[A report of 7 cases of toxic liver disease caused by mixed gas in a shoe factory].

Trichloromethane and dichloromethane have toxic effects on the liver, and incidents of toxic liver disease caused by them have been reported from time to time. In November 2021, an occupational chemical poisoning incident occurred in a shoe factory in Huidong County, Guangdong Province. After testing the air at the scene and analyzing the clinical data of the poisoning patients, it was preliminarily determined that the poisoning was caused by a mixed gas poisoning incident dominated by trichoromethane. At admission, the liver function of 7 patients was tested for different degrees of impairment (alanine aminotransferase 145-2501 IU/L, aspartate aminotransferase 66-1286 IU/L). The volatile organic components of on-site raw and auxiliary materials were analyzed. The percentages of trichloromethane and dichloromethane detected in 103A powder glue used in the poisoning workshop site accounted for 21.11% and 6.77% respectively.

Impact of meteorological and geographical factors on the distribution of Phlebotomus chinensis in northwestern mainland China.

Phlebotomine sandflies (Diptera: Phlebotomidae) are vectors of the zoonotic disease leishmaniasis. To better understand the distribution of phlebotomine sandflies in order to facilitate control of leishmaniasis transmission, the present study explored the impacts of climate and landscape on local abundances of Phlebotomus chinensis in northwestern mainland China. Identification records were used to create a geodatabase for the locations at which P. chinensis had been collected in the region, and a regional-scale map was developed to show the distribution of P. chinensis. Location data and data on environmental factors during the years in which the samples were collected were incorporated, and a presence-only modelling method was used to evaluate the species' habitat preferences and to predict its potential distribution in northwestern mainland China. Jackknife analysis revealed that several meteorological variables, including maximum temperature in the warmest quarter, precipitation in the driest month, daily average temperature and daily precipitation, significantly affected the presence of this species. Moreover, the presence of P. chinensis was significantly associated with grassland and shrubland. Probability distributions using maximum entropy were used to map the distribution ranges of P. chinensis based on suitable habitats in northwestern mainland China. The models generated can be used to develop detailed strategies for the prevention and control of leishmaniasis.

[Impairments of gray matter in MRI-negative epileptic patients with different seizure types].

Objective: To investigate the damage of gray matter structure in MRI-negative epilepsy patients with different symptoms by voxel-based morphometry (VBM). Methods: From June, 2009 to October, 2016, ninety MRI-negative epilepsy patients and thirty-five healthy volunteers underwent the 3T magnetic resonance imaging scan in Nanjing General Hospital. The patients were divided into three groups, including idiopathic generalized tonic-clonic seizure (I-GTCS), secondarily generalized tonic-clonic seizure (S-GTCS), and partial seizure (PS) according to different symptoms. The three-dimensional high-resolution T1 structural MRI data was obtained for the voxel-based morphometry. Data of gray matter structure from four groups were compared using one-way analysis of variance (ANOVA). An independent-sample t test was performed in order to compare gray matter volume of the three patient groups with controls respectively. According the results of ANOVA, impaired brain regions were selected as regions of interest in order to carry out correlation analysis between gray matter volume and disease duration. Results: ANOVA showed significant differences in gray matter structure of bilateral thalamus and frontal lobe between four groups (alphasim correction, P<0.01). Independent-sample t test showed that the volume of bilateral thalamus and frontal lobe decreased in all three patients groups (alphasim correction, P<0.01) .The volume of bilateral thalamus showed significantly negatively correlation with disease duration in I-GTCS patients (r=-0.466, P<0.01). Conclusions: Generalized seizures and partial seizures all can cause damage to the gray matter structure, especially in thalamus and frontal lobe. The impairments of thalamus and frontal lobe in patients with different seizure types are different with the progression of disease, which suggests that influences of different epilepsy seizures on the thalamo-cortical network are different.

The transformer genes in the fig wasp Ceratosolen solmsi provide new evidence for duplications independent of complementary sex determination.

Transformer (tra) is the key gene that turns on the sex-determination cascade in Drosophila melanogaster and in some other insects. The honeybee Apis mellifera has two duplicates of tra, one of which (complementary sex determiner, csd) is the primary signal for complementary sex-determination (CSD), regulating the other duplicate (feminizer). Two tra duplicates have been found in some other hymenopteran species, resulting in the assumption that a single ancestral duplication of tra took place in the Hymenoptera. Here, we searched for tra homologues and pseudogenes in the Hymenoptera, focusing on five newly published hymenopteran genomes. We found three tra copies in the fig wasp Ceratosolen solmsi. Further evolutionary and expression analyses also showed that the two duplicates (Csoltra-B and Csoltra-C) are under positive selection, and have female-specific expression, suggesting possible sex-related functions. Moreover, Aculeata species exhibit many pseudogenes generated by lineage-specific duplications. We conclude that phylogenetic reconstruction and pseudogene screening provide novel evidence supporting the hypothesis of independent duplications rather an ancestral origin of multiple tra paralogues in the Hymenoptera. The case of C. solmsi is the first example of a non-CSD species with duplicated tra, contrary to the previous assumption that derived tra paralogues function as the CSD locus.

Diversity and evolution of Ty1-copia retroelements within Chalcidoidea by reverse transcriptase domain analysis.

Ty1-copia retrotransposons are widespread and diverse in insects. Some features of their hosts, such as mating and genetic systems, are predicted to influence the spread of selfish genetic elements like Ty1-copia. Using part of the reverse transcriptase gene as a reference, we experimentally surveyed Ty1-copia elements in eight species of fig wasps (Hymenoptera: Chalcidoidea), and performed an in silico analysis of six available genomes of chalcid wasps. Contrary to initial expectations that selfish elements such as Ty1-copia would be purged from the genomes of these species because of inbreeding and haplodiploidy, almost all of these wasps harbour an abundance of diverse Ty1-copia elements. Phylogenetic analyses suggest that the families of Ty1-copia elements found in these species have had a long association with their chalcid hosts. These results suggest an evolutionary scenario in which there was ancestral polymorphism followed by some taxa-specific events including stochastic loss and further diversification. Furthermore, estimating natural selection within the internal and terminal portions of the Ty1-copia phylogenies demonstrated that the elements are under strong evolutionary constraints for their long-term survival, but evolve like pseudogenes in the short term, accompanied by the rise and fall of parasitic elements in the history of wasp lineage.

Association between the rs3795879 G/A polymorphism of the SERPINE2 gene and chronic obstructive pulmonary disease: a meta-analysis.

The present study aimed to investigate the effects of the rs3795879 polymorphism of the SERPINE2 gene on the development of chronic obstructive pulmonary disease (COPD) based on a systematic meta-analysis. An extensive literature search was performed to retrieve previously published case-control studies on the polymorphisms of SERPINE2 in COPD patients. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the association between SERPINE2 polymorphisms and risk of developing COPD. A total of 5 studies including 3034 COPD cases and 3068 controls were incorporated in the present meta-analysis. Generally, no significant association was identified between the rs3795879 polymorphism of SERPINE2 and the risk of developing COPD (G allele vs A allele: OR = 1.23, 95%CI = 0.97-1.32; GG vs GA: OR = 1.19, 95%CI = 0.81-1.76; GG vs AA: OR = 1.23, 95%CI = 0.89-1.70; dominant model: OR = 1.18, 95%CI = 0.85- 1.62; recessive model: OR = 1.19, 95%CI = 0.85-1.66). In addition, subgroup analyses according to different ethnicities and the source of controls suggest no statistically significant association between the rs3795879 polymorphism of SERPINE2 and COPD risk. The results suggest that the rs3795879 polymorphism of SERPINE2 is not a risk factor for COPD.

Odorant-binding protein (OBP) genes affect host specificity in a fig-pollinator mutualistic system.

The interaction between figs and their pollinating wasps is regarded as a model system for studying specialized co-evolved mutualism. Chemoreception of fig wasps plays an important role in this interaction, and odorant-binding proteins (OBP) function in the first step of odorant detection. The OBP repertoire of the fig wasp Ceratosolen solmsi is reported to be one of the smallest among insects; however, it is unknown how these OBPs are related to the complicated mating process occurring within the fig cavity and the extreme host specificity of the species. In the present study, we combined a structural analysis of the conserved cysteine pattern and motif order, a phylogenetic analysis, and previous studies on ligand-binding assays to deduce the function of OBPs. We also quantified the expression of OBP genes in different life stages of female and male fig wasps by using real-time quantitative PCR, which can help to predict the function of these genes. The results indicated that CsolOBP1 and CsolOBP2 (or CsolOBP5) in males may bind to pheromones and play important roles in mate choice, whereas CsolOBP4 and CsolOBP5 may primarily function in host localization by females through binding of volatile compounds emitted by receptive figs.

Multiple ancient horizontal gene transfers and duplications in lepidopteran species.

Eukaryotic horizontal gene transfer (HGT) events are increasingly being discovered yet few reports have summarized multiple occurrences in a wide range of species. We systematically investigated HGT events in the order Lepidoptera by employing a series of filters. Bombyx mori, Danaus plexippus and Heliconius melpomene had 13, 12 and 12 HGTs, respectively, from bacteria and fungi. These HGTs contributed a total of 64 predicted genes: 22 to B. mori, 22 to D. plexippus and 20 to H. melpomene. Several new genes were generated by post-transfer duplications. Post-transfer duplication of a suite of functional HGTs has rarely been reported in higher organisms. The distributional patterns of paralogues for certain genes differed in the three species, indicating potential independent duplication or loss events. All of these HGTs had homologues expressed in some other lepidopterans, indicating ancient transfer events. Most HGTs were involved in the metabolism of sugar and amino acids. These HGTs appeared to have experienced amelioration, purifying selection and accelerated evolution to adapt to the background genome of the recipient. The discovery of ancient, massive HGTs and duplications in lepidopterans and their adaptive evolution provides further insights into the evolutionary significance of the events from donors to multicellular host recipients.

Apis mellifera has two isoforms of cytoplasmic HSP90.

Unlike most other insects, annotated genomic data suggest that Apis mellifera has two homologous copies of the cytoplasmic gene HSP90. In this study, we did a phylogenetic analysis on these two copies with some other insects HSP90 genes, and we also manipulated a reverse transcript (RT)-PCR to find all the putative transcripts for both copies. Phylogenetic analysis indicates that A. mellifera possesses two isoforms of cytoplasmic HSP90: The 'traditional' isoform clusters with cytoplasmic HSP90 of other insects. The other isoform, which occurs phylogenetically as the sister group of all insects, may be a new gene and specific to A. mellifera. The results of RT-PCR indicate that this new isoform contains at least eight transcripts derived from the same genomic locus by complicated alternative splicing (GenBank accession numbers: FJ713701, FJ713702, FJ713703, FJ713704, FJ713705, FJ713706, FJ713707 and FJ713708, respectively). The existence of this specific HSP90 might be related to the caste differentiation of bees.

[A multicenter study of the condition of children's rheumatic disease associated medical resources in Fujian province].

Objective: To investigate general condition of children's rheumatic disease associated medical resources in Fujian Province. Methods: This questionnaire-based survey was conducted in 19 hospitals in Fujian province from December 2, 2018 to May 1, 2019. The questionnaire was designed to survey the general condition of the medical resources and the hospitalization of patients with rheumatic diseases from January 1, 2014 to December 1, 2018. Results: In the 19 hospitals, there were 15 general hospitals and 4 children's hospitals, and only 5 hospitals had children's rheumatic specialist clinic. There were only 53-62 beds for rheumatic disease patients in the 19 hospitals, accounting for 1.7%-2.0% of the total inpatient beds (3 137). There are 29 pediatric rheumatologists in total, accounting for 2.6% (29/1 120) of the total pediatricians. In the past five years, 613 patients with rheumatic diseases, accounting for 0.1% (613/625 214) of total hospitalized patients, were treated in these hospitals. Among them, 201 had juvenile idiopathic arthritis, 295 had systemic lupus erythematosus, 39 had dermatomyositis, 7 had scleroderma, and 57 had inflammatory bowel disease, 9 had Sjogren's syndrome, 5 had Behcet's disease, and none had overlap syndrome or mixed connective tissue disease. Conclusion: The medical resources of children rheumatic diseases in Fujian province are insufficient which need to be developed.

Porphyrin with amino acid moieties: a tumor photosensitizer.

A porphyrin with amino acid moieties was synthesized in this work, which may be a latent photosensitizer for photodynamic therapy (PDT). Adler's strategy was used to synthesize meso-tetra (4-nitrophenyl) porphyrin (TNPP) through cyclolization of 4-nitrobenzaldhyde and pyrrole in refluxed nitrobenzene. Reduction of TNPP yielded meso-tetra(4-aminophenyl) porphyrin (TAPP). The synthesis was improved by employing lactic acid as a catalyst. Based on TAPP, porphyrin with valine (TAPP-4Val) was obtained. The application of the resultant TAPP-4Val as tumor photosensitizer on human breast tumor cells for photodynamic therapy (PDT) was preliminarily explored. Dark-toxicity evaluations showed that, under a concentration at up to 6 x 10(-6) M, the survival of MCF-7 cells was larger than 90%, which means TAPP-4Val is almost of non-cytotoxicity. However, TAPP-4Val showed remarkable phototoxicity after visible light irradiation. Effects of irradiation time on the survival of cells under typical concentrations of TAPP-4Val were also studied. The new porphyrin with amino acid moieties, TAPP-4Val, is of high phototoxicity but minimal or no dark-toxicity, which can be used as an effective photosensitizer for PDT.

Transcriptional activation by simian virus 40 large T antigen: interactions with multiple components of the transcription complex.

Simian virus 40 (SV40) large T antigen is a potent transcriptional activator of both viral and cellular promoters. Within the SV40 late promoter, a specific upstream element necessary for T-antigen transcriptional activation is the binding site for transcription-enhancing factor 1 (TEF-1). The promoter structure necessary for T-antigen-mediated transcriptional activation appears to be simple. For example, a promoter consisting of upstream TEF-1 binding sites (or other factor-binding sites) and a downstream TATA or initiator element is efficiently activated. It has been demonstrated that transcriptional activation by T antigen does not require direct binding to the DNA; thus, the most direct effect that T antigen could have on these simple promoters would be through protein-protein interactions with either upstream-bound transcription factors, the basal transcription complex, or both. To determine whether such interactions occur, full-length T antigen or segments of it was fused to the glutathione-binding site (GST fusions) or to the Gal4 DNA-binding domain (amino acids 1 to 147) (Gal4 fusions). With the GST fusions, it was found that TEF-1 and the TATA-binding protein (TBP) bound different regions of T antigen. A GST fusion containing amino acids 5 to 172 (region T1) efficiently bound TBP. TEF-1 bound neither region T1 nor a region between amino acids 168 and 373 (region T2); however, it bound efficiently to the combined region (T5) containing amino acids 5 to 383.(ABSTRACT TRUNCATED AT 250 WORDS)

Isolation and expression of GA 2-oxidase2 in tomato.

GA 2-oxidases, a key enzyme involves GA biosynthesis, catalyze the degradation of active C(19)-Gibberellins (GAs) through 2-hydroxylation yields inactive GA product. Searching public tomato database, the putative GA2ox2 sequences were assembled. We isolated a full-length GA2ox2 cDNA with primers designed from the assembled sequence. This gene was designed as SlGA2ox2 (GenBank accession No. EF017805). The full-length GA2ox2 gene contained a complete open reading frame (ORF) of 1203 bp, which encoded 322 amino acid residues. Amino acid sequence homology analysis of SlGA2ox2 showed an 88% identity with NtGA2ox2 in tobacco. And alignments of SlGA2ox2 with other known GA2ox from Arabidopsis, Pea, Adzuki Bean, Winter Squash etc indicate low similarity of 47-70%. Semi-quantitative RT-PCR analysis showed a specific expression profile of SlGA2ox2 in different tissues, which mainly expressed in flowers and traces were detected in roots, stems, leaves and immature fruits.

Temporally-controlled site-specific mutagenesis in the basal layer of the epidermis: comparison of the recombinase activity of the tamoxifen-inducible Cre-ER(T) and Cre-ER(T2) recombinases.

Conditional DNA excision between two LoxP sites can be achieved in the mouse using Cre-ER(T), a fusion protein between a mutated ligand binding domain of the human estrogen receptor (ER) and the Cre recombinase, the activity of which can be induced by 4-hydroxy-tamoxifen (OHT), but not natural ER ligands. We have recently characterized a new ligand-dependent recombinase, Cre-ER(T2), which was approximately 4-fold more efficiently induced by OHT than Cre-ER(T) in cultured cells. In order to compare the in vivo efficiency of these two ligand-inducible recombinases to generate temporally-controlled somatic mutations, we have engineered transgenic mice expressing a LoxP-flanked (floxed) transgene reporter and either Cre-ER(T) or Cre-ER(T2) under the control of the bovine keratin 5 promoter that is specifically active in the epidermis basal cell layer. No background recombinase activity could be detected, while recombination was induced in basal keratinocytes upon OHT administration. Interestingly, a dose-response study showed that Cre-ER(T2) was approximately 10-fold more sensitive to OHT induction than Cre-ER(T).

1,25-Dihydroxyvitamin D3 increases nuclear vitamin D3 receptors by blocking ubiquitin/proteasome-mediated degradation in human skin.

1,25-Dihydroxyvitamin D3 (D3) exerts its effects by binding to and activating nuclear vitamin D3 receptors (VDRs) that regulate transcription of target genes. We have investigated regulation of VDR levels in human skin in vivo and in cultured human keratinocytes. Quantitative ligand-binding analysis revealed that human skin expressed approximately 220 VDRs per cell, which bound D3 with high affinity [(dissociation constant (Kd) = 0.22 nM]. In human skin nuclear extracts, VDR exclusively bound to DNA containing vitamin D3 response elements as heterodimers with retinoid X receptors. Topical application of D3 to human skin elevated VDR protein levels 2-fold, as measured by both ligand-binding and DNA-binding assays. In contrast, the D3 analog calcipotriene had no effect on VDR levels. Topical D3 had no effect on VDR mRNA, indicating that D3 either stimulated synthesis and/or inhibited degradation of VDRs. To investigate this latter possibility, recombinant VDRs were incubated with skin lysates in the presence or absence of D3. The presence of D3 substantially protected VDRs against degradation by human skin lysates. VDR degradation was inhibited by proteasome inhibitors, but not lysosome or serine protease inhibitors. In cultured keratinocytes, D3 or proteasome inhibitors increased VDR protein without affecting VDR mRNA levels. In cells, VDR was ubiquitinated and this ubiquitination was inhibited by D3. Proteasome inhibitors in combination with D3 enhanced VDR-mediated gene expression, as measured by induction of vitamin D3 24-hydroxylase mRNA in cultured keratinocytes. Taken together, our findings indicate that low VDR levels are maintained, in part, through ubiquitin/proteasome-mediated degradation and that low VDR levels limit D3 signaling. D3 exerts dual positive influences on its nuclear receptor, simultaneously stimulating VDR transactivation activity and retarding VDR degradation.

Retinoid X receptor-specific ligands synergistically upregulate 1, 25-dihydroxyvitamin D3-dependent transcription in epidermal keratinocytes in vitro and in vivo.

We have examined the mechanism by which endogenous retinoid X receptor (RXR), vitamin D3 receptor (VDR), and cognate ligands regulate nuclear 1,25-dihydroxyvitamin D3 (D3) signaling in epidermal keratinocytes from skin, a physiologic D3 target. In vitro, RXR and VDR-specific antibodies identified endogenous RXR and VDR bound to a vitamin D3-responsive element (DR3) as heterodimers (VDR-RXR). In cultured keratinocytes, 9-cis retinoic acid (9cRA), a panagonist for RXR and retinoic acid receptor (RAR), and an RXR-selective agonist, SR11237, synergized with D3 to activate DR3 via endogenous as well as overexpressed VDR-RXR, whereas both of these RXR agonists alone were ineffective. In contrast, SR11237 did not synergize with but antagonized an RAR-selective ligand activation of a retinoic acid-responsive element (DR5) via endogenous RAR-RXR. Furthermore, expression of RXR mutated in transactivation domain AF-2 inhibited endogenous VDR-RXR activity over DR3. This mutant efficiently bound to DR3 as VDR-RXR but showed reduced capacity to transactivate DR3 in response to D3 and SR11237. In vivo, D3 and SR11237 synergistically induced the naturally occurring D3-responsive 24-hydroxylase gene in epidermis of mouse skin, whereas SR11237 alone was ineffective. Our data suggest that allosteric changes caused by VDR in DR3-bound VDR-RXR do not block access of ligands to RXR. RXR ligand-induced conformational changes permit VDR-RXR, via both VDR and RXR activation function domains, to mediate maximal D3 signaling in keratinocytes.

Keratinocyte-specific retinoid regulation of human cellular retinoic acid binding protein-II (hCRABPII) gene promoter requires an evolutionarily conserved DR1 retinoic acid-responsive element.

Transcription of the hCRABPII gene is retinoid inducible in human skin keratinocytes (KC) but, surprisingly, not in cultured cells. The promoter for the gene harbors three putative nuclear receptor binding sites: DR5, upstream of the transcription start site; DR1 (DR1d), distal to the site; and DR1 (DR1p), a proximal variant. DR1d, but not DR1p, is conserved between human and mouse. Although DR5 has been found to be a retinoid receptor target in COS-1 cells, the function of DR1 remains unknown. We examined the functions of these DR in retinoid regulation of the hCRABPII promoter in human KC. In reporter gene assays, no significant retinoid response was observed in the promoter in cultured KC; however, overexpression of retinoid receptor heterodimers RARgamma x RXRalpha restored the response. Gel supershift assays showed that endogenous RARgamma x RXRalpha levels are much lower in cultured KC than in skin in vivo. Ligand-binding assays showed that cultured KC contain only one-third of the level of retinoic acid receptor (RAR) and one-eighth of the level of retinoid X receptor found in KC in skin. Deletion of the DR1d or DR5 sites reduced retinoid-induced promoter activity by 63% and 27%, respectively. Isolated DR1d and DR5 sites, but not DR1p, efficiently bound RARgamma-RXRalpha and conferred RAR-selective retinoid responsiveness on a heterologous promoter. These data indicate that: (i) the previously reported lack of retinoid regulation of endogenous hCRABPII gene transcription in cultured KC is likely due to insufficient levels of RARgamma x RXRalpha, but not their cofactors; (ii) the conserved DR1d site is the major functional target in RARgamma x RXRalpha regulation of hCRABPII in KC; (iii) the DR1p site is nonfunctional due to its lack of affinity for RARgamma x RXRalpha, although its half-sites share high sequence homology with the consensus retinoid receptor-binding half-site.

[Accidental methyl alcohol poisoning].

An accidental poisoning due to drinking methyl alcohol in Chaoyang county is reported, analysing the accident. The poison came from the "retail white spirit" which was contaminated with methyl alcohol. Twenty-nine persons drank the wine, fourteen of them died, two of them became blind. After drinking this "retail white spirit" the drinkers showed symptoms of vertigo, headache, weakness, vomiting, night sweat, dyspnea and blurring of vision etc. within 6-120 hours. On examining the remaining spirit, we found the content of methyl alcohol to be between 16.6 and 40.69 g/100 ml. Some of the patients' urine and blood also contained methyl alcohol. We reckoned that each one of the twenty patients had taken more than 27 g of methyl alcohol and each of the ten dead drank more than 40 ml of the alcohol.

[Comparison of the repetitive DNA sequences between Paragonimus westermani and Pagumogonimus skrjabini from six areas].

The genomic DNA of the two lung flukes (P. westermani and P. skrjabini) from six areas was digested separately by three restriction endonucleases BamHI, Hae III and Hind III, followed by agarose gel electrophoresis. Repetitive DNA were visualized as distinct bands in stained gels. Restriction fragment length differences were detected between the two species. The majority of bands of repetitive DNA were similar with minor differences within the same species collected from different areas, upon digestion with certain restriction endonucleases. The results demonstrated that the technique for demonstrating the band pattern of repetitive DNA with three restriction endonucleases can be used for the identification of P. westermani and P. skrjabini and the geographic relationship of the same species from different areas (Figs. 1-3).