Risk factors for initial and recurrent severe infections in first hospitalized patients with systemic lupus erythematosus: A retrospective study of a Chinese cohort.

OBJECTIVE: To evaluate the incidence and associated factors of initial and recurrent severe infections in hospitalized patients with systemic lupus erythematosus (SLE). METHODS: SLE patients that first hospitalized between 2010 and 2021 were studied retrospectively and divided into SLE with and without baseline severe infection groups. The primary outcome was the occurrence of severe infection during follow-up. Cox regression models were used to calculate the hazard ratio (HR) and 95% confidence interval (CI) for initial and recurrent severe infections. RESULTS: Among 1051 first hospitalized SLE patients, 164 (15.6%) had severe infection on admission. During a median follow-up of 4.1 years, 113 (10.8%) patients reached severe infection outcomes, including 27 with reinfection and 86 with initial severe infection (16.5% vs. 9.7%, p = .010). Patients with baseline severe infection had a higher cumulative incidence of reinfection (p = .007). After adjusting for confounding factors, renal involvement, elevated serum creatinine, hypoalbuminemia, cyclophosphamide, and mycophenolate mofetil treatment were associated with an increased risk of severe infection, especially initial severe infection. Low immunoglobulin, anti-dsDNA antibody positivity, and cyclophosphamide use significantly increased the risk of recurrent severe infection, with adjusted HR (95% CI) of 3.15 (1.22, 8.14), 3.60 (1.56, 8.28), and 2.14 (1.01, 5.76), respectively. Moreover, baseline severe infection and low immunoglobulin had a multiplicative interaction on reinfection, with adjusted RHR (95% CI) of 3.91 (1.27, 12.09). CONCLUSION: In this cohort of SLE, patients with severe infection had a higher risk of reinfection, and low immunoglobulin, anti-dsDNA antibody positivity, and cyclophosphamide use were independent risk factors for recurrent severe infection.

Design, selective synthesis and biological activities evaluation of novel thiazol-2-ylbenzamide and thiazole-2-ylbenzimidoyl chloride derivatives.

To promote the development and exploitation of novel antifungal agents, a series of thiazol-2-ylbenzamide derivatives (3A-3V) and thiazole-2-ylbenzimidoyl chloride derivatives (4A-4V) were designed and selective synthesis. The bioassay results showed that most of the target compounds exhibited excellent in vitro antifungal activities against five plant pathogenic fungi (Valsa mali, Sclerotinia scleotiorum, Botrytis cinerea, Rhizoctonia solani and Trichoderma viride). The antifungal effects of compounds 3B (EC50 = 0.72 mg/L) and 4B (EC50 = 0.65 mg/L) against S. scleotiorum were comparable to succinate dehydrogenase inhibitors (SDHIs) thifluzamide (EC50 = 1.08 mg/L) and boscalid (EC50 = 0.78 mg/L). Especially, compounds 3B (EC50 = 0.87 mg/L) and 4B (EC50 = 1.08 mg/L) showed higher activity against R. solani than boscalid (EC50 = 2.25 mg/L). In vivo experiments in rice leaves revealed that compounds 3B (86.8 %) and 4B (85.3 %) exhibited excellent protective activities against R. solani comparable to thifluzamide (88.5 %). Scanning electron microscopy (SEM) results exhibited that compounds 3B and 4B dramatically disrupted the typical structure and morphology of R. solani mycelium. Molecular docking demonstrated that compounds 3B and 4B had significant interactions with succinate dehydrogenase (SDH). Meanwhile, SDH inhibition assay results further proved their potential as SDHIs. In addition, acute oral toxicity tests on A. mellifera L. showed only low toxicity for compounds 3B and 4B to A. mellifera L. populations. These results suggested that these two series of compounds had merit for further investigation as potential low-risk agricultural SDHI fungicides.

White adipose tissue, a novel antirheumatic target: Clues from its secretory capability and adipectomy-based therapy.

BACKGROUND AND PURPOSE: White adipose tissue (WAT) is involved in rheumatoid arthritis (RA). This study explored its potential as an antirheumatic target. EXPERIMENTAL APPROACH: WAT status of healthy and adjuvant-induced arthritis (AIA) rats were compared. The contribution of WAT to RA pathology was evaluated by pre-adipocyte transplant experiments and by dissecting perirenal fat pads of AIA rats. The impact of RA on WAT was investigated by culturing pre-adipocytes. Proteins differentially expressed in WAT of healthy and AIA rats were identified by the UPLC/MS2 method. These together with PPARγ siRNA and agonist were used to treat pre-adipocytes in vitro. The medium was used for THP-1 monocyte culture. KEY RESULTS: Compared with healthy controls, AIA WAT was smaller but secreted more leptin, eNAMPT, MCP-1, TNF-α, and IL-6. AIA rat pre-adipocytes increased the levels of these adipokines in healthy recipients. RA patients' serum induced a similar secretion change and impaired differentiation of pre-adipocytes. Adipectomy eased AIA-related immune abnormalities and arthritic manifestations. Hepatokines PON1, IGFBP4, and GPIHBP1 were among the differential proteins in high levels in RA blood, and induced inflammatory secretions by pre-adipocytes. GPIHBP1 inhibited PPARγ expression and caused differentiation impairment and inflammatory secretion by pre-adipocytes, a similar outcome to PPARγ-silencing. This endowed the cells with an ability to activate monocytes, which can be abrogated by rosiglitazone. CONCLUSION AND IMPLICATIONS: Certain hepatokines potentiate inflammatory secretions by pre-adipocytes and expedite RA progression by inhibiting PPARγ. Targeting this signalling or abnormal WAT secretion by various approaches may reduce RA severity.

Complex association of body mass index and outcomes in patients with relapsed and refractory multiple myeloma treated with CAR-T cell immunotherapy.

BACKGROUND AIMS: Chimeric antigen receptor-T (CAR-T) cells have exhibited remarkable efficacy in treating refractory or relapsed multiple myeloma (R/R MM). Although obesity has a favorable value in enhancing the response to immunotherapy, less is known about its predictive value regarding the efficacy and prognosis of CAR-T cell immunotherapy. METHODS: We conducted a retrospective study of 111 patients with R/R MM who underwent CAR-T cell treatment. Using the body mass index (BMI) classification, the patients were divided into a normal-weight group (73/111) and an overweight group (38/111). We investigated the effect of BMI on CAR-T cell therapy outcomes in patients with R/R MM. RESULTS: The objective remission rates after CAR-T cell infusion were 94.7% and 89.0% in the overweight and normal-weight groups, respectively. The duration of response and overall survival were not significant difference between BMI groups. Compared to normal-weight patients, overweight patients had an improved median progression-free survival. There was no significant difference in cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome between the subgroups. In terms of hematological toxicity, the erythrocyte, hemoglobin, platelet, leukocyte and neutrophil recovery was accelerated in the overweight group. Fewer patients in the overweight group displayed moderate percent CD4 and CD4/CD8 ratios compared to the normal-weight group. Furthermore, the percent CD4 ratios were positively correlated with the levels of cytokines [interleukin-2 (IL-2) (day 14), interferon gamma (IFN-γ) (day 7) and tumor necrosis factor alpha (TNF-α) (days 14 and 21)] after cells infusion. On the other hand, BMI was positively associated with the levels of IFN-γ (day 7) and TNF-α (days 14 and 21) after CAR-T cells infusion. CONCLUSIONS: Overall, this study highlights the potential beneficial effect of a higher BMI on CAR-T cell therapy outcomes.

A nomogram based on contrast-enhanced ultrasound for evaluating the glomerulosclerosis rate in transplanted kidneys.

Background: A high rate of glomerulosclerosis serves as an important signal of poor response to treatment and a high risk of disease progression or adverse prognosis in transplanted kidneys. We hypothesized that contrast-enhanced ultrasound (CEUS) could serve as a novel imaging biomarker in the early prediction of glomerulosclerosis rate by evaluating renal allograft microcirculation. Methods: A retrospective analysis was performed on 143 transplanted kidney recipients with confirmed pathology, including 100 in the training group and 43 in the validation group. All patients underwent conventional ultrasound (CUS) and CEUS examinations. The patients were divided into two groups: those with >50% glomerulosclerosis and those with ≤50% glomerulosclerosis. The nomograms derived from independent predictors identified by multivariate logistic analysis were assessed using receiver operating characteristic (ROC) curve analysis, 1,000 bootstrap resamples, calibration curves, and decision curve analysis (DCA). Results: The patients with >50% glomerulosclerosis and those with ≤50% glomerulosclerosis showed statistically significant differences in CEUS parameters, including in peak intensity (PI) (25 vs. 30; P<0.001), absolute time to peak (ATTP) (10 vs. 9; P=0.004), and time to peak (TTP) (22 vs. 19.5; P=0.026). Multivariate analysis revealed that PI [odds ratio (OR) =0.852; 95% confidence interval (CI): 0.737-0.986], peak systolic velocity (PSV) of the interlobar artery (OR =0.850; 95% CI: 0.758-0.954), cortical echogenicity (OR =38.429; 95% CI: 3.695-399.641), and time since transplantation (OR =1.017; 95% CI: 1.006-1.028) were independent predictors of whether the glomerulosclerosis rate was >50% and were incorporated into the construction of a nomogram. The area under the curve (AUC) of the nomogram in the training and validation groups was 0.914 (95% CI: 0.840-0.960) and 0.909 (95% CI: 0.781-0.975), respectively, with a bootstrap resampling AUC of 0.877. The calibration curve and DCA confirmed the diagnostic performance of the nomogram model. Conclusions: The nomogram, which combined CUS, CEUS, and clinical indicators, exhibited notable predictive efficacy for the glomerulosclerosis rate in transplanted kidneys, thereby demonstrating the potential to improve clinical decision-making.

Simultaneous quantification of six proteins related to liver injury using nano liquid chromatography-tandem mass spectrometry.

RATIONALE: In clinical diagnosis of liver injury, which is an important health concern, serum aminotransferase assays have been the go-to method used worldwide. However, the measurement of serum enzyme activity has limitations, including inadequate disease specificity and enzyme specificity. METHODS: With the high selectivity and specificity provided by nano liquid chromatography-tandem mass spectrometry (LC/MS/MS), this work describes a method for the simultaneous determination of six proteins in liver that can be potentially used as biomarkers for liver injury: glutamic-pyruvic transaminase 1 (GPT1), glutamic oxaloacetic transaminase 1 (GOT1), methionine adenosyl transferase 1A (MAT1A), glutathione peroxidase 1 (GPX1), cytokeratin 18 (KRT18) and apolipoprotein E (APOE). RESULTS: In validation, the method was shown to have good selectivity and sensitivity (limits of detection at pg/mL level). The analytical method revealed that, compared with normal mice, in carbon tetrachloride-induced acute liver injury mice, liver MAT1A and GPX1 were significantly lower (p < 0.01 and p < 0.05, respectively), KRT18 was significantly higher (p < 0.05) and APOE and GPT1 were marginally significantly lower (p between 0.05 and 0.1). This is the first work reporting the absolute contents of GPT1, GOT1, MAT1A, GPX1 and KRT18 proteins based on LC/MS. CONCLUSIONS: The proposed method provides a basis for establishing more specific diagnostic indicators of liver injury.

Light-Initiated Imprinted Membrane-Based Biomimetic SERS Sensor toward Selective Detection of Trace MC-LR.

Microcystin-LR (MC-LR) is a severe threat to human and animal health; thus, monitoring it in the environment is essential, especially in water quality protections. Herein, in this work, we synthesize PVDF/CNT/Ag molecular imprinted membranes (PCA-MIMs) via an innovative combination of surface-enhanced Raman spectroscopy (SERS) detection, membrane separation, and molecular-imprinted technique toward the analysis of MC-LR in water. In particular, a light-initiated imprint is employed to protect the chemical structure of the MC-LR molecules. Furthermore, in order to ensure the detection sensitivity, the SERS substrates are combined with the membrane via the assistance of magnetism. The effect of synthesis conditions on the SERS sensitivity was investigated in detail. It is demonstrated from the characteristic results that the PCA-MIMs present high sensitivity to the MC-LR molecules with excellent selectivity against the interfere molecules. Results clearly show that the as-prepared PCA-MIMs hold great potential applications to detect trace MC-LR for the protection of water quality.

A negative feedback loop between TET2 and leptin in adipocyte regulates body weight.

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.

In vitro suppression of porcine epidemic diarrhea virus by Panax notoginseng saponins: assessing antiviral potential.

Porcine epidemic diarrhea virus (PEDV) causes severe diarrhea and high mortality in neonatal suckling piglets, leading to significant economic losses to the swine industry. Panax notoginseng saponins (PNS) are bioactive extracts derived from the P. notoginseng plant. In this study, we investigated the anti-PEDV effect of PNS by employing various methodologies to assess their impact on PEDV in Vero cells. Using a CCK-8 (Cell Counting Kit-8) assay, we found that PNS had no significant cytotoxicity below the concentration of 128 µg/mL in Vero cells. Using immunofluorescence assays (IFAs), an enzyme-linked immunosorbent assay (ELISA), and plaque formation assays, we observed a dose-dependent inhibition of PEDV infection by PNS within 24-48 hours postinfection. PNS exerts its anti-PEDV activity specifically at the genome replication stage, and mRNA-seq analysis demonstrated that treatment with PNS resulted in increased expression of various genes, including IFIT1 (interferon-induced protein with tetratricopeptide repeats 1), IFIT3 (interferon-induced protein with tetratricopeptide repeats 3), CFH (complement factor H), IGSF10 (immunoglobulin superfamily member 10), ID2 (inhibitor of DNA binding 2), SPP1 (secreted phosphoprotein 1), PLCB4 (phospholipase C beta 4), and FABP4 (fatty acid binding protein 4), but it resulted in decreased expression of IL1A (interleukin 1 alpha), TNFRSF19 (TNF receptor superfamily member 19), CDH8 (cadherin 8), DDIT3 (DNA damage inducible transcript 3), GADD45A (growth arrest and DNA damage inducible alpha), PTPRG (protein tyrosine phosphatase receptor type G), PCK2 (phosphoenolpyruvate carboxykinase 2), and ADGRA2 (adhesion G protein-coupled receptor A2). This study provides insights into the potential mechanisms underlying the antiviral effects of PNS. Taken together, the results suggest that the PNS might effectively regulate the defense response to the virus and have potential to be used in antiviral therapies.

Dynamic Changes of Capsular-Intraocular Lens Adhesion in Plate-Haptic Hydrophilic and Loop-Haptic Hydrophobic Eyes.

INTRODUCTION: The aim of this work is to investigate the dynamic changes of capsular-intraocular lens (IOL) adhesion in plate-haptic hydrophilic and loop-haptic hydrophobic eyes. METHODS: Cataract eyes that met the inclusion criteria were randomly assigned to receive implantation of a plate-haptic hydrophilic or loop-haptic IOL. The anterior capsular adhesion, posterior capsular adhesion, and the configurations of the capsular bend were evaluated using swept-source optical coherence tomography at 1 day, 1 week, 1 month, and 3 months postoperatively. RESULTS: In total, 66 eyes of 66 patients were eligible for the analysis: 33 in the plate-haptic group and 33 in the loop-haptic group. The contact between the anterior capsule and IOL in the plate-haptic group was earlier than that in the loop-haptic group upon comparing the measurements taken at 1 day and 1 week (p = 0.001, p = 0.003, respectively). The complete attachment of the posterior capsule and IOL in the plate-haptic group was significantly greater at 1 week, 1 month, and 3 months (p = 0.001, p = 0.000, p = 0.001, respectively). The capsular bend index of the plate-haptic group was significantly greater than that of the loop-haptic group at each time points except at 1 day (p = 0.007, p = 0.049, p = 0.005, respectively). Furthermore, a new type of capsular bend, "cocked adhesion," was observed in the plate-haptic eyes. CONCLUSIONS: The plate-haptic IOL demonstrated excellent capsular adhesion compared to the loop-haptic IOL, which was probably attributed to haptic compressibility. A special cocked configuration of the capsular bend in plate-haptic IOL was observed for the first time. Further studies are warranted to confirm the effect of the new type of capsular bend.

BCAA-nitrogen flux in brown fat controls metabolic health independent of thermogenesis.

Brown adipose tissue (BAT) is best known for thermogenesis. Rodent studies demonstrated that enhanced BAT thermogenesis is tightly associated with increased energy expenditure, reduced body weight, and improved glucose homeostasis. However, human BAT is protective against type 2 diabetes, independent of body weight. The mechanism underlying this dissociation remains unclear. Here, we report that impaired mitochondrial catabolism of branched-chain amino acids (BCAAs) in BAT, by deleting mitochondrial BCAA carriers (MBCs), caused systemic insulin resistance without affecting energy expenditure and body weight. Brown adipocytes catabolized BCAA in the mitochondria as nitrogen donors for the biosynthesis of non-essential amino acids and glutathione. Impaired mitochondrial BCAA-nitrogen flux in BAT resulted in increased oxidative stress, decreased hepatic insulin signaling, and decreased circulating BCAA-derived metabolites. A high-fat diet attenuated BCAA-nitrogen flux and metabolite synthesis in BAT, whereas cold-activated BAT enhanced the synthesis. This work uncovers a metabolite-mediated pathway through which BAT controls metabolic health beyond thermogenesis.

Cell membrane vesicles derived from hBMSCs and hUVECs enhance bone regeneration.

Bone tissue renewal can be enhanced through co-transplantation of bone mesenchymal stem cells (BMSCs) and vascular endothelial cells (ECs). However, there are apparent limitations in stem cell-based therapy which hinder its clinic translation. Hence, we investigated the potential of alternative stem cell substitutes for facilitating bone regeneration. In this study, we successfully prepared cell membrane vesicles (CMVs) from BMSCs and ECs. The results showed that BMSC-derived cell membrane vesicles (BMSC-CMVs) possessed membrane receptors involved in juxtacrine signaling and growth factors derived from their parental cells. EC-derived cell membrane vesicles (EC-CMVs) also contained BMP2 and VEGF derived from their parental cells. BMSC-CMVs enhanced tube formation and migration ability of hUVECs, while EC-CMVs promoted the osteogenic differentiation of hBMSCs in vitro. Using a rat skull defect model, we found that co-transplantation of BMSC-CMVs and EC-CMVs could stimulate angiogenesis and bone formation in vivo. Therefore, our research might provide an innovative and feasible approach for cell-free therapy in bone tissue regeneration.

Resolvin D1 level during different trimesters of pregnancy for predicting the risk of fetal growth retardation in elderly pregnancy.

Resolvin D1 (RvD1) is potentially associated with fetal growth retardation (FGR) through alleviating maternal inflammation and its linkage with several pregnancy complications. Thus, this study detected RvD1 levels at different trimesters of pregnancy, aiming to investigate its role in predicting FGR risk of elderly pregnant women. This prospective, observational cohort study enrolled 165 elderly pregnant women aged ≥35 years. Serum RvD1 was detected at 10-13 weeks (early pregnancy), 20-23 weeks (middle pregnancy), and 30-33 weeks (late pregnancy) of gestational week by enzyme-linked immunosorbent assay. RvD1 was varied among different trimesters of pregnancy in elderly pregnant women (p < 0.001). FGR occurred in 25 (15.2%) women in this study. RvD1 at early (p = 0.009), middle (p = 0.002), and late (p = 0.003) pregnancy was decreased in women with FGR versus those without. By multivariate analysis, RvD1 at middle pregnancy (odds ratio (OR): 0.477, p < 0.001), pre-pregnancy body mass index (OR: 0.763, p = 0.025), and gestational diabetes mellitus (yes versus no) (OR: 0.071, p = 0.031) were independently correlated with declined FGR risk. While age (OR: 1.382, p = 0.009) was independently associated with elevated risk of FGR. Furthermore, the combination of these independent factors as a predictive model exhibited a good potential for assessing FGR risk (area under the curve: 0.802, 95% confidence interval: 0.711-0.894). In conclusion, RvD1 at different trimesters of pregnancy is negatively linked with the risk of FGR, whose level at middle pregnancy serves as an independent factor for FGR risk in elderly pregnant women.

Defective Lamtor5 Leads to Autoimmunity by Deregulating v-ATPase and Lysosomal Acidification.

Despite accumulating evidence linking defective lysosome function with autoimmune diseases, how the catabolic machinery is regulated to maintain immune homeostasis remains unknown. Late endosomal/lysosomal adaptor, MAPK and mTOR activator 5 (Lamtor5) is a subunit of the Ragulator mediating mechanistic target of rapamycin complex 1 (mTORC1) activation in response to amino acids, but its action mode and physiological role are still unclear. Here it is demonstrated that Lamtor5 level is markedly decreased in peripheral blood mononuclear cells (PBMCs) of patients with systemic lupus erythematosus (SLE). In parallel, the mice with myeloid Lamtor5 ablation developed SLE-like manifestation. Impaired lysosomal function and aberrant activation of mTORC1 are evidenced in Lamtor5 deficient macrophages and PBMCs of SLE patients, accompanied by blunted autolysosomal pathway and undesirable inflammatory responses. Mechanistically, it is shown that Lamtor5 is physically associated with ATP6V1A, an essential subunit of vacuolar H+-ATPase (v-ATPase), and promoted the V0/V1 holoenzyme assembly to facilitate lysosome acidification. The binding of Lamtor5 to v-ATPase affected the lysosomal tethering of Rag GTPase and weakened its interaction with mTORC1 for activation. Overall, Lamtor5 is identified as a critical factor for immune homeostasis by intergrading v-ATPase activity, lysosome function, and mTOR pathway. The findings provide a potential therapeutic target for SLE and/or other autoimmune diseases.

Exploring the causal relationship between female reproductive traits and frailty: a two-sample mendelian randomization study.

Background: The impact of female reproductive factors, including age at menarche (AAM), age at first birth (AFB), age at first sexual intercourse (AFS), age at natural menopause (ANM), and pregnancy abortion (PA), on the risk of developing frailty remains uncertain. Our objective is to examine the potential causal relationship between female reproductive traits and frailty through the utilization of two-sample univariable Mendelian Randomization (UVMR) and multivariable Mendelian Randomization (MVMR) analyses. Methods: Leveraging large-scale Genome-Wide Association Study (GWAS) data from individuals of European ancestry, we performed two-sample UVMR and MVMR analyses to examine the causal relationship between female reproductive traits and frailty. The primary analysis employed inverse-variance-weighted (IVW) estimation, and sensitivity analyses were conducted to assess the robustness of the findings. Results: The UVMR analysis revealed a significant causal relationship between female reproductive traits (AFS, AFB, AAM) and frailty [IVW: OR = 0.74, 95%CI(0.70-0.79), p = 0.000; OR = 0.93, 95%CI(0.92-0.95), p = 0.000; OR = 0.96, 95%CI(0.95-0.98), p = 0.000]. However, there was no significant effect of ANM and PA on frailty (p > 0.05). The sensitivity analysis results were robust, supporting the findings. Furthermore, this association remained significant even after adjusting for body mass index (BMI) and educational attainment (EA) in the MVMR analysis [IVW: OR = 0.94, 95%Cl (0.91-0.97), p = 0.000; OR = 0.77, 95%Cl (0.70-0.86), p = 0.000; OR = 0.95, 95%Cl (0.94-0.97), p = 0.000]. BMI and EA serve as mediators in this process. Conclusion: Our research has established a significant causal relationship between female reproductive traits (AFS, AFB, AAM) and frailty, with BMI and EA acting as mediating factors in this process. However, further research is warranted to validate our findings and elucidate the underlying biological mechanisms.

Stronger Coupling of Quantum Dots in Hole Transport Layer Through Intermediate Ligand Exchange to Enhance the Efficiency of PbS Quantum Dot Solar Cells.

Nowadays, the extensively used lead sulfide (PbS) quantum dot (QD) hole transport layer (HTL) relies on layer-by-layer method to replace long chain oleic acid (OA) ligands with short 1,2-ethanedithiol (EDT) ligands for preparation. However, the inevitable significant volume shrinkage caused by this traditional method will result in undesired cracks and disordered QD arrangement in the film, along with adverse increased defect density and inhomogeneous energy landscape. To solve the problem, a novel method for EDT passivated PbS QD (PbS-EDT) HTL preparation using small-sized benzoic acid (BA) as intermediate ligands is proposed in this work. BA is substituted for OA ligands in solution followed by ligand exchange with EDT layer by layer. With the new method, smoother PbS-EDT films with more ordered and closer QD packing are gained. It is demonstrated stronger coupling between QDs and reduced defects in the QD HTL owing to the intermediate BA ligand exchange. As a result, the suppressed nonradiative recombination and enhanced carrier mobility are achieved, contributing to ≈20% growth in short circuit current density (Jsc) and a 23.4% higher power conversion efficiency (PCE) of 13.2%. This work provides a general framework for layer-by-layer QD film manufacturing optimization.

Living Artificial Skin: Photosensitizer and Cell Sandwiched Bacterial Cellulose for Chronic Wound Healing.

Chronic wounds pose a significant global public health challenge due to their suboptimal treatment efficacy caused by bacterial infections and microcirculatory disturbances. Inspired by the biofunctionality of natural skin, an artificial skin (HV@BC@TBG) is bioengineered with bacterial cellulose (BC) sandwiched between photosensitizers (PS) and functionalized living cells. Glucose-modified PS (TBG) and vascular endothelial growth factor (VEGF)-functionalized living cells (HV) are successively modified on each side of BC through biological metabolism and bio-orthogonal reaction. As the outermost layer, the TBG layer can generate reactive oxygen species (ROS) upon light illumination to efficiently combat bacterial infections. The HV layer is the inner layer near the diabetic wound, which servs as a living factory to continuously secrete VEGF to accelerate wound repair by promoting fibroblast proliferation and angiogenesis. The sandwiched structural artificial skin HV@BC@TBG is nontoxic, biocompatible, and demonstrated its ability to significantly accelerate the healing process of infected diabetic wounds, rendering it a promising next-generation medical therapy for chronic wound management.

Potential of niacin skin flush response in adolescent depression identification and severity assessment: a case-control study.

BACKGROUND: The diagnosis of adolescent Depressive Disorder (DD) lacks specific biomarkers, posing significant challenges. This study investigates the potential of Niacin Skin Flush Response (NSFR) as a biomarker for identifying and assessing the severity of adolescent Depressive Disorder, as well as distinguishing it from Behavioral and Emotional Disorders typically emerging in childhood and adolescence(BED). METHODS: In a case-control study involving 196 adolescents, including 128 Depressive Disorder, 32 Behavioral and Emotional Disorders, and 36 healthy controls (HCs), NSFR was assessed. Depressive symptoms were measured using the Patient Health Questionnaire-9 (PHQ-9) and anxious symptoms with the Generalized Anxiety Disorder 7-item scale (GAD-7). Pearson correlation analysis determined the relationships between NSFR and the severity of depression in DD patients. Receiver Operating Characteristic (ROC) was used to identify DD from BED integrating NSFR data with clinical symptom measures. RESULTS: The adolescent Depressive Disorder group exhibited a higher rate of severe blunted NSFR (21.4%) compared to BED (12.5%) and HC ( 8.3%). Adolescent Depressive Disorder with psychotic symptoms showed a significant increase in blunted NSFR (p = 0.016). NSFR had negative correlations with depressive (r = -0.240, p = 0.006) and anxious (r = -0.2, p = 0.023) symptoms in adolescent Depressive Disorder. Integrating NSFR with three clinical scales improved the differentiation between adolescent Depressive Disorder and BED (AUC increased from 0.694 to 0.712). CONCLUSION: The NSFR demonstrates potential as an objective biomarker for adolescent Depressive Disorder, aiding in screening, assessing severity, and enhancing insights into its pathophysiology and diagnostic precision.

Using deep learning-based artificial intelligence electronic images in improving middle school teachers' literacy.

With the rapid development of societal information, electronic educational resources have become an indispensable component of modern education. In response to the increasingly formidable challenges faced by secondary school teachers, this study endeavors to analyze and explore the application of artificial intelligence (AI) methods to enhance their cognitive literacy. Initially, this discourse delves into the application of AI-generated electronic images in the training and instruction of middle school educators, subjecting it to thorough analysis. Emphasis is placed on elucidating the pivotal role played by AI electronic images in elevating the proficiency of middle school teachers. Subsequently, an integrated intelligent device serves as the foundation for establishing a model that applies intelligent classification and algorithms based on the Structure of the Observed Learning Outcome (SOLO). This model is designed to assess the cognitive literacy and teaching efficacy of middle school educators, and its performance is juxtaposed with classification algorithms such as support vector machine (SVM) and decision trees. The findings reveal that, following 600 iterations of the model, the SVM algorithm achieves a 77% accuracy rate in recognizing teacher literacy, whereas the SOLO algorithm attains 80%. Concurrently, the spatial complexities of the SVM-based and SOLO-based intelligent literacy improvement models are determined to be 45 and 22, respectively. Notably, it is discerned that, with escalating iterations, the SOLO algorithm exhibits higher accuracy and reduced spatial complexity in evaluating teachers' pedagogical literacy. Consequently, the utilization of AI methodologies proves highly efficacious in advancing electronic imaging technology and enhancing the efficacy of image recognition in educational instruction.

Constraints of Sedimentary Environment on Shale Organic Matter Enrichment: Insights from Elemental Geochemistry and Multiple Factor Analysis.

The organic-rich shale of the Wufeng-Longmaxi formation is an important section for shale gas exploration. The traditional univariate or bivariate analysis causes researchers to have great controversy about its enrichment mechanism. This study explores the combination of multiple factor analysis (MFA) and element geochemistry to calculate the contribution rate of a paleoenvironment to organic matter enrichment and clarify the main controlling factors of organic matter enrichment. Research has shown that there is generally high productivity from the Wufeng (O3w)-Longmaxi formation (S1l) deposition. The degree of terrigenous clastic input and weathering during the period of the O3w is relatively low, and sedimentary water restriction is strong, mainly developing an anoxic-dysoxic sedimentary environment. During the deposition of S1l1, the input intensity and weathering of terrigenous debris were slightly enhanced, and the increase of the water column led to the development of an anoxic environment at the bottom of the water layer. During the S1l2+3 period, the degree of terrigenous debris and weathering is the largest, and the high oxygen content of the water column is mainly a normal oxic environment. An MFA calculation shows that the paleoproductivity and paleoredox environment of the organic-rich shale section have the highest contribution rate of about 59.57% to the enrichment of organic matter, which is higher than that of paleoclimate conditions and terrigenous clastic input, indicating that the enrichment of organic matter is mainly controlled by paleoproductivity and the preservation environment. This study provides a basis for the application of MFA in element geochemistry and can serve as a model for other studies.