[Multi-objective Identification Method for Influencing Factors of Soil Heavy Metal Content Change].

Identifying the influencing factors of soil heavy metal content changes is the basis for reducing or preventing soil heavy metal pollution. Taking an agricultural experimental field in Changping District of Beijing as an example, the heavy metal content changes in As, Cr, Cu, Ni, Pb, and Zn from 2012 to 2022 were firstly analyzed. Secondly, the influencing factors of the heavy metal content changes were detected based on the geographical detector at the single-target and multi-target levels, respectively. Finally, comparative experiments with the correlation analysis method and existing studies were set up to evaluate the effectiveness of the identification method of influencing factors developed in this study. The results showed that human activity factors have exacerbated the changes in soil heavy metal content in the study area as follows： ① At the single-target level, the land use type was the main influencing factor on the changes in Cr, Cu, and Zn contents, and the annual deposition flux influenced the changes in As. The results of the interaction detection showed that there was an enhancement effect among the factors, and the interaction of the human activity factors dominated for the factor identification. ② The results of the multi-target level detection covered the results of the single-target level detection, which could identify more influencing factors. The land use type affected the changes in Cu, Zn, Cr, Ni, and As, and the changes in As and Zn were influenced by the annual deposition fluxes. ③ The multi-target identification method coupled with geographical detector and principal component analysis could effectively identify the influencing factors of soil heavy metal content changes, which was much more effective than the single soil heavy metal correlation method. The developed multi-target identification method for influencing factors of heavy metal content changes can provide technical support for the regional pollution monitoring and macro-management of soil heavy metals.

Preparation of micron-sized benzamidine-modified magnetic agarose beads for trypsin purification from fish viscera.

The effective method for trypsin purification should be established because trypsin has important economic value. In this work, a novel and simple strategy was proposed for fabricating micron-sized magnetic Fe3O4@agarose-benzamidine beads (MABB) with benzamidine as a ligand, which can efficiently and selectively capture trypsin. The micro-sized MABB, with clear spherical core-shell structure and average particle size of 6.6 µm, showed excellent suspension ability and magnetic responsiveness in aqueous solution. The adsorption capacity and selectivity of MABB towards target trypsin were significantly better than those of non-target lysozyme. According to the Langmuir equation, the maximum adsorption capacity of MABB for trypsin was 1946 mg g-1 at 25 °C, and the adsorption should be a physical sorption process. Furthermore, the initial adsorption rate and half equilibrium time of MABB toward trypsin were 787.4 mg g-1 min-1 and 0.71 min, respectively. To prove the practicability, MABB-based magnetic solid-phase extraction (MSPE) was proposed, and the related parameters were optimized in detail to improve the purification efficiency. With Tris-HCl buffer (50 mM, 10 mM CaCl2, pH 8.0) as extraction buffer, Tris-HCl buffer (50 mM, 100 mM CaCl2, pH 8.0) as rinsing buffer, acidic eluent (0.01 M HCl, 0.5 M NaCl, pH 2.0) as eluent buffer and alkaline buffer (1 M Tris-HCl buffer, pH 10.0) as neutralization solution, the MABB-based MSPE was successfully used for trypsin purification from the viscera of grass carp (Ctenopharyngodon idella). The molecular weight of purified trypsin was determined as approximate 23 kDa through sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The purified trypsin was highly active from 30 °C to 60 °C, with an optimum temperature of 50 °C, and was tolerant to pH variation, exhibiting 85 % of maximum enzyme activity from pH 7.0 to 10.0. The results demonstrated that the proposed MABB-based MSPE could effectively purify trypsin and ensure the biological activity of purified trypsin. Therefore, we believe that the novel MABB could be applicable for efficient purification of trypsin from complex biological systems.

A hot-emitter transistor based on stimulated emission of heated carriers.

Hot-carrier transistors are a class of devices that leverage the excess kinetic energy of carriers. Unlike regular transistors, which rely on steady-state carrier transport, hot-carrier transistors modulate carriers to high-energy states, resulting in enhanced device speed and functionality. These characteristics are essential for applications that demand rapid switching and high-frequency operations, such as advanced telecommunications and cutting-edge computing technologies1-5. However, the traditional mechanisms of hot-carrier generation are either carrier injection6-11 or acceleration12,13, which limit device performance in terms of power consumption and negative differential resistance14-17. Mixed-dimensional devices, which combine bulk and low-dimensional materials, can offer different mechanisms for hot-carrier generation by leveraging the diverse potential barriers formed by energy-band combinations18-21. Here we report a hot-emitter transistor based on double mixed-dimensional graphene/germanium Schottky junctions that uses stimulated emission of heated carriers to achieve a subthreshold swing lower than 1 millivolt per decade beyond the Boltzmann limit and a negative differential resistance with a peak-to-valley current ratio greater than 100 at room temperature. Multi-valued logic with a high inverter gain and reconfigurable logic states are further demonstrated. This work reports a multifunctional hot-emitter transistor with significant potential for low-power and negative-differential-resistance applications, marking a promising advancement for the post-Moore era.

The protective role of Cordyceps cicadae and its active ingredient myriocin against sodium iodate-induced age-related macular degeneration via an anti-necroptotic TNF-RIPK1/3 pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Cordyceps cicadae (C.cicadae), named "Chan Hua", an anamorph of Isaria cicadae Miquel, is an entomogenous complex formed by fungi parasitizing on the larvae of cicadas and belongs to the Claviciptaceae family and the genus Codyceps, which traditionally holds a significant place in Chinese ethnopharmacology, specifically for eye clarity and as a remedy for age-related ocular conditions. The underlying mechanisms contributing to its eyesight enhancement and potential effectiveness against Age-related macular degeneration (AMD) remain unexplored. AIM OF THE STUDY: This study aims to elucidate the protective role of C.cicadae and its active ingredient, Myriocin (Myr), against AMD. MATERIALS AND METHODS: A chemical inducer was employed to make retinal pigment epithelium (RPE) damage in vitro and in vivo. The key ingredients of C.cicadae and their related mechanisms for anti-AMD were studied through bioinformatic analysis and molecular biological approaches. RESULTS: Myr was identified through high-performance liquid chromatography (HPLC) as an active ingredient in C.cicadae, and demonstrated a protective effect on RPE cells, reducing the structural damage and cell death induced by sodium iodate (SI). Further, Myr reduced eyelid secretions in AMD mice and restored their retinal structure and function. The differentially expressed genes (DEGs) in Myr treatment are primarily associated with TNF and Necroptosis signaling pathways. Molecular docking indicated a strong affinity between TNF and Myr. Myr inhibited the TNF signaling pathway thereby reducing the expression of inflammatory factors in ARPE-19 cells. Additionally, Myr had consistent action with the necroptosis inhibitor Necrostatin-1 (Nec-1), inhibited the RIPK1/RIPK3/MLKL pathway thereby protecting ARPE-19 cells. CONCLUSION: The findings present Myr, as a potent protector against SI-induced AMD, predominantly through modulation of the TNF-RIPK1/RIPK3/MLKL signaling pathway, offering the insights of therapeutic C.cicadae as viable candidates for AMD treatment.

Genome mining of sulfonated lanthipeptides reveals unique cyclic peptide sulfotransferases.

Although sulfonation plays crucial roles in various biological processes and is frequently utilized in medicinal chemistry to improve water solubility and chemical diversity of drug leads, it is rare and underexplored in ribosomally synthesized and post-translationally modified peptides (RiPPs). Biosynthesis of RiPPs typically entails modification of hydrophilic residues, which substantially increases their chemical stability and bioactivity, albeit at the expense of reducing water solubility. To explore sulfonated RiPPs that may have improved solubility, we conducted co-occurrence analysis of RiPP class-defining enzymes and sulfotransferase (ST), and discovered two distinctive biosynthetic gene clusters (BGCs) encoding both lanthipeptide synthetase (LanM) and ST. Upon expressing these BGCs, we characterized the structures of novel sulfonated lanthipeptides and determined the catalytic details of LanM and ST. We demonstrate that SslST-catalyzed sulfonation is leader-independent but relies on the presence of A ring formed by LanM. Both LanM and ST are promiscuous towards residues in the A ring, but ST displays strict regioselectivity toward Tyr5. The recognition of cyclic peptide by ST was further discussed. Bioactivity evaluation underscores the significance of the ST-catalyzed sulfonation. This study sets up the starting point to engineering the novel lanthipeptide STs as biocatalysts for hydrophobic lanthipeptides improvement.

A synergistic mechanism of Liquiritin and Licochalcone B from Glycyrrhiza uralensis against COPD.

BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) is a refractory respiratory disease mainly attributed to multiple pathological factors such as oxidative stress, infectious inflammation, and idiopathic fibrosis for decades. The medicinal plant Glycyrrhiza uralensis extract (ULE) was widely used to control respiratory diseases in China. However, the regulatory mechanism of scientific evidence to support the therapeutic benefits of ULE in the management of COPD is greatly limited. PURPOSE: This study aims to discover the potential protection mechanism of ULE on COPD via a muti-targets strategy. STUDY DESIGN AND METHODS: The present study set out to determine the potential protective effects of ULE on COPD through a multi-target strategy. In vivo and in vitro models of COPD were established using cigarette smoke and lipopolysaccharide to assess the protective effects of ULE. It was evaluated by measuring inflammatory cytokines and assessing pulmonary pathological changes. HPLC was used to verify the active compounds of the potential compounds that were collected and screened using HERB, works of literature, and ADME tools. The mechanisms of ULE in the treatment of COPD were explored using transcriptomics, connectivity-map, and network pharmacology approaches. The relevant targets were further investigated using RT-PCR, western blot, and immunohistochemistry. The HCK inhibitor (iHCK-37) was used to evaluate the potential mechanism of ULE's active compounds in the prevention of COPD. RESULTS: ULE effectively protected the lungs of COPD mice from oxidative stress, inflammation, and fibrosis damage. After screening and verification using ADME properties and HPLC, 4 active compounds were identified in ULE: liquiritin (LQ), licochalcone B (LCB), licochalcone A (LCA), and echinatin (ET). Network pharmacology integrated with transcriptomics analysis showed that ULE mitigated oxidative stress, inflammation, and fibrosis in COPD by suppressing HCK. The combination of LCB and LQ was optimized for anti-inflammation, antioxidation, and anti-fibrosis activities. The iHCK-37 further validated the preventive treatment of LCB and LQ on COPD by inhibiting HCK to exert antioxidant, anti-inflammatory, and anti-fibrotic effects. The combination of LCB and LQ, in a 1:1 ratio, exerted synergistic antioxidative, anti-inflammatory, and anti-fibrotic effects in the treatment of COPD by downregulating HCK. CONCLUSION: The combination of LCB and LQ performed a significant anti-COPD effect via downregulating HCK.

Ciprofol suppresses proliferation, invasion and migration of human pancreatic cancer cells.

Pancreatic cancer (PC) is heterogeneous cancer having a high death rate and poor prognosis. The perioperative variables, such as anesthetics, may affect the cancer progression. Ciprofol is an intravenous anesthetic widely used recently. We aimed to explore the influence of ciprofol on PC and investigate its possible pathway. The proliferation, migration and invasion roles and apoptosis of ciprofol in human PC cells were examined using methylthiazolyldiphenyl-tetrazolium bromide, trans well and flow cytometery analysis. Then the putative targeted genes were examined using RNA-sequencing (RNA-seq) analysis. When differentially expressed genes (DEGs) were found, a protein-protein interaction network and pathway analyses were made. Moreover, MMP1 gene expression was confirmed in PC cells using quantitative real-time PCR. PANC-1 cells of PC were significantly suppressed with ciprofol in a dose-dependent and time-dependent way, and 20µg/mL ciprofol significantly suppressed tumor cell aggressiveness. Additionally, the RNA-seq analysis demonstrated that ciprofol controls the expression of 929 DEGs. 5 of 20 hub genes with increased connection were selected. Survival analysis demonstrated that MMP1 may be involved in the carcinogenesis and establishment of PC, reflecting the possible roles associated with ciprofol. Moreover, one target miRNA (hsa-miR-330-5p) of MMP1 was identified.

Pancreatic stellate cells: Key players in pancreatic health and diseases (Review).

As a pluripotent cell, activated pancreatic stellate cells (PSCs) can differentiate into various pancreatic parenchymal cells and participate in the secretion of extracellular matrix and the repair of pancreatic damage. Additionally, PSCs characteristics allow them to contribute to pancreatic inflammation and carcinogenesis. Moreover, a detailed study of the pathogenesis of activated PSCs in pancreatic disease can offer promise for the development of innovative therapeutic strategies and improved patient prognoses. Therefore, the present study review aimed to examine the involvement of activated PSCs in pancreatic diseases and elucidate the underlying mechanisms to provide a viable therapeutic strategy for the management of pancreas­related diseases.

6-O-angeloylplenolin inhibits osteoclastogenesis in vitro via suppressing c-Src/NF-κB/NFATc1 pathways and ameliorates bone resorption in collagen-induced arthritis mouse model.

One of the effective therapeutic strategies to treat rheumatoid arthritis (RA)-related bone resorption is to target excessive activation of osteoclasts. We discovered that 6-O-angeloylplenolin (6-OAP), a pseudoguaianolide from Euphorbia thymifolia Linn widely used for the treatment of RA in traditional Chinese medicine, could inhibit RANKL-induced osteoclastogenesis and bone resorption in both RAW264.7 cells and BMMs from 1 µM and protect a collagen-induced arthritis (CIA) mouse model from bone destruction in vivo. The severity of arthritis and bone erosion observed in paw joints and the femurs of the CIA model were attenuated by 6-OAP administered at both dosages (1 or 5 mg/kg, i.g.). BMD, Tb.N and BV/TV were also improved by 6-OAP treatment. Histological analysis and TRAP staining of femurs further confirmed the protective effects of 6-OAP on bone erosion, which is mainly due to reduced osteoclasts. Molecular docking indicated that c-Src might be a target of 6-OAP and phosphorylation of c-Src was suppressed by 6-OAP treatment. CETSA and SPR assay further confirmed the potential interaction between 6-OAP and c-Src. Three signaling molecules downstream of c-Src that are vital to the differentiation and function of osteoclasts, NF-κB, c-Fos and NFATc1, were also suppressed by 6-OAP in vitro. In summary, the results demonstrated that the function of c-Src was disrupted by 6-OAP, which led to the suppression of downstream signaling vital to osteoclast differentiation and function. In conclusion, 6-OAP has the potential to be further developed for the treatment of RA-related bone erosion.

Tertiary treatment of municipal wastewater in an IBFR dominated by PD/A with unique niche.

To explore the feasibility of biofilter reactor to treat municipal secondary effluent deeply without extra carbon source, this paper proposed an integrated biofilter reactor (IBFR) coupling partial denitrification (PD) with anammox (A) to treat the secondary effluent and raw sewage with the flow ratio of 3:1 together. The results show that the effluent concentration of TN and COD in IBFR could be reduced to 10 mg/L and 15 mg/L, respectively, under hydraulic retention time of 1.5 h and nitrogen loading rate of 0.55 kg/(m3·d). The highest specific anammox activity (19.2 mg N/(g TVS·d)) and the maximum extracellular polymeric substance (EPS) content (107.21 mg/g TVS) occurred at the 25-50 cm section of IBFR, where Thauera, Candidatus Anammoximicrobium and Candidatus Brocadia were the dominant denitrifiers and anammox bacteria. Furthermore, the cyclic self-stratification occurred along the reactor height, where the utilization, decomposition, transformation and cross-feeding of EPS enhanced the performance stability of nitrogen and carbon removal, strengthened the niche structure and promoted the synergistic symbiosis. In conclusion, IBFR coupling PD and A demonstrated the possibility to treat secondary effluent without additional carbon sources, which is expected as an alternative approach for tertiary treatment of municipal wastewater.

Evaluation of the Thermal Stability and Micro-Modification Mechanism of SBR/PP-Modified Asphalt.

To evaluate the thermal stability of composite polymer-modified asphalt, thermoplastic elastomer styrene-butadiene rubber (SBR)/polypropylene (PP) pellets were prepared using a hot-melt blending technique, with butyl rubber powder and waste polypropylene pellets as raw materials. The effects of different evaluation indexes on the thermal stability of SBR/PP-modified asphalt were investigated using a frequency scan test and a multi-stress creep recovery (MSCR) test, and the compatibility of SBR/PP particles with asphalt was studied using the Cole-Cole diagram and microstructure images. The tests show that, firstly, the performance grade (PG) classification of asphalt can be improved by adding an SBR/PP thermoplastic elastomer to enhance the adaptability of asphalt in high- and low-temperature environments, and the evaluation separation index can reflect the high-temperature storage stability of composite-modified asphalt more reasonably. Additionally, the larger the rubber-to-plastic ratio the worse the high-temperature thermal stability of composite-modified asphalt. Moreover, the addition of additives to the composite particles can promote the SBR/PP particles in the asphalt to be more uniformly dispersed, forming a more desirable microstructure and improving the thermal stability of composite-modified asphalt. Ultimately, the semicircular curve of the Cole-Cole diagram can reflect the compatibility characteristics of the two-phase structure of SBR/PP-modified asphalt, which can be used as an auxiliary index to evaluate the compatibility of polymer-modified asphalt.

[Intestinal absorption components and absorption characteristics of Wuwei Qingzhuo San by everted intestinal sac models].

This study investigated the absorption profile of Wuwei Qingzhuo San in different intestinal segments and the absorption characteristics of its alkaloids(piperine, piperanine, piperlonguminine, and dihydropiperlonguminine). The everted gut sac model was established, and the chemical components of Wuwei Qingzhuo San in different intestinal segments were detected by UPLC-Q-TOF-MS. The content of piperine, piperanine, piperlonguminine, and dihydropiperlonguminine in intestinal absorption fluid was determined by UPLC-Q-TRAP-MS and the absorption parameters were calculated. The absorption characteristics in different intestinal segments at different time were analyzed. As a result, 27, 27, 8, and 6 absorbent components from Wuwei Qingzhuo San were detected in the intestinal cyst fluid of jejunum, ileum, duodenum, and colon by UPLC-Q-TOF-MS technology, respectively. It was also found that piperine, piperanine, piperlonguminine, and dihydropiperlonguminine from Wuwei Qingzhuo San showed linear absorption in various intestinal segments, with r values exceeding 0.9. In terms of absorption content, the components were ranked as piperine>piperanine>dihydropiperlonguminine>piperlonguminine in various intestinal segments, but the absorption rate and mechanism of each component varied. The results demonstrate that the absorption of the components of Wuwei Qingzhuo San in different intestinal segments is selective and is not a simple semi-permeable membrane permeation process.

Alfalfa MsbHLH115 confers tolerance to cadmium stress through activating the iron deficiency response in Arabidopsis thaliana.

Cadmium (Cd) pollution severely affects plant growth and development, posing risks to human health throughout the food chain. Improved iron (Fe) nutrients could mitigate Cd toxicity in plants, but the regulatory network involving Cd and Fe interplay remains unresolved. Here, a transcription factor gene of alfalfa, MsbHLH115 was verified to respond to iron deficiency and Cd stress. Overexpression of MsbHLH115 enhanced tolerance to Cd stress, showing better growth and less ROS accumulation in Arabidopsis thaliana. Overexpression of MsbHLH115 significantly enhanced Fe and Zn accumulation and did not affect Cd, Mn, and Cu concentration in Arabidopsis. Further investigations revealed that MsbHLH115 up-regulated iron homeostasis regulation genes, ROS-related genes, and metal chelation and detoxification genes, contributing to attenuating Cd toxicity. Y1H, EMSA, and LUC assays confirmed the physical interaction between MsbHLH115 and E-box, which is present in the promoter regions of most of the above-mentioned iron homeostasis regulatory genes. The transient expression experiment showed that MsbHLH115 interacted with MsbHLH121pro. The results suggest that MsbHLH115 may directly regulate the iron-deficiency response system and indirectly regulate the metal detoxification response mechanism, thereby enhancing plant Cd tolerance. In summary, enhancing iron accumulation through transcription factor regulation holds promise for improving plant tolerance to Cd toxicity, and MsbHLH115 is a potential candidate for addressing Cd toxicity issues.

Heterozygous CAPZA2 mutations cause global developmental delay, hypotonia with epilepsy: a case report and the literature review.

CAPZA2 encodes the α2 subunit of CAPZA, which is vital for actin polymerization and depolymerization in humans. However, understanding of diseases associated with CAPZA2 remains limited. To date, only three cases have been documented with neurodevelopmental abnormalities such as delayed motor development, speech delay, intellectual disability, hypotonia, and a history of seizures. In this study, we document a patient who exhibited seizures, mild intellectual disability, and impaired motor development yet did not demonstrate speech delay or hypotonia. The patient also suffered from recurrent instances of respiratory infections, gastrointestinal and allergic diseases. A novel de novo splicing variant c.219+1 G > A was detected in the CAPZA2 gene through whole-exome sequencing. This variant led to exon 4 skipping in mRNA splicing, confirmed by RT-PCR and Sanger sequencing. To our knowledge, this is the third study on human CAPZA2 defects, documenting the fourth unambiguously diagnosed case. Furthermore, this splicing mutation type is reported here for the first time. Our research offers additional support for the existence of a CAPZA2-related non-syndromic neurodevelopmental disorder. Our findings augment our understanding of the phenotypic range associated with CAPZA2 deficiency and enrich the knowledge of the mutational spectrum of the CAPZA2 gene.

Divergent Biosynthesis of Bridged Polycyclic Sesquiterpenoids by a Minimal Fungal Biosynthetic Gene Cluster.

The bridged polycyclic sesquiterpenoids derived from sativene, isosativene, and longifolene have unique structures, and many chemical synthesis approaches with at least 10 steps have been reported. However, their biosynthetic pathway remains undescribed. A minimal biosynthetic gene cluster (BGC), named bip, encoding a sesquiterpene cyclase (BipA) and a cytochrome P450 (BipB) is characterized to produce such complex sesquiterpenoids with multiple carbon skeletons based on enzymatic assays, heterologous expression, and precursor experiments. BipA is demonstrated as a versatile cyclase with (-)-sativene as the dominant product and (-)-isosativene and (-)-longifolene as minor ones. BipB is capable of hydroxylating different enantiomeric sesquiterpenes, such as (-)-longifolene and (+)-longifolene, at C-15 and C-14 in turn. The C-15- or both C-15- and C-14-hydroxylated products are then further oxidized by unclustered oxidases, resulting in a structurally diverse array of sesquiterpenoids. Bioinformatic analysis reveals the BipB homologues as a discrete clade of fungal sesquiterpene P450s. These findings elucidate the concise and divergent biosynthesis of such intricate bridged polycyclic sesquiterpenoids, offer valuable biocatalysts for biotransformation, and highlight the distinct biosynthetic strategy employed by nature compared to chemical synthesis.

Sast1-mediated manifold effects inhibit Plutella xylostella fertility.

BACKGROUND: Plutella xylostella (Linnaeus) is a destructive pest of cruciferous crops due to its strong reproductive capacity and extensive resistance to pesticides. Seminal fluid proteins (SFPs) are the main effective factors that determine the reproductive physiology and behaviour of both sexes. Although an increasing number of SFPs have been identified, the effects of astacins in SFPs on agricultural pests have not yet been reported. Here, we elucidated the mechanisms by which Sast1 (seminal astacin 1) regulates the fertility of Plutella xylostella (L.). RESULTS: PxSast1 was specifically expressed in the testis and accesssory gland. CRISPR/Cas9-induced PxSast1 knockout successfully constructed two homozygous mutant strains. Sast1 impaired the fertility of P. xylostella by separately regulating the reproductive capacity of males and females. Loss of PxSast1, on the one hand, significantly decreased the ability of males to mate and fertilize, mainly manifested as shortened mating duration, reduced mating competitiveness and decreased eupyrene sperm production; on the other hand, it significantly inhibited the expression of chorion genes in females, resulting in oogenesis deficits. Simultaneously, for mated females, the differentially expressed genes in signalling pathways related to oogenesis and chorion formation were significantly enriched after PxSast1 knockout. CONCLUSION: These analyses of the functions of PxSast1 as the regulator of spermatogenesis and oogenesis establish its importance in the fertility process of P. xylostella, as well as its potential as a promising target for genetic regulation-based pest control. © 2024 Society of Chemical Industry.

A biomarker panel of C-reactive protein, procalcitonin and serum amyloid A is a predictor of sepsis in severe trauma patients.

Severe trauma could induce sepsis due to the loss of control of the infection, which may eventually lead to death. Accurate and timely diagnosis of sepsis with severe trauma remains challenging both for clinician and laboratory. Combinations of markers, as opposed to single ones, may improve diagnosis. We compared the diagnostic characteristics of routinely used biomarkers of sepsis alone and in combination, trying to define a biomarker panel to predict sepsis in severe patients. This prospective observational study included patients with severe trauma (Injury severity score, ISS = 16 or more) in the emergency intensive care unit (EICU) at a university hospital. Blood samples were collected and plasma levels of procalcitonin (PCT), C-reactive protein (CRP), interleukin-6 (IL-6) and serum amyloid A (SAA) were measured using commercial enzyme linked immunosorbent assay (ELISA) kits. A total of 100 patients were eligible for analysis. Of these, 52 were diagnosed with sepsis. CRP yielded the highest discriminative value followed by PCT. In multiple logistic regression, SAA, CRP, and PCT were found to be independent predictors of sepsis. Bioscore which was composed of SAA, CRP, and PCT was shown to be far superior to that of each individual biomarker taken individually. Therefore, compared with single markers, the biomarker panel of PCT, CRP, and SAA was more predictive of sepsis in severe polytrauma patients.

Increased expression of NLRP3 associated with elevated levels of HMGB1 in children with febrile seizures: a case-control study.

BACKGROUND: High mobility group box-1 (HMGB1) is an endogenous danger signal that mediates activation of the innate immune response including NLR pyrin domain containing 3 (NLRP3) inflammasome activation and proinflammatory cytokine release. Although HMGB1 and NLRP3 have been implicated in the pathophysiology of seizures, the correlation between HMGB1 and NLRP3 expression has not been determined in children with febrile seizures (FS). To explore the relationship between extra-cellular HMGB1 and NLRP3 in children with FS, we analyzed serum HMGB1, NLRP3, caspase-1, and proinflammatory cytokines in patients with FS. METHODS: Thirty children with FS and thirty age-matched febrile controls were included in this study. Blood was obtained from the children with FS within 1 h of the time of the seizure; subsequently, the serum contents of HMGB1, NLRP3, caspase-1, interleukin (IL)-1ß, interleukin (IL)-6, and tumour necrosis factor-α (TNF-α) were determined by enzyme-linked immunosorbent assay. The Mann‒Whitney U test was used to compare serum cytokine levels between FS patients and controls. Spearman's rank correlation coefficient was calculated to detect significant correlations between cytokine levels. RESULTS: Serum levels of HMGB1, NLRP3, caspase-1, IL-1ß, IL-6, and TNF-α were significantly higher in FS patients than in febrile controls (p < 0.05). Serum levels of HMGB1 were significantly correlated with levels of NLRP3 and caspase-1 (both, p < 0.05). Serum levels of caspase-1 were significantly correlated with levels of IL-1ß (p < 0.05). Serum levels of IL-1ß were significantly correlated with levels of IL-6 and TNF-α (p < 0.05). CONCLUSIONS: HMGB1 is up-regulated in the peripheral serum of FS patients, which may be responsible, at least in part, for the increased expression of NLRP3 and Caspase-1. Increased expression of caspase-1 was significantly associated with elevated serum levels of IL-1ß. Given that activated Caspase-1 directly regulates the expression of mature IL-1ß and positively correlates with activation of the NLRP3 inflammasome, our data suggest that increased levels of peripheral HMGB1 possibly mediate IL-1ß secretion through the activation of the NLRP3 inflammasome in children with FS. Thus, both HMGB1 and NLRP3 might be potential targets for preventing or limiting FS.

Nafamostat mesylate versus regional citrate anticoagulation for continuous renal replacement therapy in patients at high risk of bleeding: a retrospective single-center study.

PURPOSE: The choice of continuous renal replacement therapy (CRRT) anticoagulation program for patients at high risk of bleeding has always been a complex problem in clinical practice. Clinical regimens include regional citrate anticoagulation (RCA) and nafamostat mesylate (NM). This study aimed to evaluate the efficacy and safety of these two anticoagulants for CRRT in patients at high risk of bleeding to guide their clinical use better. PATIENTS AND METHODS: Between January 2021 and December 2022, 307 patients were screened for this study. Forty-six patients were finally enrolled: 22 in the regional citrate anticoagulation group and 24 in the nafamostat mesylate group. We collected patients' baseline characteristics, laboratory indicators before CRRT, and CRRT-related data. We then performed a statistical analysis of the data from both groups of patients. RESULTS: In our study, the baseline characteristics did not differ significantly between the two groups; the baseline laboratory indicators before CRRT of patients in the two groups were not significantly different. The duration of CRRT was 600 min in the regional citrate anticoagulation (RCA) group, 615 min in the nafamostat mesylate (NM) group; the success rate was 90.7% in the RCA group, and 85.6% in the NM group, the anticoagulant efficacy between the two groups was comparable. There was no significant difference in the safety of anticoagulation between the two groups. We used Generalized Estimating Equations (GEE) to test whether different anticoagulation methods significantly affected the success rate of CRRT and found no statistical difference between RCA and NM. CONCLUSION: Our study suggests that nafamostat mesylate's anticoagulant efficacy and safety are not inferior to regional citrate anticoagulation for continuous renal replacement therapy in patients at high risk of bleeding.