Circ_0008146 Exacerbates Ferroptosis via Regulating the miR-342-5p/ACSL4 Axis After Cerebral Ischemic/Reperfusion.

Purpose: Acute ischemic stroke (AIS) has seriously threatened people's health worldwide and there is an urge need for early diagnosis and effective treatment of AIS. This research intended to clarify the regulatory role of circ_0008146/miR-342-5p/ACSL4 axis in AIS. Methods: High-throughput small RNA sequencing analysis was adapted to identify differentially expressed miRNAs between the AIS and control group. The circ_0008146, miR-342-5p, and ACSL4 levels were detected by qRT-PCR. Middle cerebral artery occlusion/reperfusion (MCAO/R) models were constructed in C57BL/6J mice. Assay kits were used to determine Fe2+ levels and a battery of oxidative stress and lipid peroxidation indicators, including ROS, MDA, LPO, SOD and GSH/GSSG ratio. The protein levels of ACSL4 were measured by Western blot. The behavioral function was assessed using neurobehavioral tests. TTC staining was employed to visualize infarction size. Nissl staining was adapted to detect histopathological changes. Receiver operating characteristic curve and correlation analysis were applied to investigate the clinical value and association of miR-342-5p and ACSL4. Results: A total of 44 AIS patients and 49 healthy controls were enrolled in our study. The small RNA sequencing unveiled a significant decrease in miR-342-5p levels in AIS patients. MiR-342-5p inhibited oxidative stress and RSL3-induced ferroptosis after cerebral ischemic/reperfusion injury in vivo by targeting ferroptosis-related gene ACSL4. Circ_0008146 acted as a sponge of miR-342-5p, and overexpression of circ_0008146 increased neurological deficits and brain injury in mice. Circ_0008146 contributed to ferroptosis in cerebral infarction via sponging miR-342-5p to regulate ACSL4. Plasma miR-342-5p and ACSL4 demonstrated significant correlation and good diagnostic value for AIS patients. Conclusion: This study provides the first in vivo evidence to show that circ_0008146 exacerbates neuronal ferroptosis after AIS via the miR-342-5p/ACSL4 axis. Furthermore, miR-342-5p/ACSL4 axis holds promise as a viable therapeutic target and practical biomarkers for AIS patients.

Effect of different treatment protocols on in vitro fertilisation/intracytoplasmic sperm injection (IVF/ICSI) outcomes in adenomyosis women: a systematic review and meta-analysis.

OBJECTIVES: Pregnancy outcomes of different ovarian stimulation protocols for in vitro fertilisation/intracytoplasmic sperm injection (IVF/ICSI) in patients with adenomyosis are not explicit. This meta-analysis aimed to systematically evaluate the effects of different IVF/ICSI protocols on pregnancy outcomes. DESIGN: Meta-analysis. DATA SOURCES: PubMed, Web of Science and Cochrane library were searched up to October 2023. ELIGIBILITY CRITERIA: Comparative studies on IVF/ICSI outcomes in the adenomyosis population were eligible. Studies on preimplantation genetic testing, reviews, case reports and animal experiments were excluded. DATA EXTRACTION AND SYNTHESIS: Valid information was extracted by two independent authors according to a standard data format. All analyses were conducted using Review Manager (RevMan, V.5.3). RESULTS: Compared with the non-adenomyosis population, adenomyosis was responsible for a 26% reduction in clinical pregnancy rate (CPR; 42.47% vs 55.89%, OR: 0.74, 95% CI: 0.66 to 0.82, p<0.00001), a 35% reduction in live birth rate (LBR; 30.72% vs 47.77%, OR: 0.65, 95% CI: 0.58 to 0.73, p<0.00001) and a 1.9-fold increase in miscarriage rate (MR; 27.82% vs 13.9%, OR: 1.90, 95% CI: 1.56 to 2.31, p<0.00001). Subgroup analysis suggested that, in fresh embryo transfer (ET) cycles, the CPR (34.4% vs 58.25%) in the long/short/antagonist protocol group was poorer than that in the ultralong protocol group. In frozen ET (FET) cycles, there were no statistical differences in CPR ((GnRHa+FET) AM(adenomyosis) vs non-AM: 51.32% vs 43.48%, p=0.31; (non-GnRHa+FET) AM vs non-AM: 50.25% vs 60.10%, p=0.82), MR ((GnRHa+FET) AM vs non-AM:12.82% vs 12.50%, p=0.97; (non-GnRHa+FET) AM vs non-AM: 30.5% vs 15.54%, p=0.15) and LBR ((GnRHa+FET) AM vs non-AM:44.74% vs 36.96%, p=0.31; (non-GnRHa+FET) AM vs non-AM: 34.42% vs 50.25%, p=0.28). The MR in the adenomyosis group was high in the fresh ET and FET cycles. CONCLUSIONS: FET might be a better choice for women with adenomyosis, especially those pretreated with GnRHa. In fresh ET cycles, pregnancy outcomes of the long/short/antagonist protocols were poorer than those of the ultralong protocol. TRIAL REGISTRATION NUMBER: CRD42022340743.

Metagenomics-based gene exploration and biochemical characterization of novel glucoamylases and α-amylases in Daqu and Pu-erh tea microorganisms.

α-Amylases and glucoamylases play a crucial role in starch degradation for various industrial applications. Further exploration of novel α-amylases and glucoamylases with diverse enzymatic characteristics is necessary. In this study, metagenomics analysis revealed a high abundance of these enzymes in the microorganisms of Daqu and Pu-erh tea, identifying 271 glucoamylases and 232 α-amylases with significant sequence identity to known enzymes. Functional studies indicated that these enzymes have broad optimal temperatures (30 °C to 70 °C) and acidic or neutral pH optima. Additionally, two novel low-temperature glucoamylases and one novel low-temperature α-amylases were characterized, demonstrating potential for use in industries operating under low temperature conditions. Further analysis suggested that fewer molecular interactions and more flexible coli regions may contribute to their high activity at low temperatures. In summary, this study not only highlights the feasibility of exploring enzymes through metagenomic approaches, but also presents a library of novel and diverse α-amylases and glucoamylases for potential industrial applications.

pH-responsive albumin-mimetic synthetic nanoprobes for magnetic resonance/fluorescence imaging of thyroid cancer.

The combination of magnetic resonance and fluorescence imaging in dual-modality imaging not only resolves the limitations of conventional single molecular imaging techniques in terms of specificity, sensitivity, and resolution but also expands the possibilities of molecular imaging techniques in diagnostics and therapeutic monitoring. Herein, a novel pH-responsive magnetic resonance/near-infrared fluorescence (MR/NIRF) nanoprobe (MnO2@BSA-Cy5.5) was successfully prepared by biomineralizing manganese dioxide (MnO2) with bovine serum albumin (BSA) while coupling fluorescent dye Cy5.5 for precise tumor detection and visualization. The synthesized MnO2@BSA-Cy5.5 nanoprobes were spherical particles of approximately 22.62 ± 3.31 nm in size, and their relaxation rates and T1 imaging signals were activated-enhanced in an acidic environment. Cytotoxicity assay and hematoxylin and eosin staining demonstrated that MnO2@BSA-Cy5.5 had low cytotoxicity and good biocompatibility. More importantly, active targeting via solid tumor albumin-binding protein receptor and enhanced permeability and retention effect, the probe can be specifically aggregated to the tumor site of the 8305C tumor model and exhibit excellent MR/NIRF imaging properties. Our results show that MnO2@BSA-Cy5.5 has high resolution and sensitivity in tumor imaging and is expected to be applied as an MR/NIRF contrast agent for accurate diagnosis of thyroid cancer.

Rhodium-catalyzed three-component C(sp3)/C(sp2)-H activation enabled by a two-fold directing group strategy.

Rh-catalyzed three-component C(sp3)/C(sp2)-H activation has been achieved through a two-directing group strategy. This protocol provides a convenient and efficient pathway for the construction of diverse 8-alkyl quinoline derivatives in one-pot. Furthermore, mechanistic studies revealed that the first C-H amidation was significantly faster than the sequential C-H alkylation.

Nucleophilic Aromatic Substitution (SNAr) as an Approach to Challenging Nitrogen-Bridged BODIPY Oligomers.

A series of nitrogen-bridged BODIPY oligomers were synthesized via nucleophilic aromatic substitution (SNAr) as a convenient approach. Further transformations achieved novel α,α-aryl BODIPY dimers as well as a BODIPY hexamer efficiently. These BODIPY oligomers showed good photophysical properties, such as apparent absorption and emission both in visible and near-infrared regions. Interestingly, the high air and photothermal stability, strong NIR absorption, and high photothermal conversion rates of hexamer B6 suggest potential applications in photothermal therapy.

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OBJECTIVES: To explore the risk factors associated with cow's milk protein allergy (CMPA) in infants. METHODS: This study was a multicenter prospective nested case-control study conducted in seven medical centers in Beijing, China. Infants aged 0-12 months were included, with 200 cases of CMPA infants and 799 control infants without CMPA. Univariate and multivariate logistic regression analyses were used to investigate the risk factors for the occurrence of CMPA. RESULTS: Univariate logistic regression analysis showed that preterm birth, low birth weight, birth from the first pregnancy, firstborn, spring birth, summer birth, mixed/artificial feeding, and parental history of allergic diseases were associated with an increased risk of CMPA in infants (P<0.05). Multivariate logistic regression analysis revealed that firstborn (OR=1.89, 95%CI: 1.14-3.13), spring birth (OR=3.42, 95%CI: 1.70-6.58), summer birth (OR=2.29, 95%CI: 1.22-4.27), mixed/artificial feeding (OR=1.57, 95%CI: 1.10-2.26), parental history of allergies (OR=2.13, 95%CI: 1.51-3.02), and both parents having allergies (OR=3.15, 95%CI: 1.78-5.56) were risk factors for CMPA in infants (P<0.05). CONCLUSIONS: Firstborn, spring birth, summer birth, mixed/artificial feeding, and a family history of allergies are associated with an increased risk of CMPA in infants.

Mechanisms of benzene and benzo[a]pyrene biodegradation in the individually and mixed contaminated soils.

There is a lack of knowledge on the biodegradation mechanisms of benzene and benzo [a]pyrene (BaP), representative compounds of polycyclic aromatic hydrocarbons (PAHs), and benzene, toluene, ethylbenzene, and xylene (BTEX), under individually and mixed contaminated soils. Therefore, a set of microcosm experiments were conducted to explore the influence of benzene and BaP on biodegradation under individual and mixed contaminated condition, and their subsequent influence on native microbial consortium. The results revealed that the total mass loss of benzene was 56.0% under benzene and BaP mixed contamination, which was less than that of individual benzene contamination (78.3%). On the other hand, the mass loss of BaP was slightly boosted to 17.6% under the condition of benzene mixed contamination with BaP from that of individual BaP contamination (14.4%). The significant differences between the microbial and biocide treatments for both benzene and BaP removal demonstrated that microbial degradation played a crucial role in the mass loss for both contaminants. In addition, the microbial analyses revealed that the contamination of benzene played a major role in the fluctuations of microbial compositions under co-contaminated conditions. Rhodococcus, Nocardioides, Gailla, and norank_c_Gitt-GS-136 performed a major role in benzene biodegradation under individual and mixed contaminated conditions while Rhodococcus, Noviherbaspirillum, and Phenylobacterium were highly involved in BaP biodegradation. Moreover, binary benzene and BaP contamination highly reduced the Rhodococcus abundance, indicating the toxic influence of co-contamination on the functional key genus. Enzymatic activities revealed that catalase, lipase, and dehydrogenase activities proliferated while polyphenol oxidase was reduced with contamination compared to the control treatment. These results provided the fundamental information to facilitate the development of more efficient bioremediation strategies, which can be tailored to specific remediation of different contamination scenarios.

Development of a virus-based affinity ultrafiltration method for screening virus-surface-protein-targeted compounds from complex matrixes: Herbal medicines as a case study.

Herbal medicines (HMs) are one of the main sources for the development of lead antiviral compounds. However, due to the complex composition of HMs, the screening of active compounds within these is inefficient and requires a significant time investment. We report a novel and efficient virus-based screening method for antiviral active compounds in HMs. This method involves the centrifugal ultrafiltration of viruses, known as the virus-based affinity ultrafiltration method (VAUM). This method is suitable to identify virus specific active compounds from complex matrices such as HMs. The effectiveness of the VAUM was evaluated using influenza A virus (IAV) H1N1. Using this method, four compounds that bind to the surface protein of H1N1 were identified from dried fruits of Terminalia chebula (TC). Through competitive inhibition assays, the influenza surface protein, neuraminidase (NA), was identified as the target protein of these four TC-derived compounds. Three compounds were identified by high performance liquid chromatography (HPLC) and liquid chromatography/mass spectrometry (LC/MS), and their anti-H1N1 activities were verified by examining the cytopathic effect (CPE) and by performing a virus yield reduction assay. Further mechanistic studies demonstrated that these three compounds directly bind to NA and inhibit its activity. In summary, we describe here a VAUM that we designed, one that can be used to accurately screen antiviral active compounds in HMs and also help improve the efficiency of screening antiviral drugs found in natural products.

NLRP1 restricts porcine deltacoronavirus infection via IL-11 inhibiting the phosphorylation of the ERK signaling pathway.

Continuously emerging highly pathogenic coronaviruses remain a major threat to human and animal health. Porcine deltacoronavirus (PDCoV) is a newly emerging enterotropic swine coronavirus that causes large-scale outbreaks of severe diarrhea disease in piglets. Unlike other porcine coronaviruses, PDCoV has a wide range of species tissue tropism, including primary human cells, which poses a significant risk of cross-species transmission. Nucleotide-binding oligomerization domain-like receptor (NLR) family pyrin domain-containing 1 (NLRP1) has a key role in linking host innate immunity to microbes and the regulation of inflammatory pathways. We now report a role for NLRP1 in the control of PDCoV infection. Overexpression of NLRP1 remarkably suppressed PDCoV infection, whereas knockout of NLRP1 led to a significant increase in PDCoV replication. A mechanistic study revealed that NLRP1 suppressed PDCoV replication in cells by upregulating IL-11 expression, which in turn inhibited the phosphorylation of the ERK signaling pathway. Furthermore, the ERK phosphorylation inhibitor U0126 effectively hindered PDCoV replication in pigs. Together, our results demonstrated that NLRP1 exerted an anti-PDCoV effect by IL-11-mediated inhibition of the phosphorylation of the ERK signaling pathway, providing a novel antiviral signal axis of NLRP1-IL-11-ERK. This study expands our understanding of the regulatory network of NLRP1 in the host defense against virus infection and provides a new insight into the treatment of coronaviruses and the development of corresponding drugs.IMPORTANCECoronavirus, which mainly infects gastrointestinal and respiratory epithelial cells in vivo, poses a huge threat to both humans and animals. Although porcine deltacoronavirus (PDCoV) is known to primarily cause fatal diarrhea in piglets, reports detected in plasma samples from Haitian children emphasize the potential risk of animal-to-human spillover. Finding effective therapeutics against coronaviruses is crucial for controlling viral infection. Nucleotide-binding oligomerization-like receptor (NLR) family pyrin domain-containing 1 (NLRP1), a key regulatory factor in the innate immune system, is highly expressed in epithelial cells and associated with the pathogenesis of viruses. We demonstrate here that NLRP1 inhibits the infection of the intestinal coronavirus PDCoV through IL-11-mediated phosphorylation inhibition of the ERK signaling pathway. Furthermore, the ERK phosphorylation inhibitor can control the infection of PDCoV in pigs. Our study emphasizes the importance of NLRP1 as an immune regulatory factor and may open up new avenues for the treatment of coronavirus infection.

The Value of Dual-Energy Computed Tomography-Based Radiomics in the Evaluation of Interstitial Fibers of Clear Cell Renal Carcinoma.

OBJECTIVE: We investigated the potential of dual-energy computed tomography (DECT) radiomics in assessing cancer-associated fibroblasts in clear cell renal carcinoma (ccRCC). METHODS: A retrospective analysis was conducted on 132 patients with ccRCC. The arterial and venous phase iodine-based material decomposition images (IMDIs), virtual non-contrast images, 70 keV, 100 keV, and 150 keV virtual monoenergetic images, and mixed energy images (MEIs) were obtained from the DECT datasets. On the Radcloud platform, radiomics feature extraction, feature selection, and model establishment were performed. Seven radiomics models were established using the support vector machine. The predictive performance was evaluated by utilizing receiver operating characteristic and the area under the curve (AUC) was calculated. Nomograms were constructed. RESULTS: The combined model demonstrated high efficiency in evaluating pseudocapsule thickness with AUC, specificity, and sensitivity of 0.833, 0.870, and 0.750, respectively in the validation set, surpassing those of other models. The precision, F1-score, and Youden index were also higher for the combined model. For evaluating the number of collagen fibers, the combined model exhibited the highest AUC (0.741) among all models, with a specificity of 0.830 and a sensitivity of 0.330. The AUC in the 150 kv model and IMDI model were slightly lower than those in the combined model (0.728 and 0.710, respectively), with corresponding sensitivity and specificity of 0.560/0.780 and 0.670/0.830. The nomogram exhibited that Rad-score had good prediction efficiency. CONCLUSION: DECT radiomics features have significant value in evaluating the interstitial fibers of ccRCC. The combined model of IMDI + MEI exhibits superior performance in assessing the thickness of the pseudocapsule, while the combined, 150 keV, and IMDI models demonstrate higher efficacy in evaluating collagen fiber number. Radiomics, combined with imaging features and clinical features, has excellent predictive performance. These findings offer crucial support for the clinical diagnosis, treatment, and prognosis of ccRCC and provide valuable insights into the application of DECT.

Different Infectivity of Swine Enteric Coronaviruses in Cells of Various Species.

Swine enteric coronaviruses (SECoVs), including porcine deltacoronavirus (PDCoV), transmissible gastroenteritis virus (TGEV), porcine epidemic diarrhea virus (PEDV), and swine acute diarrhea syndrome coronavirus (SADS-CoV), have caused high mortality in piglets and, therefore, pose serious threats to the pork industry. Coronaviruses exhibit a trend of interspecies transmission, and understanding the host range of SECoVs is crucial for improving our ability to predict and control future epidemics. Here, the replication of PDCoV, TGEV, and PEDV in cells from different host species was compared by measuring viral genomic RNA transcription and protein synthesis. We demonstrated that PDCoV had a higher efficiency in infecting human lung adenocarcinoma cells (A549), Madin-Darby bovine kidney cells (MDBK), Madin-Darby canine kidney cells (MDCK), and chicken embryonic fibroblast cells (DF-1) than PEDV and TGEV. Moreover, trypsin can enhance the infectivity of PDCoV to MDCK cells that are nonsusceptible to TGEV. Additionally, structural analyses of the receptor ectodomain indicate that PDCoV S1 engages Aminopeptidase N (APN) via domain II, which is highly conserved among animal species of different vertebrates. Our findings provide a basis for understanding the interspecies transmission potential of these three porcine coronaviruses.

METTL3-dependent N6-methyladenosine modification is involved in berberine-mediated neuroprotection in ischemic stroke by enhancing the stability of NEAT1 in astrocytes.

Ischemic stroke (IS) is one of the principal causes of disability and death worldwide. Berberine (BBR), derived from the traditional Chinese herbal medicine Huang Lian, has been reported to inhibit the progression of stroke, but the specific mechanism whereby BBR modulates the progression of ischemic stroke remains unclear. N6-methyladenosine (m6A) modification is the most typical epigenetic modification of mRNA post-transcriptional modifications, among which METTL3 is the most common methylation transferase. During the study, the middle cerebral artery occlusion/reperfusion (MCAO/R) was established in mice, and the mice primary astrocytes and neurons induced by oxygen-glucose deprivation/reoxygenation (OGD/R) was simulated in vitro. Level of LncNEAT1, miR-377-3p was detected via RT-qPCR. The levels of Nampt and METTL3 were measured by Western blot. CCK8 and LDH assay was performed to detect cell viability. Here, we found that berberine alleviates MCAO/R-induced ischemic injury and up-regulates the expression of Nampt in astrocytes, miR-377-3p inhibits the expression of Nampt in astrocytes after OGD/R, thus promoting neuronal injury. NEAT1 binds to miR-377-3p in OGD/R astrocytes and plays a neuronal protective role as a ceRNA. METTL3 can enhance NEAT1 stability in OGD/R astrocytes by modulating m6A modification of NEAT1. Taken together, our results demonstrate that berberine exerts neuroprotective effects via the m6A methyltransferase METTL3, which regulates the NEAT1/miR-377-3p/Nampt axis in mouse astrocytes to ameliorate cerebral ischemia/reperfusion (I/R) injury.

Venture capital, innovation channels, and regional resource dependence: Evidence from China.

Although the literature predominantly emphasises the crucial role of technological innovation in alleviating resource dependence, limited attention has been given to the pivotal role of capital in driving such innovation. As a critical factor in technological advancements and productivity enhancement, venture capital has a substantial function in the utilisation of resources and the development of sustainable energy sources. Drawing upon panel data from 30 provinces in China, this study explores how venture capital and resource dependence are interrelated. Our research reveals that venture capital effectively mitigates regional resource dependence by facilitating increased investment in innovation channels. However, the weakening of regional human resources mitigates venture capital's diminishing impacts on resource dependence. These findings provide valuable insights for countries seeking to reduce their dependence on natural resources and achieve long-term economic sustainability.

Trends in suicide mortality among cancer survivors in the US, 1975-2020.

BACKGROUND: Suicide in cancer survivors is a major public health concern, but its trends and risk factors are not well understood. This study aimed to investigate the standardized mortality rate (SMR) and trends in suicide among cancer survivors in the United States. METHODS: Using data from the SEER-9 database and US Mortality data, we identified 3,684,040 cancer survivors diagnosed between 1975 and 2020. The SMR of suicide among cancer survivors was calculated, and Poisson regression analysis was used to evaluate trends in suicide risk. Subgroup analyses were performed based on age, gender, race, tumor site, and stage. A competing risk model was used to calculate the 10-year cumulative incidence of suicide. RESULTS: Among cancer survivors, the overall SMR of suicide was 1.49 (95%CI: 1.46-1.53) times higher than that of the general population in the US. The risk of suicide varied significantly by cancer site, with the highest risk found in patients with malignant respiratory system cancer. Overall, we observed a significant downward trend in the suicide mortality rate among cancer patients. The cumulative incidence of suicide mortality among cancer survivors across four study periods exhibited significant statistical differences (P<0.001). CONCLUSIONS: Our study highlights the need for targeted suicide prevention efforts for cancer survivors, particularly those diagnosed with respiratory system cancer. The trend of declining suicide mortality rates among cancer survivors is promising, but continued efforts are needed to understand and address the underlying risk factors.

Theaflavin pretreatment ameliorates renal ischemia/reperfusion injury by attenuating apoptosis and oxidative stress in vivo and in vitro.

Oxidative stress-induced apoptosis is an important pathological process in renal ischemia/reperfusion injury (RIRI). Theaflavin (TF) is the main active pigment and polyphenol in black tea. It has been widely reported because of its biological activity that can reduce oxidative stress and protect against many diseases. Here, we explored the role of theaflavin in the pathological process of RIRI. In the present study, the RIRI model of 45 min ischemia and 24 h reperfusion was established in C57BL/6 J male mice, and theaflavin was used as an intervention. Compared with the RIRI group, the renal filtration function, renal tissue damage and antioxidant capacity of the theaflavin intervention group were significantly improved, while the level of apoptosis was reduced. TCMK-1 cells were incubated under hypoxia for 48 h and then reoxygenated for 6 h to simulate RIRI in vitro. The application of theaflavin significantly promoted the translocation of p53 from cytoplasm to nucleus, upregulated the expression of glutathione peroxidase 1 (GPx-1) in cells, and inhibited oxidative stress damage and apoptosis. Transfection with p53 siRNA can partially inhibit the effect of theaflavin. Thus, theaflavin exerted a protective effect against RIRI by inhibiting apoptosis and oxidative stress via regulating the p53/GPx-1 pathway. We conclude that theaflavin has the potential to become a candidate drug for the prevention and treatment of RIRI.

Rhodium-Catalyzed Two-Fold, Regioselective and Enantioselective C-H Activation: an Efficient Strategy to Chiral Single-Benzene-Based Fluorophores.

A Rh-catalyzed two-fold, regioselective and enantioselective C-H activation via chiral transient directing group strategy has been demonstrated in moderate to good yields with commendable enantioselectivities. The newly synthesized chiral fluorophores exhibit favorable photophysical properties, including large Stokes shifts, good fluorescence quantum yields, aggregation-induced emission in aqueous solution, and intense emission and circularly polarized luminescence in the solid state, indicating great potential applications as chiral fluorescent probes or optoelectronic materials.

Utilizing different types of biomass materials to modify steel slag for the preparation of composite materials used in the adsorption and solidification of Pb in solutions and soil.

This study utilized discarded steel slag (SS) as raw material and prepared modified steel slag materials (SS-SBC, SS-NBC, SS-BHA) through modification with biomass materials such as straw biochar (SBC), nutshell biochar (NBC), and biochemical humic acid (BHA). These materials were then applied for the removal of Pb from both solution and soil. The physical and chemical properties of the materials were analyzed using characterization techniques such as SEM, EDS, XRD, and BET. The specific surface area of the modified materials increased from the original 3.8584 m2/g to 34.7133 m2/g, 181.7329 m2/g, and 7.7384 m2/g, respectively. The study then explored the influence of different adsorption conditions on the adsorption capacity of Pb in solution, determining the optimal conditions as follows: initial concentration of 200 mg/L, adsorbent mass of 0.04 g, temperature of 15 °C, and pH = 2. To further investigate the adsorption process, kinetic and isotherm models were established. The results indicated that the adsorption process for all three materials followed a pseudo-second-order kinetic model and Freundlich isotherm model, suggesting a multi-layer chemical adsorption. Thermodynamic analysis revealed that the adsorption process was an exothermic spontaneous reaction. Soil cultivation experiments were conducted to explore the effects of different material addition amounts and cultivation times on the passivation of Pb-polluted soil. Analysis of heavy metal forms in the soil revealed that the addition of modified materials reduced the acid-extractable form of Pb in the soil and increased the residual form, which is beneficial for reducing the migration of Pb in the soil. FT-IR and XPS analyses were employed to study the functional groups, element composition, and valence states before and after adsorption passivation of Pb by the three materials. The results confirmed that the adsorption mechanisms of SS-SBC, SS-NBC, and SS-BHA mainly involved electrostatic adsorption, ion and ligand exchange, and surface precipitation. This study not only provides a new material for adsorbing and immobilizing heavy metals in soil and water but also offers a new approach for the resource utilization of steel slag waste.

Integrated serum pharmacochemistry and investigation of the anti-influenza A virus pneumonia effect of Qingjin Huatan decoction.

ETHNOPHARMACOLOGICAL RELEVANCE: Qingjin Huatan Decoction (QJHTT) consists of 11 herbal medicines: Scutellaria baicalensis Georgi, Gardenia jasminoides J. Ellis, Platycodon grandiflorus (Jacq.) A. DC., Ophiopogon japonicus (Thunb.) Ker Gawl., Morus alba L., Fritillaria thunbergii Miq., Anemarrhena asphodeloides Bunge, Trichosanthes kirilowii Maxim., Citrus reticulata Blanco, Poria cocos (Schw.) Wolf, and Glycyrrhiza uralensis Fisch. As a traditional Chinese medicinal formula, QJHTT has been used for more than 400 years in China. It has shown promising results in treating influenza A virus (IAV) pneumonia. AIM OF THE STUDY: To elusive the specific pharmacological constituents and mechanisms underlying its anti-IAV pneumonia effects. MATERIALS AND METHODS: The components in QJHTT were analyzed through the use of a serum pharmacology-based ultra high-performance liquid chromatography Q- Exactive Orbitrap mass spectrometry (UHPLC-Q Exactive Orbitrap-MS) method. Simultaneously, the dynamic changes in IAV-infected mouse lung viral load, lung index, and expression of lung inflammation factors were monitored by qRT-PCR. RESULTS: We successfully identified 152 chemical components within QJHTT, along with 59 absorbed chemical prototype constituents found in the serum of mice treated with QJHTT. 43.45% of these chemical components and 43.10% of the prototype constituents were derived from the monarch drugs, namely Huangqin and Zhizi, aligning perfectly with traditional Chinese medicine theory. Notably, our analysis led to the discovery of 14 compounds within QJHTT for the first time, three of which were absorbed into the bloodstream. Simultaneously, we observed that QJHTT not only reduced the viral load but also modulated the expression of inflammation factors in the lung tissue including TNF-α, IL-1ß, IL-4, IL-6, IFN-γ, and IL17A. A time-effect analysis further revealed that QJHTT intervention effectively suppressed the peak of inflammatory responses, demonstrating a robust anti-IAV pneumonia effect. CONCLUSIONS: We comprehensively analyzed the pharmacological material basis of QJHTT by a highly sensitive and high-resolution UHPLC-Q Exactive Orbitrap-MS method, and demonstrated its efficacy in combating IAV pneumonia by reducing lung viral load and inflammatory factors. This study has significant importance for elucidating the pharmacological basis and pharmacological mechanism of QJHTT in combating IAV pneumonia.

In Vitro Virulence Contrast of Seven Genetically Distinct Toxoplasma gondii Isolates After Rejuvenation In Vivo.

BACKGROUND: In the past for more than 100 years at least 300 genotypes of Toxoplasma gondii were recorded and several traditional isolates such as RH, GT1, ME49, PRU and VEG were used repeatedly to clarify the pathogenic mechanisms and the epidemiological significance to human, but for if their virulence was mutative post-iterative passages it remains confused. OBJECTIVE: Therefore, in the study, seven genetically distinct T. gondii including C7 and PYS previously discovered in China were reidentified by sequencing the head of hsp40 locus to distinguish their virulence in vitro post-rejuvenation in vivo. RESULTS: Our data showed the nucleotides were different in 18 positions and 7 of them can be used to type T. gondii isolates. Total 634 plaques of T. gondii without two or more overlaps indicated that RH and GT1 tachyzoites possess stronger power than other five isolates in vitro (p < 0.001), followed by ME49, PRU, C7, PYS, and the weakest VEG. Based on the shapes of plaques, we found the ratio of their width/length was associated with the virulence of T. gondii, and speculated it could be used to judge T. gondii tachyzoites in vitro, whereas the data of simple linear regression analyses did not agree. CONCLUSIONS: Together, virulence of seven genetically distinct T. gondii isolates that can be distinguished by seven mutative nucleotides in hsp40 was redefined in vitro post-rejuvenation in vivo, and it cannot be directly judged just according to the shapes of plaques formed in vitro.