Preparation of PLCL/ECM nerve conduits by electrostatic spinning technique and evaluationin vitroandin vivo.

Objective. Artificial nerve scaffolds composed of polymers have attracted great attention as an alternative for autologous nerve grafts recently. Due to their poor bioactivity, satisfactory nerve repair could not be achieved. To solve this problem, we introduced extracellular matrix (ECM) to optimize the materials.Approach.In this study, the ECM extracted from porcine nerves was mixed with Poly(L-Lactide-co-ϵ-caprolactone) (PLCL), and the innovative PLCL/ECM nerve repair conduits were prepared by electrostatic spinning technology. The novel conduits were characterized by scanning electron microscopy (SEM), tensile properties, and suture retention strength test for micromorphology and mechanical strength. The biosafety and biocompatibility of PLCL/ECM nerve conduits were evaluated by cytotoxicity assay with Mouse fibroblast cells and cell adhesion assay with RSC 96 cells, and the effects of PLCL/ECM nerve conduits on the gene expression in Schwann cells was analyzed by real-time polymerase chain reaction (RT-PCR). Moreover, a 10 mm rat (Male Wistar rat) sciatic defect was bridged with a PLCL/ECM nerve conduit, and nerve regeneration was evaluated by walking track, mid-shank circumference, electrophysiology, and histomorphology analyses.Main results.The results showed that PLCL/ECM conduits have similar microstructure and mechanical strength compared with PLCL conduits. The cytotoxicity assay demonstrates better biosafety and biocompatibility of PLCL/ECM nerve conduits. And the cell adhesion assay further verifies that the addition of ECM is more beneficial to cell adhesion and proliferation. RT-PCR showed that the PLCL/ECM nerve conduit was more favorable to the gene expression of functional proteins of Schwann cells. Thein vivoresults indicated that PLCL/ECM nerve conduits possess excellent biocompatibility and exhibit a superior capacity to promote peripheral nerve repair.Significance.The addition of ECM significantly improved the biocompatibility and bioactivity of PLCL, while the PLCL/ECM nerve conduit gained the appropriate mechanical strength from PLCL, which has great potential for clinical repair of peripheral nerve injuries.

Effects of organic trace minerals chelated with oligosaccharides on growth performance, blood parameters, slaughter performance and meat quality in sheep.

The present study assessed the effects of oligosaccharide-chelated organic trace minerals (OTM) on the growth performance, digestive enzyme activity, blood parameters, slaughter performance, and meat quality indexes of mutton sheep. A total of 60 East Ujumuqin × small-tailed Han crossbred mutton sheep were assigned to two groups (10 duplicates per group) by body weight (26.12 ± 3.22 kg) according to a completely randomized design. Compared to the CON group, the results of the OTM group showed: (1) no significant changes in the initial body weight, final body weight, dry matter intake, average daily gain, and feed conversion ratio (p > 0.05); (2) the activities of trypsin, lipase, and amylase in the jejunum were significantly increased (p < 0.05); (3) serum total protein, albumin, and globulin of the blood were significantly increased (p < 0.05), and the growth factor interleukin IL-10 was significantly higher (p < 0.05), while IL-2, IL-6, and γ-interferon were significantly lower (p < 0.05). Immunoglobulins A, M, and G were significantly higher (p < 0.05); (4) the live weight before slaughter, carcass weights, dressing percentage, eye muscle areas, and GR values did not differ significantly (p > 0.05); (5) shear force of mutton was significantly lower (p < 0.05), while the pH45min, pH24h, drip loss, and cooking loss did not show a significant difference (p > 0.05). The content of crude protein was significantly higher (p < 0.05), while the ether extract content was significantly reduced (p < 0.05), but no significant difference was detected between moisture and ash content; (6) the total amino acids, essential amino acids, semi-essential amino acids, and umami amino acids were significantly increased (p < 0.05). Although umami amino acids were not significant, the total volume increased (p > 0.05). Among these, the essential amino acids, threonine, valine, leucine, lysine in essential amino acids and arginine were significantly increased (p < 0.05). Also, non-essential amino acids, glycine, serine, proline, tyrosine, cysteine, and aspartic acid, were significantly higher (p < 0.05). The content of alanine, aspartate, glutamic acid, phenylalanine, and tyrosine in umami amino acids was significantly higher (p < 0.05).

Manure replacing synthetic fertilizer improves crop yield sustainability and reduces carbon footprint under winter wheat-summer maize cropping system.

Manure replacing synthetic fertilizer is a viable practice to ensure crop yield and increase soil organic carbon (SOC), but its impact on greenhouse gas (GHG) emissions is inconsistent, thus remains its effect on CF unclear. In this study, a 7-year field experiment was conducted to assess the impact of replacing synthetic fertilizer with manure on crop productivity, SOC sequestration, GHG emissions and crop CF under winter wheat-summer maize cropping system. Five treatments were involved: synthetic nitrogen, phosphorus, and potassium fertilizer (NPK) and 25%, 50%, 75%, and 100% of manure replacing synthetic N (25%M, 50%M, 75%M, and 100%M). Compared with NPK treatment, 25%M and 50%M treatments maintained annual yield (winter wheat plus summer maize) and sustainable yield index (SYI), but 75%M and 100%M treatments significantly decreased annual yield, and 100%M treatment also significantly reduced annual SYI. The SOC content exhibited a significant increasing trend over years in all treatments. After 7 years, SOC storage in manure treatments increased by 3.06-11.82 Mg ha-1 relative to NPK treatment. Manure treatments reduced annual GHG emissions by 14%-60% over NPK treatment. The CF of the cropping system ranged from 0.16 to 0.39 kg CO2 eq kg-1 of grain without considering SOC sequestration, in which the CF of manure treatments lowered by 18%-58% relative to NPK treatment. When SOC sequestration was involved in, the CF varied from -0.39 to 0.37 kg CO2 eq kg-1 of grain, manure treatments significantly reduced the CF by 22%-208% over NPK treatment. It was concluded that replacing 50% of synthetic fertilizer with manure was a sound option for achieving high crop yield and SYI but low CF under the tested cropping system.

Discovery of baloxavir sodium as a novel anti-CCHFV inhibitor: biological evaluation of in vitro and in vivo.

Crimean-Congo hemorrhagic fever virus (CCHFV) is a highly pathogenic bunyavirus with a fatality rate of up to 40%. Currently, there are no licensed antiviral drugs for the treatment of CCHF; thus, the World Health Organization (WHO) listed the disease as a priority. A unique viral transcription initiation mechanism called "cap-snatching" is shared by influenza viruses and bunyaviruses. Thus, we tested whether baloxavir (an FDA-approved anti-influenza drug that targets the "cap-snatching" mechanism) could inhibit CCHFV infection. In cell culture, baloxavir acid effectively inhibited CCHFV infection and targeted CCHFV RNA transcription/replication. However, it has weak oral bioavailability. Baloxavir marboxil (the oral prodrug of baloxavir) failed to protect mice against a lethal dose challenge of CCHFV. To solve this problem, baloxavir sodium was synthesized owing to its enhanced aqueous solubility and pharmacokinetic properties. It consistently and significantly improved survival rates and decreased tissue viral loads. This study identified baloxavir sodium as a novel scaffold structure and mechanism of anti-CCHF compound, providing a promising new strategy for clinical treatment of CCHF after further optimization.

Synthesis and Biological Evaluation of ß-Lactam Derivatives Targeting Speckle-Type POZ Protein (SPOP).

Speckle-type POZ protein (SPOP) acts as a cullin3-RING ubiquitin ligase adaptor, which facilitates the recognition and ubiquitination of substrate proteins. Previous research suggests that targeting SPOP holds promise in the treatment of clear cell renal cell carcinoma (ccRCC). On the basis of the reported SPOP inhibitor 230D7, a series of ß-lactam derivatives were synthesized in this study. The biological activity assessment of these compounds revealed E1 as the most potent inhibitor, which can disrupt the SPOP-substrate interactions in vitro and suppress the colony formation of ccRCC cells. Taken together, this study provided compound E1 as a potent inhibitor against ccRCC and offered insight into the development of the ß-lactam SPOP inhibitor.

Transfer learning enhanced graph neural network for aldehyde oxidase metabolism prediction and its experimental application.

Aldehyde oxidase (AOX) is a molybdoenzyme that is primarily expressed in the liver and is involved in the metabolism of drugs and other xenobiotics. AOX-mediated metabolism can result in unexpected outcomes, such as the production of toxic metabolites and high metabolic clearance, which can lead to the clinical failure of novel therapeutic agents. Computational models can assist medicinal chemists in rapidly evaluating the AOX metabolic risk of compounds during the early phases of drug discovery and provide valuable clues for manipulating AOX-mediated metabolism liability. In this study, we developed a novel graph neural network called AOMP for predicting AOX-mediated metabolism. AOMP integrated the tasks of metabolic substrate/non-substrate classification and metabolic site prediction, while utilizing transfer learning from 13C nuclear magnetic resonance data to enhance its performance on both tasks. AOMP significantly outperformed the benchmark methods in both cross-validation and external testing. Using AOMP, we systematically assessed the AOX-mediated metabolism of common fragments in kinase inhibitors and successfully identified four new scaffolds with AOX metabolism liability, which were validated through in vitro experiments. Furthermore, for the convenience of the community, we established the first online service for AOX metabolism prediction based on AOMP, which is freely available at https://aomp.alphama.com.cn.

Advancing Global Health Surveillance of Mycotoxin Exposures using Minimally Invasive Sampling Techniques: A State-of-the-Science Review.

Mycotoxins are a heterogeneous group of toxins produced by fungi that can grow in staple crops (e.g., maize, cereals), resulting in health risks due to widespread exposure from human consumption and inhalation. Dried blood spot (DBS), dried serum spot (DSS), and volumetric tip microsampling (VTS) assays were developed and validated for several important mycotoxins. This review summarizes studies that have developed these assays to monitor mycotoxin exposures in human biological samples and highlights future directions to facilitate minimally invasive sampling techniques as global public health tools. A systematic search of PubMed (MEDLINE), Embase (Elsevier), and CINAHL (EBSCO) was conducted. Key assay performance metrics were extracted to provide a critical review of the available methods. This search identified 11 published reports related to measuring mycotoxins (ochratoxins, aflatoxins, and fumonisins) using DBS/DSS and VTS assays. Multimycotoxin assays adapted for DBS/DSS and VTS have undergone sufficient laboratory validation for applications in large-scale population health and human biomonitoring studies. Future work should expand the number of mycotoxins that can be measured in multimycotoxin assays, continue to improve multimycotoxin assay sensitivities of several biomarkers with low detection rates, and validate multimycotoxin assays across diverse populations with varying exposure levels. Validated low-cost and ultrasensitive minimally invasive sampling methods should be deployed in human biomonitoring and public health surveillance studies to guide policy interventions to reduce inequities in global mycotoxin exposures.

Differences in three instars of four carrion nitidulids (Coleoptera, Nitidulidae, Nitidula and Omosita) revealed using SEM.

The genera Omosita and Nitidula from the family Nitidulidae, are often reported to be associated with rotten animal carcasses. However, morphological descriptions of their larval stages are limited and are usually only from the third instar larvae, which does not provide enough systematic data. In this study, the overall structure of three instar larvae from the four Nitidulidae species was compared using optical microscopy, and the resolution was not satisfactory. To compensate, a large number of structures and organs were observed by scanning electron microscopy (SEM). Results showed that the number and distribution of chaetotaxy in different parts, including the macrosetae, setae, and microtrichia, have important identification values between the genera, species, and even instars. We also discuss the possible role of microtrichia in the biology of Nitidulidae larvae. Additionally, we described the number and types of sensilla in three sensory organs, and the morphologic parameters of the head capsule and urogomphi as determined by SEM images, are provided. An identification key with application value for storage products and forensic entomology was also compiled.

GNAS locus: bone related diseases and mouse models.

GNASis a complex locus characterized by multiple transcripts and an imprinting effect. It orchestrates a variety of physiological processes via numerous signaling pathways. Human diseases associated with the GNAS gene encompass fibrous dysplasia (FD), Albright's Hereditary Osteodystrophy (AHO), parathyroid hormone(PTH) resistance, and Progressive Osseous Heteroplasia (POH), among others. To facilitate the study of the GNAS locus and its associated diseases, researchers have developed a range of mouse models. In this review, we will systematically explore the GNAS locus, its related signaling pathways, the bone diseases associated with it, and the mouse models pertinent to these bone diseases.

Cadmium facilitates the formation of large lipid droplets via PLCß2-DAG-DGKε-PA signal pathway in Leydig cells.

Cadmium (Cd) exposure damages the reproductive system. Lipid droplets (LDs) play an important role in steroid-producing cells to provide raw material for steroid hormone. We have found that the LDs of Leydig cells exposed to Cd are bigger than those of normal cells, but the effects on steroidogenesis and its underlying mechanism remains unclear. Using Isobaric tag for relative and absolute quantitation (iTARQ) proteomics, phosphodiesterase beta-2 (PLCß2) was identified as the most significantly up-regulated protein in immature Leydig cells (ILCs) and adult Leydig cells (ALCs) derived from male rats exposed to maternal Cd. Consistent with high expression of PLCß2, the size of LDs was increased in Leydig cells exposed to Cd, accompanied by reduction in cholesterol and progesterone (P4) levels. However, the high PLCß2 did not result in high diacylglycerol (DAG) level, because Cd exposure up-regulated diacylglycerol kinases ε (DGKε) to promote the conversion from DAG to phosphatidic acid (PA). Exogenous PA, which was consistent with the intracellular PA concentration induced by Cd, facilitated the formation of large LDs in R2C cells, followed by reduced P4 level in the culture medium. When PLCß2 expression was knocked down, the increased DGKε caused by Cd was reversed, and then the PA level was decreased to normal. As results, large LDs returned to normal size, and the level of total cholesterol was improved to restore steroidogenesis. The accumulation of PA regulated by PLCß2-DAG-DGKε signal pathway is responsible for the formation of large LDs and insufficient steroid hormone synthesis in Leydig cells exposed to Cd. These data highlight that LD is an important target organelle for Cd-induced steroid hormone deficiency in males.

Effect of Deformation Conditions on Strain-Induced Precipitation of 7Mo Super-Austenitic Stainless Steel.

Strain-induced precipitation (SIP) behaviors of 7Mo super-austenitic stainless steel (SASS) under various deformation conditions were studied by stress relaxation tests. The research demonstrates that sigma phases are the primary SIP phases of 7Mo SASS. Generally, SIP is mainly distributed in granular shape at the boundaries of deformed grains or recrystallized grains, as well as around the deformed microstructure, such as deformation twin layers/matrix interfaces. The variation of deformation parameters can lead to changes in microstructure, therefore influencing the distribution of SIP. For instance, with the temperature increases, the SIP distribution gradually evolves from deformed grain boundaries to recrystallized grain boundaries. The average size of SIP increases with increasing temperature and strain, as well as decreasing strain rate. The SIP content also increases with increasing strain and decreasing strain rate, while exhibiting an initial rise followed by a decline with increasing temperature, reaching its maximum value at 850 °C. The presence of SIP can promote recrystallization by particle-induced nucleation (PSN) mechanism during the hot deformation process. Moreover, the boundaries of these recrystallized grains can also serve as nucleation sites for SIP, therefore promoting SIP. This process can be simplified as SIP→PSNRecrystallization→Nucleation sitesSIP. With the increase in holding time and the consumption of stored energy, the process gradually slows down, leading to the formation of a multi-layer structure, namely SIPs/Recrystallized grains/SIPs structure. Moreover, SIP at recrystallized grain boundaries can hinder the growth of recrystallized grains. Through this study, a comprehensive understanding of the SIP behaviors in 7Mo SASS under different deformation conditions has been achieved, as well as the interaction between SIP and recrystallization. This finding provides valuable insights for effective control or regulation of SIP and optimizing the hot working processes of 7Mo SASS.

LogD7.4 prediction enhanced by transferring knowledge from chromatographic retention time, microscopic pKa and logP.

Lipophilicity is a fundamental physical property that significantly affects various aspects of drug behavior, including solubility, permeability, metabolism, distribution, protein binding, and toxicity. Accurate prediction of lipophilicity, measured by the logD7.4 value (the distribution coefficient between n-octanol and buffer at physiological pH 7.4), is crucial for successful drug discovery and design. However, the limited availability of data for logD modeling poses a significant challenge to achieving satisfactory generalization capability. To address this challenge, we have developed a novel logD7.4 prediction model called RTlogD, which leverages knowledge from multiple sources. RTlogD combines pre-training on a chromatographic retention time (RT) dataset since the RT is influenced by lipophilicity. Additionally, microscopic pKa values are incorporated as atomic features, providing valuable insights into ionizable sites and ionization capacity. Furthermore, logP is integrated as an auxiliary task within a multitask learning framework. We conducted ablation studies and presented a detailed analysis, showcasing the effectiveness and interpretability of RT, pKa, and logP in the RTlogD model. Notably, our RTlogD model demonstrated superior performance compared to commonly used algorithms and prediction tools. These results underscore the potential of the RTlogD model to improve the accuracy and generalization of logD prediction in drug discovery and design. In summary, the RTlogD model addresses the challenge of limited data availability in logD modeling by leveraging knowledge from RT, microscopic pKa, and logP. Incorporating these factors enhances the predictive capabilities of our model, and it holds promise for real-world applications in drug discovery and design scenarios.

Hydrogenation of levulinic acid to γ-valerolactone over single-atom Pt confined in Sn-modified MIL-101(Fe).

We synthesize a Sn-modified MIL-101(Fe), which can confine Pt to the single-atom scale. This novel Pt@MIL(FeSn) catalyst efficiently hydrogenates levulinic acid to γ-valerolactone (TOF: 1386 h-1, yield: >99%) at only 100 °C and 1 MPa of H2via α-angelica lactone as an intermediate. This could be the first report on switching the reaction path from 4-hydroxypentanoic acid to α-angelica lactone under very mild conditions. Incorporating Sn into MIL-101(Fe) enables the creation of abundant micro-pores less than 1 nm and Lewis acidic sites that stabilize Pt0 atoms. The ensemble of active Pt atoms and a Lewis acid can synergistically enhance adsorption of the CO bond and facilitate dehydrative cyclization of levulinic acid.

Small change, big difference: A promising praziquantel derivative designated P96 with broad-spectrum antischistosomal activity for chemotherapy of schistosomiasis japonica.

BACKGROUND: Praziquantel (PZQ) has been the first line antischistosomal drug for all species of Schistosoma, and the only available drug for schistosomiasis japonica, without any alternative drugs since the 1980s. However, PZQ cannot prevent reinfection, and cannot cure schistosomiasis thoroughly because of its poor activity against juvenile schistosomes. In addition, reliance on a single drug is extremely dangerous, the development and spread of resistance to PZQ is becoming a great concern. Therefore, development of novel drug candidates for treatment and control of schistosomiasis is urgently needed. METHODOLOGYS/PRINCIPAL FINDINGS: One of the PZQ derivative christened P96 with the substitution of cyclohexyl by cyclopentyl was synthesized by School of Pharmaceutical Sciences of Shandong University. We investigated the in vitro and in vivo activities of P96 against different developmental stages of S. japonicum. Parasitological studies and scanning electron microscopy were used to study the primary action characteristics of P96 in vitro. Both mouse and rabbit models were employed to evaluate schistosomicidal efficacy of P96 in vivo. Besides calculation of worm reduction rate and egg reduction rate, quantitative real-time PCR was used to evaluate the in vivo antischistosomal activity of P96 at molecular level. In vitro, after 24h exposure, P96 demonstrated the highest activities against both juvenile and adult worm of S. japonicum in comparison to PZQ. The antischistosomal efficacy was concentration-dependent, with P96 at 50µM demonstrating the most evident schistosomicidal effect. Scanning electron microscopy demonstrated that P96 caused more severe damages to schistosomula and adult worm tegument compared to PZQ. In vivo, our results showed that P96 was effective against S. japonicum at all developmental stages. Notably, its efficacy against young stage worms was significantly improved compared to PZQ. Moreover, P96 retained the high activity comparable to PZQ against the adult worm of S. japonicum. CONCLUSIONS: P96 is a promising drug candidate for chemotherapy of schistosomiasis japonica, which has broad spectrum of action against various developmental stage, potentially addressing the deficiency of PZQ. It might be promoted as a drug candidate for use either alone or in combination with PZQ for the treatment of schistosomiasis.

Tora3D: an autoregressive torsion angle prediction model for molecular 3D conformation generation.

Three-dimensional (3D) conformations of a small molecule profoundly affect its binding to the target of interest, the resulting biological effects, and its disposition in living organisms, but it is challenging to accurately characterize the conformational ensemble experimentally. Here, we proposed an autoregressive torsion angle prediction model Tora3D for molecular 3D conformer generation. Rather than directly predicting the conformations in an end-to-end way, Tora3D predicts a set of torsion angles of rotatable bonds by an interpretable autoregressive method and reconstructs the 3D conformations from them, which keeps structural validity during reconstruction. Another advancement of our method over other conformational generation methods is the ability to use energy to guide the conformation generation. In addition, we propose a new message-passing mechanism that applies the Transformer to the graph to solve the difficulty of remote message passing. Tora3D shows superior performance to prior computational models in the trade-off between accuracy and efficiency, and ensures conformational validity, accuracy, and diversity in an interpretable way. Overall, Tora3D can be used for the quick generation of diverse molecular conformations and 3D-based molecular representation, contributing to a wide range of downstream drug design tasks.

Cobalt/Rhodium-Catalyzed Diversified Amidation of Benzocyclobutenols via C-C Cleavage under Catalyst and Condition Control.

Cobalt(III) and rhodium(III)-catalyzed regio- and chemoselective amidation of benzocyclobutenols has been realized using dioxazolone as the amidating reagent to afford three classes of C-N-coupled products via ß-carbon elimination of the benzocyclobutenol. The Co(III)-catalyzed coupling initially afforded an isolable o-(N-acylamino)arylmethyl ketone, which could further cyclize to the corresponding indole derivatives under condition control. In contrast, efficient stepwise diamidation has been achieved under Rh(III) catalyst control. The chemoselectivities are jointly controlled by the catalyst and reactions conditions.

A controllably fabricated polypyrrole nanorods network by doping a tetra-ß-carboxylate cobalt phthalocyanine tetrasodium salt for enhanced ammonia sensing at room temperature.

The morphology adjustment and functional doping optimization of polypyrrole (PPy) are of great significance in improving its gas sensing performance. Here, the PPy-0.5TcCoPc nanorods with a uniform dispersed 3-D network were prepared using one-step in situ polymerization using the electrostatic interaction between dopant counterion substituents in tetra-ß-carboxylate cobalt phthalocyanine tetrasodium salt (TcCoPcTs) with larger space structure and pyrrole (Py) molecules, in which TcCoPcTs is not only used as a dopant molecule crosslinking PPy chains to obtain a 3-D network, thus improving the conductivity, but also as a sensor accelerator to improve the gas-sensing performance. The resulting PPy-TcCoPc hybrid exhibits superior NH3-sensing properties than PPy and tetra-ß-carboxylate cobalt phthalocyanine (TcCoPc) under the same test conditions, especially the PPy-0.5TcCoPc sensor shows ultrafast response/recovery time to 50 ppm NH3 (8.1 s/370.8 s), low detection limit of 8.1 ppb and excellent gas selectivity at room temperature (20 °C). Besides, the PPy-0.5TcCoPc sensor also maintains superior response (49.3% to 50 ppm NH3), humidity resistance and conspicuous stability over 45 days. The excellent NH3-sensing performance of the PPy-0.5TcCoPc hybrid arises from the excellent gas selectivity of TcCoPc, the remarkable response mechanism between PPy and NH3, the high electrical conductivity, abundant active sites and good electron transport ability of the unique 3-D network with large specific surface area. The morphology regulation and functional doping optimization strategy of TcCoPcTs doped PPy broaden the research direction of ideal gas sensor materials.

The Optimized Homogenization Process of Cast 7Mo Super Austenitic Stainless Steel.

Super austenitic stainless steels are expected to replace expensive alloys in harsh environments due to their superior corrosion resistance and mechanical properties. However, the ultra-high alloy contents drive serious segregation in cast steels, where the σ phase is difficult to eliminate. In this study, the microstructural evolution of 7Mo super austenitic stainless steels under different homogenization methods was investigated. The results showed that after isothermal treatment for 30 h at 1250 °C, the σ phase in steels dissolved, while the remelting morphologies appeared at the phase boundaries. Therefore, the stepped solution heat treatment was further conducted to optimize the homogenized microstructure. The samples were heated up to 1220 °C, 1235 °C and 1250 °C with a slow heating rate, and held at these temperatures for 2 h, respectively. The elemental segregation was greatly reduced without incipient remelting and the σ phase was eventually reduced to less than 0.6%. A prolonged incubation below the dissolution temperature will lead to a spontaneous compositional adjustment of the eutectic σ phase, resulting in uphill diffusion of Cr and Mn, and reducing the homogenization efficiency of ISHT, which is avoided by SSHT. The hardness reduced from 228~236 Hv to 220~232 Hv by adopting the cooling process of "furnace cooling + water quench". In addition, the study noticed that increasing the Ce content or decreasing the Mn content can both refine the homogenized grain size and accelerate diffusion processes. This study provides a theoretical and experimental basis for the process and composition optimization of super austenitic stainless steels.

Quantitative Assessment of Interfacial Interactions Governing Ultrafiltration Membrane Fouling by the Mixture of Silica Nanoparticles (SiO2 NPs) and Natural Organic Matter (NOM): Effects of Solution Chemistry.

Mixtures of silica nanoparticles (SiO2 NPs) and natural organic matter (NOM) are ubiquitous in natural aquatic environments and pose risks to organisms. Ultrafiltration (UF) membranes can effectively remove SiO2 NP-NOM mixtures. However, the corresponding membrane fouling mechanisms, particularly under different solution conditions, have not yet been studied. In this work, the effect of solution chemistry on polyethersulfone (PES) UF membrane fouling caused by a SiO2 NP-NOM mixture was investigated at different pH levels, ionic strengths, and calcium concentrations. The corresponding membrane fouling mechanisms, i.e., Lifshitz-van der Waals (LW), electrostatic (EL), and acid-base (AB) interactions, were quantitatively evaluated using the extended Derjaguin-Landau-Verwey-Overbeek (xDLVO) theory. It was found that the extent of membrane fouling increased with decreasing pH, increasing ionic strength, and increasing calcium concentration. The attractive AB interaction between the clean/fouled membrane and foulant was the major fouling mechanism in both the initial adhesion and later cohesion stages, while the attractive LW and repulsive EL interactions were less important. The change of fouling potential with solution chemistry was negatively correlated with the calculated interaction energy, indicating that the UF membrane fouling behavior under different solution conditions can be effectively explained and predicted using the xDLVO theory.

Optimal treatment strategy and prognostic analysis for hypopharyngeal squamous-cell carcinoma patients with T3-T4 or node-positive: A population-based study.

PURPOSE: To explore the optimal treatment strategy and relevant prognostic analysis for hypopharyngeal squamous-cell carcinoma patients (HSCC) with T3-T4 or node-positive. METHODS AND MATERIALS: From 2004 to 2018, data for 2574 patients from the Surveillance, Epidemiology, and End Results database (SEER) and 66 patients treated at our center from 2013 to 2022 with T3-T4 or N + HSCC were collected. Patients in the SEER cohort were randomly assigned to the training set or validation set at a 7:3 ratio. Variables with statistically significant (P < 0.05) in univariate COX regression analysis or clinical significance were included in the multivariate COX regression model and subsequently used to construct the nomogram. RESULTS: The 3-year OS (52.9%vs44.4%, P < 0.01) and 3-year CSS rate (58.7%vs51.5%, P < 0.01) rates in the surgery combined with postoperative adjuvant therapy (S + ADT) group were superior to the radiotherapy combined with chemotherapy (CRT) group. The multivariate Cox regression analysis of the training group showed that age, race, marital status, primary site, T stage, N stage, and treatment modalities were correlated with OS and CSS. Based on those variables, we constructed nomograms for OS and CSS. Both the internal and external validation showed high prediction accuracy of the nomogram. CONCLUSION: Among patients with T3-T4 or node-positive, S + ADT was associated with superior OS and CSS compared to those treated with primary CRT, while the survival rate in the CRT group was comparable to S + ADT group in T2-T3 disease. The internal and external verification shows that the prognostic model has good discrimination ability and accuracy.