Optimization of Dendritic Polypeptide Delivery System for Antisense Antibacterial Agents Targeting ftsZ.

There is an urgent requirement for a novel treatment strategy for drug-resistant Staphylococcus aureus (S. aureus) infection. Antisense antimicrobials are promising antimicrobials, and efficient drug delivery systems are necessary for the further development of antisense antimicrobials. To develop new antisense drugs and further improve delivery efficiency and safety, we designed and screened new antisense sequences and optimized dendritic polypeptide nanoparticles (DP-AD) discovered in previous studies. The N/P ratio is optimized from 8:1 to 6:1, and the positive charge number of the optimized DP-AD is studied comprehensively. The results show that the N/P ratio and positive charge number have no significant effect on the particle size distribution and transport efficiency of DP-AD. Reducing the N/P ratio can significantly reduce the cytotoxicity of DP-AD, but it does not affect its delivery efficiency and antibacterial activity. However, in drug-resistant strains, the antibacterial activity of DP-AD76:1 with 10 positive charges is higher than that of DP-AD86:1 with 8 positive charges. Our research discovered a novel ASOs targeting ftsZ and concluded that DP-AD76:1 with 10 positive charges was the optimal choice at the current stage, which provided a promising strategy for the treatment of drug-resistant S. aureus.

Novel MIP gene mutation causes autosomal-dominant congenital cataract.

AIM: To identify disease-causative mutations in families with congenital cataract. METHODS: Two Chinese families with autosomal-dominant congenital cataract (ADCC) were recruited and underwent comprehensive eye examinations. Gene panel next-generation sequencing of common pathogenic genes of congenital cataract was performed in the proband of each family. Sanger sequencing was used to valid the candidate gene mutations and sequence the other family members for co-segregation analysis. The effect of sequence changes on protein structure and function was predicted through bioinformatics analysis. Major intrinsic protein (MIP)-wildtype and MIP-G29R plasmids were constructed and microinjected into zebrafish single-cell stage embryos. Zebrafish embryonic lens phenotypes were screened using confocal microscopy. RESULTS: A novel heterozygous mutation (c.85G>A; p.G29R) in the MIP gene was identified in the proband of one family. A known heterozygous mutation (c.97C>T; p.R33C; rs864309693) in MIP was found in the proband of another family. In-silico prediction indicated that the novel mutation might affect the MIP protein function. Zebrafish embryonic lens was uniformly transparent in both wild-type PCS2+MIP and mutant PCS2+MIP. CONCLUSION: Two missense mutations in the MIP gene in Chinese cataract families are identified, and one of which is novel. These findings expand the genetic spectrum of MIP mutations associated with cataracts. The functional studies suggest that the novel MIP mutation might not be a gain-of-function but a loss-of-function mutation.

Endoplasmic reticulum protein ALTERED MERISTEM PROGRAM 1 negatively regulates senescence in Arabidopsis.

Plant senescence is a highly regulated developmental program crucial for nutrient reallocation and stress adaptation in response to developmental and environmental cues. Stress-induced and age-dependent natural senescence share both overlapping and distinct molecular responses and regulatory schemes. Previously, we have utilized a carbon-deprivation (C-deprivation) senescence assay using Arabidopsis (Arabidopsis thaliana) seedlings to investigate senescence regulation. Here we conducted a comprehensive time-resolved transcriptomic analysis of Arabidopsis wild type seedlings subjected to C-deprivation treatment at multiple time points, unveiling substantial temporal changes and distinct gene expression patterns. Moreover, we identified ALTERED MERISTEM PROGRAM 1 (AMP1), encoding an endoplasmic reticulum protein, as a potential regulator of senescence based on its expression profile. By characterizing loss-of-function alleles and overexpression lines of AMP1, we confirmed its role as a negative regulator of plant senescence. Genetic analyses further revealed a synergistic interaction between AMP1 and the autophagy pathway in regulating senescence. Additionally, we discovered a functional association between AMP1 and the endosome-localized ABNORMAL SHOOT3 (ABS3)-mediated senescence pathway and positioned key senescence-promoting transcription factors downstream of AMP1. Overall, our findings shed light on the molecular intricacies of transcriptome reprogramming during C-deprivation-induced senescence and the functional interplay among endomembrane compartments in controlling plant senescence.

P. gingivalis in oral-prostate axis exacerbates benign prostatic hyperplasia via IL-6/IL-6R pathway.

BACKGROUND: Benign prostatic hyperplasia (BPH) is the most common disease in elderly men. There is increasing evidence that periodontitis increases the risk of BPH, but the specific mechanism remains unclear. This study aimed to explore the role and mechanism of the key periodontal pathogen Porphyromonas gingivalis (P. gingivalis) in the development of BPH. METHODS: The subgingival plaque (Sp) and prostatic fluid (Pf) of patients with BPH concurrent periodontitis were extracted and cultured for 16S rDNA sequencing. Ligature-induced periodontitis, testosterone-induced BPH and the composite models in rats were established. The P. gingivalis and its toxic factor P. gingivalis lipopolysaccharide (P.g-LPS) were injected into the ventral lobe of prostate in rats to simulate its colonization of prostate. P.g-LPS was used to construct the prostate cell infection model for mechanism exploration. RESULTS: P. gingivalis, Streptococcus oralis, Capnocytophaga ochracea and other oral pathogens were simultaneously detected in the Pf and Sp of patients with BPH concurrent periodontitis, and the average relative abundance of P. gingivalis was found to be the highest. P. gingivalis was detected in both Pf and Sp in 62.5% of patients. Simultaneous periodontitis and BPH synergistically aggravated prostate histological changes. P. gingivalis and P.g-LPS infection could induce obvious hyperplasia of the prostate epithelium and stroma (epithelial thickness was 2.97- and 3.08-fold that of control group, respectively), and increase of collagen fibrosis (3.81- and 5.02-fold that of control group, respectively). P. gingivalis infection promoted prostate cell proliferation, inhibited apoptosis, and upregulated the expression of inflammatory cytokines interleukin-6 (IL-6; 4.47-fold), interleukin-6 receptor-α (IL-6Rα; 5.74-fold) and glycoprotein 130 (gp130; 4.47-fold) in prostatic tissue. P.g-LPS could significantly inhibit cell apoptosis, promote mitosis and proliferation of cells. P.g-LPS activates the Akt pathway through IL-6/IL-6Rα/gp130 complex, which destroys the imbalance between proliferation and apoptosis of prostate cells, induces BPH. CONCLUSION: P. gingivalis was abundant in the Pf of patients with BPH concurrent periodontitis. P. gingivalis infection can promote BPH, which may affect the progression of BPH via inflammation and the Akt signaling pathway.

Trends in prevalence of multimorbidity for chronic diseases in China: serial cross-sectional surveys from 2009 to 2018.

BACKGROUND: Multimorbidity, individuals suffering from two or more chronic diseases, has become a major health challenge worldwide, especially in populous and prosperous cities, where studies of this phenomenon in China are limited. We examined the prevalence, trends, patterns, and associated factors of multimorbidity from 2009 to 2018 among community-dwelling adults in Guangzhou, China. METHODS: We conducted serial cross-sectional surveys for chronic diseases in Guangzhou, China, in 2009, 2013, and 2018. General and stratified prevalence were standardized using demographic data. Multivariable logistic regression and hierarchical cluster analysis were applied to identify associated factors and to assess the correlations and patterns of multimorbidity, respectively. RESULTS: This study included 23,284 adults aged 18 and over in 2009, 18,551 in 2013, and 15,727 in 2018. The standardized prevalence of multimorbidity increased substantially, with 12.69% (95% CI: 10.45-15.33) in 2009, 25.44% (95% CI: 23.47-27.52) in 2013, and 35.13% (95% CI:32.64-37.70) in 2018 (P for trend <0.001). The highest bi- and triple-conditions of multimorbidity were dyslipidemia (DP) and overweight or obesity (OO) (12.54%, 95% CI: 11.68-13.46), and DP, OO, and Hypertension (HT) (3.99%, 95% CI: 3.47-4.58) in 2018. From 2009 to 2018, (1) The majority of multimorbidity patterns showed a high prevalence; (2) The percentage of participants with only one chronic condition was found lower, while the percentage with multiple conditions was higher. CONCLUSIONS: The prevalence of chronic disease multimorbidity in Guangzhou China, has increased substantially among adults. Effective policies targeting multimorbidity are urgently needed, especially for the health management of primary medical institutions.

Rapid one-pot isothermal amplification reassembled of fluorescent RNA aptamer for SARS-CoV-2 detection.

The outbreak of SARS-CoV-2 poses a serious threat to human life and health. A rapid nucleic acid tests can effectively curb the spread of the disease. With the advantages of fluorescent RNA aptamers, low background and high sensitivity. A variety of fluorescent RNA aptamer sensors have been developed for the detection of nucleic acid. Here, we report a hypersensitive detection platform in which SARS-CoV-2 initiates RTF-EXPAR to amplify trigger fragments. This activation leads to the reassembled of the SRB2 fluorescent RNA aptamer, restoring its secondary structure for SR-DN binding and turn-on fluorescence. The platform completes the assay in 30 min and all reactions occur in one tube. The detection limit is as low as 116 aM. Significantly, the platform's quantitative analyses were almost identical to qPCR results in simulated tests of positive samples. In conclusion, the platform is sensitive, accurate and provides a new protocol for point-of-care testing of viruses.

The combined effect of handgrip strength and obesity phenotype on the risk of stroke in Chinese middle-aged and elderly: A cohort study.

OBJECTIVE: The aim of this study was to investigate the combined effect of handgrip strength (HGS) and obesity phenotype on the risk of stroke in Chinese middle-aged and elderly people. METHODS: The data was used from the China Health and Retirement Longitudinal Study (CHARLS). Middle-aged and older adults who participated in surveys between 2011 and 2018 were included in the study. They were divided into 4 different types of obesity phenotypes based on obesity and metabolic status: metabolically healthy non-overweight/obesity (MHNO), metabolically healthy overweight/obesity (MHO), metabolically abnormal non-overweight/obesity (MANO), and metabolically abnormal overweight/obesity (MAO). The HGS level was divided into low and high groups according to the median values. Cox proportional risk regression model was used to analyze the joint effect of HGS and obesity phenotype on the risk of stroke among participants. RESULTS: A total of 7904 participants aged 58.89±9.08 years were included in this study. After adjusting for potential confounders, high HGS&MHO (HR=1.86, 95 % CI=1.12-3.09), high HGS&MANO (HR=2.01, 95 %CI=1.42-2.86), high HGS&MAO (HR=2.01, 95 % CI=1.37-2.93), low HGS&MHNO (HR=1.57, 95 % CI=1.00-2.46), low HGS&MHO (HR=2.09, 95 % CI=1.29-3.38), low HGS&MANO (HR=2.02, 95 % CI=1.35-3.03), and low HGS&MAO (HR=2.48, 95 % CI=1.72-3.58) group had significantly higher risks of stroke than the high HGS&MHNO group. CONCLUSION: The coexistence of metabolically unhealthy and low HGS can synergistically increase the risk of stroke in Chinese middle-aged and elderly people.

The Association of Malnutrition and Health-Related Factors among 474,467 Older Community-Dwellers: A Population-Based Data Mining Study in Guangzhou, China.

BACKGROUND: This study aimed to examine the prevalence and associated factors of malnutrition in older community-dwellers and explore the interaction between associated factors. METHODS: A total of 474,467 older community-dwellers aged 65 or above were selected in Guangzhou, China. We used a two-step methodology to detect the associated factors of malnutrition and constructed logistic regression models to explore the influencing factors and interactive effects on three patterns of malnutrition. RESULTS: The prevalence of malnutrition was 22.28%. Older adults with both hypertension and diabetes (RERI = 0.13), both meat or fish diet and hypertension (RERI = 0.79), and both meat or fish diet and diabetes (RERI = 0.81) had positive additive interaction effects on the risk of obesity, whereas those on a vegetarian diet with hypertension (RERI = -0.25) or diabetes (RERI = -0.19) had negative additive interaction effects. Moreover, the interactions of physical activity with a meat or fish diet (RERI = -0.84) or dyslipidemia (RERI = -0.09) could lower the risk of obesity. CONCLUSIONS: Malnutrition was influenced by different health factors, and there were interactions between these influencing factors. Pertinent dietary instruction should be given according to different nutritional status indexes and the prevalence of metabolic diseases to avoid the occurrences of malnutrition among older adults.

Constructing an Asymmetric Covalent Triazine Framework to Boost the Efficiency and Selectivity of Visible-Light-Driven CO2 Photoreduction.

The photocatalytic reduction of CO2 represents an environmentally friendly and sustainable approach for generating valuable chemicals. In this study, a thiophene-modified highly conjugated asymmetric covalent triazine framework (As-CTF-S) is developed for this purpose. Significantly, single-component intramolecular energy transfer can enhance the photogenerated charge separation, leading to the efficient conversion of CO2 to CO during photocatalysis. As a result, without the need for additional photosensitizers or organic sacrificial agents, As-CTF-S demonstrates the highest photocatalytic ability of 353.2 µmol g-1 and achieves a selectivity of ≈99.95% within a 4 h period under visible light irradiation. This study provides molecular insights into the rational control of charge transfer pathways for high-efficiency CO2 photoreduction using single-component organic semiconductor catalysts.

Enterococcus faecalis provides protection during scavenging in carrion crow ( Corvus corone).

The gut microbiota significantly influences host physiology and provides essential ecosystem services. While diet can affect the composition of the gut microbiota, the gut microbiota can also help the host adapt to specific dietary habits. The carrion crow ( Corvus corone), an urban facultative scavenger bird, hosts an abundance of pathogens due to its scavenging behavior. Despite this, carrion crows infrequently exhibit illness, a phenomenon related to their unique physiological adaptability. At present, however, the role of the gut microbiota remains incompletely understood. In this study, we performed a comparative analysis using 16S rRNA amplicon sequencing technology to assess colonic content in carrion crows and 16 other bird species with different diets in Beijing, China. Our findings revealed that the dominant gut microbiota in carrion crows was primarily composed of Proteobacteria (75.51%) and Firmicutes (22.37%). Significant differences were observed in the relative abundance of Enterococcus faecalis among groups, highlighting its potential as a biomarker of facultative scavenging behavior in carrion crows. Subsequently, E. faecalis isolated from carrion crows was transplanted into model mice to explore the protective effects of this bacterial community against Salmonella enterica infection. Results showed that E. faecalis down-regulated the expression of pro-inflammatory cytokines tumor necrosis factor alpha (TNF-α), interferon gamma (IFN-γ), and interleukin 6 (IL-6), prevented S. enterica colonization, and regulated the composition of gut microbiota in mice, thereby modulating the host's immune regulatory capacity. Therefore, E. faecalis exerts immunoregulatory and anti-pathogenic functions in carrion crows engaged in scavenging behavior, offering a representative case of how the gut microbiota contributes to the protection of hosts with specialized diets.

Lower extremity peripherally inserted central catheter placement ectopic to the ascending lumbar vein: A case report.

BACKGROUND: Peripherally inserted central catheters (PICCs) are an essential infusion route for oncology patients receiving intravenous treatments, but lower extremity venipuncture is the preferred technique for patients with superior vena cava syndrome (SVCS). We report the case of a patient with a lower extremity PICC ectopic to the ascending lumbar vein, to indicate and verify PICC catheterisation in the lower extremity is safe and feasible. And hope to provide different perspectives for clinical PICC venipuncture to get the attention of peers. CASE SUMMARY: On 24 August 2022, a 58-year-old male was admitted to our department due to an intermittent cough persisting for over a month, which worsened 10 d prior. Imaging and laboratory investigations suggested the patient with pulmonary malignancy and SVCS. Chemotherapy was not an absolute contraindication in this patient. Lower extremity venipuncture is the preferred technique because administering upper extremity venous transfusion to patients with SVCS can exacerbate oedema in the head, neck, and upper extremities. The patient and his family were informed about the procedure, and informed consent was obtained. After successful puncture and prompt treatment, the patient was discharged, experiencing some relief from symptoms. CONCLUSION: Inferior vena cava catheterisation is rare and important for cancer patients with SVCS, particularly in complex situations involving ectopic placement.

Engineering surface framework TiO6 single sites for unprecedented deep oxidative desulfurization.

Catalytic oxidative desulfurization (ODS) using titanium silicate catalysts has emerged as an efficient technique for the complete removal of organosulfur compounds from automotive fuels. However, the precise control of highly accessible and stable-framework Ti active sites remains highly challenging. Here we reveal for the first time by using density functional theory calculations that framework hexa-coordinated Ti (TiO6) species of mesoporous titanium silicates are the most active sites for ODS and lead to a lower-energy pathway of ODS. A novel method to achieve highly accessible and homogeneously distributed framework TiO6 active single sites at the mesoporous surface has been developed. Such surface framework TiO6 species exhibit an exceptional ODS performance. A removal of 920 ppm of benzothiophene is achieved at 60°C in 60 min, which is 1.67 times that of the best catalyst reported so far. For bulky molecules such as 4,6-dimethyldibenzothiophene (DMDBT), it takes only 3 min to remove 500 ppm of DMDBT at 60°C with our catalyst, which is five times faster than that with the current best catalyst. Such a catalyst can be easily upscaled and could be used for concrete industrial application in the ODS of bulky organosulfur compounds with minimized energy consumption and high reaction efficiency.

Association of sleep timing with all-cause and cardiovascular mortality: the Sleep Heart Health Study and the Osteoporotic Fractures in Men Study.

STUDY OBJECTIVES: Previous studies have highlighted the importance of sleep patterns for human health. This study aimed to investigate the association of sleep timing with all-cause and cardiovascular disease mortality. METHODS: Participants were screened from two cohort studies: the Sleep Heart Health Study (SHHS; n = 4,824) and the Osteoporotic Fractures in Men Study (n = 2,658). Sleep timing, including bedtime and wake-up time, was obtained from sleep habit questionnaires at baseline. The sleep midpoint was defined as the halfway point between the bedtime and wake-up time. Restricted cubic splines and Cox proportional hazards regression analyses were used to examine the association between sleep timing and mortality. RESULTS: We observed a U-shaped association between bedtime and all-cause mortality in both the SHHS and Osteoporotic Fractures in Men Study groups. Specifically, bedtime at 11:00 pm and waking up at 7:00 am was the nadir for all-cause and cardiovascular disease mortality risks. Individuals with late bedtime (> 12:00 am) had an increased risk of all-cause mortality in SHHS (hazard ratio 1.53, 95% confidence interval 1.28-1.84) and Osteoporotic Fractures in Men Study (hazard ratio 1.27, 95% confidence interval 1.01-1.58). In the SHHS, late wake-up time (> 8:00 am) was associated with increased all-cause mortality (hazard ratio 1.39, 95% confidence interval 1.13-1.72). No significant association was found between wake-up time and cardiovascular disease mortality. Delaying sleep midpoint (> 4:00 am) was also significantly associated with all-cause mortality in the SHHS and Osteoporotic Fractures in Men Study. CONCLUSIONS: Sleep timing is associated with all-cause and cardiovascular disease mortality. Our findings highlight the importance of appropriate sleep timing in reducing mortality risk. CITATION: Ma M, Fan Y, Peng Y, et al. Association of sleep timing with all-cause and cardiovascular mortality: the Sleep Heart Health Study and the Osteoporotic Fractures in Men Study. J Clin Sleep Med. 2024;20(4):545-553.

The effects of anti-TNF-α biologics on insulin resistance and insulin sensitivity in patients with rheumatoid arthritis: An update systematic review and meta-analysis.

BACKGROUND AND AIM: Increasing evidence demonstrates a link between the chronic inflammatory state in patients with rheumatoid arthritis (RA) and the development of insulin resistance. It is thought that anti-TNF-α biologic therapy may improve insulin sensitivity and ameliorate insulin resistance by the downregulation of inflammatory cytokines, however, pre-clinical and clinical studies have yielded conflicting results. A meta-analysis on this topic is necessary to summarize current evidence and generate hypotheses for future research. METHODS: Literature search was performed in four databases, namely PubMed, EMBASE, Scopus, and The Cochrane Library, from inception till April 9, 2023, querying studies reporting peripheral insulin resistance with and without anti-TNF-α use in patients with RA. Peripheral insulin resistance or sensitivity was quantified by the Homeostasis Model Assessment of Insulin Resistance (HOMA) index or the Quantitative Insulin Sensitivity Check Index (QUICKI) respectively. The difference in insulin resistance or sensitivity between the treatment and control group was calculated using standardized mean difference (SMD) for the purposes of the meta-analysis. RESULTS: Twelve articles were reviewed, with 10 longitudinal studies with a total of 297 patients included in the meta-analysis. The pooled standardized mean difference (SMD) from baseline HOMA was -0.82 (95% CI: -1.38 to -0.25) suggesting significant beneficial effects of anti-TNF-α therapy on insulin resistance. CONCLUSION: Current evidence supports the significant clinical efficacy of anti-TNF-α biologics in alleviating insulin resistance and improving insulin sensitivity in patients with active RA.

Optimizing early neurological deterioration prediction in acute ischemic stroke patients following intravenous thrombolysis: a LASSO regression model approach.

Background: Acute ischemic stroke (AIS) remains a leading cause of disability and mortality globally among adults. Despite Intravenous Thrombolysis (IVT) with recombinant tissue plasminogen activator (rt-PA) emerging as the standard treatment for AIS, approximately 6-40% of patients undergoing IVT experience Early Neurological Deterioration (END), significantly impacting treatment efficacy and patient prognosis. Objective: This study aimed to develop and validate a predictive model for END in AIS patients post rt-PA administration using the Least Absolute Shrinkage and Selection Operator (LASSO) regression approach. Methods: In this retrospective cohort study, data from 531 AIS patients treated with intravenous alteplase across two hospitals were analyzed. LASSO regression was employed to identify significant predictors of END, leading to the construction of a multivariate predictive model. Results: Six key predictors significantly associated with END were identified through LASSO regression analysis: previous stroke history, Body Mass Index (BMI), age, Onset to Treatment Time (OTT), lymphocyte count, and glucose levels. A predictive nomogram incorporating these factors was developed, effectively estimating the probability of END post-IVT. The model demonstrated robust predictive performance, with an Area Under the Curve (AUC) of 0.867 in the training set and 0.880 in the validation set. Conclusion: The LASSO regression-based predictive model accurately identifies critical risk factors leading to END in AIS patients following IVT. This model facilitates timely identification of high-risk patients by clinicians, enabling more personalized treatment strategies and optimizing patient management and outcomes.

Genotype of dengue virus serotype 1 in relation to severe dengue in Guangzhou, China.

Guangzhou has been the city most affected by the dengue virus (DENV) in China, with a predominance of DENV serotype 1 (DENV-1). Viral factors such as dengue serotype and genotype are associated with severe dengue (SD). However, none of the studies have investigated the relationship between DENV-1 genotypes and SD. To understand the association between DENV-1 genotypes and SD, the clinical manifestations of patients infected with different genotypes were investigated. A total of 122 patients with confirmed DENV-1 genotype infection were recruited for this study. The clinical manifestations, laboratory tests, and levels of inflammatory mediator factors were statistically analyzed to investigate the characteristics of clinical manifestations and immune response on the DENV-1 genotype. In the case of DENV-1 infection, the incidence of SD with genotype V infection was significantly higher than that with genotype I infection. Meanwhile, patients infected with genotype V were more common in ostealgia and bleeding significantly. In addition, levels of inflammatory mediator factors including IFN-γ, TNF-α, IL-10, and soluble vascular cell adhesion molecule 1 were higher in patients with SD infected with genotype V. Meanwhile, the concentrations of regulated upon activation normal T-cell expressed and secreted and growth-related gene alpha were lower in patients with SD infected with genotype V. The higher incidence of SD in patients infected with DENV-1 genotype V may be attributed to elevated cytokines and adhesion molecules, along with decreased chemokines.

Amylopectin chain length distributions and amylose content are determinants of viscoelasticity and digestibility differences in mung bean starch and proso millet starch.

This study aimed to reveal the underlying mechanisms of the differences in viscoelasticity and digestibility between mung bean starch (MBS) and proso millet starch (PMS) from the viewpoint of starch fine molecular structure. The contents of amylopectin B2 chains (14.94-15.09 %), amylopectin B3 chains (14.48-15.07 %) and amylose long chains (183.55-198.84) in MBS were significantly higher than PMS (10.45-10.76 %, 12.48-14.07 % and 70.59-88.03, respectively). MBS with higher amylose content (AC, 28.45-31.80 %) not only exhibited a lower weight-average molar mass (91,750.65-128,120.44 kDa) and R1047/1022 (1.1520-1.1904), but also was significantly lower than PMS in relative crystallinity (15.22-23.18 %, p < 0.05). MBS displayed a higher storage modulus (G') and loss modulus (G'') than PMS. Although only MBS-1 showed two distinct and discontinuous phases, MBS exhibited a higher resistant starch (RS) content than PMS (31.63-39.23 %), with MBS-3 having the highest RS content (56.15 %). Correlation analysis suggested that the amylopectin chain length distributions and AC played an important role in affecting the crystal structure, viscoelastic properties and in vitro starch digestibility of MBS and PMS. These results will provide a theoretical and scientific basis for the development of starch science and industrial production of low glycemic index starchy food.

Evaluation of the inhibitory effects of antigout drugs on human carboxylesterases in vitro.

Gout is an immune-metabolic disease that frequently coexists with multiple comorbidities such as chronic kidney disease, cardiovascular disease and metabolic syndrome, therefore, it is often treated in combination with these complications. The present study aimed to evaluate the inhibitory effect of antigout drugs (allopurinol, febuxostat, topiroxostat, benzbromarone, lesinurad and probenecid) on the activity of the crucial phase I drug-metabolizing enzymes, carboxylesterases (CESs). 2-(2-benzoyl-3-methoxyphenyl) benzothiazole (BMBT) and fluorescein diacetate (FD) were utilized as the probe reactions to determine the activity of CES1 and CES2, respectively, through in vitro culturing with human liver microsomes. Benzbromarone and lesinurad exhibited strong inhibition towards CESs with Ki values of 2.16 and 5.15 µM for benzbromarone towards CES1 and CES2, respectively, and 2.94 µM for lesinurad towards CES2. In vitro-in vivo extrapolation (IVIVE) indicated that benzbromarone and lesinurad might disturb the metabolic hydrolysis of clinical drugs in vivo by inhibiting CESs. In silico docking showed that hydrogen bonds and hydrophobic interactions contributed to the intermolecular interactions of antigout drugs on CESs. Therefore, vigilant monitoring of potential drug-drug interactions (DDIs) is imperative when co-administering antigout drugs in clinical practice.

Systematic Optimization of Universal Real-Time Hypersensitive Fast Detection Method for HBsAg in Serum Based on SERS.

Hepatitis B virus (HBV) is a major cause of liver cirrhosis and hepatocellular carcinoma, with HBV surface antigen (HBsAg) being a crucial marker in the clinical detection of HBV. Due to the significant harm and ease of transmission associated with HBV, HBsAg testing has become an essential part of preoperative assessments, particularly for emergency surgeries where healthcare professionals face exposure risks. Therefore, a timely and accurate detection method for HBsAg is urgently needed. In this study, a surface-enhanced Raman scattering (SERS) sensor with a sandwich structure was developed for HBsAg detection. Leveraging the ultrasensitive and rapid detection capabilities of SERS, this sensor enables quick detection results, significantly reducing waiting times. By systematically optimizing critical factors in the detection process, such as the composition and concentration of the incubation solution as well as the modification conditions and amount of probe particles, the sensitivity of the SERS immune assay system was improved. Ultimately, the sensor achieved a sensitivity of 0.00576 IU/mL within 12 min, surpassing the clinical requirement of 0.05 IU/mL by an order of magnitude. In clinical serum assay validation, the issue of false positives was effectively addressed by adding a blocker. The final sensor demonstrated 100% specificity and sensitivity at the threshold of 0.05 IU/mL. Therefore, this study not only designed an ultrasensitive SERS sensor for detecting HBsAg in actual clinical serum samples but also provided theoretical support for similar systems, filling the knowledge gap in existing literature.

New Phenol Derivatives from the Haima Cold Seep-Derived Fungus Aspergillus subversicolor CYH-17.

Seven new phenol derivatives, subversins A-E (1-5), subversic acid A (6) and epi-wortmannine G (7); one new natural product, 4-hydroxy-7-methoxyphthalide (8); and five known compounds (9-13) were isolated from the fungus Aspergillus subversicolor CYH-17 collected from the Haima cold seep. The structures and absolute configurations of these compounds were determined via NMR, MS, optical rotation, electronic circular dichroism (ECD) calculation, X-ray diffraction analysis and comparison with the literature. Compounds 2 and 5 were two pairs of enantiomers. All compounds were tested for their α-glucosidase and acetylcholinesterase (AChE) inhibitory activity, antioxidant activity and antibacterial activity, but no obvious activity was observed among these studied compounds.