Competency in responding to infectious disease outbreaks among nurses in primary healthcare institutions: a quantitative, cross-sectional multicentre study.

Background: Nurses' competencies are crucial for infectious disease prevention and control. We aimed to investigate competencies in responding to infectious disease outbreaks of nurses in primary healthcare institutions and identify their training needs. Methods: A cross-sectional study was conducted from June to September 2022, recruiting nurses from primary healthcare institutions across Sichuan Province. Their competencies and training needs were assessed using a modified Emergency Response Competency Scale for Infectious Diseases. Additionally, their sociodemographic characteristics and experience in infectious disease outbreak trainings were collected. Univariate analyses were used to compare competencies and training needs by participant characteristics. Multiple linear regression was conducted to identify determinants of their competencies. Results: A total of 1,439 nurses from 44 primary healthcare institutions participated in this study. The overall competency and training needs had a median of 3.6 (IQR [3.1, 4.0]) and 4.0 (IQR [3.9, 4.7]), respectively. Age (ß = -0.074, p = 0.005), experience in higher authority hospitals (ß = 0.057, p = 0.035), infectious disease outbreak trainings attended within the last 5 years (ß = 0.212, p < 0.001), and regions where the institutions located were determinants of the competencies. Conclusion: The competencies in responding to infectious disease outbreaks among nurses in primary healthcare institutions were at a moderate level, influenced by varied factors.

Well-Defined Homopolymer Nanoparticles with Uniaxial Molecular Orientation by Synchronized Polymerization and Self-Assembly.

Synthesizing anisotropic polymeric nanoparticles (NPs) with well-defined shapes, dimensions, and molecular orientations is a very challenging task. Herein, we report the synthesis of surprisingly highly uniform shape-anisotropic polymer NPs with uniaxial internal molecular orientation. Keys to our method are synchronized polymerization and self-assembly (SPSA), which can even be realized by regular dispersion polymerization. This is demonstrated using a monomer containing a rigid 4-nitroazobenzene (NAB) side group. The short nucleation period, the completion of microphase separation before molecular motion is frozen, and sufficient low particle/solvent interfacial tension are shown to be the origins of the highly uniform dimensions, single liquid crystal domains, and well-defined anisotropic shape of particles. The liquid crystallization ability of the polymers, control of molecular weight distribution, and the polymerization kinetics are identified as three key factors controlling the NP formation. The uniformity of these NPs facilitates their SA formation into colloidal crystals. The particles exhibit optically anisotropic properties depending on orientations and, in particular, show intriguing photoswitchable LC-glass (order-disorder) transition, which can be used for the detection of ultraviolet (UV) light and allows the fabrication of photoreversible colloidal films.

Revealing the Mechanism of Converting CO2 into Methanol by the Cu2O and Oxygen Vacancy on MgO: Experiments and Density Functional Theory.

Given the great significance of defect and Cu compounds for the reduction of CO2 as well as the few reaction mechanisms of converting CO2 into different hydrocarbons, the effects of oxygen vacancies and Cu2O on the reduction of CO2 were thoroughly investigated, and possible mechanisms were also proposed. A series of Cu2O/Ov-MgO catalysts were synthesized for photothermal catalytic reduction of CO2 to methanol under visible-light irradiation, among which the 7%Cu2O/Ov-MgO composite exhibited the best reduction activity and the yield of methanol was 19.78 µmol·g-1·h-1. The successful composite of Cu2O and Ov-MgO can yield a loose and porous nanosheet, uniform distribution, favorable absorbance and photoelectric performance, and increased specific surface area and adsorption ability of CO2, which are all vital to the adsorption and conversion of CO2. The introduction of oxygen vacancy and Cu2O not only promotes the adsorption of CO2 but also provides more electron-triggered CO2 activation. Density functional theory (DFT) calculation was also performed to reveal the reaction mechanism for effective enhanced CO2 reduction to ethanol or methanol by the comparison of CuO/MgO and Cu2O/Ov-MgO composites, illustrating the reaction pathways of different products. By comparing the key steps in determining the selectivity of C1 or C2, the kinetic barriers of obtaining CH3OH for the Cu2O/Ov-MgO composite with CH3OH as the main product were found to be lower than those of generating CH2*, while the opposite is true for CuO/MgO composites, whereby it may be easier to obtain more C2 products. These insights into the reaction mechanism of converting CO2 into different hydrocarbons are expected to provide guidance for the further design of high-performance photothermal catalytic CO2 reduction catalysts.

Enhancing Dengue Virus Production and Immunogenicity with Celcradle™ Bioreactor: A Comparative Study with Traditional Cell Culture Methods.

The dengue virus, the primary cause of dengue fever, dengue hemorrhagic fever, and dengue shock syndrome, is the most widespread mosquito-borne virus worldwide. In recent decades, the prevalence of dengue fever has increased markedly, presenting substantial public health challenges. Consequently, the development of an efficacious vaccine against dengue remains a critical goal for mitigating its spread. Our research utilized Celcradle™, an innovative tidal bioreactor optimized for high-density cell cultures, to grow Vero cells for dengue virus production. By maintaining optimal pH levels (7.0 to 7.4) and glucose concentrations (1.5 g/L to 3.5 g/L) during the proliferation of cells and viruses, we achieved a peak Vero cell count of approximately 2.46 × 109, nearly ten times the initial count. The use of Celcradle™ substantially decreased the time required for cell yield and virus production compared to conventional Petri dish methods. Moreover, our evaluation of the immunogenicity of the Celcradle™-produced inactivated DENV4 through immunization of mice revealed that sera from these mice demonstrated cross-reactivity with DENV4 cultured in Petri dishes and showed elevated antibody titers compared to those from mice immunized with virus from Petri dishes. These results indicate that the dengue virus cultivated using the Celcradle™ system exhibited enhanced immunogenicity relative to that produced in traditional methods. In conclusion, our study highlights the potential of the Celcradle™ bioreactor for large-scale production of inactivated dengue virus vaccines, offering significant promise for reducing the global impact of dengue virus infections and accelerating the development of effective vaccination strategies.

Standardized uptake valuemax of the primary lesion combined with tumor markers for clinically predicting distant metastasis in de novo lung adenocarcinoma.

BACKGROUND: To examine standardized uptake valuemax of the primary lesion (pSUVmax) and tumor markers (TMs) for clinically predicting distant metastasis in novo lung adenocarcinoma. METHODS: The current retrospective observational study examined individuals diagnosed with de novo lung adenocarcinoma at Shanxi Cancer Hospital between February 2015 and December 2019. RESULTS: Totally, 532 de novo lung adenocarcinoma cases were included. They were aged 60.8 ± 9.7 years and comprised 224 women and 268 patients with distant metastasis. The areas under the curves (AUCs) of pSUVmax, lactate dehydrogenase (LDH), carcinoembryonic antigen (CEA), cytokeratin-19 fragment (CYFRA21-1), carbohydrate antigen 125 (CA125), and Grade of TMs for predicting distant metastasis were 0.742, 0.601, 0.671, 0.700, 0.736, and 0.745, respectively. The combination of pSUVmax, LDH, CEA, CYFRA21-1, CA125, and grade of TMs in predicting distant metastasis had an AUC value of 0.816 (95%CI: 0.781-0.851), with sensitivity of 89.2%, specificity of 58.7%, positive predictive value of 73.7%, and negative predictive value of 79.7%, respectively. CONCLUSIONS: pSUVmax combined with serum levels of LDH, CEA, CYFRA21-1, CA125, and the grade of TMs may have good performance in predicting distant metastasis of de novo lung adenocarcinoma.

Is managerial ability a catalyst for driving digital transformation in enterprises? An empirical analysis from internal and external pressure perspectives.

In a dynamic and competitive business environment, managerial ability emerges as a pivotal strategic factor for capitalizing on new opportunities within the technological revolution and digital transformation of enterprises. Based on data from Chinese A-share listed firms spanning from 2009 to 2019, this study integrates insights from the upper echelons theory and the behavioral theory of the firm to investigate the moderating roles of historical aspiration shortfalls and industrial competitiveness on the relationship between managerial ability and enterprise digital transformation from internal and external pressure perspectives. Our findings indicate a positive impact of managerial ability on digital transformation. The relationship between managerial ability and digital transformation is reinforced by historical aspiration shortfalls; nevertheless, industrial competitiveness has attenuated the aforementioned relationship. This study contributes to a better understanding of the strategic implications of managerial ability within the context of organizational innovation strategies. It offers valuable insights into the decision-making processes of firms as they navigate the challenges of digital transformation within an ever-evolving business environment.

Controlled synthesis of 2D-2D conductive metal-organic framework/g-C3N4 heterojunctions for efficient photocatalytic hydrogen evolution.

Designing photocatalysts with efficient charge separation and electron transport capabilities to achieve efficient visible-driven hydrogen production remains a challenge. Herein, 2D-2D conductive metal-organic framework/g-C3N4 heterojunctions were successfully prepared by an in situ assembly. Compared to pristine g-C3N4, the ratio-optimized Ni-CAT-1/g-C3N4 exhibits approximately 3.6 times higher visible-light H2 production activity, reaching 14 mmol g-1. Through investigations using time-resolved photoluminescence, surface photovoltage, and wavelength-dependent photocurrent action spectroscopies, it is determined that the improved photocatalytic performance is attributed to enhanced charge transfer and separation, specifically the efficient transfer of excited high-energy-level electrons from g-C3N4 to Ni-CAT in the heterojunctions. Furthermore, the high electrical conductivity of Ni-CAT enables rapid electron transport, contributing to the overall enhanced performance. This work provides a feasible strategy to construct efficient dimension-matched g-C3N4-based heterojunction photocatalysts with high-efficiency charge separation for solar-driven H2 production.

NADPH oxidase 2 inhibitor GSK2795039 prevents doxorubicin-induced cardiac atrophy by attenuating cardiac sympathetic nerve terminal abnormalities and myocyte autophagy.

Doxorubicin is widely used for the treatment of human cancer, but its clinical use is limited by a cumulative dose-dependent cardiotoxicity. However, the mechanism of doxorubicin-induced cardiac atrophy and failure remains to be fully understood. In this study, we tested whether the specific NADPH oxidase 2 (Nox2) inhibitor GSK2795039 attenuates cardiac sympathetic nerve terminal abnormalities and myocyte autophagy, leading to the amelioration of cardiac atrophy and dysfunction in chronic doxorubicin-induced cardiomyopathy. Mice were randomized to receive saline, doxorubicin (2.5 mg/kg, every other day, 6 times) or doxorubicin plus GSK2795039 (2.5 mg/kg, twice a day, 9 weeks). Left ventricular (LV) total wall thickness and LV ejection fraction were decreased in doxorubicin-treated mice compared with saline-treated mice and the decreases were prevented by the treatment of the specific Nox2 inhibitor GSK2795039. The ratio of total heart weight to tibia length and myocyte cross-sectional area were decreased in doxorubicin-treated mice, and the decreases were attenuated by the GSK2795039 treatment. In doxorubicin-treated mice, myocardial Nox2 and 4-hydroxynonenal levels were increased, myocardial expression of GAP43, tyrosine hydroxylase and norepinephrine transporter, markers of sympathetic nerve terminals, was decreased, and these changes were prevented by the GSK2795039 treatment. The ratio of LC3 II/I, a marker of autophagy, and Atg5, Atg12 and Atg12-Atg5 conjugate proteins were increased in doxorubicin-treated mice, and the increases were attenuated by the GSK2795039 treatment. These findings suggest that inhibition of Nox2 by GSK2795039 attenuates cardiac sympathetic nerve terminal abnormalities and myocyte autophagy, thereby ameliorating cardiac atrophy and dysfunction after chronic doxorubicin treatment.

Molecular Dynamics Simulation Study on Self-Assembly of Polymer-Grafted Nanocrystals: From Isotropic Cores to Anisotropic Cores.

The self-assembly of polymer-grafted nanocrystals (PGNCs) is an important method to manufacture novel nanomaterials. Herein, we focus on the self-assembly of three types of PGNCs with differently shaped cores including sphere, octahedron, and cube by molecular dynamics simulation. By characterizing the positional and orientational order of the assembled superlattices, we construct the phase diagrams as a function of the grafting density and polymer chain length. For PGNCs with spherical cores, we observe the transition from the FCC phase to the BCC phase due to the packing entropy of the ligand polymer chains. For PGNCs with anisotropic cores, the close-packed FCC phase is replaced by the C-BCC phase (octahedral cores) or the C-triclinic phase (cubic cores) due to the directional entropy of core shape. We also study the assembly dynamics by tracking the time evolution of the positional and orientational order. We elucidate the relationship of grafting density and polymer chain length to the packing entropy and directional entropy and reveal their important effects on assembled structures. In general, our simulation results provide useful guidelines for the programmable assembly of PGNCs.

Nonequilibrium Behaviors of Entangled Diblock Copolymers at the Entangled Polymer-Polymer Interface under Steady Shear Flow.

The slip phenomena and the individual configuration dynamics of interfacial copolymer chains in the entangled polymer-polymer interface under fast shear flow are analyzed using mDPD simulations on ternary blends of A125/B125/C125D125 with different incompatibilities or interface strengths. We observe two distinct power-law regions of slip velocity against interfacial shear stress: from Vs ∼ σ5 to Vs ∼ σ1 at an increasing shear rate with the interface strength. At the micro level, the two regions correspond to the integrated and incomplete interfacial entanglement network with the shear-induced disentanglement of interfacial chains, respectively. For the individual chain dynamics of interfacial copolymers, we clarify that for the weak incompatibility, the tumbling event of interfacial copolymer chains is irregular and occasional and includes six processes: align and flip, collapse, tumble, stretch, reflip, and recoil and tumble. For the system with strong incompatibility, the interfacial copolymer chain undergoes the stretched-coil conformational transition via elastic retraction. As the interfacial entanglement network disintegrates, the hairpin-like configuration is dominant during the tumbling motion or elastic retraction of the interfacial copolymer chain.

Non-Rouse behavior of short ring polymers in melts by molecular dynamics simulations.

Short ring polymers are expected to behave nearly Rouse-like due to the little effect of topological constraints of non-knot and non-concatenation. However, this notion is questioned because of several simulation and experiment findings in recent times, which requires a further more quantitative study. Therefore, we perform a deep investigation of statics and dynamics of flexible short ring polymers (N < 2Ne) in melts via molecular dynamics simulations by further taking linear analogues as well as all-crossing ring and linear polymers with switched off topological constraints for comparisons and demonstrate the noticeable deviations from the Rouse model in terms of local and global scales. Although the overall size is compact, the subchains are swollen, which is traced back to the deeper "segmental correlation hole" effect. The same scaling relationship of the non-Gaussian deviation of the static structure factor holds, but the deviation magnitude of rings is larger than that of linear analogues. By checking the non-Gaussian parameter and autocorrelation function of center-of-mass velocity, the physical origin of anomalous sub-diffusions of short rings is identified as unscreened viscoelastic hydrodynamic interactions and not correlation hole effects, like linear analogues.

The cutoff value and prognosis of anti-PLA2R antibody for idiopathic membranous nephropathy: a single-center retrospective study in China.

Serum anti-phospholipase A2 receptor (anti-PLA2R) antibody is used for the noninvasive diagnosis of idiopathic membranous nephropathy (IMN). However, the cutoff value of anti-PLA2R antibodies in IMN patients is debatable. This study aimed to investigate the cutoff value of anti-PLA2R antibodies for diagnosing IMN and the correlation of anti-PLA2R antibodies with clinical parameters and prognosis. A total of 252 IMN patients and 521 non-IMN patients with both renal biopsy and serum anti-PLA2R antibody data from April 2017 to November 2019 were enrolled. Anti-PLA2R antibody was detected by an enzyme-linked immunosorbent assay. The anti-PLA2R antibody titer was higher in the IMN group than in the non-IMN group (153.1 ± 22.4 vs. 2.0 ± 0.2 RU/mL, p < 0.001). The optimal anti-PLA2R antibody cutoff value for diagnosing IMN was 2.5 RU/mL, with a sensitivity, specificity, and Youden index of 85.7%, 88.3%, and 0.740, respectively. There was a significant positive correlation between anti-PLA2R antibody and 24-h urinary protein levels (r = 0.341, p < 0.001), and a significant negative correlation between anti-PLA2R antibody and serum albumin levels (r=-0.274, p < 0.001) in patients with IMN. The remission rates positively correlated with the immunosuppressive usage rates and increased from the low- to the high-titer subgroup. Multivariable Cox regression analysis showed that immunosuppressive therapy (adjusted HR = 4.656; 95% confidence interval [CI], 1.461-14.839; p = 0.009) was associated with a higher remission rate in patients with IMN. The optimal Anti-PLA2R antibody cutoff value for diagnosing IMN was 2.5 RU/mL, which was much lower than that indicated by the manufacturer. If IMN is actively treated, patients can have much better prognoses.Trial registration: retrospectively registered.

Complex Karyotype Acute Basophilic Leukemia with Reactive Mast Cell Hyperplasia.

BACKGROUND: The goal of the study is to improve the understanding of complex karyotype acute basophilic leukemia with reactive mast cell hyperplasia. METHODS: A case of clinical and laboratory characteristics of complex karyotype acute basophilic leukemia with reactive mast cell hyperplasia and review of related literature of patient with acute basophilic leukemia were retrospectively analyzed. RESULTS: Laboratory tests: alanine aminotransferase 225 U/L, aspartate aminotransferase 129 U/L, total protein 3.0 g/L, albumin 25.0 g/L, globulin 17.8 g/L, total bilirubin 183.9 µmol/L, indirect bilirubin 65.6 µmol/L, D-dimer 13.02 mg/L, prothrombin time 19.30 S, white blood cell 37.30 x 109/L, red blood cells 2.06 x 1012/L, hemoglobin 71 g/L, platelets 13 x 109/L, and basophilic granulocyte cells 5.01 x 109/L. Bone marrow smear: a large number of abnormal primitive cells were scattered and distributed. The characteristics of these cells were as follows: the cell body size was different, most of them were round or quasi-round, the cytoplasm volume was medium, and the cytoplasm was stained gray blue. The cytoplasmic processes were visible, and basophilic particles were visible in part of the cytoplasm and/or on the nucleus. The nuclei were mostly round or almost round, with distortion and folding. The chromatin was detailed, the nucleoli varied in number, and some nucleoli were deeply stained. The cells showed double and multiple nuclei, scattered and occasionally small clumps. Bone marrow biopsy: acute myeloid leukemia, not excluding basophilic leukemia. Bone marrow molecular biology: All 29 myeloid leukemia genes, including RARA and BCR-ABL fusion genes, were negative. Flow cytometry results showed abnormal cell population which accounted for 21.98% of nuclear cells. The phenotypes are CD33++, CD38+, CD13+, CD123+, CD7+, CD36+, CD203c+, CD81+, part of CD34+, part of HLA-DR+, CD4 weak+, weak CD117+, the TDT-, cCD3-, cCD79a-, MPO-, CD11c-, CD25-, CD2-. In addition, mast cells accounted for 1.15% of nuclear cells, expressing CD203c, but not CD25 and CD2. Karyotype analysis results were 46, XY, -7, psudic (9; 19) (p24; p13.3), add (15) (p12), add (21) (q22), +r, +1 - 2 mar [cp20]. CONCLUSIONS: Acute basophilic leukemia (ABL) is a rare malignant hematologic tumor. Bone marrow smears, biopsies, flow cytometry, and cytogenetic tests play an important role in the diagnosis and differentiation of complex karyotype acute basophilic leukemia with reactive mast cell hyperplasia.

TP53 Exon 5 Mutation Indicates Poor Progression-Free Survival for Patients with Stage IV NSCLC.

BACKGROUND: Genetic mutations are quite common in non-small cell lung cancer (NSCLC), however, their prognostic value remains controversial. METHODS: This study explored the mutational landscape of tumor samples from patients with advanced NSCLC by next-generation sequencing (NGS). A total of 101 NSCLC patients in stage III or IV receiving first-line treatment were included. RESULTS: TP53 mutation was the most frequent genetic alteration in NSCLC tumors (68%), followed by EGFR (49%), CDKN2A (12%), LRP1B (9%), and FAT3 (9%) mutations. Among 85 patients with stage IV NSCLC, first-line targeted therapy remarkably prolonged progression-free survival (PFS) of patients compared with first-line chemotherapy (p = 0.0028). Among 65 patients with stage IV NSCLC whose tumors harbored EGFR, ALK, ROS, or BRAF mutations, first-line targeted therapy substantially prolonged the PFS of patients (p = 0.0027). In patients with TP53 mutations who received first-line targeted therapy or chemotherapy, missense mutation was the most common mutation type (36/78), and exon 5 represented the most common mutated site (16/78). CONCLUSIONS: TP53 mutation in exon 5 could independently predict poor PFS of patients with stage IV NSCLC after the first- line treatment. Moreover, mutations in TP53 exon 5 and LRP1B were associated with shorter PFS of such patients whether after first-line chemotherapy or targeted therapy, respectively. Thus, these patients should be given immunotherapy or immunochemotherapy.

Risk factors associated with trigeminocardiac reflex in patients with trigeminal neuralgia during percutaneous balloon compression: A retrospective cohort study.

BACKGROUND: The trigeminocardiac reflex (TCR) is a brainstem reflex commonly elicited during percutaneous balloon compression (PBC) for the treatment of trigeminal neuralgia (TN), which is characterized by drastic hemodynamic disturbances, such as bradycardia, arrhythmias and even cardiac arrest. In order to prevent catastrophic consequences, it is vital to screen the risk factors of TCR during perioperative period. The primary purpose of this study was to identify potential risk factors associated with TCR in patients with TN undergoing PBC, and to summarize the enlightenment of clinical anesthesia management. METHODS: The clinical data of 165 patients diagnosed with TN undergoing PBC from January 2021 to December 2021 were retrospectively analyzed. TCR was defined as a sudden decrease in heart rate of 20% or more compared with baseline, and / or cardiac arrest, coinciding with the stimulus of any branch of the trigeminal nerve. And a clear cause-effect relationship between heart rate reduction and PBC-related intervention was required. All demographic characteristics as well as surgical and anesthetic data were compared between TCR group and TCR-free group. Univariate and multivariate logistic regression analysis were used to further analyze TCR-related risk factors. RESULTS: Of the 165 patients enrolled in this study, 73 (44.2%) were male and 92 (55.8%) were female, and the average age was 64.22 ± 9.72 years. The incidence of TCR in the patients with TN during PBC was 54.5%. The results of multivariate regression analysis indicated that the risk factor for TCR was heart rate < 60 beats/min immediately before foramen ovale puncture (OR: 4.622; 95%CI: 1.470-14.531; P < 0.05). CONCLUSION: Heart rate < 60 beats/min immediately before foramen ovale puncture was independently associated with TCR. Therefore, it is necessary for anesthesiologists to raise heart rate appropriately to prevent TCR during PBC.

Developing a core competency framework for advanced practice nursing in mainland China: a sequential exploratory study.

BACKGROUND: Advanced Practice Nursing (APN) have been highly valued and an integral part of the health care system. Development and establishment of new APN roles is a complex process that has resulted from a wide variety of reasons, key component is a lack of a competency map delineation and role evaluation. Currently, however, competence framework has not been compared at an international level. In mainland China, APN have been introduced in some organizations but their competency domains have not yet been clearly defined, this study aimed to identify the core competencies for advanced practice nursing. METHODS: This study was performed in two phases: first, in-depth and semi-structured individual interviews with 46 participants from key stakeholders were carried out followed by a qualitative content analysis, then an item pool of core competencies was constructed by extracting data from the first phase and the results from previous studies, scales and documents; second, a Delphi technique was conducted with the participation of 28 experts from 7 areas of China to form the final core competency framework for advanced practice nursing. RESULTS: Through the qualitative phase, the core competency framework with six domains and 70 items emerged and then entered into the Delphi phase. Twenty-eight of 30 experts finished 2 rounds of Delphi approaches. The final core competencies for advanced practice nursing consisted of six domains with 61 items, including direct clinical nursing practice, research and evidence-based nursing practice, professional development, organization and management, mentoring and consultation, and ethical/legal practice. CONCLUSION: This core competency framework consisted of six domains with 61 items can be used in competency-based education to cultivate advanced practice nurses as well as competency level assessment.

Reduced circulating Tregs and positive pANCA were robustly associated with the occurrence of antiphospholipid syndrome in patients with systemic lupus erythematosus.

BACKGROUND: Systemic lupus erythematosus (SLE) is a typical chronic immune disorder with clinical heterogeneity. The systemic abnormal immune response not only challenges the diagnosis and treatment of the disease itself but also the secondary antiphospholipid syndrome (APS), characterized by recurrent arterial or venous thrombosis, recurrent spontaneous abortion, or stillbirth. Clinical interest has primarily focused on primary APS's pathological and clinical features. However, differences in clinical features and laboratory indicators between SLE with or without APS are still lacking, especially differences between circulating lymphocytes, which are critical in the pathogenesis of SLE and its complications. METHODS: In this retrospective study, we collected and analyzed clinical characteristics, general laboratory indicators, immunological indicators, and circulating lymphocyte subsets of SLE with or without APS. RESULTS: Systemic lupus erythematosus with APS (SLE-APS) had elevated SLEDAI scores, hospitalization costs and time, and frequencies of central nervous system symptoms and spontaneous abortion compared with those without APS. SLE-APS had higher positive anti-Cardiolipin antibodies, anti-ß2 Glycoprotein 1 antibodies, and perinuclear antineutrophil cytoplasmic antibody (pANCA) than none-APS patients. Compared with healthy controls (HCs), the circulating lymphocyte subsets were altered to some extent in all patients, especially in patients with SLE-APS. Reduced Tregs and positive pANCA were independent risk factors for SLE secondary APS. CONCLUSION: The present study revealed a robust association between APS secondary to SLE and reduced Tregs and positive pANCA, which provides essential information regarding the diagnosis and therapeutic possibilities of APS secondary to SLE.

Microbe community composition differences of hand skin on similar lifestyle volunteers: a small-scale study.

AIMS: Human skin is the first barrier against pathogens and environmental hazards and the highest contact frequency occurs with the hands. Environmental and personal metabolic factors may affect skin microbes. This study was conducted to clarify the diversity in the skin microbial community that was mainly due to individual skin metabolites rather than lifestyle and environmental factors. METHODS AND RESULTS: Skin microbiota samples were collected from 11 volunteers who met similar lifestyle inclusion criteria. The V3-V4 region of the 16S rRNA gene was amplified. After library construction and sequencing, we compared the composition and diversity of the hand skin microbiota in different sexes and BMI groups with bioinformation analysis. The whole sequence data were annotated as 42 phyla, 538 families, and 1215 genera. Four dominant phyla accounted for 97% of the total including Actinobacteriota (50.18%), Firmicutes (23.85%), Proteobacteria (21.64%) and Bacteroidota (2.05%). The genera that were detected in all subjects with high relative abundance were Cutibacterium, Staphylococcus, Corynebacterium, Streptococcus, Lawsonella, Enhydrobacter, Escherichia-Shigella, Asaia and Micrococcus. CONCLUSIONS: The diversity and richness of the microbiota of male hand skin in our study was higher than that of females. Interestingly, Cutibacterium, Staphylococcus, and Corynebacterium might serve as important skin microbiota to distinguish sexes.

GSK2795039 prevents RIP1-RIP3-MLKL-mediated cardiomyocyte necroptosis in doxorubicin-induced heart failure through inhibition of NADPH oxidase-derived oxidative stress.

Doxorubicin (DOX), which is widely used for the treatment of cancer, induces cardiomyopathy associated with NADPH oxidase-derived reactive oxygen species. GSK2795039 is a novel small molecular NADPH oxidase 2 (Nox2) inhibitor. In this study, we investigated whether GSK2795039 prevents receptor-interacting protein kinase 1 (RIP1)-RIP3-mixed lineage kinase domain-like protein (MLKL)-mediated cardiomyocyte necroptosis in DOX-induced heart failure through NADPH oxidase inhibition. Eight-week old mice were randomly divided into 4 groups: control, GSK2795039, DOX and DOX plus GSK2795039. H9C2 cardiomyocytes were treated with DOX and GSK2795039. In DOX-treated mice, the survival rate was reduced, left ventricular (LV) end-systolic dimension was increased and LV fractional shortening was decreased, and these alterations were attenuated by the GSK2795039 treatment. GSK2795039 inhibited not only myocardial NADPH oxidase subunit gp91phox (Nox2) protein, but also p22phox, p47phox and p67phox proteins and prevented oxidative stress 8-hydroxy-2'-deoxyguanosine levels in DOX-treated mice. RIP3 protein and phosphorylated RIP1 (p-RIP1), p-RIP3 and p-MLKL proteins, reflective of their respective kinase activities, markers of necroptosis, were markedly increased in DOX-treated mice, and the increases were prevented by GSK2795039. GSK2795039 prevented the increases in serum lactate dehydrogenase and myocardial fibrosis in DOX-treated mice. Similarly, in DOX-treated cardiomyocytes, GSK2795039 improved cell viability, attenuated apoptosis and necrosis and prevented the increases in p-RIP1, p-RIP3 and p-MLKL expression. In conclusion, GSK2795039 prevents RIP1-RIP3-MLKL-mediated cardiomyocyte necroptosis through inhibition of NADPH oxidase-derived oxidative stress, leading to the improvement of myocardial remodeling and function in DOX-induced heart failure. These findings suggest that GSK2795039 may have implications for the treatment of DOX-induced cardiomyopathy.

Molecular Self-Assembled Ether-Based Polyrotaxane Solid Electrolyte for Lithium Metal Batteries.

Poly(ethylene oxide) has been widely investigated as a potential separator for solid-state lithium metal batteries. However, its applications were significantly restricted by low ionic conductivity and a narrow electrochemical stability window (<4.0 V vs Li/Li+) at room temperature. Herein, a novel molecular self-assembled ether-based polyrotaxane electrolyte was designed using different functional units and prepared by threading cyclic 18-crown ether-6 (18C6) to linear poly(ethylene glycol) (PEG) via intermolecular hydrogen bond and terminating with hexamethylene diisocyanate trimer (HDIt), which was strongly confirmed by local structure-sensitive solid/liquid-state nuclear magnetic resonance (NMR) techniques. The designed electrolyte has shown an obviously increased room-temperature ionic conductivity of 3.48 × 10-4 S cm-1 compared to 1.12 × 10-5 S cm-1 without assembling polyrotaxane functional units, contributing to the enhanced cycling stability of batteries with both LiFePO4 and LiNi0.8Co0.15Al0.05O2 cathode materials. This advanced molecular self-assembled strategy provides a new paradigm in designing solid polymer electrolytes with demanded performance for lithium metal batteries.