Heralded Three-Photon Entanglement from a Single-Photon Source on a Photonic Chip.

In the quest to build general-purpose photonic quantum computers, fusion-based quantum computation has risen to prominence as a promising strategy. This model allows a ballistic construction of large cluster states which are universal for quantum computation, in a scalable and loss-tolerant way without feed forward, by fusing many small n-photon entangled resource states. However, a key obstacle to this architecture lies in efficiently generating the required essential resource states on photonic chips. One such critical seed state that has not yet been achieved is the heralded three-photon Greenberger-Horne-Zeilinger (3-GHZ) state. Here, we address this elementary resource gap, by reporting the first experimental realization of a heralded 3-GHZ state. Our implementation employs a low-loss and fully programmable photonic chip that manipulates six indistinguishable single photons of wavelengths in the telecommunication regime. Conditional on the heralding detection, we obtain the desired 3-GHZ state with a fidelity 0.573±0.024. Our Letter marks an important step for the future fault-tolerant photonic quantum computing, leading to the acceleration of building a large-scale optical quantum computer.

[Safety and efficacy analysis of endovascular thrombectomy in patients with large vascular occlusion with low Alberta Stroke Program Early Computed Tomography Score].

Objective: To evaluate the safety and efficacy of endovascular thrombectomy (EVT) in acute anterior circulation large vessel occlusive stroke (ALVOS) and explore the related influencing factors for prognoses in patients with low Alberta Stroke Program Early Computed Tomography Score (ASPECT). Methods: Patients with acute ALVOS who underwent EVT in Yijishan Hospital of Wannan Medical College from January 2019 to June 2022 were sequentially enrolled. (1) Patients were divided into a low ASPECT group (0-5) and a non-low ASPECT group (6-10), and the differences between the two groups were compared with respect to incidence of perioperative complications and good prognosis rate [modified Rankin scale (mRS) score≤2] 90 days after onset. (2) According to the prognoses 90 days after onset, the low ASPECT group was divided into the good prognosis (mRS score≤2) and poor prognosis (mRS score>2) subgroup. Univariate analysis and multivariate logistic regression analysis were used to investigate the independent risk factors for prognoses of the low ASPECT patients after EVT. Results: A total of 582 patients [age 26-94(69±11) years, 345 male patients (59.3%)] were enrolled for analysis. The baseline ASPECT score was 8 (7, 10), and the baseline NIHSS score was 14 (11, 18). Among them, 102 (17.5%) patients were in the low ASPECT score group and 480 (82.5%) patients were in the non-low ASPECT score group. In the total cohort, patients in the low ASPECT score group had a higher incidence of symptomatic intracranial hemorrhage, lower 90-day good prognosis rate, and higher 90-day mortality rate. Further, propensity score matching statistical analysis showed that patients in the low ASPECT score group had a significantly higher incidence of malignant brain edema after EVT treatment (40.0% vs. 17.6%, χ2=9.13, P=0.003), and a significantly lower 90-day good prognosis rate (24.7% vs. 41.6%, χ2=4.96, P=0.026), but there was no significant difference in the incidence of symptomatic intracranial hemorrhage and 90-day mortality between the two groups (40.3% vs. 26.0%, χ2=3.55, P=0.060). Among 102 patients with low ASPECT score, 22 (21.6%) patients had good prognosis and 80 (78.4%) had poor prognosis. Multivariate logistic regression analysis showed that history of atrial fibrillation (OR=4.478, 95%CI 1.186-16.913, P=0.027) was an independent risk factor for poor prognosis of EVT in patients with low ASPECT score, while good collateral circulation (grade 2 vs. grade 0: OR=0.206, 95%CI 0.051-0.842, P=0.028) was a protective factor for good prognosis of EVT in patients with low ASPECT score. Conclusions: Although the 90-day good prognosis rate of EVT treatment for patients with low ASPECT score was lower than that of the non-low ASPECT group, 21.6% patients still benefitted from EVT treatment, especially patients with non-atrial fibrillation and good collateral circulation. Future studies involving more patients are needed to validate our observations.

[Clinical analysis of 7 cases with anti-Caspr2 antibody-associated autoimmune encephalitis].

Objective: To investigate the clinical features, laboratory tests, imaging features, electroencephalogram (EEG) manifestations, treatment and prognosis of anti-CASPR2 antibody-associated autoimmune encephalitis with the purpose to improve the understanding of the disease. Methods: Seven patients diagnosed with CASPR2 antibody-associated encephalitis in the Fifth and first Affiliated Hospital of Zhengzhou University from January 2017 to January 2019 were selected. The clinical manifestations, course of disease, imaging, treatment plan and prognosis of the patients were retrospectively analyzed. Results: Of the 7 patients, 4 were male and 3 were female. The median age of onset was 34 years old (range, 11-66 years). Seizures (6/7), memory decline(5/7), and neuropsychiatric disorders (4/7) were common clinical manifestations. CASPR2 antibody was detected in the CSF of 3 patients (3/7) and the serum of all patients (7/7). Notable imaging changes were observed in 5 patients (5/7). All patients received immunotherapy and were followed up for 1 month to 2 years. One patient was diagnosed with rectal cancer with a poor prognosis; all the others got a good prognosis. Conclusions: CASPR2 antibody-related encephalitis is a rare autoimmune disease. It is considered to present with seizures, memory loss, psychiatric symptoms, dizziness and sleep disorders as the main clinical manifestations. Early identification and treatment of the disease can help the patients achieve a good prognosis.

The development of anti-heat stress clothing for construction workers in hot and humid weather.

The purpose of this study was to develop anti-heat stress clothing for construction workers in hot and humid weather. Following DeJonge's functional clothing design process, the design situation was explored, including clothing fabric heat/moisture transporting properties and UV protection and the aspects of clothing ergonomic design (mobility, convenience, and safety). The problem structure was derived from the results of the surveys in three local construction sites, which agreed well with the task requirements and observations. Specifications were consequently described and 30 commercially available fabrics were identified and tested. Fabric testing data and design considerations were inputted in S-smart system to predict the thermal functional performance of the clothing. A new uniform prototype was developed and evaluated. The results of all measurements suggest that the new uniform which incorporated fabrics with superior heat/moisture transporting properties and loose-fitting design could reduce the workers' heat stress and improve their comfort and work performance. Practitioner Summary: The construction workers' uniform currently used in Hong Kong during summer was unsatisfactory. Following DeJonge's functional clothing design process, an anti-heat stress uniform was developed by testing 30 fabrics and predicting clothing thermal functional performance using S-smart system. The new uniform could reduce the workers' heat stress and improve their comfort and work performance.

In situ TEM observation of buffering the anode volume change by using NiTi alloy during electrochemical lithiation/delithiation.

A novel Ti3Sn/NiTi shape memory alloy anode with a sandwich structure was fabricated by arc melting. In order to characterize in situ the Ti3Sn/NiTi anode microstructure changes and phase transformations during cycling, a nanoscale lithium battery was set up inside a transmission electron microscope, which consists of Li metal as the cathode, the native Li2O layer on the surface of Li metal as the solid electrolyte, and the Ti3Sn/NiTi as the anode. Only the Ti3Sn intermetallic compound experienced the electrochemical reaction, while the NiTi alloy (inactive with Li(+)) was applied for buffering the Ti3Sn volume change during cycling. An obvious reaction front of Ti3Sn migrated from one end to the other during lithiation, which can also return after delithiation. It provides direct evidence that the NiTi alloy can effectively accommodate the anode volume change during electrochemical lithiation and delithiation.

Diet selection of sheep shifted from quality to quantity characteristics of forages as sward availability decreased.

Understanding the dynamic inter-relationship between grazing animals and the pasture sward is critical for sustainable grazing management. A field study was conducted to investigate the relationships between the quantity and quality characteristics of forages and diet selection of 30-kg Mongolian ewes in different seasons in Bromus inermis improved meadow steppe. Using a residual herbage mass method (1 000 kg/ha in spring, 800 kg/ha in summer and 600 kg/ha in autumn) to adjust stocking rate, three seasonal rest grazing strategies (spring rest, summer rest and autumn rest) combined with continuous grazing were studied. In each season, diet selection of sheep, quantified by diet composition and selectivity index, was estimated using a plant wax marker technique. Quantity (dry weight proportion, coverage, frequency, density and height) and quality (CP, NDF, ADF and DM digestibility) characteristics of forages consumed by sheep were determined simultaneously. Our results showed that in spring with the highest sward availability (herbage mass), diet selection of sheep could be predicted by the positive linear relationship between quality characteristics of forages and their selectivity index. In summer, the diet selection could be predicted by both positive linear relationship between quality characteristics and selectivity index, and the relationship between quantity characteristics and diet composition. While in autumn with the lowest sward availability, it could be predicted by the positive linear relationship between quantity characteristics and diet composition. During the whole grazing season, the diet composition of B. inermis (40.4%) and Leymus chinensis (35.1%) were larger than that of Potentilla bifurca (9.5%) and Carex (15.1%) and the selectivity index of P. bifurca was the highest (0.62), followed by Carex (0.17) and B. inermis (0.05), and L. chinensis (-0.29) was the lowest. The two parameters of diet selection above were positively related to their quantity and quality characteristics, respectively. These results suggested that the influence of quality characteristics on diet selection of sheep decreased gradually as a result of the decline in sward availability, while the influence of quantity characteristics increased. This study provides a comprehensive understanding of diet selection of sheep examining the trade-offs between quantity and quality characteristics of forages. The knowledge of diet selection of sheep and the corresponding prediction regressions acquired in this study could give the basis for designing appropriate grazing management strategies.

[A multicenter epidemiological study of acute bacterial meningitis in children].

Objective: To analyze the clinical epidemiological characteristics including composition of pathogens , clinical characteristics, and disease prognosis acute bacterial meningitis (ABM) in Chinese children. Methods: A retrospective analysis was performed on the clinical and laboratory data of 1 610 children <15 years of age with ABM in 33 tertiary hospitals in China from January 2019 to December 2020. Patients were divided into different groups according to age,<28 days group, 28 days to <3 months group, 3 months to <1 year group, 1-<5 years of age group, 5-<15 years of age group; etiology confirmed group and clinically diagnosed group according to etiology diagnosis. Non-numeric variables were analyzed with the Chi-square test or Fisher's exact test, while non-normal distrituction numeric variables were compared with nonparametric test. Results: Among 1 610 children with ABM, 955 were male and 650 were female (5 cases were not provided with gender information), and the age of onset was 1.5 (0.5, 5.5) months. There were 588 cases age from <28 days, 462 cases age from 28 days to <3 months, 302 cases age from 3 months to <1 year of age group, 156 cases in the 1-<5 years of age and 101 cases in the 5-<15 years of age. The detection rates were 38.8% (95/245) and 31.5% (70/222) of Escherichia coli and 27.8% (68/245) and 35.1% (78/222) of Streptococcus agalactiae in infants younger than 28 days of age and 28 days to 3 months of age; the detection rates of Streptococcus pneumonia, Escherichia coli, and Streptococcus agalactiae were 34.3% (61/178), 14.0% (25/178) and 13.5% (24/178) in the 3 months of age to <1 year of age group; the dominant pathogens were Streptococcus pneumoniae and the detection rate were 67.9% (74/109) and 44.4% (16/36) in the 1-<5 years of age and 5-<15 years of age . There were 9.7% (19/195) strains of Escherichia coli producing ultra-broad-spectrum ß-lactamases. The positive rates of cerebrospinal fluid (CSF) culture and blood culture were 32.2% (515/1 598) and 25.0% (400/1 598), while 38.2% (126/330)and 25.3% (21/83) in CSF metagenomics next generation sequencing and Streptococcus pneumoniae antigen detection. There were 4.3% (32/790) cases of which CSF white blood cell counts were normal in etiology confirmed group. Among 1 610 children with ABM, main intracranial imaging complications were subdural effusion and (or) empyema in 349 cases (21.7%), hydrocephalus in 233 cases (14.5%), brain abscess in 178 cases (11.1%), and other cerebrovascular diseases, including encephalomalacia, cerebral infarction, and encephalatrophy, in 174 cases (10.8%). Among the 166 cases (10.3%) with unfavorable outcome, 32 cases (2.0%) died among whom 24 cases died before 1 year of age, and 37 cases (2.3%) had recurrence among whom 25 cases had recurrence within 3 weeks. The incidences of subdural effusion and (or) empyema, brain abscess and ependymitis in the etiology confirmed group were significantly higher than those in the clinically diagnosed group (26.2% (207/790) vs. 17.3% (142/820), 13.0% (103/790) vs. 9.1% (75/820), 4.6% (36/790) vs. 2.7% (22/820), χ2=18.71, 6.20, 4.07, all P<0.05), but there was no significant difference in the unfavorable outcomes, mortility, and recurrence between these 2 groups (all P>0.05). Conclusions: The onset age of ABM in children is usually within 1 year of age, especially <3 months. The common pathogens in infants <3 months of age are Escherichia coli and Streptococcus agalactiae, and the dominant pathogen in infant ≥3 months is Streptococcus pneumoniae. Subdural effusion and (or) empyema and hydrocephalus are common complications. ABM should not be excluded even if CSF white blood cell counts is within normal range. Standardized bacteriological examination should be paid more attention to increase the pathogenic detection rate. Non-culture CSF detection methods may facilitate the pathogenic diagnosis.

Effects of oregano essential oil as an antibiotic growth promoter alternative on growth performance, antioxidant status, and intestinal health of broilers.

This experiment was conducted to assess the comparative effects of dietary antibiotics and oregano essential oil (OEO) addition on growth performance, antioxidant status and intestinal health of broilers. A total of 384 one-day-old broilers were randomly allocated to 4 treatments with 6 replicates of 16 broilers each. The 4 treatments were: an antibiotic-free control diet (control), control + 20 mg/kg colistin sulfate and 20 mg/kg virginiamycin (antibiotics), control + 200 mg/kg natural oregano essential oil (NOEO), and control + 200 mg/kg synthetic oregano essential oil (SOEO). The experiment lasted for 42 d. Results showed that birds fed with OEO had greater (P < 0.05) average daily gain (ADG) and lower (P < 0.05) feed conversion ratio (FCR) than those fed with control diet during d 1 to 21. Besides, birds fed with NOEO had the greatest (P < 0.05) ADG in the four groups during d 22 to 42. The serum oxidative stress parameters showed that OEO improved (P < 0.05) the activities of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and glutathione reductase (GR) of birds on day 21 and the activity of total antioxidant capacity (T-AOC) of birds on d 42. Relative to control, NOEO increased (P < 0.05) the activity of T-AOC in jejunum and decreased (P < 0.05) the level of malondialdehyde (MDA) in serum and jejunum. Moreover, OEO supplementation increased (P < 0.05) the concentrations of sIgA in duodenum and jejunum, Lactobacillus and total anaerobes in cecum, as well as activities of trypsin, chymotrypsin, lipase and amylase in duodenum, but restrained (P < 0.05) the amount of Escherichia coli. The NOEO supplementation increased (P < 0.05) total anaerobes of broilers on d 42 and the villus height to crypt depth ratio (VH/CD) of ileum. These results suggest that OEO improved antioxidant status and intestinal health of broilers which contributed to the growth performance improvement of broilers. Dietary OEO supplementation can be a promising alternative to antibiotic growth promoters for improving poultry production.

Effects of dietary pyrroloquinoline quinone disodium supplementation on inflammatory responses, oxidative stress, and intestinal morphology in broiler chickens challenged with lipopolysaccharide.

This study was conducted to investigate the effects of pyrroloquinoline quinone disodium (PQQ·Na2) on inflammatory responses, oxidative stress, and intestinal morphology of broiler chickens challenged with lipopolysaccharide (LPS). A 2 × 2 factorial arrangement in a complete randomized design experiment was used to study the effect of dietary PQQ·Na2 (0 or 1 mg/kg) on broiler chickens with or without a challenge with LPS. A total of two hundred eighty-eight 1-day-old Arbor Acre broiler chickens were randomly assigned to 4 treatments with 6 replicate cages of 12 birds per cage. All experimental broilers were injected intraperitoneally with 0.5 mg/kg body weight of either Escherichia coli LPS or sterile saline at 16, 18, and 20 d of age. Results showed that injecting LPS significantly increased the concentrations of interleukin-1beta (IL-1ß) in serum of birds on day 20 and day 21. Meanwhile, LPS injection increased (P < 0.05) the relative mRNA expression of interleukin-6 (IL-6) in the duodenal mucosa of broilers on day 21. However, dietary supplementation with PQQ·Na2 decreased (P < 0.05) the concentration of IL-6 in serum of birds on day 20 and the levels of IL-1ß, IL-6, and interleukin-10 (IL-10) in serum of broiler chickens on day 21. Besides, supplementation of PQQ·Na2 within diet decreased (P < 0.05) the mRNA expressions of IL-1ß and IL-10 in the duodenal mucosa of birds on day 20. Relative to saline injection, the activity of glutathione peroxidase (GSH-Px) in serum and the activities of total superoxide dismutase (T-SOD) and catalase (CAT) in liver were found to be lower (P < 0.05) in broilers after LPS challenge on day 21. However, birds fed with PQQ·Na2 showed higher (P < 0.05) GSH-Px activity in serum and higher (P < 0.05) T-SOD activities in liver on day 21 and day 42. Pyrroloquinoline quinone disodium also significantly attenuated the LPS-induced decreases in villus height to crypt depth ratio in the duodenum of broilers. In conclusion, dietary PQQ·Na2 supplementation significantly exerted protective effects on inflammation damage and oxidant stress of broilers under LPS challenge by regulating the expression of inflammatory cytokines (IL-1ß, IL-6, and IL-10) and activities of antioxidant enzymes (GSH-Px, T-SOD, and CAT). Moreover, dietary PQQ·Na2 supplementation significantly ameliorated the LPS-impaired intestinal morphology in broilers. Therefore, it has been considered that PQQ·Na2 can be used as a potential feed additive in broiler production.

Comparing mask fit and usability of traditional and nanofibre N95 filtering facepiece respirators before and after nursing procedures.

BACKGROUND: The reliability of N95 filtering facepiece respirators (FFRs) depends on correct fitting. The perceived usability of FFRs is equally important because discomfort during usage may affect compliance. Body movements during nursing procedures may also increase the risk of face seal leakage. AIM: To evaluate the mask fit and usability of the best-fitting 3M N95 FFR and the nanofibre N95 FFR before and after nursing procedures. The physical properties of these FFRs were also examined. METHODS: This experimental study had a one-group multiple comparison design. In total, 104 nursing students participated, and performed nursing procedures for 10 min when wearing the best-fitting 3M FFR and the nanofibre FFR. Mask fit and perceived usability of the FFRs were evaluated. FINDINGS: More participants failed to obtain a fit factor ≥100 when using the best-fitting 3M FFR than when wearing the nanofibre FFR (33.7% vs 21.2%) after the procedures (P=0.417). The nanofibre FFR also demonstrated higher usability than the 3M FFRs in terms of facial heat, breathability, facial pressure, speech intelligibility, itchiness, difficulty of maintaining the mask in place, and comfort level (P<0.001). The nanofibre FFR was also lighter, thinner and had slightly higher bacterial filtration efficiency than the 3M FFRs. CONCLUSION: The nanofibre FFR demonstrated significantly better usability than the 3M FFRs. None of the respirators were able to provide consistent protection for the wearer, as detected by face seal leakage after performing nursing procedures. Further improvement in the prototype design is needed to increase compliance and ensure the respiratory protection of users.

Mechanisms of organophosphate resistance in a field population of oriental migratory locust, Locusta migratoria manilensis (Meyen).

The susceptibilities to three organophosphate (OP) insecticides (malathion, chlorpyrifos, and phoxim), responses to three metabolic synergists [triphenyl phosphate (TPP), piperonyl butoxide (PBO), and diethyl maleate (DEM)], activities of major detoxification enzymes [general esterases (ESTs), glutathione S-transferases (GSTs), and cytochrome P450 monooxygenases (P450s)], and sensitivity of the target enzyme acetylcholinesterase (AChE) were compared between a laboratory-susceptible strain (LS) and a field-resistant population (FR) of the oriental migratory locust, Locusta migratoria manilensis (Meyen). The FR was significantly resistant to malathion (57.5-fold), but marginally resistant to chlorpyrifos (5.4) and phoxim (2.9). The malathion resistance of the FR was significantly diminished by TPP (synergism ratio: 16.2) and DEM (3.3), but was unchanged by PBO. In contrast, none of these synergists significantly affected the toxicity of malathion in the LS. Biochemical studies indicated that EST and GST activities in the FR were 2.1- to 3.2-fold and 1.2- to 2.0-fold, respectively, higher than those in the LS, but there was no significant difference in P450 activity between the LS and FR. Furthermore, AChE from the FR showed 4.0-fold higher activity but was 3.2-, 2.2-, and 1.1-fold less sensitive to inhibition by malaoxon, chlorpyrifos-oxon, and phoxim, respectively, than that from the LS. All these results clearly indicated that the observed malathion resistance in the FR was conferred by multiple mechanisms, including increased detoxification by ESTs and GSTs, and increased activity and reduced sensitivity of AChE to OP inhibition.

The potential application of plant wax markers from alfalfa for estimating the total feed intake of sheep.

Estimating the feed intake of grazing herbivores is critical for determining their nutrition, overall productivity and utilization of grassland resources. A 17-day indoor feeding experiment was conducted to evaluate the potential use of Medicago sativa as a natural supplement for estimating the total feed intake of sheep. A total of 16 sheep were randomly assigned to four diets (four sheep per diet) containing a known amount of M. sativa together with up to seven forages common to typical steppes. The diets were: diet 1, M. sativa + Leymus chinensis + Puccinellia distans; diet 2, species in diet 1 + Phragmites australis; diet 3, species in diet 2 + Chenopodium album + Elymus sibiricus; and diet 4, species in diet 3 + Artemisia scoparia + Artemisia tanacetifolia. After faecal marker concentrations were corrected by individual sheep recovery, treatment mean recovery or overall recovery, the proportions of M. sativa and other dietary forages were estimated from a combination of alkanes and long-chain alcohols using a least-square procedure. Total intake was the ratio of the known intake of M. sativa to its estimated dietary proportion. Each dietary component intake was obtained using total intake and the corresponding dietary proportions. The estimated values were compared with actual values to assess the estimation accuracy. The results showed that M. sativa exhibited a distinguishable marker pattern in comparison to the other dietary forage species. The accuracy of the dietary composition estimates was significantly (P < 0.001) affected by both diet diversity and the faecal recovery method. The proportion of M. sativa and total intake across all diets could be accurately estimated using the individual sheep or the treatment mean recovery methods. The largest differences between the estimated and observed total intake were 2.6 g and 19.2 g, respectively, representing only 0.4% and 2.6% of the total intake. However, they were significantly (P < 0.05) biased for most diets when using the overall recovery method. Due to the difficulty in obtaining individual sheep recovery under field conditions, treatment mean recovery is recommended. This study suggests that M. sativa, a natural roughage instead of a labelled concentrate, can be utilized as a dietary supplement to accurately estimate the total feed intake of sheep indoors and further indicates that it has potential to be used in steppe grassland of northern China, where the marker patterns of M. sativa differ markedly from commonly occurring plant species.

Molecular Characterization of Six Small Heat Shock Proteins and Their Responses Under Cadmium Stress in Oxya chinensis (Orthoptera: Acridoidea).

Small heat shock proteins (sHSPs) have been implicated in many physiological processes and play important roles in the response to various stresses. In this study, the full-length sequences of six sHSPs: OcHSP19.1, 19.8, 20.4, 20.7, 21.1, and 23.8 were obtained from the rice grasshopper Oxya chinensis transcriptome database. The deduced amino acid sequences of the six OcsHSPs contain a typical α-crystallin domain, which consists of approximately 100 amino acid residues and five ß-strands. The phylogenetic analysis suggested that OcHSP23.8 was orthologous to the sHSPs of other species and that OcHSP19.1, 20.4, 20.7, and 21.1 were species specific, whereas OcHSP19.8 did not cluster closely to Orthoptera but was placed on the basal end of the cluster. Developmental stage-dependent and tissue-specific expression patterns were evaluated using quantitative real-time polymerase chain reaction. The six genes were expressed in all developmental stages and showed clear tissue specificity. The cadmium acute experiment indicates that Cd(2+) can induce the six genes. However, various response patterns were observed among these genes under Cd(2+) stress conditions. OcHSP19.1, 19.8, 20.4, and 20.7 were highly induced by 2.61 mM Cd(2+) at 24 h. OcHSP23.8 was significantly upregulated by 2.61 mM Cd(2+) at 6 h. For OcHSP21.1, the highest expression levels were found after treatment with 0.87 mM Cd(2+) for 24 h, 1.74 mM Cd(2+) for 36 h, and 2.61 mM Cd(2+) for 12 h. These differential characteristics will facilitate future investigations into the physiological functions of sHSPs.

Growth factors and stromal matrix proteins associated with mammographic densities.

Extensive radiologically dense breast tissue is associated with a marked increase in breast cancer risk. To explore the biological basis for this association, we have examined the association of growth factors and stromal matrix proteins in breast tissue with mammographic densities. Ninety-two formalin-fixed paraffin blocks of breast tissues surrounding benign lesions were obtained, half from breasts with little or no density and half from breasts with extensive density, matched for age at biopsy. Sections were stained for cell nuclei, total collagen, the stromal matrix regulatory protein tissue metalloproteinase-3 (TIMP-3), and the growth factors, transforming growth factor-alpha and insulin-like growth factor (IGF-I). The area of immunoreactive staining was measured using quantitative microscopy. Breast tissue from subjects with extensive densities had a greater nuclear area (P = 0.007), as well as larger stained areas of total collagen (P = 0.003), TIMP-3 (P = 0.08), and IGF-I (P = 0.02) when compared with subjects with little breast density. Differences were greater for subjects less than 50 years of age. These data indicate that increased tissue cellularity, greater amounts of collagen, and increased IGF-I and TIMP-3 expression are found in tissue from mammographically dense breasts and suggest mechanisms that may mediate the associated increased risk of breast cancer.

Cell proliferation and death in the irradiated pituitary gland and its modification by growth stimulants.

PURPOSE: This study was undertaken to show whether the rate of expression of radiation injury in the rat pituitary gland could be accelerated by the use of growth stimulants. METHODS AND MATERIALS: Rat pituitary glands were irradiated in situ with a range of single doses up to 20 Gy. The rats were then given subcutaneous slow-release implants containing 17beta-estradiol (E2) and sulpiride (S) to stimulate lactotroph proliferation. Two sequential cycles were used, each consisting of stimulation (3 weeks) and withdrawal (2 weeks). Measurements were made of gland weight; BrdU-labeled, giant, and apoptotic cells; lactotrophs; as well as pituitary prolactin content, in response to exogenous thyroid-releasing hormone (TRH). RESULTS: The two cycles of stimulation/withdrawal resulted in marked changes in gland weight, BrdU-labeling index, and serum prolactin (PRL) levels in unirradiated rats. The proportion of immunopositive growth-hormone-producing (GH) cells increased after irradiation. Radiation inhibited the hypertrophic response to E2 + S and also inhibited increases in BrdU-labeling index and serum PRL levels. Also, giant lactotrophs were observed in the irradiated pituitaries. However, they were not seen in the unirradiated rats or in the irradiated rats treated with E2 + S. TRH promoted PRL secretion in the unirradiated rat. In contrast, TRH inhibited PRL secretion in the irradiated rat and in all treatment groups receiving E2 + S. Apoptosis was induced by irradiation and was substantially increased in lactotrophs and in other cell types by withdrawal of the E2 and S stimulus, although the highest observed incidence was only 7 per 10,000 cells. CONCLUSION: Both irradiation and E2 + S treatment removed the hypothalamic control of PRL secretion, which reveals this important inhibitory action of TRH upon PRL secretion. This suggests that it is not suitable as a dynamic test of pituitary PRL reserves in such abnormal situations, where there may also be damage to the hypothalamic-pituitary vasculature. The increasing proportion of GH cells after irradiation indicates that lactotrophs respond more rapidly to irradiation. The stimulation by E2 + S somehow prevented the radiation-damaged lactotrophs from becoming giant cells. Also, the ratio of apoptotic cells to BrdU-labeled cells was increased by the E2 + S treatment, indicating that the E2 + S did enhance radiation-induced cell death relative to cell renewal. However, overall, the E2 + S stimulus protocol did not promote a dramatic increase in cell death (apoptosis) nor a marked decrease in residual gland weight after irradiation. Hence, its use would probably not be beneficial in the treatment of slow-responding prolactinomas, if malignant lactotrophs respond similarly to the normal pituitary lactotrophs. However, the observation of induced apoptosis after hormone and drug withdrawal suggests that agents which promote tumor shrinkage may be effective by causing rapid apoptosis of tumor cells in vivo.

Potentiation of excitotoxic injury by high concentrations of extracellular reduced glutathione.

Glutathione is present in the central nervous system in millimolar concentrations, and is a predominant intracellular antioxidant and detoxicant. In addition, glutathione is released into the extracellular space via a depolarization-enhanced process. Although the role of extracellular glutathione has not been precisely defined, a growing body of experimental evidence suggests that it has multifaceted electrophysiological effects. At low micromolar concentrations, glutathione depolarizes neurons by binding to its own receptors and modulates glutamatergic excitatory neurotransmission by displacing glutamate from its ionotropic receptors. At higher concentrations, reduced glutathione may increase N-methyl-D-aspartate receptor responses by interacting with its redox sites. In this study, the effect of extracellular glutathione on excitotoxic neuronal injury was quantitatively assessed in murine cortical cell cultures. Neuronal death due to 20-25 h exposure to 6-9 microM N-methyl-D-aspartate was not altered by 10-100 microM reduced glutathione but was markedly enhanced by 300-1000 microM reduced glutathione; kainate neurotoxicity was unaffected. Two related compounds that lack a sulfhydryl group, oxidized glutathione and S-hexylglutathione, had no significant effect on N-methyl-D-aspartate neurotoxicity alone but completely blocked the effect of reduced glutathione. Mercaptoethanol, a sulfhydryl reducing agent that increases N-methyl-D-aspartate receptor responses by interacting with redox sites, increased N-methyl-D-aspartate neurotoxicity to a degree comparable to that of reduced glutathione; this effect was also blocked by equimolar S-hexylglutathione or oxidized glutathione. Addition of reduced glutathione to mercaptoethanol did not further increase N- methyl-D-aspartate-induced neuronal death. These results suggest that release of reduced glutathione from central nervous system cells that are subjected to traumatic or ischemic insults may enhance excitotoxic neuronal loss. Although multiple mechanisms may account for this phenomenon, the high concentrations required suggest that it is at least partly mediated by reduction of N-methyl-D-aspartate receptor redox sites.

Time course of radiation-induced apoptosis in the adult rat spinal cord.

Radiation-induced apoptosis has been reported in thymic, lymphoid, haematopoietic cells and intestinal epithelium but is infrequently documented in other adult mammalian cell types. In this study, we examined the time course of radiation-induced apoptosis in the adult cervical rat spinal cord following a single dose of 8 or 22 Gy. Apoptosis was assessed by morphological criteria under light and electron microscopy, and immunohistochemically in-situ using Apoptag to detect 3' -OH ends of DNA fragments. Little evidence of apoptosis (0.3 +/- 0.1 apoptotic nuclei per spinal cord section) was observed in control un-irradiated spinal cord. A significant increase in the number of apoptotic cells per spinal cord section was seen at 4 h after 8 (13.6 +/- 1.3) or 22 Gy (22.0 +/- 2.7). The number of apoptotic nuclei reached a peak at 8 h (44.7 +/- 3.7 after 8 Gy, 49.5 +/- 4.3 after 22 Gy), and returned to the baseline level by 24 h (2.4 +/- 0.7 after 8 Gy, 3.3 +/- 0.7 after 22 Gy). A dose of 22 Gy induced significantly more apoptoses than 8 Gy at 4, 6, 10 and 12 h (P < or = 0.033), but not at 8 h. More apoptotic nuclei were observed in white matter (64-92%) than gray matter (8-36%). All the apoptotic cells were observed in glial cells, and there was no evidence of radiation-induced apoptosis in the vascular endothelial cells or neurons. The morphological features of the apoptotic cells under electron microscopy and the absence of GFAP staining suggested that they were oligodendrocytes. We conclude that radiation induces apoptosis in the adult rat spinal cord, and that the development of apoptosis follows a specific time course.

L-propionyl carnitine, an endogenous ester in fatty acid metabolism, exerts anti-shock and endothelial protective effects in rat splanchnic ischemia-reperfusion injury.

Splanchnic artery occlusion (SAO) results in a severe form of circulatory shock in which oxygen-derived free radicals play an important role. L-Propionyl carnitine (LPC), an endogenous ester that plays a crucial role in cellular fatty acid oxidation and metabolism, has been shown to exert a protective effect in myocardial ischemia/reperfusion injury. Our purpose was to investigate the effects of LPC in an SAO model of ischemia/reperfusion injury. Pentobarbital-anesthetized rats were subjected to 60 min of SAO followed by 120 min of reperfusion. An intravenous bolus of LPC (200 microg/kg) administered 2 min before reperfusion prolonged survival time (116+/-4 vs. 81+/-3 min in 1 mL/kg .9% NaCl vehicle, p < .01), increased survival rate (88 vs. 13.6%, p < .01), and attenuated the percent increase in hematocrits (27+/4% vs. 43+/-3%, p < .05), and the increases in tissue myeloperoxidase activity (1.76+/-.4 U/100 mg vs. 3.79+/-.2 U/100 mg, p < .05). In addition, LPC increased mean arterial blood pressures at 60 min (p < .05), 80 min (p < .05), 100 min (p < .05), and 120 min (p < .05) postreperfusion. Moreover, LPC markedly attenuated splanchnic artery endothelial dysfunction induced by SAO ischemia/reperfusion injury (maximal vasorelaxation to ACh, 74+/-2.7% vs. 57+/-1.9% in vehicle, p < .01). In this murine SAO model of ischemia/reperfusion injury, LPC affords significant protection that may be achieved through inhibiting leukocyte infiltration into intestinal tissue and preserving endothelial function, thereby decreasing microvascular permeability and maintaining tissue perfusion.

Virus-induced subacute spongiform encephalopathy (Creutzfeldt-Jakob disease). A report of two Chinese cases with clinico-pathologic studies.

Two Chinese cases of Creutzfeldt-Jakob disease (CJD) are described which show the typical clinical, EEG and neuropathological changes of a subacute spongiform encephalopathy. One case was sporadic and the other was probably familial. This is the first formal report of CJD occurring in China.

Becker muscular dystrophy.

Five patients from 3 families with Becker muscular dystrophy (BMD) were reported. The main clinical and laboratory findings were in common. Pairs of affected brothers are quite resembled each other. However, there are also some variations among different families. The disease occurred later in the first pair of brothers and was accompanied by macroglossia and red-green color blindness, while the second pair got the disease earlier, which was accompanied by heart impairment. It is interesting that both myogenic and neurogenic changes of EMG can be found in the same patient with BMD in our series.