Heavy metal ions exchange driven protein phosphorylation cascade functions in genomic instability in spermatocytes and male infertility.

DNA double-strand breaks (DSBs) are functionally linked to genomic instability in spermatocytes and to male infertility. The heavy metal cadmium (Cd) is known to induce DNA damage in spermatocytes by unknown mechanisms. Here, we showed that Cd ions impaired the canonical non-homologous end-joining (NHEJ) repair pathway, but not the homologous recombination (HR) repair pathway, through stimulation of Ser2056 and Thr2609 phosphorylation of DNA-PKcs at DSB sites. Hyper-phosphorylation of DNA-PKcs led to its premature dissociation from DNA ends and the Ku complex, preventing recruitment of processing enzymes and further ligation of DNA ends. Specifically, this cascade was initiated by the loss of PP5 phosphatase activity, which results from the dissociation of PP5 from its activating ions (Mn), that is antagonized by Cd ions through a competitive mechanism. In accordance, in a mouse model Cd-induced genomic instability and consequential male reproductive dysfunction were effectively reversed by a high dosage of Mn ions. Together, our findings corroborate a protein phosphorylation-mediated genomic instability pathway in spermatocytes that is triggered by exchange of heavy metal ions.

Anti-intercellular adhesion molecule 1 monomaintenance therapy induced long-term liver allograft survival without chronic rejection.

Calcineurin inhibitors (CNIs) are essential in liver transplantation (LT); however, their long-term use leads to various adverse effects. The anti-intercellular adhesion molecule (ICAM)-1 monoclonal antibody MD3 is a potential alternative to CNI. Despite its promising results with short-term therapy, overcoming the challenge of chronic rejection remains important. Thus, we aimed to investigate the outcomes of long-term MD3 therapy with monthly MD3 monomaintenance in nonhuman primate LT models. Rhesus macaques underwent major histocompatibility complex-mismatched allogeneic LT. The conventional immunosuppression group (Con-IS, n = 4) received steroid, tacrolimus, and sirolimus by 4 months posttransplantation. The induction MD3 group (IN-MD3, n = 5) received short-term MD3 therapy for 3 months with Con-IS. The maintenance MD3 group (MA-MD3, n = 4) received MD3 for 3 months, monthly doses by 2 years, and then quarterly. The MA-MD3 group exhibited stable liver function without overt infection and had significantly better liver allograft survival than the IN-MD3 group. Development of donor-specific antibody and chronic rejection were suppressed in the MA-MD3 group but not in the IN-MD3 group. Donor-specific T cell responses were attenuated in the MA-MD3 group. In conclusion, MD3 monomaintenance therapy without maintenance CNI provides long-term liver allograft survival by suppressing chronic rejection, offering a potential breakthrough for future human trials.

ICF-PR-Net: a deep phase retrieval neural network for X-ray phase contrast imaging of inertial confinement fusion capsules.

X-ray phase contrast imaging (XPCI) has demonstrated capability to characterize inertial confinement fusion (ICF) capsules, and phase retrieval can reconstruct phase information from intensity images. This study introduces ICF-PR-Net, a novel deep learning-based phase retrieval method for ICF-XPCI. We numerically constructed datasets based on ICF capsule shape features, and proposed an object-image loss function to add image formation physics to network training. ICF-PR-Net outperformed traditional methods as it exhibited satisfactory robustness against strong noise and nonuniform background and was well-suited for ICF-XPCI's constrained experimental conditions and single exposure limit. Numerical and experimental results showed that ICF-PR-Net accurately retrieved the phase and absorption while maintaining retrieval quality in different situations. Overall, the ICF-PR-Net enables the diagnosis of the inner interface and electron density of capsules to address ignition-preventing problems, such as hydrodynamic instability growth.

Molecular incompatibility between pig CD200 and human CD200 receptor in in vitro xenogeneic immune responses.

Overexpression of human CD200 (hCD200) in porcine endothelial cells (PECs) has been reported to suppress xenogeneic immune responses of human macrophages against porcine endothelial cells. The current study aimed to address whether the above-mentioned beneficial effect of hCD200 is mediated by overcoming the molecular incompatibility between porcine CD200 (pCD200) and hCD200 receptor or simply by increasing the expression levels of CD200 without any molecular incompatibility across the two species. We overexpressed hCD200 or pCD200 using lentiviral vectors with V5 marker in porcine endothelial cells and compared their suppressive activity against U937-derived human macrophage-like cells (hMCs) and primary macrophages. In xenogeneic coculture of porcine endothelial cells and human macrophage-like cells or macrophages, hCD200-porcine endothelial cells suppressed phagocytosis and cytotoxicity of human macrophages to a greater extent than pCD200-porcine endothelial cells. Secretion of tumor necrosis factor-α, interleukin-1ß, and monocyte chemoattractant protein-1 from human macrophages and expression of M1 phenotypes (inducible nitric oxide synthase, dectin-1, and CD86) were also suppressed by hCD200 to a greater extent than pCD200. Furthermore, in signal transduction downstream of CD200 receptor, hCD200 induced Dok2 phosphorylation and suppressed IκB phosphorylation to a greater extent than pCD200. The above data supported the possibility of a significant molecular incompatibility between pCD200 and human CD200 receptor, suggesting that the beneficial effects of hCD200 overexpression in porcine endothelial cells could be mediated by overcoming the molecular incompatibility across the species barrier rather than by simple overexpression effects of CD200.

Chemokine CCL2 promotes cardiac regeneration and repair in myocardial infarction mice via activation of the JNK/STAT3 axis.

Stimulation of adult cardiomyocyte proliferation is a promising strategy for treating myocardial infarction (MI). Earlier studies have shown increased CCL2 levels in plasma and cardiac tissue both in MI patients and mouse models. In present study we investigated the role of CCL2 in cardiac regeneration and the underlying mechanisms. MI was induced in adult mice by permanent ligation of the left anterior descending artery, we showed that the serum and cardiac CCL2 levels were significantly increased in MI mice. Intramyocardial injection of recombinant CCL2 (rCCL2, 1 µg) immediately after the surgery significantly promoted cardiomyocyte proliferation, improved survival rate and cardiac function, and diminished scar sizes in post-MI mice. Alongside these beneficial effects, we observed an increased angiogenesis and decreased cardiomyocyte apoptosis in post-MI mice. Conversely, treatment with a selective CCL2 synthesis inhibitor Bindarit (30 µM) suppressed both CCL2 expression and cardiomyocyte proliferation in P1 neonatal rat ventricle myocytes (NRVMs). We demonstrated in NRVMs that the CCL2 stimulated cardiomyocyte proliferation through STAT3 signaling: treatment with rCCL2 (100 ng/mL) significantly increased the phosphorylation levels of STAT3, whereas a STAT3 phosphorylation inhibitor Stattic (30 µM) suppressed rCCL2-induced cardiomyocyte proliferation. In conclusion, this study suggests that CCL2 promotes cardiac regeneration via activation of STAT3 signaling, underscoring its potential as a therapeutic agent for managing MI and associated heart failure.

Porcupine inhibitor CGX1321 alleviates heart failure with preserved ejection fraction in mice by blocking WNT signaling.

Heart failure with preserved ejection fraction (HFpEF) is highly prevalent, and lacks effective treatment. The aberration of WNT pathway underlies many pathological processes including cardiac fibrosis and hypertrophy, while porcupine is an acyltransferase essential for the secretion of WNT ligands. In this study we investigated the role of WNT signaling pathway in HFpEF as well as whether blocking WNT signaling by a novel porcupine inhibitor CGX1321 alleviated HFpEF. We established two experimental HFpEF mouse models, namely the UNX/DOCA model and high fat diet/L-NAME ("two-hit") model. The UNX/DOCA and "two-hit" mice were treated with CGX1321 (3 mg·kg-1·d-1) for 4 and 10 weeks, respectively. We showed that CGX1321 treatment significantly alleviated cardiac hypertrophy and fibrosis, thereby improving cardiac diastolic function and exercise performance in both models. Furthermore, both canonical and non-canonical WNT signaling pathways were activated, and most WNT proteins, especially WNT3a and WNT5a, were upregulated during the development of HEpEF in mice. CGX1321 treatment inhibited the secretion of WNT ligands and repressed both canonical and non-canonical WNT pathways, evidenced by the reduced phosphorylation of c-Jun and the nuclear translocation of ß-catenin and NFATc3. In an in vitro HFpEF model, MCM and ISO-treated cardiomyocytes, knockdown of porcupine by siRNA leads to a similar inhibitory effect on WNT pathways, cardiomyocyte hypertrophy and cardiac fibroblast activation as CGX1321 did, whereas supplementation of WNT3a and WNT5a reversed the anti-hypertrophy and anti-fibrosis effect of CGX1321. We conclude that WNT signaling activation plays an essential role in the pathogenesis of HFpEF, and porcupine inhibitor CGX1321 exerts a therapeutic effect on HFpEF in mice by attenuating cardiac hypertrophy, alleviating cardiac fibrosis and improving cardiac diastolic function.

A Multicenter Randomized Controlled Study of Contrast-enhanced US versus US-guided Biopsy of Focal Liver Lesions.

Background Retrospective or single-center prospective studies with relatively small samples have shown that contrast-enhanced US (CEUS) can improve the diagnostic accuracy of percutaneous biopsy, but larger prospective studies are lacking. Purpose To assess the diagnostic performance of CEUS-guided biopsy (CEUS-GB) of focal liver lesions (FLLs) compared with US-guided biopsy (US-GB) in a prospective multicenter study. Materials and Methods In this randomized controlled study conducted in nine hospitals in China between March 2016 and August 2019, adult participants with FLLs detected with US, CT, or MRI and planned for percutaneous biopsy were randomly assigned to undergo either US-GB or CEUS-GB. Lesions diagnosed as malignant at histopathologic analysis were considered true-positive findings. Benign or indeterminate lesions required further confirmation with either repeat biopsy or clinical follow-up at 6 months or later. The primary endpoint was the diagnostic accuracy rate, and comparison between groups was made using the χ2 test. Results In this study, 2056 participants (1297 men, 759 women; mean age, 58 years ± 11 [SD]) were analyzed: 1030 underwent biopsy with US guidance and 1026 underwent biopsy with CEUS guidance. The overall diagnostic accuracy rate of CEUS-GB was 96% (983 of 1026) versus 93% (953 of 1030) for US-GB (P = .002), CEUS-GB enabled correct identification in 96% of participants (983 of 1026) compared with 92% (953 of 1030) with US-GB (P = .002). The negative predictive value (NPV) for both biopsy methods was moderate but significantly higher for CEUS-GB than for US-GB (74% vs 57%, P = .001). The difference was remarkable for lesions smaller than 2.0 cm, with CEUS-GB showing higher diagnostic accuracy (96% vs 88%, P = .004) and sensitivity (95% vs 87%, P = .007) than US-GB. Among lesions smaller than 2.0 cm, the accuracy of CEUS-GB and US-GB for detection of hepatocellular carcinoma was 93% and 80%, respectively (P = .008), while it was comparable for liver metastases (98% vs 95%, P = .63). Conclusion Contrast-enhanced US-guided biopsy of focal liver lesions is an effective and safe procedure with a higher diagnostic accuracy than US-guided biopsy, especially for lesions smaller than 2.0 cm and for hepatocellular carcinoma diagnosis. Clinical trial registration no. NCT02413437 © RSNA, 2022 Online supplemental material is available for this article.

First Indirect Drive Experiment Using a Six-Cylinder-Port Hohlraum.

The new hohlraum experimental platform and the quasi-3D simulation model are developed to enable the study of the indirect drive experiment using the six-cylinder-port hohlraum for the first time. It is also the first implosion experiment for the six laser-entrance-hole hohlraum to effectively use all the laser beams of the laser facility that is primarily designed for the cylindrical hohlraum. The experiments performed at the 100 kJ Laser Facility produce a peak hohlraum radiation temperature of ∼222 eV for ∼80 kJ and 2 ns square laser pulse. The inferred x-ray conversion efficiency η∼87% is similar to the cylindrical hohlraum and higher than the octahedral spherical hohlraum at the same laser facility, while the low laser backscatter is similar to the outer cone of the cylindrical hohlraum. The hohlraum radiation temperature and M-band (>1.6 keV) flux can be well reproduced by the quasi-3D simulation. The variations of the yield-over-clean and the hot spot shape can also be semiquantitatively explained by the calculated major radiation asymmetry of the quasi-3D simulation. Our work demonstrates the capability for the study of the indirect drive with the six-cylinder-port hohlraum at the cylindrically configured laser facility, which is essential for numerically assessing the laser energy required by the ignition-scale six-cylinder-port hohlraum.

Leucine-rich repeat kinase 2 is protective during acute kidney injury through its activation of autophagy in podocytes.

Leucine-rich repeat kinase 2 (LRRK2) is a known regulator of autophagy in a range of cell types. Here, we investigated the role of LRRK2-associated autophagy during acute kidney injury (AKI) and its underlying mechanism(s) of action. Male mice aged 8-weeks were treated with the LRRK2 inhibitor MLi-2 and exposed to lipopolysaccharide (LPS) through intraperitoneal injection or ischemia-reperfusion (IR) surgery. Mice were sacrificed 12 or 24 h post-LPS injection or IR operation and blood was collected for serum creatinine measurements. Kidney cortical tissues were collected for western blot analysis of podocyte-specific markers and autophagy-associated proteins. Renal histopathology was observed through hematoxylin-eosin staining. For cell-based assays, immortalized mouse podocytes were silenced for LRRK2 through siRNA transfection and exposed to LPS or cobalt chloride. Changes in cell viability were investigated using cell counting kit-8, flow cytometry and MTT assays. Expression of podocyte-specific markers and autophagy-associated proteins were analyzed by western blotting. We observed an increase in LRRK2 expression at 12 h post-LPS injection and IR surgery that was accompanied by enhanced autophagy. At 24 h post-treatment, both LRRK2 expression and autophagy declined. Kidney injury was most pronounced in mice treated with MLi-2. Podocytes silenced for LRRK2 showed a loss of cell viability, decreased levels of podocyte-specific protein expression and a suppression of autophagy. Together, these data reveal the protective effects of LRRK2 during AKI through enhanced podocyte autophagy and cell viability.

Advancements in MAFLD Modeling with Human Cell and Organoid Models.

Metabolic (dysfunction) associated fatty liver disease (MAFLD) is one of the most prevalent liver diseases and has no approved therapeutics. The high failure rates witnessed in late-phase MAFLD drug trials reflect the complexity of the disease, and how the disease develops and progresses remains to be fully understood. In vitro, human disease models play a pivotal role in mechanistic studies to unravel novel disease drivers and in drug testing studies to evaluate human-specific responses. This review focuses on MAFLD disease modeling using human cell and organoid models. The spectrum of patient-derived primary cells and immortalized cell lines employed to model various liver parenchymal and non-parenchymal cell types essential for MAFLD development and progression is discussed. Diverse forms of cell culture platforms utilized to recapitulate tissue-level pathophysiology in different stages of the disease are also reviewed.

[Integrated smart hyperspectral imaging and CARS-based characteristic band selection for rapid determination of SO_2 content in sulphur-fumigated Achyranthis Bidentatae Radix].

In order to realize the rapid and non-destructive detection of SO_2 content in sulphur-fumigated Achyranthis Bidentatae Radix, this paper first prepared the sulphur-fumigated Achyranthis Bidentatae Radix samples with the usage amount of sulphur being 0, 2.5%, and 5% of the mass of Achyranthis Bidentatae Radix pieces. The SO_2 content in different batches of sulphur-fumigated Achyranthis Bidentatae Radix was determined using the method in Chinese Pharmacopoeia, followed by the acquisition of their hyperspectral data within both visible-near infrared(435-1 042 nm) and short-wave infrared(898-1 751 nm) regions by hyperspectral imaging. Meanwhile, the first derivative, AUTO, multiplicative scatter correction, Savitzky-Golay(SG) smoothing, and standard normal variable transformation algorithms were used to pre-process the original hyperspectral data, which were then subjected to characteristic band extraction based on competitive adaptive reweighted sampling(CARS) and the partial least square regression analysis for building a quantitative model of SO_2 content in sulphur-fumigated Achyranthis Bidentatae Radix. It was found that the accuracy of the quantitative model built depending on the visible-near infrared spectra was high, with the determination coefficient of prediction set(R■) reaching 0.900 1. The established quantitative model has enabled the rapid and non-destructive detection of SO_2 content in sulphur-fumigated Achyranthis Bidentatae Radix, which can serve as an effective supplement to the method described in Chinese Pharmacopeia.

[Discrimination of quality markers of Shujin Huoxue Capsules based on five principles coupled with cobweb model].

The quality markers(Q-markers) of Shujin Huoxue Capsules were comprehensively discriminated based on the five principles of transfer and traceability, specificity, compatibility, effectiveness and measurability. The compounds that could be transferred from the original medicinal materials to the preparation were selected with the principle of transfer and traceability. The specific components in the prescription were screened by reviewing literature with the principle of specificity. According to the principle of compatibility, the attributes of compounds were evaluated by the sovereign, minister, assistant and guide combination rules of the original medicinal materials in the prescription. According to the principle of measurability, the measurable components were summarized by reference to the pharmacopoeia and literature combined with the content. The mechanism of Shujin Huoxue Capsules in the treatment of osteoporosis was studied through network pharmacology based on the principle of effectiveness, which was the evaluation index of effectiveness. The chemical components screened out above were regarded as candidate Q-markers, and the cobweb model was plotted to obtain the comprehensive score of Q-markers. Hydroxysafflor yellow A, trachelosid, eleutheroside B, α-cyperone, protocatechuic acid, protocatechualdehyde and 4-methoxy salicylaldehyde were discriminated as the Q-markers of Shujin Huoxue Capsules based on the five principles combined with cobweb model.

First Inertial Confinement Fusion Implosion Experiment in Octahedral Spherical Hohlraum.

In inertial confinement approaches to fusion, the asymmetry of target implosion is a major obstacle to achieving high gain in the laboratory. A recently proposed octahedral spherical hohlraum makes it possible to naturally create spherical target irradiation without supplementary symmetry control. Before any decision is made to pursue an ignition-scale laser system based on the octahedral hohlraum, one needs to test the concept with the existing facilities. Here, we report a proof-of-concept experiment for the novel octahedral hohlraum geometry on the cylindrically configured SGIII laser facility without a symmetry control. All polar and equatorial self-emission images of the compressed target show a near round shape of convergence ratio 15 under both square and shaped laser pulses. The observed implosion performances agree well with the ideal spherical implosion simulation. It also shows limitations with using the existing facilities and adds further weight to the need to move to a spherical port geometry for future ignition laser facilities.

FTO overexpression inhibits apoptosis of hypoxia/reoxygenation-treated myocardial cells by regulating m6A modification of Mhrt.

Heart failure (HF) is the end stage of many cardiovascular diseases and seriously threatens people's health. This article aimed to explore the biological role of fat-mass and obesity-associated gene (FTO) in HF. We constructed HF mouse model by transverse aortic constriction or intraperitoneal injection of doxorubicin. Mouse myocardial cells were exposed to hypoxia/reoxygenation (H/R). FTO and Mhrt were downregulated in heart tissues of HF mice. HF mice exhibited an increase in the total levels of N6 methyladenosine (m6A) and the m6A levels of Mhrt. Moreover, FTO overexpression caused an upregulation of Mhrt and reduced m6A modification of Mhrt in the H/R-treated myocardial cells. FTO upregulation repressed apoptosis of H/R-treated myocardial cells. FTO knockdown had the opposite results. Mhrt overexpression reduced apoptosis of H/R-treated myocardial cells. Moreover, the influence conferred by FTO upregulation was abolished by Mhrt knockdown. In conclusion, our data demonstrate that FTO overexpression inhibits apoptosis of hypoxia/reoxygenation-treated myocardial cells by regulating m6A modification of Mhrt. Thus, FTO may be a target gene for HF treatment.

A Mixed-ligand Pb(II)-coordination Polymer: Photocatalytic Performance and Reduction Activity of the Inflammatory Response After Severe Burns by Inhibiting NF-κB Signaling Pathway.

Via the employment of a mixed-ligand method, a novel Pb(II)-coordination polymer with the chemical formula of [Pb(pdc)(bdc)]·2DMF (1, H2bdc = 1,4-benzenedicarboxylic acid and H2pdc = 3,5-pyridinedicarboxylic acid) has been produced via reaction of Pb(NO3)2 with the two organic linkers in a mixed solvent of DMF and water. Complex 1 has high photocatalytic degradation efficiency for methylene blue and rhodamine B under ultraviolet light irradiation. The mechanism of photocatalysis was hypothesized and verified in detail by the r photocatalysis reaction in the existence of the hydroxyl radical scavenger mannitol. Furthermore, the influence of the inflammatory response in the severe burns rats was evaluated. Firstly, the inflammatory response levels were assessed by measuring the content of IL-6 and TNF-α in the plasma after treated with compound. Next, the real time RT-PCR was carried out to determine the signaling pathway of NF-κB relative expression in inflammatory cells.

LRTM1 promotes the differentiation of myoblast cells by negatively regulating the FGFR1 signaling pathway.

The proliferation and differentiation of myoblast cells are regulated by the fibroblast growth factor receptor (FGFR) signaling pathway. Although the regulation of FGFR signaling cascades has been widely investigated, the inhibitory mechanism that particularly function in skeletal muscle myogenesis remains obscure. In this study, we determined that LRTM1, an inhibitory regulator of the FGFR signaling pathway, negatively modulates the activation of ERK and promotes the differentiation of myoblast cells. LRTM1 is dynamically expressed during myoblast differentiation and skeletal muscle regeneration after injury. In mouse myoblast C2C12 cells, knockout (KO) of Lrtm1 significantly prevents the differentiation of myoblast cells; this effect is associated with the reduction of MyoD transcriptional activity and the overactivation of ERK kinase. Notably, further studies demonstrated that LRTM1 associates with p52Shc and inhibits the recruitment of p52Shc to FGFR1. Taken together, our findings identify a novel negative regulator of FGFR1, which plays an important role in regulating the differentiation of myoblast cells.

Granulocyte Colony-Stimulating Factor Attenuates Renal Ischemia-Reperfusion Injury by Inducing Myeloid-Derived Suppressor Cells.

BACKGROUND: Granulocyte colony-stimulating factor (G-CSF) can increase populations of myeloid-derived suppressor cells, innate immune suppressors that play an immunoregulatory role in antitumor immunity. However, the roles of myeloid-derived suppressor cells and G-CSF in renal ischemia-reperfusion injury remain unclear. METHODS: We used mouse models of ischemia-reperfusion injury to investigate whether G-CSF can attenuate renal injury by increasing infiltration of myeloid-derived suppressor cells into kidney tissue. RESULTS: G-CSF treatment before ischemia-reperfusion injury subsequently attenuated acute renal dysfunction, tissue injury, and tubular apoptosis. Additionally, G-CSF treatment suppressed renal infiltration of macrophages and T cells as well as renal levels of IL-6, MCP-1, IL-12, TNF-α, and IFN-γ, but it increased levels of IL-10, arginase-1, and reactive oxygen species. Moreover, administering G-CSF after ischemia-reperfusion injury improved the recovery of renal function and attenuated renal fibrosis on day 28. G-CSF treatment increased renal infiltration of myeloid-derived suppressor cells (F4/80-CD11b+Gr-1int), especially the granulocytic myeloid-derived suppressor cell population (CD11b+Ly6GintLy6Clow); splenic F4/80-CD11b+Gr-1+ cells sorted from G-CSF-treated mice displayed higher levels of arginase-1, IL-10, and reactive oxygen species relative to those from control mice. Furthermore, these splenic cells effectively suppressed in vitro T cell activation mainly through arginase-1 and reactive oxygen species, and their adoptive transfer attenuated renal injury. Combined treatment with anti-Gr-1 and G-CSF showed better renoprotective effects than G-CSF alone, whereas preferential depletion of myeloid-derived suppressor cells by pep-G3 or gemcitabine abrogated the beneficial effects of G-CSF against renal injury. CONCLUSIONS: G-CSF induced renal myeloid-derived suppressor cells, thereby attenuating acute renal injury and chronic renal fibrosis after ischemia-reperfusion injury. These results suggest therapeutic potential of myeloid-derived suppressor cells and G-CSF in renal ischemia-reperfusion injury.

Zinc finger protein A20 regulates the development and progression of osteoarthritis by affecting the activity of NF-κB p65.

OBJECTIVE: To investigate the role of Zinc finger protein A20 in osteoarthritis (OA) by regulating NF-κB p65. METHODS: A20, MMP1, MMP13 and IL-1ß expressions in human OA cartilage samples were detected by qRT-PCR. IL-1ß-induced chondrocyte was treated with A20 lentivirus activation particle, pyrrolidine dithiocarbamate (PDTC, a NF-κB inhibitor) with/without A20 siRNA. IL-6, TNF-α, and PGE2 levels were measured by ELISA, and NO production by Greiss reaction. Destabilization of the medial meniscus (DMM) surgery was used to construct the OA models, followed by injection of A20 adenovirus. MMP1 and MMP13 expression was measured by immunohistochemistry. The mRNA and protein expression were performed by qRT-PCR and western blotting, respectively. RESULTS: A20 was down-regulated in human OA cartilage samples, and negatively correlated with the expressions of MMP1, MMP13 and IL-1ß. The IL-1ß-induced chondrocyte manifested decreased A20 with increased NF-κB p65 activity. A20 overexpression suppressed the NF-κB p65 activity in IL-1ß-induced chondrocyte. Furthermore, PDTC decreased IL-1ß-induced chondrocyte apoptosis with the upregulated COL1A1, COL2A1, COL10A1 and ACAN, as well as the down-regulated MMP1, MMP13, COX2, iNOS, IL-6, TNF-α, NO and PGE2, which was reversed by A20 siRNA. In vivo, OA mice gained higher OARSI score and Mankin's score, exhibited up-regulations of MMP1 and MMP13, and decreased NF-κB p65 activity, which was improved after injection of A20 adenovirus. CONCLUSION: A20 was reduced in OA cartilage samples, and its overexpression, by suppressing the activity of NF-κB p65, could improve IL-1ß-induced chondrocyte degradation and apoptosis in vitro, as well as mitigate the inflammation in OA mice.

An investigation of the intention and reasons of senior high school students in China to choose medical school.

BACKGROUND: Shortages of qualified health workers have been a global concern, especially in developing countries. China also faces this dilemma, which hinders the development of public health services. Senior high school students are a group who are considering their college majors and careers after graduation. They are also a potential and basic talent reserve for the health sector. This survey focused on senior high school students' intention to learn clinical medicine and explored potential influencing factors. METHODS: An anonymous questionnaire containing 20 items was distributed to 5344 senior high school students. The questions covered the following topics: students' intention to learn clinical medicine, personal and family information, understanding of medical education, cognition of doctors' working conditions, and doctor-patient relationships. Logistic regression and the chi-square test were used to compare students with and without a clear intention to learn clinical medicine to explore influencing factors. RESULTS: Only 5.6% of senior high school students had a clear intention to learn medicine (CILCM). Personal and family information had distinct impacts. Interest and anatomy course were also associated with students' choice. There was a positive correlation between understanding of medical education and students' intention Meanwhile, students' cognition of doctors, career prospects, and social status had significant impacts. The more optimistic students were about doctors' working conditions and doctor-patient relationships, the more likely they were to have a CILCM. CONCLUSION: To some extent, this survey reflects the shortage of medical talent in China and provides possible clues for solving this problem. In addition, these findings may provide a perspective for understanding the development of health services in developing countries.

[Identification of Armeniacae Semen Amarum and Persicae Semen from different origins based on near infrared hyperspectral imaging technology].

In order to establish a rapid and non-destructive evaluation method for the identification of Armeniacae Semen Amarum and Persicae Semen from different origins, the spectral information of Armeniacae Semen Amarum and Persicae Semen in the range of 898-1 751 nm was collected based on hyperspectral imaging technology. Armeniacae Semen Amarum and Persicae Semen from different origins were collected as research objects, and a total of 720 Armeniacae Semen Amarum samples and 600 Persicae Semen samples were used for authenticity discrimination. The region of interest(ROI) and the average reflection spectrum in the ROI were obtained, followed by comparing five pre-processing methods. Then, partial least squares discriminant analysis(PLS-DA), support vector machine(SVM), and random forest(RF) method were established for classification models, which were evaluated by the confusion matrix of prediction results and receiver operating characteristic curve(ROC). The results showed that in the three sample sets, the se-cond derivative pre-processing method and PLS-DA were the best model combinations. The classification accuracy of the test set under the 5-fold cross-va-lidation was 93.27%, 96.19%, and 100.0%, respectively. It was consistent with the confusion matrix of the predicted results. The area under the ROC curve obtained the highest values of 0.992 3, 0.999 6, and 1.000, respectively. The study revealed that the near-infrared hyperspectral imaging technology could accurately identify the medicinal materials of Armeniacae Semen Amarum and Persicae Semen from different origins and distinguish the authentication of these two varieties.