Inhibition of jarosite heterogeneous crystallization on anglesite via in-situ formation of competitive substrate.

Heterogeneous crystallization is a common occurrence during the formation of solid wastes. It leads to the encapsulation of valuable/hazardous metals within the primary phase, presenting significant challenges for waste treatment and metal recovery. Herein, we proposed a novel method involving the in-situ formation of a competitive substrate during the precipitation of jarosite waste, which is an essential process for removing iron in zinc hydrometallurgy. We observed that the in-situ-formed competitive substrate effectively inhibits the heterogeneous crystallization of jarosite on the surface of anglesite, a lead-rich phase present in the jarosite waste. As a result, the iron content on the anglesite surface decreases from 34.8% to 1.65%. The competitive substrate was identified as schwertmannite, characterized by its loose structure and large surface area. Furthermore, we have elucidated a novel mechanism underlying this inhibition of heterogeneous crystallization, which involves the local supersaturation of jarosite caused by the release of ferric and sulfate ions from the competitive substrate. The local supersaturation promotes the preferential heterogeneous crystallization of jarosite on the competitive substrate. Interestingly, during the formation of jarosite, the competitive substrate gradually vanished through a dissolution-recrystallization process following the Ostwald rule, where a metastable phase slowly transitions to a stable phase. This effectively precluded the introduction of impurities and reduced waste volume. The goal of this study is to provide fresh insights into the mechanism of heterogeneous crystallization control, and to offer practical crystallization strategies conducive to metal separation and recovery from solid waste in industries.

Ginsenoside Rg1 ameliorates stress-exacerbated Parkinson's disease in mice by eliminating RTP801 and α-synuclein autophagic degradation obstacle.

Emerging evidence shows that psychological stress promotes the progression of Parkinson's disease (PD) and the onset of dyskinesia in non-PD individuals, highlighting a potential avenue for therapeutic intervention. We previously reported that chronic restraint-induced psychological stress precipitated the onset of parkinsonism in 10-month-old transgenic mice expressing mutant human α-synuclein (αSyn) (hαSyn A53T). We refer to these as chronic stress-genetic susceptibility (CSGS) PD model mice. In this study we investigated whether ginsenoside Rg1, a principal compound in ginseng notable for soothing the mind, could alleviate PD deterioration induced by psychological stress. Ten-month-old transgenic hαSyn A53T mice were subjected to 4 weeks' restraint stress to simulate chronic stress conditions that worsen PD, meanwhile the mice were treated with Rg1 (40 mg· kg-1 ·d-1, i.g.), and followed by functional magnetic resonance imaging (fMRI) and a variety of neurobehavioral tests. We showed that treatment with Rg1 significantly alleviated both motor and non-motor symptoms associated with PD. Functional MRI revealed that Rg1 treatment enhanced connectivity between brain regions implicated in PD, and in vivo multi-channel electrophysiological assay showed improvements in dyskinesia-related electrical activity. In addition, Rg1 treatment significantly attenuated the degeneration of dopaminergic neurons and reduced the pathological aggregation of αSyn in the striatum and SNc. We revealed that Rg1 treatment selectively reduced the level of the stress-sensitive protein RTP801 in SNc under chronic stress conditions, without impacting the acute stress response. HPLC-MS/MS analysis coupled with site-directed mutation showed that Rg1 promoted the ubiquitination and subsequent degradation of RTP801 at residues K188 and K218, a process mediated by the Parkin RING2 domain. Utilizing αSyn A53T+; RTP801-/- mice, we confirmed the critical role of RTP801 in stress-aggravated PD and its necessity for Rg1's protective effects. Moreover, Rg1 alleviated obstacles in αSyn autophagic degradation by ameliorating the RTP801-TXNIP-mediated deficiency of ATP13A2. Collectively, our results suggest that ginsenoside Rg1 holds promise as a therapeutic choice for treating PD-sensitive individuals who especially experience high levels of stress and self-imposed expectations.

Predictive value of mono-exponential and multiple mathematical models in locally advanced rectal cancer response to neoadjuvant chemoradiotherapy.

PURPOSE: This prospective study aimed to assess the predictive value of mono-exponential and multiple mathematical diffusion-weighted imaging (DWI) models in determining the response to neoadjuvant chemoradiotherapy (nCRT) in patients with locally advanced rectal cancer (LARC). METHODS: The study included 103 LARC patients scheduled for preoperative chemoradiotherapy between December 2021 and June 2023 Magnetic resonance imaging (MRI) scans were performed using a 3.0-T MR scanner, encompassing sagittal, axial, and oblique coronal T2-weighted images without fat saturation, along with DWI perpendicular to the rectum's long axis. Various DWI parameters, including apparent diffusion coefficient (ADC), stretched exponential model (SEM), continuous-time random-walk model (CTRW), and fractional-order calculus model (FROC), were measured. The pathologic complete response (pCR) rate and tumor downstaging (T-downstage) rate were determined. RESULTS: After nCRT, SEM-α, SEM-DDC, CTRW-α, CTRW-ß, CTRW-D, FROC-ß, and ADC values were significantly higher in the pCR group compared to the non-pCR group (all P < 0.05). SEM-DDC, CTRW-α, CTRW-D, FROC-ß, FROC-µ, and ADC values were significantly higher in the T-downstage group (ypT0-1) than in the non-T-downstage group (ypT2-4) (P < 0.05). The combination of CTRW (α + ß + D) exhibited the best diagnostic performance for assessing pCR after nCRT (AUC = 0.840, P < 0.001). Pre-nCRT CTRW (α + ß) demonstrated a predictive AUC of 0.652 (95%CI: 0.552-0.743), 90.3% sensitivity, and 43.1% specificity for pCR. Regarding T-downstage assessment after nCRT, the combination of CTRW (α + D) yielded the best diagnostic performance (AUC = 0.877, P = 0.048). CONCLUSION: In LARC patients, imaging markers derived from CTRW show promise in predicting tumor response before nCRT and assessing pCR after nCRT.

Novel Strategy for Efficient Recovery of CuO-Based Multiple-Metals from Copper Smelter Dust toward CO2 Electrocatalytic Reduction.

Copper smelter dust, a typical hazardous waste that is abundant in valuable heavy metals, holds the potential to be regarded as a promising resource. This study introduces a new approach that integrates chlorination roasting and cascade condensation to efficiently recover heavy metals from copper smelter dust. The findings demonstrate the successful separation of heavy metals (Cu, Pb, and Zn) as chlorides at nearly 100% efficiency while also effectively converting trivalent arsenic (As(III)) into pentavalent arsenic (As(V)) and immobilizing it in the roasting residues, thereby reducing environmental risk. Through the utilization of thermogravimetric mass spectrum analysis and thermodynamic equilibrium calculations, the chlorination process for heavy metals was investigated, revealing both direct and indirect chlorination processes. Additionally, the study resulted in the development of a CuO-based multiple-metals electrocatalyst from the oxidized roasting-recovered heavy metal chlorides, exhibiting significantly enhanced catalytic activity and faradaic efficiency for the electroreduction of CO2 into CO and CH4 compared to pure CuO electrocatalyst under similar electrocatalytic conditions. Overall, this work presents a sustainable and scalable method and new insights for addressing environmental risks while repurposing copper smelter dust.

Latent Profile Analysis of Pressure Injury Knowledge Levels Among Nursing Staff in Tertiary General Hospitals.

Aims/Background The prevalence of pressure injuries (PIs) is a widely used clinical indicator of patient safety and quality of care. Nurses' understanding of pressure injury (PI) can significantly impact the treatment outcomes for patients. This study, based on latent profile analysis (LPA), reveals the characteristics associated with PI knowledge levels among clinical nurses in district and county tertiary medical institutions. We aim to help nursing managers formulate training plans accurately so that clinical nurses can provide high-level skin care services for patients. Method In June 2023, 1482 nurse staff from 4 tertiary general hospitals at the district and county level in Chengdu were chosen as research subjects using the convenience sampling method. Responses to the general information questionnaire, the Chinese Version of Pressure Ulcer Knowledge Assessment Tool (C-PUKAT), and the Chinese Version of Attitude towards Pressure ulcer Prevention (C-APuP) were used to compare the population's characteristics based on LPA. Results Three latent profiles of nurses' PI knowledge were identified: weak foundation type (46.3%), strengthening foundation type (42.7%), and special improvement type (11.0%). Subjects' departments, administrative positions, highest degrees and PI prevention attitude scores, as well as whether they have participated in the training, all differed significantly between latent profile groups (p < 0.05). Conclusion The PI knowledge level of nursing staff at the district and county tertiary general hospitals requires urgent improvement. Nursing managers should prioritize the management level and quality of PI training among clinical nursing staff. Precise training programs can be developed based on different categories of nursing staff to enhance their PI knowledge, thereby effectively improving the quality of healthcare for inpatients.

Portable and Hand-Held Ammonia Gas Sensor Enables Noninvasive Prediagnosis of Helicobacter pylori Infection.

Disease diagnosis of Helicobacter pylori (Hp) through human exhaled breath analysis has attracted considerable attention. However, conventional methods, such as carbon 13 (13C) breath test and infrared spectrometers, are facing the challenge of achieving portability and reliability synchronously. Herein, we report a portable and hand-held Hp analyzer using a bimetallic PtRu@SnO2-based gas sensor for the prediagnosis of Hp infection, which is based on detecting ammonia (NH3) as a potential biomarker in exhaled breath. Owing to the surface functionalization through highly catalytically active bimetallic PtRu nanoparticles (NPs) prepared by a photochemical reduction strategy, the PtRu@SnO2-based sensor exhibits high sensitivity and selectivity toward trace-level (200 ppb) NH3 even at high-humidity surroundings (80% RH). Consequently, the designed portable and hand-held Hp analyzer makes the accurate determination of NH3 at 800 ppb in exhaled breath. The tuning of energy band structure and electrical characteristics and the catalytic modulation of NH3 oxidation by PtRu NPs are proposed to be the reasons behind the enhanced NH3 gas-sensing performance, as confirmed by in situ analysis using an online MKS MultiGas 2030 FTIR gas analyzer. This work paves the way for the prediagnosis of Hp infection using a metal oxide gas sensor.

Acceleration of Fenton-like Reaction by Bimetal-Mediated Sludge Biochar for Tetracycline Removal.

The production of sludge biochar (SBC) from residual sludge offers a solution to the challenges associated with sludge disposal and facilitates the reutilization of resources. In the present research, a bimetallic-modified sludge biochar, designated as FeCu-SBC, was synthesized by varying the doping ratios of FeSO4 and CuSO4. This material was intended for the effective degradation of tetracycline (TC) in aqueous environments via the activation of peroxydisulfate. The FeCu2-SBC (90% degradation rate) composite, synthesized through the incorporation of Fe and Cu in a 1:2 ratio with SBC, exhibited a degradation rate of TC, which was 2.7 times higher than that of SBC (32.85% degradation rate) and 1.8 times higher than that of FeCu (50% degradation rate). Research examining the mechanisms involved revealed that FeCu underwent degradation solely through the radical (•OH) pathway, whereas FeCu2-SBC was subject to degradation through both radical (SO4•-) and nonradical (1O2) pathways. This phenomenon was attributed to the distinct π-π, C═O, and defect structures in FeCu2-SBC compared to FeCu, which facilitated the activation process leading to the production of reactive species. This investigation presented a cost-effective approach for producing bimetallic-modified sludge biochar, offering perspectives on determining the crucial elements influencing the streamlined TC degradation pathway.

A convenient colorimetric assay for Cr(VI) detection based on homogeneous Cu(II)-GMP system with oxidoreductase-like activity.

Hexavalent chromium (Cr(VI)) is an environmental pollutant and recognized as a human carcinogen. Therefore, it is necessary to develop a simple and sensitive detection technique for Cr(VI). Herein, it is found that Cu2+ interacts with guanosine 5'-monophosphate (GMP) to form a homogeneous Cu(II)-GMP complex (Cu2+·GMP) that efficiently displays the oxidoreductase-like catalytic activity. Cu2+·GMP can catalyze the oxidation between Cr(VI) and substrate 3,3',5,5'- tetramethylbenzidine (TMB), resulting in color change recognized by the naked eyes. Base on this, a convenient colorimetric assay for Cr(VI) detection was developed. The detection limit (3σ/s) of this sensor for Cr(VI) was 23 nM with a linear range of 0.1-25 µM. Moreover, the proposed assay was successfully applied to detect Cr(VI) in different environmental water samples with satisfactory recoveries. Our method is simple, efficient, rapid and cost-effective for Cr(VI) detection without the need for complicated material preparation or special separation, which shows great potential in environmental monitoring.

EGB761 ameliorates mild cognitive impairment by inhibiting the pyroptosis and apoptosis in both in vivo and in vitro experiments.

Mild cognitive impairment (MCI) is a neurodegenerative condition that is clinically prevalent among the elderly. EGB761 is widely recognized for its promising therapeutic properties in both the prevention and treatment of neurodegenerative disorders. The aim of this study was to investigate the effects of EGB761 in MCI and the underlying molecular mechanism. Four-month-old SAMP8 mice were used as an in vivo MCI model, and BV2 microglial cells were treated with ß-amyloid (Aß) 1-42 to establish an in vitro model. First, the cognitive function was evaluated by the Morris water maze. Then, Aß levels were measured by enzyme-linked immunosorbent assay. Finally, the underlying molecular mechanism was investigated both in vivo and in vitro. It was found that EGB761 treatment improved the cognitive impairment of SAMP8 mice. In addition, EGB761 inhibited NOD-like receptor protein 3 inflammasome-mediated pyroptosis-related mRNAs and proteins and reduced pyroptosis markers, including gasdermin D fluorescence intensity, propidium iodide-positive cell count, and the lactate dehydrogenase content. Furthermore, EGB761 inhibited extrinsic and intrinsic apoptosis. Thus, EGB761 had protective effects against pyroptosis and apoptosis in BV2 microglial cells induced by Aß1-42 and SAMP8 mice.

Metal Halide Perovskite Nanocrystals-Intermediated Hydrogel for Boosting the Biosensing Performance.

Metal-halide perovskites have become attractive nanomaterials for advanced biosensors, yet the structural design remains challenging due to the trade-off between environmental stability and sensing sensitivity. Herein, a trinity strategy is proposed to address this issue by integrating Mn (II) substitution with CsPb2Cl5 inert shell and NH2-PEG-COOH coating for designing Mn2+-doped CsPbCl3/CsPb2Cl5 core/shell hetero perovskite nanocrystals (PMCP PNCs). The trinity strategy isolates the emissive Mn2+-doped CsPbCl3 core from water and the Mn2+ d-d transition generates photoluminescence with a long lifetime, endowing the NH2-PEG-COOH capped Mn2+-doped CsPbCl3/CsPb2Cl5 PNCs with robust water stability and oxygen-sensitive property. Given the structural integration, photoluminescent hydrogel biosensors are designed by embedding the PMCP PNCs into the hydrogel system to deliver on-site pesticide information on food products. Impressively, benefiting from the dual enzyme triggered-responsive property of PMCP PNCs, the hydrogel biosensor is endowed with ultra-high sensitivity toward chlorpyrifos pesticide at the nanogram per milliliter level. Such a robust PMCP PNCs-based hydrogel sensor can provide accurate pesticide information while guiding the construction of photoluminescent biosensors for upcoming on-site applications.

Biomechanical study of spinal cord and nerve root in idiopathic scoliosis: based on finite element analysis.

BACKGROUND: Current research lacks comprehensive investigation into the biomechanical changes in the spinal cord and nerve roots during scoliosis correction. This study employs finite element analysis to extensively explore these biomechanical variations across different Cobb angles, providing valuable insights for clinical treatment. METHODS: A personalized finite element model, incorporating vertebrae, ligaments, spinal cord, and nerve roots, was constructed using engineering software. Forces and displacements were applied to achieve Cobb angle improvements, designating T1/2-T4/5 as the upper segment, T5/6-T8/9 as the middle segment, and T9/10-L1/2 as the lower segment. Simulations under traction, pushing, and traction + torsion conditions were conducted, and biomechanical changes in each spinal cord segment and nerve roots were analyzed. RESULTS: Throughout the scoliosis correction process, the middle spinal cord segment consistently exhibited a risk of injury under various conditions and displacements. The lower spinal cord segment showed no significant injury changes under traction + torsion conditions. In the early correction phase, the upper spinal cord segment demonstrated a risk of injury under all conditions, and the lower spinal cord segment presented a risk of injury under pushing conditions. Traction conditions posed a risk of nerve injury on both sides in the middle and lower segments. Under pushing conditions, there was a risk of nerve injury on both sides in all segments. Traction + torsion conditions implicated a risk of injury to the right nerves in the upper segment, both sides in the middle segment, and the left side in the lower segment. In the later correction stage, there was a risk of injury to the upper spinal cord segment under traction + torsion conditions, the left nerves in the middle segment under traction conditions, and the right nerves in the upper segment under pushing conditions. CONCLUSION: When the correction rate reaches 61-68%, particular attention should be given to the upper-mid spinal cord. Pushing conditions also warrant attention to the lower spinal cord and the nerve roots on both sides of the main thoracic curve. Traction conditions require attention to nerve roots bilaterally in the middle and lower segments, while traction combined with torsion conditions necessitate focus on the right-side nerve roots in the upper segment, both sides in the middle segment, and the left-side nerve roots in the lower segment.

Molecular characterization of the SP3a gene, a negative regulator of viral infection in the orange-spotted grouper, Epinephelus coioides.

SP3 (specificity protein 3) is a transcription factor characterized by three conserved Cys2His2 zinc finger motifs that exert a transregulatory effect by binding to GC boxes, either upregulating or downregulating multiple genes or by co-regulating gene expression in coordination with other proteins. SP3 potentially regulates a series of processes, such as the cell cycle, growth, metabolic pathways, and apoptosis, and plays an important role in antiviral effect. The function of sp3 in fish is poorly understood. In this study, the Sp3a open reading frame was cloned from the orange-spotted grouper, Epinephelus coioides. The full-length open reading frame of Sp3a was 2034 bp, encoding 677 amino acids, with a predicted molecular weight of 72.34 kDa and an isoelectric point of 5.05. Phylogenetically, Sp3a in Epinephelus coioides was the most closely related to Sp3a in the Malabar grouper, Epinephelus malabaricus. RT-qPCR revealed ubiquitous expression of Sp3a in all examined grouper tissues, with no significant differences in expression levels among tissues. A eukaryotic expression vector, pEGFP-Sp3a, was constructed and transfected into grouper spleen (GS) cells. Subcellular localization of Sp3a was observed using an inverted fluorescence microscope. When Spa3 was overexpressed in GS cells, the expression of orange-spotted grouper nerve necrosis virus (RGNNV) genes (CP and RdRp) decreased significantly, indicating that Sp3a significantly inhibited RGNNV replication. siRNA inhibition of Sp3a accelerated the intracellular replication of RGNNV, implying the antiviral effect of Sp3a. Conclusively, our findings contribute to further research on the antiviral capabilities of Sp3a in grouper and other fish. Therefore, our research has potential implications on the development of the aquaculture industry.

Machine learning predicts heavy metal adsorption on iron (oxyhydr)oxides: A combined insight into the adsorption efficiency and binding configuration.

The adsorption of heavy metal on iron (oxyhydr)oxides is one of the most vital geochemical/chemical processes controlling the environmental fate of these contaminants in natural and engineered systems. Traditional experimental methods to investigate this process are often time-consuming and labor-intensive due to the complexity of influencing factors. Herein, a comprehensive database containing the adsorption data of 11 heavy metals on 7 iron (oxyhydr)oxides was constructed, and the machine learning models was successfully developed to predict the adsorption efficiency. The random forest (RF) models achieved high prediction performance (R2 > 0.9, RMSE < 0.1, and MAE < 0.07) and interpretability. Key factors influencing heavy metal adsorption efficiency were identified as mineral surface area, solution pH, metal concentration, and mineral concentration. Additionally, by integrating our previous binding configuration models, we elucidated the simultaneous effects of input features on adsorption efficiency and binding configuration through partial dependence analysis. Higher pH simultaneously enhanced adsorption efficiency and affinity for cations, whereas lower pH benefited that for oxyanions. While higher mineral surface area improved the metal adsorption efficiency, the adsorption affinity could be weakened. This work presents a data-driven approach for investigating metal adsorption behavior and elucidating the influencing mechanisms from macroscopic to microcosmic scale, thereby offering comprehensive guidance for predicting and managing the environmental behavior of heavy metals.

Atmospheric pressure plasma preconditioning reduces oxygen and glucose deprivation induced human neuronal SH-SY5Y cells apoptosis by activating protective autophagy and ROS/AMPK/mTOR pathway.

Reactive oxygen species (ROS)/reactive nitrogen species (RNS) exert a "double edged" effect on the occurrence and development of ischemic stroke. We previously indicate that atmospheric pressure plasma (APP) shows a neuroprotective effect in vitro based on the ROS/RNS generations. However, the mechanism is still unknown. In this work, SH-SY5Y cells were treated with oxygen and glucose deprivation (OGD) injuries for stimulating the ischemic stroke pathological injury process. A helium APP was used for SH-SY5Y cell treatment for evaluating the neuroprotective impacts of APP preconditioning against OGD injuries with the optimized parameters. During the preconditioning, APP significantly raised the extracellular and intracellular ROS/RNS production. As a result, APP preconditioning increased SH-SY5Y cell autophagy by elevating LC3-II/LC3-I ratio and autophagosome formation. Meanwhile, APP preconditioning reduced cell apoptosis caused by OGD with the increased APP treatment time, which was abolished by pretreatment with autophagy inhibitor 3-methyladenine (3-MA). The ROS scavenger N-acetyl-L-cysteine (NAC) alone or combined with NO scavenger carboxy-PTIO abolished the APP preconditioning induced SH-SY5Y autophagy and the cytoprotection, whereas the NO scavenger alone did not. In addition, we observed the elevated phosphorylation of AMP-activated protein kinase (AMPK) and decreased phosphorylation of mammalian target of rapamycin (mTOR) in APP treated SH-SY5Y cells. This effect was attenuated by AMPK inhibitor Compound C (CC), the ROS scavenger NAC and autophagy inhibitor 3-MA. Furthermore, the cytoprotective effect of APP was preliminarily confirmed in the rats of middle cerebral artery occlusion (MCAO) model. Results showed that APP inhalation by rats during MCAO process could improve neurological functions, reduce cell apoptosis in brain tissues and decrease cerebral infarct volume. Our data suggested that ROS produced by APP preconditioning played a vital role in the neuroprotective effect of SH-SY5Y cells against OGD injuries by activating autophagy and ROS/AMPK/mTOR pathway.

Esculetin facilitates post-stroke rehabilitation by inhibiting CKLF1-mediated neutrophil infiltration.

Esculetin (ESC) is a coumarin-derived phytochemical prevalent in traditional Chinese medicine that exhibits anti-acute ischemic stroke activities. Our previous studies demonstrate that CKLF1 is a potential anti-stroke target for coumarin-derived compound. In this study we investigated whether CKLF1 was involved in the neuroprotective effects of ESC against photothrombotic stroke in mice. The mice were treated with ESC (20, 40 or 80 mg·kg-1·d-1, i.g.) for two weeks. The therapeutic effect of ESC was assessed using MRI, neurological function evaluation, and a range of behavioral tests on D1, 3, 7 and 14 of ESC administration. We showed that oral administration of ESC dose-dependently reduced the cerebral infarction volume within one week after stroke, improved behavioral performance, and alleviated neuropathological damage within two weeks. Functional MRI revealed that ESC significantly enhanced the abnormal low-frequency fluctuation (ALFF) value of the motor cortex and promoted functional connectivity between the supplementary motor area (SMA) and multiple brain regions. We demonstrated that ESC significantly reduced the protein levels of CKLF1 and CCR5, as well as the CKLF1/CCR5 protein complex in the peri-infarcted area. We showed that ESC (0.1-10 µM) dose-dependently blocked CKLF1-induced chemotactic movement of neutrophils in the Transwell assay, reducing the interaction of CKLF1/CCR5 on the surface of neutrophils, thereby reducing neutrophil infiltration, and decreasing the expression of ICAM-1, VCAM-1 and MMP-9 in the peri-infarct tissue. Knockout of CKLF1 reduced brain infarction volume and motor dysfunction after stroke but also negated the anti-stroke efficacy and neutrophil infiltration of ESC. These results suggest that the efficacy of ESC in promoting post-stroke neural repair depends on its inhibition on CKLF1-mediated neutrophil infiltration, which offering novel perspectives for elucidating the therapeutic properties of coumarins.

Upconversion-based chiral nanoprobe for highly selective dual-mode sensing and bioimaging of hydrogen sulfide in vitro and in vivo.

Chiral assemblies have become one of the most active research areas due to their versatility, playing an increasingly important role in bio-detection, imaging and therapy. In this work, chiral UCNPs/CuxOS@ZIF nanoprobes are prepared by encapsulating upconversion nanoparticles (UCNPs) and CuxOS nanoparticles (NPs) into zeolitic imidazolate framework-8 (ZIF-8). The novel excited-state energy distribution-modulated upconversion nanostructure (NaYbF4@NaYF4: Yb, Er) is selected as the fluorescence source and energy donor for highly efficient fluorescence resonance energy transfer (FRET). CuxOS NP is employed as chiral source and energy acceptor to quench upconversion luminescence (UCL) and provide circular dichroism (CD) signal. Utilizing the natural adsorption and sorting advantages of ZIF-8, the designed nanoprobe can isolate the influence of other common disruptors, thus achieve ultra-sensitive and highly selective UCL/CD dual-mode quantification of H2S in aqueous solution and in living cells. Notably, the nanoprobe is also capable of in vivo intra-tumoral H2S tracking. Our work highlights the multifunctional properties of chiral nanocomposites in sensing and opens a new vision and idea for the preparation and application of chiral nanomaterials in biomedical and biological analysis.

MCC950 as a promising candidate for blocking NLRP3 inflammasome activation: A review of preclinical research and future directions.

The NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome is a key component of the innate immune system that triggers inflammation and pyroptosis and contributes to the development of several diseases. Therefore, blocking the activation of the NLRP3 inflammasome has therapeutic potential for the treatment of these diseases. MCC950, a selective small molecule inhibitor, has emerged as a promising candidate for blocking NLRP3 inflammasome activation. Ongoing research is focused on elucidating the specific targets of MCC950 as well as assessfing its metabolism and safety profile. This review discusses the diseases that have been studied in relation to MCC950, with a focus on stroke, Alzheimer's disease, liver injury, atherosclerosis, diabetes mellitus, and sepsis, using bibliometric analysis. It then summarizes the potential pharmacological targets of MCC950 and discusses its toxicity. Furthermore, it traces the progression from preclinical to clinical research for the treatment of these diseases. Overall, this review provides a solid foundation for the clinical therapeutic potential of MCC950 and offers insights for future research and therapeutic approaches.

Intravoxel incoherent motion diffusion-weighted imaging in evaluating preoperative staging of esophageal squamous cell carcinoma : Evaluation of preoperative stage of primary tumour and prediction of lymph node metastases from esophageal cancer using IVIM: a prospective study.

BACKGROUND: The aim of this research is to prospectively investigate the diagnostic performance of intravoxel incoherent motion (IVIM) using the integrated slice-specific dynamic shimming (iShim) technique in staging primary esophageal squamous cell carcinoma (ESCC) and predicting presence of lymph node metastases from ESCC. METHODS: Sixty-three patients with ESCC were prospectively enrolled from April 2016 to April 2019. MR and IVIM using iShim technique (b = 0, 25, 50, 75, 100, 200, 400, 600, 800 s/mm2) were performed on 3.0T MRI system before operation. Primary tumour apparent diffusion coefficient (ADC) and IVIM parameters, including true diffusion coefficient (D), pseudodiffusion coefficient (D*), pseudodiffusion fraction (f) were measured by two independent radiologists. The differences in D, D*, f and ADC values of different T and N stages were assessed. Intraclass correlation coefficients (ICCs) were calculated to evaluate the interobserver agreement between two readers. The diagnostic performances of D, D*, f and ADC values in primary tumour staging and prediction of lymph node metastasis of ESCC were determined using receiver operating characteristic (ROC) curve analysis. RESULTS: The inter-observer consensus was excellent for IVIM parameters and ADC (D: ICC = 0.922; D*: ICC = 0.892; f: ICC = 0.948; ADC: ICC = 0.958). The ADC, D, D* and f values of group T1 + T2 were significantly higher than those of group T3 + T4a [ADC: (2.55 ± 0.43) ×10- 3 mm2/s vs. (2.27 ± 0.40) ×10- 3 mm2/s, t = 2.670, P = 0.010; D: (1.82 ± 0.39) ×10- 3 mm2/s vs. (1.53 ± 0.33) ×10- 3 mm2/s, t = 3.189, P = 0.002; D*: 46.45 (30.30,55.53) ×10- 3 mm2/s vs. 32.30 (18.60,40.95) ×10- 3 mm2/s, z=-2.408, P = 0.016; f: 0.45 ± 0.12 vs. 0.37 ± 0.12, t = 2.538, P = 0.014]. The ADC, D and f values of the lymph nodes-positive (N+) group were significantly lower than those of lymph nodes-negative (N0) group [ADC: (2.10 ± 0.33) ×10- 3 mm2/s vs. (2.55 ± 0.40) ×10- 3 mm2/s, t=-4.564, P < 0.001; D: (1.44 ± 0.30) ×10- 3 mm2/s vs. (1.78 ± 0.37) ×10- 3 mm2/s, t=-3.726, P < 0.001; f: 0.32 ± 0.10 vs. 0.45 ± 0.11, t=-4.524, P < 0.001]. The combination of D, D* and f yielded the highest area under the curve (AUC) (0.814) in distinguishing group T1 + T2 from group T3 + T4a. D combined with f provided the highest diagnostic performance (AUC = 0.849) in identifying group N + and group N0 of ESCC. CONCLUSIONS: IVIM may be used as an effective functional imaging technique to evaluate preoperative stage of primary tumour and predict presence of lymph node metastases from ESCC.

Exosomes from myoblasts induced by hypoxic preconditioning improved ventricular conduction by increasing Cx43 expression in hypothermia ischemia reperfusion hearts.

Myocardial ischemia-reperfusion arrhythmia after cardiac surgery is common and seriously affects quality of life. Remote ischemic preconditioning can reduce the myocardial damage caused by severe ischemia. However, the underlying mechanism is not well understood. This study aimed to investigate the effects of exosomes derived from C2C12 mouse myoblasts after hypoxic preconditioning (HP) on ventricular conduction in hypothermic ischemia-reperfusion hearts. Myocardial ischemia-reperfusion model rats were established using the Langendorff cardiac perfusion system. Exosomes derived from normoxic (ExoA) and hypoxia-preconditioned (ExoB) C2C12 cells were injected into the jugular vein of the model rats. The time to heartbeat restoration, arrhythmia type and duration, and heart rate were recorded after myocardial ischemia-reperfusion. Conduction velocity on the surface of left ventricle was measured using a microelectrode array after 30 min of balanced perfusion, 15 min of reperfusion, and 30 min of reperfusion. Immunohistochemistry and western blotting were performed to determine the distribution and relative expression of connexin 43 (Cx43). ExoB contained more exosomes than ExoA, showing that HP stimulated the release of exosomes. The IR + ExoB group showed faster recovery of ventricular myocardial activity, a lower arrhythmia score, faster conduction velocity, and better electrical conductivity than the IR group. ExoB increased the expression of Cx43 and reduced its lateralization in the ventricular muscle. Our study showed that exosomes induced by hypoxic preconditioning can improve ventricular myocardial conduction and reperfusion arrhythmia in isolated hearts after hypothermic ischemia-reperfusion.