Triple three-dimensional MS/MS spectrum facilitates quantitative ginsenosides-targeted sub-metabolome characterization in notoginseng.

Although serving as the workhorse, MS/MS cannot fully satisfy the analytical requirements of quantitative sub-metabolome characterization. Because more information intrinsically correlates to more structural and concentration clues, here, efforts were devoted to comprehensively tracing and deciphering MS/MS behaviors through constructing triple three-dimensional (3×3D)-MS/MS spectrum. Ginsenosides-targeted metabolomics of notoginseng, one of the most famous edible medicinal plants, was employed as a proof-of-concept. Serial authentic ginsenosides were deployed to build the correlations between 3×3D-MS/MS spectra and structure/concentration features. Through assaying ginsenosides with progressive concentrations using QTOF-MS to configure 1st 3D spectrum, the generations of MS1 spectral signals, particularly multi-charged multimer anions, e.g., [2M-2H]2- and [2M+2HCOO]2- ions, relied on both concentration and the amount of sugar chains. By programming progressive collision energies to the front collision cell of Qtrap-MS device to gain 2nd 3D spectrum, optimal collision energy (OCE) corresponding to the glycosidic bond fission was primarily correlated with the masses of precursor and fragment ions and partially governed by the glycosidation site. The quantitative relationships between OCEs and masses of precursor and fragment ions were utilized to build large-scale quantitative program for ginsenosides. After applying progressive exciting energies to the back collision chamber to build 3rd 3D spectrum, the fragment ion and the decomposition product anion exhibited identical dissociation trajectories when they shared the same molecular geometry. After ginsenosides-focused quantitative metabolomics, significant differences occurred for sub-metabolome amongst different parts of notoginseng. The differential ginsenosides were confirmatively identified by applying the correlations between 3×3D-MS/MS spectra and structures. Together, 3×3D-MS/MS spectrum covers all MS/MS behaviors and dramatically facilitates sub-metabolome characterization from both quantitative program development and structural identification.

Aucklandiae radix targeted PKM2 to alleviate ulcerative colitis: Insights from the photocrosslinking target fishing technique.

BACKGROUND: Inflammatory bowel disease (IBD) is a chronic and relapsing disease marked by chronic tissue inflammation that alters the integrity and function of the gut, seriously impacting patient health and quality of life. Aucklandiae Radix (AR), known as Mu Xiang in Chinese, is a traditional Chinese medicine documented in Chinese Pharmacopoeia with effects of strengthening the intestine and stopping diarrhea. However, the potential of AR in treating intestinal inflammation and its underlying mechanism have yet to be further elucidated. PURPOSE: The objective of this study was to explore the protective effect and the potential mechanism attributable to AR for treating ulcerative colitis (UC). STUDY DESIGN AND METHODS: A murine model of UC was constructed using dextran sulfate sodium (DSS) to examine the therapeutic potential of AR in alleviating inflammation and modulating the immune response. Advanced techniques such as photocrosslinking target fishing technique, click chemistry, Western blot analysis, real-time quantitative PCR, flow cytometry, immunofluorescence, and immunohistochemistry were employed to unveil the therapeutic mechanism of AR for treating IBD. RESULTS: AR decreased disease activity index (DAI) score to alleviate the course of IBD through ameliorating intestinal barrier function in DSS-induced mice. Furthermore, AR suppressed NF-κB and NLRP3 pathways to reduce the release of pro-inflammatory factors interleukin-6 and 1ß (IL-6 and IL-1ß) and tumor necrosis factor α (TNF-α), allowing to alleviate the inflammatory response. Flow cytometry revealed that AR could reduce the accumulation of intestinal macrophages and neutrophils, maintaining intestinal immune balance by regulating the ratio of Treg to Th17 cells. It was worth noting that pyruvate kinase isozyme type M2 (PKM2) served as a potential target of AR using the photocrosslinking target fishing technology, which was further supported by cellular thermal shift assay (CETSA), drug affinity target stability (DARTS), and PKM2 knockdown experiments. CONCLUSION: AR targeted PKM2 to inhibit NF-κB and NLRP3 pathways, thereby modulating the inflammatory response and immunity to alleviate DSS-induced UC. These findings suggested the potential of AR in the treatment of UC and AR as a candidate for developing PKM2 regulators.

Radical Cascade Reaction of Heterocyclic Ketene Aminals with Thiocyanates Promoted by Visible Light: Synthesis of Functionalized Fused 2-Iminothiazolines.

Herein, a visible-light-promoted radical cascade cyclization of heterocyclic ketene aminals (HKAs) and thiocyanates was developed to access functionalized fused 2-iminothiazolines. This novel cascade reaction can be realized under only visible-light irradiation without the help of external photocatalysts, oxidants, and additives. These multicomponent cascade reactions demonstrate excellent selectivity for the Z-isomers and ensure the formation of the products only in their isomeric form. Preliminary mechanism investigations demonstrated that HKAs and thiocyanates can form electron donor-acceptor complexes for harvesting the energy of visible light to activate substrates and generate reactive radicals. This protocol can be used for synthesizing various natural-like products such as fused 2-iminothiazolines. This approach demonstrates multiple advantages such as commercially available substrates, convenient operation, environmentally friendly, mild conditions, and an efficient multicomponent reaction (2A + B).

Ultrasonic features of hidradenoma papilliferum: An unexpected mass in the vulvar.

Hidradenoma papilliferum is a rare superficial mass with distinct ultrasonic features. It originates from mammary structures and is commonly observed in the anogenital region of women. We report a hidradenoma papilliferum with clear ultrasound images which have never be described before.

Study on the anti-HBV activity of matrine alkaloids from Oxytropis ochrocephala by MTT, 3d-QSAR, molecular docking and molecular dynamics simulation.

To elucidate the structure-activity relationship of 17 matrine alkaloids from Oxytropis ochrocephala Bunge, their effect on hepatitis B surface antigen (HBsAg) secretion was studied using the MTT assay. A 3D-QSAR analysis showed a strong correlation between chemical structures and biological activities (q2 = 0.625, r2 = 0.859). Molecular docking and molecular dynamics simulations revealed that hydrogen bonding and hydrophobic interactions with hepatitis B core protein (PDB:5T2P) are key to inhibiting HBsAg secretion, suggesting potential for developing natural anti-hepatitis B drugs.

Meta-analysis of probiotics efficacy in the treatment of minimum hepatic encephalopathy.

OBJECTIVE: This study aims to systematically evaluate the efficacy of probiotics in treating minimum hepatic encephalopathy (MHE). METHODS: A systematic search was conducted across three major databases: PubMed, China National Knowledge Infrastructure and Wanfang. The search period spanned from the inception of each database to 9 March 2023. The objective was to identify all randomised controlled trials (RCTs) examining the efficacy of probiotic preparations in treating MHE. The search terms included 'probiotics' along with other clinically relevant terms to comprehensively capture all pertinent studies. RESULTS: A total of 18 RCTs were included. The meta-analysis showed that probiotic treatment outperformed control groups in reducing blood ammonia levels (standard mean difference [MD] = -2.68, 95% confidence interval [CI]: -3.90 to -1.46, p < .0001), improving the remission rate of MHE (risk ratio [RR] = 2.79, 95% CI: 1.23-6.35, p = .01) and lowering alanine aminotransferase levels (MD = -11.10, 95% CI: -16.17 to -6.03, p < .0001). It also significantly reduced the Model for End-Stage Liver Disease scores (MD = -2.55, 95% CI: -3.56 to -1.54, p < .00001) and the incidence of MHE (RR = .18, 95% CI: .09-.34, p < .00001). CONCLUSION: Our study demonstrates that probiotics effectively improve blood ammonia levels, liver function and cognitive function in patients with MHE. They significantly enhance the remission rate of MHE and effectively reduce its incidence, providing solid new evidence for treating MHE with probiotics.

A Study on the Relationship between the Thermoelectric Properties and Infrared Emission Performance of ZnO/SrTiO3 Composite Materials.

The thermoelectric properties and infrared emissivity of materials may seem unrelated, but both are influenced by electrical conductivity and thermal conductivity. The photothermal effect of SrTiO3 can establish a connection between the Seebeck coefficient and infrared absorption in the 8-14 µm range. However, there is currently limited research on the relationship between thermoelectric performance and infrared emissivity. In this study, ZnO/SrTiO3 composites were prepared using a hydrothermal method combined with spark plasma sintering. The intrinsic relationship between the thermoelectric and infrared emission performance of the composites was investigated by varying the ZnO content. As the ZnO content increased, the grain boundary barrier of the samples changed, affecting both electrical and thermal conductivities. The infrared emissivity initially decreased and then increased with increasing ZnO content, which contrasted with the trend observed in electrical conductivity, in accordance with the Hagen-Rubens relationship. The ZT value and infrared emissivity exhibited opposite trends, with the ZnO-5 sample having the highest thermoelectric performance and the lowest infrared emissivity, making it the most representative sample. The relationship between the thermoelectric performance and infrared emissivity of SrTiO3 is of significant importance for developing multifunctional materials with both thermoelectric and infrared properties.

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Neonatal sepsis is a common and severe infectious disease with a high mortality rate. Its pathogenesis is complex, lacks specific manifestations, and has a low positive culture rate, making early diagnosis and personalized treatment still a challenge for clinicians. Epidemiological studies on twins have shown that genetic factors are associated with neonatal sepsis. Gene polymorphisms are closely related to susceptibility, disease development, and prognosis. This article provides a review of gene polymorphisms related to neonatal sepsis, including interleukins, tumor necrosis factor, Toll-like receptors, NOD-like receptors, CD14, triggering receptor expressed on myeloid cells-1, mannose-binding lectin, and other immune proteins, aiming to promote precision medicine for this disease.

Molecular dynamics simulation of DNAN/DNB cocrystal PBXs.

CONTEXT: The DNAN/DNB eutectic is a high-energy explosive eutectic with superior safety and thermal stability compared to traditional melt-cast explosives. However, the addition of polymer binders can effectively enhance its mechanical properties, allowing for continued production demands without the need for changes to existing factory equipment. In this paper, a model of the DNAN/DNB eutectic explosive was established, and five different types of polymers-cis-1,4-polybutadiene (BR), ethylene-vinyl acetate copolymer (EVA), polyethylene glycol (PEG), fluorinated polymer (F2603), and polyvinylidene fluoride (PVDF)-were added to the (1 0 - 1), (1 0 1), and (0 1 1) cleavage planes, respectively, to form polymer-bonded explosives (PBXs). The stability, trigger bond length, mechanical properties, and detonation performance of the various polymer-bound PBXs were predicted retrogressively. Among the five PBX models, the DNAN/DNB/PEG model exhibited the highest binding energy and the shortest trigger bond length, indicating a significant improvement in stability, compatibility, and sensitivity compared to the original eutectic. Additionally, although the detonation performance of DNAN/DNB decreased after the addition of binders, the final results were still satisfactory. Overall, the DNAN/DNB/PEG model demonstrated excellent comprehensive performance, proving that among the many polymer binders, PEG is the optimal choice for DNAN/DNB. METHODS: Within the Materials Studio software, molecular dynamics (MD) simulations were employed to predict the properties of the DNAN/DNB eutectic PBX. The MD simulation timestep was set to 1 fs, with a cumulative simulation duration of 2 ns. A 2 ns MD simulation was conducted using the isothermal-isobaric ensemble (NPT). The COMPASS force field was applied, and the temperature was fixed at 295 K.

Chemical Isotope Labeling and Dual-Filtering Strategy for Comprehensive Profiling of Urinary Glucuronide Conjugates.

Glucuronidation, a crucial process in phase II metabolism, plays a vital role in the detoxification and elimination of endogenous substances and xenobiotics. A comprehensive and confident profiling of glucuronate-conjugated metabolites is imperative to understanding their roles in physiological and pathological processes. In this study, a chemical isotope labeling and dual-filtering strategy was developed for global profiling of glucuronide metabolites in biological samples. N,N-Dimethyl ethylenediamine (DMED-d0) and its deuterated counterpart DMED-d6 were used to label carboxylic acids through an amidation reaction. First, carboxyl-containing compounds were extracted based on a characteristic mass difference (Δm/z, 6.037 Da) observed in MS between light- and heavy-labeled metabolites (filter I). Subsequently, within the pool of carboxyl-containing compounds, glucuronides were identified using two pairs of diagnostic ions (m/z 247.1294/253.1665 and 229.1188/235.1559 for DMED-d0/DMED-d6-labeled glucuronides) originating from the fragmentation of the derivatized glucuronic acid group in MS/MS (filter II). Compared with non-derivatization, DEMD labeling significantly enhanced the detection sensitivity of glucuronides, as evidenced by a 3- to 55-fold decrease in limits of detection for representative standards. The strategy was applied to profiling glucuronide metabolites in urine samples from colorectal cancer (CRC) patients. A total of 685 features were screened as potential glucuronides, among which 181 were annotated, mainly including glucuronides derived from lipids, organic oxygen, and phenylpropanoids. Enzymatic biosynthesis was employed to accurately identify unknown glucuronides without standards, demonstrating the reliability of the dual-filtering strategy. Our strategy exhibits great potential for profiling the glucuronide metabolome with high coverage and confidence to reveal changes in CRC and other diseases.

Bibliometric study of sepsis-associated liver injury from 2000 to 2023.

BACKGROUND: Sepsis-associated liver injury (SLI) is a severe and prevalent complication of sepsis. AIM: To explore the literature on SLI via a bibliometric approach. METHODS: Reviews and articles correlated with SLI published from January 1, 2000 to October 28, 2023 were searched from the Web of Science Core Collection. Then, the searched data were analyzed using VOSviewer, CiteSpace, and R language. RESULTS: There were 787 publications involved in this paper, comprising 745 articles and 42 reviews. China, the United States, and Germany are the primary publication sources in this area. Studies related to SLI primarily focused on mechanisms of pathogenesis, as evidenced by analyzing keywords, references, and the counting of original research. These studies mainly involved tumor necrosis factor alpha, inflammation, oxidative stress, and nuclear factor-kappa B. CONCLUSION: There is significant growth in the research on SLI. Current investigations primarily involve basic experiments that aimed at uncovering pathogenic mechanisms. According to the analyzed literature, the identified pathogenic mechanisms and potential therapeutic targets serve as the foundation for translating findings from basic research to clinical applications.

OGG1: An emerging multifunctional therapeutic target for the treatment of diseases caused by oxidative DNA damage.

Oxidative DNA damage-related diseases, such as incurable inflammation, malignant tumors, and age-related disorders, present significant challenges in modern medicine due to their complex molecular mechanisms and limitations in identifying effective treatment targets. Recently, 8-oxoguanine DNA glycosylase 1 (OGG1) has emerged as a promising multifunctional therapeutic target for the treatment of these challenging diseases. In this review, we systematically summarize the multiple functions and mechanisms of OGG1, including pro-inflammatory, tumorigenic, and aging regulatory mechanisms. We also highlight the potential of OGG1 inhibitors and activators as potent therapeutic agents for the aforementioned life-limiting diseases. We conclude that OGG1 serves as a multifunctional hub; the inhibition of OGG1 may provide a novel approach for preventing and treating inflammation and cancer, and the activation of OGG1 could be a strategy for preventing age-related disorders. Furthermore, we provide an extensive overview of successful applications of OGG1 regulation in treating inflammatory, cancerous, and aging-related diseases. Finally, we discuss the current challenges and future directions of OGG1 as an emerging multifunctional therapeutic marker for the aforementioned challenging diseases. The aim of this review is to provide a robust reference for scientific researchers and clinical drug developers in the development of novel clinical targeted drugs for life-limiting diseases, especially for incurable inflammation, malignant tumors, and age-related disorders.

Rapid, sensitive, and visual detection of swine Japanese encephalitis virus with a one-pot RPA-CRISPR/EsCas13d-based dual readout portable platform.

Japanese encephalitis (JE), a mosquito-borne zoonotic disease caused by the Japanese encephalitis virus (JEV), poses a serious threat to global public health. The low viremia levels typical in JEV infections make RNA detection challenging, necessitating early and rapid diagnostic methods for effective control and prevention. This study introduces a novel one-pot detection method that combines recombinant enzyme polymerase isothermal amplification (RPA) with CRISPR/EsCas13d targeting, providing visual fluorescence and lateral flow assay (LFA) results. Our portable one-pot RPA-EsCas13d platform can detect as few as two copies of JEV nucleic acid within 1 h, without cross-reactivity with other pathogens. Validation against clinical samples showed 100 % concordance with real-time PCR results, underscoring the method's simplicity, sensitivity, and specificity. This efficacy confirms the platform's suitability as a novel point-of-care testing (POCT) solution for detecting and monitoring the JE virus in clinical and vector samples, especially valuable in remote and resource-limited settings.

Study on hormone induction of the male parent and embryonic development, gonad differentiation, and growth of "All-female No.1" Culter alburnus.

Female Culter alburnus was faster in growth rate than males. In this study, the gynogenetic G2 and the pseudo-male G2' were used as the female and male parents, respectively, to breed a new national variety "All-female No.1" C. alburnus (AFC). Hormone induction, embryonic development, gonadal differentiation, and growth of AFC were studied. The results showed induction with low concentrations of 17α-methyltestosterone in a indoor-net cage culture was not effective. Under the stimulation of 17α-methyltestosterone, some gonads had a tendency to transform into testis, but not completely. There were three types of gonads in 5-month-old and four types of gonads in 12-month-old fishes, however, they all differentiated into ovaries in 15-month-old fishes. Testosterone propionate and high concentrations of 17α-methyltestosterone in pond culture induction had a good effect resulting in ①a functional pseudo-male with normal testis development that could successfully extrude semen during the breeding period, ②a pseudo-male with normal testis development, but could not extrude semen, and ③the appearance of intersexual glands. The second experiment revealed that with common fish, all-female fish embryo had normal embryonic development. The development time and morphological characteristics of each stage were similar, but the development of the all-female embryo was slightly slower than the common embryos. The gonad differentiation of the all-female embryo were normal and none differentiated into testis, which indicated that all-female could ensure the female sex without affecting the normal gonad differentiation. The correlation between body weight, length, and month-age of all-female and common fish was strong. The all-female had faster growth rate and more uniform growth specification than the common fish. Therefore, the use of testosterone propionate and high concentrations of 17α-methyltestosterone in pond culture induction could avoid complete degeneration of gonads into ovaries. The all-female embryo had the advantages of normal embryonic development and gonadal differentiation, faster growth, and uniform growth specification.

[Discussion on reference sample research of traditional Chinese medicine compound preparations developed from catalogued ancient classical prescriptions].

The concept of reference sample was put forward in the Guidance on CMC of Traditional Chinese Medicine Compound Preparations Developed from Catalogued Ancient Classical Prescriptions(Interim). The research on reference sample is a key link in the research and development of traditional Chinese medicine(TCM) compound prescriptions from catalogued ancient classical prescriptions(known as Category 3.1 TCM). This paper discusses the content of research on reference sample by analyzing the characteristics of Category 3.1 TCM and the purpose of research on reference sample. Furthermore, suggestions on the research of reference sample are proposed according to the development and evaluation practice of Category 3.1 TCM and research achievements of TCM regulatory science, aiming to provide reference for colleagues in this industry.

Online identification of chemical constituents in Mongolian medicine Zhachong-13 pills by UHPLC-Q-exactive Orbitrap MS.

Zhachong-13 pills (ZC-13), as a traditional prescription of Mongolian medicine, are often used in the clinical practice of Mongolian hospitals for the treatment of stroke and rheumatic arthritis. In this experiment, UHPLC-Q-Exactive Orbitrap MS was used to explore the chemical composition of ZC-13. The results showed that 315 compounds were identified or inferred, including 56 alkaloids, 77 2-(2-phenylethyl)chromones, 61 flavonoids, 31 tannins, 8 coumarins, 16 lignans, 21 terpenoids, 5 amino acids, 19 organic acids, and 21 other components. In addition, the pharmacological activities related to anti-cerebral ischemia of these components were summarized. This result laid a foundation for further study on the pharmacodynamic material basis of ZC-13 and provided a scientific basis for the formulation of ZC-13 quality specifications.

The association between weight change patterns and obesity-related complex multimorbidity: evidence from NHANES.

Objective: Obesity is a major risk factor for non-communicable diseases (NCDs), which has been the leading cause of death nowadays. The aim of this study is to examine the association between total changes in body mass index (BMI) across adulthood and the risk of obesity-related complex multimorbidity in elderly, characterizing the capacity of BMI waves in predicting major chronic diseases. Methods: In this retrospective study, 15,520 participants were analyzed from the National Health and Nutrition Examination Survey (NHANES) from 1999 and 2018. BMI was categorized as obesity (≥30.0 kg/m²), overweight (25.0-29.9 kg/m²), normal weight (18.5-24.9 kg/m²), and underweight (<18.5 kg/m²). Odds ratios (ORs) with 95% confidence interval (CIs) for the relationship between BMI change patterns and major health outcomes included hypertension, cancer, chronic obstructive pulmonary disease, cardiovascular disease, and diabetes, and population attributable fractions (PAFs) of BMI were evaluated. Results: In comparison with participants who remained non-obese, those who are stable obese showed the highest risks of developing at least one chronic disease in later life, with odds ratios of 2.76 (95% CI: 2.20 to 3.45) from age 25 years to 10 years before baseline, 2.90 (2.28 to 3.68) from age 25 years to baseline, and 2.49 (2.11 to 2.95) in the 10-year period before baseline. Moving from non-obese to obese weight-change pattern in all periods (from age 25 years to 10 years before baseline: OR = 1.82; 95% CI, 1.57 to 2.11; from age 25 years to baseline: OR = 1.87; 95% CI, 1.59 to 2.19; from 10 years before baseline to baseline: OR = 1.62; 95% CI, 1.26 to 2.08) and moving from obese to non-obese, the 10-year period before baseline (OR = 1.89; 95% CI, 1.39 to 2.57) was associated with increased risk of chronic diseases. Midlife obesity status can explain the 8.6% risk of occurrence of the chronic diseases in elderly. Conclusions: Maintaining a stable healthy weight and losing weight in early adulthood and midlife are important for better life quality during the aging process. More effective strategies and policies to reduce the prevalence of obesity are needed.

Rapid, sensitive, and visual detection of pseudorabies virus with an RPA-CRISPR/EsCas13d-based dual-readout portable platform.

Pseudorabies viruses (PRV) pose a major threat to the global pig industry and public health. Rapid, intuitive, affordable, and accurate diagnostic testing is critical for controlling and eradicating infectious diseases. In this study, a portable detection platform based on RPA-CRISPR/EsCas13d was developed. The platform exhibits high sensitivity (1 copy/µL), good specificity, and no cross-reactivity with common pathogens. The platform uses rapid preamplification technology to provide visualization results (lateral flow assays or visual fluorescence) within 1 h. Fifty pig samples (including tissues, oral fluids, and serum) were tested using this platform and real-time quantitative polymerase chain reaction (qPCR), showing 34.0 % (17 of 50) PRV positivity with the portable CRISPR/EsCas13d dual-readout platform, consistent with the qPCR results. These results highlight the stability, sensitivity, efficiency, and low equipment requirements of the portable platform. Additionally, a novel point-of-care test is being developed for clinical use in remote rural and resource-limited areas, which could be a prospective measure for monitoring the progression of pseudorabies and other infectious diseases worldwide.

Distinct Thalamo-Subcortical Circuits Underlie Painful Behavior and Depression-Like Behavior Following Nerve Injury.

Clinically, chronic pain and depression often coexist in multiple diseases and reciprocally reinforce each other, which greatly escalates the difficulty of treatment. The neural circuit mechanism underlying the chronic pain/depression comorbidity remains unclear. The present study reports that two distinct subregions in the paraventricular thalamus (PVT) play different roles in this pathological process. In the first subregion PVT posterior (PVP), glutamatergic neurons (PVPGlu) send signals to GABAergic neurons (VLPAGGABA) in the ventrolateral periaqueductal gray (VLPAG), which mediates painful behavior in comorbidity. Meanwhile, in another subregion PVT anterior (PVA), glutamatergic neurons (PVAGlu) send signals to the nucleus accumbens D1-positive neurons and D2-positive neurons (NAcD1→D2), which is involved in depression-like behavior in comorbidity. This study demonstrates that the distinct thalamo-subcortical circuits PVPGlu→VLPAGGABA and PVAGlu→NAcD1→D2 mediated painful behavior and depression-like behavior following spared nerve injury (SNI), respectively, which provides the circuit-based potential targets for preventing and treating comorbidity.