Global health impacts of ambient fine particulate pollution associated with climate variability.

Air pollution is a key global environmental problem raising human health concern. It is essential to comprehensively assess the long-term characteristics of air pollution and the resultant health impacts. We first assessed the global trends of fine particulate matter (PM2.5) during 1980-2020 using a monthly global PM2.5 reanalysis dataset, and evaluated their association with three types of climate variability including El Niño-Southern Oscillation, Indian Ocean Dipole and North Atlantic Oscillation. We then estimated PM2.5-attributable premature deaths using integrated exposure-response functions. Results show a significant increasing trend of ambient PM2.5 during 1980-2020 due to increases in anthropogenic emissions. Ambient PM2.5 caused a total of âˆ¼ 135 million premature deaths globally during the four decades. Occurrence of air pollution episodes was strongly associated with climate variability, which were associated with up to 14 % increase in annual global PM2.5-attributable premature deaths.

Influences of approaching tropical cyclones on water vapor and aerosols in the atmospheric boundary layer of Guangdong-Hong Kong-Macau Greater Bay Area of China.

The outer circulation of tropical cyclones (TCs) on the western North Pacific has been reported to substantially influence the atmospheric environment over the Guangdong-Hong Kong-Macau Greater Bay Area (GBA) of China, whereas dynamic evolution and redistribution of water vapor and aerosol in the atmospheric boundary layer (ABL) responding to moving TCs have yet to be understood. This study aims to answer three key research questions related to the influences of the approaching TCs: (1) how do water vapor and aerosol particles over the GBA change during the TC approaching stage? (2) how does the ABL in terms of vertical wind structure respond to the approaching TCs? and (3) how does turbulence influence the vertical profile of aerosol during the approaching stage? Based on an intensive analysis of three-year reanalysis and Doppler LiDAR data, this study identified a dry-polluted time over the GBA when a TC was located at ~1000 km away on South China Sea. Before that, horizontal wind has consistently come from the northeast, creating a favorable condition for weak transboundary air pollution to the GBA. During the dry-polluted time, the highest surface PM2.5 concentration was resulted from the enhanced downdraft and early-stage wind shear, i.e., stronger wind started occurring at upper-level ABL, while the further turbulent mixing induced by wind shear enhancement and updrafts recovery pumped surface pollution upward to the upper level when TCs became closer. Our findings are expected to improve both weather and PM2.5 forecasts under the impacts of approaching TCs.

Active Volcanism Revealed from a Seismicity Conduit in the Long-resting Tatun Volcano Group of Northern Taiwan.

Abundant earthquakes clustered within a particular zone often reflect an active geological feature, such as clustering seismicity along a fault zone and a huge number of volcanic-earthquakes around the erupting conduit. Herein we perform a double-difference tomographic inversion and relocate the seismicity at the long-resting Tatun volcano group (TVG) in northern Taiwan. A dramatic improvement of the earthquake location model surprisingly show that, from 2014 to 2017, two clustered seismic zones are identified in the TVG. One major group of events (>1000) persistently clustered within a ~500 m diameter vertical conduit with a ~2 km height. The clustering seismicity conduit is just located nearby Dayoukeng, one of the strongest fumaroles in the TVG, and is connected to a fracture zone characterized by low Vp/Vs in the shallow crust. The other group of events is clustered within a sphere-like zone beneath Mt. Chihsin around the depths between 0.5 km and 2 km. Both seismic zones are probably triggered by the significantly volcanic gases and fluids ascending from the deep magma reservoir. Combined with a variety of results from literature, the seismicity conduit near the strong fumarole is the evidence for an active volcano and also identifies a likely pathway for ascending magma if the TVG erupts again in the future. But possibility of developing different magma pathways at other clustered seismic zones such as beneath Mt. Chihsin may not be totally excluded.

The amino-terminal peptide of HIV-1 glycoprotein 41 fuses human erythrocytes.

The ability of synthetic peptides based on the amino-terminus of HIV-1 glycoprotein 41,000 (gp41) to fuse human erythrocytes was investigated. Previous site-directed mutagenesis studies have shown an important role for the N-terminal gp41 domain in HIV-fusion, in which replacement of hydrophobic amino acids with polar residues inhibits viral infection and syncytia formation. Here, a synthetic peptide (FP; 23 amino acid residues 519-541) corresponding to the N-terminus of HIV-1 gp41, and also a FP analog (FP526L/R) with Arg replacing Leu-526, were prepared with solid phase techniques. The lipid mixing and leakage of resealed ghosts triggered by these peptides were examined with fluorescence quenching techniques. Peptide-induced aggregation of human erythrocytes was studied using Coulter counter sizing and scanning electron microscopy (SEM). Using resealed erythrocyte ghosts at physiologic pH, FP induces rapid lipid mixing between red cell membranes at doses previously shown to hemolyze intact cells. FP also causes leakage from resealed ghosts, and promotes the formation of multicelled aggregates with whole erythrocytes. Contrarily, similar FP526L/R concentrations did not induce red cell lysis, lipid mixing, leakage or aggregation. Since the fusogenic potency of FP and FP526L/R parallels earlier gp41 mutagenesis studies showing that substitution of Arg for Leu-526 blocks fusion activity, these data suggest that the N-terminal gp41 domain in intact HIV participates in fusion.

Identification of immunodominant, group-specific and subcomplex-specific, continuous epitopes in the core regions of Japanese encephalitis virus using synthetic peptides.

Two flaviviruses, Japanese encephalitis (JE) virus and Dengue (DEN) virus which have high pathogenicity for humans, continue to pose a serious public health problem in tropical and subtropical countries of the world. In order to identify the immunodominant B-cell epitopes for diagnostic application, we have prepared a series of 15-mer synthetic peptides from JE virus core protein based on computer analysis. Four linear, immunodominant epitopes corresponding to amino acids 91-105 (P78), 1-15 (P73), 8-22 (P74), and 34-48 (P75) of JE virus core proteins were identified by employing an enzyme-linked immunosorbent assay (ELISA), using high-titered immune sera from JE-vaccinated children. P78 was found to be the most immunodominant. The sero-specificity of these peptides was tested by binding to seroconverted samples from JE and DEN-1 patients. P78 and P74 belonged to group-specific epitopes which reacted with both JE and DEN-1 patient sera. P73 and P75 belonged to subcomplex-specific epitopes which reacted only with JE but not with DEN-1 patient sera. The study suggests that these peptides corresponding to the immunodominant epitopes of JE virus core protein might have the potential to be used as peptide-based diagnostic reagents for the detection and differentiation of JE and DEN antibody responses.

Increased invasive activity of human hepatocellular carcinoma cells is associated with an overexpression of thyroid hormone beta 1 nuclear receptor and low expression of the anti-metastatic nm23 gene.

To understand the role of thyroid hormone in metastasis, we studied the expression of the anti-metastatic nm23 gene in eight human hepatocellular carcinoma (HCC) cell lines. These cells differentially expressed the anti-metastatic nm23 gene. A low level of nm23 proteins was found to have a high in vitro invasive activity which correlated closely with an overexpression of the thyroid hormone beta 1 nuclear receptor (h-TR beta 1). Concurrent with the down-regulation of h-TR beta 1, the invasive activity of HCC cells was suppressed by the thyroid hormone, 3,3',5-triiodo-L-thyronine (T3). These results indicate that the invasive activity of HCC cells was regulated by T3, suggesting that T3 could be involved in modulating the functions of nm23.

Formation and photodissociation of M(+)-C(6)H(6) (M(+) = V(+) and Ta(+)) and Ta(+)-C(6)H(4) complexes in a time-of-flight mass spectrometer.

A series of cyclic hydrocarbons were introduced to react with V(+) and Ta(+) using a pulsed beam expansion source in a time-of-flight mass spectrometer. The third-row metal Ta(+) displayed high reactivity in dehydrogenation to form benzyne complexes, whereas benzene complexes were the terminal products for V(+). M(+)-C(6)H(6) (M(+) = V(+) and Ta(+)) and Ta(+)-C(6)H(4) were selected to perform the photodissociation experiments. In contrast to the V(+) fragment formation via simple cleavage of the V(+)-C(6)H(6) bond, a photoinduced loss of C(2)H(2) occurred in both the Ta(+)-C(6)H(6) and Ta(+)-C(6)H(4) complexes. Plausible explanations involved in the formation of Ta(+)-C(6)H(6) and Ta(+)-C(6)H(4) complexes are given for observing such photo-induced dissociation. The observed photodissociation in Ta(+)-C(6)H(6) is analogous to the dissociative process previously investigated in metal ion-molecule reactions. The photodissociation spectrum of Ta(+)-C(6)H(4) was obtained by recording the appearance of Ta(+)-C(4)H(2) as a function of wavelength and yielded a dissociation energy of 91 +/- 1 kcal mol(-1).

[Immunity against diphtheria in Taiwan].

The vaccination of combined diphtheria, pertussis, and tetanus (DPT) vaccine provides good immunity against childhood diphtheria in Taiwan. However, a waning protective antibody level has been observed with an increase in age. Therefore, we assessed diphtheria immunoglobulin (DIG) level in Taipei City as representatives of urban dwellers and in King-Shan County as representatives of rural dwellers to evaluate the status of immunity against diphtheria in the population of Taiwan. In total, 1239 serum samples collected from the resident population, age 0-91 years, were detected by toxin neutralization test with VERO cells. The DIG level > or = 0.01 IU/mL was considered to be seropositive and > or = 0.1 IU/mL was considered to be fully protective. The positive rate and fully protective rate for all persons were 79.9% and 36.6%, respectively. The age specific positive rate and fully protective rate for children under 14 years of age were 97.0% and 78.0%, for 20-29 years of age group, were 38.0% and 8.3%, respectively, to be the lowest record among tested age groups. Then, both rates increased proportionately with age. Among those birth cohorts born in the diphtheria immunization era (since 1955), the antibody levels were inversely correlated with age, suggesting a decreased opportunity for exposure to natural diphtheria infection in the recent years and the duration of the vaccine inoculation. This finding indicates the need of a booster vaccination for young adults to ensure a full term protection and a long lasting diphtheria control.

Low molecular weight protamine (LMWP) as nontoxic heparin/low molecular weight heparin antidote (I): preparation and characterization.

Low molecular weight protamine (LMWP) appears to be a promising solution for heparin neutralization without the protamine-associated catastrophic toxic effects. The feasibility of this hypothesis was proven previously by using a peptide mixture produced from proteolytic digestion of protamine. To further examine the utility of this compound as an ultimate nontoxic protamine substitute, detailed studies on the purification and characterization of LMWP including the precise amino acid sequence, structure-function relationship, and possible mechanism were conducted. A number of LWMP fragments, composed of highly cationic peptides with molecular weights ranging from 700 to 1900 d, were prepared by digestion of native protamine with the protease thermolysin. These fragments were fractionated using a heparin affinity chromatography, and their relative binding strengths toward heparin were elucidated. Five distinct fractions were eluted at NaCl concentration ranging from 0.4 to 1.0 M and were denoted as TDSP1 to TDSP5, in increasing order of eluting ionic strength. Among these 5 fractions, TDSP4 and TDSP5 contained 3 LMWP peptide fragments, and they were found to retain the complete heparin-neutralizing function of protamine. By using a peptide mass spectrometry (MS) fingerprint mapping technique, the amino acid sequences of the microheterogeneous LMWP fragments in all these 5 elution fractions were readily identified. A typical structural scaffold made by arginine clusters in the middle and nonarginine residues at the N-terminal of the peptide sequence was observed for all these LMWP fragments. By aligning the sequences with the potency in heparin neutralization of these LMWP fragments, it was found that retention of potency similar to that of protamine required the presence of at least 2 arginine clusters in the LMWP fragments; such as the sequence of VSRRRRRRGGRRRR seen in the most potent LMWP fraction-TDSP5. The above finding was further validated by using a synthetic LMWP analogue-CRRRRRRR-and it was found that its heparin-neutralizing ability was increased by changing from a monomeric to a dimeric structure of this analogue peptide. Based on these results, the structural requirement for a compound to function as an effective heparin antidote and the possible mechanism involved in heparin neutralization were established.

Low molecular weight protamine (LMWP) as nontoxic heparin/low molecular weight heparin antidote (II): in vitro evaluation of efficacy and toxicity.

Patients undergoing anticoagulation with heparin or low molecular weight heparin (LMWH) require a superior antidote that possesses more selective biological actions and a better safety profile than protamine. We had previously developed 2 low molecular weight protamine (LMWP) fractions (TDSP4 and TDSP5) from thermolysin-digested protamine as potential nontoxic, heparin-neutralizing agents. In this, the second article in this series, studies focused on in vitro evaluation of heparin/LMWH-neutralizing efficacy and putative toxicity. These LMWP fractions, particularly TDSP5, were effective and fully capable of neutralizing a broad spectrum of heparin-induced anticoagulant activities (ie, aPTT, anti-Xa, and anti-IIa activities). Additionally, these LMWP fractions could neutralize the activities of commercial LMWH. As assessed by the anti-Xa assay, TDSP5 was as effective as, although less potent than, protamine in reversing the activity of Mono-Embolex (molecular weight 5000-7000) and 2 other different sizes (molecular weight of 3000 and 5000 d) of LMWH preparations. Furthermore, compared with protamine, TDSP5 exhibited a much-reduced toxicity and thus an improved safety profile, as reflected by its reduced ability to activate the complement system and cross-react with the antiprotamine antibodies, which are 2 primary indices of protamine toxicity.

The life cycle of Echinoparyphium ralphaudyi sp. n. (Trematoda: Echinostomatidae).

The life cycel and morphology of Echinoparyphium ralphaudyi sp. n. is described. Natural infections were found in Bulinus truncatus from Egypt, Ethiopia, and the Yemen Arab Republic, and later in B. forskalii and B. sericinus from Ethiopia. Sporocysts develop near the places of miracidial entry into the snail (the head-foot region, mantle edge, pseudobranch, and antennae). Rediae occur mainly in the ovotestis and in tissues anterior to the liver. The first cercariae are released 24 days postexposure. Metacercariae encyst in various freshwater snails and are localized in the pericardial sac and the posterior part of the kidney. Adult worms live in the small intestine of a variety of experimental animals: hamsters, rats, mice, chicks, ducklings, pigeons, and finches.

Sclerotherapy--an adjuvant therapy to endometriosis.

OBJECTIVE: Recurrent endometriomas after medical or surgical treatment is a difficult clinical problem for those patients who wish to perform ovulation induction. Therefore we tried to investigate the efficacy of sclerotherapy as an adjuvant management before ovulation induction to preserve more ovarian tissue for folliculogenesis in ART program. METHODS: Thirty-two patients with persistent or recurrent endometrioma after surgical or medical treatment were included in this study. Transvaginal ultrasound needle guided aspiration of the cyst followed by tetracycline instillation was performed before ovulation induction. RESULTS: There is an encouraging clinical pregnancy rate of 34.37%. Also, there is a disappointing recurrent rate of 46.87% in 12 months follow-up course. CONCLUSION: The increased interest in cost-effective outpatient therapy and the expected difficulty in surgical treatment of recurrent endometriomas made aspiration and sclerotherapy of endometrioma an attractive option before ovulation induction.

Energy value of medium-chain triglycerides and their efficacy in improving survival of neonatal pigs.

Two experiments were conducted to determine the energy value of medium-chain triglycerides (MCT) and to assess whether oral doses of MCT could improve the survival of neonatal pigs. Twenty 6-d-old pigs from seven litters were fed a milk replacer containing 0, 5, 10, or 20% MCT. Feces and urine were collected for 10 d to determine the energy value of MCT. The determined GE, DE, ME, and N-corrected ME of MCT were 8,279, 8,693, 7,867, and 7,781 kcal/kg, respectively. Two hundred forty-eight neonatal pigs from 23 litters were orally dosed with 6 mL/kg.75 of either MCT or saline twice (14 and 26 h of age), and the growth and mortality of pigs at 1, 2, 3, 7, 14, and 28 d of age were observed. The growth of pigs from birth to 28 d of age was not affected (P > .05) by MCT. Medium-chain triglycerides increased (P < .05) the mortality of large (> 1.5 kg) pigs during 0 to 7 and 0 to 28 d of age and did not reduce (P > .05) the mortality of small (< 1 kg) or medium (1 to 1.5 kg) pigs. In summary, MCT was effective as an energy source for pigs, but neonatal pigs dosed with MCT did not have improved growth or survival from birth to weaning.

Causes of reduced survival of neonatal pigs by medium-chain triglycerides: blood metabolite and behavioral activity approaches.

Two experiments were conducted to investigate the causes of the failure of orally dosed medium-chain triglycerides (MCT) in improving the survival of neonatal pigs. In Exp. 1, four litters consisting of 24 unsuckled neonatal pigs were either dosed with 6 mL/kg BW.75 of MCT or the dosing process was mimicked by inserting and withdrawing the feeding tube at 10 and 18 h after birth. Blood beta-hydroxybutyrate concentration was increased (P < .06) and the depletion of liver glycogen was reduced (P < .05) by MCT. Plasma octanoate (C8) concentration peaked at 1 h and was minimized at 4 to 8 h after each MCT dosage; decanoate (C10) concentration increased (P < .001) gradually after each dosage. Activity of pigs was decreased (P < .01) by MCT. In Exp. 2, 94 litters consisting of 887 neonatal pigs were dosed with either 6 mL/kg BW.75 of MCT, coconut oil (CO), or saline at 10 to 14 and 20 to 28 h after birth. Milk intake (P < .05) and weight gain were reduced (P < .01) in 1- to 2-d-old pigs dosed with MCT compared with intake and gain of pigs dosed with saline. Mortality of large pigs (> 1 kg) was increased (P < .05) but mortality of small pigs (< 1 kg) was not affected by MCT. Mortality of small pigs was reduced (P < .05) but mortality of large pigs (> 1 kg) was not affected by CO. Standing, walking, and suckling behaviors of pigs were not affected by MCT or CO. Coma was evident in 9.7% of pigs dosed with MCT.(ABSTRACT TRUNCATED AT 250 WORDS)

Zellweger syndrome: report of one case.

Zellweger syndrome is a fatal autosomal-recessive hereditary disease characterized by the absence of peroxisomes in liver and kidneys. The absence of peroxisomes results in impairment of many metabolic pathways, especially beta-oxidation of very long chain fatty acids (VLCFAs). We report a case of a three-month-old male infant with facial dysmorphism, hypotonia, psychomotor retardation, and hepatomegaly. He had an elder brother with the same facial features and hypotonia who died of hepatic failure at four months of age. Biochemical studies revealed elevation of blood pipecolic acid and VLCFAs, compatible with peroxisomal disorder. Electron microscopy of liver biopsy revealed absence of peroxisomes. Zellweger syndrome was diagnosed. Because this syndrome is usually fatal in early life, genetic counseling and prenatal diagnosis are crucial.

Essential role of transient receptor potential vanilloid type 1 in evodiamine-mediated protection against atherosclerosis.

AIM: We investigated whether transient receptor potential vanilloid type 1 (TRPV1) was involved in the therapeutic effect of evodiamine, a main bioactive component in the fruit of Evodiae rutaecarpa, on the development of atherosclerosis in apolipoprotein E-deficient (ApoE(-/-)) mice and ApoE(-/-)TRPV1(-/-) mice. METHODS: Histopathology was examined by haematoxylin and eosin staining, levels of cytokines and mediators were evaluated by ELISA kits, and protein expression was determined by Western blotting. RESULTS: Chronic administration with evodiamine (10 mg kg(-1) body weight) reduced the size of atherosclerotic lesions and alleviated the hyperlipidaemia and systemic inflammation, as well as hepatic macrovesicular steatosis, in ApoE(-/-) mice. Treating ApoE(-/-) mice with evodiamine enhanced hepatic cholesterol clearance, as revealed by upregulation of hepatic low-density lipoprotein receptor and ATP-binding cassette (ABC) transporters ABCG5, ABCG8 and cholesterol 7α-hydrolase. Genetic deletion of TRPV1 in ApoE(-/-) mice promoted the progression of atherosclerosis; elevated the serum levels of cholesterol, cytokines and chemokines; and exacerbated hepatic macrovesicular steatosis. Moreover, genetic deletion of TRPV1 abrogated the evodiamine-evoked atheroprotection but not anti-obesity effect in ApoE(-/-) mice. CONCLUSION: Evodiamine may confer novel TRPV1-dependent atheroprotection and TRPV1-independent anti-obesity action.