Measurement of the

The ^{18}O(α,γ)^{22}Ne reaction is critical for AGB star nucleosynthesis due to its connection to the abundances of several key isotopes, such as ^{21}Ne and ^{22}Ne. However, the ambiguous resonance energy and spin-parity of the dominant 470 keV resonance leads to substantial uncertainty in the ^{18}O(α,γ)^{22}Ne reaction rate for the temperature of interest. We have measured the resonance energies and strengths of the low-energy resonances in ^{18}O(α,γ)^{22}Ne at the Jinping Underground Nuclear Astrophysics experimental facility (JUNA) with improved precision. The key 470 keV resonance energy has been measured to be E_{α}=474.0±1.1 keV, with such high precision achieved for the first time. The spin-parity of this resonance state is determined to be 1^{-}, removing discrepancies in the resonance strengths in earlier studies. The results significantly improve the precision of the ^{18}O(α,γ)^{22}Ne reaction rates by up to about 10 times compared with the previous data at typical AGB temperatures of 0.1-0.3 GK. We demonstrate that such improvement leads to precise ^{21}Ne abundance predictions, with an impact on probing the origin of meteoritic stardust SiC grains from AGB stars.

Deep Underground Laboratory Measurement of

The ^{13}C(α,n)^{16}O reaction is the main neutron source for the slow-neutron-capture process in asymptotic giant branch stars and for the intermediate process. Direct measurements at astrophysical energies in above-ground laboratories are hindered by the extremely small cross sections and vast cosmic-ray-induced background. We performed the first consistent direct measurement in the range of E_{c.m.}=0.24 to 1.9 MeV using the accelerators at the China Jinping Underground Laboratory and Sichuan University. Our measurement covers almost the entire intermediate process Gamow window in which the large uncertainty of the previous experiments has been reduced from 60% down to 15%, eliminates the large systematic uncertainty in the extrapolation arising from the inconsistency of existing datasets, and provides a more reliable reaction rate for the studies of the slow-neutron-capture and intermediate processes along with the first direct determination of the alpha strength for the near-threshold state.

[Clinicopathological characteristics and molecular alterations of primary cardiac leiomyosarcoma: report of five cases].

Objective: To investigate the clinical, pathologic and radiologic features and molecular alterations in patients with primary cardiac leiomyosarcoma (PCLMS). Methods: Five cases of PCLMS were collected in Beijing Anzhen Hospital from January 2016 to December 2020. The clinical, pathologic and radiologic data, and molecular alterations were analyzed, and the patients were followed up. Results: All five patients were female, and had no history of leiomyosarcoma in other parts of the body. The age of patients ranged from 37 to 62 years (median 47 years). The main clinical symptoms were chest pain and dyspnea, one also presented with palpitation and lower limb weakness and one with dizziness. Two tumors were located in the left atrium, two in the right atrium, and one in the right ventricle, and they maximal diameter ranged from 2.5 to 14.0 cm (mean 6.2 cm). The neoplasms presented as medium-echo masses with a broad base in the echocardiography, and as a low-density, solid mass when detected by contrast-enhanced CT. Histologically, two tumors were well-differentiated and three were moderately and poorly differentiated, and two included extensive, loose myxoid stroma. Immunohistochemical staining showed that PCLMS was positive for SMA, desmin, MDM2, and epidermal growth factor receptor. Fluorescence in situ hybridization showed ALK gene rearrangement in two cases, and COL1A1-PDGFB fusion in three cases. All cases received surgical excision and two cases received chemotherapy. Three patients died within 0-11 months (mean survival of 7.7 months) and two patients were alive. Conclusions: PCLMS is a malignant tumor with a high recurrence rate and poor prognosis. These cases may provide useful information to improve the diagnosis and management of PCLMS.

Direct Measurement of the Astrophysical

Fluorine is one of the most interesting elements in nuclear astrophysics, where the ^{19}F(p,α)^{16}O reaction is of crucial importance for Galactic ^{19}F abundances and CNO cycle loss in first generation Population III stars. As a day-one campaign at the Jinping Underground Nuclear Astrophysics experimental facility, we report direct measurements of the essential ^{19}F(p,αγ)^{16}O reaction channel. The γ-ray yields were measured over E_{c.m.}=72.4-344 keV, covering the Gamow window; our energy of 72.4 keV is unprecedentedly low, reported here for the first time. The experiment was performed under the extremely low cosmic-ray-induced background environment of the China JinPing Underground Laboratory, one of the deepest underground laboratories in the world. The present low-energy S factors deviate significantly from previous theoretical predictions, and the uncertainties are significantly reduced. The thermonuclear ^{19}F(p,αγ)^{16}O reaction rate has been determined directly at the relevant astrophysical energies.

[Application of deep learning neural network in pathological image classification of non-inflammatory aortic membrane degeneration].

Objective: To investigate the value of deep learning in classifying non-inflammatory aortic membrane degeneration. Methods: Eighty-nine cases of non-inflammatory aortic media degeneration diagnosed from January to June 2018 were collected at Beijing Anzhen Hospital, Capital Medical University, China and scanned into digital sections. 1 627 hematoxylin and eosin stained photomicrographs were extracted. Combined with the ResNet18-based deep convolution neural network model, 4-category classification of pathological images were performed to diagnose the non-inflammatory aortic lesion. Results: The prediction model of artificial intelligence assisted diagnosis had the best accuracy, sensitivity and precision in identifying lesions with smooth muscle cell nuclei loss, which were 99.39%, 98.36% and 98.36%, respectively. The classification accuracy of elastic fiber fragmentation and/or loss lesions was 98.08%, while that of intralamellar mucoid extracellular matrix accumulation lesions was 96.93%. The overall accuracy of the classification model was 96.32%, and the area under the curve was 0.982. Conclusions: The accuracy of deep learning neural network model in the 4-category classification of non-inflammatory aortic lesionsis confirmed based on digital photomicrographs. This method can effectively improve the diagnostic efficiency of pathologists.

Constraining the External Capture to the

The ^{12}C(α,γ)^{16}O reaction is one of the most crucial reactions in nuclear astrophysics. The E2 external capture to the ^{16}O ground state (GS) has not been emphasized in previous analyses but may make a significant contribution to the ^{12}C(α,γ)^{16}O cross section depending on the value of the GS asymptotic normalization coefficient (ANC). In the present work, we determine this ANC to be 337±45 fm^{-1/2} through the ^{12}C(^{11}B,^{7}Li)^{16}O reaction using a high-precision magnetic spectrograph. This sheds light on the existing large discrepancy of more than 2 orders of magnitude between the previously reported ANC values. Based on the new ANC, we experimentally constrain the GS external capture and show that through interference with the high energy tail of the 2^{+} subthreshold state, a substantial enhancement in the GS S_{E2}(300) factor can be obtained (70±7 keV b) compared to that of a recent review (45 keV b), resulting in an increase of the total S factor from 140 to 162 keV b, which is now in good agreement with the value obtained by reproducing supernova nucleosynthesis calculations with the solar-system abundances. This work emphasizes that the external capture contribution for the ground state transition cannot be neglected in future analyses of the ^{12}C(α,γ)^{16}O reaction.

Birth weight, childhood body mass index and height and risks of endometriosis and adenomyosis.

Background: Body size in adult life is likely associated with risks of endometriosis and adenomyosis, yet little is known about associations with body size earlier in life.Aim: To examine whether birth weight, childhood body mass index (BMI) and height are associated with risks of endometriosis and adenomyosis.Subjects and methods: From the Copenhagen School Health Records Register, 171,447 girls born 1930-1996, with measured weights and heights at ages 7-13 were included. Outcomes were obtained from health registers. Cox regressions were performed to estimate hazard ratios (HR) and 95% confidence intervals (CI).Results: During follow-up, 2149 endometriosis cases and 1410 adenomyosis cases were diagnosed. Childhood BMI was inversely associated with endometriosis (HR = 0.92 [95% CI: 0.88-0.96] per z-score at age 7). In contrast, childhood height was positively associated with endometriosis (HR = 1.09 [95% CI: 1.05-1.14] per z-score at age 7). Associations with childhood body size did not differ by endometriosis location. Childhood BMI and height had limited associations with adenomyosis. Birth weight was not associated with endometriosis or adenomyosis.Conclusion: Lean and tall girls are more often diagnosed with endometriosis, but not adenomyosis. These findings suggest that indicators of endometriosis risk are already apparent at early ages.

Childhood Overweight, Tallness, and Growth Increase Risks of Ovarian Cancer.

BACKGROUND: Adult body size is related to ovarian cancer risks, but size in childhood may also influence risks. We investigated if childhood body mass index (kg/m2), height, and growth patterns were associated with ovarian cancer overall and by histologic subtypes, including effects of birthweight. METHODS: A cohort of 155,958 girls from the Copenhagen School Health Records Register, born 1930 to 1989 with measured weights and heights from 7 to 13 years, were included. During follow-up, 1,041 ovarian cancers were recorded. Overweight was defined using International Obesity Task Force criteria. Cox regressions were performed. RESULTS: Compared with non-overweight girls, at most ages girls with overweight had increased risks of ovarian cancer overall (HR range: 1.24-1.34), mucinous, endometrioid, and clear cell ovarian cancers, but not serous and other ovarian cancers. Childhood height had positive and significant associations with ovarian cancer overall (HR range: 1.07-1.10 per z-score) and the endometrioid subtype but not with the other subtypes. Adjusting for birthweight minimally altered the associations with childhood body size. In growth analyses, girls with overweight or who were tall at 7 and 13 years had increased risks of ovarian cancer overall compared with average-sized girls at both ages. CONCLUSIONS: Ovarian carcinogenesis is linked to childhood overweight, tallness, and growth, with variations across histological subtypes, suggesting that early life plays a role in the origins of this disease. IMPACT: These findings emphasize that healthy body size and growth during childhood are important as they may contribute to reducing ovarian cancer risks.

[Role of TNF-α in vascular remodeling in rats with chronic thromboembolic pulmonary hypertension].

Objective: To analyze the relationship between TNF-α and pulmonary vascular remodeling in order to explore the pathogenesis of CTEPH. Methods: Autologous blood clots were repeatedly injected into the left jugular vein of rats to establish the CTEPH model. Then mean pulmonary artery pressure (mPAP), histopathology, the plasma level of TNF-α, and the expressions of mRNA and protein of TNF-α in pulmonary artery were measured. Results: In the experiment group, the mPAP and vessel wall area/total area (WA/TA) ratio gradually increased as emblism extended, and increased significantly compared with the sham operation group. The plasma TNF-α concentration in the experimental group increased significantly (P<0.05). The TNF-α proteins expressed in pulmonary artery in the 1-week, 2-week, and 4-week subgroups of experimental group increased significantly compared with the sham operation group (1.62±0.08 vs 0.85±0.12, P<0.05; 1.85±0.08 vs 0.89±0.13, P<0.05; 1.37±0.12 vs 0.91±0.15, P<0.05, respectively). Immunohistochemical results showed that TNF-α expression was higher in pulmonary artery endothelial cells of the experimental group compared with the sham operation group. The expression of pulmonary artery TNF-α protein was positively related with mPAP (r=0.605, P<0.01), and with WA/TA (r=0.629, P<0.01). The expression of serum TNF-α was positively related with that of pulmonary artery TNF-α protein (r=0.721, P<0.01). Conclusion: A rat model of CTEPH can be established by repeatedly introducing autologous blood clots into the pulmonary artery with injecting TXA. Thrombosis induced higher expression of TNF-α in pulmonary arterial endothelial cells, and released into the blood. TNF-α may play an important role in the development of CTEPH, especially by contributing to vascular remodeling and PH.

Tyr1-ψ[( Z)CF═CH]-Gly2 Fluorinated Peptidomimetic Improves Distribution and Metabolism Properties of Leu-Enkephalin.

Opioid peptides are key regulators in cellular and intercellular physiological responses, and could be therapeutically useful for modulating several pathological conditions. Unfortunately, the use of peptide-based agonists to target centrally located opioid receptors is limited by poor physicochemical (PC), distribution, metabolic, and pharmacokinetic (DMPK) properties that restrict penetration across the blood-brain barrier via passive diffusion. To address these problems, the present paper exploits fluorinated peptidomimetics to simultaneously modify PC and DMPK properties, thus facilitating entry into the central nervous system. As an initial example, the present paper exploited the Tyr1-ψ[( Z)CF═CH]-Gly2 peptidomimetic to improve PC druglike characteristics (computational), plasma and microsomal degradation, and systemic and CNS distribution of Leu-enkephalin (Tyr-Gly-Gly-Phe-Leu). Thus, the fluoroalkene replacement transformed an instable in vitro tool compound into a stable and centrally distributed in vivo probe. In contrast, the Tyr1-ψ[CF3CH2-NH]-Gly2 peptidomimetic decreased stability by accelerating proteolysis at the Gly3-Phe4 position.

Birth weight and the risk of histological subtypes of ovarian and endometrial cancers: Results from the Copenhagen School Health Records Register.

BACKGROUND: Studies of birth weight associations with ovarian and endometrial cancer risks are limited with inconsistent results, and none has evaluated associations by histologic subtype. We utilized prospectively collected birth weight information to investigate the association with risk of ovarian and endometrial cancers overall and by histologic subtype. METHODS: 162,559 girls, born from 1930 to 1989, from the Copenhagen School Health Records Register (CSHRR) were followed prospectively via linkage with the Danish health registers. Ovarian (n=666) and endometrial (n=694) cancers were identified from 1978 to 2014. Cox regression was used to estimate hazard ratios (HR) and 95% confidence intervals (CI). RESULTS: Women with lower (2.0-3.25 vs. 3.26-3.75kg) and higher (3.75-5.5 vs. 3.26-3.75kg) birth weights had increased risks of ovarian cancer overall [HR (95% CI): 1.27 (1.06-1.52); 1.51 (1.21-1.87), respectively] and serous ovarian cancers [1.54 (1.19-1.98); 1.98 (1.47-2.67), respectively]. A decreased risk of Type II endometrial tumors was suggested per kilogram increase in birth weight [HR (95% CI): 0.63 (0.40-1.00)]. CONCLUSIONS: Our results suggest that both lower and higher birth weights were associated with increased ovarian cancer risk and associations were particularly strong for serous ovarian cancer, the most common subtype. Birth weight was not associated with most types of endometrial cancer.

Establishment and evaluation of an indirect immunofluorescence assay for the detection of salmonid alphavirus.

Salmonid alphaviruses (SAV) severely infect farmed salmonids and rainbow trout. Owing to the recent increase in fish import trade, several SAV unreported countries, such as China, may face serious threat of this infection. Thus, it is necessary to develop efficient detection methods for the prevention and diagnosis of SAV infection. In this study, we selected a conserved segment of the SAV E1 protein as a target immunogen for the preparation of monoclonal antibodies (mAbs) specific to SAV. A sensitive indirect immunofluorescence (IF) method was developed using 26E9C2 mAb that detected E1 protein and identified subtypes 1, 2 and 5 of SAV. Thus, this assay provides a sensitive and specific detection method, and an improved technical support for the clinical diagnosis and epidemiological study of SAV. SIGNIFICANCE AND IMPACT OF THE STUDY: In this study, we successfully prepared two monoclonal antibodies (mAbs) against three subtypes of salmonid alphavirus (SAV), and established an indirect immunofluorescence assay that can be used to diagnose and prevent SAV from entering SAV unreported countries, such as China, through international trade. The application of this method will contribute to controlling SAV infection and reducing economic losses.

Investigation of pH effect on cationic solute binding to keratin and partition to hair.

OBJECTIVE: In the process of hair treatment, various cationic actives contained in hair care products can be absorbed into hair fibre to modulate the physicochemical properties of hair such as colour, strength, style and volume. There have been very limited studies on the binding and partition properties of hair care actives to hair. This study aimed to investigate the pH effects on cationic solute absorption into hair and binding to keratin. METHODS: The keratin binding and hair partition properties of three cationic solutes (theophylline, nortriptyline and amitriptyline) have been measured at different pH using fluorescence spectroscopy and equilibrium absorption experiment. The binding constants, thermodynamic parameters and hair-water partition coefficients determined at different pH were compared and analysed. RESULTS: Increasing the pH from 2.0 to 6.0 resulted in the net charge of hair keratin changed from positive to negative. As a consequence, the binding constants of the three cationic solutes with keratin increased with the increasing pH. This correlated with the variation of the electrostatic interaction between cationic solutes and keratin from repulsion to attraction. The positive ΔH and ΔS values indicated that hydrophobic interaction also played a major role in the binding of the three cationic solutes to keratin. There was a good correlation between solutes binding to keratin and hair-water partition of solutes. CONCLUSION: It appears that solute binding to hair keratin is driven first by hydrophobic interaction and then by electrostatic interaction. The fitted thermodynamic parameters suggested that hydrophobic interaction dominates for the binding of the three cationic solutes to keratin. That binding of cationic solutes to keratin correlates with the partition of the solutes to hair could provide theoretical guidance for further developing mathematical models of hair partition and penetration properties.

[Clinicopathologic study of cardiac myxofibrosarcomas].

Objective: To investigate the clinicopathologic features of cardiac myxofibrosarcomas. Methods: The clinical data, pathomorphologic and immunohistochemical features were evaluated in five cases of cardiac myxofibrosarcoma collected from January 2009 to December 2014, with relevant literature review. Results: Five patients with cardiac myxofibrosarcoma, including four women and one man [age range 39-61 years; mean (50.4±9.0) years] were included. All tumors were broadbased and located mainly in the left atrium, with one case extending through the atrial wall and pericardium to the left lower lung lobe. The morphological grade was low in one case, intermediate in one, and high in three. Using Fédération Nationale des Centres de Lutte Contre le Cancer (FNLCC) grading system, one case was grade 1 and four cases were grade 2. Immunohistochemical analysis revealed diffuse and strong expression for vimentin in all cases. Smooth muscle actin and muscle specific actin were variably expressed. Complete tumor excision was performed in one case, and tumor debulking was performed in the other four cases. Clinical follow-up was available in three cases. One patient with en bloc excision of the tumor mass survived 13 months and the other two with tumor debulking died one month after surgery. Conclusions: The most common location for cardiac myxofibrosarcoma is the left atrium. Some myxofibrosarcoma may be histologically bland and misdiagnosed as myxoma due to histological similarities. Thus caution should be exercised in their microscopic differentiation. Precise imaging, multidisciplinary approach and adequate initial surgery may contribute to improving the clinical outcomes of myxofibrosarcoma.

Childhood body mass index growth trajectories and endometrial cancer risk.

Previously, we found that excess weight already in childhood has positive associations with endometrial cancer; however, associations with changes in body mass index (BMI) during childhood are not well understood. Therefore, we examined whether growth in childhood BMI is associated with endometrial cancer and its sub-types. A cohort of 155,505 girls from the Copenhagen School Health Records Register with measured weights and heights at the ages of 6-14 years and born 1930-1989 formed the analytical population. BMI was transformed to age-specific z scores. Using linear spline multilevel models, each girl's BMI growth trajectory was estimated as the deviance from the average trajectory for three different growth periods (6.25-7.99, 8.0-10.99, 11.0-14.0 years). Via a link to health registers, 1,020 endometrial cancer cases were identified, and Cox regressions were performed. A greater gain in BMI during childhood was positively associated with endometrial cancer but no differences between the different growth periods were detected in models adjusted for baseline BMI. The hazard ratios for the associations with overall growth during childhood per 0.1 z score increase were 1.15 (95% confidence interval [CI]: 1.07-1.24) for all endometrial cancers, 1.12 (95% CI: 1.04-1.21) for estrogen-dependent cancers, 1.16 (95% CI: 1.06-1.26) for endometrioid adenocarcinomas and 1.46 (95% CI: 1.16-1.84) for non-estrogen-dependent cancers. Growth in BMI in early life is positively linked to later endometrial cancer risk. We did not identify any sensitive childhood growth period, which suggests that excess gain in BMI during the entire childhood period should be avoided.

Virulence and serological studies of recombinant infectious hematopoietic necrosis virus (IHNV) in rainbow trout.

Infectious hematopoietic necrosis virus is a highly contagious disease of juvenile salmonid species. From the IHNV HLJ-09 isolated in China, two recombinant viruses were generated by reverse genetics using the RNA polymerase II transcription system. The recombinant viruses were confirmed by RT-PCR, indirect immunofluorescence assay and electron microscopy. They were referred to as rIHNV HLJ-09 and rIHNV-EGFP. rIHNV HLJ-09 and rIHNV-EGFP could stably replicate in EPC cell lines and had the same cellular tropism as wtIHNV HLJ-09. But the titer of rIHNV-EGFP was significantly lower than rIHNV HLJ-09 and wtIHNV HLJ-09. rIHNV-EGFP strain could express EGFP stably at least in 20 passages, and the fluorescence could be observed clearly. To assess the virulence and pathogenicity of the recombinant viruses in vivo, juvenile rainbow trout were challenged by intraperitoneal injection with 20µl of rIHNV HLJ-09, rIHNV-EGFP or wtIHNV HLJ-09 (1×10(6)pfuml(-1)). Fish challenged with rIHNV HLJ-09 and wtIHNV HLJ-09 exhibited clinical signs typical of IHN disease and both produced 90% cumulative percent mortality, whlie rIHNV-EGFP produced only 5%. Pathological sectioning results showed that the tissues (liver, kidney, heart muscle, back muscle) of the fish infected with rIHNV HLJ-09 exhibited pathological changes, with the exception of cerebral neurons and the cheek. However, no lesions of liver, kidney, heart, muscle, brain in rainbow trout of rIHNV-EGFP or the control group were observed. Indirect ELISA results showed that a high level of serum antibody was detected in the experimental fish challenged with rIHNV HLJ-09, just as the same as wtIHNV HLJ-09, while a lower titer was detecred in the fish infected with rIHNV-EGFP. This indicated that the recombinant viruses could induce humoral immune response in the experimental fish. The recombinant viruses had unique genetic tags and could be used for genetic engineering, laying new ground for further investigation of IHNV pathopoiesis molecular mechanism, host tropism and the development of novel vaccines against IHN.

Distribution and clinical significance of tumour-associated macrophages in pancreatic ductal adenocarcinoma: a retrospective analysis in China.

BACKGROUND: We aimed to characterize the localization and prognostic significance of tumour-associated macrophages (tams) in pancreatic ductal adenocarcinoma (pdac). METHODS: Tumour specimens from 70 patients with pdac and inflammatory specimens from 13 patients with chronic pancreatitis were collected and analyzed for tam and M2 macrophage counts by immunohistochemistry. Correlations between tam distributions and clinicopathologic features were determined. RESULTS: Immunohistochemical analysis showed that tam and M2 macrophage counts were higher in tissues from pdac than from chronic pancreatitis. The tams and M2 macrophages both infiltrated more into peritumour. Both macrophage types were positively associated with lymph node metastasis (p = 0.041 for tams in peritumour, p = 0.013 for M2 macrophages in introtumour, p = 0.006 for M2 macrophage in peritumour). In addition, abdominal pain was significantly more frequent in pdac patients with a greater tams count. The survival rate was much lower in patients having high infiltration by M2 macrophages than in those having low infiltration. CONCLUSIONS: The tam count might be associated with neural invasion in pdac, and M2 macrophages might play an important role in lymph node metastasis. Higher counts of either macrophage type were associated with increased risk of lymph node metastasis, and the M2 macrophage count could potentially be a marker for evaluating prognosis.