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Colorectal cancer (CRC) is a frequent gastrointestinal malignancy with high rates of morbidity and mortality; 85% of these tumours are proficient mismatch repair (pMMR)‐microsatellite instability‐low (MSI‐L)/microsatellite stable (MSS) CRC known as 'cold' tumours that are resistant to immunosuppressive drugs. Monotherapy with programmed death 1 (PD‐1)/programmed death ligand 1 (PD‐L1) inhibitors is ineffective for treating MSS CRC, making immunotherapy for MSS CRC a bottleneck. Recent studies have found that the multi‐pathway regimens combined with PD‐1/PD‐L1 inhibitors can enhance the efficacy of anti‐PD‐1/PD‐L1 in MSS CRC by increasing the number of CD8+ T cells, upregulating PD‐L1 expression and improving the tumour microenvironment. This paper reviews the research progress of PD‐1/PD‐L1 inhibitors in combination with cytotoxic T‐lymphocyte–associated antigen 4 (CTLA‐4) inhibitors, oncolytic virus, intestinal flora, antiangiogenic agents, chemotherapy, radiotherapy and epigenetic drugs for the treatment of pMMR‐MSI‐L/MSS CRC. [ABSTRACT FROM AUTHOR]

Urgent detection of calculous pyonephrosis is crucial for surgical planning and preventing severe outcomes. This study aims to evaluate the performance of computed tomography (CT)-based radiomics and a three-dimensional convolutional neural network (3D-CNN) model, integrated with independent clinical factors, to identify patients with calculous pyonephrosis. We recruited 182 patients receiving either percutaneous nephrostomy tube placement or percutaneous nephrolithotomy for calculous hydronephrosis or pyonephrosis. The regions of interest were manually delineated on plain CT images and the CT attenuation value (HU) was measured. Radiomics analysis was performed using least absolute shrinkage and selection operator (LASSO). A 3D-CNN model was also developed. The better-performing machine-learning model was combined with independent clinical factors to build a comprehensive clinical machine-learning model. The performance of these models was assessed using receiver operating characteristic analysis and decision curve analysis. Fever, blood neutrophils, and urine leukocytes were independent risk factors for pyonephrosis. The radiomics model showed higher area under the curve (AUC) than the 3D-CNN model and HU (0.876 vs. 0.599, 0.578; p = 0.003, 0.002) in the testing cohort. The clinical machine-learning model surpassed the clinical model in both the training (0.975 vs. 0.904, p = 0.019) and testing (0.967 vs. 0.889, p = 0.045) cohorts. [ABSTRACT FROM AUTHOR]

Aim: To explore the relationship between proinflammatory diet, habitual salt intake and the onset of type 2 diabetes. Methods: This prospective study was conducted among 171 094 UK Biobank participants who completed at least one 24‐h dietary questionnaire and were free of diabetes at baseline. Participants were followed up until 1 March 2023 for type 2 diabetes incidence, with diagnosis information obtained from linked medical records. An Energy‐adjusted Diet Inflammatory Index (E‐DII) was calculated based on 28 food parameters. Habitual salt intake was determined through the self‐reported frequency of adding salt to foods. The associations between E‐DII, habitual salt intake and type 2 diabetes incidence were tested by the Cox proportional hazard regression model. Results: Over a median follow‐up period of 13.5 years, 6216 cases of type 2 diabetes were documented. Compared with participants with a low E‐DII (indicative of an anti‐inflammatory diet), participants with a high E‐DII (indicative of a proinflammatory diet) had an 18% heightened risk of developing type 2 diabetes. The association between E‐DII and type 2 diabetes tends to be linear after adjustment for major confounders. Participants with a proinflammatory diet and always adding salt to foods had the highest risk of type 2 diabetes incidence (hazard ratio 1.60, 95% confidence interval 1.32‐1.94). Conclusions: Our findings indicate that a proinflammatory diet and higher habitual salt intake were associated with an increased risk of type 2 diabetes. These results support the public health promotion of an anti‐inflammatory diet and reducing salt intake to prevent the onset of type 2 diabetes. [ABSTRACT FROM AUTHOR]

Aim: This study aims to investigate the association of glycemia risk index (GRI), a novel composite metric derived from continuous glucose monitoring (CGM), with arterial stiffness in patients with type 2 diabetes. Materials and Methods: A total of 342 adults with type 2 diabetes were enrolled between April and June 2023 from 11 communities in Shanghai, China. Medical examinations, including measurements of anthropometric parameters, blood pressure, and venous blood samples were conducted. Brachial‐ankle pulse wave velocity (baPWV) was examined to evaluate arterial stiffness. All the participants underwent a 14 day CGM recording and GRI was calculated from the CGM data. Results: The mean age was 70.3 ± 6.8 years, and 162 (47.4%) were male. Participants with a higher baPWV had significantly higher levels of GRI and hyperglycemia component (both P for trend < 0.05). Linear regression revealed the significant positive linear associations of the GRI with baPWV in unadjusted or adjusted models (All P < 0.05). In the multivariable logistic analysis, each increase in the GRI quartile was associated with a 1.30‐fold (95% CI 1.01–1.68, P for trend < 0.05) higher prevalence of increased arterial stiffness after adjustment for age, sex, BMI, diabetes duration, current smoking status, blood pressure, and lipid profile. Subgroup analyses showed that the association between the GRI quartiles and increased arterial stiffness was stronger among participants with a diabetes duration ≥15 years (P for interaction = 0.014). Conclusion: Glycemia risk index assessed by continuous glucose monitoring is associated with increased arterial stiffness in type 2 diabetes. [ABSTRACT FROM AUTHOR]

Background: Low-carbohydrate diet (LCD) is effective for weight loss and glycaemic control in humans. Here, the study aimed to explore the effects of LCD/high-fat diet (HFD) in both humans and mice. Methods: Twenty-two overweight or obese participants received LCD for 3 weeks. Based on carbohydrate intake > 10% or ≤ 10% of calories, the participants were divided into moderate LCD (MLCD) and very LCD (VLCD) groups. The participants completed a 10-question food preference survey. Meanwhile, C57BL/6J mice were assigned to five groups: chow diet (CD, 10% fat), HFD with 60%, 70%, and 75% fat from cocoa butter (HFD-C), and HFD with 60% fat from lard (HFD-L) and fed for 24 weeks. Eight mice were acclimatised for the food-choice test. Results: LCD decreased the total energy intake in humans. The VLCD group showed greater weight loss and better glycaemic control than the MLCD group. A food preference survey showed that 65% of participants tended to choose high-carbohydrate foods. In mice, HFD resulted in energy overconsumption, obesity, and metabolic disorders. When CD and HFD-L were administered simultaneously, mice rarely consumed CD. In the HFD-C groups, the energy intake and body weight increased with increasing dietary fat content. Compared with the HFD-C group, the HFD-L group consumed more energy and had poorer metabolism. Conclusions: Lower carbohydrate intake contributed to lower energy intake and improved metabolism in humans. In mice, diets with a higher proportion of fat become more attractive and obesogenic by fixing the fat sources. Since the mice preferred lard to cocoa butter, lard induced excess energy intake and poorer metabolism. Different food preferences may be the underlying mechanism behind the opposite effects of the LCD/HFD in humans and mice. Trial registration: The clinical trial was registered with the Chinese Clinical Trial Registry (www.chictr.org.cn). The registration number is ChiCTR1800016786. All participants provided written informed consent prior to enrolment. [ABSTRACT FROM AUTHOR]

An increasing number of studies have reported the role of gut microbes in colorectal cancer (CRC) development, as they can be influenced by dietary metabolism and mediate alterations in host epigenetics, ultimately affecting CRC. Intake of specific dietary components can affect gut microbial composition and function, and their metabolism regulates important epigenetic functions that may influence CRC risk. Gut microbes can regulate epigenetic modifications through nutrient metabolism, including histone modification, DNA methylation, and noncoding RNAs. Epigenetics, in turn, determines the gut microbial composition and thus influences the risk of developing CRC. This review discusses the complex crosstalk between metabolic reprogramming, gut microbiota, and epigenetics in CRC and highlights the potential applications of the gut microbiota as a biomarker for the prevention, diagnosis, and therapy of CRC. [ABSTRACT FROM AUTHOR]

• The CDPN material can effectively capture both gaseous and liquid iodine, with a high iodine uptake capacity of 2.73 g/g. • The captured iodine can be easily released from the CDPN material by simply soaking it in methanol, achieving nearly complete release within 1 min. • The CDPN material is readily obtainable, green, and safe, making it a promising candidate for nuclear waste treatment applications. Developing a green and safe reversible iodine capture material is key for nuclear waste treatment. Herein, we report a readily obtainable β-CD-based polymer network (CDPN) that can reversibly capture iodine. This white CDPN material is able to capture both gaseous iodine and liquid iodine, with a good iodine uptake capacity of 2.73 g/g. The I 2 can be easily released from I 2 @CDPN by soaking it in methanol, achieving nearly complete release within 1 min. The CDPN powder exhibits good recyclability in its iodine capture performance. The efficient iodine capture ability of CDPN is ascribed to the cyclodextrin cavity and the crosslinked polymer network, which enhance the interactions between the host (CDPN) and guest (iodine) molecules, both intermolecularly and intramolecularly. [Display omitted] [ABSTRACT FROM AUTHOR]

Aim: To investigate the associations between ketone bodies (KB) and multiple adverse outcomes including cardiovascular disease (CVD), chronic kidney disease (CKD) and all‐cause mortality according to diabetes status. Methods: This prospective study included 222 824 participants free from CVD and CKD at baseline from the UK Biobank. Total KB including β‐hydroxybutyrate, acetoacetate and acetone were measured by nuclear magnetic resonance. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between KB and adverse outcomes among participants with normoglycaemia, prediabetes and type 2 diabetes, respectively. Results: During a mean follow‐up of 14.1 years, 24 088 incident CVD events (including 17 303 coronary heart disease events, 5172 stroke events and 5881 heart failure [HF] events), 8605 CKD events and 15 813 deaths, were documented. Higher total KB significantly increased the risk of HF among participants with normoglycaemia (HR, 1.32 [95% CI, 1.17‐1.49], per 10‐fold increase in total KB) and prediabetes (1.35 [1.04‐1.76]), and increased the risk of CKD among those with normoglycaemia (1.20 [1.09‐1.33]). Elevated KB levels were associated with an increased risk of all‐cause mortality across the glycaemic spectrum (1.32 [1.23‐1.42] for normoglycaemia, 1.45 [1.24‐1.71] for prediabetes and 1.47 [1.11‐1.94] for diabetes). Moreover, a significant additive interaction between KB and diabetes status was observed on the risk of death (P =.009), with 4.9% of deaths attributed to the interactive effects. Conclusions: Our study underscored the variation in association patterns between KB and adverse outcomes according to diabetes status and suggested that KB could interact with diabetes status in an additive manner to increase the risk of mortality. [ABSTRACT FROM AUTHOR]

Background: Dietary management is the most important and effective treatment for citrin deficiency, as well as a decisive factor in the clinical outcome of patients. However, the dietary management ability of caregivers of children with citrin deficiency is generally poor, especially in East Asia where carbohydrate-based diets are predominant. The aim of this study was to identify the difficulties that caregivers encounter in the process of home-based dietary management, and the reasons responsible for these challenges.Results: A total of 26 caregivers of children with citrin deficiency were recruited, including 24 mothers, one father, and one grandmother. Grounded theory was employed to identify three themes (covering 12 sub-themes) related to the dilemma of dietary management: dietary management that is difficult to implement; conflicts with traditional concepts; and the notion that children are only a part of family life. The first theme describes the objective difficulties that caregivers encounter in the process of dietary management; the second theme describes the underlying reasons responsible for the non-adherent behavior of caregivers; the third theme further reveals the self-compromise by caregivers in the face of multiple difficulties.Conclusions: This study reflects the adverse effects of multi-dimensional contradictions on the adherence of caregivers to dietary management. These findings reveal that the dietary management of citrin deficiency is not only a rational process, rather it is deeply embedded in family, social, and dietary traditions. [ABSTRACT FROM AUTHOR]

Background: Lifestyle interventions, including dietary adjustment and exercise, are important for weight loss in the context of obesity. Objective: This study aimed to compare the short-term effects of a low-carbohydrate diet (LCD) and exercise nondiabetic overweight and obese adults. Design: A total of 45 eligible subjects were randomized into a low-carbohydrate diet group (LC, n=22) and an exercise group (EX, n=23); the participants adopted a LCD (carbohydrate intake < 30 mins/day) for 3 weeks. Weekly follow-ups were conducted and flash glucose monitoring sensors were used.≥50 g/day) or performed moderate-to-vigorous exercise (Results: After the 3-week intervention, body mass index, total fat% and total fat mass (FM), waist circumference, visceral fat area and subcutaneous fat area decreased significantly in both the LC and EX, but the LC lost 2.32 kg more weight than the EX. Total fat-free mass (FFM) and total body water (TBW) in the LC were significantly reduced but remained unchanged in the EX. Triglycerides (TGs), total cholesterol and low-density lipoprotein cholesterol (LDL-c) decreased in the EX, while TGs decreased and LDL-c increased in the LC. Glycemic variability and insulin resistance were improved in both groups, but the effect in the LC was faster and greater. Mean sensor glucose declined significantly in the LC. Three days after stopping the intervention, body weight, FM and FFM increased significantly in the LC, and most of the FFM regained was TBW, which remained stable in the EX. Conclusion: A short-term LCD was more effective for weight loss and glycemic stability than exercise, and it mainly reduced body fat and body water. However, body weight was regained to a greater extent after stopping the LCD, which was due to body water retention. Exercise was less effective for fat loss than LCD and had no significant influence on body water. Disclosure: J. Zhou: None. L. Cai: None. J. Yin: None. X. Ma: None. Y. Mo: None. L. Cheng: None. W. Lu: None. Y. Bao: None. W. Jia: None. [ABSTRACT FROM AUTHOR]

We previously developed a method that can significantly improve Protein A chromatography's capability of removing antibody aggregates. That particular method requires polyethylene glycol (PEG) and 400 mM or more of calcium chloride/sodium chloride to be added to wash and elution buffers. Consequently, Protein A chromatography performed using this method has relatively high concentration of salt in its eluate. The high salt content prevents the neutralized eluate from binding to ion exchange columns without conductivity adjustment. In the current study we demonstrated that mixed-mode chromatography can be used as a subsequent step to Protein A chromatography with high-salt-containing eluate. As mixed-mode ligand mediates salt-tolerant adsorption, it allows the neutralized Protein A eluate to be directly loaded without the need of conductivity adjustment, and thus enables a smooth and convenient connection between capture and polishing steps. In this work we also showed that the mixed-mode chromatography, performed in bind-elute mode, removed most of PEG in the Protein A eluate. • Protein A capture step optimized for aggregate removal can be conveniently connected with mixed-mode chromatography. • Mixed-mode chromatography allows high-salt-containing Protein A eluate to be directly loaded without conductivity adjustment. • Capto MMC and CHT chromatography can effective remove antibody aggregates. • Capto MMC and CHT columns under bind-elute mode removed most of PEG in the Protein A eluate. [ABSTRACT FROM AUTHOR]

Excessive pesticide use poses a significant threat to food safety. Rapid on-site detection of multi-target pesticide residues in vegetables is crucial due to their widespread distribution and limited shelf life. In this study, a rapid on-site screening method for pesticide residues on vegetable surfaces was developed by employing a miniature mass spectrometer. A direct pretreatment method involves placing vegetables and elution solution into a customized flexible ziplock bag, allowing thorough mixing, washing, and filtration. This process effectively removes pesticide residues from vegetable surfaces with minimal organic solvent usage and can be completed within 2 min. Moreover, this study introduced a deep learning algorithm based on a one-dimensional convolutional neural network, coupled with a feature database, to autonomously discriminate detection outcomes. By combining full scan MS and tandem MS analysis methods, the proposed method achieved a qualitative recognition accuracy of 99.62%. Following the qualitative discrimination stage, the target pesticide residue and internal standard can be simultaneously isolated and fragmented in the ion trap, thus enabling on-site quantitative analysis and warning. This method achieved a quantitative detection limit of 10 μg/kg for carbendazim in cowpea. These results demonstrate the feasibility of the proposed analytical system and strategy in food safety applications. [Display omitted] • A complete and practical on-site mass spectrometry food rapid detection strategy. • Flexible ziplock bag pretreatment and one-key analysis to achieve sync detection of multi-targets. • Intelligent algorithm improves detection accuracy and reduces matrix interference. [ABSTRACT FROM AUTHOR]