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Mesalazine is a widely used medication for treating mild to moderate inflammatory bowel disease (IBD). First identified as a potential cause of acute pancreatitis (AP) in 1989, the link between mesalazine and AP has primarily been established through case reports and a limited number of retrospective studies. This study aims to explore the characteristics of mesalazine-induced AP. Methods: The databases of CNKI, Wanfang Data, VIP, PubMed and Web of Science were searched (up to March, 2024), and the case reports of mesalazine-related AP in IBD patients were collected and descriptively analyzed. Results: Thirty-four reports were included, describing 42 patients (22 males, 16 females, 4 unspecified) with mesalazine-related AP. The onset of pancreatitis occurred a median of 14 days (range 1– 730 days) after starting mesalazine. Common symptoms included abdominal pain (100%), vomiting (38.1%), fever (21.4%), and nausea (21.4%). Most patients had elevated serum amylase and lipase levels, with some showing raised C-reactive protein and erythrocyte sedimentation rate. Imaging tests, such as computed tomography and B-scan ultrasonography, revealed edematous infiltration and inflammation. Discontinuation of mesalazine led to symptom resolution in all patients, with 93.3% improving within a week. Alternative treatments or switching to other forms of 5-aminosalicylic acid may be considered for ongoing management. Rechallenge with mesalazine led to recurrence of AP in 21 cases, with a shorter median time to symptom onset. Conclusion: Mesalazine-induced AP is a rare but significant adverse reaction, not related to drug dosage, and can occur at any point during treatment, typically within two weeks. The reaction can recur upon rechallenge. Discontinuation of mesalazine and symptomatic treatment typically resolves the condition. [ABSTRACT FROM AUTHOR]

This study presents a novel transparent, sensitive electronic skin (S-TENG) using a frictional nanogenerator for energy harvesting and physiological motion monitoring. Featuring thermally treated PVDF fiber membranes and silver nanowire electrodes, the e-skin boasts 80% transparency, high sensitivity (detecting 0.13 g touch), stability, and breathability. It generates 301 V and 2.7 µA under 8N force, achieving 306 mW/m2 power density. S-TENG holds promise for self-powered wearables and health training applications, representing a significant step in e-skin innovation. [Display omitted] Against the backdrop of advancements in modern multifunctional wearable electronics, there is a growing demand for simple, sustainable, and portable electronic skin (e-skin), posing significant challenges. This study aims to delineate the development of a straightforward, transparent, highly sensitive, and high power-density electronic skin based on a triboelectric nanogenerator(S-TENG), designed for harvesting human body energy and real-time monitoring of the physiological motion status. Our e-skin incorporates thermally treated polyvinylidene fluoride (PVDF) fiber membranes as the contact layer and a film of silver nanowires as the conductive electrodes. The resulting contact-separation type e-skin exhibits an impressive transparency of 80 %, along with a nice sensitivity value, capable of detecting a light touch from a 0.13 g sponge and demonstrating good working stability and breathability. Leveraging the triboelectric effect, our e-skin generates an open-circuit voltage of 301 V and a short-circuit current of 2.7 μA under an extrinsic force of 8 N over an interaction area of 4 × 4 cm2, achieving a power density up to 306 mW/m2. With its signal processing circuitry, the integrated S-TENG showcases nice energy harvesting and signal transmission capabilities. Accordingly, we contend that S-TENG has potential applications in energy capture and real-time human motion state monitoring. This research is anticipated to blaze a novel and practical trail for self-powered wearable devices and personalized health rehabilitation training regimens. [ABSTRACT FROM AUTHOR]

A diffeomorphism is non-uniformly partially hyperbolic if it preserves an ergodic measure with at least one zero Lyapunov exponent. We prove that a C1-smooth ℤd-action has the quasi-shadowing property if one of the generators is C1+α (α > 0) non-uniformly partially hyperbolic. [ABSTRACT FROM AUTHOR]

To describe the characteristics of multiple myeloma (MM) by retrospectively analyzing data from patients with MM in hematology, nephrology, and orthopedic departments, we selected inpatients diagnosed with MM for the first time who were admitted to the hematology department of Taizhou Hospital of Zhejiang Province between January 1, 2017, and June 30, 2021 ( n = 110 ) and those admitted to the nephrology ( n = 48 ) and orthopedic ( n = 42 ) departments of Taizhou Hospital of Zhejiang Province between January 1, 2010, and June 30, 2021. For patients with MM initially diagnosed in the nephrology or orthopedic departments, age- and sex-matched patients without MM were randomly selected in a 1:1 ratio. Conditional logistic regression models were used to assess the risk of MM in hospitalized patients in the nephrology and orthopedic departments. This study included 200 patients, with a median age of 65 years. There were differences among patients in the three departments with respect to fracture, degree of anemia, proteinuria levels, red blood cell (RBC) count, hemoglobin levels, total protein (TP) levels, albumin levels, and laboratory indicators of renal function. TP levels > 68.45 g/L were independent risk factors for patients in the nephrology department (odds ratio (OR) = 1.01, 95% confidence interval (CI) = 1.001–1.024, P = 0.04), and RBC count < 3.79 × 1012/L was an independent risk factor for orthopedic inpatients (OR = 0.49, 95% CI 0.268–0.913, P = 0.02). Therefore, nephrologists should pay attention to the TP level of hospitalized patients to facilitate the early identification of MM in patients with chronic kidney disease. Orthopedic surgeons should pay attention to RBC counts in patients with fractures, and patients with low RBC counts should avoid unnecessary surgery and move to specialist care as early as possible. [ABSTRACT FROM AUTHOR]

Schematic diagram of the TWD's effects on AD. By suppressing the IL1R1/MyD88/NF-κB and NLRP3/IL-1β/IL-1R1/TOM1 pathways, regulating BACE/APP/Aβ pathways and improving microglial phagocytosis of Aβ, TWD reduces excessive neuroinflammation. Overall, TWD's diverse activities improve cognitive and memory deficits. [Display omitted] • TWD improves cognitive impairment in 3x-Tg AD mice. • TWD alleviates pathological changes in mice, alleviate neuroinflammatory responses, and inhibit microglial overactivation. • TWD regulates the NLRP3/IL-1β/IL-1R1/TOM 1 and NF-κB/MyD88/IL1R1 signaling pathway in the treatment of AD. Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the deposition of beta-amyloid (Aβ) peptides. Microglia-mediated neuroinflammation is one of the primary contributors to the pathogenesis of AD. Withanolides, the main constituents in the leaves of Datura stramonium L., exhibit anti-neuroinflammatory activity. It is unknown if total withanolide from Datura stramonium L. leaves (TWD) reduces nerve inflammation and potentially mitigates the pathogenic elements of AD. This study examined the potential effects of TWD on neuroinflammation in triple transgenic AD (3 × Tg-AD) mice and LPS-induced BV-2, as well as associated signaling pathways. HPLC-Q-TOF-MS/MS was used in this study to examine the main chemical components of the TWD extract. 3 × Tg-AD as in vivo AD models and LPS induce BV-2 cells in vitro AD models. The molecular process was investigated by ELISA, WB, IHC, and IF. In 3 × Tg-AD mice, TWD dramatically ameliorates cognitive impairment. Treatment with TWD can counteract the increased activation of microglia and Aβ deposits observed in 3 × Tg-AD mice. Further research indicates that TWD can enhance TOM 1 and mitigate inflammatory responses by reducing the levels of IL-1β, TNF-α, IL-6, IL1R1, and IL-18. Additionally, TWD may inhibit neuroinflammation through the pathways of IL1R1/MyD88/NF-κB and NLRP3/IL-1β/IL1R1. In summary, this study reveals for the first time that TWD effectively improves cognitive deficits in 3 × Tg-AD mice by modulating the IL1R1/MyD88/NF-κB and NLRP3/IL-1β/IL1R1 pathways. It also alleviates excessive activation of microglia and suppresses Aβ accumulation. Therefore, TWD has the potential as a therapeutic agent for AD. [ABSTRACT FROM AUTHOR]

Endogenous retroviruses (ERVs), deriving from exogenous retroviral infections of germ line cells occurred millions of years ago, represent ~8% of human genome. Most ERVs are highly inactivated because of the accumulation of mutations, insertions, deletions, and/or truncations. However, it is becoming increasingly apparent that ERVs influence host biology through genetic and epigenetic mechanisms under particular physiological and pathological conditions, which provide both beneficial and deleterious effects for the host. For instance, certain ERVs expression is essential for human embryonic development. Whereas abnormal activation of ERVs was found to be involved in numbers of human diseases, such as cancer and neurodegenerative diseases. Therefore, understanding the mechanisms of regulation of ERVs would provide insights into the role of ERVs in health and diseases. Here, we provide an overview of mechanisms of transcriptional regulation of ERVs and their dysregulation in human diseases. [ABSTRACT FROM AUTHOR]

According to previous studies, mental status in 1-year COVID-19 survivors might range from 6–43%. Longer-term psychological consequences in recovered COVID-19 subjects are unknown, so we analyzed longer-term quality of life and mental status in recovered COVID-19 subjects at 2 years after infection. Among 144 recovered COVID-19 subjects in the Taizhou region, 73 and 45 completed face-to-face follow-ups at the first year and second year after infection, respectively, with a 61.7% follow-up rate. The questionnaire, which was administered at both follow-ups, included questions about quality of life, psychological health, and post-traumatic stress disorder (PTSD). The Mann-Whitney U test was used to the differences of each scale between the first and second year. Among the 45 people who completed both follow-up visits, the incidence of psychological problems was 4.4% (2/45) in the first year, and no new psychological abnormalities were observed in the second year. Quality of life improved, while the General Health Questionnaire (GHQ-12) and Impact of Event Scale-Revised (IES-R) scores did not improve over time. The incidence of mental disorders was lower than those in previous studies. Multidisciplinary management for COVID-19 in this study hospital may have reduced the frequency to a certain extent. However, among those with mental health problems, such problems may exist for a long time, and long-term attention should be given to the psychological status of recovered COVID-19 subjects. [ABSTRACT FROM AUTHOR]

To enhance PI films' triboelectric nanogenerator(TENG) performance , we synthesized amino-functionalized reduced graphene oxide (FRGO)/polyimide (PI) composite films via in-situ polymerization. As a charge capturer, FRGO significantly increases the film's charge density and storage capacity, offering a novel method to boost the TENG performance of PI films. [Display omitted] As a promising sustainable power source in intelligent electronics, Triboelectric Nanogenerators (TENGs) have garnered widespread interest, with various strategies explored to enhance their output performance. However, most optimization methods for triboelectric materials have focused solely on tuning chemical compositions or fabricating surface microstructures. Here, we have prepared amino-functionalized reduced graphene oxide (FRGO)/polyimide (PI) composite films (PI-FRGO) via in-situ polymerization, aimed at enhancing PI materials' nanotribological power generation performance. By varying the doping levels of amino groups and controlling the FRGO proportion during synthesis, we can explore the optimal FRGO/PI composite film ratio. At a p-Phenylenediamine: reduced Graphene Oxide (PPDA: RGO) ratio of 1:1 and an FRGO addition of 0.1 %, the output electrical performance peaks with a voltage of 58 V, a charge of 33 nC and a current of 12 μA, nearly 2 times that of a pure PI film. We have fabricated a TENG with an optimally formulated PI-FRGO composite to explore its application potential. Under a 10 MΩ external load resistance, the TENG can deliver a power density of 3.5 mW/m2 and can be powering small devices. This work presents new effective strategies to significantly enhance TENG output performance and promote their widespread application. [ABSTRACT FROM AUTHOR]

Introduction: Protein A immunoadsorption (IA) is proving to be an effective treatment method for autoimmune diseases and other disorders. Regional citrate anticoagulation (RCA) prevents clotting in extracorporeal circuits without increasing hemorrhage risk in high bleeding risk patients, but there are no specific guidelines for its application in IA. We aimed to evaluate the safety and adverse effects of RCA used in IA therapy. Methods: We conducted a retrospective cohort study of forty-five RCA-IA sessions in 14 HLA-incompatible kidney transplant recipients with focus on the safety and adverse effects of RCA in IA. The extracorporeal circuit was equipped with 4% trisodium citrate solution as an anticoagulant and 10% calcium gluconate solution to compensate for calcium loss. The adverse events, including coagulation and blood biochemical indexes, especially calcium level, were recorded. Results: Our study found that 93.33% of the sessions were without circuit clotting or other significant complications. A slight decrease in fibrinogen level was observed, but without significant variations in other coagulation indexes or platelet count. There was a slight elevation in the potential of hydrogen, bicarbonate, and base excess after 2 h and 6 h posttreatment relative to prior treatment, but these returned to normal levels within 24 h posttreatment. Conclusion: RCA is a feasible, effective, and safe anticoagulation option for IA treatment in HLA-incompatible kidney transplant recipients. Electrolyte disturbances, especially alkalosis, hypocalcemia, hypomagnesemia, and fluid status, should be closely monitored and managed. [ABSTRACT FROM AUTHOR]

Aims: Adenoid cystic carcinoma (ACC) is a distinctive tumour. Limited studies involving a large population have reported multicentre systematic analyses of the clinical, pathological and immunohistochemical (IHC) features of ACC as well as the potential role of IHC markers in the prognosis of ACC. Methods and Results: The clinical, histopathological and IHC data of 296 cases obtained from two tertiary hospitals were analysed. The age at onset ranged from 12 to 87 years with a median age of 52 years. The male‐to‐female ratio was 1:1.3. Patients with ACC arising from the lacrimal gland were younger than those with tumours arising from other sites. Patients with tumours in the extra auditory canal and nasopharynx were older than those with tumours in other locations. Histopathologically, solid type ACC was the most frequent in the nasal cavity and paranasal sinus (6/51) group. Tumours arising from the oral cavity most commonly showed perineural invasion (10/60) and margin positivity (11/60). IHC analyses showed that CK8/18, CK7, CK14, epithelial membrane antigen and CD117 were expressed in 35/35 (100%), 87/88 (98.8%), 26/27 (96.2%), 42/43 (97.6%) and 113/120 (94.1%) patients, respectively. CK5/6, P63, smooth muscle actin, calponin and S100 were positively expressed in 73/73 (100%), 111/124 (89.5%), 38/43 (88.3%), 41/50 (82.0%) and 61/92 (66.3%) cases, respectively. S100 proteins were expressed in 54 (54/77) primary cases and two (2/9) metastatic cases (p = 0.013). Conclusions: ACC is a distinctive tumour that mainly affects middle‐aged and elderly individuals, with a mild female predominance. Loss of expression of S100 proteins may be a poor prognostic factor associated with metastasis. [ABSTRACT FROM AUTHOR]

Nitrogen and sulfur co-doped carbon dots (N,S-CDs) have been widely studied with high quantum yield (QY). The experimental conditions of three different N,S-CDs were optimized. Emission peak position of three different N,S-CDs shown almost remains unchanged or obvious excitation-dependent PL properties, that was likely owed to size distribution. In order to discuss the N,S-CDs stability of photoluminescence property in environment, various experiments such as the photostability, different pH, ionic strengths and temperature were designed. To sum up, three different N,S-CDs exhibited discrepancy property. Molecular interaction of three different N,S-CDs were produced via vary carbon source with human serum albumins have been investigate by various methods. The quenching mechanism, thermodynamic and kinetic parameters, binding sites, electrochemical behavior of three different N,S-CDs with human serum albumins have some different, but conformational change of three different N,S-CDs with human serum albumins alike. The molecular docking had successful applied to study the N,S-CDs interaction with HSA. Different N,S-CDs possessed various characteristic that will have different quenching mechanism when they interaction with human serum albumin, study the mechanism of action at molecular level will help people to choose suitable CDs to apply in nanomedical. Unlabelled Image • The three different N,S-CDs were synthesized by various carbon source. • The discrepancy property of three N,S-CDs was system discussed. • The interaction mechanism between N,S-CDs and HSA was illuminated by multiple method. • The molecular docking had been successfully applied to study the N,S-CDs interaction with HSA. • The interaction mechanism between N,S-CDs and HSA were presented. [ABSTRACT FROM AUTHOR]

The effects of mesenchymal stem cells (MSCs) and MSC-derived exosomes (MSC-exos) on serum metabolites and intestinal microbiota in rats after liver trauma were discussed. Adult Wistar Albino rats were assigned into control, model (liver trauma), MSCs, and MSC-exos groups (n = 6). The study examined changes in the inflammatory environment in liver tissues were analyzed by histological examination and analysis of macrophage phenotypes. Alterations in serum metabolites were determined by untargeted metabonomics, and gut microbiota composition was characterized by 16S rDNA sequencing. Correlations between specific gut microbiota, metabolites, and inflammatory response were calculated using Spearman correlation analysis. Rats with liver trauma after MSCs and MSC-exos treatment exhibited attenuated inflammatory infiltration and necrosis in liver tissues. MSCs and MSC-exos treatment reduced the proportion of M1 macrophages, accompanied by a decrease in inducible nitric oxide synthase (iNOS) and tumor necrosis factor-alpha (TNF-α) levels. Furthermore, MSCs and MSC-exos treatment expanded the proportion of M2 macrophages, accompanied by an increase in arginase-1 (Arg-1) and interleukin-10 (IL-10) levels. The beneficial effects of MSC-exo treatment on rats with liver trauma were superior to those of MSC treatment. The composition and abundance of the gut microbiota and metabolites were altered in pathological rats, whereas MSC and MSC-exo intervention partially restored specific gut microbiota and metabolite alterations. At the phylum level, alterations in Bacteroidota , Proteobacteria , and Verrucomicrobiota were observed after MSC and MSC-exo intervention. At the genus level, Intestinimonas , Alistipes , Aerococcus, Faecalibaculum , and Lachnospiraceae_ND3007_group were the main differential microbiota. 6-Methylnicotinamide, N-Methylnicotinamide, Glutathione, oxidized, ISOBUTYRATE, ASCORBATE, EICOSAPENTAENOATE, GLYCEROL 3-PHOSPHATE, and Ascorbate radical were selected as important differential metabolites. There was a clear correlation between Ascorbate, Intestinimonas / Faecalibaculum and inflammatory cytokines. MSC-exos promoted the repair of tissue damage in rats with liver trauma by regulating serum metabolites and intestinal microbiota, providing new insights into how MSC-exos reduced inflammation in rats with liver trauma. • MSCs and MSC-exos attenuated liver tissue inflammation in rats with liver trauma. • MSCs and MSC-exos induced a shift of macrophages from M1 to M2 in liver tissue. • Specific gut microbiota and metabolite levels were altered by MSCs and MSC-exos. • Metabolites, gut microbiota and inflammatory cytokines were closely correlated. • Our research provided new insight into the treatment of liver trauma with MSC-exos. [ABSTRACT FROM AUTHOR]

Background: Identifying specific residues for protein-DNA interactions are of considerable importance to better recognize the binding mechanism of protein-DNA complexes. Despite the fact that many computational DNA-binding residue prediction approaches have been developed, there is still significant room for improvement concerning overall performance and availability. Results: Here, we present an efficient approach termed PDRLGB that uses a light gradient boosting machine (LightGBM) to predict binding residues in protein-DNA complexes. Initially, we extract a wide variety of 913 sequence and structure features with a sliding window of 11. Then, we apply the random forest algorithm to sort the features in descending order of importance and obtain the optimal subset of features using incremental feature selection. Based on the selected feature set, we use a light gradient boosting machine to build the prediction model for DNA-binding residues. Our PDRLGB method shows better overall predictive accuracy and relatively less training time than other widely used machine learning (ML) methods such as random forest (RF), Adaboost and support vector machine (SVM). We further compare PDRLGB with various existing approaches on the independent test datasets and show improvement in results over the existing state-of-the-art approaches. Conclusions: PDRLGB is an efficient approach to predict specific residues for protein-DNA interactions. [ABSTRACT FROM AUTHOR]

Hirschsprung disease (HSCR) is a newborn colorectal disease characterized by an absence of ganglia in the distal gut. Hedgehog (Hh) and endothelin signaling serve important roles in gastrointestinal tract formation. Alterations in the signaling pathways disrupt the development of enteric neural crest cells (ENCCs). It is not known whether there is any coordination between these pathways in the pathogenesis of HSCR. In the present study, tissue samples from 35 patients with HSCR, including stenotic aganglionosis gut and normal ganglionic gut, were obtained. The expression of Gli family zinc finger 1 (Gli1) and endothelin receptor type B (EDNRB) was determined using reverse transcription‑quantitative polymerase chain reaction, immunohistochemistry and western blotting. In addition, the SK‑N‑SH cell line was used to investigate the association between Hh signaling and the expression of EDNRB. The results revealed aberrant expression of Gli1 in the aganglionic segments, as well as decreased expression of Gli1 in tissues from 7 patients with HSCR exhibited, whereas tissues from 9 patients with HSCR exhibited increased Gli1 expression compared with the expression in the normal tissues. There was a negative association between EDNRB expression and Gli1 expression in the same sample. Knockdown of Gli1 by small interfering RNA and inhibition of Hh signaling by Vismodegib in SK‑N‑SH cells increased EDNRB expression. By contrast, upregulation of Gli1 expression by plasmids and activation of Hh signaling by Purmorphamine decreased EDNRB expression. Furthermore, premature enteric ganglia were observed in 4 patients with HSCR with decreased Gli1 expression. Thus, the results of the present study suggest that altered Gli1 expression negatively regulates EDNRB expression in patients with HSCR. The increased expression of EDNRB induced by decreased Gli1 expression may represent a novel mechanism in HSCR. [ABSTRACT FROM AUTHOR]

This article presents a W‐band three‐layer reflectarray antenna that can be easily fabricated using printed circuit board (PCB) process. The proposed reflectarray element is composed of substrate integrated waveguide (SIW) structure and slot‐coupled patch. By controlling the length of SIW in each element, the compensation phases required for the reflectarray to generate focused beam at in‐band frequencies are realized. However, at the out‐of‐band frequencies, the elements fail to provide the required compensation phases as the incident electromagnetic wave cannot couple to the SIW. Thus, filtering performance is realized. A circular aperture prototype reflectarray comprising of 5024 elements are employed to yield a high‐gain narrow beam. The measured results show that the proposed reflectarray antenna attains a peak gain of 40.5 dB at 94 GHz with aperture efficiency of 41.3%, and out‐of‐band suppression higher than 22 dB. [ABSTRACT FROM AUTHOR]

• Omicron-infected with booster have more NAbs, fewer symptoms, faster viral shedding. • Hybrid immunity induces higher NAb levels than vaccine-only immunity. • NAb higher in booster-vaccinated than in two-dose-vaccinated patients. Waning vaccine-induced immunity and emergence of new severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants which may lead to immune escape, pose a major threat to the COVID-19 pandemic. Currently, enhanced efficacy of the neutralization antibodies (NAb) produced after the booster dose of vaccinations against the Omicron variant is the main focus of vaccine strategy research. In this study we have analyzed the potency of the NAbs and IgGs produced after the third vaccine dose in patients infected with Omicron variant and wild-type (WT) SARS-CoV-2. We enrolled 75 patients with Omicron variant breakthrough infections, and 87 patients with WT infections. We recorded the clinical characteristics and vaccination information of all patients and measured the NAb and anti-S1 (spike protein) + N (nucleocapsid protein) IgG-binding antibodies against SARS-CoV-2 in serum samples of Omicron variant-infected patients at admission, and patients with WT COVID-19 infection from the time of admission and discharge, and one-year to two-years follow-ups. Our results demonstrated higher NAb levels, fewer clinical symptoms, and faster viral shedding in Omicron variant infected patients vaccinated with the booster dose. Hybrid immunity (natural infection plus vaccination) induces higher NAb levels than vaccine-only immunity. NAb and IgG levels decreased significantly at one-year follow-up in WT convalescents with natural infection. The NAb and IgG levels in booster-vaccinated COVID-19 patients were higher than those in two-dose-vaccinated patients. Our results suggest that booster vaccinations are required to improve the level of protective NAbs. Moreover, our data provide important evidence for vaccination strategies based on existing vaccines. [ABSTRACT FROM AUTHOR]

In order to improve the accuracy of sense-through-foliage target recognition, a new recognition method based on sparse representation-based adaptive feature extraction and hybrid particle swarm optimization (HPSO)-optimized wavelet twin support vector machine (WTSVM) is proposed in this paper. First, an adaptive feature extraction approach based on sparse representation is applied to extract the target features from the measured radar echo waveforms, the target feature set is constructed by sparse coefficients that contain most target information. Then, a new recognition method based optimized WTSVM is developed to perform target recognition. Twin SVM (TSVM) is a powerful tool in the field of machine learning, but the kernel and parameters selection problem still affects the performance of TSVM directly. A novel HPSO is developed in this study to determine the optimal parameters for WTSVM with the highest accuracy and generalization ability. As a hybridization strategy, local search is integrated in the PSO algorithm to further refine the performance of individuals and accelerate their convergence toward the global optimality. Finally, the performance of the proposed method is verified by experiments taken in the forest, and the results conform the improved accuracy of target recognition. [ABSTRACT FROM AUTHOR]

Purpose: Although varieties of surgical repair techniques and materials have been used to repair rotator cuff defects, re-tearing frequently occurs. The purpose of this study is to evaluate the postoperative outcomes of rotator cuff repairs with a decellularized tendon slices (DTSs) graft in a rabbit model. Methods: Large defects in the infraspinatus tendons were created bilaterally in 21 rabbits. The graft group underwent reconstruction of the defects with the DTSs grafts, while the defect group did not undergo any treatment. The specimens underwent histological observation, biomechanical testing, and magnetic resonance imaging (MRI) detection at 4, 8, and 12 weeks after surgery. In addition, 2 rabbits that were not operated on were used for MRI detection as a normal reference. Results: Histological analysis revealed that the graft promoted host cell ingrowth and tissue integration, and a tendon-like structure developed at 12 weeks. The ultimate tensile load had a significant difference between specimens at 4 and 12 weeks in the graft group, but there was no significant difference between the graft group and the defect group. In the graft group, the stiffness at 12 weeks was significantly greater than that at 4 or 8 weeks, and it was also greater than the stiffness in the defect group at 12 weeks. MRI demonstrated that the signal strength of the regenerative tissue from the graft group at 12 weeks was similar to that of normal infraspinatus tendon. Conclusion: The DTSs graft allowed for incorporation of host tendon and improved the biomechanical performance of the regenerative tendon. Therefore, the graft could be a promising bioscaffold to enhance the surgical repair of large rotator cuff defects and consequently improve the clinical outcome of rotator cuff tears. [ABSTRACT FROM AUTHOR]

Eight new steroids, designated mantuoluosides A-H (1–8), were obtained from the enrichment of steroids of the Datura stramonium L. using HPD-BJQH macroporous resin. Their respective structures were elucidated based on spectroscopic methods and comparison data with literature. The anti-inflammatory activities of these compounds were evaluated on (LPS)-induced RAW264.7 cells with inhibition ratio. It was found that most isolates showed potential anti-inflammatory activity with varying degrees of inhibition rate in a concentration-dependent manner at non-cytotoxic concentrations. [Display omitted] • Eight new steroids, mantuoluosides A-H, were isolated from Datura stramonium L. • The new structures were elucidated by extensive analysis of spectroscopic data. • All steroids exhibited NO inhibitory activities in a concentration-dependent manner. [ABSTRACT FROM AUTHOR]

The lolines are a class of bioprotective alkaloids that are produced by Epichloë species, fungal endophytes of grasses. These alkaloids are saturated 1-aminopyrrolizidines with a C2 to C7 ether bridge, and are structurally differentiated by the various modifications of the 1-amino group: -NH2 (norloline), -NHCH3 (loline), -N(CH3)2 (N-methylloline), -N(CH3)Ac (N-acetylloline), -NHAc (N-acetylnorloline), and -N(CH3)CHO (N-formylloline). Other than the LolP cytochrome P450, which is required for conversion of N-methylloline to N-formylloline, the enzymatic steps for loline diversification have not yet been established. Through isotopic labeling, we determined that N-acetylnorloline is the first fully cyclized loline alkaloid, implying that deacetylation, methylation, and acetylation steps are all involved in loline alkaloid diversification. Two genes of the loline alkaloid biosynthesis (LOL) gene cluster, lolN and lolM, were predicted to encode an N-acetamidase (deacetylase) and a methyltransferase, respectively. A knockout strain lacking both lolN and lolM stopped the biosynthesis at N-acetylnorloline, and complementation with the two wild-type genes restored production of N-formylloline and N-acetylloline. These results indicated that lolN and lolM are required in the steps from N-acetylnorloline to other lolines. The function of LolM as an N-methyltransferase was confirmed by its heterologous expression in yeast resulting in conversion of norloline to loline, and of loline to N-methylloline. One of the more abundant lolines, N-acetylloline, was observed in some but not all plants with symbiotic Epichloë siegelii, and when provided with exogenous loline, asymbiotic meadow fescue (Lolium pratense) plants produced N-acetylloline, suggesting that a plant acetyltransferase catalyzes N-acetylloline formation. We conclude that although most loline alkaloid biosynthesis reactions are catalyzed by fungal enzymes, both fungal and plant enzymes are responsible for the chemical diversification steps in symbio. [ABSTRACT FROM AUTHOR]

Epichloë species are systemic, often seed-transmissible symbionts (endophytes) of cool-season grasses (Poaceae subfam. Poöideae) that produce up to four classes of bioprotective alkaloids. Whereas haploid Epichloë species may reproduce sexually and transmit between host plants (horizontally), many Epichloë species are polyploid hybrids that are exclusively transmitted via seeds (vertically). Therefore, the generation of, and selection on, chemotypic (alkaloid) profiles and diversity should differ between haploids and hybrids. We undertook a genome-level analysis of haploids and polyploid hybrids, emphasizing hybrids that produce lolines, which are potent broad-spectrum anti-invertebrate alkaloids that can accumulate to levels up to 2% of plant dry mass. Prior phylogenetic analysis had indicated that loline alkaloid gene clusters (LOL) in many hybrids are from the haploid species Epichloë bromicola, but no LOL-containing E. bromicola strains were previously identified. We discovered LOL-containing E. bromicola from host grasses Bromus tomentellus and Melica persica in a Mediterranean-climate region (MCR) in Isfahan Province, Iran, and from Thinopyrum intermedium in Poland. The isolates from B. tomentellus and M. persica were closely related and had nearly identical alkaloid gene profiles, and their LOL clusters were most closely related to those of several Epichloë hybrids. In contrast, several LOL genes in the isolate from T. intermedium were phylogenetically more basal in genus Epichloë, indicating trans-species polymorphism. While identifying likely hybrid ancestors, this study also revealed novel host ranges in central Iran, with the first observation of E. bromicola in host tribe Meliceae and of Epichloë festucae in host tribe Bromeae. We discuss the possibility that MCRs may be hotspots for diversification of grass-Epichloë symbioses via extended host ranges and interspecific hybridization of the symbionts. [ABSTRACT FROM AUTHOR]

Highlights: [•] Genomes were sequenced for four fungi with three different loline alkaloid profiles. [•] Different loline alkaloid profiles were associated with differences in loline alkaloid biosynthesis gene clusters. [•] The LolO non-heme iron oxygenase is required for loline ether bridge formation. [•] An exo-1-acetamidopyrrolizidine is a likely pathway intermediate in loline alkaloid biosynthesis. [Copyright &y& Elsevier]

Traffic congestion causes driver frustration and costs billions of dollars annually in lost time and fuel consumption. This paper presents five traffic rerouting strategies designed to be incorporated in a cost-effective and easily deployable vehicular traffic guidance system that reduces travel time. The proposed strategies proactively compute individually tailored rerouting guidance to be pushed to vehicles when signs of congestion are observed on their route. The five proposed strategies are the dynamic shortest path (DSP), the A^\ast shortest path with repulsion (\AR^\ast), the random k shortest path (RkSP), the entropy-balanced kSP (EBkSP), and the flow-balanced kSP (FBkSP). Extensive simulation results show that the proposed strategies are capable of reducing the travel time as much as a state-of-the-art dynamic traffic assignment (DTA) algorithm while avoiding the issues that make DTA impractical, such as the lack of scalability and robustness, and high computation time. Furthermore, the variety of proposed strategies allows tuning the system to different levels of tradeoffs between rerouting effectiveness and computational efficiency. In addition, the proposed traffic guidance system can significantly improve the traffic even if many drivers ignore the guidance or if the system adoption rate is relatively low. [ABSTRACT FROM PUBLISHER]

Breast cancer is a highly harmful malignant tumor, which poses a great threat to women's body and mind, and the mortality rate ranks second among all women's diseases. The incidence rate accounts for 7-10% of various malignant tumors in the whole body, second only to uterine cancer in women, and has become the main cause of threatening women's health. Advanced breast cancer is often considered an incurable disease. The family of heterogeneous nuclear ribonucleoprotein complexes is composed of about 20 hnRNP proteins with molecular weights ranging from 32 to 120 kDa, and they are named according to their molecular weights. Among them, hnRNPA2 and hnRNPB1 are the two most important members of the hnRNP family, both derived from the same gene on chromosome 7p15. Therefore, research to understand the molecular mechanism and process of breast cancer progression has an important role in promoting the current medical research on breast cancer treatment methods. Therefore, studying the mechanism of tumorigenesis is the key to tumor prevention and treatment. Therefore, this paper proposes that A2/B1 promotes the stability of NRF2 mRNA and inhibits ferroptosis and cell proliferation in breast cancer cells. The article mainly introduces the disease diagnosis method based on artificial neural network and its neural network algorithm. In the experimental part, the activity of hnRNP A2/B1 on cancer cells is deeply studied. The results show that the absorbance of the MTT method increases continuously with the extension of the culture time, and the maximum reaches 1.2. This fully shows that its absorption capacity is very strong, especially after 24 hours, the absorption rate rises from 0.6 to 0.9, which shows that 24 hours is the best absorption time. And it can also be found that hnRNPA2/B1 has a significant inhibitory effect on breast cancer cells; it can reduce the effect on breast cancer cell cycle and apoptosis. [ABSTRACT FROM AUTHOR]

• Advanced quantitative 2D-LC strategies for analyzing natural products are reviewed. • Advantages and limitations of various column couplings in 2D-LC are analyzed. • Detectors in quantitative LC×LC are discussed and recommended. • Latest chemometric algorithms for processing LC×LC data are reviewed in detail. Two-dimensional liquid chromatography (2D-LC) separation systems, based on two independent columns with different separation mechanisms, have exhibited strong resolving power for complex samples. Therefore, in recent years, the exceptional resolution of 2D-LC has significantly advanced the chemical separation of natural products, such as complex herbs, greatly facilitating their qualitative and quantitative analysis. This paper aims to review the latest strategies of 2D-LC in the quantitative analysis of complex chemical compositions in natural products. To this end, the major advantages and disadvantages of various column couplings in 2D-LC are discussed based on specific studies, along with suggested solutions to address the identified drawbacks. Moreover, the applications of different detectors combined with the latest chemometrics in 2D-LC for accurate quantitative analysis of natural products are reviewed and discussed. [ABSTRACT FROM AUTHOR]

Background: Pulmonary sarcomatoid carcinoma (PSC) is a rare and unconventional non-small-cell lung cancer (NSCLC) that appears to be aggressive, with a poor prognosis and response to conventional treatment. Approximately 30% of PSCs have potentially targetable genomic alterations, but few studies have involved RET gene fusions, and corresponding targeted therapies are lacking. Case presentation: In this report, we describe a patient with PSC harboring a KIF5B-RET gene fusion who was initially diagnosed with stage IVb lung cancer. Due to the poor performance status, the patient was unable to tolerate any radiotherapy or chemotherapy. Based on the next-generation sequencing (NGS) result of RET gene fusion, the patient was treated with pralsetinib. Two months after the treatment, the patient achieved a partial response. Conclusions: Our case indicates that RET is one of the main driver oncogenes of PSC and provides useful information for precise RET inhibitor administration in the future. Thus, the use of comprehensive genomic profiling may provide important treatment options for PSC. [ABSTRACT FROM AUTHOR]

IgA nephropathy (IgAN) is one of the most common primary glomerulonephritis, and serum Helicobacter pylori (H. pylori) antibody levels are increased in patients with IgA N, but the role of H. pylori infection in the pathogenesis of IgAN is unclear. In this study, we investigated whether there is a causal relationship and reverse causality between IgAN and H. pylori infection by using a bidirectional two-sample Mendelian randomization (MR) analysis. This study was estimated using inverse variance weighted (IVW), MR-Egger and weighted median methods, with the IVW method having the strongest statistical efficacy. Seven common serum H. pylori antibodies were selected as exposure factors for positive MR analysis. The results showed that there was no evidence of a causal relationship between H. pylori infection and IgAN. Reverse MR analysis showed that there was also no evidence that the occurrence of IgAN leads to an increased risk of H. pylori infection. [ABSTRACT FROM AUTHOR]

This paper proposes a nonreciprocal array antenna based on spatiotemporal modulation. This approach relies on the drastically different phase response during the frequency conversion processes in the time‐modulated antenna element. A prototype linear array composed of a pair of resonant patches is designed and fabricated for proof‐of‐concept validation. Measured results are in good agreement with simulation. The results show that the proposed array antenna is capable of providing versatile radiation performance for transmission and reception, including reciprocal transmission and reception radiation beams, nonreciprocal symmetric transmission and reception radiation beams, and nonreciprocal asymmetric transmission and reception radiation beams, by manipulating the RF signal phase and modulation signal phase. [ABSTRACT FROM AUTHOR]

As to the problems in current tourism recommendation, this paper proposes a tourism recommendation algorithm based on the mobile ICV service platform. Firstly, the ICV service system for the Point of Interest (POI) searching and route recommendation is designed. Secondly, the recommendation service model is set up from two aspects, namely the tourism POI clustering algorithm and the tourism POI searching and route recommendation algorithm. In the aspect of symmetrical-based matching features, the clustered POIs are matched with the tourists' interests, and the POIs in the neighborhood of the ICV dynamic locations are searched. Then, a POI recommendation algorithm based on the tourists' interests is constructed, and the POIs that best match the symmetrical interests of the tourists within the dynamic buffer zones of ICV are confirmed. Based on the recommended POIs, the ICV guidance route algorithm is constructed. The experiment verifies the advantages of the proposed algorithm on the aspect of the POI matching tourists' interests, algorithm stability, traveling time cost, traveling distance cost and computational complexity. As to the iterative sum and the iterative sum average of the POI matching function values, the proposed algorithm has a performance improvement of at least 20.2% and a stability improvement of at least 20.5% compared to the randomly selected POIs in matching tourists' interests. As to the cost of the guidance routes, the proposed algorithm reduces the average cost by 19.6% compared to the other suboptimal routes. Compared with the control group algorithms, the proposed algorithm is superior in terms of route cost, with an average cost reduction of 13.8% for the output routes compared to the control group. Also, the proposed algorithm is superior in terms of route cost compared to the control group recommendation algorithms, with an average cost reduction of 11.2%. [ABSTRACT FROM AUTHOR]

We consider the shadowing and quasi-shadowing properties for weakly hyperbolic Z d -actions in this paper. A smooth Z d -action is non-uniformly hyperbolic (or partially hyperbolic) if one of the generators is non-uniformly hyperbolic (or partially hyperbolic). We show that non-uniformly hyperbolic Z d -actions enjoy the shadowing property and partially hyperbolic Z d -actions enjoy the quasi-shadowing, as well as the L p , limit, and asymptotic quasi-shadowing properties. Furthermore, we also obtain a closing lemma for non-uniformly hyperbolic Z d -actions. [ABSTRACT FROM AUTHOR]

This paper presents a magnetless nonreciprocal diplexing antenna that uses time modulation. The device combines the functions of diplexers, filters, isolators, and antennas in a highly integrated manner. The magnetless nonreciprocity response is achieved by applying time modulation to the resonators of the filtering structures. These resonators are implemented in quarter‐wavelength microstrip lines terminated with varactors that are time modulated by low‐frequency signals fed from Coplanar Waveguides built on the ground plane of the microstrip structure. A prototype multilayer patch antenna is fabricated, which is fed through two orthogonal feedlines and the radiating square patch is coupled by a square ring slot etched in the ground plane. The experimental results show that a gain of 4 dB, out‐of band rejection of 22 dB, in‐band isolation of 20 dB, and inter‐port isolation of 35 dB is obtained at both 1.5 GHz (lower band) and 1.8 GHz (higher band). [ABSTRACT FROM AUTHOR]

Thirteen new withanolide aglycones, baimantuoluolines L-X (1 – 13) and one new withanolide glycoside, baimantuoluoside J (14) were isolated from Datura metel L. flowers. The structures of the new compounds were elucidated by the detailed analysis of 1D and 2D NMR techniques and mass spectrometry, together with the closely related literatures. Meanwhile, all isolated compounds were evaluated for their immunosuppressive activities against mice splenocyte proliferation and antiproliferative activities against human gastric adenocarcinoma cells (SGC-7901), human hepatoma (HepG2), and human breast cancer (MCF-7) in vitro. It was found that compounds 1 – 14 showed obvious immunosupressive effects and some of them have moderated antiproliferative activities. Unlabelled Image [ABSTRACT FROM AUTHOR]

Based on the analysis of the problems in material distribution routes, we propose the idea of integrating the intelligent connected vehicle system with material distribution, and construct an intelligent connected vehicle material distribution route model based on k-center spatial cellular clustering and an improved cockroach optimization algorithm. Firstly, we set the research scope to include the distribution center, the distribution points and the geographical environment. A cellular spatial model of distribution points is constructed to quantify and visualize the neighborhood relationship between the distribution centers and distribution points. On this basis, we construct an intelligent connected vehicle material distribution route model based on the improved cockroach optimization algorithm, and the optimal material distribution center is determined by searching for the corresponding optimal distribution route of each distribution center. In the experiment, we use the concept of symmetry to design routes that start from the initial points. The route passes through the distribution point, and finally reaches the destination. In this mode, the experiment generates symmetrically round-trip routes and generates different distribution time schedules. Case studies and comparative experiments show that the proposed algorithm has a total distance cost 1.2 km lower than the distance cost generated by the Baidu Map method and 2.7 km lower than the distance cost generated by the 360 Map method. In terms of the total time cost of the proposed algorithm, it is 0.06 h lower than the time cost generated by the Baidu Map method and 0.135 h lower than the time cost generated by the 360 Map method. Compared with the commonly used Dijkstra algorithm and the A* algorithm for route optimization, our proposed algorithm also generates a lower cost than the two other types of optimization algorithms. In the case study, the distance generated by the proposed algorithm is 1.8 km lower than that of the Dijkstra algorithm, and the total time cost is 0.09 h lower than that of the Dijkstra algorithm. The distance generated by the proposed algorithm is 1.6 km lower than that of the A* algorithm, and the total time cost is 0.08 h lower than that of the A* algorithm. Meanwhile, the proposed algorithm has a lower time complexity than the two commonly used optimization algorithms. Therefore, our proposed algorithm can find the distribution route with the lowest transportation cost. Compared to the commonly used electronic maps and the optimization algorithms for distribution route planning, our proposed algorithm can output distribution routes with lower costs under the same distribution sequence, and reduce the transportation costs for intelligent connected vehicle material distribution systems to the maximum extent. [ABSTRACT FROM AUTHOR]

Zhi‐Shang‐Feng Granules are used in the clinical treatment of influenza to relieve headaches, chills and fever, bronchitis, nasal congestion, neuralgia and other symptoms. To decipher the components responsible for therapeutic effects of Zhi‐Shang‐Feng g ranules against influenza virus, an analytical method based on high‐performance liquid chromatography coupled with Q exactive focus hybrid quadrupole orbitrap high resolution mass spectrometry was developed and the chemical profile of Zhi‐Shang‐Feng granules was characterized. Then, the identified components were used to conduct network pharmacological analysis and determine the potential mechanism of Zhi‐Shang‐Feng Granules. As a result, 177 compounds were putatively identified through comprehensive analysis by liquid chromatography coupled with high‐resolution mass spectrometry, of which 23 compounds were unambiguously confirmed with reference standards. Components in Zhi‐Shang‐Feng Granules were found to specifically act on different enzymes, G‐protein‐coupled receptors, ion channels and transporters in the immune, endocrine, nervous, and circulatory systems. The potential mechanism was related to several biological processes, including cell growth and death, pattern recognition receptor signalling, signalling by interleukins, and lipid metabolism. The combination of chemical profile characterization and network construction provided useful insight into the overall chemical composition of Zhi‐Shang‐Feng granules and revealed their potential anti‐infection, anti‐inflammatory and immunoregulatory mechanisms against influenza virus infected disease. [ABSTRACT FROM AUTHOR]

Systemic pesticide exposure through nectar is a growing global concern linked to loss of insect diversity, especially pollinators. The insecticide sulfoxaflor and the fungicide tebuconazole are currently widely used systemic pesticides which are toxic to certain pollinators. However, their metabolisms in floral or extrafloral nectar under different application methods have not yet been well studied. Hibiscus rosa-sinensis was exposed to sulfoxaflor and tebuconazole via soil drenching and foliar spraying. Sulfoxaflor, tebuconazole, and their main metabolites in floral and extrafloral nectar, soil, and leaves were identified and quantified using liquid chromatography coupled with triple quadrupole mass spectrometry (LC-QqQ MS). The chemical compositions of unexposed and contaminated H. rosa-sinensis floral nectar or extrafloral nectar were compared using regular biochemical methods. The activities of two pesticide detoxifying enzymes, glutathione-s-transferase and nitrile hydratase, in H. rosa-sinensis nectar were examined using LC-MS and spectrophotometry. The floral nectar proteome of H. rosa-sinensis was analysed using high-resolution orbitrap-based MS/MS analysis to screen for sulfoxaflor and tebuconazole detoxifying enzymes. H. rosa-sinensis can absorb sulfoxaflor and tebuconazole through its roots or leaf surfaces and secrete them into floral nectar and extrafloral nectar. Both sulfoxaflor and tebuconazole and their major metabolites were present at higher concentrations in extrafloral nectar than in floral nectar. X11719474 was the dominant metabolite of sulfoxaflor in the nectars we studied. Compared with soil application, more sulfoxaflor and tebuconazole remained in their original forms in floral nectar and extrafloral nectar after foliar application. Sulfoxaflor and tebuconazole exposure did not modify the chemical composition of floral or extrafloral nectar. No active components, including proteins in the nectar, were detected to be able to detoxify sulfoxaflor. [Display omitted] • Sulfoxaflor's presence in floral nectar or extrafloral nectar affected by different application methods. • Co-application tebuconazole did not affects sulfoxaflor accumulation in the floral nectar but in extrafloral nectar. • Extrafloral nectar is not a negligible pathway for systemic pesticides to do harm to non-target animals. • Sulfoxaflor cannot be degraded by any natural components present in the tested nectar. [ABSTRACT FROM AUTHOR]

Staphylococcus aureus ( S. aureus ) is a common cause of hospital-acquired infection and has become an epidemic globally. Alpha-haemolysin (α-haemolysin), a pore-forming toxin, is one of the most important virulence factors secreted by most S. aureus strains. α-haemolysin monomers form a 232.4-kDa membrane-inserted heptamer by self-assembling to cause host cell lysis and death. Consequently, α-haemolysin plays a significant role in the pathogenesis of S. aureus , and it could be the target for the treatment of staphylococcal infection. In this study, epigallocatechin gallate (EGCg), a natural compound with little anti- S. aureus activity, was shown to reduce the haemolytic activity of α-haemolysin by inhibiting the self-assembly of the heptamer. When EGCg was added into a co-cultured system of human alveolar epithelial (A549) cells and bacterial suspension, α-haemolysin-induced cell injury was significantly attenuated. These results indicate that EGCg could effectively reduce the cytotoxicity of the toxin by interacting with α-haemolysin. This study provides the basis for the development of anti-virulence drugs for the treatment of S. aureus infection. [ABSTRACT FROM AUTHOR]

A phytochemical study of the ethanol extract of Astragalus membranaceus (Fisch) Bge. var. mongholicus (Bge) Hsiao resulted in the isolation of seven new triterpenoid saponins, astralanosaponins F–L, together with fifteen known compounds (8–22). Structure analysis of these extracted compounds was performed using 1D-NMR and 2D-NMR spectroscopy, and their data were compared with those of similar compounds previously reported in the literature. The absolute configuration of sugar was determined using GC-MS. The cell viability of SV40 MES 13 cells induced by high glucose was tested using the CCK-8 assay. Compound 19 showed obvious inhibitory effects of the high-glucose induced SV40 MES 13 cells with IC50 values of 12.2 ± 1.29 μM, while compounds 5 and 9 showed moderate inhibitory effects with IC50 less than 30 μM. Their possible structure–activity relationships were preliminarily summarized. [ABSTRACT FROM AUTHOR]

Rheumatoid Arthritis (RA), a chronic inflammatory autoimmune condition, presents a substantial challenge to public health. Dictamnus dasycarpus Turcz. (D. dasycarpus) is a traditional Chinese medicinal plant recognized for its anti-inflammatory properties and is increasingly being utilized as a potential anti-RA agent, but the underlying mechanism is still unclear. The objective of this research is to elucidate the potential active components and therapeutic properties of D. dasycarpus in experimental RA-induced DBA/1J mice, and to uncover the pharmacological basis of its action. Surface plasmon resonance (SPR) was employed to ascertain the specificity of interactions between protein targets and D. dasycarpus active ingredients for treating RA. The extract of D. dasycarpus was obtained by HP-20 microresin column chromatography, and its chemical composition was assessed using UPLC-Orbitrap-MS. This study utilized a collagen-induced arthritis (CIA) mouse model for in vivo experimentation. Body weight, foot thickness measurements, arthritis scores, immune organ index, and serum antibody levels of mice were used as indicators to evaluate the effects of D. dasycarpus components in treating RA. The serum levels of inflammatory factors in mice were measured using a cytokine antibody microarray assay. Additionally, this study quantified the protein expression levels associated with inflammatory responses through a combination of immunohistochemical staining and western blotting analyses. This research investigated the interaction between D. dasycarpus active components and target proteins, including PTPN14, using a BIACORE system. The screened active components were identified as alkaloids through mass spectrometry. The UPLC-Orbitrap-MS analysis revealed that alkaloids were the predominant constituents in the 60% EtOH extract of D. dasycarpus. Alkaloid components significantly reduced the arthritis index, foot swelling, and serum antibody levels of IgG1, IgG 2a, and IgG 2b in CIA mice. Histological staining results indicated that alkaloid components mitigate disease exacerbations in CIA mice. Bioinformatics analysis and protein level detection results show that the therapeutic mechanism of D. dasycarpus in managing RA could be attributed to the suppression of the IL-17 signaling pathway. This study was based on clarifying the therapeutic effect of D. dasycarpus on RA, identifies its effective chemical components as alkaloids. It systematically elucidates the pharmacological mechanisms of alkaloids in treating RA, thereby laying a crucial theoretical foundation for further exploration of the active constituents of D. dasycarpus. [Display omitted] • Dictamnus dasycarpus Turcz. reduced the arthritis index and foot swelling in CIA mice. • Dictamnus dasycarpus Turcz. may impact RA development by modulating immune responses. • Dictamnus dasycarpus Turcz. mitigates RA symptoms by inhibiting the IL-17 signaling pathway. [ABSTRACT FROM AUTHOR]

Two new phenylpropanoids, 4-O-(1''-O-cis-caffeoyl)-β-glucopyran osyl-1-allyl-3-methoxy-benzene (1), 4'-O-(1''-O-cis-caffeoyl)-β-glucopyranosyl-hydroxymegastigm-4-en-3-one (2), together with nine known compounds were obtained from the leaves of Solanum capsicoides. Their structures were elucidated based on spectroscopic methods, and comparing spectral data with those in literature. Meanwhile, their anti-inflammatory activities were evaluated on (LPS)-induced RAW 246.7 cells, and 1, 9, and 10 showed better inhibitory effects with IC50 values of 17.19 ± 1.12, 18.15 ± 0.47, and 19.8 ± 0.95 μM, respectively. [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI) is an important cause of chronic kidney disease (CKD), but the underlying mechanisms are unclear. Animal models are tools for studying the AKI-CKD progression. Kidney ischemia-reperfusion injury (IRI) models, especially the unilateral IRI (uIRI) model with delayed contralateral kidney resection, are commonly used to induce fibrotic progression to CKD after AKI. However, in previous studies, we found that details of the operation had a significant impact on the long-term outcomes of the kidney in this uIRI model. In this study, we investigated the effects of resection timing of the contralateral intact kidney, core body temperatures during ischemia, and time length of kidney ischemia on kidney function, histological injury and kidney fibrosis after AKI, using a mouse uIRI model with delayed contralateral nephrectomy. The results showed that all these parameters significantly affected the AKI-CKD transition. The post-AKI fibrosis worsened and the survival rate declined with a longer interval between contralateral nephrectomy and uIRI, higher ischemic body temperature, or longer ischemic duration when the other two variables were fixed. In conclusion, in the uIRI model with delayed contralateral nephrectomy, kidney fibrosis after AKI is influenced by many factors. Strictly controlling the experimental conditions is very important for the stability and consistency of the model. [ABSTRACT FROM AUTHOR]

A new aromatic glycoside (1) and twelve (2–13) known aromatic glycosides were isolated from the n-butyl alcohol of the 70% EtOH extract of the aerial part of Bupleurum chinense. Among them, compounds 4–7, 9, 11–13 were isolated from Umbelliferae plants for the first time. Their structures were elucidated by NMR and MS spectroscopy, and the absolute configuration of compound 1 was elucidated by single-crystal X-ray diffraction. Compounds 6 and 10 showed moderate cytotoxic activities on MGC-803 cell lines with IC50 values of 8.63 ± 0.08 and 13.65 ± 1.73 μM, respectively. [ABSTRACT FROM AUTHOR]

Nine previously undescribed chromones, named sadivamones O–W (1 – 9), and five known analogues (10 – 14), were isolated from the roots of Saposhnikovia divaricata (Turcz.) Schischk. The detailed structural analysis of each compound was finalized by a variety of methods including NMR (1D and 2D), mass spectrometry (HR-ESI-MS) spectroscopic data, and sugar hydrolysis. The absolute configurations of compounds (4 – 5) were determined by CD. Moreover, compounds 1 – 14 were evaluated for their inhibition of IL-1 β -induced proliferative activity in SW982 cells. The results demonstrated that compounds 2 – 4 and 11 – 12 exhibited notable inhibitory effects on IL-1 β -induced proliferation in a concentration-dependent manner, with the most pronounced inhibition observed at a concentration of 20 μM. [Display omitted] • Nine previously undescribed chromones were obtained from the S. divaricata. • Absolute configurations of sadivamones R and S were determined by CD. • Compounds 2 – 4 and 11 – 12 were remarkably effective in inhibiting IL-1 β -induced SW982 proliferation at 20 μM. [ABSTRACT FROM AUTHOR]

[Display omitted] Neurodegenerative diseases (NDs) represent a hallmark of numerous incapacitating and untreatable conditions, the incidence of which is escalating swiftly, exemplified by Alzheimer's disease and Parkinson's disease. There is an urgent necessity to create pharmaceuticals that exhibit high efficacy and minimal toxicity in order to address these debilitating diseases. The structural complexity and diversity of natural products confer upon them a broad spectrum of biological activities, thereby significantly contributing to the history of drug discovery. Nevertheless, natural products present challenges in drug discovery, including time-consuming separation processes, low content, low bioavailability, and other related issues. To address these challenges, numerous analogs of natural products have been synthesized. This methodology enables the rapid synthesis of analogs of natural products with the potential to serve as lead compounds for drug development, thereby paving the way for the discovery of novel pharmaceuticals. This paper provides a summary of 127 synthetic analogues featuring various natural product structures, including flavonoids, alkaloids, coumarins, phenylpropanoids, terpenoids, polyphenols, and amides. The compounds are categorized based on their efficacy in treating various diseases. Furthermore, this article delves into the structure–activity relationship (SAR) of certain analogues, offering a thorough point of reference for the systematic development of pharmaceuticals aimed at addressing neurodegenerative conditions. [ABSTRACT FROM AUTHOR]

Three undescribed isosteroidal alkaloids (1 – 3), along with two known ones (4 , 5) were isolated from the bulbs of Fritillaria ussuriensis Maxim, their structures were established by comprehensive analyses of the 1D, 2D-NMR and HR-ESI-MS data. Meanwhile, LPS-activated RAW 264.7 macrophages were used to determine the potential anti-inflammatory activity of all the alkaloids in vitro. Among them, compounds 1 and 4 showed significant inhibitory effects against LPS-induced NO production with IC 50 values of 7.79 μM and 11.22 μM, respectively. Compounds 1 and 4 were performed between molecular docking with TLR4/MD2. Based on the results of cell experiments and binding affinities, compound 1 (UG) was chosen for molecular dynamic analysis together with the TLR4/MD2 protein. [Display omitted] • Three undescribed isosteroidal alkaloids (1 – 3) were isolated from the bulbs of Fritillaria ussuriensis. • Compounds 1 and 4 demonstrate moderate activities with IC 50 values at 7.79 μM and 11.22 μM. • Molecular modeling studies have shown that compound 1 (UG) can stably bind to TLR4. [ABSTRACT FROM AUTHOR]

The purified neutral polysaccharide fraction, namely SBP-1, was isolated and characterized from Schisandra chinensis (Turcz.) Baill crude polysaccharides, which have anti-Parkinson's disease activity were investigated in vivo and in vitro. Experiments have shown that the main chain of SBP-1 was Glcp-(1→, →4)-Glcp-(1→ and →4,6)-Glcp-(1→. We also revealed the effect of SBP-1 on the PD mice model and the potential underlying molecular mechanism. The results showed that SBP-1 administration improved behavioral deficits, increased tyrosine hydroxylase-positive cells, attenuated loss of dopaminergic neurons in MPTP-exposed mice, and reduced cell death induced by MPP+. The MCL-1 was identified as the target of SBP-1 by the combination of docking-SPR-ITC, WB, and IF experiments. Subsequently, the study showed that SBP-1 could target MCL-1 to enhance autophagy with a change in the apoptotic response, which was further demonstrated by a change in LC3/P62, PI3K/AKT/mTOR, and possesses a change in the expression of BCL2/BAX/Caspase3. These results demonstrate that SBP-1 may protect neurons against MPP+ or MPTP-induced damage in vitro and in vivo through enhancing autophagy. In summary, these findings indicate that SBP-1 and S. chinensis show potential as effective candidates for further investigation in the prevention and treatment of PD or associated illnesses, specifically through autophagy apoptotic-based mechanisms. [Display omitted] • In the paper, a glucose glycan was extracted and characterized from Schisandra chinensis (SBP-1). • The paper has identified MCL-1 as a direct binding protein of SBP-1 by screening the interaction of SBP-1 with MCL-1. • The SBP-1 had anti-PD effects in both MPP-SHSY5Y and MPTP-induced PD mice by activating autophagy. [ABSTRACT FROM AUTHOR]

A new ent-kaurane diterpenoid, named kaurane daturoside A (1), was isolated from the 70%-EtOH extract of dried pericarps of Datura metel L., along with six known terpenoids, 16α,17-dihydroxy-ent-kauran-19-diglycoside (2), cyclosieversioside F (3), astragaloside II (4), ginsenoside Rg1 (5), astrojanoside A (6), celerioside E (7). The isolated structures were elucidated by means of spectroscopic analyses, and the compounds 2, 3, 7 were separated from Solanaceae for the first time. Meanwhile, among isolates, compounds 2 and 5 exhibited anti-inflammatory activities against LPS-activated RAW264.7 cells (IC50<11.00 μM). [ABSTRACT FROM AUTHOR]

Two new (1-2) and three known quinic acid derivatives (3-5) were isolated from the leaves of Schisandra chinensis (Turcz) Baill. The structures of the compounds were determined by spectroscopic methods, especially the NMR techniques, and also by comparison with reported data in the literature. The cytotoxicity activities of these compounds were evaluated on human tumor cell lines LN229 and three of them showed a certain activity. [ABSTRACT FROM AUTHOR]

The aerial parts of Bupleurum Chinense DC. aromatic oil (BAO) were a well-known Chinese herbal medicine plant extract used to treat epilepsy. This study aimed to explore the therapeutic effect of BAO on kainic acid- (KA-) induced epileptic rats and the possible mechanism of its antiepileptic effect. The composition and content of BAO were analyzed by GC-MS, and BAO was administered orally to alleviate the epileptic behavior induced by KA brain injection. The behavior of epileptic rats was determined by Racine grading criteria. And hematoxylin-eosin staining (HE), Nissl staining, immunohistochemistry, Elisa, Western blot, and other methods were used to study the antiepileptic mechanism of BAO, and the possible mechanism was verified by the epileptic cell model of hippocampal neurons induced by the low-Mg2+ extracellular fluid. BAO was mainly composed of terpenoids and aliphatic compounds. And BAO could improve KA-induced epilepsy-like behavior, neuroinflammation, and neurotransmitter abnormalities in the hippocampus. Furthermore, BAO could regulate the expression of GABA, NMDAR1, Notch1, and MAP2 to improve the symptoms of epilepsy. These results were also validated at the cellular level. These results indicated that BAO could alleviate the epilepsy-like behavior through the action of the Notch/NMDAR/GABA pathway. [ABSTRACT FROM AUTHOR]

Highlights: [•] Epichloë and Neotyphodium spp. are fungal symbionts of cool-season grasses. [•] Many epichloae, particularly asexual hybrids, are vertically transmitted in seeds. [•] Epichloë/Neotyphodium spp. produce any of four classes of protective alkaloids. [•] Structural variations within each alkaloid class give different spectra of activity. [•] Structures of alkaloid-biosynthesis gene loci facilitate chemotypic diversification. [ABSTRACT FROM AUTHOR]

The interactions of the four typical nucleotides with the metal ions Mg2+, Ca2+, Mn2+, Na+, and K+ were studied by using the B3LYP/6-311++G(d,p)//B3LYP/6-31G(d,p) calculations in the PCM model. A lot of initial binding sites of the metal ions were designed and optimized to determine the most stable structures of the metal ion nucleotide compounds. It has been shown that the metal ions tend to attach at the center of the negatively charged atoms of the nucleotides. Furthermore, the vertical excitation energies of the metal ion nucleotide compounds were calculated at the same level with the TDDFT method, and also NBO charges were analyzed to understand the bonding characteristics between the metal ions and the nucleotides. That was also compared with the conclusion in the gas phase. [ABSTRACT FROM AUTHOR]