Interactions among deep-sea mussels and their epibiotic and endosymbiotic chemoautotrophic bacteria: Insights from multi-omics analysis

Endosymbiosis with Gammaproteobacteria is fundamental for the success of bathymodioline mussels in deep-sea chemosynthesis-based ecosystems. However, the recent discovery of Campylobacteria on the gill surfaces of these mussels suggests that these host-bacterial relationships may be more complex than previously thought. Using the cold-seep mussel(Gigantidas haimaensis) as a model, we explored this hostbacterial system by assembling the host transcriptome and genomes of its epibiotic Campylobacteria and endosymbiotic Gammaproteobacteria and quantifying their gene and protein expression levels. We found that the epibiont applies a sulfur oxidizing(SOX)multienzyme complex with the acquisition of sox B from Gammaproteobacteria for energy production and switched from a reductive tricarboxylic acid (rTCA) cycle to a Calvin-Benson-Bassham(CBB)cycle for carbon assimilation. The host provides metabolic intermediates, inorganic carbon, and thiosulfate to satisfy the materials and energy requirements of the epibiont, but whether the epibiont benefits the host is unclear. The endosymbiont adopts methane oxidation and the ribulose monophosphate pathway(Ru MP) for energy production, providing the major source of energy for itself and the host. The host obtains most of its nutrients, such as lysine, glutamine, valine,isoleucine, leucine, histidine, and folate, from the endosymbiont. In addition, host pattern recognition receptors, including toll-like receptors, peptidoglycan recognition proteins, and C-type lectins, may participate in bacterial infection, maintenance, and population regulation. Overall, this study provides insights into the complex host-bacterial relationships that have enabled mussels and bacteria to thrive in deep-sea chemosynthetic ecosystems.

Discrimination and quantification of scar tissue by Mueller matrix imaging with machine learning

Scarring is one of the biggest areas of unmet need in the long-term success of glaucoma filtration surgery.Quantitative evaluation of the scar tissue and the post-operative structure with micron scale resolution facilitates development of anti-fibrosis techniques.However,the distinguishment of conjunctiva,sclera and the scar tissue in the surgical area still relies on pathologists'experience.Since polarized light imaging is sensitive to anisotropic properties of the media,it is ideal for discrimination of scar in the subconjunctival and episcleral area by characterizing small differences between proportion,organization and the orientation of the fibers.In this paper,we defined the conjunctiva,sclera,and the scar tissue as three target tissues after glaucoma filtration surgery and obtained their polarization characteristics from the tissue sections by a Mueller matrix microscope.Discrimination score based on parameters derived from Mueller matrix and machine learning was calculated and tested as a diagnostic index.As a result,the discrimination score of three target tissues showed significant difference between each other(p<0.001).The visualization of the discrimination results showed significant contrast between target tissues.This study proved that Mueller matrix imaging is effective in ocular scar discrimination and paves the way for its application on other forms of ocular fibrosis as a substitute or supplementary for clinical practice.

Comparative acetylome analysis reveals the potential mechanism of high fat diet function in allergic disease

Modern technological lifestyles promote allergic diseases,especially food allergies.The underlying molecular mechanisms remain to be uncovered.Protein acetylation is one of the most important post-translational modifications,and it is involved in regulating multiple body metabolic processes.This study aimed to clarify the effects of a high-fat diet(HFD)on allergy risk and the underlying mechanisms.Four-week-old male C57 BL/6 J mice were randomly divided into two groups and fed a normal fat diet(NFD)or HFD for 24 weeks.Then,serum lipids were measured,and skeletal muscle was collected for acetylome analysis.Compared with the findings in the NFD group,HFD-fed mice were obese and hyperlipidemic.Acetylome analysis also revealed 32 differentially expressed proteins between the HFD and NFD groups.Among these,eight acetylated proteins were upregulated in the HFD group.In addition,13 and 11 proteins were acetylated only in the HFD group and NFD group,respectively.These proteins were mainly involved in regulating energy metabolism and mitochondrial function.This study provides information regarding the underlying molecular mechanisms by which HFD promotes allergy.

鹿茸提取物对UVB诱导光老化小鼠皮肤的保护作用

研究鹿茸提取物(PAEs)对UVB诱导光老化小鼠皮肤的保护作用。通过HE染色和含水量测试仪检测光老化小鼠皮肤形态和含水量变化,采用双光子激发荧光(TPEF)和液晶偏光影像技术研究小鼠皮肤胶原纤维病理变化,RT-qPCR方法分析不同类型胶原蛋白、基质金属蛋白酶及基质金属蛋白酶抑制剂的表达。结果发现PAEs显著抑制UVB引起的小鼠皮肤厚度,增加光老化小鼠皮肤角质层和深层含水量。PAEs明显提高光老化小鼠真皮胶原纤维荧光信号强度,降低胶原纤维方位角的变异程度,促进光老化小鼠真皮Ⅰ型和Ⅲ型胶原蛋白mRNA表达,调控MMP-1和TIMP-2 mRNA表达。结果表明PAEs可以明显保护UVB引起皮肤的光老化,在抗衰老产品中具有重要的应用价值。

非洲猪瘟背景下的三元商品母猪养殖策略

非洲猪瘟病毒(African swine fever virus,ASFV)是一种病毒分子巨大且复杂的DNA病毒,在无有效疫苗的情况下,会引起高度传染性且通常致命的猪瘟。目前非洲猪瘟(African swine fever,ASF)导致我国母猪存栏大幅度下降,猪场引种面临了巨大的生物安全风险,采用三元商品母猪留种成为了一种较好的选择。文章结合生产实践,旨在为三元商品母猪的饲养管理和营养调控提供指导意见。

One-pot preparation of nanodispersion with readily available components for localized tumor photothermal and photodynamic therapy

Photothermal(PTT) and photodynamic(PDT) combined therapy has been hindered to clinical translation, due to the lack of available biomaterials, difficult designs of functions,and complex chemical synthetic or preparation procedures. To actualize a high-efficiency combination therapy for cancer via a feasible approach, three readily available materials are simply associated together in one-pot, namely the single-walled carbon nanohorns(SWCNH), zinc phthalocyanine(ZnPc), and surfactant TPGS. The established nanodispersion is recorded as PCT. The association of SWCNH/ZnPc/TPGS was confirmed by energy dispersive spectrum, Raman spectrum and thermogravimetric analysis. Under lighting, PCT induced a temperature rising up to about 60 ℃ due to the presence of SWCNH, production a 7-folds of singlet oxygen level elevation because of ZnPc, which destroyed almost all4T1 tumor cells in vitro. The photothermal effect of PCT depended on both laser intensity and nanodispersion concentration in a linear and nonlinear manner, respectively. After a single peritumoral injection in mice and laser treatment, PCT exhibited the highest tumor temperature rise(to 65 ℃) among all test groups, completely destroyed primary tumor without obvious toxicity, and inhibited distant site tumor. Generally, this study demonstrated the high potential of PCT nanodispersion in tumor combined therapy.

关于轮式起重机支腿跨距识别技术的探讨

本文从支腿跨距测量,信息处理策略与提示两个方面进行轮式起重机支腿跨距识别技术研究。本技术通过设置的支腿长度传感器以及特定的控制算法与策略,对支腿跨距状态进行自动识别,解决人为进行支腿跨距判断及信息输入时可能带来的支腿状态误判风险,提升起重机吊装安全性。

一种求解偏微分方程的动态平衡物理信息神经网络

近年来,物理信息神经网络(physics-informed neural networks, PINNs)在求解非线性偏微分方程(partial differential equations, PDEs)中得到了大量应用. PINN将物理信息作为正则化约束加入神经网络损失函数,可以减少传统神经网络方法对训练数据的大量依赖.然而, PINN无法根据数据变化动态调整损失函数中各个损失项的权重,导致其在求解非线性PDEs时存在求解误差较大的问题.为此,本文提出了一种动态平衡物理信息神经网络(dynamic balanced PINN, DBPINN).首先,DBPINN为PINN损失函数的各个损失项设计了一种动态权重系数,并使用随机函数对该系数进行动态更新,能够显著提升PINN的精度.其次, DBPINN为PNNN损失函数的各个损失项之间建立了一种平衡求和方法,该方法考虑了所有损失项之间的竞争关系,使得PINN各损失项朝着有利于收敛的方向进行优化. DBPINN通过动态权重系数和平衡求和方法使得PINN可以更好地进行优化,进而解决了PINN在实际应用中求解误差较大的问题.本文选择了科学机器学习领域中4个经典的非线性PDEs对DBPINN进行了数值验证和分析.实验结果表明,相比于PINN, DBPINN在Schrodinger和Allen-Cahn方程上误差分别降低了46%和64%. DBPINN在求解Navier-Stokes方程时将系数λ_(1)和λ_(2)的误差分别降低了1~2个数量级和约50%. DBPINN在KdV方程中能够在多项系数中将误差降低1个数量级.最后,本文在多种形式的Burgers方程和Allen-Cahn方程上进行性能和参数消融验证,结果表明DBPINN不仅能够提升模型性能、处理小数据量以及拟合不同时间状态下的方程的能力,而且DBPINN相比于PINN具有更好的稳定性、准确率以及收敛性. DBPINN可以取代PINN被应用于各种非线性PDEs的高精度求解.

Ribonucleotide reductase small subunit M2 promotes the proliferation of esophageal squamous cell carcinoma cells via HuR-mediated mRNA stabilization

Esophageal squamous cell carcinoma(ESCC),a malignancy of the digestive system,is highly prevalent and the primary cause of cancer-related deaths worldwide due to the lack of early diagnostic biomarkers and effective therapeutic targets.Dysregulated ribonucleotide reductase(RNR)expression has been confirmed to be causally linked to tumorigenesis.This study demonstrated that ribonucleotide reductase small subunit M2(RRM2)is significantly upregulated in ESCC tissue and that its expression is negatively correlated with clinical outcomes.Mechanistically,HuR promotes RRM2 mRNA stabilization by binding to the adenine/uridine(AU)-rich elements(AREs)within the 3′UTR,resulting in persistent overexpression of RRM2.Furthermore,bifonazole is identified as an inhibitor of HuR via computational screening and molecular docking analysis.Bifonazole disrupts HuR-ARE interactions by competitively binding to HuR at F65,R97,I103,and R153 residues,resulting in reduced RRM2 expression.Furthermore,bifonazole exhibited antitumor effects on ESCC patient-derived xenograft(PDX)models by decreasing RRM2 expression and the dNTP pool.In summary,this study reveals the interaction network among HuR,RRM2,and bifonazole and demonstrated that bifonazole is a potential therapeutic compound for ESCC through inhibition of the HuR/RRM2 axis.

Minimizing endogenous cryptic plasmids to construct antibiotic-free expression systems for Escherichia coli Nissle 1917

The probiotic bacterium Escherichia coli Nissle 1917(EcN)holds significant promise for use in clinical and biological industries.However,the reliance on antibiotics to maintain plasmid-borne genes has overshadowed its benefits.In this study,we addressed this issue by engineering the endogenous cryptic plasmids pMUT1 and pMUT2.The non-essential elements were removed to create more stable derivatives pMUT1NR△and pMUT2HBC△.Synthetic promoters by integrating binding motifs on sigma factors were further constructed and applied for expression of Bacteroides thetaiotaomicron heparinaseⅢand the biosynthesis of ectoine.Compared to traditional antibiotic-dependent expression systems,our newly constructed antibiotic-free expression systems offer considerable advantages for clinical and synthetic biology applications.

An enzyme-responsive and transformable PD-L1 blocking peptide-photosensitizer conjugate enables efficient photothermal

Mild photothermal therapy combined with immune checkpoint blockade has received increasing attention for the treatment of advanced or metastatic cancers due to its good therapeutic efficacy.However,it remains a challenge to facilely integrate the two therapies and make it potential for clinical translation.This work designed a peptide-photosensitizer conjugate(PPC),which consisted of a PD-L1 antagonist peptide(CVRARTR),an MMP-2 specific cleavable sequence,a self-assembling motif,and the photosensitizer Purpurin 18.The single-component PPC can self-assemble into nanospheres which is suitable for intravenous injection.The PPC nanosphere is cleaved by MMP-2 when it accumulates in tumor sites,thereby initiating the cancer-specific release of the antagonist peptide.Simultaneously,the nanospheres gradually transform into co-assembled nanofibers,which promotes the retention of the remaining parts within the tumor.In vivo studies demonstrated that PPC nanospheres under laser irradiation promote the infiltration of cytotoxic T lymphocytes and maturation of DCs,which sensitize 4T1 tumor cells to immune checkpoint blockade therapy.Therefore,PPC nanospheres inhibit tumor growth efficiently both in situ and distally and blocked the formation of lung metastases.The present study provides a simple and efficient integrated strategy for breast cancer photoimmunotherapy.

SARS-CoV-2 spike protein induces IL-18-mediated cardiopulmonary inflammation via reduced mitophagy

Cardiopulmonary complications are major drivers of mortality caused by the SARS-CoV-2 virus.Interleukin-18,an inflammasomeinduced cytokine,has emerged as a novel mediator of cardiopulmonary pathologies but its regulation via SARS-CoV-2 signaling remains unknown.Based on a screening panel,IL-18 was identified amongst 19 cytokines to stratify mortality and hospitalization burden in patients hospitalized with COVID-19.Supporting clinical data,administration of SARS-CoV-2 Spike 1(S1)glycoprotein or receptor-binding domain(RBD)proteins into human angiotensin-converting enzyme 2(hACE2)transgenic mice induced cardiac fibrosis and dysfunction associated with higher NF-κB phosphorylation(pNF-κB)and cardiopulmonary-derived IL-18 and NLRP3 expression.IL-18 inhibition via IL-18BP resulted in decreased cardiac pNF-κB and improved cardiac fibrosis and dysfunction in S1-or RBD-exposed hACE2 mice.Through in vivo and in vitro work,both S1 and RBD proteins induced NLRP3 inflammasome and IL-18 expression by inhibiting mitophagy and increasing mitochondrial reactive oxygenation species.Enhancing mitophagy prevented Spike protein-mediated IL-18 expression.Moreover,IL-18 inhibition reduced Spike protein-mediated pNF-κB and EC permeability.Overall,the link between reduced mitophagy and inflammasome activation represents a novel mechanism during COVID-19 pathogenesis and suggests IL-18 and mitophagy as potential therapeutic targets.

Cellular proteomic profiling of esophageal epithelial cells cultured under physioxia or normoxia reveals high correlation of radiation response

Objective To investigate the radiation response and proteomic profiling of esophageal epithelial cells cultured under physioxia and normoxia.Methods The human immortalized normal esophageal epithelial cell line SHEE cells were cultured under normoxia(21%)and physioxia(4%),respectively.A clonogenic assay was performed to evaluate the radiation response of SHEE cells.Cellular proteomic profiling of SHEE cells maintained under physioxia and normoxia was conducted to determine the differentially expressed proteins.Then,the identified differentially expressed proteins were validated by Western blot.Results SHEE cells exposed to normoxia showed an increased radiation response compared to physioxia(irradiation dose≥10Gy,P<0.05).Over 1200 non-redundant proteins were identified in the collected samples.Protein expression was compared between physioxia and normoxia,42 proteins were downregulated and 45 proteins upregulated,in which oxidative phosphorylation was the most significantly enriched pathway.When cells were cultured under normoxia conditions,the induction of antioxidant genes appeared to contribute to form a phenotype adapted to the environment with high oxygen-content.Further analysis validated NRF2,BIP,VCP,SOD1,and YAP1 were the key regulators of this phenotype.Conclusions Compared with physioxia,normoxic cell culture condition can enhance the radiation response.This study could stimulate in vivo microenvironment,and provide a basis for radiation-induced normal tissue damage.

Bcr-Abl癌基因与A-MuLV病毒诱导肿瘤发生的机理

Bcr-Abl癌基因是由人类9号染色体的c-Abl基因与22号染色体的Bcr基因易位融合而成,其编码的融合蛋白Bcr-Abl可以诱导人类白血病的发生。Abelson鼠白血病病毒(A-MuLV)是一种逆转录病毒,其癌基因v-Abl可以诱导小鼠B淋巴细胞癌变。Bcr-Abl癌基因和A-MuLV病毒的共同特点是表达Abl癌蛋白(Bcr-Abl和v-Abl)。Abl癌蛋白诱导肿瘤发生与多条信号转导通路的异常活化密切相关。这些信号转导通路主要包括JAK/STAT/Pim、PI3K/AKT/mTOR和RAS/RAF/MEK。此外,Abl癌蛋白诱导肿瘤发生也与重要信号分子的突变或异常修饰,以及关键长链非编码RNA(lncRNA)的异常表达有关。文中对Abl癌基因如何激活主要的3条信号通路进行综述,并介绍参与细胞增殖、抗细胞凋亡等过程的重要蛋白及其与肿瘤发生的关系,为Abl阳性肿瘤的治疗提供了科学参考。

Preparation and properties of CMAS resistant bixbyite structured high-entropy oxides RE_(2)O_(3)(RE=Sm,Eu,Er,Lu,Y,and Yb):Promising environmental barrier coating materials for Al_(2)O_(3)f/Al_(2)O_(3) composites

Y_(2)O_(3) is regarded as one of the potential environmental barrier coating(EBC)materials for Al_(2)O_(3)f/Al_(2)O_(3)ceramic matrix composites owing to its high melting point and close thermal expansion coefficient to Al_(2)O_(3).However,the relatively high thermal conductivity and unsatisfactory calcium-magnesium-aluminosilicate(CMAS)resistance are the main obstacles for the practical application of Y_(2)O_(3).In order to reduce the thermal conductivity and increase the CMAS resistance,four cubic bixbyite structured high-entropy oxides RE_(2)O_(3),including(Eu_(0.2)Er_(0.2)Lu_(0.2)Y_(0.2)Yb_(0.2))2O_(3),(Sm_(0.2)Er_(0.2)Lu_(0.2)Y_(0.2)Yb_(0.2))2O_(3),(Sm_(0.2)Eu_(0.2)Er_(0.2)Y_(0.2)Yb_(0.2))2O_(3),and(Sm_(0.2)Eu_(0.2)Lu_(0.2)Y_(0.2)Yb_(0.2))2O_(3)were designed and synthesized,among which(Eu_(0.2)Er_(0.2)Lu_(0.2)Y_(0.2)Yb_(0.2))2O_(3)and(Sm_(0.2)Er_(0.2)Lu_(0.2)Y_(0.2)Yb_(0.2))2O_(3)bulks were prepared by spark plasma sintering(SPS)to investigate their mechanical and thermal properties as well as CMAS resistance.The mechanical properties of(Eu_(0.2)Er_(0.2)Lu_(0.2)Y_(0.2)Yb_(0.2))2O_(3)and(Sm_(0.2)Er_(0.2)Lu_(0.2)Y_(0.2)Yb_(0.2))2O_(3) are close to those of Y_(2)O_(3) but become more brittle than Y_(2)O_(3).The thermal conductivities of(Eu_(0.2)Er_(0.2)Lu_(0.2)Y_(0.2)Yb_(0.2))2O_(3) and(Sm_(0.2)Er_(0.2)Lu_(0.2)Y_(0.2)Yb02)2O_(3)(5.1 and 4.6 W·m^(-1)·K^(-1))are only 23.8%and 21.5%respectively of that of Y_(2)O_(3)(21.4 W·m^(-1)·K^(-1)),while their thermal expansion coefficients are close to those of Y_(2)O_(3) and A12O_(3).Most importantly,HE RE_(2)O_(3) ceramics exhibit good CMAS resistance.After being attacked by CMAS at 1350℃for 4 h,the HE RE_(2)O_(3) ceramics maintain their original morphologies without forming pores or cracks,making them promising as EBC materials for Al_(2)O_(3)f/Al_(2)O_(3) composites.

Visual sensing of picric acid in 100% aqueous media based on supramolecular polythiophene assemblies with colorimetric and fluorescent dual response

A colorimetric and fluorometric dual probe based on a water-soluble polythiophene derivative(PMTPBA)was designed and synthesized.It can be applied to determination of picric acid(PA) in 100% aqueous solution.The approach relies on the formation of supramolecular polythiophene assemblies in the presence of PA through electrostatic,charge transfer and π-π stacking interactions.This probe could be utilized for the rapid and visual detection of PA both in aqueous solution and solid support with high specificity and sensitivity.The detection limit of this sensor is as low as 5.0 × 10^-8 mol/L.

A mini review: Constructing perovskite p-n homojunction solar cells

Organic metal halide perovskite materials have excellent photoelectric properties, and the power conversion efficiency(PCE) of the perovskite solar cells(PSCs) has increased from 3.8% to more than 25%. In the development of PSCs, innovative architectures were being proposed constantly. However, the use of the electron transport layer(ETL) and hole transport layer(HTL) increases manufacturing costs and process complexity. Perovskite material has ambipolar charge transport characteristics, so it could functionalize as both the optical absorption layer and carrier transport layer(CTL). In this review, we analyzed the p/n-type perovskite materials, perovskite p-n homojunction solar cells, and carrier transport layers-free(CTLs-free) devices. Finally, we propose some innovative device architectures. We hope that this mini review could pave way for the simplification of the architectures, promote the preparation of the low-cost and high-efficiency devices, and accelerate the commercialization of the PSCs.

Functions of the adaptor protein p66shc in solid tumors

p66she is a 66 kDa Src homology 2 domain containing （Shc） adaptor protein homolog. Previous studies have demonstrated that p66she is a proapoptotic protein involved in the cellular response to oxidative stress and in regulating mammalian lifespan. However, accumulating evidence also indicates its critical role in solid tumor progression. The expression of p66she varies in different types of solid tumors, and it can paradoxically promote as well as suppress tumor progression, survival, and metastasis, depending on the cellular context. In this review, we discuss its functions in various solid tumors, the mechanisms by which it mediates the process of anoikis （detachment-induced cell death）, and the epigenetic mechanisms that regulate its expression. These studies indicate the potential of p66she as a novel prognostic marker and therapeutic target for the prevention of tumor progression and metastasis.