Reliability of Droplet Digital PCR Alone and in Combination with Interleukin-6 and Procalcitonin for Prognosis of Bloodstream Infection.

Purpose: Bloodstream infection(BSI) is linked with high mortality, underscoring the significance of prompt etiological diagnosis for timely and precise treatment. This study aims to investigate the diagnostic value of droplet digital polymerase chain reaction(ddPCR) in combination with conventional inflammatory markers [interleukin-6(IL-6) and procalcitonin(PCT)] concerning disease progression and treatment prognosis in BSI patients. Furthermore, the study aims to explore a more efficient clinical application strategy. Patients and Methods: This prospective case seried study centers on 176 patients suspected of or confirmed with BSI. Blood samples were collected to extract nucleic acids for identifying pathogens (bacteria, fungi, and viruses) and determining copy loads via ddPCR. Results: The sensitivity of ddPCR was markedly higher compared to the culture method (74.71% vs 31.03%). A positive correlation existed between bacterial load and levels of inflammatory markers [IL-6 (P=0.0182), PCT (P=0.0029), and CRP (P=0.0005)]. In suspected BSI cases, the combination of ddPCR and inflammatory markers could predict sepsis risk [ROC: Area under the curve(AUC)=0.6071, P=0.0383]. Within confirmed BSI patients, the ddPCR bacterial load of those with SOFA<7 was lower than that of the SOFA≥7 (P=0.0334). ddPCR (OR: 1.789, P=0.035) monitoring combined with PCT (OR: 1.787, P=0.035) holded predictive value for SOFA progression (AUC=0.7913, P=0.0003). Similarly, BSI survivors displayed a lower burden than non-survivors (P=0.0170). Additionally, ddPCR combinated with IL-6 provided a more accurate and expedited insight into clinical outcomes prediction for BSI confirmed patients (AUC=0.7352, P=0.0030). Serial monitoring of bacterial load by ddPCR effectively mirrored the clinical course of BSI in patients. Notably, patients with positive ddPCR virus infection exhibited significantly reduced lymphocyte counts (P=0.0003). Conclusion: In a clinical context, qualitative ddPCR results and quantitative continuous monitoring can more precisely assess sepsis progression and treatment prognosis in BSI patients. Furthermore, ddPCR results offer quicker and more accurate reference points for clinical antibacterial and antiviral interventions.

Bacterial heat shock protein: A new crosstalk between T lymphocyte and macrophage via JAK2/STAT1 pathway in bloodstream infection.

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.

The m6A reader YTHDF2 alleviates the inflammatory response by inhibiting IL-6R/JAK2/STAT1 pathway-mediated high-mobility group box-1 release.

Background: Sepsis is a common severe complication in major burn victims and is characterized by a dysregulated systemic response to inflammation. YTH domain family 2 (YTHDF2), a well-studied N6-methyladenosine (m6A) reader that specifically recognizes and binds to m6A-modified transcripts to mediate their degradation, is connected to pathogenic and physiological processes in eukaryotes, but its effect on sepsis is still unknown. We aimed to discover the effects and mechanisms of YTHDF2 in sepsis. Methods: Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and western blot analyses were used to measure the expression of YTHDF2, the interleukin 6 receptor (IL-6R), high-mobility group box-1 (HMGB1), Janus kinase 2 (JAK2) and signal transducer and activator of transcription 1 (STAT1) under different in vitro conditions. Enzyme-linked immunosorbent assays were utilized to evaluate the expression of HMGB1, IL-6, IL-1ß and tumor necrosis factor-α. To confirm that YTHDF2 specifically targets IL-6R mRNA, RNA immunoprecipitation and dual-luciferase reporter assays were performed. Finally, we utilized a mouse model of lipopolysaccharide (LPS)-induced sepsis to verify the effects of YTHDF2 in vivo. Results: According to our findings, YTHDF2 was expressed at a low level in peripheral blood mononuclear cells from septic mice and patients as well as in LPS-induced RAW264.7 cells. Overexpression of YTHDF2 alleviated the inflammatory response by inhibiting HMGB1 release and JAK2/STAT1 signalling in LPS-stimulated cells. Mechanistically, YTHDF2 suppressed JAK2/STAT1 signalling by directly recognizing the m6A-modified site in IL-6R and decreasing the stability of IL-6R mRNA, thereby inhibiting HMGB1 release. In vivo experiments showed that YTHDF2 played a protective role in septic mice by suppressing the IL-6R/JAK2/STAT1/HMGB1 axis. Conclusions: In summary, these findings demonstrate that YTHDF2 plays an essential role as an inhibitor of inflammation to reduce the release of HMGB1 by inhibiting the IL-6R/JAK2/STAT1 pathway, indicating that YTHDF2 is a novel target for therapeutic interventions in sepsis.

Comparative genomics and DNA methylation analysis of Pseudomonas aeruginosa clinical isolate PA3 by single-molecule real-time sequencing reveals new targets for antimicrobials.

Introduction: Pseudomonas aeruginosa (P.aeruginosa) is an important opportunistic pathogen with broad environmental adaptability and complex drug resistance. Single-molecule real-time (SMRT) sequencing technique has longer read-length sequences, more accuracy, and the ability to identify epigenetic DNA alterations. Methods: This study applied SMRT technology to sequence a clinical strain P. aeruginosa PA3 to obtain its genome sequence and methylation modification information. Genomic, comparative, pan-genomic, and epigenetic analyses of PA3 were conducted. Results: General genome annotations of PA3 were discovered, as well as information about virulence factors, regulatory proteins (RPs), secreted proteins, type II toxin-antitoxin (TA) pairs, and genomic islands. A genome-wide comparison revealed that PA3 was comparable to other P. aeruginosa strains in terms of identity, but varied in areas of horizontal gene transfer (HGT). Phylogenetic analysis showed that PA3 was closely related to P. aeruginosa 60503 and P. aeruginosa 8380. P. aeruginosa's pan-genome consists of a core genome of roughly 4,300 genes and an accessory genome of at least 5,500 genes. The results of the epigenetic analysis identified one main methylation sites, N6-methyladenosine (m6A) and 1 motif (CATNNNNNNNTCCT/AGGANNNNNNNATG). 16 meaningful methylated sites were picked. Among these, purH, phaZ, and lexA are of great significance playing an important role in the drug resistance and biological environment adaptability of PA3, and the targeting of these genes may benefit further antibacterial studies. Disucssion: This study provided a detailed visualization and DNA methylation information of the PA3 genome and set a foundation for subsequent research into the molecular mechanism of DNA methyltransferase-controlled P. aeruginosa pathogenicity.

BL02, a phage against carbapenem- and polymyxin-B resistant Klebsiella pneumoniae, isolated from sewage: A preclinical study.

The emergence of Carbapenem-resistant Klebsiella pneumoniae (CRKP) represents a threat to public health. Polymyxin-B is generally considered a last-resort antibiotic. In this study, we isolated a carbapenem- and polymyxin-B resistant K. pneumoniae phage BL02 for the first time in Southwestern China and evaluated its biological characteristics and whole-genome sequence. Polymyxin-B resistant K. pneumoniae, (CK02), was isolated from the blood of a male with severe septic shock, and phage BL02 was screened and purified from the hospital sewage. BL02 could lyse 40 out of 46 CRKP isolates (86.96%) and has high activity in the pH range of 6-10 and the temperature range of 4-55 °C. The latency period of BL02 was about 10 min and the lysis period was about 50 min. The genome results showed that BL02 was a linear dsDNA with a total length of 175,595 bp and a GC content of 41.83%. A total of 275 ORFs were predicted and no tRNA, rRNA, drug resistance genes, or virulence genes were found in the genome. Phylogenetic analysis showed that BL02 belongs to the family Straboviridae. Treatment of infected mice with two antibiotics (tigecycline or ceftazidime/avibactam) resulted in 7-day survival rates of 28.57% and 42.86%, respectively. In contrast, the survival rate of mice in the single-dose BL02-treated group was 71.43%. In summary, this preclinical study isolated a phage capable of lysing polymyxin-B resistant K. pneumoniae and validated its safety and efficacy in an in vivo model, which provides a reference for further research on controlling MDR pathogens.

Efficacy and safety of extracorporeal membrane oxygenation for burn patients: a comprehensive systematic review and meta-analysis.

Background: Respiratory and circulatory dysfunction are common complications and the leading causes of death among burn patients, especially in severe burns and inhalation injury. Recently, extracorporeal membrane oxygenation (ECMO) has been increasingly applied in burn patients. However, current clinical evidence is weak and conflicting. This study aimed to comprehensively evaluate the efficacy and safety of ECMO in burn patients. Methods: A comprehensive search of PubMed, Web of Science and Embase from inception to 18 March 2022 was performed to identify clinical studies on ECMO in burn patients. The main outcome was in-hospital mortality. Secondary outcomes included successful weaning from ECMO and complications associated with ECMO. Meta-analysis, meta-regression and subgroup analyses were conducted to pool the clinical efficacy and identify influencing factors. Results: Fifteen retrospective studies with 318 patients were finally included, without any control groups. The commonest indication for ECMO was severe acute respiratory distress syndrome (42.1%). Veno-venous ECMO was the commonest mode (75.29%). Pooled in-hospital mortality was 49% [95% confidence interval (CI) 41-58%] in the total population, 55% in adults and 35% in pediatrics. Meta-regression and subgroup analysis found that mortality significantly increased with inhalation injury but decreased with ECMO duration. For studies with percentage inhalation injury ≥50%, pooled mortality (55%, 95% CI 40-70%) was higher than in studies with percentage inhalation injury <50% (32%, 95% CI 18-46%). For studies with ECMO duration ≥10 days, pooled mortality (31%, 95% CI 20-43%) was lower than in studies with ECMO duration <10 days (61%, 95% CI 46-76%). In minor and major burns, pooled mortality was lower than in severe burns. Pooled percentage of successful weaning from ECMO was 65% (95% CI 46-84%) and inversely correlated with burn area. The overall rate of ECMO-related complications was 67.46%, and infection (30.77%) and bleedings (23.08%) were the two most common complications. About 49.26% of patients required continuous renal replacement therapy. Conclusions: ECMO seems to be an appropriate rescue therapy for burn patients despite the relatively high mortality and complication rate. Inhalation injury, burn area and ECMO duration are the main factors influencing clinical outcomes.

LncRNA GAS5 suppresses inflammatory responses by inhibiting HMGB1 release via miR-155-5p/SIRT1 axis in sepsis.

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.

Extracorporeal Membrane Oxygenation in Acute Respiratory Distress Syndrome Caused by Anhydrous Ammonia Burns: Two Case Reports.

Acute anhydrous ammonia burns are relatively rare but lethal and often occur as a mass occupational incident worldwide. Anhydrous ammonia mainly leads to severe inhalation injury and skin/mucosa wound because of its high water solubility and strong alkalinity. Acute respiratory distress syndrome (ARDS) induced by inhalation injury is the main cause of death. Extracorporeal membrane oxygenation (ECMO), also known as extracorporeal life support, has been recommended as the salvage treatment for severe ARDS based on low-level evidence. However, the application of ECMO in ammonia burns is still limited. Here, we presented two cases of anhydrous ammonia burn patients, one 62-year-old man with 15% total body surface area (TBSA) and one 47-year-old man with 27% TBSA, accompanying severe inhalation injury. They both developed severe ARDS and started vv ECMO on 3, 6, and 15 days after injury, respectively. ECMO lasted 118, 247, and 72 h, respectively. All ECMO were successfully weaned off although only one patient survived. Meanwhile, one patient had the coagulopathy complication of ECMO, mainly bleeding, deep vein thrombosis, and hemolysis. In conclusion, this report provided evidence for use of ECMO as supportive care in ammonia burn patients with severe ARDS.

A new indicator: The diagnostic value of CD8+T/B lymphocyte ratio in sepsis progression.

OBJECTIVE: To reveal the value of single lymphocyte subpopulation and their ratios in the progression of sepsis. METHODS: From January 2019 to March 2021, 39 sepsis patients, 16 septic shock patients, and 50 healthy volunteers were recruited in the Second Xiangya Hospital for this cross-sectional study. The absolute quantitation of CD4+T, CD8+T, B lymphocytes, and NK cells in peripheral blood were determined by flow cytometry. SPSS Software was used to analyze the results. RESULTS: On the whole, the numbers of lymphocytes in the sepsis group and in the septic shock group were lower than that in the healthy control group. Surprisingly, the percentage of CD8+T lymphocytes in the septic shock group was slightly higher than that in the sepsis group. The percentage of B lymphocytes in the sepsis group was higher than that in the healthy control group. The AUC of CD8+T/B was 0.724, with the sensitivity and specificity being 75.00% and 71.79%, respectively. CONCLUSION: The immune expression pattern of patients with sepsis was not a simple decrease in the number of lymphocytes. The change in the ratios of lymphocyte subpopulation might be more meaningful along the development and progression of sepsis. The ratio of CD8+T/B could be used to diagnose the progression of sepsis and reduce the misdiagnosis rate to a certain extent.

Emergence of a Carbapenem-Resistant Klebsiella pneumoniae Isolate Co-harbouring Dual bla NDM- 6 -Carrying Plasmids in China.

The widespread emergence of carbapenem-resistant Klebsiella pneumoniae (CRKP) with limited therapeutic options has become a global concern. In this study, a K. pneumoniae strain called KP2e was recovered from a human case of fatal septic shock in a Chinese hospital. Polymerase chain reaction and sequencing, antimicrobial susceptibility testing, conjugation experiments, S1 nuclease-pulsed field gel electrophoresis/southern blot, whole genome sequencing and comparative genomics were performed to investigate the phenotypic and molecular characteristics of this isolate. KP2e possessed the NDM-6-encoding gene and exhibited resistance to almost all ß-lactams except for monobactam. This strain belonged to sequence type 4024, the complete genome of which was composed of one chromosome and three plasmids. Furthermore, bla NDM-6 coexisted on two self-transmissible plasmids, which were assigned to types IncFIB and IncN. A structure of IS26-composite transposon capturing an identical Tn125 remnant (ΔISAba125-bla NDM-6 -ble MBL -trpF-dsbC-cutA-groES-ΔgroEL) was identified in the two plasmids, and this conserved bla NDM -surrounding genetic context was similar to that of few IncN plasmids found in other regions of China. Our research appears to be the first description of a clinical strain that emerged co-harbouring dual bla NDM -carrying plasmids, and the first report of NDM-6-positive CRKP in China. These findings demonstrated that IncN is a key medium in the evolution and expanding dissemination of bla NDM genes among various species, which indicates that close monitoring and rapid detection of bla NDM -harbouring plasmids is necessary.

Late-Onset Acute Kidney Injury is a Poor Prognostic Sign for Severe Burn Patients.

Background: Acute kidney injury (AKI) is a morbid complication and the main cause of multiple organ failure and death in severely burned patients. The objective of this study was to explore epidemiology, risk factors, and outcomes of AKI for severely burned patients. Methods: This retrospective study was performed with prospectively collected data of severely burned patients from the Institute of Burn Research in Southwest Hospital during 2011-2017. AKI was diagnosed according to Kidney Disease Improving Global Outcomes (KDIGO) criteria (2012), and it was divided into early and late AKIs depending on its onset time (within the first 3 days or >3 days post burn). The baseline characteristics, clinical data, and outcomes of the three groups (early AKI, late AKI and non-AKI) were compared using logistic regression analysis. Mortality predictors of patients with AKI were assessed. Results: A total of 637 adult patients were included in analysis. The incidence of AKI was 36.9% (early AKI 29.4%, late AKI 10.0%). Multiple logistic regression analysis revealed that age, gender, total burn surface area (TBSA), full-thickness burns of TBSA, chronic comorbidities (hypertension or/and diabetes), hypovolemic shock of early burn, and tracheotomy were independent risk factors for both early and late AKIs. However, sepsis was only an independent risk factor for late AKI. Decompression escharotomy was a protective factor for both AKIs. The mortality of patients with AKI was 32.3% (early AKI 25.7%, late AKI 56.3%), and that of patients without AKI was 2.5%. AKI was independently associated with obviously increased mortality of severely burned patients [early AKI, OR = 12.98 (6.08-27.72); late AKI, OR = 34.02 (15.69-73.75)]. Compared with patients with early AKI, patients with late AKI had higher 28-day mortality (34.9% vs. 19.4%, p = 0.007), 90-day mortality (57.1% vs. 27.4%, p < 0.0001). Conclusions: AKI remains prevalent and is associated with high mortality in severely burned patients. Late-onset acute kidney injury had greater severity and worse prognosis.

Cost analysis of severe burn victims in Southwest China: A 7-year retrospective study.

Background: Severe burn injury can be a life-threatening experience and can also lead to financial issues for suffers. The purpose of the current study was to analyze the direct hospitalization costs of severe burn inpatients in Southwest China. Methods: Data related to all inpatients admitted with severe burns [total body surface area (TBSA) ≥30%] pooled from 2015 to 2021 were reviewed retrospectively at the Institute of Burn Research of Army Medical University. Demographic parameters, medical economics, and clinical data were obtained from medical records. Results: A total of 668 cases were identified. The average age was 37.49 ± 21.00 years, and 72.3% were men. The average TBSA was 51.35 ± 19.49%. The median length of stay of inpatients in the burn intensive care unit was 14 [interquartile range (IQR): 5.0-34.8] days, and the median length of stay (LOS) was 41 (IQR: 22.0-73.8) days. The mortality rate was 1.6%. The median total cost was 212,755.45 CNY (IQR: 83,908.80-551,621.57 CNY) per patient varying from 3,521.30 to 4,822,357.19 CNY. The direct cost of scald burns was dramatically lower compared with that of other types of burns, with 11,213.43 to 2,819,019.14 CNY. Medical consumables presented the largest portion of total costs, with a median cost of 65,942.64 CNY (IQR: 18,771.86-171,197.97 CNY). The crucial risk factors for medical cost in our study were TBSA, surgical frequency, LOS, depth of burn, and outcome. Conclusion: We conclude that an effective burn prevention program, shorter hospital stays, and facilitating the healing of wounds should be focused on with tailored precautionary protocols to reduce the medical costs of inpatients with severe burns.

Extracorporeal membrane oxygenation combined with continuous renal replacement therapy for the treatment of severe burns: current status and challenges.

Severe burns often cause various systemic complications and multiple organ dysfunction syndrome, which is the main cause of death. The lungs and kidneys are vulnerable organs in patients with multiple organ dysfunction syndrome after burns. Extracorporeal membrane oxygenation (ECMO) and continuous renal replacement therapy (CRRT) have been gradually applied in clinical practice and are beneficial for severe burn patients with refractory respiratory failure or renal dysfunction. However, the literature on ECMO combined with CRRT for the treatment of severe burns is limited. Here, we focus on the current status of ECMO combined with CRRT for the treatment of severe burns and the associated challenges, including the timing of treatment, nutrition support, heparinization and wound management, catheter-related infection and drug dosing in CRRT. With the advancement of medical technology, ECMO combined with CRRT will be further optimized to improve the outcomes of patients with severe burns.

Different Infection Profiles and Antimicrobial Resistance Patterns Between Burn ICU and Common Wards.

Infection is the leading cause of complications and deaths after burns. However, the difference in infection patterns between the burn intensive care unit (BICU) and burn common wards (BCW) have not been clearly investigated. The present study aimed to compare the infection profile, antimicrobial resistance, and their changing patterns in burn patients in BICU and BCW. Clinical samples were analyzed between January 1, 2011, and December 31, 2019, in the Institute of Burn Research in Southwest China. The patient information, pathogen distribution, sources, and antimicrobial resistance were retrospectively collected. A total of 3457 and 4219 strains were detected in BICU and BCW, respectively. Wound secretions accounted for 86.6% and 44.9% in BCW and BICU, respectively. Compared with samples in BCW, samples in BICU had more fungi (11.8% vs. 8.1%), more Gram-negative bacteria (60.0% vs. 50.8%), and less Gram-positive bacteria (28.2% vs. 41.1%). Acinetobacter baumannii were the most common pathogen in BICU, compared with Staphylococcus aureus in BCW. S. aureus was the most frequent pathogen in wound secretions and tissues from both BICU and BCW. However, A. baumannii were the first in blood, sputum, and catheter samples from BICU. Overall, the multidrug-resistance (MDR) rate was higher in BICU than in BCW. However, the gap between BICU and BCW gradually shortened from 2011 to 2019. The prevalence of MDR A. baumannii and Klebsiella pneumonia significantly increased, especially in BCW. Furthermore, Carbapenem resistance among K. pneumoniae significantly increased in BICU (4.5% in 2011 vs. 40% in 2019) and BCW (0 in 2011 vs. 40% in 2019). However, the percentage of MDR P. aeruginosa sharply dropped from 85.7% to 24.5% in BICU. The incidence of MRSA was significantly higher in BICU than in BCW (94.2% vs. 71.0%) and stayed at a high level in BICU (89.5% to 96.3%). C. tropicalis and C. albicans were the two most frequent fungi. No resistance to Amphotericin B was detected. Our study shows that the infection profile is different between BICU and BCW, and multidrug resistance is more serious in BICU than BCW. Therefore, different infection-control strategies should be emphasized in different burn populations.

Nucleation and growth mechanisms of an electrodeposited Ni-Se-Cu coating on nickel foam.

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 Ea 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 Ni3Se2, and a Ni(Cu) solid solution forms after the incorporation of Cu atoms into a Ni lattice.

Stenotrophomonas-maltophilia inhibits host cellular immunity by activating PD-1/PD-L1 signaling pathway to induce T-cell exhaustion.

BACKGROUND: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Extracellular vesicles of bacteria as potential targets for immune interventions.

Bacterial infection is one of the most common and serious diseases. Extracellular vesicles (EVs) expressed by bacterial cells during infection and their biological functions have been a growing field in recent years. The study of the immune interaction mechanism between EVs and bacteria has become more significant. EVs are released into the extracellular microenvironment during bacterial infection. EVs carry various lipids, proteins, nucleic acids, and other substances of host bacteria and participate in various physiological and pathological processes. EV-based vaccines against bacterial infection are also being evaluated. This review focuses on the biological characteristics of EVs, the interaction between EVs and the host immune system, and the potential of EVs as new vaccines. A deeper understanding of the interaction between EVs and the immune system informs on the biological function and heterogeneity of EVs. This knowledge also can facilitate the development and application of EVs and their potential as vaccines.

Novel heterostructure Cu2S/Ni3S2 coral-like nanoarrays on Ni foam to enhance hydrogen evolution reaction in alkaline media.

Exploring efficient alternatives to precious noble metal catalysts is a challenge. Here, a new type of non-noble metal Cu2S/Ni3S2 heterostructure nanosheet array is fabricated on 3D Ni foam. This electrocatalyst has excellent activity and durability to Hydrogen Evolution Reaction (HER) under alkaline conditions. The synergistic catalysis produced by the {2̄10} and (034) crystal planes and the increase in charge transfer and the number of active sites caused by lattice defects greatly improve the electrocatalytic activity of Ni3S2. In the HER process, the Cu2S/Ni3S2 interface increases the formation of S-H bonds, and Cu2S promotes the transformation during the HER process into S-doped CuO, optimizing the adsorption capacity of S-doped sites for H. Among electrocatalysts made with different feed ratios, Cu2S/Ni3S2/NF-3, for HER, only needs an overpotential of 50 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.

Significance of the ratio interferon-γ/interleukin-4 in early diagnosis and immune mechanism of unexplained recurrent spontaneous abortion.

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.

Predictive Value of the Prognostic Nutrition Index for the Prognosis of Patients With Severe Burns Treated With the Meek Graft.

The Meek technique is currently a key method for treating wounds in severely burned patients. The survival rate of skin grafts is an important factor affecting the success rate of treatment. The purpose of this study was to investigate the effect of the preoperative prognostic nutritional index (PNI) on the survival rate of skin grafts in patients treated with the Meek technique in the early stage of severe burns. We retrospectively analyzed the data of severely burned patients who were treated at the burn center between January 2013 and December 2019 and met the inclusion criteria. The albumin (ALB) level and lymphocyte count obtained 1 day before the operation was used to calculate the preoperative PNI (PNI = serum ALB level [g/L] + 5 × total number of peripheral blood lymphocytes [×109/L]). According to the survival rates of skin grafts 14 days after the operation, patients with severe burns were divided into a group with good skin graft survival (survival rate ≥75%, abbreviated as group G) and a group with poor skin graft survival (survival rate <75%, abbreviated as group P). Receiver-operating characteristic (ROC) curves and univariate and multivariate analyses were used to evaluate the predictive value of the preoperative PNI for the prognosis of patients treated with the Meek technique. One hundred and twenty-one patients were enrolled in this study. Groups G (n = 66 cases) and P (n = 55 cases) did not have significant differences in age, sex, and body mass index (P > .05). The total burned surface area, burn index, platelet-to-lymphocyte ratio, preoperative platelet count, operative time, total protein, albumin level, globulin level, and PNI were the risk factors affecting the survival of Meek grafts. The burn index was an independent risk factor for poor skin graft survival (odds ratio [OR]: 1.049, 95% confidence interval [CI]: 1.020-1.079; P < .05). The preoperative PNI was a protective factor against poor skin graft survival (OR: 0.646, 95% CI: 0.547-0.761; P < .05). The ROC curve determined that the optimal cut-off value for the preoperative PNI was 34.98. There were 59 cases with PNI > 34.98 (the high PNI group) and 62 cases with PNI < 34.98 (the low PNI group). The survival rate of skin grafts in patients with a high PNI was generally significantly higher than that of patients with a low preoperative PNI (P < .05). Five (8.47%) patients in the high PNI group died, compared with 16 (25.8%) patients in the low PNI group. The difference in the mortality rate between the two groups was significant (P < .05). Preoperative PNI can be used as a predictor of the survival rate of skin grafts in patients treated with the Meek technique in the early stage of severe burns.