Hepatic steatosis is associated with dysregulated cholesterol metabolism and altered protein acetylation dynamics in chickens

Background Hepatic steatosis is a prevalent manifestation of fatty liver, that has detrimental effect on the health and productivity of laying hens, resulting in economic losses to the poultry industry. Here, we aimed to systematically investigate the genetic regulatory mechanisms of hepatic steatosis in laying hens.Methods Ninety individuals with the most prominent characteristics were selected from 686 laying hens according to the accumulation of lipid droplets in the liver, and were graded into three groups, including the control, mild hepatic steatosis and severe hepatic steatosis groups. A combination of transcriptome, proteome, acetylome and lipidome analyses, along with bioinformatics analysis were used to screen the key biological processes, modifications and lipids associated with hepatic steatosis.Results The rationality of the hepatic steatosis grouping was verified through liver biochemical assays and RNA-seq. Hepatic steatosis was characterized by increased lipid deposition and multiple metabolic abnormalities. Integration of proteome and acetylome revealed that differentially expressed proteins(DEPs) interacted with differentially acetylated proteins(DAPs) and were involved in maintaining the metabolic balance in the liver. Acetylation alterations mainly occurred in the progression from mild to severe hepatic steatosis, i.e., the enzymes in the fatty acid oxidation and bile acid synthesis pathways were significantly less acetylated in severe hepatic steatosis group than that in mild group(P < 0.05). Lipidomics detected a variety of sphingolipids(SPs) and glycerophospholipids(GPs) were negatively correlated with hepatic steatosis(r ≤-0.5, P < 0.05). Furthermore, the severity of hepatic steatosis was associated with a decrease in cholesterol and bile acid synthesis and an increase in exogenous cholesterol transport.Conclusions In addition to acquiring a global and thorough picture of hepatic steatosis in laying hens, we were able to reveal the role of acetylation in hepatic steatosis and depict the changes in hepatic cholesterol metabolism. The findings provides a wealth of information to facilitate a deeper understanding of the pathophysiology of fatty liver and contributes to the development of therapeutic strategies.

A review of clinical practice guidelines on the management of preeclampsia and nursing inspiration

Objectives:To review,evaluate,and synthesize the recommendations of guidelines on preeclampsia(PE)from a nursing perspective.Methods:This is a systematic review of international and national guidelines on PE.Electronic databases and related guideline websites were searched from 2013 to 2023.After systematic retrieval and screening,we used the AGREE II tool to appraise the methodological quality of guidelines that met the eligibility criteria.Then,we analyzed and summarized the recommendations using descriptive analysis and the framework method.Furthermore,we rated the quality of evidence and the strength of the recommendations using the GRADE approach.Results:Ten guidelines were included,among which eight were deemed“clinically useful”and records were extracted.In total,31 recommendations,including 46 items on the nursing management of PE,were summarized from three aspects:1)antenatal care(18 recommendations),including the assessment and regular monitoring of PE,standardized blood pressure(BP)measurement,prevention education for PE,antihypertensive agent monitoring,and magnesium sulfate(MgSO_(4))use;2)intrapartum care(4 recommendations),including childbirth care;3)postpartum care(9 recommendations),including regular nursing monitoring,breastfeeding care and longer-term health counseling.Most of the evidence was rated as“very low”(19/46)or“moderate”(15/46)quality.For the strength of the recommendations,30 items were graded as“strong”and 16 items were rated as“weak”.Conclusions:This study provides professional,evidence-based nursing care resources both for preservice education for nursing staff and health care education for women with PE to help them detect and treat PE in a timely manner.

Minimal invasive microscopic tooth preparation in esthetic restoration: a specialist consensus

By removing a part of the structure,the tooth preparation provides restorative space,bonding surface,and finish line for various restorations on abutment.Preparation technique plays critical role in achieving the optimal result of tooth preparation.With successful application of microscope in endodontics for>30 years,there is a full expectation of microscopic dentistry.However,as relatively little progress has been made in the application of microscopic dentistry in prosthodontics,the following assumptions have been proposed:Is it suitable to choose the tooth preparation technique under the naked eye in the microscopic vision?Is there a more accurate preparation technology intended for the microscope?To obtain long-term stable therapeutic effects,is it much easier to achieve maximum tooth preservation and retinal protection and maintain periodontal tissue and oral function health under microscopic vision?Whether the microscopic prosthodontics is a gimmick or a breakthrough in obtaining an ideal tooth preparation should be resolved in microscopic tooth preparation.This article attempts to illustrate the concept,core elements,and indications of microscopic minimally invasive tooth preparation,physiological basis of dental pulp,periodontium and functions involved in tool preparation,position ergonomics and visual basis for dentists,comparison of tooth preparation by naked eyes and a microscope,and comparison of different designs of microscopic minimally invasive tooth preparation techniques.Furthermore,a clinical protocol for microscopic minimally invasive tooth preparation based on target restorative space guide plate has been put forward and new insights on the quantity and shape of microscopic minimally invasive tooth preparation has been provided.

Proteo-transcriptomic profiles reveal key regulatory pathways and functions of LDHA in the ovulation of domestic chickens(Gallus gallus)

Background In poultry, the smooth transition of follicles from the preovulatory-to-postovulatory phase impacts egg production in hens and can benefit the poultry industry. However, the regulatory mechanism underlying follicular ovulation in avians is a complex biological process that remains unclear.Results Critical biochemical events involved in ovulation in domestic chickens(Gallus gallus) were evaluated by transcriptomics, proteomics, and in vitro assays. Comparative transcriptome analyses of the largest preovulatory follicle(F1) and postovulatory follicle(POF1) in continuous laying(CL) and intermittent laying(IL) chickens indicated the greatest difference between CL_F1 and IL_F1, with 950 differentially expressed genes(DEGs), and the smallest difference between CL_POF1 and IL_POF1, with 14 DEGs. Additionally, data-independent acquisition proteomics revealed 252 differentially abundant proteins between CL_F1 and IL_F1. Perivitelline membrane synthesis, steroid biosynthesis, lysosomes, and oxidative phosphorylation were identified as pivotal pathways contributing to ovulation regulation. In particular, the regulation of zona pellucida sperm-binding protein 3, plasminogen activator, cathepsin A, and lactate dehydrogenase A(LDHA) was shown to be essential for ovulation. Furthermore, the inhibition of LDHA decreased cell viability and promoted apoptosis of ovarian follicles in vitro.Conclusions This study reveals several important biochemical events involved in the process of ovulation, as well as crucial role of LDHA. These findings improve our understanding of ovulation and its regulatory mechanisms in avian species.

The m6A methylation regulates gonadal sex differentiation in chicken embryo

Background:As a ubiquitous reversible epigenetic RNA modification,N6-methyladenosine(m6A)plays crucial regulatory roles in multiple biological pathways.However,its functional mechanisms in sex determination and differentiation during gonadal development of chicken embryos are not clear.Therefore,we established a transcriptome-wide m6A map in the female and male chicken left gonads of embryonic day 7(E7)by methylated RNA immunoprecipitation sequencing(MeRIP-seq)to offer insight into the landscape of m6A methylation and investigate the post-transcriptional modification underlying gonadal differentiation.Results:The chicken embryonic gonadal transcriptome was extensively methylated.We found 15,191 and 16,111 m6A peaks in the female and male left gonads,respectively,which were mainly enriched in the coding sequence(CDS)and stop codon.Among these m6A peaks,we identified that 1013 and 751 were hypermethylated in females and males,respectively.These differential peaks covered 281 and 327 genes,such as BMP2,SMAD2,SOX9 and CYP19A1,which were primarily associated with development,morphogenesis and sex differentiation by functional enrichment.Further analysis revealed that the m6A methylation level was positively correlated with gene expression abundance.Furthermore,we found that YTHDC2 could regulate the expression of sex-related genes,especially HEMGN and SOX9,in male mesonephros/gonad mingle cells,which was verified by in vitro experiments,suggesting a regulatory role of m6A methylation in chicken gonad differentiation.Conclusions:This work provided a comprehensive m6A methylation profile of chicken embryonic gonads and revealed YTHDC2 as a key regulator responsible for sex differentiation.Our results contribute to a better understanding of epigenetic factors involved in chicken sex determination and differentiation and to promoting the future development of sex manipulation in poultry industry.

Neuroprotective effects of Ginkgo biloba dropping pills in Parkinson's disease

Parkinson's disease(PD) is the second most common neurodegenerative disease in the world;however,it lacks effective and safe treatments. Ginkgo biloba dropping pill(GBDP), a unique Chinese G. biloba leaf extract preparation, exhibits antioxidant and neuroprotective effects and has a potential as an alternative therapy for PD. Thus, the aims of this study were to evaluate the effects of GBDP in in vitro and in vivo PD models and to compare the chemical constituents and pharmacological activities of GBDP and the G. biloba extract EGb 761. Using liquid chromatography tandem-mass spectrometry, 46 GBDP constituents were identified. Principal component analysis identified differences in the chemical profiles of GBDP and EGb 761. A quantitative analysis of 12 constituents showed that GBDP had higher levels of several flavonoids and terpene trilactones than EGb 761, whereas EGb 761 had higher levels of organic acids.Moreover, we found that GBDP prevented 6-hydroxydopamine-induced dopaminergic neuron loss in zebrafish and improved cognitive impairment and neuronal damage in methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced PD mice. Although similar effects were observed after EGb 761 treatment,the neuroprotective effects were greater after GBDP treatment on several endpoints. In addition, in vitro results suggested that the Akt/GSK3β pathway may be involved in the neuroprotective effects of GBDP.These findings demonstrated that GBDP have potential neuroprotective effects in the treatment of PD.

Detrimental effects of excessive fatty acid secretion on female sperm storage in chickens

Background:Female sperm storage(FSS),the maintenance of sperm inside the female reproductive tract for an extended period of time,is pervasive among organisms with internal fertilization.Because FSS enables asynchronous mating and fertilization,it could be extremely important to reproduction.However,the physiological mechanisms underlying prolonged preservation and maintenance are poorly understood.Here,we used chicken,a typical oviparous animal,to determine the mechanisms ensuring sperm functionality in sperm storage tubules(SSTs).Results:We performed an insemination experiment on over two thousand hens at two periods,and found that the FSS capabilities varied widely among individuals.Except for the differences in the SST density between the two groups with distinct FSS abilities,we quantitatively profiled small-molecule metabolites derived from SST cells,and identified 28 metabolites with differential expression.In particular,high levels of lipids,fatty acids and lipid peroxidation product were observed in hens with low FSS capability.Pathway analysis showed that these differential metabolites were significantly enriched in the biosynthesis of unsaturated fatty acids.Moreover,we detected the total antioxidant capacity and lipid peroxidation level of SSTs,and found that chickens with a lower FSS ability had a significantly higher content of lipid peroxidation end-product,which was 2.4-fold greater than chickens with a higher FSS capability,and no significant difference was found in the total antioxidant capacity between these two groups.Conclusions:Our findings reveal that the long-term storage of sperm and the maintenance of their function in the female reproductive tract require an adequate microenvironment.The superabundance of fatty acids secreted by SST cells had detrimental effects on sperm storage in the female reproductive tract.Lipid peroxidation produces toxic biological substances that may cause irreversible damage to resident spermatozoa,resulting in short-term sperm retention and decreased fertility.Our findings provide new avenues for studying sperm storage and sustaining fertility.

Scalable Skin Lesion Multi-Classification Recognition System

Skin lesion recognition is an important challenge in the medical field.In this paper,we have implemented an intelligent classification system based on convolutional neural network.First of all,this system can classify whether the input image is a dermascopic image with an accuracy of 99%.And then diagnose the dermoscopic image and the non-skin mirror image separately.Due to the limitation of the data,we can only realize the recognition of vitiligo by non-skin mirror.We propose a vitiligo recognition based on the probability average of three structurally identical CNN models.The method is more efficient and robust than the traditional RGB color space-based image recognition method.For the dermoscopic classification model,we were able to classify 7 skin lesions,use weighted optimization to overcome the unbalanced data set,and greatly improve the sensitivity of the model by means of model fusion.The optimization and expansion of the system depend on the increase of database.

Analysis of the impact of COVID-19 on some medical institutions in a certain region

Objective:This study is designed to analyze the impact of COVID-19 on hospitals in a certain region through the statistical comparison of outpatient,emergency and inpatient data of three representative AAA hospitals in this region from January and February of 2019 and 2020.Methods:Relevant outpatient,emergency and inpatient data of three representative AAA hospitals in a certain region from January and February of 2019 and 2020 were collected,and the statistical analysis was conducted by using EXCEL 2019 and SPSS20.0.Results:In January and February of 2020,the number of the outpatient,the emergency,the inpatient and the inpatient surgical interventions in the three hospitals was significantly decreased in comparison with the same period in 2019,and the change of the emergency dispatching amount was relatively small.The mortality of the inpatient in January and February in 2020 was about 2.82%,and that in the same period in 2019 was about 1.51%,with an increase of about 1.31%,which presented a statistically significant difference(χ^(2)=348.422;p=.000).Conclusions:The outbreak of COVID-19 had a great impact on the normal operation of the hospital.

Electrically programmable phase-change photonic memory for optical neural networks with nanoseconds in situ training capability

Optical neural networks (ONNs), enabling low latency and high parallel data processing withoutelectromagnetic interference, have become a viable player for fast and energy-efficient processing andcalculation to meet the increasing demand for hash rate. Photonic memories employing nonvolatile phase-change materials could achieve zero static power consumption, low thermal cross talk, large-scale, andhigh-energy-efficient photonic neural networks. Nevertheless, the switching speed and dynamic energyconsumption of phase-change material-based photonic memories make them inapplicable for in situ training.Here, by integrating a patch of phase change thin film with a PIN-diode-embedded microring resonator,a bifunctional photonic memory enabling both 5-bit storage and nanoseconds volatile modulation wasdemonstrated. For the first time, a concept is presented for electrically programmable phase-changematerial-driven photonic memory integrated with nanosecond modulation to allow fast in situ training and zerostatic power consumption data processing in ONNs. ONNs with an optical convolution kernel constructedby our photonic memory theoretically achieved an accuracy of predictions higher than 95% when testedby the MNIST handwritten digit database. This provides a feasible solution to constructing large-scalenonvolatile ONNs with high-speed in situ training capability.

Passive devices at 2 μm wavelength on 200 mm CMOS-compatible silicon photonics platform [Invited]

As a promising spectral window for optical communication and sensing, it is of great significance to realize on-chip devices at the 2 μm waveband.The development of the 2 μm silicon photonic platform mainly depends on the performance of passive devices.In this work, the passive devices were fabricated in the silicon photonic multi-project wafer process.The designed micro-ring resonator with a 0.6 μm wide silicon ridge waveguide based on a 220 nm silicon-on-insulator platform achieves a high intrinsic quality factor of 3.0 × 105.The propagation loss is calculated as 1.62 d B/cm.In addition,the waveguide crossing, multimode interferometer, and Mach–Zehnder interferometer were demonstrated at 2 μm with good performances.

PML–LRIF1 interactions form a novel link between promyelocytic leukemia bodies and centromeres

Dear Editor,Promyelocytic leukemia(PML)is the scaffold protein that organizes PML bod-ies,which are nuclear membraneless organelles involved in various biologi-cal processes,including tumor suppres-sion and antiviral responses(Ugge et al.,2022).Early electron microscopic analy-ses revealed contacts between the sur-face of PML bodies and chromatin struc-ture(Corpet et al.,2020).In fact,sev-eral chromatin and cell cycle regulators,such as TIP60,P300,and heterochro-matin protein 1(HP1),are localized in PML bodies in interphase cells(Corpet et al.,2020).

Properties and nucleotide sequence of linear plasmid-like DNA pC4 from mitochondria of Cucumis sativus

Four kinds of mitochondrial plasmid-like DNAs, designated pC1, pC2, pC3 and pC4, were detected in Cucumis sativus Jinyan No. 4. The electron microscopy observation showed that pC4 was linear conformation. Complete sequence of pC4 was cloned into pUC19 with E. coli JM109 as host. Sequence analysis revealed that pC4 was 370 bp long, the shortest one among all the reported mitochondrial plasmid-like DNAs. pC4 was AT rich. It contained terminal direct repeat sequence (35 bp in length)as well as many short direct and inverted repeats. ORFs in pC4 were short. pC4 was found to be homologous to nuclear DNAs, but lack homology with main mitochondrial and chloroplast DNAs. pC4-homologous sequence also occurred in nuclear genome of Jinyan No. 7 which contained no mitochondrial plasmid-like DNAs. The hybridization pattern of Jinyan No. 7 was slightly different from that of Jinyan No. 4. This suggested that pC4 occurred at the forepart of Cucumis sativus species divergence and integrated into the nuclear genome,

PICC相关性静脉血栓风险评估量表的编制及信效度检验

目的构建PICC相关性静脉血栓风险评估量表,并检验其信效度。方法结合国内外相关文献,构建PICC相关性静脉血栓风险评估量表条目池;通过专家咨询法、层次分析法,形成PICC相关性静脉血栓风险评估初始量表,采用该量表对130例患者进行血栓风险评估,以验证该量表的信度、效度;描绘受试者操作特征曲线,找出最佳高危临界值及其对应的识别能力。结果 PICC相关性静脉血栓风险评估量表包括3个维度和22个条目;量表的3个维度和总量表的Cronbach’s α系数分别为0.805、0.683、0.751、0.794;受试者操作特征曲线结果显示,曲线下面积为0.728[P=0.013,95%CI(0.594, 0.862)],最佳高危临界值为5.5,其对应的灵敏度为0.909,特异度为0.471。结论本研究构建的PICC相关性静脉血栓风险评估量表具有良好的信效度,可以作为临床工作中筛查PICC置管患者静脉血栓风险的评估工具。

LRIF1 interacts with HPla to coordinate accurate chromosome segregation during mitosis

Heterochromatin protein 1α (HP1α)regulates chromatin specification and plasticity during cell fate decision.Different structural determinants account for HP1α Localization and function during cell division cycle.Our earlier study showed that centromeric Localization of HP1α depends on the epigenetic mark H3K9me3 in interphase,while its centromeric location in mitosis relies on uncharacterized PXVXL-containing factors.Here,we identified a PXVXL-containing protein,Ligand-dependent nuclear receptorinteracting factor 1 (LRIF1),which recruits HPla to the centromere of mitotic chromosomes and its interaction with HP1α is essential for accurate chromosome segregation during mitosis.LRIF1 interacts directly with HPla chromoshadow domain via an evolutionariLy conserved PXVXL motif within its C-terminus.Importantly,the LRIF1-HPla interaction is critical for Aurora B activity in the inner centromere.Mutation of PXVXL motif of LRIF1 Leads to defects in HPla centromere targeting and aberrant chromosome segregation.These findings reveal a previously unrecognized direct Link between LRIF1 and HP1α in centromere plasticity control and illustrate the critical role of LRIF1-HP1α interaction in orchestrating accurate cell division.

Graphene-based all-optical modulators

All-optical devices,which are utilized to process optical signals without electro-optical conversion,play an essential role in the next generation ultrafast,ultralow power-consumption optical information processing systems.To satisfy the performance requirement,nonlinear optical materials that are associated with fast response,high nonlinearity,broad wavelength operation,low optical loss,low fabrication cost,and integration compatibility with optical components are required.Graphene is a promising candidate,particularly considering its electrically or optically tunable optical properties,ultrafast large nonlinearity,and high integration compatibility with various nanostructures.Thus far,three all-optical modulation systems utilize graphene,namely free-space modulators,fiber-based modulators,and on-chip modulators.This paper aims to provide a broad view of state-of-the-art researches on the graphene-based all-optical modulation systems.The performances of different devices are reviewed and compared to present a comprehensive analysis and perspective of graphene-based all-optical modulation devices.

Mitotic motor CENP-E cooperates with PRC1 in temporal control of central spindle assembly

Error-free cell division depends on the accurate assembly of the spindle midzone from dynamic spindle microtubules to ensure chromatid segregation during metaphase-anaphase transition.However,the mechanism underlying the key transition from the mitotic spindle to central spindle before anaphase onset remains elusive.Given the prevalence of chromosome instability phenotype in gastric tumorigenesis,we developed a strategy to model context-dependent cell division using a combination of light sheet microscope and 3D gastric organoids.Light sheet microscopic image analyses of 3D organoids showed that CENP-E inhibited cells undergoing aberrant metaphase-anaphase transition and exhibiting chromosome segregation errors during mitosis.Highresolution real-time imaging analyses of 2D cell culture revealed that CENP-E inhibited cells undergoing central spindle splitting and chromosome instability phenotype.Using biotinylated syntelin as an affinity matrix,we found that CENP-E forms a complex with PRC1 in mitotic cells.Chemical inhibition of CENP-E in metaphase by syntelin prevented accurate central spindle assembly by perturbing temporal assembly of PRC1 to the midzone.Thus,CENP-E-mediated PRC1 assembly to the central spindle constitutes a temporal switch to organize dynamic kinetochore microtubules into stable midzone arrays.These findings reveal a previously uncharacterized role of CENP-E in temporal control of central spindle assembly.Since CENP-E is absent from yeast,we reasoned that metazoans evolved an elaborate central spindle organization machinery to ensure accurate sister chromatid segregation during anaphase and cytokinesis.

Mechanisms and regulation underlying membraneless organelle plasticity control

Evolution has enabled living cells to adopt their structural and functional complexity by organizing intricate cellular compartments,such as membrane-bound and membraneless organelles(MLOs),for spatiotemporal catalysis of physiochemical reactions essential for cell plasticity control.Emerging evidence and view support the notion that MLOs are built by multivalent interactions of biomolecules via phase separation and transition mechanisms.In healthy cells,dynamic chemical modifications regulate MLO plasticity,and reversible phase separation is essential for cell homeostasis.Emerging evidence revealed that aberrant phase separation results in numerous neurodegenerative disorders,cancer,and other diseases.In this review,we provide molecular underpinnings on(i)mechanistic understanding of phase separation,(ii)unifying structural and mechanistic principles that underlie this phenomenon,(iii)various mechanisms that are used by cells for the regulation of phase separation,and(iv)emerging therapeutic and other applications.

Cytokine nanosponges suppressing overactive macrophages and dampening systematic cytokine storm for the treatment of hemophagocytic lymphohistiocytosis

Hemophagocytic lymphohistiocytosis(HLH)is a highly fatal condition with the positive feedback loop between continued immune cell activation and cytokine storm as the core mechanism to mediate multiple organ dysfunction.Inspired by macrophage membranes harbor the receptors with special high affinity for proin-flammation cytokines,lipopolysaccharide(LPS)-stimulated macrophage membrane-coated nanoparticles(LMNP)were developed to show strong sponge ability to both IFN-γand IL-6 and suppressed overactivation of macrophages by inhibiting JAK/STAT signaling pathway both in vitro and in vivo.Besides,LMNP also efficiently alleviated HLH-related symptoms including cytopenia,hepatosplenomegaly and hepatorenal dysfunction and save the life of mouse models.Furthermore,its sponge effect also worked well for five human HLH samples in vitro.Altogether,it’s firstly demonstrated that biocompatible LMNP could dampen HLH with high potential for clinical transformation,which also provided alternative insights for the treatment of other cytokine storm-mediated pathologic conditions such as COVID-19 infection and cytokine releasing syndrome during CAR-T therapy.

Tunable narrow-band single-channel add-drop integrated optical filter with ultrawide FSR

Free-spectral-range(FSR)-free optical filters have always been a critical challenge for photonic integrated circuits.A high-performance FSR-free filter is highly desired for communication,spectroscopy,and sensing applications.Despite significant progress in integrated optical filters,the FSR-free filter with a tunable narrow-band,high out-of-band rejection,and large fabrication tolerance has rarely been demonstrated.In this paper,we propose an exact and robust design method for add-drop filters(ADFs)with an FSR-free operation capability,a sub-nanometer optical bandwidth,and a high out-of-band rejection(OBR)ratio.The achieved filter has a 3-dB bandwidth of<0.5 nm and an OBR ratio of 21.5 dB within a large waveband of 220 nm,which to the best of our knowledge,is the largest-FSR ADF demonstrated on a silicon photonic platform.The filter exhibits large tunability of 12.3 nm with a heating efficiency of 97 pm/mW and maintains the FSR-free feature in the whole tuning process.In addition,we fabri-cated a series of ADFs with different periods,which all showed reliable and excellent performances.