[Pulmonary co-infection with Nocardia otitidiscaviarum and Aspergillus: a case report].

Nocardia is a rarely encountered opportunistic gram-positive bacterium that exhibits marked invasiveness and dissemination. Typically, acquired through trauma or inhalation, this pathogen primarily affects immunocompromised individuals and is a potentially life-threatening risk in severe cases. Nocardia otitidiscaviarum is a particularly rare subtype of Nocardia infection, and the occurrence of concurrent Aspergillus infection is extremely rare. In cases where both infections manifest concomitantly, rapid and accurate diagnosis is essential to facilitate the subsequent selection of appropriate anti-infective interventions. This paper reported the diagnostic and therapeutic experience in managing a case of pulmonary co-infection with Nocardia otitidiscaviarum and Aspergillus. The patient presented with an acute onset, rapid progression, and early manifestation of respiratory failure. The diagnostic process included respiratory pathogen culture and bronchoscopy, which was supplemented with targeted next-generation sequencing (tNGS). These comprehensive diagnostic modalities led to the identification of pulmonary co-infection with Nocardia otitidiscaviarum and Aspergillus. After adjustment of the antibiotic regimen, the patient's condition improved rapidly, culminating in a timely discharge.

Effect of combined epidural anaesthesia on tumor-infiltrating lymphocytes in lung adenocarcinoma: a prospective exploratory sub-analysis.

BACKGROUND: Regional anaesthesia may have advantages in preserving immune function. Tumor-infiltrating lymphocytes (TILs) are considered indicators of immune response in the tumor microenvironment and used as a prognostic marker in patients after cancer surgery. This study investigated the effects of combined epidural anaesthesia on the number of TILs in patients undergoing surgery for lung adenocarcinoma. METHODS: Patients undergoing radical resection for primary lung cancer were randomized to receive either combined epidural-general anaesthesia (Epi-GA) or general anaesthesia (GA) in an ongoing randomized controlled trial (ChiCTR-TRC-14004136). Excised adenocarcinoma specimens from patients enrolled between 1 June 2015 and 30 November 2015 were selected for immunohistochemical staining of CD8 and FOXP3 molecules. The numbers of positive lymphocytes were counted and expressed as the number of cells per mm2 tumor area. RESULTS: One hundred and twenty-eight patients were recruited and randomized; 64 patients were included in immunohistochemistry analysis (37 received Epi-GA vs. 27 received GA). The number of CD8+ T cells was higher in the Epi-GA group than in the GA group (median [interquartile range]: 292.8 [198.0-418.3] vs. 204.7 [131.1-305.8], P = 0.036); whereas the number of FOXP3+ T cells was less in the Epi-GA group than in the GA group (37.6 [14.7-92.3] vs. 99.8 [68.9-168.3], P < 0.001). CONCLUSIONS: For patients undergoing surgery for lung adenocarcinoma under general anesthesia, use of epidural anaesthesia increased CD8+ T cells infiltration but decreased FOXP3+ T cells accumulation in tumor tissues. Epidural anaesthesia may affect TILs in a manner that preserves immune function.

Risk-benefit perception of pregnancy among breast cancer survivors.

Helping breast cancer patients who desire a pregnancy after cancer treatment is a vital issue. Little is known about the complex context of the decision to become pregnant after breast cancer treatment. The purpose of this study was to understand the risk-benefit perception of choosing conception or contraception after treatment in Taiwan. We applied grounded theory to guide this exploratory qualitative study. Data were collected through in-depth interviews with 16 breast cancer patients. Pregnancy was addressed in the context of cancer as a potentially life-threatening diagnosis and its treatment. The verbatim transcriptions were analysed using constant comparative analysis and methods of open, axial and selective coding. The core theme that described the risk perception of pregnancy among patients with breast cancer after treatment focused on "reaching the balance of life." Seven dimensions of risk-benefit perception of pregnancy, including perceived health status, safety, expected gain, harm, loading, support and time were explored among women treated for breast cancer. We found that women treated for breast cancer applied risk-benefit perceptions to decide whether to become pregnant. Implementing contextual counselling could help to decrease perceived barriers to choose pregnancy and increase the quality of pregnancy care.

[Liver sinusoidal endothelial cells regulate adaptive immune tolerance in the liver].

Liver sinusoidal endothelial cells are a major group of nonparenchymal cells in the liver and are involved in immunological surveillance of the liver through the expression of various scavenger receptors and pattern recognition receptors. However, in case of several physiological states, viral infections, and tumor environment, liver sinusoidal endothelial cells maintain immune tolerance in the liver through various mechanisms and cause persistent viral infection and tumor metastasis. This article reviews the mechanisms of immune tolerance of CD4 + T cells and CD8 + T cells in the liver induced by liver sinusoidal endothelial cells.

Calcitonin alleviates hyperalgesia in osteoporotic rats by modulating serotonin transporter activity.

Calcitonin may relieve pain by modulating central serotonin activity. Calcitonin partly reversed the hypersensitivity to pain induced by ovariectomy. This suggests that the anti-nociceptive effects of calcitonin in the treatment of osteoporosis may be mediated by alterations in neural serotonin transporter (SERT) activity. INTRODUCTION: This study used a rat model of osteoporosis to evaluate the role of the cerebral serotonin system in the anti-nociceptive effect of calcitonin, a drug used to treat post-menopausal osteoporosis. METHODS: Osteoporosis was induced in rats by ovariectomy (OVX). Rats were then randomized to the following four groups: sham operation, OVX, OVX plus calcitonin, or OVX plus alendronate. RESULTS: OVX led to alterations in bone micro-architecture; alendronate strongly reversed this effect, and calcitonin moderately reversed this effect. OVX increased hyperalgesia (determined as the time for hind paw withdrawal from a heat source); calcitonin reduced this effect, but alendronate had no effect. OVX increased the expression of c-Fos (a neuronal marker of pain) in the thalamus; calcitonin strongly reversed this effect, and alendronate moderately reversed this effect. OVX also reduced SERT but increased 5-HT1A receptor expression and activity; calcitonin aggravated this effect, but alendronate had no effect on recovery of SERT/5-HT1A activity and expression. CONCLUSIONS: Our study of a rat model of osteoporosis suggests that OVX-induced enhancement of the serotonergic system may protect against hyperalgesia. However, the anti-nociceptive effects of calcitonin in osteoporosis may be mediated by decreased neural SERT activity and increased activation of 5-HT1 receptors in the thalamus.

A novel label-free fluorescence strategy for methyltransferase activity assay based on dsDNA-templated copper nanoparticles coupled with an endonuclease-assisted signal transduction system.

Evaluating DNA methyltransferase (MTase) activity has received considerable attention due to its significance in the fields of early cancer clinical diagnostics and drug discovery. Herein, we proposed a novel label-free fluorescence method for MTase activity assay by coupling double-stranded DNA (dsDNA)-templated copper nanoparticles (CuNPs) with an endonuclease-assisted signal transduction system. In this strategy, dsDNA molecules were first methylated by DNA adenine methylation (Dam) MTase and then cleaved by the methylation-sensitive restriction endonuclease DpnI. The cleaved DNA fragments could not act as efficient templates for the formation of fluorescent CuNPs and thus no fluorescence signal was produced. Under optimized experimental conditions, the developed strategy exhibited a sensitive fluorescence response to Dam MTase activity. This strategy was also demonstrated to provide an excellent platform to the inhibitor screening for Dam MTase. These results demonstrated the great potential for the practical applications of the proposed strategy for Dam MTase activity assay.

[Relationship between expression of HDAC2, IL-8, TNF-α in lung adenocarcinoma tissues and smoking].

OBJECTIVE: To investigate the relationship between the expression of histone acetylation enzyme 2 (HDAC2), interleukin-8 (IL-8), tumor necrosis factor-α (TNF-α) in lung adenocarcinoma tissues and smoking. METHODS: A total of 73 cases of lung adenocarcinoma confirmed by pathological examination after surgical removals were collected in the First Affiliated Hospital and Affiliated Tumor Hospital of Guangxi Medical University from April 2014 to March 2015. All patients received preoperative lung function test. Lung adenocarcinoma and para-cancer tissues were cut by the sharp blade and stored in liquid nitrogen and the sampling time was less than 30 minutes. Smokers were defined as people who had smoked more than 100 cigarettes or inhaled the smoke of cigarettes at least one day a week (more than 15 minutes every day) more than three years. According to the lung function and whether smoking or not, the cases of lung adenocarcinoma were divided into three groups: smoking without chronic obstructive pulmonary disease (COPD) group (33 cases), without smoking and COPD group (19 cases), smoking with COPD group (21 cases). The levels of HDAC2, IL-8 and TNF-α mRNA in lung adenocarcinoma and para-cancer tissues of groups were detected by real-time polymerase chain reaction (PCR) and the expression of HDAC2 protein was detected by Western blotting, and statistical analysis was carried out. RESULTS: The expression of HDAC2, IL-8 and TNF-α in lung adenocarcinoma tissues and TNM stage of lung adenocarcinoma showed no significant differences with respect to age and gender (P>0.05). Compared with the para-cancer tissues of 73 cases, the expression of HDAC2 at mRNA and protein levels in lung adenocarcinoma tissues were significantly lower (t=4.15, 8.006, all P<0.01). and the content of IL-8 and TNF-α at mRNA levels were increased (t=-4.252, -5. 576, all P<0.01). The expression of HDAC2 mRNA and protein in lung adenocarcinoma tissues in smoking without COPD group and smoking with COPD group were significantly lower than in without smoking and COPD group (0.38±0.11, 0.35±0.12 vs 0.45±0.10 and 0.26±0.09, 0.24±0.06 vs 0.33±0.10; all P<0.05), and it was the lowest expression in smoking with COPD group. IL-8 and TNF-α at mRNA levels in lung adenocarcinoma tissues in smoking without COPD group and smoking with COPD group were significantly higher than in without smoking and COPD group (0.96±0.19, 1.10±0.18 vs 0.71±0.13 and 0.62±0.21, 0.64±0.20 vs 0.45±0.14; all P<0.05), and the up-regulation was more obvious in smoking with COPD group. The TNM stage of lung adenocarcinoma in smoking group (smoking without COPD group and smoking with COPD group) was higher than without smoking group (without smoking and COPD group)(P=0.038). CONCLUSION: HDAC2 is down-regulated and IL-8, TNF-α are up-regulated in lung adenocarcinoma tissues. They are influenced by smoking and especially when combined with chronic obstructive pulmonary disease.

Biochemical properties of the recurrent LMX1b truncated mutant carried in a Taiwanese family with nail-patella syndrome.

BACKGROUND: Loss of the DNA-binding activity of a transcription factor is detrimental to its function in responsive gene regulation. We diagnosed a Taiwanese family with nail-patella syndrome (NPS) whose members inherited the mutated LMX1b transcription factor with no DNA-binding homeodomain. The loss-of-function variants cause haploinsufficiency of LMX1b, leading to the clinical manifestation of NPS. The underlying molecular mechanism is unclear. OBJECTIVES: To test whether the recurrent pathogenic truncated LMX1b-R198X reported in our patients might be a functional protein. Its biochemical properties were explored. METHODS: The luciferase reporter driven by the human interleukin (IL)-6 gene promoter was assayed to measure the transcriptional activity of LMX1b. The nuclear localization of different enhanced green fluorescent protein-tagged LMX1b proteins was observed using fluorescence microscopy. Western blotting was employed to evaluate the expression of various transfected LMX1b constructs. RESULTS: LMX1b-R198X enhanced the IL-6 promoter activity activated by the wild-type LMX1b and diminished the promoter activity induced by phorbol 12-myristate 13-acetate. LMX1b-R198X carried out its effect differentially in the expression of various human genes. The nuclear localization of the wild-type LMX1b was disrupted by the C-terminus truncation. The protein stability exhibited by LMX1b-R198X appears to be much higher than that of the wild-type protein. CONCLUSIONS: We demonstrated that loss of function might not be the only way for mutated LMX1b to cause haploinsufficiency as the main pathogenic mechanism for NPS. LMX1b-R198X has less nuclear localization and higher stability than the wild-type protein; consequently, it might function as a competitor to sequester other effectors by protein-protein interaction to interfere with downstream transcriptional events.

Perivascular epithelioid cell tumor of the liver: a case report and literature review.

Perivascular epithelioid cell tumors (PEComas) are mesenchymal tumors containing variable component of smooth muscles, fat and vessels. They occured pretty rare in the liver and no characteristic of imaging data have been demonstrated up to now. We herein present a case of a 58-year-old man with a hepatic PEComa which was correct diagnosed through immunohistochemical confirmation with HMB-45. The clinicopathological and imaging features of hepatic PEComa were analyzed retrospectively. This is the first paper which demonstrated the characteristic of imaging data among liver PEComas and other liver lesions. However, the diagnostic criteria of PEComa depends on pathology. Hepatectomy is the effective treatment.

Superficial parotid lobe-sparing delineation approach: a better method of dose optimization to protect the parotid gland in intensity-modulated radiotherapy for nasopharyngeal carcinoma.

PURPOSE: We used a superficial parotid lobe-sparing delineation approach for dose optimization with better protection for the parotid glands in intensity-modulated radiotherapy (imrt) for nasopharyngeal carcinoma (npc) patients. METHODS: Compared with traditional contouring of the entire parotid glands as organs at risk (oars) in imrt for npc, we used a superficial parotid lobe-sparing delineation approach of contouring the superficial parotid lobes as oars. Changes in dose to the parotid glands, the targets, and other oars were evaluated. RESULTS: The mean dose to the parotid glands overall decreased by more than 4 Gy in the test plans. Impressively, the mean dose to the superficial parotid lobes in the test plans was not more than 30 Gy, regardless of clinical stage. In T1-3 npc patients, the dose distributions for targets were not significantly different in the control plans and the test plans. However, for some T4 patients, the dose distributions for targets and brainstem in the test plans could not meet clinical requirements. CONCLUSIONS: The superficial parotid lobe-sparing delineation approach can significantly lower the mean dose to the entire parotid and to the superficial parotid lobe in T1-3 npc patients, which would be expected to result in less xerostomia and better quality of life for those patients.

Associations and relative risks of pulmonary hypertension and lung diseases in individuals with methamphetamine use disorder.

OBJECTIVE: Methamphetamine causes considerable short- and long-term adverse health effects. Our aim was to assess the effects of methamphetamine use on pulmonary hypertension and lung diseases at the population level. METHODS: This population-based retrospective study used data from the Taiwan National Health Insurance Research Database between 2000 and 2018 that included 18,118 individuals with methamphetamine use disorder (MUD) and 90,590 matched participants of the same age and sex without substance use disorder as the non-exposed group. A conditional logistic regression model was used to estimate associations of methamphetamine use with pulmonary hypertension and lung diseases such as lung abscess, empyema, pneumonia, emphysema, pleurisy, pneumothorax, or pulmonary hemorrhage. Incidence rate ratios (IRRs) of pulmonary hypertension and hospitalization due to lung diseases were determined between the methamphetamine group and non-methamphetamine group using negative binomial regression models. RESULTS: During an 8-year observation period, 32 (0.2%) individuals with MUD and 66 (0.1%) non-methamphetamine participants suffered from pulmonary hypertension, and 2652 (14.6%) individuals with MUD and 6157 (6.8%) non-methamphetamine participants suffered from lung diseases. After adjusting for demographic characteristics and comorbidities, individuals with MUD were 1.78 times (95% confidence interval (CI) = 1.07-2.95) more likely to have pulmonary hypertension and 1.98 times (95% CI = 1.88-2.08) more likely to have a lung disease, especially emphysema, lung abscess, and pneumonia in descending order. Furthermore, compared to the non-methamphetamine group, the methamphetamine group was associated with higher risks of hospitalization caused by pulmonary hypertension and lung diseases. The respective IRRs were 2.79 and 1.67. Individuals with polysubstance use disorder were associated with higher risks of empyema, lung abscess, and pneumonia compared to individuals with MUD alone, with respective adjusted odds ratios of 2.96, 2.21, and 1.67. However, pulmonary hypertension and emphysema did not differ significantly between MUD individuals with or without polysubstance use disorder. CONCLUSIONS: Individuals with MUD were associated with higher risks of pulmonary hypertension and lung diseases. Clinicians need to ensure that a methamphetamine exposure history is obtained as part of the workup for these pulmonary diseases and provide timely management for this contributing factor.

High-glucose environment reduces human ß-defensin-2 expression in human keratinocytes: implications for poor diabetic wound healing.

BACKGROUND: Wound healing is a dynamic and complicated process in which inflammation, re-epithelialization and angiogenesis play important roles. Intriguingly, all three processes have been found to be defective during diabetic wound healing conditions. One common denominator associated with regulation of these events is human ß-defensin-2 (hBD2). It has been shown that skin wounding induces cutaneous hBD2 expression, and diabetic wounds have been associated with inadequate hBD expression. OBJECTIVES: The current study was launched to explore the effects of a high-glucose environment on cultured human keratinocytes. METHODS: Human keratinocytes were exposed to indicated culture conditions. The mRNA and protein levels of hBD2 were determined, and activation of relevant pathways was evaluated. The small interference RNA approach was used to validate the functional role of the proposed pathway on hBD2 expression. RESULTS: We showed that high-glucose cultivated keratinocytes expressed reduced levels of hBD2 and phosphorylated signal transducer and activator of transcription (pSTAT)-1 constitutively. In addition, pSTAT-1 signalling is critically involved in hBD2 expression. Formation of advanced glycation endproducts, a direct consequence of a high-glucose environment, involves constitutive downregulation of pSTAT-1 and hBD2. The addition of interleukin-1ß, an important cytokine during the cutaneous wound healing process, enabled the upregulation of hBD2 expression of both normal- and high-glucose cultivated keratinocytes, but the absolute levels of hBD2 were still significantly lower in the high-glucose-treated group. CONCLUSIONS: As hBD2 plays multifaceted roles during the wound healing process, the inadequate expression of hBD2 during diabetic conditions contributes to impaired wound healing.

Core/shell structured NaYF4:Yb3+/Er3+/Gd+3 nanorods with Au nanoparticles or shells for flexible amorphous silicon solar cells.

A simple approach for preparing near-infrared (NIR) to visible upconversion (UC) NaYF4:Yb/Er/Gd nanorods in combination with gold nanostructures has been reported. The grown UC nanomaterials with Au nanostructures have been applied to flexible amorphous silicon solar cells on the steel substrates to investigate their responses to sub-bandgap infrared irradiation. Photocurrent­voltage measurements were performed on the solar cells. It was demonstrated that UC of NIR light led to a 16-fold to 72-fold improvement of the short-circuit current under 980 nm illumination compared to a cell without upconverters. A maximum current of 1.16 mA was obtained for the cell using UC nanorods coated with Au nanoparticles under 980 nm laser illumination. This result corresponds to an external quantum efficiency of 0.14% of the solar cell. Mechanisms of erbium luminescence in the grown UC nanorods were analyzed and discussed.

Large-scale growth of Cu2ZnSnSe4 and Cu2ZnSnSe4/Cu2ZnSnS4 core/shell nanowires.

We present a fast and simple protocol for large-scale preparation of quaternary Cu(2)ZnSnSe(4) (CZTSe), as well as CZTSe/Cu(2)ZnSnS(4) (CZTS) core/shell nanowires using CuSe nanowire bundles as self-sacrificial templates. CuSe nanowire bundles were synthesized by reacting Cu(2 - x)Se nanowire bundles with sodium citrate solution. CZTSe nanowires were prepared by reacting CuSe nanowire bundles with Zn(CH(3)COO)(2) and SnCl(2) in triethylene glycol. X-ray diffraction (XRD) and selected area electron diffraction studies show that stannite CZTSe is formed. The formed CZTSe nanowire bundles have diameters of 200-400 nm and lengths of up to hundreds of micrometers. CZTSe/CZTS nanocable bundles with similar morphologies were grown by the addition of some elemental sulfur to the reaction system for growth of CZTSe bundles. The stannite CZTSe/kesterite CZTS core/shell structure of the grown nanocables was confirmed by XRD and high-resolution transmission electron microscope investigation. The influence of S/Se molar ratio in the reaction system on the crystallographic structures and optical properties of CZTSe/CZTS nanocables was studied. The obtained CZTSe/CZTS core/shell nanocable bundles show broad and enhanced optical absorption over the visible and near-infrared region, which is promising for use in photovoltaic applications.

The role of programmed cell death in streptozotocin-induced early diabetic nephropathy.

The mechanism of autophagy in diabetic nephropathy (DN) is still unclear. The study was performed on streptozotocin (STZ) rats to investigate whether programmed cell death contribute to the pathogenesis and progression of DN. STZ rats were induced by an single intravenous injection of STZ dissolved in citrate buffer, early DN (E-DN) for STZ rats was defined as the stage from modeling to the end of the 8th week according to previous studies. A total of 36 male Sprague-Dawley rats were randomly divided into two groups: an E-DN group and a control group. After the 1st, 4th, and 8th week, the rats were sacrificed. Beclin1 and microtubule associated protein 1 light chain 3 (LC3) were examined, apoptosis level in renal tissue was detected by Tunnel assay detected as the apoptotic index. An electron microscopic examination of kidney tissues was performed at end of the 4th and 8th week. Compared with the control group, Beclin1 expression increased since the 1st week after modeling in STZ rats kidney and peaked at the end of the 8th week in western blotting and immunohistochemical stain. Meanwhile the level of LC3-II in DN group was significantly lower from the end of the 1st to the 8th week. A small amount of autophagosomes were observed in both E-DN group and control group under electron microscopic examination, and there was no significant difference between the groups. These findings indicate that an abnormality on autophagy may play an important role in the pathogenesis of E-DN.

Spin bottleneck in resonant tunneling through double quantum dots with different Zeeman splittings.

We investigated the electron transport property of the InGaAs/GaAs double quantum dots, the electron g factors of which are different from each other. We found that in a magnetic field, the resonant tunneling is suppressed even if one of the Zeeman sublevels is aligned. This is because the other misaligned Zeeman sublevels limit the total current. A finite broadening of the misaligned sublevel partially relieves this bottleneck effect, and the maximum current is reached when interdot detuning is half the Zeeman energy difference.

Topical tacrolimus has a limited direct effect on ultraviolet B-irradiated keratinocytes: implications for its photocarcinogenic potential.

BACKGROUND: Topical tacrolimus has shown remarkable clinical efficacy in treating many dermatoses. Combining ultraviolet (UV) B and tacrolimus is an intriguing therapeutic regimen, especially for treatment of vitiligo, for which combination therapy may show greater clinical efficacy than topical tacrolimus alone. The photocarcinogenic potential of such a regimen is unclear, and conflicting results have been reported by different investigators. AIM: To clarify this important clinical issue, we investigated the effects of tacrolimus on UVB-irradiated cultured keratinocytes in terms of apoptosis, differentiation, cell-cycle regulation and DNA damage. METHODS: Cultured keratinocytes were treated with tacrolimus before and after UVB irradiation and the various cellular physiological changes were evaluated using trypan blue exclusion, terminal dUTP nick-end labelling, flow cytometry and Western blotting analyses. RESULTS: Our results showed that treatment of tacrolimus before or after UVB irradiation had no significant effects on cultured keratinocytes in terms of cell apoptosis, transglutaminase-1, involucrin expression, cell-cycle progression and phospho-H(2)AX compared with UVB irradiation alone. CONCLUSION: The direct effect of tacrolimus on UVB-irradiated keratinocytes is small, suggesting that clinical regimens combining UVB and tacrolimus also have a limited direct effect on healthy skin compared with UVB irradiation alone.

Hyperglycaemic conditions hamper keratinocyte locomotion via sequential inhibition of distinct pathways: new insights on poor wound closure in patients with diabetes.

BACKGROUND: Diabetes mellitus (DM) is characterized by impaired insulin signalling, elevated plasma glucose, and predisposition towards complications involving several organs. A major complication of DM is impairment of wound healing. In the re-epithelialization process during wound healing, migration of keratinocytes is a crucial step. Our previous report demonstrated that keratinocytes cultured in hyperglycaemic media showed decreased cell mobility. OBJECTIVES: The current study aimed to explore the effects of high glucose on keratinocyte migration after different treatment durations. METHODS: Keratinocytes were cultivated for indicated time periods under various concentrations of glucose. Relevant assays including Transwell migration and in vitro wound scratch assays, flow cytometric analysis, matrix metalloproteinase-1 (MMP-1) activity assay, determination of mRNA expression and Western blotting were performed. RESULTS: We demonstrated that (i) keratinocyte motility progressively and significantly decreased; (ii) the keratinocyte activation marker K16 was significantly suppressed; (iii) expression of alpha2beta1 integrin and MMP-1, both crucial for keratinocyte locomotion on collagen type I, was significantly downregulated; and (iv) expression of the phosphorylated signal transducer and activator of transcription-1 significantly decreased after hyperglycaemic treatment. More specifically, different pathways become involved after prolonged duration of high glucose cultivation to reduce keratinocyte locomotion further. CONCLUSIONS: We have demonstrated that high glucose treatment results in progressive suppression of keratinocyte locomotion and elucidated the molecular mechanisms involved. These results provide a reasonable explanation for the poor wound healing seen in patients with DM.

Pressure Dependence of Superconductivity in Single-Phase K3C60.

The superconducting compound K(3)C(60) (with transition temperature T(c) = 19.3 kelvin at ambient pressure), formed as a single phase by reaction of alkali vapor with solids of the icosahedral C(60) molecule (buckminsterfullerene), shows a very large decrease of T(c) with increasing pressure. Susceptibility measurements on sintered pellets showing bulk superconductivity are reported up to 21 kilobars of pressure, where T(c) is already less than 8 kelvin. The results are consistent with a piling up of the density of states at the Fermi level.

Regulation of transcription by a protein methyltransferase.

The p160 family of coactivators, SRC-1, GRIP1/TIF2, and p/CIP, mediate transcriptional activation by nuclear hormone receptors. Coactivator-associated arginine methyltransferase 1 (CARM1), a previously unidentified protein that binds to the carboxyl-terminal region of p160 coactivators, enhanced transcriptional activation by nuclear receptors, but only when GRIP1 or SRC-1a was coexpressed. Thus, CARM1 functions as a secondary coactivator through its association with p160 coactivators. CARM1 can methylate histone H3 in vitro, and a mutation in the putative S-adenosylmethionine binding domain of CARM1 substantially reduced both methyltransferase and coactivator activities. Thus, coactivator-mediated methylation of proteins in the transcription machinery may contribute to transcriptional regulation.