Passivating Defects and Constructing Catalytic Sites on CsPbBr3 with ZnBr2 for Photocatalytic CO2 Reduction.

In recent years, halide perovskites have attracted considerable attention for photocatalytic CO2 reduction. However, the presence of surface defects and the lack of specific catalytic sites for CO2 reduction lead to low photocatalytic performance. In this study, we demonstrate a facile method that post-treats CsPbBr3 with ZnBr2 for photocatalytic CO2 reduction. Our experimental and characterization results show that ZnBr2 has a dual role: the Br- ions in ZnBr2 passivate Br vacancies (VBr) on the CsPbBr3 surface, while Zn2+ cations act as catalytic sites for CO2 reduction. The ZnBr2-CsPbBr3 achieves a photocatalytic CO evolution rate of 57 µmol g-1 h-1, which is nearly three times higher than that of the pristine CsPbBr3. The enhanced performance over ZnBr2-CsPbBr3 is mainly due to the decreased VBr and lower reaction energy barrier for CO2 reduction. This work presents an effective method to simultaneously passivate surface defects and introduce catalytic sites, providing useful guidance for the regulation of perovskite photoelectric properties and the design of efficient photocatalysts.

Oxymatrine attenuates sepsis-induced inflammation and organ injury via inhibition of HMGB1/RAGE/NF-κB signaling pathway.

Sepsis is a life-threatening organ dysfunction that endangers patient lives and is caused by an imbalance in the host defense against infection. Sepsis continues to be a significant cause of morbidity and mortality in critically sick patients. Oxymatrine (OMT), a quinolizidine alkaloid derived from the traditional Chinese herb Sophora flavescens Aiton, has been shown to have anti-inflammatory effects on a number of inflammatory illnesses according to research. In this study, we aimed to evaluate the therapeutic effects of OMT on sepsis and explore the underlying mechanisms. We differentiated THP-1 cells into THP-1 macrophages and studied the anti-inflammatory mechanism of OMT in a lipopolysaccharide (LPS)-induced THP-1 macrophage sepsis model. Activation of the receptor for advanced glycation end products (RAGE), as well as NF-κB, was assessed by Western blot analysis and immunofluorescence staining. ELISA was used to measure the levels of inflammatory factors. We found that OMT significantly inhibited HMGB1-mediated RAGE/NF-κB activation and downstream inflammatory cytokine production in response to LPS stimulation. Finally, an in vivo experiment was performed on septic mice to further study the effect of OMT on injured organs. The animal experiments showed that OMT significantly inhibited HMGB1-mediated RAGE/NF-κB activation, protected against the inflammatory response and organ injury induced by CLP, and prolonged the survival rate of septic mice. Herein, we provide evidence that OMT exerts a significant therapeutic effect on sepsis by inhibiting the HMGB1/RAGE/NF-κB signaling pathway.

Preclinical Evidence that Arctigenin Effectively and Selectively Targets Clear Cell Renal Cell Carcinoma Via Suppressing EGFR and RhoA.

Clear cell renal cell carcinoma (ccRCC) has poor clinical outcomes and necessitates new treatment options. Epidermal growth factor receptor (EGFR) is a potential therapeutic target, due to the associations with various carcinomas' progression. Arctigenin, a natural compound of Arctium lappa, has been shown to display anticancer abilities in various carcinomas. Cellular assays and combination studies were conducted using arctigenin and anti-ccRCC drugs. In vivo efficacy of arctigenin was determined using ccRCC xenograft mouse model. Immunoblotting and biochemistry analysis were applied to investigate the signaling affected by arctigenin. Arctigenin inhibits growth, migration, and survival of ccRCC cells while sparing normal kidney cells. Arctigenin acts synergistically with 5-FU and sorafenib but not temsirolimus in inhibiting ccRCC cells. Synergism of arctigenin with 5-FU and sorafenib was further shown in ccRCC xenograft mouse model. The combination of arctigenin with clinical anti-RCC drugs completely inhibits tumor growth without tumor progression even for an extended time period. Mechanistically, arctigenin inhibits migration in a RhoA-dependent manner while inhibits growth via suppressing EGFR-mediated signaling pathways. Our findings suggest that arctigenin performs well to add to current treatment in ccRCC and confirm the value to target EGFR to improve therapy in RCC.

Spatial Responses of Ecosystem Service Trade-offs and Synergies to Impact Factors in Liaoning Province.

Global ecosystem services (ESs) are experiencing a significant decline, necessitating the development of robust environmental governance policies. To address the lack of integrated planning with heavy industry as the research object and a lack of knowledge of ES trade-offs and synergies in China's ecological and environmental governance. In this study, the spatial and temporal variations of four ESs (water yield (WY), soil conservation (SC), carbon storage (CS), and habitat quality (HQ)) were determined in the study area of Liaoning Province. Explore the mechanisms that shape ecosystem service trade-offs and synergies and the factors that influence them. Spearman's correlation and difference analyses were proposed to determine the spatial and temporal distributions of trade-offs and synergistic relationships among ESs. In addition, we constructed a multiscale geo-weighted regression (MGWR) model to investigate driver spatial heterogeneity affecting trade-offs and synergies. The results revealed that (1) In the study area, ESs were on the rise in Liaoning Province. (2) Temporally, ESs were overwhelmingly dominated by synergies; at the spatial scale, ESs were dominated by trade-offs of varying degrees, with the area of synergy between WY and SC being the highest. (3) ESs demonstrated spatial heterogeneity in intensity and were more impacted by natural factors such as vegetation cover, elevation, and precipitation than by characteristics related to human activity. This study helps improve understanding of the interactions and dependencies among ESs and can provide a reference for ecological governance and improvements in Liaoning Province.

Hydrogen Bonding Enables Polymer Hydrogels with pH-Induced Reversible Dynamic Responsive Behaviors.

Poly(acrylic acid-co-N-vinylcaprolactam) (PAN) hydrogels containing multiple hydrogen bonds can exhibit pH-induced reversible dynamic responsive behaviors. When placing a transparent hydrogel in an acid bath, as hydrogen bonds between comonomer units involving protonated COOH groups are formed faster than water diffusion, a nonequilibrium light-scattering state is formed to turn the hydrogel opaque, while as the swelling equilibrium is reached over time, the hydrogel regains its transparency. Likewise, when the transparent, hydrogen-bonded hydrogel is subsequently immersed in DI water, faster water absorption occurs in where more COOH groups are deprotonated, which also generates a light-scattering state leading to opacity, while the transparency is slowly recovered after equilibrium. Using such two-way dynamic transparency evolution, a PAN-based hydrogel material is prepared to demonstrate a dynamic memory system for information memorizing-forgetting and recalling-forgetting.

Metabolomic study on the protective effect of isoorientin against myocardial infarction.

Myocardial infarction has become one of the largest threats to human life. Myocardial ischemia and hypoxia caused by myocardial infarction are important causes of myocardial cell injury. Compared with chemical drugs, botanical drugs that are natural antioxidants have relatively few toxic side effects. Isoorientin (ISO), a C-glucosyl flavone with a chemical nomenclature, exists in the human diet and has antioxidant and anti-inflammatory effects in other diseases. However, its role in myocardial infarction has not been reported. In this study, we investigated the effects of ISO administration on cardiac function in mice after myocardial infarction, on ROS levels in H9C2 myocardial cells after hypoxia in vitro, and on metabolomic changes in mice after myocardial infarction. We found that ISO improved cardiac function in mice after myocardial infarction and inhibited hypoxia-induced oxidative stress injury in H9C2 cells in vitro. We also found through metabolomic analysis and KEGG enrichment analysis that ISO significantly changed metabolic pathways in mice after myocardial infarction, including histidine metabolism, arachidonic acid metabolism, renin secretion and other pathways. These results lay a foundation for further exploration of the protective effect of ISO against myocardial infarction and the development of related drugs.

Fe Single-Atom Catalyst for Efficient and Rapid Fenton-Like Degradation of Organics and Disinfection against Bacteria.

The Fenton-like reaction has great potential in water treatment. Herein, an efficient and reusable catalytic system is developed based on atomically dispersed Fe catalyst by anchoring Fe atoms on nitrogen-doped porous carbon (Fe SA/NPCs). The catalyst of Fe SA/NPCs exhibits enhanced performance in activating peroxymonosulfate (PMS) for organic pollutant degradation and bacterial inactivation. The Fe SA/NPCs + PMS system demonstrates a high turnover frequency of 39.31 min-1 in Rhodamine B (RhB) degradation as well as a strong bactericidal activity that can completely sterilize an Escherichia coli culture within 5 min. Meanwhile, the degradation activity of RhB by Fe SA/NPCs is improved up to 28 to 371-fold in comparison with the controls. Complete degradation of RhB can be achieved in 30 s by the Fe SA/NPCs + PMS system, demonstrating an efficiency much higher than most traditional Fenton-like processes. Experiments with different radical scavengers and density functional theory calculations have revealed that singlet oxygen (1 O2 ) generated on the N-coordinated single Fe atom (Fe-N4 ) sites is the key reactive species for the effective and rapid pollutant degradation and bacterial inactivation. This work innovatively affords a promising single-Fe-atom catalyst/PMS system for applying Fenton-like reactions in water treatment.

Efficacy and safety of nafamostat mesilate anticoagulation in blood purification treatment of critically ill patients: a systematic review and meta-analysis.

BACKGROUND: Nafamostat mesilate (NM), a broad-spectrum and potent serine protease inhibitor, can be used as an anticoagulant during extracorporeal circulation, as well as a promising drug effective against coronavirus disease 2019 (COVID-19). We conducted a systematic meta-analysis to evaluate the safety and efficacy of NM administration in critically ill patients who underwent blood purification therapy (BPT). METHODS: The Cochrane Library, Web of Science and PubMed were comprehensively searched from inception to August 20, 2021, for potential studies. RESULTS: Four randomized controlled trials (RCTs) and seven observational studies with 2723 patients met the inclusion criteria. The meta-analysis demonstrated that conventional therapy (CT) significantly increased hospital mortality compared with NM administration (RR = 1.25, p = 0.0007). In subgroup analyses, the in-hospital mortality of the NM group was significantly lower than that of the anticoagulant-free (NA) group (RR = 1.31, p = 0.002). The CT interventions markedly elevated the risk ratio of bleeding complications by 45% (RR = 1.45, p = 0.010) compared with NM interventions. In another subgroup analysis, NM used exhibited a significantly lower risk of bleeding complications than those of the low-molecular-weight heparin (LMWH) used (RR = 4.58, p = 0.020). The filter lifespan was decreased significantly (MD = -10.59, p < 0.0001) in the NA groups compared with the NM groups. Due to the poor quality of the included RCTs, these results should be interpreted with caution. CONCLUSION: Given the better survival outcomes, lower risk of bleeding, NM anticoagulation seems to be a safe and efficient approach for BPT patients and could yield a favorable filter lifespan. More multi-center RCTs with large samples are required for further validation of this study.

Risk factors for the critical illness in SARS-CoV-2 infection: a multicenter retrospective cohort study.

BACKGROUND: Prior studies reported that 5 ~ 32% COVID-19 patients were critically ill, a situation that poses great challenge for the management of the patients and ICU resources. We aim to identify independent risk factors to serve as prediction markers for critical illness of SARS-CoV-2 infection. METHODS: Fifty-two critical and 200 non-critical SARS-CoV-2 nucleic acid positive patients hospitalized in 15 hospitals outside Wuhan from January 19 to March 6, 2020 were enrolled in this study. Multivariable logistic regression and LASSO logistic regression were performed to identify independent risk factors for critical illness. RESULTS: Age older than 60 years, dyspnea, respiratory rate > 24 breaths per min, leukocytosis > 9.5 × 109/L, neutrophilia > 6.3 × 109/L, lymphopenia < 1.1 × 109/L, neutrophil-to-lymphocyte ratio > 3.53, fibrinogen > 4 g/L, d-dimer > 0.55 µg/mL, blood urea nitrogen > 7.1 mM, elevated aspartate transaminase, elevated alanine aminotransferase, total bilirubin > 21 µM, and Sequential Organ Failure Assessment (SOFA) score ≥ 2 were identified as risk factors for critical illness. LASSO logistic regression identified the best combination of risk factors as SOFA score, age, dyspnea, and leukocytosis. The Area Under the Receiver-Operator Curve values for the risk factors in predicting critical illness were 0.921 for SOFA score, 0.776 for age, 0.764 for dyspnea, 0.658 for leukocytosis, and 0.960 for the combination of the four risk factors. CONCLUSIONS: Our findings advocate the use of risk factors SOFA score ≥ 2, age > 60, dyspnea and leukocytosis > 9.5 × 109/L on admission, alone or in combination, to determine the optimal management of the patients and health care resources.

Atorvastatin Attenuates Ischemia/Reperfusion-Induced Hippocampal Neurons Injury Via Akt-nNOS-JNK Signaling Pathway.

Ischemia-induced brain damage leads to apoptosis like delayed neuronal death in selectively vulnerable regions, which could further result in irreversible damages. Previous studies have demonstrated that neurons in the CA1 area of hippocampus are particularly sensitive to ischemic damage. Atorvastatin (ATV) has been reported to attenuate cognitive deficits after stroke, but precise mechanism for neuroprotection remains unknown. Therefore, the aims of this study were to investigate the neuroprotective mechanisms of ATV against ischemic brain injury induced by cerebral ischemia reperfusion. In this study, four-vessel occlusion model was established in rats with cerebral ischemia. Rats were divided into five groups: sham group, I/R group, I/R+ATV group, I/R+ATV+LY, and I/R+SP600125 group. Cresyl violet staining was carried out to examine the neuronal death of hippocampal CA1 region. Immunoblotting was used to detect the expression of the related proteins. Results showed that ATV significantly protected hippocampal CA1 pyramidal neurons against cerebral I/R. ATV could increase the phosphorylation of protein kinase B (Akt1) and nNOS, diminished the phosphorylation of JNK3 and c-Jun, and further inhibited the activation of caspase-3. Whereas, all of the aforementioned effects of ATV were reversed by LY294002 (an inhibitor of Akt1). Furthermore, pretreatment with SP600125 (an inhibitor of JNK) diminished the phosphorylation of JNK3 and c-Jun, and further inhibited the activation of caspase-3 after cerebral I/R. Taken together, our results implied that Akt-mediated phosphorylation of nNOS is involved in the neuroprotection of ATV against ischemic brain injury via suppressing JNK3 signaling pathway that provide a new experimental foundation for stroke therapy.

Distinct representations of symbolic ordinality and quantity: evidence from neuropsychological investigations in a Chinese patient with Gerstmann's syndrome.

A number of recent studies have shown conflicting evidence as to common or distinct representations between symbolic ordinality and quantity. We investigated this issue through a series of neuropsychological tests in a unique Chinese patient with the left angular gyrus and left supramarginal gyrus lesions. Behavioral experiments revealed that (1) the patient showed Gerstmann syndrome, with minimal anomia and alexia and (2) the patient showed the dissociation among number semantic representations with relatively preserved symbolic quantity knowledge and impaired processing of symbolic order meaning. Together with existing evidence in the literature, results of the current study suggest that there might be two separate cognitive representations of symbolic ordinality and quantity in logographic language according to this dissociation. Most importantly, another merit of this study is that the left angular gyrus and left supramarginal gyrus might be necessary to symbolic ordinality representation.

Identification of PLAC8 as a Potential Biomarker for the Diagnosis of Interstitial Cystitis.

BACKGROUND: Interstitial cystitis is a diagnosis of exclusion due to the complexity of its etiology and pathology, which is a chronic disease with an unknown etiology. To our knowledge, few studies were performed to identify predictive biomarkers for interstitial cystitis. OBJECTIVE: This study aimed to identify and validate potential biomarkers for Interstitial Cystitis (IC). METHODS: The interstitial cystitis datasets were retrieved from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified by using the R package and were subjected to functional and pathway enrichment analysis. Key biomarkers of interstitial cystitis were identified by using Lasso regression analysis and the SVM-RFE algorithm. The diagnostic value of key biomarkers was validated in internal and external datasets, and pathways that relate to biomarkers of interstitial cystitis were screened. The ssGSEA was employed to identify the immune cells closely related to biomarkers. The expression of PLAC8 in patients with interstitial cystitis was detected by Immune-Histochemistry (IHC). RESULTS: Sixteen differentially expressed genes associated with interstitial cystitis were identified, which were primarily linked to the biological process of the chemokine signaling pathway. PLAC8, identified as a biomarker for interstitial cystitis, was validated to express a significantly different between IC and normal bladder tissues. PLAC8-related pathways were analyzed, with a focus on NF-κB, TNF, Toll-like receptor, chemokine, IL-17, and JAK-STAT signaling pathways. PLAC8 was proved to be closely related to immune activations, which is similar to the pathogenesis of IC, which is a chronic dysregulated immune disease. Meanwhile, we also observed a higher level of PLAC8 in IC tissues. CONCLUSION: PLAC8 has promising application prospects as a biomarker for interstitial cystitis diagnosis. These findings could aid in the diagnosis and treatment of interstitial cystitis.

Measurement of mass force field driving water refilling of cuttage.

Cuttage is a common plant cultivation method, and the key to its survival is the restoration of water refilling, which remains unclear up to now. We report 3D dynamic imaging of water refilling of cuttage without resorting to any contrast agent. Hydrodynamics of the refilled water flow over time reveals the existence of a unit mass force field with a gradient along the refilling direction, which means that cutting plants also have a gradient force field to drive the recovery of water refilling, as predicted by Cohesion-Tension theory in normal plants. We found that force fields of different functional regions are isolated and independently distributed, which is conducive to ensure the safety of water transmission. At the same time, we also found that there is a so-called "inchworm effect" in the mass force field, which contributes to the force transfer inside the cutting through local force accumulation. Results of this paper demonstrate that the developed method for the measurement of mass force field in-vivo is applicable to help decipher the mechanism of plant water refilling.

[Change and Prediction of Water Purification Function in the South Bank of Hangzhou Bay in the Past 20 Years].

The investigation of regional water purification functionality and its influencing factors holds significant pragmatic implications in understanding the potential of regional water purification, guiding context-specific regional comprehensive planning schemes, and environmental conservation measures. The study site, situated along the southern coast of Hangzhou Bay, represents a prototypical region characterized by intricate land-sea interactions that bear substantial economic and ecological functions. By assimilating a meticulously collected topographical and land-use dataset, in conjunction with site-specific meteorological records, the water purification model embedded within the integrated valuation of ecosystem services and trade-offs (InVEST) framework was employed to scrutinize the spatiotemporal dynamics of nitrogen (N) and phosphorus (P) loads, discharges, and removals within the southern coast of Hangzhou Bay. The prime objective of this study was to unravel the differentials in water purification functionality under diverse developmental scenarios. The investigation unearthed distinct temporal discrepancies in N and P discharges and removals over two temporal dimensions. Relative to the benchmark year 2000, the total N load experienced a reduction of 276.72 t, whereas the N discharge and removals decreased by 140.86 and 137.86 t, respectively, in the year 2020. In contrast, the total P load observed an increase of 93.65 t, accompanied by a surge in P discharge and removals by 28.91 and 64.74 t, respectively. Spatially, the distribution pattern of N and P discharges exhibited a general inclination of elevated values in the northern region and subdued values in the southern region, with certain pockets in the southern region exhibiting pronounced peaks, intimately associated with land-use typologies. Simulation analyses conducted under distinct scenarios unveiled that under the natural development priority scenario, the N and P discharges within the study area amounted to 1 682.36 and 115.50 t, respectively. Conversely, under the scenario emphasizing economic development, the regional N and P discharges showed an approximate escalation of 83.02% and 79.93%, correspondingly. In contrast, under the scenario emphasizing environmental conservation, the regional N and P discharges exhibited a notable decline of approximately 79.96% and 56.44%, respectively. Hence, the scenario prioritizing the amalgamation of environmental conservation and development effectively reduced the N and P discharges within the region, bolstering the water purification functionality. The results derived from this study furnish a solid theoretical foundation for effectuating region-specific planning schemes fostering coordinated economic and ecological advancement within the study area.

MiR-145 Alleviates Sepsis-Induced Inflammatory Responses and Organ Injury by Targeting ADAM17.

BACKGROUND: Current studies have demonstrated that disintegrin and metalloproteinase 17 (ADAM17) plays a critical role in the pathogenesis of sepsis. MicroRNA (miR)-145 is known to control immune responses as an anti-inflammatory modulatory molecule. However, a fundamental understanding of how miR-145 regulates ADAM17 and, more broadly, sepsis-induced inflammatory response remains unknown. METHODS: We used western blotting and quantitative real-time PCR (qRT-PCR) to measure expression levels of ADAM17 and miR-145. Enzyme-linked immunosorbent assays (ELISA) were performed to measure cytokine production. To determine if ADAM17 is a target gene of miR-145, bioinformatics analyses and luciferase reporter assays were conducted. The impacts of ADAM17 and miR-145 on sepsis-induced inflammatory responses were accessed in vitro using human umbilical endothelial cells (HUVECs) treated with lipopolysaccharide (LPS). Sepsis-induced inflammatory response was measured in vivo using a polymicrobial septic mouse model induced by cecal ligation and puncture (CLP) with pre-injection of a miR-145 agomir. RESULTS: In HUVECs treated with LPS, miR-145 expression was downregulated and miR-145 negatively regulated ADAM17 expression through direct binding to the ADAM17 transcript 3'-UTR. MiR-145 overexpression markedly reduced LPS-induced inflammatory cytokine production by targeting ADAM17 in HUVECs. In comparison to CLP-induced septic mice treated with a control agomir, treatment with a miR-145 agomir significantly reduced the expression of ADAM17, numerous downstream cytokines such as IL-6, TNF-α, IL-1ß and MCP-1, and the endothelial injury factors ICAM-1, VCAM-1. The miR-145 agomir also alleviated acute lung and kidney injury and improved the survival rate of septic mice. CONCLUSIONS: This study showed that miR-145, by specifically targeting ADAM17, negatively regulates sepsis-induced inflammatory responses and vascular endothelial injury, and ultimately improved organ injury and survival during sepsis. The underlying mechanism for the regulation of ADAM17 expression by miR-145 and sepsis-induced inflammatory reactions may offer sepsis patients a novel therapeutic option.

Meningoencephalitis as an initial manifestation of neuromyelitis optica spectrum disorder.

Two patients presented with initial symptoms of headache and fever, and two weeks later had disturbance of consciousness. Cerebrospinal fluid (CSF) showed pleocytosis >500×10²/L. Magnetic resonance imaging (MRI) showed multiple brain lesions at sites of high aquaporin-4 (AQP-4) expression. Case 1 presented optic neuritis four years after the first attack and case 2 had symptoms of myelitis three weeks after headache. Serum AQP-4 antibody was positive in both cases, and the diagnosis of neuromyelitis optica spectrum disorder (NMOSD) was made. Accordingly, NMOSD can initially present as meningoencephalitis mimicking intracranial infection, and the characteristic MRI imaging is quite critical for differentiation.

Selective serotonin reuptake inhibitors combined with traditional Chinese medicine for premature ejaculation: A systematic review and meta-analysis.

BACKGROUND: Premature ejaculation (PE) is still a tough problem in drug treatment. Many clinical trials have proven that traditional Chinese medicine (TCM) has a significant effect in the treatment of PE. This article aims to provide the latest evidence for the efficacy and safety of TCM combined with selective serotonin reuptake inhibitors (SSRIs) in the treatment of PE. METHODS: We looked for randomized controlled trials (RCTs) from China National Knowledge Infrastructure, Wanfang, VIP Database, MEDLINE, PubMed, Web of Science, EMBASE, and Cochrane Library until June 30, 2022. STATA 15.1 software was used to analyze all data for this article. The quality of the included articles was evaluated using the Cochrane Reviewer's Handbook 5.3. RESULTS: Finally, we selected 16 high-quality RCTs in our meta-analysis, which containing 889 patients. Meta-analysis suggested that, compared with SSRIs alone, combination of TCM with SSRIs increased significantly intravaginal ejaculation latencv time and the scores of ejaculation control ability, sexual life satisfaction, PE-related distress, and communication difficulties between partners related to PE. Also, there was no significant difference in adverse effects between the two groups. In addition, the results of publication bias test showed that no significant bias occurred. CONCLUSION: The combined use of TCM and SSRIs has significant effect in the treatment of PE compared with SSRIs monotherapy and was generally well tolerated. Due to the small sample size, multicenter and large sample RCT is still needed in the future to further confirm the effectiveness and safety of TCM combined with SSRIs in the treatment of PE.

Stability, biomechanics and biocompatibility analysis following different preparation strategies of hierarchical zeolite coatings on titanium alloy surfaces.

Traditional titanium alloy implant surfaces are inherently smooth and often lack effective osteoinductive properties. To overcome these limitations, coating technologies are frequently employed to enhance the efficiency of bone integration at the implant-host bone interface. Hierarchical zeolites, characterized by their chemical stability, can be applied to 3D-printed porous titanium alloy (pTi) surfaces as coating. The resulting novel implants with a "microporous-mesoporous-macroporous" spatial gradient structure can influence the behavior of adjacent cells; thereby, promoting the integration of bone at the implant interface. Consequently, a thorough exploration of various preparation methods is warranted for hierarchical zeolite coatings with respect to biocompatibility, coating stability, and osteogenesis. In this study, we employed three methods: in situ crystal growth, secondary growth, and layer-by-layer assembly, to construct hierarchical zeolite coatings on pTi, resulting in the development of a gradient structure. The findings of this investigation unequivocally demonstrated that the LBL-coating method consistently produced coatings characterized by superior uniformity, heightened surface roughness, and increased hydrophilicity, as well as increased biomechanical properties. These advantages considerably amplified cell adhesion, spreading, osteogenic differentiation, and mineralization of MC3T3-E1 cells, presenting superior biological functionality when compared to alternative coating methods. The outcomes of this research provide a solid theoretical basis for the clinical translation of hierarchical zeolite coatings in surface modifications for orthopedic implants.

Genetic Arg-304-His substitution in GRK5 protects against sepsis progression by alleviating NF-κB-mediated inflammation.

BACKGROUND: Previous studies have demonstrated that G protein-coupled receptor kinase 5 (GRK5) exerts a pivotal regulatory effect on the inflammation associated with sepsis. The present study aimed to investigate the clinical association of GRK5 genetic variants with sepsis and to further explore the underlying genetic mechanisms involved in regulating sepsis-induced inflammatory responses and the pathogenesis of sepsis. METHODS: This case-control study enrolled 1081 septic patients and 1147 matched controls for genotyping of GRK5 rs2230349 and rs2230345 polymorphisms. The effect of these genetic variants on GRK5-mediated inflammatory responses was analyzed in peripheral blood mononuclear cells (PBMCs) and THP-1 macrophages. A clinically relevant polymicrobial sepsis model was established by subjecting wild-type (WT) and GRK5-knockout mice to cecal ligation and puncture (CLP) to evaluate the role of GRK5 in sepsis. RESULTS: We identified significant differences in the genotype/allele distribution of rs2230349 G > A, but not rs2230345, between the sepsis subtype and septic shock subgroups (GA + AA vs. GG genotype, OR = 0.698, 95% CI = 0.547-0.893, P = 0.004; A vs. G allele, OR = 0.753, 95% CI = 0.620-0.919, P = 0.005) and between the survivor and nonsurvivor subgroups (GA + AA vs. GG genotype, OR = 0.702, 95% CI = 0.531-0.929, P = 0.015; A vs. G allele, OR = 0.753, 95% CI = 0.298-0.949, P = 0.017). PBMCs carrying the sepsis-associated protective A allele produced significantly lower levels of TNF-α and IL-1ß upon LPS stimulation. The results from the in vitro experiment showed that the Arg-304-His substitution caused by the rs2230349 G-to-A mutation in GRK5 significantly decreased the LPS-induced production of several proinflammatory cytokines, such as TNF-α, IL-6, IL-1ß and MCP-1, via the IκB-α/NF-κB signaling pathway in THP-1 macrophages. Furthermore, GRK5-knockout mice exhibited a significant decrease in IκB-α phosphorylation/degradation, the p-p65/p65 ratio, the p-p50/p50 ratio, p65 nuclear translocation and downstream cytokine (TNF-α, IL-6, IL-1ß and VCAM-1) production compared to WT mice after CLP surgery. A significant improvement in 7-day survival rate in GRK5-KO septic mice was observed in the presence of antibiotics. CONCLUSIONS: The Arg-304-His substitution caused by the rs2230349 G-to-A mutation in GRK5 might disrupt GRK5 function and alleviate IKB-α/NF-κB-mediated inflammatory responses, which ultimately conferred a genetic protective effect against susceptibility to sepsis progression and mortality. These results may, to some extent, explain the heterogeneity of the clinical prognoses of septic patients and provide novel opportunities for individualized approaches for sepsis treatment.

Screening plasma metabolites as potential biomarkers for type B aortic dissection.

Background: Aortic dissection (AD) is a serious aortic disease. Although current imaging methods can provide accurate diagnosis for AD, they do not include essential biological information. The aim of this study is to identify plasma metabolites for the risk and severity of type B AD (TBAD). Methods: In this cross-sectional study, we enrolled 16 hypertensive patients with TBAD and 7 hypertensive patients without TBAD in Jieyang People's Hospital between December 2021 and April 2022. After plasma metabolomics analysis, a metabolites risk score (MRS) model was conducted through logistic regression and least absolute shrinkage and selection operator (LASSO) regression to predict the risk of TBAD. Subsequently, TBAD group was divided into uncomplicated and complicated TBAD subgroups for further screening for metabolites related to the severity of TBAD. Results: Three metabolites, including 1,5-anhydro-D-glucitol, D-(+)-sucrose and PC(O-16:0/0:0) were related to the risk of TBAD. Compared to hypertensive patients without TBAD, the abundance of 1,5-anhydro-D-glucitol and D-(+)-sucrose were significantly increased while PC(O-16:0/0:0) was significantly reduced in hypertensive patients with TBAD (P<0.001). We subsequently built an MRS model based on these three metabolites. Furthermore, we found that hydrocinnamic acid (r=0.741, P<0.001) was independently correlated with the TBAD severity, while glycine deoxycholic acid (r=-0.538, P=0.008) and glycochenodeoxycholic acid (r=-0.538, P=0.008) were inversely correlated with the TBAD severity independently. Conclusions: The present study screened out three plasma metabolites associated with the risk of TBAD, constructed an MRS model, and identified three metabolites that were independently associated with the severity of TBAD. These findings may serve to identify more TBAD-related biomarkers and shed light on exploring potential mechanisms of TBAD.