HIV Activist Identity, Commitment, and Orientation Scale (HAICOS): Psychometric Evaluation to Assess Clinician's Propensity Towards HIV Activism in Malaysia.

HIV activism has a long history of advancing HIV treatment and is critical in dismantling HIV-related stigma. This study evaluated the psychometric quality of the HIV Activist Identity, Commitment, and Orientation Scale (HAICOS) to assess clinicians' propensity towards HIV activism in Malaysia. From November 2022 to March 2023, 74 general practitioners and primary care physicians in Malaysia participated in the study. The exploratory factor analysis (EFA) extracted an internally consistent three-factor solution with 13 items: (1) HIV activist identity and commitment, orientation towards (2) day-to-day, and (3) structural activism. The Cronbach's alpha value was 0.91, and intra-class correlation coefficient for test-retest reliability was 0.86. Stigma-related (prejudice and discrimination intent) and clinical practice (comfort in performing clinical tasks with key populations and knowledge about HIV pre-exposure prophylaxis) measures supported the construct validity of the scale. The study provided concise, structurally valid, and reliable measures to evaluate HIV activism among clinicians.

RESUMEN: El activismo del VIH tiene una larga historia de avanzar el tratamiento del VIH y es crítico para desmantelar el estigma relacionado al VIH. Este estudio evaluó la calidad psicométrica de la Escala de Identidad, Compromiso y Orientación de Activistas del VIH (HAICOS) para evaluar la propensión de los médicos hacia el activismo del VIH en Malasia. Desde noviembre del 2022 hasta marzo del 2023, 74 médicos generales y de atención primaria en Malasia participaron en este estudio. El análisis factorial exploratorio (AFE) extrajo una solución de tres factores internamente consistente con 13 ítems: (1) identidad y compromiso del activismo del VIH; orientación hacia (2) el activismo cotidiano y (3) el activismo estructural. El valor alfa de Cronbach fue de 0.91 y el coeficiente de correlación intraclase para la confiabilidad prueba-reprueba fue de 0.86. Las medidas relacionadas con el estigma (prejuicio e intención de discriminación) y la práctica clínica (comodidad realizando tareas clínicas con poblaciones claves y conocimiento sobre la profilaxis pre-exposición del VIH) respaldaron la validez de constructo de la escala. El estudio proporcionó medidas concisas, estructuralmente válidas y confiables para evaluar el activismo de VIH entre los médicos.

Seed Priming with Dynamically Transformed Selenium Nanoparticles to Enhance Salt Tolerance in Rice.

Seed priming with nanomaterials is an emerging approach for improving plant stress tolerance. Here, we demonstrated a mechanism for enhancing salt tolerance in rice under salt stress via priming with nonstimulatory nanoparticles such as selenium nanoparticles (SeNPs), distinct from stimulatory nanomaterials. Due to the dynamic transformation ability of SeNPs, SeNP priming could enhance rice salt tolerance by mediating the glutathione cycle to eliminate excess reactive oxygen species (ROS). During priming, SeNPs penetrated rice seeds and transitioned into a soluble form (99.9%) within the embryo endosperm. Subsequently, the soluble selenium (Se) was transported to rice roots and metabolized into various Se-related derivatives, including selenomethionine (SeMet), Na2SeO3 (Se IV), selenocysteine (SeCys2), and methylselenocysteine (MeSeCys). These derivatives significantly enhanced the root activities of key enzymes such as glutathione peroxidase (GSH-PX), glutathione reductase (GR), catalase (CAT), peroxidase (POD), and superoxide dismutase (SOD) by 24.97%, 47.98%, 16.23%, 16.81%, and 14.82%, respectively, thus reinforcing the glutathione cycle and ROS scavenging pathways. Moreover, these alterations induced transcriptional changes in rice seedlings, with genes involved in signal transduction, transcription factors (TFs), ROS scavenging, and protein folding being upregulated, activating signal perception and self-repair mechanisms. These findings offer valuable insights for the agricultural application of nanomaterials.

Lymph node metastasis diagnosis of postoperative OSCC patients by analyzing extracellular vesicles in drainage fluid based on microfluidic isolation.

Lymph node metastasis (LNM) is a typical marker in oral squamous cell carcinoma (OSCC) indicating poor prognosis. Pathological examination by artificial image acquisition and analysis, as the main diagnostic method for LNM, often takes a week or longer which may cause great anxiety of the patient and also retard timely treatment. However, there are few efficient fast LNM diagnosis methods in clinical applications currently. Our previous study profiled the proteomics of extracellular vesicles (EVs) derived from postoperative drainage fluid (PDF) and showed the potential of detecting specific EVs that expressed aspartate ß-hydroxylase (ASPH) for LNM diagnosis in OSCC patients. Considering that the analysis of ASPH+ PDF-EVs is challenging due to their low abundance (counting less than 10% of total EVs in PDF) and the complex EV isolation process of ultra-centrifugation, we developed a facile platform containing two microfluidic chips filled with antibody-modified microbeads to isolate ASPH+ PDF-EVs, with both the capture and retrieval rate reaching around 90%. Clinical sample analysis based on our method revealed that a mean of 6 × 106 /mL ASPH+ PDF-EVs could be isolated from LNM+ OSCC patients compared to 2.5 × 106 /mL in LNM- OSCC ones. When combined with enzyme-linked immunosorbent assay (ELISA) technique that was commonly used in clinical laboratories in hospitals, this microfluidic platform could precisely distinguish postoperative OSCC patients with LNM or not in several hours, which were validated by a double-blind test containing 6 OSCC patients. We believe this strategy has promise for early diagnosis of LNM in postoperative OSCC patients and finally helps guiding timely and reasonable treatment in clinic.

Carrier-Free ATP-Activated Nanoparticles for Combined Photodynamic Therapy and Chemotherapy under Near-Infrared Light.

The combination of photodynamic therapy (PDT) and chemotherapy (chemo-photodynamic therapy) for enhancing cancer therapeutic efficiency has attracted tremendous attention in the recent years. However, limitations, such as low local concentration, non-suitable treatment light source, and uncontrollable release of therapeutic agents, result in reduced combined treatment efficacy. This study considered adenosine triphosphate (ATP), which is highly upregulated in tumor cells, as a biomarker and developed ingenious ATP-activated nanoparticles (CDNPs) that are directly self-assembled from near-infrared photosensitizer (Cy-I) and amphiphilic Cd(II) complex (DPA-Cd). After selective entry into tumor cells, the positively charged CDNPs would escape from lysosomes and be disintegrated by the high ATP concentration in the cytoplasm. The released Cy-I is capable of producing single oxygen (1 O2 ) for PDT with 808 nm irradiation and DPA-Cd can concurrently function for chemotherapy. Irradiation with 808 nm light can lead to tumor ablation in tumor-bearing mice after intravenous injection of CDNPs. This carrier-free nanoparticle offers a new platform for chemo-photodynamic therapy.

Red-light is an environmental effector for mutualism between begomovirus and its vector whitefly.

Environments such as light condition influence the spread of infectious diseases by affecting insect vector behavior. However, whether and how light affects the host defense which further affects insect preference and performance, remains unclear, nor has been demonstrated how pathogens co-adapt light condition to facilitate vector transmission. We previously showed that begomoviral ßC1 inhibits MYC2-mediated jasmonate signaling to establish plant-dependent mutualism with its insect vector. Here we show red-light as an environmental catalyzer to promote mutualism of whitefly-begomovirus by stabilizing ßC1, which interacts with PHYTOCHROME-INTERACTING FACTORS (PIFs) transcription factors. PIFs positively control plant defenses against whitefly by directly binding to the promoter of terpene synthase genes and promoting their transcription. Moreover, PIFs interact with MYC2 to integrate light and jasmonate signaling and regulate the transcription of terpene synthase genes. However, begomovirus encoded ßC1 inhibits PIFs' and MYC2' transcriptional activity via disturbing their dimerization, thereby impairing plant defenses against whitefly-transmitted begomoviruses. Our results thus describe how a viral pathogen hijacks host external and internal signaling to enhance the mutualistic relationship with its insect vector.

Structure-function analyses of coiled-coil immune receptors define a hydrophobic module for improving plant virus resistance.

Plant immunity relies on nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs) that detect microbial patterns released by pathogens, and activate localized cell death to prevent the spread of pathogens. Tsw is the only identified resistance (R) gene encoding an NLR, conferring resistance to tomato spotted wilt orthotospovirus (TSWV) in pepper species (Capsicum, Solanaceae). However, molecular and cellular mechanisms of Tsw-mediated resistance are still elusive. Here, we analysed the structural and cellular functional features of Tsw protein, and defined a hydrophobic module to improve NLR-mediated virus resistance. The plasma membrane associated N-terminal 137 amino acid in the coiled-coil (CC) domain of Tsw is the minimum fragment sufficient to trigger cell death in Nicotiana benthamiana plants. Transient and transgenic expression assays in plants indicated that the amino acids of the hydrophobic groove (134th-137th amino acid) in the CC domain is critical for its full function and can be modified for enhanced disease resistance. Based on the structural features of Tsw, a super-hydrophobic funnel-like mutant, TswY137W, was identified to confer higher resistance to TSWV in a SGT1 (Suppressor of G-two allele of Skp1)-dependent manner. The same point mutation in a tomato Tsw-like NLR protein also improved resistance to pathogens, suggesting a feasible way of structure-assisted improvement of NLRs.

Insight into the purification of algael water by a novel flocculant with enhanced branched nanochitosan structure.

For improving inadequate nanostructural stability and promote algal removal efficiency, a novel nanochitosan-grafted flocculant (PAD-g-MNC) with an enhanced branched nanostructure and high molecular weight (MW) was fabricated via maleic anhydride acylation polymerization. Characterization results verified the successful synthesis of the flocculant and the formation of an irregular particle nanostructure. PAD-g-MNC exhibited superior algal and extracellular organic matter (EOM) removal and obtained the turbidity and chlorophyll-a removal rates of 93.46%-95.39% and 95.10%-97.31%, respectively, at the dosage of 4-5 mg L-1. The growth rate, strength factor, and recovery factor of algal flocs flocculated by PAD-g-MNC were 90.36, 0.63, and 0.27 (100 rpm), respectively, and were higher than other flocculants prepared through conventional methods. Results indicated that the high intrinsic viscosity and stability branched nanostructure promoted the formation of stable flocs and regeneration ability of flocs. MW distribution and three-dimensional fluorescence analyses revealed that the special structure of PAD-g-MNC was beneficial to the removal of tryptophan-like proteins in EOM. Strong adsorption-adhesion and bridging-netting effects of the nanostructure chain were the dominated mechanisms in the improvement of flocculation efficiency. This study provided theoretical and experimental guidance for the design of flocculants with superior performance and efficient algal water purification performance.

Protection of Exogenous Phosphocreatine for Myocardium in Percutaneous Coronary Intervention Related to Inflammation.

OBJECTIVES: Although injury of myocardium after percutaneous coronary intervention (PCI) has been reported, the mechanism and effect of exogenous phosphocreatine (PCr) supplementation on the injury are yet to be elucidated. Biomarkers, such as interleukin-6 (IL-6) and variations in white blood cells for inflammation, and serum cardiac troponin I (cTnI) for myocardial injury are examined. METHODS: A total of 105 patients undergoing PCI were included and randomly divided into two groups: control (treated with routine hydration therapy) and PCr (treated with additional intravenous infusion of exogenous PCr). The serum levels of biomarkers were detected at administration and 4, 12, 24, and 48 h after PCI, with natural logarithmic (loge) transformation of data when modeling assumptions were not fulfilled. RESULTS: The level of loge-transformed IL-6 increased in both groups, especially at 12 and 24 h after the operation, and that of PCr group was less than the control group at 48 h. The content of loge-transformed cTnI was significantly increased in both groups, while that of the PCr group was markedly lower than the control group at all time points after PCI. Moreover, the ratio of neutrophils was elevated at all time points after PCI, while that of the PCr group was lower at 48 h, and the variations in the ratio of lymphocytes showed opposite results. CONCLUSIONS: Exogenous phosphocreatine reduces stent implantation, triggers inflammation manifested as decreased serum levels of IL-6 and the aggregation of neutrophils, and protects the myocardium of the patients undergoing PCI. These findings provided the potential mechanism and treatment for myocardial injury associated with PCI.

Delayed HIV testing and treatment seeking, and associated support needs among people living with HIV in Malaysia: a qualitative study.

Background By the end of 2017, an estimated 83% of people living with HIV in Malaysia knew their serostatus. However, the Ministry of Health reported a high proportion of those newly diagnosed had low CD4 counts <200 cells/µL, indicating late presentation for testing may be pervasive. METHODS: A qualitative study was conducted to explore the context and experiences of people at risk of HIV infection testing and seeking treatment later in the course of their infection. Participants recruited (n = 20) were HIV positive, aged >18 years who fit the description of late presentation (World Health Organization defined as CD4 cell count <350 cells/µL). Semi-structured interviews were conducted, and a framework approach was used to interrogate the data. RESULTS: Many participants perceived themselves at low risk of HIV infection and did not undergo routine voluntary testing; rather, they were diagnosed when seeking treatment for serious illness or as part of mandatory employment-related testing. Perceived lack of confidentiality and potential discriminatory behaviour at public health facilities were significant deterrents to testing. Participants were satisfied with HIV treatment, but rarely sought psychosocial support in order to 'protect' their privacy. CONCLUSION: Unless drivers of HIV infection are effectively addressed, including stigmatising and discriminatory practices, and low health literacy, the occurrence of late presentation will persist. Their collective impact will not only jeopardise efforts to improve the treatment cascade, but may also impact engagement with other biomedical prevention and care technologies.

Nile-Red-Based Fluorescence Probe for Selective Detection of Biothiols, Computational Study, and Application in Cell Imaging.

A new colorimetric and fluorescence probe NRSH based on Nile-red chromophore for the detection of biothiols has been developed, exhibiting high selectivity towards biothiols over other interfering species. NRSH shows a blue shift in absorption peak upon reacting with biothiols, from 587 nm to 567 nm, which induces an obvious color change from blue to pink and exhibits a 35-fold fluorescence enhancement at 645 nm in red emission range. NRSH displays rapid (<1 min) response for H2S, which is faster than other biothiols (>5 min). The detection limits of probe NRSH towards biothiols are very low (22.05 nM for H2S, 34.04 nM for Cys, 107.28 nM for GSH and 113.65 nM for Hcy). Furthermore, NRSH is low cytotoxic and can be successfully applied as a bioimaging tool for real-time monitoring biothiols in HeLa cells. In addition, fluorescence mechanism of probe NRSH is further understood by theoretical calculations.

Hydrogen peroxide as a mediator of 5-aminolevulinic acid-induced Na+ retention in roots for improving salt tolerance of strawberries.

To explore the mechanisms of 5-aminolevulinic acid (ALA)-improved plant salt tolerance, strawberries (Fragaria × ananassa Duch. cv. 'Benihoppe') were treated with 10 mg l-1 ALA under 100 mmol l-1 NaCl stress. We found that the amount of Na+ increased in the roots but decreased in the leaves. Laser scanning confocal microscopy (LSCM) observations showed that ALA-induced roots had more Na+ accumulation than NaCl alone. Measurement of the xylem sap revealed that ALA repressed Na+ concentrations to a large extent. The electron microprobe X-ray assay also confirmed ALA-induced Na+ retention in roots. qRT-PCR showed that ALA upregulated the gene expressions of SOS1 (encoding a plasma membrane Na+ /H+ antiporter), NHX1 (encoding a vacuolar Na+ /H+ antiporter) and HKT1 (encoding a protein of high-affinity K+ uptake), which are associated with Na+ exclusion in the roots, Na+ sequestration in vacuoles and Na+ unloading from the xylem vessels to the parenchyma cells, respectively. Furthermore, we found that ALA treatment reduced the H2 O2 content in the leaves but increased it in the roots. The exogenous H2 O2 promoted plant growth, increased root Na+ retention and stimulated the gene expressions of NHX1, SOS1 and HKT1. Diphenyleneiodonium (DPI), an inhibitor of H2 O2 generation, suppressed the effects of ALA or H2 O2 on Na+ retention, gene expressions and salt tolerance. Therefore, we propose that ALA induces H2 O2 accumulation in roots, which mediates Na+ transporter gene expression and more Na+ retention in roots, thereby improving plant salt tolerance.

Differential expression of vacuolar and defective cell wall invertase genes in roots and seeds of metalliferous and non-metalliferous populations of Rumex dentatus under copper stress.

Acid invertase activities in roots and young seeds of a metalliferous population (MP) of Rumex dentatus were previously observed to be significantly higher than those of a non-metalliferous population (NMP) under Cu stress. To date, no acid invertase gene has been cloned from R. dentatus. Here, we isolated four full-length cDNAs from the two populations of R. dentatus, presumably encoding cell wall (RdnCIN1 and RdmCIN1 from the NMP and MP, respectively) and vacuolar invertases (RdnVIN1 and RdmVIN1 from the NMP and MP, respectively). Unexpectedly, RdnCIN1 and RdmCIN1 most likely encode special defective invertases with highly attenuated sucrose-hydrolyzing capacity. The transcript levels of RdmCIN1 were significantly higher than those of RdnCIN1 in roots and young seeds under Cu stress, whereas under control conditions, the former was initially lower than the latter. Unexpected high correlations were observed between the transcript levels of RdnCIN1 and RdmCIN1 and the activity of cell wall invertase, even though RdnCIN1 and RdmCIN1 do not encode catalytically active invertases. Similarly, the transcript levels of RdmVIN1 in roots and young seeds were increased under Cu stress, whereas those of RdnVIN1 were decreased. The high correlations between the transcript levels of RdnVIN1 and RdmVIN1 and the activity of vacuolar invertase indicate that RdnVIN1 and RdmVIN1 might control distinct vacuolar invertase activities in the two populations. Moreover, a possible indirect role for acid invertases in Cu tolerance, mediated by generating a range of sugars used as nutrients and signaling molecules, is discussed.

Nitrogen Use Efficiency Is Mediated by Vacuolar Nitrate Sequestration Capacity in Roots of Brassica napus.

Enhancing nitrogen use efficiency (NUE) in crop plants is an important breeding target to reduce excessive use of chemical fertilizers, with substantial benefits to farmers and the environment. In Arabidopsis (Arabidopsis thaliana), allocation of more NO3 (-) to shoots was associated with higher NUE; however, the commonality of this process across plant species have not been sufficiently studied. Two Brassica napus genotypes were identified with high and low NUE. We found that activities of V-ATPase and V-PPase, the two tonoplast proton-pumps, were significantly lower in roots of the high-NUE genotype (Xiangyou15) than in the low-NUE genotype (814); and consequently, less vacuolar NO3 (-) was retained in roots of Xiangyou15. Moreover, NO3 (-) concentration in xylem sap, [(15)N] shoot:root (S:R) and [NO3 (-)] S:R ratios were significantly higher in Xiangyou15. BnNRT1.5 expression was higher in roots of Xiangyou15 compared with 814, while BnNRT1.8 expression was lower. In both B. napus treated with proton pump inhibitors or Arabidopsis mutants impaired in proton pump activity, vacuolar sequestration capacity (VSC) of NO3 (-) in roots substantially decreased. Expression of NRT1.5 was up-regulated, but NRT1.8 was down-regulated, driving greater NO3 (-) long-distance transport from roots to shoots. NUE in Arabidopsis mutants impaired in proton pumps was also significantly higher than in the wild type col-0. Taken together, these data suggest that decrease in VSC of NO3 (-) in roots will enhance transport to shoot and essentially contribute to higher NUE by promoting NO3 (-) allocation to aerial parts, likely through coordinated regulation of NRT1.5 and NRT1.8.

Effect of oil gauze silver dressings on diabetic foot ulcers in the elderly.

OBJECTIVE: To compare the clinical efficacy and safety of oil gauze silver dressing and silver ions dressing on diabetic ulcers in elderly outpatients. METHODS: Twenty-two patients with Type-2 diabetic foot ulcers were included in the study conducted at Yantai Yuhuangding Hospital between April 2013 and April 2014. At the time of enrolment they were divided into the silver ions and oil gauze silver groups based on the order of admission. Dressings were changed twice weekly until the ulcer had healed. Clinical efficacy measures were healing outcomes and speed of healing. Adverse events were recorded. RESULTS: The silver ions and oil gauze silver groups were comparable at baseline (P>0.05). Before treatment, the fasting blood glucose (FBG) and two hour postprandial blood glucose (2h PBG) levels were 6.88±0.50 mmol /L and 15.55±2.47 mmol/L in the oil gauze silver group, and 6.93±0.41 mmol/L and 15.23±2.58 mmol/L in the silver ions group, respectively. After treatment, the FBG and 2h PBG levels were 6.82±0.32 mmol/L and 8.67±0.86 mmol/L in the oil gauze silver group, and 6.85±0.27 mmol/L and 8.83 ± 0.61 mmol/L in the silver ions group, respectively. The healing time of foot ulcers was 23.8±2.7 days in the silver ions group and 15.8±2.5 days in the oil gauze silver group (P<0.05). CONCLUSION: Oil gauze silver dressings for diabetic foot ulcers were associated with favorable clinical outcomes compared with silver ion dressings, especially with respect to ulcer healing speed.

[Protection of Fufang Zhenzhu Tiaozhi Formula on NAFLD in Mice by Regulating ERS].

Objective: To investigate the effect of Fufang Zhenzhu Tiaozhi formula( FZT) in a long-term high-fat diet-induced nonalcoholic fatty liver disease( NAFLD) mouse model and to study the regulation of hepatic endoplasmic reticulum stress( ERS). Methods: Mice model with NAFLD was established by feeding purified high-fat diet,and treated with FZT at the same time. After treatment with FZT for 20 weeks, the plasma total cholesterol( TC),hepatic TG, triglyceride( TG) level,liver tissue pathology morphology and expression of lipid metabolism, ERS related genes were observed,and measured the effect of FZT on NAFLD in mice. Results: Compared with normal control group,plasma and hepatic TC,TG level were significantly increased in model group( P < 0. 05); compared with model group,the plasma and hepatic TC,TG level were significantly lower in FZT high and low-dose group( P < 0. 05); XBP-1,PERK and SREBP-1c mRNA expression of liver tissue were significantly lower( P < 0. 05). Conclusion: FZT can significantly alleviate NAFLD in mice which induced by a long-term high-fat diet, reduction of the hepatic ERS activity may be one of its mechanisms alleviate NAFLD.

The periplasmic PDZ domain-containing protein Prc modulates full virulence, envelops stress responses, and directly interacts with dipeptidyl peptidase of Xanthomonas oryzae pv. oryzae.

PDZ domain-containing proteases, also known as HtrA family proteases, play important roles in bacterial cells by modulating disease pathogenesis and cell-envelope stress responses. These proteases have diverse functions through proteolysis- and nonproteolysis-dependent modes. Here, we report that the genome of the causative agent of rice bacterial blight, Xanthomonas oryzae pv. oryzae, encodes seven PDZ domain-containing proteins. Systematic inactivation of their encoding genes revealed that PXO_01122 and PXO_04290 (prc) are involved in virulence. prc encodes a putative HtrA family protease that localizes in the bacterial periplasm. Mutation of prc also resulted in susceptibility to multiple environmental stresses, including H2O2, sodium dodecylsulfate, and osmolarity stresses. Comparative subproteomic analyses showed that the amounts of 34 periplasmic proteins were lower in the prc mutant than in wild-type. These proteins were associated with proteolysis, biosynthesis of macromolecules, carbohydrate or energy metabolism, signal transduction, and protein translocation or folding. We provide in vivo and in vitro evidence demonstrating that Prc stabilizes and directly binds to one of these proteins, DppP, a dipeptidyl peptidase contributing to full virulence. Taken together, our results suggest that Prc contributes to bacterial virulence by acting as a periplasmic modulator of cell-envelope stress responses.

A three-component signalling system fine-tunes expression kinetics of HPPK responsible for folate synthesis by positive feedback loop during stress response of Xanthomonas campestris.

During adaptation to environments, bacteria employ two-component signal transduction systems, which contain histidine kinases and response regulators, to sense and respond to exogenous and cellular stimuli in an accurate spatio-temporal manner. Although the protein phosphorylation process between histidine kinase and response regulator has been well documented, the molecular mechanism fine-tuning phosphorylation levels of response regulators is comparatively less studied. Here we combined genetic and biochemical approaches to reveal that a hybrid histidine kinase, SreS, is involved in the SreK-SreR phosphotransfer process to control salt stress response in the bacterium Xanthomonas campestris. The N-terminal receiver domain of SreS acts as a phosphate sink by competing with the response regulator SreR to accept the phosphoryl group from the latter's cognate histidine kinase SreK. This regulatory process is critical for bacterial survival because the dephosphorylated SreR protein participates in activating one of the tandem promoters (P2) at the 5' end of the sreK-sreR-sreS-hppK operon, and then modulates a transcriptional surge of the stress-responsive gene hppK, which is required for folic acid synthesis. Therefore, our study dissects the biochemical process of a positive feedback loop in which a 'three-component' signalling system fine-tunes expression kinetics of downstream genes.

Correlation between Vascular Endothelial Growth Factor and Somatostatin Receptor with Progression and Prognosis in Gastric Cancer.

BACKGROUND/AIMS: To investigate the expression of vascular endothelial growth factor (VEGF) and somatostatin receptor (SSTR) and their clinicopathological and prognostic value in gastric cancer (GC). METHODOLOGY: The expression of VEGF and SSTR in 107 cases of GC tissue and 30 cases of gastric mucosa were detected by immunohistochemistry. Clinicopathological and prognostic association of VEGF and SSTR in GC was analyzed RESULTS: The expression of VEGF in GC (70.1%) was significantly higher than that in gastric mucosa (20.0%) The expression of SSTR in GC (62.6%) was significantly lower than that in normal tissues (93.3%). VEGF and SSTR expression were both associated with histological differentiation, depth of invasion, TNM stage, and lymph node metastasis (P < 0.05). The negative expression of VEGF or the positive expression of SSTR was correlated with better overall survival of GC patients. The Cox analysis demonstrated that the expression of VEGF and SSTR, pathological type, TNM stage, and lymph node metastasis were the independent predictors for overall survival in GC (P = 0.005, P = 0.006, P = 0.003, P = 0.002, and P = 0.001, respectively). CONCLUSIONS: The expression of VEGF and SSTR were associated with progression and prognosis of GC.

Safety and efficacy of endoscopic retrograde cholangiopancreatography for common bile duct stones in liver cirrhotic patients.

In order to investigate the safety and efficacy of endoscopic retrograde cholangiopancreatograpy (ERCP) in liver cirrhosis patients with common bile duct stones, we retrospectively analyzed data of 46 common bile duct stones patients with liver cirrhosis who underwent ERCP between 2000 and 2008. There were 12 cases of Child-Pugh A, 26 cases of Child-Pugh B, and 8 cases of Child-Pugh C. 100 common bile duct stones patients without liver cirrhosis were randomly selected. All the patients were subjected to ERCP for biliary stones extraction. The rates of bile duct clearance and complications were compared between cirrhotic and non-cirrhotic patients. The success rate of selective biliary cannulation was 95.6% in liver cirrhotic patients versus 97% in non-cirrhotic patients (P>0.05). The bile duct clearance rate was 87% in cirrhotic patients versus 96% in non-cirrhotic patients, but the difference was not statistically significant. Two liver cirrhotic patients (4.35%, 2/46) who were scored Child-Pugh C had hematemesis and melena 24 h after ERCP. The hemorrhage rate after ERCP in non-cirrhotic patients was 3%. The hemorrhage rate associated with ERCP in Child-Pugh C patients was significantly higher (25%, 2/8) than that (3%, 3/100) in non-cirrhotic patients (P<0.01%). There was no significant difference between these two groups in the rate of post-ERCP pancreatitis (PEP) and cholangitis. ERCP is safe and effective for Child-Pugh A and B cirrhotic patients with common bile duct stones. Hemorrhage risk in ERCP is higher in Child-Pugh C patients.

The blockade of the TGF-ß pathway alleviates abnormal glucose and lipid metabolism of lipodystrophy not obesity.

TGF-ß is thought to be involved in the physiological functions of early organ development and pathological changes in substantial organ fibrosis, while studies around adipose tissue function and systemic disorders of glucolipid metabolism are still scarce. In this investigation, two animal models, aP2-SREBP-1c mice and ob/ob mice, were used. TGF-ß pathway showed up-regulated in the inguinal white adipose tissue (iWAT) of the two models. SB431542, a TGF-ß inhibitor, successfully increased inguinal white adipocyte size by more than 1.5 times and decreased the weight of Peripheral organs including liver, Spleen and Kidney to 73.05%/62.18%/73.23% of pre-administration weights. The iWAT showed elevated expression of GLUTs and lipases, followed by a recovery of circulation GLU, TG, NEFA, and GLYCEROL to the wild-type levels in aP2-SREBP-1c mice. In contrast, TGF-ß inhibition did not have similar effects on that of ob/ob mice. In vitro, TGF-ß blocker treated mature adipocytes had considerably higher levels of glycerol and triglycerides than the control group, whereas GLUTs and lipases expression levels were unchanged. These findings show that inhibiting the abnormally upregulated TGF-ß pathway will only restore iWAT expansion and ameliorate the global metabolic malfunction of glucose and lipids in lipodystrophy, not obesity.