A novel thermo-responsive phospholipase A1 with high selectivity and efficiency in enzymatic oil degumming.

The limited availability of phospholipase A1 (PLA1) has posed significant challenges in enzymatic degumming. In this study, a novel PLA1 (UM2) was introduced to address this limitation, which had a unique thermo-responsive ability to switch phospholipase and lipase activities in response to temperature variations. Remarkably, UM2 displayed an unprecedented selectivity under optimized conditions, preferentially hydrolyzing phospholipids over triacylglycerols-a specificity superior to that of commercial PLA1. Moreover, UM2 demonstrated high efficiency in hydrolyzing phospholipids with a predilection for phosphatidylcholine (PC) and phosphatidylethanolamine (PE). A practical application of UM2 on crude flaxseed oil led to a dramatic reduction in phosphorus content, plummeting from an initial 384.06 mg/kg to 4.38 mg/kg. Broadening its industrial applicability, UM2 effectively performed enzymatic degumming for other distinct crude vegetable oils with a unique phospholipid composition. Collectively, these results highlighted the promising application of UM2 in the field of oil degumming.

Divergent Synthesis of Enantioenriched Silicon-Stereogenic Benzyl-, Vinyl- and Borylsilanes via Asymmetric Aryl to Alkyl 1,5-Palladium Migration.

Functionalization of Si-bound methyl group provides an efficient access to diverse organosilanes. However, the asymmetric construction of silicon-stereogenic architectures by functionalization of Si-bound methyl group has not yet been described despite recent significant progress in producing chiral silicon. Herein, we disclosed the enantioselective silylmethyl functionalization involving the aryl to alkyl 1,5-palladium migration to access diverse naphthalenes possessing an enantioenriched stereogenic silicon center, which are inaccessible before. It is worthy to note that the realization of asymmetric induction at the step of metal migration itself remains challenging. Our study constitutes the first enantioselective aryl to alkyl 1,5-palladium migration reaction. The key to the success is the discovery and fine-tuning of the different substituents of α,α,α,α-tetraaryl-1,3-dioxolane-4,5-dimethanol (TADDOL)-based phosphoramidites, which ensure the enantioselectivity and desired reactivity.

Nomogram construction and validation of axial deviation in patients with tibial defects treated with the Ilizarov bone transport technique.

INTRODUCTION: The Ilizarov bone transport technique is widely recognised as an effective method for treating large segment bone defects in clinical practice. However, axial deviation is a common complication in the treatment of tibial large segment bone defects, which can have a serious impact on the clinical efficacy of bone transport. Our study aims to construct and validate a nomogram for predicting axial deviation of tibial bone transport. METHOD: This study retrospectively collected data from 363 patients who underwent the tibial Ilizarov technique for bone transport. Univariate and multivariate logistic regression analyses were performed to determine the independent risk factors for axial deviation, which were later used to construct a nomogram. The nomogram was evaluated using the decision curve analysis (DCA), the calibration curve, and the area under the receiver operating characteristic curve (AUC). RESULTS: Of the 363 patients who underwent Ilizarov tibial bone transport, 31.7% (115/363) experienced axial deviation. Multivariate logistic regression analysis showed that gender, height, defect site, and external fixation index were important risk factors for axial deviation. The AUC value of the nomogram model was 0.705. The calibration curve and the decision curve analysis showed a good consistency between the actual axial deviation and the predicted probability. CONCLUSION: The model assigns a quantitative risk score to each variable, which can be used to predict the risk of axial deviation during tibial bone transport.

Effects of Silybum marianum, Pueraria lobate, combined with Salvia miltiorrhiza tablets on non-alcoholic fatty liver disease in adults: A triple-blind, randomized, placebo-controlled clinical trial.

BACKGROUND & AIMS: Several medicinal plant extracts have demonstrated hepatoprotective effects. However, data are scarce regarding their combined effects on non-alcoholic fatty liver disease (NAFLD). This study aimed to investigate the effects of tablets containing Silybum marianum, Pueraria lobata, and Salvia miltiorrhiza (SPS) on NAFLD progression in Chinese adults. METHODS: In this randomized, triple-blind, placebo-controlled clinical trial, 121 NAFLD patients (60 female and 61 male), diagnosed via magnetic resonance imaging (MRI) and aged 18-65 years, were enrolled. Participants were randomly allocated to receive SPS tablets (n = 60; three tablets per dose, twice daily) or placebo (n = 61) for 24 weeks. Each SPS tablet contained approximately 23.0 mg of silybin, 11.4 mg of puerarin, and 10.9 mg of salvianolic acid. There were no differences in appearance, taste and odour between the SPS tablets and placebo manufactured by BYHEALTH Co., LTD (Guangzhou, China). The primary endpoints were changes in the liver fat content (LFC) and steatosis grade from baseline to 24 weeks. Secondary outcomes included changes in biomarkers/scores of liver fibrosis and steatosis, oxidative stress, inflammatory cytokines, alcohol metabolism, and glucose metabolism. RESULTS: A total of 112 participants completed the research. The intention-to-treat results showed a trend toward reduction in both absolute LFC (-0.52%) and percentage of LFC (-4.57%) in the SPS group compared to the placebo group after 24 weeks, but these changes didn't reach statistical significance (p > 0.05). The SPS intervention (vs. placebo) significantly decreased hypersensitive C-reactive protein level (-6.76%) and increased aldehyde dehydrogenase activity (+18.1%) at 24 weeks post-intervention (all p < 0.05). Per-protocol analysis further supported these effects. This trial is registered at Clinical Trials.gov (NCT05076058). CONCLUSION: SPS supplementation may have potential benefits in improving NAFLD, but further larger-scale trials are necessary to confirm these findings.

Enantioselective Synthesis of Oxazocines via MQ-Phos Enabled Palladium-Catalyzed Asymmetric Formal [4+4]-Cycloadditions.

Oxazocines are key structural intermediates in the synthesis of natural products and pharmaceutical molecules. However, the synthesis of oxazocines especially in a highly enantioselective manner, is a long-standing formidable challenge due to unfavorable energetics involved in cyclization. Herein, a series of new PNP-Ligand P-chiral stereocenter is first designed and synthesized, called MQ-Phos, and successfully applied it in the Pd-catalyzed enantioselective higher-order formal [4+4]-cycloaddition of α, ß-unsaturated imines with 2-(hydroxymethyl)-1-arylallyl carbonates. The reaction features mild conditions, excellent regio- and enantiocontrol and a broad substrate scope (54 examples). Various medium-sized rings can be afforded in moderate to excellent yields (up to 92%) and excellent enantioselectivity (up to 99% ee). The newly developed MQ-Phos is critical for synthesis of the medium-sized ring in excellent catalytic reactivity and enantioselectivity.

Dynamic observation and risk factors analysis of deep vein thrombosis after hip fracture.

OBJECTIVE: To dynamically observe the occurrence of deep vein thrombosis (DVT) after a hip fracture and analyze of the risk factors affecting the dynamic alteration of DVT. METHODS: Data of patients with hip fractures from January 1, 2017 to August 31, 2021 were collected. Patients were divided into DVT and non-DVT groups according to their daily Doppler ultrasonography findings. Survival analysis was used to describe dynamic changes in DVT occurrence with time. Log-rank tests were used to compare the influence of individual factors of patients with DVT occurrence, and a Cox proportional hazards regression model was used to identify the risk factors affecting the dynamic alteration of DVT occurrence. RESULTS: A total of 331 patients were included: 148(44.7%) had preoperative DVT, and 143 (96.6%) had DVT in the first 3days after admission. The probability of DVT was 0.42 on Day 1, 0.11 on Day 2, 0.10 on Day 3, 0.08 on Day 4, 0.20 on Day 5, and 0.00 on Day 6-7, with a median survival time of 3.30 d. Age>70 years, intertrochanteric fracture, admission hemoglobin<130g/L, and admission hematocrit<40% had a significantly higher occurrence rate of DVT. A hematocrit level of <40% (Hazard Ratio 2.079, 95% Confidence Interval:1.148-3.764, P = 0.016) was an independent risk factor for DVT. CONCLUSION: DVT after hip fractures mainly occurred in the first three days after admission, the trend was stabilized within one week, and day 1 had the highest rate of DVT incidence. Age, fracture type, HGB level, and Hct level affected dynamic occurrence of DVT. At constant other factors, Hct<40% was 2.079-fold incidence in the risk of preoperative DVT formation than those with Hct≥40% after hip fracture.

Abnormal function of EPHA2/p.R957P mutant in congenital cataract.

AIM: To identify genetic defects in a Chinese family with congenital posterior polar cataracts and assess the pathogenicity. METHODS: A four-generation Chinese family affected with autosomal dominant congenital cataract was recruited. Nineteen individuals took part in this study including 5 affected and 14 unaffected individuals. Sanger sequencing targeted hot-spot regions of 27 congenital cataract-causing genes for variant discovery. The pathogenicity of the variant was evaluated by the guidelines of American College of Medical Genetics and InterVar software. Confocal microscopy was applied to detect the subcellular localization of fluorescence-labeled ephrin type-A receptor 2 (EPHA2). Co-immunoprecipitation assay was implemented to estimate the interaction between EphA2 and other lens membrane proteins. The mRNA and protein expression were analyzed by reverse transcription-polymerase chain reaction (qRT-PCR) and Western blotting assay, respectively. The cell migration was analyzed by wound healing assay. Zebrafish model was generated by ectopic expression of human EPHA2/p.R957P mutant to demonstrate whether the mutant could cause lens opacity in vivo. RESULTS: A novel missense and pathogenic variant c.2870G>C was identified in the sterile alpha motif (SAM) domain of EPHA2. Functional studies demonstrated the variant's impact: reduced EPHA2 protein expression, altered subcellular localization, and disrupted interactions with other lens membrane proteins. This mutant notably enhanced human lens epithelial cell migration, and induced a central cloudy region and roughness in zebrafish lenses with ectopic expression of human EPHA2/p.R957P mutant under differential interference contrast (DIC) optics. CONCLUSION: Novel pathogenic c.2870G>C variant of EPHA2 in a Chinese congenital cataract family contributes to disease pathogenesis.

Emergence of Eurasian Avian-Like Swine Influenza A (H1N1) virus in a child in Shandong Province, China.

BACKGROUND: Influenza A virus infections can occur in multiple species. Eurasian avian-like swine influenza A (H1N1) viruses (EAS-H1N1) are predominant in swine and occasionally infect humans. A Eurasian avian-like swine influenza A (H1N1) virus was isolated from a boy who was suffering from fever; this strain was designated A/Shandong-binzhou/01/2021 (H1N1). The aims of this study were to investigate the characteristics of this virus and to draw attention to the need for surveillance of influenza virus infection in swine and humans. METHODS: Throat-swab specimens were collected and subjected to real-time fluorescent quantitative polymerase chain reaction (RT‒PCR). Positive clinical specimens were inoculated onto Madin-Darby canine kidney (MDCK) cells to isolate the virus, which was confirmed by a haemagglutination assay. Then, whole-genome sequencing was carried out using an Illumina MiSeq platform, and phylogenetic analysis was performed with MEGA X software. RESULTS: RT‒PCR revealed that the throat-swab specimens were positive for EAS-H1N1, and the virus was subsequently successfully isolated from MDCK cells; this strain was named A/Shandong-binzhou/01/2021 (H1N1). Whole-genome sequencing and phylogenetic analysis revealed that A/Shandong-binzhou/01/2021 (H1N1) is a novel triple-reassortant EAS-H1N1 lineage that contains gene segments from EAS-H1N1 (HA and NA), triple-reassortant swine influenza H1N2 virus (NS) and A(H1N1) pdm09 viruses (PB2, PB1, PA, NP and MP). CONCLUSIONS: The isolation and analysis of the A/Shandong-binzhou/01/2021 (H1N1) virus provide further evidence that EAS-H1N1 poses a threat to human health, and greater attention should be given to the surveillance of influenza virus infections in swine and humans.

Corrosive Pseudomonas aeruginosa detection by measuring pyocyanin with a lab-on-fiber optical surface plasmon resonance biosensor in aquatic environments.

Oceanic facilities and equipment corrosion present considerable economic and safety concerns, predominantly due to microbial corrosion. Early detection of corrosive microbes is pivotal for effective monitoring and prevention. Yet, traditional detection methods often lack specificity, require extensive processing time, and yield inaccurate results. Hence, the need for an efficient real-time corrosive microbe monitoring technology is evident. Pseudomonas aeruginosa, a widely distributed microorganism in aquatic environments, utilizes its production of quinone-like compounds, specifically pyocyanin (PYO), to corrode metals. Here, we report a novel fiber optic surface plasmon resonance (SPR) sensor modified by the C-terminal of BrlR protein (BrlR-C), which is a specific receptor of PYO molecule, to detect P. aeruginosa in aquatic environments. The results showed that the sensor had a good ability to recognize PYO in the concentration range of 0-1 µg/mL, and showed excellent sensing performance in real-time monitoring the growth status of P. aeruginosa. With a strong selectivity of PYO, the sensor could clearly detect P. aeruginosa against other bacteria in seawater environment, and exhibited excellent anti-interference ability against variations in pH, temperature and pressure and other interfering substances. This study provides a useful tool for monitoring corrosive P. aeruginosa biofilm in aquatic environments, which is a first of its kind example that serves as a laboratory model for the application of fiber optic technology in real-world scenarios to monitoring biofilms in microbial corrosion and biofouling.

Neuroprotective Effect and Mechanism of Tanreqing Injection on Ischemic Stroke: Insights from Network Pharmacology and in vivo Experiments.

OBJECTIVE: To explore the neuroprotective effects and mechanism of Tanreqing Injection (TRQ) on treating ischemic stroke based on network pharmacology and in vivo experimental validation. METHODS: The chemical compounds of TRQ were retrieved based on published data, with targets retrieved from PubChem, Therapeutic Target Database and DrugBank. Network visualization and analysis were performed using Cytoscape, with protein-protein interaction networks derived from the STRING database. Enrichment analysis was performed using Kyoto Encyclopedia of Genes Genomes pathway and Gene Ontology analysis. In in vivo experiments, the middle cerebral artery occlusion (MCAO) model was used. Infarct volume was determined by 2,3,5-triphenyltetrazolium hydrochloride staining and protein expressions were analyzed by Western blot. Molecular docking was performed to predict ligand-receptor interactions. RESULTS: We screened 81 chemical compounds in TRQ and retrieved their therapeutic targets. Of the targets, 116 were therapeutic targets for stroke. The enrichment analysis showed that the apelin signaling pathway was a key pathway for ischemic stroke. Furthermore, in in vivo experiment we found that administering with intraperitoneal injection of 2.5 mL/kg TRQ every 6 h could significantly reduce the infarct volume of MCAO rats (P<0.05). In addition, protein levels of the apelin receptor (APJ)/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) pathway were increased by TRQ (P<0.05). In addition, 41 chemical compounds in TRQ could bind to APJ. CONCLUSIONS: The neuroprotective effect of TRQ may be related to the APJ/PI3K/AKT signaling pathway. However, further studies are needed to confirm the findings.

Early onset and liver failure indicating poor prognosis of infant liver failure syndrome type 1.

BACKGROUND: Infantile liver failure syndrome type 1 (ILFS1, OMIM #615,438), caused by leucyl-tRNA synthase 1 (LARS1, OMIM *151,350) deficiency, is a rare autosomal-recessive disorder. The clinical manifestations, molecular-genetic features, and prognosis of LARS1 disease remain largely elusive. METHODS: Three new instances of ILFS1 with confirmed variants in LARS1, encoding LARS1, were identified. Disease characteristics were summarized together with those of 33 reported cases. Kaplan-Meier analysis was performed to assess prognostic factors in ILFS1 patients. RESULTS: The 3 new ILFS1 patients harbored 6 novel variants in LARS1. Among the 36 known patients, 12 died or underwent liver transplantation. The main clinical features of ILFS1 were intrauterine growth restriction (31/32 patients in whom this finding was specifically described), failure to thrive (30/31), hypoalbuminemia (32/32), microcytic anemia (32/33), acute liver failure (24/34), neurodevelopmental delay (25/30), seizures (22/29), and muscular hypotonia (13/27). No significant correlations were observed between genotype and either presence of liver failure or clinical severity of disease. Kaplan-Meier analysis indicated that age of onset < 3mo (p = 0.0015, hazard ratio = 12.29, 95% confidence interval [CI] = 3.74-40.3), like liver failure (p = 0.0343, hazard ratio = 6.57, 95% CI = 1.96-22.0), conferred poor prognosis. CONCLUSIONS: Early age of presentation, like liver failure, confers poor prognosis in ILFS1. Genotype-phenotype correlations remain to be established.

Structuring restricted amorphous molecular chains in the reinforced cellulose film by uniaxial stretching.

The construction of the preferred orientation structure by stretching is an efficient strategy to fabricate high-performance cellulose film and it is still an open issue whether crystalline structure or amorphous molecular chain is the key factor in determining the enhanced mechanical performance. Herein, uniaxial stretching with constant width followed by drying in a stretching state was carried out to cellulose hydrogels with physical and chemical double cross-linking networks, achieving high-performance regenerated cellulose films (RCFs) with an impressive tensile strength of 154.5 MPa and an elastic modulus of 5.4 GPa. The hierarchical structure of RCFs during uniaxial stretching and drying was systematically characterized from micro- to nanoscale, including microscopic morphology, crystalline structure as well as relaxation behavior at a molecular level. The two-dimensional correlation spectra of dynamic mechanical analysis and Havriliak-Negami fitting results verified that the enhanced mechanical properties of RCFs were mainly attributed to the stretch-induced tight packing and restricted relaxation of amorphous molecular chains. The new insight concerning the contribution of molecular chains in the amorphous region to the enhancement of mechanical performance for RCFs is expected to provide valuable guidance for designing and fabricating high-performance eco-friendly cellulose-based films.

Targeting lysosomal quality control as a therapeutic strategy against aging and diseases.

Previously, lysosomes were primarily referred to as the digestive organelles and recycling centers within cells. Recent discoveries have expanded the lysosomal functional scope and revealed their critical roles in nutrient sensing, epigenetic regulation, plasma membrane repair, lipid transport, ion homeostasis, and cellular stress response. Lysosomal dysfunction is also found to be associated with aging and several diseases. Therefore, function of macroautophagy, a lysosome-dependent intracellular degradation system, has been identified as one of the updated twelve hallmarks of aging. In this review, we begin by introducing the concept of lysosomal quality control (LQC), which is a cellular machinery that maintains the number, morphology, and function of lysosomes through different processes such as lysosomal biogenesis, reformation, fission, fusion, turnover, lysophagy, exocytosis, and membrane permeabilization and repair. Next, we summarize the results from studies reporting the association between LQC dysregulation and aging/various disorders. Subsequently, we explore the emerging therapeutic strategies that target distinct aspects of LQC for treating diseases and combatting aging. Lastly, we underscore the existing knowledge gap and propose potential avenues for future research.

Identification and coregulation pattern analysis of long noncoding RNAs in the mouse brain after Angiostrongylus cantonensis infection.

BACKGROUND: Angiostrongyliasis is a highly dangerous infectious disease. Angiostrongylus cantonensis larvae migrate to the mouse brain and cause symptoms, such as brain swelling and bleeding. Noncoding RNAs (ncRNAs) are novel targets for the control of parasitic infections. However, the role of these molecules in A. cantonensis infection has not been fully clarified. METHODS: In total, 32 BALB/c mice were randomly divided into four groups, and the infection groups were inoculated with 40 A. cantonensis larvae by gavage. Hematoxylin and eosin (H&E) staining and RNA library construction were performed on brain tissues from infected mice. Differential expression of long noncoding RNAs (lncRNAs) and mRNAs in brain tissues was identified by high-throughput sequencing. The pathways and functions of the differentially expressed lncRNAs were determined by Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses. The functions of the differentially expressed lncRNAs were further characterized by lncRNA‒microRNA (miRNA) target interactions. The potential host lncRNAs involved in larval infection of the brain were validated by quantitative real-time polymerase chain reaction (qRT‒PCR). RESULTS: The pathological results showed that the degree of brain tissue damage increased with the duration of infection. The transcriptome results showed that 859 lncRNAs and 1895 mRNAs were differentially expressed compared with those in the control group, and several lncRNAs were highly expressed in the middle-late stages of mouse infection. GO and KEGG pathway analyses revealed that the differentially expressed target genes were enriched mainly in immune system processes and inflammatory response, among others, and several potential regulatory networks were constructed. CONCLUSIONS: This study revealed the expression profiles of lncRNAs in the brains of mice after infection with A. cantonensis. The lncRNAs H19, F630028O10Rik, Lockd, AI662270, AU020206, and Mexis were shown to play important roles in the infection of mice with A. cantonensis infection.

Waist subcutaneous soft tissue metastasis of rectal mucinous adenocarcinoma: A case report.

BACKGROUND: Rectal mucinous adenocarcinoma (MAC) is a rare pathological type of rectal cancer with unique pathological features and a poor prognosis. It is difficult to diagnose and treat early because of the lack of specific manifestations in some aspects of the disease. The common metastatic organs of rectal cancer are the liver and lung; however, rectal carcinoma with metastasis to subcutaneous soft tissue is a rare finding. CASE SUMMARY: In this report, the clinical data, diagnosis and treatment process, and postoperative pathological features of a patient with left waist subcutaneous soft tissue masses were retrospectively analyzed. The patient underwent surgical treatment after admission and recovered well after surgery. The final pathological diagnosis was rectal MAC with left waist subcutaneous soft tissue metastasis. CONCLUSION: Subcutaneous soft tissue metastasis of rectal MAC is rare, and it can suggest that the tumor is disseminated, and it can appear even earlier than the primary malignant tumor, which is occult and leads to a missed diagnosis and misdiagnosis clinically. When a subcutaneous soft tissue mass of unknown origin appears in a patient with rectal cancer, a malignant tumor should be considered.

Uncovering the characteristics of the gut microbiota in patients with ischemic stroke and hemorrhagic stroke.

This study aimed to explore the gut microbiota characteristics of ischemic and hemorrhagic stroke patients. A case-control study was conducted, and high-throughput sequencing of the V4-V5 region of 16S rRNA was used to analyze the differences in gut microbiota. The results showed that Proteobacteria was significantly increased in the ischemic stroke group compared with the healthy control group, while Fusobacteria was significantly increased in the hemorrhagic stroke group. In the ischemic stroke group, Butyricimonas, Alloprevotella, and Escherichia were significantly more abundant than in the healthy control group. In the hemorrhagic stroke group, Atopobium, Hungatella, Eisenbergiella, Butyricimonas, Odonbacter, Lachnociostridium, Alistipes, Parabacteroides, and Fusobacterium were significantly more abundant than in the healthy control group. Additionally, Alloprevotella, Ruminococcus, and Prevotella were significantly more abundant in the ischemic stroke group than in the hemorrhagic stroke group. The gut microbiota of ischemic and hemorrhagic stroke patients has significant diversity characteristics. These results provide new theoretical basis for exploring the prevention and treatment of different types of stroke through gut microbiota research.

Design, Synthesis, and Bioactivity of Trifluoroethylthio-Substituted Phenylpyrazole Derivatives.

As the first marketed phenylpyrazole insecticide, fipronil exhibited remarkable broad-spectrum insecticidal activity. However, it poses a significant threat to aquatic organisms and bees due to its high toxicity. Herein, 35 phenylpyrazole derivatives containing a trifluoroethylthio group on the 4 position of the pyrazole ring were designed and synthesized. The predicted physicochemical properties of all of the compounds were within a reasonable range. The biological assay results revealed that compound 7 showed 69.7% lethality against Aedes albopictus (A. albopictus) at the concentration of 0.125 mg/L. Compounds 7, 7g, 8d, and 10j showed superior insecticidal activity for the control of Plutella xylostella (P. xylostella). Notably, compound 7 showed similar insecticidal activity against Aphis craccivora (A. craccivora) compared with fipronil. Potential surface calculation and molecular docking suggested that different lipophilicity and binding models to the Musca domestica (M. domestica) gamma-aminobutyric acid receptors may be responsible for the decreased activity of the tested derivatives. Toxicity tests indicated that compound 8d (LC50 = 14.28 mg/L) induced obviously 14-fold lower toxicity than fipronil (LC50 = 1.05 mg/L) on embryonic-juvenile zebrafish development.

Computational Modeling Oriented Substructure Splicing Application in the Identification of Thiazolidine Derivatives as Potential Low Honeybee Toxic Neonicotinoids.

With the aim of identifying novel neonicotinoid insecticides with low bee toxicity, a series of compounds bearing thiazolidine moiety, which has been shown to be low bee toxic, were rationally designed through substructure splicing strategy and evaluated insecticidal activities. The optimal compounds A24 and A29 exhibited LC50 values of 30.01 and 17.08 mg/L against Aphis craccivora, respectively. Electrophysiological studies performed on Xenopus oocytes indicated that compound A29 acted on insect nAChR, with EC50 value of 50.11 µM. Docking binding mode analysis demonstrated that A29 bound to Lymnaea stagnalis acetylcholine binding protein through H-bonds with the residues of D_Arg55, D_Leu102, and D_Val114. Quantum mechanics calculation showed that A29 had a higher highest occupied molecular orbit (HOMO) energy and lower vertical ionization potential (IP) value compared to the high bee toxic imidacloprid, showing potentially low bee toxicity. Bee toxicity predictive model also indicated that A29 was nontoxic to honeybees. Our present work identified an innovative insecticidal scaffold and might facilitate the further exploration of low bee toxic neonicotinoid insecticides.

In-situ and label-free measurement of cytochrome C concentration with a Ti2C-MXene sensitized fiber-optic MZI sensor.

BACKGROUND: The concentration of cytochrome C is demonstrated to be an effective indicator of the microbial corrosion strength of metals. Traditional cytochrome C sensor can detect cytochrome C with a low detection limit, but their use is limited by their high cost, cumbersome operation, and susceptibility to malignant environments. In addition, studies on the monitoring of cytochrome C in the field of microbial corrosion has still not been carried out. Therefore, there is a need for a highly sensitive, selective, low-cost, anti-interference, and stable cytochrome C sensor with online monitoring and remote sensing capabilities for in-situ measurement of microbial corrosion strength. RESULTS: This paper proposed a highly sensitive label-free fiber-optic sensor based on Mach-Zehnder interferometer (MZI) for in-situ measurement of the microbial corrosion marker cytochrome C. Two-dimensional Ti2C-MXene material is uniformly immobilized onto the surface of the sensing area to improve the sensitivity, hydrophilicity, and specific surface area of the sensing area, as well as to facilitate the immobilization of specific sensitive materials. The cytochrome C antibody is modified on the surface of Ti2C-MXene to specifically recognize cytochrome C, whose concentration variation can be measured by monitoring the spectral shift of MZI sensor. Results demonstrate a measurement sensitivity of 1.428 nm/µM for cytochrome C concentrations ranging from 0 to 7.04 µM. The detection limit of the sensor is calculated to be 0.392 µM with remarkable performance, including selectivity, stability, and reliability. Besides, the measurement result of the proposed sensor in real microbial corrosive environment is consistent with that of the ideal environment. SIGNIFICANCE AND NOVELTY: This is the first instance of achieving in-situ and label-free measurement of cytochrome C by using a fiber-optic MZI sensor, which undoubtedly provides a feasible solution for the effective monitoring of microbial metal corrosion in the environment.

Developing and validating a nomogram for early predicting the need for intestinal resection in pediatric intussusception.

Purpose: Develop and validate a nomogram for predicting intestinal resection in pediatric intussusception suspecting intestinal necrosis. Patients & methods: Children with intussusception were retrospectively enrolled after a failed air-enema reduction in the outpatient setting and divided into two groups: the intestinal resection group and the non-intestinal resection group. The enrolled cases were randomly selected for training and validation sets with a split ratio of 3:1. A nomogram for predicting the risk of intestinal resection was visualized using logistic regression analysis with calibration curve, C-index, and decision curve analysis to evaluate the model. Results: A total of 547 cases were included in the final analysis, of which 414 had non-intestinal necrosis and 133 had intestinal necrosis and underwent intestinal resection. The training set consisted of 411 patients and the validation cohort included 136 patients. Through forward stepwise regression, four variables (duration of symptoms, C-reaction protein, white blood cells, ascites) were selected for inclusion in the nomogram with a concordance index 0.871 (95% confidence interval: 0.834-0.908). Conclusion: We developed a nomogram for predicting intestinal resection in children with intussusception suspecting intestinal necrosis after a failed air-enema based on multivariate regression. This nomogram could be directly applied to facilitate predicting intestinal resection in pediatric intussusception suspecting necrosis.