Mated-Atom Nanozymes with Efficient Assisted NAD+ Replenishment for Skin Regeneration.

Excessive accumulation of reduced nicotinamide adenine dinucleotide (NADH) within biological organisms is closely associated with many diseases. It remains a challenge to efficiently convert superfluous and detrimental NADH to NAD+. NADH oxidase (NOX) is a crucial oxidoreductase that catalyzes the oxidation of NADH to NAD+. Herein, M1M2 (Mi=V/Mn/Fe/Co/Cu/Mo/Rh/Ru/Pd, i = 1 or 2) mated-atom nanozymes (MANs) are designed by mimicking natural enzymes with polymetallic active centers. Excitingly, RhCo MAN possesses excellent and sustainable NOX-like activity, with Km-NADH (16.11 µM) being lower than that of NOX-mimics reported so far. Thus, RhCo MAN can significantly promote the regeneration of NAD+ and regulate macrophage polarization toward the M2 phenotype through down-regulation of TLR4 expression, which may help to recover skin regeneration. However, RhRu MAN with peroxidase-like activity and RhMn MAN with superoxide dismutase-like activity exhibit little modulating effects on eczema. This work provides a new strategy to inhibit skin inflammation and promote skin regeneration.

MitoAMPK inhibits the Warburg effect by MZF1-SIRT6 with glycosis related genes in NSCLC.

MitoAMPK was proved to inhibit the Warburg effect, but the specific mechanisms on non-small-cell lung cancer remain unclear. Here, we selected SIRT6 and MZF1 to clarify the mechanism. By western blotting, quantitative polymerase chain reaction, the CCK-8 assay, and immunohistochemistry assays, we found SIRT6 expression was lower in NSCLC tissues and cell lines than normal tissues and cells. Moreover, SIRT6 could inhibit the Warburg effect by regulating glycolysis-related genes of SLC2A2, SLC2A4 and PKM2. Finally, we demonstrated the interaction between SIRT6 and MZF1 using ChIP-qPCR. In conclusion, mitoAMPK inhibits the Warburg effect by regulating the expression of the MZF1-SIRT6 complex.

Analysis of Codon Usage Bias in the Plastid Genome of Diplandrorchis sinica (Orchidaceae).

In order to understand the bias and main affecting factors of codon usage in the plastid genome of Diplandrorchis sinica, which is a rare and endangered plant species in the Orchidaceae family, the complete plastid genome sequence of D. sinica was downloaded from the GenBank database and 20 protein-coding sequences that met the analysis requirements were finally selected. The GC content, length of the amino acid (Laa), relative synonymous codon usage (RSCU), and effective number of codon (ENC) of each gene and codon were calculated using the CodonW and EMBOSS online programs. Neutral plot analysis, ENC-plot analysis, PR2-plot analysis, and correspondence analysis were performed using Origin Pro 2024 software, and correlation analysis between various indicators was performed using SPSS 23.0 software. The results showed that the third base of the codon in the plastid genome of D. sinica was rich in A and T, with a GC3 content of 27%, which was lower than that of GC1 (45%) and GC2 (39%). The ENC value ranged from 35 to 57, with an average of 47. The codon usage bias was relatively low, and there was a significant positive correlation between ENC and GC3. There were a total of 32 codons with RSCU values greater than 1, of which 30 ended with either A or U. There were a total of nine optimal codons identified, namely, UCU, UCC, UCA, GCA, UUG, AUA, CGU, CGA, and GGU. This study indicated that the dominant factor affecting codon usage bias in the plastid genome of D. sinica was natural selection pressure, while the impact of base mutations was limited. The codon usage patterns were not closely related to gene types, and the distribution of photosynthetic system genes and ribosomal protein-coding gene loci was relatively scattered, indicating significant differences in the usage patterns of these gene codons. In addition, the codon usage patterns may not be related to whether the plant is a photosynthetic autotrophic or heterotrophic nutritional type. The results of this study could provide scientific references for the genomic evolution and phylogenetic research of plant species in the family Orchidaceae.

PDZK1 confers sensitivity to sunitinib in clear cell renal cell carcinoma by suppressing the PDGFR-ß pathway.

BACKGROUND: Sunitinib has emerged as the primary treatment for advanced or metastatic clear cell renal cell carcinoma (ccRCC) due to its significant improvement in patients' average survival time. However, drug resistance and adverse effects of sunitinib pose challenges to its clinical benefits. METHODS: The differentially expressed genes (DEGs) associated with sunitinib sensitivity and resistance in ccRCC were investigated. Cell counting kit-8, plate colony formation, flow cytometry and subcutaneous xenograft tumor model assays were employed to explore the effects of PDZK1 on ccRCC. Further research on the molecular mechanism was conducted through western blot, co-immunoprecipitation, immunofluorescence co-localization and immunohistochemical staining. RESULTS: We elucidated that PDZK1 is significantly downregulated in sunitinib-resistant ccRCC specimens, and PDZK1 negatively regulates the phosphorylation of PDGFR-ß and the activation of its downstream pathways through interaction with PDGFR-ß. The dysregulated low levels of PDZK1 contribute to inadequate inhibition of cell proliferation, tumor growth, and insensitivity to sunitinib treatment. Notably, our preclinical investigations showed that miR-15b antagomirs enhance sunitinib cytotoxic effects against ccRCC cells by upregulating PDZK1 levels, suggesting their potential in overcoming sunitinib resistance. CONCLUSIONS: Our findings establish the miR-15b/PDZK1/PDGFR-ß axis as a promising therapeutic target and a novel predictor for ccRCC patients' response to sunitinib treatment.

Detecting Cellular Microstructural Changes of Liver Fibrosis with Time-Dependent Diffusion MRI.

Background The potential of time-dependent diffusion MRI in imaging the progression from liver fibrosis to cirrhosis has not been established. Purpose To assess the effectiveness of time-dependent diffusion MRI in mapping the microstructure and characterizing cellular attributes during the progression of liver fibrosis to cirrhosis and to investigate its potential in grading liver fibrosis. Materials and Methods This prospective study, performed between December 2022 and October 2023, used 60 rats to establish a liver fibrosis model by means of diethylnitrosamine administration, with five additional rats serving as control animals. Time-dependent diffusion MRI was performed with equivalent diffusion time of 5.4, 10.7, and 69.3 msec on a 3.0-T scanner. Time-dependent diffusion MRI-based microstructural parameters, including cell diameter, intracellular volume fraction (ICVF), cellularity, and extracellular diffusivity, were estimated with use of the imaging microstructural parameters using limited spectrally edited diffusion, or IMPULSED, model. The fitted microstructural parameters were validated with histopathologic measurements. Results All 60 rats developed liver fibrosis, with a noticeable decrease in cell diameter and an increase in ICVF and cellularity observed as liver fibrosis progressed. The diameter measured at pathologic examination ranged from 11.4 µm to 35.4 µm, aligning with the range of 12.4-33.4 µm observed in time-dependent diffusion MRI, which indicated a strong correlation (r = 0.84; P < .001). The quantified ICVF at pathologic examination ranged from 0.28 to 0.89 and varied from 0.23 to 0.85 at time-dependent diffusion MRI, showing a high correlation (r = 0.62; P < .001). The cellularity observed at pathologic examination increased from 0.74 to 5.85, while the cellularity measured at time-dependent diffusion MRI ranged from 0.77 to 3.70, showing a correlation (r = 0.44; P < .001). Conclusion This study revealed the changes in quantitative microstructural mapping across the spectrum from liver fibrosis to cirrhosis. Cell diameter, ICVF, and cellularity are reliable markers for liver fibrosis, with diameter and ICVF presenting good discrimination ability. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Matos and Metens in this issue.

Long-term radiological and pulmonary function abnormalities at 3†years after COVID-19 hospitalisation: a longitudinal cohort study.

BACKGROUND: This study aimed to evaluate the longitudinal progression of residual lung abnormalities (ground-glass opacities, reticulation and fibrotic-like changes) and pulmonary function at 3 years following coronavirus disease 2019 (COVID-19). METHODS: This prospective, longitudinal cohort study enrolled COVID-19 survivors who exhibited residual lung abnormalities upon discharge from two hospitals. Follow-up assessments were conducted at 6 months, 12 months, 2 years and 3 years post-discharge, and included pulmonary function tests, 6-min walk distance (6MWD), chest computed tomography (CT) scans and symptom questionnaires. Non-COVID-19 controls were retrospectively recruited for comparative analysis. RESULTS: 728 COVID-19 survivors and 792 controls were included. From 6 months to 3 years, there was a gradual improvement in reduced diffusing capacity of the lung for carbon monoxide (D LCO <80% predicted: 49% versus 38%; p=0.001), 6MWD (496 versus 510 m; p=0.002) and residual lung abnormalities (46% versus 36%; p<0.001), regardless of disease severity. Patients with residual lung abnormalities at 3 years more commonly had respiratory symptoms (32% versus 16%; p<0.001), lower 6MWD (494 versus 510 m; p=0.003) and abnormal D LCO (57% versus 27%; p<0.001) compared with those with complete resolution. Compared with controls, the proportions of D LCO impairment (38% versus 17%; p<0.001) and respiratory symptoms (23% versus 2.2%; p<0.001) were significantly higher in the matched COVID-19 survivors at the 3-year follow-up. CONCLUSIONS: Most patients exhibited improvement in radiological abnormalities and pulmonary function over time following COVID-19. However, more than a third continued to have persistent lung abnormalities at the 3-year mark, which were associated with respiratory symptoms and reduced diffusion capacity.

Nanomaterials in 4D Printing: Expanding the Frontiers of Advanced Manufacturing.

As an innovative technology, four-dimentional (4D) printing is built upon the principles of three-dimentional (3D) printing with an additional dimension: time. While traditional 3D printing creates static objects, 4D printing generates "responsive 3D printed structures", enabling them to transform or self-assemble in response to external stimuli. Due to the dynamic nature, 4D printing has demonstrated tremendous potential in a range of industries, encompassing aerospace, healthcare, and intelligent devices. Nanotechnology has gained considerable attention owing to the exceptional properties and functions of nanomaterials. Incorporating nanomaterials into an intelligent matrix enhances the physiochemical properties of 4D printed constructs, introducing novel functions. This review provides a comprehensive overview of current applications of nanomaterials in 4D printing, exploring their synergistic potential to create dynamic and responsive structures. Nanomaterials play diverse roles as rheology modifiers, mechanical enhancers, function introducers, and more. The overarching goal of this review is to inspire researchers to delve into the vast potential of nanomaterial-enabled 4D printing, propelling advancements in this rapidly evolving field.

Color-Tunable Perovskite Nanomaterials with Intense Circularly Polarized Luminescence and Tailorable Compositions.

The ability to design halide perovskite nanocrystals (PNCs) with circularly polarized luminescence (CPL) offers exceptional potential in photonic technologies. Despite recent inspiring advances, the creation of PNCs with full-color tailorablity, outstanding CPL, and long-term stability remains a substantial challenge. Herein, a robust strategy to craft CPL-active PNCs is reported, exhibiting appealing full-color tunable wavelengths, enhanced CPL, and prolonged stability. In contrast to conventional methodologies, this strategy utilizes chiral nematic mesoporous silica (CNMS) as host to render in situ confined growth of diverse achiral PNCs. By strategically engineering photonic bandgap, adjusting loading amount of PNCs, and manipulating cations/anion compositions of PNCs, robust CPL responses with tunable wavelength and intensity are successfully obtained. The resulting PNCs-CNMS achieves stable CPL emissions with full-color tunability and impressive luminescent dissymmetric factors up to -0.17. Remarkably, silica-based hosts as a protective barrier confer exceptional resistance to humidity, photodegradation, and thermal stability, even up to 95 °C. Furthermore, the ability to achieve reversible CPL switching within PNCs-CNMS is attainable by leveraging the responsiveness of CNMS matrix or dynamic behavior of impregnated PNCs. Additionally, circularly polarized light-emitting diode devices based on PNCs-CNMS can be conveniently fabricated. This research affords a powerful platform for designing functional chiroptical materials.

ANGPTL3 is a novel HDL component that regulates HDL function.

BACKGROUND: Angiopoietin-like protein 3 (ANGPTL3) is secreted by hepatocytes and inhibits lipoprotein lipase and endothelial lipase activity. Previous studies reported the correlation between plasma ANGPTL3 levels and high-density lipoprotein (HDL). Recently ANGPTL3 was found to preferentially bind to HDL in healthy human circulation. Here, we examined whether ANGPTL3, as a component of HDL, modulates HDL function and affects HDL other components in human and mice with non-diabetes or type 2 diabetes mellitus. METHODS: HDL was isolated from the plasma of female non-diabetic subjects and type-2 diabetic mellitus (T2DM) patients. Immunoprecipitation, western blot, and ELISA assays were used to examine ANGPTL3 levels in HDL. Db/m and db/db mice, AAV virus mediated ANGPTL3 overexpression and knockdown models and ANGPTL3 knockout mice were used. The cholesterol efflux capacity induced by HDL was analyzed in macrophages preloaded with fluorescent cholesterol. The anti-inflammation capacity of HDL was assessed using flow cytometry to measure VCAM-1 and ICAM-1 expression levels in TNF-α-stimulated endothelial cells pretreated with HDL. RESULTS: ANGPTL3 was found to bind to HDL and be a component of HDL in both non-diabetic subjects and T2DM patients. Flag-ANGPTL3 was found in the HDL of transgenic mice overexpressing Flag-ANGPTL3. ANGPLT3 of HDL was positively associated with cholesterol efflux in female non-diabetic controls (r = 0.4102, p = 0.0117) but not in female T2DM patients (r = - 0.1725, p = 0.3224). Lower ANGPTL3 levels of HDL were found in diabetic (db/db) mice compared to control (db/m) mice and were associated with reduced cholesterol efflux and inhibition of VCAM-1 and ICAM-1 expression in endothelial cells (p < 0.05 for all). Following AAV-mediated ANGPTL3 cDNA transfer in db/db mice, ANGPTL3 levels were found to be increased in HDL, and corresponded to increased cholesterol efflux and decreased ICAM-1 expression. In contrast, knockdown of ANGPTL3 levels in HDL by AAV-mediated shRNA transfer led to a reduction in HDL function (p < 0.05 for both). Plasma total cholesterol, total triglycerides, HDL-c, protein components of HDL and the cholesterol efflux function of HDL were lower in ANGPTL3-/- mice than ANGPTL3+/+ mice, suggesting that ANGPTL3 in HDL may regulate HDL function by disrupting the balance of protein components in HDL. CONCLUSION: ANGPTL3 was identified as a component of HDL in humans and mice. ANGPTL3 of HDL regulated cholesterol efflux and the anti-inflammatory functions of HDL in T2DM mice. Both the protein components of HDL and cholesterol efflux capacity of HDL were decreased in ANGPTL3-/- mice. Our findings suggest that ANGPTL3 in HDL may regulate HDL function by disrupting the balance of protein components in HDL. Our study contributes to a more comprehensive understanding of the role of ANGPTL3 in lipid metabolism.

In Vivo Toxicology of Metabolizable Atomically Precise Au25 Clusters at Ultrahigh Doses.

Ultrasmall Au25(MPA)18 clusters show great potential in biocatalysts and bioimaging due to their well-defined, tunable structure and properties. Hence, in vivo pharmacokinetics and toxicity of Au nanoclusters (Au NCs) are very important for clinical translation, especially at high dosages. Herein, the in vivo hematological, tissue, and neurological effects following exposure to Au NCs (300 and 500 mg kg-1) were investigated, in which the concentration is 10 times higher than in therapeutic use. The biochemical and hematological parameters of the injected Au NCs were within normal limits, even at the ultrahigh level of 500 mg kg-1. Meanwhile, no histopathological changes were observed in the Au NC group, and immunofluorescence staining showed no obvious lesions in the major organs. Furthermore, real-time near-infrared-II (NIR-II) imaging showed that most of the Au25(MPA)18 and Au24Zn1(MPA)18 can be metabolized via the kidney. The results demonstrated that Au NCs exhibit good biosafety by evaluating the manifestation of toxic effects on major organs at ultrahigh doses, providing reliable data for their application in biomedicine.

Utility and predictive value of the CRAFITY score in advanced hepatocellular carcinoma treated with transarterial chemoembolization plus tyrosine kinase inhibitors and PD-1 inhibitor.

BACKGROUND: The prognostic significance of the CRAFITY score (CRP and AFP in ImmunoTherapY) has been demonstrated in hepatocellular carcinoma (HCC) patients receiving immunotherapy. The purpose of this study was to investigate the utility and the predictive value of CRAFITY score in HCC after transarterial chemoembolization (TACE) in combination with tyrosine kinase inhibitors (TKIs) and immunotherapy. MATERIALS AND METHODS: Data from patients with advanced HCC treated with TACE plus TKIs and PD-1 inhibitor from January 2019 to June 2022 were collected and analyzed retrospectively. Patients with AFP ≥ 100 ng/mL and those with CRP ≥ 1 mg/dL were assigned a CRAFITY score of 1 point. Patients were divided into three groups according to their CRAFITY score (CRAFITY-low, 0 points; CRAFITY-intermediate, 1 point; and CRAFITY-high, 2 points). The differences in overall survival (OS), progression-free survival (PFS) and adverse events (AEs) were compared among the three groups. Tumor response was evaluated at 3, 6 and 12 months after the first combination treatment. Risk factors for OS and PFS were assessed. RESULTS: A total of 70 patients were included. The patients were assigned CRAFITY scores of 0 points (CRAFITY-low, n = 25 [35.71%]), 1 point (CRAFITY-intermediate, n = 29 [41.42%]), and 2 points (CRAFITY-high, n = 16 [22.81%]). Multivariate analysis showed that lower CRAFITY score was an independent factor for the improved OS (P =.045) and PFS (P <.001). TACE session was also associated with the OS (P =.048) in the multivariate analysis. The CRAFITY-low cohort achieved a higher objective response rate (ORR) at the 3-month evaluation of tumor response. However, there was no significant difference in ORR and disease control rate (DCR) observed at the 6-month follow-up. DCR showed a statistically significant difference among three groups during the 12-month follow-up period. The percentage of patients with protein urea was highest in the CRAFITY-high group. No significance differences were observed in grade ≥ 3 AEs in three groups. CONCLUSION: The CRAFITY score is simple and could be useful for predicting treatment outcomes, tumor response and AEs of the HCC patients receiving TACE plus TKIs and PD-1 inhibitor therapy.

Improved Photovoltaic Performance of Inverted Two-Dimensional Perovskite Solar Cells via a Simple Molecular Bridge on Buried Interface.

NiOx-based two-dimensional perovskite solar cells (2D-PSCs) have the advantages of low fabrication temperature, suitable energy level matching, suppressed hysteresis, and superior stability, while the poor interfacial contacts between NiOx and perovskite layers limit the perovskite film growth and charge transfer. Herein, a simple molecule, urea, was used as a molecular modifier to form bifacial passivation on the buried interface of NiOx/perovskite, resulting in better interfacial contact and efficient bifacial passivation. We demonstrated that efficient bifacial passivation mainly comes from strong interactions between urea and NiOx or perovskite, which make urea a molecular bridge for smoother charge transfer. Moreover, urea can regulate the ratio of Ni3+/Ni2+, therefore boosting the conductivity of NiOx, and adjust the morphology of the NiOx film for better 2D-perovskite crystal growth. Besides, urea also passivates the bifacial defect states of both NiOx and perovskite film, yielding reduced defect density of the perovskite film and superior charge transfer on the buried interface. Consequently, inverted 2D-PSCs with urea modification proved significant improvements in short-circuit current density and fill factor, resulting in improved power conversion efficiency from 14.64 to 16.84% with better stability in air.

Vanillic acid restores homeostasis of intestinal epithelium in colitis through inhibiting CA9/STIM1-mediated ferroptosis.

The damage of integrated epithelial epithelium is a key pathogenic factor and closely associated with the recurrence of ulcerative colitis (UC). Here, we reported that vanillic acid (VA) exerted potent therapeutic effects on DSS-induced colitis by restoring intestinal epithelium homeostasis via the inhibition of ferroptosis. By the CETSA assay and DARTS assay, we identified carbonic anhydrase IX (CAIX, CA9) as the direct target of VA. The binding of VA to CA9 causes insulin-induced gene-2 (INSIG2) to interact with stromal interaction molecule 1 (STIM1), rather than SREBP cleavage-activating protein (SCAP), leading to the translocation of SCAP-SREBP1 from the endoplasmic reticulum (ER) to the Golgi apparatus for cleavage into mature SREBP1. The activation of SREBP1 induced by VA then significantly facilitated the transcription of stearoyl-CoA desaturase 1 (SCD1) to exert an inhibitory effect on ferroptosis. By inhibiting the excessive death of intestinal epithelial cells caused by ferroptosis, VA effectively preserved the integrity of intestinal barrier and prevented the progression of unresolved inflammation. In conclusion, our study demonstrated that VA could alleviate colitis by restoring intestinal epithelium homeostasis through CA9/STIM1-mediated inhibition of ferroptosis, providing a promising therapeutic candidate for UC.

Evaluating tuberculosis knowledge and awareness of effective control practices among health care workers in primary- and secondary-level medical institutions in Beijing, China.

OBJECTIVE: Inadequate tuberculosis (TB) knowledge and awareness of proper TB control practices among health care workers (HCWs) may increase the risk of nosocomial TB transmission. This study aimed to assess HCWs' TB-related knowledge and control practices to guide the development of more effective targeted TB health education and training programs. METHODS: In January 2023 a cross-sectional survey was administered to 323 HCWs employed by five primary health care centers and three secondary comprehensive medical institutions in Beijing, China. Survey data were collected using a standard questionnaire. RESULTS: Analysis of survey responses revealed TB knowledge and practices awareness rates of 60.4% and 90.6%, respectively. The overall average awareness rate across all 19 TB knowledge- and practice-related questions was 70.0%. Intermediate- and senior-level HCW's average TB knowledge score was respectively 2.225 and 8.175 times higher than that of primary-level HCWs, while the average TB knowledge score of HCWs in secondary comprehensive medical institutions was 3.052 times higher than that of HCWs in primary health care centers. Higher average TB knowledge score correlated with higher-level professional titles and higher level work units, but higher average TB control practices score correlated with employment at primary health care center rather than secondary comprehensive medical institution. Notably, 13.6% of HCWs had not received TB training during the past three years, while 86.1% expressed willingness to undergo online TB training. CONCLUSION: These findings highlight inadequate TB knowledge and awareness of proper TB control practices among HCWs in primary health care centers and secondary comprehensive medical institutions in Beijing, underscoring the urgent need for targeted educational and training initiatives to improve TB awareness and control efforts.

Treatment outcomes of retreated patients with isoniazid/rifampicin resistant pulmonary tuberculosis.

BACKGROUND: About 8% of TB cases worldwide are estimated to have rifampicin-susceptible, isoniazid-resistant tuberculosis (Hr-TB), ranging from 5 to 11% regions. However, Hr-TB has not received much attention while comparing to be given high priority to the management of rifampicin-resistant tuberculosis (RR-TB). This study aimed to compare the differences of treatment effects for Hr-TB and RR-TB, so as to intensify the treatment and management of Hr-TB. METHODS: A retrospective study was used to collect bacteriologically positive retreated patients with isoniazid/rifampicin resistant pulmonary tuberculosis, who were conducted at 29 tuberculosis control institutions in China from July 2009 to June 2021. We assessed effectiveness and safety of retreated patients with isoniazid/ rifampicin resistant pulmonary tuberculosis. RESULTS: A total of 147 with either positive smear or cultures were enrolled, and 80 cases were in Hr-TB group and 67 cases were in RR-TB group. There was no significant difference in terms of age, sex, body mass, type of retreatment and comorbid diabetes between the two groups (P > 0.05). The rate of number of lesions involving lung fields ≥ 3 in Hr-TB group 75.9% (60/79) was significantly higher than RR-TB group 56.7% (38/67) (χ2 = 6.077, P = 0.014). There was no statistically significant difference (P = 0.166) with regard to the treatment outcomes of the two groups, the cure rates were 54.7% (41/75) and 53.6% (30/56), respectively, and the failure rate in Hr-TB group 22.7% (17/75) was 10% higher than RR-TB group 10.7% (6/56). The rate of negative sputum smear at the end of the second month (65.7%) in the Hr-TB group was significantly lower than that in the RR-TB group (85.7%) (P = 0.025). There were no significant differences in the incidences of serious adverse reactions and chest X-ray changes between the two groups (P > 0.05). During the 5-year follow-up, recurrence in the Hr-TB group (7 cases, 14.9%) was no significantly lower than that in the RR-TB group (4 cases, 11.8%) (P = 0.754). CONCLUSION: The treatment of retreated Hr-TB patients was difficult and could be statistically similar or considerably worse than RR-TB. It's urgent to conduct further evaluation of the treatment status quo to guide the guideline development and clinical practice of Hr-TB patients.

Blocking the TRAIL-DR5 Pathway Reduces Cardiac Ischemia-Reperfusion Injury by Decreasing Neutrophil Infiltration and Neutrophil Extracellular Traps Formation.

PURPOSE: Acute myocardial infarction (AMI) is a leading cause of mortality. Neutrophils penetrate injured heart tissue during AMI or ischemia-reperfusion (I/R) injury and produce inflammatory factors, chemokines, and extracellular traps that exacerbate heart injury. Inhibition of the TRAIL-DR5 pathway has been demonstrated to alleviate cardiac ischemia-reperfusion injury in a leukocyte-dependent manner. However, it remains unknown whether TRAIL-DR5 signaling is involved in regulating neutrophil extracellular traps (NETs) release. METHODS: This study used various models to examine the effects of activating the TRAIL-DR5 pathway with soluble mouse TRAIL protein and inhibiting the TRAIL-DR5 signaling pathway using DR5 knockout mice or mDR5-Fc fusion protein on NETs formation and cardiac injury. The models used included a co-culture model involving bone marrow-derived neutrophils and primary cardiomyocytes and a model of myocardial I/R in mice. RESULTS: NETs formation is suppressed by TRAIL-DR5 signaling pathway inhibition, which can lessen cardiac I/R injury. This intervention reduces the release of adhesion molecules and chemokines, resulting in decreased neutrophil infiltration and inhibiting NETs production by downregulating PAD4 in neutrophils. CONCLUSION: This work clarifies how the TRAIL-DR5 signaling pathway regulates the neutrophil response during myocardial I/R damage, thereby providing a scientific basis for therapeutic intervention targeting the TRAIL-DR5 signaling pathway in myocardial infarction.

Brain connectivity modulation by Bayesian surprise in relation to control demand drives cognitive flexibility via control engagement.

Human control is characterized by its flexibility and adaptability in response to the conditional probability in the environment. Previous studies have revealed that efficient conflict control could be attained by predicting and adapting to the changing control demand. However, it is unclear whether cognitive flexibility could also be gained by predicting and adapting to the changing control demand. The present study aimed to explore this issue by combining the model-based analyses of behavioral and neuroimaging data with a probabilistic cued task switching paradigm. We demonstrated that the Bayesian surprise (i.e. unsigned precision-weighted prediction error [PE]) negatively modulated the connections among stimulus processing brain regions and control regions/networks. The effect of Bayesian surprise modulation on these connections guided control engagement as reflected by the control PE effect on behavior, which in turn facilitated cognitive flexibility. These results bridge a gap in the literature by illustrating the neural and behavioral effect of control demand prediction (or PE) on cognitive flexibility and offer novel insights into the source of switch cost and the mechanism of cognitive flexibility.

Research on the application of heterotrophic nitrification-aerobic denitrification bacteria in membrane bioreactor (MBR).

Inoculating heterotrophic nitrification-aerobic denitrification bacteria (HN-AD) to enhance membrane bioreactor (MBR) efficiency may result in the loss of functional bacteria. Therefore, this study compares the application results of enhancing MBR with a self-designed biological amplifier coupled with HN-AD against the performance of conventional MBR. After enhancement, the MBR achieved a removal efficiency of 96.7% for NH4+-N (100 mg/L) and 96.4% for COD (400 mg/L) in synthetic wastewater. There was a 33% increase in TN (100 mg/L) removal efficiency. The dominant bacteria in the MBR were Alcaligenes (48.4%) and Thauera (15.2%). Additionally, the abundance of denitrification genes (nirK, norB, nosZ) increased in the enhanced MBR, contributing to improved TN removal efficiency. The use of a biological amplifier effectively solved the problem of HN-AD loss in sewage treatment.

Gestational diabetes mellitus affects the differentiation of hematopoietic stem cells in neonatal umbilical cord blood.

PURPOSE: There are abundant hematopoietic stem cells (HSCs) in cord blood. It is known that HSCs continue to differentiate to CLP, CMP and erythroid progenitor cells (EPC), EPC ultimately differentiated to platelets and erythrocytes. It has been reported that the proportion of HSCs in cord blood was higher than that in healthy pregnant women, so as the incidence of neonatal polycythemia in gestational diabetes mellitus (GDM) patients. We aimed to investigate whether the hyperglycemic and/or hyperinsulin environment in GDM patients has effects on the differentiation of HSCs into erythrocytes in offspring cord blood. METHODS: In this study, we collected cord blood from 23 GDM patients and 52 healthy pregnant women at delivery. HSCs, CLP, CMP and EPCs in cord blood of the two groups were identified and quantified by flow cytometry. HSCs were sorted out and treated with glucose and insulin, respectively, and then, the changes of HSCs proliferation and differentiation were detected. RESULTS: Compared to healthy controls, HSCs, CMP and EPC numbers in cord blood from GDM group were significantly increased, while CLP cell number was decreased. The differentiation of HSCs into EPC was promoted after treatment with glucose or insulin. CONCLUSION: There were more HSCs in the cord blood of GDM group, and the differentiation of HSCs to EPCs was increased. These findings were probably caused by the high-glucose microenvironment and insulin medication in GDM patients, and the HSCs differentiation changes might be influencing factors of the high incidence of neonatal erythrocytosis in GDM patients.

Two-Dimensional Artificial Ge Superlattice Confining in Electronic Kagome Lattice Potential Valleys.

Constructing two-dimensional (2D) artificial superlattices based on single-atom and few-atom nanoclusters is of great interest for exploring exotic physics. Here we report the realization of two types of artificial germanium (Ge) superlattice self-confined by a 37×37 R25.3° superstructure of bismuth (Bi) induced electronic kagome lattice potential valleys. Scanning tunneling microscopy measurements demonstrate that Ge atoms prefer to be confined in the center of the Bi electronic kagome lattice, forming a single-atom superlattice at 120 K. In contrast, room temperature grown Ge atoms and clusters are confined in the sharing triangle corner and the center, respectively, of the kagome lattice potential valleys, forming an artificial honeycomb superlattice. First-principle calculations and Mulliken population analysis corroborate that our reported atomically thin Bi superstructure on Au(111) has a kagome surface potential valley with the center of the inner Bi hexagon and the space between the outer Bi hexagons being energetically favorable for trapping Ge atoms.