Crohn's disease treatment and memory T-cell subset changes: insights from a case series.

Background: Crohn's disease (CD) is a chronic inflammatory bowel disease with significant morbidity, affecting millions worldwide. The intricacies of immune responses in CD, especially post-treatment, remain a vital area of exploration. While memory T (Tm)-cell subsets play a pivotal role in adaptive immunity, their specific function in patients with CD after treatment is not well-understood. This study aims to investigate the effect and function of Tm-cell subsets in these patients, addressing a crucial knowledge gap in the context of CD therapeutics. Methods: A total of eight patients diagnosed with CD were selected based on predefined inclusion criteria. All patients were treated with either anti-inflammatory agents, immunosuppressive drugs, or a combination of both. For comparison, healthy donors were enrolled based on exclusion of autoimmune or inflammatory diseases. Peripheral blood mononuclear cells (PBMCs) and lymphocytes were isolated from blood and lymph node tissue respectively. The phenotype and cytokine production of T lymphocytes from both CD patients and healthy donors were analyzed using flow cytometry. Statistical comparisons of the outcomes between CD patients and healthy donors were made using Mann-Whitney test (two-tailed) and Student t-test. Results: Post-treatment CD patients exhibited an altered T cell distribution with a notable increase in CD8+ T cells in PBMCs (P=0.0005), and altered frequencies of CD4+ and CD8+ T cells in mesenteric lymph nodes (MLNs). Tm cells showed decreased interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) production, with significant alterations in the frequency of IFN-γ-producing CD8+ stem cell-like Tm (Tscm) cells in lesions of the MLNs from patients with CD (CD-M-Lys) compared to healthy MLNs from patients with CD (N-M-Lys) (P=0.0152). Differences in tissue-resident Tm (Trm)-cell subset frequencies were observed between the MLNs and small intestinal mucosa in CD patients. Conclusions: The treatments with anti-inflammatory agents and/or immunosuppressive drugs have a significant effect on the frequency and function of Tm-cell subsets. Clinically, these findings suggest a potential therapeutic avenue in modulating Tm-cell responses, which might be particularly beneficial for conditions where immune response modulation is crucial. Further clinical studies are warranted to explore the full therapeutic implications of these findings.

Bio-promoter mediated denitrification recovery from Cd(II) stress: Microbial activity resilience, electron behavior enhancement and microbial community evolution.

Denitrification is fragile to toxic substances, while currently there are few regulation strategies for toxic substance-stressed denitrification. This study proposed a combined bio-promoter composed of basic bio-promoter (cytokinin, biotin, L-cysteine, and flavin adenine dinucleotide) and phosphomolybdic acid (PMo12) to recover cadmium(II) (Cd(II)) stressed denitrification. By inhibiting 58.02% and 48.84% of nitrate reductase and nitrite reductase activities, Cd(II) caused all the influent nitrogen to accumulate as NO3--N and NO2--N. Combined bio-promoter shortened the recovery time by 21 cycles and improved nitrogen removal efficiency by 10% as the synergistic effect of basic bio-promoter and PMo12. Basic bio-promoter enhanced antioxidant enzyme activities for reactive oxygen species clearance and recovered 23.30% of nicotinamide adenine dinucleotide for sufficient electron donors. Meanwhile, PMo12 recovered electron carriers contents, increasing the electron transfer activity by 60.81% compared with self-recovery. Bio-promoters enhanced the abundance of denitrifiers Seminibacterium and Dechloromonas, which was positively correlated with rapid recovery of denitrification performance.

Observation of Anisotropic Second Harmonic Generation in Two-Dimensional Niobium Diselenide.

The intrinsic anisotropy of NbSe2 provides a favorable prerequisite of second harmonic generation (SHG) and rich possibilities for tailoring its nonlinear optical (NLO) properties. Here we report the highly efficient SHG of mechanically exfoliated NbSe2 flakes. The nonlinear optical response changes with excitation wavelengths, layer thicknesses, and polarizations of the excitation laser. The anisotropic SHG response further exhibits the intrinsic non-centrosymmetric crystal structure and could effectively assign the crystalline orientation of NbSe2 flakes. Interestingly, although NbSe2 flakes with tens of nanometers thickness experience attenuations in SHG performance, more efficient SHG anisotropy ratios were obtained, which are around 4 times higher than that of the 5-layer counterpart. The determined second-order nonlinearities of NbSe2 flakes (monolayer: ∼1.0 × 103 pm/V; 3-layer: ∼73 pm/V) are comparable to those of the commonly reported two-dimensional materials (e.g., MoS2, WSe2, graphene) with the same number of layers and much higher than those of commercial nonlinear optical crystals.

Constructing heterogeneous interface between Co3O4 and RuO2 with enhanced electronic regulation for efficient oxygen evolution reaction at large current density.

Exploring effective strategies for developing new high-efficiency catalysts for water splitting is essential for advancing hydrogen energy technology. Herein, Co3O4/RuO2 heterojunction interface is construct through ion exchange reaction and pyrolysis. The as-synthesized Co3O4/RuO2-4 exhibits outstanding oxygen evolution reaction (OER) activity at the current density of 100 mA cm-2 with a low overpotential of 276 mV, and remarkable stability (maintaining activity for 60 h at 100 mA cm-2). Experimental results and theoretical calculations reveal that the electrons around the heterogeneous interface transferred from RuO2 to Co3O4, resulting in electron redistribution and optimization of energy barriers for OER intermediates. This unique composite catalyst structure offers a new potential for designing efficient oxygen electrocatalysts at large current density.

Double-layer hollow mesoporous silica nanoparticles for ultrasound-guided photodynamic treatment.

Cervical carcinoma persists as a major global public health burden. While conventional therapeutic modalities inevitably cause ablation of adjacent non-tumorous tissues, photodynamic therapy (PDT) offers a targeted cytotoxic strategy through a photosensitizing agent (PS). However, the hydrophobicity and lack of selective accumulation of promising PS compounds such as zinc(II) phthalocyanine (ZnPc) impedes their clinical translation as standalone agents. The present study sought to incorporate ZnPc within double-layer hollow mesoporous silica nanoparticles (DHMSN) as nanocarriers to enhance aqueous dispersibility and tumor specificity. Owing to their compartmentalized design, the hollow mesoporous silica nanoparticles (HMSN) demonstrated enhanced ultrasonic imaging contrast. Combined with the vaporization of the perfluorocarbon perfluoropentane (PFP), the HMSN-encapsulated ZnPc enabled real-time ultrasound monitoring of PDT treatment.In vivo, the innate thermal energy induced vaporization of the DHMSN-carried PFP to significantly amplify ultrasound signals from the tumor site. Results demonstrated biocompatibility, efficient PFP microbubble generation, and robust photocatalytic activity. Collectively, this investigation establishes ultrasound-guided PDT utilizing multi-layer HMSN as a targeted therapeutic strategy for cervical malignancies with mitigated toxicity.

The complete chloroplast genome sequence and phylogenetic analysis of Strobilanthes dalzielii (W.W.Sm.) Benoist 1935 (Acanthaceae).

Strobilanthes dalzielii of Acanthaceae is an herb species with potentially extensive applications for its pharmaceutical and ornamental values. Due to taxonomic complications and limited genetic information, the structural characteristics, and phylogenetic relationships of the S. dalzielii chloroplast genome were assembled and characterized here for the first time. The complete chloroplast genome of S. dalzielii was 144,580 bp in length. The genome is quadripartite in structure and consists of a large single-copy region (92,137 bp) and a small single-copy region (17,669 bp), which are separated by a pair of inverted repeats (each 17,387 bp). A total of 125 genes were annotated, including 80 protein-coding, 37 transfer RNA, and eight ribosomal RNA genes. The overall GC content was 36.4%. Phylogenetic analysis based on the complete chloroplast genome sequence of 21 taxa within the tribe Ruellieae of Acanthaceae using the maximum likelihood and Bayesian inference methods revealed that Strobilanthes diverged after Ruellia; S. dalzielii is closely related to S. tonkinensis. The genomic data obtained from this study will serve as valuable information to the species delimitation and genetic classification of Strobilanthes.

Total intracorporeal laparoscopic ileal ureter replacement in a single position for ureteral stricture based on membrane anatomy.

PURPOSE: The aim of this study was to present our initial experience and prove the feasibility of total intracorporeal laparoscopic ileal ureter replacement (TILIUR) in a single position for ureteral stricture based on membrane anatomy. MATERIALS AND METHODS: Between January 2021 and April 2023, six patients underwent TILIUR in a single position for ureteral strictures based on membrane anatomy. All patients with a past medical history underwent radical hysterectomy with bilateral pelvic lymph node dissection as well as extensive ureteral stricture due to radiotherapy. The procedure is performed completely laparoscopically. Dissection of the digestive system as well as ureteral stricture or renal pelvis is based on membrane anatomy. The surgery is performed in a single position. RESULTS: TILIUR in a single position for ureteral stricture based on membrane anatomy was successfully performed without open conversion in all patients. Among the 6 patients, 3 patients underwent combined ileal ureter replacement (IUR) and abdominal wall ostomy, 2 underwent unilateral IUR, and 1 underwent bilateral IUR. The mean length of the ileal substitution was 22.83 cm (range: 15-28). The average operative time was 458 ± 72.77 min (range 385-575 min), and the average intraoperative blood loss was 158 mL (range 50-400 mL). The median postoperative hospital stay was 15.1 d (range: 8-32). The median duration of postoperative follow-up was 15 months (range: 3-29 months). The success rate was 100%. CONCLUSIONS: TILIUR in a single position may be a promising option for ureteral stricture based on membrane anatomy in selected patients. Moreover, it has a positive effect on patients with renal insufficiency and urinary incontinence. Although IUR is difficult and risky, proficient surgeons can perform the procedure safely and effectively.

Fe-Mn binary oxides improve the methanogenic performance and reduce the environmental health risks associated with antibiotic resistance genes during anaerobic digestion.

Increasing evidence indicates that metal oxides can improve the methanogenic performance during anaerobic digestion (AD) of piggery wastewater. However, the impacts of composite metal oxides on the methanogenic performance and risk of antibiotic resistance gene (ARG) transmission during AD are not fully understood. In this study, different concentrations of Fe-Mn binary oxides (FMBO at 0, 250, 500, and 1000 mg/L) were added to AD to explore the effects of FMBO on the process. The methane yield was 7825.1 mL under FMBO at 250 mg/L, 35.2% higher than that with FMBO at 0 mg/L. PICRUSt2 functional predictions showed that FMBO promoted the oxidation of acetate and propionate, and the production of methane from the substrate, as well as increasing the abundances of most methanogens and genes encoding related enzymes. Furthermore, under FMBO at 250 mg/L, the relative abundances of 14 ARGs (excluding tetC and sul2) and four mobile gene elements (MGEs) decreased by 24.7% and 55.8%, respectively. Most of the changes in the abundances of ARGs were explained by microorganisms, especially Bacteroidetes (51.20%), followed by MGEs (11.98%). Thus, the methanogenic performance of AD improved and the risk of horizontal ARG transfer decreased with FMBO, especially at 250 mg/L.

Adequate iodine nutrition and higher salt intake in Chinese adults aged 18-59 years recommended by international organizations.

Iodine deficiency and excessive salt intake have adverse health effects. This study evaluated the iodine level and salt intake in Chinese adults aged 18-59 years after implementing the salt reduction program and compared with both the World Health Organization (WHO) and Chinese recommendations. Adults aged 18-59 years were randomly selected using multi-stage stratified random sampling in coastal urban area (CUA), non-coastal urban area (Non-CUA), coastal rural area (CRA), and non-coastal rural area (Non-CRA) of Fujian Province, China. Iodine, sodium, and creatinine concentrations in spot urine samples were measured. Knudsen equation was used to determine 24-h urinary iodine and sodium excretion. The median urinary iodine concentration (mUIC) and urinary sodium concentration (mUNaC) among adults (n = 3513) were 132.0 µg/L and 4.0 g/d, respectively. The mUIC and median daily iodine intake in CUA, Non-CUA, CRA and Non-CRA were 112.1, 127.5, 128.5, 167.5 µg/L and 189.6, 182.5, 199.4, 236.0 µg/d, respectively. The mUNaC and median daily salt intake (mDSI) in these four areas were 2.4, 2.8, 2.9, 2.9 g/L and 9.8, 10.4, 10.4, 10.6 g/d, respectively. The mUIC and DII of residents were higher in the Non-CRA than in the other three areas (P < 0.05). The UNaC and DSI of residents were lower in the CUA than in the other three areas (P < 0.05). The logistic regression demonstrated that the people living in CUA and Non-CUA consumed less salt compared with those in Non-CRA. Except for Non-CUA, the DII was lower (< 150 µg/d) among women of childbearing age in the low-salt intake group (< 5 g/d) compared with the high-salt intake group (≥ 5 g/d) (P < 0.05). Iodine nutrition in Chinese adults aged 18-59 years was sufficient, but the salt intake was substantially higher than the WHO and Chinese recommendations. Further policy implementation is needed to reduce salt intake and improve the monitoring of iodine levels in Chinese adults, especially in women of childbearing age.

Comparative analysis of [18F]F-FAPI PET/CT, [18F]F-FDG PET/CT and magnetization transfer MR imaging to detect intestinal fibrosis in Crohn's disease: A prospective animal model and human cohort study.

PURPOSE: Accurately and early detection of intestinal fibrosis in Crohn's disease (CD) is crucial for clinical management yet remains an unmet need. Fibroblast activation protein inhibitor (FAPI) PET/CT has emerged as a promising tool to assess fibrosis. We aimed to investigate the diagnostic capability of [18F]F-FAPI PET/CT in detecting intestinal fibrosis and compared it with[18F]F-FDG PET/CT and magnetization transfer MR imaging (MTI). METHODS: Twenty-two rats underwent TNBS treatment to simulate fibrosis development, followed by three quantitative imaging sessions within one week. Mean and maximum standardized uptake values (SUVmean and SUVmax) were calculated on[18F]F-FAPI and [18F]F-FDG PET/CT, along with normalized magnetization transfer ratio on MTI. Intestinal fibrosis was assessed pathologically, with MTI serving as imaging standard for fibrosis. The diagnostic efficacy of imaging parameters in fibrosis was compared using pathological and imaging standards. Ten patients with 34 bowel strictures were prospectively recruited to validate their diagnostic performance, using the identical imaging protocol. RESULTS: In CD patients, the accuracy of FAPI uptake (both AUCs = 0.87, both P ≤ 0.01) in distinguishing non-to-mild from moderate-to-severe fibrosis was higher than FDG uptake (both AUCs = 0.82, P ≤ 0.01) and comparable to MTI (AUCs = 0.90, P ≤ 0.001). In rats, FAPI uptake responded earlier to fibrosis development than FDG and MTI; consistently, during early phase, FAPI uptake showed a stronger correlation (SUVmean: R = 0.69) with pathological fibrosis than FDG (SUVmean: R = 0.17) and MTI (R = 0.52). CONCLUSION: The diagnostic efficacy of [18F]F-FAPI PET/CT in detecting CD fibrosis is superior to [18F]F-FDG PET/CT and comparable to MTI, exhibiting great potential for early detection of intestinal fibrosis.

Frequency selection rule for the HDHF Lissajous scanning imaging with a low-voltage one axis actuated PZT scanner based on an asymmetric fiber cantilever.

Lissajous micro scanners are very attractive in compact laser scanning applications for biomedical endoscopic imaging, such as confocal microscopy, endomicroscopy or optical coherence tomography. The scanning frequencies have a very important effect on the quality of the resulting Lissajous scanning imaging. In this paper, we propose a frequency selection rule for high definition and high frame-rate (HDHF) Lissajous scanning imaging, by deriving the relationship among the scanning field of view (FOV), actuation frequencies and pixel size based on the characteristics of the scanning trajectory. The minimum sampling rate based on the proposed frequency selection rule is further discussed. We report a lead zirconate titanate piezoelectric ceramic (PZT) based Lissajous fiber scanner to achieve HDHF Lissajous scanning imaging. Based on the frequency selection rule, different frequency combinations are calculated, under which the Lissajous fiber scanner can work at the frame rate (FR) of 10 Hz, 20 Hz, 40 Hz and 52 Hz. The trajectory evolution of the Lissajous scanning at the frame rate of 10 Hz has been obtained to verify the applicability of the proposed rule. The measured resolution of the scanner is 50.8 lp/mm at the unit optical magnification, and the measured FOV at the FR of 10 Hz and 40 Hz are 1.620 mm ×1.095 mm and 0.405 mm ×0.27 mm, respectively. HDHF Lissajous scanning images of the customized spatial varying binary pattern are obtained and reconstructed at the FR of 10 Hz and 40 Hz, demonstrating the practicability of the frequency selection rule.

Deep learning model to differentiate Crohn's disease from intestinal tuberculosis using histopathological whole slide images from intestinal specimens.

Crohn's disease (CD) and intestinal tuberculosis (ITB) share similar histopathological characteristics, and differential diagnosis can be a dilemma for pathologists. This study aimed to apply deep learning (DL) to analyze whole slide images (WSI) of surgical resection specimens to distinguish CD from ITB. Overall, 1973 WSI from 85 cases from 3 centers were obtained. The DL model was established in internal training and validated in external test cohort, evaluated by area under receiver operator characteristic curve (AUC). Diagnostic results of pathologists were compared with those of the DL model using DeLong's test. DL model had case level AUC of 0.886, 0.893 and slide level AUC of 0.954, 0.827 in training and test cohorts. Attention maps highlighted discriminative areas and top 10 features were extracted from CD and ITB. DL model's diagnostic efficiency (AUC = 0.886) was better than junior pathologists (*1 AUC = 0.701, P = 0.088; *2 AUC = 0.861, P = 0.788) and inferior to senior GI pathologists (*3 AUC = 0.910, P = 0.800; *4 AUC = 0.946, P = 0.507) in training cohort. In the test cohort, model (AUC = 0.893) outperformed senior non-GI pathologists (*5 AUC = 0.782, P = 0.327; *6 AUC = 0.821, P = 0.516). We developed a DL model for the classification of CD and ITB, improving pathological diagnosis accuracy effectively.

Constructing a Nomogram Model to Estimate the Risk of Ventilator-Associated Pneumonia for Elderly Patients in the Intensive Care Unit.

BACKGROUND: Ventilator-associated pneumonia (VAP) causes heavy losses in terms of finances, hospitalization, and death for elderly patients in the intensive care unit (ICU); however, the risk is difficult to evaluate due to a lack of reliable assessment tools. We aimed to create and validate a nomogram to estimate VAP risk to provide early intervention for high-risk patients. METHODS: Between January 2016 and March 2021, 293 patients from a tertiary hospital in China were retrospectively reviewed as a training set. Another 84 patients were enrolled for model validation from April 2021 to February 2022. Least absolute shrinkage and selection operator (LASSO) regression and multivariable logistic regression analysis were employed to select predictors, and a nomogram model was constructed. The calibration, discrimination, and clinical utility of the nomogram were verified. Finally, a web-based online scoring system was created to make the model more practical. RESULTS: The predictors were hypoproteinemia, long-term combined antibiotic use, intubation time, length of mechanical ventilation, and tracheotomy/intubation. The area under the curve (AUC) was 0.937 and 0.925 in the training and validation dataset, respectively, suggesting the model exhibited effective discrimination. The calibration curve demonstrated high consistency with the observed result and the estimated values. Decision curve analysis (DCA) demonstrated that the nomogram was clinically applicable. CONCLUSIONS: We have created a novel nomogram model that can be utilized to anticipate VAP risk in elderly ICU patients, which is helpful for healthcare professionals to detect patients at high risk early and adopt protective interventions.

Effects of dietary Nisin on growth performance, immune function, and gut health of broilers challenged by Clostridium perfringens.

Nisin (Ni) is a polypeptide bacteriocin produced by lactic streptococci (probiotics) that can inhibit the majority of gram-positive bacteria, and improve the growth performance of broilers, and exert antioxidative and anti-inflammatory properties. The present study investigated the potential preventive effect of Nisin on necrotic enteritis induced by Clostridium perfringens (Cp) challenge. A total of 288 Arbor Acres broiler chickens of 1-d-olds were allocated using 2 × 2 factorial arrangement into four groups with six replicates (12 chickens per replicate), including: (1) control group (Con, basal diet), (2) Cp challenge group (Cp, basal diet + 1.0 × 108 CFU/mL Cp), (3) Ni group (Ni, basal diet + 100 mg/kg Ni), and (4) Ni + Cp group (Ni + Cp, basal diet + 100 mg/kg Ni + 1.0 × 108 CFU/mL Cp). The results showed that Cp challenge decreased the average daily gain (ADG) of days 15 to 21 (P<0.05) and increased interleukin-6 (IL-6) content in the serum (P < 0.05), as well as a significant reduction in villus height (VH) and the ratio of VH to crypt depth (VCR) (P<0.05) and a significant increase in crypt depth (CD) of jejunum (P<0.05). Furthermore, the mRNA expressions of Occludin and Claudin-1 were downregulated (P<0.05), while the mRNA expressions of Caspase3, Caspase9, Bax, and Bax/Bcl-2 were upregulated (P<0.05) in the jejunum. However, the inclusion of dietary Ni supplementation significantly improved body weight (BW) on days 21 and 28, ADG of days 15 to 21 (P<0.05), decreased CD in the jejunum, and reduced tumor necrosis factor-α (TNF-α) content in the serum (P<0.05). Ni addition upregulated the mRNA levels of Claudin-1 expression and downregulated the mRNA expression levels of Caspase9 in the jejunum (P<0.05). Moreover, Cp challenge and Ni altered the cecal microbiota composition, which manifested that Cp challenge decreased the relative abundance of phylum Fusobacteriota and increased Shannon index (P<0.05) and the trend of phylum Proteobacteria (0.05

Necrotic enteritis (NE), a severe digestive disorder in broiler chickens caused by Clostridium perfringens (Cp), a gram-positive bacterium, is a widespread issue in the global poultry industry, leading to significant economic losses. Nisin (Ni), a polypeptide bacteriocin produced by probiotic lactic streptococci, has been found to enhance daily weight gain and feed intake, while also exhibiting inhibitory effects on gram-positive bacteria and anti-inflammatory properties. In this study, a NE infection model in broilers was established to examine the potential preventive effects of Ni. These results demonstrated that Cp challenge reduced growth performance, caused inflammatory responses and intestinal apoptosis, damaged intestinal morphology and barrier function, and was accompanied by changes in the composition of the gut microbiota. Dietary supplementation with Ni improved growth performance and protected intestine against Cp challenge-induced damage in broilers. As a result, Ni may be a potential safe and effective additive for NE prevention in broiler production.

Effect of injectable calcium alginate-amelogenin hydrogel on macrophage polarization and promotion of jawbone osteogenesis.

Due to persistent inflammation and limited osteogenesis, jawbone defects present a considerable challenge in regenerative medicine. Amelogenin, a major protein constituent of the developing enamel matrix, demonstrates promising capabilities in inducing regeneration of periodontal supporting tissues and exerting immunomodulatory effects. These properties render it a potential therapeutic agent for enhancing jawbone osteogenesis. Nevertheless, its clinical application is hindered by the limitations of monotherapy and its rapid release characteristics, which compromise its efficacy and delivery efficiency. In this context, calcium alginate hydrogel, recognized for its superior physicochemical properties and biocompatibility, emerges as a candidate for developing a synergistic bioengineered drug delivery system. This study describes the synthesis of an injectable calcium amelogenin/calcium alginate hydrogel using calcium alginate loaded with amelogenin. We comprehensively investigated its physical properties, its role in modulating the immunological environment conducive to bone healing, and its osteogenic efficacy in areas of jawbone defects. Our experimental findings indicate that this synthesized composite hydrogel possesses desirable mechanical properties such as injectability, biocompatibility, and biodegradability. Furthermore, it facilitates jawbone formation by regulating the bone-healing microenvironment and directly inducing osteogenesis. This research provides novel insights into the development of bone-tissue regeneration materials, potentially advancing their clinical application.

CT-based radiomics signature of visceral adipose tissue and bowel lesions for identifying patients with Crohn's disease resistant to infliximab.

PURPOSE: To develop a CT-based radiomics model combining with VAT and bowel features to improve the predictive efficacy of IFX therapy on the basis of bowel model. METHODS: This retrospective study included 231 CD patients (training cohort, n = 112; internal validation cohort, n = 48; external validation cohort, n = 71) from two tertiary centers. Machine-learning VAT model and bowel model were developed separately to identify CD patients with primary nonresponse to IFX. A comprehensive model incorporating VAT and bowel radiomics features was further established to verify whether CT features extracted from VAT would improve the predictive efficacy of bowel model. Area under the curve (AUC) and decision curve analysis were used to compare the prediction performance. Clinical utility was assessed by integrated differentiation improvement (IDI). RESULTS: VAT model and bowel model exhibited comparable performance for identifying patients with primary nonresponse in both internal (AUC: VAT model vs bowel model, 0.737 (95% CI, 0.590-0.854) vs. 0.832 (95% CI, 0.750-0.896)) and external validation cohort [AUC: VAT model vs. bowel model, 0.714 (95% CI, 0.595-0.815) vs. 0.799 (95% CI, 0.687-0.885)), exhibiting a relatively good net benefit. The comprehensive model incorporating VAT into bowel model yielded a satisfactory predictive efficacy in both internal (AUC, 0.840 (95% CI, 0.706-0.930)) and external validation cohort (AUC, 0.833 (95% CI, 0.726-0.911)), significantly better than bowel alone (IDI = 4.2% and 3.7% in internal and external validation cohorts, both p < 0.05). CONCLUSION: VAT has an effect on IFX treatment response. It improves the performance for identification of CD patients at high risk of primary nonresponse to IFX therapy with selected features from RM. CRITICAL RELEVANCE STATEMENT: Our radiomics model (RM) for VAT-bowel analysis captured the pathophysiological changes occurring in VAT and whole bowel lesion, which could help to identify CD patients who would not response to infliximab at the beginning of therapy. KEY POINTS: • Radiomics signatures with VAT and bowel alone or in combination predicting infliximab efficacy. • VAT features contribute to the prediction of IFX treatment efficacy. • Comprehensive model improved the performance compared with the bowel model alone.

TaTHI2 interacts with Ca2+-dependent protein kinase TaCPK5 to suppress virus infection by regulating ROS accumulation.

Thiamine (vitamin B1) biosynthesis involves key enzymes known as thiazole moieties (THI1/THI2), which have been shown to participate in plant responses to abiotic stress. However, the role of THI1/THI2 in plant immunity remains unclear. In this study, we cloned TaTHI2 from wheat and investigated its function in Chinese wheat mosaic virus (CWMV) infection. Overexpression of TaTHI2 (TaTHI2-OE) inhibited CWMV infection, while TaTHI2 silencing enhanced viral infection in wheat. Interestingly, the membrane-localized TaTHI2 protein was increased during CWMV infection. TaTHI2 also interacted with the Ca2+-dependent protein kinase 5 (TaCPK5), which is localized in the plasma membrane, and promoted reactive oxygen species (ROS) production by repressing TaCPK5-mediated activity of the catalase protein TaCAT1. CWMV CP disrupted the interaction between TaTHI2 and TaCAT1, reducing ROS accumulation and facilitating viral infection. Additionally, transgenic plants overexpressing TaTHI2 showed increased seed number per ear and 1000-kernel weight compared to control plants. Our findings reveal a novel function of TaTHI2 in plant immunity and suggest its potential as a valuable gene for balancing disease resistance and wheat yield. Furthermore, the disruption of the TaTHI2-mediated plant immune pathway by CWMV CP provides further evidence for the evolutionary arms race between plants and viruses.

Phenotypic and Proteomic Insights into Differential Cadmium Accumulation in Maize Kernels.

The contamination of agricultural soil with cadmium (Cd), a heavy metal, poses a significant environmental challenge, affecting crop growth, development, and human health. Previous studies have established the pivotal role of the ZmHMA3 gene, a P-type ATPase heavy metal transporter, in determining variable Cd accumulation in maize grains among 513 inbred lines. To decipher the molecular mechanism underlying mutation-induced phenotypic differences mediated by ZmHMA3, we conducted a quantitative tandem mass tag (TMT)-based proteomic analysis of immature maize kernels. This analysis aimed to identify differentially expressed proteins (DEPs) in wild-type B73 and ZmHMA3 null mutant under Cd stress. The findings demonstrated that ZmHMA3 accumulated higher levels of Cd compared to B73 when exposed to varying Cd concentrations in the soil. In comparison to soil with a low Cd concentration, B73 and ZmHMA3 exhibited 75 and 142 DEPs, respectively, with 24 common DEPs shared between them. ZmHMA3 showed a higher induction of upregulated genes related to Cd stress than B73. Amino sugar and nucleotide sugar metabolism was specifically enriched in B73, while phenylpropanoid biosynthesis, nitrogen metabolism, and glyoxylate and dicarboxylate metabolism appeared to play a more significant role in ZmHMA3. This study provides proteomics insights into unraveling the molecular mechanism underlying the differences in Cd accumulation in maize kernels.

Mechanism Underlying Bacillus subtilis BS-Z15 Metabolite-Induced Prevention of Grain Contamination by Aspergillus flavus.

Aspergillus flavus can cause mildew in corn, peanuts, and other foods as well as animal feed, which seriously endangers human and livestock health; thus, preventing A. flavus contamination is imperative. Previous studies have found that the secondary metabolites of Bacillus subtilis BS-Z15 have broad-spectrum-inhibiting fungal activity, further confirming that the main active inhibiting fungal substance is Mycosubtilin (Myco). In this paper, corn and peanuts were treated with 0, 100, and 200 µg/mL BS-Z15 secondary metabolites (BS-Z15-SMA) for 7 days, and the aflatoxin contamination prevention effect was examined. The results showed that with increasing BS-Z15-SMA concentration, the aflatoxin contamination prevention effect was significantly enhanced. The above toxicity phenomena became more significant with extended BS-Z15-SMA treatment time. Scanning electron microscopy showed that 4 µg/mL Myco treatment resulted in a dented A. flavus surface and breakage of both the conidial stem and the mycelium. Transcriptome results showed that Myco significantly affected gene expression in A. flavus spores. The downregulated genes were significantly enriched in cell wall synthesis, transcription and translation, transmembrane transport pathways, and pathways related to key enzymes for aflatoxin synthesis. These results suggest that Myco could be used as a new bioactive material to prevent aflatoxin synthesis and contamination.