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A double-stranded RNA (dsRNA) mycovirus from the phytopathogenic fungus Alternaria alternata, which causes watermelon leaf blight, was characterized. The genome of this virus has eight dsRNA segments, ranging from 1039 bp to 2398 bp. DsRNAs 1-6 each contain a single large open reading frame (ORF), while dsRNAs 7 and 8 each dsRNA contain two ORFs. The RNA-dependent RNA polymerase (RdRp) encoded by dsRNA1 and the viral methyltransferase encoded by dsRNA3 share 97.6% and 98.9% amino acid sequence identity, respectively, with the corresponding proteins of Plasmopara viticola lesion associated polymycovirus 1. The dsRNA5-encoded proline-alanine-serine-rich protein shows 48.1% sequence identity to that of Beauveria bassiana polymycovirus 3. The proteins encoded on dsRNAs 2, 4, and 8 have 99.7%, 98.2%, and 65.1% sequence identity, respectively, to the corresponding proteins of a mycovirus identified in Alternaria sp. FA0703 (AltR1). The proteins encoded by dsRNAs 6 and 7 do not match any known proteins of mycoviruses. Phylogenetic analysis of the RdRp domain showed that the virus clustered with members of the family Polymycoviridae. Based on these characteristics, the mycovirus was identified as a polymycovirus and designated as "Alternaria alternata polymycovirus 1" (AaPmV1). This is the first report of a polymycovirus associated with A. alternata.

Objective: To explore the influencing factors and logistic regression characteristics of cryptogenic stroke in patients with positive transcranial doppler bubble test (c-TCD). Methods: A total of 134 cases of cryptogenic stroke that were diagnosed by Tianshui First People’s Hospital from November 2018 to April 2020 were selected according to the TOAST (Trial of ORG 10172 in Acute Stroke Treatment) classification criteria. According to c-TCD results, there were 70 cases of right to left shunt that were included in the positive group and 64 cases without right to left shunt in the negative group. Gender, age, smoking, diabetes, hypertension, and factors affecting the positive rate of foam were analyzed. According to the abnormal embolism scale scores, logistic regression equation was used to analyze the independent influencing factors. Results: The influencing factors of cryptogenic stroke in patients with positive c-TCD were correlated with age, gender, and abnormal embolism scale scores (p < 0.05). For each grade increase in age, the proportion of positive foam test was calculated to be 3.21 times, and the proportion of female to male was calculated to be 2.25 times. For each grade increase in the scores, the proportion of positive foam test was calculated to be 2.55 times. Conclusion: Female, older age, and higher scores in the abnormal embolism scale are the influencing factors for cryptogenic stroke in patients with positive c-TCD.

Watermelon is an economically important crop in China and is commonly affected by Alternaria-like leaf blight that can result in significant economic losses. In this study, 830 Alternaria isolates, recovered from symptomatic watermelon leaves, were identified based on morphological traits, pathogenicity, and multilocus sequence analyses of glyceraldehyde-3-phosphate dehydrogenase (GAPDH), histone 3 (HIS3), the internal transcribed spacer of ribosomal DNA (rDNA ITS), and the RNA polymerase II second largest subunit (RPB2). Watermelon isolates grouped to five Alternaria species and one unclassified Alternaria species. They were A. tenuissima, A. alternata, A. cucumerina, A. infectoria, A. gaisen, and Alternaria sp. Notably, A. tenuissima was the most prevalent (73.5%) of the six isolated species, followed by A. alternata (25.0%), A. cucumerina (1.1%), Alternaria sp. (0.2%), A. infectoria (0.1%), and A. gaisen (0.1%). Pathogenicity tests demonstrated that all six Alternaria species could produce brown necrotic lesions on detached leaves of watermelon. The average disease incidence (75.1%) and average disease index (60.8) of watermelon resulting from inoculation of leaves with A. cucumerina were significantly higher than levels resulting from A. alternata (52.9% and 37.2) and A. tenuissima (47.5% and 30.8). Inoculation with Alternaria sp. resulted in a disease incidence (70.0%) and disease index (51.5), which were lower than those of A. cucumerina. The disease incidence and disease index in watermelon leaves inoculated with the one isolate of A. infectoria and the one isolate of A. gaisen present in the inoculated leaves were 28.9% and 16.4, and 48.9% and 31.4, respectively. Results of the study indicate that Alternaria species associated with watermelon leaf blight in China are more diverse than that has been previously reported. This is the first report globally of A. infectoria, A. gaisen, and an unclassified Alternaria species as causal agents of leaf blight on watermelon.

Background: The triglyceride glucose index (TyG index), a reliable alternative marker of insulin resistance (IR), has been regarded as an independent predictor of cardiovascular disease (CVD). However, the relationship between TyG index and coronary artery disease (CAD) in premenopausal women remains unclear. We aimed to investigate the prognostic value of TyG index in premenopausal women with CAD. Methods: A total of 158 Chinese female subjects were enrolled in this retrospective study. Clinical data were collected from medical records. The severity of CAD was assessed by coronary angiography. CAD was defined as Coronary artery stenosis ≥50% in at least one major coronary artery. Patients were divided into different groups according to their TyG index and whether they had CAD. Multivariate logistic regression model was used to evaluate the relationship between TyG index and CAD. Results: The patients with high TyG index had a higher risk of CAD than those with low TyG index (PP=0.030). Conclusions: Elevated TyG index is associated with increased risk of CAD in Chinese premenopausal women, suggesting that the TyG index may be used as a marker of CAD risk in premenopausal women in China.

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Introduction Deltonin, an active component extracted from Dioscorea zingiberensis C.H. WRIGHT, was widely utilized in traditional Chinese medicines. It has been shown to have anti-cancer functions such as colon cancer, breast cancer, and head and neck squamous carcinoma. Herein, we will investigate the role of deltonin in cerebral ischemia/reperfusion injuries. Methods Ly294002 and anisomycin were used as inhibitors to monitor the effects of deltonin. Middle cerebral artery occlusion I/R model was constructed. Infarct volumes, neurological deficits and brain water contents were evaluated under different conditions. Rotarod test, ELISA, and Western blotting were carried to investigate the effects in vitro. Results We found that deltonin in ischemia/reperfusion (I/R) rats greatly enhanced brain damages as well as neurological functions through up-regulating p-Akt and p-mTOR as well as inhibiting the expressions of LC3-II/LC3-I, Beclin-1, IL-1, TLR4, and p-p38. Deltonin exerted neuroprotection effect through relieving autophagy activity by regulating PI3K/Akt/mTOR signaling. Deltonin suppressed inflammation reactions through modulation TLR4/p38/MAPK signaling as well. Conclusion Overall, our data suggested that deltonin could suppress ischemic brain injury by regulating autophagy and inflammation during I/R. Deltonin can be a potential therapeutic method for patient with I/R.

Cardiorenal syndrome (CRS), a clinical syndrome involving multiple pathological mechanisms, exhibits high morbidity and mortality. According to the primary activity of the disease, CRS can be divided into cardiorenal syndrome (type I and type II), renal heart syndrome (type III and type IV), and secondary heart and kidney disease (type V). The renin-angiotensin-aldosterone system (RAAS) is an important humoral regulatory system of the body that exists widely in various tissues and organs. As a compensatory mechanism, the RAAS is typically activated to participate in the regulation of target organ function. RAAS activation plays a key role in the pathogenesis of CRS. The RAAS induces the onset and development of CRS by mediating oxidative stress, uremic toxin overload, and asymmetric dimethylarginine production. Research on the mechanism of RAAS-induced CRS can provide multiple intervention methods that are of great significance for reducing end-stage organ damage and further improving the quality of life of patients with CRS.

Mycoviruses are widespread in all major groups of plant-pathogenic fungi. So far, only one mycovirus has been reported to be associated with Fusarium pseudograminearum, the causal agent of Fusarium crown rot of wheat. In this study, a double-stranded RNA (dsRNA) segment was isolated from F. pseudograminearum strain JW2-1, and the sequence of its full-length cDNA (3077 nucleotides) was determined. Sequence analysis using the fungal mitochondrial genetic code (UGA coding for tryptophan) indicated that a single large open reading frame (ORF) is present on the positive strand of this dsRNA segment. The ORF encodes a putative RNA-dependent RNA polymerase (RdRp) of 748 amino acids (aa) with a molecular mass of 83.46 kDa. BLASTp analysis revealed that its aa sequence was 28.49-44.03% identical to those of viruses of the family Mitoviridae, with the most similarity to the corresponding RdRp sequences of Ophiostoma mitovirus 1c (44.03% identity) and Ophiostoma mitovirus 1b (40.33% identity). Phylogenetic analysis showed that this mycovirus, designated as "Fusarium pseudograminearum mitovirus 1" (FpgMV1), should be classified as a member of a new species in the earlier proposed genus "Duamitovirus" within the family Mitoviridae. To our best of our knowledge, this is the first report of a mitovirus infecting F. pseudograminearum.

BackgroundThe main purpose is to establish an ideal arrhythmia model with isoproterenol and explore its mechanism.MethodsFifty healthy male SD rats were randomly divided into the control (CON) group, subcutaneous injection (SC) group(ISO 5 mg/kg for 2 consecutive days), intraperitoneal injection (IP) group (ISO 5 mg/kg for 2 consecutive days), 2+1 group (ISO 5mg/kg by SC for 2 consecutive days, then ISO 3mg /kg by IP for 1 day), 6+1 group ( ISO 5mg/kg by SC for 6 consecutive days, then ISO 3mg /kg by IP for 1 day).The ECG were recorded by BL-420F system. The pathological changes in myocardial tissue were observed by HE and Masson staining. The serum cTnI, TNF-α, IL-6, and IL-1β levels were detected by ELISA. Serum CK, LDH and oxidative stress-related indicators were detected by an automatic biochemical analyser. ResultsThe cardiomyocytes in the CON group rats were normal, while those in the other groups showed signs of disorder, unclear borders, and lysis and necrosis, especially in the 6+1 group. The incidence of arrhythmia, arrhythmia score, and the levels of serum myocardial enzymes, troponin, and some inflammatory factors in the 2+1 group and 6+1 group were higher than those in the single injection way (P＜0.01 or P＜0.05). The indicators in the 6+1 group were mostly higher than those in the 2+1 group (P＜0.01), and the SOD level in the 6+1 group was lower than that in the CON group; the MDA and NO higher(P＜0.01 or P＜0.05). Conclusion The combined mode of ISO injection (SC with IP) is more likely to induce arrhythmia than single ISO injection. The "6+1" method of ISO injection can establish a more stable arrhythmia model. Cardiomyocyte damage induced by oxidative stress and inflammation is an important mechanism.

Leaf blight of sunflower caused by Alternaria spp. occurs frequently in the Beijing municipality of China. A total of 482 Alternaria isolates were obtained from sunflower leaves with typical dark f...

Head lettuce (Lactuca sativa L.) is an important crop for fresh consumption in China. In Shandong Province, head lettuce is planted in spring and in autumn each year. Because of the on-and-off rain for three weeks, head lettuce plants planted directly into the field in Jiyang City, in July 2017, 20% of the plants rapidly showed symptoms of rotting, water-soaked lesions on roots and stem bases, and then death. The diseased plants first appeared in low-lying areas prone to water accumulation. One-millimeter pieces were excised from water-soaked roots and stem bases, dipped in a 0.2% calcium hypochlorite solution for 10 min, then placed on V8 medium, and incubated in the dark at 28°C for 5 d. Two Pythium-like strains were isolated from the roots and stems. The isolates transferred to CMA and grown for 7 d, and the morphological characteristics of the two isolates on corn meal agar (CMA) were white with dense, cottony, aerial and well-branched mycelia. The two isolates produced sporangia, oogonia, antheridia and oospores. Most of the sporangia were lobate. The oogonia were smooth, nearly globose and terminal. Oospores were globose, smooth and aplerotic. The average dimensions of 50 oogonia and oospores respectively ranged from 19.5 to 25.2 (av. 23.1) µm and 17.8 to 22.3 (av. 19.9) µm. The antheridia were broadly sac-shaped. The isolates morphological characteristics were consistent with P. aphanidermatum (van der Plaats-Niterink, 1981). The COI gene and ITS region of the rDNA were amplified and sequenced using primers FM55/FM52R (Long et al. 2012) and ITS1/ITS4 (White et al. 1990), respectively. The two aligned COI sequences were identical for both isolates, as were the two ITS sequences. BLASTn analysis of the 1,133-bp COI sequence (accession no. MT952703) resulted in a 100% identity with accession number AY129164 from Lactuca sativa, which belongs to P. aphanidermatum, and the 808-bp ITS sequence (accession no. MT921597) showed a 99% identity with Genbank accession number HQ643442 belonging to P. aphanidermatum. Koch's postulates were conducted by first soaking corn kernels for 24 h in water, and then autoclaving for 2 h at 121˚C. Isolate SDHL-1 was grown on CMA for 10 days, after which agar plugs were transferred to the sterilized corn kernels and incubated at 28℃ for approximately 15 d, until the corn kernels were covered in white hyphae. Ten healthy head lettuce plants were transplanted into a sterilized loam potting soil artificially infested with the corn inoculum (3 g inoculum per 100 g loam mixture). Inoculated plants and noninoculated controls were maintained in a greenhouse at 28°C and 100% relative humidity with a 12-h photoperiod; the experiment was repeated once. All twenty inoculated plants exhibited symptoms within one week similar to those observed. Pythium aphanidermatum was recovered only from the water-soaked roots and stem bases of inoculated plants and the re-isolated cultures again identified based on morphological characteristics and sequencing of the ITS and COI genes. No symptoms were observed on the control plants. Sclerotinia sclerotiorum is reported to cause stem base rot of L. sativa in China (Zhou et al. 2011). To our knowledge, however, this is the first report of root rot of head lettuce caused by Pythium aphanidermatum. Identification of the pathogen will assist in devising strategies to reduce yield loss.

Ventricular arrhythmia (VA) is a highly fatal arrhythmia that involves multiple ion channels. Of all sudden cardiac death events, ~85% result from VAs, including ventricular tachycardia and ventricular fibrillation. Calcium/calmodulin-dependent pro-tein kinase II (CaMKII) is an important ion channel regulator that participates in the excitation-contraction coupling of the heart, and as such is important for regulating its electrophysiological function. CaMKII can be activated in a Ca2+/calmodulin (CaM)-dependent or Ca2+/CaM-independent manner, serving a key role in the occurrence and development of VA. The present review aimed to determine whether activated CaMKII induces early afterdepolarizations and delayed afterdepolarizations that result in VA by regulating sodium, potassium and calcium ions. Assessing VA mechanisms based on the CaMKII pathway is of great significance to the clinical treatment of VA and the de-velopment of effective drugs for use in clinical practice.

Chronic kidney disease (CKD) is a major public health issue that is highly prevalent worldwide. Pyroptosis is an important pathological mechanism underlying kidney cell damage in CKD and is associated with the classic caspase-1-mediated pathway and nonclassic caspase-4/5/11-mediated pathway. The NLRP3-caspase-1-GSDMD signaling pathway is the key mechanism of kidney cell pyroptosis in CKD, and noncoding RNAs such as lncRNAs and miRNAs are important regulators of kidney cell pyroptosis in CKD. In addition, the NLRP1/AIM2-caspase-1-GSDMD and caspase-3-GSDME signaling pathways have also been shown to mediate kidney cell pyroptosis. Traditional Chinese medicine (TCM) and extracts can interfere with the occurrence and development of kidney cell pyroptosis in CKD by inhibiting the NLRP3 signaling pathway and oxidative stress, activating Nrf-2 signaling, protecting mitochondrial integrity, regulating AMPK signaling, and regulating TXNIP/NLRP3 axis, which have become increasingly prominent. It is critical to explore the effects of TCM on kidney cell pyroptosis in CKD and its mechanisms to identify targets and develop new and effective drugs.

Objective. To observe the effect of berberine (BBR) on kidney cell pyroptosis in golden hamsters with diabetic nephropathy (DN) and to explore the molecular mechanism of its renal protection. Methods. Fifty clean-grade male golden hamsters were randomly divided into a control group (10) and a model building group (40). The DN model was established by high-sugar and high-fat feeding and injection of a small amount of STZ. After successful establishment of the model, they were randomly divided into a model group, western medicine group, and berberine high- and low-dose groups. The western medicine group was given irbesartan 13.5 mg/kg, and the berberine high- and low-dose groups were given BBR 200 mg/kg and 100 mg/kg, respectively, for 8 consecutive weeks. An automatic biochemical analyser was used to measure blood glucose, blood lipids, kidney function, MDA, and other indicators; radioimmunoassay was used to assess serum insulin; enzyme-linked immunosorbent assay (ELISA) was used to quantify IL-1β, IL-6, IL-18, TNF-α; HE, PAS, and Masson staining were used to observe kidney pathological tissue morphology; western blot and real-time fluorescent quantitative PCR were used to assess protein and mRNA expression of molecules, such as Nrf2, NLRP3, Caspase-1, and GSDMD; and TUNEL staining was used to detect DNA damage. SPSS statistical software was used for the data analysis. Results. The kidney tissues of golden hamsters in the control group were normal; Nrf2 was highly expressed, serum MDA level was low, NLRP3 expression in kidney tissue was not obvious, Caspase-1 and GSDMD were weakly expressed, and only a few TUNEL-positive cells were observed. Compared with the control group, the golden hamsters in the model group had obvious renal pathological damage; blood glucose, blood lipids, renal function-related indexes, insulin, and inflammatory factors IL-1β, IL-6, IL-18, and TNF-α were increased ( P < 0.05 ); NLRP3, Caspase-1, and GSDMD expression was increased; Nrf2 expression was decreased; MDA level was increased ( P < 0.05 ); and the number of TUNEL-positive cells was increased. Compared with the model group, the pathological morphology of the kidney tissue of golden hamsters in the three treatment groups was significantly improved; blood glucose, blood lipids, renal function, and the expression of inflammatory factors IL-1β and IL-6 were reduced ( P < 0.05 ); NLRP3, Caspase-1, GSDMD, and other molecular proteins and mRNA expression were decreased; Nrf2 expression was increased; MDA level was decreased ( P < 0.05 ); and the number of TUNEL-positive cells was decreased. Conclusion. DN golden hamster kidney NLRP3-Caspase-1-GSDMD signalling was enhanced. BBR can reduce oxidative stress damage by regulating antioxidative Nrf2 and then regulating NLRP3-Caspase-1-GSDMD signalling to inhibit pyroptosis, antagonizing DN inflammation-induced damage.

Watermelon is an economically important crop in China and is commonly affected by

Transgenic therapy for central neuralgia faces the problems of low expression and weak targeting and affects superficial but not deep neurons. In this study, we generated a lentivirus vector with human preproenkephalin gene (hPPE) expression driven by the transcriptional amplification strategy system (TAS) and established a primary bone marrow-derived mesenchymal stromal cell (BMSC) line stably expressing hPPE for transplantation into a rat model of neuropathic pain rat. The paw thermal withdrawal latency assay and paw mechanical withdrawal threshold assay showed that unlike control BMSCs and BMSCs with hPPE overexpression driven by the CMV or Synapsin 1 (SYN1) promoter, TAS-hPPE BMSCs had a robust and lasting analgesic effect. The TAS-hPPE BMSC-treated group exhibited higher expression of TAS-driven hPPE and a higher ratio of BMSCs in the midbrain, spinal cord and cortex then the CMV-hPPE BMSC- and SYN1-hPPE BMSC-treated groups. Moreover, we also observed that TAS-hPPE BMSCs displayed a greater tendency to differentiate into neurons and exhibit neuronal-like distribution than CMV-hPPE or SYN1-hPPE BMSCs. In conclusion, our study shows that the TAS improves BMSC transgenic therapy for neuropathic pain treatment.

Potato leaves with symptoms of foliar diseases were collected from eight different geographical areas in southern China. A total of 109 Alternaria isolates were recovered and identified to three sp...

A total of 32,284 unigenes were obtained from the transcriptome of Alternaria tenuissima, a pathogenic fungus causing foliar disease in tomato, using next-generation sequencing (NGS) technology. In total, 24,670 unigenes were annotated using five databases, including NCBI non-redundant protein, Swiss-Prot, euKaryotic Orthologous Groups, Kyoto Encyclopedia of Genes and Genomes, and the Gene Ontology. A total of 1,140 simple sequence repeats were also identified for use as molecular markers. Sixteen of the simple sequence repeat loci were selected to study the population structure of A. tenuissima. A population genetic analysis of 191 A. tenuissima isolates, sampled from four geographic regions in China, indicated that A. tenuissima had a high level of genetic diversity, and that the selected simple sequence repeat markers could reliably capture the genetic variation. The null hypothesis of random mating was rejected for all four geographic regions in China. Isolation by distance was observed for the entire data set, but not within clusters, which is indicative of barriers to gene flow among geographic regions. The analyses of Bayesian and principal coordinates, however, did not separate four geographic regions into four separate genetic clusters. The different levels of historical migration rates suggest that isolation by distance did not represent a major biological obstacle to the spread of A. tenuissima. The potential epidemic spread of A. tenuissima in China may occur through the transport of plant products or other factors. The presented results provide a basis for a comprehensive understanding of the population genetics of A. tenuissima in China.

Background: About 5-10% of all myocardial infarction patients undergoing diagnostic coronary angiography for typical chest pain have no significant coronary stenosis (stenosis severity

A total of 41 Alternaria isolates was recovered from diseased muskmelon leaves with foliar disease symptoms, which were collected from Beijing municipality of China. Thirty-one isolates were identified as Alternaria tenuissima and 10 isolates as A. alternata based on morphological traits, ITS and histone 3 nucleotide sequences. The Alternaria isolates induced the original symptoms including chlorosis and brown lesions on detached muskmelon leaves, with disease incidence ranging from 33.3 to 87.5 %. No significant differences in disease index were detected between the two species. This is the first report of A. tenuissima causing foliar diseases on muskmelon plants in Beijing.

The Ce-TiO 2 /KL (diatomite) ball photocatalyst was prepared and characterized based on the pretreated diatomite. The results showed that comparing with the crude diatomite, proper pretreatment could significantly improve its SiO 2 purity and specific surface area. The surface of diatomite was clear with uniform pore structure and big pore size. With diatomite ball as carrier, the supported Ce-TiO 2 /KL ball photocatalyst was prepared by sol-gel method. The photocatalytic performances of the supported Ce-TiO 2 / KL ball and Ce-TiO 2 /KL powder photocatalysts under various preparation conditions were studied in view of photocatalytic degradation rate of Rhodamine B (Rh B) solution. The degradation rate of the ball photocatalysts for Rh B reached 94.6% and could be reused for many times, which showed much better photocatalytic performance and stability than powder photocatalysts.

Objective Postoperative chronic pain is characterized by high incidence, long duration, and complex pathogenesis. The purpose of this study was to investigate the correlation between the single nucleotide polymorphisms of the CCL2 gene rs4586 (g.5974T>C), CALCA rs3781719 (-692T>C), CX3CL1 rs614230 (2342C>T), and the risk of postoperative chronic pain in Chinese Han women. Methods We analyzed the CCL2 gene rs4586, CALCA rs3781719, CX3CL1 rs614230 single nucleotide polymorphism (SNPs) of 350 Chinese Han women with chronic postsurgical pain (CPSP) 6 months after cesarean section and 350 healthy women without chronic pain (HC). The levels of CCL2, CALCA, and CX3CL1 in serum were detected by enzyme-linked immunosorbent assay (ELISA). Results The CCL2 rs4586 T allele and the CX3CL1 gene rs614230C allele were protective factors for CPSP risk (adjusted OR = 0.766, 95% CI: 0.675-0.865 and OR = 0.336, 95% CI: 0.644-0.835). The CALCA gene rs3781719C allele was a risk factor for CPSP (adjusted OR = 1.273, 95% CI: 1.125-1.424). CCL2 rs4586, CX3CL1 gene rs614230, and CALCA gene rs3781719 locus gene polymorphisms were associated with serum CCL2, CX3CL1, and CALCA protein levels. Conclusion Our results support that CCL2 gene rs4586, CALCA rs3781719, CX3CL1 rs614230 gene polymorphism are associated with the occurrence of chronic pain after cesarean section in Chinese Han women.

Objective Rheumatoid arthritis (RA) synovial hyperplasia is related in part to a resistance to apoptosis exhibited by fibroblast-like synoviocytes (FLS). Since hypoxia is a regulator of apoptosis, and since RA synovium is hypoxic, we conducted this study to examine the effects of hypoxia on the Bcl-2 pathway and the role this may play in regulating apoptosis in FLS. Methods Synovium samples from RA patients, osteoarthritis (OA) patients, and normal subjects were used for immunohistologic assessments and for generating FLS lines in vitro. FLS were stimulated under conditions of hypoxia (1% O2) and using 100 μM CoCl2 to simulate the effects of severe hypoxia. Changes in the gene expression profile of FLS were evaluated using microarrays and were confirmed by quantitative polymerase chain reaction (PCR). Changes in protein expression were detected by Western blotting. The effect of transient transfection with a BNIP3 plasmid on the apoptosis of FLS was evaluated in the presence and absence of cytokines. Results Gene expression profiling demonstrated that BNIP3 was unique among the BCL2 family, in that it was induced by hypoxia in FLS. Quantitative PCR indicated a 2–3-fold induction of BNIP3 messenger RNA, and Western blotting showed a 3–5-fold increase in the 30-kd Bcl-2/adenovirus E1B 19-kd protein–interacting protein 3 (BNIP-3) monomer. BNIP-3 was widely expressed in RA synovium and was prominent in FLS from the lining layer. Overexpression of BNIP3 increased FLS apoptosis under hypoxic conditions, an effect that was inhibited by tumor necrosis factor α and interleukin-1β. Conclusion The proapoptotic protein BNIP-3 is induced in FLS by hypoxia and is widely expressed in RA synovium, but its proapoptotic effects may be inhibited in vivo by proinflammatory cytokines. Since overexpression of BNIP3 in FLS increases apoptosis, this may provide a novel approach for controlling synovial hyperplasia in RA.

Bronchial rupture occurred during bronchoscopic visualization and extraction of a fishbone from the bronchus in a 2-year-old male patient with a 5-month history of foreign body aspiration. Emergency thoracotomy was scheduled for examination and surgical repair of the bronchus. The pressure of the airway and circuit fell sharply and ventilation could not be maintained after muscle relaxants were injected and spontaneous respiration ceased. Oxygenation worsened rapidly with the peripheral oxygen saturation level decreasing below 60%. An endotracheal tube was inserted into one of the main bronchi. Peripheral oxygen saturation improved from 60% to 90%, and subsequent surgery was performed without complications.

Objective Stromal cell–derived factor 1 (SDF-1; or, CXCL12) is a potent chemotactic and angiogenic factor that has been proposed to play a role in the recruitment of lymphocytes into rheumatoid arthritis (RA) synovium. We tested the hypothesis that synovial SDF-1 expression is regulated by cytokine and hypoxic stimulation, the latter being mediated by hypoxia-inducible factor 1α (HIF-1α). These factors regulate the expression of vascular endothelial growth factor (VEGF), itself an important angiogenic mediator. Methods RA and osteoarthritic synovial fibroblasts and whole tissue explants were cultured under normoxic or hypoxic (1% O2) conditions for up to 72 hours in the presence or absence of interleukin-1β (IL-1β), tumor necrosis factor (TNF), or transforming growth factor β (TGFβ). Expression of HIF-1α, VEGF, and SDF-1 was detected in synovial tissue and cells by immunohistochemistry and Western blotting. VEGF and SDF-1 expression by cultured synovial fibroblasts was evaluated by reverse transcription–polymerase chain reaction and enzyme-linked immunosorbent assay. Results Immunohistochemistry revealed the presence of HIF-1α, VEGF, and SDF-1 in RA synovium. Patchy expression of HIF-1α was detected primarily in the synovial lining and sublining areas; expression in synovial fibroblasts and in the lining cells of whole synovial tissue explants was markedly augmented by hypoxic culture conditions. Hypoxia enhanced the expression of VEGF and SDF-1 messenger RNA in synovial fibroblasts. The production of VEGF and SDF-1 protein by synovial fibroblasts was augmented by 50% and 132%, respectively, after 24 hours of hypoxia. VEGF production was potently induced by TGFβ, and to a lesser extent by IL-1β and TNF, and was further augmented by hypoxia. In contrast, none of the tested cytokines induced SDF-1 production. Conclusion As with VEGF, SDF-1 expression is induced by hypoxia; however, cytokines induce VEGF but not SDF-1. Hypoxic conditions in RA synovium, which are likely to be transient and episodic, may contribute to the persistence of synovitis by inducing VEGF and SDF-1.