Ginsenoside Rb3 alleviates the formation of osteoclasts induced by periodontal ligament fibroblasts in the periodontitis microenvironment through the STAT3 pathway.

This study explores the potential role and mechanism of Ginsenoside Rb3 (Rb3) in modulating osteoclastogenesis induced by human periodontal ligament fibroblasts (hPLFs) within the periodontitis microenvironment. We investigated the anti-inflammatory effects of Rb3 on hPLFs stimulated with Porphyromonas gingivalis lipopolysaccharide (P.g-LPS) utilizing quantitative polymerase chain reaction (qPCR) and enzyme-linked immunosorbent assay techniques. Moreover, the functional role of Rb3 in hPLFs-induced osteoclast formation was assessed by treating human bone marrow-derived macrophages (hBMMs) with conditioned medium from hPLFs, followed by analyses through qPCR, western blot analysis, and staining for tartrate-resistant acid phosphatase (TRAP) and phalloidin. The impact of Rb3 on the activation of the STAT3 signaling pathway was determined via western blot analysis. Results indicated that Rb3 treatment significantly suppressed the upregulation of pro-inflammatory cytokines (TNF-α, IL-1ß, IL-6, MCP-1, and IL-18) at both gene and protein levels in hPLFs induced by P.g-LPS. Furthermore, conditioned medium from Rb3 plus P.g-LPS treated hPLFs notably decreased the number of TRAP-positive cells, actin ring formations, and the expression of osteoclast marker genes (including CTSK, NFATC1, and ACP5). Rb3 also inhibited the P.g-LPS-induced activation of the STAT3 pathway, with the activation of STAT3 partially reversing the effects of Rb3 on inflammation and osteoclast differentiation. Collectively, Rb3 ameliorates inflammation in P.g-LPS-stimulated hPLFs and reduces hPLFs-induced osteoclastogenesis by inhibiting the STAT3 signaling pathway, suggesting its potential as a therapeutic agent for periodontitis.

Insight into the Dynamic Nature of the Pt-CeO2 Interface in Dry Reforming of Methane.

Single-atom catalysts (SACs) are attractive in one-carbon (C1) chemistry because of their high atom efficiency. However, it is a great challenge for understanding the dynamic roles of SACs under operating conditions. Here, isolated Pt atoms trapped on defective CeO2 surface are investigated by experiments, especially operando techniques, which offers basic understanding of the nature and dynamic evolution of the Pt-CeO2 interface in dry reforming of methane (DRM). The Pt-Olattice configuration is highly active for CH4 dissociation at the expense of the Olattice atoms, which in turn promotes the H-assisted dissociation of CO2. The transformation of Pt atoms between positive and metallic states is driven by the DRM reaction, which is essential for rendering highly efficient catalysis. The dynamic evolution of Pt atoms favors to eliminate the reactive intermediates, such as carbonates and formates. The dynamic nature of the Pt-CeO2 interface in the DRM reaction shows a similar picture to the Yin and Yang transformation in ancient Chinese Tai Ji wisdom.

Enhancing L-asparagine Production Through In Vivo ATP Regeneration System Utilizing Glucose Metabolism of Escherichia coli.

L-asparaginase synthetase, an ATP-dependent enzyme, necessitates ATP for its catalytic activity. However, the integration of L-asparaginase synthetase into industrial processes is curtailed by the prohibitive cost of ATP. To address this limitation, this study explores the construction of an efficient ATP regeneration system using the glucose metabolism of Escherichia coli, synergistically coupled with L-asparaginase synthetase catalysis. The optimal conditions for L-asparagine yield were determined in shake flasks. A total of 2.7 g/L was the highest yield achieved under specific parameters, including 0.1 mol/L of substrate, 0.2 mol/L glucose, 0.01 mol/L MgCl2 at pH 7.5, a temperature of 37 °C, and agitation at 300 r/min over 12 h. The process was then scaled to a 3-L fermenter, optimizing the addition rates of the substrate and magnesium chloride, and employing a constant glucose feed of 10 g/L/h. The scale-up process led to a significant enhancement in the production of L-asparagine. The yield of L-asparagine was increased to 38.49 g/L after 20 h of conversion, and the molar conversion rate reached 29.16%. This strategy has proven to be effective in improving the efficiency of L-asparagine production. When compared to in vitro ATP regeneration methods, this in vivo approach showcased superior efficiency and reduced costs. These findings furnish pivotal insights that may propel the enzymatic synthesis of L-asparagine toward viable industrial application.

Qualification of a 21-valent pneumococcal urine antigen detection assay and development of clinical positivity cutoffs.

Aim: Serotype-specific assays detecting pneumococcal polysaccharides in bodily fluids are needed to understand the pneumococcal serotype distribution in non-bacteremic pneumonia. Methods: We developed a urine antigen detection assay and using urine samples from adult outpatients without pneumonia developed positivity cutoffs for both a previously published 15-valent and the new 21-valent assay. Clinical sensitivity was confirmed with samples from patients with invasive pneumococcal disease. Results: Total assay precision ranged from 7.6 to 17.8% coefficient of variation while accuracy ranged between 80 and 150% recovery, except for three serotypes where recoveries ranged from 32 to 60%. Clinical sensitivity was 86.4% and specificity was 96.5% across all 30 serotypes. Conclusion: The assay could potentially assess serotype-distribution in non-infected and infected participants with pneumococcal disease.

[Box: see text].

Probabilistic risk assessment of dietary exposure to lead in residents of Guangzhou, China.

Lead and its compounds can have cumulative harmful effects on the nervous, cardiovascular, and other systems, and especially affect the brain development of children. We collected 4918 samples from 15 food categories in 11 districts of Guangzhou, China, from 2017 to 2022, to investigate the extent of lead contamination in commercial foods and assess the health risk from dietary lead intake of the residents. Lead was measured in the samples using inductively coupled plasma mass spectrometry. Dietary exposure to lead was calculated based on the food consumption survey of Guangzhou residents in 2011, and the health risk of the population was evaluated using the margin of exposure (MOE) method. Lead was detected in 76.5% of the overall samples, with an average lead content of 29.4 µg kg-1. The highest lead level was found in bivalves. The mean daily dietary lead intakes were as follows: 0.44, 0.34, 0.25, and 0.28 µg kg-1 body weight (bw) day-1 for groups aged 3-6, 7-17, 18-59, and ≥ 60 years, respectively. Rice and rice products, leafy vegetables, and wheat flour and wheat products were identified as the primary sources of dietary lead exposure, accounting for 73.1%. The MOE values demonstrated the following tendency: younger age groups had lower MOEs, and 95% confidence ranges for the groups aged 3-6 and 7-17 began at 0.6 and 0.7, respectively, indicating the potential health risk of children, while those for other age groups were all above 1.0. Continued efforts are needed to reduce dietary lead exposure in Guangzhou.

A smartphone-combined ratiometric fluorescence molecularly imprinted probe based on biomass-derived carbon dots for determination of tyramine in fermented meat products.

A ratiometric fluorescence molecularly imprinted probe employing two distinct emission wavelengths of biomass carbon dots was developed for highly selective and visual quantitative detection of tyramine in fermented meat products. The red emission biomass carbon dots were employed as responsive elements, and the blue ones were utilized as the reference elements. The molecularly imprinted polymers were incorporated in the ratiometric sensing to distinguish and adsorb tyramine. With the linear range of 1-60 µg/L, the ratiometric fluorescence molecularly imprinted probe was successfully applied to detect tyramine in real samples with the satisfactory recoveries of 79.74-112.12% and the detect limitation of 1.3 µg/kg, indicating that this probe has great potential applications for the detection of tyramine in real samples. Moreover, smartphone-based fluorescence signal recognition analysis on hand has been developed for the quantitative analysis of tyramine, providing a portable visual optical analysis terminal for rapid on-site determination of tyramine.

Preoperative pancreatic stent placement before the enucleation of insulinoma located in the head and neck of the pancreas in proximity to the main pancreatic duct: study protocol for a multicentre randomised clinical trial in Chinese tertiary medical centres.

INTRODUCTION: The surgical intervention approach to insulinomas in proximity to the main pancreatic duct remains controversial. Standard pancreatic resection is recommended by several guidelines; however, enucleation (EN) still attracts surgeons with less risk of late exocrine/endocrine insufficiency, despite a higher postoperative pancreatic fistula (POPF) rate. Recently, the efficacy and safety of preoperative pancreatic stent placement before the EN have been demonstrated. Thus, a multicentre open-label study is being conducted to evaluate the efficacy and safety of stent placement in improving the outcome of EN of insulinomas in proximity to the main pancreatic duct. METHODS AND ANALYSIS: This is a prospective, randomised, open-label, superiority clinical trial conducted at multiple tertiary centres in China. The major eligibility criterion is the presence of insulinoma located in the head and neck of the pancreas in proximity (≤2 mm) to the main pancreatic duct. Blocked randomisation will be performed to allocate patients into the stent EN group and the direct EN group. Patients in the stent EN group will go through stent placement by the endoscopist within 24 hours before the EN surgery, whereas other patients will receive EN surgery directly. The primary outcome is the assessment of the superiority of stent placement in reducing POPF rate measured by the International Study Group of Pancreatic Surgery standard. Both interventions will be performed in an inpatient setting and regular follow-up will be performed. The primary outcome (POPF rate) will be tested for superiority with the Χ2 test. The difference in secondary outcomes between the two groups will be analysed using appropriate tests. ETHICS AND DISSEMINATION: The study has been approved by the Peking Union Medical College Hospital Institutional Review Board (K23C0195), Ruijin Hospital Ethics Committee (2023-314), Peking University First Hospital Ethics Committee (2024033-001), Institutional Review Board of Xuanwu Hospital of Capital Medical University (2023223-002), Ethics Committee of the First Affiliated Hospital of Xi'an Jiaotong University (XJTU1AF2023LSK-473), Institutional Review Board of Tongji Medical College Tongji Hospital (TJ-IRB202402059), Ethics Committee of Tongji Medical College Union Hospital (2023-0929) and Shanghai Cancer Center Institutional Review Board (2309282-16). The results of the study will be published in an international peer-reviewed journal. TRIAL REGISTRATION NUMBER: NCT05523778.

Advances in understanding the reproductive toxicity of endocrine-disrupting chemicals in women.

Recently, there has been a noticeable increase in disorders of the female reproductive system, accompanied by a rise in adverse pregnancy outcomes. This trend is increasingly being linked to environmental pollution, particularly through the lens of Endocrine Disrupting Chemicals (EDCs). These external agents disrupt natural processes of hormones, including synthesis, metabolism, secretion, transport, binding, as well as elimination. These disruptions can significantly impair human reproductive functions. A wealth of animal studies and epidemiological research indicates that exposure to toxic environmental factors can interfere with the endocrine system's normal functioning, resulting in negative reproductive outcomes. However, the mechanisms of these adverse effects are largely unknown. This work reviews the reproductive toxicity of five major environmental EDCs-Bisphenol A (BPA), Phthalates (PAEs), Triclocarban Triclosan and Disinfection Byproducts (DBPs)-to lay a foundational theoretical basis for further toxicological study of EDCs. Additionally, it aims to spark advancements in the prevention and treatment of female reproductive toxicity caused by these chemicals.

Gastrointestinal contrast-enhanced ultrasonography for diagnosis and treatment of peptic ulcer in children.

BACKGROUND: The detection rate of peptic ulcer in children is improving, with development of diagnostic procedures. Gastroscopy is the gold standard for the diagnosis of peptic ulcer, but it is an invasive procedure. Gastrointestinal contrast-enhanced ultrasonography (CEUS) has the advantages of being painless, noninvasive, nonradioactive, easy to use, and safe. AIM: To investigate the clinical value of CEUS for diagnosis and treatment of peptic ulcer in children. METHODS: We investigated 43 children with digestive tract symptoms in our hospital from January 2021 to June 2022. All children were examined by routine ultrasound, gastrointestinal CEUS, and gastroscopy. The pathological results of gastroscopy were taken as the gold standard. Routine ultrasonography was performed before gastrointestinal CEUS. Conventional ultrasound showed the thickness of the gastroduodenal wall, gastric peristalsis, and the adjacent organs and tissues around the abdominal cavity. Gastrointestinal CEUS recorded the thickness of the gastroduodenal wall; the size, location and shape of the ulcer; gastric peristalsis; and adjacent organs and tissues around the abdominal cavity. The results of routine ultrasound and gastrointestinal ultrasound were compared with those of gastroscopy to evaluate the diagnostic results and coincidence rate of routine ultrasound and gastrointestinal CEUS. All children received informed consent from their guardians for CEUS. This study was reviewed and approved by the hospital medical ethics committee. RESULTS: Among the 43 children, 17 (15 male, 2 female) were diagnosed with peptic ulcer by gastroscopy. There were 26 children with nonpeptic ulcer. There were eight cases of peptic ulcer and 35 of nonpeptic ulcer diagnosed by conventional ultrasound. The diagnostic coincidence rate of peptic ulcer in children diagnosed by conventional ultrasound was 79.1% (34/43), which was significantly different from that of gastroscopy (P = 0.033). It indicates that the coincidence rate of gastrointestinal contrast-enhanced ultrasound and gastroscope is low. Fifteen cases of peptic ulcer and 28 of nonpeptic ulcer were diagnosed by CEUS. The diagnostic coincidence rate of peptic ulcer in children was 95.3% (41/43). There was no significant difference between CEUS and gastroscopy (P = 0.655). It indicates that the coincidence rate of gastrointestinal contrast-enhanced ultrasound and gastroscope is high. CONCLUSION: Gastrointestinal CEUS has a high coincidence rate in the diagnosis of peptic ulcer in children, and can be used as a preliminary examination method.

CLLU1 as an emerging biomarker in chronic lymphoid leukemia.

CLLU1, a disease-specific gene associated with chronic lymphoid leukemia (CLL), is located on chromosome 12q22. Previous studies considered CLLU1 to be a non-coding RNA; however, recent research has discovered that its coding sequence region possesses the potential to encode a short peptide similar to interleukin-4. Remarkably, abnormally elevated expression of CLLU1 has only been detected in chronic lymphoid leukemia among all hematological cancers. High CLLU1 expression often indicates more malignant pathological features and an unfavorable prognosis for patients. Importantly, the expression level of CLLU1 remains unaffected by the passage of time or therapeutic interventions, thus rendering it a novel prognostic marker. This article provides a comprehensive summary of relevant research findings on CLLU1 in the context of CLL prognosis and clinical applications, aiming to guide subsequent theoretical and clinical investigations in this field.

Enhancing L-Asparagine Bioproduction Efficiency Through L-Asparagine Synthetase and Polyphosphate Kinase-Coupled Conversion and ATP Regeneration.

L-Asparagine, a crucial amino acid widely used in both food and medicine, presents pollution-related and side reaction challenges when prepared using chemical synthesis method. Although biotransformation methods offer significant advantages such as high efficiency and mild reaction conditions, they also entail increased costs due to the need for ATP supplementation. This study aimed to address the challenges associated with biopreparation of L-asparagine. Firstly, the functionality and characteristics of recombinant L-asparagine synthetase enzymes derived from Escherichia coli and Lactobacillus salivarius were evaluated to determine their practical applicability. Subsequently, recombinant expression of polyphosphate kinase from Erysipelotrichaceae bacterium was conducted. A reaction system for L-asparagine synthesis was established using a dual enzyme-coupled conversion approach. Under the optimal reaction conditions, a maximum yield of 11.67 g/L of L-asparagine was achieved, with an 88.43% conversion rate, representing a 5.03-fold increase compared to the initial conversion conditions. Notably, the initial addition of ATP was reduced to only 5.66% of the theoretical demand, indicating the effectiveness of our ATP regeneration system. These findings highlight the potential of our approach in enhancing the efficiency of L-asparagine preparation, offering promising prospects for the food and medical industries.

Traditional Uses, Chemical Constituents and Pharmacological Activities of the Toona sinensis Plant.

Toona sinensis (A. Juss.) Roem., which is widely distributed in China, is a homologous plant resource of medicine and food. The leaves, seeds, barks, buds and pericarps of T. sinensis can be used as medicine with traditional efficacy. Due to its extensive use in traditional medicine in the ancient world, the T. sinensis plant has significant development potential. In this review, 206 compounds, including triterpenoids (1-133), sesquiterpenoids (134-135), diterpenoids (136-142), sterols (143-147), phenols (148-167), flavonoids (168-186), phenylpropanoids (187-192) and others (193-206), are isolated from the T. sinensis plant. The mass spectrum cracking laws of representative compounds (64, 128, 129, 154-156, 175, 177, 179 and 183) are reviewed, which are conducive to the discovery of novel active substances. Modern pharmacological studies have shown that T. sinensis extracts and their compounds have antidiabetic, antidiabetic nephropathy, antioxidant, anti-inflammatory, antitumor, hepatoprotective, antiviral, antibacterial, immunopotentiation and other biological activities. The traditional uses, chemical constituents, compound cracking laws and pharmacological activities of different parts of T. sinensis are reviewed, laying the foundation for improving the development and utilization of its medicinal value.

Role of macrophages in regression of myocardial fibrosis following alleviation of left ventricular pressure overload.

Sustained hemodynamic pressure overload (PO) produced by murine transverse aortic constriction (TAC) causes myocardial fibrosis; removal of TAC (unTAC) returns left ventricle (LV) hemodynamic load to normal and results in significant, but incomplete regression of myocardial fibrosis. However, the cellular mechanisms that result in these outcomes have not been defined. The objective was to determine temporal changes in myocardial macrophage phenotype in TAC and unTAC and determine whether macrophage depletion alters collagen degradation after unTAC. Myocardial macrophage abundance and phenotype were assessed by immunohistochemistry, flow cytometry, and gene expression by RT-PCR in control (non-TAC), 2 wk, 4 wk TAC, and 2 wk, 4 wk, and 6 wk unTAC. Myocardial cytokine profiles and collagen-degrading enzymes were determined by immunoassay and immunoblots. Initial collagen degradation was detected with collagen-hybridizing peptide (CHP). At unTAC, macrophages were depleted with clodronate liposomes, and endpoints were measured at 2 wk unTAC. Macrophage number had a defined temporal pattern: increased in 2 wk and 4 wk TAC, followed by increases at 2 wk unTAC (over 4 wk TAC) that then decreased at 4 wk and 6 wk unTAC. At 2 wk unTAC, macrophage area was significantly increased and was regionally associated with CHP reactivity. Cytokine profiles in unTAC reflected a proinflammatory milieu versus the TAC-induced profibrotic milieu. Single-cell sequencing analysis of 2 wk TAC versus 2 and 6 wk unTAC revealed distinct macrophage gene expression profiles at each time point demonstrating unique macrophage populations in unTAC versus TAC myocardium. Clodronate liposome depletion at unTAC reduced CHP reactivity and decreased cathepsin K and proMMP2. We conclude that temporal changes in number and phenotype of macrophages play a critical role in both TAC-induced development and unTAC-mediated partial, but incomplete, regression of myocardial fibrosis.NEW & NOTEWORTHY Our novel findings highlight the dynamic changes in myocardial macrophage populations that occur in response to PO and after alleviation of PO. Our data demonstrated, for the first time, a potential benefit of macrophages in contributing to collagen degradation and the partial regression of interstitial fibrosis following normalization of hemodynamic load.

Substrip-based registration and automatic montaging of adaptive optics retinal images.

Precise registration and montage are critical for high-resolution adaptive optics retinal image analysis but are challenged by rapid eye movement. We present a substrip-based method to improve image registration and facilitate the automatic montaging of adaptive optics scanning laser ophthalmoscopy (AOSLO). The program first batches the consecutive images into groups based on a translation threshold and selects an image with minimal distortion within each group as the reference. Within each group, the software divides each image into multiple strips and calculates the Normalized Cross-Correlation with the reference frame using two substrips at both ends of the whole strip to estimate the strip translation, producing a registered image. Then, the software aligns the registered images of all groups also using a substrip based registration, thereby generating a montage with cell-for-cell precision in the overlapping areas of adjacent frames. The algorithm was evaluated with AOSLO images acquired in human subjects with normal macular health and patients with age-related macular degeneration (AMD). Images with a motion amplitude of up to 448 pixels in the fast scanner direction over a frame of 512 × 512 pixels can be precisely registered. Automatic montage spanning up to 22.6 degrees on the retina was achieved on a cell-to-cell precision with a low misplacement rate of 0.07% (11/16,501 frames) in normal eyes and 0.51% (149/29,051 frames) in eyes with AMD. Substrip based registration significantly improved AOSLO registration accuracy.

Rapid and sensitive detection of Mycoplasma synoviae using RPA combined with Pyrococcus furiosus Argonaute.

Mycoplasma synoviae (MS) is an important pathogen in laying hens and causes serious economic losses in poultry production. Rapid, accurate and specific detection is important for the prevention and control of MS. Argonaute from Pyrococcus furiosus (PfAgo) is emerging as a nucleic acid detector that works via "dual-step" sequence-specific cleavage. In this study, an MS detection method combining recombinase polymerase amplification (RPA) and PfAgo was established. Through elaborate design and screening of RPA primers and PfAgo gDNA and condition optimization, amplification and detection procedures can be completed within 40 min, whereas the results were superficially interpreted under UV and blue light. The sensitivity for MS detection was 2 copies/µL, and the specificity results showed no cross reaction with other pathogens. For the detection of 31 clinical samples, the results of this method and qPCR were completely consistent. This method provides a reliable and convenient method for the on-site detection of MS that is easy to operate without complex instruments and equipment.

Diversity of evolution in MDR monophasic S. Typhimurium among food animals and food products in Southern China from 2011 to 2018.

The monophasic variant of Salmonella enterica serovar Typhimurium with the antigenic formula 1,4,[5],12:i:- is one of the most common pathogenic bacteria causing global food-borne outbreaks. However, the research on molecular characteristics and evolution of monophasic S. typhimurium in China is still lacking. In the current study, 59 monophasic S. typhimurium strains were isolated from food animals and food products in South China between 2011 and 2018. A total of 87.5 % of monophasic S. typhimurium isolates were grouped into one independent clade with other monophasic S. typhimurium strains in China distinct from other countries by phylogenomic analysis. These isolates possess variable genotypes, including multiple ARGs on plasmid IncHI2, diverse evolutions at the fljAB locus, and virulence factors. Our results suggest that the monophasic S. typhimurium isolates currently circulating in China might be an independent epidemic subtype.

Seven new species and four new records of Psychomyiidae (Insecta, Trichoptera) from China.

Seven new species of the family Psychomyiidae Walker, 1852 are described and illustrated from China; they are Psychomyiashunisp. nov., Ps.mangshanensissp. nov., Ps.capricornissp. nov., Lypesagittalissp. nov., Paduniellafasciariasp. nov., Pa.sanyaensissp. nov., and Tinodesaviformissp. nov. The genus Lype is reported for the first time from mainland China. In addition, four psychomyiids are found to be new to the Chinese caddis fauna: Psychomyiaindra Malicky & Chantaramongkol, 1993; Paduniellaandamanensis Malicky, 1979; Pa.dendrobia Malicky & Chantaramongkol, 1993; and Tinodesgapbona Johanson & Oláh, 2008. Moreover, Psychomyiapolyacantha Li, Qiu & Morse, 2021 is reviewed and synonymized with Psychomyiaimamiah Malicky, 2020.