甜瓜HDM基因家族鉴定及特性分析

组蛋白去甲基化酶(histone demethylase,HDM)是生物生长过程中的重要调节因子之一,在植物的生长发育和环境适应过程中发挥着重要的调控作用。本研究通过生物信息学方法对甜瓜(Cucumis melo L.) HDM基因家族进行了鉴定,并通过转录组数据检测了其成员在甜瓜组织的表达特性。结果显示,在甜瓜基因组中鉴定得到了20个CmHDM基因,在各条染色体上非均匀分布;其成员可以分成LSD1和JmjC两大类,而JmjC类群又可划分为5个亚群,各类群成员数量不等;种内和种间的共线性关系显示,甜瓜HDM基因仅存在一对片段重复,与番茄(Solanum lycopersicum) HDM基因共线性区域较多,亲缘关系较近;各成员所含保守结构域数量不等,且外显子和内含子在数量上有所差异;在启动子区域存在多种与激素和环境信号响应的顺式作用元件,表达特性分析显示各基因成员在甜瓜雄花、雌花、根、茎、叶、子房和成熟果实中均存在不同程度的表达。这些结果将有助于更好地理解HDM基因的潜在功能以及它们在参与调节甜瓜生长发育和环境自适中可能发挥的作用。

Ultra-Robust and High-Performance Rotational Triboelectric Nanogenerator by Bearing Charge Pumping

As an emerging technology to convert environmental high-entropy energy into electrical energy,triboelectric nanogenerator(TENG)has great demands for further enhancing the service lifetime and output performance in practical applications.Here,an ultra-robust and high-performance rotational triboelectric nanogenerator(R-TENG)by bearing charge pumping is proposed.The R-TENG composes of a pumping TENG(P-TENG),an output TENG(O-TENG),a voltage-multiplying circuit(VMC),and a buffer capacitor.The P-TENG is designed with freestanding mode based on a rolling ball bearing,which can also act as the rotating mechanical energy harvester.The output low charge from the P-TENG is accumulated and pumped to the non-contact O-TENG,which can simultaneously realize ultralow mechanical wear and high output performance.The matched instantaneous power of R-TENG is increased by 32 times under 300 r/min.Furthermore,the transferring charge of R-TENG can remain 95%during 15 days(6.4×10^(6)cycles)continuous operation.This work presents a realizable method to further enhance the durability of TENG,which would facilitate the practical applications of high-performance TENG in harvesting distributed ambient micro mechanical energy.

Simultaneous fluorescence and Compton scattering computed tomography based on linear polarization X-ray

Purpose To propose a method for simultaneous fluorescence and Compton scattering computed tomography by using linearly polarized X-rays.Methods Monte Carlo simulations were adopted to demonstrate the feasibility of the proposed method.In the simulations,the phantom is a polytetrafluoroethylene cylinder inside which are cylindrical columns containing aluminum,water,and gold(Au)-loaded water solutions with Au concentrations ranging between 0.5 and 4.0 wt%,and a parallel-hole collimator imaging geometry was adopted.The light source was modeled based on a Thomson scattering X-ray source.The phantom images for both imaging modalities were reconstructed using a maximumlikelihood expectation maximization algorithm.Results Both the X-ray fluorescence computed tomography(XFCT)and Compton scattering computed tomography(CSCT)images of the phantom were accurately reconstructed.A similar attenuation contrast problem for the different cylindrical columns in the phantom can be resolved in the XFCT and CSCT images.The interplay between XFCT and CSCT was analyzed,and the contrast-to-noise ratio(CNR)of the reconstruction was improved by correcting for the mutual influence between the two imaging modalities.Compared with K-edge subtraction imaging,XFCT exhibits a CNR advantage for the phantom.Conclusion Simultaneous XFCT and CSCT can be realized by using linearly polarized X-rays.The synergy between the two imaging modalities would have an important application in cancer radiation therapy.

Towards designing high mechanical performance low-alloyed wrought magnesium alloys via grain boundary segregation strategy:A review

Low-alloyed magnesium(Mg)alloys have emerged as one of the most promising candidates for lightweight materials.However,their further application potential has been hampered by limitations such as low strength,poor plasticity at room temperature,and unsatisfactory formability.To address these challenges,grain refinement and grain structure control have been identified as crucial factors to achieving high performance in low-alloyed Mg alloys.An effective way for regulating grain structure is through grain boundary(GB)segregation.This review presents a comprehensive summary of the distribution criteria of segregated atoms and the effects of solute segregation on grain size and growth in Mg alloys.The analysis encompasses both single element segregation and multi-element co-segregation behavior,considering coherent interfaces and incoherent interfaces.Furthermore,we introduce the high mechanical performance low-alloyed wrought Mg alloys that utilize GB segregation and analyze the potential impact mechanisms through which GB segregation influences materials properties.Drawing upon these studies,we propose strategies for the design of high mechanical performance Mg alloys with desirable properties,including high strength,excellent ductility,and good formability,achieved through the implementation of GB segregation.The findings of this review contribute to advancing the understanding of grain boundary engineering in Mg alloys and provide valuable insights for future alloy design and optimization.

Graphene-loaded nickel−vanadium bimetal oxides as hydrogen pumps to boost solid-state hydrogen storage kinetic performance of magnesium hydride

To modify the thermodynamics and kinetic performance of magnesium hydride(MgH_(2))for solid-state hydrogen storage,Ni_(3)V_(2)O_(8)-rGO(rGO represents reduced graphene oxide)and Ni_(3)V_(2)O_(8)nanocomposites were prepared by hydrothermal and subsequent heat treatment.The beginning hydrogen desorption temperature of 7 wt.%Ni_(3)V_(2)O_(8)-rGO modified MgH_(2)was reduced to 208℃,while the additive-free MgH_(2)and 7 wt.%Ni_(3)V_(2)O_(8)doped MgH_(2)appeared to discharge hydrogen at 340 and 226℃,respectively.A charging capacity of about 4.7 wt.%H_(2)for MgH_(2)+7 wt.%Ni_(3)V_(2)O_(8)-rGO was achieved at 125℃ in 10 min,while the dehydrogenated MgH_(2)took 60 min to absorb only 4.6 wt.%H_(2)at 215℃.The microstructure analysis confirmed that the in-situ generated Mg_(2)Ni/Mg_(2)N_(i)H_(4) and metallic V contributed significantly to the enhanced performance of MgH_(2).In addition,the presence of rGO in the MgH_(2)+7 wt.%Ni_(3)V_(2)O_(8)-rGO composite reduced particle aggregation tendency of Mg/MgH_(2),leading to improving the cyclic stability of MgH_(2)during 20 cycles.

Absent in melanoma 2 attenuates proliferation and migration and promotes apoptosis of human colorectal cancer cells by activating P38MAPK signaling pathway

Colorectal cancer(CRC)stands among the top prevalent cancers worldwide and holds a prominent position as a major contributor to cancer-related mortality globally.Absent in melanoma 2(AIM2),a constituent of the interferoninducible hematopoietic interferon-inducible nuclear antigens with 200 amino acid repeats protein family,contributes to both cancer progression and inflammasome activation.Despite this understanding,the precise biological functions and molecular mechanisms governed by AIM2 in CRC remain elusive.Consequently,this study endeavors to assess AIM2’s expression levels,explore its potential antitumor effects,elucidate associated cancer-related processes,and decipher the underlying signaling pathways in CRC.Our findings showed a reduced AIM2 expression in most CRC cell lines.Elevation of AIM2 levels suppressed CRC cell proliferation and migration,altered cell cycle by inhibiting G1/S transition,and induced cell apoptosis.Further research uncovered the participation of P38 mitogen-activated protein kinase(P38MAPK)in AIM2-mediated modulation of CRC cell apoptosis and proliferation.Altogether,our achievements distinctly underscored AIM2’s antitumor role in CRC.AIM2 overexpression inhibited proliferation and migration and induced apoptosis of CRC cells via activating P38MAPK signaling pathway,indicating AIM2 as a prospective and novel therapeutic target for CRC.

Vascular endothelial growth factor pathway’s influence on bevacizumab efficacy in metastatic colorectal cancer treatment

In this article,an article published in the World Journal of Gastrointestinal Oncology,which focuses on whether the expression of programmed death-ligand 1(PD-L1)affects the effectiveness of chemotherapy regimens,including bevacizumab,in treating patients with colorectal cancer(CRC).Through neutralization of vascular endothelial growth factor(VEGF),bevacizumab inhibits tumor angiogenesis,impairing neovascularization and thereby depriving the tumor of essential nutrients and oxygen.Conversely,PD-L1 binding to VEGF receptor 2 promotes angiogenesis,supporting tumor vasculature.The interplay between these pathways complicates the assessment of bevacizumab’s efficacy in cancer therapy,notably in CRC,where VEGF and PD-L1 significantly affect treatment response.This review examines metastatic CRC treatment strategies,focusing on bevacizumab’s mechanism of action and the role of PD-L1 in this therapeutic context.

Clinicopathological analysis of small intestinal metastasis from extra-abdominal/extra-pelvic malignancy

BACKGROUND The metastatic tumors in the small intestine secondary to extra-abdominal/extrapelvic malignancy are extremely rare.However,the small intestine metastases are extremely prone to misdiagnosis and missed diagnosis due to the lack of specific clinical manifestations and examination methods,thus delaying its treatment.Therefore,in order to improve clinical diagnosis and treatment capabilities,it is necessary to summarize its clinical pathological characteristics and prognosis.AIM To summarize the clinicopathological characteristics of patients with small intestinal metastases from extra-abdominal/extra-pelvic malignancy,and to improve the clinical capability of diagnosis and treatment for rare metastatic tumors in the small intestine.METHODS The clinical data of patients with small intestinal metastases from extra-abdominal/extra-pelvic malignancy were retrieved and summarized,who admitted to and treated in the Air Force Medical Center,Chinese People’s Liberation Army.Then descriptive statistics were performed on the general conditions,primary tumors,secondary tumors in the small intestine,diagnosis and treatment processes,and prognosis.RESULTS Totally 11 patients(9 males and 2 females)were enrolled in this study,including 8 cases(72.3%)of primary lung cancer,1 case(9.1%)of malignant lymphoma of the thyroid,1 case(9.1%)of cutaneous malignant melanoma,and 1 case(9.1%)of testicular cancer.The median age at the diagnosis of primary tumors was 57.9 years old,the median age at the diagnosis of metastatic tumors in the small intestine was 58.81 years old,and the average duration from initial diagnosis of primary tumors to definite diagnosis of small intestinal metastases was 9 months(0-36 months).Moreover,small intestinal metastases was identified at the diagnosis of primary tumors in 4 cases.The small intestinal metastases were distributed in the jejunum and ileum,with such clinical manifestations as hematochezia(5,45.4%)and abdominal pain,vomiting and other obstruction(4,36.4%).In addition,2 patients had no obvious symptoms at the diagnosis of small intestinal metastases,and 5 patients underwent radical resection of small intestinal malignancies and recovered well after surgery.A total of 3 patients did not receive subsequent treatment due to advanced conditions.CONCLUSION Small intestinal metastases of extra-abdominal/extra-pelvic malignancy is rare with high malignancy and great difficulty in diagnosis and treatment.Clinically,patients with extra-abdominal/extra-pelvic malignancy should be alert to the occurrence of this disease,and their prognosis may be improved through active surgery combined with standard targeted therapy.

铁电极化增强C/Bi/Bi_(2)MoO_(6)复合材料光催化性能的研究——推荐一个综合化学实验

本文围绕环境问题设计了一个综合化学实验。制备了C/Bi/Bi_(2)MoO_(6)复合材料,并对其施加直流电压进行电极化处理,通过扫描电镜和X射线粉末衍射等表征得出电极化法不影响材料的形貌和组成结构,并且能有效增强复合材料的光催化降解活性。本实验实现了化学、环境、能源与材料等多学科交叉融合,实验可操作性强且绿色环保。通过实验改进和仪器表征,激发学生的科研热情,培养创新思维和动手能力。

High-intensity spatial-mode steerable frequency up-converter toward on-chip integration

Integrated photonic devices are essential for on-chip optical communication,optical-electronic systems,and quantum information sciences.To develop a high-fidelity interface between photonics in various frequency domains without disturbing their quantum properties,nonlinear frequency conversion,typically steered with the quadratic(χ2)process,should be considered.Furthermore,another degree of freedom in steering the spatial modes during theχ2 process,with unprecedent mode intensity is proposed here by modulating the lithium niobate(LN)waveguide-based inter-mode quasi-phasematching conditions with both temperature and wavelength parameters.Under high incident light intensities(25 and 27.8 dBm for the pump and the signal lights,respectively),mode conversion at the sum-frequency wavelength with sufficient high output power(−7–8 dBm)among the TM01,TM10,and TM00 modes is realized automatically with characterized broad temperature(ΔT≥8°C)and wavelength windows(Δλ≥1 nm),avoiding the previous efforts in carefully preparing the signal or pump modes.The results prove that high-intensity spatial modes can be prepared at arbitrary transparent wavelength of theχ2 media toward on-chip integration,which facilitates the development of chip-based communication and quantum information systems because spatial correlations can be applied to generate hyperentangled states and provide additional robustness in quantum error correction with the extended Hilbert space.

Model Predictive Control for Cascaded H-Bridge PV Inverter with Capacitor Voltage Balance

We designed an improved direct-current capacitor voltage balancing control model predictive control(MPC)for single-phase cascaded H-bridge multilevel photovoltaic(PV)inverters.Compared with conventional voltage balanc-ing control methods,the method proposed could make the PV strings of each submodule operate at their maximum power point by independent capacitor voltage control.Besides,the predicted and reference value of the grid-connected current was obtained according to the maximum power output of the maximum power point tracking.A cost function was con-structed to achieve the high-precision grid-connected control of the CHB inverter.Finally,the effectiveness of the proposed control method was verified through a semi-physical simulation platform with three submodules.

Clinical features,diagnosis,and treatment of Peutz-Jeghers syndrome:Experience with 566 Chinese cases

BACKGROUND Peutz-Jeghers syndrome(PJS)is a clinically rare disease with pigmented spots on the lips and mucous membranes and extremities,scattered gastrointestinal polyps,and susceptibility to tumors as clinical manifestations.Effective preventive and curative methods are still lacking.Here we summarize our experience with 566 Chinese patients with PJS from a Chinese medical center with regard to the clinical features,diagnosis,and treatment.AIM To explore the clinical features,diagnosis,and treatment of PJS in a Chinese medical center.METHODS The diagnosis and treatment information of 566 cases of PJS admitted to the Air Force Medical Center from January 1994 to October 2022 was summarized.A clinical database was established covering age,gender,ethnicity,family history,age at first treatment,time and sequence of appearance of mucocutaneous pigmentation,polyp distribution,quantity,and diameter,frequency of hospitalization,fre-quency of surgical operations,etc.The clinical data was retrospectively analyzed using SPSS 26.0 software,with P<0.05 considered statistically significant.RESULTS Of all the patients included,55.3%were male and 44.7%were female.Median time to the appearance of mucocutaneous pigmentation was 2 years,and median time from the appearance of mucocutaneous pigmentation to the occurrence of abdominal symptoms was 10 years.The vast majority(92.2%)of patients underwent small bowel endoscopy and treatment,with 2.3%having serious complications.There was a statistically significant difference in the number of enteroscopies between patients with and without canceration(P=0.004,Z=-2.882);71.2%of patients underwent surgical operation,75.6%of patients underwent surgical operation before the age of 35 years,and there was a statistically significant difference in the frequency of surgical operations between patients with and without cancer(P=0.000,Z=-5.127).At 40 years of age,the cumulative risk of intussusception in PJS was approximately 72.0%,and at 50 years,the cumulative risk of intussusception in PJS was approximately 89.6%.At 50 years of age,the cumulative risk of cancer in PJS was approximately 49.3%,and at 60 years of age,the cumulative risk of cancer in PJS was approximately 71.7%.CONCLUSION The risk of intussusception and cancer of PJS polyps increases with age.PJS patients≥10 years old should undergo annual enteroscopy.Endoscopic treatment has a good safety profile and can reduce the occurrence of polyps intussusception and cancer.Surgery should be conducted to protect the gastrointestinal system by removing polyps.

Designing new low alloyed Mg-RE alloys with high strength and ductility via high-speed extrusion

Two new low-alloyed Mg-2RE-0.8Mn-0.6Ca-0.5Zn(wt%,RE=Sm or Y)alloys are developed,which can be produced on an in-dustrial scale via relatively high-speed extrusion.These two alloys are not only comparable to commercial AZ31 alloy in extrudability,but also have superior mechanical properties,especially in terms of yield strength(YS).The excellent extrudability is related to less coarse second-phase particles and high initial melting point of the two as-cast alloys.The high strength-ductility mainly comes from the formation of fine grains,nano-spaced submicron/nano precipitates,and weak texture.Moreover,it is worth noting that the YS of the two alloys can maintain above 160 MPa at elevated temperature of 250°C,significantly higher than that of AZ31 alloy(YS:45 MPa).The Zn/Ca solute segregation at grain boundaries,the improved heat resistance of matrix due to addition of RE,and the high melting points of strengthening particles(Mn,MgZn_(2),and Mg-Zn-RE/Mg-Zn-RE-Ca)are mainly responsible for the excellent high-temperature strength.

Joint Flexible Duplexing and Power Allocation with Deep Reinforcement Learning in Cell-Free Massive MIMO System

Network-assisted full duplex(NAFD)cellfree(CF)massive MIMO has drawn increasing attention in 6G evolvement.In this paper,we build an NAFD CF system in which the users and access points(APs)can flexibly select their duplex modes to increase the link spectral efficiency.Then we formulate a joint flexible duplexing and power allocation problem to balance the user fairness and system spectral efficiency.We further transform the problem into a probability optimization to accommodate the shortterm communications.In contrast with the instant performance optimization,the probability optimization belongs to a sequential decision making problem,and thus we reformulate it as a Markov Decision Process(MDP).We utilizes deep reinforcement learning(DRL)algorithm to search the solution from a large state-action space,and propose an asynchronous advantage actor-critic(A3C)-based scheme to reduce the chance of converging to the suboptimal policy.Simulation results demonstrate that the A3C-based scheme is superior to the baseline schemes in term of the complexity,accumulated log spectral efficiency,and stability.

Tribotronics: an emerging field by coupling triboelectricity and semiconductors

Tribotronics is an emerging research field that focuses on the coupling of triboelectricity and semiconductors.In this review,we summarise and explore three branches of tribotronics.Firstly,we introduce the tribovoltaic effect,which involves direct-current power generation through mechanical friction on semiconductor interfaces.This effect offers significant advantages in terms of high power density compared to traditional insulator-based triboelectric nanogenerators.Secondly,we elaborate on triboelectric modulation,which utilises the triboelectric potential on field-effect transistors.This approach enables active mechanosensation and nanoscale tactile perception.Additionally,we present triboelectric management,which aims to improve energy supply efficiency using semiconductor device technology.This strategy provides an effective microenergy solution for sensors and microsystems.For the interactions between triboelectricity and semiconductors,the research of tribotronics has exhibited the electronics of interfacial friction systems,and the triboelectric technology by electronics.This review demonstrates the promising prospects of tribotronics in the development of new functional devices and self-powered microsystems for intelligent manufacturing,robotic sensing,and the industrial Internet of Things.

Peutz-Jeghers syndrome without STK11 mutation may correlate with less severe clinical manifestations in Chinese patients

BACKGROUND Peutz-Jeghers syndrome(PJS) is an autosomal dominant genetic disease with skin mucosal pigment spots and gastrointestinal(GI) multiple hamartoma polyps as clinical characteristics. At present, it is considered that the germline mutation of STK11 gene is the genetic cause of PJS. However, not all PJS patients can be detected STK11 germline mutations. The specific clinical characteristics of these PJS patients without STK11 mutation is an interesting clinical question. Or, like wild type GI stromal tumor, whether these PJS without STK11 mutation are also called PJS is worth discussing. Therefore, we designed the study to understand the clinical characteristics of these PJS patients without STK11 mutation.AIM To investigates whether PJS patients with known STK11 mutations have a more severe spectrum of clinical phenotypes compared to those without.METHODS A total of 92 patients with PJS admitted to the Air Force Medical Center from 2010 to 2022 were randomly selected for study. Genomic DNA samples were extracted from peripheral blood samples, and pathogenic germline mutations of STK11 were detected by high-throughput next-generation gene sequencing. Clinicalpathologic manifestations of patients with and without STK11/LKB1 mutations were compared.RESULTS STK11 germline mutations were observed in 73 patients with PJS. Among 19 patients with no detectable STK11 mutations, six had no pathogenic germline mutations of other genes, while 13 had other genetic mutations. Compared with PJS patients with STK11 mutations, those without tended to be older at the age of initial treatment, age of first intussusception and age of initial surgery. They also had a lower number of total hospitalizations relating to intussusception or intestinal obstruction, and a lower load of small intestine polyps.CONCLUSION PJS patients without STK11 mutations might have less severe clinical-pathologic manifestations than those with.

Developing new Mg alloy as potential bone repair material via constructing weak anode nano-lamellar structure

The mechanics-corrosion and strength-ductility tradeoffs of magnesium(Mg)alloys have limited their applications in fields such as orthopedic implants.Herein,a fine-grain structure consisting of weak anodic nano-lamellar solute-enriched stacking faults(SESFs)with the average thickness of 8 nm and spacing of 16 nm is constructed in an as-extruded Mg96.9Y1.2Ho1.2Zn0.6Zr0.1(at.%)alloy,obtaining a high yield strength(YS)of 370 MPa,an excellent elongation(EL)of 17%,and a low corrosion rate of 0.30 mm y−1(close to that of high-pure Mg)in a uniform corrosion mode.Through scanning Kelvin probe force microscopy(SKPFM),one-dimensional nanostructured SESFs are identified as the weak anode(∼24 mV)for the first time.The excellent corrosion resistance is mainly related to the weak anodic nature of SESFs and their nano-lamellar structure,leading to the more uniform potential distribution to weaken galvanic corrosion and the release of abundant Y^(3+)/Ho^(3+)from SESFs to form a more protective film with an outer Ca_(10)(PO_(4))_(6)(OH)_(2)/Y_(2)O_(3)/Ho_(2)O_(3) layer(thickness percentage of this layer:72.45%).For comparison,the as-cast alloy containing block 18R long period stacking ordered(LPSO)phase and the heat-treated alloy with fine lamellar 18R-LPSO phase(thickness:80 nm,spacing:120 nm)are also studied,and the characteristics of SESFs and 18R-LPSO phase,such as the weak anode nature of the former and the cathode nature of the latter(37-90 mV),are distinguished under the same alloy composition.Ultimately,we put forward the idea of designing Mg alloys with high mechanical and anti-corrosion properties by constructing"homogeneous potential strengthening microstructure",such as the weak anode nano-lamellar SESFs structure.

Dihydroergotamine ameliorates liver fibrosis by targeting transforming growth factor β type Ⅱ receptor

BACKGROUND The transforming growth factor β(TGFβ) signaling pathway plays a crucial role in the development of liver fibrosis by activating TGFβ type Ⅱ receptor(TGFβR2), followed by the recruitment of TGFβR1 finally triggering downstream signaling pathway.AIM To find drugs targeting TGFβR2 that inhibit TGFβR1/TGFβR2 complex formation, theoretically inhibit TGFβ signaling pathway, and thereby ameliorate liver fibrosis.METHODS Food and Drug Administration-approved drugs were screened for binding affinity with TGFβR2 by virtual molecular docking. We identified 6 candidates and further explored their potential by Cell Counting Kit-8(CCK-8) cell cytotoxic experiment to validate toxicity and titrated the best cellular working concentrations. Next, we further demonstrated the detailed molecular working mechanisms using mutagenesis analysis. Finally, we used a mouse model to investigate its potential anti-liver fibrosis effect.RESULTS We identified 6 drug candidates. Among these 6 drugs, dihydroergotamine(DHE) shows great ability in reducing fibrotic gene expressions such as collagen, p-SMAD3, and α-SMA in TGFβ induced cellular model of liver fibrosis in LX-2 cells. Furthermore, we demonstrated that DHE binds to TGFβR2. Moreover, mutation of Leu27, Phe30, Thr51, Ser52, Ile53, and Glu55 of TGFβR2 disrupted the binding of TGFβR2 with DHE. In addition, DHE significantly improved liver fibrosis, as evidenced by Masson’s trichrome staining of liver sections. This is further supported by the width and the velocity of the portal vein, and serum markers of liver function. In line with those observations, DHE also decreased macrophages infiltration and extracellular matrix deposition in the liver.CONCLUSION DHE alleviates liver fibrosis by binding to TGFβR2 thereby suppressing TGFβ signaling pathway. We show here that as far as drug repurposing, DHE has great potential to treat liver fibrosis.

High drug loading hydrophobic cross-linked dextran microspheres as novel drug delivery systems for the treatment of osteoarthritis

Drug delivery via intra-articular(IA)injection has proved to be effective in osteoarthritis(OA)therapy,limited by the drug efficiency and short retention time of the drug delivery systems(DDSs).Herein,a series of modified cross-linked dextran(Sephadex,S0)was fabricated by respectively grafting with linear alkyl chains,branched alkyl chains or aromatic chain,and acted as DDSs after ibuprofen(Ibu)loading for OA therapy.This DDSs expressed sustained drug release,excellent anti-inflammatory and chondroprotective effects both in IL-1βinduced chondrocytes and OA joints.Specifically,the introduction of a longer hydrophobic chain,particularly an aromatic chain,distinctly improved the hydrophobicity of S0,increased Ibu loading efficiency,and further led to significantly improving OA therapeutic effects.Therefore,hydrophobic microspheres with greatly improved drug loading ratio and prolonged degradation rates show great potential to act as DDSs for OA therapy.

Analysis of clinicopathological features and prognostic factors of breast cancer brain metastasis

BACKGROUND Breast cancer(BC)has become the most common malignancy in women.The incidence and detection rates of BC brain metastasis(BCBM)have increased with the progress of imaging,multidisciplinary treatment techniques and the extension of survival time of BC patients.BM seriously affects the quality of life and survival prognosis of BC patients.Therefore,clinical research on the clinicopathological features and prognostic factors of BCBM is valuable.By analyzing the clinicopathological parameters of BCBM patients,and assessing the risk factors and prognostic indicators,we can perform hierarchical diagnosis and treatment on the high-risk population of BCBM,and achieve clinical benefits of early diagnosis and treatment.AIM To explore the clinicopathological features and prognostic factors of BCBM,and provide references for diagnosis,treatment and management of BCBM.METHODS The clinicopathological data of 68 BCBM patients admitted to the Air Force Medical Center,Chinese People’s Liberation Army(formerly Air Force General Hospital)from 2000 to 2022 were collected.Another 136 BC patients without BM were matched at a ratio of 1:2 based on the age and site of onset for retrospective analysis.Categorical data were subjected to χ^(2) test or Fisher’s exact probability test,and the variables with P<0.05 in the univariate Cox proportional hazards model were incorporated into the multivariate model to identify high-risk factors and independent prognostic factors of BCBM,with a hazard ratio(HR)>1 suggesting poor prognostic factors.The survival time of patients was estimated by the Kaplan-Meier method,and overall survival was compared between groups by log-rank test.RESULTS Multivariate Cox regression analysis showed that patients with stage Ⅲ/Ⅳ tumor at initial diagnosis[HR:5.58,95% confidence interval(CI):1.99–15.68],lung metastasis(HR:24.18,95%CI:6.40-91.43),human epidermal growth factor receptor 2(HER2)-overexpressing BC and triple-negative BC were more prone to BM.As can be seen from the prognostic data,52 of the 68 BCBM patients had died by the end of follow-up,and the median time from diagnosis of BC to the occurrence of BM and from the occurrence of BM to death or last follow-up was 33.5 and 14 mo,respectively.It was confirmed by multivariate Cox regression analysis that patients with neurological symptoms(HR:1.923,95%CI:1.005-3.680),with bone metastasis(HR:2.011,95%CI:1.056-3.831),and BM of HER2-overexpressing and triple-negative BC had shorter survival time.CONCLUSION HER2-overexpressing,triple-negative BC,late tumor stage and lung metastasis are risk factors of BM.The presence of neurological symptoms,bone metastasis,and molecular type are influencing prognosis factors of BCBM.