Combining experiment and energy landscapes to explore anaerobic heme breakdown in multifunctional hemoproteins.

To survive, many pathogens extract heme from their host organism and break down the porphyrin scaffold to sequester the Fe2+ ion via a heme oxygenase. Recent studies have revealed that certain pathogens can anaerobically degrade heme. Our own research has shown that one such pathway proceeds via NADH-dependent heme degradation, which has been identified in a family of hemoproteins from a range of bacteria. HemS, from Yersinia enterocolitica, is the main focus of this work, along with HmuS (Yersinia pestis), ChuS (Escherichia coli) and ShuS (Shigella dysenteriae). We combine experiments, Energy Landscape Theory, and a bioinformatic investigation to place these homologues within a wider phylogenetic context. A subset of these hemoproteins are known to bind certain DNA promoter regions, suggesting not only that they can catalytically degrade heme, but that they are also involved in transcriptional modulation responding to heme flux. Many of the bacterial species responsible for these hemoproteins (including those that produce HemS, ChuS and ShuS) are known to specifically target oxygen-depleted regions of the gastrointestinal tract. A deeper understanding of anaerobic heme breakdown processes exploited by these pathogens could therefore prove useful in the development of future strategies for disease prevention.

1 × 2 mode-independent polymeric thermo-optic switch based on a Mach-Zehnder interferometer with a multimode interferometer.

We present the design and performances of a broadband 1 × 2 mode-independent thermo-optic (TO) switch based on Mach-Zehnder interferometer (MZI) with multimode interferometer (MMI). The MZI adopts a Y-branch structure as the 3-dB power splitter and a MMI as the coupler, which are designed to be insensitive to the guided modes. By optimizing the structural parameters of the waveguides, mode-independent transmission and switching functions for E11 and E12 modes can be implemented in the C + L band, and the mode content of the outputs is the same as the mode content of the inputs. We proved the working principle of our design based on polymer platform, which was fabricated by using ultraviolet lithography and wet-etching methods. The transmission characteristics for E11 and E12 modes were also analyzed. With the driving power of 5.9 mW, the measured extinction ratios of the switch for E11 and E12 modes are larger than 13.3 dB and 13.1 dB, respectively, over a wavelength range of 1530 nm to 1610 nm. The insertion losses of the device are 11.7 dB and 14.2 dB for E11 and E12 modes, respectively, at 1550 nm wavelength. The switching times of the device are less than 840 µs. The presented mode-independent switch can be applied in reconfigurable mode-division multiplexing systems.

Mode-independent thermo-optic switch based on the total-internal-reflection effect.

A broadband mode-independent thermo-optic (TO) switch using the total-internal-reflection (TIR) effect is proposed and experimentally demonstrated on a polymer waveguide platform. By optimizing geometric parameters of the TIR switch, a mode-independent TO switching function with a large bandwidth and extinction ratio can be realized for E11, E12, and E21 modes. The measurement results show an extinction ratio larger than 18.1 dB with a driving power of 160 mW for each mode over the wavelength range of 1500-1620 nm. The designed structure can also be cascaded to form a 1 × N switch network for mode-division multiplexing (MDM) systems, which greatly improves the network flexibility.

Multimode optical switch based on cascaded Mach-Zehnder interferometer waveguides.

We present a 1 × 1 multimode optical switch for E11, E21, E12, and E22 modes based on cascaded Mach-Zehnder interferometer (MZI) waveguides, where the primary MZI is used to split E11, E21, E12, and E22 modes into E11 or E12 mode and then couple back to the original mode at the output, and the secondary MZIs are the modulation arms of the primary MZI. In addition, the secondary MZIs are designed to be mode-insensitive for switching E11 and E12 modes simultaneously. As a proof of concept, we fabricate the device with polymer material to achieve thermo-optic switching for the four modes. Our experimental device exhibits the extinction ratios of larger than 10.2 dB with a power consumption of 5.5 mW and response times of less than 1.28 ms for each mode. The presented device can be widely applied in mode-division multiplexing (MDM) systems where multimode switching is needed.

A new scheme of global feature management improved the performance and stability of radiomics model: a study based on CT images of acute brainstem infarction.

OBJECTIVE: The performance and stability of radiomics model caused by dimension reduction remain being confronted with major challenges. In this study, we aimed to propose a new scheme of global feature management independent of dimension reduction to improve it. METHODS: The non-contrast computed tomography (NCCT) images of acute brainstem infarction (ABI) from two medical centers were used as test and validation sets. A new scheme was constructed based on global feature management, and the traditional scheme dependent on dimension reduction was used as control. The radiomic features of NCCT images were extracted in Matlab R2013a. The performance of prediction model was evaluated by the generalized linear model (GLM) and multivariate logistic regression. And, the stability of radiomics model was evaluated with the difference of area under curve (AUC) between the test and validation sets. RESULTS: Compared with the traditional scheme, the new scheme presented a similar detection performance (AUC: 0.875 vs. 0.883), yet a better performance in predicting prognosis (AUC: 0.864, OR = 0.917, p = 0.021 vs. AUC:0.806, OR = 0.972, p = 0.007). All these results were well verified in an independent validation set. Moreover, the new scheme showed stronger stability in both the detection model (ΔAUC: 0.013 vs. 0.039) and prediction model (ΔAUC = 0.004 vs. 0.044). CONCLUSION: Although there might be several limitations, this study proved that the scheme of global feature management independent of dimension reduction could be a powerful supplement to the radiomics methodology. KEY POINTS: • The new scheme (Swavelet) presented similar detection performances for ABI with the traditional scheme. • A better predictive performance for END was found in the new scheme (Swavelet) compared with the traditional scheme. • Stronger model stability was found in both the detection and prediction models based on the new scheme.

Neuron secrete exosomes containing miR-9-5p to promote polarization of M1 microglia in depression.

BACKGROUND: Neuroinflammation is an important component mechanism in the development of depression. Exosomal transfer of MDD-associated microRNAs (miRNAs) from neurons to microglia might exacerbate neuronal cell inflammatory injury. RESULTS: By sequence identification, we found significantly higher miR-9-5p expression levels in serum exosomes from MDD patients than healthy control (HC) subjects. Then, in cultured cell model, we observed that BV2 microglial cells internalized PC12 neuron cell-derived exosomes while successfully transferring miR-9-5p. MiR-9-5p promoted M1 polarization in microglia and led to over releasing of proinflammatory cytokines, such as interleukin-1ß (IL-1ß), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), which exacerbated neurological damage. Furthermore, we identified suppressor of cytokine signaling 2 (SOCS2) as a direct target of miR-9-5p. Overexpression of miR-9-5p suppressed SOCS2 expression and reactivated SOCS2-repressed Janus kinase (JAK)/signal transducer and activator of transcription 3 (STAT3) pathways. Consistently, we confirmed that adeno-associated virus (AAV)-mediated overexpression of miR-9-5p polarized microglia toward the M1 phenotype and exacerbated depressive symptoms in chronic unpredictable mild stress (CUMS) mouse mode. CONCLUSION: MiR-9-5p was transferred from neurons to microglia in an exosomal way, leading to M1 polarization of microglia and further neuronal injury. The expression and secretion of miR-9-5p might be novel therapeutic targets for MDD.

The Application of Metal-Organic Frameworks in Water Treatment and Their Large-Scale Preparation: A Review.

Over the last few decades, there has been a growing discourse surrounding environmental and health issues stemming from drinking water and the discharge of effluents into the environment. The rapid advancement of various sewage treatment methodologies has prompted a thorough exploration of promising materials to capitalize on their benefits. Metal-organic frameworks (MOFs), as porous materials, have garnered considerable attention from researchers in recent years. These materials boast exceptional properties: unparalleled porosity, expansive specific surface areas, unique electronic characteristics including semi-conductivity, and a versatile affinity for organic molecules. These attributes have fueled a spike in research activity. This paper reviews the current MOF-based wastewater removal technologies, including separation, catalysis, and related pollutant monitoring methods, and briefly introduces the basic mechanism of some methods. The scale production problems faced by MOF in water treatment applications are evaluated, and two pioneering methods for MOF mass production are highlighted. In closing, we propose targeted recommendations and future perspectives to navigate the challenges of MOF implementation in water purification, enhancing the efficiency of material synthesis for environmental stewardship.

A sodium carboxymethyl cellulose-induced emission and gelation system for time-dependent information encryption and anti-counterfeiting.

Many lanthanide complexes do not form gel or even exhibit characteristic luminescence of lanthanide ions, which limits their applications in many fields. Therefore, there is an urgent need for a third component that can not only promote emission but also gel the lanthanide complex system to construct new smart materials such as time-dependent information encryption and anti-counterfeiting materials. Herein, a luminescent lanthanide metallogel was successfully prepared by using the third component sodium carboxymethyl cellulose (NaCMC) to induce the gelation and luminescence of the complex (H3L/Tb3+) of 4,4',4″-((benzene-1,3,5-tricarbonyl)tris(azanediyl)) tris(2-hydroxybenzoic acid) (H3L) and Tb3+. The H3L/Tb3+ complex itself does not form gel and has no characteristic luminescence of Tb3+. Moreover, the multicolor emission of H3L/Tb3+/NaCMC gels was prepared based on Förster resonance energy transfer (FRET) platforms to obtain a high-security level information encryption and anti-counterfeiting materials. These multicolor emission gels exhibit emission color tunability with time dependence due to the different energy transfer efficiencies at each pH node controlled by glucono-δ-lactone hydrolysis time. Based on the time response characteristics, the time-dependent information encryption and anti-counterfeiting materials are developed.

Giant Parotid Abscess With Significant Skin Necrosis: A Case Report.

Poor blood glucose control is a common predisposing factor for parotid abscesses; however, extensive skin necrosis secondary to parotid abscesses has rarely been reported. In this article, we present the case of a 70-year-old man with poor glycemic control admitted to our hospital with swelling, congestion, and pain in the right parotid region that had gradually increased over 15 days prior to presentation. Based on the clinical, imaging, and laboratory findings, the patient was diagnosed with a giant parotid abscess with extensive skin necrosis caused by Klebsiella pneumoniae. The abscess responded poorly to long-term treatment with intravenous broad-spectrum antibiotics, and the patient underwent daily Bacillus exchange with blood glucose level management and electrolyte monitoring via routine blood tests. At the 3 month follow-up, complete resolution of the right parotid gland abscess and skin rupture was observed.

Development and Validation of a Pathomics Model Using Machine Learning to Predict CXCL8 Expression and Prognosis in Head and Neck Cancer.

OBJECTIVES: The necessity to develop a method for prognostication and to identify novel biomarkers for personalized medicine in patients with head and neck squamous cell carcinoma (HNSCC) cannot be overstated. Recently, pathomics, which relies on quantitative analysis of medical imaging, has come to the forefront. CXCL8, an essential inflammatory cytokine, has been shown to correlate with overall survival (OS). This study examined the relationship between CXCL8 mRNA expression and pathomics features and aimed to explore the biological underpinnings of CXCL8. METHODS: Clinical information and transcripts per million mRNA sequencing data were obtained from The Cancer Genome Atlas (TCGA)-HNSCC dataset. We identified correlations between CXCL8 mRNA expression and patient survival rates using a Kaplan-Meier survival curve. A retrospective analysis of 313 samples diagnosed with HNSCC in the TCGA database was conducted. Pathomics features were extracted from hematoxylin and eosin-stained images, and then the minimum redundancy maximum relevance, with recursive feature elimination (mRMR-RFE) method was applied, followed by screening with the logistic regression algorithm. RESULTS: Kaplan-Meier curves indicated that high expression of CXCL8 was significantly associated with decreased OS. The logistic regression pathomics model incorporated 16 radiomics features identified by the mRMR-RFE method in the training set and demonstrated strong performance in the testing set. Calibration plots showed that the probability of high gene expression predicted by the pathomics model was in good agreement with actual observations, suggesting the model's high clinical applicability. CONCLUSION: The pathomics model of CXCL8 mRNA expression serves as an effective tool for predicting prognosis in patients with HNSCC and can aid in clinical decision-making. Elevated levels of CXCL8 expression may lead to reduced DNA damage and are associated with a pro-inflammatory tumor microenvironment, offering a potential therapeutic target.

A sulfur-modified pore-blocking method to enhance the electrocatalytic stability of carbon-supported platinum nanoparticles.

Currently, the durability of electrode materials remains a big obstacle to the widespread adoption of proton exchange membrane fuel cells (PEMFCs). Herein thiourea and sodium dodecyl benzene sulfonate (SDS) were employed as sulfur source and carbon source to modify the pristine carbon black (Ketjen black EC300 J). A highly durable carbon supported Pt nanosized catalyst with higher platinum utilization for oxygen reduction reaction (ORR) in PEMFCs was produced by doping elemental sulfur into carbon supports and decreasing the carbon pore sizes and volume through a successive impregnation technique. The catalyst exhibits an initial activity of 0.167 A mgPt -1 at 0.90 V and demonstrates minimal activity loss after acceleration stress test (30,000 cycles of AST). The half-wave potential loss for representative sample (Pt/S-C-3) is only 14 mV with only 21.8 % ECSA decrease, 27.5 % MA loss and 5.9 % SA loss. A sintering test at various temperature shows a minor average size increase for sulfur-doped carbon (S-C) supported one (from 2.09 to 2.52 nm). In single-cell test, the MEA sample employing the platinum catalyst on modified carbon as cathode exhibited almost negligible performance loss after 30,000 cycles of AST.

Squaramide-catalyzed enantioselective Michael addition of nitromethane to 2-enoylazaarenes: synthesis of chiral azaarene-containing γ-nitroketones.

Bifunctional chiral squaramide-catalyzed highly enantioselective Michael addition of nitromethane to diverse 2-enoylazaarenes was successfully performed. This protocol provided a set of chiral azaarene-containing γ-nitroketones with up to 98% yield and 98% ee in a solvent-free catalytic system under mild conditions. Furthermore, gram-scale synthetic utility was also showcased.

Dehydroabietane-type bifunctional organocatalysts in asymmetric synthesis: recent progress.

Dehydroabietane-type bifunctional organocatalysts derived from rosane-type diterpenes of dehydroabietic acid (DHAA) and dehydroabietylamine (DA) have been utilized in a wide variety of highly enantioselective reactions. Since one well-documented review exclusively reported on the development of terpene-derived bifunctional thioureas in asymmetric organocatalysis in 2013, fragmentary progress on the dehydroabietane-type bifunctional thioureas and squaramides has been mentioned in other reviews. In this mini-review, we systematically analyze and reorganize the published literature on dehydroabietane-type bifunctional organocatalysts in the recent decade according to the type of catalysts. Our aim is for this review to provide helpful research information and serve as a foundation for further design and application of rosin-based organocatalysts.

GSDME-dependent pyroptosis signaling pathway in diabetic nephropathy.

Diabetic nephropathy (DN) is one of the serious chronic microvascular complications of diabetes, and leads to the increased morbidity and mortality in diabetic patients. Gasdermin E (GSDME)-dependent pyroptosis signaling pathway plays important roles in a variety of physiological and pathological processes. However, its role and mechanism in DN are still unclear. In this study, we established a rat DN model by intraperitoneal injection of streptozotocin (STZ) successfully. Structural and functional disorders in the kidney were exhibited on the 12th week after STZ injection; the expressions of caspase-3 and GSDME at protein level in renal cortex were significantly up-regulated. At the 20th week, GSDME-N increased significantly, accompanied by the upregulation of caspase-1 in renal cortex and the release of mature IL-1ß (mIL-1ß) in serum. Furthermore, we found the protein levels of GSDME, caspase-3, caspase-1 and IL-1ß were all increased in HK2 and HBZY-1 cells under high-glucose conditions. We also found that the expression of GSDME-N significantly decreased when caspase-3 was knockdown. In contrast, knockdown of GSDME has no effect on caspase-3. Interestingly, either caspase-3, caspase-1 or GSDME knockdown reduced the release of mIL-1ß. Finally, injection of adeno-associated virus (AAV) 9-shGSDME into the rat kidney reduced kidney damage and renal cell pyroptosis in comparison with wild-type diabetic rats. These results indicated that the activation of caspase-1 induced IL-1ß maturation, and the activation of caspase-3 mediated cleavage of GSDME responsible for the formation of plasma membrane pore, followed by cytoplasmic release of mIL-1ß. Overall, we identified a pro-pyroptosis role for GSDME in DN, which does provide an important basis for clinical therapeutic studies.

The predictive value of renal parenchymal information for renal function impairment in patients with ADPKD: a multicenter prospective study.

OBJECTIVE: Although the guideline indicates that total kidney volume (TKV) is an important detection indicator in patients with autosomal dominant polycystic kidney disease (ADPKD), this study attempted to demonstrate that renal parenchymal information, combined with parenchymal volume and radiomics features, may have more valuable clinical guiding significance. METHODS: A totals of 340 ADPKD patients with normal renal function were prospectively collected and followed-up for five years, with renal function tests and non-contrast computed tomography (CT) performed every six months. The relationship between renal function impairment and renal parenchymal volume (RPV) as along with radiomics features was explored using a multiple linear regression model and multiple logistic regression. Then, a combined model of RPV with radiomics features was constructed to comprehensively evaluate its predictive value. RESULTS: Compared with TKV, decreased RPV presented a closer relationship with renal function impairment, namely, with the impairment rate (RPV: 82.3% vs. TVK: 67.1%) and eGFR (RPV: r = 0.614, p < 0.001 vs. TKV: r = -0.452, p < 0.001), and showed higher predictive power (RPV: AUC = 0.752 [95%CI 0.692-0.805], p < 0.001 vs. TKV: AUC = 0.711 [95%CI 0.649-0.768], p < 0.001). Correspondingly, the radiomics analysis that was derived from the renal parenchyma also showed a satisfactory result (AUC = 0.849 [95%Cl 0.797-0.892], p < 0.001). Importantly, the predictive power for renal function impairment was further improved in the combined model of RPV and radiomics features (AUC = 0.902 [95%Cl 0.857-0.937], p < 0.001). CONCLUSION: Renal parenchyma information may be a sensitive biomarker of renal function impairment in ADPKD, which can provide a new approach for clinically monitoring renal function, and may greatly improve the pre-hospital prevention and treatment effects.

Interleukin-6-white matter network differences explained the susceptibility to depression after stressful life events.

BACKGROUND: Stressful life events (SLEs) are well-established proximal predictors of the onset of depression. However, the fundamental causes of interindividual differences in depression outcomes are poorly understood. This study addressed this depression susceptibility mechanism using a well-powered sample of adults living in China. METHODS: Healthy participants with SLEs (n = 185; mean = 47.51 years, 49.73% female), drawn from a longitudinal study on the development of depression, underwent diffusion tensor imaging, interleukin-6 (IL-6) level measurement, and trimonthly standardized clinical and scale evaluations within a two-year period. RESULTS: Receiver operating characteristic analyses indicated that reduced feeder connection and HIP.R nodal efficiency improved the predictive accuracy of post-SLEs depression (ORfeeder = 0.623, AUC = 0.869, P < 0.001; ORHIP = 0.459, AUC = 0.855, P < 0.001). The successfully established path analysis model confirmed the significant partial effect of SLEs-IL-6-white matter (WM) network differences-depression (onset and severity) (x2/8 = 1.453, goodness-of-fit [GFI] = 0.935, standard root-mean-square error of approximation [SRMR] = 0.024). Females, individuals with lower exercise frequency (EF) or annual household income (AHI) were more likely to have higher IL-6 level after SLEs (ßint-female⁎SLEs = -0.420, P < 0.001; ßint-exercise⁎SLEs = -0.412, P < 0.001; ßint-income⁎SLEs = -0.302, P = 0.005). LIMITATIONS: The sample size was restricted due to the limited incidence rate and prospective follow-up design. CONCLUSIONS: Our results suggested that among healthy adults after SLEs, those who exhibited abnormal IL-6-WM differences were susceptible to developing depression. Females, lower AHI or EF might account for an increased risk of developing these abnormal IL-6-WM differences.

A Systematic Screening of ADHD-Susceptible Variants From 25 Chinese Parents-Offspring Trios.

Attention-deficit/hyperactivity disorder (ADHD) is one of the most prevalent and heritable childhood behavioral disorders. Although a number of ADHD-susceptible regions had been identified, details about the variations of genes and their related patterns involved in ADHD are still lacking. In this study, we collected 25 Chinese parents-offspring trios, each of which consisted of a child diagnosed with ADHD and his/her unaffected parents, and analyzed the variations from whole-genome sequencing data. SNVs in reported ADHD-susceptible regions and on the genes whose functions were related to dopamine were screened, and we identified a set of variants with functional annotations which were specifically detected in ADHD children, including most SNVs in the gene coding region that might impair protein functions and a few SNVs in promoter or 3' untranslated region (3'-UTR) that might affect the regulation of relative gene expression in a transcriptional or posttranscriptional level. All the information may further contribute to the understanding, prediction, prevention, and treatment of ADHD in clinical.

Quantitative Susceptibility Mapping of Brain Iron Deposition in Patients With Recurrent Depression.

OBJECTIVE: Recurrence is the most significant feature of depression and the relationship between iron and recurrent depression is still lack of direct evidence in vivo. METHODS: Twenty-one patients with depression and twenty control subjects were included. Gradient-recalled echo, T1 and T2 images were acquired using a 3.0T MRI system. After quantitative susceptibility mapping were reconstructed and standardized, a whole-brain and the regions of interest were respectively analyzed. RESULTS: Significant increases in susceptibility were found in multiple recurrent depression patients, which involved several brain regions (frontal lobes, temporal lobe structures, occipital lobes hippocampal regions, putamen, thalamus, cingulum, and cerebellum). Interestingly, no susceptibility changes after treatment compared to pre-treatment (all p>0.05) and no significant correlation between susceptibility and Hamilton Depression Rating Scale were found. Besides, it was close to significance that those with a higher relapse frequency or a longer mean duration of single episode had a higher susceptibility in the putamen, thalamus, and hippocampus. Further studies showed susceptibility across the putamen (ρ2=0.27, p<0.001), thalamus (ρ2=0.21, p<0.001), and hippocampus (ρ2=0.19, p<0.001) were strongly correlated with total course of disease onset. CONCLUSION: Brain iron deposition is related to the total course of disease onset, but not the severity of depression, which suggest that brain iron deposition may be a sign of brain damage in multiple recurrent depression.

Metformin Attenuates Cardiac Hypertrophy Via the HIF-1α/PPAR-γ Signaling Pathway in High-Fat Diet Rats.

Coronary artery disease (CAD) and cardiac hypertrophy (CH) are two main causes of ischemic heart disease. Acute CAD may lead to left ventricular hypertrophy (LVH). Long-term and sustained CH is harmful and can gradually develop into cardiac insufficiency and heart failure. It is known that metformin (Met) can alleviate CH; however, the molecular mechanism is not fully understood. Herein, we used high-fat diet (HFD) rats and H9c2 cells to induce CH and clarify the potential mechanism of Met on CH. We found that Met treatment significantly decreased the cardiomyocyte size, reduced lactate dehydrogenase (LDH) release, and downregulated the expressions of hypertrophy markers ANP, VEGF-A, and GLUT1 either in vivo or in vitro. Meanwhile, the protein levels of HIF-1α and PPAR-γ were both decreased after Met treatment, and administrations of their agonists, deferoxamine (DFO) or rosiglitazone (Ros), markedly abolished the protective effect of Met on CH. In addition, DFO treatment upregulated the expression of PPAR-γ, whereas Ros treatment did not affect the expression of HIF-1α. In conclusion, Met attenuates CH via the HIF-1α/PPAR-γ signaling pathway.

Highly Dispersed CoNi Alloy Embedded in N-doped Graphitic Carbon for Catalytic Transfer Hydrogenation of Biomass-derived Furfural.

The development of efficient, stable, and cost-effective heterogeneous catalysts for catalytic transfer hydrogenation (CTH) of biomass-derived furfural (FAL) is highly desired. Herein, series of N-doped graphitic carbon embedded CoNi bimetallic alloy nanoparticles were fabricated and used for the CTH of FAL to value-added furfuryl alcohol (FOL) with renewable isopropanol as hydrogen donor. Intrinsic catalytic activity examination indicated the catalytic performance of Nix Coy @NGC (x:y=1 : 3, 1 : 1, 3 : 1) nanocatalysts were sensitive to their chemical compositions. The optimal Ni1 Co1 @NGC nanocatalyst with Ni/Co mole ratio of 1 : 1 afforded a largest FOL yield of 89.3% with nearly full conversion of FAL. The synergistic effect enabled by bimetallic alloys and the abundant N-based Lewis base sites and surface Co-N active species were revealed based on systematic structural characterization, responsible for the excellent catalytic efficiency of bimetallic Ni1 Co1 @NGC nanocatalyst for CTH of FAL.