sensitive motif [ESM] technology aims to deliver ESM-conjugated compounds to human mononuclear myeloid cells, based on their expression of carboxylesterase 1 [CES1]. This study aims to investigate utility of an ESM-tagged HDACi in inflammatory bowel disease [IBD].MethodsCES1 expression was assessed in human blood, in vitro differentiated macrophage and dendritic cells, and Crohn’s disease [CD] colon mucosa, by mass cytometry, quantitative polymerase chain reaction [PCR], and immunofluorescence staining, respectively. ESM-HDAC528 intracellular retention was evaluated by mass spectrometry. Clinical efficacy of ESM-HDAC528 was tested in dextran sulphate sodium [DSS]-induced colitis and T cell transfer colitis models using transgenic mice expressing human CES1 under the CD68 promoter.ResultsCES1 mRNA was highly expressed in human blood CD14+ monocytes, in vitro differentiated and lipopolysaccharide [LPS]-stimulated macrophages, and dendritic cells. Specific hydrolysis and intracellular retention of ESM-HDAC528 in CES1+ cells was demonstrated. ESM-HDAC528 inhibited LPS-stimulated IL-6 and TNF-α production 1000 times more potently than its control, HDAC800, in CES1high monocytes. In healthy donor peripheral blood, CES1 expression was significantly higher in CD14++CD16- monocytes compared with CD14+CD16++ monocytes. In CD-inflamed colon, a higher number of mucosal CD68+ macrophages expressed CES1 compared with non-inflamed mucosa. In vivo, ESM-HDAC528 reduced monocyte differentiation in the colon and significantly improved colitis in a T cell transfer model, while having limited potential in ameliorating DSS-induced colitis.ConclusionsWe demonstrate that monocytes and inflammatory macrophages specifically express CES1, and can be preferentially targeted by ESM-HDAC528 to achieve therapeutic benefit in IBD.

In this article, we propose a novel switching-table-based direct torque control (ST-DTC) method to eliminate the current harmonics in dual-three-phase permanent-magnet synchronous machines due to the back electromotive force (back EMF) harmonics and voltage vector selection. By employing a novel space voltage vector selection strategy and the optimal action time for different groups of vectors, a novel ST-DTC method is developed. Furthermore, in order to implement standard pulsewidth modulation (PWM) switching sequence, a centralization PWM method for 36 voltage vectors is introduced. The proposed method can effectively reduce the phase current harmonics caused by both back EMF distortion and voltage vector selection, and still reserve the advantages of the conventional ST-DTC, such as fast torque response and simple structure. Its effectiveness is verified by simulations and experiments.

The S3 level clinical practice guideline for the treatment of stage Ⅳperiodontitis, developed by the European Federation of Periodontology, was published in April 22, 2022 (DOI: 10.1111/jcpe.13639). According to the severity and complexity, stage Ⅳ periodontitis was grouped into four case types, and comprehensive treatment plans were formulated correspondingly in the guideline, including tooth splinting, occlusal adjustment, orthodontic therapy, restorative therapy, and personalized supportive periodontal care as well. The aim of present work is to intensively interpret the key points of the guideline and help the clinicians to understand this guideline better, in order to improve the treatment level of stage Ⅳ periodontitis in China.欧洲牙周病学会（European Federation of Periodontology）于2022年4月发布了Ⅳ期牙周炎治疗S3级临床指南（DOI：10.1111/jcpe.13639），该指南根据Ⅳ期牙周炎的严重性和复杂性，将其分为4种类型，并制订了相应的综合治疗方案，包括牙周夹板、调（牙合）、正畸、修复治疗和个性化的牙周支持治疗，以防止其复发。本文旨在对该指南进行要点梳理和解读，以帮助临床医师更好地理解这一指南，提高我国Ⅳ期牙周炎的治疗水平。.

Calibration-free laser-induced breakdown spectroscopy (CF-LIBS) is a very useful elemental analysis technique. However, it requires knowledge of transition probabilities of the analytical lines. To solve this problem, a variant one-point calibration (OPC) LIBS method was proposed. Quantitative elemental analysis on Cu-Zn-Ag-Au alloys was realized with this method capable of using zinc analytical lines with unknown transition probabilities. The relative error was demonstrated to be less than 3.3%. This variant OPC method will be helpful for quantitative elemental analysis of different samples using CF-LIBS, no matter whether the transition probabilities of the observed lines are known or unknown.

Coherent elastic neutrino-nucleus scattering (CE$\nu$NS) represents a powerful tool to investigate key electroweak physics parameters and neutrino properties since its first observation in 2017 by the COHERENT experiment exploiting the spallation neutron source at Oak Ridge National Laboratory. In light of the recent detection of such a process with antineutrinos produced by the Dresden-II reactor scattering off a germanium detector, we revisit the limits so far set on the neutrino magnetic moments, charge radii and millicharges as well as on the weak mixing angle. In order to do so, we also include the contribution of elastic neutrino-electron scattering, whose effect becomes non negligible in some beyond the Standard Model theories. By using different hypotheses for the germanium quenching factor and the reactor antineutrino flux, we provide a measurement of the weak mixing angle at the low-energy scale of the Dresden-II reactor experiment and, thanks to a combined analysis with the latest cesium iodide and argon data set released by the COHERENT Collaboration, we deliver updated limits for the neutrino electromagnetic properties. Interestingly, we are able to set a new best upper limit on the electron neutrino charge radius and significantly improve the other CE$\nu$NS-related limits on the neutrino electric charge and magnetic moment., Comment: Matches the published version. 33 pages, 11 figures

Prediction of endoscopic post-operative recurrence (POR) in Crohn’s disease (CD) patients following ileocolonic resection (ICR) using clinical risk factors alone has thus far been inadequate. While peripheral blood leukocyte (PBL) DNA methylation has shown promise as a tool for predicting recurrence in cancer, no data in CD patients exists. Therefore, this study explored the association and predictive value of PBL DNA methylation in CD patients following ICR. From a cohort of 117 CD patients undergoing ICR, epigenome-wide PBL methylation profiles from 25 carefully selected patients presenting either clear endoscopic remission (n = 12) or severe recurrence (n = 13) were assessed using the Illumina MethylationEPIC (850K) array. No statistically significant differentially methylated positions (DMPs) or regions (DMRs) associated with endoscopic POR were identified (FDR p ≤ 0.05), further evidenced by the low accuracy (0.625) following elastic net classification analysis. Nonetheless, interrogating the most significant differences in methylation suggested POR-associated hypermethylation in the MBNL1, RAB29 and LEPR genes, respectively, which are involved in intestinal fibrosis, inflammation and wound healing. Notably, we observed a higher estimated proportion of monocytes in endoscopic POR compared to remission. Altogether, we observed limited differences in the genome-wide DNA methylome among CD patients with and without endoscopic POR. We therefore conclude that PBL DNA methylation is not a feasible predictive tool in post-operative CD.

Background SP140 is a bromodomain-containing protein expressed predominantly in immune cells. Genetic polymorphisms and epigenetic modifications in the SP140 locus have been linked to Crohn’s disease (CD), suggesting a role in inflammation. Results We report the development of the first small molecule SP140 inhibitor (GSK761) and utilize this to elucidate SP140 function in macrophages. We show that SP140 is highly expressed in CD mucosal macrophages and in in vitro-generated inflammatory macrophages. SP140 inhibition through GSK761 reduced monocyte-to-inflammatory macrophage differentiation and lipopolysaccharide (LPS)-induced inflammatory activation, while inducing the generation of CD206+ regulatory macrophages that were shown to associate with a therapeutic response to anti-TNF in CD patients. SP140 preferentially occupies transcriptional start sites in inflammatory macrophages, with enrichment at gene loci encoding pro-inflammatory cytokines/chemokines and inflammatory pathways. GSK761 specifically reduces SP140 chromatin binding and thereby expression of SP140-regulated genes. GSK761 inhibits the expression of cytokines, including TNF, by CD14+ macrophages isolated from CD intestinal mucosa. Conclusions This study identifies SP140 as a druggable epigenetic therapeutic target for CD.

Preventive chemotherapy is one of the pivotal interventions for the control and elimination of schistosomiasis, which is effective to reduce the morbidity and prevalence of schistosomiasis. In order to promote the United Nations' sustainable development goals and the targets set for schistosomiasis control in the

Background Vagus nerve stimulation has been suggested to affect immune responses, partly through a neuronal circuit requiring sympathetic innervation of the splenic nerve bundle and norepinephrine (NE) release. Molecular and cellular mechanisms of action remain elusive. Here, we investigated the therapeutic value of this neuromodulation in inflammatory bowel disease (IBD) by applying electrical splenic nerve bundle stimulation (SpNS) in mice with dextran sulfate sodium (DSS)-induced colitis. Methods Cuff electrodes were implanted around the splenic nerve bundle in mice, whereupon mice received SpNS or sham stimulation. Stimulation was applied 6 times daily for 12 days during DSS-induced colitis. Colonic and splenic tissues were collected for transcriptional analyses by qPCR and RNA-sequencing (RNA-seq). In addition, murine and human splenocytes were stimulated with lipopolysaccharide (LPS) in the absence or presence of NE. Single-cell RNA-seq data from publicly available data sets were analyzed for expression of β-adrenergic receptors (β-ARs). Results Colitic mice undergoing SpNS displayed reduced colon weight/length ratios and showed improved Disease Activity Index scores with reduced Tumor Necrosis Factor α mRNA expression in the colon compared with sham stimulated mice. Analyses of splenocytes from SpNS mice using RNA-seq demonstrated specific immune metabolism transcriptome profile changes in myeloid cells. Splenocytes showed expression of β-ARs in myeloid and T cells. Cytokine production was reduced by NE in mouse and human LPS-stimulated splenocytes. Conclusions Together, our results demonstrate that SpNS reduces clinical features of colonic inflammation in mice with DSS-induced colitis possibly by inhibiting splenic myeloid cell activation. Our data further support exploration of the clinical use of SpNS for patients with IBD.

Five strategies were recommended by the American Association of Clinical Endocrinologists/American College of Endocrinology (AACE/ACE) guidelines for the treatment of postmenopausal osteoporosis (PMO) patients with a very high fracture risk. We aimed to assess their cost-effectiveness in the United States (US).A microsimulation Markov model was created to compare the cost-effectiveness of five treatment strategies, including zoledronate, denosumab, abaloparatide, teriparatide, and romosozumab in PMO patients with a recent fracture from the healthcare perspective of the US. The data used in the model were obtained from published studies or online resources. Base-case analysis, one-way deterministic sensitivity analysis (DSA) and probability sensitivity analysis (PSA) were conducted for 65-, 70-, 75-, and 80-year-old patients.In base case, at 65 years, zoledronate was the cheapest strategy. The incremental cost-effectiveness ratios (ICER, which represent incremental costs per QALY gained) of denosumab, teriparatide, abaloparatide, and romosozumab against zoledronate were $13,020/QALY (quality-adjusted years), $477,331 /QALY, $176,287/QALY, and $98,953/QALY, respectively. Under a willing-to-pay (WTP, which means the highest price a consumer will pay for one unit of a good of service) threshold of $150,000/QALY, denosumab and romosozumab were cost-effective against zoledronate. The PSA results showed that denosumab was the most cost-effective option with WTP thresholds of $50,000/QALY, $100,000/QALY and $150,000/QALY. The results were similar in other age groups. The DSA results indicated that the most common parameters that have important influence on the outcome were drug persistence, incidence of adverse events, the efficacy of drugs on hip fractures and the cost of the drug.Among PMO patients with a very high fracture risk in the US, zoledronate is the cheapest strategy and denosumab is the most cost-effective choice among these five strategies.

Partially-depleted silicon-on-insulator (PDSOI) MOSFETs with full dielectric isolation structure are widely used in the high temperature field of 225 °C, but affected by the threshold voltage and carrier mobility, the saturated output current has a rate of change as high as 24.9% at 25 °C–300 °C, which will reduce the working speed and accuracy of the analog circuit. This paper studies the high temperature output current characteristics of ultra-thin body and buried oxide (UTBB) fully-depleted silicon-on-insulator (FDSOI) MOSFETs with the 28 nm low voltage threshold structure. The experimental results show that when the gate voltage of the device is constant, the saturation current change of 28 nm short-channel FDSOI device is 1.93% in the temperature range from 25 °C to 300 °C, which is 12.9 times more stable than that of 0.13 μm PDSOI device, 4.5 times and 8.4 times higher than that of 0.3 μm and 2 μm long-channel FDSOI device. When the gate voltage of the device drifts from the zero-temperature coefficient (ZTC) point by ±10%–±20%, the output current change of the short-channel FDSOI device is still the lowest. It is proved by theory and simulation that the low temperature change rate of the carrier velocity of the short-channel FDSOI device is the main factor affecting the stability of the output current. From the analysis of the saturation current model and the ZTC operating point, reducing the gate operating voltage of the device or increasing the threshold voltage of the device can further improve the stability of the output current at high temperatures. The research in this paper proves that the 28 nm UTBB FDSOI device has good high temperature saturation current stability, which can well meet the output current stability requirements of high temperature analog circuits.

The most serious fire scene in a subway system is that a train catching on fire has to stop in the tunnel. The objective of this paper is to discuss safety evacuation of this scenario. A subway tunnel in Beijing was selecting as research object, and adopting numerical simulation methods to analyze smoke propagation in the tunnel and train carriage. In addition, the influence of train carriage door opening on the smoke spread was studied in the double narrow space formed by the carriage and tunnel. Results show that the opening method of door would affect the smoke spreading path, and the range of high temperature area. For a fire occurred in train carriage, opening of the end door of train can effectively enhance diffusion of smoke into the tunnel. This research is not only helpful to guide the cabin crew to evacuate efficiently and orderly, but also provide guidance for the planning of subway tunnels.

BackgroundPrimary sclerosing cholangitis (PSC) is a chronic inflammatory liver disease affecting the intra- and extrahepatic bile ducts, and is strongly associated with ulcerative colitis (UC). In this study, we explored the peripheral blood DNA methylome and its immune cell composition in patients with PSC-UC, UC, and healthy controls (HC) with the aim to develop a predictive assay in distinguishing patients with PSC-UC from those with UC alone.MethodsThe peripheral blood DNA methylome of male patients with PSC and concomitant UC, UC and HCs was profiled using the Illumina HumanMethylation Infinium EPIC BeadChip (850K) array. Differentially methylated CpG position (DMP) and region (DMR) analyses were performed alongside gradient boosting classification analyses to discern PSC-UC from UC patients. As observed differences in the DNA methylome could be the result of differences in cellular populations, we additionally employed mass cytometry (CyTOF) to characterize the immune cell compositions.ResultsGenome wide methylation analysis did not reveal large differences between PSC-UC and UC patients nor HCs. Nonetheless, using gradient boosting we were capable of discerning PSC-UC from UC with an area under the receiver operator curve (AUROC) of 0.80. Four CpG sites annotated to the NINJ2 gene were found to strongly contribute to the predictive performance. While CyTOF analyses corroborated the largely similar blood cell composition among patients with PSC-UC, UC and HC, a higher abundance of myeloid cells was observed in UC compared to PSC-UC patients.ConclusionDNA methylation enables discerning PSC-UC from UC patients, with a potential for biomarker development.

To explore the in vitro and in vivo experimental study of thioredoxin-1(Trx1) inhibitor 1-methylpropyl 2-imidazolyl disulfide (PX-12) promoting multiple myeloma H929 cell apoptosis, investigate the relationship between the inhibitory effect of PX-12 on H929 cells and reactive oxygen species (ROS).Inhibition of PX-12 on H929 cells in relation to reactive oxygen species (ROS), cell cycle, and apoptosis were assessed by flow cytometry. ELISA kit, IVIS Imaging, Hematoxylin and eosin (HE) staining and immunohistochemical staining assessment were applied to assess the anti-myeloma effect in the SCID mice model established by H929EL cells.PX-12 inhibited proliferation of H929 cells performed time and dose dependent style. Furthermore, it significantly induced a G2/M phase arrest of the cell cycle in H929 cells. It also increased intracellular ROS and caspase-3 activity in H929 cells indicating that cells have undergone apoptosis. There was an almost 3-5-fold decrease in tumor viability measured by the Living-Imaging system after 21 and 28 days after PX-12 injection compared with the control group. Importantly, PX-12 caused significant decrease in expression of Kappa chain in vivo assessed by immunohistochemical staining.The results suggest that PX-12 may be a potential strategy for the treatment of MM, and the inhibition of TRX-1 in the treatment of myeloma deserves further research.

We present the constraints on the parameters of several light boson mediator models obtained from the analysis of the current data of the COHERENT CE$\nu$NS experiment. We consider a variety of vector boson mediator models: the so-called universal, the $B-L$ and other anomaly-free $U(1)'$ gauge models with direct couplings of the new vector boson with neutrinos and quarks, and the anomaly-free $L_e-L_\mu$, $L_e-L_\tau$, and $L_\mu-L_\tau$ gauge models where the coupling of the new vector boson with the quarks is generated by kinetic mixing with the photon at the one-loop level. We consider also a model with a new light scalar boson mediator that is assumed, for simplicity, to have universal coupling with quarks and leptons. Since the COHERENT CE$\nu$NS data are well-fitted with the cross section predicted by the Standard Model, the analysis of the data yields constraints for the mass and coupling of the new boson mediator that depend on the charges of quarks and neutrinos in each model under consideration. We compare these constraints with the limits obtained in other experiments and with the values that can explain the muon $g-2$ anomaly in the models where the muon couples to the new boson mediator., Comment: 31 pages, 9 figures, published in JHEP

Peripheral nerve injuries are mainly related to severe trauma, fracture and tumor surgery, leading to reduced quality of life and impaired physical and mental health. The repair of peripheral nerve still faces great challenges in clinic, and the research on the regeneration and repair of peripheral nerve has become a hot issue in related disciplines. Cell therapy plays an irreplaceable role in tissue regeneration and repair. Schwann cells are ideal cells for peripheral nerve repair, but their limited sources inhibit the clinical application. Dental pulp stem cells are derived from neural crest, which provides a new cell source for nerve regeneration. The purpose of this article is to review the research progress of dental pulp stem cells for peripheral nerve repair.周围神经损伤（peripheral nerve injury，PNI）严重影响患者的生命质量及身心健康，并且损伤后的修复在临床上仍面临巨大挑战，PNI与再生修复研究是当今各相关学科研究的热点问题。细胞疗法在组织再生与修复中具有不可替代的作用。施万细胞是周围神经修复的理想细胞，但来源有限等缺点限制了其临床应用。牙髓干细胞来源于神经嵴，为神经再生提供了新的细胞来源。本文就牙髓干细胞修复PNI的研究现状进行综述。.

Additional file 1. SplX did not affect outcome of DSS-induced colitis. [A] Bodyweight loss of mice over time, compared with day 0. Data are expressed as mean and standard deviation (SD). [B] Disease activity index. [C] Colon length. [D] mRNA levels of IL-1β, IL-6 and TNF-α. mRNA levels are normalized against the reference genes Cyclophilin and RPLP0. N = 8–10 per group. Data are expressed as mean or median and individual data points. * indicates a significant difference compared to control. Statistical differences between control and DSS-treated mice and between sham mice and SplX were assessed using an independent t-test or a Mann–Whitney U test. P < 0.05 was considered significant. DSS: dextran sulfate sodium; Splx: absence of splenic innervation; TNF: tumor necrosis factor; IL: interleukin; LPS: lipopolysaccharide; RPLP0: Ribosomal Protein Lateral Stalk Subunit P0.

Additional file 3. Implanted cuff electrodes in this study. [A] Picture of implanted 100 µm micro cuff sling (CorTec GmbH) around splenic nerve bundle. [B] Scheme of electrical pulse parameters used.

Additional file 2. VNS does not affect DSS-induced colitis. [A] Bodyweight loss of mice over time, compared with day 0. Data are expressed as mean and SD. [B] Histology score. [C] Colon weight/length ratio, endoscopy score and DAI. [D] mRNA levels of TNF-α, IL-6, IL-1α, IL-1β, IL-10, IL-12. mRNA levels are normalized for reference genes Nono and RPLP0. N = 16, only female mice. Data are expressed as median and individual data points. Statistical differences between sham and stim mice were assessed using an independent Mann–Whitney U test. P < 0.05 was considered significant. VNS: vagus nerve stimulation; TNF: tumor necrosis factor; IL: interleukin; Nono: Non-POU domain-containing octamer-binding protein; RPLP0: Ribosomal Protein Lateral Stalk Subunit P0.

Additional file 4. Schematic overview of experimental setup for SpNS. Differentially expressed genes were assessed between colonic samples of mice that did not receive stimulation or DSS, sham stimulated mice with DSS-induced colitis, and SpNS-treated mice with DSS-induced colitis. SpNS: splenic nerve bundle stimulation; DSS: dextran sulfate sodium.

Cystic echinococcosis (CE), caused by the cestode Echinococcus granulosus, is a worldwide chronic zoonosis. Albendazole (ABZ) and mebendazole are effective against CE, but a high dosage in a long-term period is usually required. In this study, we evaluate the effects of DNA damage repair inhibitor (i.e., Veliparib) in combination with artesunate (AS) on hydatid cysts. For the in vitro assay, protoscoleces of E. granulosus (E.g PSCs) were incubated with low AS (AS-L, 65 μM), moderate AS (AS-M, 130 μM), and high AS (AS-H, 325 μM), AS-L/M/H+Veliparib (10 μM), and ABZ (25 μM), respectively. The AS-H+Veliparib group showed the maximal protoscolicidal effects. Ultrastructural change revealed that germinal layer (GL) cells were reduced, and lipid droplets appeared. AS could induce DNA injuries in PSCs. The 8-OHdG was expressed in the PSCs and GL of the cysts in mice, especially in the presence of Veliparib. The most severe DNA damages were observed in the AS-H+Veliparib group. Meanwhile, the expression of ribosomal protein S9 (RPS9) gene in the AS-H+Veliparib group was significantly lower than that in the AS-H group. The in vivo chemotherapeutic effects of AS-L (50 mg/kg), AS-H (200 mg/kg), and AS-H+Veliparib (25 mg/kg) were assessed in experimentally infected mice. Upon 6 weeks of oral administration, ultrasonography was used to monitor the volume change of vesicles. Maximum potentiation was seen on day 15 with values (versus AS) of 34 (P<0.05) for AS-H + Veliparib. It led to the reduction of cyst weight (55.40%) compared with the model group (P<0.01), which was better than AS alone (52.84%) and ABZ-treated mice (55.35%). Analysis of cysts collected from AS-H+Veliparib-treated mice by transmission electron microscopy revealed a drug-induced structural destruction. The structural integrity of the germinal layer was lost, and the majority of the microtriches disappeared. In conclusion, our study demonstrates that AS or AS in combination with Veliparib is effective for treating CE, especially the combination group. On this basis, AS represented promising drug candidates in anti-CE chemotherapy.

We consider a compound Poisson insurance risk model perturbed by diffusion with stochastic return on investment and debit interest. If the initial surplus is nonnegative, then the insurance company can invest this surplus in a risky asset and risk-free asset based on a fixed proportion. Otherwise, if the surplus is negative, then the insurance company can get the business loan. The integrodifferential equations for the function generating moments of the values of cumulative dividends are obtained for the barrier and threshold dividend strategies, respectively. The expected dividend value is obtained in the closed form in the case where the claim amount is exponentially distributed.

目的 探讨急性髓系白血病（AML）自发缓解的临床特点及可能的机制。 方法 回顾性分析郑州大学第一附属医院诊治的1例伴有MLL-AF9基因重排和肝功能损伤的AML自发缓解患者的临床资料，并进行相关文献报道病例汇总分析。 结果 该患者伴有MLL-AF9基因重排，经历了肺部感染、发热、肝功能损伤，治疗上给予抗感染、输注血制品，未经化疗，患者获完全缓解（CR），随访35个月，仍处于CR，期间伴有轻度间接胆红素升高。1990年至2021年6月文献报道的有骨髓检测支持的AML（非急性早幼粒细胞白血病）自发缓解患者56例，与本次报道的1例汇总分析，共57例患者，其中男37例，女20例，中位年龄51（20～83）岁，中位缓解时间为5个月，52例患者获得CR，5例具有染色体核型资料的长期缓解且至今未复发的病例，3例为正常染色体核型，2例伴有t（9;11）（q21;q23）异常。 结论 AML自发缓解罕见，可能与免疫抑制、基因均有关。

SummaryAnastomotic leakage (AL) is a frequent and potentially life-threatening postoperative complication in patients undergoing colorectal surgery with a multifactorial yet unknown pathophysiology. In the present study, we aimed to unravel AL etiology and intestinal anastomotic healing (AH) physiology focusing on both host epithelial and gut microbial components. We make use of patients-related samples and two high throughput next generation sequencing analysis approaches, including anastomotic tissue-associated bulk RNA sequencing and preoperative fecal 16S rRNA gene sequencing. We find that in the absence of host epithelial gene expression differences, the preoperative fecal microbiota of patients who undergo colorectal resection with successful AH differs in the group of patients who develop AL in the abundance of Prevotella and suggests a potential beneficial role of Prevotella that may prove useful as predictive biomarker for AH.

Temporomandibular joint (TMJ) is a unique synovial joint in mammals. There have been many reports on the structure and function of TMJ during embryonic development.Although studies on TMJ related signal molecules and transcription factors during embryonic development have been carried out since the last century, there are few reports on the molecular genetic regulation of TMJ compared with the abundant molecular regulation information of synovial joint. The studies on signal molecules and transcription factors of TMJ embryonic development were mainly conducted in rodents.There were few studies on the regulatory molecules and their regulatory mechanisms related to the development of TMJ conducted in large mammals and human embryos. This article reviews the research progress of key signal molecules and transcription factors of TMJ in embryonic development on the basis of modern molecular biology technology in order to find more core regulatory molecules and understand their regulation mechanism on TMJ development.颞下颌关节（temporomandibular joint，TMJ）是哺乳动物特有的滑膜关节，在胚胎发育期的结构和功能已多有报道。尽管自20世纪就开展了胚胎发育期TMJ相关信号分子与转录因子的研究，然而与四肢滑膜关节丰富的分子调控信息相比，对TMJ的分子遗传控制信息还知之甚少。关于TMJ胚胎发育的信号分子与转录因子研究主要以啮齿类动物为主，大型哺乳动物与人类胚胎期TMJ发育相关调控分子以及它们的调控机制研究鲜有报道。为了在现代分子生物学技术的基础上发现更多、更核心的调控分子并了解其对TMJ发育的调控机制，本文对当前TMJ胚胎发育中的关键信号分子与转录因子的研究进展进行综述。.

Background: Myeloid cells are critical determinants of the sustained inflammation in Crohn’s Disease (CD). Targeting such cells may be an effective therapeutic approach for refractory CD patients. Bromodomain and extra-terminal domain protein inhibitors (iBET) are potent anti-inflammatory agents; however, they also possess wide-ranging toxicities. In the current study, we make use of a BET inhibitor containing an esterase sensitive motif (ESM-iBET), which is cleaved by carboxylesterase-1 (CES1), a highly expressed esterase in mononuclear myeloid cells. Methods: We profiled CES1 protein expression in the intestinal biopsies, peripheral blood, and CD fistula tract (fCD) cells of CD patients using mass cytometry. The anti-inflammatory effect of ESM-iBET or its control (iBET) were evaluated in healthy donor CD14+ monocytes and fCD cells, using cytometric beads assay or RNA-sequencing. Results: CES1 was specifically expressed in monocyte, macrophage, and dendritic cell populations in the intestinal tissue, peripheral blood, and fCD cells of CD patients. ESM-iBET inhibited IL1β, IL6, and TNFα secretion from healthy donor CD14+ monocytes and fCD immune cells, with 10- to 26-fold more potency over iBET in isolated CD14+ monocytes. Transcriptomic analysis revealed that ESM-iBET inhibited multiple inflammatory pathways, including TNF, JAK-STAT, NF-kB, NOD2, and AKT signaling, with superior potency over iBET. Conclusions: We demonstrate specific CES1 expression in mononuclear myeloid cell subsets in peripheral blood and inflamed tissues of CD patients. We report that low dose ESM-iBET accumulates in CES1-expressing cells and exerts robust anti-inflammatory effects, which could be beneficial in refractory CD patients.

Myopia has become an important global public health problem, especially in East Asia. Due to its high prevalence and multiple ocular complications, it is imperative to take effective measures against the development of myopia. Recent studies have shown that outdoor activity is one of the protective factors for myopia and sunlight can delay the progression of myopia. As a possible mediator between sunlight and myopia, vitamin D gradually comes into public view. Vitamin D refers to a kind of secosteroids responsible for regulating calcium and phosphate metabolism. In addition to this main function, it is also correlated with many eye diseases like diabetic retinopathy, age-related macular degeneration, glaucoma etc. This review summarizes relevant epidemiologic and genetic studies as well as possible biological mechanisms to provide theoretical reference for the plausible application of vitamin D in the prevention and therapy of myopia. (近视眼已成为一个重要的全球性健康问题，在东亚地区尤为严重。鉴于其患病率高，眼部并发症多，目前急需采取有效措施遏止近视眼患病人数的迅猛发展。近期研究结果表明，户外活动是近视眼的保护因素，且日光可以延缓近视眼的进展，因而作为日光与近视眼之间潜在媒介的维生素D便逐渐进入人们的视野中。维生素D是一种脂溶性维生素，主要负责调节钙磷代谢，此外它还与多种眼病相关，例如糖尿病视网膜病变、年龄相关性黄斑变性、青光眼等。本文总结了与维生素D和近视眼相关的流行病学研究和遗传学研究成果，并探讨了可能的生物学机制，为利用维生素D进行近视眼防治提供理论参考

In this study, we sought to characterize synovial tissue obtained from individuals with arthralgia and disease-specific auto-antibodies, and patients with established rheumatoid arthritis (RA) by applying an integrative multi-omics approach where we investigated changes at the level of DNA methylation and gene expression and its relation to disease pathogenesis. We performed genome-wide DNA methylation and gene expression profiling of synovial tissue obtained from the knee and ankle from 4 auto-antibody positive arthralgia patients and thirteen RA patients. Through multi-omics factor analysis we observed that the latent factor explaining the variance in gene expression and DNA methylation was associated with Swollen Joint Count 66 (SJC66) where patients with SJC66 of 9 or more displayed reasonable separation from the rest. Specifically, combined DNA methylation and gene expression patterns of patients with SJC66 ≥ 9 displayed activation of the immune response as well as dysregulation of cell adhesion pathways. Through an integrative analysis framework, we reveal differences in both methylation and expression at 59 genes associated with the difference between SJC66 ≥ 9 and 0 < SJC66 ≤ 8, for which we identify specific transcripts correlated with differential methylation. Our results highlight the utility of genome-wide multi-omics profiling of synovial samples for improved understanding of the changes associated with an increasing number of swollen joints in RA patients, and point to novel candidate targets for the treatment of the disease. Funding Statement: AYFLY was funded by the European Union’s Horizon 2020 research and innovation program under Grant Agreement No. ITN-2014-EID-641665. Declaration of Interests: AYFLY, KM, GR, EC, HDL, DFT, CL, DG, and RB are employees of GSK. EF and PPT are employees of Novartis and Kintai Therapeutics, respectively. WJJ is financially supported by GSK and Mead Johnson. All declarations are correct for the time of writing and/or conducting this study. Ethics Approval Statement: All subjects provided written informed consent and the collection and use of the samples received Institutional Review Board review and approval. Characteristics of patients included in this study are listed in Table S1.

Ordered Co-Ni core-shell magnetic nanorod arrays were fabricated by a two-step electrodeposition into a self-assembled anodic alumina oxide template. The characterizations of the morphology and elemental distribution indicated the successful fabrication of ∼260 nm Co core nanorods surrounded by ∼20 nm concentric Ni shell. The magnetization measurement revealed that the synthesized Co-Ni core-shell nanorod arrays exhibited lower coercivity and higher remanence ratio than plain Co nanorod arrays, offering a possibility to regulate suitable coercivity at the nanoscale. It was also demonstrated combing tube and rod to form core-shell structure offered the perspective for engineering the magnetic properties without changing geometric parameters or with minimally altered crystalline structure.

Interfacial stress transfer of single-walled carbon nanotube-reinforced polymer composites subjected to uniaxial tension was investigated by a newly developed shear-lag model integrated with a spring layer model. A linear relationship between the tangential relative displacement and the interfacial shear stress was assumed for the interface which is determined by van der Waals forces. The interface stiffness parameter was determined through comparing the stress distribution of the shear-lag model with multiscale simulation results. The effect of the interface stiffness and the nanotube’s aspect ratios on the distribution of stress in CNT-reinforced composites was studied.

Magnetic nanowire arrays grown in anodized alumina templates offer a fertile ground to investigate the interplay among the exchange interaction, dipolar interaction, and magnetocrystalline anisotropy. In this study, we have successfully fabricated Co nanowire arrays with gradient diameter while maintaining the nanowire separation. Consequently, we are able to obtain nanowire arrays with dominant exchange interaction at one end with small nanowire dimeter and dominant dipolar interaction at the other with large nanowire diameter. These samples show very different magnetic properties from those observed in magnetic nanowire arrays with uniformly diameter. The easy magnetization axis, coercivity, saturation field, and reversal processes are all controlled collectively by both ends of the nanowires, which cannot be viewed as the combination of magnetic nanowire arrays with thin and thick diameters.

The efficiency is affected by the parameters of components in the DC high current generator. The leakage inductance of the rectifier transformer will affect the output and filtering effect of the device and reduce the power quality of the public network. To improve the output and filtering effect of the DC high current generator, the 3-phase 6-pulsation rectifier bridge arm with the transformer T-type equivalent circuit is proposed. Through the topology model of each conduction state circuit of the semiconductor components, the expressions of load output, high-order harmonic content, and transformer leakage inductance are calculated. Then the actual generator is simulated in the MATLAB-Simulink module and variation law between the primary and secondary side leakage inductance and the output DC voltage, the total harmonic distortion(THD), and the fifth harmonic content rate is obtained. Finally, the output waveform is analyzed under the rated condition. The results show that the influence of transformer leakage inductance on output efficiency and high order harmonic filtering effect can be obtained by the proposed calculation method, and the simulation results verify the validity and correctness of the theoretical analysis.