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Abstract In this paper, a double-layer patterned graphene-based frequency-selective absorber (DGFSA) is proposed as a means of reducing an antenna’s radar cross-section (RCS) while simultaneously increasing its gain. The antenna consists of a patch antenna with Multi-Graphene Frequency Selective Absorber (MGFSA) mounted on top. The DGFSA consists of double-layer patterned graphene and a band-pass frequency selective surface (FSS). Two patterned graphene lossy layers with different square resistances are used, which broaden the electromagnetic (EM) wave absorption bandwidth of the DGFSA, thus greatly reducing the out-band monostatic RCSs of the patch antenna. Meanwhile, due to the quasi-Fabry-Perot (F-P) effect, the gain of the proposed antenna is enhanced by 2.4 dB. Additionally, the low-RCS antenna reduces the monostatic RCS from 1.32 to 17 GHz under y-polarization and from 1.4 to 16.8 GHz under x-polarization, respectively. Furthermore, a decrease in the bistatic RCS is accomplished. Results from simulations and measurements match up nicely, which means the antenna we proposed has a good application on the stealth platform.

Abstract Background The variants of nucleoporins are extremely rare in hereditary steroid-resistant nephrotic syndrome (SRNS). Most of the patients carrying such variants progress to end stage kidney disease (ESKD) in their childhood. More clinical and genetic data from these patients are needed to characterize their genotype–phenotype relationships and elucidate the role of nucleoporins in SRNS. Methods Four patients of SRNS carrying biallelic variants in the NUP93, NUP107 and NUP160 genes were presented. The clinical and molecular genetic characteristics of these patients were summarized, and relevant literature was reviewed. Results All four patients in this study were female and initially presented with SRNS. The median age at the onset of the disease was 5.08 years, ranging from 1 to 10.5 years. Among the four patients, three progressed to ESKD at a median age of 7 years, ranging from 1.5 to 10.5 years, while one patient reached stage 3 chronic kidney disease (CKD3). Kidney biopsies revealed focal segmental glomerulosclerosis in three patients. Biallelic variants were detected in NUP93 in one patient, NUP107 in two patients, as well as NUP160 in one patient respectively. Among these variants, five yielded single amino acid substitutions, one led to nonsense mutation causing premature termination of NUP107 translation, one caused a single nucleotide deletion resulting in frameshift and truncation of NUP107. Furthermore, one splicing donor mutation was observed in NUP160. None of these variants had been reported previously. Conclusion This report indicates that biallelic variants in NUP93, NUP107 and NUP160 can cause severe early-onset SRNS, which rapidly progresses to ESKD. Moreover, these findings expand the spectrum of phenotypes and genotypes and highlight the importance of next-generation sequencing in elucidating the molecular basis of SRNS and allowing rational treatment for affected individuals.

Abstract Background Hearing impairment (HI) has become a major public health issue in China. Currently, due to the limitations of primary health care, the gold standard for HI diagnosis (pure-tone hearing test) is not suitable for large-scale use in community settings. Therefore, the purpose of this study was to develop a cost-effective HI screening model for the general population using machine learning (ML) methods and data gathered from community-based scenarios, aiming to help improve the hearing-related health outcomes of community residents. Methods This study recruited 3371 community residents from 7 health centres in Zhejiang, China. Sixty-eight indicators derived from questionnaire surveys and routine haematological tests were delivered and used for modelling. Seven commonly used ML models (the naive Bayes (NB), K-nearest neighbours (KNN), support vector machine (SVM), random forest (RF), eXtreme Gradient Boosting (XGBoost), boosting, and least absolute shrinkage and selection operator (LASSO regression)) were adopted and compared to develop the final high-frequency hearing impairment (HFHI) screening model for community residents. The model was constructed with a nomogram to obtain the risk score of the probability of individuals suffering from HFHI. According to the risk score, the population was divided into three risk stratifications (low, medium and high) and the risk factor characteristics of each dimension under different risk stratifications were identified. Results Among all the algorithms used, the LASSO-based model achieved the best performance on the validation set by attaining an area under the curve (AUC) of 0.868 (95% confidence interval (CI): 0.847–0.889) and reaching precision, specificity and F-score values all greater than 80%. Five demographic indicators, 7 disease-related features, 5 behavioural factors, 2 environmental exposures, 2 hearing cognitive factors, and 13 blood test indicators were identified in the final screening model. A total of 91.42% (1235/1129) of the subjects in the high-risk group were confirmed to have HI by audiometry, which was 3.99 times greater than that in the low-risk group (22.91%, 301/1314). The high-risk population was mainly characterized as older, low-income and low-educated males, especially those with multiple chronic conditions, noise exposure, poor lifestyle, abnormal blood indices (e.g., red cell distribution width (RDW) and platelet distribution width (PDW)) and liver function indicators (e.g., triglyceride (TG), indirect bilirubin (IBIL), aspartate aminotransferase (AST) and low-density lipoprotein (LDL)). An HFHI nomogram was further generated to improve the operability of the screening model for community applications. Conclusions The HFHI risk screening model developed based on ML algorithms can more accurately identify residents with HFHI by categorizing them into the high-risk groups, which can further help to identify modifiable and immutable risk factors for residents at high risk of HI and promote their personalized HI prevention or intervention.

Abstract Background Research on the fatty acid metabolism related gene SLC27A2 is currently mainly focused on solid tumors, and its mechanism of action in hematological tumors has not been reported. Method This study aims to explore the pathological and immune mechanisms of the fatty acid metabolism related gene SLC27A2 in hematological tumors and verify its functional role in hematological tumors through cell experiments to improve treatment decisions and clinical outcomes of hematological tumors. Result This study identified the fatty acid metabolism related gene SLC27A2 as a common differentially expressed gene between DLBCL and AML. Immune microenvironment analysis showed that SLC27A2 was significantly positively correlated with T cell CD4 + , T cell CD8 + , endothelial cells, macrophages, and NK cells in DLBCL. In AML, there is a significant negative correlation between SLC27A2 and B cells, T cell CD8 + , and macrophages. SLC27A2 participates in the immune process of hematological tumors through T cell CD8 + and macrophages. The GESA results indicate that high expression of SLC27A2 is mainly involved in the fatty acid pathway, immune pathway, and cell cycle pathway of DLBCL. The low expression of SLC27A2 is mainly involved in the immune pathway of AML. Therefore, SLC27A2 is mainly involved in the pathological mechanisms of hematological tumors through immune pathways, and cell experiments have also confirmed that SLC27A2 is involved in the regulation of DLBCL cells. Conclusion In summary, our research results comprehensively report for the first time the mechanism of action of SLC27A2 in the immune microenvironment of DLBCL and AML, and for the first time verify the cycle and apoptotic effects of the fatty acid related gene SLC27A2 in DLBCL cells through cell experiments. Research can help improve the treatment of AML and DLBCL patients.

Abstract Background Early assessment of the risk of nonunion in osteoporotic vertebral compression fracture (OVCF) is beneficial to early clinical decision making. However, a comprehensive understanding of the risk factors for OVCF nonunion is lacking. Methods We conducted a case–control study to investigate risk factors for OVCF nonunion. Patients who underwent surgery for nonunited OVCFs between January 2011 and December 2021 were eligible for inclusion as cases. Patients with successful OVCF healing confirmed by MRI over the same period were identified as controls. Patient demographics, comorbidities, and fasting blood test data were extracted for analysis. Results A total of 201 patients with nonunited OVCFs and 1044 controls were included to evaluate the risk factors for nonunited OVCFs. There were statistically significant differences in sex, age, number of patients with hypertension, number of patients on bed rest after OVCF and T-score of BMD between the two groups. Logistic regression showed that female patients had a higher risk of OVCF nonunion than male patients and that smoking, drinking, diabetes, and hypertension were risk factors for nonunion of OVCFs, while bed rest and spinal support were protective factors against nonunion of OVCFs. We also found that age, BMD, FBG, and β-CTX were positively correlated with nonunited OVCFs, and that HGB and 1,25-(OH)2VitD3 level were negatively correlated with nonunited OVCFs. Conclusion Smoking, drinking, diabetes and hypertension were risk factors for nonunion of OVCFs, while bed rest and spinal support were protective factors against nonunion of OVCFs. Age, BMD, FBG and β-CTX were positively correlated with nonunited OVCFs, while HGB and 1,25-(OH)2VitD3 level were negatively correlated with nonunited OVCFs. Based on the results of our study, we suggest that bed rest or spinal support for at least 3 consecutive weeks is necessary to reduce the risk of OVCFs nonunion.

Abstract Alongside academic learning, there is increasing recognition that educational systems must also cater to students’ well-being. This study examines the key factors that predict adolescent students’ subjective well-being, indexed by life satisfaction, positive affect, and negative affect. Data from 522,836 secondary school students from 71 countries/regions across eight different cultural contexts were analyzed. Underpinned by Bronfenbrenner’s bioecological theory, both machine learning (i.e., light gradient-boosting machine) and conventional statistics (i.e., hierarchical linear modeling) were used to examine the roles of person, process, and context factors. Among the multiple predictors examined, school belonging and sense of meaning emerged as the common predictors of the various well-being dimensions. Different well-being dimensions also had distinct predictors. Life satisfaction was best predicted by a sense of meaning, school belonging, parental support, fear of failure, and GDP per capita. Positive affect was most strongly predicted by resilience, sense of meaning, school belonging, parental support, and GDP per capita. Negative affect was most strongly predicted by fear of failure, gender, being bullied, school belonging, and sense of meaning. There was a remarkable level of cross-cultural similarity in terms of the top predictors of well-being across the globe. Theoretical and practical implications are discussed.

Abstract Background Olfactory dysfunction occurs frequently in Parkinson’s disease (PD). In this study, we aimed to explore the potential biomarkers and underlying molecular pathways of nicotine for the treatment of olfactory dysfunction in 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-induced PD mice. Methods MPTP was introduced into C57BL/6 male mice to generate a PD model. Regarding in vivo experiments, we performed behavioral tests to estimate the protective effects of nicotine in MPTP-induced PD mice. RNA sequencing and traditional molecular methods were used to identify molecules, pathways, and biological processes in the olfactory bulb of PD mouse models. Then, in vitro experiments were conducted to evaluate whether nicotine can activate the prok2R/Akt/FoxO3a signaling pathway in both HEK293T cell lines and primary olfactory neurons treated with 1-methyl-4-phenylpyridinium (MPP+). Next, prok2R overexpression (prok2R+) and knockdown (prok2R−) were introduced with lentivirus, and the Akt/FoxO3a signaling pathway was further explored. Finally, the damaging effects of MPP+ were evaluated in prok2R overexpression (prok2R+) HEK293T cell lines. Results Nicotine intervention significantly alleviated olfactory and motor dysfunctions in mice with PD. The prok2R/Akt/FoxO3a signaling pathway was activated after nicotine treatment. Consequently, apoptosis of olfactory sensory neurons was significantly reduced. Furthermore, prok2R+ and prok2R− HEK293T cell lines exhibited upregulation and downregulation of the Akt/FoxO3a signaling pathway, respectively. Additionally, prok2R+ HEK293T cells were resistant to MPP+-induced apoptosis. Conclusions This study showed the effectiveness and underlying mechanisms of nicotine in improving hyposmia in PD mice. These improvements were correlated with reduced apoptosis of olfactory sensory neurons via activated prok2R/Akt/FoxO3a axis. These results explained the potential protective functions of nicotine in PD patients.

Abstract Using (27.12 ± 0.14) × 108 ψ(3686) events collected with the BESIII detector at BEPCII, the decay of ψ(3686) → Ω − K + Ξ ¯ 0 $$ {\varOmega}^{-}{K}^{+}{\overline{\Xi}}^0 $$ + c.c. is observed for the first time. The branching fraction of this decay is measured to be B ψ 3686 → Ω − K + Ξ ¯ 0 + c . c . $$ {\mathcal{B}}_{\psi (3686)\to {\varOmega}^{-}{K}^{+}{\overline{\Xi}}^0+\textrm{c}.\textrm{c}.} $$ = (2.78 ± 0.40 ± 0.18) × 10 −6, where the first uncertainty is statistical and the second is systematic. Possible baryon excited states are searched for in this decay, but no evident intermediate state is observed with the current sample size.

Abstract Improving the efficiency of antiseizure medication entering the brain is the key to reducing its peripheral toxicity. A combination of intranasal administration and nanomedicine presents a practical approach for treating epileptic seizures via bypassing the blood-brain barrier. In this study, phenytoin (PHT) loaded layered double hydroxide nanoparticles (BSA-LDHs-PHT) were fabricated via a coprecipitation − hydrothermal method for epileptic seizure control. In this study, we expound on the preparation method and characterization of BSA-LDHs-PHT. In-vitro drug release experiment shows both rapid and continuous drug release from BSA-LDHs-PHT, which is crucial for acute seizure control and chronic epilepsy therapy. In-vivo biodistribution assays after intranasal administration indicate excellent brain targeting ability of BSA-LDHs. Compared to BSA-Cyanine5.5, BSA-LDHs-Cyanine5.5 were associated with a higher brain/peripheral ratio across all tested time points. Following intranasal delivery with small doses of BSA-LDHs-PHT, the latency of seizures in the pentylenetetrazole-induced mouse models was effectively improved. Collectively, the present study successfully designed and applied BSA-LDHs-PHT as a promising strategy for treating epileptic seizures with an enhanced therapeutic effect.

Abstract Background Chromosomal microarray analysis (CMA) has emerged as a critical instrument in prenatal diagnostic procedures, notably in assessing congenital heart diseases (CHD). Nonetheless, current research focuses solely on CHD, overlooking the necessity for thorough comparative investigations encompassing fetuses with varied structural abnormalities or those without apparent structural anomalies. Objective This study sought to assess the relation of single nucleotide polymorphism-based chromosomal microarray analysis (SNP-based CMA) in identifying the underlying causes of fetal cardiac ultrasound abnormalities. Methods A total of 2092 pregnant women who underwent prenatal diagnosis from 2017 to 2022 were included in the study and divided into four groups based on the presence of ultrasound structural abnormalities and the specific type of abnormality. The results of the SNP-Array test conducted on amniotic fluid samples from these groups were analyzed. Results Findings from the study revealed that the non-isolated CHD group exhibited the highest incidence of aneuploidy, overall chromosomal abnormalities, and trisomy 18, demonstrating statistically significant differences from the other groups (p 0.05). The occurrence rates of 22q11.2 and 15q11.2 were also not statistically different between the isolated CHD group and the non-isolated congenital heart defect group (p > 0.05). Conclusion SNP-based CMA enhances the capacity to detect abnormal CNVs in CHD fetuses, offering valuable insights for diagnosing chromosomal etiology and facilitating genetic counseling. This research contributes to the broader understanding of the utility of SNP-based CMA in the context of fetal cardiac ultrasound abnormalities.

Supramolecular peptide nanofiber hydrogels are emerging biomaterials for tissue engineering, but it is difficult to fabricate multi-functional systems by simply mixing several short-motif-modified supramolecular peptides because relatively abundant motifs generally hinder nanofiber cross-linking or the formation of long nanofiber. Coupling bioactive factors to the assembling backbone is an ideal strategy to design multi-functional supramolecular peptides in spite of challenging synthesis and purification. Herein, a multi-functional supramolecular peptide, P1R16, is developed by coupling a bioactive factor, parathyroid hormone related peptide 1 (PTHrP-1), to the basic supramolecular peptide RADA16-Ⅰ via solid-phase synthesis. It is found that P1R16 self-assembles into long nanofibers and co-assembles with RADA16-Ⅰ to form nanofiber hydrogels, thus coupling PTHrP-1 to hydrogel matrix. P1R16 nanofiber retains osteoinductive activity in a dose-dependent manner, and P1R16/RADA16-Ⅰ nanofiber hydrogels promote osteogenesis, angiogenesis and osteoclastogenesis in vitro and induce multi-functionalized osteoregeneration by intramembranous ossification and bone remodeling in vivo when loaded to collagen (Col) scaffolds. Abundant red blood marrow formation, ideal osteointegration and adapted degradation are observed in the 50% P1R16/Col scaffold group. Therefore, this study provides a promising strategy to develop multi-functional supramolecular peptides and a new method to topically administrate parathyroid hormone or parathyroid hormone related peptides for non-healing bone defects.

Tetrabromobisphenol A (TBBPA) is one of the brominated flame retardants (BFRs) widely used in industry, which has a broad toxic effect on organisms. However, there is still limited research on the neurotoxic mechanism of TBBPA. Using mouse hippocampal neurons (HT22) cells, the toxicity of TBBPA was evaluated, especially focusing on its alteration on the key molecules in FAM171A2-GRN-NF-κB signaling pathway. The results showed that TBBPA exposure could lead to an increase in the production of inflammation-related genes IL-6, iNOS, TGF-β1, COX2, and TNF-α in both HT22 cells and HT22-AD-model, intensifying the inflammatory response; it inhibits the mRNA expression of antioxidative enzymes genes Sod1, Cat, Gpx1, and Gsta1, resulting in reduced antioxidant enzyme activities of SOD, CAT, and GSH-Px/GPX. Mechanistically, TBBPA caused the upregulation of FAM171A2 expression level, alongside increased GRN, IκBα and p65 levels; whereas the expression of GRN, IκBα and p65 was decreased after FAM171A2 knockdown, demonstrating TBBPA-induced upregulation of FAM171A2 should be responsible for the increased GRN, IκBα and p65 expression. Therefore, for the first time, our data indicate that TBBPA-induced oxidative stress and inflammatory response is closely related to the FAM171A2-GRN-NF-κB pathway.

Neurofibromatosis type 1 (NF-1) is commonly associated with a variety of rare tumors. However, no case of multiple gastric gastrointestinal stromal tumors (GISTs) or duodenal ampulla neuroendocrine tumors (NETs) with multiple liver metastases in a patient with NF-1 has yet been reported. Here, we describe a case of a 55-year-old female patient with NF-1 whose serum Pro-Gastrin-Releasing Peptide (pro-GRP) levels were elevated. Gastrointestinal endoscopy and biopsy showed duodenal papilla space-occupying mass, and the pathological diagnosis turned out to be neuroendocrine tumors (NETs). During surgical exploration, multiple tumors were found on the serosal surface of the stomach and numerous miliary metastases in the liver. Following histopathological examination, it was determined that the liver metastases were NF-1 and the tumors in the gastric wall were GISTs. The patient benefited from targeted therapy and had an uneventful hospital stay. In this case, we emphasize treating patients with neurofibromatosis type 1 who exhibit abdominal symptoms with a high degree of clinical suspicion and performing thorough evaluations to rule out multiple tumors.

Abstract For lithium‐sulfur batteries (Li‐S batteries), a high‐content electrolyte typically can exacerbate the shuttle effect, while a lean electrolyte may lead to decreased Li‐ion conductivity and reduced catalytic conversion efficiency, so achieving an appropriate electrolyte‐to‐sulfur ratio (E/S ratio) is essential for improving the battery cycling efficiency. A quasi‐solid electrolyte (COF‐SH@PVDF‐HFP) with strong adsorption and high catalytic conversion was constructed for in situ covalent organic framework (COF) growth on highly polarized polyvinylidene fluoride‐hexafluoropropylene (PVDF‐HFP) fibers. COF‐SH@PVDF‐HFP enables efficient Li‐ion conductivity with low‐content liquid electrolyte and effectively suppresses the shuttle effect. The results based on in situ Fourier‐transform infrared, in situ Raman, UV–Vis, X‐ray photoelectron, and density functional theory calculations confirmed the high catalytic conversion of COF‐SH layer containing sulfhydryl and imine groups for the lithium polysulfides. Lithium plating/stripping tests based on Li/COF‐SH@PVDF‐HFP/Li show excellent lithium compatibility (5 mAh cm−2 for 1400 h). The assembled Li‐S battery exhibits excellent rate (2 C 688.7 mAh g−1) and cycle performance (at 2 C of 568.8 mAh g−1 with a capacity retention of 77.3% after 800 cycles). This is the first report to improve the cycling stability of quasi‐solid‐state Li‐S batteries by reducing both the E/S ratio and the designing strategy of sulfhydryl‐functionalized COF for quasi‐solid electrolytes. This process opens up the possibility of the high performance of solid‐state Li‐S batteries.

Abstract Background The aim of this study was to investigate the association between systemic immune‐inflammation index (SII) and all‐cause mortality in individuals with chronic kidney disease (CKD). Patients and Methods This prospective cohort study was carried out among 9303 participants with CKD from the National Health and Nutrition Examination Survey cycles spanning 1999 to 2018. The mortality data were ascertained by linking participant records to the National Death Index up to December 31, 2019. Complex sampling‐weighted multivariate Cox proportional hazards models were employed to estimate the association between SII level and all‐cause mortality, providing hazard ratios (HR) and 95% confidence intervals (CI). A restricted cubic spline analysis was conducted to explore potential nonlinear correlation. Subgroup analyses and sensitivity analyses were also conducted. Results During a median follow‐up period of 86 months, 3400 (36.54%) all‐cause deaths were documented. A distinctive “J”‐shaped relationship between SII level and all‐cause mortality was discerned among individuals with CKD, with the nadir observed at an SII level of 478.93 within the second quartile. After adjusting for potential covariates, the risk of all‐cause mortality escalated by 13% per increment of one standard deviation of SII, once SII exceeded 478.93 (HR = 1.13; 95% CI = 1.08–1.18). An elevated SII was associated with an increased risk of all‐cause mortality among patients with CKD (Q4 vs. Q2: HR = 1.23; 95% CI = 1.01–1.48). Subgroup analyses indicated that the correlation between SII and CKD mortality was particularly pronounced among participants over 60 years old and individuals with diabetes. Sensitivity analyses revealed a linear positive association between SII and all‐cause mortality after removing the extreme 5% outliers of SII. Conclusions A distinctive “J”‐shaped relationship between SII level and all‐cause mortality was identified among individuals with CKD. Further research is warranted to validate and expand upon these findings.

The activated B-cell–like subtype of diffuse large B-cell lymphoma (ABC-DLBCL) displays a worse outcome than the germinal center B-cell–like subtype (GCB-DLBCL). Currently, targeting tumor microenvironment (TME) is the promising approach to cure DLBCL with profound molecular heterogeneity, however, the factors affecting the tumor-promoting TME of ABCDLBCL are elusive. Here, cytokine interleukin-16 (IL-16) is expressed in tumor cells of ABCDLBCL and secreted by the cleavage of active caspase-3. The serum IL-16 levels are not only a sensitive marker of treatment response but also positively correlated with unfavorable prognosis in DLBCL patients. While IL-16 shows few direct promotional effects on tumor cell growth in vitro, its bioactive form significantly promotes tumor progression in vivo. Mechanically, IL-16 increases the infiltration of macrophages by the chemotaxis of CD4+ monocytes in the TME enhancing angiogenesis, and the expression of cytokine IL-6 and IL-10, as well as decreasing T cell infiltration to accelerate tumor progression. This study demonstrates that IL-16 exerts a novel role in coordinating the bidirectional interactions between tumor progression and the TME. IMM0306, a fusion protein of CD20 mAb with the CD47 binding domain of SIRPα, reverses the tumorpromoting effects of IL-16,which provides new insight into treatment strategy in ABC-DLBCL.

IntroductionThe hair follicle (HF) is a micro-organ capable of regeneration. A HF cycle consists of an anagen, catagen and telogen. Abnormalities in the HF cycle can lead to many hair disorders such as hair loss. The pig is a good biomedical model, but there are few data on their HF cycle. The aim of this study was to classify the pig HF cycle and determine the feasibility of the pig as an animal model for human HF cycle.MethodsSkin samples from 10 different postnatal (P) days Yorkshire pigs was collected to determine the key time points of the first HF cycle in pig by H&E staining, immunofluorescence staining, q-PCR and western-blot.ResultsBy morphological observation and detection of markers at different stages, pig HF cycle was classified into three main periods - the first anagen until P45, catagen (P45–P85), telogen (P85–P100), and next anagen (>P100). In addition, we examined the expression of important genes AE15, CD34, Versican, Ki67 et al. related to the HF cycle at different stages of pig HF, indicating that pig and human share similarities in morphology and marker gene expression patterns of HF cycle.DiscussionOur findings will facilitate the study of HF cycle and offer researchers a suitable model for human hair research.

Maintaining metabolic homeostasis is crucial for cellular and organismal health throughout their lifespans. The intricate link between metabolism and inflammation through immunometabolism is pivotal in maintaining overall health and disease progression. The multifactorial nature of metabolic and inflammatory processes makes study of the relationship between them challenging. Homologs of Saccharomyces cerevisiae silent information regulator 2 protein, known as Sirtuins (SIRTs), have been demonstrated to promote longevity in various organisms. As nicotinamide adenine dinucleotide-dependent deacetylases, members of the Sirtuin family (SIRT1–7) regulate energy metabolism and inflammation. In this review, we provide an extensive analysis of SIRTs involved in regulating key metabolic pathways, including glucose, lipid, and amino acid metabolism. Furthermore, we systematically describe how the SIRTs influence inflammatory responses by modulating metabolic pathways, as well as inflammatory cells, mediators, and pathways. Current research findings on the preferential roles of different SIRTs in metabolic disorders and inflammation underscore the potential of SIRTs as viable pharmacological and therapeutic targets. Future research should focus on the development of promising compounds that target SIRTs, with the aim of enhancing their anti-inflammatory activity by influencing metabolic pathways within inflammatory cells.

Melioidosis is a fatal infectious disease caused by Burkholderia pseudomallei. Its clinical manifestations are so varied that it has been called a great mimic. The primary melioidotic prostatic disease usually presents as an abscess of the prostate. This is the only documented case misdiagnosed as benign prostatic hyperplasia (BPH) because it does not show as a prostate abscess. The patient was a 66 years old male with a history of hypertension and alcoholism. Symptoms of difficulty urinating and fever had persisted for three days. Laboratory tests of the patient showed a marked increase in inflammatory markers. The first urine culture was performed to isolate Acinetobacter lwoffii, not Burkholderia pseudomallei. And CT showed prostatic hyperplasia with calcification. Thus, the preliminary diagnosis was BPH, urinary tract infection, and pulmonary infection. Cefmenoxime and Piperacillin were given for anti-infective treatment, but both of the effects were not satisfactory. Then, the second urine culture and multiple hemocultures were performed to isolate Burkholderia pseudomallei. The final diagnosis was primary melioidotic prostatic disease, BPH, pulmonary infection, bacteremia and multiple organ damage. The patient was treated with imipenem for two weeks and cured. Trimethoprim-sulfamethoxazole (TMP-SMX) was administered orally for twelve weeks after discharge. Therefore, clinicians need to have an understanding of primary melioidotic prostate disease to avoid misdiagnosis and mistreatment to improve the cure rate and survival rate of patients.

Abstract Despite being one of the most prevalent RNA modifications, the role of N6‐methyladenosine (m6A) in amyotrophic lateral sclerosis (ALS) remains ambiguous. In this investigation, we explore the contribution of genetic defects of m6A‐related genes to ALS pathogenesis. We scrutinized the mutation landscape of m6A genes through a comprehensive analysis of whole‐exome sequencing cohorts, encompassing 508 ALS patients and 1660 population‐matched controls. Our findings reveal a noteworthy enrichment of RNA binding motif protein X‐linked (RBMX) variants among ALS patients, with a significant correlation between pathogenic m6A variants and adverse clinical outcomes. Furthermore, Rbmx knockdown in NSC‐34 cells overexpressing mutant TDP43Q331K results in cell death mediated by an augmented p53 response. Similarly, RBMX knockdown in ALS motor neurons derived from induced pluripotent stem cells (iPSCs) manifests morphological defects and activation of the p53 pathway. Transcriptional analysis using publicly available single‐cell sequencing data from the primary motor cortex indicates that RBMX‐regulated genes selectively influence excitatory neurons and exhibit enrichment in ALS‐implicated pathways. Through integrated analyses, our study underscores the emerging roles played by RBMX in ALS, suggesting a potential nexus between the disease and dysregulated m6A‐mediated mRNA metabolism.

ObjectiveTo investigate the relationship between circulating receptor activator of nuclear factor-kappa B ligand (RANKL) levels and marrow adipose tissue in postmenopausal females.MethodsA total of 164 postmenopausal females were included in the study. Serum levels of osteoprotegerin (OPG) and RANKL were measured using ELISA kits. Body composition and bone mineral density (BMD) were assessed using dual-energy X-ray absorptiometry. Complex-based chemical shift imaging-based MRI was employed to evaluate the vertebral marrow proton density fat fraction (PDFF). A multivariate linear regression model was utilized to analyze the predictive effects of PDFF and BMD on circulating levels of OPG and RANKL.ResultsSimple regression analysis showed significant associations among the marrow PDFF, BMD at either site, serum RANKL, and the RANKL/OPG ratio. In multivariate linear regression models, marrow PDFF was found to have a positive correlation (β = 3.15, 95% CI 2.60 to 3.70) and BMD had negative correlations (β = −0.200, 95% CI −0.348 to −0.051 for vertebral BMD; β = −0.383, 95% CI −0.589 to −0.177 for total hip BMD; and β =−0.393, 95% CI −0.598 to −0.188 for femoral neck BMD, all p < 0.01) with circulating soluble RANKL levels after adjusting for age, body mass index, physical activity, total fat mass, android/gynoid ratio, and lean mass. Similar results were observed for the RANKL/OPG ratio. Additionally, multivariate linear regression analyses revealed that marrow PDFF was a significant independent contributor of circulating soluble RANKL (β = 1.34, 95% CI 1.10 to 1.58, p < 0.001) after further controlling for BMD. However, marrow PDFF or BMD had no associations with circulating levels of OPG after adjusting for all potential confounders mentioned above.ConclusionsVertebral marrow fat fraction is independently associated with circulating soluble RANKL levels in postmenopausal females.

Although immobilization-free and label-free electrochemical DNA (E-DNA) biosensors have engaged tremendous interest due to their superior properties, such as easy operation, time-saving and cost-saving, most of them are fabricated in homogeneous modes and usually produce high background current. In the present work, we proposed a new immobilization-free and label-free heterogeneous E-DNA assay based on a dual-blocker-aided multibranched hybridization chain reaction (HCR) for one-pot nucleic acid detection with zero background. The target nucleic acid triggers the HCR involving cascaded hybridization between two metastable hairpins, resulting in the generation of HCR products with multibranched arms, which can be captured onto the electrode via π-π stacking interactions between multibranched arms and reduced graphene oxide (rGO). Prior to the incubation process with an electrode, two blockers are designed to prohibit the nonspecific absorption of unreacted hairpin probes. Thus, an immobilization-free and label-free heterogeneous electrochemical assay for one-pot nucleic acid detection with zero background is readily realized. This strategy also presents additional merits of simplicity and cheap cost, since probe immobilization, signal tag labeling, and multiple incubation processes are avoided. Therefore, the as-proposed effective and versatile biosensor has great potential to be applied in nucleic acid-related practical biosensing.

As an effective treatment for diabetes, islet transplantation has garnered significant attention and research in recent years. However, immune rejection and the toxicity of immunosuppressive drugs remain critical factors influencing the success of islet transplantation. While immunosuppressants are essential in reducing immune rejection reactions and can significantly improve the survival rate of islet transplants, improper use of these drugs can markedly increase mortality rates following transplantation. Additionally, the current availability of islet organ donations fails to meet the demand for organ transplants, making xenotransplantation a crucial method for addressing organ shortages. This review will cover the following three aspects: 1) the immune responses occurring during allogeneic islet transplantation, including three stages: inflammation and IBMIR, allogeneic immune response, and autoimmune recurrence; 2) commonly used immunosuppressants in allogeneic islet transplantation, including calcineurin inhibitors (Cyclosporine A, Tacrolimus), mycophenolate mofetil, glucocorticoids, and Bortezomib; and 3) early and late immune responses in xenogeneic islet transplantation and the immune effects of triple therapy (ECDI-fixed donor spleen cells (ECDI-SP) + anti-CD20 + Sirolimus) on xenotransplantation.

Purpose: Sepsis is a disease that is typically treated in intensive care units with high mortality and morbidity. Pyroptosis is a newly identified type of programmed cell death and is characterized by inflammatory cytokine secretion. However, the role of pyroptosis in sepsis remains unclear. Methods: GSE28750 and GSE134347 datasets were obtained from the Gene Expression Omnibus (GEO) database. Differentially expressed pyroptosis genes (DEPGs) were identified between sepsis and healthy controls. Machine learning was used to further narrow the gene range. Receiver operating curves (ROC) were generated to estimate the diagnostic efficacy. Immune infiltration levels were estimated via single-sample gene set enrichment analysis (ssGSEA). A network database was used to predict the upstream transcription factors and miRNAs of DEPGs. Finally, the expression of the genes was validated by qRT-PCR between sepsis patients and healthy controls. Results: We found that the pyroptosis pathway was enriched and activated in sepsis. 8 DEPGs were identified. A heatmap showed that the genes, NLRC4, NAIP, IL-18, AIM2 and ELANE, were abundant in the sepsis samples, and the genes, NLRP1, CHMP7 and TP53, were abundant in the healthy control samples. The ssGSEA results showed that the abundances of activated dendritic cells, MDSC, macrophage, plasmacytoid dendritic cells, regulatory T-cells, and Th17-cells were significantly higher, while the activated B-cell, activated CD8 T-cell, CD56 dim tural killer cell, immature B-cell, monocyte, and T follicular helper cell abundances were lower in sepsis samples compared to healthy controls. The qRT-PCR results showed that the expression levels of NAIP, IL-18, TP53, CHMP7, NLRC4, ELANE and NLRP1 were consistant with the bioinformatic analyses, while the expression level of AIM2 has no significant difference. Conclusion: Our study identified seven potential pyroptosis-related genes, NAIP, IL-18, TP53, CHMP7, NLRC4, ELANE and NLRP1. This study revealed that pyroptosis may promote sepsis development by activating the immune response.

Immunotherapy using inflammatory cytokines, such as interleukin (IL)-2 and interferon (IFN)-α, has been clinically validated in treating various cancers. However, systemic immunocytokine-based therapies are limited by the short half-life of recombinant proteins and severe dose-limiting toxicities. In this study, we exploited local immunotherapy by intratumoral administration of lipid nanoparticle (LNP)-encapsulated mRNA cocktail encoding cytokines IL-12, IL-7, and IFN-α. The cytokine mRNA cocktail induced tumor regression in multiple syngeneic mouse models and anti-tumor immune memory in one syngeneic mouse model. Additionally, immune checkpoint blockade further enhanced the anti-tumor efficacy of the cytokine mRNAs. Furthermore, human cytokine mRNAs exhibited robust anti-tumor efficacy in humanized mouse tumor models. Mechanistically, cytokine mRNAs induced tumor microenvironment inflammation, characterized by robust T cell infiltration and significant inflammatory cytokine and chemokine production.

Di(2-ethylhexyl) phthalate (DEHP) is a widely recognized environmental endocrine disruptor that potentially impacts female reproductive function, although the specific mechanisms leading to such impairment remain unclear. A growing body of research has revealed that the endoplasmic reticulum and mitochondrial function significantly influence oocyte quality. The structure of mitochondria-associated endoplasmic reticulum membranes (MAMs) is crucial for facilitating the exchange of Ca2+, lipids, and metabolites. This study aimed to investigate the alterations in the composition and function of MAMs after DEHP exposure and to elucidate the underlying mechanisms of ovarian toxicity. The female mice were exposed to DEHP at doses of 5 and 500 mg/kg/day for one month. The results revealed that DEHP exposure led to reduced serum anti-Müllerian hormone levels and increased atretic follicles in mice. DEHP induced endoplasmic reticulum stress and disrupted calcium homeostasis in oocytes. Furthermore, DEHP impaired the mitochondrial function of oocytes and reduced their membrane potential, and promoting apoptosis. Similar results were observed in human granulosa cells after exposure to mono-(2-ethylhexyl) phthalate (MEHP, metabolites of DEHP) in vitro. Proteomic analysis and transmission electron microscopy revealed modifications in the functional proteins and structure of the MAMs, and the suppression of oxidative phosphorylation pathways. The findings of this investigation provide a new perspective on the mechanism underlying the reproductive toxicity of DEHP in females.

Abstract Remarkable progress has characterized the field of electrocatalysis in recent decades, driven in part by an enhanced comprehension of catalyst structures and mechanisms at the nanoscale. Atomically precise metal nanoclusters, serving as exemplary models, significantly expand the range of accessible structures through diverse cores and ligands, creating an exceptional platform for the investigation of catalytic reactions. Notably, ligand‐protected Au nanoclusters (NCs) with precisely defined core numbers offer a distinct advantage in elucidating the correlation between their specific structures and the reaction mechanisms in electrocatalysis. The strategic modulation of the fine microstructures of Au NCs presents crucial opportunities for tailoring their electrocatalytic performance across various reactions. This review delves into the profound structural effects of Au NC cores and ligands in electrocatalysis, elucidating their underlying mechanisms. A detailed exploration of the fundamentals of Au NCs, considering core and ligand structures, follows. Subsequently, the interaction between the core and ligand structures of Au NCs and their impact on electrocatalytic performance in diverse reactions are examined. Concluding the discourse, challenges and personal prospects are presented to guide the rational design of efficient electrocatalysts and advance electrocatalytic reactions.

BackgroundGlioma is a highly heterogeneous malignancy of the central nervous system. This heterogeneity is driven by various molecular processes, including neoplastic transformation, cell cycle dysregulation, and angiogenesis. Among these biomolecular events, inflammation and stress pathways in the development and driving factors of glioma heterogeneity have been reported. However, the mechanisms of glioma heterogeneity under stress response remain unclear, especially from a spatial aspect.MethodsThis study employed single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics (ST) to explore the impact of oxidative stress response genes in oligodendrocyte precursor cells (OPCs). Our analysis identified distinct pathways activated by oxidative stress in two different types of gliomas: high- and low- grade (HG and LG) gliomas.ResultsIn HG gliomas, oxidative stress induced a metabolic shift from oxidative phosphorylation to glycolysis, promoting cell survival by preventing apoptosis. This metabolic reprogramming was accompanied by epithelial-to-mesenchymal transition (EMT) and an upregulation of stress response genes. Furthermore, SCENIC (Single-Cell rEgulatory Network Inference and Clustering) analysis revealed that oxidative stress activated the AP1 transcription factor in HG gliomas, thereby enhancing tumor cell survival and proliferation.ConclusionOur findings provide a novel perspective on the mechanisms of oxidative stress responses across various grades of gliomas. This insight enhances our comprehension of the evolutionary processes and heterogeneity within gliomas, potentially guiding future research and therapeutic strategies.

Abstract Background Severe bacterial infections can trigger acute lung injury (ALI) and acute respiratory distress syndrome, with bacterial pathogen‐associated molecular patterns (PAMPs) exacerbating the inflammatory response, particularly in COVID‐19 patients. Cyclic‐di‐GMP (CDG), one of the PAMPs, is synthesized by various Gram‐positve and Gram‐negative bacteria. Previous studies mainly focused on the inflammatory responses triggered by intracellular bacteria‐released CDG. However, how extracellular CDG, which is released by bacterial autolysis or rupture, activates the inflammatory response remains unclear. Methods The interaction between extracellular CDG and myeloid differentiation protein 2 (MD2) was investigated using in vivo and in vitro models. MD2 blockade was achieved using specific inhibitor and genetic knockout mice. Site‐directed mutagenesis, co‐immunoprecipitation, SPR and Bis‐ANS displacement assays were used to identify the potential binding sites of MD2 on CDG. Results Our data show that extracellular CDG directly interacts with MD2, leading to activation of the TLR4 signalling pathway and lung injury. Specific inhibitors or genetic knockout of MD2 in mice significantly alleviated CDG‐induced lung injury. Moreover, isoleucine residues at positions 80 and 94, along with phenylalanine at position 121, are essential for the binding of MD2 to CDG. Conclusion These results reveal that extracellular CDG induces lung injury through direct interaction with MD2 and activation of the TLR4 signalling pathway, providing valuable insights into bacteria‐induced ALI mechanisms and new therapeutic approaches for the treatment of bacterial co‐infection in COVID‐19 patients.

Abstract Background Chronic inflammation contributes to the progression of isoproterenol (ISO)‐induced heart failure (HF). Caspase‐associated recruitment domain (CARD) families are crucial proteins for initiation of inflammation in innate immunity. Nonetheless, the relevance of CARDs in ISO‐driven cardiac remodelling is little explored. Methods This study utilized Card9−/− mice and reconstituted C57BL/6 mice with either Card9−/− or Otud1−/− marrow‐derived cells. Mechanistic studies were conducted in primary macrophages, cardiomyocytes, fibroblasts and HEK‐293T cells. Results Here, we demonstrated that CARD9 was substantially upregulated in murine hearts infused with ISO. Either whole‐body CARD9 knockout or myeloid‐specific CARD9 deletion inhibited ISO‐driven murine cardiac inflammation, remodelling and dysfunction. CARD9 deficiency in macrophages prevented ISO‐induced inflammation and alleviated remodelling changes in cardiomyocytes and fibroblasts. Mechanistically, we found that ISO enhances the activity of CARD9 by upregulating ovarian tumour deubiquitinase 1 (OTUD1) in macrophages. We further demonstrated that OTUD1 directly binds to the CARD9 and then removes the K33‐linked ubiquitin from CARD9 to promote the assembly of the CARD9‐BCL10‐MALT1 (CBM) complex, without affecting CARD9 stability. The ISO‐activated CBM complex results in NF‐κB activation and macrophage‐based inflammatory gene overproduction, which then enhances cardiomyocyte hypertrophy and fibroblast fibrosis, respectively. Myeloid‐specific OTUD1 deletion also attenuated ISO‐induced murine cardiac inflammation and remodelling. Conclusions These results suggested that the OTUD1‐CARD9 axis is a new pro‐inflammatory signal in ISO‐challenged macrophages and targeting this axis has a protective effect against ISO‐induced HF. Key points Macrophage CARD9 was elevated in heart tissues of mice under chronic ISO administration. Either whole‐body CARD9 knockout or myeloid‐specific CARD9 deficiency protected mice from ISO‐induced inflammatory heart remodeling. ISO promoted the assembly of CBM complex and then activated NF‐κB signaling in macrophages through OTUD1‐mediated deubiquitinating modification. OTUD1 deletion in myeloid cells protected hearts from ISO‐induced injuries in mice.

Abstract Organic carbon (OC) sedimentation in marine sediments is the largest long‐term sink of atmospheric CO2 after silicate weathering. Understanding the mechanistic and quantitative aspects of OC delivery and preservation in marine sediments is critical for predicting the role of the oceans in modulating global climate. Yet, estimates of the global OC sedimentation in marginal settings span an order of magnitude, and the primary controls of OC preservation remain highly debated. Here, we provide the first global bottom‐up estimate of OC sedimentation along the margins using a synthesis of literature data. We quantify both terrestrial‐ and marine‐sourced OC fluxes and perform a statistical analysis to discern the key factors influencing their magnitude. We find that the margins host 23.2 ± 3.5 Tmol of OC sedimentation annually, with approximately 84% of marine origin. Accordingly, we calculate that only 2%–3% of OC exported from the euphotic zone escapes remineralization before sedimentation. Surprisingly, over half of all global OC sedimentation occurs below bottom waters with oxygen concentrations greater than 180 μM, while less than 4% occurs in settings with

We synthesized a core-shell resin structure with abundant architecture and excellent thermal stability through polymerization. Imidazole ionic liquid with varying carbon chain lengths was immobilized on the surface, resulting in the preparation of metal-free, halogen-free core-shell catalysts with different carbon chain lengths via HCO3- exchange. Characterization using FT-IR, XPS, and various techniques revealed the exceptional performance of our synthetic catalyst in terms of its internal structure. After extensive experimentation, we discovered that the synthesized catalyst exhibits dual functionality for epoxidation and CO2 cycloaddition reactions without requiring solvents or co-catalysts. The epoxidation system demonstrated remarkable conversion rates and selectivity while also exhibiting strong recyclability in heterogeneous reactions, according to kinetic parameters, the reaction order of styrene, TBHP and catalyst during epoxidation is approximately 1, the reference factor for this reaction was calculated to be 6.7×109 (L2·mol−2·min−1), with an activation energy of 48.9 kJ/mol obtained from analyzing reaction rates at different temperatures. In the CO2 cycloaddition reaction, our catalyst exhibited an advantage in catalyzing ring-opening reactions, achieving a conversion rate of 95 % for styrene oxide within six hours along with over 99 % selectivity towards cyclic carbonate formation. It is suggested that the epoxide reaction is carried out in steps, and it is inferred that the catalyst PS-ImC4HCO3 and TBHP are produced into peroxy intermediate active species TBA and HCO4, and the reaction between HCO4- and styrene is the determination step of the total reaction. The reaction rate constant k=0.009 of the absolute step is calculated based on the global optimization algorithm

BackgroundRosacea has a high incidence, significantly impacts quality of life, and lacks sufficient diagnostic techniques. This study aimed to investigate the feasibility of laser speckle contrast imaging (LSCI) for measuring facial blood perfusion in patients with rosacea and to identify differences in blood flow among various facial regions associated with different rosacea subtypes.MethodsFrom June to December 2023, 45 patients were recruited, with 9 excluded, leaving 36 subjects: 12 with erythematotelangiectatic rosacea (ETR), 12 with papulopustular rosacea (PPR), and 12 healthy controls. The Think View multispectral imaging analyzer assessed inflammation via gray reading values across the full face and five facial areas: forehead, nose, cheeks, and chin. LSCI measured and analyzed blood perfusion in the same areas. Plasma biomarkers interleukin-6 (IL-6), IL-1β, and tumor necrosis factor-α (TNF-α) were tested in different groups.ResultsBoth ETR and PPR groups showed increased average blood perfusion and facial inflammation intensity by gray values compared to controls, with statistically significant differences. Average blood perfusion of ETR and PPR groups showed increased values in the forehead, cheeks, and nose, compared to controls, and the values in the cheeks were statistically different between ETR and PPR. The facial inflammation intensity of the ETR group showed increased values in the forehead and cheeks, and the PPR group showed increased gray values in the forehead, cheeks, nose, and chin compared to controls, and the values for the cheeks, nose, and chin were statistically significantly different between ETR and PPR. Plasma biomarkers IL-6, IL-1β, and TNF-α were significantly elevated in both ETR and PPR groups compared to controls.ConclusionLSCI is a valuable, non-invasive tool for assessing blood flow dynamics in rosacea, providing a data foundation for clinical research. Different rosacea subtypes exhibit distinct lesion distribution and blood flow patterns, and both ETR and PPR could affect all facial areas, particularly the cheeks in ETR and the forehead, nose, and chin in PPR.

ObjectiveThis retrospective cohort study aimed to assess the clinical features, treatment outcomes, and short-term prognosis in kidney transplant recipients (KTRs) with concurrent coronavirus disease 2019 (COVID-19) pneumonia.MethodsKTRs with COVID-19 pneumonia who were admitted to our hospital from December 28, 2022, to March 28, 2023 were included in the study. Their clinical symptoms, responses to antiviral medications, and short-term prognosis were analyzed.ResultsA total of 64 KTRs with initial diagnosis of COVID-19 pneumonia were included in this study. The primary symptoms were fever, cough, and myalgia, with an incidence of 79.7%, 89.1%, and 46.9%, respectively. The administration of antiviral drugs (paxlovid or molnupiravir) within 1–5 days and for over 5 days demonstrated a statistically significant reduction in viral shedding time compared to the group without antiviral medication (P=0.002). Both the paxlovid and molnupiravir treatment groups exhibited a significantly shorter duration of viral shedding time in comparison to the group without antiviral drugs (P=0.002). After 6 months of recovery, there was no significantly negative impact on transplant kidney function (P=0.294).ConclusionFever, cough, and myalgia remain common initial symptoms of concurrent COVID-19 pneumonia in KTRs. Early use of antiviral drugs (paxlovid or molnupiravir) is associated with better therapeutic outcomes. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) had a limited impact on the short-term renal function of the KTRs with concurrent moderate or severe COVID-19 pneumonia.

BackgroundDuring the coronavirus disease 2019 (COVID-19) pandemic, the infection of Mycoplasma pneumoniae (MP) decreased significantly. At the beginning of the summer of 2023, there was an increasing trend of MP infection in China and the MP pneumonia (MPP) is surging when it comes to the school season and lasts for several months which has attracted widespread attention.ObjectiveThis study aims to investigate the prevalent characteristics of the MP and the difference between the COVID-19 pandemic and the post in Shanghai, China.MethodsThe demographic information and the results of laboratory pathogen detection from July 2021 to May 2024 were collected and analyzed to find out the prevalent characteristics of MP. Two periods, during the COVID-19 pandemic and the post-pandemic, were divided and compared. The P1 genotyping and macrolide resistance-associated gene of 23 s rRNA were detected using the remaining MP-positive samples.ResultsDuring the COVID-19 pandemic, the prevalence of the MP has significantly decreased. Female children are more susceptible to MP infection than the male. The school-aged group (>6 years) had the highest infection rate. The rate of MP P1 genotype during post panel is higher than that during COVID-19 pandemic, which is dominant from July 2021 to May 2024, while the macrolide-resistant associated mutations (A2063G) keep high percentage during or post pandemic.ConclusionAfter the COVID-19 pandemic, an outbreak of MP infection occurred from summer onwards in 2023 with children in Shanghai, China. Immunity debt and high rate of macrolide-resistance may take effects in this MP epidemic. Continuous surveillance of MP is necessary to help to alert the prevalence of MPP.

BackgroundProtein Energy Wasting (PEW) has high incidence in adult hemodialysis patients and refers to a state of decreased protein and energy substance. It has been demonstrated that PEW highly affects the quality of survival and increases the risk of death. Nevertheless, its diagnostic criteria are complex in clinic. To simplify the diagnosis method of PEW in adult hemodialysis patients, we previously established a novel clinical prediction model that was well-validated internally using bootstrapping. In this multicenter cross-sectional study, we aimed to externally validate this nomogram in a new cohort of adult hemodialysis patients.MethodsThe novel prediction model was built by combining four independent variables with part of the International Society of Renal Nutrition and Metabolism (ISRNM) diagnostic criteria including albumin, total cholesterol, and body mass index (BMI). We evaluated the performance of the new model using discrimination (Concordance Index), calibration plots, and Clinical Impact Curve to assess its predictive utility.ResultsFrom September 1st, 2022 to August 31st, 2023, 1,158 patients were screened in five medical centers in Shanghai. 622 (53.7%) hemodialysis patients were included for analysis. The PEW predictive model was acceptable discrimination with the area under the curve of 0.777 (95% CI 0.741–0.814). Additionally, the model revealed well-fitted calibration curves. The McNemar test showed the novel model had similar diagnostic efficacy with the gold standard diagnostic method (p > 0.05).ConclusionOur results from this cross-sectional external validation study further demonstrate that the novel model is a valid tool to identify PEW in adult hemodialysis patients effectively.

We proposed a non-contact photoacoustic (PA) detection method using spectral domain optical coherence tomography (SDOCT). Two interference spectrums (A-lines) were acquired before and after the PA excitation with SDOCT. PA signal propagated within the sample causing the vibration. The vibration inner the sample introduced phase change between the acquired two A-lines. Thus, the PA signal can be detected by evaluating the difference in phase between the two A-lines. Based on the method, an OCT-PAM dual-mode imaging system was constructed. In the system, SDOCT served as the detection unit for PAM. Thus, the combination of the two imaging modalities was simplified. Another advantage of the system is that it realizes non-contact all-optic detection, which is attractive for biomedical imaging. Using the system, we imaged phantoms of carbon fibers, asparagus leaves and human hairs. Furthermore, the cortical vasculature of rat was imaged in vivo and the flow status was evaluated quantitatively.

Abstract A comprehensive immune landscape for Brucella infection is crucial for developing new treatments for brucellosis. Here, we utilized single‐cell RNA sequencing (scRNA‐seq) of 290,369 cells from 35 individuals, including 29 brucellosis patients from acute (n = 10), sub‐acute (n = 9), and chronic (n = 10) phases as well as six healthy donors. Enzyme‐linked immunosorbent assays were applied for validation within this cohort. Brucella infection caused a significant change in the composition of peripheral immune cells and inflammation was a key feature of brucellosis. Acute patients are characterized by potential cytokine storms resulting from systemic upregulation of S100A8/A9, primarily due to classical monocytes. Cytokine storm may be mediated by activating S100A8/A9‐TLR4‐MyD88 signaling pathway. Moreover, monocytic myeloid‐derived suppressor cells were the probable contributors to immune paralysis in acute patients. Chronic patients are characterized by a dysregulated Th1 response, marked by reduced expression of IFN‐γ and Th1 signatures as well as a high exhausted state. Additionally, Brucella infection can suppress apoptosis in myeloid cells (e.g., mDCs, classical monocytes), inhibit antigen presentation in professional antigen‐presenting cells (APCs; e.g., mDC) and nonprofessional APCs (e.g., monocytes), and induce exhaustion in CD8+ T/NK cells, potentially resulting in the establishment of chronic infection. Overall, our study systemically deciphered the coordinated immune responses of Brucella at different phases of the infection, which facilitated a full understanding of the immunopathogenesis of brucellosis and may aid the development of new effective therapeutic strategies, especially for those with chronic infection.

Mycoplasma pneumoniae is a significant pathogen responsible for community-acquired pneumonia, predominantly affecting children and adolescents. Here, we devised a rapid method for M. pneumoniae that combined multiple cross displacement amplification (MCDA) with real-time fluorescence technology. A set of ten primers, which were specifically designed for M. pneumoniae detection, were employed in a real-time fluorescence MCDA reaction. Of these, one primer incorporated a restriction endonuclease recognition sequence, a fluorophore, and a quencher, facilitating real-time fluorescence detection. The real-time (RT)-MCDA reactions were monitored in a simple real-time fluorescence instrument and conducted under optimised conditions (64°C for 40 min). The detection limit of the M. pneumoniae RT-MCDA assay for genomic DNA extracted from M. pneumoniae culture was down to 43 fg/µl. This assay accurately identified M. pneumoniae strains without cross-reacting with other bacteria. To validate its practical application, we tested the M. pneumoniae RT-MCDA assay using genomic DNA extracted from clinical samples. The assay’s detection capability proved comparable with real-time PCR, MCDA-based biosensor detection, and visual inspection under blue light. The entire process, including rapid DNA extraction and real-time MCDA detection, was completed within 1 h. Overall, the M. pneumoniae RT-MCDA assay reported here is a simple and effective diagnostic tool for rapid M. pneumoniae detection, which holds significant potential for point-of-care testing and in resource-limited regions.

ABSTRACT Physicochemical methods for remediating phenol-contaminated soils are costly and inefficient, making biodegradation an environmentally friendly alternative approach. This study aims to screen for potential phenol-degrading bacteria and to verify the removal capacities of a selected strain in a bioaugmentation experiment at the greenhouse level using Brassica chinensis L. (Chinese cabbage) as the model plant and phenol-contaminated soil. In parallel, pot experiments were conducted using a collaborative approach based on this model system. We found that Myroides xuanwuensis strain H13 showed a high degradation capability, with a 97.67% efficiency in degrading 100 mg/L phenol. Under shaking flask conditions, H13 facilitated the solubilization of tricalcium phosphate and potassium feldspar powder. Pot experiments suggested a phenol removal percentage of 89.22% and enhanced availability of soil phosphorus and potassium for plants with H13 inoculation. In this case, the abundance of soil microbes and the activity of soil enzymes significantly increased as well. Furthermore, both photosynthesis and the antioxidant system in Chinese cabbage were enhanced following H13 inoculation, resulting in its increased yield and quality. Partial least squares path modeling revealed that H13 can primarily affect plant root growth, with a secondary impact on photosynthesis. These findings highlight the potential of biodegradation from phenol-degrading bacteria as a promising strategy for efficient phenol removal from soil while promoting plant growth and health.IMPORTANCEThis study is significant for environmental remediation and agriculture by its exploration of a more environmentally friendly and cost-effective bio-strategy in treating phenol-contaminated soil. These findings have essential implications for environmental remediation efforts and sustainable agriculture. By utilizing the biodegradation capabilities of Myroides xuanwuensis strain H13, it is possible to remove phenol contaminants from the soil efficiently, reducing their negative effects. Furthermore, the enhanced growth and health of the Chinese cabbage plants indicate the potential of this approach to promote sustainable crop production.

T cells express an enormous repertoire of T cell receptors, enabling them to recognize any potential antigen. This large repertoire undergoes stringent selections in the thymus, where receptors that react to self- or non-danger-associated- antigens are purged. We know that thymic tolerance depends on signals and antigens presented by the thymic antigen presenting cells, but we still do not understand precisely how many of these cells actually contribute to tolerance. This is especially true for thymic dendritic cells (DC), which are composed of diverse subpopulations that are derived from different progenitors. Although the importance of thymic DCs has long been known, the functions of specific DC subsets have been difficult to untangle. There remains insufficient systematic characterization of the ontogeny and phenotype of thymic APCs in general. As a result, validated experimental models for studying thymic DCs are limited. Recent technological advancement, such as multi-omics analyses, has enabled new insights into thymic DC biology. These recent findings indicate a need to re-evaluate the current tools used to study the function of these cells within the thymus. This review will discuss how thymic DC subpopulations can be defined, the models that have been used to assess functions in the thymus, and models developed for other settings that can be potentially used for studying thymic DCs.

Background: Increased osteoclast activity constitutes the primary etiology of excessive bone erosion in postmenopausal osteoporosis. ERp57, otherwise referred to as protein disulfide isomerase A3 (PDIA3), plays a crucial role in the regulation of intracellular calcium signaling. This is documented to exert a profound impact on osteoclast differentiation and functionality. Methods: To ascertain the potential role of ERp57 in disease progression, prevention, and treatment, network pharmacology and bioinformatics analyses were conducted in relation to postmenopausal osteoporosis and ERp57 inhibitor (Loc14). Then, subsequent experimental verifications were employed in vitro on osteoclast and osteoblast, and in vivo on ovariectomy (OVX) mice models. Results: Multiple enrichment analyses suggested that the “calcium signaling pathway” may constitute a potential avenue for therapeutic intervention by Loc14 in the treatment of postmenopausal osteoporosis. In vitro experiments demonstrated inhibition of ERp57 could block osteoclast differentiation and function by interfering with the expression of osteoclast marker genes (Traf6, Nfatc1, and Ctsk). Further mechanisms studies based on calcium imaging, qPCR, and WB established that ERp57 inhibitor (Loc14) could obstruct calcium oscillation in osteoclast precursor cells (OPCs) by limiting the entry sources of cytosolic Ca2+ and interfering with calmodulin/calcineurin/Nfatc1 pathway. Evidence from Micro-CT scanning and double calcein labeling confirmed that the application of Loc14 in vivo could alleviate bone loss and partially reversed the osteogenic impairment caused by OVX in mice. Conclusions: Our findings proved the suppressive effects of Loc14 on osteoclastogenesis via attenuating calcium oscillation and associated singling pathways, providing ERp57 as a potential therapeutic target for postmenopausal osteoporosis.

Low temperature is one of the most important environmental factors that inhibits rice growth and grain yield. Transcription factors (TFs) play crucial roles in chilling acclimation by regulating gene expression. However, transcriptional dynamics and key regulators responding to low temperature remain largely unclear in rice. In this study, a transcriptome-based comparative analysis was performed to explore genome-wide gene expression profiles between a chilling-resistant cultivar DC90 and a chilling-susceptible cultivar 9311 at a series of time points under low temperature treatment and recovery condition. A total of 3,590 differentially expressed genes (DEGs) between two cultivars were determined and divided into 12 co-expression modules. Meanwhile, several biological processes participating in the chilling response such as abscisic acid (ABA) responses, water deprivation, protein metabolic processes, and transcription regulator activities were revealed. Through weighted gene co-expression network analysis (WGCNA), 15 hub TFs involved in chilling conditions were identified. Further, we used the gene regulatory network (GRN) to evaluate the top 50 TFs, which might have potential roles responding to chilling stress. Finally, five TFs, including a C-repeat binding factor (OsCBF3), a zinc finger-homeodomain protein (OsZHD8), a tandem zinc finger protein (OsTZF1), carbon starved anther (CSA), and indeterminate gametophyte1 (OsIG1) were identified as crucial candidates responsible for chilling resistance in rice. This study deepens our understanding in the gene regulation networks of chilling stress in rice and offers potential gene resources for breeding climate-resilient crops.

BackgroundThis study investigated the association between vasoactive medication exposure and mortality risk in patients with sepsis using the norepinephrine equivalent (NEE) score and vasoactive-inotropic score (VIS).MethodsThis retrospective cohort study included adult patients with sepsis requiring vasoactive agents. The data were extracted from the Medical Information Mart for Intensive Care IV database. The primary outcome was 28-day mortality. Multivariate Cox regression was used to elucidate the relationship between vasoactive medication exposure and 28-day mortality, as quantified by the VIS and NEE score. Hazard ratios with 95% confidence intervals (CI) for 28-day mortality were generated, and forest plots were constructed to present the results of univariate and multivariate analyses. The Kaplan–Meier method was used to analyze the cumulative incidence of 28-day mortality. A nomogram was constructed to predict the prognosis of patients with sepsis.ResultsThe present study encompassed 9,032 patients diagnosed with sepsis who received vasoactive therapy, of which 4,229 patients were further analyzed at the second hour after the onset of sepsis. Distinct variations in demographic data were observed between survivors (n = 3,265, 77.21%) and non-survivors (n = 964, 22.79%). Multivariate analysis indicated that several factors, including VIS >15.04 (p = 0.001), NEE >0.10 (p

Humic electron mediators can facilitate the reductive dehalogenation of organohalogenated compounds by accelerating electron transfer. To investigate the effect of humic electron mediators on the microbial anaerobic reductive dechlorination of Polychlorinated biphenyls (PCBs), three types of humic electron mediators, humin (HM), humic acid (HA), and anthraquinone-2,6-disulfonic acid (AQDS, HA analogs), were added to PCB dechlorination cultures enriched from different sources in terrestrial and marine environments (T and M cultures). The results showed that meta- and para-site dechlorination occurred in the M culture, while only meta-site dechlorination occurred in the T culture. The dechlorination process N and the dechlorination process H or H′ are presented in both cultures. HM enhanced PCB dechlorination metabolic activity in both cultures mainly by promoting meta-site dechlorination. HA showed a weak promoting effect on the M culture by promoting para-chlorine removal but inhibited the dechlorination metabolism of the terrestrial-origin culture, inhibiting meta-chlorine removal. AQDS showed inhibitory effects on both cultures by inhibiting the microbial removal of meta-chlorine. High-throughput sequencing and qPCR results suggest that HM is not a carbon source for the potential dechlorinating metabolism of Dehalococcoides but may promote reductive dechlorination by changing the community structure, and AQDS may inhibit anaerobic reductive dechlorination of PCBs by inhibiting the growth of Dehalococcoides. This study provides insights into the mechanism of enhancing PCB microbial dechlorination mediated by humic substances and plays a significant role in extending the application prospects of PCBs bioremediation technology.

Despite the rapid development of the application of tissue engineering techniques in regenerative bone repair, the repair of severe pathologic bone defects, represented by osteoporotic bone defects, is still a huge challenge. Recent studies have identified local delivery of parathyroid hormone relative peptides (PTHrPs) as a novel pathway for bone repair as well, but how to load and locally release PTHrPs for good bone repair is a major obstacle. Here, a biopolymer of PLGA-PLL loaded with PTHrP1 is electrospunned into nanofiber membranes for guided bone regeneration. In vitro experiments show that PLGA-PLL synergized with PTHrP1 significantly promote osteogenic differentiation and angiogenesis, providing a favorable bone regeneration microenvironment. In vivo experiments show that the membrane recruits endogenous stem cells and promotes their ectopic osteogenic differentiation in an osteoporotic environment. Furthermore, the membrane can promote osteogenic differentiation and angiogenesis in situ and improve the local osteoporotic microenvironment, ultimately promoting the repair of bone defects. Therefore, present study provides a promising strategy for local delivery of PTH, which opens a new pathway for the treatment of osteoporotic bone defects.