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Rheumatoid arthritis (RA) is a systemic, chronic autoimmune disease. Many studies have shown that microorganisms may be an important pathological factor leading to the onset of RA. Some infectious or non-infectious pathogenic microorganisms and their metabolites may be the initiating factors of the early onset of RA. The aim of this study was to alleviate RA by regulating the imbalance of the gut microbiota in the early stage of RA using mixed bacterial strains. The mixed strains of Lactobacillus acidophilus (BD18, NCFM, BD1802, BD3545, BD5032) significantly reduced the clinical score and swelling thickness of the paws of collagen-induced arthritis (CIA) rats. The expression of TNF-α and MMP-13 proteins in the joints of CIA rats was also inhibited. The levels of specific antibodies (anti-CII IgG, anti-CII IgG1, anti-CII IgG2a, and anti-CII IgG2b) and inflammatory factor IL-6 in the serum of CIA rats were also significantly reduced. The relative abundance of Lactobacillus , Clostridia _UCG-014, Ruminococcus , Candidatus _ Saccharimonas , Romboutsia , Turicibacter , and Clostridium _ sensu _ stricto _1 in the gut microbiota of CIA rats receiving oral administration of the mixed strains of L. acidophilus was significantly reduced, bringing their microbiota closer to that of healthy rats. Moreover, the levels of intestinal metabolites of short chain fatty acids in CIA rats, acetic acid and butyric acid, were significantly increased. The mixed strains of L. acidophilus could recover the relative abundance of Ligilactobacillus , Clostridia _UCG-014_unclassified, Ruminococcus , Candidatus_Saccharimonas , Romboutsia and Turicibacter , affecting purine metabolism, transcription factors and alanine metabolism, and reducing the levels of specific antibodies and inflammatory factors in the blood, finally slowing the development of experimental arthritis induced by CII, which exerts the protective effect of probiotics. Mixed L. acidophilus strains are more effective than a single strain, and the effect is not the result of a single strain, but of a combination of strains.

Lactiplantibacillus plantarum NUC08, a novel probiotic strain, has demonstrated potential for synergistic fermentation with starter cultures. This study investigates its functional properties in fermented milk and examines how mulberry fruit extract (MFE), rich in bioactive compounds, may influence its fermentation performance. MFE significantly boosted LAB growth, improved texture and rheological properties, and enhanced antioxidant capacity in the probiotic yogurt. GC-MS analysis revealed that MFE enriched the flavor profile by increasing key flavor-related metabolites, contributing to superior sensory qualities. Furthermore, the combination of L. plantarum NUC08 and MFE led to distinct shifts in metabolic pathways, as shown by LC-MS analysis, amplifying the regulatory effects on antioxidant activity. These findings demonstrate the synergy between MFE and L. plantarum NUC08, where MFE enhances the growth and functionality of L. plantarum NUC08, improving the yogurt's physicochemical properties, antioxidant capacity, and flavor, with potential for functional dairy product development., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Purpose: To investigate the efficacy of high-dose vitamin D supplementation (VDS) plus standard urotherapy (SU) in managing pediatric overactive bladder dry (OAB-dry), specifically in children with (1) vitamin D levels between 20 and 35 ng/mL and (2) heightened baseline symptom severity., Methods: In this secondary analysis of a randomized controlled trial, eligible children (n = 303) were assigned to 8 weeks of VDS + SU group, solifenacin (SOL) + SU group, or SU alone group. The primary outcome was voiding frequency; secondary outcomes included urgency, nocturia, quality of life (QoL), pediatric lower urinary tract symptoms scores, and patient satisfaction., Results: Among 303 participants, 197 (65%) had vitamin D levels between 20 and 35 ng/mL, and 119 (39%) exhibited heightened baseline symptom severity. In both subgroups, VDS + SU resulted in significantly greater improvements in voiding frequency compared to SOL + SU and SU alone. In the vitamin D subgroup (20-35 ng/mL), the median difference in voids/day between VDS + SU and SOL + SU was 2.0 (95% CI, 1.0 to 3.0; P = 0.003) and 3.2 compared to SU alone (P < 0.001). In the heightened symptom subgroup, the median difference was 3.0 (95% CI, 2.0 to 4.0; P < 0.001) vs. SOL + SU and 5.0 (95% CI, 4.0 to 6.0; P < 0.001) vs. SU alone. The VDS + SU group generally outperformed the other groups in various secondary outcome measures., Conclusion: High-dose VDS plus SU has significant therapeutic benefit in children with OAB-dry in those with vitamin D levels between 20 and 35 ng/mL and with more severe symptoms, compared to SOL + SU or SU alone., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

A simple one-pot green synthesis method was used to prepare urease-inorganic hybrid nanoflowers (UE-HNFs), which had a high surface-to-volume ratio to improve enzyme catalytic efficiency and make urease reusable. A portable colorimetric microliter tube based on urease-inorganic hybrid nanoflowers (UE-HNFs-PCMT), as an urea colorimetric biosensor, was developed for determining urea concentration in milk. The combination of urea colorimetric biosensor and a smartphone is used for capturing the colour change of milk after reaction. There was a good linear relationship between colour intensity of the image (Δ intensity) and urea concentration (43-600 mg L -1 ), with a detection limit of 12.81 mg L -1 . UE-HNFs-PCMT has the advantages of no need for complex equipment, easy operation, reusability, low detection cost, good portability, and environmental friendliness and can achieve urea detection in milk., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

To elucidate the thermal transport mechanisms at interfaces in micro- and nanoscale electronic devices, real-time monitoring of temperature variations at the microscopic and nanoscopic levels is crucial. Micro-nano fiber Bragg grating (FBG) sensors have been demonstrated as effective in-situ optical temperature probes for measuring local temperatures. Time-stretch dispersion Fourier transform (TS-DFT) that enables fast, continuous, single-shot measurements in optical sensing has been integrated with a micro-nano FBG probe (FBG P ) for local temperature sensing. However, its temperature sensitivity and interrogation resolution are limited by the detection sensitivity. In this paper, we propose a hybrid amplified dispersion Fourier transform (ADFT) method to achieve ultrafast interrogation of FBG P 's weak signal. Thanks to the combined effect of TS-DFT and hybrid optical amplification, the reflection signal of the FBG P is amplified, and the wavelength shift of the FBG P sensor is converted to a temporal spacing change between two dispersed pulses through dispersion-induced wavelength-to-time mapping. The proposed method uses a homemade dissipative soliton mode-locked laser as the light source. The hybrid optical amplification technique comprises a L-band erbium-doped fiber amplifier and a distributed Raman amplifier. Their noise figure and net gain for the FBG P are 4.81 dB and 15.93 dB, respectively. In addition, the temperature calibration experiments show that a sampling rate of 51.43 MHz and the maximum temperature measurement error of 1.98°C are achieved within the temperature range of 20.3°C to 97°C. The stability of the net gain provided by the hybrid ADFT system is demonstrated by the coefficient of variation, which ranges from 2.22% to 2.95% in the peak voltage signal of the FBG P . This approach applies to scenarios requiring the handling of weak optical signals, particularly in temperature measurement at the micro-nano scale.

Background: Rab25 is a member of the Rab family, functioning as a regulatory molecule in intracellular transport. Although its involvement in cellular functions and disease development is well-established, its precise roles in male reproductive physiology remain elusive., Methods: To explore the specific roles of Rab25 in testicular development and spermatogenesis, we established the Rab25 -/- mouse model and Rab25 knockdown germ cell line (GC-2). We compared the fertility, sperm analysis, and testicular tissues between Rab25 -/- and wild-type male mice. To delve deeper into potential mechanisms, we employed immunohistochemistry, TUNEL assay, Western Blotting, CCK-8 assay, etc. to evaluate cell proliferation and apoptosis in testicular tissues and GC-2 cells., Results: Our findings indicated that Rab25 was expressed in germ cells and Leydig cells in the testes. Although the weight of Rab25 -/- mice testes exhibited no significant changes, fertility was compromised, with a decrease in sperm quantity and reduced motility. HE staining revealed a disorganized arrangement of germ cells and vacuolization. Additionally, chromatin marginalization and nuclear pyknosis were observed in the Rab25 -/- mice. In both Rab25 -/- mice testes and Rab25 knockdown GC-2 cells, we found that germ cell proliferation was reduced, while apoptosis was increased., Conclusions: In conclusion, our study proposes that Rab25 plays a vital role in spermatogenesis by regulating the proliferation and apoptosis of germ cells., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

MAFB is essential for regulating male-type urethral differentiation, and especially, its variation can contribute to hypospadias in mice. However, the potential mechanism is still unclear. Here we observed that the basic leucine zipper (bZIP) transcription factor MAFB and CCAAT/enhancer-binding protein alpha (CEBPA) could promote human urothelium SV-HUC-1 growth. Moreover, MAFB and CEBPA expression were reduced in the prepuce tissues of hypospadias patients. Based on transcriptome sequencing analysis and Western blot, MAFB knockdown was found to suppress CEBPA protein expression and repress Wnt/β-catenin signaling in urothelium cells. Meanwhile, we observed blocked cell-cycle progression from the G1 to the S phase, inhibited cell proliferation, and activated apoptosis. Furthermore, MAFB could facilitate CEBPA transcription and regulate the proliferation of urothelium. The above results indicated that MAFB-mediated inhibition of urothelial SV-HUC-1 growth resulted from inhibiting the Wnt/β-catenin signaling pathway by down-regulating CEBPA. Our findings provide new insight into the understanding of genes associated with hypospadias and the pathogenic mechanism of this disorder., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co., Ltd.)

Context: Milk has nutrient-rich but thermal sensitive matrix that undergoes varying degrees of Maillard reaction (MR) at heating conditions. The MR mainly occurs between lysine residues (Lys) and lactose composed of glucose (Glc) and galactose (Gal), which are abundantly sourced from dairy products. In the present study, the MRs of Glc and Gal with Lys at the initial and intermediate stages have been investigated theoretically using density functional theory (DFT) to simulate the gaseous and aqueous phases. Reaction mechanisms have been proposed, and relative energy changes of different steps were calculated according to the total mass balance. The calculations reveal that both N α - and N ε -amine groups of Lys can react with the carbonyl functional group of Glc and Gal with the similar potential energy profiles, and Gal is more reactive than Glc. However, the barrier in N ε -channel is lower than in N α -channel, indicating a faster reaction rate through the former channel compared with the latter. The 5-hydroxymethyl-2-furfural (HMF) and derivative are formed under 3-deoxysone route in the intermediate stage. The calculation results are helpful for proposing a reasonable MR mechanism and suggesting possible control methods of the MRs., Methods: In this study, different levels of DFT calculations have been conducted to investigate the mechanisms and favorability of generating MR products in Glc-Lys and Gal-Lys models at initial and intermediate stages in the gaseous and aqueous conditions. In order to elucidate the molecular models from the perspectives of chemistry and geometry, DFT calculations were performed by the mean of B3LYP functional at basis sets of 6-311 +  + G (d, p) and 6-311 +  + G (2df, 2p) with optional solvation settings. To examine the solvation effect, the study further constructed models with solvent H 2 O and calculated in wB97XD functional with 6-31 + G (d) basis set. All computations were carried out Gaussian 09 suite of quantum chemistry software., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Metabolic syndrome (MetS) is a global epidemic complex and will cause serious metabolic comorbidities without treatment. A prevention strategy for MetS development has been proposed to modulate gut microbiota by probiotic administration to improve intestinal dysbiosis and benefit the host. Lacticaseibacillus casei LC2W has exhibited positive effects in preventing colitis and anti-hypertension in vivo. However, the effect of L. casei LC2W on subjects at high risk of MetS is unknown. Here, a randomized, double-blinded, placebo-controlled study was conducted on 60 subjects with high risk of MetS, and the hypoglycemic and hypolipidemic activity and possible pathways of L. casei LC2W were inferred from the correlation analysis with gut microbiome composition, function, and clinical phenotypic indicators. The results showed that oral administration of L. casei LC2W could exert significant benefits on weight control, glucose and lipid metabolism, inflammatory and oxidative stress parameters, and SCFA production, as well as modulate the composition of gut microbiota. The relative abundance of Lacticaseibacillus, Bifidobacterium, Dorea, and Blautia was enriched, and their interaction with other gut microbes was strengthened by oral administration of L. casei LC2W, which was beneficial in ameliorating gut inflammation, promoting glucose and lipids degradation pathways, thus alleviated MetS. The present study confirmed the prevention effects of L. casei LC2W towards MetS from aspects of clinical outcomes and microflora modulation, providing an alternative strategy for people at high risk of MetS.Trial registration: The study was proactively registered in ClinicalTrial.gov with the registration number of ChiCTR2000031833 on April 09, 2020., (© 2024. The Author(s).)

A fluorescent immunosorbent assay incorporating signal amplification away from the surface of spherical nucleic acid (SNA) was developed for the detection of chloramphenicol (CAP). Through the conjugation of antibodies and poly-adenine (polyA) DNA onto the surface of gold nanoparticles (AuNPs), the fabrication of the nano-immunoprobe was achieved in a more straightforward and cost-effective manner. Moreover, a strategy utilizing the hybridization chain reaction (HCR) in the amplification step was devised, with particular attention given to the enzyme inhibition associated with SNA. The results demonstrated good performance on CAP detection with a linear range of 0.01-5 ng/L with a detection limit of 0.005 ng/L. The significance of this work mainly lies in the polyA-SNA-based immunoprobe and the thoughtful design to prevent enzyme inhibition., (© 2024. The Author(s), under exclusive licence to The Japan Society for Analytical Chemistry.)

Background: Organophosphorus compounds, widely used in agriculture and industry, pose a serious threat to human health due to their acute neurotoxicity. Although traditional interventions for organophosphate poisoning are effective, they often come with significant side effects., Objective: This paper aims to evaluate the potential of enzymes within biological organisms as organophosphorus bioclearing agents. It analyses the technical challenges in current enzyme research, such as substrate specificity, stereoselectivity, and immunogenicity, while exploring recent advancements in the field., Methods: A comprehensive review of literature related to detoxifying enzymes or proteins was conducted. Existing studies on organophosphorus bioclearing agents were summarised, elucidating the biological detoxification mechanisms, with a particular focus on advancements in protein engineering and novel delivery methods., Results: Current bioclearing agents can be categorised into stoichiometric and catalytic bioclearing agents, both of which have shown some success in preventing organophosphate poisoning. Technological advancements have significantly improved various properties of bioclearing agents, yet challenges remain, particularly in substrate specificity, stereoselectivity, and immunogenicity. Future research will focus on expanding the substrate spectrum, enhancing catalytic efficiency, prolonging in vivo half-life, and developing convenient administration methods., Conclusion: With the progression of clinical trials, bioclearing agents are expected to become widely used as a new generation of therapeutic organophosphate detoxifiers., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

In this study, Pediococcus pentosaceus C-2-1 and C23221 contained genes encoding penocin and pediocin PA-1, mined by antiSMASH. The penocin structural gene pedA from Pediococcus pentosaceus C-2-1 was successfully expressed in Escherichia coli BL21. The presence of a 6.5 kDa recombinant penocin was confirmed by Tricine-SDS-PAGE, and the specific activity increased by 1.54-fold. The bacteriocins produced by Pediococcus pentosaceus C23221 were purified using acetic ether extraction, Sepharose Fast Flow, Sephadex G-25 gel chromatography, and reversed-phase high-performance liquid chromatography (RP-HPLC); the amino acid sequence of this bacteriocin was identical to pediocin PA-1 by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS), which confirmed the expression of pediocin PA-1 gene; and the specific activity increased by 24.39-fold. The heterologous expression and purification of bacteriocins have proved the expression of pediocin-like produced by Pediococcus pentosaceus. This provides a theoretical basis for the subsequent development and application of pediocin-like., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

This study aims to identify lactic acid bacteria (LAB) isolates possessing physiological characteristics suitable for use as probiotics in yogurt fermentation. Following acid and bile salt tolerance tests, Lactiplantibacillus plantarum (NUC08 and NUC101), Lacticaseibacillus rhamnosus (NUC55 and NUC201), and Lacticaseibacillus paracasei (NUC159, NUC216, and NUC351) were shortlisted based on intraspecies distribution for further evaluation. Their physiological probiotic properties, including transit tolerance, adhesion, autoaggregation, surface hydrophobicity, biofilm formation, and antibacterial activity, were assessed. Principal component analysis indicated that Lactiplantibacillus plantarum NUC08 was the preferred choice among the evaluated strains. Subsequent investigations revealed that co-culturing Lactiplantibacillus plantarum NUC08 with 2 yogurt starter strains resulted in a cooperative and synergistic effect, enhancing the growth of mixed strains and increasing their tolerance to simulated gastric and intestinal conditions. Additionally, when Vibrio harveyi bioluminescent reporter strain was used, the 3 cocultured strains cooperated to induce the activity of a quorum sensing (QS) molecule autoinducer-2 (AI-2), hinting a potential connection between phenotypic traits and QS in the cocultured strains. Importantly, LAB viable counts were significantly higher in yogurt co-fermented with Lactiplantibacillus plantarum NUC08, consistently throughout the storage period. In conclusion, the study demonstrates that the probiotic strain Lactiplantibacillus plantarum NUC08 can be employed in synergy with yogurt starter strains, affirming its potential for use in the development of functional fermented dairy products., (The Authors. Published by Elsevier Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

Intestinal barrier hyperpermeability, which is characterised by impaired tight junction proteins, is associated with a variety of gastrointestinal and systemic diseases. Therefore, maintaining intestinal barrier integrity is considered one of the effective strategies to reduce the risk of such disorders. This study aims to investigate the potential benefits of two probiotic strains ( Lactiplantibacillus plantarum ST-III and Lacticaseibacillus rhamnosus KF7) on intestinal barrier function by using a physiologically relevant in vitro model of the intestinal epithelium. Our results demonstrate that both strains increased transepithelial electrical resistance, a measure of intestinal barrier integrity. Immunolocalisation studies indicated that this improvement in barrier function was not due to changes in the co-localisation of the tight junction (TJ) proteins ZO-1 and occludin. However, we observed several modifications in TJ-related genes in response to the probiotics, including the upregulation of transmembrane and cytosolic TJ proteins, as well as TJ signalling proteins. Gene expression modulation was strain- and time-dependent, with a greater number of differentially expressed genes and higher fold-change being observed in the L. plantarum ST-III group and at the latter timepoint. Further studies to investigate how the observed gene expression changes can lead to enhanced barrier function will aid in the development of probiotic foods to help improve intestinal barrier function.

An exopolysaccharide, designated F1, was purified from the fermented milk by Lacticaseibacillus rhamnosus strain B6 (CGMCC No. 13310). F1, with the weight average molecular weight of 1.577 × 10 6  Da, is consisted of rhamnose, glucose and galactose in a molar ratio of 3.7:1.5: 1. The backbone included 1,3-linked Rha, 1,2,3-linked Rha, 1,2-linked Glc and 1,3-linked Glc residues, with the branching point located at O2 position of 1,2,3-linked Rha residue, and the branch chain composed of terminal linked galactose residue with a pyruvate substituent. F1 could significantly stimulate the phagocytic activity and TNF-α expression in RAW 264.7 macrophages in a dose-dependent manner, and the release of NO at 200 μg/mL as well. F1 at 200 μg/mL could stimulate the expression of the pro-inflammatory cytokine encoding genes including TNF-α and iNOS, but with a negligible upregulating effect on the mRNA expression of IL-10. F1 could up-regulate the expression of NF-κBp65 and skew macrophage polarization towards M1 phenotype. These results suggest F1 elicit an immunomodulatory effect through the NF-κB signaling pathway., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

In eukaryotes, methylation of histone H3 at lysine 4 (H3K4me) catalyzed by the complex of proteins associated with Set1 (COMPASS) is crucial for the transcriptional regulation of genes and the development of organisms. In Monascus, the functions of COMPASS in establishing H3K4me remain unclear. This study first identified the conserved COMPASS core subunits MpSet1 and MpSwd3 in Monascus purpureus and confirmed their roles in establishing H3K4me2/3. Loss of MpSet1 and MpSwd3 resulted in slower growth and development and inhibited the formation of cleistothecia, ascospores, and conidia. The loss of these core subunits also decreased the production of extracellular and intracellular Monascus pigments (MPs) by 94.2%, 93.5%, 82.7%, and 82.5%, respectively. In addition, RNA high-throughput sequencing and quantitative real-time polymerase chain reaction (qRT-PCR) showed that the loss of MpSet1 and MpSwd3 altered the expression of 2646 and 2659 genes, respectively, and repressed the transcription of MPs synthesis-related genes. In addition, the ΔMpset1 and ΔMpswd3 strains demonstrated increased sensitivity to cell wall stress with the downregulation of chitin synthase-coding genes. These results indicated that the COMPASS core subunits MpSet1 and MpSwd3 help establish H3K4me2/3 for growth and development, spore formation, and pigment synthesis in Monascus. These core subunits also assist in maintaining cell wall integrity., (© 2024 Wiley‐VCH GmbH.)

This study aimed to explore the association of carbohydrate to fiber ratio (CFR) with metabolic dysfunction-associated fatty liver disease (MAFLD) in adults. In this study, data from the 2 cycles (2017-2018 and 2019-2020) of the NHANES were used. Univariate and multivariate weighted logistic regression analyses were applied to evaluate the association between CFR and MAFLD. Odds ratios (ORs) and 95% confidence levels (CIs) were estimated. Subgroup analysis was further performed in terms of gender, age and comorbidity (diabetes, hypertension). A total of 3180 individuals were included, with 1408 (44.28%) in the non-MAFLD group and 1772 (55.72%) in the MAFLD group. After adjusting different variables, a dietary fiber intake of 11.15-18.40 g was associated with significantly lower odds of MAFLD compared with a fiber intake < 11.15 g (OR = 0.71, 95% CI 0.54-0.93). In contrast to a dietary CFR < 12.58, a CFR > 19.91 was associated with significantly higher odds of MAFLD (OR = 1.57, 95% CI 1.09-2.27). Compared with females with a dietary CFR < 12.58, those with a CFR > 19.91 had significantly increased odds of MAFLD (OR = 1.87, 95% CI 1.29-2.73). Among individuals aged < 65 years, a dietary CFR > 19.91 was associated with higher odds of MAFLD than a dietary CFR < 12.58 (OR = 1.52, 95% CI 1.02-2.25). For participants without diabetes (OR = 1.79, 95% CI 1.26-2.54) or hypertension (OR = 1.93, 95% CI 1.02-3.65), a dietary CFR > 19.91 was associated with elevated odds of MAFLD than a CFR < 12.58. In summary, a higher CFR was associated with significantly greater odds of MAFLD, indicating the negative association between carbohydrate quality and MAFLD. The research would be conducive to metabolic dysfunction-associated fatty liver disease treatment., (© 2024. The Author(s).)

Background: Hypospadias is a common congenital abnormality of the penile. Abnormal regulation of critical genes involved in urethral development leads to hypospadias. We used the Rab25 -/- mice and foreskin fibroblasts transfected with lentivirus in vitro and in vivo to investigate the role of Rab25 in hypospadias., Methods: The expression levels of various molecules in tissue samples and foreskin fibroblasts were confirmed using molecular biology methods (western blotting, PCR, immunohistochemistry, etc.). A scanning electron microscope (SEM) was used to visualize the external morphology of genital tubercles (GTs) of gestation day (GD) 18.5 male wild-type (WT) and Rab25 -/- mice., Results: An expanded distal cleft and V-shaped urethral opening were observed in GD 18.5 Rab25 -/- mice. We demonstrated that Rab25 mediated hypospadias through the β1 integrin/EGFR pathway. In addition, silencing Rab25 inhibited cell proliferation and migration and promoted apoptosis in the foreskin fibroblasts; Ki-67- and TUNEL-positive cells were mainly concentrated near the urethral seam., Conclusion: These findings suggest that Rab25 plays an essential role in hypospadias by activation of β1 integrin/EGFR pathway, and Rab25 is a critical mediator of urethral seam formation in GD18.5 male fetal mice., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Rheumatoid arthritis (RA) is a systemic autoimmune disorder characterized by swollen joints, discomfort, stiffness, osteoporosis, and reduced functionality. Genetics, smoking, dust inhalation, high BMI, and hormonal and gut microbiota dysbiosis are all likely causes of the onset or development of RA, but the underlying mechanism remains unknown. Compared to healthy controls, patients with RA have a significantly different composition of gut microbiota. It is well known that the human gut microbiota plays a key role in the initiation, maintenance, and operation of the host immune system. Gut microbiota dysbiosis has local or systematic adverse effects on the host immune system, resulting in host susceptibility to various diseases, including RA. Studies on the intestinal microbiota modulation and immunomodulatory properties of probiotics have been reported, in order to identify their potential possibility in prevention and disease activity control of RA. This review summarized current studies on the role and potential mechanisms of gut microbiota in the development and progression of RA, as well as the preventative and therapeutic effects and potential mechanisms of probiotics on RA. Additionally, we proposed the challenges and difficulties in the application of probiotics in RA, providing the direction for the research and application of probiotics in the prevention of RA., Competing Interests: Authors YY, QH, and ZL were employed by the company Bright Dairy & Food Co., Ltd. The remaining author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Yang, Hong, Zhang and Liu.)

Therapeutic drug monitoring of doxorubicin (DOX) is important to study pharmacokinetics in patients undergoing chemotherapy for reduction of side effects and improve patient survival by rationally controlling the dose of DOX. A fast and ultra-sensitive surface plasmon resonance (SPR) detector without sample pre-handling was developed for DOX monitoring. First, the two-dimensional metal-organic framework was modified on the Au film to enhance SPR, and then, the supramolecular probes with tunable cavity structure were self-assembled at the sensing interface for direct detection of DOX through specific host-guest interactions with a low detection limit of 60.24 pM. The precise monitoring of DOX in serum proved the possibility of clinical application with recoveries in the range 102.86-109.47%. The mechanisms of host-guest interactions between supramolecular and small-molecule drugs were explored in depth through first-principles calculations combined with SPR experiments. The study paves the way for designing facile and sensitive detectors and provides theoretical support and a new methodology for the specific detection of small molecules through calixarene cavity modulation., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Heavy metal pollution has become one of the most important global environmental issues. The human health risk posed by heavy metals encountered through the food chain and occupational and environmental exposure is increasing, resulting in a series of serious diseases. Ingested heavy metals might disturb the function of the gut barrier and cause toxicity to organs or tissues in other sites of the body. Probiotics, including some lactic acid bacteria (LAB), can be used as an alternative strategy to detoxify heavy metals in the host body due to their safety and effectiveness. Exopolysaccharides (EPS) produced by LAB possess varied chemical structures and functional properties and take part in the adsorption of heavy metals via keeping the producing cells vigorous. The main objective of this paper was to summarize the roles of LAB and their EPS in the adsorption and detoxification of heavy metals in the gut. Accumulated evidence has demonstrated that microbial EPS play a pivotal role in heavy metal biosorption. Specifically, EPS-producing LAB have been reported to show superior absorption, tolerance, and efficient abatement of the toxicity of heavy metals in vitro and/or in vivo to non-EPS-producing species. The mechanisms underlying EPS-metal binding are mainly related to the negatively charged acidic groups and unique steric structure on the surface of EPS. However, whether the enriched heavy metals on the bacterial cell surface increase toxicity to local mammal cells or tissues in the intestine and whether they are released during excretion remain to be elucidated., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The metabolite and peptide profiles of fresh cheese fermented by three novel probiotics, Lacticaseibacillus rhamnosus B6, Limosylactobacillus fermentum B44 and Lacticaseibacillus rhamnosus KF7, were investigated using LC-MS/MS-based metabolomics and peptidomics. The multivariate analysis revealed significant differences in metabolite composition between the probiotic fresh cheese and the control sample. The differential metabolites were primarily lipids and lipid-like molecules and organic oxygen compounds, which were associated with fatty acid and carbohydrate-related pathways. Among three probiotics, L. rhamnosus KF7 showed the highest effectiveness in sucrose decomposition. 147 potential bioactive peptides, mainly derived from casein, were identified in probiotic fresh cheese. Furthermore, 112 bioactive peptides were significantly up-regulated in probiotic fresh cheese. Molecular docking analysis indicated that two short peptides (LVYPFPGPIP and YPQRDMPIQ) in the B44 and KF7 groups exhibited low estimated binding energy values (-9.9 and -6.9 kcal/mol) with ACE. These findings provide a theoretical basis for developing novel probiotic-enriched fresh cheese., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Context: Overactive bladder is treated mainly with behavioral and drug therapy, and symptoms of urinary frequency and incontinence are challenging to eliminate. There is thus a continuous unmet need for new drugs with a substitution effect mechanism., Objective: It not known whether vitamin D deficiency can lead to overactive bladder or urinary incontinence or whether vitamin D supplementation alleviates bladder symptoms. This comprehensive systematic review with meta-analysis was conducted to determine whether overactive bladder is associated with vitamin D deficiency., Data Sources: The PubMed and Cochrane Library databases were searched systematically up to July 3, 2022., Data Extraction: Initially, 706 articles were identified in the literature search, of which 13 were included in the systematic review: 4 randomized controlled trials, 3 cohort studies, 3 cross-sectional studies, and 3 case-control studies., Data Analysis: An increased risk of overactive bladder and urinary incontinence was observed with vitamin D deficiency (odds ratio [OR] = 4.46; 95%CI, 1.03-19.33; P = 0.046 and OR = 1.30; 95%CI, 1.01-1.66; P = 0.036, respectively). Vitamin D levels were relatively low in patients with overactive bladder or urinary incontinence (SMD = -0.33; 95%CI, -0.61 to -0.06, P = 0.019). On the basis of existing data, the risk of urinary incontinence was reduced by 66% after vitamin D supplementation (OR = 0.34; 95%CI, 0.18-0.66; P = 0.001). Egger test was conducted to assess publication bias, and the results were tested for robustness using a sensitivity analysis., Conclusions: Vitamin D deficiency increases the risk of overactive bladder and urinary incontinence, and vitamin D supplementation reduces the risk of urinary incontinence. The development of new strategies to prevent or alleviate bladder symptoms is crucial. Vitamin D supplementation may be gaining recognition as an effective strategy for prevention or alleviation of bladder symptoms such as overactive bladder and incontinence., Systematic Review Registration: PROSPERO registration no. CRD42022351443., (© The Author(s) 2023. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Aim: To investigate the antibacterial effects of Corydalis Saxicola bunting total alkaloid (CSBTA) on Porphyromonas gingivalis . Methods: SEM, chemical staining, RT-qPCR and ELISA were used to detect effects of CSBTA on P. gingivalis . Results: CSBTA treatment caused shrinkage and rupture of P. gingivalis morphology, decreased biofilm density and live bacteria in biofilm, as well as reduced mRNA expression of virulence genes hagA , hagB , kgp , rgpA and rgpB of P. gingivalis . Furthermore, NOK cells induced by CSBTA-treated P. gingivalis exhibited lower IL-6 and TNF-α expression levels. Conclusion: CSBTA is able to kill free P. gingivalis , disrupt the biofilm and weaken the pathogenicity of P. gingivalis . It has the potential to be developed as a drug against P. gingivalis infection.

The simultaneous analysis and removal of highly toxic hexavalent chromium (Cr (VI)) in contaminated water via an easy method remain a serious task. Based on the guidance of bibliometric analysis, a thiadiazole ligand-modified zirconium metal-organic framework (Zr-MOF) heralds a new and simple approach to Cr (VI) treatment. The concentration can be determined by fluorescence quenching with a low detection limit of 1.4 μM and a high quenching constant of 6.88 × 10 3 M -1 . For the sensing mechanism, the fluorescence intensity of the Zr-MOF decreased rapidly due to the competition of Cr (VI) with the Zr-MOF for absorption excitation energy and the induction of Zr-MOF aggregation. The analysis system also displayed satisfactory stability and applicability. Apart from sensing application, Zr-MOF can convert Cr (VI) to Cr (III), and the reduction rate constant was 0.004 min -1 under irradiation. Therefore, the bifunctional Zr-MOF provided a potential application method for controlling the pollution caused by Cr (VI) in wastewater.

To investigate the effects of cimifugin on adipogenesis and tumor necrosis factor (TNF-α)-induced insulin resistance (IR) and inflammation in 3T3-L1 adipocytes. 3T3-L1 adipocytes were treated with 3-isobutyl-1-methyl-xanthine, dexamethasone, and insulin or cimifugin and then Oil Red O staining and intracellular triglyceride content detection were performed to assess adipogenesis. Subsequently, after cimifugin treatment, TNF-α was used to induce IR and inflammation. The results showed that cimifugin reduced intracellular lipids accumulation of 3T3-L1 adipocytes. Cimifugin improved IR of 3T3-L1 adipocytes induced by TNF-α, as reflected in decreased adiponectin, GLUT-4, and IRS-1 mRNA and protein expression. Moreover, cimifugin reduced TNF-α-induced pro-inflammatory factors production and phospho-P65 expression, and MAPK pathway activation in the 3T3-L1 adipocytes. These findings suggested that cimifugin might be useful for the prevention and therapy of obesity-related IR and inflammation., Competing Interests: Conflict of interest: The authors state that there are no conflicts of interest to disclose., (© 2023 the author(s), published by De Gruyter.)

Strain BD7642 T was isolated from Chinese pickled potherb mustard ( Brassica juncea Coss.) purchased from a local market in Shanghai, PR China. A polyphasic approach, including 16S rRNA gene sequence, housekeeping gene, average nucleotide identity (ANI), digital DNA-DNA hybridization (dDDH), G+C content and phenotypic analyses, was employed to characterize strain BD7642 T . Cells of the bacterium were short round rods, Gram-stain-positive, non-spore-forming and catalase-negative. The strain grew at 30-45 °C and pH 4.0-8.0. Optimum growth occurred at 35-40 °C and pH 6.0-7.0. The strain exhibited growth with salt (NaCl) concentrations of up to 5 % (w/v). The G+C content of the strain's genomic DNA was 31.37 mol%. The major fatty acids were C 16 : 0 , C 18 : 1  c9 and summed feature 10 (C 18 : 1  c11/t9/t6). 16S rRNA gene sequencing revealed that strain BD7642 T represents a member of the genus Ligilactobacillus and it had high sequence similarity to Ligilactobacillus aviarius NBRC 102162 T (96.73 %), Ligilactobacillus araffinosus LGM 23560 (96.66 %) and Ligilactobacillus salivarius JCM 1231 T (95.82 %). The dDDH values between strain BD7642 T and its phylogenetically related species within the genus Ligilactobacillus ranged from 12.6 to 25.4 %. The ANI values between strain BD7642 T and its closely related taxa were far lower than the threshold (95 %-96 %) used for species differentiation. Results of phylogenetic, physiological and phenotypic characterization confirmed that strain BD7642 T represents a novel species within the genus Ligilactobacillus , for which the name Ligilactobacillus cholophilus sp. nov. is proposed. The type strain is BD7642 T (=CCTCC AB 2022398 T =JCM 36074 T ).

Helicobacter pylori ( H. pylori ) is a gram-negative bacterium exhibiting high pathogenicity. Traditional antibiotic treatments are considered ineffective as the H. pylori resistance has increased. Recently, a quadruple therapy strategy of probiotics and antibiotics to eliminate H. pylori was proposed. Probiotics play a therapeutic role as supplements in this process. The present research screened a probiotic strain ( Lactobacillus crispatus FSCDJY67L3) that co-aggregates strongly with H. pylori . L. crispatus FSCDJY67L3 was demonstrated to significantly reduce H. pylori load ( 14 C breath test) in clinical trials with H. pylori- positive patients. The Gastrointestinal Symptom Rating Scale (GSRS) score decreased, indicating improvement in the gastrointestinal discomfort of patients. Furthermore, L. crispatus FSCDJY67L3 showed no change in the structure of the intestinal flora of patients. Routine blood indices and blood biochemical indices related to liver and kidney function were also not affected in the patients. Therefore, L. crispatus FSCDJY67L3 may be used clinically as a supplement for the treatment of H. pylori ., Clinical Trial Registration: https://www.chictr.org.cn/, Chinese Clinical Trial Registry (ChiCTR2100053710)., Competing Interests: Authors QH, JW, and ZL were employed by the company Bright Dairy & Food Co., Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Hong, Wang, Zhang, Liu and Liu.)

Background: Observational studies have shown an association between major depressive disorder (MDD), anxiety, and prostatitis. However, the causal relationship between MDD, anxiety, and prostatitis remains controversial. Therefore, we aimed to use two-sample Mendelian randomization (MR) to assess the causal effects of MDD and anxiety on prostatitis., Methods: We conducted univariable and multivariable MR analyses using summary statistics from publicly available genome-wide association studies to estimate the causal relationships between MDD, anxiety, and prostatitis risk. In the main MR analysis, the inverse-variance weighted (IVW) method was used, while secondary methods included the weighted median, weighted mode, MR-Egger regression, and MR pleiotropy residual and outlier (MR-PRESSO) tests to detect and correct for the presence of pleiotropy., Results: MDD had 97 independent instrumental variables (IVs) and anxiety had 15 IVs. Univariable MR analysis showed that genetically determined MDD had a detrimental causal effect on prostatitis (IVW: odds ratio [OR] = 1.47, 95% confidence interval [CI] = 1.12-1.92, p = 0.005), while no causal relationship was found between anxiety and prostatitis (IVW: OR = 0.25, 95% CI = 0.02-2.82, p = 0.26). More convincingly, after adjusting for confounding factors such as body mass index, alcohol consumption, and smoking, the genetic liability for MDD remained associated with prostatitis risk, with no strong evidence of anxiety affecting prostatitis incidence., Conclusion: This study supports the notion that MDD has a detrimental effect on prostatitis risk, and strategies focused on addressing MDD may be one of the cornerstones for treating prostatitis. The potential preventive value of treating MDD for prostatitis should be further investigated in future research., (© 2023 Wiley Periodicals LLC.)

Background: Hypospadias, a congenital malformation of the penis, is one of the newborns' most common developmental defects. The incidence of hypospadias is increasing yearly, and its pathogenesis is closely related to genetic susceptibility and environmental exposure to endocrine disruptors. Exploring the hypospadias' key molecular regulatory mechanism is crucial to reducing its incidence., Objective: To examine the differential expression of Rab25 in hypospadias and normal penile tissue and to identify whether it is a candidate gene for exploring the mechanism of hypospadias., Study Design: This study included 18 children aged 1-6 years undergoing hypospadias repair surgery at the Children's Hospital of Chongqing Medical University, and foreskin samples were collected. Children diagnosed with cryptorchidism, intersex status, or endocrine abnormalities were excluded from this study. Another 18 children aged 3-8 years with phimosis were included in the control group. The specimens were used for immunohistochemistry, western blotting, immunofluorescence, and polymerase chain reaction to assess the expression of Rab25., Results: Rab25 protein expression was lower in the hypospadias group than in the control group [ (2.101 ± 0.1845), (0.7506 ± 0.1779), p = 0.0008 < 0.05). The hypospadias group showed decreased expression of Rab25 protein in the epithelial cell layer. Rab25 mRNA levels were downregulated in the foreskin of children with hypospadias compared with controls [(1.697 ± 0.2005), (0.7687 ± 0.2130), p = 0.0053 < 0.05)]., Discussion: Rab25 mRNA and protein expressions in the hypospadias group were significantly downregulated compared with the control group. This was consistent with the results of single-cell sequencing of fetal mice reproductive nodules at 15.5 days of gestation (Zhang Z, Liu Z, Zhang Q, et al., unpublished observations). Our study represents the first report of abnormal Rab25 expression in the foreskin tissue of patients with hypospadias. More detailed research on the relationship between Rab25 and urethral development could be conducted to reveal the molecular mechanism of hypospadias., Conclusion: The expression of Rab25 in foreskin tissue was lower in the hypospadias group than in the control group. Rab25 is involved in the formation of the urethral seam and the occurrence of hypospadias. The potential mechanism by which Rab25 affects the canalization of the urethral plate needs to be further investigated., Competing Interests: Conflict of interest The authors declare no conflict of interest., (Copyright © 2023 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

This study investigated the effect of Corydalis saxicola Bunting total alkaloids (CSBTA) on pyroptosis in macrophages (Mϕ). In the Mϕ pyroptosis model, an inverted fluorescence microscope was used to assess cell pyroptosis, while a scanning electron microscope was used to observe morphological changes in Mϕ. NLR family pyrin domain-containing 3 (NLRP3), caspase-1, and gasdermin D (GSDMD) expression levels were detected by polymerase chain reaction and western blotting, whereas interleukin-1 (IL-1) and interleukin-18 (IL-18) expression levels were measured by an enzyme-linked immunosorbent assay. After pretreatment with CSBTA or the caspase-1 inhibitor, acetyl-tyrosyl-valyl-alanyl-aspartyl-chloromethylketone (Ac-YVAD-cmk), it was discovered that NLRP3, caspase-1, and GSDMD expressions were significantly reduced at both the mRNA and protein levels, as were IL-1 and IL-18 levels. The inhibitory effects of CSBTA and Ac-YVAD-cmk did not differ significantly. These findings indicate that CSBTA blocks Porphyromonas gingivalis-lipopolysaccharide-induced Mϕ pyroptosis., (© 2023 Wiley-VHCA AG, Zurich, Switzerland.)

Listeria monocytogenes is a common microorganism that causes food spoilage. Pediocins are some biologically active peptides or proteins encoded by ribosomes, which have a strong antimicrobial activity against L. monocytogenes. In this study, the antimicrobial activity of previously isolated P. pentosaceus C-2-1 was enhanced by ultraviolet (UV) mutagenesis. A positive mutant strain P. pentosaceus C23221 was obtained after 8 rounds of UV irradiation with increased antimicrobial activity of 1448 IU/mL, which was 8.47 folds higher than that of wild-type C-2-1. The genome of strain C23221 and wild-type C-2-1 was compared with identify the key genes for higher activity. The genome of the mutant strain C23221 consists of a chromosome of 1,742,268 bp, with 2052 protein-coding genes, 4 rRNA operons, and 47 tRNA genes, which is 79,769 bp less than the original strain. Compared with strain C-2-1, a total of 19 deduced proteins involved in 47 genes are unique to C23221 analyzed by GO database; the specific ped gene related to bacteriocin biosynthesis were detected using antiSMASH in mutant C23221, indicating mutant C23221 produced a new bacteriocin under mutagenesis conditions. This study provides genetic basis for further constituting a rational strategy to genetically engineer wild-type C-2-1 into an overproducer., Competing Interests: Declaration of competing interest We declared that there was no conflict of commercial interest or correlative interest in relation to the work submitted., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: The aim of this study was to use bioinformatics approaches to screen and identify the key genes of idiopathic calcium oxalate nephrolithiasis, and explore its potential molecular mechanism., Methods: The GSE73680 kidney stone data set was downloaded from the Gene Expression Omnibus (GEO). R software (The R Foundation for Statistical Computing) was used to screen differentially expressed genes. GeneMANIA and Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) databases were used to analyze related genes interacting with crucial genes, and a protein-protein interaction (PPI) network was constructed. The differential genes were then subjected to the Gene Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway enrichment analysis using the Database for Annotation, Visualization, and Integrated Discovery (DAVID) database. The clinical data of 156 patients who received percutaneous nephrolithotomy (PCNL) therapy at our facility between January 2013 and December 2017 were retrospectively analyzed. The various parameters associated with postoperative urogenous sepsis were identified using multivariable logistic regression analysis., Results: The study discovered one differentially expressed gene was nucleotide-binding oligomerization domain-containing protein 2 ( NOD2 ). GO and KEGG analysis showed that NOD2 might affect the occurrence of idiopathic calcium oxalate kidney stones by affecting inflammation, receptor expression, immune environment, necrosis, apoptosis, and other pathways. The clinical parameter of patients who participated in the study, including preoperative urinary white blood cell (WBC) count, preoperative urinary nitrite, stone diameter, operation time, WBC count, and WBC D values, were statistically different between the systemic inflammatory response syndrome (SIRS) group and the urosepsis group. According to multivariate logistic regression analysis, the preoperative urine nitrite, calculus diameter, blood WBC, and NOD2 expression 3 hours after surgery were all independently associated with the urosepsis development., Conclusions: Preoperative urinary nitrite positive status, postoperative WBC count ≥2.98×10 9 /L 3 hours after operation, stone diameter >6 cm, and low expression of NOD2 in renal papillary tissue are more likely to cause the urinary source of idiopathic calcium oxalate nephrolithiasis after PCNL urogenous sepsis. These parameters also offer a viable treatment paradigm for the perioperative management of PCNL in treating idiopathic calcium oxalate kidney stones., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tau.amegroups.com/article/view/10.21037/tau-23-219/coif). The authors have no conflicts of interest to declare., (2023 Translational Andrology and Urology. All rights reserved.)

To accurately measure the local temperatures of the micro-nano area, we propose an optical method using a tapered fiber Bragg grating (FBG) probe with a nano tip for scanning probe microscopy (SPM). When the tapered FBG probe senses local temperature through near-field heat transfer, the intensity of the reflected spectrum decreases, along with a broadening bandwidth and a shift in the central peak position. Modeling the heat transfer between the probe and the sample shows that the tapered FBG probe is in a non-uniform temperature field when approaching the sample surface. Simulation of the probe's reflection spectrum reveals that the central peak position shifts nonlinearly with increasing local temperature. In addition, the near-field temperature calibration experiments show that the temperature sensitivity of the FBG probe increases nonlinearly from 6.2 pm/°C to 9.4 pm/°C as the sample surface temperature increases from 25.3°C to 160.4°C. The agreement of the experimental results with the theory and the reproducibility demonstrate that this method offers a promising approach for exploring micro-nano temperature.

A capture systematic evolution of ligands by exponential enrichment (Capture-SELEX) was described to discover novel aptamers specific for 5-hydroxymethylfurfural (5-HMF), and a biosensor based on molecular beacon was constructed to detect 5-HMF. The ssDNA library was immobilized to streptavidin (SA) resin to select the specific aptamer. The selection progress was monitored using real-time quantitative PCR (Q-PCR), and the enriched library was sequenced by high-throughput sequencing (HTS). Candidate and mutant aptamers were selected and identified by Isothermal Titration Calorimetry (ITC). The FAM-aptamer and BHQ1-cDNA were designed as the quenching biosensor to detect 5-HMF in milk matrix. After the 18th round selection, the Ct value decreased from 9.09 to 8.79, indicating that the library was enriched. The HTS results indicated that the total sequence numbers for 9th, 13th, 16th, and 18th were 417054, 407987, 307666, and 259867, but the number of sequences for the top 300 sequences was gradually increased from 9th to 18th, and the ClustalX2 analysis showed that there were four families with high homology rate. ITC results indicated that the K d values of H1 and its mutants H1-8, H1-12, H1-14, and H1-21 were 2.5 μM, 1.8 μM, 1.2 μM, 6.5 μM, and 4.7 μM. The linear range of the quenching biosensor was from 0 μM to 75 μM, and it had a similar linear range in the 0.1% milk matrix. This is the first report to select a novel aptamer specific for 5-HMF and develop quenching biosensor for the rapid detection of 5-HMF in milk matrix.

Background: The protein-polyphenol interaction mechanism has always been a research hotspot, but their interaction is affected by heat treatment, which is widely applied in food processing. Moreover, the effects of microwave or water-bath heating on the protein-polyphenol interaction mechanism have been not clarified. The pasteurization condition (65 °C, 30 min) was selected to compare the effects of microwave or water bath on binding behavior, structure, and cell proliferation between α-lactalbumin (α-LA) and safflower yellow (SY), thus providing a guide for the selection of functional dairy processing conditions., Results: Microwave heat treatment of α-LA-SY resulted in stronger fluorescence quenching than that of conventional heat treatment. Moreover, the binding constant K a of all α-LA-SY samples was augmented significantly after microwave or water bath treatment, and microwave-heated α-LA-SY showed the maximum K a . Fourier transform infrared spectroscopy showed that microwave heating resulted in more ordered structures of α-LA into its disordered structures than water bath heating. However, the ferric reducing antioxidant power and chroma value of α-LA-SY were more reduced by microwave heating than by water bath heating. Moreover, microwave heating facilitated the cell proliferation of α-LA-SY compared with water bath treatment., Conclusion: It was demonstrated that microwave heating promoted interaction between α-LA and SY more than water bath heating did. Microwave heat treatment was a safe and effective way to enhance the binding affinity of α-LA to SY, being a potential application in food industry. © 2022 Society of Chemical Industry., (© 2022 Society of Chemical Industry.)

Background: Metastasis and drug resistance are the main causes of renal cell carcinoma (RCC) mortality. Currently, there are still a limited number of targeted therapies against advanced RCC. It is critical to develop new effective clinical biomarkers and drug targets in RCC. Several studies have shown that centromere protein F (CENPF), a microtubule binding protein, promotes cancer progression in various types of cancer. The purpose of this study was to explore the role of CENPF in RCC., Methods: Peripheral blood and corresponding tissue samples of 23 RCC patients and 23 normal physical examination patients who were treated in our hospital from 2018 to 2020 were collected, and CENPF expression was detected by quantitative real-time polymerase chain reaction (qRT-PCR), western blot, and immunohistochemical (IHC) methods. The expression of CENPF was downregulated by small interfering RNA (siRNA) transfection, and the proliferation of the corresponding RCC cells and the corresponding cell cycle were detected., Results: According to The Cancer Genome Atlas (TCGA) data analysis, CENPF is highly expressed in RCC, and its expression level is significantly related to the overall survival (OS) and recurrence-free survival (RFS) of RCC. In addition, high expression of CENPF was found in the tissues of RCC patients in our hospital. Knockdown of CENPF significantly reduced the proliferation of RCC cells in vitro, and knockdown of CENPF regulated the cell cycle by inhibiting the expression of cyclins such as CDK4, CDK6, and CyclinD1., Conclusions: CENPF can be used as an independent prognostic factor of RCC and regulate the proliferation ability and cell cycle of RCC cells. CENPF is a potential oncogene and prognostic marker in RCC., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tau.amegroups.com/article/view/10.21037/tau-22-797/coif). The authors have no conflicts of interest to declare., (2023 Translational Andrology and Urology. All rights reserved.)

Probiotic treatment might improve autism spectrum disorder (ASD) behavior. In this study, we investigated the improvement effects of Lactobacillus plantarum ST-III on a mouse model of ASD, which was constructed using triclosan. After two weeks of L. plantarum ST-III oral feeding, autism-like social deficits in male mouse models were ameliorated. L. plantarum ST-III also attenuated the self-grooming and freezing times of female mice. High-throughput sequencing revealed changes in the gut microbiota after L. plantarum ST-III intervention. In the female probiotic group, the abundance of beneficial Lachnospiraceae bacteria increased, whereas that of harmful Alistipes bacteria decreased. Correlation analysis showed that amelioration of abnormal behavior in a mouse model of ASD was related to the involvement of certain metabolic pathways. A reduction in the abundance of Alistipes was involved in stereotyped behavioral improvement. Thus, oral supplementation with L. plantarum ST-III can help improve social behavior in a male mouse model of ASD and contribute to more balanced intestinal homeostasis., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2022. Published by Elsevier Inc.)

Capsaicin (Cap) is a promising bioactive compound having many health-promoting benefits. However, it is difficult to be applied in food due to its poor aqueous solubility, low stability and bioavailability. Besides, its strong spicy taste and irritation to the gastrointestinal tract further limit the application of Cap in food. To solve this problem, Cap was loaded into a self-assembled nanocarrier formed by partial hydrolysis of α-lactalbumin (α-lac). The Cap was successfully loaded into the 21.2 nm micelles with a loading capacity of 123.4 ± 6.1 mg g -1 . The aqueous solubility was greatly improved. Besides, nanomicelles also showed intestinal responsive release behavior. The in vivo bioavailability of Cap was improved by nanomicelles for 3.1 times. The Cap loaded nanomicelles in the milk system showed good colloidal stability compared to solely Cap in milk. Therefore, the Cap loaded nanocarriers were added into the de-fatted milk to prepare de-fatted cheese with an acceptable spicy flavor. The nanocarriers were clearly captured in the cheese casein network as confirmed by confocal microscopy. The sensory evaluation results showed the spicy taste of capsaicin was reduced in the nanomicelle system and further reduced in the nanomicelle-cheese systems. We postulated that it might be due to the nanomicelles reducing the contact of capsaicin with sensory neurons in the tongue thus masking the spicy taste. The cheese casein network structure further masked their contact. The above results indicated that Cap embedding via α-lac nanocarriers was feasible for masking their spicy taste and applying Cap to food systems such as milk and cheese.

Introduction: Autism spectrum disorder (ASD) is a serious neurodevelopmental disorder with a rising incidence. More and more studies have shown that abnormal microbiota composition may aggravate the behavioral symptoms and biological signs of ASD, and interventions of probiotics and diet have emerged as a potential improvement measure., Methods: Lactiplantibacillus plantarum ST-III-fermented milk was applied as an oral intervention in a valproic acid (VPA)-induced ASD mice model, and the effect of probiotic intake on autistic-related behaviors and gut microbiota composition was evaluated by behavioral tests and 16S rRNA gene sequencing., Results: Gender specificity was shown in VPA-induced behavioral abnormalities in a mouse model, and L. plantarum ST-III-fermented milk was effective in ameliorating the impaired social interaction in male ASD mouse models, but not for the anxiety behavior exhibited by female ASD mouse models. Meanwhile, dietary changes were found to be the main cause of the altered gut microbiota in mice, and additional intake of L. plantarum ST-III-fermented milk seemed to improve autistic-like behaviors in male ASD mouse models by modulating specific gut microbes., Discussion: These findings suggest that L. plantarum ST-III-fermented milk may play a beneficial role in improving the behavioral symptoms of ASD and is expected to be one of the candidate functional foods for ASD., Competing Interests: Authors YZ, HoZ, RL, ZL, and CY were employed by Bright Dairy & Food Co., Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhang, Guo, Zhang, Wang, Li, Liu, Zheng and You.)

With the development of human genome sequencing and techniques such as intestinal microbial culture and fecal microbial transplantation, newly discovered microorganisms have been isolated, cultured, and researched. Consequently, many beneficial probiotics have emerged as next-generation probiotics (NGPs). Currently, "safety," "individualized treatment," and "internal interaction within the flora" are requirements of a potential NGPs. Furthermore, in the complex ecosystem of humans and microbes, it is challenging to identify the relationship between specific strains, specific flora, and hosts to warrant a therapeutic intervention in case of a disease. Thus, this review focuses on the progress made in NGPs and human health research by elucidating the limitations of traditional probiotics; summarizing the functions and strengths of Akkermansia muciniphila , Faecalibacterium prausnitzii , Bacteroides fragilis , Eubacterium hallii , and Roseburia spp. as NGPs; and determining the role of their intervention in treatment of certain diseases. Finally, we aim to provide a reference for developing new probiotics in the future., Competing Interests: The authors declare that no conflict of interests exists., (Copyright © 2022 Huanchang Zhang et al.)

Fructooligosaccharides (FOS) promote the proliferation of Bifidobacterium , especially Bifidobacterium pseudolongum in C57BL/6J mice. However, the response of intestinal microbes to FOS is influenced by host genotypes. Therefore, we compared the intestinal microbiota of four commonly used mice before and after FOS intervention, including C57BL/6J, BALB/c, Institute Cancer Research (ICR), and Kunming (KM) mice. The intestinal microbiota of the four genotypes exhibited similarities in composition but differences in relative abundance. Bifidobacterium was significantly increased to different degrees in the four genotypes of mice after FOS intervention, and Akkermansia and Bacteroides were also significantly increased in BALB/c and KM mice. Lactobacillus and Alistipes levels were unchanged or decreased. Within the genus Bifidobacterium , B. pseudolongum was the dominant species in the four genotypes of mice and proliferated significantly after FOS intervention, with dramatic proliferation in C57BL/6J mice (9.49%). Furthermore, eight strains of B. pseudolongum were screened from the feces of mice with four genotypes, and there was a great difference in the ability and manner of utilizing FOS among the strains. The strains from C57BL/6J mice exhibited the strongest utilization of 1-kestose (GF2), whereas other strains could utilize both GF2 and nistose (GF3) weakly. The gut microbial analysis of mice with different genotypes complemented our previous studies. The results provided the background strains of the different mouse genotypes and suggested a correlation between the utilization ability and the response of the strains to FOS. Further studies on the utilization ability of strains and competition in the intestine will contribute to the understanding of the mechanisms of the intestinal microbial response to diet., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

5-Hydroxymethylfurfural (5-HMF) is a useful indicator of thermal damage degree and freshness of milk. It is of great importance to develop simple, rapid and accurate analytical methods for the sensitive detection of 5-HMF in milk and milk-based products. In this work, surface-enhance Raman spectroscopy (SERS) was used for rapid determination of 5-HMF in processed cheese by colloidal Au nanoparticles (AuNPs) substrate synthesized by the classical solvothermal reduction method. Density functional theory (DFT) calculations were carried out to determine the vibration assignments of 5-HMF and the surface enhancement effect of AuNPs substrate. The results found that a good linear response on the AuNPs substrate for 5-HMF in the concentration range of 0.1-75 mM was established with the detection limit of 75 μM (S/N = 3). Furthermore, the present method could be applied to the determination of 5-HMF in a cheese real sample which revealed its promising application in food safety and analysis., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Five fractions from crude Hericium erinaceus polysaccharides (HEPs), including HEP-1, HEP-2, HEP-3, HEP-4 and HEP-5, were obtained through column chromatography with a DEAE Cellulose-52 column and Sephadex G-100 column. The contents of total carbohydrates and uronic acid in HEPs were 53.36% and 32.56%, respectively. HEPs were mainly composed of Fuc, Gal and Glu in a molar ratio of 7.9:68.4:23.7. Its chemical structure was characterized by sugar and methylation analysis, along with 1 H and 13 C NMR spectroscopy. HEP-1 contains the backbone composed of (1→6)-linked-galactose with branches attached to O-2 of some glucose. The immunological activity assay indicated that HEP-1 significantly promoted the production of nitric oxide, interleukin-6, interleukin-10, interferon-γ and tumor necrosis factor-α and the phosphorylation of signaling molecules. Collectively, these results suggested that HEP-1 could improve immunity via NF-κB, MAPK and PI3K/Akt pathways. Hericium erinaceus polysaccharides might be explored as an immunomodulatory agent for use in dietary supplements.

Background: Fructooligosaccharides (FOS) are a kind of prebiotic. Previous studies concerning the effect of FOS on intestinal microbiota have focused on Bifidobacterium and Lactobacillus. However, the presence of other FOS-utilizing bacteria makes it necessary to investigate the quantitative changes in these bacterial species in the intestine after FOS intake. In this study, the composition of cecal and fecal microbiota was analyzed using MiSeq sequencing, and the abundance of FOS-utilizing bacteria was detected using quantitative polymerase chain reaction after the oral administration of FOS., Results: Species-specific primers for FOS-utilizing bacteria were designed with superior amplification efficiency for quantification. After FOS intervention, the relative abundance of Bifidobacterium pseudolongum in feces increased to 17.37% and the abundance reached 2.28 × 10 10  CFU g -1 . The abundance of Bifidobacterium longum and Bifidobacterium breve did not change significantly. Whereas the abundance of Ligilactobacillus murinus decreased, that of Lactiplantibacillus plantarum, Lacticaseibacillus paracasei, and Lacticaseibacillus rhamnosus remained at approximately 10 4  CFU g -1 ., Conclusion: Species-specific primers for FOS-utilizing bacteria were successfully developed, and we confirmed that FOS significantly increased the relative abundance and the abundance of B. pseudolongum in mice, while decreasing the proportion of Lactobacillus. The detection of these species using 16S ribosomal DNA sequencing and quantitative polymerase chain reaction showed the same results. Further investigations are needed to reveal the response of the intestinal microbiota to different FOS compositions. These techniques will contribute to future studies about the composition and dynamics of the intestinal microflora. © 2022 Society of Chemical Industry., (© 2022 Society of Chemical Industry.)

Mafb plays a significant role in the development and differentiation of various organs, tissues and cells. Nevertheless, its role in the control of external genital cell proliferation and function in the mechanism of hypospadias remains unknown. In this study, the expression of Mafb in foreskin fibroblasts was inhibited by siRNA. The Cell Count Kit-8 (CCK-8) assay showed cell proliferation increased after transfection, and the number of cells entered the S phase significantly increased via flow cytometry. Both mRNA and protein levels of cyclin E, cyclin-dependent kinase 2 (CDK2) and proliferating cell nuclear antigen (PCNA) were significantly upregulated in the siRNA group. Meanwhile, twenty-five prepuce tissue samples were collected from hypospadias repair surgery. These samples were divided into two groups: the severe and mild groups. Normal prepuce tissue specimens were obtained during circumcision as the normal control. The upregulated expression of cyclin E, CDK2 and PCNA and downregulated Mafb expression were observed in the hypospadias group. This study reveals for the first time that the reduction in Mafb promotes the foreskin fibroblast proliferation. Thus, downregulated Mafb expression may cause hypospadias by upregulating CDK2, cyclin E and PCNA. These findings can shed new light on the embryonic development of the urethra., (© 2022 Wiley-VCH GmbH.)

Background: The most abundant human milk oligosaccharide in breast milk, 2'-fucosyllactose (2'-FL), has been approved as an additive to infant formula due to its multifarious nutraceutical and pharmaceutical functions in promoting neonate health. However, the low efficiency of de novo synthesis limits the cost-efficient bioproduction of 2'-FL., Results: This study achieved 2'-FL de novo synthesis in a generally recognized as safe (GRAS) strain Bacillus subtilis. First, a de novo biosynthetic pathway for 2'-FL was introduced by expressing the manB, manC, gmd, wcaG, and futC genes from Escherichia coli and Helicobacter pylori in B. subtilis, resulting in 2'-FL production of 1.12 g/L. Subsequently, a 2'-FL titer of 2.57 g/L was obtained by reducing the competitive lactose consumption, increasing the regeneration of the cofactor guanosine-5'-triphosphate (GTP), and enhancing the supply of the precursor mannose-6-phosphate (M6P). By replacing the native promoter of endogenous manA gene (encoding M6P isomerase) with a constitutive promoter P7, the 2'-FL titer in shake flask reached 18.27 g/L. The finally engineered strain BS21 could produce 88.3 g/L 2'-FL with a yield of 0.61 g/g lactose in a 3-L bioreactor, without the addition of antibiotics and chemical inducers., Conclusions: The efficient de novo synthesis of 2'-FL can be achieved by the engineered B. subtilis, paving the way for the large-scale bioproduction of 2'-FL titer in the future., (© 2022. The Author(s).)

Accurate and low-cost onsite assay of residual antibiotics in food and agriculture-related matrixes (e.g., milk) is of significant importance for evaluating and controlling food pollution risk. Herein, we employed hybrid Cu-doped-g-C 3 N 4 nanozyme to engineer smartphone-assisted onsite visual sensor for reliable and precise reporting the levels of tetracycline (TC) residues in milk through π-π stacking-triggered blocking effect. Benefiting from the synergetic effects of Cu 2+ and g-C 3 N 4 nanosheet, Cu-doped-g-C 3 N 4 nanocomposite exhibited an improved peroxidase-like activity, which could effectively catalyze H 2 O 2 to oxidate colorless TMB into steel-blue product oxTMB. Interestingly, owing to the blocking effect caused by the π-π stacking interaction between TC tetraphenyl skeleton and Cu-doped-g-C 3 N 4 nanozyme, the affinity of Cu-doped-g-C 3 N 4 nanocomposite toward the catalytic substrates was remarkably blocked, resulting in a TC concentration-dependent fading of solution color. Using smartphone-assisted detection a simple, low-cost, reliable, and sensitive portable colorimetric sensor-based nanozyme for onsite visual monitoring the residual TC in milk was successfully developed with a detection limit of 86.27 nM. Of particular mention is that this detection limit is comparable to most other reported colorimetric methods and below most official allowable residue thresholds in milk matrixes. This work gave a novel insight to integrate two-dimensional (2D) artificial nanozymes-based π-π stacking-triggered blocking effect with smartphone-assisted detection for developing efficient and low-cost colorimetric point-of-care testing of the risk factors in food and agriculture-related matrixes., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

To evaluate the effect of probiotics on gingival inflammation and oral microbiota in patients suffering from plaque-induced gingivitis. PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), and EMBASE were electronically searched until December 2020. The quality of included studies was assessed with the Cochrane Collaboration's Risk of Bias tool. The differences were expressed as weighted mean differences (WMD) and 95% of confidence interval (95% CI). I 2 test was performed to evaluate the heterogeneity of the studies. All analyses were performed using Review Manager (version 5.3). Eleven randomized and controlled trials were included, enrolling 554 patients. All comparisons displayed that oral probiotics had no significant improvement in the Gingival Index (GI), Plaque Index (PI), and bleeding on probing (BOP) of patients with plaque-induced gingivitis. In terms of microecology, no significant difference in the volumes of gingival crevicular fluid (GCF), the concentration of IL-1β, and the counts of Aggregatibacter actinomycetemcomitans (Aa), Porphyromonas gingivalis (Pg), Prevotella intermedia (Pi), and Fusobacterium nucleatum (Fn) were found between the probiotic group and the placebo group. There exists no clear evidence that oral probiotics have positive effect on gingival inflammation and oral microecological environment of patients with plaque-induced gingivitis., (© 2021 Wiley Periodicals LLC.)