ODA二胺单体双酮酐型聚酰亚胺的合成与性能

以4,4'-对苯二甲酰二邻苯二甲酸酐(TDPA)为二酐单体,4,4'-二氨基二苯醚(4,4'-ODA)和3,4'-二氨基二苯醚(3,4'-ODA)为二胺单体,采用两步法低温溶液缩聚分别合成了2种聚酰亚胺(PI)。采用红外光谱、X射线衍射、差示扫描量热分析、热重分析、拉伸强度测试等对聚合物的结构与性能进行了表征。研究结果表明,制得的聚酰亚胺均具有良好的成膜性,PI(4,4'-ODA)膜的拉伸强度达到262 MPa,玻璃化转变温度(Tg)为297℃; PI(3,4'-ODA)膜的拉伸强度为149 MPa,Tg为261℃。热分解温度都在520℃以上,具有优良的耐热性能及力学性能。

The dependences of osteocyte network on bone compartment, age, and disease

Osteocytes, the most abundant bone cells, form an interconnected network in the lacunar-canalicular pore system （LCS） buried within the mineralized matrix, which allows osteocytes to obtain nutrients from the blood supply, sense external mechanical signals, and communicate among themselves and with other cells on bone surfaces. In this study, we examined key features of the LCS network including the topological parameter and the detailed structure of individual connections and their variations in cortical and cancellous compa~ tments, at different ages, and in two disease conditions with altered mechanosensing （perlecan deficiency and diabetes）. LCS network showed both topological stability, in terms of conservation of connectivity among osteocyte lacunae （similar to the ＂nodes＂ in a computer network）, and considerable variability the pericellular annular fluid gap surrounding lacunae and canaliculi （similar to the ＂bandwidth＂ of individual links in a computer network）. Age, in the range of our study （15-32 weeks）, affected only the pericellular fluid annulus in cortical bone but not in cancellous bone. Diabetes impacted the spacing of the lacunae, while the perlecan deficiency had a profound influence on the pericellular fluid annulus. The LCS network features play important roles in osteocyte signaling and regulation of bone growth and adaptation.

Targeted Ptpn11 deletion in mice reveals the essential role of SHP2 in osteoblast differentiation and skeletal homeostasis

The maturation and function of osteoblasts(OBs)rely heavily on the reversible phosphorylation of signaling proteins.To date,most of the work in OBs has focused on phosphorylation by tyrosyl kinases,but little has been revealed about dephosphorylation by protein tyrosine phosphatases(PTPases).SHP2(encoded by PTPN11)is a ubiquitously expressed PTPase.PTPN11 mutations are associated with both bone and cartilage manifestations in patients with Noonan syndrome(NS)and metachondromatosis(MC),although the underlying mechanisms remain elusive.Here,we report that SHP2 deletion in bone gamma-carboxyglutamate protein-expressing(Bglap+)bone cells leads to massive osteopenia in both trabecular and cortical bones due to the failure of bone cell maturation and enhanced osteoclast activity,and its deletion in Bglap+chondrocytes results in the onset of enchondroma and osteochondroma in aged mice with increased tubular bone length.Mechanistically,SHP2 was found to be required for osteoblastic differentiation by promoting RUNX2/OSTERIX signaling and for the suppression of osteoclastogenesis by inhibiting STAT3-mediated RANKL production by osteoblasts and osteocytes.These findings are likely to explain the compromised skeletal system in NS and MC patients and to inform the development of novel therapeutics to combat skeletal disorders.

A multiscale 3D finite element analysis of fluid/solute transport in mechanically loaded bone

The transport of fluid, nutrients, and signaling molecules in the bone lacunar-canalicular system （LCS） is critical for osteocyte survival and function. We have applied the fluorescence recovery after photobleaching （FRAP） approach to quantify load-induced fluid and solute transport in the LCS in situ, but the measurements were limited to cortical regions 30-50 μm underneath the periosteum due to the constrains of laser penetration. With this work, we aimed to expand our understanding of load-induced fluid and solute transport in both trabecular and cortical bone using a multiscaled image-based finite element analysis （FEA） approach. An intact murine tibia was first re-constructed from microCT images into a three-dimensional （3D） linear elastic FEA model, and the matrix deformations at various locations were calculated under axial loading. A segment of the above 3D model was then imported to the biphasic poroelasticity analysis platform （FEBio） to predict load-induced fluid pressure fields, and interstitial solute/fluid flows through LCS in both cortical and trabecular regions. Further, secondary flow effects such as the shear stress and/or drag force acting on osteocytes, the presumed mechano-sensors in bone, were derived using the previously developed ultrastructural model of Brinkman flow in the canaliculi. The material properties assumed in the FEA models were validated against previously obtained strain and FRAP transport data measured on the cortical cortex. Our results demonstrated the feasibility of this computational approach in estimating the fluid flux in the LCS and the cellular stimulation forces （shear and drag forces） for osteocytes in any cortical and trabecular bone locations, allowing further studies of how the activation of osteocytes correlates with in vivo functional bone formation. The study provides a promising platform to reveal potential cellular mechanisms underlying the anabolic power of exercises and physical activities in treating patients with skeletal deficiencies.

Bisphosphonate rescue post-traumatic osteoarthritis by promoting the calcium signaling in chondrocytes

Introduction Post-traumatic osteoarthritis(PTOA)is a long-term adverse consequence of joint trauma,e.g.,meniscus or ligament tears,which are among the most common injuries for young adults with excessive physical activities,such as athletes and military employees.Currently,few preventive treatments exist for PTOA,with typical outcomes being gradual cartilage degeneration and eventual loss of joint function.Apoptosis and altered etabolism of chondrocytes,the sole cell type in cartilage,may be responsible for the development of PTOA in a subset of patients without traumatic cartilage destruction but with persistent altered joint loading post-trauma,which is the focus of this study.

Intracellular calcium signaling in osteocytes:A mechano-transduction-mechano paradigm

Osteocytes in vivo are embedded in the mineralized extracellular bone matrix,where their cell bodies reside in the lacunae and are interconnected to neighboring osteocytes through numerous intercellular processes.The 3-dimensional（3D）osteocyte network positioning and ability to communicate with other bone cells make osteocytes ideal mechanosensors of bone.Thus the role of osteocyte network and intercellular communication between osteocytes in response to mechanical stimulation may clarify the mechanisms behind normal bone adaptation to mechanical loading.We have been using intracellular calcium([Ca2+]i)as a ubiquitous real-time signaling indicator for studying mechanotransduction in osteocytic network

Perlecan/Hspg2 Deficiency Impairs Bone’s Calcium Signaling and Associated Transcriptome in Response to Mechanical Loading

Perlecan,a heparan sulfate proteoglycan,acts as a mechanical sensor for bone to detect external loading.Deficiency of perlecan increases the risk of osteoporosis in patients with Schwartz-Jampel Syndrome(SJS)and attenuates loading4nduced bone formation in perlecan deficient mice(Hypo).Considering that intracellular calcium[Ca2+]i is an ubiquitous messenger controlling numerous cellular processes including mechanotransduction,we hypothesized that perlecan deficiency impairs bone’s calcium signaling in response to loading.To test this,we performed real-time[Ca2+]i imaging on in situ osteocytes of adult murine tibiae under cyclic loading(8 N,Figure 1).Relative to wild type(WT),Hypo osteocytes showed decreases in the overall[Ca2+]i response rate(-58%),calcium peaks(-33%),cells with multiple peaks(-53%),peak magnitude(-6.8%),and recovery speed to baseline(-23%).RNA sequencing and pathway analysis of tibiae from mice subjected to one or seven days of unilateral loading demonstrated that perlecan deficiency significantly suppressed the calcium signaling,ECM-receptor interaction,and focal adhesion pathways following repetitive loading.Defects in the endoplasmic reticulum(ER)calcium cycling regulators such as Ryr1/ryanodine receptors and Atp2a1/Sercal calcium pumps were identified in Hypo bones.Taken together,impaired calcium signaling may contribute to bone’s reduced anabolic response to loading,underlying the osteoporosis risk for the SJS patients.

A meta-analysis on the effects of probiotics on the performance of pre-weaning dairy calves

Background:Probiotics have been used in livestock production for many years,but information on their benefits during the early life of calves is inconsistent.This study aimed to assess the effects of probiotics on the performance of pre-weaning dairy calves and identify the factors influencing their effect sizes.Results:Forty-nine studies were selected for meta-analysis based on the inclusion and exclusion criteria.The study qualities were evaluated using a predefined risk assessment tool following GRADE guidelines.Meta-analysis results showed that probiotics increased the growth performance(body weight by 1.988 kg and average daily gain by40.689 g/d),decreased digestibility and feed efficiency(feed conversion rate by 0.073),altered rumen parameter(decreased acetate by 2.815 mmol/L and increased butyrate by 0.788 mmol/L),altered blood parameter(decreased AST by 4.188 U/L,increased BHBA by 0.029 mmol/L and IgG by 0.698 g/L),increased faecal parameter(faecal bacteria counts by 0.680 log10CFU/g),based on the strict criteria(P_(SMD)<0.05,I^(2)<50%).Additionally,probiotics increased digestibility and feed efficiency(starter dry matter intake by 0.034 kg/d and total dry matter intake by 0.020 kg/d),altered blood parameter(increased IgA by 0.313 g/L,IgM by 0.262 g/L and total antioxidant capacity by 0.441 U/mL,decreased MDA by 0.404 nmol/mL),decreased faecal parameter(faecal score by 0.052),based on the loose criteria(P_(SMD)<0.05,I^(2)>50%).Regression and sub-group analyses showed that probiotic strains,supplementation dosage,and methods significantly affected the performance of calves.The probiotics supplied with more than 9.5 log10CFU/d significantly increased IgA and IgM contents(P_(SMD)<0.05).Additionally,the compound probiotics significantly increased TDMI,IgA,and IgM(P_(SMD)≤0.001).Furthermore,probiotics supplemented in liquid(whole milk or milk replacer)significantly increased TDMI and decreased faecal score(P_(SMD)<0.05),while in whole milk,they significantly increased body weight,IgA,and IgM(P_(SMD)<0.001).Conclusions:Probiotics could improve the growth performance,feed intake and efficiency,rumen fermentation,immune and antioxidant capacity,and health of pre-weaning calves.However,the effect sizes were related to the dosage,composition,and supplementation methods of probiotics.

Evolution and Effectiveness of Loss Functions in Generative Adversarial Networks

Recently,the evolution of Generative Adversarial Networks(GANs)has embarked on a journey of revolutionizing the field of artificial and computational intelligence.To improve the generating ability of GANs,various loss functions are introduced to measure the degree of similarity between the samples generated by the generator and the real data samples,and the effectiveness of the loss functions in improving the generating ability of GANs.In this paper,we present a detailed survey for the loss functions used in GANs,and provide a critical analysis on the pros and cons of these loss functions.First,the basic theory of GANs along with the training mechanism are introduced.Then,the most commonly used loss functions in GANs are introduced and analyzed.Third,the experimental analyses and comparison of these loss functions are presented in different GAN architectures.Finally,several suggestions on choosing suitable loss functions for image synthesis tasks are given.

Breast Cancer Induced Bone Osteolysis Prediction Using Temporal Variational Autoencoders

Objective and Impact Statement.We adopt a deep learning model for bone osteolysis prediction on computed tomography(CT)images of murine breast cancer bone metastases.Given the bone CT scans at previous time steps,the model incorporates the bone-cancer interactions learned from the sequential images and generates future CT images.Its ability of predicting the development of bone lesions in cancer-invading bones can assist in assessing the risk of impending fractures and choosing proper treatments in breast cancer bone metastasis.Introduction.Breast cancer often metastasizes to bone,causes osteolytic lesions,and results in skeletal-related events(SREs)including severe pain and even fatal fractures.Although current imaging techniques can detect macroscopic bone lesions,predicting the occurrence and progression of bone lesions remains a challenge.Methods.We adopt a temporal variational autoencoder(T-VAE)model that utilizes a combination of variational autoencoders and long short-term memory networks to predict bone lesion emergence on our micro-CT dataset containing sequential images of murine tibiae.Given the CT scans of murine tibiae at early weeks,our model can learn the distribution of their future states from data.Results.We test our model against other deep learning-based prediction models on the bone lesion progression prediction task.Our model produces much more accurate predictions than existing models under various evaluation metrics.Conclusion.We develop a deep learning framework that can accurately predict and visualize the progression of osteolytic bone lesions.It will assist in planning and evaluating treatment strategies to prevent SREs in breast cancer patients.

Progress in nanomedicine for sonodynamic immunotherapy of tumors

Cancer remains a leading cause of mortality worldwide,with conventional treatments,such as chemotherapy and immunotherapy,exhibiting limitations,such as drug resistance and immune evasion.Therefore,novel therapeutic strategies are required.Sonodynamic therapy has emerged as an innovative approach in which sonosensitizers are activated by ultrasound to achieve antitumor effects through mechanisms,such as cavitation,thermal effects,and reactive oxygen species generation.Notably,sonodynamic therapy also exhibits immunomodulatory effects and strongly impacts the tumor microenvironment and immune system in the body.The immune effects of sonodynamic therapy indicate that it can be applied with immunotherapy to exert synergistic effects.This review describes the design of sonosensitizers and basic mechanisms of sonodynamic therapy,highlighting their immune effects and recent advancements in sonodynamic therapy-based cancer immunotherapy.In addition,we introduce the applications of gas and metabolic regulation therapies in sonodynamic immunotherapy.

A Thermal Event in the Ordos Basin:Insights from Illite ^40Ar-^39Ar Dating with Regression Analysis

Four samples from a Permian reservoir in the Ordos Basin of North China were separated into twelve fractions in grain sizes of 〈0.5, 0.5-1 and 1-2 μm. Using the ^40Ar-^39Ar step-heating method, all of the fractions essentially yielded plateau ages ranging from 172.5 to 217.1 Ma. These scattered plateau ages might not have been obtained from pure diagenetic illites but from mixed clay minerals, although the samples were disaggregated using a gentle freeze-thaw cycle to free them of non-clay minerals. A regional thermal event, as suggested by several proxies, led to intensive iHitization as a distinct diagenetic process when the Yanshanian Movement triggered magmatism around the entire North China Block during the Jurassic to Cretaceous. Thermal illites formed during a short time period, whereas detrital illites came from various sources. The scattered plateau ages could have resulted from mixed degassing of thermal and detrital illites. Within one sample, the plateau ages decrease with the diminution of grain sizes, but it is difficult to extrapolate to the detrital-illite-free ages. Because the plateau age is a mixture of ages for thermal and detrital illites, this regression analysis studies the dependence of the plateau ages on the synthetic values of contents and ages of detrital illites instead of on the grain sizes. Comparing the samples to one another, the plateau ages show the same trend among the different grain sizes. Weighted by the contents and ages of detrital illites, linear regression analysis revealed the relationship between the plateau ages and the relative weight proportions. Based on iterated calculations, a thermal event age and a set of weight proportions were derived. The regressed thermal event age is 163.3±1.6 Ma, which coincides with regional thermal activities and links to gas accumulation.

Structures,properties,and challenges of emerging 2D materials in bioelectronics and biosensors

Bioelectronics are powerful tools for monitoring and stimulating biological and biochemical processes,with applications ranging from neural interface simulation to biosensing.The increasing demand for bioelectronics has greatly promoted the development of new nanomaterials as detection platforms.Recently,owing to their ultrathin structures and excellent physicochemical properties,emerging two-dimensional(2D)materials have become one of the most researched areas in the fields of bioelectronics and biosensors.In this timely review,the physicochemical structures of the most representative emerging 2D materials and the design of their nanostructures for engineering highperformance bioelectronic and biosensing devices are presented.We focus on the structural optimization of emerging 2D material-based composites to achieve better regulation for enhancing the performance of bioelectronics.Subsequently,the recent developments of emerging 2D materials in bioelectronics,such as neural interface simulation,biomolecular/biomarker detection,and skin sensors are discussed thoroughly.Finally,we provide conclusive views on the current challenges and future perspectives on utilizing emerging 2D materials and their composites for bioelectronics and biosensors.This review will offer important guidance in designing and applying emerging 2D materials in bioelectronics,thus further promoting their prospects in a wide biomedical field.

Study on the microwave-assisted extraction of polyphenols from tea

This study demonstrated a promising method for quickly extracting tea polyphenol(TP)by microwaveassisted extraction(MAE)technology.Some influential parameters,including MAE temperature,microwave power,concentration of extraction solvent,MAE time and the solid/liquid ratio,were investigated.The optimum condition of MAE was obtained by dual extraction with 60%ethanol(v/v)and the solid/liquid ratio 1:12 g/mL at 80℃ for 10 minutes under the microwave power 600W.The yield of TP was 96.5%under the described condition.Compared with traditional methods,including hot reflux extraction(HRE),ultrasound-assisted extraction(UAE)and supercritical fluid extraction(SFE),the extraction time was saved 8 times than that of HRE,and the yield was increased by 17.5%.The extraction time at comparable levels of production was saved 2 times,and the energy consumption was one fourth that of UAE.The extraction time was saved 5 times than that of SFE,and the yield of TP was increased by 40%.Moreover,compared with MAE of TP studied by others,it decreased the solid/liquid ratio from 1∶20 to 1∶12 g/mL without 90-min pre-leaching time,and the yield of TP was increased by 6%-40%.

Ultrasound augmenting injectable chemotaxis hydrogel for articular cartilage repair in osteoarthritis

The increasing incidence of osteoarthritis(OA) seriously affects life quality,posing a huge socioeco nomic burden.Tissue engineering technology has become a hot topic in articular cartilage repair as one of the key treatment methods to alleviate OA.Hydrogel,one of the most commonly used scaffold materials,ca n provide a good extracellular matrix microenvironment fo r seed cells such as bone marrow mesenchymal stem cells(BMSCs),which can promote cartilage regeneration.However,the low homing rate of stem cells severely limits their role in promoting articular cartilage regeneration.Stro mal cell-derived factor-1α(SDF-1α) plays a crucial role in the activatio n,mobilization,homing,and migration of MSCs.He rein,a novel injectable chemotaxis hydrogel,composed of chitosan-based injectable hydrogel and embedding SDF-1α-loaded nanodroplets(PFP@NDs-PEG-SDF-1α) was designed and fabricated.The ultrasound was then used to augment the injectable chemotaxis hydrogel and promote the homing migration of BMSCs for OA cartilage repair.The effect of ultrasound augmenting injectable PFP@NDs-PEG-SDF-1α/hydrogel on the migration of BMSCs was verified in vitro and in vivo,which re markably promotes stem cell homing and the repair of cartilage in the OA model.Therefore,the treatment strategy of ultrasound augmenting injectable chemotaxis hydrogel has a bright potential for OA articular cartilage repair.

Ti-MOF-based biosafety materials for efficient and long-life disinfection via synergistic photodynamic and photothermal effects

Pathogenic bacterial infection is severely threatening public health globally.The multi-modal antibacterial nanoplatforms could significantly improve the antibacterial efficiency.Here,we report a metal(Ti)-organic framework(MOF)derived nanocarbon(C-Ti-MOF)as a biosafety material for synergistic sterilization of pathogenic bacteria via efficient photodynamic catalysis and robust photothermal effects.The C-Ti-MOF consists of abundant TiO_(2) nanodots embedded in graphitic carbon frameworks.Under visible light irradiation,TiO_(2) nanodots can catalyze H_(2)O_(2) and O_(2) to produce superoxide anion(•O_(2)^(–))and singlet oxygen(1O2),respectively.Meanwhile,under near-infrared irradiation(NIR),C-Ti-MOF can generate massive heat to destroy bacterial membranes.Systematic antibacterial experiments reveal that the C-Ti-MOF nanoagents have a long-lasting and nearly 100%bactericidal ratio at an extremely low dose(0.16 mg/mL),which is much better than the state-of-the-art TiO_(2)(Commercial TiO_(2)(P25),0.64 mg/mL).Furthermore,the C-Ti-MOF can be electrospun into an antibacterial nanofiber membrane via mixing with polymeric matrix for treating bacteriacontaminated wastewater,and the membranes possess integrated antibacterial activity and excellent biocompatibility.Our study demonstrates a promising Ti-MOF-based biosafety material for efficient and long-life disinfection,which may stimulate new research in MOF-related biological applications in various disciplines ranging from water decontaminations to nanotherapeutics.

Comparison of prevention and treatment of portal vein thrombosis between proximal splenic vein ligation followed by postoperative transcatheter anticoagulant therapy and systemic anticoagulant therapy in patients with cirrhotic portal hypertension

Aims:Splenectomy combined with pericardial devascularization is one of the important methods to treat hypersplenism,gastrointestinal bleeding,and other complications caused by liver cirrhosis;however,it is accompanied by a high risk of portal vein thrombosis(PVT).This study aimed to explore the preventive and therapeutic effects of proximal splenic vein ligation(PSVL)with postoperative transcatheter anticoagulant therapy(TCAT)on PVT.Methods:This study retrospectively selected 143 patients with liver cirrhosis and portal hypertension,who received splenectomy combined with pericardial devascularization from June 30,2018 to June 30,2021.According to computed tomography photography,within 1 week before the operation,the patients were divided into a prevention group(without preoperative PVT,n=112)and a treatment group(preoperative PVT,n=31).Then,each group was subdivided based on the treatment and prevention measures into PSVL+TCAT(n=70)and systemic anticoagulant therapy(SAT)subgroups(n=73).The preventive and therapeutic effects of PSVL followed by TCAT on PVT were analyzed.Results:The operation time in the PSVL+TCAT subgroups was longer than that in the SAT subgroups(185±76 min vs.161±55 min;p<0.01).There was no difference between the two subgroups in terms of operative bleeding(345±82 mL vs.336±65 mL;p>0.50).There was no operative death,and all patients recovered uneventfully.In the prevention group,procedure-related complications occurred in two patients in the PSVL+TCAT subgroup(3.7%[2/54]),including one patient with slight pancreatitis and one patient with chylous leakage,owing to mobilization of the pancreas.The PVT incidence in the prevention group was significantly different between the two subgroups at postoperative 7th day,3rd month,and 6th month(PSVL+TCAT:0%,11.1%,and 5.6%vs.SAT:39.7%,31.0%,and 20.7%,respectively;all p<0.05).In the treatment group,the thrombus regression rate at postoperative 7th day and disappearance rates at the 3rd month and the 6th month of the PSVL+TCAT subgroup were significantly higher than those in the SAT subgroup after anticoagulant and thrombolysis therapy(PSVL+TCAT:75.0%,68.8%,and 87.5%vs.SAT:20.0%,26.7%,and 40.0%;all p<0.05).Conclusions:PSVL+TCAT reduces the risk of PVT after splenectomy and is safe and effective in treating PVT during surgery for portal hypertension.