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Abstract Background Up to 17% of cancer survivors have been reported to develop second primary cancers (SPC), which cause significant physical and economic distress and often complicate clinical decision-making. However, understanding of SPC remains limited and superficial. Human leukocyte antigen (HLA) is characterized by its polymorphism and has been associated with various diseases. This study aims to explore the role of HLA diversity in SPC incidence. Methods We analyzed a cohort of 47,550 cancer patients from the UK Biobank. SNP-derived HLA alleles were used and SPC-related HLA alleles were identified using logistic regression, followed by stepwise filtering based on the Akaike information criterion (AIC) and permutation tests. Additionally, we examined the association between extragenetic factors and the risk of SPC in patients carrying hazardous HLA alleles. Results During a median follow-up of 3.11 years, a total of 2894 (6.09%) participants developed SPC. We identified three protective HLA alleles (DRB1*04:03 and DPA1*02:02 for males and DRB5*01:01 for females) and two hazardous alleles (A*26:01 for males and DPB1*11:01 for females) about SPC. The presence of the protective alleles was associated with a reduced SPC risk (males: hazard ratio [HR] 0.72, 95% confidence interval [CI] 0.59–0.89; females: HR 0.81, 95% CI 0.70–0.93), while the hazardous alleles were linked to an increased risk (males: HR 1.27, 95% CI 1.03–1.56; females: HR 1.35, 95% CI 1.07–1.70). The hazardous allele A*26:01 indicated skin-lung organ-specific SPC occurrence in males. Animal fat and vitamin C were associated with SPC risk in males carrying the hazardous alleles, while free sugar and vegetable fat were linked to SPC risk in females. Conclusions These results suggest that HLA alleles may serve as biomarkers for the susceptibility and organ-specific occurrence of SPC, while dietary modulation may mitigate hazardous alleles-related SPC risk, potentially aiding in the early prediction and prevention of SPC.

Abstract Ovine contagious pustular dermatitis (ORF) is one of the main diseases of sheep and is a zoonotic disease caused by Ovine contagious pustular dermatitis virus (ORFV) infection, posing a significant constraint on sheep breeding industry and human health. The Tibetan medical formulation composed of Polygonum leucoides, Polygonum xanthoxylum and Acanthophora rotunda significantly regulated lymphocyte immune function following ORFV stimulation, although the mechanism remains unclear. In order to study the immunomodulatory effects and mechanism of three Tibetan medicinal extracts (Polygonum leucoides, Polygonum xanthoxylum, and Acanthophora rotunda) against ORFV in vitro, sheep peripheral blood lymphocytes were isolated in vitro and treated with different concentrations of Tibetan medicine compound extract solution after ORFV infection. The cytokine expression levels in lymphocytes were measured at 4 h, 8 h and 12 h. Additionally endogenous metabolites in lymphocytes at 0 h, 4 h, 8 h and 12 h were quantified by untargeted metabolomics method. The results showed that, the extracts could regulate the lymphocyte immune factors altered by ORFV, and regulate the lymphocyte immune function through cysteine and methionine metabolic pathways as well as the pyrimidine metabolic pathways, potentially alleviating the immune evasion induced by ORFV.

Abstract The cryopreservation and transplantation of ovarian tissue underscore its paramount importance in safeguarding reproductive capacity and ameliorating reproductive disorders. However, challenges persist in ovarian tissue cryopreservation and transplantation (OTC-T), including the risk of tissue damage and dysfunction. Consequently, there has been a compelling exploration into the realm of nanoregulators to refine and enhance these procedures. This review embarks on a meticulous examination of the intricate anatomical structure of the ovary and its microenvironment, thereby establishing a robust groundwork for the development of nanomodulators. It systematically categorizes nanoregulators and delves deeply into their functions and mechanisms, meticulously tailored for optimizing ovarian tissue cryopreservation and transplantation. Furthermore, the review imparts valuable insights into the practical applications and obstacles encountered in clinical settings associated with OTC-T. Moreover, the review advocates for the utilization of microbially derived nanomodulators as a potent therapeutic intervention in ovarian tissue cryopreservation. The progression of these approaches holds the promise of seamlessly integrating nanoregulators into OTC-T practices, thereby heralding a new era of expansive applications and auspicious prospects in this pivotal domain. Graphical Abstract

Radiotherapy is a common treatment for abdominal and pelvic tumors, while the radiation-induced intestinal injury (RIII) is one of the major side-effects of radiotherapy, which reduces the life quality and impedes the treatment completion of cancer patients. Previous studies have demonstrated that environmental pollutant microplastics led to various kinds of injury in the gut, but its effects on RIII are still uncovered. In this study, we fed the C57BL/6J mice with distilled water or 50 μg/d polystyrene microplastics (PSMPs) for 17 days and exposed the mice to total abdominal irradiation (TAI) at day 14. Then the severity of RIII was examined by performing histopathological analysis and microbial community analysis. The results demonstrated that PSMPs significantly aggravated RIII in small intestine rather than colon of mice upon TAI. PSMPs increased levels of the histopathological damage and the microbial community disturbance in mice small intestine, shown by the overabundance of Akkermansiaceae and the decrease of microflora including Lactobacillaceae, Muribaculaceae and Bifidobacteriaceae. In conclusion, our results suggested that more microplastics exposure might led to more severe RIII, which should be considered in patients’ daily diet adjustment and clinical radiotherapy plan evaluation. Furthermore, this study also called for the further researches to uncover the underlying mechanism and develop novel strategies to attenuate RIII in mice intestine.

Abstract Ten-eleven translocation (TET) 2 is an enzyme that catalyzes DNA demethylation to regulate gene expression by oxidizing 5-methylcytosine to 5-hydroxymethylcytosine, functioning as an essential epigenetic regulator in various biological processes. However, the regulation and function of TET2 in adipocytes during obesity are poorly understood. In this study, we demonstrate that leptin, a key adipokine in mammalian energy homeostasis regulation, suppresses adipocyte TET2 levels via JAK2-STAT3 signaling. Adipocyte Tet2 deficiency protects against high-fat diet-induced weight gain by reducing leptin levels and further improving leptin sensitivity in obese male mice. By interacting with C/EBPα, adipocyte TET2 increases the hydroxymethylcytosine levels of the leptin gene promoter, thereby promoting leptin gene expression. A decrease in adipose TET2 is associated with obesity-related hyperleptinemia in humans. Inhibition of TET2 suppresses the production of leptin in mature human adipocytes. Our findings support the existence of a negative feedback loop between TET2 and leptin in adipocytes and reveal a compensatory mechanism for the body to counteract the metabolic dysfunction caused by obesity.

Copy number variants (CNVs) are an important source of normal and pathogenic genome variations. Unbalanced chromosome abnormalities are either gains or losses of large genomic regions that do not or only minimally clinically affect the individual. Noninvasive prenatal testing (NIPT) is widely used in the screening of common fetal chromosome aneuploidy. One example is the duplication of 10q11.21q11.23, which includes the 10q11.2 region. This region contains a complex set of low-copy repeats that may lead to various genomic alterations through non-allelic homologous recombination. In this report, we present a case of a de novo 10q11.21q11.23 duplication with a normal phenotype. This case may be helpful for prenatal diagnosis and genetic counseling. A combination of NIPT, prenatal ultrasound, karyotype analysis, copy number variation sequencing, and genetic counseling is helpful for the prenatal diagnosis of CNVs.

Abstract Activatable type I photosensitizers are an effective way to overcome the insufficiency and imprecision of photodynamic therapy in the treatment of hypoxic tumors, however, the incompletely inhibited photoactivity of pro‐photosensitizer and the limited oxidative phototoxicity of post‐photosensitizer are major limitations. It is still a great challenge to address these issues using a single and facile design. Herein, a series of totally caged type I pro‐photosensitizers (Pro‐I‐PSs) are rationally developed that are only activated in tumor hypoxic environment and combine two oxygen‐independent therapeutic mechanisms under single‐pulse laser irradiation to enhance the phototherapeutic efficacy. Specifically, five benzophenothiazine‐based dyes modified with different nitroaromatic groups, BPN 1−5, are designed and explored as latent hypoxia‐activatable Pro‐I‐PSs. By comparing their optical responses to nitroreductase (NTR), it is identified that the 2‐methoxy‐4‐nitrophenyl decorated dye (BPN 2) is the optimal Pro‐I‐PSs, which can achieve NTR‐activated background‐free fluorescence/photoacoustic dual‐modality tumor imaging. Furthermore, upon activation, BPN 2 can simultaneously produce an oxygen‐independent photoacoustic cavitation effect and a photodynamic type I process at single‐pulse laser irradiation. Detailed studies in vitro and in vivo indicated that BPN 2 can effectively induce cancer cell apoptosis through synergistic effects. This study provides promising potential for overcoming the pitfalls of hypoxic‐tumor photodynamic therapy.

Abstract Background China is a country burdened with a high incidence of both tuberculosis (TB) and HIV, Paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) is an important early complication in TB and HIV co-infected patients, but data from China are limited. Additionally, as an integrase strand transfer inhibitor (INSTI)-based antiretroviral therapy (ART) regimen becomes the first-line treatment, concerns have arisen regarding the potential increase in the incidence of paradoxical TB-IRIS. Nevertheless, the existing data are inconclusive and contradictory. Methods We conducted a retrospective study at Chongqing Public Health Clinical Center from January 2018 to December 2021. We collected demographic and clinical data of HIV/TB co-infected patients who initiated ART. We described the patient characteristics, identified predictors for TB-IRIS, and determined clinical outcomes. The Statistical Package for Social Science (SPSS 25) was used to analyse the data. Continuous variables were compared using Student’s t-test or rank sum test. Counting data were compared using the chi-square test or Fisher’s exact test. The variables with statistical significance in the univariate analysis were added to the binary logistic regression. A p-value less than 0.05 was considered statistically significant. Results A total of 384 patients co-infected with naive HIV and pulmonary TB (PTB) who were given ATT and ART combination were included. 72 patients (18.8%) developed paradoxical TB-IRIS with a median of 15 (12, 21) days after initiating ART. Baseline age ≤ 40years, CD4 + T-cell counts ≤ 50cells/µL, HIV viral load ≥ 500,000 copies/mL were found to be significantly associated with development of paradoxical TB-IRIS. Mortality rates were similar in the TB-IRIS (n = 5, 6.9%) group and non-TB-IRIS (n = 13, 4.2%) group. Interestingly, CD4+ T-cell counts recovery post-ART was significant higher in the TB-IRIS group when compared to the non-TB-IRIS group at the end of 24 weeks (P = 0.004), as well as at 48 weeks (P = 0.015). In addition, we consider that INSTI- based ART regimen do not increased the risk of Paradoxical TB-IRIS. Conclusion Paradoxical TB-IRIS, while often leading to clinical deterioration and hospitalization, is generally manageable. It appears to have a positive impact on the recovery of CD4 + T-cell counts over time. Importantly, our data suggest that INSTI-based ART regimens do not elevate the risk of TB-IRIS. Thus, paradoxical TB-IRIS should not be considered an impediment to initiating ART in adults with advanced immunodeficiency, except in the case of tuberculous meningitis (TBM).

BackgroundThe immune microenvironment assumes a significant role in the pathogenesis of osteoarthritis (OA). However, the current biomarkers for the diagnosis and treatment of OA are not satisfactory. Our study aims to identify new OA immune-related biomarkers to direct the prevention and treatment of OA using multi-omics data.MethodsThe discovery dataset integrated the GSE89408 and GSE143514 datasets to identify biomarkers that were significantly associated with the OA immune microenvironment through multiple machine learning methods and weighted gene co-expression network analysis (WGCNA). The identified signature genes were confirmed using two independent validation datasets. We also performed a two-sample mendelian randomization (MR) study to generate causal relationships between biomarkers and OA using OA genome-wide association study (GWAS) summary data (cases n = 24,955, controls n = 378,169). Inverse-variance weighting (IVW) method was used as the main method of causal estimates. Sensitivity analyses were performed to assess the robustness and reliability of the IVW results.ResultsThree signature genes (FCER1G, HLA-DMB, and HHLA-DPA1) associated with the OA immune microenvironment were identified as having good diagnostic performances, which can be used as biomarkers. MR results showed increased levels of FCER1G (OR = 1.118, 95% CI 1.031-1.212, P = 0.041), HLA-DMB (OR = 1.057, 95% CI 1.045 -1.069, P = 1.11E-21) and HLA-DPA1 (OR = 1.030, 95% CI 1.005-1.056, P = 0.017) were causally and positively associated with the risk of developing OA.ConclusionThe present study identified the 3 potential immune-related biomarkers for OA, providing new perspectives for the prevention and treatment of OA. The MR study provides genetic support for the causal effects of the 3 biomarkers with OA and may provide new insights into the molecular mechanisms leading to the development of OA.

Summary: T cell infiltration into white adipose tissue (WAT) drives obesity-induced adipose inflammation, but the mechanisms of obesity-induced T cell infiltration into WAT remain unclear. Our single-cell RNA sequencing reveals a significant impact of adipose stem cells (ASCs) on T cells. Transplanting ASCs from obese mice into WAT enhances T cell accumulation. C-C motif chemokine ligand 5 (CCL5) is upregulated in ASCs as early as 4 weeks of high-fat diet feeding, coinciding with the onset of T cell infiltration into WAT during obesity. ASCs and bone marrow transplantation experiments demonstrate that CCL5 from ASCs plays a crucial role in T cell accumulation during obesity. The production of CCL5 in ASCs is induced by tumor necrosis factor alpha via the nuclear factor κB pathway. Overall, our findings underscore the pivotal role of ASCs in regulating T cell accumulation in WAT during the early phases of obesity, emphasizing their importance in modulating adaptive immunity in obesity-induced adipose inflammation.

Tendon Sheath Giant Cell Tumor (TGCT) is a benign tumor that primarily grows within joints and bursae. However, it has a high postoperative recurrence rate, ranging from 15% to 45%. Although radiotherapy may reduce this recurrence rate, its applicability as a standard treatment is still controversial. Furthermore, the pathogenic mechanisms of TGCT are not clear, which limits the development of effective treatment methods. The unpredictable growth and high recurrence rate of TGCT adds to the challenges of disease management. Currently, our understanding of TGCT mainly depends on pathological slice analysis due to a lack of stable cell models. In this study, we first reviewed the medical records of two female TGCT patients who had undergone radiotherapy. Then, by combining bioinformatics and machine learning, we interpreted the pathogenesis of TGCT and its associations with other diseases from multiple perspectives. Based on a deep analysis of the case data, we provided empirical support for postoperative radiotherapy in TGCT patients. Additionally, our further analysis revealed the signaling pathways of differentially expressed genes in TGCT, as well as its potential associations with osteoarthritis and synovial sarcomas.

Abstract Background Simulation is an increasingly used novel method for the education of medical professionals. This study aimed to systematically review the efficacy of high-fidelity (HF) simulation compared with low-fidelity (LF) simulation or no simulation in advanced life support (ALS) training. Methods A comprehensive search of the PubMed, Chinese Biomedicine Database, Embase, CENTRAL, ISI, and China Knowledge Resource Integrated Database was performed to identify randomized controlled trials (RCTs) that evaluated the use of HF simulation in ALS training. Quality assessment was based on the Cochrane Handbook for Systematic Reviews of Interventions version 5.0.1. The primary outcome was the improvement of knowledge and skill performance. The secondary outcomes included the participants’ confidence and satisfaction at the course conclusion, skill performance at one year, skill performance in actual resuscitation, and patient outcomes. Data were synthesized using the RevMan 5.4 software. Results Altogether, 25 RCTs with a total of 1,987 trainees were included in the meta-analysis. In the intervention group, 998 participants used HF manikins, whereas 989 participants received LF simulation-based or traditional training (classical training without simulation). Pooled data from the RCTs demonstrated a benefit in improvement of knowledge [standardized mean difference (SMD) = 0.38; 95% confidence interval (CI): 0.18–0.59, P = 0.0003, I 2 = 70%] and skill performance (SMD = 0.63; 95% CI: 0.21–1.04, P = 0.003, I 2 = 92%) for HF simulation when compared with LF simulation and traditional training. The subgroup analysis revealed a greater benefit in knowledge with HF simulation compared with traditional training at the course conclusion (SMD = 0.51; 95% CI: 0.20–0.83, P = 0.003, I 2 = 61%). Studies measuring knowledge at three months, skill performance at one year, teamwork behaviors, participants’ satisfaction and confidence demonstrated no significant benefit for HF simulation. Conclusions Learners using HF simulation more significantly benefited from the ALS training in terms of knowledge and skill performance at the course conclusion. However, further research is necessary to enhance long-term retention of knowledge and skill in actual resuscitation and patient’s outcomes.

BackgroundRupture of abdominal aortic aneurysm (rAAA) is a fatal event in the elderly. Elevated blood pressure and weakening of vessel wall strength are major risk factors for this devastating event. This present study examined whether the expression profile of mechanosensitive genes correlates with the phenotype and outcome, thus, serving as a biomarker for AAA development.MethodsIn this study, we identified mechanosensitive genes involved in AAA development using general bioinformatics methods and machine learning with six human datasets publicly available from the GEO database. Differentially expressed mechanosensitive genes (DEMGs) in AAAs were identified by differential expression analysis. Molecular biological functions of genes were explored using functional clustering, Protein-protein interaction (PPI), and weighted gene co-expression network analysis (WGCNA). According to the datasets (GSE98278, GSE205071 and GSE165470), the changes of diameter and aortic wall strength of AAA induced by DEMGs were verified by consensus clustering analysis, machine learning models, and statistical analysis. In addition, a model for identifying AAA subtypes was built using machine learning methods.Results38 DEMGs clustered in pathways regulating 'Smooth muscle cell biology' and 'Cell or Tissue connectivity'. By analyzing the GSE205071 and GSE165470 datasets, DEMGs were found to respond to differences in aneurysm diameter and vessel wall strength. Thus, in the merged datasets, we formally created subgroups of AAAs and found differences in immune characteristics between the subgroups. Finally, a model that accurately predicts the AAA subtype that is more likely to rupture was successfully developed.ConclusionWe identified 38 DEMGs that may be involved in AAA. This gene cluster is involved in regulating the maximum vessel diameter, degree of immunoinflammatory infiltration, and strength of the local vessel wall in AAA. The prognostic model we developed can accurately identify the AAA subtypes that tend to rupture.

Bone tumors, particularly osteosarcoma, are prevalent among children and adolescents. This ailment has emerged as the second most frequent cause of cancer-related mortality in adolescents. Conventional treatment methods comprise extensive surgical resection, radiotherapy, and chemotherapy. Consequently, the management of bone tumors and bone regeneration poses significant clinical challenges. Photothermal tumor therapy has attracted considerable attention owing to its minimal invasiveness and high selectivity. However, key challenges have limited its widespread clinical use. Enhancing the tumor specificity of photosensitizers through targeting or localized activation holds potential for better outcomes with fewer adverse effects. Combinations with chemotherapies or immunotherapies also present avenues for improvement. In this review, we provide an overview of the most recent strategies aimed at overcoming the limitations of photothermal therapy (PTT), along with current research directions in the context of bone tumors, including (1) target strategies, (2) photothermal therapy combined with multiple therapies (immunotherapies, chemotherapies, and chemodynamic therapies, magnetic, and photodynamic therapies), and (3) bifunctional scaffolds for photothermal therapy and bone regeneration. We delve into the pros and cons of these combination methods and explore current research focal points. Lastly, we address the challenges and prospects of photothermal combination therapy.

Osteoimmunology is a concept involving molecular and cellular crosstalk between the skeletal and immune systems. Toll-like receptors (TLRs) are widely expressed both on mesenchymal stromal cells (MSCs), the hematopoietic cells, and immune cells in the osteogenic microenvironment for bone development or repair. TLRs can sense both exogenous pathogen-associated molecular patterns (PAMPs) derived from microorganisms, and damage-associated molecular patterns (DAMPs) derived from normal cells subjected to injury, inflammation, or cell apoptosis under physiological or pathological conditions. Emerging studies reported that TLR signaling plays an important role in bone remodeling by directly impacting MSC osteogenic differentiation or osteoimmunology. However, how to regulate TLR signaling is critical and remains to be elucidated to promote the osteogenic differentiation of MSCs and new bone formation for bone tissue repair. This review outlines distinct TLR variants on MSCs from various tissues, detailing the impact of TLR pathway activation or inhibition on MSC osteogenic differentiation. It also elucidates TLR pathways’ interplay with osteoclasts, immune cells, and extracellular vesicles (EVs) derived from MSCs. Furthermore, we explore biomaterial-based activation to guide MSCs’ osteogenic differentiation. Therefore, understanding TLRs’ role in this context has significant implications for advancing bone regeneration and repair strategies.

A field trial in Changsha, China, involving the release of a triple Wolbachia-infected strain of the mosquito, Aedes albopictus, demonstrates the feasibility of using an incompatible insect technique to suppress disease vector mosquito populations in urban subtropic environments.

Abstract Background Vitrectomy and peeling of the internal limiting membrane (ILM) was an effective therapeutic approach for myopic foveoschisis with progressive visual loss. This study investigated the anatomical and visual outcomes of fovea-sparing ILM peeling with or without the inverted flap technique for patients with symptomatic myopic foveoschisis (MF). Methods We retrospectively reviewed the clinical data of patients with MF. Vitrectomy with fovea-sparing ILM peeling and air tamponade was performed in all patients. The primary outcome measures included best-corrected visual acuity (BCVA), mean macular thickness (MMT), and central foveal thickness (CFT). Depending on whether an inverted ILM flap technique was utilized, further subgroup comparisons between the inverted flap group and the non-inverted flap group were conducted. Results Twenty-six eyes of 22 patients were included. Fifteen eyes were underwent fovea-sparing ILM peeling without inverted ILM flap and 11 of the 26 eyes were treated with fovea-sparing ILM peeling and an inverted ILM flap technique. In the mean follow-up period of 10.74 ± 4.58 months, a significant improvement in BCVA was observed from 0.97 ± 0.45 logMAR to 0.58 ± 0.51 logMAR (P 0.05). Conclusion Fovea-sparing ILM peeling with or without inverted flap technique resulted in favorable visual and anatomical outcomes for the treatment of MF. An important factor affecting the postoperative visual outcome was the preoperative visual acuity. Our study found no significant difference between the presence and absence of the inverted ILM flap.

ObjectivesGalactose-deficient IgA1 (Gd-IgA1) is a critical effector molecule in the pathogenesis of IgA nephropathy (IgAN), a leading renal disease without noninvasive assessment options. This updated systematic review aimed to determine the diagnostic and prognostic value of Gd-IgA1 assessment in biological fluids in patients with IgAN.MethodsPRISMA guidelines were followed in this review. We searched PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, China Biology Medicine disc, VIP Information/China Science and Technology Journal Database, and WANFANG for studies published between database inception and January 31, 2023. Eligible studies that evaluated aberrant IgA1 glycosylation in IgAN patients relative to controls were identified, and random effects meta-analyses were used to compare Gd-IgA1 levels in different groups. The quality of the evidence was assessed using the Newcastle-Ottawa Scale. This study was registered on PROSPERO (CRD42022375246).FindingsOf the 2727 records identified, 50 were eligible and had available data. The mean Newcastle-Ottawa Scale score was 7.1 (range, 6–8). Data synthesis suggested that IgAN patients had higher levels of blood and/or urine Gd-IgA1 compared with healthy controls (standard mean difference [SMD]=1.43, 95% confidence interval [CI]=1.19−1.68, P

The design concept of a Small High-flux Multipurpose LBE(Lead Bismuth Eutectic) cooled Fast Reactor (SHMLFR) was proposed in the paper. The primary cooling system of the reactor is forced circulation, and the fuel element form is arc-plate loaded high enrichment MOX fuel. The core is cylindrical with a flux trap set in the center of the core, which can be used as an irradiation channel. According to the requirements of the core physical design, a series of physical design criteria and constraints were given, and the steady and transient parameters of the reactor were calculated and analyzed. Regarding the thermal and hydraulic phenomena of the reactor, a simplified model was used to conduct a preliminary analysis of the fuel plates at special positions, and the temperature field distribution of the fuel plate with the highest power density under different coolant flow rates was simulated. The results show that the various parameters of SHMLFR meet the requirements and design criteria of the physical design of the core and the thermal design of the reactor. This implies that the conceptual design of SHMLFR is feasible.

Abstract Background The most appropriate alternative to induction therapy for HIV-associated cryptococcal meningitis (CM) remains unclear when standard treatment is unavailable, inaccessible, intolerable, or ineffective. Methods A prospective, multi-centre cohort study was conducted to analyze the data of 156 HIV-infected patients with CM who were treated with amphotericin B deoxycholate (AmB-D) + flucytosine (5FC), voriconazole (VCZ) + 5FC, or AmB-D + Fluconazole (Flu) as induction regimens. Clinical efficacy, cumulative mortality, and adverse effects were compared among the three treatment groups. Results Fewer deaths occurred by week 4 and week 10 among patients receiving AmB-D + 5FC than among those receiving AmB-D + Flu [4 (5.1%) vs. 8 (16.0%) deaths by week 4; hazard ratio, 1.8; 95% confidence interval [CI], 1.0 to 3.3; p = 0.039; and 8 (10.3%) vs. 14 (28.0%) deaths by week 10; hazard ratio, 1.8; 95% CI, 1.1 to 2.7; p = 0.008, respectively]. AmB-D plus 5FC was found to result in significantly higher rates of cerebrospinal fluid (CSF) culture sterility (57.6% vs. 34% by week 2; 87.9% vs. 70% by week 10; p

Upconversion nanoparticles can be used to both image and treat tumors. Here, the authors describe an upconversion nanoparticle that can switch from imaging to phototherapy by altering the NIR emission.

Background: Previous studies have suggested that point-of-care ultrasound could help to evaluate and diagnose pediatric skull fracture for the closed scalp hematoma from blunt trauma. However, relevant data in Chinese children are missing, especially in children 0–6 years old. Objectives: Our study aimed to evaluate the efficacy of point-of-care ultrasound to diagnose skull fracture in children 0–6 years old with scalp hematoma in China. Methods: We performed a prospective observational study and screened children 0–6 years old with closed scalp hematoma and a Glasgow coma scale of 14–15 at Hospital in China. Enrolled children (N = 152) were first evaluated for skull fracture with point-of-care ultrasound by the emergency physician and then received a head computed tomography scan. Results: The point-of-care ultrasound examination and computed tomography scan revealed skull fracture in 13 (8.6%) and 12 (7.9%) children, respectively. The kappa test showed a satisfactory agreement between two examinations (P

Abstract Background Phoebe zhennan S.Lee (nanmu) is listed as a threatened tree species in China, whose growth and development, especially during the seedling stage, can be severely limited by drought. Previous studies on nanmu responses to drought stress involved physiological and biochemical analyses, while the molecular mechanisms remained unclear. Therefore, it is of great significance to carry out molecular biology research on the drought resistance of nanmu and reveal the genetic background and molecular regulation mechanism of nanmu drought resistance. Results Drought stress enhanced the soluble sugar (SS), free proline(PRO), superoxide anion (O2·−), and hydrogen peroxide (H2O2) contents as well as the peroxidase (POD) and monodehydroascorbate reductase (MDHAR) activities of nanmu. However, glutathione S-transferase (GST) activity was sensitive to drought stress. Further transcriptomic and proteomic analyses revealed the abundant members of the differentially expressed genes(DEGs) and differentially expressed proteins(DEPs) that were related to phenylpropanoid and flavonoid biosynthesis, hormone biosynthesis and signal transduction, chlorophyll metabolism, photosynthesis, and oxidation-reduction reaction, which suggested their involvement in the drought response of nanmu. These enhanced the osmotic regulation, detoxification, and enzyme-induced and non-enzyme-induced antioxidant ability of nanmu. Moreover, 52% (447/867) of proteins that were up-regulated and 34% (307/892) down-regulated ones were attributed to the increase and decrease of transcription abundance. Transcript up (TU) and protein up (PU) groups had 447 overlaps, while transcript down (TD) and protein down (PD) groups had 307 overlaps, accounting for 54% of up and 35% of down-regulated proteins. The lack of overlap between DEGs and DEPs also suggested that post-transcriptional regulation has a critical role in nanmu response to drought. Conclusions Our research results provide significant insights into the regulatory mechanisms of drought stress in nanmu.

Abstract SARS-CoV-2 inactivated vaccines have shown remarkable efficacy in clinical trials, especially in reducing severe illness and casualty. However, the waning of humoral immunity over time has raised concern over the durability of immune memory following vaccination. Thus, we conducted a nonrandomized trial among the healthcare workers (HCWs) to investigate the long-term sustainability of SARS-CoV-2-specific B cells and T cells stimulated by inactivated vaccines and the potential need for a third booster dose. Although neutralizing antibodies elicited by the standard two-dose vaccination schedule dropped from a peak of 29.3 arbitrary units (AU)/mL to 8.8 AU/mL 5 months after the second vaccination, spike-specific memory B and T cells were still detectable, forming the basis for a quick recall response. As expected, the faded humoral immune response was vigorously elevated to 63.6 AU/mL by 7.2 folds 1 week after the third dose along with abundant spike-specific circulating follicular helper T cells in parallel. Meanwhile, spike-specific CD4+ and CD8+ T cells were also robustly elevated by 5.9 and 2.7 folds respectively. Robust expansion of memory pools by the third dose potentiated greater durability of protective immune responses. Another key finding in this trial was that HCWs with low serological response to two doses were not truly “non-responders” but fully equipped with immune memory that could be quickly recalled by a third dose even 5 months after the second vaccination. Collectively, these data provide insights into the generation of long-term immunological memory by the inactivated vaccine, which could be rapidly recalled and further boosted by a third dose.

The retaining wall is a passive engineering measure to prevent and control unsafe factors caused by rock collapse in the valleys. Existing studies have mainly focused on its functional robustness and safety features, with few exploring its visual quality in the landscape. A multiple regression analysis was applied to evaluate the Scenic Beauty Estimation (SBE) of the giant retaining wall in Jiuzhaigou's (a world natural heritage site) Heye Village, then the factors affecting SBE were analyzed. It is found that enhancing the sense of perspective and spatial hierarchy of retaining-wall murals in narrow roads contributes to the extension of observers' sight, which is the key to improving SBE. Furthermore, the showcase of folk culture in murals can realize the beautification function of the giant retaining walls. In addition, the SBE of giant retaining walls is also linked to coordination, where the walls embellished with the natural landscape and folk culture murals have better SBE performance than those with local stones. This study provides a reference for constructing scenic beauty after fulfilling the safety function of retaining wall engineering.

Accumulation and activation of immunocytes in adipose tissues are essential to obesity-induced inflammation and insulin resistance. Chemokines are pivotal for the recruitment of immunocytes in adipose tissue during obesity. Chemokine (C-C motif) ligand 5 (CCL5) plays a vital role in the recruitment of immunocytes to sites of inflammation. CCL5 expression level is increased in obese adipose tissue from humans and mice. However, the role of CCL5 in obesity-induced adipose inflammation remains unclear. Our study found that the CCL5 expression level was increased in the epididymal white adipose tissue (eWAT) of obese mice, particularly in CD8+ T cells. CCL5 knockout (KO) mice exhibited better glucose tolerance than wild-type (WT) mice under lean conditions. In contrast, CCL5 KO mice were more insulin resistant and had severe hepatic steatosis than WT mice under obese conditions. Increased T cells in adipose tissue heaven adipose inflammation in obese CCL5 KO mice. The compensatory increased T cell-associated chemokines may account for increased T cell content in the eWAT of obese CCL5 KO mice. These findings imply that CCL5 deficiency exacerbates adipose inflammation and impairs insulin sensitivity in the metabolic tissues of obese mice.

Abstract Recent clinical studies show activating multiple innate immune pathways drives robust responses in infection and cancer. Biomaterials offer useful features to deliver multiple cargos, but add translational complexity and intrinsic immune signatures that complicate rational design. Here a modular adjuvant platform is created using self‐assembly to build nanostructured capsules comprised entirely of antigens and multiple classes of toll‐like receptor agonists (TLRas). These assemblies sequester TLR to endolysosomes, allowing programmable control over the relative signaling levels transduced through these receptors. Strikingly, this combinatorial control of innate signaling can generate divergent antigen‐specific responses against a particular antigen. These assemblies drive reorganization of lymph node stroma to a pro‐immune microenvironment, expanding antigen‐specific T cells. Excitingly, assemblies built from antigen and multiple TLRas enhance T cell function and antitumor efficacy compared to ad‐mixed formulations or capsules with a single TLRa. Finally, capsules built from a clinically relevant human melanoma antigen and up to three TLRa classes enable simultaneous control of signal transduction across each pathway. This creates a facile adjuvant design platform to tailor signaling for vaccines and immunotherapies without using carrier components. The modular nature supports precision juxtaposition of antigen with agonists relevant for several innate receptor families, such as toll, STING, NOD, and RIG.

Abstract Jianpi Qushi Heluo Formula (JQHF) is an empirical traditional Chinese medicine prescription for treating Membranous Nephropathy (MN) clinically in China. The therapeutic effect of JQHF has been reported in our previous studies. However, the exact mechanism is still unknown. In this study, by establishing an experimental rat model of MN induced by Sheep anti-rat Fx1A serum, we evaluated the effects of JQHF and Tetrandrine (TET), and Benazepril was used as a positive control. As an autophagy agonist, TET is one of the most active components in JQHF. After 4 weeks, significant kidney damage was observed in the rats in the Model group; comparatively, JQHF markedly decreased 24 h urinary protein, Total Cholesterol (TC), and increased serum total Albumin (ALB). Histology showed that JQHF caused significant improvements in glomerular hyperplasia, renal tubular damage, IgG immune complex deposition, and the ultrastructure of mitochondria in MN rats. Flow cytometry analysis showed that treatment with JQHF reduced the level of reactive oxygen species and apoptosis rate, and upregulated mitochondrial membrane potential. Western blot analysis demonstrated that JQHF could protect against mitochondrial dysfunction and apoptosis by upregulating the expression of PINK1, Mitochondrial Parkin, and LC3-II/I, downregulating the expression of Cytoplasmic Parkin, P62, Cytochrome c, and Caspase-3 in the kidneys of MN rats. From images of co-immunofluorescence, it is observed significantly increase in the co-localization of PINK1 and Parkin, as well as LC3 and mitochondria. Similarly, TET treatment significantly upregulated the mitochondrial autophagy and reduced apoptosis in rats after 4 weeks compared with the model group. Comparatively, the ability of JQHF to alleviate renal damage was significantly higher than those of Benazepril and TET. It was demonstrated that JQHF could delay pathology damage to the kidney and hold back from the progression of MN by inhibiting apoptosis and upregulating the mitochondrial autophagy by PINK1/Parkin pathways.

Competition for the migration of interfering cations limits the scale-up and implementation of the Donnan dialysis process for the recovery of ammonia nitrogen (NH4+-N) from wastewater in practice. Highly efficient selective permeation of NH4+ through a cation exchange membrane (CEM) is expected to be modulated via tuning the surface charge and structure of CEM. In this work, a novel CEM was designed to form a graphene oxide (GO)-polyethyleneimine (PEI) cross-linked layer by introducing self-assembling layers of GO and PEI on the surface of a commercial CEM, which rationally regulates the surface charge and structure of the membrane. The resulting positively charged membrane surface exhibits stronger repulsion for divalent cations compared to monovalent cations according to Coulomb’s law, while, simultaneously, GO forms π–metal cation conjugates between metal cations (e.g., Mg2+ and Ca2+), thus limiting metal cation transport across the membrane. During the DD process, higher NH4+ concentrations resulted in a longer time to reach Donnan equilibrium and higher NH4+ flux, while increased Mg2+ concentrations resulted in lower NH4+ flux (from 0.414 to 0.213 mol·m−2·h−1). Using the synergistic effect of electrostatic interaction and non-covalent cross-linking, the designed membrane, referred to as GO-PEI (20) and prepared by a 20 min impregnation in the GO-PEI mixture, exhibited an NH4+ transport rate of 0.429 mol·m−2·h−1 and a Mg2+ transport rate of 0.003 mol·m−2·h−1 in single-salt solution tests and an NH4+/Mg2+ selectivity of 15.46, outperforming those of the unmodified and PEI membranes (1.30 and 5.74, respectively). In mixed salt solution tests, the GO-PEI (20) membrane showed a selectivity of 15.46 (~1.36, the unmodified membrane) for NH4+/Mg2+ and a good structural stability after 72 h of continuous operation. Therefore, this facile surface charge modulation approach provides a promising avenue for achieving efficient NH4+-selective separation by modified CEMs.

Two novel ionic red/near-infrared Ir(III) complexes (Ir1 and Ir2) were reasonably designed and prepared using 2-(1-isoquinolinyl)-9,10-anthraquinone as the main ligand and 4,4′-dimethyl-2,2′-bipyridyl and 4,4′-dimethoxy-2,2′-bipyridyl as the auxiliary ligands, respectively. Both complexes showed bright phosphorescence in solution (peak at 618 nm with a shoulder at 670 nm). Interestingly, the phosphorescence peak of two Ir(III) complexes showed a blue-shift of about 36 nm after being ground. Simultaneously, both complexes exhibited mechanical force-induced enhanced emission, and the intensity of the luminescence for Ir1 and Ir2 increased by around two times compared to the one before being ground, respectively. Powder X-ray diffraction (PXRD) and time-dependent density functional theory (TD-DFT) calculation were utilized to understand well the mechanism of this phenomenon and suggested that the destruction of the well-ordered crystalline nature and the decline in triplet-triplet annihilation maybe responsible for the pressure-induced blue-shift and the enhancement of the phosphorescence.

Two novel neutral phosphorescent iridium(III) complexes (Ir1 and Ir2) were rationally designed and synthesized with high yields using 10,11,12,13-tetrahydrodibenzo[a,c]phenazine as the main ligand. The two complexes showed bright-red phosphorescence (625 nm for Ir1, and 620 nm for Ir2, in CH2Cl2), high-luminescence quantum efficiency (0.32 for Ir1, and 0.35 for Ir2), obvious solvatochromism and good thermostability. Then, they were used to fabricate high-efficiency red OLEDs via vacuum evaporation; the maximum current efficiency, power efficiency, and external quantum efficiency of the red devices based on Ir1 and Ir2 are 13.47/15.22 cd/A, 10.35/12.26 lm/W, and 10.08/7.48%, respectively.

Abstract Background Serum Deprivation Protein Response (SDPR) plays an important role in formation of pulmonary alveoli. However, the functions and values of SDPR in lung cancer remain unknown. We explored prognostic value, expression pattern, and biological function of SDPR in non-small cell lung cancer (NSCLC) and KRAS-mutant lung cancers. Methods SDPR expression was evaluated by quantitative real-time PCR (RT-qPCR), immunohistochemistry (IHC), and Western blot on human NSCLC cells, lung adenocarcinoma tissue array, KRAS-mutant transgenic mice, TCGA and GEO datasets. Prognostic values of SDPR were evaluated by Kaplan–Meier and Cox regression analysis. Bioinformatics implications of SDPR including SDPR-combined transcription factors (TFs) and microRNAs were predicted. In addition, correlations between SDPR, immune checkpoint molecules, and tumor infiltration models were illustrated. Results SDPR expression was downregulated in tumor cells and tissues. Low SDPR expression was an independent factor that correlated with shorter overall survival of patients both in lung cancer and KRAS-mutant subgroups. Meanwhile, ceRNA network was constructed to clarify the regulatory and biological functions of SDPR. Negative correlations were found between SDPR and immune checkpoint molecules (PD-L1, TNFRSF18, TNFRSF9, and TDO2). Moreover, diversity immune infiltration models were observed in NSCLC with different SDPR expression and copy number variation (CNV) patterns. Conclusions This study elucidated regulation network of SDPR in KRAS-mutant NSCLC, and it illustrated correlations between low SDPR expression and suppressed immune system, unfolding a prognostic factor and potential target for the treatment of lung cancer, especially for KRAS-mutant NSCLC.

Hybrid rice cultivars are widely planted around the world. Here, the authors resequence 1,143 indica accessions, focusing on the parents of superior hybrid rice lines in China, and reveal genetic loci that are associated with heterosis via measuring frequency of parental variation difference (FPVD).

Abstract Rice (Oryza sativa L.) is a staple food crop, feeding more than 50% of the world’s population. Diseases caused by bacterial, fungal, and viral pathogens constantly threaten the rice production and lead to enormous yield losses. Bacterial blight (BB) and bacterial leaf streak (BLS), caused respectively by gram-negative bacteria Xanthomonas oryzae pv. oryzae (Xoo) and Xanthomonas oryzae pv. oryzicola (Xoc), are two important diseases affecting rice production worldwide. Due to the economic importance, extensive genetic and genomic studies have been conducted to elucidate the molecular mechanism of rice response to Xoo and Xoc in the last two decades. A series of resistance (R) genes and their cognate avirulence and virulence effector genes have been characterized. Here, we summarize the recent advances in studies on interactions between rice and the two pathogens through these R genes or their products and effectors. Breeding strategies to develop varieties with durable and broad-spectrum resistance to Xanthomonas oryzae based on the published studies are also discussed.

Entropy weight model (EWM) is the most widely used objective weighting method for evaluating water quality. However, for the pollutant the data of which concentrate on the high polluted grade, EWM often neglects its importance, for its discrimination degree is low. To solve this problem, a pollution scale weighting model (PSWM) is proposed based on the improved fuzzy variable theory. In PSWM, the importance of the indicator is quantified by its relative membership to the vague concept: “pollution”. The higher the pollution degree is, the larger its weight is; and vice versa. And then, PSWM is applied into the water quality evaluation of Southeastern Poyang Lake. Results are as follows. (1) The relative memberships of CODMn, NH3-N, and TP to the vague concept “pollution” are 0.39, 0.33, and 0.99, respectively. And according to PSWM, their weights are 0.227, 0.193, and 0.580, respectively. (2) The comprehensive water quality indices of the Nanjishan wetland, lake region, Xin River estuary, and Rao River estuary are 36.2, 28.6, 25.7 and 21.1, respectively, all of which belong to “bad” grade. The environment of Southeastern Poyang Lake suffers serious damage, and the aquatic ecosystem faces a high threat. (3) Compared with EWM, PSWM can highlight the seriously polluted index and emphasize its practical significance in water resources management, thereby effectively improving the accuracy and rationality of water quality evaluation.

Th1 cell activation is considered a key mediator of the pathogenesis of type 1 diabetes. Targeting IL-12-induced Th1 cell differentiation seems to be an effective way to block the development of type 1 diabetes. However, given the critical function of Th1 in the immune system, the potential side effects hinder the application of anti-Th1 therapy in the treatment of type 1 diabetes. To identify safe anti-Th1 treatment(s), we screened the FDA-approved tyrosine kinase inhibitor (TKI) drug library using an IL-12-induced Th1 differentiation cell model. We found that among the TKIs with little effect on T cell viability, sorafenib is the top contender for the inhibition of Th1 differentiation. Treatment of NOD mice with sorafenib significantly impeded the development of type 1 diabetes and ameliorated insulitis, which coincided with a specifically decreased accumulation of Th1 cell population in the pancreas but not in peripheral immune organs. Mechanistically, sorafenib indirectly inhibited janus kinase 2 (JAK2) activity and blocked IL-12-induced phosphorylations of JAK2 and signal transducer and activator of transcription 4 (STAT4). Since sorafenib is classified as an FDA-approved drug, it serves as a preliminary lead point for additional experimentation and may be a promising therapy for type 1 diabetes in humans.

Background: Jianpi-Qushi-Heluo formula (JQHF) has been used to treat idiopathic membranous nephropathy (IMN) in hospitals for many years. Purpose: Elucidating the protective effect and exploring the potential mechanism of JQHF against IMN. Methods: Passive Heymann nephritis (PHN) was induced in rats by a single tail vein injection of anti-Fx1A antiserum. Then, the animals were treated with JQHF at 16.2 g/kg or 32.4 g/kg, with benzepril (10 mg/kg) as a positive control. Renal function was evaluated by biochemical measurements and pathological testing. Fecal samples were collected before and after treatment to analyze the gut microbiota composition by shotgun whole metagenome sequencing. Results: JQHF exhibited potent efficacy in ameliorating PHN at both doses, as revealed by decreasing the deposition of IgG and C5b-9, relieving podocyte injury, and reducing glomerular and tubular cell apoptosis. The lower dose was corresponding to the clinical dosage and showed better therapeutic effects than the higher dose. Metagenomic analysis showed that gavage with 16.2 g/kg of JQHF shifted the structure of the gut microbiota in PHN rats and significantly increased the relative abundances of Prevotella copri, Lactobacillus vaginalis and Subdoligranulum variabile. Particularly, S. variabile was strongly negatively correlated with serum levels of TC and TG, the deposition of IgG and C5b-9, and apoptosis of glomerular cells. Conclusions: The JQHF is an effective agent for the treatment of experimental PHN. The PHN-allevating effect of JQHF is associated with specific alternation of gut microbiota.

Long non-coding RNAs (lncRNA), a class of RNA molecules without protein coding potential, are more than 200 nucleotides in length and widely present in a variety of species. Although increasing progress in regard to the determination of lncRNA function has been made in vertebrates, Aedes aegypti lncRNAs were only identified recently and the functions of few lncRNAs have been annotated so far. Herein, the genome-wide alteration of the lncRNA expression profile trigged by Wolbachia wAlbB infection was investigated by comparing A. aegypti Aag2 cells and W-Aag2 cells infected with Wolbachia wAlbB. Based on lncRNA sequencing, 3035 differentially expressed lncRNAs (DE lncRNAs) in total were identified upon Wolbachia infection, which were further validated by quantitative PCR. The constructed co-expression network of DE lncRNAs and mRNAs revealed that Wolbachia-induced DE lncRNAs were highly enriched in the oxidative phosphorylation pathway via trans-activity, according to the KEGG pathway enrichment analyses. In addition, the established competitive endogenous RNA (ceRNA) network identifies the DE lncRNAs enriched in cellular oxidant detoxification based on GO enrichment analysis. Furthermore, silencing of aae-lnc-7598, the significantly up-regulated lncRNA with the highest fold change induced by Wolbachia, caused a significant reduction of antioxidant catalase 1B (CAT1B) gene expression as well as the enhancement of mitochondrial reactive oxygen species (ROS) production in living cells. These findings indicate that Wolbachia manipulates lncRNA to balance intracellular ROS stress and ensure its endosymbiosis in host A. aegypti. Notably, the function assay demonstrated that aae-lnc-0165 suppressed by Wolbachia could induce expression of the REL1 gene, the key regulator of downstream Toll pathway, through the sequence-specific binding of aae-miR-980-5p, which contributes to the activation of Toll pathway. Moreover, the depletion of aae-lnc-0165 caused the suppression of mitochondrial ROS levels in living cells. Our data reveal that Wolbachia activates the anti-dengue Toll pathway through a lncRNA-ceRNA pattern. Taken together, our finding suggested that Wolbachia utilizes lncRNAs to activate host anti-dengue Toll pathway via a ceRNA network. Moreover, Wolbachia employs lncRNAs to ensure ROS homeostasis for ROS-based anti-dengue defense through either trans-regulation or the ceRNA network. This study identifies novel potential molecular biomarkers for prevention and control of epidemic dengue.

Improving the hazard identification ability of workers is an important way to reduce safety accidents at construction sites. Although previous studies have succeeded in improving hazard identification performance, an important gap is that they consider only two factors, the worker’s safety experience and objective environmental conditions, to analyze the impact on hazard identification performance. To fill the above gap, a visual cognitive model of hazard identification was established. Sixteen field scenes were selected to represent construction sites in each environmental condition. Eye-movement data were extracted through eye-tracking experiments, and the differences between experts’ and novices’ gazes during danger recognition in these scenes were analyzed. The results indicate the following: bright construction sites can significantly improve the correct recognition rate and information processing in hazard identification; tidy construction sites can improve the search efficiency and correct recognition rate of hazard identification; safety experience can improve workers’ correct recognition rates and information processing; and reducing distractions can effectively improve the correct identification rate of hazards. Overall, optimal site brightness needs to be further studied to improve the efficiency of hazard search and reduce the distraction effect. This study provides recommendations for the direction of safety training and safety management on site.

Store-operated Ca2+ release-activated Ca2+ (CRAC) channel is the main Ca2+ influx pathway in lymphocytes and is essential for immune response. Lupus nephritis (LN) is an autoimmune disease characterized by the production of autoantibodies due to widespread loss of immune tolerance. In this study, RNA-seq analysis revealed that calcium transmembrane transport and calcium channel activity were enhanced in naive B cells from patients with LN. The increased expression of ORAI1, ORAI2, and STIM2 in naive B cells from patients with LN was confirmed by flow cytometry and Western blot, implying a role of CRAC channel in B-cell dysregulation in LN. For in vitro study, CRAC channel inhibition by YM-58483 or downregulation by ORAI1-specific small-interfering RNA (siRNA) decreased the phosphorylation of Ca2+/calmodulin-dependent protein kinase2 (CaMK2) and suppressed Blimp-1 expression in primary human B cells, resulting in decreased B-cell differentiation and immunoglobulin G (IgG) production. B cells treated with CaMK2-specific siRNA showed defects in plasma cell differentiation and IgG production. For in vivo study, YM-58483 not only ameliorated the progression of LN but also prevented the development of LN. MRL/lpr lupus mice treated with YM-58483 showed lower percentage of plasma cells in the spleen and reduced concentration of anti-double-stranded DNA antibodies in the sera significantly. Importantly, mice treated with YM-58483 showed decreased immune deposition in the glomeruli and alleviated kidney damage, which was further confirmed in NZM2328 lupus mice. Collectively, CRAC channel controlled the differentiation of pathogenic B cells and promoted the progression of LN. This study provides insights into the pathogenic mechanisms of LN and that CRAC channel could serve as a potential therapeutic target for LN.

Abstract Background Preserving the integrity of the blood-brain barrier (BBB) is beneficial to avoid further brain damage after acute ischemic stroke (AIS). Astrocytes, an important component of the BBB, promote BBB breakdown in subjects with AIS by secreting inflammatory factors. The glucagon-like peptide-1 receptor (GLP-1R) agonist exendin-4 (Ex-4) protects the BBB and reduces brain inflammation from cerebral ischemia, and GLP-1R is expressed on astrocytes. However, the effect of Ex-4 on astrocytes in subjects with AIS remains unclear. Methods In the present study, we investigated the effect of Ex-4 on astrocytes cultured under oxygen-glucose deprivation (OGD) plus reoxygenation conditions and determined whether the effect influences bEnd.3 cells. We used various methods, including permeability assays, western blotting, immunofluorescence staining, and gelatin zymography, in vitro and in vivo. Results Ex-4 reduced OGD-induced astrocyte-derived vascular endothelial growth factor (VEGF-A), matrix metalloproteinase-9 (MMP-9), chemokine monocyte chemoattractant protein-1 (MCP-1), and chemokine C-X-C motif ligand 1 (CXCL-1). The reduction in astrocyte-derived VEGF-A and MMP-9 was related to the increased expression of tight junction proteins (TJPs) in bEnd.3 cells. Ex-4 improved neurologic deficit scores, reduced the infarct area, and ameliorated BBB breakdown as well as decreased astrocyte-derived VEGF-A, MMP-9, CXCL-1, and MCP-1 levels in ischemic brain tissues from rats subjected to middle cerebral artery occlusion. Ex-4 reduced the activation of the JAK2/STAT3 signaling pathway in astrocytes following OGD. Conclusion Based on these findings, ischemia-induced inflammation and BBB breakdown can be improved by Ex-4 through an astrocyte-dependent manner.

Two new and efficient cationic yellow-emissive Ir (III) complexes (Ir1 and Ir2) are rationally designed by using 2-(4-chloro-3-(trifluoromethyl)phenyl)-4-methylquinoline as the main ligand, and, respectively, 4,4′-dimethyl-2,2′-bipyridyl and 4,4′-dimethoxy-2,2′-bipyridyl as the ancillary ligands. Both complexes show enhanced phosphorescence (546 nm with 572 nm as shoulder and high phosphorescent quantum efficiency in solution, which is in favor of efficient solution-processed phosphorescent organic light-emitting diodes. Compared with Ir2, the Ir1-based device displays excellent device performance, with maximum external quantum efficiency, current efficiency, and power efficiency of up to 7.92%, 26.32 cd/A and 15.31 lm/W, respectively, thus proving that the two new ionic Ir (III) complexes exhibit great potential for future solution-processed electroluminescence.

Vascular endothelial growth factor (VEGF) and its receptor (VEGFR) are highly expressed in nasopharyngeal carcinoma; therefore, blocking the binding of VEGF and VEGFR may be a potential way to treat nasopharyngeal carcinoma. Apatinib inhibits tumor angiogenesis. Previous studies have suggested that treatment with apatinib has an antitumor effect on nasopharyngeal carcinoma. This study will investigate the effect of apatinib combined with radiotherapy. In this study, nude mice injected with CNE-2 nasopharyngeal carcinoma cells were randomly divided into 6 groups. Therapeutic effects were assessed by evaluating tumor inhibition rate, phosphorylation of VEGFR-2, CD31, partial oxygen pressure, and tumor metabolism. We found that the tumor inhibition of mice in the treated groups was better compared to that of the control group. In mice treated with apatinib alone, angiogenesis was prevented, and the tumor tissue partial oxygen pressure was reduced, thereby achieving an antitumor effect. Moreover, the tumor inhibitory effect of combined treatment was stronger than treatment with either apatinib or radiotherapy alone. Compared with monotherapy treatment, combined treatment better resisted angiogenesis. Apatinib combined with radiotherapy to treat nasopharyngeal carcinoma has synergistic effects, which may be related to enhanced antiangiogenesis.

Prediction of residual strength and residual life of corrosion pipelines is the key to ensuring pipeline safety. Accurate assessment and prediction make it possible to prevent unnecessary accidents and casualties, and avoid the waste of resources caused by the large-scale replacement of pipelines. However, due to many factors affecting pipeline corrosion, it is difficult to achieve accurate predictions. This paper reviews the research on residual strength and residual life of pipelines in the past decade. Through careful reading, this paper compared several traditional evaluation methods horizontally, extracted 71 intelligent models, discussed the publishing time, the evaluation accuracy of traditional models, and the prediction accuracy of intelligent models, input variables, and output value. This paper’s main contributions and findings are as follows: (1) Comparing several traditional evaluation methods, PCORRC and DNV-RP-F101 perform well in evaluating low-strength pipelines, and DNV-RP-F101 has a better performance in evaluating medium–high strength pipelines. (2) In intelligent models, the most frequently used error indicators are mean square error, goodness of fit, mean absolute percentage error, root mean square error, and mean absolute error. Among them, mean absolute percentage error was in the range of 0.0123–0.1499. Goodness of fit was in the range of 0.619–0.999. (3) The size of the data set of different models and the data division ratio was counted. The proportion of the test data set was between 0.015 and 0.4. (4) The input variables and output value of predictions were summarized.

Sarcophaga scopariiformis (Diptera: Sarcophagidae), a potential vector of pathogens as well as one of the important flesh fly specie in forensic entomology. We have firstly sequenced and assembled the whole mitogenome of S. scopariiformis in this study. The circular mitogenome is 15,325 bp in length, consisting of A (39.3%), G (9.4%), T (36.8%), and C (14.5%). It showed in a typical mitochondrial genome similar to other sarcophagids species, which is composed of 13 protein-coding genes (PCGs), 22 transfer RNA genes (tRNA), 2 ribosomal RNA genes (rRNA), and a non-coding AT-rich region. Moreover, the phylogenetic analysis based on 13 PCGs has been conducted. The topological structure of the phylogenetic tree clearly indicated that S. scopariiformis was more closed to the species of Sarcophaga peregrina in genetic distance, compared to the other sarcophagids species. This study provided a useful data reference for genetic structure and phylogenetic analysis of Sarcophagidae.

Sarcophaga kanoi Park, 1962, a widely distributed flesh fly in Southeast Asia, is important in forensic entomology. Notably, its mitochondrial genome could provide the unique and accurate molecular information in species identification which facilitate forensic practices in estimation of postmortem interval especially in putrefied cadaver cases. Thus, we sequenced and characterized the whole mitochondrial genome (mitogenome) of S. kanoi for the first time, which was collected from Southern China in this study. The 15,319 bp mitogenome contained 13 protein-coding genes (PCGs), 22 transfer RNA genes (tRNA), 2 ribosomal RNA genes (rRNA), and a putative control region. The total nucleotide composition of this circular genome was 39.7% for A, 9.3% for G, 14.2% for C, and 36.8% for T. To better understand the genetic relationship, the phylogenetic analysis was constructed according to the 13 PCGs sequence of S. kanoi and other 11 species. The phylogenetic tree showed that the S. kanoi was placed in a sub-clade with S. similis. Our study updated the new genetic information for dipteran mitogenomes, which could broaden the background knowledge for forensic entomology, molecular genetics and developmental biology. It has the potential application on the species identification using genetic markers.