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Parathyroid hormone (PTH) and PTH-related peptide (PTHrP) are two endogenous hormones recognized by PTH receptor -1 (PTH1R), a member of class B G protein couple receptors (GPCRs). Both PTH and PTHrP analogs including teriparatide and abaloparatide, are approved drugs for osteoporosis, but they exhibit distinct pharmacology. Here we report two cryo-EM structures of human PTH1R bound to PTH and PTHrP in the G protein-bound state at resolutions of 2.6 and 3.2 Å, respectively. Detailed analysis of these structures uncovers both common and unique features for the agonism of PTH and PTHrP. Molecular dynamics (MD) simulation and together with site-directed mutagenesis studies reveal the molecular basis of endogenous hormones recognition specificity and selectivity to PTH1R. These results provide a rational template for the clinical use of PTH and PTHrP analogs as an anabolic therapy for osteoporosis and other disorders.

To explore the relationship between frailty and community-acquired pneumonia (CAP) in older patients.A prospective observational study included 109 older patients(≥ 65 years) hospitalized with CAP in respiratory department of Fuxing hospital, Capital Medical University from June 2018 to December 2020. Frailty scores(Frail Scale, range 0-5) and pneumonia severity CURB-65 scale(mild = 1, modest = 2, and severe ≥ 3) were measured. We extracted clinical variables including white blood cell(WBC), neutrophil-to-lymphocyte ratio (NLR), C-reactive protein(CRP), hemoglobin, and albumin. Charlson Comorbidity Index(CCI) was calculated as well. The correlations between the variables and frailty scores were investigated, respectively. After adjusting for covariates, binomial logistic regression analysis was used to assess independent effect of frailty scores on the outcome(discharge or death/progression) in older CAP patients.The subjects had a median age 87(interquartile range,8.5) years, 60.6% male, 45.9% pre-frail, and 32.1% frail. There were positive correlations between frailty scores and CURB-65 scale (p = 0.000, r = 0.542), CCI(p = 0.000, r = 0.359) and NLR(p = 0.005, r = 0.268). Negative correlations were observed between frailty scores and hemoglobin (p = 0.002, r = - 0.298), albumin (p = 0.000, r = - 0.465). In multivariable logistic regression analysis, the factors associated with discharge or death/progression of CAP were frailty scores (OR = 1.623, p = 0.037), NLR (OR = 1.086, p = 0.008) and albumin (OR = 0.869, p = 0.034).Frailty is correlated with CURB-65 scale, CCI and hemoglobin, and albumin in older patients with CAP. Frailty is also a correlate of increased risk for death or progression in these older people.

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Tax1 banding protein 1 (Tax1bp1) was originally identified as an NF-κB regulatory protein that participated in inflammatory, antiviral and innate immune processes. Tax1bp1 also functions as an autophagy receptor that plays a role in autophagy. Our previous study shows that Tax1bp1 protects against cardiomyopathy in STZ-induced diabetic mice. In this study we investigated the role of Tax1bp1 in heart failure. Pressure overload-induced heart failure model was established in mice by aortic banding (AB) surgery, and angiotensin II (Ang II)-induced heart failure model was established by infusion of Ang II through osmotic minipump for 4 weeks. We showed that the expression levels of Tax1bp1 in the heart were markedly increased 2 and 4 weeks after AB surgery. Knockdown of Tax1bp1 in mouse hearts significantly ameliorated both AB- and Ang II infusion-induced heart failure parameters. On the contrary, AB-induced heart failure was aggravated in cardiac-specific Tax1bp1 transgenic mice. Similar results were observed in neonatal rat cardiomyocytes (NRCMs) under Ang II insult. We demonstrated that the pro-heart failure effect of Tax1bp1 resulted from its interaction with the E3 ligase ITCH to promote the transcription factor P73 ubiquitination and degradation, causing enhanced BCL2 interacting protein 3 (BNIP3)-mediated cardiomyocyte apoptosis. Knockdown ITCH or BNIP3 in NRCMs significantly reduced Ang II-induced apoptosis in vitro. Similarly, BNIP3 knockdown attenuated heart failure in cardiac-specific Tax1bp1 transgenic mice. In the left ventricles of heart failure patients, Tax1bp1 expression level was significantly increased; Tax1bp1 gene expression was negatively correlated with left ventricular ejection fraction in heart failure patients. Collectively, the Tax1bp1 increase in heart failure enhances ITCH-P73-BNIP3-mediated cardiomyocyte apoptosis and induced cardiac injury. Tax1bp1 may serve as a potent therapeutic target for the treatment of heart failure.• Cardiac Tax1bp1 transgene mice were more vulnerable to cardiac dysfunction under stress.• Cardiac Tax1bp1 transgene mice were more vulnerable to cardiac dysfunction under stress.• Knockout of Tax1bp1 in mouse hearts ameliorated heart failure induced by pressure overload.• Tax1bp1 interacts with the E3 ligase Itch to promote P73 ubiquitination and degradation, causing enhanced BNIP3-mediated apoptosis.• Tax1bp1 may become a target of new therapeutic methods for treating heart failure.

The real structure and in situ evolution of catalysts under working conditions are of paramount importance, especially for bifunctional electrocatalysis. Here, we report asymmetric structural evolution and dynamic hydrogen-bonding promotion mechanism of an atomically dispersed electrocatalyst. Pyrolysis of Co/Ni-doped MAF-4/ZIF-8 yielded nitrogen-doped porous carbons functionalized by atomically dispersed Co–Ni dual-metal sites with an unprecedented N8V4 structure, which can serve as an efficient bifunctional electrocatalyst for overall water splitting. More importantly, the electrocatalyst showed remarkable activation behavior due to the in situ oxidation of the carbon substrate to form C–OH groups. Density functional theory calculations suggested that the flexible C–OH groups can form reversible hydrogen bonds with the oxygen evolution reaction intermediates, giving a bridge between elementary reactions to break the conventional scaling relationship.

In recent years, the research of Phenylethynylcopper (PhC2Cu) in the field of photocatalysis has attracted much attention. However, its preparation requires two steps, which take lengthy 9 days. In this paper, A highly rapid and facile one-step method that directly used copper acetate and phenylacetylene as raw materials and ascorbic acid as reducing agent to synthesize PhC2Cu nanowires was successfully developed. The kinetic studies indicated that the synthetic reaction follows a pseudo-second-order equation through electrical conductivity. Comparative studies on the crystal structures, morphologies, optical properties of PhC2Cu prepared by the traditional two-step and this one-step method were conducted by using XRD, SEM, UV–vis Drs, FT-IR, Raman Spectra and Photocurrent. Meanwhile, the PhC2Cu nanowires exhibited excellent photocatalytic activity for the degradation of MV (methyl violet) and glyphosate. Importantly, this facile and rapid method greatly improves the preparation efficiency of PhC2Cu, and the obtained PhC2Cu also shows higher photocatalytic activity. This remarkable progress enables the possibility of large-scale and efficient preparation of PhC2Cu with high photocatalytic activity, indicating their good application prospect in the fields of photocatalysis.

Acute kidney injury (AKI) refers to a group of common clinical syndromes characterized by acute renal dysfunction, which may lead to chronic kidney disease (CKD), and this process is called the AKI-CKD transition. The transcriptional coactivator YAP can promote the AKI-CKD transition by regulating the expression of profibrotic factors, and 14-3-3 protein zeta (14-3-3ζ), an important regulatory protein of YAP, may prevent the AKI-CKD transition. We established an AKI-CKD model in mice by unilateral renal ischemia-reperfusion injury and overexpressed 14-3-3ζ in mice using a fluid dynamics-based gene transfection technique. We also overexpressed and knocked down 14-3-3ζ in vitro. In AKI-CKD model mice, 14-3-3ζ expression was significantly increased at the AKI stage. During the development of chronic disease, the expression of 14-3-3ζ tended to decrease, whereas active YAP was consistently overexpressed. In vitro, we found that 14-3-3ζ can combine with YAP, promote the phosphorylation of YAP, inhibit YAP nuclear translocation, and reduce the expression of fibrosis-related proteins. In an in vivo intervention experiment, we found that the overexpression of 14-3-3ζ slowed the process of renal fibrosis in a mouse model of AKI-CKD. These findings suggest that 14-3-3ζ can affect the expression of fibrosis-related proteins by regulating YAP, inhibit the maladaptive repair of renal tubular epithelial cells, and prevent the AKI-CKD transition.

Nicotinamide adenine dinucleotide (NAD) is a critical cosubstrate for enzymes involved in supplying energy to the brain. Nicotinamide riboside (NR), an NAD

According to previous studies, traditional laboratory safety courses are delivered in a classroom setting where the instructor teaches and the students listen and read the course materials passively. The course content is also uninspiring and dull. Additionally, the teaching period is spread out, which adds to the instructor's workload. As a result, students become less motivated to learn. In contrast, artificially intelligent educational robots (AIERs), help students learn while lessening the workload on instructors by enhancing teaching strategies, using robots to substitute for teachers, giving students access to a variety of instructional content, and improving interaction with students through the use of intelligent voice interactions and Q&A systems to promote student engagement in learning. If the robot is used for a long time for learning, it may lead to a decrease in students' interest in learning. Therefore, this study introduces the GAFCC model (the theory-driven gamification goal, access, feedback, challenge, collaboration design model) as an instructional design model to guide the development of a gamified AIER system, aiming to improve students' motivation and learning effectiveness for laboratory safety courses. To test the effectiveness of the system, this study conducted an experimental study at a university in China in the summer of 2022. 53 participants participated in the research, with a random sample taken from each group. Each participant was able to choose the time of their free time to engage in the experiment. There were 18, 19, and 16 participants in experimental group 1, experimental group 2, and the traditional group, respectively. Students in experimental group 1 learned using the gamified AIER system, students in experimental group 2 learned on a general anthropomorphic robot system and the control group received traditional classroom learning. The experimental results showed that compared to the other two groups, the gamified AIER system guided by the GAFCC model significantly improved students' learning achievement and enhanced their learning motivation, flow experience, and problem-solving tendency. In addition, students who adopted this approach exhibited more positive behaviors and reduced cognitive load in the learning process.

Background In plants, cytokinin is activated into trans-zeatin to fight abiotic stresses. However, the mechanism of the effect of trans-zeatin on 2-acetyl-1-pyrroline (2-AP) biosynthesis in fragrant rice has yet to be studied. The present study was conducted to explore the effects of exogenous trans-zeatin on enzymes activities, genes expression, and precursors involved in 2-AP biosynthesis and 2-AP contents as well as the seedling quality of a fragrant rice cultivar viz., Meixiangzhan2. Four concentrations of trans-zeatin solutions at 20, 40, and 80 μmol L− 1 (ZT1, ZT2, and ZT3) were sprayed onto rice seedlings. Results Compared to the control, trans-zeatin treatments showed significantly higher 2-AP contents of fragrant rice seedlings. Increased plant height and stem width were observed due to trans-zeatin treatments. The trans-zeatin application increased 1-pyrroline, methylglyoxal, proline, and P5C contents, enhanced P5CS and OAT activities, and reduced glutamic acid contents. In addition, expressions of ProDH, P5CS2, and DAO4 were comparatively higher under trans-zeatin treatments than CK in fragrant rice seedlings. Conclusions Overall, up-regulation of P5C, 1-pyrroline, and proline and down-regulation of glutamic acid under appropriate trans-zeatin concentrations (20 and 40 μmol L− 1) resulted in enhanced 2-AP biosynthesis in fragrant rice seedlings and 20–40 μmol L− 1 was considered as the suggested concentrations of trans-zeatin application in fragrant rice seedling.

Halophilic phage are a type of virus that exist in salty environments within halophilic archaeal or bacterial hosts. However, relatively few reports on halophilic bacteriophages exist, and our overall understanding of halophilic bacteriophages is quite limited. We used SYBR Green I fluorescent staining to detect the abundance of viruses in Yuncheng Saline Lake, China. Using the double-layer plate method, a lytic phage that could infect halophilic bacterium Salinivibrio sp. YM-43 was isolated and named YXM43. We studied host range, optimal host, morphological characteristics, nucleic acid type, protein composition, and other biological characteristics of the virus. Results reveal a high abundance of this halophilic virus in Yuncheng Saline Lake. The newly isolated bacteriophage YXM43 has a narrow host range, with the most suitable host being Virgibacillus sp. SK39. After purification and enrichment, YXM43 is observed as a spherical particle with a diameter of approximately 30 nm, with no tail. No lipid envelope can be seen in YXM43. The capsid protein of the virus can be separated into seven proteins with molecular weights ranging from 62.0 to 13.0 kDa. YXM43 is a DNA virus with a genome approximately 23 kb. The virus is tolerant of low salinity, and its activity is highest at a temperature of 60 °C and a pH of 10. YXM43 is temperature and pH tolerant, and can adapt to environmental change, even withstanding chloroform treatment. The results indicate that bacteriophage YXM43 is a novel halophilic bacteriophage with broad tolerance to environmental change.

BackgroundNursing experts regularly visited the community to deliver safety education on the prevention of unintentional injuries in children to the parents of children aged 0–6 years and to pregnant women in a maternity school. This was undertaken to explore the effects of the measure on preventing unintentional injuries in children in Chizhou, China.MethodsUsing the convenience sampling method, the guardians(it means mother in this study)of children were investigated. The nursing experts visited communities in which the number of nursing experts is declining. Data on unintentional injuries in children in the previous year were collected retrospectively.ResultsAfter the nursing experts delivered safety education to the community, the scores of the questionnaire on unintentional injury prevention knowledge completed by children’s guardians increased significantly (p p p > 0.05). However, there were significant differences in terms of gender ratio and location (p ConclusionIn conjunction with the maternity school for pregnant women and the vaccination programme, nursing experts delivered safety education regarding unintentional injuries in children; this may have promoted safety and protection awareness in the children’s guardians and reduced unintentional injuries.

Introduction Hepatocellular carcinoma (HCC) is one of the most common malignant tumours in the world and has a high mortality rate. However, the pathogenesis of HCC remains unclear. This study aimed to investigate the potential biomarkers of HCC. Methods ONCOMINE, HCCDB and THE HUMAN PROTEIN ATLAS were used to identify myelin expression factor 2 (MYEF2) as a potential biomarker for HCC. The Cancer Genome Atlas database was used to further validate and analyse the value of MYEF2. Kaplan–Meier Plotter was used for the prognostic analysis. The COX regression model and Kaplan–Meier method were used to investigate the clinical value of MYEF2 in the prognosis of HCC by reviewing the survival status of patients. Fluorescent quantitative polymerase chain reaction (qPCR) and immunohistochemistry were used to detect the expressions of the MYEF2 mRNA and protein in HCC tissues and cell lines. qPCR and Western blotting were used to validate the efficiency of MYEF2 knockout and overexpression in HCC cells. The invasion and migration abilities regulated by MYEF2 were detected by performing transwell and wound healing assays. Results MYEF2 is significantly upregulated in HCC and is mainly located in the nucleus of HCC cells. MYEF2 expression is significantly associated with the tumour stage, histological grade and TNM stage. High MYEF2 expression is an independent prognostic factor for patients with HCC. Functionally, elevated MYEF2 facilitated cell migration and invasion in vitro. In contrast, decreased MYEF2 inhibited cell migration and invasion. Conclusions MYEF2 may be a novel biomarker with potential diagnosis and prognosis values and as a potential therapeutic target for HCC.

Mg-6Gd-3Y-0.5Zr (VW63K) alloy is widely used in the aerospace field because of its excellent mechanical properties not only at room temperature but also under high service temperature. In this study, the effect of minor changes to the Y alloying levels on the hot tearing behavior of VW63K alloys was researched by using a "T" mold, with pouring temperature of 720 °C and mold temperature of 150 °C. The results show that the hot tearing susceptibility of the alloy decreases gradually with the increase of Y content from 2.8 to 3.4 wt%. The reason for this phenomenon is that high content of Y element narrows the susceptible freezing range and increases the eutectic liquid fraction of the alloy, which is helpful for the alloy to have a better compensation at the late stage of solidification and, thereby decreasing the hot tearing susceptibility.

HSCCC was widely used as a reliable and efficient tool for isolation of natural production. Multiple active compounds were separated and purified from ginger essential oil. But the remaining ginger powder (RGP), which was obtained from ginger without volatile oil, was discarded commonly. The crude flavonoids were extracted from RGP using ethanol at 80°C. The purification of flavonoids was performed by rotary evaporator and X-5 macroporous adsorption resin. The high-speed counter-current chromatography (HSCCC) was implemented by employing a two-phase solvent system which consist of n-hexane–ethyl acetate–methanol-water (4:5:4:5, v/v/v/v) and n-hexane–ethyl acetate–methanol-water (1:5:1:5, v/v/v/v) to separate flavonoid into five fractions. The purity of individual flavonoid in each of the fraction was analyzed by high-performance liquid chromatography (HPLC). The chemical structures of the isolated compounds were identified by liquid chromatograph mass spectrometry-ion trap-time of flight (LCMS-IT-TOF). Rutin (16.6%), tangeretin (13.1%), vitexin (18.37%), myricetin-3-O-glucopyranoside (3.3%), and isoquercitrin (15.2%) were identified in RGP at the purity of all over 90%. The HSCCC appeared to be an efficient and reliable method for the isolation of flavonoids in RGP. 3-(4,5-Dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was performed to determine the anti-tumor abilities of five flavonoid compounds. The results showed that rutin and myricetin-3-O-glucopyranoside had better anti-tumor activities than other three flavonoid compounds from RGP. The research revealed that RGP was a bioactive product and contributed to development of ginger.

Population and income growth are increasing global food demand at a time when a third of the world’s agricultural soils are degraded and climate variability threatens the sustainability of food production. Intercropping, the practice of growing two or more spatially intermingled crops, often increases yields, but whether such yield increases, their stability and soil fertility can be sustained over time remains unclear. Using four long-term (10–16 years) experiments on soils of differing fertility, we found that grain yields in intercropped systems were on average 22% greater than in matched monocultures and had greater year-to-year stability. Moreover, relative to monocultures, yield benefits of intercropping increased through time, suggesting that intercropping may increase soil fertility via observed increases in soil organic matter, total nitrogen and macro-aggregates when comparing intercropped with monoculture soils. Our results suggest that wider adoption of intercropping could increase both crop production and its long-term sustainability. Growing demand for food is confronting constraints to its sustainable production. This study finds that intercropping increases grain yields and their stability and that yield benefits increase over time.

Background Increased serum carcinoembryonic antigen (CEA) levels are reported to be associated with various metabolic and inflammatory diseases. This study assessed whether high-normal serum CEA is related to diabetic peripheral neuropathy (DPN) in patients with type 2 diabetes (T2D). Methods All subjects received DPN assessment based on neuropathic symptoms, neuropathic signs, and nerve conduction studies to calculate composite Z scores of nerve latency, amplitude and conduction velocity (NCV). DPN was confirmed by both at least a presentation of neuropathic symptoms/signs and an abnormal nerve conduction index. Serum CEA levels and other clinical indices were also synchronously detected. Multivariable linear regression analyses were used to determine the independent effects of serum CEA levels on nerve conduction indices, multivariable logistic regression analyses were used to determine the independent impact of CEA levels on the risk of DPN, and receiver operating characteristic (ROC) curve analysis was used to assess the diagnostic capability of CEA levels to discriminate DPN. Results We ultimately recruited 402 eligible subjects with normal ranges of serum CEA for this study, and 25.4% (n = 102) were determined to have DPN. After adjusting for other clinical covariates, serum CEA levels were independently associated with the composite Z score for latency (β = 0.132, t = 2.330, p = 0.021), amplitude (β = − 0.164, t = − 2.838, p = 0.005) and NCV (β = − 0.210, t = − 3.662, p p for trend Conclusions Increased serum CEA levels within the normal range are closely linked to dysfunction of peripheral nerve conduction and the risk of DPN, and high-normal serum CEA levels are a potential risk factor for DPN in T2D.

Herein, the Cu target is prepared by combining different pieces, with a large variation in grain size, and installed in a UDP-650 closed-field unbalanced ion coating machine for sputtering experiments. The influence of grain size on surface morphology and sputtering performance of Cu targets is studied under the same process conditions. In the constant current mode, the sputtering voltage of target continues to decrease during the target lifetime, which is consistent with the increase of magnetic field intensity on the target surface due to the decrease of target thickness. During the first 7.5 h of sputtering erosion, the sputtering yield of Cu target slightly increases with sputtering time, followed by a gradual decrease. The results reveal that the grain size renders a significant effect on surface morphology of the Cu target after sputtering. The Cu target with small grain size renders high particle density in the edge area of sputter erosion groove, however, the particle-like morphology size is not influenced by the grain size. In the deepest region of sputtering erosion, the Cu target with two distinct grain sizes presents a flat morphology and the smaller grain size results in more flat morphology. At each stage of the life cycle of target material, the Cu target sputtering voltage initially decreases and, then, gradually becomes stable, while the cavity pressure initially increases and gradually becomes stable. The sputtering yield of the samples, with the grain size of 10–20 μm, is found to be greater than the samples with the grain size of 120–150 μm during each stage. Therefore, the Cu target with a small grain size should be selected to ensure the desired film deposition rate and stability of the sputtering process.

In the decision-making process, retaining the original data information has become a most crucial step. Dual hesitant fuzzy sets (DHFS), which can reflect the original membership degree and non-membership degree information given by the DMs, is a kind of new tool for the DMs to provide the original information as much as possible. In this paper, we focus on the decision- making problem by a projection model (Algorithm I) whose attribute values are given in the forms of dual hesitant fuzzy elements (DHFEs). In order to reflect the information of the data more accurately, we first divide the dual hesitant fuzzy decision matrix into membership degree matrix and non-membership degree matrix. Then we gain the virtual positive ideal solution from the membership degree matrix and the negative positive ideal solution from the non-membership degree matrix. And then the projection values from every solution to the virtual positive ideal solution and the negative positive ideal solution are calculated. In combination with the two projection values, the relative consistent degree is further calculated to rank all the alternatives. At the same time, in order to guarantee the rationality of the decision-making result, a variation coefficient method is developed to determine the weights of the attributes under dual hesitant fuzzy environment objectively. Finally, the existing algorithms (Algorithm II and Algorithm III, Algorithm IV, Algorithm V) are compared with our algorithm (Algorithm I). The comparison result shows that Algorithm I is a valuable tool for decision making.

Two new coordination polymers (CPs), namely, {[Zn(tib)(SO4)]·2H2O}n (1) and {[Cd(tib)(2,6-pydc)(H2O)]·H2O}n (2), have been hydrothermally synthesized based on the rigid 1,3,5-tris(imidazol-1-yl)benzene (tib) and 2,6-pyridinedicarboxylate (2,6-pydc2−) ligands. Both CPs were structurally characterized by single-crystal X-ray diffraction. In 1, the Zn(II) centers are connected by tib to generate a 2D → 2D polythreading honeycomb 63 bilayer structure with the SO42− as rods. The bilayers are further connected by O–H···O hydrogen bonds to result in a 3D supramolecular structure. In 2, the Cd(II) centers are coordinated by 2,6-pydc2− to form binuclear Cd2 units which are linked by µ2-tib into 1D chain. The 1D chains are further connected by O–H···O hydrogen bonds, leading to the 2D hydrogen bonded network. Finally, it shows a 2D → 3D interdigitated architecture based on the 2D hydrogen bonded layers through the uncoordinated imidazole rings of tib ligands. The thermogravimetric properties and solid-state photoluminescence of 1 and 2 were investigated. Two new photoluminescent Zn(II) and Cd(II) coordination polymers of 1,3,5-tris(1-imidazolyl)benzene were investigated in this work.

The hot tearing susceptibility of Mg-1Ca-xSr (x=0, 0.2, 0.4, 0.6, wt.%) alloys was investigated by CRC mold with a contraction force measurement system with a load cell and a temperature monitor. The results showed that the hot tearing susceptibility of Mg-1Ca-xSr alloys significantly improved with increasing of Sr content. Especially in Mg-1Ca-0.6Sr alloy, no visible tear was found on the casting sample. The force dropped and the final force value from the time-force-temperature curve derived from the hot tearing instruments could reflect the hot tearing susceptibility of different alloys. The mechanism of improved hot tearing resistance of Mg-1Ca-xSr alloys was clarified. In addition to susceptible temperature range and eutectic liquid fraction, it is found that the formation tendency of divorced eutectic also plays an important role on the hot tearing behavior of Mg-1Ca-xSr alloys.

Living in a disadvantaged neighborhood is associated with adverse clinical outcomes among breast cancer patients, but the underlying pathway is still unclear. Limited evidence has suggested that accelerated biological aging may play an important role. In this study, using a sub-sample of 906 women with newly diagnosed breast cancer at M.D. Anderson, we examined whether levels of selected markers of biological aging (e.g., allostatic load, telomere length, and global DNA methylation) were affected by neighborhood disadvantage. The Area Deprivation Index was used to determine the neighborhood disadvantage. Based on the median ADI at the national level, the study population was divided into low and high ADI groups. Overall, breast cancer patients from the high ADI group were more likely to be younger and non-Hispanic Black than those from the low ADI group (P P = 0.029 and 0.019, respectively). For the relationship with markers, compared to the low ADI group, high ADI group had higher median levels of allostatic load (P = 0.046) and lower median levels of global DNA methylation (P

A multifunctional nanoplatform with core–shell structure was constructed in one-pot for the synergistic photothermal, photodynamic, and chemotherapy against breast cancer. In the presence of gambogic acid (GA) as the heat-shock protein 90 (HSP90) inhibitor and the gold nanostars (AuNS) as the photothermal reagent, the assembly of Zr4+ with tetrakis (4-carboxyphenyl) porphyrin (TCPP) gave rise to the nanocomposite AuNS@ZrTCPP-GA (AZG), which in turn, further coated with PEGylated liposome (LP) to enhance the stability and biocompatibility, and consequently the antitumor effect of the particle. Upon cellular uptake, the nanoscale metal − organic framework (NMOF) of ZrTCPP in the resulted AuNS@ZrTCPP-GA@LP (AZGL) could be slowly degraded in the weak acidic tumor microenvironment to release AuNS, Zr4+, TCPP, and GA to exert the synergistic treatment of tumors via the combination of AuNS-mediated mild photothermal therapy (PTT) and TCPP-mediated photodynamic therapy (PDT). The introduction of GA serves to reduce the thermal resistance of the cell to re-sensitize PTT and the constructed nanoplatform demonstrated remarkable anti-tumor activity in vitro and in vivo. Our work highlights a facile strategy to prepare a pH-dissociable nanoplatform for the effective synergistic treatment of breast cancer. Graphical Abstract

Saikosaponin a and saikosaponin d are used as chemical standards for the quality evaluation of Bupleurum chinense DC. by the high-performance liquid chromatography method in current Chinese Pharmacopoeia. However, other saikosaponins, such as saikosaponin c and saikosaponin b2, also possess pharmaceutical activity, but are not used as chemical standards. In this study, a quantitative proton nuclear magnetic resonance (1H NMR) method was developed to determine the total mass percentage (mg/g) of SSa, SSb1, SSb2 and SSd in B. chinense DC., using the H-24 (δH 0.71) signal. Furthermore, the molality (mol/kg) of type I saikosaponins (epoxy-ether structure) was also determined by quantitative 1H NMR in the area of H-11 (δH 5.95) for a more accurate quality evaluation. Validation of the method confirmed that it has acceptable selectivity, precision, stability, and repeatability. The results indicated that this method has the potential to be a reliable method for the quantification of saikosaponins in Bupleurum scorzonerifolium Willd., vinegar baked B. chinense DC. and B. scorzonerifolium Willd., Chaihu Koufuye (oral liquid of Chaihu).

As an important functional thin-film material in the field of electronic information, high-purity titanium (Ti) is widely used in different industries, such as integrated circuits, flat-panel displays and solar energy, indicating the importance of further research on Ti targets. Herein, a titanium target is placed in a UDP-650 closed-field nonequilibrium magnetron sputtering ion coating machine for deep etching to form racetrack grooves, and different positions of etching grooves are analyzed to understand the target etched behavior. The sputtering-induced etching of the Ti target, from shallow to deep regions, changes from the preferential sputtering of scratches and other defects in the edge area to the surface sputtering pits, with discontinuous distribution and uneven size, to grain boundary sputtering and, finally, to closely packed grain surface sputtering. The etching behavior of different regions exhibits different characteristics, mainly showing selective sputtering. The surface roughness of the sputtered area initially increases with the increase of sputtering depth and plasma density, followed by a slight decrease. Moreover, different degrees of incomplete recrystallization occur in different sputtering areas due to the uneven distribution of plasma on the target surface. The grain size increased from the transition area between sputtering and non-sputtering (112 μm) to the deepest sputtering area (139 μm). Moreover, the relationship between the cross-sectional grain size and sputter surface roughness renders a correlation coefficient of 0.802, indicating a strong influence of grain size on surface roughness. Therefore, it is of utmost importance to refine grains and increase the sputtering yield of the target as well as reduce the surface roughness of the target after etching to obtain a high-quality thin film.

Allostatic load (AL), a composite index, has been used to capture variation in life-course stresses. However, few studies have been carried out among breast cancer patients. In this study, we examined the cross-sectional association of AL with demographics, healthy behaviors, tumor characteristics, and mitochondrial DNA copy number in breast cancer patients. The study used a sub-sample of 934 women with newly diagnosed breast cancer at M.D. Anderson from 2013 to 2018. To construct the AL score, the study used a battery of seventeen factors that represents the activity of five physiological systems: metabolic, cardiovascular, immunological, renal, and liver. AL was positively associated with the age of disease diagnosis (P = 0.002), and was higher in Black and Hispanic populations than White (P = 0.001 and 0.032, respectively). AL was also found more abundant in those who experienced marital dissolution (P = 0.006), lacked a college education (P = 0.045), currently smoked (P = 0.011), and had low levels of physical activity (P = 0.037) than their counterparts. The study then found that higher AL was associated with increased odds of having poorly differentiated tumors (Odds ratio (OR): 1.40, 95% confidence interval (CI): 1.28, 1.62). An additional significant association was observed between AL with estrogen receptor negative (ER-) (OR = 1.56, 95%CI: 1.02, 2.36) among Black patients. Finally, we observed a significant positive correlation between AL with leukocyte mitochondrial DNA copy number variation (P

Laminates of carbon fibre reinforced polymer (CFRP) and titanium (Ti) alloy are used in aerospace applications and require holes for joining to other components, which can weaken them. In this study, to determine the influences of drilling and helical milling on the geometric accuracy of holes, holes were made in a CFRP/Ti-laminated structure by these two techniques, and variations in aperture and roundness at different positions were investigated. In two processes, apertures are larger in the middle and smaller at the ends, and most are larger than the apertures of standard holes (6 mm). With drilling, roundness is relatively high at hole entrances and exits. In helical milling, the maximum roundness occurs just underneath the hole entrance, while the minimum occurs at the exit. In the drilling of Ti alloy, the maximum aperture occurs at the entrance; however, with helical milling, the hole entrance aperture is smaller. The aperture at other positions is relatively small. During drilling, the maximum roundness occurs at hole entrances, while the minimum occurs just underneath and then increases with depth. Helical milling produces a relatively large roundness at hole entrances, with consistent variation in other positions. Generally, helical milling of a laminated structure produces better geometric accuracy in holes in the Ti alloy layer, better hole roundness in the CFRP layer, and smaller roundness in the transition zone. However, drilling achieves better aperture accuracy in CFRP and smaller aperture errors in the transition zone. These results will help to produce stronger CFRP/Ti-laminated structures.