High-Resolution Crossed-Beam Dynamics Studies of the D + Para-H2 → HD + H Reaction at 1.21 eV.

Understanding kinetic isotope effects is important in the study of the reaction dynamics of elementary chemical reactions, particularly those involving hydrogen atoms and molecules. As one of the isotopic variants of the hydrogen exchange reaction, the D + para-H2 reaction has attracted much attention. However, experimental studies of this reaction have been limited primarily due to its strong experimental background noise. In this study, by using the velocity map ion imaging method and the near-threshold ionization technique, together with improvements on the vacuum condition in the vicinity of the collision zone, background noise was reduced significantly, and quantum state-resolved differential cross sections (DCSs) for the D + para-H2 reaction at a collision energy of 1.21 eV were acquired in a crossed molecular beams experiment. Interestingly, clear rotational state-dependent angular distributions were noticed in the quantum state-resolved DCSs. The most intense peak's positions for HD (v', j') products shift to different scattering directions as the product's ro-vibrational quantum number increases. Two different microscopic reaction mechanisms are found to be involved in this reaction for HD products in different vibrational states. The results show a direct correlation between the scattering angle and the product's rotational quantum number, revealing that the contributions of impact parameters are strongly influenced by the corresponding centrifugal barrier.

High-Resolution Imaging Study on Photodissociation of OCS+ [A2ΠΩ=1/2,3/2 (ν1 0 ν3)].

The development of the velocity map ion imaging (VMI) technique has greatly advanced the study of photodissociation dynamics. The high-resolution imaging study of the photodissociation allows for the acquisition of precise and detailed information on the fragments. This information can further provide more insight into the energy partition and potential pathways involved in the photodissociation process. In this study, we report the investigation on the photodissociation of OCS+ via the A2ΠΩ=1/2,3/2 states following the excitation of A2Π (ν1 0 ν3) ← X2Π (0 0 0) by using time-sliced VMI techniques in the ultraviolet region. Our investigation revealed significant mode-dependent recoil anisotropies and branching ratios of two product channels for both Ω = 1/2 and Ω = 3/2. The photolysis products also exhibited dramatic deviation in angular distributions and generally comparable kinetic energy distributions following the excitation to the same vibrational modes of A2ΠΩ states with two separate spin-orbit components. According to the observation in this study and previously reported photodissociation mechanisms of the OCS+ cations, the decay from the A2Π3/2 state was more likely via the internal conversion to high rovibrational states of the X2Π state, in comparison to the A2Π1/2 state.

Vibrational state-specific nonadiabatic photodissociation dynamics of OCS+ via A2Π1/2 (ν1 0 ν3) states.

The identification and analysis of quantum state-specific effects can significantly deepen our understanding of detailed photodissociation dynamics. Here, we report an experimental investigation on the vibrational state-mediated photodissociation of the OCS+ cation via the A2Π1/2 (ν1 0 ν3) states by using the velocity map ion imaging technique over the photolysis wavelength range of 263-294 nm. It was found that the electronically excited S+ product channel S+(2Du) + CO (X1Σ+) was significantly enhanced when the ν1 and ν3 vibrational modes were excited. Clear deviations in the branching ratios of the electronically excited S+ channel were observed when the vibrational modes ν1 and ν3 were selectively excited. The results reveal that vibrationally excited states play a vital role in influencing the nonadiabatic couplings in the photodissociation process.

Advances in the Research on Plant WRKY Transcription Factors Responsive to External Stresses.

The WRKY transcription factors are a class of transcriptional regulators that are ubiquitous in plants, wherein they play key roles in various physiological activities, including responses to stress. Specifically, WRKY transcription factors mediate plant responses to biotic and abiotic stresses through the binding of their conserved domain to the W-box element of the target gene promoter and the subsequent activation or inhibition of transcription (self-regulation or cross-regulation). In this review, the progress in the research on the regulatory effects of WRKY transcription factors on plant responses to external stresses is summarized, with a particular focus on the structural characteristics, classifications, biological functions, effects on plant secondary metabolism, regulatory networks, and other aspects of WRKY transcription factors. Future research and prospects in this field are also proposed.

Advances in Research on the Regulation of Floral Development by CYC-like Genes.

CYCLOIDEA (CYC)-like genes belong to the TCP transcription factor family and play important roles associated with flower development. The CYC-like genes in the CYC1, CYC2, and CYC3 clades resulted from gene duplication events. The CYC2 clade includes the largest number of members that are crucial regulators of floral symmetry. To date, studies on CYC-like genes have mainly focused on plants with actinomorphic and zygomorphic flowers, including Fabaceae, Asteraceae, Scrophulariaceae, and Gesneriaceae species and the effects of CYC-like gene duplication events and diverse spatiotemporal expression patterns on flower development. The CYC-like genes generally affect petal morphological characteristics and stamen development, as well as stem and leaf growth, flower differentiation and development, and branching in most angiosperms. As the relevant research scope has expanded, studies have increasingly focused on the molecular mechanisms regulating CYC-like genes with different functions related to flower development and the phylogenetic relationships among these genes. We summarize the status of research on the CYC-like genes in angiosperms, such as the limited research conducted on CYC1 and CYC3 clade members, the necessity to functionally characterize the CYC-like genes in more plant groups, the need for investigation of the regulatory elements upstream of CYC-like genes, and exploration of the phylogenetic relationships and expression of CYC-like genes with new techniques and methods. This review provides theoretical guidance and ideas for future research on CYC-like genes.

Old age promotes retinal fibrosis in choroidal neovascularization through circulating fibrocytes and profibrotic macrophages.

BACKGROUND: Retinal fibrosis affects 40-70% of neovascular age-related macular degeneration patients. This study investigated the effect of ageing on subretinal fibrosis secondary to choroidal neovascularization and the mechanism of action. METHODS: Subretinal fibrosis was induced in young (2.5-month) and aged (15-16-month) C57BL/6J mice using the two-stage laser protocol. Five and 30 days later, eyes were collected and stained for CD45 and collagen-1 and observed by confocal microscopy. Fibrocytes (CD45+collagen-1+) were detected in the bone marrow (BM), blood and fibrotic lesions by flow cytometry and confocal microscopy, respectively. BM-derived macrophages (BMDMs) were cultured from young and aged mice with or without TGF-ß1 (10 ng/mL) treatment. The expression of mesenchymal marker αSMA (Acta2), fibronectin (Fn1) and collagen-1 (Col1a1) was examined by qPCR and immunocytochemistry, whereas cytokine/chemokine production was measured using the Luminex multiplex cytokine assay. BM were transplanted from 22-month (Ly5.2) aged mice into 2.5-month (Ly5.1) young mice and vice versa. Six weeks later, subretinal fibrosis was induced in recipient mice and eyes were collected for evaluation of fibrotic lesion size. RESULTS: Under normal conditions, the number of circulating fibrocytes (CD45+collagen-1+) and the expression levels of Tgfb1, Col1a1, Acta2 and Fn1 in BMDMs were significantly higher in aged mice compared to young mice. Induction of subretinal fibrosis significantly increased the number of circulating fibrocytes, enhanced the expression of Col1a1, Acta2 and Fn1 and the production of soluble urokinase plasminogen activator surface receptor (suPAR) but decreased the production of CXCL10 in BMDMs. BMDMs from aged subretinal fibrosis mice produced significantly higher levels of VEGF, angiopoietin-2 and osteopontin than cells from young subretinal fibrosis mice. The subretinal fibrotic lesion in 15-16-month aged mice was 62% larger than that in 2.5-month young mice. The lesion in aged mice contained a significantly higher number of fibrocytes compared to that in young mice. The number of circulating fibrocytes positively correlated with the size of subretinal fibrotic lesion. Transplantation of BM from aged mice significantly increased subretinal fibrosis in young mice. CONCLUSIONS: A retina-BM-blood-retina pathway of fibrocyte/macrophage recruitment exists during retinal injury. Ageing promotes subretinal fibrosis through higher numbers of circulating fibrocytes and profibrotic potential of BM-derived macrophages.

Gut microbiome alterations in patients with COVID-19-related coagulopathy.

COVID-19 is characterized by a predominantly prothrombotic state, which underlies severe disease and poor outcomes. Imbalances of the gut microbiome have been linked with abnormal hemostatic processes. Understanding the relationship between the gut microbiome and abnormal coagulation parameters in COVID-19 could provide a novel framework for the diagnosis and management of COVID-related coagulopathies (CRC). This cross-sectional study used shotgun metagenomic sequencing to examine the gut microbiota of patients with CRC (n = 66) and compared it to COVID control (CCs) (n = 27) and non-COVID control (NCs) (n = 22) groups. Three, 1, and 3 taxa were found enriched in CRCs, CCs, and NCs. Next, random forest models using 7 microbial biomarkers and differential clinical characteristics were constructed and achieved strong diagnostic potential in distinguishing CRC. Specifically, the most promising biomarker species for CRC were Streptococcus thermophilus, Enterococcus faecium, and Citrobacter portucalensis. Conversely, Enterobacteriaceae family and Fusicatenibacter genus are potentially protective against CRC in COVID patients. We further identified 4 species contributing to 20 MetaCyc pathways that were differentially abundant among groups, with S. thermophilus as the main coding species in CRCs. Our findings suggest that the alterations of gut microbiota compositional and functional profiles may influence the pathogenesis of CRC and that microbiota-based diagnosis and treatment could potentially benefit COVID patients in preventing and alleviating thrombosis-related clinical outcomes.

Vacuum ultraviolet photodissociation dynamics of OCS via the F Rydberg state: The O (3PJ=2,1,0) product channels.

We study the vacuum ultraviolet (VUV) photodissociation dynamics of carbonyl sulfide (OCS) by using the time sliced velocity map ion imaging technique. Experimental images of the dissociative O (3PJ=0,1,2) products were acquired at five VUV photolysis wavelengths from 133.26 to 139.96 nm that correspond to the F Rydberg state of OCS. High vibrational states of the carbon monosulfide (CS) co-products are partially resolved in the images. The product total kinetic energy releases, angular distributions, and the product state branching ratios were derived from the experimental images. Notably, it is found that the anisotropic parameters change systematically with the photolysis wavelength. The anisotropic parameters and the product state branching ratios are significantly sensitive to the J quantum number of the O (3PJ) products. The phenomenon indicates that multiple nonadiabatic pathways are strongly involved in the photodissociation processes.

Dealloyed Porous NiFe2O4/NiO with Dual-Network Structure as High-Performance Anodes for Lithium-Ion Batteries.

As high-capacity anode materials, spinel NiFe2O4 aroused extensive attention due to its natural abundance and safe working voltage. For widespread commercialization, some drawbacks, such as rapid capacity fading and poor reversibility due to large volume variation and inferior conductivity, urgently require amelioration. In this work, NiFe2O4/NiO composites with a dual-network structure were fabricated by a simple dealloying method. Benefiting from the dual-network structure and composed of nanosheet networks and ligament-pore networks, this material provides sufficient space for volume expansion and is able to boost the rapid transfer of electrons and Li ions. As a result, the material exhibits excellent electrochemical performance, retaining 756.9 mAh g-1 at 200 mA g-1 after cycling for 100 cycles and retaining 641.1 mAh g-1 after 1000 cycles at 500 mA g-1. This work provides a facile way to prepare a novel dual-network structured spinel oxide material, which can promote the development of oxide anodes and also dealloying techniques in broad fields.

Attitudes toward dementia screening and influential factors in older adults in China.

BACKGROUND: Dementia will likely be an ongoing concern for future generations, and according to the World Health Organization, two-thirds of dementia cases are missed diagnoses. We aimed to explore the attitudes of older adults toward dementia screening and the related influencing factors. METHODS: A multicentre cross-sectional study was conducted. Data were collected using questionnaires between 2020 December and 2021 June from five provinces in China. The study included older adults aged 60 years or older, living in China. A sociodemographic questionnaire and the Perceptions Regarding Investigational Screening for Memory in Primary Care scale were used to assess attitudes toward and influencing factors of dementia screening. RESULTS: A total of 279 participants completed the questionnaires. The results revealed housing status as a positive factor in the acceptance dimension, while high income was the primary positive factor in the benefits of screening dimension. Having religious beliefs, low income, and never participating in social activities were positive factors for the stigma dimension. Widowed marital status and participation in social activities were negative factors for the independence dimension, while having religious beliefs positively influenced the suffering dimension. CONCLUSIONS: This study showed that participants held a relatively positive attitude toward dementia screening, although they had concerns about stigma and negative impact on independence. Further studies are required to develop intervention strategies to help older adults improve their attitudes and quality of life, promote cognitive health, and facilitate healthy ageing.

Resveratrol pretreatment alleviates NLRP3 inflammasome-mediated cardiomyocyte pyroptosis by targeting TLR4/MyD88/NF-κB signaling cascade in coronary microembolization-induced myocardial damage.

Percutaneous coronary intervention and acute coronary syndrome are both closely tied to the frequently occurring complication of coronary microembolization (CME). Resveratrol (RES) has been shown to have a substantial cardioprotective influence in a variety of cardiac diseases, though its function and potential mechanistic involvement in CME are still unclear. The forty Sprague-Dawley rats were divided into four groups randomly: CME, CME + RES (25 mg/kg), CME + RES (50 mg/kg), and sham (10 rats per group). The CME model was developed. Echocardiography, levels of myocardial injury markers in the serum, and histopathology of the myocardium were used to assess the function of the cardiac muscle. For the detection of the signaling of TLR4/MyD88/NF-κB along with the expression of pyroptosis-related molecules, ELISA, qRT-PCR, immunofluorescence, and Western blotting were used, among other techniques. The findings revealed that myocardial injury and pyroptosis occurred in the myocardium following CME, with a decreased function of cardiac, increased levels of serum myocardial injury markers, increased area of microinfarct, as well as a rise in the expression levels of pyroptosis-related molecules. In addition to this, pretreatment with resveratrol reduced the severity of myocardial injury after CME by improving cardiac dysfunction, decreasing serum myocardial injury markers, decreasing microinfarct area, and decreasing cardiomyocyte pyroptosis, primarily by blocking the signaling of TLR4/MyD88/NF-κB and also reducing the NLRP3 inflammasome activation. Resveratrol may be able to alleviate CME-induced myocardial pyroptosis and cardiac dysfunction by impeding the activation of NLRP3 inflammasome and the signaling pathway of TLR4/MyD88/NF-κB.

[Characteristic changes of blood stasis syndrome in rat model of steroid-induced femoral head necrosis based on the combination of disease, syndrome, and symptom].

The approach combining disease, syndrome, and symptom was employed to investigate the characteristic changes of blood stasis syndrome in a rat model of steroid-induced osteonecrosis of the femoral head(SONFH) during disease onset and progression. Seventy-two male SD rats were randomized into a healthy control group and a model group. The rat model of SONFH was established by injection of lipopolysaccharide(LPS) in the tail vein at a dose of 20 µg·kg~(-1)·d~(-1) on days 1 and 2 and gluteal intramuscular injection of methylprednisolone sodium succinate(MPS) at a dose of 40 mg·kg~(-1)·d~(-1) on days 3-5, while the healthy control group received an equal volume of saline. The mechanical pain test, tongue color RGB technique, gait detection, open field test, and inclined plane test were employed to assess hip pain, tongue color, limping, joint activity, and lower limb strength, respectively, at different time points within 21 weeks of modeling. At weeks 2, 4, 8, 12, 16, and 21 after modeling, histopathological changes of the femoral head were observed by hematoxylin-eosin(HE) staining and micro-CT scanning; four coagulation items were measured by rotational thromboelastometry; and enzyme-linked immunosorbent assay(ELISA) was employed to determine the levels of six blood lipids, vascular endothelial growth factor(VEGF), endothelin-1(ET-1), nitric oxide(NO), tissue-type plasminogen activator(t-PA), plasminogen activator inhibitor factor-1(PAI-1), bone gla protein(BGP), alkaline phosphatase(ALP), receptor activator of nuclear factor-κB(RANKL), osteoprotegerin(OPG), and tartrate-resistant acid phosphatase 5b(TRAP5b) in the serum, as well as the levels of 6-keto-prostaglandin 1α(6-keto-PGF1α) and thromboxane B2(TXB2) in the plasma. The results demonstrated that the pathological alterations in the SONFH rats were severer over time. The bone trabecular area ratio, adipocyte number, empty lacuna rate, bone mineral density(BMD), bone volume/tissue volume(BV/TV), trabecular thickness(Tb.Th), trabecular number(Tb.N), bone surface area/bone volume(BS/BV), and trabecular separation(Tb.Sp) all significantly increased or decreased over the modeling time after week 4. Compared with the healthy control group, the mechanical pain threshold, gait swing speed, stride, standing time, and walking cycle of SONFH rats changed significantly within 21 weeks after modeling, with the greatest difference observed 12 weeks after modeling. The time spent in the central zone, rearing score, and maximum tilt angle in the open field test of SONFH rats also changed significantly over the modeling time. Compared with the healthy control group, the R, G, and B values of the tongue color of the model rats decreased significantly, with the greatest difference observed 11 weeks after modeling. The levels of total cholesterol(TC), total triglycerides(TG), low-density lipoprotein-cholesterol(LDL-C), and apoprotein B(ApoB) in the SONFH rats changed significantly 4 and 8 weeks after modeling. The levels of VEGF, ET-1, NO, t-PA, PAI-1, 6-keto-PGF1α, TXB2, four coagulation items, and TXB2/6-keto-PGF1α ratio in the serum of SONFH rats changed significantly 4-16 weeks after modeling, with the greatest differences observed 12 weeks after modeling. The levels of BGP, TRAP5b, RANKL, OPG, and RANKL/OPG ratio in the serum of SONFH rats changed significantly 8-21 weeks after modeling. During the entire onset and progression of SONFH in rats, the blood stasis syndrome characteristics such as hyperalgesia, tongue color darkening, gait abnormalities, platelet, vascular, and coagulation dysfunctions were observed, which gradually worsened and then gradually alleviated in the disease course(2-21 weeks), with the most notable differences occurred around 12 weeks after modeling.

Macrophage elastase (MMP12) critically contributes to the development of subretinal fibrosis.

BACKGROUND: Macular subretinal fibrosis is the end-stage complication of neovascular age-related macular degeneration (nAMD). We previously developed a mouse model of two-stage laser-induced subretinal fibrosis that mimics closely the dynamic course of macular fibrosis in nAMD patients. This study was aimed to understand the molecular mechanism of subretinal fibrosis. METHODS: Subretinal fibrosis was induced in C57BL/6J mice using the two-stage laser-induced protocol. Twenty days later, eyes were collected and processed for RNA sequencing (RNA-seq) analysis. DESeq2 was used to determine the differentially expressed genes (DEGs). Gene Ontology (GO) and KEGG were used to analyze the enriched pathways. The expression of the selected DEGs including Mmp12 was verified by qPCR. The expression of MMP12 in subretinal fibrosis of mouse and nAMD donor eyes was examined by immunofluorescence and confocal microscopy. The expression of collagen 1, αSMA and fibronectin and cytokines in bone marrow-derived macrophages from control and subretinal fibrosis mice were examined by qPCR, immunocytochemistry and Luminex multiplex cytokine assay. The MMP12 specific inhibitor MMP408 was used to evaluate the effect of MMP12 on TGFß-induced macrophage-to-myofibroblast transition (MMT) in vitro and its role in subretinal fibrosis in vivo. RESULTS: RNA-seq analysis of RPE-choroid from subretinal fibrosis eyes uncovered 139 DEGs (fold change log2(fc) ≥ 0.5, FDR < 0.05), including 104 up-regulated and 35 were down-regulated genes. The top 25 enrichment GO terms were related to inflammation, blood vessels/cardiovascular development and angiogenesis. One of the most significantly upregulated genes, Mmp12, contributed to 12 of the top 25 GO terms. Higher levels of MMP12 were detected in subretinal fibrotic lesions in nAMD patients and the mouse model, including in F4/80+ or Iba1+ macrophages. BMDMs from subretinal fibrosis mice expressed higher levels of MMP12, collagen-1, αSMA and fibronectin. MMP408 dose-dependently suppressed TGFß-induced MMT in BMDMs. In vivo treatment with MMP408 (5 mg/kg) significantly reduced subretinal fibrosis accompanied by reduced F4/80+ macrophage infiltration. CONCLUSIONS: MMP12 critically contributes to the development of subretinal fibrosis, partially through promoting MMT.

CmHY5 functions in apigenin biosynthesis by regulating flavone synthase II expression in chrysanthemum flowers.

MAIN CONCLUSION: The predominant flavones in the ray florets of chrysanthemum flowers are apigenin and its derivatives. CmHY5 participates in apigenin biosynthesis by directly regulating the expression of FNSII-1 in chrysanthemum. Chrysanthemum (Chrysanthemum morifolium) flowers have been used for centuries as functional food and in herbal tea and traditional medicine. The chrysanthemum flower contains significant amounts of the biologically active compound flavones, which has medicinal properties. However, the mechanism regulating flavones biosynthesis in chrysanthemum flowers organs is still unclear. Here, we compared the transcriptomes and metabolomes of different floral organs between two cultivars with contrasting flavone levels in their flowers. We identified 186 flavonoids by metabolome analysis. The predominant flavones in the ray florets of chrysanthemum flowers are apigenin and its derivatives, of which the contents are highly correlated with the expression of flavones synthase II gene CmFNSII-1. We also determined that CmHY5 is a direct upstream regulator of CmFNSII-1 transcription. We showed that CmHY5 RNAi interference lines in chrysanthemum have lower contents of apigenin compared to wild-type chrysanthemum. Our results demonstrated that CmHY5 participates in flavone biosynthesis by directly regulating the expression of FNSII-1 in chrysanthemum.

Crossed Molecular Beam Study of the H + HD → H2 + D Reaction at 0.60 and 1.26 eV Using the Near-Threshold Ionization Velocity Map Ion Imaging.

By using the 1 + 1' near-threshold ionization velocity map ion imaging technique, state-to-state reactive differential cross sections have been measured for the H + HD → H2 + D reaction. High-resolution images of the D products, with the rotational states of the H2 co-products clearly resolved, were acquired at the collision energies of 0.60 and 1.26 eV, respectively. It is found that the angular distribution is predominantly backward-scattering at the collision energy of 0.60 eV. However, at 1.26 eV, where the collision energy is higher, the angular distribution becomes forward-backward-scattering. Notably, at both collision energies, the main peaks of backward-scattered products gradually shift from backward toward sideways direction as the rotational quantum number of H2 increases. Moreover, in the forward direction, fast angular oscillations, which are induced by specific partial waves have also been observed at 1.26 eV. These features show a strong correlation between the product states and angular distributions and also indicate the unique role of partial waves in quantum reactive scattering.

[Effect of Jianpi Huogu Formula on function damage of vascular endothelial cells induced by glucocorticoid].

This study aimed to observe the intervention effect of Jianpi Huogu Formula(JPHGF) on the functional damage of vascular endothelial cells caused by glucocorticoid, and explore its action mechanism from the PI3 K/Akt and mitogen activated protein kinase(MAPK) signaling pathways. The extracted thoracic aorta ring of normal SD rats were intervened first with vascularendothelial growth factor(VEGF, 20 µg·L-1) and/or sodium succinate(MPS, 0. 04 g·L-1) in vitro and then with JPHGF(8, 16, and 32 µg·L-1) for five mcontinuous ethylpdays, rednisolofollowed nebythe statistics of the number, length, and area of microvessels budding fromvascular rings. In addition, the human umbilical vein endothelial cells(HUVECs) induced by VEGF(20 µg·L-1) were added with MPS(0. 04 g·L-1) and then with JPHGF(8, 16, and 32 µg·L-1) for observing the migration, invasion, and luminal formation abilities of HUVECs in the migration, invasion and luminal formation experiments. The protein expression levels of PI3 K, p-Akt, p-JN K, and p-ERK in HUVECs were assayed by Western blot. The results showed that JPHGF dose-dependently improved the num-ber,length, and area of microvessels in MPS-induced rat thoracic aortic ring, reversed the migration, invasion and lumen formation abiliti es of HUVECs reduced by MPS, and up-regulated the protein expression levels of PI3 K, p-Akt, and p-JNK in HUVECs. All thesehave suggested that JPHGF exerts the protective effect against hormone-induced damage to the angiogenesis of vascular endothelial cells by activating the PI3 K/Akt and MAPK signaling pathways, which has provided reference for exploring the mechanism of JPHGF in treating s teroid-induced avascular necrosis of femoral head(SANFH) and also the experimental evidence for enriching the scientific connotationof spleen-invigorating and blood-activating therapy.

[Mechanism of Panlongqi Tablets intervening in vertebral artery type of cervical spondylosis in rats through PI3K/AKT signaling pathway based on network pharmacology and experimental verification].

This study aimed to further explore the relevant mechanism of action by network pharmacology integrated with animal experimental verification based on previous proven effective treatment of vertebral artery type of cervical spondylosis(CSA) by Panlongqi Tablets. Bionetwork analysis was performed to establish drug-disease interaction network, and it was found that the key candidate targets of Panlongqi Tablets were enriched in multiple signaling pathways related to CSA pathological links, among which phosphatidylinositol 3-kinase(PI3 K)/serine-threonine kinase(AKT/PKB) signaling pathway was the most significant. Further, mixed modeling method was used to build the CSA rat model, and the rats were divided into normal, model, Panlongqi Tablets low-, medium-and high-dose(0.16, 0.32, 0.64 g·kg~(-1)) and Jingfukang Granules(positive drug, 1.35 g·kg~(-1)) groups. After successful modeling, the rats were administered for 8 consecutive weeks. Pathological changes of rat cervical muscle tissues were detected by hematoxylin-eosin(HE) staining, and the content of interleukin-1ß(IL-1ß), tumor necrosis factor-α(TNF-α), vascular endothelial cell growth factor(VEGF) and chemokine(C-C motif) ligand 2(CCL2) in rat serum and/or cervical tissues was determined by enzyme-linked immunosorbent assay(ELISA). Western blot was employed to detect the protein expression levels of chemokine(C-C motif) receptor 2(CCR2), PI3 K, AKT, phosphorylated AKT(p-AKT), I-kappa-B-kinase beta(IKK-beta/IKKß), nuclear factor kappa B(NF-κB P65) and phosphorylated nuclear factor kappa B(NF-κB p-P65) in rat cervical tissues, and positive expression of p-NF-κB P65 in rat cervical muscle tissues was detected by immunofluorescence. The results showed that Panlongqi Tablets at different doses improved the degree of muscle fibrosis and inflammation in cervical muscle tissues of CSA rats, and reduced the content of inflammatory factors IL-1ß, TNF-α, VEGF, CCL2 and CCR2 in serum and/or cervical tissues. The protein expression levels of PI3 K, p-AKT, IKKß and p-NF-κB P65 as well as the nuclear entry of p-NF-κB P65 in cervical tissues were down-regulated. These findings suggest that Panlongqi Tablets can significantly inhibit the inflammatory response of CSA rats, and the mechanism of action may be related to the down-regulation of the activation of PI3 K/AKT signaling pathway.

[Therapeutic effect of Baimai Ointment on peripheral sensitization of chronic inflammatory pain in mice].

Chronic inflammatory pain is mainly manifested by peripheral sensitization. Baimai Ointment(BMO), a classical Tibetan medicine for external use, has good clinical efficacy in the treatment of chronic inflammatory pain, while its pharmacodynamics and mechanism for relieving peripheral sensitization remain unclear. This study established an animal model of chronic inflammatory pain induced by complete Freund's adjuvant to explore the mechanism of BMO in the treatment of chronic inflammatory pain by behavioral test, side effect assessment, network analysis, and experimental verification. The pharmacodynamics experiment showed that BMO increased the thresholds of mechanical pain sensitivity and thermal radiation pain sensitivity of chronic inflammatory pain mice in a dose-dependent manner, and had inhibitory effect on foot swelling, inflammatory mediator, and the expression of transient receptor potential vanilloid-1(TRPV1) and transient receptor potential A1(TRPA1). The results of body weight monitoring, pain sensitivity threshold detection in normal mice, rotarod performance test, and forced swimming test showed that BMO had no obvious toxic or side effect. The network analysis of 51 candidate active molecules selected according to the efficacy of BMO, content of main components, and ADME parameters showed that the inhibitory effect of BMO on chronic inflammatory pain was associated with the core regulatory elements of tumor necrosis factor(TNF) and T cell receptor signaling pathways. BMO down-regulated the protein levels of mitogen-activated protein kinase 14(MAPK14), MAPK1, and prostaglandin-endoperoxide synthase 2(PTGS2), and up-regulated the phosphorylation le-vel of glycogen synthase kinase 3 beta(GSK3 B) in the plantar tissue of mice. In conclusion, BMO can effectively relieve peripheral sensitization of chronic inflammatory pain without inducing tolerance and obvious toxic and side effects. The relevant mechanism may be related to the regulation of BMO on core regulatory elements of TNF and T cell receptor signaling pathways in surrounding tissues.

Human leukocyte antigen disparities reduce relapse after hematopoietic stem cell transplantation in children with juvenile myelomonocytic leukemia: A single-center retrospective study from China.

BACKGROUND: HSCT is the only proven curative therapy for JMML. Matching donor and recipient HLA alleles is considered optimal to reduce the risk of GVHD after HSCT but is not always possible. Only a limited number of studies have compared the influence of HLA disparities on HSCT outcomes for patients with JMML. METHODS: We conducted a retrospective study among 47 children with JMML who received related or unrelated unmanipulated HSCT (March 2010-October 2018). Among our participants, 27 (57.4%) donor-recipient pairs had 0-1 HLA disparities (Group 1: HLA-matched or ≤1 allele/antigen mismatch donor) and 20 (42.6%) had ≥2 HLA disparities (Group 2: 2-3 mismatched/haploidentical donors). RESULTS: The median follow-up period was 26.0 months (range: 1-105 months), and the 5-year probabilities of DFS and RI for the whole cohort were 54.6 ± 7.7% and 34.8 ± 15.0%, respectively. Compared to Group 1, Group 2 patients had a significantly lower RI (5.3 ± 10.5% vs 55.5 ± 20.9%, P Ë‚ .001), though similar rates of grade II-IV acute GVHD (60.0 ± 22.4% vs 33.3 ± 18.2%, P = .08), grade III-IV acute GVHD (25.0 ± 19.5% vs 7.4 ± 10.1%, P = .08), chronic GVHD (30.0 ± 20.9% vs 34.9 ± 18.8%, P = .85), NRM (20.0 ± 18.0% vs 3.9 ± 7.7%, P = .07), and DFS (74.4 ± 9.9% vs 41.3 ± 10.0%, P = .08). CONCLUSIONS: Disease relapse remains the major cause of treatment failure in JMML patients, especially in patients receiving HLA-matched and limited HLA-mismatched HSCT. Our findings suggest that donor-recipient HLA disparities may improve the outcome of HSCT in children with JMML.

Development of a Deep Learning-Based Model for Diagnosing Breast Nodules With Ultrasound.

OBJECTIVES: Artificial intelligence (AI) has been an important addition to medicine. We aimed to explore the use of deep learning (DL) to distinguish benign from malignant lesions with breast ultrasound (BUS). METHODS: The DL model was trained with BUS nodule data using a standard protocol (1271 malignant nodules, 1053 benign nodules, and 2144 images of the contralateral normal breast). The model was tested with 692 images of 256 breast nodules. We used the accuracy, precision, recall, harmonic mean of recall and precision, and mean average precision as the indices to assess the DL model. We used 100 BUS images to evaluate differences in diagnostic accuracy among the AI system, experts (>25 years of experience), and physicians with varying levels of experience. A receiver operating characteristic curve was generated to evaluate the accuracy for distinguishing between benign and malignant breast nodules. RESULTS: The DL model showed 73.3% sensitivity and 94.9% specificity for the diagnosis of benign versus malignant breast nodules (area under the curve, 0.943). No significant difference in diagnostic ability was found between the AI system and the expert group (P = .951), although the physicians with lower levels of experience showed significant differences from the AI and expert groups (P = .01 and .03, respectively). CONCLUSIONS: Deep learning could distinguish between benign and malignant breast nodules with BUS. On BUS images, DL achieved diagnostic accuracy equivalent to that of expert physicians.