Roles of Thermosensitive Transient Receptor Channels TRPV1 and TRPM8 in Paclitaxel-Induced Peripheral Neuropathic Pain.

Paclitaxel, a microtubule-stabilizing chemotherapy drug, can cause severe paclitaxel-induced peripheral neuropathic pain (PIPNP). The roles of transient receptor potential (TRP) ion channel vanilloid 1 (TRPV1, a nociceptor and heat sensor) and melastatin 8 (TRPM8, a cold sensor) in PIPNP remain controversial. In this study, Western blotting, immunofluorescence staining, and calcium imaging revealed that the expression and functional activity of TRPV1 were upregulated in rat dorsal root ganglion (DRG) neurons in PIPNP. Behavioral assessments using the von Frey and brush tests demonstrated that mechanical hyperalgesia in PIPNP was significantly inhibited by intraperitoneal or intrathecal administration of the TRPV1 antagonist capsazepine, indicating that TRPV1 played a key role in PIPNP. Conversely, the expression of TRPM8 protein decreased and its channel activity was reduced in DRG neurons. Furthermore, activation of TRPM8 via topical application of menthol or intrathecal injection of WS-12 attenuated the mechanical pain. Mechanistically, the TRPV1 activity triggered by capsaicin (a TRPV1 agonist) was reduced after menthol application in cultured DRG neurons, especially in the paclitaxel-treated group. These findings showed that upregulation of TRPV1 and inhibition of TRPM8 are involved in the generation of PIPNP, and they suggested that inhibition of TRPV1 function in DRG neurons via activation of TRPM8 might underlie the analgesic effects of menthol.

A Paternò-Büchi Reaction of Aromatics with Quinones under Visible Light Irradiation.

Reported herein is a Paternò-Büchi reaction of aromatic double bonds with quinones under visible light irradiation. The reactions of aromatics with quinones exposed to blue LED irradiation yielded oxetanes at -78 °C, which was attributed to both the activation of double bonds in aromatics and the stabilization of oxetanes by thiadiazole, oxadiazole, or selenadiazole groups. The addition of Cu(OTf)2 to the reaction system at room temperature resulted in the formation of diaryl ethers via the copper-catalyzed ring opening of oxetanes in situ. Notably, the substrate scope was extended to general aromatics.

Association of serum vitamin D levels on Helicobacter pylori infection: a retrospective study with real-world data.

OBJECTIVE: The aim of this study was to determine whether serum vitamin D levels are associated with H. pylori infection and whether low serum vitamin D levels are an independent risk factor for H. pylori infection. METHODS: We conducted a retrospective analysis of a multicenter cohort study from 2017 to 2019. A total of 415 H. pylori+ patients and 257 H. pylori- patients aged between 18 and 75 years with both 13 C-urea breath test and serum vitamin D level results were included from four hospitals. A questionnaire was used to collect information on potential factors influencing H. pylori infection. RESULTS: Serum vitamin D levels were significantly lower in the H. pylori+ group than in the H. pylori- group (16.7 ± 6.6 ng/ml vs. 19.2 ± 8.0 ng/ml, p < 0.05). Using a cutoff value of 20 ng/ml, the H. pylori infection rate was significantly higher in the vitamin D-deficient group (< 20 ng/ml) than in the vitamin D-nondeficiency group (≥ 20 ng/ml) (66.5% vs. 51.0%, p < 0.001). Ordered logistic regression analysis showed that serum vitamin D levels < 20 ng/ml (OR: 1.652, 95% CI: 1.160-2.351, p = 0.005), higher education levels (OR: 1.774, 95% CI: 1.483-2.119, p < 0.001), family size ≥ 4 (OR: 1.516, 95% CI: 1.081-2.123, p = 0.016), and lower annual income (OR: 1.508, 95% CI: 1.289-1.766, p < 0.001) were independent risk factors for H. pylori infection. CONCLUSION: Lower serum vitamin D levels may be associated with an increased risk of H. pylori infection, and lower serum vitamin D levels are an independent risk factor for increasing H. pylori infection rates. Randomized controlled trials are needed to determine whether supplementation with vitamin D can reduce H. pylori infection rates.

Clinical effects of Chemotherapy combined with Immunotherapy in patients with advanced NSCLC and the effect on their nutritional status and immune function.

Objectives: To evaluate the clinical effects of chemotherapy combined with immunotherapy in patients with advanced non-small-cell lung cancer (NSCLC) and the effect on their nutritional status and immune function. Methods: Total 120 patients with advanced NSCLC admitted to Affiliated Hospital of Hebei University from May 2019 to October 2021 were randomly divided into two groups (n= 60, respectively). Patients in the control group were treated by chemotherapy with cisplatin-paclitaxel (TP) alone: 120 mg/m2 paclitaxel was used on d1; and 25mg/m2 cisplatin (CDDP) was used for more than two hour, once every 14 days, for three consecutive three cycles. Patients in the study group were additionally given 200 mg sindilizumab by intravenous drip, once every three weeks. The contrastive analysis of clinical effects, the incidence of adverse reactions, improvement of the nutrient index and the changes in levels of CD3+, CD4+, CD8+, and CD4+/CD8+ in T-lymphocyte subsets was performed between the two groups. Result: The overall response rate (ORR) was 80% and 61% in the study group and the control group, respectively; and the difference was statistically significant (p=0.03); the contrast analysis of the incidence of post-treatment adverse drug reactions (ADRs) in patients in the two groups suggested that the incidence of adverse reactions was 33.3% and 45% in the study group and the control group, respectively; and the difference was not statistically significant (p=0.19). After the treatment, the improvement of hemoglobin, albumin, serum iron and ferritin levels in the study group was more significant than that in the control group; and the difference was statistically significant (p < 0.05). After the treatment, the levels of CD3+, CD4+ and CD4+/CD8+ in the study group were much higher than those in the control group; and the difference was statistically significant (p < 0.05). Conclusion: Chemotherapy combined with immunotherapy is effective in treating patients with advanced NSCLC without increasing the incidence of adverse reactions, and can significantly improve their nutritional status and T-lymphocyte function. This therapeutic regimen is of much higher clinical value than the chemotherapy-only regimen.

Reducing lipofuscin accumulation and cardiomyocytic senescence of aging heart by enhancing autophagy.

Cardiomyocytes are particularly prone to lipofuscin accumulation. In the aging heart, lipofuscin accumulation is augmented. This study examined distribution of lipofuscin and senescent cardiomyocytes and evaluated improvement of lipofuscin accumulation and cardiomyocytic senescence of the aging heart after treatment with rapamycin. The results of Schmorl staining, Sudan black staining and autofluorescence detection showed that there was more lipofuscin in the myocardium of the ventricles especially in the left ventricle. The conductive tissue contained less lipofuscin than the myocardium. In the aged hearts, lipofuscin accumulation and senescent cardiomyocytes were increased, and the level of autophagy was reduced. In double staining of Sudan black B and senescence-associated ß-galactosidase, 10%-20% lipofuscin-loaded cardiomyocytes became senescent. All senescent cardiomyocytes contained lipofuscin deposits. After enhancing autophagy with feed of rapamycin for six months, lipofuscin accumulation and senescence of cardiomyocytes were improved in old rats. Colocalization of autophagic structure and lipofuscin as well as electron micrographs showed that some lipofuscin-loaded lysosomes were sequestrated by autophagic structures. This study suggests that rapamycin-enhanced autopahgy is effective for reducing lipofuscinogenesis and promoting degradation of lipofuscin. Therefore, enhancing autophagy is a novel therapy for alleviating lipofuscin accumulation and myocardial senescence.

Appropriate intraprocedural initial heparin dosing in patients undergoing catheter ablation for atrial fibrillation receiving uninterrupted non-vitamin-K antagonist oral anticoagulant treatment.

BACKGROUND: To clarify the appropriate initial dosage of heparin during radiofrequency catheter ablation (RFCA) in patients with atrial fibrillation (AF) receiving uninterrupted nonvitamin K antagonist oral anticoagulant (NOAC) treatment. METHODS: A total of 187 consecutive AF patients who underwent their first RFCA in our center were included. In the warfarin group (WG), an initial heparin dose of 100 U/kg was administered (control group: n = 38). The patients who were on NOACs were randomly divided into 3 NOAC groups (NG: n = 149), NG110, NG120, and NG130, and were administered initial heparin doses of 110 U/kg, 120 U/kg, and 130 U/kg, respectively. During RFCA, the activated clotting time (ACT) was measured every 15 min, and the target ACT was maintained at 250-350 s by intermittent heparin infusion. The baseline ACT and ACTs at each 15-min interval, the average percentage of measurements at the target ACT, and the incidence of periprocedural bleeding and thromboembolic complications were recorded and analyzed. RESULTS: There was no significant difference in sex, age, weight, or baseline ACT among the four groups. The 15 min-ACT, 30 min-ACT, and 45 min-ACT were significantly longer in the WG than in NG110 and NG120. However, no significant difference in 60 min-ACT or 75 min-ACT was detected. The average percentages of measurements at the target ACT in NG120 (82.2 ± 23.6%) and NG130 (84.8 ± 23.7%) were remarkably higher than those in the WG (63.4 ± 36.2%, p = 0.007, 0.003, respectively). These differences were independent of the type of NOAC. The proportion of ACTs in 300-350 s in NG130 was higher than in WG (32.4 ± 31.8 vs. 34.7 ± 30.6, p = 0.735). Severe periprocedural thromboembolic and bleeding complications were not observed. CONCLUSIONS: For patients with AF receiving uninterrupted NOAC treatment who underwent RFCA, an initial heparin dosage of 120 U/kg or 130 U/kg can provide an adequate intraprocedural anticoagulant effect, and 130 U/kg allowed ACT to reach the target earlier. TRIAL REGISTRATION: Registration number: ChiCTR1800016491, First Registration Date: 04/06/2018 (Chinese Clinical Trial Registry http://www.chictr.org.cn/index.aspx ).

Clinical efficacy of immunotherapy combined with chemotherapy in patients with advanced gastric cancer, its effect on nutritional status and Changes of peripheral blood T lymphocyte subsets.

OBJECTIVES: To evaluate the clinical efficacy of immunotherapy combined with chemotherapy in patients with advanced gastric cancer and its effect on nutritional status and changes of peripheral blood T lymphocyte subsets. METHODS: Sixty patients with locally advanced gastric cancer who were admitted by Affiliated Hospital of Hebei University from March 2020 to February 2021 were enrolled and randomly divided into two groups, with 30 cases in each group. The control group was treated with FOLFOX4 chemotherapy, while the experimental group was additively treated with cindilizumab on the basis of control group. The incidence of adverse reactions, clinical efficacy, improvement of nutritional and physical status, and changes in the levels of T lymphocyte subgroups in the two groups were compared and analyzed. RESULTS: The total effective rate was 70% in the experimental group, which was better than 43.3% of the control group (p=0.04). The improvement rate of performance status (ECOG) score and nutritional indicators in the experimental group was significantly better than that in the control group (p<0.05). Moreover, the indicators of CD3+, CD4+, CD4+/CD8+ in the experimental group were significantly higher than those in the control group after treatment, with statistically significant differences (CD3+, p=0.01; CD4 +, p= 0.02; CD4+/CD8+, p=0.01). CONCLUSION: Immunotherapy combined with chemotherapy has a significant effect on locally advanced gastric cancer patients, with significant improvement in physical strength and nutritional status, significant improvement in T lymphocyte function, and no obvious adverse reactions. It is worth promoting in clinical application.

Hydrogen sulfide accumulates LDL receptor precursor via downregulating PCSK9 in HepG2 cells.

Endogenous hydrogen sulfide (H2S) affects cholesterol homeostasis and liver X receptor α (LXRα) expression. However, whether low-density lipoprotein (LDL) receptor (LDLR), a key player in cholesterol homeostasis, is regulated by exogenous H2S through LXRα signaling has not been determined. We investigated the effects of sodium hydrosulfide (NaHS, H2S donor) on LDLR expression in the presence or absence of LXR agonists, T0901317 or GW3965 in HepG2 cells. We found that H2S strongly accumulated LDLR precursor in the presence of T0901317. Hence, LDLR transcription and the genes involved in LDLR precursor maturation and degradation were studied. T0901317 increased the LDLR mRNA level, whereas H2S did not affect LDLR transcription. H2S had no significant effect on the expression of LXRα and inducible degrader of LDLR (IDOL). H2S and T0901317 altered mRNA levels of several enzymes for N- and O-glycosylation and endoplasmic reticulum (ER) chaperones assisting LDLR maturation, but did not affect their protein levels. H2S decreased proprotein convertase subtilisin/kexin type 9 (PCSK9) protein levels and its mRNA level elevated by T0901317. T0901317 with PCSK9 siRNA also accumulated LDLR precursor as did T0901317 with H2S. High glucose increased PCSK9 protein levels and attenuated LDLR precursor accumulation induced by T0901317 with H2S. Taken together, H2S accumulates LDLR precursor by downregulating PCSK9 expression but not through the LXRα-IDOL pathway, LDLR transcriptional activation, or dysfunction of glycosylation enzymes and ER chaperones. These results also indicate that PCSK9 plays an important role in LDLR maturation in addition to its well-known effect on the degradation of LDLR mature form.

mTORC1 inhibitor RAD001 (everolimus) enhances non-small cell lung cancer cell radiosensitivity in vitro via suppressing epithelial-mesenchymal transition.

Resistance to radiotherapy causes non-small cell lung cancer (NSCLC) treatment failure associated with local recurrence and metastasis. Thus, understanding the radiosensitization of NSCLC cells is crucial for developing new treatments and improving prognostics. mTORC1 has been shown to regulate tumor cell radiosensitivity, but the underlying mechanisms are unclear. Moreover, mTORC1 also regulates epithelial-mesenchymal transition (EMT) that is important to metastasis and recurrence. In this study we explored whether mTORC1 regulated NSCLC cell radiosensitivity by altering EMT. We performed immunohistichemical analysis using tumor, adjacent and normal tissues from 50 NSCLC patients, which confirmed significantly elevated mTOR protein expression in NSCLC tissue. Then we used NCI-H460 and NCI-H661 cell lines to examine the effects of the mTORC1 inhibitor RAD001 (everolimus) on in vitro radiosensitivity, protein expression and dose-survival curves. RAD001 (10 nmol/L) significantly inhibited the mTORC1 pathway in both the cell lines. Pretreatment with RAD001 (0.1 nmol/L) enhanced the radiosensitivity in NCI-H661 cells with wild-type PIK3CA and KRAS but not in NCI-H460 cells with mutant PIK3CA and KRAS; the sensitivity enhancement ratios in the two NSCLC cell lines were 1.40 and 1.03, respectively. Furthermore, pretreatment with RAD001 (0.1 nmol/L) significantly decreased the migration and invasion with altered expression of several EMT-associated proteins (significantly increased E-cadherin and decreased vimentin expression) in irradiated NCI-H661 cells. Publicly available expression data confirmed that irradiation affected mTOR and EMT-associated genes at the transcript level in NSCLC cells. These results suggest that mTORC1 inhibition enhances the in vitro radiosensitivity of NSCLC cells with wild-type PIK3CA and KRAS by affecting EMT. Our preclinical data may provide a potential new strategy for NSCLC treatment.

Basilic vein transposition-radial artery fistula created using the no-touch technique
.

OBJECTIVE: To compare the functions and complications of forearm basilic vein transposition-arteriovenous fistula (BVT-AVF) created using the no-touch technique with that of conventional radiocephalic arteriovenous fistula (RC-AVF). MATERIALS AND METHODS: The no-touch technique was used to created basilic vein transposition-radial artery fistula in 22 patients. Another 30 patients received surgeries for RC-AVF. The fistula functions and complications were compared between these two groups. RESULTS: The two groups did not differ significantly in the incidence of postoperative bleeding, limb swelling, infection, steal syndrome, fistula thrombosis, fistula aneurysm, fistula flow, fistula maturation time, Kt/v, and fistula median survival. CONCLUSION: Forearm BVT-AVF created by the no-touch technique is a good alternative access for patients in whom the standard arteriovenous fistula cannot be established.

Sustained low-efficiency diafiltration is superior to hemodialysis in promoting renal function recovery in elderly wasp sting victims with stage III acute kidney injury: a retrospective study.

Objective: To study the efficacy and safety of sustained low-efficiency diafiltration (SLEDf) versus hemodialysis (HD) for patients with wasp stings who developed stage III acute kidney injury (AKI). Methods: We retrospectively analyzed the clinical data of consecutive patients who developed AKI following wasp stings. All eligible patients received renal replacement therapy in combination with hemoperfusion. Thereafter, blood purification therapy and HD were performed with a volumetrically controlled machine and 1.7 m2 surface, Fresenius Polysulfone HD filter and SLEDf was undertaken with a volumetrically controlled machine and 1.3 m2 surface, Fresenius Polysulfone HD filter. Results: Forty patients developed stage III AKI following wasp stings, including 14 patients that received SLEDf and 26 patients underwent HD. Thirteen patients were aged less than 60 years and underwent HD (group I), 27 patients were aged at least 60 years, including 13 patients undergoing HD (group II) and 14 patients receiving SLEDf (group III). Groups I and II completed 150 and 162 sessions of HD, respectively, and group III completed 156 sessions of sustained low-efficiency blood purification therapy, including 50 sessions of SLEDf. The time to return to normal serum creatinine levels was 38.8 ± 2.7 days for group I, 47.2 ± 5.3 days for group II, and 39.2 ± 3.3 days for group III. A statistically significant difference was observed in time to normal serum creatinine levels among the three groups. Conclusion: Elderly wasp victims have more severe illness than younger wasp victims and SLEDf is safe and superior to HD in recovery of renal function of elderly wasp victims.

Application of the Scorpion Neurotoxin AaIT against Insect Pests.

Androctonus australis Hector insect toxin (AaIT), an insect-selective toxin, was identified in the venom of the scorpion Androctonus australis. The exclusive and specific target of the toxin is the voltage-gated sodium channels of the insect, resulting in fast excitatory paralysis and even death. Because of its strict toxic selectivity and high bioactivity, AaIT has been widely used in experiments exploring pest bio-control. Recombinant expression of AaIT in a baculovirus or a fungus can increase their virulence to insect pests and diseases vectors. Likewise, transgenic plants expressing AaIT have notable anti-insect activity. AaIT is an efficient toxin and has great potential to be used in the development of commercial insecticides.

Phytophthora pseudopolonica sp. nov., a new species recovered from stream water in subtropical forests of China.

A new species of the genus Phytophthora was isolated from stream water in the subtropical forests of China during a survey of forest Phytophthora from 2011 to 2013. This new species is formally described here and named Phytophthora pseudopolonica sp. nov. This new homothallic species is distinct from other known Phytophthora species in morphology and produces nonpapillate and noncaducous sporangia with internal proliferation. Spherical hyphal swellings and thin-walled chlamydospores are abundant when the species is kept in sterile water. The P. pseudopolonica sp. nov. forms smooth oogonia with paragynous and sometimes amphigynous antheridia. The optimum growth temperature of the species is 30 °C in V8-juice agar with ß-sitosterol, yet it barely grows at 5 °C and 35 °C. Based on sequences of the internal transcribed spacer and the combined ß-tubulin and elongation factor 1α gene sequence data, isolates of the new species cluster together into a single branch and are close to Phytophthora polonicabelonging to clade 9.

Xinxuekang Regulates Reverse Cholesterol Transport by Improving High-density Lipoprotein Synthesis, Maturation, and Catabolism.

Di'ao Xinxuekang (XXK) is an herbal product in China and the Netherlands that has been clinically shown to attenuate atherosclerosis; however, the underlying antiatherosclerotic mechanism remains unclear. Because of its role in cholesterol homeostasis, reverse cholesterol transport (RCT) is a potential target for these beneficial effects. This study investigated the effects of XXK on RCT and related proteins. After treating ApoE-deficient mice with XXK for 8 weeks, we observed an increase in the expression level of ATP-binding cassette transporter A1 and ATP-binding cassette transporter G1, which in turn stimulated cholesterol efflux and reduced aortic atherosclerotic lesion area. XXK also increased high-density lipoprotein (HDL) synthesis by modulating the peroxisome proliferator-activated receptor γ/liver X receptor α/ATP-binding cassette transporter A1 pathway and promoted HDL maturity by increasing serum lecithin-cholesterol acyltransferase. In addition, XXK improved the selective uptake of HDL-cholesteryl ester by increasing the expression of scavenger receptor class B type I. This is the first study to show that XXK confers a regulation of RCT, at least in part, by improving HDL synthesis, maturation, and catabolism.

A Novel Molecular Model of Plant Lectin-Induced Programmed Cell Death in Cancer.

Plant lectin, a class of highly diverse non-immune origin and carbohydrate-binding proteins, has been reported to specially induce cancer cell through programmed cell death (PCD) pathways (apoptosis and/or autophagy), shedding lights on screening promising anti-cancer candidate agent for further therapeutic trials. However, the complicated molecular mechanisms by which plant lectins induced the programmed death of tumor cells, have not yet been fully clarified. Here, we summarized a novel model, based on vast amount of research, by which plant lectins eliminate various types of cancer cells via three major pathways, including a) direct ribosome inactivating, b) endocytosis-dependent mitochondrial dysfunction and c) sugar-containing receptors binding. A better understanding of the role of plant lectins played and further elucidation of the strategies targeting PCD would provide a new clue for the applications and modifications of plant lectin as a potential anti-cancer agent from bench to clinic.

[Effects of Gubentongluo Formula on Oxidative Stress Reflected by Expressions of PPARα and L-FABP in Mice with IgA Nephropathy].

OBJECTIVES: To determine the underlying mechanism of Gubentongluo Formula in the treatment of IgA nephropathy (IgAN). METHODS: C57BL/6 mice were randomly divided into four groups: normal group (n =10), IgAN group (n =10), control group (n =10) and treatment group (n =10). Mice in the normal and IgAN groups were intragastricly administered with normal saline for 12 weeks; while those in the control and treatment groups were given fenofibrate [30 mg/(kg!$d) and Gubentongluo Formula [1.67 mL/(g!$d)], respectively. Urinary albumin was detected at week 0 and 12. At week 12, protein expressions of peroxisome proliferstor activated receptor α (PPARα), liver fatty acid-binding proteins (L-FABP), 4-hydroxy-2-nonenal (4-HNE), and hemeoxygenase-1(HO-1) in renal tissues were determined by Western blot; mRNA expressions of PPARα and L-FABP in renal tissues were determined by florescent quantitative reverse transcription-polymerase chain reaction (qRT-PCR). RESULTS: At week 12, higher levels of urinary albumin, pathological injuries in glomerular mesangial area, and lower expressions of protein and mRNA of PPARα and L-FABP were found in mice in the IgAN group compared with those in the normal group (P <0.01). The levels of those indicators decreased in those treated with fenofibrate and Gubentongluo Formule, but still higher than the normal controls (P <0.01). The mice treated with Gubentongluo Formula had more significant improvement than those treated with fenofibrate (P <0.05). CONCLUSION: [CM(155.3mm]Gubentongluo formula can improve proteinuria and pathological injuries in glomerular mesangial area of IgAN mice, due to reduction of oxidative stress in renal tissues through regulating the expressions of PPARα and L-FABP.

Hydrogen sulfide promotes angiogenesis by downregulating miR-640 via the VEGFR2/mTOR pathway.

We previously found hydrogen sulfide (H2S) to be a new proangiogenic factor. However, the mechanisms underlying the cardiovascular effect of this small gas molecule remain largely unknown. The aim of the present study was to identify the essential microRNAs (miRNAs) involved in the transduction of H2S signals in vascular endothelial cells (ECs). The expression of miR-640 and its signaling elements, vascular endothelial growth factor receptor 2 (VEGFR2), hypoxia inducible factor 1-α (HIF1A), and mammalian target of rapamycin (mTOR), was measured using quantitative PCR and Western blotting. Overexpression and inhibition of miR-640 were performed to clarify their roles in mediating the effect of H2S. In addition, knockdown of VEGFR2, HIF1A, and mTOR was performed using siRNAs, dominant negative mutants, or inhibitors to examine their roles in the transduction of the H2S signals. miR-640 levels decreased in vascular ECs that were treated with H2S, whereas overexpression of miR-640 blunted the proangiogenic effect of H2S. Knockdown of either VEGFR2 or mTOR blunted the downregulation of miR-640 and the proangiogenic effect induced by H2S. In addition, miR-640 bound to the 3'-UTR of HIF1A mRNA and then inhibited the expression of HIF1A. The inhibition could be recovered by treating cells with H2S. Thus we concluded that miR-640 plays a pivotal role in mediating the proangiogenic effect of H2S; H2S acts through downregulation of the expression of miR-640 and increasing the levels of HIF1A through the VEGFR2-mTOR pathway.

Transcription Factor PAX6 (Paired Box 6) Controls Limbal Stem Cell Lineage in Development and Disease.

PAX6 is a master regulatory gene involved in neuronal cell fate specification. It also plays a critical role in early eye field and subsequent limbal stem cell (LSC) determination during eye development. Defects in Pax6 cause aniridia and LSC deficiency in humans and the Sey (Small eye) phenotype in mice (Massé, K., Bhamra, S., Eason, R., Dale, N., and Jones, E. A. (2007) Nature 449, 1058-1062). However, how PAX6 specifies LSC and corneal fates during eye development is not well understood. Here, we show that PAX6 is expressed in the primitive eye cup and later in corneal tissue progenitors in early embryonic development. In contrast, p63 expression commences after that of PAX6 in ocular adnexal and skin tissue progenitors and later in LSCs. Using an in vitro feeder-free culture system, we show that PAX6 knockdown in LSCs led to up-regulation of skin epidermis-specific keratins concomitant with differentiation to a skin fate. Using gene expression analysis, we identified the involvement of Notch, Wnt, and TGF-ß signaling pathways in LSC fate determination. Thus, loss of PAX6 converts LSCs to epidermal stem cells, as demonstrated by a switch in the keratin gene expression profile and by the appearance of congenital dermoid tissue.

The complete mitochondrial genomes of Gnathostoma doloresi from China and Japan.

Gnathostoma doloresi is one of the neglected pathogens causing gnathostomiasis. Although this zoonotic parasite leads to significant socioeconomic concerns globally, little is known of its genetics and systematics. In the present study, we sequenced and characterized the complete mitochondrial (mt) genomes of G. doloresi isolates from China and Japan. The lengths of the mt genomes of the G. doloresi China and Japan isolates are 13,809 and 13,812 bp, respectively. Both mt genomes encode 36 genes, including 12 protein-coding genes (PCGs), 2 ribosomal RNA genes, and 22 transfer RNA genes. The gene order, transcription direction, and genome content are identical with its congener G. spinigerum. Phylogenetic analyses based on concatenated amino acid sequences of 12 PCGs by Bayesian inference (BI) indicated that G. doloresi are closely related to G. spinigerum. Our data provide an invaluable resource for studying the molecular epidemiology, phylogenetics, and population genetics of Gnathostoma spp. and should have implications for further studies of the diagnosis, prevention, and control of gnathostomiasis in humans and animals.

[The Use of Telemedicine Interventions to Improve Hypertension Management Among Racial Ethnic Minorities: A Systematic Review].

BACKGROUND: Racial ethnic minorities are one of the fastest growing populations in Taiwan. In recent years, there has been an increase in literature addressing the efficacy of home blood-pressure (BP) management that uses telemedicine interventions in general healthcare and community settings. However, no study or systematic literature review has yet assessed the effectiveness of using telemedicine HTN interventions in Taiwan's indigenous, new-immigrant, and other minority populations. PURPOSE: The purpose of the present paper is to review the current literature on the use of telemedicine interventions to assist HTN management among racial ethnic minorities. METHODS: A comprehensive literature search was conducted for full-text articles that were published between January 2000 and December 2015 using the following databases: PubMed, WEB of Science, CINAHL (Cumulative Index to Nursing & Allied Health Literature), PsycINFO, Science Direct, ProQuest, Medline, Cochrane Library, National Dissertations and Theses, and airiti Library. The search used the following key search terms both alone and in combination: hypertension, blood pressure, management, telemedicine, telehealth, ehealth, and digital health. The studies were thoroughly assessed under the guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). A total of 6 articles met the criteria for using keywords related to racial ethnic minority populations and were used in the present review. RESULTS: Findings of this systematic review show that telemedicine interventions significantly improve HTN management. The intervention that combined home telemonitoring with culturally competent nurse counseling calls was identified as the best intervention for reducing BP. As the current literature on this topic is limited to African-Americans, more research is necessary to validate our findings. CONCLUSIONS / IMPLICATIONS FOR PRACTICE: Future studies should target racial ethnic minorities in Taiwan in order to better understand how to provide culturally appropriate, telemedicine-based HTN management to Taiwan's minority populations. Further studies with a long-term follow-up plan, randomized controlled trials, and larger sample sizes are required to support these results.