Three-dimensional printed titanium chest wall reconstruction for tumor removal in the sternal region.

Resection of thoracic wall tumors results in significant defects in the chest wall, leading to various complications. In recent years, the use of three-dimensional (3D) printed titanium alloy prostheses in clinical practice has demonstrated enhanced outcomes in chest wall reconstruction surgery. A cohort of seven patients with sternal tumors was identified for this study. Following a helical CT scan, a digital model was generated for the design of the prosthesis. Subsequently, the tumors were then removed together with the affected sternum and ribs. The chest wall was then reconstructed using 3D-printed titanium alloy prosthesis for bone reconstruction, mesh for pleural reconstruction, and flap for soft tissue reconstruction. Patients were monitored for a period of one year post-surgery. In the seven cases examined, the tumors were found in various locations with varying degrees of invasion. Based on the scope of surgical resection and the size of the defect, 3D-printed titanium alloy prosthesis was custom-designed for chest wall reconstruction. Prior to bone reconstruction, pleural reconstruction was achieved with Bard Composix E/X Mesh, while soft tissue repair involved muscle flap and musculocutaneous flap procedures. A one-year follow-up assessment revealed that the utilization of the 3D-printed titanium alloy prosthesis led to secure fixation, favorable histocompatibility, and enhanced lung function. The findings demonstrate that the utilization of 3D printed titanium alloy prostheses represents a significant advancement in the field of chest wall reconstruction and thoracic surgical procedures.

Source to risk receptor transport and spatial hotspots of heavy metals pollution in peri-urban agricultural soils of the largest megacity in China.

The traditional concentration-based health risk assessment of heavy metal (HMs) pollution in soil has often overlooked the initial loading and toxicity differences of HMs from various sources. This oversight hinders effective identification of the risky source, complicating precise risk management of soil HMs pollution. This study applied a source-oriented health risk assessment framework that integrates source profiling, exposure risk assessment, and spatial cluster analysis. Taking the Shanghai City, the largest megacity in China as a case, the findings revealed that overall environmental quality of peri-urban agricultural soil in Shanghai remains good, though 3.03 % of Cd concentrations exceeded the national reference standards. Industrial & traffic activities, primarily contributing Hg, Cd, and Pb, accounted for the highest proportion (44.3 %) of total metal concentrations and posed the greatest non-cancer risk (54.6 % for children and 53.1 % for adults). Notably, natural activities, mainly contributing Cr, ranked only third in concentration contribution (26.55 %) but induced the highest cancer risk (58.55 % for children and 57.08 % for adults). These findings suggest that sources with lower concentration contributions may still pose significant health risk. Integrating source apportionment with health risk assessment can more precisely identify the risky source and target areas for mitigating the human health hazards.

Development of a Monte Carlo simulation platform for the systematic evaluation of photon-counting detector-based micro-CT.

PURPOSE: This study aimed to develop a photon-counting detector (PCD) based micro-CT simulation platform for assessing the performance of three different PCD sensor materials: cadmium telluride (CdTe), gallium arsenide (GaAs), and silicon (Si). The evaluation encompasses the components of primary and scatter signals, performance of imaging contrast agents, and detector efficiency. METHODS: Simulations were performed using the Geant4 Monte Carlo toolkit, and a micro-PCD-CT system was meticulously modeled based on realistic geometric parameters. RESULTS: The simulation can obtain HU values consistent with measured results for iodine and calcium hydroxyapatite contrast agents. The two major components of scatter signals for CdTe and GaAs based PCD are fluorescent X-ray photons and photoelectrons, whereas for Si, the components are photoelectrons and Compton electrons. Scattering counts of CdTe and GaAs sensors can be effectively reduced by using energy thresholds, whereas those of Si sensor are insensitive to the applied threshold. The optimal threshold values for CdTe and GaAs are 30 and 15 keV, respectively. For contrast agent imaging, GaAs exhibits enhanced sensitivity to low photon energies compared to CdTe, while it's contrast-to-noise ratio (CNR) values are slightly lower than those of CdTe at the same contrast agent concentration. Among the three sensor materials, Si has the lowest CNR and detector efficiency; CdTe exhibits the highest efficiency, except in low-energy ranges (< 45 keV), where GaAs has superior efficiency. CONCLUSIONS: The proposed methods are expected to benefit PCD optimization and applications, including energy threshold selection, scattering correction, and may reduce the need for large-scale experiments.

Appropriate sulfur fertilization in contaminated soil enhanced the cadmium uptake by hyperaccumulator Sedum alfredii Hance.

The biogeochemical processes of sulfur and heavy metals in the environment are closely related to each other. We investigated the influence of sulfur addition on hyperaccumulator Sedum alfredii Hance growth, cadmium (Cd) accumulation, soil Cd bioavailability, soil bacterial communities and plant transcriptome responses. The results showed that an appropriate rate of sulfur addition (1.0 or 2.5 g/kg) enhanced the growth of Sedum alfredii Hance plants as well as their accumulation of Cd. A high rate of sulfur addition (5.0 or 10.0 g/kg) causes toxicity to Sedum alfredii Hance plants. The application of an appropriate amount of sulfur to the soil increased the abundance of sulfur-oxidizing bacteria such as Sulfuriferula and Thiobacillus; acid-fast bacillus such as Alicyclobacillus; and cadmium-tolerant bacteria such as Bacillus and Rhodanobacter. This led to a decrease in pH and an increase in bioavailable Cd in the soil. RNA sequencing revealed that the addition of sulfur to soils led to the up regulation of most of the differentially expressed genes (DEGs) involved in "photosynthesis" and "photosynthesis, light reaction" in Sedum alfredii Hance leaves. Moreover, the "plant hormone signal transduction" pathway was significantly enriched with sulfur addition. Sulfur assimilation in Sedum alfredii Hance plants may promote photosynthesis and hormone synthesis, leading to Cd tolerance in these plants. Our study revealed that sulfur fertilization enhanced the efficiency of Cd phytoremediation in Sedum alfredii Hance plants.

Comparison of linear energy transfer measurement for therapeutic carbon beam using CR-39 and TLD.

The measurement of linear energy transfer (LET) is crucial for the evaluation of the radiation effect in heavy ion therapy. As two detectors which are convenient to implant into the phantom, the performance of CR-39 and thermoluminescence detector (TLD) for LET measurement was compared by experiment and simulation in this study. The results confirmed the applicability of both detectors for LET measurements, but also revealed that the CR-39 detector would lead to potential overestimation of dose-averaged LET compared with the simulation by PHITS, while the TLD would have a large uncertainty measuring ions with LET larger than 20 keVµm-1. The results of this study were expected to improve the detection method of LET for therapeutic carbon beam and would finally be benefit to the quality assurance of heavy ion radiotherapy.

Evaluating the protective capacity of soil heavy metals regulation limits on human health: A critical analysis concerning risk assessment - Importance of localization.

Heavy metal pollution of agricultural soil is a major global concern, prompting the establishment of maximum allowable limits (MALs) to ensure food safety and protect human health. This study collected and compared MALs for six heavy metals (As, Cd, Hg, Pb, Zn, and Cu) in agricultural soils from representative countries and organizations (EU and WHO/FAO). The research evaluated the critical health risks and efficacy of these MALs under the hypothetical scenario of metals concentrations reaching the maximum allowable level. Safe thresholds for heavy metals were then derived based on maximum acceptable health risk levels. The comparative analysis revealed significant variations in the specific limit values and terms of MALs across countries and organizations, even for the same metal. This suggests that there is no consensus among countries and organizations regarding the level of metal-related health risks. Furthermore, the risk analysis of metal concentrations reaching the maximum level accentuated heightened risks associated with As, suggesting that the current risk of soil As exposure was underestimated, particularly for children. However, soil Cu, Cd, and Zn limits generally resulted in low health risks, implying that the current limits may overestimate their hazard. Overall, the results highlight that the current MALs for soil heavy metals may not fully safeguard human health. There is a critical need to optimize current soil MALs based on localized risks and the actual impact of these metals on human health. It is suggested to appropriately lower the limits of metals (such as As) whose impact on health risks is underestimated, and cautiously increase the limits of metals (such as Cu, Cd, and Zn) that currently pose minor health risks. This approach aims to reduce both over and insufficient protection problems of soil heavy metal MALs, emphasizing the importance of considering the locality in setting these limits.

Chinese herbal decoction, Yi-Qi-Jian-Pi formula exerts anti-hepatic fibrosis effects in mouse models of CCl4-induced liver fibrosis.

Background: Yi-Qi-Jian-Pi Formula (YQJPF) is a herbal medicine that is used to treat patients with liver failure. However, scientific evidence supporting the treatment of hepatic fibrosis with YQJPF has not been forthcoming. The present study aimed to determine the mechanisms underlying the anti-fibrotic effects of YQJPF in mouse models of hepatic fibrosis. Methods: Mice were randomly assigned to control, hepatic fibrosis model, silymarin (positive treated), and low-, medium- and high-dose YQJPF (7.5, 15, and 30 g/kg, respectively) groups. Liver function, inflammatory cytokines, and oxygen stress were analyzed using ELISA kits. Sections were histopathologically stained with hematoxylin-eosin, Masson trichrome, and Sirius red. Macrophage polarization was measured by flow cytometry and immunofluorescence. Potential targets of YQJPF against hepatic fibrosis were analyzed by network pharmacology of Chinese herbal compound and the effects of YQJPF on the transforming growth factor-beta (TGF-ß)/Suppressor of Mothers against Decapentaplegic family member 3 (Smad3) signaling pathway were assessed using qRT-PCR and immunohistochemical staining. Finally, metagenomics and LC-MS/MS were used to detect the intestinal flora and metabolites of the mice, and an in-depth correlation analysis was performed by spearman correlation analysis. The data were compared by one-way ANOVA and least significant differences (LSDs) or ANOVA-Dunnett's T3 method used when no homogeneity was detected. Results: We induced hepatic fibrosis using CCl4 to establish mouse models and found that YQJPF dose-dependently increased body weight, improved liver function, and reversed hepatic fibrosis. Elevated levels of the pro-inflammatory factors IL-1ß, IL-6, and TNF-α in the model mice were substantially decreased by YQJPF, particularly at the highest dose. Levels of serum malondialdehyde and superoxide dismutase (SOD) activity were elevated and reduced, respectively. The malondialdehyde concentration decreased and SOD activity increased in the high-dose group. M1 polarized macrophages (CD86) in the mouse models were significantly decreased and M2 polarization was mildly decreased without significance. However, high-dose YQJPF increased the numbers of M2 macrophages and inhibited TGF-ß/Smad3 signaling. Metagenomic and non-targeted metabolomics detection results showed that YQJPF could regulate intestinal homeostasis, and Spearman correlation analysis showed that the abundance of Calditerrivibrio_nitroreducens was significantly negatively correlated with 18ß-glycyrrhetinic acid. It is suggested that Calditerrivibrio_nitroreducens may reduce the anti-fibrosis effect of licorice and other Chinese herbs by digesting 18ß-glycyrrhetinic acid. Conclusions: YQJPF can reverse liver fibrosis by inhibiting inflammation, suppressing oxidative stress, regulating the immunological response initiated by macrophages, inhibiting TGF-ß/Smad3 signaling and regulating intestinal flora homeostasis. Therefore, YQJPF may be included in clinical regimens to treat hepatic fibrosis.

Phosphate Transporter OsPT4, Ubiquitinated by E3 Ligase OsAIRP2, Plays a Crucial Role in Phosphorus and Nitrogen Translocation and Consumption in Germinating Seed.

Phosphorus (P) and nitrogen (N) are essential macronutrients necessary for plant growth and development. OsPT4 is a high-affinity phosphate (Pi) transporter that has a positive impact on nutrient uptake and seed development. In this study, the expression patterns of different Pi transporter genes in germinating seeds were determined, and the relative expression of OsPT4 was induced in Pi-deficient seeds and gradually increased with the passage of germination time. The analysis of P, N, Pi, and amino acid concentrations in germinating seeds of OsPT4 mutants showed that the OsPT4 mutation caused P and N retention and a continuous reduction in multiple amino acid concentrations in germinating seeds. Transcriptome analysis and qRT-PCR results also indicated that the OsPT4 mutation inhibits the expression of genes related to P and N transportation and amino acid synthesis in germinating seeds. In addition, the paraffin section and TUNEL assay of OsPT4 mutant germinating seeds suggests that OsPT4 mutation causes programmed cell death (PCD) delayed in the aleurone layer and inhibition of leaf outgrowth. Moreover, we also found that OsPT4 was ubiquitinated by OsAIRP2, which is a C3HC4-type RING E3 Ub ligase. Our studies illustrate that OsPT4 plays a crucial role in P and N collaborative translocation and consumption in germinating seeds. It also provides a theoretical basis for the molecules and physiological mechanisms of P and N cross-talk under suppressed Pi uptake conditions.

Predictive Value of Carotid Plaque Contrast-Enhanced Ultrasound Score and Homocysteine in Senile Metabolic Syndrome Complicated by Cerebral Infarction.

OBJECTIVE: To investigate the predictive value of the carotid plaque contrast-enhanced ultrasound (CEUS) score and blood homocysteine (HCY) in senile metabolic syndrome (MetS) complicated by cerebral infarction. STUDY DESIGN: Observational study. Place and Duration of the Study: Department of Ultrasound Imaging, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, China, from July 2020 to December 2021. METHODOLOGY: A total of 118 senile MetS patients complicated by cerebral infarction were selected as Group A, and 103 senile MetS patients without cerebral infarction were selected as Group B. Both groups were compared in terms of cardiovascular risk factors and ultrasonic examination of carotid plaques. The independent risk factors for cerebral infarction among senile MetS patients were analysed using logistic regression. An ROC curve was used to assess the predictive value of statistically significant risk factors in senile MetS complicated by cerebral infarction. RESULTS: Significant differences were observed in smoking, abdominal circumference, blood pressure, HCY, fasting blood glucose, high-density and low-density lipoprotein cholesterol, triacylglycerol, carotid plaque thickness, CEUS score, lumen stenosis, and ulcer plaque between the two groups. Logistic regression analysis showed that the plaque CEUS score and HCY were independent risk factors for senile MetS complicated by cerebral infarction. The areas under the ROC curve for the CEUS score and HCY were 0.795 and 0.812, respectively, and was 0.858 for the combined diagnosis of both. When the CEUS score was ≥2 and HCY was ≥16.45 mmol/l, the sensitivity and specificity of predicted senile MetS complicated by cerebral infarction were 83.1% and 74.8%, respectively. CONCLUSION: The carotid plaque CEUS score and blood HCY exhibit a substantial predictive capacity for cerebral infarction in elderly MetS patients. The combined diagnostic efficacy of the two is superior. KEY WORDS: Contrast-enhanced ultrasound, Homocysteine, Elderly, Metabolic syndrome, Cerebral infarction, Carotid plaque.

A prospective health risks analysis of regulatory limits for heavy metals in rice from representative organizations and countries worldwide: Are they protective?

Heavy metals contamination in rice has been one of the most public concerns globally; thus, many countries and organizations issued the maximum acceptable limits (MALs) of their concentrations in rice to regulate food safety and health risks. However, the applicability of these MALs has rarely been thoroughly evaluated. This study collected the MALs of heavy metals for rice from representative countries and organizations around the world. We assessed the critical health risks in the case of metal concentrations that reached the MALs for the first time. Results showed great variability of rice regulation limits owing to different processing methods (paddy, polished, and brown rice) and metal types (mainly focusing on inorganic As, Cd, and Pb). Risk analysis revealed that the inorganic As limits and part of Cd limits for polished rice generated relatively high health risks, indicating that their risks may be underestimated. Monte Carlo simulation further showed that the daily intake rate of rice (IRrice) is the largest contributor to total variances for the derivation of MALs, and regulation limits decreased with the augment of IRrice. Overall, we suggest a cautious reduction in the allowable limits of certain metals (such as inorganic As and part of Cd) in rice as their health risks and toxicity may be underestimated.

European NCAP Driver State Monitoring Protocols: Prevalence of Distraction in Naturalistic Driving.

OBJECTIVE: examine the prevalence of driver distraction in naturalistic driving when implementing European New Car Assessment Program (Euro NCAP)-defined distraction behaviours. BACKGROUND: The 2023 introduction of Occupant Status monitoring (OSM) into Euro NCAP will accelerate uptake of Driver State Monitoring (DSM). Euro NCAP outlines distraction behaviours that DSM must detect to earn maximum safety points. Distraction behaviour prevalence and driver alerting and intervention frequency have yet to be examined in naturalistic driving. METHOD: Twenty healthcare workers were provided with an instrumented vehicle for approximately two weeks. Data were continuously monitored with automotive grade DSM during daily work commutes, resulting in 168.8 hours of driver head, eye and gaze tracking. RESULTS: Single long distraction events were the most prevalent, with .89 events/hour. Implementing different thresholds for driving-related and driving-unrelated glance regions impacts alerting rates. Lizard glances (primarily gaze movement) occurred more frequently than owl glances (primarily head movement). Visual time-sharing events occurred at a rate of .21 events/hour. CONCLUSION: Euro NCAP-described driver distraction occurs naturalistically. Lizard glances, requiring gaze tracking, occurred in high frequency relative to owl glances, which only require head tracking, indicating that less sophisticated DSM will miss a substantial amount of distraction events. APPLICATION: This work informs OEMs, DSM manufacturers and regulators of the expected alerting rate of Euro NCAP defined distraction behaviours. Alerting rates will vary with protocol implementation, technology capability, and HMI strategies adopted by the OEMs, in turn impacting safety outcomes, user experience and acceptance of DSM technology.

Incorporating structural plasticity into self-organization recurrent networks for sequence learning.

Introduction: Spiking neural networks (SNNs), inspired by biological neural networks, have received a surge of interest due to its temporal encoding. Biological neural networks are driven by multiple plasticities, including spike timing-dependent plasticity (STDP), structural plasticity, and homeostatic plasticity, making network connection patterns and weights to change continuously during the lifecycle. However, it is unclear how these plasticities interact to shape neural networks and affect neural signal processing. Method: Here, we propose a reward-modulated self-organization recurrent network with structural plasticity (RSRN-SP) to investigate this issue. Specifically, RSRN-SP uses spikes to encode information, and incorporate multiple plasticities including reward-modulated spike timing-dependent plasticity (R-STDP), homeostatic plasticity, and structural plasticity. On the one hand, combined with homeostatic plasticity, R-STDP is presented to guide the updating of synaptic weights. On the other hand, structural plasticity is utilized to simulate the growth and pruning of synaptic connections. Results and discussion: Extensive experiments for sequential learning tasks are conducted to demonstrate the representational ability of the RSRN-SP, including counting task, motion prediction, and motion generation. Furthermore, the simulations also indicate that the characteristics arose from the RSRN-SP are consistent with biological observations.

Nanoscale Morphologies on the Surface of 3D-Printed Titanium Implants for Improved Osseointegration: A Systematic Review of the Literature.

Three-dimensional (3D) printing is serving as the most promising approach to fabricate personalized titanium (Ti) implants for the precise treatment of complex bone defects. However, the bio-inert nature of Ti material limits its capability for rapid osseointegration and thus influences the implant lifetime in vivo. Despite the macroscale porosity for promoting osseointegration, 3D-printed Ti implant surface morphologies at the nanoscale have gained considerable attention for their potential to improve specific outcomes. To evaluate the influence of nanoscale surface morphologies on osseointegration outcomes of 3D-printed Ti implants and discuss the available strategies, we systematically searched evidence according to the PRISMA on PubMed, Embase, Web of Science, and Cochrane (until June 2022). The inclusion criteria were in vivo (animal) studies reporting the osseointegration outcomes of nanoscale morphologies on the surface of 3D-printed Ti implants. The risk of bias (RoB) was assessed using the Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE's) tool. The quality of the studies was evaluated using the Animal Research: Reporting of In Vivo Experiments (ARRIVE) guidelines. (PROSPERO: CRD42022334222). Out of 119 retrieved articles, 9 studies met the inclusion criteria. The evidence suggests that irregular nano-texture, nanodots and nanotubes with a diameter of 40-105nm on the surface of porous/solid 3D-printed Ti implants result in better osseointegration and vertical bone ingrowth compared to the untreated/polished ones by significantly promoting cell adhesion, matrix mineralization, and osteogenic differentiation through increasing integrin expression. The RoB was low in 41.1% of items, unclear in 53.3%, and high in 5.6%. The quality of the studies achieved a mean score of 17.67. Our study demonstrates that nanostructures with specific controlled properties on the surface of 3D-printed Ti implants improve their osseointegration. However, given the small number of studies, the variability in experimental designs, and lack of reporting across studies, the results should be interpreted with caution.

Yi-Qi-Jian-Pi formula inhibits hepatocyte pyroptosis through the IDH2-driven tricarboxylic acid cycle to reduce liver injury in acute-on-chronic liver failure.

ETHNOPHARMACOLOGICAL RELEVANCE: Yi-Qi-Jian-Pi formula (YQJPF) is a commonly used traditional Chinese medicine (TCM) compound used to treat acute-on-chronic liver failure (ACLF) in China, but its specific mechanism of action has not been fully clarified. AIM OF THE STUDY: The aim of this study was to determine the effect of YQJPF on liver injury and hepatocyte pyroptosis in rats and further explore its molecular mechanism of action. MATERIALS AND METHODS: This study established carbon tetrachloride (CCl4)-, lipopolysaccharide (LPS)- and D-galactose (D-Gal)-induced in vivo models of ACLF in rats and in vitro LPS-induced hepatocyte injury models. Animal experiments were divided into the following groups: control, ACLF model, groups with different doses of YQJPF (5.4, 10.8, and 21.6 g/kg), and western medicine (methylprednisolone). There were 7 rats in the control group and 11 in the other groups. Serological, immunohistochemical, and pathological analyses were used to observe the effect of YQJPF on the liver of ACLF rats. The protective effect of YQJPF on hepatocytes was further verified by RT-qPCR, western blotting, flow cytometry, enzyme-linked immunosorbent assay (ELISA), and other methods. RESULTS: YQJPF significantly improved liver injury in vivo and in vitro, which depended on the regulation of hepatocyte NLRP3/GSDMD-induced pyroptosis. In addition, we found that mitochondrial membrane potential and ATP production decreased after LPS treatment of hepatocytes, which suggested that YQJPF may improve mitochondrial energy metabolism disorders in hepatocytes. We administered a hepatocyte mitochondrial uncoupling agent, FCCP, to determine whether mitochondrial metabolic disorders affected cell pyroptosis. The results showed that the expression of IL-18, IL-1ß, and NLRP3 proteins increased significantly, indicating that the effect of this drug on hepatocyte pyroptosis may be related to mitochondrial metabolism disorders. We found that YQJPF significantly restored the tricarboxylic acid (TCA) cycle rate-limiting enzyme activity and affected the content of TCA metabolites. Furthermore, we revealed that the IDH2 gene, which plays a unique role in ACLF, is a key factor in the regulation of the mitochondrial TCA cycle and can be upregulated under the action of YQJPF. CONCLUSIONS: YQJPF can inhibit classical pyroptosis in hepatocytes by regulating TCA cycle metabolism, thus alleviating liver injury, and IDH2 may be a potential upstream regulatory target of YQJPF.

Yellow tea: more than turning green leaves to yellow.

Yellow tea (YT), a slightly-fermented tea originated from Ming Dynasty with distinctive "Three yellows," mild-sweet smell, and mellow taste attributed to the unique yellowing process. Based on current literature and our previous work, we aim to comprehensively illustrate the key processing procedures, characteristic chemical compounds, health benefits and applications, as well as the interlocking relationships among them. Yellowing is the most vital procedure anchored on the organoleptic quality, characteristic chemical components, and bioactivities of YT, which is influenced by temperature, moisture content, duration, and ventilation conditions. Pheophorbides, carotenoids, thearubigins and theabrownins are the major pigments contributing to the "three yellows" appearance. Alcohols, such as terpinol and nerol, are attributed to the refreshing and sweet aroma of bud and small-leaf YT, while heterocyclics and aromatics forming during roasting result in the crispy rice-like large-leaf YT. Hygrothermal effects and enzymatic reactions during yellowing result in the decline of astringent substances. Meanwhile, multiple bioactive compounds such as catechins, ellagitannins, and vitexin, endow YT with antioxidant, anti-metabolic syndrome, anti-cancer, gut microbiota regulation, and organ injury protection effects. Future studies focusing on the standard yellowing process technology, quality evaluation system, and functional factors and mechanisms, possible orientations, and perspectives are guaranteed.

Yi-Qi-Jian-Pi formula ameliorates immune function in acute-on-chronic liver failure by upregulating autophagy and mitochondrial biogenesis in CD8+ T lymphocytes.

ETHNOPHARMACOLOGICAL RELEVANCE: A key event in the pathogenesis of acute-on-chronic liver failure (ACLF) is the imbalance in the systemic immune response; immunosuppression in patients with ACLF contributes to poor prognosis. The Yi-Qi-Jian-Pi formula (YQJPF) may improve T lymphocyte immune function in patients with ACLF. AIM OF THE STUDY: To investigate the immune mechanism of YQJPF in vivo and in vitro. MATERIALS AND METHODS: An ACLF rat model was established by injection of CCl4, lipopolysaccharide, and D-galactosamine. We examined the effect of different doses of YQJPF (6.43, 12.87, 25.74 g/kg) on liver injury and immune function in the ACLF rat model. Magnetic-activated cell sorting was used to sort the CD8+ T lymphocytes in the spleen for lymphocyte function detection. In primary CD8+ T lymphocytes and Jurkat cell lines, the expression of mitochondrial function and biogenesis and autophagy related markers were detected using molecular biological methods and flow cytometry analysis. RESULTS: YQJPF improved the peripheral blood lymphocyte count and proportion of CD8+ T lymphocytes in ACLF rats, increased pro-inflammatory factors (IL-2, IFN-λ, and TNF-α), and reduced anti-inflammatory factors (IL-10 and TGF ß1). YQJPF also improved metabolism and mitochondrial homeostasis in CD8+ T lymphocytes, alleviated lymphocyte immune dysfunction by promoting autophagy, upregulated mitochondrial biogenesis by promoting PGC-1α, NRF-1, and TFAM expression, and regulated the relationship between autophagy and mitochondrial biogenesis via PGC-1α. CONCLUSIONS: Our results suggest that YQJPF could improve immune function in a rat model of ACLF, possibly via affecting the homeostasis of lymphatic mitochondria in CD8+ T lymphocytes. YQJPF may enhance lymphocyte mitochondrial biosynthesis and promote lymphocyte autophagy. PGC-1α is a possible upstream regulatory target of YQJPF.

Tracking cadmium pollution from source to receptor: A health-risk focused transfer continuum approach.

Cadmium (Cd) exposure poses a substantial risk to human health. Despite this, the multi-stage process through which Cd is released to the environment before being taken up and impacting human receptors has rarely been investigated. Here we utilized an integrated model involving Cd emissions, atmospheric transport, deposition, uptake by rice, receptor ingestion and metabolic processing in quantifying the critical emission sources and human health risks of Cd. Atmospheric Cd emissions in the study area in southeastern China were estimated at 147 kg (2016), with >53 % of emissions from non-ferrous metals (NFM) smelting activities. Atmospheric Cd depositions caused elevated Cd content in soil and rice, accounting for 3-79 % and 50-85 % of, respectively, soil and rice Cd. Cumulative frequency analysis showed that an estimated 1.3 % of predicted urine Cd through the consumption of Cd-contaminated rice and exceeded existing safety standards (1 µg g-1), thus highlighting the risks posed to health from high levels of Cd pollution. Applying stricter industrial emission standards to the NFM sector in particular and effective soil management practices could substantially reduce exposure to Cd pollution. The results contribute to understanding of the Cd transfer process and draw attention to the relative health benefits of interventions aimed at mitigating Cd levels and exposure risks at different stages along the Cd transfer continuum from source to receptor.

Towards an integrated health risk assessment framework of soil heavy metals pollution: Theoretical basis, conceptual model, and perspectives.

The health risk of soil heavy metals pollution has been gaining increasing public concern. However, many countries have not set their own health risk assessment (HRA) framework and most of the existing studies directly referred to the USEPA risk assessment model and parameters. For those countries that do not propose an original HRA framework, the experience of developed countries is crucial for advancing their own HRA system. This study systematically reviewed the development of HRA framework in some representative developed countries. The theoretical basis, conceptual model, progress, and challenges of HRA researches concerning soil heavy metals pollution were summarized. By recalling and comparing the health risk-related laws and guidance in the USA, UK, and Japan, results showed that the construction of HRA framework varied between these countries, but HRA has become the main method for deriving their soil environmental criteria. We further summarized the evaluation scales, land use types, exposure pathways, and sensitive receptors of HRA studies, and highlighted the key parameters affecting health risk outputs. There has been a shift toward the incorporation of probabilistic modeling, metals bioavailability, and sources emission characteristics into recent HRA studies. Nonetheless, challenges remained on how to minimize the uncertainty of generating probability distribution and detecting metal bioavailability. To facilitate the development of HRA framework, it was advised that developing countries should strengthen the theoretical researches of health risk and localization researches of exposure factors. Future directions are suggested to tend to: 1) promote sensitive analysis to quantify the impact of distribution assumptions on health risk outputs, 2) derive reasonable risk threshold and consistent evaluation protocol for bioavailability-based health risk assessment method, and 3) strive to explore the combined health effect of exposure to heavy metals in soil through source-media-receptor integrated studies.

Hydroxyls on the B ring and gallic acyl are essential for catechins to restrain ADP-induced thrombosis.

Platelet hyperactivation could lead to various cardiovascular and cerebrovascular diseases, while epidemiological analyses have found that long-term tea drinking could prevent and restrain cardiovascular diseases. Existing studies have shown that catechins, especially epigallocatechin gallate (EGCG), are the main functional factors of tea in alleviating thrombosis, which could inhibit arterial thrombosis and platelet aggregation induced by a variety of agonists. However, their structure-activity relationship and the underlying mechanisms are still unclear. Based on the above background, this study took six typical catechins as research objects, constructed platelet activation models with different inducers, and explored the inhibitory effects and potential mechanisms of catechins with different structures on platelet aggregation through flow cytometry, immunoblotting, cell spreading, and other experiments. It was found that ester catechins could inhibit platelet aggregation induced by adenosine diphosphate (ADP), while epigallocatechin (EGC) with three hydroxyls on the B ring in non-ester catechins was also able to effectively inhibit platelet aggregation. Our data suggested that gallic acyl on the C ring and three hydroxyls on the B ring were the main functional groups affecting the antithrombotic effect of catechins, and the effect of gallic acyl on platelets was significantly stronger than that of the hydroxyl.