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Bloodstream infection (BSI) refers to the infection of blood by pathogens. Severe immune response to BSI can lead to sepsis, a systemic infection leading to multiple organ dysfunction, coupled with drug resistance, mortality, and limited clinical treatment options. This work aims to further investigate the new interplay between bacterial exocrine regulatory protein and host immune cells in the context of highly drug-resistant malignant BSI. Whether interfering with related regulatory signaling pathways can reverse the inflammatory disorder of immune cells. In-depth analysis of single-cell sequencing results in Septic patients for potential immunodeficiency factors. Analysis of key proteins enriched by host cells and key pathways using proteomics. Cell models and animal models validate the pathological effects of DnaK on T cells, MAITs, macrophages, and osteoclasts. The blood of patients was analyzed for the immunosuppression of T cells and MAITs. We identified that S. maltophilia -DnaK was enriched in immunodeficient T cells. The activation of the JAK2/STAT1 axis initiated the exhaustion of T cells. Septic patients with Gram-negative bacterial infections exhibited deficiencies in MAITs, which correspond to IFN-γ. Cellular and animal experiments confirmed that DnaK could facilitate MAIT depletion and M1 polarization of macrophages. Additionally, Fludarabine mitigated M1 polarization of blood, liver, and spleen in mice. Interestingly, DnaK also repressed osteoclastogenesis of macrophages stimulated by RANKL. S.maltophilia -DnaK prompts the activation of the JAK2/STAT1 axis in T cells and the M1 polarization of macrophages. Targeting the DnaK's crosstalk can be a potentially effective approach for treating the inflammatory disorder in the broad-spectrum drug-resistant BSI. [Display omitted] • The mechanism of S. maltophilia -DnaK in the immune interaction between T cells and macrophages during bloodstream infection. • The exocrine of S. maltophilia promotes the activation of the JAK2/STAT1 axis in T lymphocytes and initiates the process of apoptosis. • Septic patients infected with Gram-negative bacteria have quantitative and functional deficits in MAIT in peripheral blood, which correlated with IFN-γ concentrations. • DnaK can promote MAIT depletion and macrophage M1 polarization. Fludarabine attenuates M1 polarization in peripheral blood, liver, and spleen macrophages in mice with S. maltophilia bloodstream infection. Interestingly, DnaK inhibits osteoclastogenesis. [ABSTRACT FROM AUTHOR]

The exploration of non-precious metal catalysts has always been a hot topic. Here, a new type of Ni–La-Nd-Y film was electrodeposited on nickel foam (NF). The Ni–La-Nd-Y film shows outstanding HER activity and stability under alkaline conditions. La 2 NiO 4 makes the electrode surface present a regular layered structure, which greatly increases the number of electrochemically active sites. Ni–La-Nd-Y only needs 46 mV overpotential driving current density of 10 mA cm−2 in 1MKOH solution, which is very close to the HER performance of metal Pt. By doping rare earth elements and taking advantage of the shrinkage characteristics of lanthanides, this work took advantage of the shrinkage characteristics of the lanthanide series and found new ideas for improving catalysts through the combination of different rare earth elements. We fabricated a Ni–La-Nd-Y film, which can accelerate charge transfer and provide more active sites. Among electrocatalysts made with Ni, La, Nd, Y, Ni–La-Nd-Y, for HER, only needs an overpotential of 46 mV to deliver a current density of 10 mA cm−2. This work provides a promising non-noble metal electrocatalyst for water splitting under alkaline conditions. [Display omitted] • One-step electrodeposition Ni–La-Nd-Y technology is convenient and fast. • Ni–La-Nd-Y catalyst η 10 = 42 mV. • La 2 NiO 4 perovskite structure contributes to the improvement of HER performance. [ABSTRACT FROM AUTHOR]

Objective: To investigate the significance of T helper type 1 (Th1)/Th2 cytokines in the pathogenesis of unexplained recurrent spontaneous abortion (URSA), and reveal the value of single cytokines and their proportions in early diagnosis. Methods: A total of 44 URSA patients (URSA group), 51 patients with adverse pregnancy history (ad‐pregnancy group), and 42 healthy volunteers with normal pregnancy (pregnancy group) were recruited for a cross‐sectional study from July 2018 to April 2019 in the Second Xiangya Hospital. Pregnancies involving chromosomal abnormalities, infection, autoimmune diseases, and anatomical abnormalities were excluded. Flow cytometry was used to determine the level of Th1/Th2 cytokines in peripheral blood. Results: The level of interleukin‐6 (IL‐6) in the peripheral blood of the ad‐pregnancy group was significantly higher than in the other two groups. The ratio of interferon‐γ (IFN‐γ)/IL‐4 in the URSA group was significantly higher than that of the pregnancy group. The area under the curve for IFN‐γ/IL‐4 was 0.821, with high diagnostic efficiency, and sensitivity as high as 84.09%. Conclusion: Laboratory testing for IL‐6 is not recommended for the diagnosis or monitoring of URSA. The variable IFN‐γ/IL‐4 can be used for the initial diagnosis of URSA to reduce the rate of missed diagnosis. This ratio was more important than the expression of a single cytokine in the Th1/Th2 immune response. Synopsis: The ratio of interferon‐γ/interleukin‐4 could be used in the early diagnosis of unexplained recurrent spontaneous abortion, which is more effective than single cytokines. [ABSTRACT FROM AUTHOR]

Abstract: Aim: This study presents fungi and their characteristics identified from burn patients at a major Chinese burn centre. Methods: All burns patients admitted to our Burn Research Institute from 2003 to 2006 inclusive were included in this study. Once fungal infection was suspected clinically, samples including wound tissue, blood, urine, stool and sputum were harvested for the culture of yeast. The sensitivities of the identified yeast were determined and the positive samples and cases were analysed. Results: Out of a total of 3909 cases, 467 patients were clinically suspected of fungal infection, of which 1970 samples were taken for yeast culture. A total of 38 samples and 36 patients tested positive. The three most positive samples were urine, blood and catheter. Candida tropicalis was identified as the most common yeast type (42.1%), followed by Candida albicans (31.6%), Candida famata (T. Famata) (10.5%) and Candida glabrata (T. Glabrata) (7.9%). Except for C. galbrata, most of the yeast strains found in the study were sensitive to the routine antimycotic agents. There were eight deaths in the 36 positive patients. As much as 83.3% of the positive cases suffered burns of more than 50% total body surface area (TBSA) and half of the positive cases were greater than 80% TBSA. A total of 78.95% of the positive samples were taken from patients after 2 weeks post-burn injury. Conclusion: A profile of the fungi isolated from burn patients in a major Chinese burn centre is presented. [Copyright &y& Elsevier]

Abstract: Aim: This study aims to review the changes in management of inhalation injury and the associated reduction in mortality over the past 2 decades. Methods: The records of burn patients with inhalation injury hospitalised in our institute from 1986 to 2005 were retrospectively analysed. The incidence of inhalation injury and the associated mortality were analysed. Meanwhile, the relationship of inhalation injury with age, total burn area, tracheostomy intubation and mechanical ventilation were studied. Results: The incidence of inhalation injury was 8.01% in the total 10 608 hospitalised burn patients during the 20 years surveyed. Inhalation injury was always associated with large-sized burn and was more common in adults. The incidence of tracheostomy and mechanical ventilation increased from 39.46 and 30.28% in the period from 1986 to 1995 to 70.12 and 39.74% from 1996 to 2005, respectively. The overall mortality of inhalation-injured burn patients was 15.88% compared with 0.82% of the non-inhalation group. The mortality of the burn patients with inhalation injury dropped from 25.29% during the first 10 years to 11.71% during the second decade (p <0.01). Mortality secondary to inhalation injury as the lead cause decreased from 14.56 to 6.29% (p <0.01). Conclusion: The care of inhalation injury has made significant progress over the past 2 decades. The early diagnosis of inhalation injury, early airway control and pulmonary function assistance with mechanical ventilation contribute to the reduction of mortality. [Copyright &y& Elsevier]

Abstract: Background: Fluid resuscitation is one of the critical treatments for the major burn patient in the early phases after injury. We evaluated the practice of fluid resuscitation for severely burned patients with the Third Military Medical University (TMMU) protocol, which is most widely used in many regions of China. Methods: Patients with major burns (>30% total body surface area (TBSA)) presenting to Southwest Hospital, Third Military Medical University, between January 2005 and October 2007, were included in this study. Fluid resuscitation was initiated by the TMMU protocol. Results: A total of 71 patients were (46 adults and 25 children) included in this study. All patients survived the first 48h after injury smoothly and none developed abdominal compartment syndrome or other recognised complications associated with fluid resuscitation. The average quantity of fluid infused was 3.3–61.33% more than that calculated based on the TMMU protocol in both adult and paediatric groups. The average urine output during the first 24h after injury was about 1.2ml per kg body weight per hour in the two groups, but reached 1.2ml and 1.7ml during the second 24h in adult and pediatric groups, respectively. Conclusion: This study indicates that the TMMU protocol for fluid resuscitation is a feasible option for burn patients. Individualised resuscitation – guided by the physiological response to fluid administration – is still important as in other protocols. [Copyright &y& Elsevier]

1. Hypoxia-induced cardiomyocyte apoptosis contributes significantly to cardiac dysfunction following trauma, shock and burn injury. There is evidence that heat shock protein (HSP) 90 is anti-apoptotic in cardiomyocytes subjected to a variety of apoptotic stimuli. Because HSP90 acts as an upstream regulator of the serine/threonine protein kinase Akt survival pathway during cellular stress, we hypothesized that HSP90 exerts a cardioprotetive effect via the phosphatidylinositol 3-kinase (PI3-K)/Akt pathway. 2. Neonatal rat cardiomyocytes were subjected to normoxia or hypoxia in the absence or presence of the HSP90 inhibitor geldanamycin (1 µg/mL). Cardiomyocyte apoptosis was assessed by release of lactate dehydrogenase (LDH), terminal deoxyribonucleotidyl transferase-mediated dUTP–digoxigenin nick end-labelling (TUNEL) staining and caspase 3 activity. Expression of HSP90, Akt, Bad and cytochrome c release was determined by western blot analysis. 3. Following exposure of cells to hypoxia, HSP90 was markedly elevated in a time-dependent manner, reaching a peak at 6 h (eightfold increase). Geldanamycin significantly increased hypoxia-induced release of LDH by 114%, the percentage of apoptotic cardiomyocytes by 102% and caspase 3 activity by 78%. Pretreatment of cells with geldanamycin also suppressed phosphorylation of both Akt and its downstream target Bad, but promoted the mitochondrial release of cytochrome c. 4. In conclusion, HSP90 activity is enhanced in cardiomyocytes following hypoxic insult. The anti-apoptotic effect of HSP90 on cardiomyocytes subjected to hypoxia is mediated, at least in part, by the PI3-K/Akt pathway. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To study the epidemiologic characteristics of burns in the elderly patients to reduce risks. Methods: Features, including causes, seasonality, co-morbidities and mortality among 280 burned patients over 60 years old, admitted to Burn Unit, Southwest Hospital from 1999 to 2006, were analyzed retrospectively. Results: The incidence of burns in the elderly has been decreasing gradually from 4.35% in 1999 to 3.81% in 2006. The geriatric burns could happen any time during a year, but most frequently in summer and winter. Seventy percent of the geriatric burns were related to activities of daily life. The co-morbid conditions in the elderly, which comprised 83.9% of the victims, contributed to the burn outcomes. No difference in morbidity was found between rural and urban patients. However, mortality was significantly higher in the rural patients with 30% over TBSA burns. Conclusion: The incidence of geriatric burns has been decreasing associated with social and individual living levels in China. However, the disparity in the mortality rates between rural and urban suggests investment in rural China is needed to reduce health inequalities. [Copyright &y& Elsevier]

Abstract: Objective:: To evaluate the effect of veno-venous continuous renal replacement therapy (CRRT) on the plasma levels of endotoxin and cytokines in severely burned patients with sepsis. Methods:: Twenty adult severely burned patients with sepsis were studied. For the diagnosis of sepsis, patients were randomly divided into CRRT (n =10) and Control (n =10). Both groups received conventional therapy after admission. Veno-venous CRRT was administered to 10 patients in the CRRT group whenever patients were determined to be septic. The plasma level of endotoxin, TNF-alpha, IL-1 beta, IL-6 and IL-8 were measured at 0, 1, 2, 6, 12, 36 and 60h after CRRT initiation, and at 0, 12, 36 and 60h after the patients were diagnosed as having sepsis in the Control group. Main Results:: Plasma level of endotoxin and all the cytokines after CRRT initiation were significantly lower than those before the treatment (P &#60;0.01). The serial change of endotoxin, IL-1 beta, IL-6 and IL-8 was significantly lower at 12, 36 and 60h after treatment compared with Control groups (P &#60;0.01). A significant decrease in plasma TNF-alpha levels was seen at 36 and 60h after treatment compared with Control groups (P &#60;0.01). Conclusion:: Plasma endotoxin and cytokines (TNF-alpha, IL-1 beta, IL-6 and IL-8) can be removed effectively with CRRT in severely burned patients with sepsis. [Copyright &y& Elsevier]

• We first described the epidemiological characteristics of patients with SARS-CoV-2 in Hunan and these patients were early mild cases. • The clinical symptoms, laboratory results, and imaging reports of patients with COVID-19 in the Hunan area were different from Wuhan area. • For non-Wuhan epidemic areas, more attention should be paid to the nucleic acid test results of throat swabs and stools. • Reduced whole blood lymph count can be used as an adjuvant diagnosis of early SARS-CoV-2 infection. • Attention should be paid to asymptomatic carriers, and this is of great significance for the control of the global epidemic. In December 2019, coronavirus Disease 2019 (COVID-19) occurred in Wuhan, Hubei Province, China. The disease has rapidly spread from Wuhan to other regions. To describe the clinical manifestations and epidemiological characteristics of patients with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection in Hunan Province in 2020. From January 19 to February 7, 2020, 33 patients with positive in nucleic acid test of pharyngeal swab were retrospectively collected and analyzed. There are 33 COVID-19 patients (16 male, 17 female), and the median age was 46 years. Nineteen patients (48 %) were associated with a family cluster outbreak. Seventeen patients (52 %) had traveled or lived in Hubei Province. These patients are early mild cases, most common symptoms are fever [23 (70 %)] and cough [13 (39 %)]. Most patients' white blood cell counts are normal, while they manifest as significant reduction in lymphocytes [17/28 (61 %)]. The levels of c-reactive protein and erythrocyte sedimentation rate suggest a typical viral infection. Procalcitonin did not increase and D-dimer increased slightly. Lactate dehydrogenase (LDH) levels have elevated in most patients. CT images of these patients showed bilateral multiple plaques or nodular ground-glass opacities (68.4 %). Fecal nucleic acid results were positive in eight COVID-19 patients accompanied with diarrhea. Tear nucleic acid results were negative in six COVID-19 patients. And four asymptomatic patients were infected with SARS-CoV-2. The clinical symptoms, laboratory results and imaging reports of patients with COVID-19 in Hunan area are significantly different from those in Wuhan area. For non-Wuhan epidemic areas, more attention should be paid to nucleic acid test results of throat swabs and stools, and it is not easily to diagnose based on clinical symptoms and CT results. Reduced whole blood lymph count can be used as an adjuvant diagnosis of early SARS-CoV-2 infection. Attention should be paid to asymptomatic carriers, which is of great significance for the control of the global epidemic. [ABSTRACT FROM AUTHOR]

COVID-19 is spreading almost all over the world at present, which is caused by the 2019 novel coronavirus (2019-nCoV). It was an epidemic firstly in Hubei province of China. The Chinese government has formally set COVID-19 in the statutory notification and control system for infectious diseases according to the Law of the People's Republic of China on the Prevention and Treatment of Infectious Diseases. China currently is still struggling to respond to COVID-19 though intensive actions with progress made. The Burn Department of our hospital is one of sections with the highest infectious risk of COVID-19. Based on our own experience and the guidelines on the diagnosis and treatment of COVID-19 (7th Version) with other regulations and literature, we describe our experience with suggestions for medical practices for burn units during the COVID-19 outbreak. We hope these experiences and suggestions benefit our international colleagues during the pandemic of the COVID-19. [ABSTRACT FROM AUTHOR]

While screening for alternative antibiotics against multidrug-resistant Acinetobacter baumannii, we isolated a virulent A. baumannii bacteriophage Abp1. Transmission electron microscopy revealed that the phage had an icosahedral head with a short tail and should be classified as a member of the Podoviridae family. SDS-PAGE showed that Abp1 contained at least one major and nine minor proteins. In a single-step growth test, we demonstrated that Abp1 had a latent period of 10 min and a burst size of 350. Abp1 also had a relatively narrow host range. The entire genome was sequenced, and the final assembly yielded a 42,185 bp, linear, double-stranded DNA molecule with a G+C content of 39.15 % and containing 54 putative genes. Among these genes, 26 were functionally known, leaving 28 unknown putative genes. Abp1 is a new member of the phiKMV-like virus subgroup of the T7 group; its genome sequence is very similar to that of the A. baumannii phage phiAB1. [ABSTRACT FROM AUTHOR]

[Display omitted] Electrocatalysts for water splitting have been widely explored among recent years. In this study, nickel–selenium–copper (Ni–Se–Cu) coating was synthesized on nickel foam through potentiostatic electrodeposition. The electrochemical kinetics and nucleation mechanisms of the deposition were investigated, and the diffusion coefficient D from different deposition potentials and temperatures was calculated. Results reveal that the electrodeposition of Ni–Se–Cu follows an instantaneous nucleation and diffusion-controlled three-dimensional (3D) growth mechanism. Deposition potential and bath temperature slightly effect the nucleation mechanism of electrodeposition. The apparent activation energy E a of the hydrogen evolution reaction (HER) in 1.0 M KOH electrolyte of Ni–Se–Cu is 21.1 kJ·mol−1, which is lower than that of Ni–Se (37.7 kJ·mol−1). The majority phase formed by nickel and selenium is Ni 3 Se 2 , and a Ni(Cu) solid solution forms after the incorporation of Cu atoms into a Ni lattice. [ABSTRACT FROM AUTHOR]

• We first described the S.maltophilia immunosuppressive effect on T cells and it is meaningful for immunosuppressed patients or co-infections. • T cells stimulated by S.maltophilia with CD4 and CD8 degraded via PD-1/PD-L1 pathway, which led to the massive apoptosis of T cells. • T cells were stimulated by S. maltophilia to secrete IFN-γ. Blocking the PD-1/PD-L1 pathway, apoptosis was suppressed. • S.maltophilia down-regulates host immunity by inhibiting immune cells. Smalotrophomonas maltophilia (S. maltophilia) is common in nosocomial infections. However, few studies have revealed the effect of S. maltophilia on cellular immunity in the host's immune system up to now. In clinical work, we accidentally discovered that S. maltophilia directly stimulated T cells to secrete IFN-γ. S. maltophilia was co-cultured with PBMCs to detect secretion of cytokines (IFN-γ, TNF-α and IL-2) and expression of cell surface molecules (CD3, CD4, CD8, CD69, CD147 and CD152) of T cells. We used light microscopy and electron microscopy to observe the cell morphology and subcellular structure of S. maltophilia co-cultured with lymphocytes. Flow cytometry and Western Blot were used to detect the expression of PD-1/PD-L1 and annexin V in cells. T cells stimulated by S. maltophilia secreted a large amount of IL-2, IFN-γ, and TNF-α. The expression of CD4 and CD8 on the cell surface were declined, accompanied by the activation of the PD-1/PD-L1 pathway, which eventually led to the massive apoptosis of T cells. Electron microscopy showed that cells showed significant apoptotic morphology. Blocking the PD-1/PD-L1 pathway can inhibit the apoptosis-inducing effect of S. maltophilia on T cells. These indicates that T cells are inhibited after being stimulated by S. maltophilia , and then accelerated to induce death without the initiation of an immunologic cascade. This paper demonstrates for the first time the inhibitory effect of S. maltophilia on cellular immunity, and the immunosuppressive effect induced by infection of S. maltophilia should be considered. [ABSTRACT FROM AUTHOR]

COVID-19 pandemic is sweeping the globe. Any outpatient or new inpatient especial in burn department during the pandemic should be as a potential infectious source of COVID-19. It is very important to manage the patients and wards carefully and correctly to prevent epidemic of the virus in burn centers. This paper provides some strategies regarding management of burn ward during the epidemic of COVID-19 or other respiratory infectious diseases. [ABSTRACT FROM AUTHOR]

Exploring efficient, abundant, low-cost and stable materials for hydrogen evolution reaction (HER) is highly desired but still a challenging task. Herein, Ni–Se–Mo electrocatalysts supported on nickel foam (NF) substrate were synthesized by a facile one-step electrodeposition method. The Ni–Se–Mo film presents high electrocatalytic activity and stability toward HER, with a low overpotential of 101 mV to afford a current density of 10 mA cm−2 in 1.0 M KOH medium. Such excellent HER performance of Ni–Se–Mo film induced by the synergistic effects from Mo-doped Ni–Se film leads to the fast electron transfer. This work provides the validity of interface engineering strategy in preparing highly efficient transition metal chalcogenides based HER electrocatalysts. • Ni–Se–Mo electrocatalyst is prepared by a one-step potentiostatic electrodeposition method. • Ni–Se–Mo electrocatalyst presents very good electrocatalytic activity in HER. • Low overpotential of 101 mV at 10 mA cm−2 for HER. • Mo dopants in Ni–Se electrocatalyst lead to higher conductivity and intrinsic HER activity. [ABSTRACT FROM AUTHOR]

Carbapenem-resistant Klebsiella pneumoniae (CRKP) has spread globally and emerged as an urgent public health threat. Bacteriophages are considered an effective weapon against multidrug-resistant pathogens. In this study, we report a novel lytic phage, kpssk3, which is able to lyse CRKP and degrade exopolysaccharide (EPS). The morphological characteristics of kpssk3 observed by transmission electron microscopy, including a polyhedral head and a short tail, indicate that it belongs to the family Podoviridae. A one-step growth curve revealed that kpssk3 has a latent period of 10 min and a burst size of 200 plaque-forming units (pfu) per cell. kpssk3 was able to lyse 25 out of 27 (92.59%) clinically isolated CRKP strains, and it also exhibited high stability to changes in temperature and pH. kpssk3 has a linear dsDNA genome of 40,539 bp with 52.80% G+C content and 42 putative open reading frames (ORFs). No antibiotic resistance genes, virulence factors, or integrases were identified in the genome. Based on bioinformatic analysis, the tail fiber protein of phage kpssk3 was speculated to possess depolymerase activity towards EPS. By comparative genomics and phylogenetic analysis, it was determined that kpssk3 is a new T7-like virus and belongs to the subfamily Autographivirinae. The characterization and genomic analysis of kpssk3 will promote our understanding of phage biology and diversity and provide a potential strategy for controlling CRKP infection. [ABSTRACT FROM AUTHOR]

A novel virulent bacteriophage, φAbp2, infecting multidrug-resistant (MDR) Acinetobacter baumannii was isolated from the wastewater of a sewage management centre at Southwest Hospital, China. Transmission electron microscopy and phylogenetic analysis revealed that φAbp2 belongs to the subfamily Peduovirinae. A one-step growth curve demonstrated that φAbp2 had a latent period of 15 min, a lysis period of 35 min, and a burst size of 222 particles per infected host cell. Moreover, φAbp2 showed a relatively broad host range in local A. baumannii, and it also exhibited tolerance over a wider range of thermal and pH conditions. Genomic sequencing revealed that φAbp2 has a circular double-stranded DNA genome with no sequence similarity to our previously isolated φAbp1. Eighty-eight putative open reading frames (ORFs) encoding 41 proteins of known function and 47 of unknown function were identified, and the G/C content was 37.84%. φAbp2 is a new member of the subfamily Peduovirinae of the family Myoviridae. Its genome sequence is very similar to that of the A. baumannii phage LZ35. [ABSTRACT FROM AUTHOR]

β-Galactosidase is an essential enzyme for the metabolism of lactose in human beings and has an important role in the treatment of lactose intolerance (LI). β-Galactosidase expressed by intestinal microflora, such as lactic acid bacteria (LAB), also alleviates LI. A promising approach to LI management is to exploit a food-grade LAB delivery system that can inhabit the human intestine and overproduce β-galactosidase. In this study, we constructed a food-grade β-galactosidase surface display delivery system and then integrated into the chromosome of Lactococcus lactis (L. lactis) NZ9000 using recombination. Western blot and immunofluorescence analyses confirmed that β-galactosidase was expressed on the cell surface of recombinant L. lactis stain NZ-SDL. The whole-cell biocatalyst exhibits Vmax and Km values of 121.38 ± 7.17 UONPG/g and 65.36 ± 5.54 mM, based on ONPG hydrolysis. The optimum temperature for enzyme activity is 37 °C and the optimum pH is 5.0. Activity of the whole-cell biocatalyst is promoted by Mg2+, Ca2+, and K+, but inhibited by Zn2+, Fe2+, and Fe3+. The system has a thermal stability similar to purified β-galactosidase but better pH stability, and is also more stable in artificial intestinal juice. Oral administration and intraperitoneal injections of NZ-SDL in mice cause no detectable health effects. In conclusion, we have successfully constructed a food-grade gene expression system in L. lactis that displays β-galactosidase on the cell surface. This system exhibits good enzyme activity and stability in vitro, and is safe in vivo. It is therefore a promising candidate for use in LI management. [ABSTRACT FROM AUTHOR]

Key points: Cav3.1 T‐type Ca2+ channel current (ICa‐T) contributes to heart rate genesis but is not known to contribute to heart rate regulation by the sympathetic/β‐adrenergic system (SAS). We show that the loss of Cav3.1 makes the beating rates of the heart in vivo and perfused hearts ex vivo, as well as sinoatrial node cells, less sensitive to β‐adrenergic stimulation; it also renders less conduction acceleration through the atrioventricular node by β‐adrenergic stimulation. Increasing Cav3.1 in cardiomyocytes has the opposite effects. ICa‐T in sinoatrial nodal cells can be upregulated by β‐adrenergic stimulation. The results of the present study add a new contribution to heart rate regulation by the SAS system and provide potential new mechanisms for the dysregulation of heart rate and conduction by the SAS in the heart. T‐type Ca2+ channel can be a target for heart disease treatments that aim to slow down the heart rate Abstract: Cav3.1 (α1G) T‐type Ca2+ channel (TTCC) is expressed in mouse sinoatrial node cells (SANCs) and atrioventricular (AV) nodal cells and contributes to heart rate (HR) genesis and AV conduction. However, its role in HR regulation and AV conduction acceleration by the β‐adrenergic system (SAS) is unclear. In the present study, L‐ (ICa‐L) and T‐type (ICa‐T) Ca2+ currents were recorded in SANCs from Cav3.1 transgenic (TG) and knockout (KO), and control mice. ICa‐T was absent in KO SANCs but enhanced in TG SANCs. In anaesthetized animals, different doses of isoproterenol (ISO) were infused via the jugular vein and the HR was recorded. The EC50 of the HR response to ISO was lower in TG mice but higher in KO mice, and the maximal percentage of HR increase by ISO was greater in TG mice but less in KO mice. In Langendorff‐perfused hearts, ISO increased HR and shortened PR intervals to a greater extent in TG but to a less extent in KO hearts. KO SANCs had significantly slower spontaneous beating rates than control SANCs before and after ISO; TG SANCs had similar basal beating rates as control SANCs probably as a result of decreased ICa‐L but a greater response to ISO than control SANCs. ICa‐T in SANCs was significantly increased by ISO. ICa‐T upregulation by β‐adrenergic stimulation contributes to HR and conduction regulation by the SAS. TTCC can be a target for slowing the HR. [ABSTRACT FROM AUTHOR]

Methicillin-resistant S. aureus (MRSA) has attracted more and more attention in recent years, especially in burn medical centers. Here we conducted a 5-year period study to evaluate the MRSA infection in our burn center. The staphylococcal chromosomal cassette mec ( SCCmec ) typing, antimicrobials susceptibility and virulence profiles were also performed among the MRSA isolates. Of the 259 S. aureus isolates, 239 (92.28%) isolates were identified as MRSA. A decreased trend of MRSA isolation rate over time was found ( P = 0.0063). Majority of MRSA isolates in our center belonged to SCCmec type III (230/239, 96.23%). Antimicrobials susceptibility tests of the MRSA isolates revealed significantly decreased resistance to clindamycin ( P = 0.0183), and increased resistance to chloramphenicol ( P = 0.0020) and minocycline ( P < 0.0001) over time. Trimethoprim/sulfamethoxazole, clindamycin, vancomycin, teicoplanin and linezolid were suggested to be good choice for MRSA infection in our center. Virulence factors profiling showed that most of MRSA isolates in our center carried the virulence factor pattern of cna - clfA - clfB - eno - fib - icaA - icaD - sea - psmα - lukED - hlg - hlgv - hla - hld (214/239, 89.54%). In conclusion, our study suggests that MRSA infection is serious in our burn center, but presented decreased trend over time. Most of MRSA isolates in our center presented the same virulence factor profile. More attention should be attached to nosocomial infection in burn medical center. Antimicrobials susceptibility changing over time was observed. Antimicrobials susceptibility monitoring is necessary and helps to select appropriate drugs against MRSA infections. [ABSTRACT FROM AUTHOR]

Background/Aims: As an "ESKAPE" pathogen, Acinetobacter baumannii is one of the leading causes of drug-resistant infections in humans. Phage therapy may be a useful strategy in treating infections caused by drug-resistant A. baumannii. Among 21 phage strains that were isolated and described earlier, we investigated the therapeutic efficacy of Abp1 because of its relatively wide host range. Methods: Phage stability assays were used to evaluate thermal and pH stability of Abp1. Abp1 was co-cultured with A. baumannii (AB1) over a range of multiplicities of infection to determine its bactericidal efficacy. HeLa or THP-1 cells were used in the cytotoxicity and protection assays. Finally, the therapeutic effects of Abp1 on local and systemic A. baumannii infection in mice were determined. Results: We found that Abp1 exhibits high thermal and pH stability and has a low frequency of lysogeny. Bacteriophage resistance also occurs at a very low frequency (3.51±0.46×10-8), and Abp1 can lyse almost all host cells at a MOI as low as 0.1. Abp1 has no detectable cytotoxicity to HeLa or THP-1 cells as determined by LDH release assay. Abp1 can rescue HeLa cells from A. baumannii infection, even if introduced 2 hours post infection. In both local and systemic A. baumannii infection mouse models, Abp1 treatment exhibits good therapeutic effects. Conclusion: Abp1 is an excellent candidate for phage therapy against drug-resistant A. baumannii infections. [ABSTRACT FROM AUTHOR]

Sepsis comprises a lethal immunologic response due to infection. Increasingly, evidence has demonstrated the important role of long non-coding RNA growth arrest-specific transcript 5 (GAS5) in the regulation of sepsis. Nevertheless, the mechanisms by which GAS5 participates in the progression of sepsis remain unclear. Our study demonstrated the role and underlying mechanism of GAS5 in regulating lipopolysaccharide (LPS)-induced inflammation. In this study, GAS5 expression was found to be markedly decreased in serum samples of sepsis patients and a sepsis mouse model, and was negatively related with HMGB1 expression. GAS5 overexpression inhibited cell inflammatory responses by decreasing HMGB1 release. Furthermore, GAS5 inhibited LPS-mediated hyperacetylation and the release of HMGB1 by increasing the expression of sirtuin1 (SIRT1). Additionally, upregulated GAS5 attenuated inflammatory responses in vitro and vivo , and the knockdown of a miR-155-5p mimic and SIRT1 rescued the effects of GAS5 upregulation. Mechanistically, GAS5 sponged miR-155-5p to upregulate SIRT1, thereby inhibiting HMGB1 acetylation and release. In conclusion, our findings indicate that GAS5 suppresses inflammatory responses by modulating the miR-155-5p/SIRT1/HMGB1 axis in sepsis, providing a novel therapeutic target for inflammation in sepsis. [ABSTRACT FROM AUTHOR]

Background: Thermal injury is the main cause of pulmonary disease in stroke after burn and can be life threatening. Heat-induced inflammation is an important factor that triggers a series ofinduces pathological changes. However, this mechanism underlying heat-induced inflammation in thermal inhalation injury remains unclear. Studies have revealed that astragaloside-IV (AS-IV), a natural compound extracted from Astragalus membranaceus, has protective effects in inflammatory diseases. Here, we investigated whether the protective effects of AS-IV occur because of the suppression of heat- induced endoplasmic reticulum (ER) stress and excessive autophagy. Methods: AS-IV was administered to Wistar rats after thermal inhalation injury and 16HBE140-cells were treated with AS-IV. TNF-α, IL-6, and IL-8 levels were determined by ELISA and real-time PCR. ER stress and autophagy were determined by western blot. Autophagic flux was measured by recording the fluorescence emission of the fusion protein mRFP-GFP-LC3 by dynamic live-cell imaging. Results: AS-IV had protective effects against heat-induced reactive oxygen species production and attenuated ER stress. AS-IV alleviated heat- induced excessive autophagy in vitro and in vivo. Excessive autophagy was attenuated by the PERK inhibitor GSK2656157 and eIF2α siRNA, suggesting that heat stress-induced autophagy can activate the PERK-eIF2α pathway. Beclin 1 and Atg5 siRNAs inhibited the upregulation of the inflammatory cytokines TNF-α, IL-6, and IL-8 after heat exposure. Conclusions: Thus, AS-IV may attenuate inflammatory responses by disrupting the crosstalk between autophagy and the PERK-eIF2α pathway and may be an ideal agent for treating inflammatory pulmonary diseases. [ABSTRACT FROM AUTHOR]

Background/Aims: Skin transplantation aims to cover skin defects but often fails due to immune rejection of the transplantated tissue. Immature dendritic cells (imDCs) induce immune tolerance but have a low migration rate. After stimulation, imDCs transform into mature DCs, which activate immune rejection. Thus, inducing imDC to obtain a high migration counteracts development of immune tolerance. Methods & Results: We transfected imDCs with a recombinant adenovirus carrying the CCR7 gene (Ad-CCR7) and a small interfering RNA targeting RelB (RelB-siRNA) to concurrently overexpress CCR7 and downregulate RelB expression. Functionally, such cells showed a significantly enhanced migration rate in the chemotactic assay and decreased T-cell proliferation after lipopolysaccharide stimulation in mixed lymphocyte reactions. Cotransfected cells showed an increased ability to induce immune tolerance by upregulating T regulatory (Treg) cells and shifting the Th1/Th2 ratio. Cotransfection of Ad-CCR7 and RelB-siRNA endowed imDCs with resistance to apoptosis and cell death. CCR7 overexpression and RelB knockdown (KD) in imDCs improve skin-graft survival in a murine skin-transplantation model. Conclusion: Transfection with Ad-CCR7 and RelB KD in imDCs may be an effective approach inducing immune tolerance, thus being potentially valuable for inhibiting allograft rejection. [ABSTRACT FROM AUTHOR]

Background: Heat causes airway damage during inhalation injury because of bronchial epithelial cell damage. Accumulating evidence shows that mitochondrial uniporter (MCU) is involved in cell damage. We investigated the MCU activity after heat treatment and assessed whether Astragaloside-IV (AS-IV) suppresses heat-induced apoptosis in bronchial epithelial cells by inhibiting the activation of the mitochondrial Ca2+ uniporter (MCU), mitochondrial depolarisation and reactive oxygen species (ROS) production. Methods: The bronchial epithelial cell line 16HBE14o- was heat treated, and cell apoptosis was induced in vitro and in vivo. AS-IV was inorganically administered to Wistar rats twice a day after thermal inhalation injury, and 16HBE140- cells were treated with AS-IV after incubation at 47∘C for 5 min. Protein expression was determined using Western blotting and commercial kits, apoptosis with TUNEL staining, mitochondrial channel activity by patch clamp, reactive oxygen species by MitoSOXTM fluorescence, ATP levels and enzyme activities by commercial kits as well as mitochondrial respiration and calcium by fluorescence. Results: AS-IV markedly inhibited heat-induced apoptosis, as indicated by the increased expression of the pro-apoptotic genes Bak, Bik and Bmf and increased expression of the apoptosis markers Bax, cleaved parp, cleaved caspase3 and cytochrome C. We found that MCU activation promoted mitochondrial Ca2+ overload, ATP depletion, mitochondrial ROS production and cytochrome c release and rapidly induced apoptosis. However, AS-IV treatment reduced excessive MCU activation and led to resistance against mitochondrial Ca2+ overload and excessive cytochrome C release; these effects were blocked by the MCU activator spermine. AS-IV treatment elevated ATP production and decreased ROS activity. Conclusions: MCU plays crucial roles in heat-induced mitochondrial apoptosis in 16HBE140- cells, suggesting a potential target for AS-IV treatment. [ABSTRACT FROM AUTHOR]

Background Electrical burns are important causes of trauma worldwide. This study aims to analyze the clinical characteristics, wound management, and outcome of electric burns. Methods This retrospective study was performed at the Institute of Burn Research of the Third Military Medical University during 2013-2015. Data including the demographics, injury patterns, wound treatment, and outcomes were collected and analyzed. Results A total of 595 electrical burn patients (93.8% males) were included. The average age was 37.3 ± 14.6 y, and most patients (73.5%) were aged 19∼50 years. Most patients (67.2%) were injured in work-related circumstances. The mean total body surface area was 8.8 ± 11.8% and most wounds (63.5%) were full-thickness burns. Operation times of high-voltage burns and current burns were higher than those of low-voltage burns and arc burns, respectively. Of the 375 operated patients, 83.2% ( n = 312) underwent skin autografting and 49.3% ( n = 185) required skin flap coverage. Common types of skin flaps were adjacent (50.3%), random (42.2%), and pedicle (35.7%). Amputation was performed in 107 cases (18.0%) and concentrated on the hands (43.9%) and upper limbs (39.3%). The mean length of stay was 42.9 ± 46.3 d and only one death occurred (0.2%). Current burns and higher numbers of operations were major risk factors for amputation and length of stay, respectively. Conclusions Electrical burns mainly affected adult males with occupational exposures in China. Skin autografts and various skin flaps were commonly used for electric burn wound management. More standardized and effective strategies of treatment and prevention are still needed to decrease amputation rates. [ABSTRACT FROM AUTHOR]

Background: CFTR is implicated in cutaneous wound healing although the underlying mechanisms are not fully understood. In other cell types, CFTR is reported to regulate MAPK/ NF-κB signaling. We undertook the present study to explore a possible role of CFTR in regulating MAPK/NF-κB during cutaneous wound healing. Methods& Results: The splintexcisional and incisional wound healing models were used in CFTR mutant (DF508) mice. The cell-scratch model was used in a human keratinocyte line, HaCaT, in conjunction with CFTR knockdown or overexpression. The epidermal inflammation, keratinocyte proliferation and differentiation, as well as MAPK/NF-κB signaling were examined. Inhibitors of MAPK/NF-κB were also used. Results: Both DF508 mice and HaCaT cells with CFTR knockdown exhibited delayed cutaneous wound healing with exuberant inflammation, increased proliferation and aberrant differentiation. Knockdown of CFTR in HaCaT cells resulted in phosphorylation of ERK, p38 and IκBα. The disturbance of inflammation, proliferation and differentiation in HaCaT cells were reversed by CFTR overexpression or inhibition of MAPK or NF-κB. Conclusion: CFTR plays a role in suppressing MAPK/NF-κB to relieve inflammation, reduce proliferation and promote differentiation of keratinocytes, and thus promotes cutaneous wound healing. [ABSTRACT FROM AUTHOR]

Acinetobacter baumannii infection is a serious threat to burn patients. Bacteremia due to A. baumannii is becoming the most common cause of mortality following burn. However, the epidemiology of A. baumannii causing burn-related bloodstream infections has rarely been reported. We retrospectively collected 81 A. baumannii isolates from the bloodstream of burn patients over a three-year period. Antibiotic susceptibility tests, the prevalence of antibiotic-resistant genes and sequence typing (ST) were conducted to characterize these strains. Most of the isolates showed an extensive drug-resistant phenotype. The resistance frequencies to imipenem and meropenem were 94% and 91%, respectively. The blaOXA-23-like gene, AmpC, IS-AmpC, PER and SIM are the five most prevalent resistant genes, and their prevalence rates are 93% (75/81), 86% (70/81), 73% (59/81), 73% (59/81) and 52% (42/81), respectively. The 81 isolates were grouped into 10 known and 18 unknown ST types, with ST368 (38%) being the most prevalent. Except for ST457 and four new types (STn2, STn6, STn11 and STn14), the remaining 23 ST types belonged to one clonal complex 92, which is most common among clinical isolate in China. The above results indicated that ST368 isolates possessing both the blaOXA-23-like gene and ampC gene were the main culprits of the increasing nosocomial A. baumannii infection in this study. More attention should be paid to monitoring the molecular epidemiology of A. baumannii isolates from burn patients to prevent further distribution. Such information may help clinicians with therapeutic decisions and infection control in the Burns Institute. [ABSTRACT FROM AUTHOR]

Peroxisome proliferator-activated receptor gamma (PPARγ) belongs to the nuclear receptor superfamily and it has received much attention because of its anti-inflammatory activity. However, the underlying molecular mechanism is not completely understood. In the present study, we demonstrated that the level of PPARγ is inversely correlated with that of high mobility group box 1 (HMGB1, a late proinflammatory mediator) in patients with sepsis. Activation of PPARγ inhibits the basal and LPS-induced expression of HMGB1. The PPARγ-mediated inhibition of HMGB1 is associated with the upregulation of miR-142-3p, which can target the 3′-UTR of HMGB1, by directly binding to the PPRE in the miR-142-3p promoter region. Functional experiments reveal that the PPARγ-induced miR-142-3p suppresses inflammatory response in vivo. These results suggest that PPARγ-mediated upregulation of miR-142-3p inhibits the HMGB1 expression, which, in turn, is a novel anti-inflammatory mechanism of PPARγ and has an important role in the treatment of inflammatory diseases. [ABSTRACT FROM AUTHOR]

Background: Previous studies have established that estrogen is capable of accelerating cutaneous wound healing through multiple mechanisms, one of which involves affecting keratinocytes biological properties, such as migration, proliferation, etc. This study aims to reveal the underlying molecular mechanisms of estrogen promoting epidermal keratinocytes proliferation. Method & Results: We found that compared with female mice with a normal estrous cycle, female mice with their ovaries removed before puberty exhibited a delayed cutaneous wound healing, thinner epidermis, and significantly fewer proliferating cell nuclear antigen (PCNA)-positive keratinocytes. Moreover, a significant increase in HaCaT proliferation was detected by a CCK8 assay when treated with 17 β-estradiol compared with those treated with control vehicle. Consistent with the results of the CCK8 assay, flow cytometry indicated a high proportion of 17 β-estradiol-treated HaCaT cells in S phase compared with vehicletreated cells. Western blot analysis demonstrated the activation of Akt, Erk and upregulation of PCNA in HaCaT cells treated with 17 β-estradiol. Interestingly, Erk activation occurred prior to Akt activation. Upregulation of PCNA expression, elevated proliferation and high S phase fraction of HaCaT cell by 17 β-estradiol could be reversed by an Akt or Erk inhibitor. Moreover, Erk inhibition reversed 17 β-estradiol-induced Akt activation, whereas an Akt inhibitor exhibited no effect on Erk, further suggesting that Erk was on the upstream while Akt on the downstream of the signaling pathway. Conclusion: This study demonstrates that one of the critical mechanisms underlying 17 β-estradiol promoting skin wound healing is through regulation of keratinocyte proliferation via Erk/Akt signaling pathway. [ABSTRACT FROM AUTHOR]

Aim: The aim of this study was to evaluate the efficacy of the topical administration of mupirocin and other practices in central venous catheter (CVC) care to prevent central line-associated bloodstream infections (CLABSI) in patients with major burns.Methods: Patients with major burns admitted to a burn ICU were divided into four groups and disinfected at the CVC exit site with single povidone iodine (PVP-I) or PVP-I plus topical mupirocin ointment three times a day or once a day, respectively. The bacterial colonization of the skin at the CVC exit site and CVC tips and the incidence of CLABSI were recorded, and the risk factors were analyzed.Results: Administering mupirocin (RR=0.316, p=0.001), increasing the frequency of insertion-site care (RR=0.604, p=0.008), and avoiding cannulation at the burn site (RR=0.148, p<0.001) reduced skin colonization at the CVC insertion site. Topical administration of mupirocin significantly reduces both the bacterial colonization rate at CVC tips (RR=0.316, p=0.001) and the incidence of CLABSI (5.3 vs. 29.1 per 1000 catheter days, p<0.001).Conclusions: Mupirocin is effective in the prophylaxis of CLABSI. Other CVC care practices were also found to affect the level of bacterial colonization, but their efficacy in preventing CLABSI needs to be evaluated further. [ABSTRACT FROM AUTHOR]

Finding non-precious metal hydrogen evolution reaction (HER) electrocatalysts with high efficiency and low cost is a great challenge. A novel HER electrocatalyst of amorphous Nickel–Cerium–Praseodymium–Holmium coating supported on nickel foam (Ni–Ce–Pr–Ho/NF) was successfully synthesized through one-step galvanostatic electrodeposition. The Ni–Ce–Pr–Ho catalyst exhibited excellent electrocatalytic activity toward HER with a low overpotential of 78 mV at 10 mA cm−2 in 1 M KOH. The Tafel slope of Ni–Ce–Pr–Ho electrocatalyst (121.6 mV·dec−1) indicated that the hydrogen reaction mechanism for Ni–Ce–Pr–Ho electrocatalysts followed a typical Volmer–Heyrovsky step. The remarkable HER performance was attributed to Pr and Ho doping, which resulted in the development of an amorphous structure, satisfactory intrinsic activity, and high conductivity. • Ni–Ce–Pr–Ho catalyst is developed via a facile and simple galvanostatic electrodeposition method. • Ni–Ce–Pr–Ho catalyst showed excellent HER activity with low overpotential of 78 mV at 10 mA cm−2. • Enhanced catalytic performance resulted in the amorphous structure, satisfactory intrinsic activity, and high conductivity. [ABSTRACT FROM AUTHOR]

Aims To determine whether altered beta-adrenergic responses contribute to early cardiac dysfunction in mdx (X-linked muscular dystrophy) mice, an animal model for human Duchenne muscular dystrophy. Methods and results Replacement fibrosis in mdx hearts gradually increased with age, suggesting a gradual loss of cardiomyocytes. Echocardiography and intra-left ventricular haemodynamic measurements detected baseline cardiac dysfunction in mdx mice at ≥8 months. However, a reduction of cardiac beta-adrenergic response to isoproterenol (ISO) was already present in mdx mice at 4 months. Ventricular myocytes (VMs) isolated from 4- and 8-month-old mdx mice had greater baseline contractile function {fractional shortening, [Ca2+]i, and sarcoplasmic reticulum (SR) Ca2+ content} and ICa-L than age-matched control VMs and than myocytes isolated from 2-month-old mdx mice. ISO increased myocyte function in the VMs of 4- and 8-month-old mdx mice to the same level as in age-matched control VMs. In the VMs of 12-month-old mdx mice, ISO failed to increase myocyte function to the level in VMs of 12-month-old control mice and could not further increaseICa-L. No differences were observed in the expression of Cav1.2α1c, Cav1.2β1, Cav1.2β2, sarco/endoplasmic reticulum Ca2+ ATPase (SERCA), and the Na+/Ca2+ exchanger. In contrast, total ryanodine receptor 2 (RyR2) and basal phosphorylation of RyR2, phospholamban, and Cav1.2α1c were found to be increased in hearts of 4-month-old mdx mice; baseline protein kinase A activity was also increased. After ISO treatment, phosphorylation levels were the same in mdx and control hearts. VMs of 4-month-old mdx mice had reduced beta1-adrenergic receptor (β1-AR) density and beta-adrenergic sensitivity. Conclusion In young mdx mice, the myocyte increases its contractile function to compensate for myocyte loss. However, these myocytes with enhanced baseline function have reduced potential for stimulation, decreased β1-AR density/sensitivity, leading to blunted cardiac beta-adrenergic response. [ABSTRACT FROM PUBLISHER]

Intestinal trefoil factor (ITF) is a small polypeptide with potential medical values whose main pharmacological effects are to alleviate gastrointestinal mucosal injury caused by various injury factors and promote the repair of damaged mucosa. However, its low yield limits its application. The purpose of our study was to construct a recombinant adenoviral vector containing the hITF gene and observe the therapeutic effect of burn-induced intestinal mucosal injury using in vitro and in vivo analysis. First, a recombinant shuttle plasmid was constructed by ligating a pAdTrack-CMV vector with a full-length hITF gene containing a signal peptide and the mature peptide, followed by the recombinant Ad-hITF adenovirus vector after linearization and homologous recombination with the backbone plasmid in the competent BJ5183 strain. Second, the hITF expression level was detected using reverse transcription polymerase chain reaction and western blotting after Ad-hITF infection of colon cancer HT-29 cells. The recombinant adenovirus significantly promoted cell migration in an in vitro wounding model. Finally, we confirmed that the recombinant adenovirus could significantly expedite the healing of intestinal mucosal injury after establishing a mouse model in which severe burns were stimulated and the recombinant adenovirus was delivered by intragastric injection. In summary, we constructed a recombinant adenoviral vector containing the hITF gene and confirmed its role in promoting repair of the intestinal mucosa. Our study provides a novel way to treat burn-induced intestinal mucosal injury. [ABSTRACT FROM AUTHOR]

Introduction: Variations in genetic background are the leading cause of differential susceptibility to traumatic infection. Heat shock protein 90 (HSP90), a broadly distributed and conserved molecule, regulates inflammation under stressful and traumatic conditions. However, the relationships between HSP90 genetic polymorphisms, post-traumatic inflammatory responses and organ function remain unknown. Methods: A total of 286 healthy volunteers and patients with severe trauma took part in a single nucleotide polymorphism (SNP)-based analysis of the HSP90beta gene and a clinical association analysis. HSP90beta and TNF-alpha levels were determined using quantitative PCR and western blot. The transcriptional activity of the HSP90beta promoter was assayed using the Dual-Luciferase Reporter Assay System. Results: The minor allele frequencies for the SNP located at −144 bp relative to the HSP90beta transcriptional start site were 28.47% and 28.52% in the normal and trauma populations, respectively; no significant differences were found between these two distributions. However, the results showed that a promoter containing the -144A allele had a higher transcriptional activity than did a promoter containing the wild-type -144C allele. Furthermore, the -144A promoter induced high expression of HSP90beta and low expression of the inflammatory factor TNF-alpha in a lipopolysaccharide-induced inflammatory model. A clinical association analysis showed that the multiple organ dysfunction scores for -144AA genotype carriers were significantly lower than those of -144CC carriers following trauma. No significant correlations were found between the presence of the two alleles and the incidence of sepsis. Conclusions: These results indicate that differences in expression caused by the -144 polymorphism in the HSP90beta promoter are associated with cellular inflammatory responses and the severity of organ injury. These findings will aid in risk assessment and early prevention of complications for patients with severe trauma. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: To improve the accuracy of blood loss estimation during extensive escharectomy and auto-microskin grafting on extremities in adult male major burn patients. Method: All adult male major burn patients admitted to our center who underwent extensive escharectomy and auto-microskin graft on extremities for more than 10%TBSA during the period 1 January 2008 to 31 December 2009 were involved in this study. The blood loss during the operation was estimated by the surgeons or calculated according to the changes in hemoglobin levels. Results: The average burn and escharectomy areas for the 64 burn patients included in the study were 74.16±16.96% and 30.27±15.63%TBSA respectively. The auto-microskin donor area was 3.81%TBSA. The volumes of intra-operative calculated and estimated blood losses and transfused blood during the operation were 0.47ml/cm2, 0.13ml/cm2 and 0.20ml/cm2 surgical area 77.29ml, 20.51ml and 32.83ml per 1%TBSA), respectively. Within two weeks after injury surgical blood loss appeared to be greater the later the operation was carried out. Within the first week after injury the mean proportional blood loss was increased with area excised. Conclusion: In this study the average calculated blood loss for the operation of extensive escharectomy and microskin graft in adult male major burn patient was 0.47ml/cm2 (77.29ml per 1% TBSA). This result will help us to predict expected blood loss more accurately. [Copyright &y& Elsevier]

Abstract: Recent studies indicate that the High Mobility Group Box-1 protein (HMGB1) acts as a potent proinflammatory cytokine that contributes to the pathogenesis of diverse inflammatory and infectious disorders. The proinflammatory cytokine activity of HMGB1 has become a therapeutic target. In this study, we cloned the cDNA encoding human HMGB1 and constructed HMGB1 mutants using a one-step opposite direction PCR. The binding of the HMGB1 mutants to THP-1 cell and the cytokine activities of these HMGB1 mutants were observed. Results showed that the HMGB1 Mut (102–105), one of the HMGB1 mutants, in which amino acids 102–105 (FFLF) were replaced with two Glys, significantly decreased the full-length HMGB1 protein induced TNF-α release in human monocyte cultures. The results indicate that we have developed a novel recombinant HMGB1 mutant that competitively antagonizes the proinflammatory activity of HMGB1. This may be of significant importance in providing a new anti-inflammatory strategy for the treatment of severe sepsis and other inflammatory disorders. [Copyright &y& Elsevier]

Abstract: Objective: To investigate and evaluate the clinical efficacy and safety of Acticoat with nanocrystalline silver for external use on the management of the residual wounds post-burn. Methods: One hundred and sixty-six wounds of 98 burn patients were enrolled and divided into Acticoat group and silver sulfadiazine group in the multi-center randomized clinical trial. Acticoat was used as the treated group for those who have redness, swelling, and excessive secretion (“heavy” exudates) in the wound, Acticoat was changed once a day. When there is not much secretion in the wound, or redness and swelling were not obvious, the dressings were changed once every 3 days. Silver sulfadiazine (SD-Ag) was used as control group, which was treated under the usual clinical routine. Healing time was observed up to 20 days. Healing percentage on the 15th day after treatment was determined. Results: Healing time was 12.42±5.40 days after the application of Acticoat. This was significantly shorter than that of control wounds. The wounds of the trial group healed nearly 3.35 days earlier than the control ones. Healing percentage at 15 days in the trial wounds was 97.37%, which was higher than the control, but there was no significant difference between them. The bacterial clearance rate of the Acticoat group on the 6th and 12th day post-treatment was 16.67 and 26.67%, respectively, which was significantly higher than the control. Conclusions: Acticoat with nanocrystalline silver promotes the healing process of residual wounds post-burn effectively. No adverse reaction of Acticoat was found during the study. [Copyright &y& Elsevier]

Currently, designing and constructing multifunctional electrodes is highly desirable for energy conversion and storage devices. Spinel cobaltites have attracted considerable attention owing to the relative high conductivity and rich redox chemistry, but the limited electroactive sites and poor surface chemical reactivity are the highly concerned issues. Taking Co–Cu oxides as the model material, here we demonstrate that a surface restructuring strategy by constructing core-shell arrays can achieve simultaneous modulation of electroactive sites and surface chemical reactivity. Strating from the hydrothermal and annealing process, CuCo 2 O 4 /CuO nanoneedles are synthesized directly on the conductive Ni foam, and followed by electrodeposited RuO 2 nanoparticles (denoted as CuCo 2 O 4 /CuO@RuO 2). Core-shell CuCo 2 O 4 /CuO@RuO 2 arrays show a high areal capacity up to 862.5 mAh cm−2 and a high capacity retention of about 90.1% after 8000 cycles. Moreover, the hybrid supercapacitor by CuCo 2 O 4 /CuO@RuO 2 and activated carbon can achieve 0.84 mWh cm−2 energy density at 8 mW cm−2 power density, as well as good long-term stability. In addtion, working as water oxidation catalysis, CuCo 2 O 4 /CuO@RuO 2 shows the low overpotential of 279 mV at 10 mA cm−2, as well as a low Tafel slope and stable long-term performance. This work provides a novel strategy to engineer surface nanostructure for energy conversion and storage devices. Image 1 • CuCo 2 O 4 /CuO@RuO 2 is synthsized by hydrothermal, annealing and electrodeposition. • Core-shell CuCo 2 O 4 /CuO@RuO 2 arrays are constructed for supercapacitors and OER. • The synergistic contribution can favor better electrochemical performances. [ABSTRACT FROM AUTHOR]

Summary Ca 2+ dynamics and oxidative signaling are fundamental mechanisms for mitochondrial bioenergetics and cell function. The MCU complex is the major pathway by which these signals are integrated in mitochondria. Whether and how these coactive elements interact with MCU have not been established. As an approach toward understanding the regulation of MCU channel by oxidative milieu, we adapted inflammatory and hypoxia models. We identified the conserved cysteine 97 (Cys-97) to be the only reactive thiol in human MCU that undergoes S-glutathionylation. Furthermore, biochemical, structural, and superresolution imaging analysis revealed that MCU oxidation promotes MCU higher order oligomer formation. Both oxidation and mutation of MCU Cys-97 exhibited persistent MCU channel activity with higher [Ca 2+ ] m uptake rate, elevated mROS, and enhanced [Ca 2+ ] m overload-induced cell death. In contrast, these effects were largely independent of MCU interaction with its regulators. These findings reveal a distinct functional role for Cys-97 in ROS sensing and regulation of MCU activity. [ABSTRACT FROM AUTHOR]