Premature aging of skeletal stem/progenitor cells rather than osteoblasts causes bone loss with decreased mechanosensation

A distinct population of skeletal stem/progenitor cells(SSPCs)has been identified that is indispensable for the maintenance and remodeling of the adult skeleton.However,the cell types that are responsible for age-related bone loss and the characteristic changes in these cells during aging remain to be determined.Here,we established models of premature aging by conditional depletion of Zmpste24(Z24)in mice and found that Prx1-dependent Z24 deletion,but not Osx-dependent Z24 deletion,caused significant bone loss.However,Acan-associated Z24 depletion caused only trabecular bone loss.Single-cell RNA sequencing(sc RNA-seq)revealed that two populations of SSPCs,one that differentiates into trabecular bone cells and another that differentiates into cortical bone cells,were significantly decreased in Prx1-Cre;Z24^(f/f)mice.Both premature SSPC populations exhibited apoptotic signaling pathway activation and decreased mechanosensation.Physical exercise reversed the effects of Z24depletion on cellular apoptosis,extracellular matrix expression and bone mass.This study identified two populations of SSPCs that are responsible for premature aging-related bone loss.The impairment of mechanosensation in Z24-deficient SSPCs provides new insight into how physical exercise can be used to prevent bone aging.

Inhibition of fibroblast activation protein ameliorates cartilage matrix degradation and osteoarthritis progression

Fibroblast activation protein(Fap)is a serine protease that degrades denatured type I collagen,α2-antiplasmin and FGF21.Fap is highly expressed in bone marrow stromal cells and functions as an osteogenic suppressor and can be inhibited by the bone growth factor Osteolectin(Oln).Fap is also expressed in synovial fibroblasts and positively correlated with the severity of rheumatoid arthritis(RA).However,whether Fap plays a critical role in osteoarthritis(OA)remains poorly understood.Here,we found that Fap is significantly elevated in osteoarthritic synovium,while the genetic deletion or pharmacological inhibition of Fap significantly ameliorated posttraumatic OA in mice.Mechanistically,we found that Fap degrades denatured type II collagen(Col II)and Mmp13-cleaved native Col II.Intra-articular injection of r Fap significantly accelerated Col II degradation and OA progression.In contrast,Oln is expressed in the superficial layer of articular cartilage and is significantly downregulated in OA.Genetic deletion of Oln significantly exacerbated OA progression,which was partially rescued by Fap deletion or inhibition.Intra-articular injection of r Oln significantly ameliorated OA progression.Taken together,these findings identify Fap as a critical pathogenic factor in OA that could be targeted by both synthetic and endogenous inhibitors to ameliorate articular cartilage degradation.

Primary cilia support cartilage regeneration after injury

In growing children,growth plate cartilage has limited self-repair ability upon fracture injury always leading to limb growth arrest.Interestingly,one type of fracture injuries within the growth plate achieve amazing self-healing,however,the mechanism is unclear.Using this type of fracture mouse model,we discovered the activation of Hedgehog(Hh)signaling in the injured growth plate,which could activate chondrocytes in growth plate and promote cartilage repair.

乳腺癌术后经外周静脉穿刺中心静脉置管侧上肢静脉血栓形成的危险因素与应对策略分析

目的探讨乳腺癌术后经外周静脉穿刺中心静脉置管(PICC)侧上肢静脉血栓形成(UEVT)的危险因素与应对策略。方法收集2020年1月至2023年1月于南京鼓楼医院集团安庆市石化医院就诊的93例乳腺癌术后PICC置管侧发生UEVT患者的临床资料,采用倾向匹配法根据患者年龄按1:2比例及是否发生UEVT将其分为UEVT组(n=31,发生UEVT)和NUEVT组(n=62,未发生UEVT),比较两组患者的年龄、体重指数、乳腺癌临床分期、分化程度、合并症、置管位置、D-二聚体(D-D)、C-反应蛋白(CRP)、低密度脂蛋白胆固醇(LDL-C)、血小板计数(PLT)等,分析乳腺癌患者术后发生UEVT的相关因素及应对策略。结果PICC置管位置、D-D、CRP、PLT均为乳腺癌术后PICC置管侧UEVT形成的危险因素(OR﹥1,P﹤0.05)。PICC肘下置管对同侧UEVT形成具有较低预警价值(AUC=0.581),D-D、CRP、PLT均具有较高预警价值(AUC=0.844、0.755、0.827),其中,预警值为D-D≥517.67 ng/ml、PLT≥376.91×10^(9)/L、CRP≥5.22 mg/L。结论乳腺癌术后PICC置管患者应及时进行D-D、CRP、PLT水平检测,若发现检测结果高于预警值时应积极进行抗凝、抗炎、抗血小板治疗,同时应尽量选取肘上穿刺置管等,能够降低患者置管侧UEVT的发生风险。

LncRNA Nron regulates osteoclastogenesis during orthodontic bone resorption

Activation of osteoclasts during orthodontic tooth treatment is a prerequisite for alveolar bone resorption and tooth movement.However,the key regulatory molecules involved in osteoclastogenesis during this process remain unclear.Long noncoding RNAs(lnc RNAs)are a newly identified class of functional RNAs that regulate cellular processes,such as gene expression and translation regulation.Recently,lnc RNAs have been reported to be involved in osteogenesis and bone formation.However,as the most abundant noncoding RNAs in vivo,the potential regulatory role of lnc RNAs in osteoclast formation and bone resorption urgently needs to be clarified.We recently found that the lnc RNA Nron(long noncoding RNA repressor of the nuclear factor of activated T cells)is highly expressed in osteoclast precursors.Nron is downregulated during osteoclastogenesis and bone ageing.To further determine whether Nron regulates osteoclast activity during orthodontic treatment,osteoclastic Nron transgenic(Nron c TG)and osteoclastic knockout(Nron CKO)mouse models were generated.When Nron was overexpressed,the orthodontic tooth movement rate was reduced.In addition,the number of osteoclasts decreased,and the activity of osteoclasts was inhibited.Mechanistically,Nron controlled the maturation of osteoclasts by regulating NFATc1 nuclear translocation.In contrast,by deleting Nron specifically in osteoclasts,tooth movement speed increased in Nron CKO mice.These results indicate that lnc RNAs could be potential targets to regulate osteoclastogenesis and orthodontic tooth movement speed in the clinic in the future.

Influence of rheo-diecasting processing parameters on microstructure and mechanical properties of hypereutectic Al-30%Si alloy

The effects of pouring temperature,vibration frequency,and the number of curves in a serpentine channel,on themicrostructure and mechanical properties of Al-30%Si alloy processed by rheo-diecasting(RDC)were investigated.The semisolidAl-30%Si alloy slurry was prepared by vibration serpentine channel pouring(VSCP)process in the RDC process.The results showthat the pouring temperature,the vibration frequency,and the number of the curves strongly affect the microstructure and mechanicalproperties of Al-30%Si alloy.Under experimental conditions of a pouring temperature of850°C,a twelve-curve copper channel anda vibration frequency of80Hz,the primary Si grains are refined into fine compact grains with average grain size of about24.6μm inthe RDC samples assisted with VSCP.Moreover,the ultimate tensile strength(UTS),elongation and hardness of the RDC sample are296MPa,0.87%and HB155,respectively.It is concluded that the VSCP process can effectively refine the primary Si grains.Therefinement of primary Si grains is the major cause for the improvement of the mechanical properties of the RDC sample.

Investigation of rheo-diecasting mold filling of semi-solid A380 aluminum alloy slurry

The rheo-diecasting mold filling capacity and the microstructure of the semi-solid A380 aluminum alloy slurry were investigated. The results show that the mold filling capacity was strengthened with increasing pouring temperature or increasing injection pressure. Under certain process parameters, the mold cavity was fully filled. However, the mold filling capacity decreased with increasing holding time. The mold filling capacity was improved with increasing shape factor of primary α(Al) grains; however, the solid fraction and the grain size significantly increased at the same time. In addition, the microstructures along the route of the spiral samples obviously differed. The grain size decreased gradually from the near-end to the far-end, whereas the shape factor increased gradually.

Effects of Sr addition on microstructure, mechanical properties and in vitro degradation behavior of as-extruded Zn-Sr binary alloys

The microstructures,mechanical properties and in vitro degradation behavior of as-extruded pure Zn and Zn-x Sr(x=0.1,0.4,0.8 wt.%)alloys were investigated systematically.For the microstructure and mechanical properties,Sr Zn13 phase was newly formed due to the addition of 0.1 wt.%Sr,improving the yield strength,ultimate tensile strength and elongation from(85.33±2.86)MPa,(106.00±1.41)MPa and(15.37±0.57)%for pure Zn to(107.67±2.05)MPa,(115.67±2.52)MPa and(20.80±2.19)%for Zn-0.1Sr,respectively.However,further increase of Sr content led to the deterioration of the mechanical properties due to the stress concentration and cracks initiation caused by the coarsening Sr Zn13 particles during tensile tests.For in vitro degradation,since micro galvanic corrosion was enhanced owing to the formation of the inhomogeneously distributed Sr Zn13 phase,the corrosion mode became non-uniform.Corrosion rate is gradually increased with the addition of Sr,which is increased from(11.45±2.02)μm/a(a=year)for pure Zn to(32.59±3.40)μm/a for Zn-0.8Sr.To sum up,the as-extruded Zn-0.1Sr alloy exhibited the best combination of mechanical properties and degradation behavior.

Refinement of primary Si grains in Al–20%Si alloy slurry through serpentine channel pouring process

In this study, a serpentine channel pouring process was used to prepare the semi-solid A1-20%Si alloy slurry and refine primary Si grains in the alloy. The effects of the pouring temperature, number of curves in the serpentine channel, and material of the serpentine channel on the size of primary Si grains in the semi-solid A1-20%Si alloy slurry were investigated. The results showed that the pouting temperature, number of the curves, and material of the channel strongly affected the size and distribution of the primary Si grains. The pouring tempera- ture exerted the strongest effect, followed by the number of the curves and then the material of the channel. Under experimental conditions of a four-curve copper channel and a pouring temperature of 701℃, primary Si grains in the semi-solid A1-20%Si alloy slurry were refined to the greatest extent, and the lath-like grains were changed into granular grains. Moreover, the equivalent grain diameter and the average shape coefficient of primary Si grains in the satisfactory semi-solid A1-20%Si alloy slurry were 24.4 μm and 0.89, respectively. Finally, the re- finement mechanism and distribution rule of primary Si grains in the slurry prepared through the serpentine channel pouring process were analyzed and discussed.

Refinement of primary Si grains of A390 alloy slurry through serpentine channel pouring process

In this paper, the serpentine channel pouring process for preparing a semi-solid A390 alloy slurry and refining the primary Si grains of the A390 alloy, was used. The effects of the pouring temperature, the cooling water flow and the number of the curves on the size of the primary Si grains in the semi-solid A390 alloy slurry were investigated. The results show that the pouring temperature, the cooling water flow and the number of the curves have a major effect on the size and the distribution of primary Si grains. Under the experimental condition of the four-curve copper channel whose cooling water flow was 500 L·h-1 and the pouring temperature was 690 oC, the primary Si grains of the semi-solid A390 alloy slurry were refined to the greatest extent and the lath-like grains were changed into granular ones. Additionally, the equivalent grain diameter and the average shape factor of the primary Si grains of the satisfactory semi-solid A390 alloy slurry are 18.6 μm and 0.8, respectively. Further, the refinement mechanism of the primary Si grains through the serpentine channel pouring process was analyzed and discussed. In summary, the primary Si nuclei could be easily precipitated due to the chilling effect of the channel inner wall, thus the primary Si grains were greatly refined. Meanwhile, the subsequent alloy melt fluid also promoted the separation of primary Si grains from the inner wall, further refining the primary Si grains.

基于扎根理论的苏北传统村落环境归属感重塑研究

本研究运用扎根理论的研究方法,以村民的角度对苏北传统村落的环境归属感进行研究。通过对原始资料及理论的比对分析,研究运用开放性译码、主轴译码、选择性译码的方法先概括出42个概念、16个范畴,进而提升理论维度得到8个主范畴,最后提取出了重塑苏北传统村落村民环境归属感的核心任务——即应从"传统村落人地生态景观、传统村落居住生活景观"这一核心概念入手重塑苏北传统村落村民环境归属感。

Generation of functional oligopeptides that promote osteogenesis based on unsupervised deep learning of protein IDRs

Deep learning(DL)is currently revolutionizing peptide drug development due to both computational advances and the substantial recent expansion of digitized biological data.However,progress in oligopeptide drug development has been limited,likely due to the lack of suitable datasets and difficulty in identifying informative features to use as inputs for DL models.Here,we utilized an unsupervised deep learning model to learn a semantic pattern based on the intrinsically disordered regions of~171 known osteogenic proteins.Subsequently,oligopeptides were generated from this semantic pattern based on Monte Carlo simulation,followed by in vivo functional characterization.A five amino acid oligopeptide(AIB5P)had strong bone-formation-promoting effects,as determined in multiple mouse models(e.g.,osteoporosis,fracture,and osseointegration of implants).Mechanistically,we showed that AIB5P promotes osteogenesis by binding to the integrinα5 subunit and thereby activating FAK signaling.In summary,we successfully established an oligopeptide discovery strategy based on a DL model and demonstrated its utility from cytological screening to animal experimental verification.

Application of Ethylparaben in Quality Control of Favoring Agents and Fragrances Used for Cigarette Production

This study was conducted to evaluate the antimierobial activity of ethylparaben （ethyl para-hydroxybenzoate） in flavoring agents and fragrances used tot cigarette production. In brief, different levels of ethylparaben were added to Ziyun and Ruanzhen fragrance concentrates, and fermented with or without the additiorl of extra microbial strains. The aroma components in the fermented samples were detected via gas chromatography-mass spectrometry （GC/MS） assay. The results showed that ethylparaben had good antimicrobial activity on the microorganism in Ziyun and Ruanzhen fragrances, and as it significantly inhibited the growth of Sac- charomyces sp. Aeetobacter sp. , Agrobacterium sp. and Bacillus sp. , with an inhibition rate of 53%. Under natural fermentation condition, 91. 885% of the micro- organisms were inhibited by adding 0. 1 g/kg ethylparaben, 97.69% were inhibited by adding 0.3 g/kg ethylparaben, and 100% were inhibited by adding 0.5 g/kg ethylparaben. Moreover, the addition of ethylparaben had no obvious influence on the aroma components of the favoring agents and fragrances. So, it carl be used as a preservative for the quality control of favoring agents and fragrances for cigarette production.

Causes of Deterioration and Changes of Aroma Components in Cigarette Raw Materials

The quality of the favoring agents and fragrances degenerated frequently during the storage and transportation process in a cigarette factory in Yunnan Province, causing huge economic losses. In order to ascertain the causes of deterioration, the microbial population, quantity and aroma components of the raw mate- rials were analyzed in the present study. The results showed that a total of 28 bacterial strains and one fungal strain were isolated and identified, belonging to 13 genera. The 29 strains were Bacillus sp. , Microbacterium sp. , Sphingomonas sp. , Leclercia sp. and Acinetobacter sp. isolated from normal ZY material; Bacil- lus sp. , Microbacterium sp. , Sphingomonas sp. , Brevundimonus sp. , Acinetobacter sp. , Agrobacterium sp. , Ralstonia sp. , Acetobacterium sp. , Saccharomyces sp. and Acidovorax sp. isolated from deteriorated ZY material; Agrobacterium sp. , Microbacterium sp. , Burkholderia sp. , Bacillus subtilis strain, Acetobacterium sp. and Leclercia sp. isolated from normal RZ material ; Agrobacterium sp. , Microbacterium sp. , Bacillus subtilis strain, Acetobacterium sp. , Lec/erc/a sp. , Enter- obacter sp. , Acinetobacter sp. and Saccharomyces sp. isolated from deteriorated RZ material. Microbacterium was the dominant genus by number in normal ZY ma- terial, and the population of this genus accounted for 55.6% of the total. In deteriorated ZY material, Acetobacterium, Bacillus and Saccharomyces were dominant genera, as the population of the three genera occupied 75.0% of the total. The total population of microorganisms in the deteriorated ZY material was 90 times of that in normal ZY material. In normal RZ material, the population of each of Microbacterium, Agrobacterium and Bacillus accounted for 25%, while that of each of Leclercia and Burkholderia accounted for 12.5%. In deteriorated RZ material, the population of Bacillus accounted for 65.0% of the total. The total population of the microorganisms in deteriorated RZ material was 29 times of that in normal RZ material, indicating that the deterioration of the materials was caused by microor- ganisms. The contents of aroma components were detected using two-dimensional gas chromatography-mass spectrometry （GC-MS）. The results showed that in nor- mal ZY material, the content of β-damascone was higher than that of other aroma components. And normal ZY material had higher contents of benzaldehyde, β-damascone, β-damascone, β-damascone, menthol and benzyl benzoate than deteriorated ZY material, and the differences in the contents of β-ddamascone and β-damascone were most significant between the two materials. In normal RZ material, the content of β-damascone was higher than that of other aroma components. And normal RZ material had higher contents of menthol, ethyl capratc, β-damascone, β-damascone and tabanane C than deteriorated RZ material, and the differ- ences in the contents of ethyl caprate and capric acid were most significant between the two materials. The results revealed that aroma components changed greatly in deteriorated tobacco materials.

Goaf risk prediction based on IAOA-SVM and numerical simulation:A case study

In regard to goaf risk prediction,due to the low accuracy and single prediction method,this study proposes a method that combines the improved arithmetic optimization algorithm(IAOA)–support vector machines(SVM)with GoCAD–FLAC^(3D)numerical simulation.Thus,goaf risk is comprehensively predicted.From the perspectives of geological and engineering conditions,eight factors that affect goaf stability and 176 sets of sample data were determined.We utilized eight influencing factors such as rock mass structure,geological structure,and goaf burial depth as inputs,and the goaf risk level as the output.Moreover,an IAOA–SVM goaf risk prediction model was established.The 30 goaf areas of Yangla Copper Mine in Yunnan Province were selected as the research subject.First,the rationality of mechanical parameter values in the numerical model was verified using the parameter inversion method.Second,based on the GoCAD–FLAC^(3D)numerical simulation method,the goaf risk analysis in Yangla Copper Mine was performed.Subsequently,using numerical simulation verification,the goaf filling effect was analyzed.Finally,the prediction results of the IAOA–SVM model were compared with that of other intelligent algorithms.The results indicate that the numerical simulation results of the GoCAD–FLAC^(3D)model are consistent with those of IAOA–SVM and the actual results,which further verifies the effectiveness and superiority of the IAOA–SVM prediction model.Therefore,an innovative approach for goaf risk prediction is developed.

Biomarkers of aging

Aging biomarkers are a combination of biological parameters to(i)assess age-related changes,(ii)track the physiological aging process,and(iii)predict the transition into a pathological status.Although a broad spectrum of aging biomarkers has been developed,their potential uses and limitations remain poorly characterized.An immediate goal of biomarkers is to help us answer the following three fundamental questions in aging research:How old are we?Why do we get old?And how can we age slower?This review aims to address this need.Here,we summarize our current knowledge of biomarkers developed for cellular,organ,and organismal levels of aging,comprising six pillars:physiological characteristics,medical imaging,histological features,cellular alterations,molecular changes,and secretory factors.To fulfill all these requisites,we propose that aging biomarkers should qualify for being specific,systemic,and clinically relevant.

Glycosylation of dentin matrix protein 1 is critical for fracture healing via promoting chondrogenesis

Fractures are frequently occurring diseases that endanger human health. Crucial to fracture healing is cartilage formation, which provides a bone-regeneration environment. Cartilage consists of both chondrocytes and extracellular matrix (ECM). The ECM of cartilage includes collagens and various types of proteoglycans (PGs), which play important roles in maintaining primary stability in fracture healing. The PG form of dentin matrix protein 1 (DMP1-PG) is involved in maintaining the health of articular cartilage and bone. Our previous data have shown that DMP1-PG is richly expressed in the cartilaginous calluses of fracture sites. However, the possible significant role of DMP1-PG in chondrogenesis and fracture healing is unknown. To further detect the potential role of DMP1-PG in fracture repair, we established a mouse fracture model by using a glycosylation site mutant DMP1 mouse (S89G-DMP1 mouse). Upon inspection, fewer cartilaginous calluses and down-regulated expression levels of chondrogenesis genes were observed in the fracture sites of S89G-DMP1 mice. Given the deficiency of DMP1-PG, the impaired IL-6/JAK/STAT signaling pathway was observed to affect the chondrogenesis of fracture healing. Overall, these results suggest that DMP1-PG is an indispensable proteoglycan in chondrogenesis during fracture healing.

Combination of steam-enhanced extraction and electrical resistance heating for efficient remediation of perchloroethylene-contaminated soil:Coupling merits and energy consumption

In situ thermal desorption(ISTD)technology effectively remediates soil contaminated by dense nonaqueous phase liquids(DNAPLs).However,more efforts are required to minimize the energy consumption of ISTD technology.This study developed a laboratory-scale experimental device to explore the coupling merits of two traditional desorption technologies:steam-enhanced extraction(SEE)and electrical resistance heating(ERH).The results showed that injecting high-density steam(>1 g/min)into loam or clay with relatively high moisture content(>13.3%)could fracture the soil matrix and lead to the occurrence of the preferential flow of steam.For ERH alone,the electrical resistance and soil moisture loss were critical factors influencing heating power.When ERH and SEE were combined,preheating soil by ERH could increase soil permeability,effectively alleviating the problem of preferential flow of SEE.Meanwhile,steam injection heated the soil and provided moisture for maintaining soil electrical conductivity,thereby ensuring power stability in the ERH process.Compared with ERH alone(8 V/cm)and SEE alone(1 g/min steam),the energy consumption of combined method in remediating perchloroethylene-contaminated soil was reduced by 39.3%and 52.9%,respectively.These findings indicate that the combined method is more favorable than ERH or SEE alone for remediating DNAPL-contaminated subsurfaces when considering ISTD technology.

Graphene/phosphorene nano-heterojunction:facile synthesis, nonlinear optics, and ultrafast photonics applications with enhanced performance

Owing to its thickness-modulated direct energy band gap, relatively strong light–matter interaction, and unique nonlinear optical response at a long wavelength, few-layer black phosphorus, or phosphorene, becomes very attractive in ultrafast photonics applications. Herein, we synthesized a graphene/phosphorene nano-heterojunction using a liquid phase-stripping method. Tiny lattice distortions in graphene and phosphorene suggest the formation of a nano-heterojunction between graphene and phosphorene nanosheets. In addition, we systematically investigate their nonlinear optical responses at different wavelength regimes. Our experiments indicate that the combined advantages of ultrafast relaxation, broadband response in graphene, and the strong light–matter interaction in phosphorene can be combined together by nano-heterojunction. We have further fabricated two-dimensional(2D) nano-heterojunction based optical saturable absorbers and integrated them into an erbium-doped fiber laser to demonstrate the generation of a stable ultrashort pulse down to 148 fs. Our results indicate that a graphene/phosphorene nano-heterojunction can operate as a promising saturable absorber for ultrafast laser systems with ultrahigh pulse energy and ultranarrow pulse duration. We believe this work opens up a new approach to designing 2D heterointerfaces for applications in ultrafast photonics and other research.The fabrication of a 2D nano-heterojunction assembled from stacking different 2D materials, via this facile and scalable growth approach, paves the way for the formation and tuning of new 2D materials with desirable photonic properties and applications.