Search

Toward accurately simulating both hardening and softening effects for metals up to failure, a new finite strain elastoplastic J2-flow model is proposed with the yield strength therein as a function of the plastic work in the explicit form. With no need to identify any adjustable parameters, the uniaxial stress-strain response predicted from this new model is shown to automatically and accurately match any given data from monotonic uniaxial extension tests of bars. As such, the objectives in three respects are achieved for the first time, i.e., (i) both the hardening and softening effects up to failure can be simulated in the sense of matching test data with no errors, (ii) the usual tedious implicit procedures toward identifying numerous unknown parameters need not be involved and can be totally bypassed, and (iii) the model applicability can be ensured in a broad sense for various metallic materials with markedly different transition effects from hardening to softening. With the new model, the complete response features of stretched bars and twisted tubes up to failure are studied, including the failure effects of bars under monotonic extension and tubes under monotonic torsion and, furthermore, the fatigue failure effects of bars under cyclic loading. The results show accurate agreement with the uniaxial data, and the results for both the shear stress and the normal stress at the finite torsion display realistic hardening-to-softening transition effects for the first time.

Kaempferol (KAE) is a natural flavonoid compound with antitumor activity. However, the low aqueous solubility, poor chemical stability and suboptimal bioavailability greatly restricted its clinical application of cancer. In order to overcome these shortages and enhance the antitumor effect of KAE, we developed a kaempferol nanosuspensions (KAE-NSps) with D-α-Tocopherol polyethylene glycol 1000 succinate (TPGS) as stabilizer, screened the optimal preparation process, and investigated the basic properties and the antitumor effect in the study. The results demonstrated that the particle size was 186.6 ± 2.6 nm of the TPGS-KAE-NSps optimized, the shape of which was fusiform under the transmission electron microscope. The 2% (w/v) glucose was used as the cryoprotectant for TPGS-KAE-NSps, whose drug loading content was 70.31 ± 2.11%, and the solubility was improved prominently compared to KAE. The stability and biocompatibility of TPGS-KAE-NSps were favorable, which had a certain sustained release effect. Moreover, TPGS-KAE-NSps clearly seen to be taken in the cytoplasm exhibited a stronger cytotoxicity and suppression of cell migration, higher apoptosis rate and more intracellular ROS production compared to KAE in vitro cell experiments. In addition, TPGS-KAE-NSps showed a stronger inhibition of tumor growth (the tumor inhibition rate of high dose intravenous injection group was 68.9 ± 1.46%) than KAE with no obvious toxicity on 4T1 tumor-bearing mice. Overall, TPGS-KAE-NSps prepared improved the defect and the antitumor effect of KAE notably, which was a promising nanodrug delivery system for KAE and was expected to become a clinical antitumor drug.

Based on both positive psychology and the gene × environment research paradigm, the current study constructed a moderated mediation model to explore the relationship between childhood maltreatment ...

Biological cells in vivo typically reside in a dynamic flowing microenvironment with extensive biomechanical and biochemical cues varying in time and space. These dynamic biomechanical and biochemical signals together act to regulate cellular behaviors and functions. Microfluidic technology is an important experimental platform for mimicking extracellular flowing microenvironment in vitro. However, most existing microfluidic chips for generating dynamic shear stress and biochemical signals require expensive, large peripheral pumps and external control systems, unsuitable for being placed inside cell incubators to conduct cell biology experiments. This study has developed a microfluidic generator of dynamic shear stress and biochemical signals based on autonomously oscillatory flow. Further, based on the lumped-parameter and distributed-parameter models of multiscale fluid dynamics, the oscillatory flow field and the concentration field of biochemical factors has been simulated at the cell culture region within the designed microfluidic chip. Using the constructed experimental system, the feasibility of the designed microfluidic chip has been validated by simulating biochemical factors with red dye. The simulation results demonstrate that dynamic shear stress and biochemical signals with adjustable period and amplitude can be generated at the cell culture chamber within the microfluidic chip. The amplitudes of dynamic shear stress and biochemical signals is proportional to the pressure difference and inversely proportional to the flow resistance, while their periods are correlated positively with the flow capacity and the flow resistance. The experimental results reveal the feasibility of the designed microfluidic chip. Conclusively, the proposed microfluidic generator based on autonomously oscillatory flow can generate dynamic shear stress and biochemical signals without peripheral pumps and external control systems. In addition to reducing the experimental cost, due to the tiny volume, it is beneficial to be integrated into cell incubators for cell biology experiments. Thus, the proposed microfluidic chip provides a novel experimental platform for cell biology investigations.

Using the differential susceptibility model, the present study examined how (mediator = Internet addiction) and when (moderator = 5-HTR1A gene rs6449693) did negative life events influence college students’ depression. A total of 301 Chinese college students (mean age = 19.15 years, SD = 0.93) from southern China completed anonymous questionnaires (the Center for Epidemiological Studies Depression Scale, the Adolescent Self-Rating Life Events Check List, and the Chinese Version of the Internet Addiction Scale). Our findings revealed that negative life events, Internet addiction, and college students’ depression were significantly and positively associated with each other. Internet addiction mediated the relationship between negative life events and college students’ depression. Further, 5-HTR1A gene rs6449693 polymorphism moderated the relationship between negative life events and college students’ depression; specifically, allele G is the susceptibility reason which is manifested, as depression scores of individuals with high level of allele G are significantly lower than those with low level allele A. These findings underscore the importance of the differential susceptibility model in understanding how and when negative life events impact college students’ depression.

Heat stress (HS) affects the development of porcine gametes and embryos negatively, induces the decrease of reproductive ability significantly, threatens global pig production. Ginsenoside Re (GRe), is a main bioactive component of ginseng, shows very specific anti-apoptotic, antioxidant and anti-inflammatory activities. To investigate the alleviating effect of GRe on the in vitro maturation of porcine oocyte under the HS, the polar body extrusion rate, intracellular levels of reactive oxygen species (ROS) and glutathione (GSH), ATP content, mitochondrial membrane potential (MMP) were assessed. For the current study, porcine cumulus-oocyte complexes (COCs) randomly divided into four groups: the control, GRe, HS and HS + GRe group. The results showed that HS inhibited the cumulus cell expansion and polar body extrusion rate, the levels of GSH and MMP, the ATP content, the gene expression of Nrf2 of porcine oocytes and the parthenogenetic activation (PA) embryo development competence, but GRe treatment could partly neutralize these adverse effects. Furthermore, HS increased the ROS formation and percentage of apoptosis, the gene expression of HSP90, CASP3 and CytoC of porcine oocytes, but GRe could weaken the effect on Cyto C and BAX expression induced by HS. Taken together, these results showed that the presence of GRe during in vitro maturation protects porcine oocytes from HS. These findings lay a foundation for GRe may be used as a potential protective drug to protect porcine oocytes against HS damage.

Methylprednisolone pulse treatment is currently used for optic neuritis. It can speed visual recovery, but does not improve the ultimate visual outcomes. Recent studies have reported that miR-125a-5p has immunomodulatory effects on autoimmune diseases. However, it remains unclear whether miR-125a-5p has effects on optic neuritis. In this study, we used adeno-associated virus to overexpress or silence miR-125a-5p in mice. We found that silencing miR-125a-5p increased the latency of visual evoked potential and aggravated inflammation of the optic nerve. Overexpression of miR-125a-5p suppressed inflammation of the optic nerve, protected retinal ganglion cells, and increased the percentage of Treg cells. Our findings show that miR-125a-5p exhibits anti-inflammatory effects through promoting the differentiation of Treg cells.

The impact of use of sodium-glucose transporter 2 (SGLT2) inhibitors on occurrence of various kinds of respiratory disorders has not been established. We aimed at evaluating the relationship between use of SGLT2 inhibitors and occurrence of 9 kinds of noninfectious respiratory disorders. Large randomized controlled trials (RCTs) of SGLT2 inhibitors were included in this study. We conducted fixed-effects meta-analysis to synthesize risk ratios (RRs) and 95% confidence intervals (CIs). We did subgroup analysis respectively stratified by type of underlying diseases and type of SGLT2 inhibitors. Nine Large RCTs were included for analysis. Compared with placebo, SGLT2 inhibitors significantly reduced the occurrence of overall respiratory disorders (RR 0.75, 95% CI 0.62–0.91), acute pulmonary oedema (RR 0.51, 95% CI 0.29–0.88), asthma (RR 0.57, 95% CI 0.33–0.995), and sleep apnoea syndrome (RR 0.35, 95% CI 0.12–0.99). SGLT2 inhibitors showed the reduced trends in the risks of chronic obstructive pulmonary disease (COPD) (RR 0.79, 95% CI 0.61–1.02; P = 0.073) and pulmonary hypertension (RR 0.43, 95% CI 0.16–1.17; P = 0.098). SGLT2 inhibitors had no significant effects on three other respiratory disorders. These effects exhibited by SGLT2 inhibitors were consistent across different underlying diseases (Psubgroup ≥0.209) and different SGLT2 inhibitors (Psubgroup ≥0.192). SGLT2 inhibitors can significantly reduce the occurrence of acute pulmonary oedema, asthma, and sleep apnoea syndrome; and produce the reduced trends in the risks of COPD and pulmonary hypertension. These findings will prompt further investigation on SGLT2 inhibitors for primary and secondary prevention of various respiratory disorders.

PurposeTo assess and describe patient-reported outcomes (PROs) in women with locally advanced/unresectable or metastatic breast cancer (aBC/mBC) with hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR + /HER2 −) status receiving palbociclib combination therapy in a US real-world setting.MethodsA prospective, noninterventional, multicenter longitudinal study was conducted in US patients initiating treatment with palbociclib combination therapy for HR + /HER2 − aBC/mBC. PRO data (SF-12; CES-D-10; mood; pain; fatigue; interference of aBC/mBC or its treatment on family life, social life, physical activity, energy, and productivity; overall health rating; and quality of life [QOL]) were collected via a custom-developed mobile application at daily, weekly, and cycle-based intervals. Patient medical information (demographics, clinical characteristics, treatment information, and adverse events) was collected from medical records at baseline and at the end of the 6-month follow-up period.ResultsPatients’ general health status (SF-12) remained consistent throughout treatment and was generally consistent with published norms for individuals diagnosed with cancer. The presence of depression (CES-D-10) was low and did not change substantially over time. Mean pain and fatigue scores using an 11-point numeric rating scale were low and remained stable. Patients, on average, reported neutral or positive moods. Patient-reported QOL and overall health was primarily “Good,” “Very good,” or “Excellent.” Findings were consistent regardless of patient experience with neutropenia.ConclusionsPatients treated with palbociclib, on average, reported consistently low levels of pain and fatigue as well as good QOL and overall health that remained stable throughout the first 6 months of treatment regardless of episodes of neutropenia.

Spotted fever group rickettsiae, mainly maintained and transmitted by ticks, are important etiological agents of (re)emerging zoonotic diseases worldwide. It is of great significance to investigate spotted fever group rickettsiae in ticks in different areas for the prevention and control of rickettsioses. In this study, a total of 305 ticks were collected from wild and domestic animals in Chongqing, Guizhou, Yunnan, and Guangxi provinces of southwestern China during 2017–2019 and examined for the presence of spotted fever group rickettsiae by PCR with primers targeting the partial gltA, ompA, rrs, and htrA genes. Results showed that two spotted fever group rickettsiae species, including the pathogenic Candidatus Rickettsia jingxinensis (Rickettsiales: Rickettsiaceae) and a potential novel species Rickettsia sp. sw (Rickettsiales: Rickettsiaceae), were identified. The Ca. R. jingxinensis sequences were recovered from Rhipicephalus microplus (Ixodida: Ixodidae) and Haemaphysalis longicornis (Ixodida: Ixodidae) ticks and phylogenetically clustered with previous Ca. R. jingxinensis, Ca. R. longicornii (Rickettsiales: Rickettsiaceae), and Rickettsia sp. XY118 (Rickettsiales: Rickettsiaceae) strains. Rickettsia sp. sw was detected in Amblyomma geoemydae (Ixodida: Ixodidae) and Rh. microplus. Interestingly, as far as we know, this was the first report of Rickettsia (Rickettsiales: Rickettsiaceae) in A. geoemydae. Phylogenetic analyses indicated that this potential novel species was closely related to R. aeschlimannii (Rickettsiales: Rickettsiaceae) with gltA and ompA genes and grouped in a cluster composed of R. montanensis (Rickettsiales: Rickettsiaceae), R. raoultii (Rickettsiales: Rickettsiaceae), R. aeschlimannii, R. massiliae (Rickettsiales: Rickettsiaceae), and R. rhipicephali (Rickettsiales: Rickettsiaceae) with htrA, while formed a separate clade with rrs. The pathogenicity of Rickettsia sp. sw should be further confirmed. These results expand the knowledge of the geographical distribution and vector distribution of spotted fever group rickettsiae in China and are useful for assessing the potential public health risk.